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）随机试验最近导致新的国家