Associations Between Maternal Gestational Diabetes Metformin or Insulin Treatment and Offspring Growth Trajectories from Birth to 60 months of Age: Findings from the Born in Bradford (BiB) Study

Overview

Journal Diabet Med

Specialty Endocrinology

Date 2023 Aug 19

PMID 37597238

Authors

Gilberte Martine-Edith

William Johnson

Emily S Petherick

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate the associations between gestational diabetes mellitus (GDM) metformin or insulin treatment and offspring growth trajectories from 0 to 60 months.

Methods: Participants were from the Born in Bradford birth cohort study. Using covariate-adjusted multilevel linear spline models (4 splines: 0-1.6, 1.6-6, 6-17 and 17-60 months), we compared weight, height and body mass index (BMI) z-score trajectories of: (1) 76 offspring exposed to metformin (OGDM-Metformin) and 420 offspring exposed to insulin (OGDM-Insulin); (2) OGDM-Metformin and 9171 offspring not exposed to GDM (No-GDM); (3) OGDM-Insulin and No-GDM.

Results: (1) OGDM-Metformin had comparable growth trajectories to OGDM-Insulin from 0 to 60 months. (2) OGDM-Metformin had a lower mean birthweight z-score than No-GDM. OGDM-Metformin had faster changes in height z-score (0.13 [95% CI 0.026, 0.24]) from 17 to 60 months and by 60 months, had comparable mean BMI z-score to No-GDM. (3) OGDM-insulin had lower mean birthweight and height z-scores than No-GDM. OGDM-Insulin had faster changes in weight (0.32 [0.021, 0.62]) and height (0.50 [0.087, 0.91]) from 1.6 to 6 months and by 60 months, had comparable mean BMI z-score to No-GDM.

Conclusions: GDM metformin treatment was not associated with differences in offspring growth trajectories compared to insulin treatment. Both metformin and insulin-exposed offspring had comparable BMI z-score to No-GDM by 60 months.

Citing Articles

Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis.

Fu J, Tabbara N, Tomlinson G, Murphy K, Hamilton J, Feig D BMJ Open. 2025; 15(1):e088653.

PMID: 39779258 PMC: 11749820. DOI: 10.1136/bmjopen-2024-088653.

Associations between maternal gestational diabetes metformin or insulin treatment and offspring growth trajectories from birth to 60 months of age: Findings from the Born in Bradford (BiB) study.

Martine-Edith G, Johnson W, Petherick E Diabet Med. 2023; 40(11):e15204.

PMID: 37597238 PMC: 10946820. DOI: 10.1111/dme.15204.

References

Ijas H, Vaarasmaki M, Saarela T, Keravuo R, Raudaskoski T . A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG. 2014; 122(7):994-1000. DOI: 10.1111/1471-0528.12964. View

Crume T, Ogden L, Mayer-Davis E, Hamman R, Norris J, Bischoff K . The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study. Int J Obes (Lond). 2012; 36(4):529-34. PMC: 3323752. DOI: 10.1038/ijo.2011.254. View

Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L . IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group's Criteria. Diabetes Res Clin Pract. 2021; 183:109050. DOI: 10.1016/j.diabres.2021.109050. View

Rowan J, Rush E, Plank L, Lu J, Obolonkin V, Coat S . 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. PMC: 5905785. DOI: 10.1136/bmjdrc-2017-000456. View

Sidell M, Martinez M, Chow T, Xiang A . Types of diabetes during pregnancy and longitudinal BMI in offspring from birth to age 10 years. Pediatr Obes. 2021; 16(8):e12776. DOI: 10.1111/ijpo.12776. View

Brand K, Saarelainen L, Sonajalg J, Boutmy E, Foch C, Vaarasmaki M . Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study. BMJ Open Diabetes Res Care. 2022; 10(1). PMC: 8734020. DOI: 10.1136/bmjdrc-2021-002363. View

West J, Santorelli G, Whincup P, Smith L, Sattar N, Cameron N . Association of maternal exposures with adiposity at age 4/5 years in white British and Pakistani children: findings from the Born in Bradford study. Diabetologia. 2017; 61(1):242-252. PMC: 6046463. DOI: 10.1007/s00125-017-4457-2. View

Tarry-Adkins J, Robinson I, Reynolds R, Aye I, Charnock-Jones D, Jenkins B . Impact of Metformin Treatment on Human Placental Energy Production and Oxidative Stress. Front Cell Dev Biol. 2022; 10:935403. PMC: 9247405. DOI: 10.3389/fcell.2022.935403. View

Tam W, Ma R, Ozaki R, Li A, Chan M, Yuen L . In Utero Exposure to Maternal Hyperglycemia Increases Childhood Cardiometabolic Risk in Offspring. Diabetes Care. 2017; 40(5):679-686. PMC: 5399651. DOI: 10.2337/dc16-2397. View

10.

Wright J, Small N, Raynor P, Tuffnell D, Bhopal R, Cameron N . Cohort Profile: the Born in Bradford multi-ethnic family cohort study. Int J Epidemiol. 2012; 42(4):978-91. DOI: 10.1093/ije/dys112. View

11.

Tarry-Adkins J, Aiken C, Ozanne S . 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. PMC: 6684046. DOI: 10.1371/journal.pmed.1002848. View

12.

Martine-Edith G, Johnson W, Hunsicker E, Hamer M, Petherick E . Associations between maternal characteristics and pharmaceutical treatment of gestational diabetes: an analysis of the UK Born in Bradford (BiB) cohort study. BMJ Open. 2021; 11(11):e053753. PMC: 8572403. DOI: 10.1136/bmjopen-2021-053753. View

13.

Prentice P, Olga L, Petry C, Simmons D, Murphy H, Hughes I . Reduced size at birth and persisting reductions in adiposity in recent, compared with earlier, cohorts of infants born to mothers with gestational diabetes mellitus. Diabetologia. 2019; 62(11):1977-1987. PMC: 6805804. DOI: 10.1007/s00125-019-4970-6. View

14.

. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2019; 43(Suppl 1):S14-S31. DOI: 10.2337/dc20-S002. View

15.

Martine-Edith G, Johnson W, Petherick E . Associations between maternal gestational diabetes metformin or insulin treatment and offspring growth trajectories from birth to 60 months of age: Findings from the Born in Bradford (BiB) study. Diabet Med. 2023; 40(11):e15204. PMC: 10946820. DOI: 10.1111/dme.15204. View

16.

West J, Lawlor D, Fairley L, Bhopal R, Cameron N, McKinney P . UK-born Pakistani-origin infants are relatively more adipose than white British infants: findings from 8704 mother-offspring pairs in the Born-in-Bradford prospective birth cohort. J Epidemiol Community Health. 2013; 67(7):544-51. PMC: 3859677. DOI: 10.1136/jech-2012-201891. View

17.

Tertti K, Ekblad U, Koskinen P, Vahlberg T, Ronnemaa T . Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2012; 15(3):246-51. DOI: 10.1111/dom.12017. View

18.

Toftemo I, Jenum A, Sletner L . Body mass index trajectories up to preschool age in a multi-ethnic population; relations with maternal gestational diabetes, BMI and gestational weight gain. Acta Paediatr. 2020; 110(4):1239-1248. DOI: 10.1111/apa.15637. View

19.

Rowan J, Hague W, Gao W, Battin M, Moore M . Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008; 358(19):2003-15. DOI: 10.1056/NEJMoa0707193. View

20.

Howe L, Tilling K, Matijasevich A, Petherick E, Santos A, Fairley L . Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts. Stat Methods Med Res. 2013; 25(5):1854-1874. PMC: 4074455. DOI: 10.1177/0962280213503925. View