Different intensities of glycaemic control for women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) has major short- and long-term implications for both the mother and her baby. GDM is defined as a carbohydrate intolerance resulting in hyperglycaemia or any degree of glucose intolerance with onset or first recognition during pregnancy from 24 weeks' gestation onwards and which resolves following the birth of the baby. Rates for GDM can be as high as 25% depending on the population and diagnostic criteria used, and overall rates are increasing globally. There is wide variation internationally in glycaemic treatment target recommendations for women with GDM that are based on consensus rather than high-quality trials. OBJECTIVES: To assess the effect of different intensities of glycaemic control in pregnant women with GDM on maternal and infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (26 September 2022), and reference lists of the retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs. Trials were eligible for inclusion if women were diagnosed with GDM during pregnancy and the trial compared tighter and less-tight glycaemic targets during management. We defined tighter glycaemic targets as lower numerical glycaemic concentrations, and less-tight glycaemic targets as higher numerical glycaemic concentrations. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for carrying out data collection, assessing risk of bias, and analysing results. Two review authors independently assessed trial eligibility for inclusion, evaluated risk of bias, and extracted data for the four included studies. We assessed the certainty of evidence for selected outcomes using the GRADE approach. Primary maternal outcomes included hypertensive disorders of pregnancy and subsequent development of type 2 diabetes. Primary infant outcomes included perinatal mortality, large-for-gestational-age, composite of mortality or serious morbidity, and neurosensory disability. MAIN RESULTS: This was an update of a previous review completed in 2016. We included four RCTs (reporting on 1731 women) that compared a tighter glycaemic control with less-tight glycaemic control in women diagnosed with GDM. Three studies were parallel RCTs, and one study was a stepped-wedged cluster-RCT. The trials took place in Canada, New Zealand, Russia, and the USA. We judged the overall risk of bias to be unclear. Two trials were only published in abstract form. Tight glycaemic targets used in the trials ranged between ≤ 5.0 and 5.1 mmol/L for fasting plasma glucose and ≤ 6.7 and 7.4 mmol/L postprandial. Less-tight targets for glycaemic control used in the included trials ranged between < 5.3 and 5.8 mmol/L for fasting plasma glucose and < 7.8 and 8.0 mmol/L postprandial. For the maternal outcomes, compared with less-tight glycaemic control, the evidence suggests a possible increase in hypertensive disorders of pregnancy with tighter glycaemic control (risk ratio (RR) 1.16, 95% confidence interval (CI) 0.80 to 1.69, 2 trials, 1491 women; low certainty evidence); however, the 95% CI is compatible with a wide range of effects that encompass both benefit and harm. Tighter glycaemic control likely results in little to no difference in caesarean section rates (RR 0.98, 95% CI 0.82 to 1.17, 3 studies, 1662 women; moderate certainty evidence) or induction of labour rates (RR 0.96, 95% CI 0.78 to 1.18, 1 study, 1096 women; moderate certainty evidence) compared with less-tight control. No data were reported for the outcomes of subsequent development of type 2 diabetes, perineal trauma, return to pre-pregnancy weight, and postnatal depression. For the infant outcomes, it was difficult to determine if there was a difference in perinatal mortality (RR not estimable, 2 studies, 1499 infants; low certainty evidence), and there was likely no difference in being large-for-gestational-age (RR 0.96, 95% CI 0.72 to 1.29, 3 studies, 1556 infants; moderate certainty evidence). The evidence suggests a possible reduction in the composite of mortality or serious morbidity with tighter glycaemic control (RR 0.84, 95% CI 0.55 to 1.29, 3 trials, 1559 infants; low certainty evidence); however, the 95% CI is compatible with a wide range of effects that encompass both benefit and harm. There is probably little difference between groups in infant hypoglycaemia (RR 0.92, 95% CI 0.72 to 1.18, 3 studies, 1556 infants; moderate certainty evidence). Tighter glycaemic control may not reduce adiposity in infants of women with GDM compared with less-tight control (mean difference -0.62%, 95% CI -3.23 to 1.99, 1 study, 60 infants; low certainty evidence), but the wide CI suggests significant uncertainty. We found no data for the long-term outcomes of diabetes or neurosensory disability. Women assigned to tighter glycaemic control experienced an increase in the use of pharmacological therapy compared with women assigned to less-tight glycaemic control (RR 1.37, 95% CI 1.17 to 1.59, 4 trials, 1718 women). Tighter glycaemic control reducedadherence with treatment compared with less-tight glycaemic control (RR 0.41, 95% CI 0.32 to 0.51, 1 trial, 395 women). Overall the certainty of evidence assessed using GRADE ranged from low to moderate, downgraded primarily due to risk of bias and imprecision. AUTHORS' CONCLUSIONS: This review is based on four trials (1731 women) with an overall unclear risk of bias. The trials provided data on most primary outcomes and suggest that tighter glycaemic control may increase the risk of hypertensive disorders of pregnancy. The risk of birth of a large-for-gestational-age infant and perinatal mortality may be similar between groups, and tighter glycaemic targets may result in a possible reduction in composite of death or severe infant morbidity. However, the CIs for these outcomes are wide, suggesting both benefit and harm. There remains limited evidence regarding the benefit of different glycaemic targets for women with GDM to minimise adverse effects on maternal and infant health. Glycaemic target recommendations from international professional organisations vary widely and are currently reliant on consensus given the lack of high-certainty evidence. Further high-quality trials are needed, and these should assess both short- and long-term health outcomes for women and their babies; include women's experiences; and assess health services costs in order to confirm the current findings. Two trials are ongoing.

Glycemic control in gestational diabetes and impact on biomarkers in women and infants.

BACKGROUND: Gestational diabetes mellitus (GDM) is linked to the dysregulation of inflammatory markers in women with GDM compared to women without. It is unclear whether the intensity of glycemic control influences these biomarkers. We aimed to assess whether different glycemic targets for women with GDM and compliance influence maternal and infant biomarkers. METHODS: Maternity hospitals caring for women with GDM were randomized in the TARGET Trial to tight or less tight glycemic targets. Maternal blood was collected at study entry, 36 weeks' gestation, and 6 months postpartum, and cord plasma after birth. We assessed compliance to targets and concentrations of maternal serum and infant biomarkers. RESULTS: Eighty-two women and infants were included in the study. Concentrations of maternal and infant biomarkers did not differ between women assigned to tighter and less tight glycemic targets; however, concentrations were altered in maternal serum leptin and CRP and infant cord C-peptide, leptin, and IGF in women who complied with tighter targets. CONCLUSIONS: Use of tighter glycemic targets in women with GDM does not change the concentrations of maternal and infant biomarkers compared to less tight targets. However, when compliance is achieved to tighter targets, maternal and infant biomarkers are altered. IMPACT: The use of tighter glycemic targets in gestational diabetes does not result in changes to maternal or cord plasma biomarkers. However, for women who complied with tighter targets, maternal serum leptin and CRP and infant cord C-peptide, leptin and IGF were altered compared with women who complied with the use of the less tight targets. This article adds to the current evidence base regarding the impact of gestational diabetes on maternal and infant biomarkers. This article highlights the need for further research to assess enablers to meet the tighter target recommendations and to assess the impact on relevant biomarkers.

Maternal and infant morbidity following administration of repeat dexamethasone or betamethasone prior to preterm birth: A secondary analysis of the ASTEROID Trial.

BACKGROUND: Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less than 35 weeks' gestation. If women remain at risk of preterm birth seven or more days after an initial course of ACS, most guidelines recommend administration of a repeat dose(s). No randomised trials have assessed the efficacy of dexamethasone as a repeat steroid compared to betamethasone. AIM: We aimed to determine if there were differences between the use of dexamethasone or betamethasone as repeat ACS, for women who remain at risk of preterm birth after an initial course, on maternal, infant, and childhood health outcomes. METHODS: We performed a secondary analysis of data from the ASTEROID randomised trial, where women at risk of preterm birth were allocated to either betamethasone or dexamethasone. Infant, childhood, and maternal outcomes were compared according to whether women received a repeat dose(s) of dexamethasone or betamethasone. The primary outcome was a composite outcome of death or any neurosensory disability at age two years (corrected for prematurity). The ASTEROID trial is registered with ANZCTR, ACTRN12608000631303. RESULTS: 168 women and their infants were included, with 86 women receiving dexamethasone and 82 women receiving betamethasone as a repeat dose. Women in the two ACS groups had similar baseline characteristics. We observed little to no difference in the incidence of death or any neurosensory disability at age two years (OR 0.89, 95% CI 0.39 to 2.06, p = 0.79) or in the incidence of other infant, childhood, and maternal adverse health outcomes between women who received dexamethasone and those who received betamethasone. CONCLUSION: Use of dexamethasone for a repeat dose(s) compared to betamethasone did not result in any differences in infant, childhood, and maternal health outcomes. These results can be used to support clinical practice guideline recommendations.

Dietary recommendations for women with gestational diabetes mellitus: a systematic review of clinical practice guidelines.

CONTEXT: Dietary advice is the cornerstone of care for women with gestational diabetes mellitus (GDM) to improve maternal and infant health. OBJECTIVES: This study aimed to compare dietary recommendations made in clinical practice guidelines (CPGs) for the management of GDM, evaluate their evidence base, identify research gaps, and assess CPG quality. The PRISMA guidelines were used. DATA SOURCES: Six databases were searched for CPGs, published between 2000 and 2019, that included dietary advice for the management of GDM. DATA EXTRACTION: Two reviewers independently assessed CPG quality (using the AGREE II tool) with respect to dietary recommendations (their strength, evidence base, and research gaps). DATA ANALYSIS: Of the 31 CPGs, 68% were assessed as low quality, mainly due to lack of editorial independence. Dietary advice was recommended as the first-line treatment by all CPGs, although the dietary recommendations themselves varied and sometimes were contradictory. Most dietary recommendations were strongly made (70%), but they were often based on very low-quality (54%), or low-quality (15%) evidence. Research gaps were identified for all diet-related recommendations. CONCLUSION: High-quality research is needed to improve the evidence base and address the research gaps identified. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019147848.

Antenatal corticosteroids, maternal body mass index and infant morbidity within the ASTEROID trial.

BACKGROUND: Antenatal corticosteroids (ACSs) administered to women before preterm birth improve neonatal health. Proportionately more women are obese or overweight in current obstetric populations than those who were included in the original trials of ACSs, and it remains uncertain if higher doses are required for such women. AIM: Our aim was to assess the association between maternal body mass index (BMI) and infant morbidity after the administration of ACSs. METHODS: In the secondary analysis of the ASTEROID trial cohort, women at risk of preterm birth at <34 weeks' gestation were randomised to betamethasone or dexamethasone. Infant outcomes were compared according to whether women were of normal weight (BMI < 25 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) or obese (BMI ≥ 30 kg/m2 ). RESULTS: Of 982 women with a singleton pregnancy and BMI data, 519 (52.9%) were of normal size, 241 (24.5%) were overweight and 222 (22.6%) were obese. Compared with infants born to women of normal weight, there was little or no difference in respiratory distress syndrome in infants born to women who were overweight (odds ratio (OR) = 0.92, 95% confidence interval (CI) 0.57, 1.49) or obese (OR = 1.44, 95% CI 0.90, 2.31). Similarly, there were no significant differences between infants born to women in the three BMI groups for other morbidities, including bronchopulmonary dysplasia, mechanical ventilation, intraventricular haemorrhage, retinopathy of prematurity, patent ductus arteriosus, necrotising enterocolitis, perinatal death or combined serious morbidity. CONCLUSIONS: Maternal body size is not associated with infant morbidity after ACS exposure. Dose adjustment for women with higher BMI is not required.