Research Article: Lipid based nutrient supplements during pregnancy may improve foetal growth in HIV infected women – A cohort study

Date Published: May 2, 2019

Publisher: Public Library of Science

Author(s): Minyanga Nkhoma, Per Ashorn, Ulla Ashorn, Kathryn G. Dewey, Austrida Gondwe, Kenneth Maleta, Karel Allegaert.


Both maternal HIV infection and antiretroviral therapy are associated with adverse birth outcomes. The role of antenatal nutrient supplements with regard to adverse birth outcomes in HIV infected women exposed to antiretroviral therapy is not well known. We assessed the association between HIV and birth outcomes and explored whether antenatal lipid-based nutrient supplements (LNS) modulated this association.

We analysed a nested cohort of pregnant Malawian women who received daily LNS, multiple micronutrients (MMN) or iron and folic acid (IFA). Birth weight, length-for-age z-score (LAZ) and weight-for-age z-score (WAZ) were analysed as continuous outcomes and proportion of stunting and small-for-gestational age (SGA) as dichotomous outcomes.

134 HIV infected (46 LNS, 39 MMN, 49 IFA) and 833 HIV uninfected (271 LNS, 287 MMN, 275 IFA) women were included. Maternal HIV infection was associated with a lower mean birth weight (-129g (-209, -48), P = 0.002); LAZ (-0.34 (-0.54, -0.13), P = 0.002) and WAZ (-0.21 (-0.40, -0.02), P = 0.041) and a higher risk of stunting (RR (95% confidence interval), 1.87 (1.24, 2.83), P = 0.003) and SGA (1.66 (1.21, 2.26), P = 0.001) in the newborn. If the women received LNS, HIV was not associated with LAZ (mean difference (95%); -0.02 (-0.35, 0.31), P = 0.918) or newborn stunting (RR (95% CI), 0.84 (0.34, 2.03), P = 0.691). However HIV tended to be associated with LAZ if the women received MMN (-0.42 (-0.80, -0.03), P = 0.053); and was significantly associated with LAZ if the women received IFA (-0.52 (-0.89, -0.14), P = 0.021) and with newborn stunting if they received MMN (2.40 (1.15, 4.98), P = 0.029) or IFA (2.40 (1.26, 4.59), P = 0.024).

Further research to investigate the impact of LNS on various aspects of foetal growth in HIV infected women is warranted.

Partial Text

Global estimates indicate that 17.8 million women aged >15 years were living with human immunodeficiency virus (HIV) in 2016 [1]. Following the rapid scale-up of antiretroviral therapy (ART) [2] there has been a considerable reduction in vertical transmission and HIV associated maternal and child mortality [1]. However, maternal HIV continues to be associated with adverse birth outcomes such as preterm birth (PTB) and low birth weight (LBW) even in the context of ART use [3]. Indeed, different aspects of maternal ART including timing of initiation of therapy (pre-conception vs post-conception) or type of antiretroviral regimen have been reported to influence the risk of adverse birth outcomes in HIV infected women [4,5].

We conducted a secondary cohort analysis of data collected from pregnant women who participated in the iLiNS-DYAD-Malawi trial (Trial Registration, Identifier: NCT01239693). This was a randomized controlled nutrient intervention trial that evaluated the impact of LNS on pregnancy outcomes. The analysis we are reporting now was defined a priori in the iLiNS-DYAD-Malawi study protocol. Ethical approval for the trial was obtained from the College of Medicine Research and Ethics Committee, University of Malawi and the Ethics Committee of Pirkanmaa Hospital District, Finland. Written informed consent was sought from all study participants prior to study participation.

Out of the 1391 women enrolled into the iLiNS-DYAD-M study, 967 were eligible for analysis. We performed our outcome analyses on this cohort of 134 HIV infected and 833 HIV uninfected pregnant women. Women excluded from the outcome analyses (n = 424) due to missing HIV test results, twin gestation, miscarriage, stillbirth, dropout or incomplete outcome data (Fig 1) tended to be younger (23.9 versus 25.4 y), to be wealthier (0.15 versus -0.05), to be primigravid (31.8% versus 17.5%), to have a higher BMI (22.5 versus 22.0 kg/m2) and to be anaemic (24.4% versus 19.0%) but were otherwise similar to women included in the analyses in terms of the other baseline characteristics (S1 Table).

We investigated the association between maternal HIV and pregnancy outcomes, and whether this association differed across nutrient intervention groups in a cohort of women participating in a nutrient supplementation trial in southern rural Malawi. The study findings show that maternal HIV status was inversely associated with weekly GWG, birth weight, LAZ, and WAZ and positively associated with PTB, LBW, stunting and being born SGA. HIV infected women who received LNS tended to have values of birth size or risk of adverse outcomes similar to that of HIV uninfected women regardless of the type of supplement received by the uninfected women. The association between HIV infection and PTB and newborn stunting differed according to the type of dietary supplementation received during pregnancy. Maternal HIV was not associated with PTB if the mothers received LNS or IFA; or newborn stunting if the mothers received LNS.

Further research to investigate the impact of LNS on various aspects of foetal growth in HIV infected women is warranted.