Laura A Magee1, Anne R Synnes2, Peter von Dadelszen3, Anna M Hutfield4, Jean-Pierre Chanoine5, Anne-Marie Côté6, Angela M Devlin7, Jon Dorling8, Amiram Gafni9, Wessel Ganzevoort10, Michael E Helewa11, Eileen K Hutton12, Gideon Koren13, Shoo K Lee14, Dawn Mcarthur15, Evelyne Rey16, Wendy P Robinson17, Tessa J Roseboom18, Joel Singer19, Samantha Wilson20, Jean Marie Moutquin21. 1. Department of Women and Children's Health, King's College London, UK; School of Life Course Sciences, King's College London, UK. Electronic address: laura.a.magee@kcl.ac.uk. 2. Department of Paediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada. Electronic address: asynnes@cw.bc.ca. 3. Department of Women and Children's Health, King's College London, UK; School of Life Course Sciences, King's College London, UK. Electronic address: pvd@kcl.ac.uk. 4. Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada. Electronic address: Anna.Hutfield@cw.bc.ca. 5. Department of Paediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada. Electronic address: jchanoine@cw.bc.ca. 6. Department of Medicine, Universite de Sherbrooke, Canada. Electronic address: Ann-Marie.Cote@usherbrooke.ca. 7. Department of Paediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada. Electronic address: angela.devlin@ubc.ca. 8. Queens Medical Centre, Nottingham, UK. Electronic address: Jon.Dorling@nuh.nhs.uk. 9. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada. Electronic address: gafni@mcmaster.ca. 10. Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Netherlands. Electronic address: j.w.ganzevoort@amc.uva.nl. 11. Obstetrics and Gynaecology, University of Manitoba, Canada. Electronic address: mhelewa@sbgh.mb.ca. 12. Obstetrics and Gynaecology, McMaster University, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada. Electronic address: huttone@mcmaster.ca. 13. Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada. 14. Pediatrics, The Centre for Mother, Infant and Child Research, Sunnybrook Research Institute, University of Toronto, Canada. Electronic address: sklee@mtsinai.on.ca. 15. British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada. Electronic address: dmcarthur@bcchr.ca. 16. Medicine and Obstetrics and Gynaecology, University of Montreal, Canada. Electronic address: evelyne_rey@ssss.gouv.qc.ca. 17. Department of Medical Genetics, University of British Columbia, Canada. Electronic address: wrobinson@bcchr.ca. 18. Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Netherlands. Electronic address: t.j.roseboom@amc.uva.nl. 19. School of Population and Public Health, University of British Columbia, Canada. 20. Department of Medical Genetics, University of British Columbia, Canada. Electronic address: swils6@alumni.uwo.ca. 21. Obstetrics and Gynaecology, Universite de Sherbrooke, Canada. Electronic address: jean-marie.moutquin@USherbrooke.ca.
Abstract
OBJECTIVES: As a follow-up to the CHIPS trial (Control of Hypertension In Pregnancy Study) of 'less tight' (versus 'tight') control of maternal blood pressure in pregnancy, CHIPS-Child investigated potential developmental programming of maternal blood pressure control in pregnancy, by examining measures of postnatal growth rate and hypothalamic-pituitary adrenal (HPA) axis activation. METHODS: CHIPS follow-up was extended to 12 ± 2 months corrected post-gestational age for anthropometry (weight, length, head/waist circumference). For eligible children with consent for a study visit, we collected biological samples (hair/buccal samples) to evaluate HPAaxis function (hair cortisol levels) and epigenetic change (DNA methylation analysis of buccal cells). The primary outcome was 'change in z-score for weight' between birth and 12 ± 2 mos. Secondary outcomes were hair cortisol and genome-wide DNA methylation status. RESULTS: Of 683 eligible babies, 183 (26.8%) were lost to follow-up, 83 (12.2%) declined, 3 (0.4%) agreed only to ongoing contact, and 414 (60.6%) consented. 372/414 (89.9%) had weight measured at 12mos. In 'less tight' (vs. 'tight') control, the primary outcome was similar [-0.26 (-0.53, +0.01); p = 0.14, padjusted = 0.06]; median (95% confidence interval) hair cortisol (N = 35 samples) was lower [-496 (-892, -100) ng/g; p = 0.02], and buccal swab DNA methylation (N = 16 samples) was similar. No differences in growth rate could be demonstrated up to 5 years. CONCLUSIONS: Results demonstrate no compelling evidence for developmental programming of growth or the HPA axis. Clinicians should look to the clinical findings of CHIPS to guide practice. Researchers should seek to replicate these findings and extend outcomes to paediatric blood pressure and neurodevelopment.
RCT Entities:
OBJECTIVES: As a follow-up to the CHIPS trial (Control of Hypertension In Pregnancy Study) of 'less tight' (versus 'tight') control of maternal blood pressure in pregnancy, CHIPS-Child investigated potential developmental programming of maternal blood pressure control in pregnancy, by examining measures of postnatal growth rate and hypothalamic-pituitary adrenal (HPA) axis activation. METHODS: CHIPS follow-up was extended to 12 ± 2 months corrected post-gestational age for anthropometry (weight, length, head/waist circumference). For eligible children with consent for a study visit, we collected biological samples (hair/buccal samples) to evaluate HPA axis function (hair cortisol levels) and epigenetic change (DNA methylation analysis of buccal cells). The primary outcome was 'change in z-score for weight' between birth and 12 ± 2 mos. Secondary outcomes were hair cortisol and genome-wide DNA methylation status. RESULTS: Of 683 eligible babies, 183 (26.8%) were lost to follow-up, 83 (12.2%) declined, 3 (0.4%) agreed only to ongoing contact, and 414 (60.6%) consented. 372/414 (89.9%) had weight measured at 12mos. In 'less tight' (vs. 'tight') control, the primary outcome was similar [-0.26 (-0.53, +0.01); p = 0.14, padjusted = 0.06]; median (95% confidence interval) hair cortisol (N = 35 samples) was lower [-496 (-892, -100) ng/g; p = 0.02], and buccal swab DNA methylation (N = 16 samples) was similar. No differences in growth rate could be demonstrated up to 5 years. CONCLUSIONS: Results demonstrate no compelling evidence for developmental programming of growth or the HPA axis. Clinicians should look to the clinical findings of CHIPS to guide practice. Researchers should seek to replicate these findings and extend outcomes to paediatric blood pressure and neurodevelopment.