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. The organisation conducting the trial (Society for Applied Studies, India) is a collaborator in the Healthy Birth, Growth, and Development Knowledge Integration (HBGDKi) of the Bill and Melinda Gates Foundation and the data generated from the study will be shared as part of the HBGDKi repository (https://[github.com/HBGDki][1]). Individual requests will also be considered on a case-by-case basis. The request for data should be accompanied by a detailed proposal describing the scientific questions to be addressed. Proposals should be submitted to NB (nita.bhandari@sas.org.in). [1]: http://github.com/HBGDki

中文翻译：

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在孕前、怀孕和儿童早期阶段实施的一揽子健康、营养、心理社会支持和 WaSH 干预措施对出生结果和 24 个月大时线性生长的影响：析因、个体随机对照试验

目的 确定仅在孕前、怀孕和儿童早期以及整个孕前、怀孕和儿童早期，综合和同时提供健康、营养、水、环境卫生和个人卫生 (WaSH) 和心理社会护理干预措施对儿童的影响。与常规护理相比，24 个月大时的出生结果和线性增长。设计单独随机析因试验。设置印度德里的中低收入社区。参与者 13500 名女性被随机分配接受孕前干预（n=6722）或常规护理（n=6778）。2652 和 2269 名孕妇再次随机接受妊娠和儿童早期干预或常规护理。出生结果分析包括 1290 例活产，包括孕前、妊娠、和早期儿童干预（A 组），1276 人用于孕前干预（B 组），1093 人用于妊娠和儿童早期干预（C 组），1093 人用于对照组（D 组）。到 2021 年 6 月 30 日，年龄为 24 个月的儿童被纳入 24 个月结果分析（A 组 453 人，B 组 439 人，C 组 293 人，D 组 271 人）。干预措施 健康、营养、心理社会关怀​​和支持以及WaSH 干预措施在孕前、怀孕和儿童早期阶段进行。主要结果测量 主要结果是低出生体重、小于胎龄、早产和平均出生体重。在 24 个月时，结果是平均年龄别身高 z 分数和发育迟缓比例。进行了三个预先设定的比较：孕前干预组（A+B）与无孕前干预组（C+D）；妊娠和儿童早期干预组 (A+C) 与妊娠和儿童早期常规护理 (B+D) 以及孕前、妊娠和儿童早期干预组 (A) 与对照组 (D)。结果孕前干预组的低出生体重比例（506/2235）低于未孕前干预组（502/1889；发生率比0.85，98.3%置信区间0.75～0.97；绝对风险降低-3.80% , 98.3% 置信区间 -6.99% 至 -0.60%)。妊娠干预组 (502/2096) 的低出生体重比例低于未妊娠干预组 (506/2028)，但置信区间上限交叉无效效应 (0.87, 0.76 至 1.01；-1.71 %，-4.96% 至 1.54%）。与对照组（267/934；0.76，0.62 至 0.91；-5.59%，-10.32）相比，在孕前和妊娠期接受干预的组（267/1141）对低出生体重比例的影响更大% 至 -0.85%）。与未接受这些干预的组（136/710；0.51，0.38 至 0.70；-8.32%，- 12.31% 至 -4.32%），接受孕前、妊娠和儿童早期干预的组（47/453）与对照组相比（51/271；0.49，0.32 至 0.75；-7.98%，-14.24%至-1.71%）。与无孕前干预组 (83/564) 相比，孕前干预组 (132/892) 对 24 个月发育迟缓没有影响。结论 在孕前、怀孕和儿童早期实施的干预包显着降低了 24 个月时的低出生体重和发育迟缓。仅怀孕和儿童早期干预对出生结局和 24 个月结局的影响较小但很重要。单独的孕前干预对出生结果有重要影响，但对 24 个月的结果没有影响。试验注册临床试验注册——印度 CTRI/2017/06/008908。开展试验的组织（印度应用研究协会）是比尔和梅琳达·盖茨基金会健康出生、成长和发展知识整合 (HBGDKi) 的合作者，该研究产生的数据将作为HBGDKi 存储库 (https://[github.com/HBGDki][1])。个人请求也将根据具体情况进行考虑。数据请求应附有描述要解决的科学问题的详细提案。提案应提交给 NB (nita.bhandari@sas.org.in)。[1]：http://github.com/HBGDki