Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection — 15 Jurisdictions, 2013–2017

Jennita Reefhuis, PhD; Lauren F. FitzHarris, MPH; Kristen Mahle Gray, MPH; Steven Nesheim, MD; Sarah C. Tinker, PhD; Jennifer Isenburg, MSPH; Benjamin T. Laffoon; Joseph Lowry, MPH; Karalee Poschman, MPH; Janet D. Cragan, MD; Fay K. Stephens, MPH; Jane E. Fornoff, DPhil; Cheryl A. Ward, MA; Tri Tran, MD; Ashley E. Hoover, MPH; Eirini Nestoridi, MD; Laura Kersanske, MPH; Monika Piccardi, MS; Morgan Boyer, MSPH; Mary M. Knapp, MSN; Abdel R. Ibrahim, PhD; Marilyn L. Browne, PhD; Bridget J. Anderson, PhD; Dipal Shah, MPH; Nina E. Forestieri, MPH; Jason Maxwell; Kimberlea W. Hauser, MBA; Godwin U. Obiri, DrPH; Rachel Blumenfeld, MPH; Dana Higgins, MPH; Carla P. Espinet, MPH; Bernardita López, MS; Katherine Zielke, MPH; Latoya P. Jackson, MPH; Charles Shumate, DrPH; Kacey Russell, MPH; Margaret A. Lampe, MPH


Morbidity and Mortality Weekly Report. 2020;69(1):1-5. 

In This Article

Abstract and Introduction


In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens.[1] The World Health Organization* (WHO) and the U.S. Department of Health and Human Services (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS)[2] and birth defects[3] in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013–2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

In the United States, many aspects of adult HIV surveillance are standardized across all 50 states, the District of Columbia, and six territories, but surveillance for pregnancy outcomes among women with diagnosed HIV infection varies across jurisdictions.[2] A comprehensive national surveillance approach for birth defects does not exist. Not all jurisdictions have birth defects surveillance programs, and among those that do, there is variability in surveillance methods and in the program's authority to ascertain cases that end in a stillbirth or termination. Active birth defects surveillance programs send abstractors to hospitals and other data sources to identify pregnancies affected by birth defects; passive birth defects surveillance programs receive notifications from hospitals and health care practitioners about pregnancies affected by birth defects, and some passive surveillance programs use a hybrid method where notifications lead to abstractions for verifying reported cases.[4]

CDC contacted the 20 jurisdictions with the highest numbers of women of reproductive age living with diagnosed HIV infection that also had birth defects surveillance programs with data available from 2013 to 2017. This period was chosen to ascertain birth defects during the 5 years after DTG was approved for use in the United States by the Food and Drug Administration in 2013. Certain jurisdictions were not able to obtain the required legal agreements between the different governmental departments responsible for each program to perform the data linkage or were otherwise not able to contribute to this effort.

After obtaining required agreements, the birth defects surveillance programs in 15 jurisdictions (including 11 states, Atlanta metropolitan area, New York City, Philadelphia, and Puerto Rico) identified pregnancies affected by NTDs (on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code range 740–742.0 and ICD-10-CM codes Q00.0–Q01.9, Q05.0–Q05.9, Q07.01, and Q07.03) for the period 2013 through 2017. U.S. jurisdictions have varying levels of authority to ascertain nonlive births. For this report, pregnancies include live births, stillbirths, and induced terminations. Identifying data for the mothers was matched to HIV surveillance records, using locally established linking algorithms, to ascertain whether any data related to the women with an NTD-affected pregnancy were also available in the HIV surveillance system.

Total population prevalence estimates for NTDs were calculated by dividing the number of pregnancies affected by NTDs by the total number of live births during 2013–2017 in the reporting jurisdictions. Denominators for prevalence calculations of HIV-exposed births were the number of live births that occurred during 2013–2017 among women with diagnosed HIV infection. To establish these denominators, most jurisdictions matched HIV surveillance data to birth certificates; one state used data from their comprehensive newborn HIV screening program. Variability was assessed using 95% confidence intervals (CIs) calculated with the Poisson methods. Nonoverlapping confidence intervals were used as a measure of statistical difference to acknowledge the imprecision of the estimate on the basis of small numbers. SAS (version 9.4; SAS Institute) was used to conduct all analyses.

Participating jurisdictions had surveillance information on 64,272 women aged 13–44 years with diagnosed HIV infection in 2015,** which represents approximately 70% of all women aged 13–44 years living with diagnosed HIV infection in the United States in 2015. Among 8,043,489 live births from these jurisdictions during 2013–2017, the prevalence of NTDs was 5.8 per 10,000 live births (Table). Data linkage between the two independent surveillance systems in each jurisdiction identified eight NTD cases, and there were 11,425 live births to women with diagnosed HIV infection during 2013–2017, for a prevalence of 7.0 per 10,000 HIV-exposed live births; this did not significantly differ from the general population prevalence, on the basis of the overlapping confidence intervals.

For the general population in these 15 jurisdictions, the NTD prevalence was higher when the analysis was limited to active surveillance programs (7.0 per 10,000 live births), which have more complete data than do passive programs (4.7 per 10,000 live births) (Table). Among women with diagnosed HIV infection, the NTD prevalence estimates based on active and passive surveillance had overlapping confidence intervals, suggesting no difference on the basis of case ascertainment. Surveillance systems that are not able to ascertain birth defects among nonlive births will usually underascertain NTDs because pregnancies affected by NTDs often lead to nonlive births. However, for these 15 jurisdictions, the NTD prevalence estimates for the general population and NTD prevalence estimates for pregnancies of women with diagnosed HIV infection were considered similar among programs that did or did not include nonlive births because the respective confidence intervals were wide and overlapped.