OS082. CHIPS-Child: Testing the developmental origins hypothesis

Abstract

CHIPS-Child is a natural test of the Developmental Origins of Health and Disease hypothesis (DOHaD) [1,2]. Reduced fetal growth rate is associated with adult cardiovascular risk markers (e.g., obesity) and disease [3,4]. Evidence worldwide indicates that this relationship is independent of birth weight. The leading theory describes 'developmental programming'in utero leading to permanent alteration of the fetal genome. While those changes are adaptive in utero, they may be maladaptive postnatally. To directly test, for the first time in humans, whether differential blood pressure (BP) control in pregnancy has developmental programming effects, independent of birth weight. We predict that, like famine or protein malnutrition, 'tight' (vs. 'less tight') control of maternal BP will be associated with fetal under-nutrition and effects will be consistent with developmental programming. CHIPS-Child is a parallel, ancillary study to the CHIPS randomized controlled trial (RCT). CHIPS is designed to determine whether 'less tight' control [target diastolic BP (dBP) 100mmHg] or 'tight' control [target dBP 85mmHg] of non-proteinuric hypertension in pregnancy is better for the baby without increasing maternal risk. CHIPS-Child will examine offspring of CHIPS participants non-invasively at 12m corrected post-gestational age (±2m) for anthropometry, hair cortisol, buccal swabs for epigenetic testing and a maternal questionnaire about infant feeding practices and background. Annual contact will be maintained in years 2-5 and will include annual parental measurement of the child's height, weight and waist circumference. CHIPS will recruit 1028 women. We estimate that 80% of CHIPS centres will participate in CHIPS-Child, approximately 97% of babies will survive, and 90% of children will be followed to 12m resulting in a sample size of 626. Power will be >80% to detect a between-group difference of ⩾0.25 in 'change in z-score for weight' between birth and 12m (2-sided alpha=0.05, SD 1). Recruitment has begun. The primary outcome will be the between-group difference in early postnatal weight gain ('change in z score for weight') between birth and 12m (p<0.05). Secondary:outcomes are (i) hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production); and (ii) between-groups differences in DNA methylation, using targeted (genes associated with growth, obesity, cardiovascular disease, and/or a developmental programming effect) and global (genome-wide microarray) methods. CHIPS-Child offers a unique opportunity to both clarify whether differential dBP control in pregnancy has developmental programming effects and contribute to our understanding of human biology and diversity in a way that a cross-sectional or other observational studies cannot.