Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Aust N Z J Psychiatry. 2023 Jul;57(7):1062-1072. doi: 10.1177/00048674221116027. Epub 2022 Aug 15.
Animal studies indicate a key role for vitamin D in brain development and function, but observational studies in humans only suggests a borderline positive association between prenatal vitamin D exposure and cognitive development in the offspring. Knowledge gaps include insights in exposure time window and differences by sex for the association. We aimed to investigate the association between blood concentrations of serum 25-hydroxyvitamin D measured at four different time points and intelligence quotient score at the age of 7 years, including analyses spilt by child sex.
In Odense child cohort, we included 1404 mother-child pairs with serum 25-hydroxyvitamin D data from early pregnancy to age 7 years. Full-scale intelligence quotient was assessed with Wechsler Intelligence Scale for Children - fifth edition. Associations were adjusted for maternal education, pre-pregnancy body mass index, gestational age, sex and head circumference. Subanalyses stratified by sex were performed.
The median (interquartile range) serum 25-hydroxyvitamin D in cord was 45.88 (31.15-61.08) nmol/L; early pregnancy, 66.45 (51.29-78.74); late pregnancy, 79.13 (59.69-97.31); 7 years, 66.29 (53.45-80.23) nmol/L. The mean (standard deviation) full-scale intelligence quotient was 99.44 (11.98). In adjusted analyses, cord serum 25-hydroxyvitamin D < 50 nmol/L was associated with 2.2 points lower full-scale intelligence quotient compared to the reference (50-75 nmol/L) in boys, β = -2.2; 95% confidence interval = [-4.3, -0.1], = 0.039. The same association with full-scale intelligence quotient was found for early pregnancy serum 25-hydroxyvitamin D, β = -2.5 [-4.6, -0.3], = 0.025, primarily driven by an association in boys, β = -4.0 [-7.2, -0.8], = 0.015; and for serum 25-hydroxyvitamin D at 7 years in girls, β = -3.0 [-6.0, -0.1], = 0.042.
In this cohort, serum 25-hydroxyvitamin D < 50 nmol/L in both early gestation and cord blood in boys and current serum 25-hydroxyvitamin D < 50 nmol/L in girls were independent risk factors for two to four points lower full-scale intelligence quotient at the age of 7 years. Vulnerability to hypovitaminosis D, especially in pregnancy, may relate to child sex.
动物研究表明维生素 D 对大脑发育和功能具有关键作用，但人类观察性研究仅表明产前维生素 D 暴露与后代认知发育之间存在边缘正相关。知识空白包括对暴露时间窗的了解以及按性别划分的关联差异。我们旨在研究在四个不同时间点测量的血清 25-羟维生素 D 浓度与 7 岁时智商评分之间的关系，包括按儿童性别进行的分析。
在奥登塞儿童队列中，我们纳入了 1404 对母子对，其中包括妊娠早期至 7 岁时的血清 25-羟维生素 D 数据。采用韦氏儿童智力量表第五版评估全量表智商。关联调整了母亲的教育程度、孕前体重指数、胎龄、性别和头围。按性别进行了分层亚组分析。
脐带血清 25-羟维生素 D 的中位数（四分位距）为 45.88（31.15-61.08）nmol/L；孕早期为 66.45（51.29-78.74）；孕晚期为 79.13（59.69-97.31）；7 岁时为 66.29（53.45-80.23）nmol/L。全量表智商的平均值（标准差）为 99.44（11.98）。在调整分析中，与脐带血清 25-羟维生素 D<50 nmol/L 相比，<50 nmol/L 与男孩全量表智商低 2.2 分相关（参考值为 50-75 nmol/L），β=-2.2；95%置信区间=-4.3，-0.1]，=0.039。与早期妊娠血清 25-羟维生素 D 也存在相同的全量表智商关联，β=-2.5[-4.6，-0.3]，=0.025，主要是由于男孩的关联，β=-4.0[-7.2，-0.8]，=0.015；在女孩中，7 岁时血清 25-羟维生素 D 与全量表智商也存在关联，β=-3.0[-6.0，-0.1]，=0.042。
在该队列中，男孩在妊娠早期和脐带血中血清 25-羟维生素 D<50 nmol/L，以及女孩在当前血清 25-羟维生素 D<50 nmol/L，均为 7 岁时全量表智商低 2 至 4 分的独立危险因素。维生素 D 缺乏症的易感性，特别是在妊娠期间，可能与儿童性别有关。
