Testing the Developmental Origins Hypothesis

INTRODUCTION: Growing evidence shows that reduced fetal growth rate is associated with adult
cardiovascular risk markers (e.g., obesity) and disease, and evidence worldwide indicates
that this relationship is independent of birthweight. 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.

OBJECTIVE: To directly test, for the first time in humans, whether differential blood
pressure (BP) control in pregnancy has developmental programming effects, independent of
birthweight. 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.

METHODS: 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 is a follow up study at 12 m corrected post-gestational age (± 2 m) limited to
non-invasive examination [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 contact will include annual parental measurement of the
child's height, weight and waist circumference.

Sample size:. 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 12 m 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 12 m
(2-sided alpha=0.05, SD 1).

Inclusion Criteria:

- All women participating in CHIPS and their children born after recruitment.

Exclusion Criteria:

- Women who have experienced the loss of their pregnancy or child after recruitment
into CHIPS.