Interventions to prevent women from developing diabetes during pregnancy: an overview of Cochrane systematic reviews

What is the issue?

Gestational diabetes mellitus (GDM) is defined as high blood glucose levels (hyperglycaemia) first detected during pregnancy. GDM can affect the health of women and their babies.

During pregnancy a woman’s body changes how it processes the nutrients from her food, to ensure that the baby is well nourished. In the first three months the mother has increased sensitivity to insulin. In the second and third trimesters her insulin sensitivity is reduced. Women with GDM have less of an initial increase in sensitivity and their insulin sensitivity is reduced beyond normal later in pregnancy, resulting in the mother developing high blood glucose levels. Her blood levels of fats are also higher than normal, which may contribute to the risk of the baby becoming large for its gestational age.

Why is this important?

Women with GDM are more likely to develop complications in pregnancy including high blood pressure and need labour to be induced. They are at increased risk later of developing type 2 diabetes. Babies born to women with GDM are more likely to be born large, and therefore to experience birth injuries. Once born, the babies are at higher risk of experiencing difficulties in breathing, jaundice and reduced blood sugar levels, and later obesity and diabetes.

There are many risk factors for GDM, making it likely that interventions before/during pregnancy could reduce the risk of women developing GDM. This overview summarises evidence from Cochrane Reviews of randomised controlled trials on interventions that might prevent GDM.

What evidence did we find?

We searched the Cochrane Library (August 2019) and identified 11 Cochrane Reviews that assessed interventions during pregnancy and reported on GDM. The reviews had findings from 71 randomised controlled trials involving 23,154 pregnant women. Interventions included diet, exercise, a combination of diet and exercise, dietary supplements, medications, and management of other health problems. The evidence from the trials ranged from very low to high quality. We identified a further 10 reviews that may provide more information on this topic in the future.

Diet and exercise

Diet and exercise together possibly reduced the risk of a woman developing GDM when compared to standard care (19 trials; 6633 women; moderate-quality evidence).

Dietary advice alone (5 trials; 1279 women; very low-quality evidence) and a low glycaemic index diet compared with a moderate to high glycaemic index diet (4 trials; 912 women; low-quality evidence) had an unclear effect on the risk of GDM. Exercise alone had an unclear effect on the risk of GDM (3 trials; 826 women; low-quality evidence).

Dietary supplements

Omega-3 fatty acid supplementation in pregnancy had no effect (12 trials; 5235 women; high-quality evidence).

Myo-inositol supplementation during pregnancy possibly reduced the risk of GDM (3 trials with 502 women; low-quality evidence).

Vitamin D supplementation in pregnancy had a possible benefit in reducing the risk of developing GDM (4 trials with 446 women; low-quality evidence). These trials were all from Asian countries and the women’s vitamin D levels before supplementation were mostly unknown.

Vitamin D given with calcium supplementation, or with calcium plus other minerals had an unclear effect.

Probiotic with dietary intervention had an unclear effect on the risk of developing GDM.

Medications

The drug metformin had a possible benefit in reducing the risk of developing GDM when given to obese pregnant women (3 trials; 892 women; moderate-quality evidence).

Low- to very low-quality evidence from eight small trials showed unclear effect on GDM risk for heparin, aspirin, leukocyte immunisation or immunoglobulin (IgG) given to women who had previously experienced a stillbirth.

Management of other health issues

Universal versus risk-based screening for thyroid problems had no effect on the risk of GDM (1 trial; 4516 women; moderate-quality evidence). Two different approaches to management of the mothers’ asthma had an unclear effect (low-quality evidence).

What does this mean?

A combination of exercise and diet, supplementation with myo-inositol and vitamin D supplementation were of possible benefit in reducing the risk of developing GDM. Further high-quality evidence from randomised controlled trials is needed to confirm these results, and to look further at the use of metformin. No trials assessed interventions before pregnancy.

Authors' conclusions: 

No interventions to prevent GDM in 11 systematic reviews were of clear benefit or harm. A combination of exercise and diet, supplementation with myo-inositol, supplementation with vitamin D and metformin were of possible benefit in reducing the risk of GDM, but further high-quality evidence is needed. Omega-3-fatty acid supplementation and universal screening for thyroid dysfunction did not alter the risk of GDM. There was insufficient high-quality evidence to establish the effect on the risk of GDM of diet or exercise alone, probiotics, vitamin D with calcium or other vitamins and minerals, interventions in pregnancy after a previous stillbirth, and different asthma management strategies in pregnancy. There is a lack of trials investigating the effect of interventions prior to or between pregnancies on risk of GDM.

Read the full abstract...
Background: 

The prevalence of gestational diabetes mellitus (GDM) is increasing, with approximately 15% of pregnant women affected worldwide, varying by country, ethnicity and diagnostic thresholds. There are associated short- and long-term health risks for women and their babies.

Objectives: 

We aimed to summarise the evidence from Cochrane systematic reviews on the effects of interventions for preventing GDM.

Methods: 

We searched the Cochrane Database of Systematic Reviews (6 August 2019) with key words ‘gestational diabetes’ OR ’GDM’ to identify reviews pre-specifying GDM as an outcome. We included reviews of interventions in women who were pregnant or planning a pregnancy, irrespective of their GDM risk status. Two overview authors independently assessed eligibility, extracted data and assessed quality of evidence using ROBIS and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm (GRADE moderate- or high-quality evidence with a confidence interval (CI) that did not cross the line of no effect); clear evidence of no effect or equivalence (GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect); possible benefit or harm (low-quality evidence with a CI that did not cross the line of no effect or GRADE moderate- or high-quality evidence with a wide CI); or unknown benefit or harm (GRADE low-quality evidence with a wide CI or very low-quality evidence).

Main results: 

We included 11 Cochrane Reviews (71 trials, 23,154 women) with data on GDM. Nine additional reviews pre-specified GDM as an outcome, but did not identify GDM data in included trials. Ten of the 11 reviews were judged to be at low risk of bias and one review at unclear risk of bias. Interventions assessed included diet, exercise, a combination of diet and exercise, dietary supplements, pharmaceuticals, and management of other health problems in pregnancy. The quality of evidence ranged from high to very low.

Diet

Unknown benefit or harm: there was unknown benefit or harm of dietary advice versus standard care, on the risk of GDM: risk ratio (RR) 0.60, 95% CI 0.35 to 1.04; 5 trials; 1279 women; very low-quality evidence. There was unknown benefit or harm of a low glycaemic index diet versus a moderate-high glycaemic index diet on the risk of GDM: RR 0.91, 95% CI 0.63 to 1.31; 4 trials; 912 women; low-quality evidence.

Exercise

Unknown benefit or harm: there was unknown benefit or harm for exercise interventions versus standard antenatal care on the risk of GDM: RR 1.10, 95% CI 0.66 to 1.84; 3 trials; 826 women; low-quality evidence.

Diet and exercise combined

Possible benefit: combined diet and exercise interventions during pregnancy versus standard care possibly reduced the risk of GDM: RR 0.85, 95% CI 0.71 to 1.01; 19 trials; 6633 women; moderate-quality evidence.

Dietary supplements

Clear evidence of no effect: omega-3 fatty acid supplementation versus none in pregnancy had no effect on the risk of GDM: RR 1.02, 95% CI 0.83 to 1.26; 12 trials; 5235 women; high-quality evidence.

Possible benefit: myo-inositol supplementation during pregnancy versus control possibly reduced the risk of GDM: RR 0.43, 95% CI 0.29 to 0.64; 3 trials; 502 women; low-quality evidence.

Possible benefit: vitamin D supplementation versus placebo or control in pregnancy possibly reduced the risk of GDM: RR 0.51, 95% CI 0.27 to 0.97; 4 trials; 446 women; low-quality evidence.

Unknown benefit or harm: there was unknown benefit or harm of probiotic with dietary intervention versus placebo with dietary intervention (RR 0.37, 95% CI 0.15 to 0.89; 1 trial; 114 women; very low-quality evidence), or probiotic with dietary intervention versus control (RR 0.38, 95% CI 0.16 to 0.92; 1 trial; 111 women; very low-quality evidence) on the risk of GDM. There was unknown benefit or harm of vitamin D + calcium supplementation versus placebo (RR 0.33, 95% CI 0.01 to 7.84; 1 trial; 54 women; very low-quality evidence) or vitamin D + calcium + other minerals versus calcium + other minerals (RR 0.42, 95% CI 0.10 to 1.73; 1 trial; 1298 women; very low-quality evidence) on the risk of GDM.

Pharmaceutical

Possible benefit: metformin versus placebo given to obese pregnant women possibly reduced the risk of GDM: RR 0.85, 95% CI 0.61 to 1.19; 3 trials; 892 women; moderate-quality evidence.

Unknown benefit or harm: eight small trials with low- to very low-quality evidence showed unknown benefit or harm for heparin, aspirin, leukocyte immunisation or IgG given to women with a previous stillbirth on the risk of GDM.

Management of other health issues

Clear evidence of no effect: universal versus risk based screening of pregnant women for thyroid dysfunction had no effect on the risk of GDM: RR 0.93, 95% CI 0.70 to 1.25; 1 trial; 4516 women; moderate-quality evidence.

Unknown benefit or harm: there was unknown benefit or harm of using fractional exhaled nitrogen oxide versus a clinical algorithm to adjust asthma therapy on the risk of GDM: RR 0.74, 95% CI 0.31 to 1.77; 1 trial; 210 women; low-quality evidence. There was unknown benefit or harm of pharmacist led multidisciplinary approach to management of maternal asthma versus standard care on the risk of GDM: RR 5.00, 95% CI 0.25 to 99.82; 1 trial; 58 women; low-quality evidence.

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