Neurodevelopment, vision and auditory outcomes at age 2 years in offspring of participants in the 'Women First' maternal preconception nutrition randomised controlled trial.

BACKGROUND: Maternal nutrition in preconception and early pregnancy influences fetal growth. Evidence for effects of prenatal maternal nutrition on early child development (ECD) in low-income and middle-income countries is limited. OBJECTIVES: To examine impact of maternal nutrition supplementation initiated prior to or during pregnancy on ECD, and to examine potential association of postnatal growth with ECD domains. DESIGN: Secondary analysis regarding the offspring of participants of a maternal multicountry, individually randomised trial. SETTING: Rural Democratic Republic of the Congo, Guatemala, India and Pakistan. PARTICIPANTS: 667 offspring of Women First trial participants, aged 24 months. INTERVENTION: Maternal lipid-based nutrient supplement initiated preconceptionally (arm 1, n=217), 12 weeks gestation (arm 2, n=230) or not (arm 3, n=220); intervention stopped at delivery. MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) cognitive, language, gross motor, fine motor, positive and negative behaviour scores; visual acuity and contrast sensitivity scores and auditory evoked response potentials (ERP). Anthropometric z-scores, family care indicators (FCI) and sociodemographic variables were examined as covariates. RESULTS: No significant differences were detected among the intervention arms for any INTER-NDA scores across domains, vision scores or ERP potentials. After adjusting for covariates, length-for-age z-score at 24 months (LAZ24), socio-economic status, maternal education and FCI significantly predicted vision and INTER-NDA scores (R2=0.11-0.38, p<0.01). CONCLUSIONS: Prenatal maternal nutrition supplementation was not associated with any neurodevelopmental outcomes at age 2 years. Maternal education, family environment and LAZ24 predicted ECD. Interventions addressing multiple components of the nurturing care model may offer greatest impact on children's developmental potential. TRIAL REGISTRATION NUMBER: NCT01883193.

Longitudinal Reduction in Diversity of Maternal Gut Microbiota During Pregnancy Is Observed in Multiple Low-Resource Settings: Results From the Women First Trial.

Objective: To characterize the changes in gut microbiota during pregnancy and determine the effects of nutritional intervention on gut microbiota in women from sub-Saharan Africa (the Democratic Republic of the Congo, DRC), South Asia (India and Pakistan), and Central America (Guatemala). Methods: Pregnant women in the Women First (WF) Preconception Maternal Nutrition Trial were included in this analysis. Participants were randomized to receive a lipid-based micronutrient supplement either ≥3 months before pregnancy (Arm 1); started the same intervention late in the first trimester (Arm 2); or received no nutrition supplements besides those self-administered or prescribed through local health services (Arm 3). Stool and blood samples were collected during the first and third trimesters. Findings presented here include fecal 16S rRNA gene-based profiling and systemic and intestinal inflammatory biomarkers, including alpha (1)-acid glycoprotein (AGP), C-reactive protein (CRP), fecal myeloperoxidase (MPO), and calprotectin. Results: Stool samples were collected from 640 women (DRC, n = 157; India, n = 102; Guatemala, n = 276; and Pakistan, n = 105). Gut microbial community structure did not differ by intervention arm but changed significantly during pregnancy. Richness, a measure of alpha-diversity, decreased over pregnancy. Community composition (beta-diversity) also showed a significant change from first to third trimester in all four sites. Of the top 10 most abundant genera, unclassified Lachnospiraceae significantly decreased in Guatemala and unclassified Ruminococcaceae significantly decreased in Guatemala and DRC. The change in the overall community structure at the genus level was associated with a decrease in the abundances of certain genera with low heterogeneity among the four sites. Intervention arms were not significantly associated with inflammatory biomarkers at 12 or 34 weeks. AGP significantly decreased from 12 to 34 weeks of pregnancy, whereas CRP, MPO, and calprotectin did not significantly change over time. None of these biomarkers were significantly associated with the gut microbiota diversity. Conclusion: The longitudinal reduction of individual genera (both commensals and potential pathogens) and alpha-diversity among all sites were consistent and suggested that the effect of pregnancy on the maternal microbiota overrides other influencing factors, such as nutrition intervention, geographical location, diet, race, and other demographical variables.

Gestational weight gain in 4 low- and middle-income countries and associations with birth outcomes: a secondary analysis of the Women First Trial.

BACKGROUND: Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions. OBJECTIVE: We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth. METHODS: This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, evaluating weight gain from enrollment to ∼12 weeks of gestation and GWG velocity (kg/wk) between ∼12 and 32 weeks of gestation. Adequacy of GWG velocity was compared with 2009 Institute of Medicine recommendations, according to maternal BMI. Early weight gain (EWG), GWG velocity, and adequacy of GWG were related to birth outcomes using linear and Poisson models. RESULTS: GWG velocity (mean ± SD) varied by site: 0.22 ± 0.15 kg/wk in DRC, 0.30 ± 0.23 in Pakistan, 0.31 ± 0.14 in Guatemala, and 0.39 ± 0.13 in India, (P <0.0001). An increase of 0.1 kg/wk in maternal GWG was associated with a 0.13 cm (95% CI: 0.07, 0.18, P <0.001) increase in birth length and a 0.032 kg (0.022, 0.042, P <0.001) increase in birth weight. Compared to women with inadequate GWG, women who had adequate GWG delivered newborns with a higher mean length and weight: 47.98 ± 2.04 cm compared with 47.40 ± 2.17 cm (P <0.001) and 2.864 ± 0.425 kg compared with 2.764 ± 0.418 kg (P <0.001). Baseline BMI, EWG, and GWG were all associated with birth length and weight. CONCLUSIONS: These results underscore the importance of adequate maternal nutrition both before and during pregnancy as a potentially modifiable factor to improve fetal growth.

Electrolyte Imbalance at Admission Does Not Predict the Length of Stay or Mortality in Dengue-Infected Patients.

Background A pattern of both clinical and biochemical abnormalities is associated with dengue virus infection (DVI). Among the various DVI-related biochemical defects, electrolyte imbalance is one that can alter the morbidity and mortality among patients. However, there is a dearth of evidence to assess the relationship between electrolyte imbalance and the length of stay or mortality in dengue-infected patients in Pakistan. In the current study, we aimed to investigate the association between electrolyte imbalance at the time of admission and the length of stay and mortality among dengue-infected patients. Methods We conducted a retrospective study at a large tertiary care hospital from November 2018 to November 2019. All patients with known chronic diseases and coinfections or those who were taking diuretics therapies or angiotensin-converting enzyme inhibitors were excluded. Our main exposure of interest was electrolytes imbalance and the outcome measure was the length of stay and mortality. Results A total of 1,008 dengue patients were enrolled with a mean length of stay of 2.56 days. Around 29.3% had hyponatremia and 23.2% had hypokalemia at the time of admission, and 21.9% of patients had a stay beyond three days. In multivariable analysis, hyponatremia [adjusted odds ratios (aOR) = 1.29; 95% confidence interval (CI): 0.59-2.84] and hypokalemia (aOR = 2.36; 95% CI: 0.91-6.10) were not found to be associated with the length of stay. However, patients with high troponin levels at admission had a prolonged stay beyond three days (aOR = 5.74; 95% CI: 2.34-14.11). There was a statistically significant association of creatinine levels (aOR = 14.74; 95% CI: 4.19-15.85) and diabetes mellitus (DM) (aOR = 4.36; 95% CI: 1.21-15.74) with mortality after controlling for potential confounders. Conclusion Electrolyte imbalance at admission is not a predictor of length of stay or fatalities in the hospital among patients with DVI. However, troponin levels at admission can increase hospitalization days whereas DM and renal injury have been found to worsen mortality rates.