Increased risk of cardiovascular and renal disease, and diabetes for all women diagnosed with gestational diabetes mellitus in New Zealand-A national retrospective cohort study.

BACKGROUND: Gestational diabetes mellitus increases the risk of developing type 2 diabetes. The aim of this study is to compare cardiometabolic and renal outcomes for all women in New Zealand with gestational diabetes (2001-2010) with women without diabetes, 10-20 years following delivery. METHODS: A retrospective cohort study, utilizing a national dataset providing information for all women who gave birth between 1 January 2001 and 31 December 2010 (n = 604 398). Adolescent girls <15 years, women ≥50 years and women with prepregnancy diabetes were excluded. In total 11 459 women were diagnosed with gestational diabetes and 11 447 were matched (for age and year of delivery) with 57 235 unexposed (control) women. A national hospital dataset was used to compare primary outcomes until 31 May 2021. RESULTS: After controlling for ethnicity, women with gestational diabetes were significantly more likely than control women to develop diabetes-adjusted hazard ratio (HR) 20.06 and 95% confidence interval (CI) 18.46-21.79; a first cardiovascular event 2.19 (1.86-2.58); renal disease 6.34 (5.35-7.51) and all-cause mortality 1.55 (1.31-1.83), all p values <.0001. The HR and 95% CI remained similar after controlling for significant covariates: diabetes 18.89 (17.36-20.56), cardiovascular events 1.79 (1.52-2.12), renal disease 5.42 (4.55-6.45), and all-cause mortality 1.44 (1.21-1.70). When time-dependent diabetes was added to the model, significance remained for cardiovascular events 1.33 (1.10-1.61), p = .003 and renal disease 2.33 (1.88-2.88), p < .0001 but not all-cause mortality. CONCLUSIONS: Women diagnosed with gestational diabetes have an increased risk of adverse cardiometabolic and renal outcomes. Findings highlight the importance of follow-up screening for diabetes, cardiovascular risk factors, and renal disease.

Impact of Gestational Diabetes Detection Thresholds on Infant Growth and Body Composition: A Prospective Cohort Study Within a Randomized Trial.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with offspring metabolic disease, including childhood obesity, but causal mediators remain to be established. We assessed the impact of lower versus higher thresholds for detection and treatment of GDM on infant risk factors for obesity, including body composition, growth, nutrition, and appetite. RESEARCH DESIGN AND METHODS: In this prospective cohort study within the Gestational Diabetes Mellitus Trial of Diagnostic Detection Thresholds (GEMS), pregnant women were randomly allocated to detection of GDM using the lower criteria of the International Association of Diabetes and Pregnancy Study Groups or higher New Zealand criteria (ACTRN12615000290594). Randomly selected control infants of women without GDM were compared with infants exposed to A) GDM by lower but not higher criteria, with usual treatment for diabetes in pregnancy; B) GDM by lower but not higher criteria, untreated; or C) GDM by higher criteria, treated. The primary outcome was whole-body fat mass at 5-6 months. RESULTS: There were 760 infants enrolled, and 432 were assessed for the primary outcome. Fat mass was not significantly different between control infants (2.05 kg) and exposure groups: A) GDM by lower but not higher criteria, treated (1.96 kg), adjusted mean difference (aMD) -0.09 (95% CI -0.29, 0.10); B) GDM by lower but not higher criteria, untreated (1.94 kg), aMD -0.15 (95% CI -0.35, 0.06); and C) GDM detected and treated using higher thresholds (1.87 kg), aMD -0.17 (95% CI -0.37, 0.03). CONCLUSIONS: GDM detected using lower but not higher criteria, was not associated with increased infant fat mass at 5-6 months, regardless of maternal treatment. GDM detected and treated using higher thresholds was also not associated with increased fat mass at 5-6 months.

Metformin in Gestational Diabetes The Offspring Follow Up (MiGTOFU): Associations between maternal characteristics and size and adiposity of boys and girls at nine years.

Data from 98 women recruited in the Metformin in Gestational Diabetes trial and dual-energy X-ray absorptiometry studies of their children at nine years were analysed to investigate associations between maternal measures during pregnancy and their children's size and adiposity. Mothers of boys (n = 56) and girls (n = 42) had been randomised to metformin or insulin treatment at 30.1 ± 2.8 and 29.3 ± 4.1 weeks gestation, respectively. In boys, fat-free mass indexed to height squared was associated with maternal weight, body mass index, maternal glycaemia and metformin treatment. In boys and girls, fat mass indexed to height squared was associated with maternal glycaemia measures before gestational diabetes treatment.

Early diabetes treatment is associated with improved outcomes in pregnant women with a first antenatal HbA1c of 41-46 mmol/mol.

BACKGROUND: It is unclear whether early treatment of women with a first antenatal HbA1c of 41-46 mmol/mol improves pregnancy outcomes. Our Hospital Guideline (HG) recommends early treatment, but the New Zealand GDM Guideline (NG) recommends lifestyle advice and a 75 g OGTT at 24-28 weeks' gestation. AIMS: The aim of this study was to compare, at a single centre, pregnancy outcomes in women who were treated before 24 weeks (HG group) with women who were managed according to the NG. Our hypothesis was that earlier treatment was associated with lower rates of pre-eclampsia and preterm birth. MATERIALS AND METHODS: Women who had a first antenatal HbA1c of 41-46 mmol/mol between January 2016 and December 2019 and delivered at our institution before August 2020 were included. Baseline characteristics, management of GDM and pregnancy outcomes were collected. Univariable and multivariable analyses were performed. RESULTS: There were 141 women in the HG group and 67 women in the NG group. The NG group had fewer Indian/Chinese/Other Asian women (P = 0.004) and BMI was higher (P = 0.05). Women in the NG group, compared with the HG group, had more infants with a customised birthweight >90th centile (19.4% vs 7.8%, P = 0.014). In addition, after adjusting for ethnicity and BMI, women in the NG group had higher rates of pre-eclampsia (ORa (95th CI), 3.7 (1.1-13.3), P = 0.04) and preterm birth (2.8 (1.1-7.0), P = 0.03). CONCLUSIONS: Management according to our Hospital Guideline, compared with the National GDM Guideline, was associated with lower rates of pre-eclampsia, preterm birth and infants with a customised birthweight >90th centile.

Lower versus higher diagnostic criteria for the detection of gestational diabetes for reducing maternal and perinatal morbidity: study protocol for the GEMS randomised trial.

BACKGROUND: Gestational diabetes mellitus (GDM) has lifelong implications for the woman and her infant. Treatment reduces adverse maternal and perinatal outcomes although uncertainty remains about the optimal diagnostic criteria. The GEMS Trial aims to assess whether detection and treatment of women with GDM using the lower International Association of Diabetes in Pregnancy Study Groups diagnostic criteria compared with the higher criteria recommended in New Zealand reduces infant morbidity without increasing maternal morbidity. METHODS: GEMS is a multicentre, randomised trial. Women with a singleton pregnancy at 24 to 34 weeks' gestation are eligible who give written informed consent. Women are randomly allocated to the Lower Criteria Group or the Higher Criteria Group. Women with a normal OGTT by their allocated criteria receive routine care (Higher criteria: fasting plasma glucose < 5.5 mmol/L, AND 2 hour < 9.0 mmol/L; Lower criteria: fasting plasma glucose < 5.1 mmol/L, AND 1 hour < 10.0 mmol/L, AND 2 hour < 8.5 mmol/l). Women with GDM on OGTT by their allocated criteria receive standard care for GDM (Higher criteria: fasting plasma glucose ≥ 5.5 mmol/L, OR 2 hour ≥ 9.0 mmol/L; Lower criteria: fasting plasma glucose ≥ 5.1 mmol/L, OR 1 hour ≥ 10.0 mmol/L, OR 2 hour ≥ 8.5 mmol/L). The primary outcome is large for gestational age (birth weight > 90th centile). Secondary outcomes for the infant include a composite of serious outcomes, gestational age, anthropometry, Apgar score < 4 at 5 minutes, lung disease, use of respiratory support, hypoglycaemia, hyperbilirubinaemia, infection, and encephalopathy; and for the woman, a composite of serious outcomes, preeclampsia, induction of labour, mode of birth, weight gain, postpartum haemorrhage and infectious morbidity. A study with 4,158 women will detect an absolute difference of 2.9% in the proportion of large for gestational age infants from 10.0% using the lower criteria to 12.9% with the higher criteria. DISCUSSION: The GEMS Trial will provide high-level evidence relevant for clinical practice. If use of the lower diagnostic criteria results in significantly fewer large for gestational age infants and/or improves maternal and perinatal outcomes these criteria should be recommended for diagnosis of gestational diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number ACTRN12615000290594 . Date registered: 27th March 2015.

Metformin in Pregnancy Study (MiPS): protocol for a systematic review with individual patient data meta-analysis.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps. METHODS AND ANALYSIS: MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD. ETHICS AND DISSEMINATION: All IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

Research Gaps in Gestational Diabetes Mellitus: Executive Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on research gaps in gestational diabetes mellitus (GDM) with a focus on 1) early pregnancy diagnosis and treatment and 2) pharmacologic treatment strategies. This article summarizes the proceedings of the workshop. In early pregnancy, the appropriate diagnostic criteria for the diagnosis of GDM remain poorly defined, and an effect of early diagnosis and treatment on the risk of adverse outcomes has not been demonstrated. Despite many small randomized controlled trials of glucose-lowering medication treatment in GDM, our understanding of medication management of GDM is incomplete as evidenced by discrepancies among professional society treatment guidelines. The comparative effectiveness of insulin, metformin, and glyburide remains uncertain, particularly with respect to long-term outcomes. Additional topics in need of further research identified by workshop participants included phenotypic heterogeneity in GDM and novel and individualized treatment approaches. Further research on these topics is likely to improve our understanding of the pathophysiology and treatment of GDM to improve both short- and long-term outcomes for mothers and their children.

Reduced Cortical Excitability, Neuroplasticity, and Salivary Cortisol in 11-13-Year-Old Children Born to Women with Gestational Diabetes Mellitus.

BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) in utero are at increased risk of neurodevelopmental difficulties, including autism and impaired motor control. However, the underlying neurophysiology is unknown. METHODS: Using transcranial magnetic stimulation, we assessed cortical excitability, long-term depression (LTD)-like neuroplasticity in 45 GDM-exposed and 12 control children aged 11-13 years. Data were analysed against salivary cortisol and maternal diabetes severity and treatment (insulin [N = 22] or metformin [N = 23]) during pregnancy. FINDINGS: GDM-exposed children had reduced cortical excitability (p = .003), LTD-like neuroplasticity (p = .005), and salivary cortisol (p < .001) when compared with control children. Higher maternal insulin resistance (IR) before and during GDM treatment was associated with a blunted neuroplastic response in children (p = .014) and this was not accounted for by maternal BMI. Additional maternal and neonatal measures, including fasting plasma glucose and inflammatory markers, predicted neurophysiological outcomes. The metformin and insulin treatment groups had similar outcomes. INTERPRETATION: These results suggest that GDM can contribute to subtle differences in child neurophysiology, and possibly cortisol secretion, persisting into early adolescence. Importantly, these effects appear to occur during second trimester, before pharmacologic treatment typically commences, and can be predicted by maternal insulin resistance. Therefore, earlier detection and treatment of GDM may be warranted. Metformin appears to be safe for these aspects of neurodevelopment.

Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age.

OBJECTIVE: To compare body composition and metabolic outcomes at 7-9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy. RESEARCH DESIGN AND METHODS: Children were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99). RESULTS: In the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar. CONCLUSIONS: Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7-9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes.

Prediabetes in pregnancy, can early intervention improve outcomes? A feasibility study for a parallel randomised clinical trial.

OBJECTIVE: Measurement of glycated haemoglobin (HbA1c) in early pregnancy is routine in New Zealand to identify women with diabetes and prediabetes. However, the benefit of early intervention in women with prediabetes is inconclusive. Our aim was to test the feasibility of a two-arm parallel randomised controlled trial of standard care versus early intervention in pregnancies complicated by prediabetes. SETTING: Two tertiary referral centres in New Zealand. PARTICIPANTS: Women <14 weeks' gestation and HbA1c ≥5.9%-6.4% (41-46 mmol/mol) measured at booking, without pre-existing diabetes. INTERVENTIONS: Randomisation was done by remote web-based allocation into one of two groups. Women in the early intervention group attended an antenatal diabetes clinic, commenced daily home blood glucose monitoring, and medication was prescribed if lifestyle measures failed to maintain target blood glucose levels. Controls received lifestyle education, continued standard care with their midwife and/or obstetrician, and were asked to perform a 75 g oral glucose tolerance test at 24 weeks' gestation with a referral to clinic if this test was positive. Both groups received lifestyle questionnaires at recruitment and in late pregnancy. OUTCOME MEASURES: Recruitment rate, adherence to protocol and validation of potential primary outcomes. RESULTS: Recruitment rates were lower than expected, especially in Maori and Pacific women. Non-adherence to allocated treatment protocol was significant, 42% (95% CI 24% to 61%) in the early intervention group and 30% (95% CI 16% to 51%) in controls. Caesarean section and pre-eclampsia were signalled as potential primary outcomes, due to both the high observed incidence in the control group and ease of measurement. CONCLUSIONS: For a future definitive trial, extending the gestation of eligibility and stepped-wedge cluster randomisation may overcome the identified feasibility issues. Consistent with published observational data, pre-eclampsia and emergency caesarean section could be included as primary outcome measures, both of which have a significant impact on maternal and neonatal morbidity and healthcare costs. TRIAL REGISTRATION NUMBER: ACTRN12615000904572; Pre-results.

Accuracy of point-of-care HbA1c testing in pregnant women.

BACKGROUND: In New Zealand, it is recommended that all pregnant women have a haemoglobin A1c (HbA1c) test performed with their booking antenatal bloods to identify previously unrecognised diabetes. However, screening rates in some groups are low. Use of a point-of-care device may improve compliance with screening. AIM: To assess the accuracy of the COBAS b101 point-of-care system referenced against a laboratory method, for measurement of HbA1c levels in pregnant women. MATERIALS AND METHODS: Convenience sample of 40 obese pregnant women enrolled in a clinical trial. HbA1c was assayed in paired capillary and venous whole blood samples using the COBAS b101 point-of-care system and Primus Ultra2 high performance liquid chromatography laboratory analyser, respectively. The accuracy of the point-of-care system was assessed by Bland-Altman analysis. RESULTS: The mean (SD) laboratory HbA1c was 35.9 (2.0) mmol/mol. The COBAS b101 point-of-care system, compared with the laboratory reference method, had a small negative bias for HbA1c (-1.0 mmol/mol, 95% CI -2.0 to -0.03, P = 0.03) and relatively wide 95% limits of agreement (-7.2 to 5.1 mmol/mol). CONCLUSION: In conclusion, we found that in pregnancy, the COBAS b101 point-of-care system has a small negative bias and modest point accuracy for HbA1c. When used to screen for previously unrecognised diabetes in pregnancy, appropriate COBAS b101 HbA1c point-of-care HbA1c thresholds for a negative and positive result are 7 mmol/mol below and 5 mmol/mol above the clinical threshold, respectively. Values between these limits should be confirmed by laboratory testing.

Oral anti-diabetic pharmacological therapies for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major public health issue with rates increasing globally. Gestational diabetes, glucose intolerance first recognised during pregnancy, usually resolves after birth and is associated with short- and long-term complications for the mother and her infant. Treatment options can include oral anti-diabetic pharmacological therapies. OBJECTIVES: To evaluate the effects of oral anti-diabetic pharmacological therapies for treating women with GDM. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 May 2016), ClinicalTrials.gov, WHO ICTRP (14 May 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included published and unpublished randomised controlled trials assessing the effects of oral anti-diabetic pharmacological therapies for treating pregnant women with GDM. We included studies comparing oral anti-diabetic pharmacological therapies with 1) placebo/standard care, 2) another oral anti-diabetic pharmacological therapy, 3) combined oral anti-diabetic pharmacological therapies. Trials using insulin as the comparator were excluded as they are the subject of a separate Cochrane systematic review.Women with pre-existing type 1 or type 2 diabetes were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted data and data were checked for accuracy. MAIN RESULTS: We included 11 studies (19 publications) (1487 women and their babies). Eight studies had data that could be included in meta-analyses. Studies were conducted in Brazil, India, Israel, UK, South Africa and USA. The studies varied in diagnostic criteria and treatment targets for glycaemic control for GDM. The overall risk of bias was 'unclear' due to inadequate reporting of methodology. Using GRADE the quality of the evidence ranged from moderate to very low quality. Evidence was downgraded for risk of bias (reporting bias, lack of blinding), inconsistency, indirectness, imprecision and for oral anti-diabetic therapy versus placebo for generalisability. Oral anti-diabetic pharmacological therapies versus placebo/standard careThere was no evidence of a difference between glibenclamide and placebo groups for hypertensive disorders of pregnancy (risk ratio (RR) 1.24, 95% confidence interval (CI) 0.81 to 1.90; one study, 375 women, very low-quality evidence), birth by caesarean section (RR 1.03, 95% CI 0.79 to 1.34; one study, 375 women, very low-quality evidence), perineal trauma (RR 0.98, 95% CI 0.06 to 15.62; one study, 375 women, very low-quality evidence) or induction of labour (RR 1.18, 95% CI 0.79 to 1.76; one study, 375 women; very low-quality evidence). No data were reported for development of type 2 diabetes or other pre-specified GRADE maternal outcomes (return to pre-pregnancy weight, postnatal depression). For the infant, there was no evidence of a difference in the risk of being born large-for-gestational age (LGA) between infants whose mothers had been treated with glibenclamide and those in the placebo group (RR 0.89, 95% CI 0.51 to 1.58; one study, 375, low-quality evidence). No data were reported for other infant primary or GRADE outcomes (perinatal mortality, death or serious morbidity composite, neurosensory disability in later childhood, neonatal hypoglycaemia, adiposity, diabetes). Metformin versus glibenclamideThere was no evidence of a difference between metformin- and glibenclamide-treated groups for the risk of hypertensive disorders of pregnancy (RR 0.70, 95% CI 0.38 to 1.30; three studies, 508 women, moderate-quality evidence), birth by caesarean section (average RR 1.20, 95% CI 1.20; 95% CI 0.83 to 1.72, four studies, 554 women, I2 = 61%, Tau2 = 0.07 low-quality evidence), induction of labour (0.81, 95% CI 0.61 to 1.07; one study, 159 women; low-quality evidence) or perineal trauma (RR 1.67, 95% CI 0.22 to 12.52; two studies, 158 women; low-quality evidence). No data were reported for development of type 2 diabetes or other pre-specified GRADE maternal outcomes (return to pre-pregnancy weight, postnatal depression). For the infant there was no evidence of a difference between the metformin- and glibenclamide-exposed groups for the risk of being born LGA (average RR 0.67, 95% CI 0.24 to 1.83; two studies, 246 infants, I2 = 54%, Tau2 = 0.30 low-quality evidence). Metformin was associated with a decrease in a death or serious morbidity composite (RR 0.54, 95% CI 0.31 to 0.94; one study, 159 infants, low-quality evidence). There was no clear difference between groups for neonatal hypoglycaemia (RR 0.86, 95% CI 0.42 to 1.77; four studies, 554 infants, low-quality evidence) or perinatal mortality (RR 0.92, 95% CI 0.06 to 14.55, two studies, 359 infants). No data were reported for neurosensory disability in later childhood or for adiposity or diabetes. Glibenclamide versus acarboseThere was no evidence of a difference between glibenclamide and acarbose from one study (43 women) for any of their maternal or infant primary outcomes (caesarean section, RR 0.95, 95% CI 0.53 to 1.70; low-quality evidence; perinatal mortality - no events; low-quality evidence; LGA , RR 2.38, 95% CI 0.54 to 10.46; low-quality evidence). There was no evidence of a difference between glibenclamide and acarbose for neonatal hypoglycaemia (RR 6.33, 95% CI 0.87 to 46.32; low-quality evidence). There were no data reported for other pre-specified GRADE or primary maternal outcomes (hypertensive disorders of pregnancy, development of type 2 diabetes, perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour) or neonatal outcomes (death or serious morbidity composite, adiposity or diabetes). AUTHORS' CONCLUSIONS: There were insufficient data comparing oral anti-diabetic pharmacological therapies with placebo/standard care (lifestyle advice) to inform clinical practice. There was insufficient high-quality evidence to be able to draw any meaningful conclusions as to the benefits of one oral anti-diabetic pharmacological therapy over another due to limited reporting of data for the primary and secondary outcomes in this review. Short- and long-term clinical outcomes for this review were inadequately reported or not reported. Current choice of oral anti-diabetic pharmacological therapy appears to be based on clinical preference, availability and national clinical practice guidelines.The benefits and potential harms of one oral anti-diabetic pharmacological therapy compared with another, or compared with placebo/standard care remains unclear and requires further research. Future trials should attempt to report on the core outcomes suggested in this review, in particular long-term outcomes for the woman and the infant that have been poorly reported to date, women's experiences and cost benefit.

Acceptance of Using an Ecosystem of Mobile Apps for Use in Diabetes Clinic for Self-Management of Gestational Diabetes Mellitus.

Mobile applications (apps) for self-management of diseases such as diabetes and for general well-being, including keeping track of food, diet, and exercise, are widely available. However, consumers face a flood of new mobile apps in the app stores and have no guidance from clinicians about choosing the appropriate app. As much as clinicians would like to support a patient-centered approach and promote health and wellness mobile apps, they may be unable to provide advice due to the lack of comprehensive and reliable app reviews. This research reviewed a selection of health and wellness mobile apps suitable for the self-management of gestational diabetes mellitus (GDM). A prototype of an ecosystem that integrated the data generated by the apps was built and its usefulness and ease of use were evaluated. The results show that the ecosystem can provide support for GDM self-management by sharing health and wellness data across the diabetes clinic.

The use of dextrose/insulin infusions during labour and delivery in women with gestational diabetes mellitus: Is there any point?

We compared, in 733 women with gestational diabetes mellitus treated with metformin and/or insulin, rates of neonatal hypoglycaemia in those who had received a dextrose/insulin infusion during labour and prior to delivery (n = 132) with those who did not (n = 601). Women who had infusions were more likely to have been treated with insulin (87.1% vs 70.4%, P < 0.01) and have higher mean capillary glucose values (measured four times daily) in the two weeks prior to delivery (P < 0.01). They had lower mean (SD) glucose values in the 12 h prior to delivery (5.1 (1.1) mmol/L vs 5.4 (0.9) mmol/L, P < 0.01). There was no difference between the groups in rates of neonatal hypoglycaemia (glucose <2.6 mmol/L on two or more occasions), 15.9% versus 17.8%, P = 0.78, or of severe neonatal hypoglycaemia (one or more glucose <1.6 mmol/L), 8.3% versus 5.2%, P = 0.15. In the absence of randomised data comparing use of infusions with no infusions, these data are reassuring for clinicians who do not routinely use infusions.

Neurodevelopmental outcome at 2†years in offspring of women randomised to metformin or insulin treatment for gestational diabetes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is increasingly being treated with metformin that crosses the placenta rather than insulin, which does not. This study seeks to examine the neurodevelopment of offspring of women treated with metformin or insulin for GDM. DESIGN: We performed a prospective follow-up study of children whose mothers had been randomly assigned at 20-33 weeks gestation to treatment with metformin or insulin for GDM. Of the 211 children followed up at 2 years, 128 were from Auckland, New Zealand (64 metformin vs 64 insulin), and 83 from Adelaide, Australia (39 metformin vs 49 insulin). Neurodevelopment was examined with the Bayley Scales of Infant Development V.2 mental development index (MDI) and psychomotor development index (PDI). Clinical and demographic background characteristics were obtained at enrolment, birth and follow-up. RESULTS: No significant differences were found between treatment groups in clinical or demographic characteristics. The MDI and PDI composite scores were tested with general linear models. No significant differences were found between metformin and insulin, respectively, in New Zealand (MDI, M=83.6 vs 86.9 and PDI, M=83.4 vs M=85.2) or Australia (MDI, M=102.5 vs M=98.4 and PDI, M=105.6 vs M=99.9) and no interactions observed. The differences in neurodevelopmental outcomes between the Auckland and Adelaide cohorts were explained by parental ethnicity, infant birth weight >4000 g, neonatal hypoglycaemia, maternal glycaemia and smoking in the household. CONCLUSIONS: This study provides additional data supporting the safety of metformin in the treatment of GDM. TRIAL REGISTRATION NUMBER: ACTRN 12605000311651.

Is There a Role for HbA1c in Pregnancy?

Outside pregnancy, HbA1c analysis is used for monitoring, screening for and diagnosing diabetes and prediabetes. During pregnancy, the role for HbA1c analysis is not yet established. Physiological changes lower HbA1c levels, and pregnancy-specific reference ranges may need to be recognised. Other factors that influence HbA1c are also important to consider, particularly since emerging data suggest that, in early pregnancy, HbA1c elevations close to the reference range may both identify women with underlying hyperglycaemia and be associated with adverse pregnancy outcomes. In later pregnancy, HbA1c analysis is less useful than an oral glucose tolerance test (OGTT) at detecting gestational diabetes. Postpartum, HbA1c analysis detects fewer women with abnormal glucose tolerance than an OGTT, but the ease of testing may improve follow-up rates and combining HbA1c analysis with fasting plasma glucose or waist circumference may improve detection rates. This article discusses the relevance of HbA1c testing at different stages of pregnancy.

Blood pressure measurement at two years in offspring of women randomized to a trial of metformin for GDM: follow up data from the MiG trial.

BACKGROUND: Offspring born following maternal gestational diabetes are at risk of excessive childhood weight gain and Type 2 diabetes in childhood, which in turn is associated with an increased rate of hypertension. We aimed to determine the systolic and diastolic blood pressure at two years of age in a cohort of children exposed to gestational diabetes mellitus using data from the MiG trial of metformin use in gestational diabetes. The secondary aim was to analyze these data by randomization of treatment to insulin or metformin. METHODS: The offspring of women who had gestational diabetes and had been assigned to either open treatment with metformin (with supplemental insulin if required) or insulin in the MiG trial were followed up at 2 years of age. Oscillometric measurement of BP in the right arm was performed by a researcher using an appropriately sized cuff. RESULTS: A total of 489 measurement blood pressure measurements were obtained in 170 of the 222 children who were seen at a median (range) age of 29 (22-38) months corrected gestational age. At the time of assessment the mean (SD) weight and height was 13.8(2) kg and 90 (4.2) cm respectively. For the whole group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic pressure was 55.7 (8.1) mmHg. No difference was found between the metformin and insulin treatment arms. In a regression model, height and weight were only two factors associated with the levels of systolic blood pressure. For each additional kg the systolic blood pressure increased by 1.0 mmHg. For each additional cm of height the systolic blood pressure increased by 0.42 mmHg. CONCLUSIONS: Blood pressure data was obtained at approximately two years of age in a substantial cohort of children whose mothers received treatment for GDM. These novel data compare favorably with published norms. CLINICAL TRIALS REGISTRY: This study was registered under the Australian New Zealand Clinical Trials Registry ( ACTRN12605000311651 ).