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

慢性高血压和妊娠妇女（CHAP 儿童）早期抗高血压治疗或先兆子痫后的后代神经发育和生长。

• 批准号: 10745527
• 负责人: Paula Catherine Chandler-Laney
• 金额: $ 163.97万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745527
• 关键词: Address; Affect; Age; Age Years; Ancillary Study; Antihypertensive Agents; Authorization documentation; Birth Weight; Blood; Blood Pressure; Body mass index; Cardiometabolic Disease; Cardiovascular system; Cerebral Palsy; Characteristics; Child; Child Health; Childhood; Chronic; Classification; Complement; Data; Desire for food; Diabetes Mellitus; Diet; Disease; Dose; Eating Behavior; Enrollment; Ethnic Origin; Fetal Growth Retardation; Follow-Up Studies; Frequencies; Funding; Future; Gestational Age; Glean; Goals; Growth; Guidelines; Health; Household; Hypertension; Impaired cognition; Impairment; Knowledge; Long-Term Effects; Low Birth Weight Infant; Measures; Mediator; Medical; Morbidity - disease rate; Mothers; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Neonatal; Neonatal Mortality; Newborn Infant; Obesity; Outcome; Overweight; Participant; Patients; Perinatal; Persons; Pharmacological Treatment; Physical activity; Pre-Eclampsia; Predictive Factor; Pregnancy; Pregnancy Tests; Pregnant Women; Premature Birth; Prevention strategy; Race; Randomized; Recommendation; Risk Factors; Safety; Site; Small for Gestational Age Infant; Specific qualifier value; Strategic Planning; Stress; Testing; Underweight; Visit; Woman; adjudication; adverse outcome; authority; blood pressure elevation; cardiometabolism; cardiorespiratory fitness; cognitive function; follow-up; functional disability; high risk population; hypertension treatment; improved; neurodevelopment; offspring; perinatal outcomes; postnatal; prenatal; primary outcome; randomized trial; social; synergism; treatment trial

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.

慢性高血压和妊娠(CHAP)随机试验最近导致了新的国家 妊娠期慢性高血压(CHTN)的降压治疗建议。 在美国61个地点对轻度CHTN(BP&lt；160/105 mm Hg)在23周前开始CHAP测试治疗(与无治疗相比) 2408例。治疗可改善孕产妇和围产儿结局，包括先兆子痫、早产和低血压 出生体重。CHAP是孕期最大的CHTN治疗试验。然而，关键的知识差距 仍然关注a)常规产前降压治疗的长期效果和b) CHTN患者暴露于子代的叠加先兆子痫。先兆子痫并发30% 在CHTN患者中，与胎儿生长受损有关，新出现的数据表明先兆子痫可能 损害神经发育(ND)和儿童生长/心脏代谢结果-包括BMI升高和 血压(BP)。小于胎龄是儿童ND和ND受损的独立危险因素 改变了生长。因此，明确产前抗高血压治疗的长期疗效至关重要。 子女(以及我们资助的CHAP母亲跟踪研究中的母亲R01HL120338)。CHAP有 随机治疗和判定的先兆子痫数据，以增强解决以下问题的严谨性： 目的1：确定轻度CHTN产前常规药物治疗对儿童ND的长期安全性 和增长。假设1a：轻度CHTN的降压治疗以BP为目标&140/90毫米汞柱比较 不接受治疗与包括一般确定的认知功能在内的更差的ND无关 概念能力(GCA，主要结果)。如果我们表现出不自卑，我们也将测试是否治疗 改善CHAP中给予ND的有益新生儿的结果。假设1b：抗高血压治疗(目标：140/90 与不治疗轻度CHTN相比，儿童生长发育较差和其他心脏代谢不良并不相关 结果包括体重指数≥第85个百分位数(主要结果)、肥胖、体重不足和血压。 目的2：确定轻度CHTN合并先兆子痫是否与儿童结局有关 包括ND、生长和其他心脏代谢结果。假设2a：先兆子痫(与无先兆子痫相比) 与儿童不良ND独立相关，包括GCA的认知功能受损 (主要结果)。假设2b：先兆子痫与儿童期发育改变独立相关 (包括体重指数≥第85百分位数的主要结果)、肥胖、体重不足、连续增长和血压。我们还将 通过评估预先指定的围产期和出生后儿童ND和异常生长的机制 作为ND和生长异常的危险和预测因素的特征。 具有里程碑意义的CHAP发现和NHLBI资助的CHAP产妇随访研究提供了真正独特的 为这项拟议的儿童跟踪研究提供机会和协同作用，以收集有关长期和长期儿童的完整情况 产前抗高血压治疗和子痫前期对子代的远期影响。