Offspring Neurodevelopment and Growth after Early Antihypertensive Therapy OR Preeclampsia in Women with Chronic Hypertension and Pregnancy (CHAP Child).

慢性高血压和妊娠（CHC）随机试验最近导致了新的国家 关于妊娠期慢性高血压（CHTN）降压治疗的建议。 在61个美国研究中心，在23周前开始轻度CHTN（BP <160/105 mmHg）的经验证的治疗（与无） （N=2408）。治疗改善了孕产妇和围产期结局，包括先兆子痫、早产和低血糖。 出生体重这是妊娠期最大的CHTN治疗试验。然而，关键的知识差距 仍然关注a）常规产前抗高血压治疗和B） CHTN妇女对暴露后代的叠加先兆子痫。先兆子痫并发症>30% 的CHTN患者，与胎儿生长受损有关，新的数据表明先兆子痫可能 神经发育受损（ND）和儿童生长/心脏代谢结果-包括BMI升高， 血压（BP）。小于胎龄儿是儿童ND受损的独立危险因素， 改变增长。因此，确定产前抗高血压治疗的长期影响是至关重要的。 后代（以及我们资助的R 01 HL 120338母亲随访研究中的母亲）。埃里哈斯 随机化治疗和判定的先兆子痫数据，以增强严谨性，以解决： 目的1：确定常规产前药物治疗轻度CHTN对儿童ND的长期安全性 和增长假设1a：轻度CHTN的降压治疗，血压目标<140/90 mmHg， 未接受治疗与ND恶化无关，包括通过一般检查确定的认知功能 概念能力（GCA，主要结局）。如果我们证明了非劣效性，我们还将测试治疗是否 改善ND -给予有益的新生儿结果，假设1b：降压治疗（目标<140/90 轻度CHTN的治疗与不治疗相比，与儿童生长和其他心脏代谢不良无关。 结果包括BMI ≥第85百分位数（主要结果）、肥胖、体重不足和BP。 目的2：确定轻度CHTN合并先兆子痫是否与儿童结局相关 包括ND、生长和其他心脏代谢结果。假设2a：先兆子痫（vs.无先兆子痫） 与儿童不良ND独立相关，包括GCA评估的认知功能受损 （主要成果）。假设2b：先兆子痫与儿童生长发育改变独立相关 （包括BMI ≥第85百分位数的主要结局）、肥胖、体重不足、连续生长和BP。我们还将 通过评估围产期和出生后，探讨儿童ND和异常生长的机制 特征作为异常ND和生长的风险和预测因素。 具有里程碑意义的研究结果和NHLBI资助的产妇随访研究提供了一个真正独特的 机会和协同作用，这项拟议的儿童后续研究，以收集完整的图片，长期- 产前抗高血压治疗和先兆子痫对后代的长期影响

The Chronic Hypertension and Pregnancy (CHAP) randomized trial recently led to new national recommendations regarding antihypertensive treatment for chronic hypertension (CHTN) during pregnancy. CHAP tested treatment (vs. none) initiated before 23 weeks for mild CHTN (BP <160/105 mmHg) at 61 US sites (N=2408). Treatment improved maternal and perinatal outcomes including preeclampsia, preterm birth and low birth weight. CHAP is the largest CHTN treatment trial in pregnancy. However, critical knowledge gaps remain concerning long-term effects of a) routine prenatal antihypertensive therapy and b) superimposed preeclampsia in women with CHTN on exposed offspring. Preeclampsia complicates >30% of patients with CHTN, is associated with impaired fetal growth, and emerging data suggest preeclampsia may impair neurodevelopment (ND) and childhood growth/cardio-metabolic outcomes– including elevated BMI and blood pressure (BP). Small for gestational age is an independent risk factor for impaired childhood ND and altered growth. Therefore, it is crucial to define the long-term effects of prenatal antihypertensive therapy on offspring (as well as mothers in our funded CHAP Maternal Follow-up study R01HL120338). CHAP has randomized treatment and adjudicated preeclampsia data to enhance rigor to address: Aim 1: Define the long-term safety of routine prenatal pharmacologic treatment of mild CHTN on childhood ND and growth. Hypothesis 1a: Antihypertensive therapy for mild CHTN to a BP goal <140/90 mmHg compared with no treatment is not associated with worse ND including cognitive functioning determined by General Conceptual Ability (GCA, primary outcome). If we demonstrate non-inferiority, we will also test whether therapy improves ND - given salutary neonatal results in CHAP. Hypothesis 1b: Antihypertensive therapy (goal <140/90 mmHg) vs. no treatment for mild CHTN is not associated with worse childhood growth and other cardio-metabolic outcomes including BMI ≥85th percentile (primary outcome), obesity, underweight, and BP. Aim 2: Determine whether preeclampsia superimposed on mild CHTN is associated with childhood outcomes including ND, growth and other cardio-metabolic outcomes. Hypothesis 2a: Preeclampsia (vs. no preeclampsia) is independently associated with adverse ND in children including impaired cognitive functioning by GCA (primary outcome). Hypothesis 2b: Preeclampsia is independently associated with altered childhood growth (including a primary outcome of BMI ≥85th percentile), obesity, underweight, serial growth and BP. We will also explore mechanisms of childhood ND and abnormal growth by evaluating pre-specified perinatal and postnatal characteristics as risk and predictive factors for abnormal ND and growth. The landmark CHAP findings and the NHLBI-funded CHAP maternal follow-up study offer a truly unique opportunity and synergy for this proposed child follow-up study in order to glean the complete picture of long- term effects of prenatal antihypertensive therapy and preeclampsia on offspring.