Testing the Developmental Origins Hypothesis

Study Overview
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Brief Summary
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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
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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).

Official Title
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CHIPS-Child:Testing the Developmental Origins Hypothesis

Conditions
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Diabetes, Stroke, Obesity

Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tight<br>Children born to women in the CHIPS RCT randomized to Tight blood pressure control [target diastolic BP 85mmHg] | |
| Less Tight<br>Children born to women in the CHIPS RCT randomized to Less Tight [target diastolic BP 100mmHg]. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference in 'change in z score for weight' at 12 m(+/- 2m) | 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. | birth to 12m (+/-2m) of age, 24m, 36m, 48m, 60m | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hypothalamic pituitary adrenal axis function | Hair collected at 12m (+/-2m) of age will be analysed for hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production). | average of 12m (+/-2m) of age | 
| differences in DNA methylation | 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. | average of 12 m (+/- 2m) of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHIPS, famine, reprogramming, developmental, blood, pressure, randomised, randomized, hypertension, anthropometry, measurement, genetics, epigenetics, methylation, cortisol, stress, DNA, growth, weight, length, height