Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF/1077FF Trial

Dorothy Sebikari, MBChB, MPH; Mona Farhad, MS; Terry Fenton, EdD; Maxensia Owor, MBChB; Jeffrey S. A. Stringer, MD; Min Qin, PhD; Nahida Chakhtoura, MD; Benjamin H. Chi, MD, MSc; Friday Saidi, MBBS; Neetal Nevrekar, MD; Avy Violari, MD; Tsungai Chipato, MBChB, MCE; James A. McIntyre, MBChB, FRCOG; Dhayendre Moodley, PhD; Taha E. Taha, MBBS, MCM, MPH, PhD; Gerhard Theron, MD; Mary Glenn Fowler, MD, MPH


J Acquir Immune Defic Syndr. 2019;81(5):521-532. 

In This Article


Between April 2011 and October 2014, 3423 participants delivered. This included 1507 women randomized to ZDV alone (arm A), 1497 women to ZDV-based ART (arm B), and 419 to TDF-based ART (arm C). The majority (97%) were black African. The median maternal age at enrollment was 26 years [interquartile range (IQR): 22–30], and the median BMI at entry was 26.1 kg/m−2 (IQR: 23.5–29.7). Almost all maternal participants (97%) were WHO clinical stage 1 (asymptomatic) and 37% enrolled at 28 weeks of gestation or later. Only 197 (6%) of participants had received ARVs for previous PMTCT, and 790 (23%) had used ARVs for PMTCT during the current pregnancy before study enrollment. A total of 681 women (20%) were nulliparous, and 115 (3%) reported at least one previous PTD (see Table S-1, Supplement Digital Content, https://links.lww.com/QAI/B322, for full baseline characteristics).

Every pregnancy with at least one live birth (n = 3333) was included in the analyses for PTD, VPTD, LBW, and VLBW outcomes. This included all the 60 multiple gestation pregnancies. For each of the 3 treatment arms, the incidence of multiple gestation was 2% (data not shown). There were also 90 singleton pregnancies where the outcome was either stillbirth or spontaneous abortion; note that these were included in the composite and severe composite outcome definitions. Among the 3333 women delivering at least 1 live born infant, median birth weight was 2900 g (IQR: 2600–3200), with 558 infants weighing <2500 g. Median GA at birth was 39 weeks (IQR: 38–40), and 557 infants were born before 37-week gestation. Among these pregnancies with at least 1 live birth, the percentages of PTD, VPTD, LBW, and VLBW were 17%, 3%, 17%, and 1%, respectively. Among all pregnancies (n = 3423), 27% had a composite and 6% had a severe composite adverse pregnancy outcome.

Predictor variables that did not meet the pre-established criteria to be included in the multivariate analyses (history of cigarette smoking, placenta previa, polyhydramnios, lower genital tract infection, and hepatitis B status) are not included in Figure 1 or in any of the Tables. The clinical variables that met the P value < 0.15 criteria for inclusion in multivariate logistic analyses include antiretroviral regimens, maternal age, maternal BMI at entry, HIV-RNA at baseline and CD4 at screening, history of alcohol use, country, GA at entry, multiple gestation, and previous preterm births. The following obstetrical complications also met the inclusion criteria: abruptio placentae, chronic hypertension, pregnancy-induced hypertension, oligohydramnios, intrauterine growth restriction, premature labor, premature rupture of membranes, urinary tract infection, and vaginal bleeding.

Figure 1.

Maternal treatment effects on adverse pregnancy outcomes after controlling for demographic/baseline clinical and obstetric factors.

Complete results, which include all variables meeting the P value < 0.15 criteria for inclusion in the multivariate models, are presented in Table S-2, Supplement Digital Content, https://links.lww.com/QAI/B322 for PTD and VPTD and S-3 for LBW and VLBW. These models also include results restricted to data from period 2. Table 1 and Table 2 present selected predictor variables, summarizing findings from these models. Table S-4, Supplement Digital Content, https://links.lww.com/QAI/B322 presents results for the composite and severe composite outcomes.

Treatment Effects on Adverse Pregnancy Outcomes Remain Significant After Controlling for Demographic/Baseline Clinical and Obstetric Factors

In multivariate analyses, for the PTD and LBW outcomes, the adjusted odds ratios of both ART regimens compared with the ZDV alone regimen remained significantly greater than 1.0, indicating increased risk, and for the composite outcomes, they showed similar patterns that were at least marginally significant. However, for VPTD and VLBW, the ZDV-based ART regimen did not differ significantly from ZDV alone, while the TDF-based ART regimen exhibited significantly greater odds ratios than ZDV alone, indicating increased risk of delivery at <34-week gestation, as well as increased risk of birth weight <1500 g. When comparing the 2 ART regimens, the TDF-based ART regimen demonstrated significantly higher risk of VLBW and VPTD compared with ZDV-based ART. These patterns held true for the univariate analyses of treatment effects, the multivariate models before backward elimination, the multivariate models subsequent to backward elimination, and multivariate models restricted to those accrued during period 2 (see Figure 1 and Tables S-2, S-3, S-4, Supplement Digital Contents, https://links.lww.com/QAI/B322).

Other Significant Predictors of Adverse Pregnancy Outcomes

In addition to the treatment effects, other factors significantly associated with PTD and/or LBW that remained in multivariate models after backward elimination, included maternal BMI at entry, HIV-RNA at baseline, GA at entry, previous preterm births, country, abruptio placentae, multiple gestation, hypertension, maternal age at delivery, oligohydramnios, intrauterine growth restriction, premature labor, preterm rupture of membranes, and vaginal bleeding (see Tables S-2 and S-3, Supplement Digital Content, https://links.lww.com/QAI/B322).