Early life interventions during the first 1,000 days of life: Data synthesis for birth outcomes and child linear growth using network meta-analyses

Jay J. H. Park, Mei Lan Fang, Ofir Harari, Louis Dron, Ellie G. Siden, Reham Majzoub, Virginia Jeziorska, Kristian Thorlund, Edward Joseph Mills, Zulfiqar A. Bhutta

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    Importance: The first 1,000 days of life (conception to child’s second birthday) is a critical window for child development. Pregnancy, exclusive breastfeeding period (EBF:0-6mo), and complementary feeding period (CF:6-24mo) have different growth requirements, so separate considerations for intervention strategies are needed. No synthesis has been attempted to quantify the effectiveness of interventions under multiple domains of micronutrient and balanced energy protein and food supplements, deworming, maternal education, and water sanitation and hygiene, across these three life periods.

    Objective: To determine the effectiveness of interventions on birth outcomes (preterm birth and birth weight) and linear growth (length/height-for-age; [LAZ/HAZ]) shown in randomized clinical trials conducted in low- and middle-income countries using Bayesian network meta-analyses.

    Data sources: MEDLINE, Embase, and Cochrane databases were searched from their inception until August 14, 2018.

    Study selection: LMIC-based RCTs of interventions provided to pregnant women, infants (0-6mo), and children (6-24mo) were included.

    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 ratio (ORs) and mean differences (MeanDiff) for dichotomous and continuous outcomes, with 95% credible intervals (CrI). We calculated probabilities of interventions being superior to standard-of-care by at least a minimal clinically importance difference (MCID).

    Main outcomes and measures: We compared effects on preterm birth and birthweight for pregnancy, LAZ for EBF, and HAZ for CF.

    Results: We found several nutritional interventions that demonstrated effectiveness against standard-of-care. For instance, versus standard-of-care, maternal supplements of multiple micronutrients (MMN) showed reduced odds for preterm birth (OR=0.54; 95%CrI: 0.27, 0.97) and improved mean birthweight (MeanDiff=0.08kg; 95%CrI: 0.00, 0.17kg), but not LAZ during EBF (MeanDiff=−0.02; 95%CrI: −0.18, 0.14). Supplementing infants and children with MMN showed improved LAZ (MeanDiff=0.20; 95%CrI: 0.03, 0.35) and HAZ (MeanDiff=0.14; 95%CrI: 0.02, 0.25). We found that pregnancy interventions generally had higher MCID probabilities than the interventions for the EBF/CF.

    Conclusions and relevance: Our analyses highlight the importance of intervening early, during pregnancy if possible. There is a need to combine interventions from multiple domains and test for their effectiveness as a package.
    Original languageEnglish
    Article numbere197871
    Number of pages17
    JournalJAMA Network Open
    Issue number7
    Publication statusPublished - 26 Jul 2019


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