CAM 119

Prenatal Screening

Category:Laboratory   Last Reviewed:April 2021
Department(s):Medical Affairs   Next Review:April 2022
Original Date:January 2016    

Description
Prenatal screening refers to testing done to determine health status of the pregnant individual and/or fetus. Prenatal screening can consist of screening for infectious diseases and conditions that may complicate the pregnancy as well as testing to determine risk of fetal abnormalities, including genetic and developmental abnormalities. Any individual undergoing screening tests, especially genetic carrier screenings, needs to realize the limitations of screening tests and the difference between screening and diagnostic testing where screening refers to testing of asymptomatic or healthy individuals to search for a condition that may affect the pregnancy or individual. Diagnostic testing is used to either confirm or refute true abnormalities in an individual (Grant & Mohide, 1982; Lockwood & Magriples, 2020).

Background
Prenatal care in the U.S. is widely available and utilized, yet according to the Health Resources and Services Administration (HRSA) nearly 1 million American women (approximately 25% of all births) give birth each year without having adequate prenatal medical care. The risks associated with lack of prenatal care are significant. According to HRSA, "Babies born to mothers who received no prenatal care are three times more likely to be born at low birth weight, and five times more likely to die, than those whose mothers received prenatal care."

Prenatal care is most effective when a timely, comprehensive approach is taken to ensure the health of the mother and the baby. Ideally, factors related to diet, exercise, drug and alcohol use, smoking, family history, ethnic background, mental state, and others are considered and addressed through education, counseling, and testing. 

This policy focuses on laboratory testing performed during pre-conception and/or prenatal periods, as part of a comprehensive prenatal care program.

Policy 

  1. The following routine prenatal screening is considered MEDICALLY NECESSARY for all pregnant women:
    1. Screening for HIV infection
    2. Screening for Chlamydia trachomatis infection
    3. Screening for Neisseria gonorrhea infection
    4. Screening for hepatitis B
    5. Screening for syphilis
    6. Screening for hepatitis C
    7. Screening for bacteriuria
    8. Screening for fetal aneuploidy in accordance with CAM 254 Prenatal Screening for Fetal Aneuploidy
    9. Screening for type 2 diabetes at the first prenatal visit
    10. Screening for gestational diabetes during gestational weeks 24 – 28 and at the first prenatal visit if risk factors are present
    11. Determination of blood type, Rh(D) status, and antibody status during the first prenatal visit, and repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24 to 28 weeks' gestation, unless the biological father is known to be Rh (D)-negative
    12. Screening for anemia meets coverage criteria with a CBC or hemoglobin and hematocrit with mean corpuscular volume
    13. Screening for Group B strep once, recommended during gestational weeks 36 to 37 by American College of Obstetricians and Gynecologists (ACOG)
    14. Urinalysis and urine culture
    15. Rubella antibody testing
    16. Testing for varicella immunity
    17. Screening for tuberculosis in pregnant women deemed to be at high risk for TB (i.e. women with close contact with individuals with active pulmonary / respiratory tuberculosis or highly contagious active tuberculosis and women who are immunocompromised)
  2. Third trimester re-screening of Chlamydia trachomatis, Neisseria gonorrhea, syphilis, and/or HIV infections is considered MEDICALLY NECESSARY for pregnant women who meet ANY one of the following high-risk criteria:
    1. Sexually active young individuals under 25 years
    2. New or multiple sexual partners
    3. Past history of sexually transmitted diseases (Bacterial Vaginosis, Chancroid, Chlamydia, Gonorrhea, Genital Herpes, Hepatitis B, Hepatitis C, HIV/AIDS, Human Papillomavirus, Lymphogranuloma Venereum, Syphilis, Trichomoniasis)
    4. Current sex workers
    5. Past or current injection drug use
  3. For pregnant women and those women seeking pre-conception care, any of the following testing* (See Note 1 below) of carrier status is considered MEDICALLY NECESSARY:
    1. Carrier testing for cystic fibrosis is in accordance with CAM 044 Genetic Testing for Cystic Fibrosis
    2. Carrier testing for Canavan disease, Tay-Sachs disease, familial dysautonomia, Gaucher disease, Fanconi Anemia, Niemann-Pick type A, Bloom syndrome and mucolipidosis IV in Ashkenazi Jewish women
    3. Carrier screening for Tay-Sachs disease in women of French-Canadian or Cajun heritage
    4. Carrier screening for Fragile X syndrome when there is a family history of Fragile X syndrome (or a family history of undefined mental retardation/developmental delay)
    5. Carrier screening for spinal muscular atrophy for all pregnant women and those seeking pre-conception care
    6. Carrier screening for hemoglobinopathies and/or thalassemia in all pregnant individuals and those who are considering pregnancy
    7. Carrier testing for other genetic disorders when there is a family history of a genetic disorder and a properly validated test is available. When there is a known familial mutation, testing should be limited to that mutation, when possible. (See General Genetic Testing policy for more details on appropriate criteria for genetic testing.)
    8. Preconception genetic testing (carrier testing) for hereditary hearing loss mutations (GJB2, GJB6, and other hereditary hearing loss-related mutations) in parents according to the policy CAM 20487 Genetic Testing for Hereditary Hearing Loss 
    9. Next generation sequencing (NGS) panel testing of either Ashkenazi Jewish-related disorders panel or panethnic carriers screening panel of 15 tests as long as a single appropriate AMA genetic sequencing procedure test code is submitted
  4. Carrier screening* (See Note 1 below) of the biological father is considered MEDICALLY NECESSARY when the biological mother is known or found to be a carrier of a recessively inherited disorder. Carrier testing limitations:
    1. Repeat carrier screening for the same disorder is considered NOT MEDICALLY NECESSARY
    2. Carrier screening should be limited to once per lifetime per disorder for which the individual is at risk
  5. Fetal Fibronectin (FFN) assays is considered MEDICALLY NECESSARY for pregnant women who meet ALL of the following criteria:
    1. Singleton or twin gestations,
    2. Intact membranes,
    3. Cervical dilation <3 cm, and
    4. Patient experiencing symptoms suggestive of preterm labor between 24 and less than 35 weeks' gestation.
  6. Testing pregnant women for thyroid dysfunction is considered MEDICALLY NECESSARY if they have any of the following:
    1. Symptoms of thyroid disease
    2. Personal history of thyroid disease
    3. Personal history of other medical conditions associated with thyroid disease (e.g. diabetes mellitus, goiter, iodine deficiency)
  7. Screening for Zika virus testing is covered in accordance with CAM 153 Zika Virus Testing.
  8. Fetal RHD genotyping using maternal plasma is considered MEDICALLY NECESSARY in RHD negative pregnant women.
  9. Pre-conception carrier screening in patients with a family history of a known inherited disorder and if positive, testing of the partner is considered MEDICALLY NECESSARY.
  10. Prenatal genetic testing of a fetus is considered MEDICALLY NECESSARY if high risk for genetic disorder and a family history is present.
  11. Carrier screening more than once per lifetime is considered NOT MEDICALLY NECESSARY.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of a patient’s illness.

  1. All other applications of the FFN assay is considered NOT MEDICALLY NECESSARY, including, but not limited to the following:
    1. As part of routine pregnancy monitoring in asymptomatic women with singleton gestation and no risk factors for preterm birth.
    2. As part of clinical monitoring of asymptomatic women at high risk for preterm birth, including but not limited to those with multiple gestations, history of preterm birth, uterine malformation, cervical incompetence, or history of two or more spontaneous second trimester abortions.
    3. As part of clinical monitoring in women with triplet or higher-order gestations, intact membranes, cervical dilation <3 cm, and who are experiencing symptoms suggestive of preterm labor.
    4. As a test to identify women at term being considered for induction who are likely to deliver within 24–48 hours and therefore, do not require induction.
  2. Pre-conceptional or prenatal genetic testing for inherited medical disorders that do not meet the above criteria is considered NOT MEDICALLY NECESSARY.
  3. Serial monitoring of salivary estriol levels as a technique of risk assessment for preterm labor or delivery is considered NOT MEDICALLY NECESSARY.

Note 1:  Carrier testing should be performed using the most appropriate carrier test (e.g. dosage/deletion for SMN1 and NOT full gene sequencing; DMD del/dup testing and NOT full gene sequencing). 

Rationale
Prenatal screening is a part of overall prenatal care to promote optimal care of both mother and baby.  Prenatal screening allows for assessment and monitoring of the fetus for the presence of congenital defects or disease. Various professional medical organizations provide guidelines for prenatal screening. “Screening is an offer on the initiative of the health system or society, rather than a medical intervention in answer to a patient’s complaint or health problem. Screening aims at obtaining population health gains through early detection that enables prevention or treatment (de Jong, Maya, & van Lith, 2015).”

Routine prenatal screening may include several laboratory tests. Hematocrit or hemoglobin testing can be performed to check for anemia and possible thalassemia, pending further diagnostic testing. Blood typing and antibody screening can be performed to prevent possible alloimmunization or hemolytic diseases. Glucose testing can screen for possible gestational diabetes mellitus. Screening for asymptomatic bacteriuria and proteinuria is recommended as well as screening for infectious disorders, such as HIV, syphilis, chlamydia, and gonorrhea (Lockwood & Magriples, 2020).

Additionally, genetic screening tests, including carrier screening for genetic mutations and fetal testing for chromosomal aneuploidy, can be a part of prenatal screening. Aneuploidy screening may be performed on cell-free DNA in maternal circulation or maternal serum levels of specific biochemical markers for trisomy (Lockwood & Magriples, 2020). These non-invasive prenatal testing (NIPT) can possibly decrease the number of more invasive procedures and the risks of unwanted side effects. A chromosomal microarray (CMA) can screen all chromosomes in a single test and “can detect many very small variants that cannot be detected by traditional karyotyping” (de Jong et al., 2015). In fact, the American College of Obstetricians and Gynecologists (ACOG) recommends CMA for instances where the ultrasound of a fetus shows a major structural abnormality (ACOG, 2016a). CMA in this situation should be performed on DNA from amniotic fluid, chorionic villus cells, or cord blood, however, rather than on maternal serum cell-free DNA since the process does not include an amplification step and the maternal DNA signal would be many times higher than the fetal DNA (Miller, 2020).

Several companies, such as LabCorp, have developed panels to test for potential genetic mutations in pregnant women, or in women planning to become pregnant. This includes the Inheritest® Carrier Screening which encompasses six different panels to identify potential genetic mutations. These six panels include the Inheritest® 500 PLUS Panel (which screens 525 genes for several clinically relevant genetic disorders), the Inheritest® Comprehensive Panel (which screens for more than 110 disorders), the Inheritest® Ashkenazi Jewish Panel (which screens for more than 40 Ashkenazi Jewish related disorders), the Inheritest® Society-Guided Panel (which screens for more than 13 disorders highlighted in the American College of Medical Genetics and Genomics and the American Congress of Obstetricians and Gynecologists guidelines), the Inheritest® Core Panel (which screens for cystic fibrosis, fragile X syndrome, and spinal muscular atrophy), and the Inheritest® CF/SMA Panel (which screens only for cystic fibrosis and spinal muscular atrophy) (LabCorp, 2020).

Red blood cell antigen discrepancy between a mother and fetus may also occur during pregnancy. This is known as hemolytic disease of the fetus and newborn (HDFN), and causes maternal antibodies to destroy the red blood cells of the neonate or fetus (Calhoun, 2020). Alloimmunization is the immune response which occurs in the mother due to foreign antigens after exposure to genetically foreign cells. This disease may arise in the ABO blood group, occurring almost exclusively in mothers with type O blood; ABO incompatibility is identified in almost 15% of pregnancies, but only results in HDFN in approximately 4% of pregnancies (Calhoun, 2020). Another important inherited antigen sometimes found on the surface of red blood cells is known as the Rhesus (Rh)D antigen. During pregnancy and delivery, women who are RhD negative may be exposed to RhD positive fetal cells, which can lead to the development of anti-RhD antibodies. This exposure typically happens during delivery and affects subsequent pregnancies; infants with RhD incompatibility tend to experience a more severe form of HDFN than those with ABO incompatibility (Calhoun, 2020). The clinical presentation of HDFN may be mild (such as hyperbilirubinemia with mild to moderate anemia) to severe and life-threatening anemia (such as hydrops fetalis) (Calhoun, 2020). Less severely affected infants may develop hyperbilirubinemia within the first day of life; infants with RhD HDFN may also present with symptomatic anemia requiring a blood transfusion. In more severe cases, infants with severe life-threatening anemia, such as hydrops fetalis, may exhibit shock at delivery requiring an emergent blood transfusion (Calhoun, 2020).

The administration of anti-D immune globulin has been able to dramatically reduce, but not eliminate, the number of RhD alloimmunization cases. “Anti-D immune globulin is manufactured from pooled plasma selected for high titers of IgG antibodies to D-positive erythrocytes (Moise, 2020).” Before the development of this anti-D immune globulin, it has been reported that 16% of women with two deliveries of RhD positive ABO compatible infants became alloimmunized; however, after routine postpartum administration of anti-D immune globulin, and an additional administration in the third trimester of pregnancy, this statistic was reduced to 0.1-0.3% (Moise, 2020).

Fetal RhD genotyping using cell-free fetal DNA from maternal plasma can be performed to identify fetal blood type most accurately after 11 weeks of gestation. While the United States has not implemented fetal RhD genotyping for routine prophylaxis and fetal monitoring protocols, several European countries, such as Denmark, the Netherlands, England, Sweden, France and Finland, do utilize fetal RhD determination so that the administration of anti-D immune globulin can be avoided when an RhD-negative fetus is identified (Moise, 2020). Daniels, Finning, Martin, and Summers (2007) report that approximately 40% of RhD-negative pregnant women are carrying a RhD-negative fetus; genotypic screening would, therefore, be very valuable in preventing the unnecessary anti-D immune globulin to these women. Another article by Kent, Farrell, and Soothill (2014) suggest that the administration of anti-D immune globulin to the 1/3 of pregnant women who do not require this administration is unethical, and that the availability of RhD genotyping to all RhD-negative pregnant women would assist in more informed choices being made regarding anti-D immune globulin administration. Finning et al. (2008) agree with the previous statements, declaring that “High throughput RHD genotyping of fetuses in all RhD negative women is feasible and would substantially reduce unnecessary administration of anti-RhD immunoglobulin to RhD negative pregnant women with an RhD negative fetus.”

Clinical Utility and Validity
Biro, Rigo, and Nagy (2020) report on a noninvasive prenatal testing method for congenital heart disease via the measurement of cell-free nucleic acid and protein biomarkers in maternal blood. Congenital heart disease is considered the most common fetal malformation. Currently, prenatal ultrasonography is most commonly used to diagnose congenital heart disease, but it is not the most accurate method. After a large review completed with PubMed and Web of Sciences databases, the authors conclude that most fetal congenital heart disease related disorders can be diagnosed by noninvasive prenatal testing (NIPT) techniques. Further, cell-free RNAs and circulating proteins are potential biomarkers for fetal congenital heart disease, and may be able to improve the detection rate in early pregnancies (Biro et al., 2020).

Implementation of prenatal screening tests can positively affect pregnancies and pregnancy outcomes. The Centers for Disease Control and Prevention (CDC) reports that implementation of the 1996 guidelines concerning Group B Streptococcus (GBS) had a profound effect. Prior to screening and widespread use of intrapartum antibiotics, invasive neonatal GBS occurred in 2 - 3 cases per 1,000 live births; however, after prenatal screening implementation, the rate declined to 0.5 cases per 1,000 live births in 1999 (Schrag, Gorwitz, Fultz-Butts, & Schuchat, 2002). The CDC also reports in a multi-year study that screening for syphilis in all pregnant women at the first prenatal visit (and then rescreening in third trimester for women at risk) is very important in preventing congenital syphilis, which can cause spontaneous abortion, stillbirth, and early infant death. They show that 88.2% of cases of congenital syphilis was avoided when proper screening was applied; moreover, 30.9% of the cases of congenital syphilis that did occur were where the mother did not receive proper prenatal care (≥45 days before delivery) (Slutsker, Hennessy, & Schillinger, 2018).

A study by Persico et al. (2016) investigated the clinical implication of cell-free DNA (cfDNA) testing in high-risk pregnancies. In their cohort of 259 singleton pregnancies, cfDNA testing provided results in 249 (96.1%). Further, cfDNA testing is identified in 97.2% (35/36) of trisomy 21, 100% (13/13) of trisomy 18, 100% of trisomy 13 (5/5), and 75% of sex chromosome aneuploidies (3/4). The authors conclude that “a policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses” (Persico et al., 2016). These data support the earlier meta-analysis that reported NIPT sensitivity of trisomy 21, trisomy 18, and trisomy 13 of 99%, 96.8%, and 92.1%, respectively and specificities of 99.92%, 99.85%, and 99.80%, respectively, for trisomies 21, 18, and 13 (Dondorp et al., 2015; Gil, Akolekar, Quezada, Bregant, & Nicolaides, 2014).

A multi-year study of more than 5,000 patients in public hospitals in Spain on the effect of NIPT on the number of invasive procedures performed shows that the introduction of NIPT drastically reduces the incidences of invasive procedures. The data shows that, even though a 60.5% reduction occurred in invasive procedures, the chromosomopathy detection rate was unaffected; moreover, the ratio of positive invasive procedures was improved to 50%, indicating that unwarranted invasive procedures had been avoided (Martinez-Payo, Bada-Bosch, Martinez-Moya, & Perez-Medina, 2018). The authors of the study concluded, “NIPT introduction has caused a significant reduction of 60.5% of IP [invasive procedures] in high chromosomopathy risk patients after combined screening without modifying detection rate” (Martinez-Payo et al., 2018).

A meta-analysis was completed by Mackie, Hemming, Allen, Morris, and Kilby (2017) which researched the accuracy of cell-free fetal DNA NIPT testing in singleton pregnancies. A total of 117 studies were included which analyzed 18 different conditions. For RHD testing, a sensitivity of 0.993 and specificity of 0.984 was identified, and for fetal sex identification, a sensitivity of 0.989 and a specificity of 0.996 was calculated (Mackie et al., 2017). With such high sensitivity and specificity calculations, NIPT testing for fetal sex and RHD status may be considered accurate diagnostic tools.

Clausen et al. (2014) completed a two-year evaluation of nationwide prenatal RhD screening in Denmark. A total of 12,668 pregnancies were analyzed, with blood samples drawn in week 25 of pregnancy. DNA was extracted from these blood samples and was analyzed for the RHD gene. Results were compared to the serological typing of the newborns after birth. “The sensitivity for the detection of fetal RHD was 99.9% (95% CI: 99.7-99.9%). Unnecessary recommendation of prenatal RhD prophylaxis was avoided in 97.3% of the women carrying an RhD-negative fetus. Fetuses that were seropositive for RhD were not detected in 11 pregnancies (0.087%) (Clausen et al., 2014).” This study shows high sensitivity of fetal RHD genotyping. These results were recently supported by another large scale meta-analysis completed by Yang et al. (2019) focusing on NIPT testing for fetal RhD status. A total of 3,921 results confirmed that “High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin (Yang et al., 2019).”

Darlington et al. (2018) completed an analysis of 11 French Obstetric Departments with a total of 949 patients to determine the effectiveness of RhD genotyping. The patients were separated into two groups (genotyping group: n=515, and control group: n=335). The authors concluded that “Early knowledge of the RHD status of the fetus using non-invasive fetal RHD genotyping significantly improved the management of RHD negative pregnancies with a small increase in cost (Darlington et al., 2018).”

A prospective cohort study by de Haas et al. (2016) completed a nationwide program in the Netherlands hoping to determine the sensitivity of fetal RhD screening for the safe guidance of targeted anti-immune globulin prophylaxis. A total of 25,789 RhD-negative pregnant woman participated in this study. Fetal testing for the RHD gene was assessed in the 27th week of pregnancy. Fetal RHD test results were compared to serological cord blood results after birth. “Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false-negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%) (de Haas et al., 2016).” Therefore, fetal RhD testing is a highly reliable testing method.

Manfroi et al. (2018) completed fetal RhD genotyping with real-time polymerase chain reaction (qPCR) using cell-free fetal DNA extracted from maternal plasma. A commercial multiple-exon assay was used to determine fetal RHD genotypic accuracy. A total of 367 plasma samples obtained between the 24th and 28th weeks of pregnancy were used for this study. Neonatal results were available for 284 of the pregnancies. The sensitivity was reported at 100% and specificity at 97.5%. The diagnostic accuracy was 96.1% with the inclusion of 9/284 inconclusive results (Manfroi et al., 2018). This is therefore an accurate and reliable tool for targeted prenatal immunoprophylaxis.

Similarly, Liang et al. (2019) used cell-free plasma DNA to assess the clinical utility of using an expanded noninvasive prenatal screening (“NIPS-Plus”) to detect aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS). Of the 94,085 women with singleton pregnancies enrolled in the study, 1,128 were suspected of having clinically significant fetal chromosome abnormalities. Follow-up testing in the study reported the positive predictive values (PPVs) of 95%, 82%, 46%, 29%, and 47% for T21, T18, T13, rare trisomies, and sex chromosome aneuploidies, respectively. For known MMS (n=32), PPVs were 93% (DiGeorge), 68% (22q11.22 microduplication), 75% (Prader-Willi/Angleman [sic]), and 50% (Cri du Chat). Thus, the researchers conclude that “the data have potential significance in demonstrating the usefulness of cfDNA profiling” and that “NIPS-Plus can be used as a first-tier pregnancy screening method to improve detection rates of clinically significant fetal chromosome abnormalities” (Liang et al., 2019).

Runkel et al. (2020) completed a systematic review to determine the benefit of NIPT for fetal RhD status in RhD-negative pregnant women because “All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status.” The meta-analysis included data from 60,000 participants, with the focus of the research on the impact of fetal and maternal morbidity. The researchers concluded that “NIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn's blood. Studies investigating patient-relevant outcomes are still lacking” (Runkel et al., 2020).

However, the field continues to evolve, with potential shifts from one testing method to another in pursuit of optimality and comprehensiveness. A multicenter retrospective study of singleton high-risk pregnancies for chromosomal abnormalities was conducted by Zhu et al. (2020) to evaluate the utility of expanded noninvasive prenatal screening as compared with chromosomal microarray analysis (CMA). The analysis enrolled subjects who underwent expanded NIPS and CMA sequentially during pregnancy from 2015 through 2019. The study demonstrated that of the 943 high‐risk pregnancies, 550 (58.3%) cases had positive NIPS results, while positive CMA results were detected in 308 (32.7%) cases, and the agreement rates between NIPS and CMA were 82.3%, 59.6% and 25.0% for trisomy 21, 18 and 13, respectively. Regarding rare aneuploidies and segmental imbalances, NIPS and CMA results were concordant in 7.5% and 33.3% of cases. However, copy number variants were better detected with CMA than with NIPS, and additional genetic aberrations were detected by CMA in 1 of 17 high-risk pregnancies that were otherwise passed over when processed with NIPS. The researchers then contend that “CMA should be offered for high‐risk pregnancies” to provide comprehensive detection of chromosomal abnormalities in high-risk pregnancies (Zhu et al., 2020)

This policy focuses on laboratory testing performed during pre-conception and/or prenatal periods as part of a comprehensive prenatal care program.

American College of Obstetricians and Gynecologists (ACOG) (2011, 2012, 2014, 2015, 2016, 2018, 2019, 2020) 
ACOG has a number of practice guidelines related to prenatal care as well as both pre-conception and prenatal testing. ACOG recommendations and guidelines include the following:

  • Vitamin D Screening: Concerning vitamin D screening, “there is insufficient evidence to support a recommendation for screening all pregnant women for vitamin D deficiency. For pregnant women thought to be at increased risk of vitamin D deficiency, maternal serum 25-hydroxyvitamin D levels can be considered and should be interpreted in the context of the individual clinical circumstance [reaffirmed in 2017] (ACOG, 2011).” 
  • Lead Screening: Concerning lead screening, they recommend risk assessment of lead exposure at earliest contact with blood lead testing if even one single risk factor is identified. This was reaffirmed in 2019 (ACOG, 2012).
  • Subclinical Hypothyroidism: ACOG Committee Opinion on subclinical hypothyroidism in pregnancy does not recommend routine screening for subclinical hypothyroidism. It states that “thyroid testing in pregnancy should be performed on symptomatic women and those with a personal history of thyroid disease or other medical conditions associated with thyroid disease (e.g., diabetes mellitus) (ACOG, 2015a).”
  • Depression and Anxiety: “All obstetrician-gynecologists and other obstetric care providers screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized, validated tool.  [They should] complete a full assessment of mood and emotional well-being (including screening for postpartum depression and anxiety with a validated instrument) during the comprehensive postpartum visit for each patient (ACOG, 2018a).”
  • Listeria monocytogenes: Concerning testing for Listeria monocytogenes (ACOG, 2014), “No testing, including blood and stool cultures, or treatment is indicated for an asymptomatic pregnant woman who reports consumption of a product that was recalled or implicated during an outbreak of listeria contamination. An asymptomatic patient should be instructed to return if she develops symptoms of listeriosis within 2 months of eating the recalled or implicated product.” If an exposed pregnant woman shows signs and symptoms consistent with infection, then blood culture testing is the standard of care.  Stool culture testing is not recommended since it has not been validated as a screening tool. This position was reaffirmed in 2019.
  • HIV: Concerning HIV, ACOG recommends that all women should be tested for HIV with the right to refuse testing. “Human immunodeficiency virus testing using the opt-out approach, which is currently permitted in every jurisdiction in the United States, should be a routine component of care for women during prepregnancy and as early in pregnancy as possible. Repeat HIV testing in the third trimester, preferably before 36 weeks of gestation, is recommended for pregnant women with initial negative HIV antibody tests who are known to be at high risk of acquiring HIV infection; who are receiving care in facilities that have an HIV incidence in pregnant women of at least 1 per 1,000 per year; who are incarcerated; who reside in jurisdictions with elevated HIV incidence; or who have signs and symptoms consistent with acute HIV infection (e.g., fever, lymphadenopathy, skin rash, myalgias, arthralgias, headache, oral ulcers, leukopenia, thrombocytopenia, or transaminase elevation). Rapid screening during labor and delivery or during the immediate postpartum period using the opt-out approach should be done for women who were not tested earlier in pregnancy or whose HIV status is otherwise unknown. Results should be available 24 hours a day and within 1 hour (Pollock, Cohan, Pecci, & Mittal, 2019).”
    • For pregnant women who test positive for HIV, “Additional laboratory work, including CD4+ count; HIV viral load; testing for antiretroviral resistance; hepatitis C virus antibody; hepatitis B surface antigen and viral load; and hepatitis A using antibody testing for immunoglobulin G for women who have hepatitis B virus infection and who have not already received the hepatitis A virus vaccine series; complete blood count with platelet count; and baseline chemistries with comprehensive metabolic testing, will be useful before prescribing antiretroviral therapy (Pollock et al., 2019).”
  • Genetic Testing and Genetic Counseling: Concerning genetic testing and genetic counseling, ACOG recommends:
    • “A hereditary cancer risk assessment is the key to identifying patients and families who may be at increased risk of developing certain types of cancer. This assessment should be performed by obstetrician–gynecologists or other obstetric–gynecologic providers and should be updated regularly. If a hereditary cancer risk assessment suggests an increased risk of a hereditary cancer syndrome, referral to a specialist in cancer genetics or a health care provider with expertise in genetics is recommended for expanded gathering of family history information, risk assessment, education, and counseling, which may lead to genetic testing [reaffirmed in 2020] (ACOG, 2015b).”
    • “The routine use of whole-genome or whole-exome sequencing for prenatal diagnosis is not recommended outside of the context of clinical trials until sufficient peer-reviewed data and validation studies are published.” This was reaffirmed in 2020 (ACOG, 2016a, 2020b).
    • Chromosomal microarray analysis (CMA) is recommended for patients with a fetus with at least one major structure abnormality identified via ultrasound. CMA can be considered for all pregnant women who undergo prenatal diagnostic testing; however, “In a patient with a structurally normal fetus who is undergoing invasive prenatal diagnostic testing, either fetal karyotyping or a chromosomal microarray analysis can be performed. Chromosomal microarray analysis of fetal tissue (i.e., amniotic fluid, placenta, or products of conception) is recommended in the evaluation of intrauterine fetal death or stillbirth when further cytogenetic analysis is desired because of the test’s increased likelihood of obtaining results and improved detection of causative abnormalities [(ACOG, 2016a)”. This was reaffirmed in 2020.
    • “All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. Fragile X premutation carrier screening is recommended for women with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome, or women with a personal history of ovarian insufficiency. Additional screening also may be indicated based on family history or specific ethnicity (Romero, Rink, Biggio, Saller, & ACOG, 2017).” This was reaffirmed in 2020 (ACOG, 2020a).
    • “Direct-to-consumer genetic testing should be discouraged because of the potential harm of a misinterpreted or inaccurate result (Rink, Biggio, Kamyar, & ACOG, 2017).”
    • ACOG “recommends considering whole-exome sequencing when specific genetic tests available for a phenotype, including targeted sequencing tests, have failed to arrive at a diagnosis in a fetus with multiple congenital anomalies suggestive of a genetic disorder (Vora, Ralston, & ACOG, 2018)”; however, they note that “Cascade testing has been shown to be cost effective in part because testing for specific mutations (eg, those identified in the affected relative) is less expensive than whole-gene sequencing (Witkop & ACOG, 2018).”
    • Prenatal Diagnostic Testing for Genetic Disorders:  Concerning prenatal diagnostic testing for genetic disorders, ACOG has published the following recommendations (ACOG, 2016b, 2021a):
      • “An abnormal FISH result should not be considered diagnostic. Therefore, clinical decision making based on information from FISH should include at least one of the following additional results: confirmatory traditional metaphase chromosome analysis or chromosomal microarray, or consistent clinical information
      • Prenatal genetic testing cannot identify all abnormalities or problems in a fetus, and any testing should be focused on the individual patient’s risks, reproductive goals and preferences
      • Genetic testing should be discussed as early as possible in pregnancy, ideally at the first obstetric visit, so that first-trimester options are available (ACOG, 2016b).” This guideline was reaffirmed in 2021 (ACOG, 2021a).
    • Prevention of Rh D Alloimmunization: Concerning the prevention of Rh D alloimmunization, ACOG has published the guidelines supporting the administration of anti-D immune globulin to women in various scenarios. However, these guidelines do not mention the use of cell-free fetal DNA for fetal RHD testing to determine if anti-D immune globulin is needed (ACOG, 2017b).
    • Newborn Screening Panel: ACOG issued the recommended uniform newborn screening panel of core conditions in 2019.  The table is listed below (ACOG, 2019a):

Table 1. Recommended Uniform Newborn Screening Panel of Core Conditions

Disease Categories

Diseases

Inborn errors of organic acid metabolism

Isovaleric acidemia
Glutaric acidemia type I
3-Hydroxy-3-methylglutaric aciduria
Holocarboxylase synthase deficiency
Methylmalonic acidemia (methylmalonyl-CoA mutase)
3-Methylcrotonyl-CoA carboxylase deficiency
Methylmalonic acidemia (cobalamin disorders)
Propionic acidemia
β-ketothiolase deficiency

Inborn errors of fatty acid metabolism

Medium-chain acyl-CoA dehydrogenase deficiency
Very long-chain acyl-CoA dehydrogenase deficiency
Long-chain L-3 hydroxyacyl-CoA dehydrogenase deficiency
Trifunctional protein deficiency
Carnitine uptake defect/transport defect

Inborn errors of amino acid metabolism

Classic phenylketonuria
Maple syrup urine disease
Homocystinuria
Citrullinemia, type I
Argininosuccinic aciduria
Tyrosinemia, type I

Hemoglobinopathies

S,S disease (Sickle cell anemia)
S,β-thalassemia
S,C disease

Miscellaneous multisystem diseases

Primary congenital hypothyroidism
Biotinidase deficiency
Congenital adrenal hyperplasia
Classic galactosemia
Cystic fibrosis

Glycogen Storage Disease Type II (Pompe)

Mucopolysaccharidosis type 1

Spinal Muscular Atrophy

X-linked adrenoleukodystrophy
Severe combined immunodeficiency

Newborn screening by methods other than by heel stick

Hearing loss
Critical congenital heart disease

  • Genetic Carrier Screening: Concerning genetic carrier screening, including testing for specific conditions, ACOG recommends ((Rink, Romero, et al., 2017) reaffirmed 2020):
    • “Carrier screening and counseling ideally should be performed before pregnancy.
    • If an individual is found to be a carrier for a specific condition, the individual’s reproductive partner should be offered testing in order to receive informed genetic counseling about potential reproductive outcomes. Concurrent screening of the patient and her partner is suggested if there are time constraints for decisions about prenatal diagnostic evaluation.
    • Carrier screening for a particular condition generally should be performed only once in a person’s lifetime, and the results should be documented in the patient’s health record. Because of the rapid evolution of genetic testing, additional mutations may be included in newer screening panels. The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations.
    • Prenatal carrier screening does not replace newborn screening, nor does newborn screening replace the potential value of prenatal carrier screening.
    • The cost of carrier screening for an individual condition may be higher than the cost of testing through commercially available expanded carrier screening panels. When selecting a carrier screening approach, the cost of each option to the patient and the health care system should be considered.
    • Screening for spinal muscular atrophy should be offered to all women who are considering pregnancy or are currently pregnant. In patients with a family history of spinal muscular atrophy, molecular testing reports of the affected individual and carrier testing of the related parent should be reviewed, if possible, before testing. If the reports are not available, SMN1 deletion testing should be recommended for the low-risk partner.
    • Cystic fibrosis carrier screening should be offered to all women who are considering pregnancy or are currently pregnant. Complete analysis of the CFTR gene by DNA sequencing is not appropriate for routine carrier screening.
    • A complete blood count with red blood cell indices should be performed in all women who are currently pregnant to assess not only their risk of anemia but also to allow assessment for risk of a hemoglobinopathy. Ideally, this testing also should be offered to women before pregnancy. A hemoglobin electrophoresis should be performed in addition to a complete blood count if there is suspicion of hemoglobinopathy based on ethnicity (African, Mediterranean, Middle Eastern, Southeast Asian, or West Indian descent). If red blood cell indices indicate a low mean corpuscular hemoglobin or mean corpuscular volume, hemoglobin electrophoresis also should be performed.
    • Fragile X premutation carrier screening is recommended for women with a family history of fragile X-related disorders or intellectual disability suggestive of fragile X syndrome and who are considering pregnancy or are currently pregnant.
    • If a woman has unexplained ovarian insufficiency or failure or an elevated follicle-stimulating hormone level before age 40 years, fragile X carrier screening is recommended to determine whether she has an FMR1 premutation.
    • All identified individuals with intermediate results and carriers of a fragile X premutation or full mutation should be provided follow-up genetic counseling to discuss the risk to their offspring of inheriting an expanded full-mutation fragile X allele and to discuss fragile X-associated disorders (premature ovarian insufficiency and fragile X tremor/ataxia syndrome).
    • Prenatal diagnostic testing for fragile X syndrome should be offered to known carriers of the fragile X premutation or full mutation.
    • DNA-based molecular analysis (e.g., Southern blot analysis and polymerase chain reaction) is the preferred method of diagnosis of fragile X syndrome and of determining FMR1 triplet repeat number (e.g., premutations). In rare cases, the size of the triplet repeat and the methylation status do not correlate, which makes it difficult to predict the clinical phenotype. In cases of this discordance, the patient should be referred to a genetics professional.
    • When only one partner is of Ashkenazi Jewish descent, that individual should be offered screening first. If it is determined that this individual is a carrier, the other partner should be offered screening. However, the couple should be informed that the carrier frequency and the detection rate in non-Jewish individuals are unknown for most of these disorders, except for Tay–Sachs disease and cystic fibrosis. Therefore, it is difficult to accurately predict the couple’s risk of having a child with the disorder.
    • Screening for Tay–Sachs disease should be offered when considering pregnancy or during pregnancy if either member of a couple is of Ashkenazi Jewish, French–Canadian, or Cajun descent. Those with a family history consistent with Tay–Sachs disease also should be offered screening. When one member of a couple is at high risk (i.e., of Ashkenazi Jewish, French–Canadian, or Cajun descent or has a family history consistent with Tay–Sachs disease) but the other partner is not, the high-risk partner should be offered screening. If the high-risk partner is found to be a carrier, the other partner also should be offered screening. Enzyme testing in pregnant women and women taking oral contraceptives should be performed using leukocyte testing because serum testing is associated with an increased false-positive rate in these populations. If Tay–Sachs disease screening is performed as part of pan-ethnic expanded carrier screening, it is important to recognize the limitations of the mutations screened in detecting carriers in the general population. In the presence of a family history of Tay–Sachs disease, expanded carrier screening panels are not the best approach to screening unless the familial mutation is included on the panel (Rink, Romero, et al., 2017).”
    • Regarding expanded carrier screening panels, ACOG recommends that “the disorders selected for inclusion should meet several of the following consensus-determined criteria: have a carrier frequency of 1 in 100 or greater, have a well-defined phenotype, have a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life.” ACOG further states that “screened conditions should be able to be diagnosed prenatally and may afford opportunities for antenatal intervention to improve perinatal outcomes, changes to delivery management to optimize newborn and infant outcomes, and education of the parents about special care needs after birth (Romero et al., 2017).”
  • Carrier Screening in the Age of Genomic Medicine: Concerning carrier screening in the age of genomic medicine, the ACOG has published the following guidelines (ACOG, 2017a, 2020a):
    • “Ethnic-specific, panethnic and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening
    • If a patient requests a screening strategy other than the one used by the obstetrician-gynecologist or other health care provider, the requested test should be made available to her after counseling on its limitations, benefits, and alternatives
    • All patients who are considering pregnancy or already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. Fragile X premutation carrier screening is also recommended for women with a family history of fragile x-related disorders or intellectual disability suggestive of fragile X syndrome, or women with a personal history of ovarian insufficiency. Additional screening also may be indicated based on family history or specific ethnicity
    • If a woman is found to be a carrier for a specific condition, her reproductive partner should be offered screening to provide accurate genetic counseling for the couple with regard to the risk of having an affected child. Additional genetic counseling should be provided to discuss the specific condition, residual risk, and options for prenatal testing.
    • Individuals with a family history of a genetic disorder may benefit from the identification of the specific familial mutation or mutations rather than carrier screening. Knowledge of the specific familial mutation may allow for more specific and rapid prenatal diagnosis.
    • Given the multitude of conditions that can be included in expanded carrier screening panels, the disorders selected for inclusion should meet several of the following consensus-determined criteria: have a carrier frequency of 1 in 100 or greater, have a well-defined phenotype, have a detrimental effect on quality of life, cause cognitive or physical impairment, require surgical or medical intervention, or have an onset early in life. Additionally, screened conditions should be able to be diagnosed prenatally and may afford opportunities for antenatal intervention to improve perinatal outcomes, changes to delivery management to optimize newborn and infant outcomes, and education of the parents about special care needs after birth.
    • Carrier screening panels should not include conditions primarily associated with a disease of adult onset (ACOG, 2017a).” This guideline was reaffirmed in 2020 (ACOG, 2020a).
  • Group B Streptococcal (GBS) Disease: “all pregnant women should undergo antepartum screening for GBS at 36 0/7–37 6/7 weeks of gestation, unless intrapartum antibiotic prophylaxis for GBS is indicated because of GBS bacteriuria during the pregnancy or because of a history of a previous GBS-infected newborn. This new recommended timing for screening provides a 5-week window for valid culture results that includes births that occur up to a gestational age of at least 41 0/7 weeks” (ACOG, 2020c)
  • Lab Tests: ACOG lists the following lab tests to be performed early in pregnancy: complete blood count (CBC), blood type, urinalysis, urine culture, rubella, hepatitis B, hepatitis C, HIV, sexually transmitted infection (STI) testing, and tuberculosis. Concerning STIs, all pregnant women should be tested for syphilis and chlamydia with proof-of-cure testing for women who are treated for either infection. Women who are at high-risk for gonorrhea should be tested (ACOG, 2017c).
    • ACOG lists the following lab tests to be performed later in pregnancy: repeat CBC, Rh antibody test, glucose screening test, and Group B streptococci (GBS) (ACOG, 2017c).
  • ZIKA Virus: The April 2019 update concerning Zika, ACOG states the following (ACOG, 2018b, 2019b):
    • “Symptomatic pregnant women with possible Zika virus exposure or women who are pregnant with a fetus showing abnormalities consistent with congenital Zika virus syndrome should be tested as soon as possible. Asymptomatic pregnant women with ongoing possible exposure can be offered nucleic acid testing during pregnancy as (ACOG, 2020c)Asymptomatic pregnant women with possible Zika virus exposure but without ongoing possible exposure are not recommended routinely to have Zika virus testing, but testing can be considered as part of a shared patient–provider decision-making model (ACOG, 2019b).” 

Finally, ACOG published a guideline on “Direct-to-Consumer” Testing. In it, they recommend that testing revolving around single nucleotide polymorphism analysis should be considered investigational at time of writing (ACOG, 2021b).

United States Preventive Services Task Force (USPSTF) (2005, 2006, 2008, 2009, 2013, 2014, 2015, 2016, 2018, 2020) 
The United States Preventive Services Task Force (USPSTF) recommends the following testing for pregnant women:

  • Screening for hepatitis B virus (HBV) infection at the first prenatal visit (Grade A) (Owens, Davidson, Krist, Barry, Cabana, Caughey, Doubeni, Epling, Kemper, et al., 2019; USPSTF, 2009, 2019)
  • Screening for asymptomatic bacteriuria with urine culture is recommended in pregnant persons (Grade B) (Owens, Davidson, Krist, Barry, Cabana, Caughey, Doubeni, Epling, Kubik, et al., 2019; USPSTF, 2008a)
  • Screening for gestational diabetes mellitus after 24 weeks of gestation (Grade B) (V. A. Moyer, 2014)
  • Screening for HIV is recommended in all pregnant persons, including those in labor or whose HIV status is unknown at delivery (Grade A) (V. A.  Moyer & USPSTF, 2013b; Owens, Davidson, Krist, Barry, Cabana, Caughey, Curry, et al., 2019)
  • Rh (D) blood typing and antibody testing during the first prenatal visit (Grade A) (USPSTF, 2005)
  • Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative women at 24-28 weeks' gestation, unless the biological father is known to be Rh (D)-negative (Grade B) (USPSTF, 2005)
  • Screening early for syphilis infection in all pregnant women (Grade A) (USPSTF, 2018)

Additional recommendations from the USPSTF that may be relevant during pregnancy include:

  • Screening for chlamydia in sexually active women aged 24 years or younger and in older women who are at increased risk for infection (Grade B) (LeFevre & USPSTF, 2014)
  • Screening for gonorrhea in sexually active women aged 24 years or younger and in older women who are at increased risk for infection (Grade B) (LeFevre & USPSTF, 2014)
  • Screening for depression in general population, including pregnant and post-partum women (Grade B) (Siu & USPSTF, 2016)
  • Screening for hepatitis C virus (HCV) infection is recommended in all adults aged 18 to 79 years (Grade B) (Chou et al., 2020; V. A.  Moyer & USPSTF, 2013a)
  • Concerning screening adults for drug use, Krist et al. (2020) state that “The USPSTF recommends screening by asking questions about unhealthy drug use in adults age 18 years or older. Screening should be implemented when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. (Screening refers to asking questions about unhealthy drug use, not testing biological specimens.)” The USPSTF also states that “This new evidence supports the current recommendation that primary care clinicians offer screening to adults 18 years or older, including those who are pregnant or postpartum, when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred.”
  • However, the USPSTF recommends against the following tests during pregnancy:
    • Screening for bacterial vaginosis in pregnant women who are not at risk for preterm delivery (grade D); further, current evidence is insufficient for screening pregnant persons who are at increased risk for preterm delivery (Owens et al., 2020; USPSTF, 2008b)
    • Serological screening for herpes simplex virus (HSV) in asymptomatic pregnant women (USPSTF, 2016)
    • Screening for elevated blood lead levels in asymptomatic pregnant women has been given an I recommendation as current evidence is insufficient to determine if this testing is beneficial or not (Curry et al., 2019; USPSTF, 2006)
    • “The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency anemia in pregnant women to prevent adverse maternal health and birth outcomes (Siu, 2015).”

American Diabetes Association (ADA) (ADA, 2018, 2020) 
The American Diabetes Association in the 2018 Standards of Medicare Care in Diabetes make the following recommendations (ADA, 2018, 2020):

  • “Test for undiagnosed prediabetes at the first prenatal visit in those with risk factors, using standard diagnostic criteria. [Grade] B
  • Test for gestational diabetes mellitus at 24–28 weeks of gestation in pregnant women not previously found to have diabetes. [Grade] A
  • Test women with gestational diabetes mellitus for prediabetes at 4–12 weeks postpartum, using the 75-g oral glucose tolerance test and clinically appropriate nonpregnancy diagnostic criteria. [Grade] E
  • Women with a history of gestational diabetes mellitus should have lifelong screening for the development of diabetes or prediabetes at least every 3 years. [Grade] B
  • Women with a history of gestational diabetes mellitus found to have prediabetes should receive intensive lifestyle interventions or metformin to prevent diabetes. [Grade] A

Centers for Disease Control and Prevention (CDC) (CDC, 2015b, 2019a, 2019b, 2020a)
The Centers for Disease Control and Prevention (CDC) recommends:

  • All pregnant women get testing for HIV, hepatitis B virus (HBV) and syphilis during each pregnancy (CDC, 2019b). Additional CDC (2019b) recommendations can be found in the table below:

 

First Prenatal Visit

Third Trimester

At Delivery

Syphilis

All pregnant women

Certain groups of pregnant womenv at 28-32 weeks

Select group of pregnant women,v  pregnant women with no previously established status, or pregnant women who deliver a stillborn infant

HIV

All pregnant womeni

Certain groups of pregnant womenvi before 36 weeks

Pregnant women not screened during pregnancy

HBV

All pregnant womenii

N/A

Pregnant women not screened during pregnancy,vii who are at high risk,viii or with signs or symptoms of hepatitis

Chlamydia

All pregnant women <25 years of age and older pregnant women at increased riskiii

Pregnant women <25 years of age or continued high riskiii

N/A

Gonorrhea

All pregnant women <25 years of age and older pregnant women at increased riskiii

Pregnant women at continued high riskiii

N/A

“Endnotes:

  1. To promote informed and timely therapeutic decisions, health care providers should test women for HIV as early as possible during each pregnancy.1
  2. All pregnant women should be tested for hepatitis B surface antigen (HBsAg) during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been vaccinated or tested previously.2
  3. “Increased risk” means new or multiple sex partners, sex partner with concurrent partners, sex partners who have a sexually transmitted disease (STD).3,4
  4. “At increased risk” means injection-drug use (IDU), had a blood transfusion before July 1992, receipt of an unregulated tattoo, long-term hemodialysis, intranasal drug use, and other percutaneous exposures.3
  5. “Certain groups” includes women who are at high risk for syphilis or live in areas of high syphilis morbidity.3
  6. “Certain groups” includes women who receive health care in areas with an elevated incidence of HIV or AIDS among women aged 15-45 years, who receive health care in facilities in which prenatal screening identifies at least one HIV-infected women per 1,000 women screened, known to be at high risk for HIV (i.e., injection-drug user and their sex partners, exchange sex for money or drugs, sex partner of HIV-infected persons, have had a new or >1 sex partner during this pregnancy), or have signs or symptoms consistent with acute HIV infection.1
  7. Women admitted for delivery at a health care facility without documentation of HBsAg test results should have blood drawn and tested as soon as possible after admission.2
  8. Having had more than one sex partner during the previous 6 months, an HBsAg-positive sex partner, evaluation or treatment for a STD, or IDU2 (CDC, 2019b).”

Further, in 2020, the CDC recommended “Hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection (HCV RNA‑positivity) is less than 0.1%” (CDC, 2020a) 

  • Repeat HIV screening in the third trimester for women at high-risk of STDs—"Women who use illicit drugs, have STDs during pregnancy, have multiple sex partners during pregnancy, live in areas with high HIV prevalence, or have partners with HIV infection (CDC, 2015b).”
  • Screening of all pregnant women for HBsAg (Hepatitis B Surface Antigen Test) during each pregnancy regardless of prior testing with a retest at time of deliver for those at high risk, including persons born in regions of high endemicity (≥2% prevalence) and HIV positive individuals (CDC, 2015b).
  • Testing of all pregnant women for syphilis during the first prenatal visit and, for individuals at high risk, retest early in the third semester as well as time of delivery (CDC, 2015b). 
  • Chlamydia trachomatis screening at the first prenatal visit and repeat testing during the third trimester for women under 25 years or at high risk for acquisition. “Pregnant women with chlamydial infection should have a test-of-cure 3-4 weeks after treatment and be retested within 3 months (CDC, 2015b).”
  • N. gonorrhea testing of all pregnant women under 25 years of age and older women at risk for infection or living in an area of high prevalence of N. gonorrhea. For pregnant women who receive treatment for gonorrhea, they should be retested 3 months after treatment (CDC, 2015b).
  • Screening for hepatitis C is recommended in pregnant women at high risk for infection and pregnant women born between 1945 – 1965 (CDC, 2015b).  It is not recommended for pregnant women who have no risk factors (CDC, 2015c).
  • Zika virus testing for symptomatic pregnant persons:
    • “For symptomatic pregnant women who had recent travel to areas with active dengue transmission and a risk of Zika, specimens should be collected as soon as possible after the onset of symptoms up to 12 weeks after symptom onset.
      • The following diagnostic testing should be performed at the same time:
          • Dengue and Zika virus NAAT testing on a serum specimen, and Zika virus NAAT on a urine specimen, and
          • IgM testing for dengue only.
        • Zika virus IgM testing is NOT recommended for symptomatic pregnant women.
          • Zika IgM antibodies can persist for months to years following infection. Therefore, detecting Zika IgM antibodies might not indicate a recent infection.
          • There is notable cross-reactivity between dengue IgM and Zika IgM antibodies in serologic tests. Antibodies generated by a recent dengue virus infection can cause the Zika IgM to be falsely positive.
        • If the Zika NAAT is positive on a single specimen, the Zika NAAT should be repeated on newly extracted RNA from the same specimen to rule out false-positive NAAT results. If the dengue NAAT is positive, this provides adequate evidence of a dengue infection and no further testing is indicated.
        • If the IgM antibody test for dengue is positive, this is adequate evidence of a dengue infection and no further testing is indicated (CDC, 2019a).”
    • ZIKA virus testing in asymptomatic pregnant women is not recommended. 
  • Cervical cancer screening intervals in pregnant women should be the same as for nonpregnant women (CDC, 2015b).
  • “Evidence does not support routine HSV-2 serologic screening among asymptomatic pregnant women. However, type-specific serologic tests might be useful for identifying pregnant women at risk for HSV infection and guiding counseling regarding the risk for acquiring genital herpes during pregnancy (CDC, 2015b, 2019a).”
  • “Evidence is insufficient to recommend routine screening for BV in asymptomatic pregnant women at high or low risk for preterm delivery for the prevention of preterm birth (CDC, 2015a).”

American College of Medical Genetics and Genomics (ACMG) (2004, 2005, 2008, 2013, 2014, 2016) 
The American College of Medical Genetics and Genomics (ACMG) recommends that the following (Gregg et al., 2016):

  • “Allowing patients to select diagnostic or screening approaches for the detection of fetal aneuploidy and/or genomic changes that are consistent with their personal goals and preferences.”
  • “Informing all pregnant women that diagnostic testing (CVS or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant CNVs [copy-number variants].”
  • “Informing all pregnant women that NIPS [non-invasive prenatal screening] is the most sensitive screening option for traditionally screened aneuploidies (i.e., Patau, Edwards, and Down syndromes).”
  • “Offering diagnostic testing when a positive screening test result is reported after NIPS.”
  • The ACMG does NOT recommend “NIPS to screen for autosomal aneuploidies other than those involving chromosomes 13, 18, and 21.”
  • “Offering diagnostic testing for a no-call NIPS result due to low fetal fraction if maternal blood for NIPS was drawn at an appropriate gestational age. A repeat blood draw is NOT appropriate.”
  • “Offering aneuploidy screening other than NIPS in cases of significant obesity.”
  • “Offering diagnostic testing when a positive screening test result is reported after screening for sex chromosome aneuploidies.”
  • “Offering diagnostic testing (CVS or amniocentesis) with CMA when NIPS identifies a CNV.”
  • ACMG does NOT recommend “NIPS to screen for genome-wide CNVs. If this level of information is desired, then diagnostic testing (e.g., chorionic villous sampling or amniocentesis) followed by CMA is recommended.”
  • “Offering aneuploidy screening other than NIPS for patients with a history of bone marrow or organ transplantation from a male donor or donor of uncertain biologic sex.”

In the ACMG practice guidelines concerning carrier screening in individuals of Ashkenazi Jewish descent, they “recommend that carrier screening for cystic fibrosis, Canavan disease, familial dysautonomia, and Tay-Sachs disease be offered to all Ashkenazi Jews who are pregnant or considering pregnancy, according to current American College of Medical Genetics and/or the American College of Obstetricians and Gynecologists (ACOG) guidelines. In addition, we recommend that carrier screening be offered for Fanconi anemia (Group C), Niemann-Pick (Type A), Bloom syndrome, mucolipidosis IV, and Gaucher disease (Gross, Pletcher, & Monaghan, 2008).”

Concerning carrier screening for spinal muscular atrophy, ACMG recommends, “Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity. Ideally, the testing should be offered before conception or early in pregnancy (Prior, 2008).” They also recommend carrier screening for Fragile X syndrome for pregnant women and those considering pregnancy who have a family history of Fragile X syndrome or undefined mental retardation (Sherman, Pletcher, & Driscoll, 2005). Cystic fibrosis carrier screening for all pregnant women and those considering pregnancy is recommended; moreover, the ACMG released the mutation frequency data of various ethnic groups within their 2004 revision of the cystic fibrosis screening guidelines (Watson et al., 2004).

In 2014, the American College of Medical Genetics and Genomics issued the following guidelines for the clinical evaluation and diagnosis of hearing loss. For individuals lacking physical findings suggestive of a known syndrome and having medical and birth histories that do not suggest an environmental cause of hearing loss, ACMG recommends that a tiered diagnostic approach should be implemented (Alford et al., 2014):

  • “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology.”
  • “In the absence of any specific clinical indications and for singleton cases and cases with apparent autosomal recessive inheritance, the next step should be testing for DFNB1-related hearing loss (due to mutations in GJB2 and adjacent deletions in GJB6).”
  • “If initial genetic testing is negative, genetic testing using gene panel tests, NGS technologies such as large sequencing panels targeted toward hearing loss–related genes, WES, or WGS may be considered.”

Also, in 2014, the ACMG released guidelines concerning the diagnosis and management of phenylalanine hydroxylase (PAH) deficiency. They recommend PAH testing be part of newborn screening and that quantitative blood amino acids testing should be performed for diagnostic testing following a positive newborn screen of PAH deficiency. “Additional testing is needed to define the cause of elevated PHE and should include analysis of pterin metabolism; PAH genotypic is indicated for improved therapy planning (Vockley et al., 2014).”

In 2013, the ACMG released guidelines concerning prenatal/preconception expanded carrier screening. These guidelines provide the following recommendations:

  • “When adult-onset disorders (disorders that could affect the offspring of the individual undergoing carrier screening once the offspring reaches adult life) are included in screening panels, patients must provide consent to screening for these conditions, especially when there may be implications for the health of the individual being screened or other family members
  • For each disorder, the causative gene(s), mutations, and mutation frequencies should be known in the population being tested, so that meaningful residual risk in individuals who test negative can be assessed
  • There must be validated clinical association between the mutation(s) detected and the severity of the disorder (Grody et al., 2013).”

World Health Organization (WHO) (WHO, 2016)
In 2016, the WHO released their publication titled, WHO recommendations on antenatal care for a positive pregnancy experience, which had the following recommendations (WHO, 2016):

  • Anemia (Context-specific recommendation)—"Full blood count testing is the recommended method for diagnosing anaemia in pregnancy.”
  • Asymptomatic bacteriuria (Context-specific recommendation)—"Midstream urine culture is the recommended method for diagnosing asymptomatic bacteriuria (ASB) in pregnancy. In settings where urine culture is not available, on-site midstream urine Gram-staining is recommended over the use of dipstick tests as the method for diagnosing ASB in pregnancy.”
  • Gestational diabetes mellitus (Recommended)—"Hyperglycaemia first detected at any time during pregnancy should be classified as either gestational diabetes mellitus (GDM) or diabetes mellitus in pregnancy, according to WHO criteria.”
  • HIV and syphilis (Recommended)—"In high-prevalence settings, provider-initiated testing and counselling (PITC) for HIV should be considered a routine component of the package of care for pregnant women in all antenatal care settings. In low-prevalence settings, PITC can be considered for pregnant women in antenatal care settings as a key component of the effort to eliminate mother-to-child transmission of HIV, and to integrate HIV testing with syphilis, viral or other key tests, as relevant to the setting, and to strengthen the underlying maternal and child health systems.”
  • Tuberculosis (Context-specific recommendation)—"In settings where the tuberculosis (TB) prevalence in the general population is 100/100 000 population or higher, systematic screening for active TB should be considered for pregnant women as part of antenatal care (WHO, 2016).”

To help circumvent prenatal transmission, the CDC also “recommends that all pregnant women get tested for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis during each pregnancy” for all women during pregnancy, as “Screening is necessary to access medical services for HCV and treatment to prevent transmission of HIV, HBV, and syphilis to the infant” (CDC, 2020b).

International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) (ISPD, 2018) 
The ISPD, SMFM and PQF published the following guidelines on the use of genome-wide sequencing for fetal diagnosis: 

  • “The use of diagnostic sequencing is currently being introduced for evaluation of fetuses for whom standard diagnostic genetic testing, such as chromosomal microarray analysis (CMA), has already been performed and is uninformative or is offered concurrently according to accepted practice guidelines, or for whom expert genetic opinion determines that standard genetic testing is less optimal than sequencing for the presenting fetal phenotype.
  • The routine use of prenatal sequencing as a diagnostic test cannot currently be supported due to insufficient validation data and knowledge about its benefits and pitfalls (ISPD, 2018).”

The Canadian National Rh Working Group and the Society of Obstetricians and Gynaecologists of Canada (SOGC) Genetics Committee (Fung & Eason, 2018; Johnson, MacDonald, Clarke, & Skoll, 2017) 
Guidelines were published by a consensus meeting of the Canadian National Rh Working Group in collaboration with the SOGC Genetics committee. The following recommendations were provided:

  • “The current optimal management of the D-negative pregnant woman is based on the prediction of the fetal D-blood group by cell-free DNA in maternal plasma with targeted antenatal anti-D prophylaxis. This approach should be adopted in Canada (II-2A).
  • While various algorithms of implementation of fetal RHD genotyping have been described, a model positioned in the first trimester appears to be most in alignment with the existing Canadian antenatal anti-D prophylaxis program and should be endorsed (II-2A).
  • While the risk of a false-negative result with RHD genotyping is very small and the benefits of knowing the fetal RHD status in terms of compliance with prophylaxis seem to outweigh the risks, the chance of immunization is not zero. Quality control at a laboratory and clinical level should be of utmost priority in program planning (II-3A) (Johnson et al., 2017).”

College of American Pathologists (CAP) Transfusion Medicine Resource Committee (TMRC) Work Group (Sandler et al., 2015) 
The following recommendations were given by the CAP RMRC work group:

  • “The Work Group recommends that RHD genotyping be performed whenever a discordant RhD typing result and/or a serological weak D phenotype is detected in patients, including pregnant women, newborns and potential transfusion recipients. It is anticipated that the immediate benefit will be fewer unnecessary injections of RhIG and increased availability of RhD-negative RBCs for transfusion
  • For women with a serological weak D phenotype associated with RHD genotypes other than weak D type 1, 2 or 3, the Work Group recommends that these women receive conventional prophylaxis with RhIG, including postpartum RhIG if the newborn is RhD-positive or has a serological weak D phenotype (Sandler et al., 2015).”

The National Institute for Health and Care Excellence (NICE) (NICE, 2016, 2020) 
The NICE published the following guideline in November 2016 regarding fetal RHD genotyping: “High-throughput non‑invasive prenatal testing (NIPT) for fetal RHD genotype is recommended as a cost-effective option to guide antenatal prophylaxis with anti‑D immunoglobulin, provided that the overall cost of testing is £24 or less. This will help reduce unnecessary use of a blood product in pregnant women, and conserve supplies by only using anti‑D immunoglobulin for those who need it (NICE, 2016).” 

In 2020, the NICE published a document through their Pathways program, synthesizing its recommendations on screening for antenatal care for uncomplicated pregnancies. The recommendation for each condition is reported below (NICE, 2020). 

Condition

Screening recommended?

Indications

Anaemia

Yes

“Screening should take place early in pregnancy (at the booking appointment) and at 28 weeks when other blood screening tests are being performed. This allows enough time for treatment if anaemia is detected.

Haemoglobin levels outside the normal UK range for pregnancy (that is, 11 g/100 ml at first contact and 10.5 g/100 ml at 28 weeks) should be investigated and iron supplementation considered if indicated.”

Down’s Syndrome

Yes

“Screening for Down's syndrome should be performed by the end of the first trimester (13 weeks 6 days), but provision should be made to allow later screening (which could be as late as 20 weeks) for women booking later in pregnancy.

The 'combined test' (nuchal translucency, beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) should be offered to screen for Down's syndrome between 11 weeks and 13 weeks 6 days. For women who book later in pregnancy the most clinically and cost-effective serum screening test (triple or quadruple test) should be offered between 15 weeks and 20 weeks.

When it is not possible to measure nuchal translucency, owing to fetal position or raised BMI, women should be offered serum screening (triple or quadruple test) between 15 weeks and 20 weeks.”

“The presence of an isolated soft marker, with the exception of increased nuchal fold, on the routine anomaly scan, should not be used to adjust the a priori risk for Down's syndrome.

The presence of an increased nuchal fold (6 millimetres or above) or two or more soft markers on the routine anomaly scan should prompt the offer of a referral to a fetal medicine specialist or an appropriate healthcare professional with a special interest in fetal medicine.”

Sickle cell diseases and thalassaemias

Yes

“Screening for sickle cell diseases and thalassaemias should be offered to all women as early as possible in pregnancy (ideally by 10 weeks). The type of screening depends upon the prevalence and can be carried out in either primary or secondary care.”

Asymptomatic bacteriuria

Yes

“Women should be offered routine screening for asymptomatic bacteriuria by midstream urine culture early in pregnancy. Identification and treatment of asymptomatic bacteriuria reduces the risk of pyelonephritis.”

Asymptomatic bacterial vaginosis

No

“Pregnant women should not be offered routine screening for bacterial vaginosis because the evidence suggests that the identification and treatment of asymptomatic bacterial vaginosis does not lower the risk of preterm birth and other adverse reproductive outcomes.”

Chlamydia trachomatis

No

“Chlamydia screening should not be offered as part of routine antenatal care.”

Cytomegalovirus

No

“The available evidence does not support routine cytomegalovirus screening in pregnant women and it should not be offered.”

Hepatitis B virus

Yes

“Serological screening for hepatitis B virus should be offered to pregnant women so that effective postnatal interventions can be offered to infected women to decrease the risk of mother-to-child transmission.”

Hepatitis C virus

No

“Pregnant women should not be offered routine screening for hepatitis C virus because there is insufficient evidence to support its clinical and cost effectiveness.”

HIV

Yes

“Pregnant women should be offered screening for HIV infection early in antenatal care because appropriate antenatal interventions can reduce mother-to-child transmission of HIV infection.”

Group B streptococcus

No

“Pregnant women should not be offered routine antenatal screening for group B streptococcus because evidence of its clinical and cost effectiveness remains uncertain.”

Syphilis

Yes

“Screening for syphilis should be offered to all pregnant women at an early stage in antenatal care because treatment of syphilis is beneficial to the mother and baby.”

Toxoplasmosis

No

“Routine antenatal serological screening for toxoplasmosis should not be offered because the risks of screening may outweigh the potential benefits.”

Pre-eclampsia

Yes

“Blood pressure measurement and urinalysis for protein should be carried out at each antenatal visit to screen for pre-eclampsia.”

Preterm labour

No

“Routine screening for preterm labour should not be offered.”

Placenta praevia

No

“Because most low-lying placentas detected at the routine anomaly scan will have resolved by the time the baby is born, only a woman whose placenta extends over the internal cervical os should be offered another transabdominal scan at 32 weeks. If the transabdominal scan is unclear, a transvaginal scan should be offered.”

Structural fetal anomalies

Yes

“Ultrasound screening for fetal anomalies should be routinely offered, normally between 18 weeks and 20 weeks 6 days.”

Department of Veterans Affairs/Department of Defense (VA/DoD) (VA & DOD, 2018) 
In the 3rd edition of the VA/DoD Clinical Practice Guideline for the Management of Pregnancy (VA & DOD, 2018), they list the following lab tests as routine for all pregnancies in the first prenatal visit: HIV, CBC, ABO Rh blood typing, Antibody screen, anemia/hemoglobinopathies screen, rapid plasma reagin, gonorrhea, chlamydia, hepatitis B surface antigen test, rubella IgG, Urinalysis and culture, and varicella IgG (if status is unknown). They also list the following among their recommendations (VA & DOD, 2018):

  • “We recommend screening for use of tobacco, alcohol, illicit drugs, and unauthorized use of prescription medication because their use is common and can result in adverse outcomes. For women who screen positive, we recommend additional evaluation and treatment.” [Strong]
  • “We recommend screening for depression using a standardized tool such as the Edinburgh Postnatal Depression Scale or the 9- item Patient Health Questionnaire periodically during pregnancy and postpartum.” [Strong]
  • “We suggest making prenatal diagnostic testing for aneuploidy available to all pregnant women.” [Weak]
  • “We recommend offering prenatal screening for aneuploidy and the most common clinically significant genetic disorders to all pregnant women. When aneuploidy screening is desired, cellfree fetal DNA screening should be considered; however, screening test selection should be individualized and take into account the patient’s age, baseline aneuploidy risk, and test performance for a given condition.” [Strong]
  • “We suggest the two-step process (one-hour oral glucose challenge test followed by three-hour oral glucose tolerance test) to screen for gestational diabetes mellitus at 24-28 weeks gestation for all pregnant women.” [Weak]
  • “We suggest that pregnant women with an unexplained elevation of maternal serum alpha-fetoprotein be evaluated and counseled by a qualified obstetric provider due to increased risk for adverse perinatal outcomes.” [Weak]
  • “We recommend against routine screening for preterm delivery using the fetal fibronectin test in asymptomatic women.” [Strong, against]
  • “We recommend considering the use of fetal fibronectin testing as a part of the evaluation strategy in women between 24 and 34 6/7 weeks gestation with signs and symptoms of preterm labor, particularly in facilities where the result might affect management of delivery.” [Strong]
  • “We suggest that women who have undergone bariatric surgery should be evaluated for nutritional deficiencies and need for nutritional supplementation where indicated (e.g., vitamin B12, folate, iron, calcium).” [Weak]

Health Resources & Services Administration (HRSA) (HRSA, 2017, 2019) 
The HRSA-supported Women’s Preventive Services Initiative (HRSA, 2017) recommends the following:

  • Screening pregnant women for gestational diabetes mellitus after 24 weeks of gestation (preferably between 24 and 28 weeks of gestation)
  • Women with risk factors for diabetes mellitus be screened for preexisting diabetes before 24 weeks of gestation—ideally at the first prenatal visit

Royal College of Obstetricians and Gynaecologists (RCOG) (RCOG, 2014) 
The RCOG have given the following recommendation for prenatal and fetal genotyping: “Non-invasive fetal genotyping using maternal blood is now possible for D, C, c, E, e and K antigens. This should be performed in the first instance for the relevant antigen when maternal red cell antibodies are present” (C recommendation) (RCOG, 2014). 

“Endnotes:

  1. To promote informed and timely therapeutic decisions, health care providers should test women for HIV as early as possible during each pregnancy.1
  2. All pregnant women should be tested for hepatitis B surface antigen (HBsAg) during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been vaccinated or tested previously.2
  3. “Increased risk” means new or multiple sex partners, sex partner with concurrent partners, sex partners who have a sexually transmitted disease (STD).3,4
  4. “At increased risk” means injection-drug use (IDU), had a blood transfusion before July 1992, receipt of an unregulated tattoo, long-term hemodialysis, intranasal drug use, and other percutaneous exposures.3
  5. “Certain groups” includes women who are at high risk for syphilis or live in areas of high syphilis morbidity.3
  6. “Certain groups” includes women who receive health care in areas with an elevated incidence of HIV or AIDS among women aged 15-45 years, who receive health care in facilities in which prenatal screening identifies at least one HIV-infected women per 1,000 women screened, known to be at high risk for HIV (i.e., injection-drug user and their sex partners, exchange sex for money or drugs, sex partner of HIV-infected persons, have had a new or >1 sex partner during this pregnancy), or have signs or symptoms consistent with acute HIV infection.1
  7. Women admitted for delivery at a health care facility without documentation of HBsAg test results should have blood drawn and tested as soon as possible after admission.2
  8. Having had more than one sex partner during the previous 6 months, an HBsAg-positive sex partner, evaluation or treatment for a STD, or IDU2 (CDC, 2019b).”

Further, in 2020, the CDC recommended “Hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection (HCV RNA‑positivity) is less than 0.1%” (CDC, 2020) 

  • Repeat HIV screening in the third trimester for women at high-risk of STDs—"Women who use illicit drugs, have STDs during pregnancy, have multiple sex partners during pregnancy, live in areas with high HIV prevalence, or have partners with HIV infection (CDC, 2015b).”
  • Screening of all pregnant women for HBsAg (Hepatitis B Surface Antigen Test) during each pregnancy regardless of prior testing with a retest at time of deliver for those at high risk, including persons born in regions of high endemicity (≥2% prevalence) and HIV positive individuals (CDC, 2015b).
  • Testing of all pregnant women for syphilis during the first prenatal visit and, for individuals at high risk, retest early in the third semester as well as time of delivery (CDC, 2015b). 
  • Chlamydia trachomatis screening at the first prenatal visit and repeat testing during the third trimester for women under 25 years or at high risk for acquisition. “Pregnant women with chlamydial infection should have a test-of-cure 3-4 weeks after treatment and be retested within 3 months (CDC, 2015b).”
  • N. gonorrhea testing of all pregnant women under 25 years of age and older women at risk for infection or living in an area of high prevalence of N. gonorrhea. For pregnant women who receive treatment for gonorrhea, they should be retested 3 months after treatment (CDC, 2015b).
  • Screening for hepatitis C is recommended in pregnant women at high risk for infection and pregnant women born between 1945 – 1965 (CDC, 2015b). It is not recommended for pregnant women who have no risk factors (CDC, 2015c).
  • Zika virus testing for symptomatic pregnant persons:
    • “For symptomatic pregnant women who had recent travel to areas with active dengue transmission and a risk of Zika, specimens should be collected as soon as possible after the onset of symptoms up to 12 weeks after symptom onset.
      • The following diagnostic testing should be performed at the same time:
        • Dengue and Zika virus NAAT testing on a serum specimen, and Zika virus NAAT on a urine specimen, and
        • IgM testing for dengue only.
        • Zika virus IgM testing is NOT recommended for symptomatic pregnant women.
          • Zika IgM antibodies can persist for months to years following infection. Therefore, detecting Zika IgM antibodies might not indicate a recent infection.
          • There is notable cross-reactivity between dengue IgM and Zika IgM antibodies in serologic tests. Antibodies generated by a recent dengue virus infection can cause the Zika IgM to be falsely positive.
        • If the Zika NAAT is positive on a single specimen, the Zika NAAT should be repeated on newly extracted RNA from the same specimen to rule out false-positive NAAT results. If the dengue NAAT is positive, this provides adequate evidence of a dengue infection and no further testing is indicated.
        • If the IgM antibody test for dengue is positive, this is adequate evidence of a dengue infection and no further testing is indicated (CDC, 2019a).”
    • ZIKA virus testing in asymptomatic pregnant women is not recommended. 
  • Cervical cancer screening intervals in pregnant women should be the same as for nonpregnant women (CDC, 2015b).
  • “Evidence does not support routine HSV-2 serologic screening among asymptomatic pregnant women. However, type-specific serologic tests might be useful for identifying pregnant women at risk for HSV infection and guiding counseling regarding the risk for acquiring genital herpes during pregnancy (CDC, 2015b, 2019a).”
  • “Evidence is insufficient to recommend routine screening for BV in asymptomatic pregnant women at high or low risk for preterm delivery for the prevention of preterm birth (CDC, 2015a).”

American College of Medical Genetics and Genomics (ACMG) (2004, 2005, 2008, 2013, 2014, 2016) 
The American College of Medical Genetics and Genomics (ACMG) recommends that the following (Gregg et al., 2016):

  • “Allowing patients to select diagnostic or screening approaches for the detection of fetal aneuploidy and/or genomic changes that are consistent with their personal goals and preferences.”
  • “Informing all pregnant women that diagnostic testing (CVS or amniocentesis) is an option for the detection of chromosome abnormalities and clinically significant CNVs [copy-number variants].”
  • “Informing all pregnant women that NIPS [non-invasive prenatal screening] is the most sensitive screening option for traditionally screened aneuploidies (i.e., Patau, Edwards, and Down syndromes).”
  • “Offering diagnostic testing when a positive screening test result is reported after NIPS.”
  • The ACMG does NOT recommend “NIPS to screen for autosomal aneuploidies other than those involving chromosomes 13, 18, and 21.”
  • “Offering diagnostic testing for a no-call NIPS result due to low fetal fraction if maternal blood for NIPS was drawn at an appropriate gestational age. A repeat blood draw is NOT appropriate.”
  • “Offering aneuploidy screening other than NIPS in cases of significant obesity.”
  • “Offering diagnostic testing when a positive screening test result is reported after screening for sex chromosome aneuploidies.”
  • “Offering diagnostic testing (CVS or amniocentesis) with CMA when NIPS identifies a CNV.”
  • ACMG does NOT recommend “NIPS to screen for genome-wide CNVs. If this level of information is desired, then diagnostic testing (e.g., chorionic villous sampling or amniocentesis) followed by CMA is recommended.”
  • “Offering aneuploidy screening other than NIPS for patients with a history of bone marrow or organ transplantation from a male donor or donor of uncertain biologic sex.”

In the ACMG practice guidelines concerning carrier screening in individuals of Ashkenazi Jewish descent, they “recommend that carrier screening for cystic fibrosis, Canavan disease, familial dysautonomia, and Tay-Sachs disease be offered to all Ashkenazi Jews who are pregnant or considering pregnancy, according to current American College of Medical Genetics and/or the American College of Obstetricians and Gynecologists (ACOG) guidelines. In addition, we recommend that carrier screening be offered for Fanconi anemia (Group C), Niemann-Pick (Type A), Bloom syndrome, mucolipidosis IV, and Gaucher disease (Gross, Pletcher, & Monaghan, 2008).”

Concerning carrier screening for spinal muscular atrophy, ACMG recommends, “Because SMA is present in all populations, carrier testing should be offered to all couples regardless of race or ethnicity. Ideally, the testing should be offered before conception or early in pregnancy (Prior, 2008).” They also recommend carrier screening for Fragile X syndrome for pregnant women and those considering pregnancy who have a family history of Fragile X syndrome or undefined mental retardation (Sherman, Pletcher, & Driscoll, 2005). Cystic fibrosis carrier screening for all pregnant women and those considering pregnancy is recommended; moreover, the ACMG released the mutation frequency data of various ethnic groups within their 2004 revision of the cystic fibrosis screening guidelines (Watson et al., 2004).

In 2014, the American College of Medical Genetics and Genomics issued the following guidelines for the clinical evaluation and diagnosis of hearing loss. For individuals lacking physical findings suggestive of a known syndrome and having medical and birth histories that do not suggest an environmental cause of hearing loss, ACMG recommends that a tiered diagnostic approach should be implemented (Alford et al., 2014):

  • “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology.”
  • “In the absence of any specific clinical indications and for singleton cases and cases with apparent autosomal recessive inheritance, the next step should be testing for DFNB1-related hearing loss (due to mutations in GJB2 and adjacent deletions in GJB6).”
  • “If initial genetic testing is negative, genetic testing using gene panel tests, NGS technologies such as large sequencing panels targeted toward hearing loss–related genes, WES, or WGS may be considered.”

Also, in 2014, the ACMG released guidelines concerning the diagnosis and management of phenylalanine hydroxylase (PAH) deficiency. They recommend PAH testing be part of newborn screening and that quantitative blood amino acids testing should be performed for diagnostic testing following a positive newborn screen of PAH deficiency. “Additional testing is needed to define the cause of elevated PHE and should include analysis of pterin metabolism; PAH genotypic is indicated for improved therapy planning (Vockley et al., 2014).”

In 2013, the ACMG released guidelines concerning prenatal/preconception expanded carrier screening. These guidelines provide the following recommendations:

  • “When adult-onset disorders (disorders that could affect the offspring of the individual undergoing carrier screening once the offspring reaches adult life) are included in screening panels, patients must provide consent to screening for these conditions, especially when there may be implications for the health of the individual being screened or other family members
  • For each disorder, the causative gene(s), mutations, and mutation frequencies should be known in the population being tested, so that meaningful residual risk in individuals who test negative can be assessed
  • There must be validated clinical association between the mutation(s) detected and the severity of the disorder (Grody et al., 2013).” 

World Health Organization (WHO) (WHO, 2016)
In 2016, the WHO released their publication titled, WHO recommendations on antenatal care for a positive pregnancy experience, which had the following recommendations (WHO, 2016):

  • Anemia (Context-specific recommendation)—"Full blood count testing is the recommended method for diagnosing anaemia in pregnancy.”
  • Asymptomatic bacteriuria (Context-specific recommendation)—"Midstream urine culture is the recommended method for diagnosing asymptomatic bacteriuria (ASB) in pregnancy. In settings where urine culture is not available, on-site midstream urine Gram-staining is recommended over the use of dipstick tests as the method for diagnosing ASB in pregnancy.”
  • Gestational diabetes mellitus (Recommended)—"Hyperglycaemia first detected at any time during pregnancy should be classified as either gestational diabetes mellitus (GDM) or diabetes mellitus in pregnancy, according to WHO criteria.”
  • HIV and syphilis (Recommended)—"In high-prevalence settings, provider-initiated testing and counselling (PITC) for HIV should be considered a routine component of the package of care for pregnant women in all antenatal care settings. In low-prevalence settings, PITC can be considered for pregnant women in antenatal care settings as a key component of the effort to eliminate mother-to-child transmission of HIV, and to integrate HIV testing with syphilis, viral or other key tests, as relevant to the setting, and to strengthen the underlying maternal and child health systems.”
  • Tuberculosis (Context-specific recommendation)—"In settings where the tuberculosis (TB) prevalence in the general population is 100/100 000 population or higher, systematic screening for active TB should be considered for pregnant women as part of antenatal care (WHO, 2016).” 

International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) (ISPD, 2018) 
The ISPD, SMFM and PQF published the following guidelines on the use of genome-wide sequencing for fetal diagnosis: 

  • “The use of diagnostic sequencing is currently being introduced for evaluation of fetuses for whom standard diagnostic genetic testing, such as chromosomal microarray analysis (CMA), has already been performed and is uninformative or is offered concurrently according to accepted practice guidelines, or for whom expert genetic opinion determines that standard genetic testing is less optimal than sequencing for the presenting fetal phenotype.
  • The routine use of prenatal sequencing as a diagnostic test cannot currently be supported due to insufficient validation data and knowledge about its benefits and pitfalls (ISPD, 2018).” 

The Canadian National Rh Working Group and the Society of Obstetricians and Gynaecologists of Canada (SOGC) Genetics Committee (Fung & Eason, 2018; Johnson, MacDonald, Clarke, & Skoll, 2017) 
Guidelines were published by a consensus meeting of the Canadian National Rh Working Group in collaboration with the SOGC Genetics committee. The following recommendations were provided:

  • “The current optimal management of the D-negative pregnant woman is based on the prediction of the fetal D-blood group by cell-free DNA in maternal plasma with targeted antenatal anti-D prophylaxis. This approach should be adopted in Canada (II-2A).
  • While various algorithms of implementation of fetal RHD genotyping have been described, a model positioned in the first trimester appears to be most in alignment with the existing Canadian antenatal anti-D prophylaxis program and should be endorsed (II-2A).
  • While the risk of a false-negative result with RHD genotyping is very small and the benefits of knowing the fetal RHD status in terms of compliance with prophylaxis seem to outweigh the risks, the chance of immunization is not zero. Quality control at a laboratory and clinical level should be of utmost priority in program planning (II-3A) (Johnson et al., 2017).” 

College of American Pathologists (CAP) Transfusion Medicine Resource Committee (TMRC) Work Group (Sandler et al., 2015) 
The following recommendations were given by the CAP RMRC work group:

  • “The Work Group recommends that RHD genotyping be performed whenever a discordant RhD typing result and/or a serological weak D phenotype is detected in patients, including pregnant women, newborns and potential transfusion recipients. It is anticipated that the immediate benefit will be fewer unnecessary injections of RhIG and increased availability of RhD-negative RBCs for transfusion
  • For women with a serological weak D phenotype associated with RHD genotypes other than weak D type 1, 2 or 3, the Work Group recommends that these women receive conventional prophylaxis with RhIG, including postpartum RhIG if the newborn is RhD-positive or has a serological weak D phenotype (Sandler et al., 2015).” 

The National Institute for Health and Care Excellence (NICE) (NICE, 2016) 
The NICE published the following guideline in November 2016 regarding fetal RHD genotyping: “High-throughput non‑invasive prenatal testing (NIPT) for fetal RHD genotype is recommended as a cost-effective option to guide antenatal prophylaxis with anti‑D immunoglobulin, provided that the overall cost of testing is £24 or less. This will help reduce unnecessary use of a blood product in pregnant women, and conserve supplies by only using anti‑D immunoglobulin for those who need it (NICE, 2016).” 

Department of Veterans Affairs/Department of Defense (VA/DoD) (VA & DOD, 2018) 
In the 3rd edition of the VA/DoD Clinical Practice Guideline for the Management of Pregnancy (VA & DOD, 2018), they list the following lab tests as routine for all pregnancies in the first prenatal visit: HIV, CBC, ABO Rh blood typing, Antibody screen, anemia/hemoglobinopathies screen, rapid plasma reagin, gonorrhea, chlamydia, hepatitis B surface antigen test, rubella IgG, Urinalysis and culture, and varicella IgG (if status is unknown).  They also list the following among their recommendations (VA & DOD, 2018):

  • “We recommend screening for use of tobacco, alcohol, illicit drugs, and unauthorized use of prescription medication because their use is common and can result in adverse outcomes. For women who screen positive, we recommend additional evaluation and treatment.” (Strong)
  • “We recommend screening for depression using a standardized tool such as the Edinburgh Postnatal Depression Scale or the 9- item Patient Health Questionnaire periodically during pregnancy and postpartum.” (Strong)
  • “We suggest making prenatal diagnostic testing for aneuploidy available to all pregnant women.” (Weak)
  • “We recommend offering prenatal screening for aneuploidy and the most common clinically significant genetic disorders to all pregnant women. When aneuploidy screening is desired, cellfree fetal DNA screening should be considered; however, screening test selection should be individualized and take into account the patient’s age, baseline aneuploidy risk, and test performance for a given condition.” (Strong)
  • “We suggest the two-step process (one-hour oral glucose challenge test followed by three-hour oral glucose tolerance test) to screen for gestational diabetes mellitus at 24-28 weeks gestation for all pregnant women.” (Weak)
  • “We suggest that pregnant women with an unexplained elevation of maternal serum alpha-fetoprotein be evaluated and counseled by a qualified obstetric provider due to increased risk for adverse perinatal outcomes.” (Weak)
  • “We recommend against routine screening for preterm delivery using the fetal fibronectin test in asymptomatic women.” (Strong, against)
  • “We recommend considering the use of fetal fibronectin testing as a part of the evaluation strategy in women between 24 and 34 6/7 weeks gestation with signs and symptoms of preterm labor, particularly in facilities where the result might affect management of delivery.” (Strong)
  • “We suggest that women who have undergone bariatric surgery should be evaluated for nutritional deficiencies and need for nutritional supplementation where indicated (e.g., vitamin B12, folate, iron, calcium).” (Weak) 

Health Resources & Services Administration (HRSA) (HRSA, 2017, 2019) 
The HRSA-supported Women’s Preventive Services Initiative (HRSA, 2017) recommends the following:

  • Screening pregnant women for gestational diabetes mellitus after 24 weeks of gestation (preferably between 24 and 28 weeks of gestation)
  • Women with risk factors for diabetes mellitus be screened for preexisting diabetes before 24 weeks of gestation—ideally at the first prenatal visit 

Royal College of Obstetricians and Gynaecologists (RCOG) (RCOG, 2014) 
The RCOG have given the following recommendation for prenatal and fetal genotyping: “Non-invasive fetal genotyping using maternal blood is now possible for D, C, c, E, e and K antigens. This should be performed in the first instance for the relevant antigen when maternal red cell antibodies are present” (C recommendation) (RCOG, 2014).

References 

  1. ACOG. (2011). ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol, 118(1), 197-198. doi:10.1097/AOG.0b013e318227f06b
  2. ACOG. (2012). Committee opinion No. 533: lead screening during pregnancy and lactation. Obstet Gynecol, 120(2 Pt 1), 416-420. doi:10.1097/AOG.0b013e31826804e8
  3. ACOG. (2014). Committee Opinion No. 614: Management of pregnant women with presumptive exposure to Listeria monocytogenes. Obstet Gynecol, 124(6), 1241-1244. doi:10.1097/01.AOG.0000457501.73326.6c
  4. ACOG. (2015a). ACOG Practice Bulletin Number 148: Thyroid disease in pregnancy. Obstet Gynecol, 125, 996-1005.
  5. ACOG. (2015b). Committee opinion no. 634: Hereditary cancer syndromes and risk assessment. Obstet Gynecol, 125(6), 1538-1543. doi:10.1097/01.Aog.0000466373.71146.51
  6. ACOG. (2015c). Committee Opinion No. 640: Cell-Free Dna Screening For Fetal Aneuploidy. 126(3), e31-e37. doi:10.1097/aog.0000000000001051
  7. ACOG. (2015d). Committee Opinion No. 643: Identification and Referral of Maternal Genetic Conditions in Pregnancy. Obstet Gynecol, 126(4), e49-51. doi:10.1097/aog.0000000000001107
  8. ACOG. (2016a). Committee Opinion No.682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. Obstet Gynecol, 128(6), e262-e268. doi:10.1097/aog.0000000000001817
  9. ACOG. (2016b). Prenatal Diagnostic Testing for Genetic Disorders. Retrieved from https://s3.amazonaws.com/cdn.smfm.org/publications/223/download-f5260f3bc6686c15e4780f8100c74448.pdf
  10. ACOG. (2017a). Carrier Screening in the Age of Genomic Medicine. Retrieved from https://www.acog.org/-/media/Committee-Opinions/Committee-on-Genetics/co690.pdf?dmc=1&ts=20170328T2033175160
  11. ACOG. (2017b). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Retrieved from https://journals.lww.com/greenjournal/fulltext/2017/08000/Practice_Bulletin_No__181__Prevention_of_Rh_D.54.aspx
  12. ACOG. (2017c, 09/2017). Routine Tests During Pregnancy. Retrieved from https://www.acog.org/Patients/FAQs/Routine-Tests-During-Pregnancy?
  13. ACOG. (2018a). Committee Opinion No. 757: Screening for Perinatal Depression. Obstet Gynecol, 132(5), e208-e212. Retrieved from https://www.acog.org/-/media/Committee-Opinions/Committee-on-Obstetric-Practice/co757.pdf?dmc=1&ts=20190107T1732311925
  14. ACOG. (2018b, 08/31/2018). Practice Advisory Interim Guidance for Care of Obstetric Patients During a Zika Virus Outbreak. Practice Advisories. Retrieved from https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Interim-Guidance-for-Care-of-Obstetric-Patients-During-a-Zika-Virus-Outbreak
  15. ACOG. (2019a). ACOG Committee Opinion No. 778: Newborn Screening and the Role of the Obstetrician-Gynecologist. Obstet Gynecol, 133(5), e357-e361. doi:10.1097/aog.0000000000003245
  16. ACOG. (2019b). Management of Patients in the Context of Zika Virus. Retrieved from https://www.acog.org/-/media/Committee-Opinions/Immunization-Infectious-Disease-and-Public-Health-Preparedness-Expert-Work-Group/co784.pdf?dmc=1&ts=20200204T1904597658
  17. ACOG. (2020a). Carrier Screening in the Age of Genomic Medicine. Retrieved from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/03/carrier-screening-in-the-age-of-genomic-medicine
  18. ACOG. (2020b). Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. Retrieved from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2016/12/microarrays-and-next-generation-sequencing-technology-the-use-of-advanced-genetic-diagnostic-tools-in-obstetrics-and-gynecology?utm_source=redirect&utm_medium=web&utm_campaign=otn
  19. ACOG. (2020c). Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797. Obstet Gynecol, 135(2), e51-e72. doi:10.1097/aog.0000000000003668
  20. ACOG. (2021a). ACOG Publications: January 2021. Obstetrics & Gynecology, 137(1). Retrieved from https://journals.lww.com/greenjournal/Fulltext/2021/01000/ACOG_Publications__January_2021.31.aspx
  21. ACOG. (2021b). Consumer Testing for Disease Risk: ACOG Committee Opinion Summary, Number 816. Obstet Gynecol, 137(1), 203-204. doi:10.1097/aog.0000000000004201
  22. ADA. (2018). 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care, 41(Suppl 1), S13-s27. doi:10.2337/dc18-S002
  23. ADA. (2020). Standards of Medical Care in Diabetes - 2020. Retrieved from https://care.diabetesjournals.org/content/diacare/suppl/2019/12/20/43.Supplement_1.DC1/DC_43_S1_2020.pdf
  24. Alford, R. L., Arnos, K. S., Fox, M., Lin, J. W., Palmer, C. G., Pandya, A., . . . Yoshinaga-Itano, C. (2014). American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss. Genet Med, 16(4), 347-355. doi:10.1038/gim.2014.2
  25. Audibert, F., De Bie, I., Johnson, J.-A., Okun, N., Wilson, R. D., Armour, C., . . . Kim, R. (2017). No. 348-Joint SOGC-CCMG Guideline: Update on Prenatal Screening for Fetal Aneuploidy, Fetal Anomalies, and Adverse Pregnancy Outcomes. Journal of Obstetrics and Gynaecology Canada, 39(9), 805-817. doi:https://doi.org/10.1016/j.jogc.2017.01.032
  26. Biro, O., Rigo, J., Jr., & Nagy, B. (2020). Noninvasive prenatal testing for congenital heart disease - cell-free nucleic acid and protein biomarkers in maternal blood. J Matern Fetal Neonatal Med, 33(6), 1044-1050. doi:10.1080/14767058.2018.1508437
  27. Calhoun, D. (2020, 3/23/2020). Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. Retrieved from https://www.uptodate.com/contents/postnatal-diagnosis-and-management-of-hemolytic-disease-of-the-fetus-and-newborn?topicRef=6773&source=see_link
  28. CDC. (2015a, 06/04/2015). Bacterial Vaginosis. Retrieved from https://www.cdc.gov/std/tg2015/bv.htm
  29. CDC. (2015b, 08/22/2016). Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. Retrieved from https://www.cdc.gov/std/tg2015/screening-recommendations.htm
  30. CDC. (2015c, 10/15/2015). Testing Recommendations for Hepatitis C Virus Infection. Retrieved from https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm
  31. CDC. (2019a). NEW Zika and Dengue Testing Guidance (Updated November 2019). Retrieved from https://www.cdc.gov/zika/hc-providers/testing-guidance.html
  32. CDC. (2019b). Pregnancy and HIV, Viral Hepatitis, STD, & TB Prevention Screening Recommendations. Retrieved from https://www.cdc.gov/nchhstp/pregnancy/screening/index.html
  33. CDC. (2020a). CDC Recommendations for Hepatitis C Screening Among Adults in the United States. Retrieved from https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm
  34. CDC. (2020b, 6/12/2020). Screening Recommendations. NCHHSTP. Retrieved from https://www.cdc.gov/nchhstp/pregnancy/screening/index.html
  35. Chou, R., Dana, T., Fu, R., Zakher, B., Wagner, J., Ramirez, S., . . . Jou, J. H. (2020). Screening for Hepatitis C Virus Infection in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. Jama. doi:10.1001/jama.2019.20788
  36. Clausen, F. B., Steffensen, R., Christiansen, M., Rudby, M., Jakobsen, M. A., Jakobsen, T. R., . . . Grunnet, N. (2014). Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women-2 years of screening experience from Denmark. Prenat Diagn, 34(10), 1000-1005. doi:10.1002/pd.4419
  37. Curry, S. J., Krist, A. H., Owens, D. K., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2019). Screening for Elevated Blood Lead Levels in Children and Pregnant Women: US Preventive Services Task Force Recommendation Statement. Jama, 321(15), 1502-1509. doi:10.1001/jama.2019.3326
  38. Daniels, G., Finning, K., Martin, P., & Summers, J. (2007). Fetal RhD genotyping: a more efficient use of anti-D immunoglobulin. Transfus Clin Biol, 14(6), 568-571. doi:10.1016/j.tracli.2008.03.007
  39. Darlington, M., Carbonne, B., Mailloux, A., Brossard, Y., Levy-Mozziconacci, A., Cortey, A., . . . Durand-Zaleski, I. (2018). Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: a French multicentric two-arm study of 850 women. BMC Pregnancy Childbirth, 18(1), 496. doi:10.1186/s12884-018-2114-5
  40. de Haas, M., Thurik, F. F., van der Ploeg, C. P., Veldhuisen, B., Hirschberg, H., Soussan, A. A., . . . Ellen van der Schoot, C. (2016). Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands. Bmj, 355, i5789. doi:10.1136/bmj.i5789
  41. de Jong, A., Maya, I., & van Lith, J. M. (2015). Prenatal screening: current practice, new developments, ethical challenges. Bioethics, 29(1), 1-8. doi:10.1111/bioe.12123
  42. Dondorp, W., de Wert, G., Bombard, Y., Bianchi, D. W., Bergmann, C., Borry, P., . . . American Society of Human, G. (2015). Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening. European journal of human genetics : EJHG, 23(11), 1438-1450. doi:10.1038/ejhg.2015.57
  43. Finning, K., Martin, P., Summers, J., Massey, E., Poole, G., & Daniels, G. (2008). Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. Bmj, 336(7648), 816-818. doi:10.1136/bmj.39518.463206.25
  44. Fung, K. F. K., & Eason, E. (2018). No. 133-Prevention of Rh Alloimmunization. J Obstet Gynaecol Can, 40(1), e1-e10. doi:10.1016/j.jogc.2017.11.007
  45. Gil, M. M., Akolekar, R., Quezada, M. S., Bregant, B., & Nicolaides, K. H. (2014). Analysis of cell-free DNA in maternal blood in screening for aneuploidies: meta-analysis. Fetal Diagn Ther, 35(3), 156-173. doi:10.1159/000358326
  46. Grant, A., & Mohide, P. (1982). Screening and diagnostic tests in antenatal care. Effectiveness and satisfaction in antenatal care, 22-59. Retrieved from https://books.google.com/books?hl=en&lr=&id=fVH-JYbe2isC&oi=fnd&pg=PA22&dq=screening+versus+diagnostic+tests&ots=WXVxt6ALwT&sig=DUy8K33sGYU72yPEjPHIyTT3ppA#v=onepage&q=screening%20versus%20diagnostic%20tests&f=false
  47. Gregg, A. R., Skotko, B. G., Benkendorf, J. L., Monaghan, K. G., Bajaj, K., Best, R. G., . . . Watson, M. S. (2016). Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med, 18(10), 1056-1065. doi:10.1038/gim.2016.97
  48. Grody, W. W., Thompson, B. H., Gregg, A. R., Bean, L. H., Monaghan, K. G., Schneider, A., & Lebo, R. V. (2013). ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med, 15(6), 482-483. doi:10.1038/gim.2013.47
  49. Gross, S. J., Pletcher, B. A., & Monaghan, K. G. (2008). Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med, 10(1), 54-56. doi:10.1097/GIM.0b013e31815f247c
  50. HRSA. (2017, October 2017). Women’s Preventive Services Guidelines. Retrieved from https://www.hrsa.gov/womens-guidelines-2016/index.html
  51. HRSA. (2019). Women’s Preventive Services Guidelines. Retrieved from https://www.hrsa.gov/womens-guidelines-2019
  52. ISPD. (2018). Joint Position Statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn, 38(1), 6-9. doi:10.1002/pd.5195
  53. Johnson, J. A., MacDonald, K., Clarke, G., & Skoll, A. (2017). No. 343-Routine Non-invasive Prenatal Prediction of Fetal RHD Genotype in Canada: The Time is Here. J Obstet Gynaecol Can, 39(5), 366-373. doi:10.1016/j.jogc.2016.12.006
  54. Kent, J., Farrell, A. M., & Soothill, P. (2014). Routine administration of Anti-D: the ethical case for offering pregnant women fetal RHD genotyping and a review of policy and practice. BMC Pregnancy Childbirth, 14, 87. doi:10.1186/1471-2393-14-87
  55. Krist, A. H., Davidson, K. W., Mangione, C. M., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2020). Screening for Unhealthy Drug Use: US Preventive Services Task Force Recommendation Statement. Jama, 323(22), 2301-2309. doi:10.1001/jama.2020.8020
  56. LabCorp. (2020). Inheritest. Retrieved from https://www.integratedgenetics.com/patients/pre-pregnancy/inheritest
  57. LeFevre, M. L., & USPSTF. (2014). Screening for Chlamydia and gonorrhea: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 161(12), 902-910. doi:10.7326/m14-1981
  58. Liang, D., Cram, D. S., Tan, H., Linpeng, S., Liu, Y., Sun, H., . . . Wu, L. (2019). Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes. Genetics in Medicine, 21(9), 1998-2006. doi:10.1038/s41436-019-0467-4
  59. Lockwood, C. J., & Magriples, U. (2020, 12/9/2020). Prenatal care: Initial assessment. UpToDate. Retrieved from https://www.uptodate.com/contents/prenatal-care-initial-assessment
  60. Mackie, F. L., Hemming, K., Allen, S., Morris, R. K., & Kilby, M. D. (2017). The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in aingleton pregnancies: a systematic review and bivariate meta-analysis. Bjog, 124(1), 32-46. doi:10.1111/1471-0528.14050
  61. Manfroi, S., Calisesi, C., Fagiani, P., Gabriele, A., Lodi, G., Nucci, S., . . . Randi, V. (2018). Prenatal non-invasive foetal RHD genotyping: diagnostic accuracy of a test as a guide for appropriate administration of antenatal anti-D immunoprophylaxis. Blood Transfus, 16(6), 514-524. doi:10.2450/2018.0270-17
  62. Martinez-Payo, C., Bada-Bosch, I., Martinez-Moya, M., & Perez-Medina, T. (2018). Clinical results after the implementation of cell-free fetal DNA detection in maternal plasma. J Obstet Gynaecol Res, 44(8), 1369-1376. doi:10.1111/jog.13672
  63. Miller, D. (2020, 7/9/2020). Use of chromosomal microarray in obstetrics. UpToDate. Retrieved from https://www.uptodate.com/contents/use-of-chromosomal-microarray-in-obstetrics
  64. Moise, K. (2020, 12/16/2020). Prevention of RhD alloimmunization in pregnancy. Retrieved from https://www.uptodate.com/contents/prevention-of-rhd-alloimmunization-in-pregnancy
  65. Moyer, V. A. (2014). Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 160(6), 414-420. doi:10.7326/m13-2905
  66. Moyer, V. A., & USPSTF. (2013a). Screening for hepatitis c virus infection in adults: U.s. preventive services task force recommendation statement. Ann Intern Med, 159(5), 349-357. doi:10.7326/0003-4819-159-5-201309030-00672
  67. Moyer, V. A., & USPSTF. (2013b). Screening for hiv: U.s. preventive services task force recommendation statement. Ann Intern Med, 159(1), 51-60. doi:10.7326/0003-4819-159-1-201307020-00645
  68. NICE. (2016). High-throughput non-invasive prenatal testing for fetal RHD genotype. Retrieved from https://www.nice.org.uk/guidance/dg25/chapter/1-Recommendations
  69. NICE. (2020). Antenatal care for uncomplicated pregnancies: screening. In: NICE.
  70. Owens, D. K., Davidson, K. W., Krist, A. H., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2019). Screening for HIV Infection: US Preventive Services Task Force Recommendation Statement. Jama, 321(23), 2326-2336. doi:10.1001/jama.2019.6587
  71. Owens, D. K., Davidson, K. W., Krist, A. H., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2020). Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement. Jama, 323(13), 1286-1292. doi:10.1001/jama.2020.2684
  72. Owens, D. K., Davidson, K. W., Krist, A. H., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2019). Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. Jama, 322(4), 349-354. doi:10.1001/jama.2019.9365
  73. Owens, D. K., Davidson, K. W., Krist, A. H., Barry, M. J., Cabana, M., Caughey, A. B., . . . Wong, J. B. (2019). Screening for Asymptomatic Bacteriuria in Adults: US Preventive Services Task Force Recommendation Statement. Jama, 322(12), 1188-1194. doi:10.1001/jama.2019.13069
  74. Persico, N., Boito, S., Ischia, B., Cordisco, A., De Robertis, V., Fabietti, I., . . . Rembouskos, G. J. P. D. V. (2016). Cell‐free DNA testing in the maternal blood in high‐risk pregnancies after first‐trimester combined screening. Prenatal Diagnosis, 36(3), 232-236.
  75. Pollock, L., Cohan, D., Pecci, C. C., & Mittal, P. (2019). ACOG Committee Opinion No. 752: Prenatal and Perinatal Human Immunodeficiency Virus Testing. Obstet Gynecol, 133(1), 187. doi:10.1097/aog.0000000000003048
  76. Prior, T. W. (2008). Carrier screening for spinal muscular atrophy. Genet Med, 10(11), 840-842. doi:10.1097/GIM.0b013e318188d069
  77. RCOG. (2014). The Management of Women with Red Cell Antibodies during Pregnancy. Retrieved from https://www.rcog.org.uk/globalassets/documents/guidelines/rbc_gtg65.pdf
  78. Rink, B., Biggio, J., Kamyar, M., & ACOG. (2017). Committee Opinion No. 724: Consumer Testing for Disease Risk. Obstet Gynecol, 130(5), e270-e273. doi:10.1097/aog.0000000000002401
  79. Rink, B., Romero, S., Biggio, J., Saller, D., Giardine, R., & ACOG. (2017). Committee Opinion No. 691: Carrier Screening for Genetic Conditions. Obstet Gynecol, 129(3), e41-e55. doi:10.1097/aog.0000000000001952
  80. Romero, S., Rink, B., Biggio, J., Saller, D., & ACOG. (2017). Committee Opinion No. 690: Carrier Screening in the Age of Genomic Medicine. Obstet Gynecol, 129(3), e35-e40. doi:10.1097/aog.0000000000001951
  81. Rose, N. C., Kaimal, A. J., Dugoff, L., Norton, M. E., Obstetricians, A. C. o., & Medicin, G. C. o. P. B. O. o. G. f. M.-F. (2020). Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstetrics & Gynecology, 136(4), e48-e69. doi:10.1097/aog.0000000000004084
  82. Runkel, B., Bein, G., Sieben, W., Sow, D., Polus, S., & Fleer, D. (2020). Targeted antenatal anti-D prophylaxis for RhD-negative pregnant women: a systematic review. BMC Pregnancy Childbirth, 20(1), 83. doi:10.1186/s12884-020-2742-4
  83. Sandler, S. G., Flegel, W. A., Westhoff, C. M., Denomme, G. A., Delaney, M., Keller, M. A., . . . Simon, C. D. (2015). It's time to phase in RHD genotyping for patients with a serologic weak D phenotype. College of American Pathologists Transfusion Medicine Resource Committee Work Group. Transfusion, 55(3), 680-689. doi:10.1111/trf.12941
  84. Schrag, S., Gorwitz, R., Fultz-Butts, K., & Schuchat, A. (2002). Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep, 51(Rr-11), 1-22. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm
  85. Sherman, S., Pletcher, B. A., & Driscoll, D. A. (2005). Fragile X syndrome: diagnostic and carrier testing. Genet Med, 7(8), 584-587. doi:10.109701.GIM.0000182468.22666.dd
  86. Siu, A. L. (2015). Screening for Iron Deficiency Anemia and Iron Supplementation in Pregnant Women to Improve Maternal Health and Birth Outcomes: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med, 163(7), 529-536. doi:10.7326/m15-1707
  87. Siu, A. L., & USPSTF. (2016). Screening for depression in adults: Us preventive services task force recommendation statement. Jama, 315(4), 380-387. doi:10.1001/jama.2015.18392
  88. Slutsker, J. S., Hennessy, R. R., & Schillinger, J. A. (2018). Factors Contributing to Congenital Syphilis Cases - New York City, 2010-2016. MMWR Morb Mortal Wkly Rep, 67(39), 1088-1093. doi:10.15585/mmwr.mm6739a3
  89. USPSTF. (2005). Screening for Rh(D) Incompatibility: Recommendation Statement. Am Fam Physician. Retrieved from https://www.aafp.org/afp/2005/0915/p1087.html
  90. USPSTF. (2006). Screening for elevated blood lead levels in children and pregnant women. Pediatrics, 118(6), 2514-2518. doi:10.1542/peds.2006-2352
  91. USPSTF. (2008a). Screening for asymptomatic bacteriuria in adults: U.s. preventive services task force reaffirmation recommendation statement. Ann Intern Med, 149(1), 43-47. doi:10.7326/0003-4819-149-1-200807010-00009
  92. USPSTF. (2008b). Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med, 148(3), 214-219.
  93. USPSTF. (2009). Screening for hepatitis B virus infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med, 150(12), 869-873, w154.
  94. USPSTF. (2016). Serologic screening for genital herpes infection: Us preventive services task force recommendation statement. Jama, 316(23), 2525-2530. doi:10.1001/jama.2016.16776
  95. USPSTF. (2018). Screening for syphilis infection in pregnant women: Us preventive services task force reaffirmation recommendation statement. Jama, 320(9), 911-917. doi:10.1001/jama.2018.11785
  96. USPSTF. (2019). Hepatitis B Virus Infection in Pregnant Women: Screening. Retrieved from https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/hepatitis-b-virus-infection-in-pregnant-women-screening?ds=1&s=hepatitis%20B
  97. VA, & DOD. (2018). VA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF PREGNANCY. Washington, D.C.: Department of Veterans Affairs Retrieved from https://www.healthquality.va.gov/guidelines/WH/up/VADoDPregnancyCPG4102018.pdf
  98. Vockley, J., Andersson, H. C., Antshel, K. M., Braverman, N. E., Burton, B. K., Frazier, D. M., . . . Berry, S. A. (2014). Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med, 16(2), 188-200. doi:10.1038/gim.2013.157
  99. Vora, N., Ralston, S., & ACOG. (2018). ACOG Technology Assessment in Obstetrics and Gynecology No. 14: Modern Genetics in Obstetrics and Gynecology. Obstet Gynecol, 132(3), e143-e168. doi:10.1097/aog.0000000000002831
  100. Watson, M. S., Cutting, G. R., Desnick, R. J., Driscoll, D. A., Klinger, K., Mennuti, M., . . . Grody, W. W. (2004). Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. Genet Med, 6(5), 387-391. doi:10.109701.Gim.0000139506.11694.7c
  101. WHO. (2016). WHO recommendations on antenatal care for a positive pregnancy experience: World Health Organization.
  102. Witkop, C., & ACOG. (2018). ACOG Committee Opinion No. 727: Cascade Testing: Testing Women for Known Hereditary Genetic Mutations Associated With Cancer. Obstet Gynecol, 131(1), e31-e34. doi:10.1097/aog.0000000000002457
  103. Yang, H., Llewellyn, A., Walker, R., Harden, M., Saramago, P., Griffin, S., & Simmonds, M. (2019). High-throughput, non-invasive prenatal testing for fetal rhesus D status in RhD-negative women: a systematic review and meta-analysis. BMC Med, 17(1), 37. doi:10.1186/s12916-019-1254-4
  104. Zhu, X., Chen, M., Wang, H., Guo, Y., Chau, M. H. K., Yan, H., . . . Choy, K. W. (2020). Clinical utility of expanded noninvasive prenatal screening and chromosomal microarray analysis in high risk pregnancies. Ultrasound Obstet Gynecol. doi:10.1002/uog.22021

Coding Section  

Codes Number Description
CPT 

0009M 

Fetal aneuploidy (trisomy 21, and 18) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy 
 

80081 

Obstetric panel (includes HIV testing) 
 

80055

Obstetric panel (must include CBC, HbSAg, Rubella antibody, RBC antibody screen, qualitative non-treponemal antibody syphilis test, ABO blood typing and Rh D typing)
 

81001 

Urinalysis, by dip stick or tablet reagent for bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrite, pH, protein, specific gravity, urobilinogen, any number of these constituents; automated, with microscopy 
 

81002 

Urinalysis, by dip stick or tablet reagent for bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrite, pH, protein, specific gravity, urobilinogen, any number of these constituents; non-automated, without microscopy 
 

81003

Urinalysis, automated, without microscopy

 

81007

Urinalysis, bacteriuria screen, except by culture or dipstick
 

81015 

Urinalysis; microscopic only 
 

81171 (effective 01/01/2019)

AFF2 (AF4/FMR2 family, member 2 [FMR2]) (eg, fragile X mental retardation 2 [FRAXE]) gene analysis; evaluation to detect abnormal (eg, expanded) alleles 
 

81172 (effective 01/01/2019) 

AFF2 (AF4/FMR2 family, member 2 [FMR2]) (eg, fragile X mental retardation 2 [FRAXE]) gene analysis; characterization of alleles (eg, expanded size and methylation status) 
 

81200

ASPA (aspartoacylase) (eg, Canavan disease) gene analysis, common variants (eg, E285A, Y231X)
 

81209

BLM (Bloom syndrome, RecQ helicase-like) (eg, Bloom syndrome) gene analysis, 2281del6ins7 variant
 

81220

CFTR (cystic fibrosis transmembrane conductance regulator) gene analysis; common variants (eg, ACMG/ACOG guidelines)
 

81221

CFTR (cystic fibrosis transmembrane conductance regulator) gene analysis; known familial variants
 

81241 

F5 (coagulation factor V) (eg, hereditary hypercoagulability) gene analysis, Leiden variant 
 

81242

FANCC (Fanconi anemia, complementation group C) (eg, Fanconi anemia, type C) gene analysis, common variant (eg, IVS4+4A>T)
 

81243

FMR1 (Fragile X mental retardation 1) gene analysis; evaluation to detect abnormal (eg, expanded) alleles

  81244 FMR1 (Fragile X mental retardation 1) gene analysis; characterization of alleles (eg, expanded size and methylation status)
 

81251

GBA (glucosidase, beta, acid) (eg, Gaucher disease) gene analysis, common variants (eg, N370S, 84GG, L444P, IVS2+1G>A);
  81252 GJB2 (gap junction protein beta 2, 26kDa, connexin 26) (eg, nonsyndromic hearing loss) gene analysis, full gene sequence
  81253 known familial variants
 

81254

GJB6 (gap junction protein, beta 6, 30kDa, connexin 30) (eg, nonsyndromic hearing loss) gene analysis, common variants (eg, 309kb  (del(GJB6-D13S1830)) and 232 kb (del(GJB6-D13S1854));
 

81255

HEXA (hexosaminidase A [alpha polypeptide]) (eg, Tay-Sachs disease) gene analysis, common variants (eg, 1278insTATC, 1421+1G>C, G269S)
 

81257

HBA1/HBA2 (alpha globin 1 and alpha globin 2) (eg, alpha thalassemia, Hb Bart hydrops fetalis syndrome, HbH disease), gene analysis, for common deletions or variant (eg, Southeast Asian, Thai, Filipino, Mediterranean, alpha3.7, alpha4.2, alpha20.5, and Constant Spring)
 

81260

IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) (eg, familial dysautonomia) gene analysis, common variants (eg, 2507+6T>C, R696P)
 

81290

MCOLN1 (mucolipin 1) (eg, Mucolipidosis, type IV) gene analysis, common variants (eg, IVS3-2A>G, del6.4kb)
 

81329 (effective 01/01/2019)

SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; dosage/deletion analysis (eg, carrier testing), includes SMN2 (survival of motor neuron 2, centromeric) analysis, if performed 
 

81330

SMPD1 (sphingomyelin phosphodiesterase 1, acid lysosomal) (eg, Niemann-Pick disease, Type A) gene analysis, common variants (eg, R496L, L302P, fsP330)
 

81336 (effective 01/01/2019) 

SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; full gene sequence 
 

81337 (effective 01/01/2019) 

SMN1 (survival of motor neuron 1, telomeric) (eg, spinal muscular atrophy) gene analysis; known familial sequence variant(s) 
  81400 Molecular pathology procedure, Level 1 (eg, identification of single germline variant [eg, SNP] by techniques such as restriction enzyme digestion or melt curve analysis)
 

81401

Molecular pathology procedure, Level 2 (eg, 2-10 SNPs, 1 methylated variant, or 1 somatic variant (typically using nonsequencing target variant analysis), or detection of a dynamic mutation disorder/triplet repeat)
 

81403

 

Molecular pathology procedure, Level 4 

 

Gene:

RHD (Rh blood group, D antigen) (eg, hemolytic disease of the fetus and newborn, Rh maternal/fetal compatibility), deletion analysis (eg, exons 4, 5 and 7, pseudogene), performed on cell free fetal DNA in maternal blood 

 

81404

Molecular pathology procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a dynamic mutation disorder/triplet repeat by Southern blot analysis)
 

81405

Molecular pathology procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 11-25 exons, regionally targeted cytogenomic array analysis)
 

81406 

Molecular pathology procedure, Level 7 (eg, analysis of 11-25 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 26-50 exons, cytogenomic array analysis for neoplasia) 
  81412  Ashkenazi Jewish associated disorders (eg, Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Tay-Sachs disease), genomic sequence analysis panel, must include sequencing of at least 9 genes, including ASPA, BLM, CFTR, FANCC, GBA, HEXA, IKBKAP, MCOLN1, and SMPD1 
  81420 Fetal chromosomal aneuploidy (eg, trisomy 21, monosomy X) genomic sequence analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis of chromosomes 13, 18, and 21
  81430 Hearing loss (eg, nonsyndromic hearing loss, Usher syndrome, Pendred syndrome); genomic sequence analysis panel, must include sequencing of at least 60 genes, including CDH23, CLRN1, GJB2, GPR98, MTRNR1, MYO7A, MYO15A, PCDH15, OTOF, SLC26A4, TMC1, TMPRSS3, USH1C, USH1G, USH2A, and WFS1 duplication/deletion analysis panel, must include copy number analyses for STRC and DFNB1 deletions in GJB2 and GJB6 genes
 

81431

Duplication/deletion analysis panel, must include copy number analyses for STRC and DFNB1 deletions in GJB2 and GJB6 genes
  81443 (effective 01/01/2019)  Genetic testing for severe inherited conditions (eg, cystic fibrosis, Ashkenazi Jewish-associated disorders [eg, Bloom syndrome, Canavan disease, Fanconi anemia type C, mucolipidosis type VI, Gaucher disease, Tay-Sachs disease], beta hemoglobinopathies, phenylketonuria, galactosemia), genomic sequence analysis panel, must include sequencing of at least 15 genes (eg, ACADM, ARSA, ASPA, ATP7B, BCKDHA, BCKDHB, BLM, CFTR, DHCR7, FANCC, G6PC, GAA, GALT, GBA, GBE1, HBB, HEXA, IKBKAP, MCOLN1, PAH) 
  81479  Unlisted molecular pathology procedure 
  81507 Fetal aneuploidy (trisomy 21, 18, and 13) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy
  82677 Estriol
  82731  Fetal fibronectin, cervicovaginal secretions, semi quantitative 
  82947 Glucose; quantitative, blood (except regent strip)
  82950  Glucose; post glucose dose (includes glucose) 
  82951  Glucose, tolerance test (GTT), 3 specimens (includes glucose) 
 

83020

Hemoglobin fractionation and quantitation; electrophoresis (eg, A2, S, C, and/or F)

 

83021 

Hemoglobin fractionation and quantitation; chromatography (eg, A2, S, C, and/or F) 
 

83036 

Hemoglobin, glycosylated (A1C) 
 

84443

Thyroid stimulating hormone (TSH)
 

84999 

Unlisted chemistry procedure 
 

85004 

Blood count; automated differential WBC count 
 

85007 

Blood smear, microscopic examination with manual differential WBC count 
 

85009 

Blood Count 
 

85014 

Hematocrit (Hct) 
 

85018 

Hemoglobin (Hgb) 
 

85025 

Complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count) and automated differential WBC count 
 

85027 

Complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count) 
 

85032 

Blood count; manual cell count (erythrocyte, leukocyte, or platelet) each 
 

85041 

Blood count; red blood cell (RBC), automated 
 

85048 

Blood count; leukocyte (WBC), automated 
 

86480 

Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon
 

86580 

Skin test; tuberculosis, intradermal
 

86592 

Syphilis test, non-treponemal antibody; qualitative (eg, VDRL, RPR, ART) 
 

86593 

Syphilis test, non-treponemal antibody; quantitative 
 

86631 

Antibody; Chlamydia 
 

86632 

Antibody; Chlamydia, IgM 
 

86701 

Antibody, HIV-1 
 

86702 

Antibody, HIV-2 
 

86703 

Antibody, HIV-1 and HIV-2, single result 
 

86762 

Rubella Antibody 
 

86787 

Antibody; varicella-zoster 
 

86780 

Antibody; Treponema pallidum 
 

86803 

Hepatitis C antibody 

 

86804 

Hepatitis C antibody; confirmatory test (eg, immunoblot) 
 

86850 

Antibody screen, RBC, each serum technique 
 

86900

Blood typing; ABO
 

86901

Blood typing; Rh (D)
 

87077 

Culture, bacterial; aerobic isolate, additional methods required for definitive identification, each isolate 
 

87081

Culture, presumptive, pathogenic organisms, screening only (use for Group B strep)
 

87086

Routine Urine Culture
 

87088 

Culture, bacterial, with isolation and presumptive identification of each isolate, urine 
 

87110 

Culture, chlamydia, any source 
 

87270 

Infectious agent antigen detection by immunofluorescent technique; Chlamydia trachomatis 
 

87320 

Infectious agent antigen detection by immunoassay technique, (eg, enzyme immunoassay [EIA], enzyme-linked immunosorbent assay [ELISA], fluorescence immunoassay [FIA], immunochemiluminometric assay [IMCA]) qualitative or semiquantitative; hepatitis B surface antigen (HBsAg)
 

87340 

Infectious agent antigen detection by immunoassay technique, (eg, enzyme immunoassay [EIA], enzyme-linked immunosorbent assay [ELISA], fluorescence immunoassay [FIA], immunochemiluminometric assay [IMCA]) qualitative or semiquantitative; hepatitis B surface antigen (HBsAg) 
 

87341 

Infectious agent antigen detection by immunoassay technique, (eg, enzyme immunoassay [EIA], enzyme-linked immunosorbent assay [ELISA], fluorescence immunoassay [FIA], immunochemiluminometric assay [IMCA]) qualitative or semiquantitative; hepatitis B surface antigen (HBsAg) neutralization 
 

87490

Chlamydia trachomatis, direct probe technique
 

87491

Chlamydia trachomatis, amplified probe technique
 

87590 

Neisseria gonorrhea, direct probe technique 
 

87591 

Neisseria gonorrhea, amplified probe technique 
 

87592 

Neisseria gonorrhea, quantification 
 

87653 

Infectious agent detection by nucleic acid (DNA or RNA); Streptococcus, group B, amplified probe technique 
 

87800 

Infectious agent detection by nucleic acid (DNA or RNA), multiple organisms; direct probe(s) technique 
 

87802 

Infectious agent antigen detection by immunoassay with direct optical (ie, visual) observation; Streptococcus, group B 
 

87810 

Chlamydia trachomatis 
 

87850 

Neisseria gonorrhea 
HCPCS    G0306 

Complete CBC, automated (HgB, HCT, RBC, WBC, without platelet count) and automated WBC differential count 

 

G0307 

Complete (CBC), automated (HgB, HCT, RBC, WBC; without platelet count) 
 

G0432 

Infectious agent antibody detection by enzyme immunoassay (EIA) technique, HIV-1 and/or HIV-2, screening 
 

G0433 

Infectious agent antibody detection by enzyme-linked immunosorbent assay (ELISA) technique, HIV-1 and/or HIV-2, screening 
 

G0435 

Infectious agent antigen detection by rapid antibody test of oral mucosa transudate, HIV-1 or HIV-2, screening 
 

G0472 

Hepatitis C antibody screening, for individual at high risk and other covered indication(s) 
 

S3844 

DNA analysis of the connexin 26 gene (GJB2) for susceptibility to congenital, profound deafness 
 

S3845 

Genetic testing for alpha-thalassemia 
 

S3846 

Genetic testing for hemoglobin e beta-thalassemia 
 

S3849 

Genetic testing for niemann-pick disease 
 

S3850 

Genetic testing for sickle cell anemia 
 

S3652 

Saliva test, hormone level; to assess preterm labor risk 
ICD-10-CM            Z34.01, Z34.02, Z34.03, Z34.80, Z34.81, Z34.82, Z34.83, Z34.90, Z34.91, Z34.92, Z34.93, O09.00, O09.01, O09.02, O09.03, O09.10, O09.11, O09.12, O09.13,O09.211, O09.212, O09.213, O09.219, O09.291, O09.292, O09.293, O09.299,O09.30, O09.31, O09.32, O09.33, O09.40, O09.41, O09.42, O09.43, O09.511, O09.512, O09.513, O09.519, O09.521, O09.522, O09.523, 09.529,O09.611, O09.612, O09.613, O09.619, O09.621, O09.622, O09.623, O09.629,O09.70, O09.71, O09.72, O09.73, O09.811, O09.812, O09.813, O09.819,O09.821, O09.822, O09.823, O09.829, O09.891, O09.892, O09.893, O09.899, O09.90, O09.91, O09.92, O09.93 

Pregnancy

 
  Z11.7 (EFFECTIVE 10/01/19) Encounter for testing for latent tuberculosis infection 
  Z15.01 - Z15.04, Z15.09, Z15.81, Z15.89  Genetic susceptibility
  Z14.01, Z14.02, Z14.1, Z14.8  Genetic carrier status 
  Z13.71, Z13.79, Z13.89  Genetic screening 
  Z31.430, Z31.440, Z31.448  Genetic testing 
  Z87.798, Z83.2, Z81.0, Z84.81, Z78.2  Family history 
  Z01.83  Encounter for bloodtyping (Rh typing) 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2015 Forward     

04/13/2021 

Annual review, updating coverage criteria related to group b strep from 35-37 weeks. to 36-37 weeks.Also updating to add criteria related to thalassemia. Updating description,coding, rationale and references. 

9/30/2020 

Interim review, updating policy language for clarity and to meet CDC guidelines. Also updating rationale and references. 

04/13/2020 

Annual review, updating policy for clarity and specificity. Adding notes to provide specific testing guidelines. Updating coding. 

09/24/2019 

Updated Coding. No other changes made. 

07/15/2019 

Correcting next annual review date. No other changes made. 

04/02/2019 

Annual review, adding statement: "Next generation sequencing (NGS) panel testing of either Ashkenazi Jewish-related disorders panel or panethnic carriers screening panel of 15 tests, as long as a single appropriate AMA genetic sequencing procedure test code is submitted." No other changes to policy intent. Updating coding. 

12/18/2018 

Updating with 2019 codes.  

07/26/2018 

Annual review, updating coding and expanding medical policy to provide coverage for Fetal RHD genotyping using maternal plasma. This was previously regarded as investigational. 

03/19/2018 

Update CPT codes with 86480 and 86481. No other changes. No change to policy intent. 

03/08/2018 

 Interim review, rewriting policy for clarity. Expanding verbiage related to blood typing and Rh antibody testing.

12/7/2017 

Updating policy with 2018 coding. No other changes. 

09/13/2017 

Interim review, removing criteria related to SMA screening requiring a family history. SMA screening is now considered medically necessary for all pregnant women and those seeking pre-conception care. No other changes made. 

08/14/2017 

Corrected formatting issues. No other changes made. 

08/03/2017 

Annual review, including language regarding thyroid testing and Zika testing, which is also addressed in other policies. No other changes made. 

04/25/2017 

Updated category to Laboratory. No other changes 

01/03/2017 

Annual review, no change to policy intent. Updated with 2017 CPT Codes. 

05/23/2016

Interim review, adding CPT 80081.

12/21/2015

NEW POLICY


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