Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH; Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX.
George Washington University Biostatistics Center, Washington, DC.
Am J Obstet Gynecol. 2023 Aug;229(2):153.e1-153.e12. doi: 10.1016/j.ajog.2023.02.016. Epub 2023 Feb 24.
Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia.
This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment.
This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group.
Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups.
This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.
子痫前期，尤其是在足月前，会增加儿童神经发育不良结局的风险。儿科学研究所和产科-胎儿药理学研究中心网络开展的生物学研究、临床前研究和初步临床试验均支持普伐他汀用于预防子痫前期的安全性和有效性。
本研究旨在确定产前普伐他汀治疗高危孕妇对子代健康、生长和神经发育的影响。
这是对参加产科-胎儿药理学研究中心网络普伐他汀与安慰剂治疗子痫前期高危人群的前瞻性、随机、安慰剂对照临床试验（ClinicalTrials.gov 注册号：NCT01717586）的子研究。在获得书面知情同意（和适当的同意）后，父母被指示完成儿童行为检查表。为了评估儿童的运动、认知和发育结果，经过认证并保持盲态的研究心理学家使用经过验证的工具完成了儿童运动、认知、情绪和行为评估。鉴于研究中的个体数量较少，10mg 和 20mg 普伐他汀组合并为 1 组，将普伐他汀组的结果与安慰剂组进行比较。
在原始试验中，有 40 名母亲所生的儿童，其中 30 名（15 名在宫内暴露于普伐他汀，15 名在宫内暴露于安慰剂）纳入了本随访研究。随访时间为 4.7 年（四分位距，2.5-6.9），普伐他汀组和安慰剂组之间无差异。2 组间儿童的性别和校正年龄的体重指数百分位数、体重指数百分位数极端值的发生率或任何其他医疗或发育并发症的报告无差异。与安慰剂组 2 名（13.3%）行走困难和 4 名（26.7%）手部运动能力降低的儿童相比，普伐他汀组出生的儿童在运动评估方面没有任何受限。此外，接受普伐他汀治疗的母亲所生的儿童的一般概念能力评分较高（98.2±16.7 比 89.7±11.0；P=.13），并且报告得分<85（即，低于均值 1 个标准差）的频率较低（15.4%比 35.7%；P=.38）。最后，2 组间父母对儿童行为检查表的报告无差异。
本研究报告了妊娠中期和妊娠晚期宫内暴露于普伐他汀的儿童的长期神经运动、认知和行为结局。尽管原始试验的样本量有限，但使用普伐他汀治疗未显示出明显的长期神经发育安全性信号。这种有利的新生儿风险效益分析证明了在临床试验中继续使用普伐他汀的合理性。
