Probiotics for preventing gestational diabetes.

Abstract

Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014. To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies. Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract camefrom the final analysis. Otherwise, the abstract wasleft awaiting classification. Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese womenand three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overallexceptforone study that had an unclear risk ofbias. We excluded two studies, eight studies were ongoingand three studies are awaiting classification. Six included studies with 1440participantsevaluated the risk of GDM.It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR)0.80, 95% confidence interval (CI)0.54to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence waslow certainty due to substantial heterogeneityand wideCIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04to 3.29; 4 studies, 955women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96to 2.01, 4studies, 955women), although the CIs for hypertensive disorders of pregnancyalso indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6studies, 1520women;high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probioticsprobably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72to 1.36;4studies, 919infants; moderate-certainty evidence) andmay make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01to 8.02; 3studies, 709infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2studies, 623infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence).No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetesorneurosensory disability. Low-certainty evidence from six trials has not clearly identified the effect of probiotics onthe risk of GDM. However, high-certainty evidence suggests thereis anincreased risk of pre-eclampsiawith probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIsand low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.