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脐带血维生素 D 与子痫前期与儿童和青少年血压的关联。

Associations of Cord Blood Vitamin D and Preeclampsia With Offspring Blood Pressure in Childhood and Adolescence.

机构信息

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.

出版信息

JAMA Netw Open. 2020 Oct 1;3(10):e2019046. doi: 10.1001/jamanetworkopen.2020.19046.

Abstract

IMPORTANCE

Maternal preeclampsia may be one of the early risk factors for childhood and adolescence elevated blood pressure (BP). It is unknown whether the intergenerational association between maternal preeclampsia and offspring BP differs by cord blood vitamin D levels.

OBJECTIVE

To assess the associations between maternal preeclampsia and offspring systolic BP (SBP) across childhood and adolescence and to test whether these associations vary by cord blood 25-hydroxyvitamin D [25(OH)D] concentrations (a biomarker of in utero vitamin D status).

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 6669 SBP observations from 754 mother-child pairs from the Boston Birth Cohort, who were enrolled from December 1998 to June 2009. Data were analyzed from October 2019 to March 2020.

EXPOSURES

Physician-diagnosed maternal preeclampsia. Plasma 25(OH)D concentrations measured in cord blood samples collected at delivery.

MAIN OUTCOMES AND MEASURES

Repeated SBP measures between 3 and 18 years of age. The SBP percentile was calculated based on the 2017 American Academy of Pediatrics hypertension guidelines. Mean difference in SBP percentile in children born to mothers with vs without preeclampsia was compared across different cord blood 25(OH)D levels.

RESULTS

There were 6669 SBP observations from the 754 children; 50.0% were female and 18.6% were born preterm. Of the 754 mothers, 62.2% were Black and 10.5% had preeclampsia. Median cord blood 25(OH)D was 12.2 (interquartile range, 7.9-17.2) ng/mL. Maternal preeclampsia was associated with 5.34 (95% CI, 1.37-9.30) percentile higher SBP after adjusting for confounders. This association varied by quartiles of cord blood 25(OH)D concentrations: the differences in SBP percentile comparing children born to mothers with vs without preeclampsia were 10.56 (95% CI, 2.54-18.56) for quartile 1 (lowest), 7.36 (95% CI, -0.17 to 14.88) for quartile 2, 4.94 (95% CI, -3.07 to 12.96) for quartile 3, and -1.87 (95% CI, -9.71 to 5.96) for quartile 4 (highest). When cord blood 25(OH)D was analyzed continuously, children born to mothers with preeclampsia had 3.47 (95% CI, 0.77-6.18) percentile lower SBP per 5 ng/mL 25(OH)D increment. These associations did not differ by child sex or developmental stages.

CONCLUSIONS AND RELEVANCE

In this study of a US high-risk birth cohort, maternal preeclampsia was associated with higher offspring SBP from early childhood to adolescence. These associations were attenuated by higher cord blood 25(OH)D levels in a dose-response fashion. Additional studies, including clinical trials, are warranted.

摘要

重要性

母亲子痫前期可能是儿童和青少年血压升高的早期风险因素之一。尚不清楚母婴子痫前期与后代血压之间的代际关联是否因脐带血维生素 D 水平而异。

目的

评估母亲子痫前期与儿童和青少年整个童年和青春期收缩压 (SBP) 之间的关联,并检验这些关联是否因脐带血 25-羟维生素 D [25(OH)D] 浓度(评估胎儿维生素 D 状况的生物标志物)而异。

设计、地点和参与者:这项前瞻性队列研究分析了来自波士顿出生队列的 754 对母子中的 6669 个 SBP 观察值,这些母子于 1998 年 12 月至 2009 年 6 月入组。数据于 2019 年 10 月至 2020 年 3 月进行分析。

暴露

经医生诊断的母亲子痫前期。在分娩时采集的脐带血样本中测量的血浆 25(OH)D 浓度。

主要结果和测量指标

3 至 18 岁之间的重复 SBP 测量值。根据 2017 年美国儿科学会高血压指南计算 SBP 百分位数。比较了患有子痫前期的母亲所生孩子与没有子痫前期的母亲所生孩子的 SBP 百分位数差异,按不同的脐带血 25(OH)D 水平进行比较。

结果

在 754 名儿童中,有 6669 个 SBP 观察值;50.0%为女性,18.6%为早产儿。在 754 位母亲中,62.2%为黑人,10.5%患有子痫前期。中位脐带血 25(OH)D 为 12.2(四分位距,7.9-17.2)ng/ml。在调整混杂因素后,母亲子痫前期与 SBP 升高 5.34(95%CI,1.37-9.30)个百分点相关。这种关联因脐带血 25(OH)D 浓度四分位数而有所不同:与没有子痫前期的母亲所生孩子相比,出生于患有子痫前期的母亲所生孩子的 SBP 百分位数差异在第 1 四分位数(最低)为 10.56(95%CI,2.54-18.56),在第 2 四分位数(-0.17 至 14.88)为 7.36,在第 3 四分位数(3.07 至 12.96)为 4.94,在第 4 四分位数(最高)为-1.87(95%CI,-9.71 至 5.96)。当连续分析脐带血 25(OH)D 时,患有子痫前期的母亲所生孩子的 SBP 每降低 5ng/ml,25(OH)D 增加 3.47(95%CI,0.77-6.18)个百分点。这些关联在儿童性别或发育阶段上没有差异。

结论和相关性

在这项针对美国高危出生队列的研究中,母亲子痫前期与儿童从早期到青春期的 SBP 升高有关。这些关联呈剂量反应关系,随脐带血 25(OH)D 水平升高而减弱。需要开展包括临床试验在内的进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3018/7536588/217e4dbc7cab/jamanetwopen-e2019046-g001.jpg

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