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Key Points: Question: How does a package of multidomain interventions addressing health, nutrition, psychosocial care and support, and environmental hygiene delivered during preconception, pregnancy, and early childhood affect child neurodevelopment at 24 months? Findings: In this second report of a randomized trial in India assessing interventions during preconception, pregnancy, and early childhood on childhood preterm births and childhood growth as primary outcomes, the secondary outcome was neurodevelopment at 24 months. Among 1712 children assessed, preconception, pregnancy, and early childhood interventions were associated with modest improvements in scores and lower incidence of moderate to severe neurodevelopmental delay in the cognitive, language, and socioemotional domains. Meaning: Multidomain interventions in the preconception period, along with those in pregnancy and early childhood, may be beneficial for child neurodevelopment. Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry–India CTRI/2017/06/008908 This randomized trial assesses interventions that span preconception through early childhood compared with usual care on neurodevelopment among children at age 24 months in low- and middle-income neighborhoods in India. [ABSTRACT FROM AUTHOR]

The global livestock system puts increasing pressures on ecosystems. Studies analyzing the ecological impacts of livestock supply chains often explain this pressure by the increasing demand for animal products. Food regime theory proposes a more nuanced perspective: it explains livestock-related pressures on ecosystems by systemic changes along the supply chains of feed and animal products, notably the liberalization of agricultural trade. This study proposes a framework supporting empirical analyses of such claims by differentiating several steps of livestock supply chains. We reconstructed "trilateral" livestock supply chains linking feed production, livestock farming, and final consumption, based on the global flows of 161 feed and 13 animal products between 222 countries from 1986 to 2013. We used the embodied Human Appropriation of Net Primary Production (eHANPP) indicator to quantify pressures on ecosystems linked to these trilateral livestock supply chains. We find that livestock induced 65 % of agriculture's pressure on ecosystems, mostly through cattle grazing. Between 1986 and 2013, the fraction of livestock-related eHANPP that was traded internationally doubled from 7.1 % to 15.6 %. eHANPP related to the trade of feed was mostly linked to soybean imported for pig meat production, whereas eHANPP associated to traded animal products was mostly linked to cattle meat. eHANPP of traded animal products was lower but increased faster than eHANPP of feed trade. eHANPP was highest at the feed production level in South and North America, and at the consumption level in Eastern Asia. In Northern Asia and Eastern Europe, eHANPP was lowest at the animal products production level. In Western Europe, the eHANPP was equal at the animal products production and consumption levels. Our findings suggest that options to reduce livestock's pressures on ecosystems exist at all levels of the supply chain, especially by reducing the production and consumption in high-consuming countries and regulating international supply chains., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care., Design: Individually randomised factorial trial., Setting: Low and middle income neighbourhoods of Delhi, India., Participants: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D)., Interventions: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods., Main Outcome Measures: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D)., Results: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564)., Conclusions: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes., Trial Registration: Clinical Trial Registry-India CTRI/2017/06/008908., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Biotechnology Industry Research Assistance Council of the Department of Biotechnology, Government of India and Bill and Melinda Gates Foundation, USA for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)