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Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood

Published online by Cambridge University Press:  17 June 2021

Liu Yang ,
Lauren Lacey ,
Sonia Whyte ,
Siobhan Quenby ,
Fiona C. Denison ,
Neeraj Dhaun ,
Jane E. Norman ,
Amanda J. Drake  and
Rebecca M. Reynolds Open the ORCID record for Rebecca M. Reynolds [Opens in a new window]
Liu Yang
Affiliation:
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Lauren Lacey
Affiliation:
Division of Reproductive Health, Warwick Medical School, University of Warwick, Warwick, UK University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Sonia Whyte
Affiliation:
Tommy’s Centre for Maternal Health, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Siobhan Quenby
Affiliation:
Division of Reproductive Health, Warwick Medical School, University of Warwick, Warwick, UK University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Fiona C. Denison
Affiliation:
Tommy’s Centre for Maternal Health, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Neeraj Dhaun
Affiliation:
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Jane E. Norman
Affiliation:
Faculty of Health Sciences, University of Bristol, Bristol, UK
Amanda J. Drake
Affiliation:
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
Rebecca M. Reynolds*
Affiliation:
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK Tommy’s Centre for Maternal Health, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
*
Address for correspondence: Rebecca M. Reynolds, Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK. Email: R.Reynolds@ed.ac.uk
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Abstract

Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child’s behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.

Keywords

Metforminchildhoodobesityvascular stiffnesscardiovascular risk
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 3 , June 2022 , pp. 390 - 394
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Cesta, CE, Cohen, JM, Pazzagli, L, et al. Antidiabetic medication use during pregnancy: an international utilization study. BMJ Open Diabetes Res Care. 2019; 7(1), e000759.CrossRefGoogle ScholarPubMed
Barbour, LA, Scifres, C, Valent, AM, et al. A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes. Am J Obstet Gynecol. 2018; 219(4), 367.e1–367.e7.CrossRefGoogle ScholarPubMed
Nguyen, L, Chan, SY, Teo, AKK. Metformin from mother to unborn child – are there unwarranted effects? EBioMedicine. 2018; 35, 394–404.CrossRefGoogle ScholarPubMed
Tarry-Adkins, JL, Aiken, CE, Ozanne, SE. Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: a systematic review and meta-analysis. PLoS Med. 2019; 16(8), e1002848.CrossRefGoogle ScholarPubMed
Hanem, LGE, Salvesen, Ø, Juliusson, PB, et al. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5–10 year follow-up of the PregMet randomised controlled trial. Lancet Child Adolesc Health. 2019; 3(3), 166–174.CrossRefGoogle ScholarPubMed
Panagiotopoulou, O, Syngelaki, A, Georgiopoulos, G, et al. Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring. Am J Obstet Gynecol. 2020; 223(2), 246.e1–246.e10.CrossRefGoogle ScholarPubMed
Chiswick, C, Reynolds, RM, Denison, F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015; 3(10), 778–786.CrossRefGoogle ScholarPubMed
Wei, W, Tölle, M, Zidek, W, van der Giet, M. Validation of the mobil-O-Graph: 24 h-blood pressure measurement device. Blood Pressure Monit. 2010; 15(4), 225–228.CrossRefGoogle ScholarPubMed
Goodman, R. The strengths and difficulties questionnaire: a research note. J Child Psychol Psychiatry 1997; 38(5), 581–586.CrossRefGoogle ScholarPubMed
Magarey, A, Golley, R, Spurrier, N, Goodwin, E, Ong, F. Reliability and validity of the Children’s Dietary Questionnaire; a new tool to measure children’s dietary patterns. Int J Pediatr Obes. 2009; 4(4), 257–265.CrossRefGoogle ScholarPubMed
Golan, M. Fifteen years of the Family Eating and Activity Habits Questionnaire (FEAHQ): an update and review. Pediatr Obes. 2014; 9(2): 92–101.CrossRefGoogle ScholarPubMed
Syngelaki, A, Nicolaides, KH, Balani, J, et al. Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med. 2016; 374(5), 434–443.CrossRefGoogle ScholarPubMed
Rowan, JA, Rush, EC, Plank, LD, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age. BMJ Open Diabetes Res Care. 2018; 6(1), e000456.CrossRefGoogle ScholarPubMed
Battin, MR, Obolonkin, V, Rush, E, Hague, W, Coat, S, Rowan, J. Blood pressure measurement at two years in offspring of women randomized to a trial of metformin for GDM: follow up data from the MiG trial. BMC Pediatr. 2015; 15, 54.CrossRefGoogle ScholarPubMed
Rø, TB, Ludvigsen, HV, Carlsen, SM, Vanky, E. Growth, body composition and metabolic profile of 8-year-old children exposed to metformin in utero . Scand J Clin Lab Invest. 2012; 72(7), 570–575.CrossRefGoogle ScholarPubMed
Menting, MD, Mintjens, S, van de Beek, C, et al. Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta-analysis of animal studies. Obes Rev. 2019; 20(5), 675–685.CrossRefGoogle ScholarPubMed
Catherine, NLA, Lever, R, Marcellus, L, et al. Retaining participants in community-based health research: a case example on standardized planning and reporting. Trials 2020; 21(1), 393.CrossRefGoogle ScholarPubMed
Dodd, JM, Grivell, RM, Deussen, AR, Hague, WM. Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes. Cochrane Database Syst Rev. 2018; 7, Cd010564.Google Scholar
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