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.

慢性高血压与妊娠 (CHAP) 随机试验最近导致了新的全国性研究 关于妊娠期慢性高血压（CHTN）的抗高血压治疗的建议。 23 周前在美国 61 个地点开始针对轻度 CHTN（血压 <160/105 mmHg）的 CHAP 测试治疗（对比无治疗） （N=2408）。治疗改善了孕产妇和围产期结局，包括先兆子痫、早产和低血压 出生体重。 CHAP 是最大的妊娠期 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) 的长期影响 患有 CHTN 的女性在暴露的后代中叠加先兆子痫。先兆子痫并发症>30% 患有 CHTN 的患者中，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——包括体重指数升高和 血压（BP）。小于胎龄是儿童 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对胎儿的长期影响至关重要。 后代（以及我们资助的 CHAP 母亲随访研究 R01HL120338 中的母亲）。 CHAP 有 随机治疗和判定的先兆子痫数据可提高解决以下问题的严谨性： 目标 1：确定针对儿童 ND 的轻度 CHTN 常规产前药物治疗的长期安全性 和成长。假设 1a：与轻度 CHTN 相比，降压治疗达到血压目标 <140/90 mmHg 不进行治疗与 ND 恶化无关，包括由一般确定的认知功能 概念能力（GCA，主要结果）。如果我们证明非劣效性，我们还将测试治疗是否有效 改善 ND - 在 CHAP 中提供有益的新生儿结果。假设 1b：抗高血压治疗（目标<140/90 mmHg）与不治疗相比，轻度 CHTN 与儿童生长和其他心脏代谢较差无关 结果包括 BMI ≥ 85%（主要结果）、肥胖、体重不足和血压。 目标 2：确定轻度 CHTN 叠加的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（与无先兆子痫相比） 与儿童不良 ND 独立相关，包括 GCA 导致的认知功能受损 （主要结果）。假设 2b：先兆子痫与儿童期生长改变独立相关 （包括 BMI ≥ 85% 的主要结果）、肥胖、体重不足、连续生长和血压。我们还将 通过评估预先指定的围产期和产后，探索儿童 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 CHAP 发现和 NHLBI 资助的 CHAP 产妇随访研究提供了真正独特的研究 这项拟议的儿童后续研究的机会和协同作用，以便收集长期的完整情况 产前抗高血压治疗和先兆子痫对后代的长期影响。