Testing the Developmental Origins Hypothesis

• Conditions: Diabetes; Stroke; Obesity

• Registration Number: NCT01545492
• Lead Sponsor: Children's & Women's Health Centre of British Columbia

Brief Summary

INTRODUCTION: 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.

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.

Detailed Description

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).

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-02-24
• Status Verified: 2012-03
• Study First Submitted QC: 2012-03-01
• Last Update Submitted: 2012-03-01
• Study First Posted: 2012-03-06
• Last Update Posted: 2012-03-06
• Primary Completion: 2019-01
• Study Completion: 2019-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 626

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
difference in 'change in z score for weight' at 12 m(+/- 2m)	birth to 12m (+/-2m) of age, 24m, 36m, 48m, 60m	Between-group difference in early postnatal weight gain ('change in z score for weight') between birth and 12 m (p\<0.05), 24m, 36m, 48m \& 60m.

Secondary Outcome Measures

Name	Time	Method
differences in DNA methylation	average of 12 m (+/- 2m) of age	Buccal swab samples collected at 12m (+/-2m) of age will be assessed for 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.
hypothalamic pituitary adrenal axis function	average of 12m (+/-2m) of age	Hair collected at 12m (+/-2m) of age will be analysed for hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production).

Trial Locations

Locations (41)

Yale-New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Norton Hospital Downtown & Suburban; 🇺🇸 Louisville, Kentucky, United States

Copper University Hospital; 🇺🇸 Camden, New Jersey, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Ipswich Hospital; 🇦🇺 Ipswich, Australia

King Edward Memorial Hospital; 🇦🇺 Subiaco, Australia

Royal Alexandra Hospital; 🇨🇦 Edmonton, Alberta, Canada

Surrey Memorial Hospital: Jim Pttison Outpatient Care & Surgery Centre; 🇨🇦 Surrey, British Columbia, Canada

BC Children & Women's Health Centre; 🇨🇦 Vancouver, British Columbia, Canada

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Scroll for more (31 remaining)