Maternal Characteristics and Pregnancy Outcomes
Antiretroviral Pregnancy Registry. APR received 265 prospective reports of dolutegravir exposure during pregnancy; 86% of the participants were from the United States, 62% were black, and the median (range) age at conception was 29.0 (16–43) years (Table 1). A majority (77%) had CD4+ cell counts ≥200 cells/μL at the time of reporting. Initial exposure to dolutegravir occurred before or during the first trimester in 173 pregnancies (65%), with 130 exposures occurring preconception and after the first trimester in 92 pregnancies (35%).
Of these 265 pregnancies, 246 (92.8%) resulted in live births that included 9 twins for a total of 255 neonates; 6 (2.3%) pregnancies reported induced abortions, 11 (4.2%) reported spontaneous abortions, and 2 reported stillbirths (Table 2). Of the 231 singleton live births without defects, 24 (10.4%) were preterm (<37 weeks of gestation) and 24 (10.4%) had LBW of 1500 to <2500 g (Table 3). VLBW(<1500 g) was reported for 5 (2.2%) of the live births, and 18 births were both preterm and LBW/VLBW. The percentages of neonates born preterm were 10.9% and 9.5% for those with the earliest dolutegravir exposure in the first and second/third trimesters, respectively.
European Pregnancy and Paediatric HIV Cohort Collaboration. One hundred women, representing 101 pregnancies, were included in the analysis of EPPICC data (84 known pregnancy outcomes, 16 pregnancies ongoing, and 1 lost to follow-up); 67% (n = 62/93) were from sub-Saharan Africa, 46% were aged 25–34 years at conception, and 71% were black (Table 4). There were 51 (57%) women with CD4+ cell counts >350 cells/μL. One pregnancy was missing data regarding maternal dolutegravir initiation. Of those with data of dolutegravir initiation, the majority had earliest exposure to dolutegravir in the first trimester (58%; 37 of 58 pregnancies were conceived while the mothers were on dolutegravir), with 24% in the second trimester and 18% in the third trimester. Of the 84 pregnancies with outcomes data, 81 resulted in live births (resulting in 83 neonates), 1 resulted in spontaneous abortion, 1 in induced abortion, and 1 in stillbirth. Overall, 11 of the 80 singleton neonates (13.8%) were delivered preterm; 9 were born between 34 and 36 weeks of gestation, and 2 were born before 34 weeks of gestation (31 weeks, n = 1; 23 weeks, n = 1; Table 5).
The median birth weight was 3120 g (interquartile range, 2750–3470). A total of 16.9% (n = 2 missing birth weights) of neonates had LBW and 18.7% were SGA (Table 5). The proportions of neonates born preterm were 7.5%, 27.3%, and 11.8% for those whose earliest dolutegravir exposures started in the first, second, and third trimesters, respectively.
Antiretroviral Pregnancy Registry. In the APR cohort, among the 255 live-born neonates (including 9 sets of twins) with prenatal exposure to dolutegravir, birth defects occurred in 7 (2.7%) neonates. Of the 121 neonates first exposed to dolutegravir at conception, 3 (2.5%) were reported to have abnormalities: a male neonate with bilateral polydactyly postaxial to both hands who was also exposed to darunavir/ritonavir; a female neonate with an ectopic right kidney who was also exposed to emtricitabine, lamivudine, raltegravir, and tenofovir disoproxil fumarate at conception, darunavir/ritonavir during the second trimester, and zidovudine during the third trimester; and a male neonate with endocardial fibroelastosis who was also exposed to abacavir and lamivudine. Ages of the mothers (ethnicity) at delivery were 26 years (black), 26 years (black), and 19 years (Hispanic), respectively. Of the 40 neonates with first exposure after conception and during the first trimester, 2 (5.0%) were reported to have abnormalities: a male neonate with polydactyly on the ulnar side and syndactyly on the second, third, and fourth fingers who was also exposed to tenofovir disoproxil fumarate and emtricitabine and a male neonate with talipes equinovarus also exposed to abacavir, lamivudine, and raltegravir. Ages of the mothers (ethnicity) at delivery were 22 years (black) and 24 years (Asian), respectively. Of the 94 neonates with first exposure during the second or third trimester, 2 (2.1%) were reported to have abnormalities: a female neonate with hypoglossia–hypodactylia syndrome with dolutegravir exposure during the third trimester who was also exposed to darunavir/ritonavir, tenofovir disoproxil fumarate, and emtricitabine during the second trimester as well as zidovudine in the third trimester and a female neonate with Down syndrome who was exposed to dolutegravir, abacavir, and lamivudine during the second trimester. Ages of the mothers (ethnicity) at delivery were 31 years (black) and 38 years (Hispanic), respectively. No neural tube defects or central nervous system defects were reported.
European Pregnancy and Paediatric HIV Cohort Collaboration. Data on congenital abnormalities in the EPPICC studies were available for 81 of 84 live-born and stillborn neonates (twin/singleton pregnancies). Overall, abnormalities were recorded in 4 neonates [4.9%; 95% confidence interval (CI): 1.4 to 12.2]: 3 from the Italian cohort and 1 from the Swiss cohort. Of the 42 neonates first exposed to dolutegravir during the first trimester, 3 male neonates (7.1%) were reported to have abnormalities: 1 neonate with a patent foramen ovale with small left-to-right interatrial shunting, who was first exposed to dolutegravir from conception and also exposed to lamivudine and abacavir; 1 neonate with bilateral hexadactyly and hypospadias, who was first exposed to dolutegravir at week 3 and also exposed to lamivudine/abacavir and emtricitabine/tenofovir disoproxil fumarate; and 1 neonate with ankyloglossia (tongue-tie), who was first exposed to dolutegravir at week 12 and was also exposed to darunavir/ritonavir, emtricitabine/tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, and raltegravir. Ages of the mothers (ethnicity) at delivery were 38 years (black African), 40 years (white), and 31 years (white), respectively. Of the 24 neonates first exposed to dolutegravir during the second trimester (week 14), 1 (4.2%) male neonate was also exposed to lamivudine and abacavir and presented with hyperpigmentation on his back. His mother was of black African ethnicity and was aged 34 years. No central nervous system defects were reported.
J Acquir Immune Defic Syndr. 2019;81(4):371-378. © 2019 Lippincott Williams & Wilkins