Maternal weight and birth outcomes among women on antiretroviral treatment from conception in a birth surveillance study in Botswana

Abstract

Introduction Antiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART‐associated weight gain on pregnancy outcomes among women living with HIV. Methods Using data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)). Results Of 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks’ gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre‐pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata. Conclusions ART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight‐based ART treatment strategies improve maternal and child health.

Neonatal deaths among infants born to women living with HIV in the UK and Ireland

“…An analysis based on Scottish national data in 1999-2009 estimated that the population attributable fraction of maternal current smoking for neonatal death was 6.7% [50]. Whilst prepregnancy weight and pregnancy weight gain (inadequate to excessive) in WLWH are current topics of interest, particularly in relation to type of antiretroviral regimen [53,54], the prevalence of obesity in pregnant WLWH in the UK is uncertain, but may be expected to be high based on a prevalence of 38% of WLWH in one English study [55]. This may be of concern, given that a large meta-analysis reported a moderate increase in relative risk (RR) of neonatal death per 5 unit increase in maternal body mass index (BMI) (RR 1.15, 95% CI 1.07, 1.23) [56].…”

Congenital malformations and preeclampsia associated with integrase inhibitor use in pregnancy: A single-center analysis

“…Pregnancies were categorized as having DTG or any INSTI exposure if a mother received these drugs at any time between conception and delivery. ART was categorized by timing of receipt, in the first (gestational age �13 weeks), second (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), or third (28-delivery) trimesters.…”

“…In contrast, the SMARTT study identified a 2-fold higher rate of preterm birth among infants with first-trimester INSTI exposure compared to no INSTI exposure [18]. Few studies have compared maternal outcomes such as preeclampsia, gestational diabetes, and laboratory abnormalities between pregnancies exposed to INSTIs versus other ART [19,20].…”

Evaluating the association of antiretroviral therapy and immune status with hypertensive disorders of pregnancy among people with HIV

“…The prevalence of both chronic and new-onset HDP in this cohort were slightly higher than that found in population-based cohorts of pregnant individuals without HIV, which have demonstrated a gradual rise in the occurrence of both conditions [23][24][25][26] U.S. data have suggested, as we hypothesized, that INSTI use may be associated with an elevated risk of HDP compared with protease-inhibitor-based regimens [9]. In Southern Africa, findings from the Botswana-based Tsepamo study found the prevalence of maternal hypertension to be higher with dolutegravir versus efavirenz-based regimens, with the ART regimen acting as an effect modifier of the relationship between weight and hypertension [28]. Recent findings from a cohort of 794 pregnant PWH in Italy demonstrated no difference in hypertension by ART category [29].…”