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.
