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

Jay J H Park, Mei Lan Fang, Ofir Harari, Louis Dron, Ellie G Siden, Reham Majzoub, Virginia Jeziorska, Kristian Thorlund, Edward J Mills (Lead / Corresponding author), Zulfiqar A Bhutta

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    Abstract

    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.

    Original languageEnglish
    Article numbere197871
    Pages (from-to)1-17
    Number of pages17
    JournalJAMA Network Open
    Volume2
    Issue number7
    DOIs
    Publication statusPublished - 26 Jul 2019

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    Infant Nutritional Physiological Phenomena
    Breast Feeding
    Micronutrients
    Standard of Care
    Randomized Controlled Trials
    Parturition
    Pregnancy
    Odds Ratio
    Premature Birth
    Growth
    Child Development
    Birth Weight
    Mothers
    Sanitation
    Information Storage and Retrieval
    Dietary Supplements
    Hygiene
    MEDLINE
    Pregnant Women
    Outcome Assessment (Health Care)

    Cite this

    Park, Jay J H ; Fang, Mei Lan ; Harari, Ofir ; Dron, Louis ; Siden, Ellie G ; Majzoub, Reham ; Jeziorska, Virginia ; Thorlund, Kristian ; Mills, Edward J ; Bhutta, Zulfiqar A. / 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. In: JAMA Network Open. 2019 ; Vol. 2, No. 7. pp. 1-17.
    @article{5e6a88c795c7404db430450afe7f002c,
    title = "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",
    abstract = "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.",
    author = "Park, {Jay J H} and Fang, {Mei Lan} and Ofir Harari and Louis Dron and Siden, {Ellie G} and Reham Majzoub and Virginia Jeziorska and Kristian Thorlund and Mills, {Edward J} and Bhutta, {Zulfiqar A}",
    note = "Funding: Bill & Melinda Gates Foundation",
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    doi = "10.1001/jamanetworkopen.2019.7871",
    language = "English",
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    }

    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. / Park, Jay J H; Fang, Mei Lan; Harari, Ofir; Dron, Louis; Siden, Ellie G; Majzoub, Reham; Jeziorska, Virginia; Thorlund, Kristian; Mills, Edward J (Lead / Corresponding author); Bhutta, Zulfiqar A.

    In: JAMA Network Open, Vol. 2, No. 7, e197871, 26.07.2019, p. 1-17.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Association of Early Interventions With Birth Outcomes and Child Linear Growth in Low-Income and Middle-Income Countries

    T2 - Bayesian Network Meta-analyses of Randomized Clinical Trials

    AU - Park, Jay J H

    AU - Fang, Mei Lan

    AU - Harari, Ofir

    AU - Dron, Louis

    AU - Siden, Ellie G

    AU - Majzoub, Reham

    AU - Jeziorska, Virginia

    AU - Thorlund, Kristian

    AU - Mills, Edward J

    AU - Bhutta, Zulfiqar A

    N1 - Funding: Bill & Melinda Gates Foundation

    PY - 2019/7/26

    Y1 - 2019/7/26

    N2 - 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.

    AB - 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.

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    DO - 10.1001/jamanetworkopen.2019.7871

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    JO - JAMA Network Open

    JF - JAMA Network Open

    SN - 2574-3805

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