Background: Small birth size, often associated with insufficient maternal nutrition, contributes to a large share of global child undernutrition, morbidity, and mortality. We developed a small-quantity lipid-based nutrient supplement (SQ-LNS) to enrich the diets of pregnant women. Objective: The objective was to test a hypothesis that home fortification of pregnant women's diets with SQ-LNS would increase birth size in an African community. Design: We enrolled 1391 women with uncomplicated pregnancies (,20 gestational weeks) in a randomized controlled trial in Malawi. The women were provided with one daily iron-folic acid (IFA) capsule, one capsule containing multiple micronutrients (MMNs), or one 20-g sachet of SQ-LNS (LNS, containing 118 kcal, protein, carbohydrates, essential fatty acids, and 21 micronutrients). Primary outcomes were birth weight and newborn length. Secondary outcomes included newborn weight, head and arm circumference, and pregnancy duration. Analysis was by intention to treat. Results: The mean 6 SD birth weight and newborn length were 2948 6 432, 2964 6 460, and 3000 6 447 g (P = 0.258) and 49.5 6 2.4, 49.7 6 2.2, and 49.9 6 2.1 cm (P = 0.104) in the IFA, MMN, and LNS groups, respectively. For newborn weight-for-age, head circumference, and arm circumference, the point estimate for the mean was also highest in the LNS group, intermediate in the MMN group, and lowest in the IFA group, but except for midupper arm circumference (P = 0.024), the differences were not statistically significant. The prevalence of low birth weight (,2500 g) was 12.7%, 13.5%, and 12.1% (P = 0.856), respectively; newborn stunting (length-for-age z score , 22) was 19.2%, 14.0%, and 14.9% (P = 0.130), respectively; and newborn small head circumference (head circumference-for-age z score , 22) was 5.8%, 3.0%, and 3.1% (P = 0.099), respectively. The associations between the intervention and the outcomes were not modified by maternal parity, age, or nutritional status (P . 0.100). Conclusion: The study findings do not support a hypothesis that provision of SQ-LNS to all pregnant women would increase the mean birth size in rural Malawi. The trial was registered at clinicaltrials.gov as NCT01239693.

Preterm birth is a major cause of neonatal mortality and morbidity worldwide. Bacterial infection and the subsequent inflammatory response are recognised as an important cause of preterm birth. It is hypothesised that these organisms ascend the cervical canal, colonise placental tissues, cause chorioamnionitis and in severe cases infect amniotic fluid and the foetus. However, the presence of bacteria within the intrauterine cavity does not always precede chorioamnionitis or preterm birth. Whereas previous studies observing the types of bacteria present have been limited in size and the specificity of a few predetermined organisms, in this study we characterised bacteria found in placental tissues from a cohort of 1391 women in rural Malawi using 16S ribosomal RNA gene sequencing. We found that specific bacteria found concurrently on placental tissues associate with chorioamnionitis and delivery of a smaller newborn. Severe chorioamnionitis was associated with a distinct difference in community members, a higher bacterial load and lower species richness. Furthermore, Sneathia sanguinengens and Peptostreptococcus anaerobius found in both matched participant vaginal and placental samples were associated with a lower newborn length-for-age Z-score. This is the largest study to date to examine the placental microbiome and its impact of birth outcomes. Our results provide data on the role of the vaginal microbiome as a source of placental infection as well as the possibility of therapeutic interventions against targeted organisms during pregnancy.

Background Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. Objectives We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. Methods We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. Results SQ-LNS provision decreased stunting (length-for-age z score < −2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < −2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < −2) by 18%, acute malnutrition (WLZ < −2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < −2) by 13%, and small head size (head circumference-for-age z score < −2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. Conclusions The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

BackgroundWhereas poor maternal nutritional status before and during pregnancy is widely associated with adverse birth outcomes, studies quantifying this association in low income countries are scarce. We examined whether maternal pre-pregnancy body mass index (BMI) and weight gain during pregnancy are associated with birth outcomes in rural Malawi.MethodsWe analyzed the associations between pre-pregnancy BMI and average weekly gestational weight gain (WWG) and birth outcomes [duration of gestation, birth weight, length-for-age z-score (LAZ), and head circumference-for-age z-score (HCZ)]. We also determined whether women with low or high pre-pregnancy BMI or women with inadequate or excessive WWG were at increased risk of adverse birth outcomes.ResultsThe analyses included 1287 women with a mean BMI of 21.8 kg/m2, of whom 5.9% were underweight (< 18.5 kg/m2), 10.9% were overweight (≥ 25 kg/m2), 71.8% had low WWG [below the lower limit of the Institute of Medicine (IOM) recommendation], and 5.2% had high WWG (above IOM recommendation). In adjusted models, pre-pregnancy BMI was not associated with duration of pregnancy (p = 0.926), but was positively associated with birth weight and HCZ (<0.001 and p = 0.003, respectively). WWG was positively associated with duration of gestation (p = 0.031), birth weight (p<0.001), LAZ (p<0.001), and HCZ (p<0.001). Compared to normal weight women, underweight women were at increased risk of having stunted infants (p = 0.029). Women with low WWG were at increased risk of having infants with low birth weight (p = 0.006) and small head circumference (p = 0.024) compared to those with normal weight gain. Those with high BMI or high WWG were not at increased risk of adverse birth outcomes.ConclusionsWWG is an important predictor of birth outcomes in rural Malawi. The high prevalence of inadequate WWG compared to low pre-pregnancy BMI highlights the need to investigate causes of inadequate weight gain in this region.