Association of Early Interventions With Birth Outcomes and Child Linear Growth in Low-Income and Middle-Income Countries: Bayesian Network Meta-analyses of Randomized Clinical Trials.

Importance: The first 1000 days of life represent a critical window for child development. Pregnancy, exclusive breastfeeding (EBF) period (0-6 months), and complementary feeding (CF) period (6-24 months) have different growth requirements, so separate considerations for intervention strategies are needed. No synthesis to date has attempted to quantify the associations of interventions under multiple domains of micronutrient and balanced energy protein and food supplements, deworming, maternal education, water sanitation, and hygiene across these 3 life periods with birth and growth outcomes. Objective: To determine the magnitude of association of interventions with birth and growth outcomes based on randomized clinical trials (RCTs) conducted in low-income and middle-income countries (LMICs) using Bayesian network meta-analyses. Data Sources: MEDLINE, Embase, and Cochrane databases were searched from their inception up to August 14, 2018. Study Selection: Included were LMIC-based RCTs of interventions provided to pregnant women, infants (0-6 months), and children (6-24 months). Data Extraction and Synthesis: Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed for each life period. Effect sizes are reported as odds ratios (ORs) and mean differences (MeanDiffs) for dichotomous and continuous outcomes, with 95% credible intervals (CrIs). This study calculated probabilities of interventions being superior to standard of care by at least a minimal clinically important difference. Main Outcomes and Measures: The study compared ORs on preterm birth and MeanDiffs on birth weight for pregnancy, length for age (LAZ) for EBF, and height for age (HAZ) for CF. Results: Among 302 061 participants in 169 randomized clinical trials, the network meta-analyses found several nutritional interventions that demonstrated greater association with improved birth and growth outcomes compared with standard of care. For instance, compared with standard of care, maternal supplements of multiple micronutrients showed reduced odds for preterm birth (OR, 0.54; 95% CrI, 0.27-0.97) and improved mean birth weight (MeanDiff, 0.08 kg; 95% CrI, 0.00-0.17 kg) but not LAZ during EBF (MeanDiff, -0.02; 95% CrI, -0.18 to 0.14). Supplementing infants and children with multiple micronutrients showed improved LAZ (MeanDiff, 0.20; 95% CrI, 0.03-0.35) and HAZ (MeanDiff, 0.14; 95% CrI, 0.02-0.25). The study found that pregnancy interventions generally had higher probabilities of a minimal clinically importance difference than the interventions for the EBF or CF in the first 1000 days of life. Conclusions and Relevance: These analyses highlight the importance of intervening early for child development, during pregnancy if possible. Results of this study suggest that there is a need to combine interventions from multiple domains and test for their effectiveness as a package.

Interventions to improve linear growth during exclusive breastfeeding life-stage for children aged 0-6 months living in low- and middle-income countries: a systematic review with network and pairwise meta-analyses.

Background: Exclusive breastfeeding (EBF) during the first six months of life is critical for child's linear growth. While there is strong evidence in favor of EBF, the evidence with regards to other interventions for linear growth is unclear. We evaluated intervention domains of micronutrients, food supplements, deworming, maternal education, water sanitation and hygiene (WASH), and kangaroo care, for their comparative effectiveness on linear growth. Methods: For this review, we searched for randomized clinical trials (RCTs) of the interventions provided to infants aged 0-6 months and/or their breastfeeding mothers in low- and middle-income countries reporting on length-for-age z-score (LAZ), stunting, length, and head circumference. We searched for reports published until September 17 th, 2019 and hand-searched bibliographies of existing reviews. For LAZ and stunting, we used network meta-analysis (NMA) to compare the effects of all interventions except for kangaroo care, where we used pairwise meta-analysis to compare its effects versus standard-of-care. For length and head circumference, we qualitatively summarized our findings. Results: We found 29 RCTs (40 papers) involving 35,119 mother and infant pairs reporting on the effects of aforementioned interventions on linear growth outcomes. Our NMA on LAZ found that compared to standard-of-care, multiple micronutrients administered to infants (MMN-C) improved LAZ (mean difference: 0.20; 95% credible interval [CrI]: 0.03,0.35), whereas supplementing breastfeeding mothers with MMN did not (MMN-M, mean difference: -0.02, 95%CrI: -0.18,0.13). No interventions including MMN-C (relative risk: 0.74; 95%CrI: 0.36,1.44) reduced risk for stunting compared to standard-of-care. Kangaroo care, on the other hand, improved head circumference (mean difference: 0.20 cm/week; 95% confidence intervals [CI]: 0.09,0.31 cm/week) and length (mean difference: 0.23 cm/week; 95%CI: 0.10,0.35 cm/week) compared to standard-of-care.   Conclusion: Our study found important improvements for kangaroo care, but we did not find sufficient evidence for other interventions. Registration: PROSPERO CRD42018110450; registered on 17 October 2018.