Supplementary Material for: Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years: A Randomized Controlled Trial

<b><i>Introduction:</i></b> Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. <b><i>Objective:</i></b> The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. <b><i>Methods:</i></b> In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score &gt;1 standard deviation below the mean was defined as “at risk” for developmental impairment. <b><i>Results:</i></b> At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were “at risk” for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), <i>p</i> = 0.02. <b><i>Conclusion:</i></b> There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were “at risk” for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

<b><i>引言：</i></b> 铁缺乏症（Iron Deficiency, ID）与不良神经发育密切相关。我们既往的研究已证实，在尼泊尔足月健康婴儿中，延迟脐带钳夹（Umbilical Cord Clamping, CC）可在婴儿8月龄时改善其铁储备，并在1岁龄时改善其神经发育水平。<b><i>研究目的：</i></b> 本研究旨在评估相较于早期脐带钳夹（≤60秒），延迟脐带钳夹（≥180秒）对3岁龄儿童神经发育的影响，评估工具采用年龄与发育进程问卷（Ages and Stages Questionnaire, ASQ）。<b><i>研究方法：</i></b> 2014年，540名尼泊尔足月健康婴儿以1:1的比例被随机分配至延迟脐带钳夹组或早期脐带钳夹组。在婴儿3岁龄时，通过对家长进行电话访谈完成年龄与发育进程问卷评估。将得分低于均值1个标准差以上者定义为存在发育障碍风险。<b><i>研究结果：</i></b> 截至3岁龄时，共350名儿童完成随访，其中早期脐带钳夹组170名（占比63.0%），延迟脐带钳夹组180名（占比66.7%）。两组在各发育维度的年龄与发育进程问卷得分均无显著差异。然而，早期脐带钳夹组中存在大运动发育迟缓风险的女童比例更高：该组为14名（18.9%），延迟组为6名（6.3%），<i>p</i> = 0.02。<b><i>研究结论：</i></b> 两组在各发育维度的年龄与发育进程问卷得分均无显著差异。亚组分析显示，接受延迟脐带钳夹的女童出现大运动发育迟缓风险的比例更低。鉴于本队列在产后8月龄时铁储备已存在显著差异，后续开展更高龄阶段的随访研究具有必要性，因为早期铁缺乏症导致的神经发育损伤可能随年龄增长而更易被检测到。