Clinical trial NCT01545492: Testing the Developmental Origins Hypothesis
Official title: CHIPS-Child:Testing the Developmental Origins Hypothesis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes
Stroke
Obesity
Keywords: CHIPS
famine
reprogramming
developmental
blood
pressure
randomised
randomized
hypertension
anthropometry
measurement
genetics
epigenetics
methylation
cortisol
stress
DNA
growth
weight
length
height
Lead sponsor: Children's & Women's Health Centre of British Columbia
Sponsor class: OTHER
First posted: 2012-03-06
Enrollment: 626
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Only women participating in the CHIPS RCT and their children born after recruitment are eligible to participate in CHIPS-Child.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: difference in 'change in z score for weight' at 12 m(+/- 2m)
timeFrame: birth to 12m (+/-2m) of age, 24m, 36m, 48m, 60m
Secondary outcomes:
measure: hypothalamic pituitary adrenal axis function
timeFrame: average of 12m (+/-2m) of age
measure: differences in DNA methylation
timeFrame: average of 12 m (+/- 2m) of age
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Louisville
country: United States
facility: Norton Hospital Downtown & Suburban
state: Kentucky
city: Camden
country: United States
facility: Copper University Hospital
state: New Jersey
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Ipswich
country: Australia
facility: Ipswich Hospital
city: Subiaco
country: Australia
facility: King Edward Memorial Hospital
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Surrey
country: Canada
facility: Surrey Memorial Hospital: Jim Pttison Outpatient Care & Surgery Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BC Children & Women's Health Centre
state: British Columbia
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Sherbrooke
country: Canada
facility: CHUS Fleurimont
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Sainte-Justine
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Osorno
country: Chile
facility: Hospital Base Osorno
city: Puente Alto
country: Chile
facility: Hospital Dr Sotero del Rio
city: Tartu
country: Estonia
facility: Tartu University Hospital - Women's Clinic
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: VU Medical Center
city: Groningen
country: Netherlands
facility: UMCG
city: Hilversum
country: Netherlands
facility: Tergooiziekenhuizen
city: Maastricht
country: Netherlands
facility: MUMC Maastricht
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis
city: Utrecht
country: Netherlands
facility: Diakonessen Ziekenhuis
city: Utrecht
country: Netherlands
facility: UMCU
city: Veldhoven
country: Netherlands
facility: Maxima Medical Centre
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
city: Christchurch
country: New Zealand
facility: Christchurch Women's Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Women's Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Ormskirk
country: United Kingdom
facility: Southport & Ormskirk Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sunderland
country: United Kingdom
facility: City Hospitals Sunderland NHS Foundation Trust
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: BC Children & Women's Health Centre
name: Laura A Magee, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363-88. doi: 10.1146/annurev.nutr.27.061406.093705.
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. doi: 10.1007/BF00439006.
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. doi: 10.1016/j.reprotox.2005.04.005.
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.
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. doi: 10.2223/JPED.1728.
citation: 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. doi: 10.1002/ajpa.10183.