Description

Prenatal screening encompasses any testing done to determine the health status of the pregnant individual and/or fetus. Biochemical prenatal screening encompasses screening for infectious diseases and conditions that may complicate the pregnancy. Screening refers to testing of asymptomatic or healthy individuals to search for a condition that may affect the pregnancy or individual, whereas diagnostic testing is used to either confirm or refute true abnormalities in an individual (Grant & Mohide, 1982; Lockwood & Magriples, 2024).

Regulatory Status
The FDA has approved many tests for conditions that can be included in a prenatal screening, such as HSV, chlamydia, gonorrhea, syphilis, and diabetes. Additionally, many labs have developed specific tests that they must validate and perform in house. These laboratory-developed tests (LDTs) are regulated by the Centers for Medicare & Medicaid Services (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). LDTs are not approved or cleared by the U.S. Food and Drug Administration; however, FDA clearance or approval is not currently required for clinical use.

Policy 

Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request. 

1.    The following routine prenatal screening is considered MEDICALLY NECESSARY for all pregnant individuals:
a.    Antigen/antibody combination assay screening for HIV infection.
b.    Screening for Chlamydia trachomatis infection.
c.    Screening for Neisseria gonorrhoeae infection.
d.    Triple panel screening (HBsAg, anti-HBs, total anti-HBc) for hepatitis B.
e.    Screening for syphilis.
f.    Antibody screening for hepatitis C.
g.    Screening for Type 2 diabetes at the first prenatal visit.
h.    Screening for gestational diabetes during gestational weeks 24 – 28 and at the first prenatal visit if risk factors are present.
i.    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 individuals at 24 to 28 weeks' gestation, unless the biological father is known to be Rh (D)-negative.
j.    Screening for anemia with a CBC or hemoglobin and hematocrit with mean corpuscular volume.
k.    Screening for Group B streptococcal disease (once per pregnancy; recommended during gestational weeks 36 to 37).
l.    Urinalysis and urine culture.
m.    Rubella antibody testing.
n.    Testing for varicella immunity.
o.    Screening for tuberculosis in pregnant individuals deemed to be at high risk for TB.
2. For pregnant individuals who are less than 25 years of age or who are at a continued high risk of infection (e.g., individual has: new or multiple sex partners, a history of sexually transmitted infections, past or current injection drug use), third trimester re-screening of Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and/or HIV infections is considered MEDICALLY NECESSARY
3.  For individuals who are pregnant with singleton or twin pregnancies and who are presenting in the ambulatory setting with signs or symptoms of preterm labor, a fetal fibronectin (FFN) assay is considered MEDICALLY NECESSARY.
4. For individuals with a normal pregnancy without complications, human chorionic gonadotropin (hCG) hormone testing 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 an individual’s illness.
5. As a technique of risk assessment for preterm labor or delivery, serial monitoring of salivary estriol levels is considered NOT MEDICALLY NECESSARY.

Table of Terminology

Rationale
Prenatal screening is a part of overall prenatal care to promote optimal care of both mother and baby and 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 et al., 2015).

Routine prenatal screening may include several laboratory tests, such as hematocrit or hemoglobin testing 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 and 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, 2024).

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, 2024). Alloimmunization is the immune response which occurs in the mother due to foreign antigens after exposure to genetically foreign cells, occurring almost exclusively in mothers with type O blood. However, while ABO blood type incompatibility is identified in almost 15% of pregnancies, HDFN is only identified in approximately 4% of pregnancies (Calhoun, 2024). 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, individuals 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, 2024). 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, 2024). 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, 2024).

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 Jr, 2024). Before the development of this anti-D immune globulin, it has been reported that 16% of pregnant RhD-negative individuals with two deliveries of RhD-positive ABO-compatible infants became alloimmunized. However, this rate falls to 1% – 2% with routine postpartum administration of a single dose of anti-D immune globulin. An additional administration in the third trimester of pregnancy further reduces the incidents of alloimmunization to 0.1% – 0.3% (Moise Jr, 2024). 

Fetal fibronectin (FFN) is a protein made during pregnancy that is found between the lining of the uterus and the amniotic sac, at the decidual-chorionic interface. FFN is often described as being the glue that holds the amniotic sac to the uterine lining (URMC, 2024). Disruption of the decidual-chorionic interface releases FFN into cervicovaginal secretions, allowing FFN to be used as a marker for predicting spontaneous preterm birth in individuals with singleton and twin gestations (Lockwood et al., 1991). A meta-analysis of 11 studies found that under 10% of pregnant people with low FFN (< 10 ng/mL) delivered before 34 weeks, while 37% – 67% of pregnant people with high FFN (> 200 ng/mL) delivered before 34 weeks (Blackwell et al., 2017). The negative predictive value of FFN in predicting preterm birth is 99.5% within seven days, 99.2% within 14 days, and 84.5% before 37 weeks (Peaceman et al., 1997). FFN is also useful in singleton and twin pregnancies, as multiple pregnancy is a risk factor for preterm birth. For singleton and multiple pregnancies, FFN has a negative predictive value of 100%, sensitivity of 100% for delivery within 10 days, but a positive predictive value of 10% and a specificity of 64% (Cornelissen et al., 2020).

Human chorionic gonadotropin (hCG) is a biomarker in the glycoprotein hormone family. Other hormones in this family include luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid stimulating hormone. Human chorionic gonadotropin in pregnancy serves as an important biomarker for the detection of pregnancy-related disorders and hCG is also measured in some prenatal tests for Down syndrome. Low levels of hCG are associated with pregnancy loss and preeclampsia, while high levels can be associated with Down syndrome pregnancies (Richard Alan Harvey, 2023). A qualitative hCG test may be used to screen for pregnancy and gives a simple positive or negative result. A quantitative hCG measurement is used to assess pregnancy viability and screen for disorders. Quantitative hCG tests measures the exact amount of hCG in blood; for example, during 10 – 12 weeks of gestation, hCG levels are expected to approximately double every 24 – 48 hours, such that abnormal measurement results for hCG may indicate issues with the pregnancy (AACC, 2023).

Clinical Utility and Validity
Education and counseling are a key factor in prenatal screening and diagnostic tests. Yesilcinar and Guvenc (2021) found that a proactive intervention approach decreased anxiety and decisional conflict in the pregnant individual and increased attitudes towards the tests, having a positive effect on the pregnant individual’s knowledge level and decision satisfaction. This allowed the individual to make more informed decisions, such as opting to have screening and diagnostic testing performed (Yesilcinar & Guvenc, 2021). 

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 two to three 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 et al., 2002). The CDC also reports from a multiyear study that screening for syphilis in all pregnant individuals at the first prenatal visit (and then rescreening in third trimester for individuals 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 happened when the mother did not receive proper prenatal care (≥ 45 days before delivery) (Slutsker et al., 2018).

American College of Obstetricians and Gynecologists (ACOG) 
The American College of Obstetricians and Gynecologists has several 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 [individuals] for vitamin D deficiency. For pregnant [individuals] 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” (ACOG, 2011). This was reaffirmed in 2024. 
• Lead Screening: Concerning lead screening, ACOG recommends “evaluating risk factors for exposure as part of a comprehensive health risk assessment and perform blood lead testing if a single risk factor is identified. Assessment of lead exposure should take place at the earliest contact with the pregnant patient” (ACOG, 2012). This position was reaffirmed in 2023.
• Depression and Anxiety: ACOG “recommends screening patients at least once during the perinatal period for depression and anxiety, and, if screening in pregnancy, it should be done again postpartum.” Further, ACOG “recommends a full assessment of physical, social, and psychological well-being within a comprehensive postpartum visit that occurs no later than 12 weeks after birth” (ACOG, 2024). 
• Listeria monocytogenes: Concerning testing for Listeria monocytogenes, “No testing, including blood and stool cultures, or treatment is indicated for an asymptomatic pregnant [individual] 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” (ACOG, 2014). If an exposed pregnant individual 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 (ACOG, 2014). This position was reaffirmed in 2023.
• HIV: Concerning HIV, ACOG recommends that all individuals 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 [individuals] 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 [individuals] 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 [individuals] 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 [individuals] 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” (ACOG, 2018). This position was reaffirmed in 2024.
  • For pregnant individuals 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 [individuals] 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” (ACOG, 2018). This opinion was reaffirmed in 2024.
• 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 individuals 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, 2017).
• Group B Streptococcal (GBS) Disease: “all pregnant [individuals] 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, 2020). This position was reaffirmed in 2022.
• Lab Tests: ACOG lists the following lab tests to be performed early in pregnancy: complete blood count (CBC), blood type and Rh factor, urinalysis, urine culture, rubella, hepatitis B, hepatitis C, HIV, sexually transmitted infection (STI) testing, and tuberculosis (ACOG, 2024). ACOG lists the following lab tests to be performed later in pregnancy: glucose screening test and Group B streptococcus (GBS) screening (ACOG, 2024).

United States Preventive Services Task Force (USPSTF) 
The United States Preventive Services Task Force (USPSTF) recommends the following testing for pregnant individuals:

• Screening for gestational diabetes in asymptomatic pregnant individuals at ≥24 weeks of gestation (Grade B) (USPSTF, 2021b). 
• Screening for hepatitis B virus (HBV) infection at the first prenatal visit (Grade A) (USPSTF, 2019d). 
• Screening for asymptomatic bacteriuria with urine culture is recommended in pregnant persons (Grade B) (USPSTF, 2019a). 
• Screening for HIV is recommended in all pregnant persons, including those in labor or whose HIV status is unknown at delivery (Grade A) (USPSTF, 2019e). 
• Rh (D) blood typing and antibody testing for all pregnant individuals during their first visit for pregnancy-related care (Grade A) (USPSTF, 2005).
• Repeated Rh (D) antibody testing for all unsensitized Rh (D)-negative individuals 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 individuals (Grade A) (USPSTF, 2018).

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

• The USPSTF recommends screening for chlamydia in all sexually active [individuals] 24 years or younger and in [individuals] 25 years or older who are at increased risk for infection (Grade B)(USPSTF, 2021a).
• The USPSTF recommends screening for gonorrhea in all sexually active [individuals] 24 years or younger and in [individuals] 25 years or older who are at increased risk for infection (Grade B) (USPSTF, 2021a).
• The USPSTF recommends that clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions (Grade B) (USPSTF, 2019b).

Screening for hepatitis C virus (HCV) infection is recommended in all adults aged 18 to 79 years (Grade B) (Graham & Trooskin, 2020). 

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 ages 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” (Krist et al., 2020). 

However, the USPSTF recommends against the following tests during pregnancy:

• Screening for bacterial vaginosis in pregnant individuals 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 (USPSTF, 2020). 
• Serological screening for herpes simplex virus (HSV) in asymptomatic pregnant individuals (USPSTF, 2023).
• Screening for elevated blood lead levels in asymptomatic pregnant individuals has been given an I recommendation as current evidence is insufficient to determine if this testing is beneficial or not (USPSTF, 2019c). 
• “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 [individuals] to prevent adverse maternal health and birth outcomes” (Siu, 2015).

American Diabetes Association (ADA) 

The American Diabetes Association in the 2023 Standards of Medical Care in Diabetes make the following recommendations (ADA, 2023):

• “Starting at puberty and continuing in all [individuals] with diabetes and reproductive potential, preconception counseling should be incorporated into routine diabetes care. [Grade] A 
• Preconception counseling should address the importance of achieving glucose levels as close to normal as is safely possible, ideally A1C < 6.5% (48 mmol/mol), to reduce the risk of congenital anomalies, preeclampsia, macrosomia, preterm birth, and other complications. [Grade] A
• Individuals with preexisting diabetes who are planning a pregnancy should ideally begin receiving care in preconception at a multidisciplinary clinic in including an endocrinologist, maternal-fetal medicine specialist, registered dietitian nutritionist, and diabetes care and education specialist, when available. [Grade] B
• In addition to focused attention on achieving glycemic targets, standard preconception care should be augmented with extra focus on nutrition, diabetes education, and screening for diabetes comorbidities and complications. [Grade] B
• Individuals with preexisting Type 1 or Type 2 diabetes who are planning pregnancy or who have become pregnant should be counseled on the risk of development and/or progression of diabetic retinopathy. Dilated eye examinations should occur ideally before pregnancy or in the first trimester, and then patients should be monitored every trimester and for 1 year postpartum as indicated by the degree of retinopathy and as recommended by the eye care provider. [Grade] B
• Screen individuals with a recent history of gestational diabetes mellitus at 4 – 12 weeks postpartum, using the 75-g oral glucose tolerance test and clinically appropriate nonpregnancy diagnostic criteria. [Grade] B
• Individuals with a history of gestational diabetes mellitus should have lifelong screening for the development of Type 2 diabetes or prediabetes every 1 – 3 years. [Grade] B
• Individuals with a history of gestational diabetes mellitus found to have prediabetes should receive intensive lifestyle interventions and/or metformin to prevent diabetes. [Grade] A
• Individuals with a history of gestational diabetes mellitus should seek preconception screening for diabetes and preconception care to identify and treat hyperglycemia and prevent congenital malformations. [Grade] E”

Centers for Disease Control and Prevention (CDC) 
The Centers for Disease Control and Prevention (CDC) recommends (CDC, 2024d):

“* Per USPSTF, sexually active [individuals] 25 years or older are at increased risk for chlamydial and gonococcal infections if they have a new partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI; practice inconsistent condom use when not in a mutually monogamous relationship; have a previous or coexisting STI; have a history of exchanging sex for money or drugs; or have a history of incarceration.

† Type-specific HSV-2 serologic assays for diagnosing HSV-2 are useful in the following scenarios: recurrent or atypical genital symptoms or lesions with a negative HSV PCR or culture result, clinical diagnosis of genital herpes without laboratory confirmation, and a patient’s partner has genital herpes. HSV-2 serologic screening among the general population is not recommended. Patients who are at higher risk for infection (e.g., those presenting for an STI evaluation, especially for persons with ≥ 10 lifetime sex partners, and persons with HIV infection) might need to be assessed for a history of genital herpes symptoms, followed by type-specific HSV serologic assays to diagnose genital herpes for those with genital symptoms” (CDC, 2024d).

• "Everyone who is pregnant should be tested for syphilis, HIV, hepatitis B, and hepatitis C starting early in pregnancy. Repeat testing may be needed" (CDC, 2024b).
• Pregnant people at risk should also be tested for chlamydia and gonorrhea starting early in pregnancy. Repeat testing may be needed in some cases” (CDC, 2024b).
• “A second test during the third trimester, preferably at < 36 weeks’ gestation, should be considered and is recommended for [individuals] who are at high risk for acquiring HIV infection, [individuals] who receive health care in jurisdictions with high rates of HIV, and [individuals] examined in clinical settings in which HIV incidence is ≥ 1 per 1,000 [individuals] screened per year” (CDC, 2021e).
• “Providers should use a laboratory-based antigen/antibody (Ag/Ab) combination assay as the first test for HIV, unless persons are unlikely to follow up with a provider to receive their HIV test results; in those cases screening with a rapid POC test can be useful” (CDC, 2021e).
• “Regardless of whether they have been previously tested or vaccinated, all pregnant [individuals] should be tested for HBsAg at the first prenatal visit and again at delivery if at high risk for HBV infection (see STI Detection Among Special Populations). Pregnant [individuals] at risk for HBV infection and without documentation of a complete hepatitis B vaccine series should receive hepatitis B vaccination” (CDC, 2021c).
• Recommendation for HBV screening in “All pregnant persons during each pregnancy, preferably in the first trimester, regardless of vaccination status or history of testing” (CDC, 2023).
• “Pregnant persons with a history of appropriately timed triple panel screening and without subsequent risk for exposure to HBV (i.e., no new HBV exposures since triple panel screening) only need HBsAg screening. Testing pregnant persons known to be chronically infected or immune enables documentation of the HBsAg test result during that pregnancy to ensure timely prophylaxis for exposed infants” (CDC, 2023).
• “Using the triple panel (HBsAg, anti-HBs, and total anti-HBc) is recommended for initial screening because it can help identify persons who have an active HBV infection and could be linked to care, have resolved infection and might be susceptible to reactivation (e.g., immunosuppressed persons), are susceptible and need vaccination, or are vaccinated. When someone receives triple panel screening, any future periodic testing can use tests as appropriate (e.g., only HBsAg and anti-HBc if the patient is unvaccinated)” (CDC, 2023).
• “[individuals] aged < 25 years and those at increased risk for chlamydia (i.e., those who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI) should be screened at the first prenatal visit and rescreened during the third trimester to prevent maternal postnatal complications and chlamydial infection in the infant” (CDC, 2021b).
• “Annual screening for N. gonorrhoeae infection is recommended for all sexually active [individuals] aged < 25 years and for older [individuals] at increased risk for infection (e.g., those aged ≥ 25 years who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI . . . [All individuals] who have been treated for gonorrhea should be retested 3 months after treatment regardless of whether they believe their sex partners were treated” (CDC, 2022).
• “CDC recommends hepatitis C screening ... all [individuals] during each pregnancy, except in settings where the prevalence of HCV infection is < 0.1%” (CDC, 2021d).
• Zika virus recommendations for asymptomatic pregnant patients:
  • “Lived in or traveled to the United States and its territories during pregnancy: Since no confirmed cases of Zika virus disease have been detected in the United States and its territories since 2018, routine Zika virus testing is not recommended.”
  • “Traveled to an area with an active CDC Zika Travel Health Notice during pregnancy: NAAT testing may be considered up to 12 weeks after travel.”
  • “Traveled to an area with current or past Zika virus transmission outside the US and its territories during pregnancy: Routine testing is not recommended. If the decision is made to test, NAAT testing can be done up to 12 weeks after travel” (CDC, 2024a).
• Zika virus recommendations for symptomatic pregnant patients:
  • “Lived in or traveled to an area with an active CDC Zika Travel Health Notice during pregnancy OR had sex during pregnancy with someone living in or with recent travel to an area with an active CDC Zika Travel Health Notice:
• Specimens should be collected as soon as possible after onset of symptoms up to 12 weeks after symptom onset.
• Perform dengue and Zika virus NAAT and IgM testing on a serum specimen and Zika virus NAAT on a urine specimen.
• If Zika NAAT is positive and the Zika IgM is negative, repeat NAAT test on newly extracted RNA from same specimen to rule out false-positive results.
• If both dengue and Zika virus NAATs are negative but either IgM antibody test is positive, confirmatory PRNTs should be performed against dengue, Zika, and other flaviviruses endemic to the region where exposure occurred.

• Lived in or traveled to an area with current or past Zika virus transmission during pregnancy:
  • Specimens should be collected as soon as possible after onset of symptoms up to 12 weeks after symptom onset
  • Perform dengue and Zika virus NAAT testing on a serum specimen and Zika virus NAAT on a urine specimen.
  • If Zika NAAT is positive, repeat test on newly extracted RNA from same specimen to rule out false-positive results.
  • Perform IgM testing for dengue only.
  • If dengue NAAT or IgM test is positive, this provides adequate evidence of dengue infection, and no further testing is indicated.
• Had sex during pregnancy with someone living in or with recent travel to an area with current or past Zika virus transmission:
  • Specimens should be collected as soon as possible after onset of symptoms up to 12 weeks after symptom onset.
  • Only Zika NAAT should be performed.
  • If Zika NAAT is positive, repeat test on newly extracted RNA from same specimen to rule out false-positive results” (CDC, 2024a).
• Zika virus recommendations for pregnant patients having a fetus with prenatal ultrasound findings consistent with congenital Zika virus infection:
  • “Lived in or traveled during pregnancy to an area with an active CDC Zika Travel Health Notice or current or past Zika virus transmission OR had sex during pregnancy with someone living in or with recent travel to an area with an active CDC Zika Travel Health Notice or current or past Zika virus transmission:
    • Zika virus NAAT and IgM testing should be performed on pregnant person's serum and NAAT on pregnant person's urine.
    • If the Zika virus NAATs are negative and the IgM is positive, confirmatory PRNTs should be performed against Zika and dengue.
    • If amniocentesis is being performed as part of clinical care, Zika virus NAAT testing of amniocentesis specimens should also be performed and results interpreted within the context of the limitations of amniotic fluid testing.
    • Testing of placental and fetal tissues may also be considered” (CDC, 2024a).
• “Evidence does not support routine screening for BV among asymptomatic pregnant [individuals] at high risk for preterm delivery (159). Symptomatic [individuals] should be evaluated and treated (see Bacterial Vaginosis). Evidence does not support routine screening for Trichomonas vaginalis among asymptomatic pregnant [individuals]. [Individuals] who report symptoms should be evaluated and treated (see Trichomoniasis). In addition, evidence does not support routine HSV-2 serologic screening among asymptomatic pregnant [individuals]. However, type-specific serologic tests might be useful for identifying pregnant [individuals] at risk for HSV-2 infection and for guiding counseling regarding the risk for acquiring genital herpes during pregnancy. Routine serial cultures for HSV are not indicated for [individuals] in the third trimester who have a history of recurrent genital herpes”(CDC, 2021a).
• “Prenatal screening for some infections (HIV, syphilis, hepatitis B virus, and hepatitis C virus) is recommended for all pregnant [individuals]. Screening for other infections (chlamydia, gonorrhea, and TB) is recommended for some [individuals] at risk for infection” (CDC, 2024c).

American College of Medical Genetics and Genomics (ACMG) 
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).

World Health Organization (WHO) 
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 HIV testing and counselling (PITC) for HIV should be considered a routine component of the package of care for pregnant [individuals] in all antenatal care settings. In low-prevalence settings, PITC can be considered for pregnant [individuals] 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 [individuals] as part of antenatal care” (WHO, 2016).

Department of Veterans Affairs/Department of Defense (VA/DoD) 

In the 4th edition of the VA/DoD Clinical Practice Guideline for the Management of Pregnancy (VA & DOD, 2023), they list the following lab tests as routine for all pregnancies in the first prenatal visit: HIV, CBC, ABO Rh blood typing, Antibody screen, gonorrhea, chlamydia, hepatitis C antibody, syphilis screen, hepatitis B surface antigen test, rubella IgG, urinalysis and culture, and varicella IgG (if status is unknown). The following tests are offered to all patients: hemoglobin electrophoresis, aneuploidy screening, cystic fibrosis carrier screening, spinal muscle atrophy carrier screening, maternal serum alpha fetoprotein (15 – 22 weeks). They also list the following among their recommendations (VA & DOD, 2023):

• “We recommend screening for use of tobacco and nicotine products, alcohol, cannabis, illicit drugs, and inappropriate use of prescription medication.” [Strong]
• “We recommend screening for depression periodically 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 recommend offering non-invasive prenatal testing as the prenatal screening test of choice for all patients with singleton pregnancies who choose aneuploidy screening.” [Weak]
• “We suggest non-invasive prenatal testing for patients with twin pregnancies who choose aneuploidy screening.” [Weak]
• “We recommend considering the use of fetal fibronectin testing as a part of the evaluation strategy in [individuals] 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 patients who have undergone bariatric surgery be evaluated for nutritional deficiencies and need for nutritional supplementation where indicated (e.g., vitamin B12, folate, iron, calcium).” [Weak]

Health Resources and Services Administration (HRSA) 
The HRSA recommends the following:

• “Screening pregnant individuals for gestational diabetes mellitus after 24 weeks of gestation (preferably between 24 and 28 weeks of gestation)
• Individuals with risk factors for diabetes mellitus be screened for preexisting diabetes before 24 weeks of gestation — ideally at the first prenatal visit.
• Screening for HIV is recommended for all pregnant [individuals] upon initiation of prenatal care with retesting during pregnancy based on risk factors. 
•  Rapid HIV testing is recommended for pregnant [individuals] who present in active labor with an undocumented HIV status” (HRSA, 2022).

References

1. AACC. (2023). Qualitative Serum Human Chorionic Gonadotropin. https://www.aacc.org/advocacy-and-outreach/optimal-testing-guide-to-lab-test-utilization/g-s/qualitative-serum-human-chorionic-gonadotropin 
2. ACOG. (2011). ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol, 118(1), 197-198. https://doi.org/10.1097/AOG.0b013e318227f06b 
3. ACOG. (2012). Committee opinion No. 533: lead screening during pregnancy and lactation. Obstet Gynecol, 120(2 Pt 1), 416-420. https://doi.org/10.1097/AOG.0b013e31826804e8 
4. ACOG. (2014). Committee Opinion No. 614: Management of pregnant women with presumptive exposure to Listeria monocytogenes. Obstet Gynecol, 124(6), 1241-1244. https://doi.org/10.1097/01.AOG.0000457501.73326.6c 
5. ACOG. (2017). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. https://journals.lww.com/greenjournal/fulltext/2017/08000/Practice_Bulletin_No__181__Prevention_of_Rh_D.54.aspx 
6. ACOG. (2018). ACOG Committee Opinion No. 752: Prenatal and Perinatal Human Immunodeficiency Virus Testing. Obstet Gynecol, 133(1), 187. https://doi.org/10.1097/aog.0000000000003048 
7. ACOG. (2020). Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, NuFmber 797. Obstet Gynecol, 135(2), e51-e72. https://doi.org/10.1097/aog.0000000000003668 
8. ACOG. (2024, 07/2021). Routine Tests During Pregnancy. ACOG. https://www.acog.org/Patients/FAQs/Routine-Tests-During-Pregnancy?
9. ADA. (2023). 15`. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2023. https://diabetesjournals.org/care/article/46/Supplement_1/S254/148052/15-Management-of-Diabetes-in-Pregnancy-Standards 
10. Blackwell, S. C., Sullivan, E. M., Petrilla, A. A., Shen, X., Troeger, K. A., & Byrne, J. D. (2017). Utilization of fetal fibronectin testing and pregnancy outcomes among women with symptoms of preterm labor. Clinicoecon Outcomes Res, 9, 585-594. https://doi.org/10.2147/ceor.S141061 
11. Calhoun, D. (2024, July 15). Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. Retrieved 2/1/2021 from https://www.uptodate.com/contents/postnatal-diagnosis-and-management-of-hemolytic-disease-of-the-fetus-and-newborn?topicRef=6773&source=see_link
12. CDC. (2021a). Pregnant Women https://www.cdc.gov/std/treatment-guidelines/pregnant.htm 
13. CDC. (2021b, July 22, 2021). STI Treatment Guidelines, 2021- Chlamydial Infection. https://www.cdc.gov/std/treatment-guidelines/chlamydia.htm
14. CDC. (2021c, July 22, 2021). STI Treatment Guidelines, 2021- Hepatitis B Virus (HBV) Infection. https://www.cdc.gov/std/treatment-guidelines/hbv.htm
15. CDC. (2021d, July 22, 2021). STI Treatment Guidelines, 2021- Hepatitis C Virus (HCV) Infection. https://www.cdc.gov/std/treatment-guidelines/hcv.htm
16. CDC. (2021e). STI Treatment Guidelines, 2021- HIV Infection: Detection, Counseling, and Referral. https://www.cdc.gov/std/treatment-guidelines/hiv.htm
17. CDC. (2022, 9/21/2022). STI Treatment Guidelines, 2021- Gonococcal Infections Among Adolescents and Adults. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm
18. CDC. (2023). Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations — United States, 2023. https://www.cdc.gov/mmwr/volumes/72/rr/rr7201a1.htm 
19. CDC. (2024a). Clinical Testing and Diagnosis for Zika Virus Disease. https://www.cdc.gov/zika/hcp/diagnosis-testing/ 
20. CDC. (2024b). Getting Tested for STIs. https://www.cdc.gov/sti/testing/index.html 
21. CDC. (2024c). HIV, Viral Hepatitis, STD & Tuberculosis Prevention in Pregnancy. https://www.cdc.gov/pregnancy-hiv-std-tb-hepatitis/about/index.html 
22. CDC. (2024d). Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. https://www.cdc.gov/std/treatment-guidelines/screening-recommendations.htm 
23. Cornelissen, L. G. H., van Oostrum, N. H. M., van der Woude, D. A. A., Rolf, C., Porath, M. M., Oei, S. G., & van Laar, J. O. E. H. (2020). The diagnostic value of fetal fibronectin testing in clinical practice. Journal of Obstetrics and Gynaecology Research, 46(3), 405-412. https://doi.org/10.1111/jog.14201 
24. de Jong, A., Maya, I., & van Lith, J. M. (2015). Prenatal screening: current practice, new developments, ethical challenges. Bioethics, 29(1), 1-8. https://doi.org/10.1111/bioe.12123 
25. Graham, C. S., & Trooskin, S. (2020). Universal Screening for Hepatitis C Virus Infection: A Step Toward Elimination. Jama, 323(10), 936-937. https://doi.org/10.1001/jama.2019.22313 
26. Grant, A., & Mohide, P. (1982). Screening and diagnostic tests in antenatal care. Effectiveness and satisfaction in antenatal care, 22-59. https://books.google.com/books?hl=en&lr=&id=fVH-JYbe2isC&oi=fnd&pg=PA22&dq#v=onepage&q&f=false 
27. HRSA. (2022, January 2022). Women’s Preventive Services Guidelines. U.S. Department of Health and Human Services. Retrieved 11/14/2018 from https://www.hrsa.gov/womens-guidelines-2016/index.html
28. Krist, A. H., Davidson, K. W., Mangione, C. M., Barry, M. J., Cabana, M., Caughey, A. B., Curry, S. J., Donahue, K., Doubeni, C. A., Epling, J. W., Jr., Kubik, M., Ogedegbe, G., Pbert, L., Silverstein, M., Simon, M. A., Tseng, C. W., & Wong, J. B. (2020). Screening for Unhealthy Drug Use: US Preventive Services Task Force Recommendation Statement. Jama, 323(22), 2301-2309. https://doi.org/10.1001/jama.2020.8020 
29. Lockwood, C. J., & Magriples, U. (2024). Prenatal care: Initial assessment. Wolters Kluwer. Retrieved 3/11/2024 from https://www.uptodate.com/contents/prenatal-care-initial-assessment
30. Lockwood, C. J., Senyei, A. E., Dische, M. R., Casal, D., Shah, K. D., Thung, S. N., Jones, L., Deligdisch, L., & Garite, T. J. (1991). Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med, 325(10), 669-674. https://doi.org/10.1056/nejm199109053251001 
31. Moise Jr, K. J. (2024, 3/07/2024). Prevention of RhD alloimmunization in pregnancy. https://www.uptodate.com/contents/prevention-of-rhd-alloimmunization-in-pregnancy
32. Peaceman, A. M., Andrews, W. W., Thorp, J. M., Cliver, S. P., Lukes, A., Iams, J. D., Coultrip, L., Eriksen, N., Holbrook, R. H., Elliott, J., Ingardia, C., & Pietrantoni, M. (1997). Fetal fibronectin as a predictor of preterm birth in patients with symptoms: a multicenter trial. Am J Obstet Gynecol, 177(1), 13-18. https://doi.org/10.1016/s0002-9378(97)70431-9 
33. Richard Alan Harvey. (2023). Human chorionic gonadotropin: Biochemistry and measurement in pregnancy and disease. https://www.uptodate.com/contents/human-chorionic-gonadotropin-biochemistry-and-measurement-in-pregnancy-and-disease#H1642469196
34. 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. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm 
35. 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. https://doi.org/10.7326/m15-1707 
36. 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. https://doi.org/10.15585/mmwr.mm6739a3 
37. URMC. (2024). Fetal Fibronectin. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=fetal_fibronectin
38. USPSTF. (2005). Screening for Rh(D) Incompatibility: Recommendation Statement. Am Fam Physician. https://www.aafp.org/afp/2005/0915/p1087.html 
39. USPSTF. (2018). Screening for syphilis infection in pregnant women: Us preventive services task force reaffirmation recommendation statement. Jama, 320(9), 911-917. https://doi.org/10.1001/jama.2018.11785 
40. USPSTF. (2019a). Screening for Asymptomatic Bacteriuria in Adults: US Preventive Services Task Force Recommendation Statement. Jama, 322(12), 1188-1194. https://doi.org/10.1001/jama.2019.13069 
41. USPSTF. (2019b). Screening for depression. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/perinatal-depression-preventive-interventions
42. USPSTF. (2019c). Screening for Elevated Blood Lead Levels in Children and Pregnant Women: US Preventive Services Task Force Recommendation Statement. Jama, 321(15), 1502-1509. https://doi.org/10.1001/jama.2019.3326 
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45. USPSTF. (2020). Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement. Jama, 323(13), 1286-1292. https://doi.org/10.1001/jama.2020.2684 
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47. USPSTF. (2021b). Screening for Gestational Diabetes: US Preventive Services Task Force Recommendation Statement. Jama, 326(6), 531-538. https://doi.org/10.1001/jama.2021.11922 
48. USPSTF. (2023). Genital Herpes Infection: Serologic Screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/genital-herpes-serologic-screening
49. VA, & DOD. (2023). 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/VA-DoD-CPG-Pregnancy-Full-CPG_508.pdf
50. Vockley, J., Andersson, H. C., Antshel, K. M., Braverman, N. E., Burton, B. K., Frazier, D. M., Mitchell, J., Smith, W. E., Thompson, B. H., & Berry, S. A. (2014). Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med, 16(2), 188-200. https://doi.org/10.1038/gim.2013.157 
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52. Yesilcinar, I., & Guvenc, G. (2021). Counselling and education for prenatal screening and diagnostic tests for pregnant women: Randomized controlled trial. Int J Nurs Pract, 27(5), e13000. https://doi.org/10.1111/ijn.13000

Coding Section

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 Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

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

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