Testing the Developmental Origins Hypothesis

Obesity Clinical Trial

— CHIPS-Child  

Official title:

CHIPS-Child:Testing the Developmental Origins Hypothesis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01545492
• Other study ID #: H08-00882CHIPS-Child
• Status: Recruiting
• Phase: N/A
• First received: February 24, 2012
• Last updated: March 1, 2012
• Start date: January 2012
• Est. completion date: January 2019

Study information

• Verified date: March 2012
• Source: Children's & Women's Health Centre of British Columbia
• Contact: Kristal T Louie, MS
• Phone: 604.875.2424
• Email: CHIPS-Child[@]cw.bc.ca
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health Research
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 626
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes
• Obesity
• Stroke

Locations

Country	Name	City	State
Australia	Ipswich Hospital	Ipswich
Australia	King Edward Memorial Hospital	Subiaco
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	London Health Sciences Centre	London	Ontario
Canada	Hopital Sainte-Justine	Montreal	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	CHUS Fleurimont	Sherbrooke	Ontario
Canada	Surrey Memorial Hospital: Jim Pttison Outpatient Care & Surgery Centre	Surrey	British Columbia
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BC Children & Women's Health Centre	Vancouver	British Columbia
Chile	Hospital Base Osorno	Osorno
Chile	Hospital Dr Sotero del Rio	Puente Alto
Estonia	Tartu University Hospital - Women's Clinic	Tartu
Netherlands	Academic Medical Center	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	VU Medical Center	Amsterdam
Netherlands	UMCG	Groningen
Netherlands	Tergooiziekenhuizen	Hilversum
Netherlands	MUMC Maastricht	Maastricht
Netherlands	St Antonius Ziekenhuis	Nieuwegein
Netherlands	Diakonessen Ziekenhuis	Utrecht
Netherlands	UMCU	Utrecht
Netherlands	Maxima Medical Centre	Veldhoven
Netherlands	Isala Klinieken Zwolle	Zwolle
New Zealand	Christchurch Women's Hospital	Christchurch
United Kingdom	Birmingham Women's Hospital	Birmingham
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Royal Lancaster Infirmary	Lancaster
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Southport & Ormskirk Hospital	Ormskirk
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	City Hospitals Sunderland NHS Foundation Trust	Sunderland
United Kingdom	Singleton Hospital	Swansea
United Kingdom	New Cross Hospital	Wolverhampton
United Kingdom	York District Hospital	York
United States	Copper University Hospital	Camden	New Jersey
United States	Norton Hospital Downtown & Suburban	Louisville	Kentucky
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Children's & Women's Health Centre of British Columbia

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  Estonia,  Netherlands,  New Zealand,  United Kingdom, 

References & Publications (7)

Cameron N, Demerath EW. Critical periods in human growth and their relationship to diseases of aging. Am J Phys Anthropol. 2002;Suppl 35:159-84. Review. — View Citation

Gilbert EF, Varakis J, Opitz JM, ZuRhein GM, Ware R, Viseskul C, Kaveggia EG, Hartmann HA. Generalized gangliosidosis type II (juvenile GM1 gangliosidosis). A pathological, histochemical and ultrastructural study. Z Kinderheilkd. 1975 Sep 11;120(3):151-80. — View Citation

Painter RC, Roseboom TJ, Bleker OP. Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol. 2005 Sep-Oct;20(3):345-52. Review. — View Citation

Silveira PP, Portella AK, Goldani MZ, Barbieri MA. Developmental origins of health and disease (DOHaD). J Pediatr (Rio J). 2007 Nov-Dec;83(6):494-504. Review. — View Citation

Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009 Nov 1;18(21):4046-53. doi: 10.1093/hmg/ddp353. Epub 2009 Aug 4. — View Citation

Wadhwa PD, Buss C, Entringer S, Swanson JM. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med. 2009 Sep;27(5):358-68. doi: 10.1055/s-0029-1237424. Epub 2009 Aug 26. Review. — View Citation

Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No