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Prenatal Screening (Nongenetic) | |
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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, 1982; Lockwood, 2024).
For guidance on thyroid screening in pregnant individuals, please see 2024026-Thyroid Disease Testing.
For guidance on screening for Zika virus infection in pregnant individuals, please see 2024-Testing for Vector-Borne Infections.
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 and Medicaid (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.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
This policy applies to health plans that utilize a routine laboratory management vendor, which include Arkansas Blue Cross and Blue Shield, Federal Employee Health Benefit Plan and Postal Service Health Benefit Plan, Health Advantage, and Octave Blue Cross and Blue Shield fully insured plans, including the Metallic and ARHOME plans and Complete/Complete Plus plans. Additionally, this policy will apply to the Farm Bureau and Level Funded plans.
Effective February 1, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Nongenetic prenatal screening meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following tests for all pregnant individuals:
For pregnant individuals in their third trimester, re-screening of Chlamydia trachomatis, Neisseria gonorrhea, syphilis, and/or HIV infections meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when any of the following high-risk criteria are met:
For pregnant individuals, fetal fibronectin (FFN) assays meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when all of the following criteria are met:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Nongenetic prenatal screening for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes including the following tests:
For members with contracts without primary coverage criteria, nongenetic prenatal screening for any indication or circumstance not described above, including the following tests, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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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, 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, 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, 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, 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, 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, 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. hCG in pregnancy serves as an important biomarker for the detection of pregnancy-related disorders and Human chorionic gonadotropin 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 (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, 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, 2002). The CDC also reports from a multi-year 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, 2018).
Guidelines and Recommendations
American College of Obstetricians and Gynecologists (ACOG)
ACOG has several practice guidelines related to prenatal care as well as both pre-conception and prenatal testing. ACOG recommendations and guidelines include the following:
United States Preventive Services Task Force (USPSTF)
The United States Preventive Services Task Force (USPSTF) recommends the following testing for pregnant individuals:
Additional recommendations from the USPSTF that may be relevant during pregnancy include:
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. 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, 2020).
However, the USPSTF recommends against the following tests during pregnancy:
American Diabetes Association (ADA)
The American Diabetes Association in the 2023 Standards of Medical Care in Diabetes make the following recommendations (ADA, 2023):
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).
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, 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):
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):
Health Resources & Services Administration (HRSA)
The HRSA recommends the following:
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CPT/HCPCS: | |
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References: |
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 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 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 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. 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. 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. ACOG(2020) Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797. Obstet Gynecol, 135(2), e51-e72. https://doi.org/10.1097/aog.0000000000003668. ACOG(2024) Routine Tests During Pregnancy. ACOG. https://www.acog.org/Patients/FAQs/Routine-Tests-During-Pregnancy? ADA(2023) Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes. https://diabetesjournals.org/care/article/46/Supplement_1/S254/148052/15-Management-of-Diabetes-in-Pregnancy-Standards. Blackwell SC, Sullivan EM, Petrilla AA, Shen X, Troeger KA, Byrne JD.(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 Calhoun, D.(2024) Postnatal diagnosis and management of hemolytic disease of the fetus and newborn. https://www.uptodate.com/contents/postnatal-diagnosis-and-management-of-hemolytic-disease-of-the-fetus-and-newborn?topicRef=6773&source=see_link CDC(2021) Pregnant Women. https://www.cdc.gov/std/treatment-guidelines/pregnant.htm CDC(2021) STI Treatment Guidelines, Chlamydial Infection. https://www.cdc.gov/std/treatment-guidelines/chlamydia.htm CDC(2021) STI Treatment Guidelines. Hepatitis B Virus (HBV) Infection. https://www.cdc.gov/std/treatment-guidelines/hbv.htm CDC(2021) STI Treatment Guidelines. Hepatitis C Virus (HCV) Infection. https://www.cdc.gov/std/treatment-guidelines/hcv.htm CDC(2021) STI Treatment Guidelines. HIV Infection: Detection, Counseling, and Referral. https://www.cdc.gov/std/treatment-guidelines/hiv.htm CDC(2022) STI Treatment Guidelines. Gonococcal Infections Among Adolescents and Adults. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm CDC(2023) Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations United States. https://www.cdc.gov/mmwr/volumes/72/rr/rr7201a1.htm. CDC(2024) Clinical Testing and Diagnosis for Zika Virus Disease. https://www.cdc.gov/zika/hcp/diagnosis-testing/ CDC(2024) Getting Tested for STIs. https://www.cdc.gov/sti/testing/index.html. CDC(2024) HIV Viral Hepatitis, STD and Tuberculosis Prevention in Pregnancy. https://www.cdc.gov/pregnancy-hiv-std-tb-hepatitis/about/index.html. CDC(2024) Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources. https://www.cdc.gov/std/treatment-guidelines/screening-recommendations.htm Cornelissen LGH, van Oostrum NHM, van der Woude DAA, et al.(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 de Jong A, Maya I, van Lith JM.(2015) Prenatal screening: current practice, new developments, ethical challenges. Bioethics, 29(1), 1-8. https://doi.org/10.1111/bioe.12123 Graham, CS, 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 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. Harvey, RA.(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 HRSA(2022) Women’s Preventive Services Guidelines. U.S. Department of Health and Human Services. https://www.hrsa.gov/womens-guidelines-2016/index.html Krist AH, Davidson KW, Mangione CM, et al.(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 Lockwood CJ, Magriples U.(2024) Prenatal care: Initial assessment. Wolters Kluwer. https://www.uptodate.com/contents/prenatal-care-initial-assessment Lockwood CJ, Senyei AE, Dische MR, et al.(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 Moise Jr, KJ.(2024) Prevention of RhD alloimmunization in pregnancy. https://www.uptodate.com/contents/prevention-of-rhd-alloimmunization-in-pregnancy Peaceman AM, Andrews WW, Thorp JM, et al.(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 Schrag S, Gorwitz R, FultzButts K, Schuchat A.(2002) Prevention of perinatal group B streptococcal disease. MMWR Recomm Rep, 51(Rr-11), 1-22. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5111a1.htm. 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 Slutsker JS, Hennessy RR, Schillinger JA.(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 URMC(2024) Fetal Fibronectin. https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=fetal_fibronectin USPSTF(2005) Screening for Rh(D) Incompatibility: Recommendation Statement. Am Fam Physician. https://www.aafp.org/afp/2005/0915/p1087.html 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 USPSTF(2019) 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 USPSTF(2019) Screening for Depression. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/perinatal-depression-preventive-interventions USPSTF(2019) Screening for Elevated Blood Lead Levels in Children and Pregnant Women: USPSTF statement Jama, 321(15), 1502-1509. https://doi.org/10.1001/jama.2019.3326 USPSTF(2019) Screening for Hepatitis B Virus Infection in Pregnant Women: USPSTF Reaffirmation Recommendation Statement. Jama, 322(4), 349-354. https://doi.org/10.1001/jama.2019.9365 USPSTF(2019) Screening for HIV Infection: USPSTF Recommendation Statement. Jama, 321(23), 2326-2336. https://doi.org/10.1001/jama.2019.6587 USPSTF(2020) Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: USPSTF Recommendation Statement. Jama, 323(13), 1286-1292. https://doi.org/10.1001/jama.2020.2684. USPSTF(2021) Screening for Chlamydia and gonorrhea: USPSTF Recommendation Statement. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/chlamydia-and-gonorrhea-screening USPSTF(2021) Screening for Gestational Diabetes: USPSTF Recommendation Statement. Jama, 326(6), 531-538. https://doi.org/10.1001/jama.2021.11922 USPSTF(2023) Genital Herpes Infection: Serologic Screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/genital-herpes-serologic-screening 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 Vockley J, Andersson HC, Antshel KM, et al.(2014) Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med, 16(2), 188-200. https://doi.org/10.1038/gim.2013.157 WHO(2016) WHO recommendations on antenatal care for a positive pregnancy experience. World Health Organization. https://www.who.int/nutrition/publications/guidelines/antenatalcare-pregnancy-positive-experience/en/ 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 |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association. |