Metformin for pregnancy and beyond: the pros and cons

Newman, C. & Dunne, F. P. | 2021| Metformin for pregnancy and beyond: the pros and cons | Diabetic Medicine | https://doi.org/10.1111/dme.14700

The authors of this review set out to review the benefits and potential pitfalls of metformin use in pregnancy. To this end they conducted a literature search of web-based databases (including PubMed, CENTRAL via the Cochrane Library and EMBASE) using identified search terms. They read the full texts of any relevant texts published in English and searched clinicaltrials.gov for relevant unpublished trials. The team included randomised controlled trials (RCTs), cluster RCTs, pilot and feasibility studies in our review. They excluded conference abstracts, case reports and case series. Observational data which were deemed to be of high quality were also considered. Additionally, the researchers searched bibliographies for all relevant publications to identify other studies.

In this paper they report their findings that metformin has many maternal advantages when taken during and after pregnancy, including reduced maternal GWG, PTD and insulin requirements, a reduction in operative delivery and possible reduction in hypertensive disorders and future type 2 diabetes. Some benefits are even greater for women with a BMI more than or equal to 30 kg/m2 (Source: Newman & Dunne, 2021).

Abstract

Context and Aim

Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period.

Methods

We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies.

Results

There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy.

Conclusion

Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.

  • Metformin has been used outside of pregnancy for decades and has multiple benefits in pregnancy including reduced weight gain and a potential decrease in pre-eclampsia (PET).
  • However, some clinicians have concerns regarding its use due to increased rates of small for gestational age (SGA) births and adiposity in infants exposed to metformin.
  • With the rising rates of obesity and gestational diabetes (GDM), cheap, acceptable and effective treatments for hyperglycaemia are needed.
  • This study follows the use of metformin from the pre-conception to the post-partum period and examines the evidence for and against its use.

The primary paper is available from the journal Diabetic Medicine

The impact of COVID-19 on the physical activity and sedentary behaviour levels of pregnant women with gestational diabetes #Covid19RftLks

Hillyard, M., Sinclair, M., Murphy, M., Casson, K. & Mulligan, C. | 2021 | The impact of COVID-19 on the physical activity and sedentary behaviour levels of pregnant women with gestational diabetes | PLoS ONE | 16 | 8 | e0254364. https://doi.org/10.1371/journal.pone.0254364

The authors’ objective was to understand how COVID-19 has affected the self-reported physical activity and sedentary behaviour levels of pregnant women with gestational diabetes mellitus (GDM). To this end they surveyed over 500 participants using an online survey to gauge levels of physical activity and sedentary behaviour in this population.

The COVID-19 pandemic has had a considerable impact on the activity levels of pregnant women with gestational diabetes and for the researchers of this study, highlights the need for targeted public health initiatives. In their paper they underline that the findings of their study will help policy makers and health service providers to understand how best to support pregnant women during subsequent waves of COVID-19 or future pandemics or situations requiring lockdown.

Abstract

Background

The aim of this study was to understand how physical activity and sedentary behaviour levels of pregnant women with gestational diabetes in the UK have been affected by COVID-19.

Methods

An online survey exploring physical activity and sedentary behaviour levels of pregnant women with gestational diabetes during COVID-19 was distributed through social media platforms. Women who had been pregnant during the COVID-19 outbreak and had gestational diabetes, were resident in the UK, were 18 years old or over and could understand written English were invited to take part.

Results

A total of 724 women accessed the survey, 553 of these met the eligibility criteria and took part in the survey. Sedentary time increased for 79 per cent of the women during the pandemic. Almost half of the women (47 per cent) were meeting the physical activity guidelines pre COVID-19 during their pregnancy, this dropped to 23 per cent during the COVID-19 pandemic. Fear of leaving the house due to COVID-19 was the most commonly reported reason for the decline. Significant associations were found between meeting the physical activity guidelines during COVID-19 and educational attainment, fitness equipment ownership and knowledge of how to exercise safely in pregnancy.

Conclusions and implications

These results show the impact of COVID-19 on physical activity and sedentary behaviour levels and highlight the need for targeted public health initiatives as the pandemic continues and for future lockdowns. Women with gestational diabetes need to know how it is safe and beneficial to them to engage in physical activity and ways to do this from their homes if fear of leaving the house due to COVID-19 is a barrier for them. Online physical activity classes provided by certified trainers in physical activity for pregnant women may help them remain active when face-to-face appointments are reduced and limited additional resources are available.

The impact of COVID-19 on the physical activity and sedentary behaviour levels of pregnant women with gestational diabetes [primary paper]

Maternal gestational diabetes linked to diabetes in children

OnMedica | April 2019 | Maternal gestational diabetes linked to diabetes in children

Children whose mothers had gestatational diabetes during their pregancy are more likely to develop diabetes, finds new research.  The study published in the Canadian Medical Association Journal (CMAJ) analysed data  from 73,180 mothers and the researchers compared data on single births from mothers with gestational diabetes to births from mothers without gestational diabetes. They found an association between gestational diabetes mellitus and incidence of childhood- and youth-onset diabetes in offspring with the incidence of  pediatric diabetes was higher in offspring born to mothers with gestational diabetes mellitus than in mothers without gestational diabetes mellitus. 

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A child or teen whose mother had gestational diabetes was therefore nearly twice as likely to develop diabetes before the age of 22 years than a child or teen whose mother did not experience gestational diabetes.

An association between gestational diabetes and diabetes in children was found from birth to age 22 years, from birth to 12 years, and from 12 to 22 years (Source: OnMedica)

OnMedica Maternal gestational diabetes linked to diabetes in children

The article is available to read in full from CMAJ 

Full referene:

Blotsky, A.L.,  Rahme, E., Dahhou, M., Nakhla, M., Dasgupta, K. | 2019| Gestational diabetes associated with incident diabetes in childhood and youth: a retrospective cohort study

Abstract

BACKGROUND: Indicators of childhood- and youth-onset diabetes may be useful for early detection of diabetes; there is a known association between composite exposure of parental type 2 diabetes and gestational diabetes mellitus with childhood- and youth-onset diabetes. We examined associations between gestational diabetes mellitus and incidence of childhood- and youth-onset diabetes in offspring.

METHODS: Using public health insurance administrative databases from Quebec, Canada, we randomly selected singleton live births with maternal gestational diabetes mellitus (1990–2007) and matched them 1:1 with singleton live births without gestational diabetes mellitus. Follow-up was to Mar. 31, 2012. We examined associations of diabetes in offspring with maternal gestational diabetes mellitus through unadjusted and adjusted Cox proportional hazards models. In secondary analyses, we separately considered age groups ranging from birth to age 12 years, and age 12 to 22 years.

RESULTS: Incidence of pediatric diabetes (per 10 000 person-years) was higher in offspring born to mothers with gestational diabetes mellitus than in mothers without gestational diabetes mellitus. In an adjusted Cox proportional hazards model, maternal gestational diabetes mellitus was associated with development of pediatric diabetes overall, during childhood, and in youth.

INTERPRETATION: Gestational diabetes mellitus is associated with incident diabetes in offspring during childhood and adolescence. Future studies are needed to examine longer-term outcomes in patients with pediatric diabetes with a maternal history of gestational diabetes mellitus, to ascertain how they compare with other patients with childhood- or youth-onset diabetes, in terms of disease severity and outcomes.

More than 90% of childhood- and youth-onset diabetes in Canada is type 1 diabetes.

The research article is available to read from CMAJ 

Diet and exercise can reduce the risk of developing diabetes during pregnancy

NIHR Signal | January 2019 | Diet and exercise can reduce the risk of developing diabetes during pregnancy

A recent NIHR Signal underlines a systematic review which found that any form of lifestyle intervention reduced the risk of gestational diabetes by 23%, with similar effects for diet, exercise or both. Interventions were most successful when targeted at high-risk populations, though body mass index alone was not associated with an effect.

Diet and exercise are effective ways of preventing the development of diabetes during pregnancy, known as gestational diabetes.

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Gestational diabetes is becoming more common and is associated with poorer outcomes for mother and baby. Diet, physical activity and weight are modifiable risk factors, but trials published to date have shown inconsistent results.

As the authors suggest, comprehensive risk assessments that consider body mass index alongside other risk factors may help to identify women who could benefit most from structured lifestyle interventions during pregnancy

NIHR Signal Diet and exercise can reduce the risk of developing diabetes during pregnancy

ABSTRACT

BACKGROUND: Diet and exercise during pregnancy have been used to prevent gestational diabetes mellitus (GDM) with some success.

OBJECTIVES: To examine the effectiveness of lifestyle intervention on GDM prevention and to identify key effectiveness moderators to improve prevention strategy.

SEARCH STRATEGY: Pubmed, Scopus, Cochrane and cross-references were searched.

SELECTION CRITERIA:
Randomized controlled trials (RCTs) evaluating lifestyle interventions during pregnancy for GDM prevention.

DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data. Random-effects model was used to analyze the relative risk and 95% confidence interval (RR and 95% CI). Meta-regressions and subgroup analyses were used to investigate important moderators of effectiveness.

MAIN RESULTS: 47 RCTs involving 15745 participants showed that diet and exercise during pregnancy were preventive of GDM (RR 0.77, 95% CI [0.69; 0.87]). Four key aspects were identified to improve the preventive effect: targeting on the high-risk population, early initiation of intervention, proper intensity and frequency of exercise, and gestational weight gain management. Although 24 RCTs targeted on overweight or obese women, BMI failed to predict the effectiveness of an intervention. Instead, interventions are most effective in high-incidence population rather than simply overweight or obese women. Furthermore, exercise of moderate intensity for 50-60 minutes twice a week could lead to about 24% reduction in GDM.

CONCLUSIONS:
The best strategy to prevent GDM is to target on high-risk population predicted by risk evaluation models and to control their gestational weight gain through intensified diet and exercise modifications early in their pregnancy. This article is protected by copyright. All rights reserved.

 

Full reference:  Guo, X. et al | 2018|  Improving the effectiveness of lifestyle interventions for gestational diabetes prevention: a meta-analysis and meta-regression| Bjog |doi.org/10.1111/1471-0528.15467