R01HD112994

Offspring neurodevelopment and growth after early antihypertensive therapy or preeclampsia in women with chronic hypertension and pregnancy (CHAP CHILD).

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.

University Of Alabama At Birmingham

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Birmingham, Alabama 352940004 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 187% from $1,639,665 to $4,709,482.