Maternal Antiretroviral Use During Pregnancy and Infant Congenital Anomalies: The NISDI Perinatal Study

Abstract

Background We evaluated the association between maternal antiretrovirals (ARVs) during pregnancy and infant congenital anomalies (CAs), utilizing data from the NISDI Perinatal Study. Methods The study population consisted of first singleton pregnancies on study, ≥ 20 weeks gestation, among women enrolled in NISDI from Argentina and Brazil who delivered between September 2002 and October 2007. CAs were defined as any major structural or chromosomal abnormality, or a cluster of two or more minor abnormalities, according to the conventions of the Antiretroviral Pregnancy Registry. CAs were identified from fetal ultrasound, study visit, and death reports. The conventions of the Antiretroviral Pregnancy Registry were used. Prevalence rates [number of CAs per 100 live births (LBs)] were calculated for specific ARVs, classes of ARVs, and overall exposure to ARVs. Results Of 1229 women enrolled, 995 pregnancy outcomes (974 LBs) met the inclusion criteria. Of these, 60 infants (59 LBs and 1 stillbirth) had at least one CA. The overall prevalence of CAs (per 100 LBs) was 6.2 (95%CI = 4.6, 7.7). The prevalence of CAs after first trimester ARVs (6.2; 95%CI = 3.1, 9.3) was similar to that after second (6.8; 95%CI = 4.5, 9.0) or third trimester (4.3; 95%CI = 1.5, 7.2) exposure. The rate of CAs identified within seven days of delivery was 2.36 (95%CI: 1.4–3.3). Conclusions The prevalence of CAs following first trimester exposure to ARVs was similar to that following second or third trimester exposure. Continued surveillance for CAs among children exposed to ARVs during gestation is needed.

Congenital Anomalies and In Utero Antiretroviral Exposure in Human Immunodeficiency Virus–Exposed Uninfected Infants

“…27 We observed an increasing trend in the rate of CAs from prior to 2002 through 2010, followed by a slight decline through 2012. The higher rates of CAs may reflect a real increase consistent with temporal trends demonstrated in various population studies, 28–29 increased ascertainment given the study-required evaluation for anomalies, and longer follow-up than some studies.…”

Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001–2011

“…[5][6][7][8][9][17][18][19] The reasons underlying this variability may include the variable definition of birth defects, underreporting, the selective reporting of cases with defects, differential use of diagnostic techniques in the ascertainment of defects, and variable concomitant medication and substance exposure. 19 We also evaluated other potential predictors of birth defects, such as age, recent substance use, time since HIV diagnosis, CD4 cell count, body mass index, and coinfections.…”

“…In general, registry data have provided reassuring data, showing no increased risk of major birth defects compared with the general population. 5 Cohort studies have reported more variable rates, [6][7][8][9] and it is particularly important to collect information on the drugs more recently introduced into clinical use, because only the older drugs have accumulated sufficient exposure data to rule out a major (usually defined as two-fold) increase in birth defects. 5 In a general scenario, characterised by the need to obtain the durable suppression of HIV replication, and prevent or circumvent the emergence of resistant strains, innovative drugs are regularly introduced into clinical practice.…”

Sexual Ambiguity Associated with "in utero" Antiretroviral Exposure

“…Although so far was considered that administering the medication in the first trimester of pregnancy, when organogenesis occurs, could cause more side effects and malformations like hypospadias (21-23) than using them in the second or third trimester of pregnancy; this assumption was not confirmed (23)(24)(25).…”