Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2020

Open Access 01-12-2020 | Obesity | Research article

Effect of metformin in addition to an antenatal diet and lifestyle intervention on fetal growth and adiposity: the GRoW randomised trial

Authors: Amanda J. Poprzeczny, Jennie Louise, Andrea R. Deussen, Jodie M. Dodd

Published in: BMC Endocrine Disorders | Issue 1/2020

Login to get access

Abstract

Background

The infants born to women who are overweight or obese in pregnancy are at an increased risk of being born macrosomic or large for gestational age. Antenatal dietary and lifestyle interventions have been shown to be ineffective at reducing this risk. Our aim was to examine the effects of metformin in addition to a diet and lifestyle intervention on fetal growth and adiposity among women with a BMI above the healthy range.

Methods

Women who had a body mass index ≥25 kg/m2 in early pregnancy, and a singleton gestation, were enrolled in the GRoW trial from three public maternity hospitals in metropolitan Adelaide. Women were invited to have a research ultrasounds at 28 and 36 weeks’ gestation at which ultrasound measures of fetal biometry and adiposity were obtained. Fetal biometry z-scores and trajectories were calculated. Measurements and calculations were compared between treatment groups. This secondary analysis was pre-specified.

Results

Ultrasound data from 511 women were included in this analysis. The difference in femur length at 36 weeks’ gestation was (0.07 cm, 95% CI 0.01–0.14 cm, p = 0.019) and this was was statistically significant, however the magnitude of effect was small. Differences between treatment groups for all other fetal biometry measures, z-scores, estimated fetal weight, and adiposity measures at 28 and 36 weeks’ gestation were similar.

Conclusions

The addition of metformin to dietary and lifestyle advice in pregnancy for overweight and obese women has no clinically relevant effect on ultrasound measures of fetal biometry or adiposity.

Trial registration

Australian and New Zealand Clinical Trials Registry (ACTRN12612001277​831).
Appendix
Available only for authorised users
Literature
1.
Dodd JM, Grivell RM, Nguyen MA, Chan A, Robinson JS. Maternal and perinatal health outcomes by body mass index category. Aust N Z J Obstet Gynaecol. 2011;51(2):136–40.PubMedCrossRef
2.
Kalliala I, Markozannes G, Gunter MJ, Paraskevaidis E, Gabra H, Mitra A, et al. Obesity and gynaecological and obstetric conditions: umbrella review of the literature. BMJ. 2017;359:j4511.PubMedPubMedCentralCrossRef
3.
Abenhaim HA, Kinch RA, Morin L, Benjamin A, Usher R. Effect of prepregnancy body mass index categories on obstetrical and neonatal outcomes. Arch Gynecol Obstet. 2007;275(1):39–43.PubMedCrossRef
4.
Chu SY, Kim SY, Schmid CH, Dietz PM, Callaghan WM, Lau J, et al. Maternal obesity and risk of cesarean delivery: a meta-analysis. Obesity Rev. 2007;8(5):385–94.CrossRef
5.
Australian Institute of Health and Welfare. A Picture of Overweight and Obesity in Australia 2017. Canberra ACT; 2017. Report No.: PHE 216.
6.
Dalenius K, BP, Smith B, Reinold C, Grummer-Strawn L. Pregnancy nutrition surveillance 2010 report. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention; 2012.
7.
Scheil WJK, Scott J, Catcheside B, Sage L, Kennare R. Pregnancy Outcome in South Australia 2014. In: Government of South Australia, editor. Pregnancy outcome (statistics) unit SH. Adelaide: SA Health; 2016.
8.
Sebire NJ, Jolly M, Harris JP, Wadsworth J, Joffe M, Beard RW, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord. 2001;25(8):1175–82.PubMedCrossRef
9.
Rosenberg TJ, Garbers S, Chavkin W, Chiasson MA. Prepregnancy weight and adverse perinatal outcomes in an ethnically diverse population. Obstet Gynecol. 2003;102(5 Pt 1):1022–7.PubMed
10.
Cedergren M. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol. 2004;103(2):219–24.PubMedCrossRef
11.
Freeman MD, Goodyear SM, Leith WM. A multistate population-based analysis of linked maternal and neonatal discharge records to identify risk factors for neonatal brachial plexus injury. Int J Gynaecol Obstetrics. 2017;136(3):331–6.CrossRef
12.
Callaway LK, Prins JB, Chang AM, McIntyre HD. The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust. 2006;184(2):56–9.PubMedCrossRef
13.
Doherty DA, Magann EF, Francis J, Morrison JC, Newnham JP. Pre-pregnancy body mass index and pregnancy outcomes. Int J Gynaecol Obstetrics. 2006;95(3):242–7.CrossRef
14.
Kitsantas P, Gaffney KF. Risk profiles for overweight/obesity among preschoolers. Early Hum Dev. 2010;86(9):563–8.PubMedCrossRef
15.
Rooney BL, Mathiason MA, Schauberger CW. Predictors of obesity in childhood, adolescence, and adulthood in a birth cohort. Matern Child Health J. 2011;15(8):1166–75.PubMedCrossRef
16.
Jharap VV, Santos S, Steegers EA, Jaddoe VW, Gaillard R. Associations of maternal obesity and excessive weight gain during pregnancy with subcutaneous fat mass in infancy. Early Hum Dev. 2017;108:23–8.PubMedPubMedCentralCrossRef
17.
Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111(3):e221–6.PubMedCrossRef
18.
i-WIP Collaborative Group. Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials. BMJ. 2017;358:j3119.
19.
Dodd JM, Cramp C, Sui Z, Yelland LN, Deussen AR, Grivell RM, et al. The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial. BMC Med. 2014;12(1):161.PubMedPubMedCentralCrossRef
20.
Poston L, Bell R, Croker H, Flynn AC, Godfrey KM, Goff L, et al. Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2015;3(10):767–77.PubMedCrossRef
21.
Rowan JA, Hague WM, Gao W, Battin MR, Moore MP. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003–15.PubMedCrossRef
22.
Hjorth-Hansen A, Salvesen O, Engen Hanem LG, Eggebo T, Salvesen KA, Vanky E, et al. Fetal growth and birth anthropometrics in metformin-exposed offspring born to mothers with PCOS. J Clin Endocrinol Metab. 2018;103(2):740–7.PubMedCrossRef
23.
Dodd JM, Louise J, Deussen AR, Grivell RM, Dekker G, McPhee AJ, et al. Effect of metformin in addition to dietary and lifestyle advice for pregnant women who are overweight or obese: the GRoW randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(1):15–24.
24.
Health SA. In: Health S, editor. South Australian perinatal practice guidelines: Normal pregnancy, labour and Puerperium management. Adelaide, South Australia: SA Health, Government of South Australia; 2015.
25.
26.
Hui L. Australian charts for assessing fetal growth: a review. ASUM Ultrasound Bulletin. 2008;2008:12–8.
27.
Hadlock FP, Harrist RB, Carpenter RJ, Deter RL, Park SK. Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements. Radiology. 1984;150(2):535–40.PubMedCrossRef
28.
Owen P, Harrold AJ, Farrell T. Fetal size and growth velocity in the prediction of intrapartum caesarean section for fetal distress. Br J Obstet Gynaecol. 1997;104(4):445–9.PubMedCrossRef
29.
Gardeil F, Greene R, Stuart B, Turner MJ. Subcutaneous fat in the fetal abdomen as a predictor of growth restriction. Obstet Gynecol. 1999;94(2):209–12.PubMed
30.
Larciprete G, Valensise H, Vasapollo B, Novelli GP, Parretti E, Altomare F, et al. Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies. Ultrasound Obstet Gynecol. 2003;22(6):591–7.PubMedCrossRef
31.
Bernstein IM, Catalano PM. Ultrasonographic estimation of fetal body composition for children of diabetic mothers. Investig Radiol. 1991;26(8):722–6.CrossRef
32.
Hill LM, Guzick D, Boyles D, Merolillo C, Ballone A, Gmiter P. Subcutaneous tissue thickness cannot be used to distinguish abnormalities of fetal growth. Obstet Gynecol. 1992;80(2):268–71.PubMed
33.
34.
Poprzeczny AJ, Louise J, Deussen AR, Dodd JM. The mediating effects of gestational diabetes on fetal growth and adiposity in women who are overweight and obese: secondary analysis of the LIMIT randomised trial. BJOG. 2018;125:1558–66.
35.
Australian Bureau of Statistics. Socio-Economic Indexes for Areas (SEIFA). In: Statistics ABo, editor. . Australian Capital Territory: Australian Bureau of Statistics; 2011.
36.
Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care. 2011;34(10):2279–84.PubMedPubMedCentralCrossRef
37.
Lovvik TS, Carlsen SM, Salvesen O, Steffensen B, Bixo M, Gomez-Real F, et al. Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(4):256–66.PubMedCrossRef
38.
Chiswick C, Reynolds RM, Denison F, Drake AJ, Forbes S, Newby DE, 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):778–86.PubMedPubMedCentralCrossRef
39.
Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, et al. Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med. 2016;374(5):434–43.PubMedCrossRef
40.
Dodd JM, Turnbull D, McPhee AJ, Deussen AR, Grivell RM, Yelland LN, et al. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. BMJ. 2014;348:g1285.PubMedPubMedCentralCrossRef
41.
Stephenson J, Heslehurst N, Hall J, Schoenaker D, Hutchinson J, Cade JE, et al. Before the beginning: nutrition and lifestyle in the preconception period and its importance for future health. Lancet. 2018;391(10132):1830–41.PubMedPubMedCentralCrossRef
42.
Barker M, Dombrowski SU, Colbourn T, Fall CHD, Kriznik NM, Lawrence WT, et al. Intervention strategies to improve nutrition and health behaviours before conception. Lancet. 2018;391(10132):1853–64.PubMedPubMedCentralCrossRef
43.
Sovio U, Murphy HR, Smith GC. Accelerated fetal growth prior to diagnosis of gestational diabetes mellitus: a prospective cohort study of nulliparous women. Diabetes Care. 2016;39(6):982–7.PubMedCrossRef
Metadata
Title
Effect of metformin in addition to an antenatal diet and lifestyle intervention on fetal growth and adiposity: the GRoW randomised trial
Authors
Amanda J. Poprzeczny
Jennie Louise
Andrea R. Deussen
Jodie M. Dodd
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2020
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-020-00618-0

Other articles of this Issue 1/2020

BMC Endocrine Disorders 1/2020 Go to the issue

Research article

Global prevalence of cardiometabolic risk factors in the military population: a systematic review and meta-analysis

Research article

Identification of independent factors affecting bone mineral density after successful parathyroidectomy for symptomatic hyperparathyroidism

Research article

Stereological assessment of the effects of vitamin D deficiency on the rat testis

Research article

The effects of testosterone on bone health in males with testosterone deficiency: a systematic review and meta-analysis

Research article

Efficacy and safety of lanreotide autogel compared with lanreotide 40 mg prolonged release in Chinese patients with active acromegaly: results from a phase 3, prospective, randomized, and open-label study (LANTERN)

Case report

Unusual ectopic ACTH syndrome in a patient with orbital neuroendocrine tumor, resulted false-positive outcome of BIPSS:a case report

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits