Jain Shipra, Fu Ting Ting, Barnes-Davis Maria E, Sahay Rashmi D, Ehrlich Shelley R, Liu Chunyan, Habli Mounira, Parikh Nehal A
The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
University of Cincinnati College of Medicine, Cincinnati, Ohio.
JAMA Netw Open. 2025 Apr 1;8(4):e257788. doi: 10.1001/jamanetworkopen.2025.7788.
Whether maternal hypertensive disorders of pregnancy (HDP) confer independent neurodevelopmental deficit risks in premature infants is controversial. Previous studies are limited by inadequate confounding variable control and other biases.
To evaluate the associations between maternal HDP, especially preeclampsia, and neurodevelopmental outcomes of preterm infants at 2 years' corrected age.
DESIGN, SETTING, AND PARTICIPANTS: Regional prospective cohort study of 395 preterm infants (≤32 weeks' gestation) from 5 level III and IV southeast Ohio neonatal intensive care units from September 2016 to November 2019. Data analysis was conducted in August 2022.
HDP, defined by maternal diagnosis of chronic or gestational hypertension or preeclampsia during pregnancy.
Structural brain magnetic resonance imaging was performed at term-equivalent age. Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development (BSID), Third Edition, between 22 and 26 months' corrected age. Multivariable regression was used to identify the independent association of HDP and preeclampsia on cognitive (primary outcome), language, and motor development, controlling for several confounders. Mediation analyses were performed to understand if the association with HDP was mediated by its association with birth weight or brain abnormalities.
In a cohort of 395 infants, the median (IQR) gestational age was 29.6 (27.6-31.4) weeks, birth weight was 1230 (950-1628) g, and 210 (53.2%) were male. Of these, 170 (43%) were HDP-exposed, of which 104 of 170 (61%) were exposed to preeclampsia. A total of 341 children (87%) completed the BSID. In adjusted analyses, HDP exposure was negatively associated with BSID cognitive scores (-3.69; 95% CI, -6.69 to -0.68; P = .02) and language scores (-4.07; 95% CI, -8.03 to -0.11; P = .04). Preeclampsia exposure showed similarly negative but greater associations for BSID scores (-4.85; 95% CI, -8.63 to -1.07; P = .01 for cognitive and -6.30; 95% CI, -11.49 to -1.09; P = .02 for language scores). Mediation analysis revealed that the association between HDP and cognitive scores was partially mediated by its adverse association with brain abnormalities at term-equivalent age (24% of the total effect; -0.82; 95% CI, -1.72 to -0.13; P = .02).
In this preterm cohort study, maternal HDP was independently associated with adverse cognitive and language development, with accentuated associations observed in preeclampsia-exposed preterm infants, emphasizing the clinical importance of recognizing HDP as a risk, enabling targeted risk management strategies for closer monitoring and aggressive early intervention in affected populations.
妊娠高血压疾病（HDP）是否会给早产儿带来独立的神经发育缺陷风险存在争议。以往的研究受到混杂变量控制不足和其他偏倚的限制。
评估母亲HDP，尤其是子痫前期，与早产婴儿矫正年龄2岁时神经发育结局之间的关联。
设计、背景和参与者：2016年9月至2019年11月，对俄亥俄州东南部5个三级和四级新生儿重症监护病房的395名早产儿（孕周≤32周）进行的区域前瞻性队列研究。2022年8月进行数据分析。
HDP，定义为孕期母亲诊断为慢性高血压、妊娠期高血压或子痫前期。
在足月等效年龄时进行结构性脑磁共振成像。在矫正年龄22至26个月之间，通过贝利婴幼儿发育量表（BSID）第三版评估神经发育情况。采用多变量回归分析，在控制多个混杂因素的情况下，确定HDP和子痫前期与认知（主要结局）、语言和运动发育之间的独立关联。进行中介分析，以了解与HDP的关联是否通过其与出生体重或脑异常的关联介导。
在395名婴儿队列中，孕周中位数（IQR）为29.6（27.6 - 31.4）周，出生体重为1230（950 - 1628）g，210名（53.2%）为男性。其中，170名（43%）暴露于HDP，其中170名中的104名（61%）暴露于子痫前期。共有341名儿童（87%）完成了BSID评估。在调整分析中，暴露于HDP与BSID认知评分呈负相关（-3.69；95%CI，-6.69至-0.68；P = 0.02）和语言评分呈负相关（-4.07；95%CI，-8.03至-0.11；P = 0.04）。暴露于子痫前期与BSID评分也呈类似的负相关，但相关性更强（认知评分为-4.85；95%CI，-8.63至-1.07；P = 0.01；语言评分为-6.30；95%CI，-11.49至-1.09；P = 0.02）。中介分析显示，HDP与认知评分之间的关联部分由其与足月等效年龄时脑异常的不良关联介导（占总效应的24%；-0.82；95%CI，-1.72至-0.13；P = 0.02）。
在这项早产儿队列研究中，母亲HDP与不良的认知和语言发育独立相关；在暴露于子痫前期的早产儿中观察到更强的相关性，这强调了将HDP识别为一种风险的临床重要性，从而能够制定有针对性的风险管理策略，以便对受影响人群进行更密切的监测和积极的早期干预。
