A Randomized Trial of Closed-Loop Insulin Delivery Postpartum in Type 1 Diabetes.

OBJECTIVE: This study aimed to evaluate the efficacy of closed-loop insulin delivery postpartum. RESEARCH DESIGN AND METHODS: In this open-label, randomized controlled trial, postpartum individuals with type 1 diabetes were randomized to hybrid closed-loop insulin delivery with the MiniMed 670G/770G system in automode or sensor-augmented pump therapy in the first 12-weeks postpartum followed by a continuation phase with closed-loop insulin delivery for all until 24 weeks postpartum. RESULTS: Eighteen participants (mean ± SD age 32 ± 3.5 years, diabetes duration 22 ± 7.3 years, and early pregnancy HbA1c 52 ± 6.8 mmol/mol [6.9 ± 0.9%]) completed 24 weeks of postpartum follow-up. In the randomized phase, percent time in range 70-180 mg/dL (3.9-10 mmol/L) did not differ between groups (79.2 ± 8.7% vs. 78.2 ± 6.0%; P = 0.41). Participants randomized to closed-loop insulin delivery spent less time <70 mg/dL (3.9 mmol/L) and <54 mg/dL (3.0 mmol/L) (1.7 ± 0.8% vs. 5.5 ± 3.3% [P < 0.001] and 0.3 ± 0.2% vs. 1.1 ± 0.9% [P = 0.008]). Time >180 mg/dL (10 mmol/L) was not different between groups (18.7 ± 8.8% vs. 15.9 ± 7.7%; P = 0.21). In the continuation phase, those initially randomized to sensor-augmented pump therapy had less time <70 mg/dL after initiation of closed-loop insulin delivery (5.5 ± 3.3% vs. 3.3 ± 2.2%; P = 0.039). The closed-loop group maintained similar glycemic metrics in both study phases. There were no episodes of diabetic ketoacidosis or severe hypoglycemia in the randomized or continuation phase in either group. CONCLUSIONS: Women randomized to closed-loop insulin delivery postpartum had less hypoglycemia than those randomized to sensor-augmented pump therapy. There were no safety concerns. These findings are reassuring for use of closed-loop insulin delivery postpartum because of its potential to reduce hypoglycemia.

Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets.

Glucose concentrations within target, appropriate gestational weight gain, adequate lifestyle, and, if necessary, antihypertensive treatment and low-dose aspirin reduces the risk of pre-eclampsia, preterm delivery, and other adverse pregnancy and neonatal outcomes in pregnancies complicated by type 1 diabetes. Despite the increasing use of diabetes technology (ie, continuous glucose monitoring and insulin pumps), the target of more than 70% time in range in pregnancy (TIRp 3·5-7·8 mmol/L) is often reached only in the final weeks of pregnancy, which is too late for beneficial effects on pregnancy outcomes. Hybrid closed-loop (HCL) insulin delivery systems are emerging as promising treatment options in pregnancy. In this Review, we discuss the latest evidence on pre-pregnancy care, management of diabetes-related complications, lifestyle recommendations, gestational weight gain, antihypertensive treatment, aspirin prophylaxis, and the use of novel technologies for achieving and maintaining glycaemic targets during pregnancy in women with type 1 diabetes. In addition, the importance of effective clinical and psychosocial support for pregnant women with type 1 diabetes is also highlighted. We also discuss the contemporary studies examining HCL systems in type 1 diabetes during pregnancies.

Real-world use of Control-IQ™ technology automated insulin delivery in pregnancy: A case series with qualitative interviews.

BACKGROUND: Most commercially available automated insulin delivery (AID) systems are not approved for pregnancy use. Information regarding use of the Tandem t:slim X2 insulin pump with Control-IQ™ technology in pregnancy is lacking. AIMS: This case series aimed to explore glycaemic and qualitative experiences of four early adopters of Control-IQ technology in pregnancy. METHODS: Participants used Control-IQ technology in pregnancy and postpartum and consented to analysis of glycaemic data and semi-structured interviews. RESULTS: Case 1 began Control-IQ technology at 10 weeks gestation. Her pregnancy glucose time-in-range (3.5-7.8 mmol/L [63-140 mg/dL]) increased from 58.7% to 73.3% by third trimester. Cases 2-4 began using Control-IQ technology 0-2 months preconception. Pregnancy time-in-range glucose increased from 73.4% to 78.7%, 78% to 83.6%, and 46.5% to 71.9% between first and third trimesters, respectively. A mid-pregnancy decline in time-in-range glucose was observed in two of the four participants related to suboptimal pump setting adjustments and delays in sensor and infusion set replacement. No diabetic ketoacidosis or severe hypoglycaemia occurred. All participants reported reduced diabetes management burden and improved sleep with Control-IQ technology use. CONCLUSIONS: Early adopters of Control-IQ technology safely used this system off-label in pregnancy and reported reduced diabetes management burden and improved sleep. The largest glycaemic improvements were observed among those with the lowest pregnancy time-in-range glucose at the beginning of pregnancy. Participants with low pregnancy glucose time-in-range increased their time-in-range with Control-IQ technology use and participants with high pregnancy glucose time-in-range maintained and increased their time-in-range with less diabetes management burden.

Existing standardised questionnaires do not adequately capture quality-of-life outcomes of greatest importance for those living with type 1 diabetes in pregnancy.

BACKGROUND: No standardised questionnaires have been specifically developed to assess the considerable demands of managing type 1 diabetes (T1D) during pregnancy. AIMS: This study aimed to explore what domains of measurement are important to quality of life during pregnancy with TID and to assess if standardised questionnaires, used by previous researchers, adequately capture patients' reported experience of TID in pregnancy. METHODS: A qualitative inquiry was conducted using semi-structured focus groups with Canadian women who have experienced T1D in pregnancy. Participants were asked open-ended questions about experiences managing T1D during pregnancy and whether options on standardised tools captured their pregnancy experiences. Audio from focus groups was transcribed verbatim. Two researchers independently analysed the transcripts using inductive thematic analysis. Salient ideas, experiences and key words were coded iteratively and grouped into broader themes and subsequently reviewed by five participants. RESULTS: The sample included nine participants. Emergent themes included changes in day-to-day routines to manage T1D in pregnancy, fear of hyperglycaemia during pregnancy and of hypoglycaemia postpartum. Participants felt that existing options on standardised questionnaires did not adequately quantify diabetes interference in work, family time, planned activities and sleep, and did not address hyperglycaemia fear. CONCLUSIONS: Existing standardised questionnaires do not adequately capture patient-reported outcomes of greatest importance for those living with T1D in pregnancy. Future research assessing the impact of therapies on quality-of-life measures in TID pregnancies should quantify their influence on day-to-day activities, adjust measures of sleep quality and capture fear of hyperglycaemia in pregnancy and hypoglycaemia postpartum.

Missed antenatal diabetes care appointments and neonatal outcomes for pregnancies with Type 1 and Type 2 diabetes.

BACKGROUND: There is limited information regarding the association between missed appointments and neonatal outcomes for diabetes in pregnancy. STUDY METHODS: This retrospective live birth cohort included pregnant women with Type 1 or 2 diabetes who attended specialized clinics from 2008 to 2020. The association between at least one missed antenatal diabetes appointments and outcomes were assessed using logistic regression and reported as adjusted odds ratios (aOR) (95% confidence interval). Mediation analyses were conducted to examine if above target HbA1c mediated these relationships. RESULTS: The cohort included 407 and 902 women with Type 1 and 2 diabetes, respectively, of whom 25.1% and 34.5% missed at least one appointment. Women with Type 1 diabetes who missed an appointment were more likely to have a caesarean section (aOR 1.95 [1.15, 3.31]) and their babies more likely to be admitted to the neonatal intensive care unit (aOR 2.25 [1.35, 3.75]). Women with Type 2 diabetes who missed an appointment were more likely to have a large-for-gestational-age infant (aOR 1.61 [1.13, 2.28]), and an extreme large-for-gestational-age infant (aOR 1.69 [1.02, 2.81]) compared with women who did not miss appointments. Above target HbA1c mediated the relationship between missed appointments and caesarean delivery in Type 1 diabetes and large-for-gestational age and extreme large-for-gestational age in Type 2 diabetes. CONCLUSION: In individuals with Type 1 and 2 diabetes, there are differences in neonatal outcomes between those who missed an appointment compared to those who did not. It remains unclear if missed diabetes appointments are causative or a marker of other health behaviours or risk factors leading to neonatal morbidity.

Determinants of Small for Gestational Age in Women With Type 2 Diabetes in Pregnancy: Who Should Receive Metformin?

OBJECTIVE: In the MiTy (Metformin in Women With Type 2 Diabetes in Pregnancy) randomized trial of metformin versus placebo added to insulin, we found numerous benefits with metformin but identified an increased proportion of infants who were small for gestational age (SGA). We aimed to determine the predictors of SGA in order to individualize care. RESEARCH DESIGN AND METHODS: Using logistic regression, we assessed baseline maternal characteristics as predictors of SGA. We compared maternal/neonatal outcomes in SGA metformin and placebo groups using the t, χ2, or Fisher exact test, as appropriate. RESULTS: Among the 502 mothers, 460 infants were eligible for this study. There were 30 infants with SGA in the metformin group (12.9%) and 15 in the placebo group (6.6%) (P = 0.026). Among SGA infants, those in the metformin group were delivered significantly later than those in the placebo group (37.2 vs. 35.3 weeks; P = 0.038). In adjusted analyses, presence of a comorbidity (chronic hypertension and/or nephropathy) (odds ratio [OR] 3.05; 95% CI 1.58-5.81) and metformin use (OR 2.26; 95% CI 1.19-4.74) were predictive of SGA. The absolute risk of SGA was much higher in women receiving metformin with comorbidity compared with women receiving metformin without comorbidity (25.0% vs. 9.8%). CONCLUSIONS: In this study, we observed a high percentage of SGA births among women with type 2 diabetes and chronic hypertension and/or nephropathy who were treated with metformin. Therefore, with the aim of reducing SGA, it is reasonable to be cautious in our use of metformin in those with type 2 diabetes and chronic hypertension or nephropathy in pregnancy.

The association between gestational diabetes and stillbirth: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth. METHODS: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case-control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939). RESULTS: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I2 86.1%) or in case-control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis. CONCLUSIONS/INTERPRETATION: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously.

Prevalence of and risk factors for excess weight gain in pregnancy: a cross-sectional study using survey data.

BACKGROUND: Maternal weight gain during pregnancy is required for fetal development; however, excess gestational weight gain is associated with increased maternal and neonatal morbidity. We aimed to determine the proportion of Canadian women who gained excess weight during pregnancy and to identify risk factors for excess gestational weight gain. METHODS: Self-reported data on maternal weight gain were collected from the 2015/16 and 2017/18 cycles of the Canadian Community Health Survey (CCHS), a cross-sectional population-based survey. We included females aged 15 to 54 years with data on height, prepregnancy weight and gestational weight gain. We defined excess gestational weight gain in terms of preconception body mass index (BMI) according to the 2009 guideline of the US Institute of Medicine. We used logistic regression to evaluate potential risk factors for excess gestational weight gain. RESULTS: Of 1 335 615 Canadian women (weighted from approximately 9300 survey respondents), 422 043 (32%) gained excess weight during pregnancy. Women with obesity had 33% lower odds of gaining excess weight relative to women with overweight (odds ratio 0.67, 95% confidence interval 0.48-0.94). Risk factors for excess gestational weight gain were lower education level, white or Indigenous identity, smoking, mood disorder, anxiety disorder and Canadian citizenship. INTERPRETATION: One-third of Canadian women in this survey had excess gestational weight gain during pregnancy, and women with obesity had lower odds of gaining excess weight during pregnancy relative to women with overweight. Strategies are needed to reduce the proportion of Canadian women who gain excess weight during pregnancy, regardless of preconception BMI.

Metformin in Pregnancy for Women with Type 2 Diabetes: a Review.

PURPOSE OF REVIEW: To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes. RECENT FINDINGS: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required. Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA.

An exploration of differences in infant feeding practices among women with and without diabetes in pregnancy: A mixed-methods study.

AIMS: (1) To determine the likelihood of full breastfeeding at 3 months postpartum in women with and without diabetes in pregnancy (DiP); (2) to explore the associations between diabetes management practices and infant feeding practices in those who had DiP and (3) to examine women's experiences of feeding their infants after having DiP. METHODS: The quantitative study used data from Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. Participants who had DiP (n = 62) were matched 1:3 to participants without DiP for pre-pregnancy BMI, parity, mode of delivery and pre-term birth. Infant feeding questionnaires, prospective breastfeeding diaries and medical chart data were analysed to determine likelihood of fully breastfeeding at 3 months postpartum. For the qualitative study, interviews were conducted with postpartum women who had DiP to explore the experiences of infant feeding. Interviews were thematically analysed, and the results were compared between women who were categorized as 'full breast feeders' or 'mixed feeders'. RESULTS: The odds of fully breastfeeding were 50% lower in women with DiP than women without DiP (OR: 0.50, 95% CI 0.25-0.99, p = 0.04). Qualitative interviews identified that although all women showed resilience in the face of infant feeding challenges, those who were fully breastfeeding reported seeking out external infant feeding supports, for example, classes or Doula's. Mixed Feeders perceived there was a lack of infant feeding information and support given to them prior to giving birth. CONCLUSION: Women with DiP may require additional prenatal and postnatal infant feeding support to be better prepared to overcome feeding challenges they may face.

Impact of levothyroxine in women with positive thyroid antibodies on pregnancy outcomes: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism with presence of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb). DESIGN: Systematic review and meta-analysis of randomised controlled trials STUDY ELIGIBILITY CRITERIA: Prespecified criteria for inclusion were: randomised trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception. DATA SOURCES: Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched from 1980 to 5 November 2020. OUTCOME MEASURES: Prespecified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth. RISK OF BIAS ASSESSMENT: Cochrane Risk of Bias Tool for Quality Assessment of Randomised Controlled Trials. RESULTS: From 3023 citations, 79 citations were identified for full-text review. Of these, six trials (total of 2263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93 to 1.13), miscarriage (RR 0.93; 95% CI 0.76 to 1.14), preterm delivery (RR 0.66; 95% CI 0.39 to 1.10) or live births (RR 1.01; 95% CI 0.89 to 1.16) in thyroid autoimmune women treated with levothyroxine compared with controls. Sensitivity analyses of preterm birth identified study quality and timing of levothyroxine initiation as sources of heterogeneity. CONCLUSIONS: Among pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use (moderate to high Grading of Recommendations, Assessment, Development and Evaluations). Recommendations to use levothyroxine in this setting need to be reconsidered. PROSPERO REGISTRATION NUMBER: CRD42019130459.

Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial.

BACKGROUND: Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. METHODS: In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m2 or ≥30 kg/m2) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5·3 mmol/L [95 mg/dL], 2-h postprandial glucose <6·7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1-4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. FINDINGS: Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [-10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference -0·2 [-0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference -0·4 [95% CI -0·5 to -0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference -1·8 [-2·7 to -0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference -218 [-353 to -82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference -1·41 [-2·6 to -0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group). INTERPRETATION: We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy. FUNDING: Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.

Thyroid function testing and management during and after pregnancy among women without thyroid disease before pregnancy.

BACKGROUND: Screening in pregnancy for subclinical hypothyroidism, often defined as thyroid-stimulating hormone (TSH) greater than 2.5 mIU/L or greater than 4.0 mIU/L, is controversial. We determined the frequency and distribution of TSH testing by gestational age, as well as TSH values associated with treatment during pregnancy and the frequency of postpartum continuation of thyroid hormone therapy. METHODS: We performed a retrospective cohort study of pregnancies in Alberta, Canada. We included women without thyroid disease who delivered between October 2014 and September 2017. We used delivery records, physician billings, and pharmacy and laboratory administrative data. Our key outcomes were characteristics of TSH testing and the initiation and continuation of thyroid hormone therapy. We calculated the proportion of pregnancies with thyroid testing and the frequency of each specific thyroid test. RESULTS: Of the 188 490 pregnancies included, 111 522 (59.2%) had at least 1 TSH measurement. The most common time for testing was at gestational week 5 to 6. Thyroid hormone therapy was initiated at a median gestational age of 7 (interquartile range 5-12) weeks. Among women with first TSH measurements of 4.01 to 9.99 mIU/L who were not immediately treated, the repeat TSH measurement was 4.00 mIU/L or below in 67.9% of pregnancies. Thyroid hormone was continued post partum for 44.6% of the women who started therapy during their pregnancy. INTERPRETATION: The findings of our study suggest that current practice patterns may contribute to overdiagnosis of hypothyroidism and overtreatment during pregnancy and post partum.

Timing of delivery in women with diabetes: A population-based study.

INTRODUCTION: Women with diabetes, and their infants, have an increased risk of adverse events due to excess fetal growth. Earlier delivery, when fetuses are smaller, may reduce these risks. This study aimed to evaluate the week-specific risks of maternal and neonatal morbidity/mortality to assist with obstetrical decision making. MATERIAL AND METHODS: In this population-based cohort study, women with type 1 diabetes (n = 5889), type 2 diabetes (n = 9422) and gestational diabetes (n = 138 917) and a comparison group without diabetes (n = 2 553 243) who delivered a singleton infant at ≥36 completed weeks of gestation between 2004 and 2014 were identified from the Canadian Institute of Health Information Discharge Abstract Database. Multivariate logistic regression was used to determine the week-specific rates of severe maternal and neonatal morbidity/mortality among women delivered iatrogenically vs those undergoing expectant management. RESULTS: For all women, the absolute risk of severe maternal morbidity/mortality was low, typically impacting less than 1% of women, and there was no significant difference in gestational age-specific severe maternal morbidity/mortality between iatrogenic delivery and expectant management among women with any form of diabetes. Among women with gestational diabetes, iatrogenic delivery was associated with an increased risk of neonatal morbidity/mortality compared with expectant management at 36 and 37 weeks' gestation (76.7 and 27.8 excess cases per 1000 deliveries, respectively) and a lower risk of neonatal morbidity/mortality at 38, 39 and 40 weeks' gestation (7.9, 27.3 and 15.9 fewer cases per 1000 deliveries, respectively). Increased risks of severe neonatal morbidity following iatrogenic delivery compared with expectant management were also observed for women with type 1 diabetes at 36 (98.3 excess cases per 1000 deliveries) and 37 weeks' gestation (44.5 excess cases per 1000 deliveries) and for women with type 2 diabetes at 36 weeks' gestation (77.9 excess cases per 1000 deliveries) weeks. CONCLUSIONS: The clinical decision regarding timing of delivery is complex and contingent on maternal-fetal wellbeing, including adequate glycemic control. This study suggests that delivery at 38, 39 or 40 weeks' gestation may optimize neonatal outcomes among women with diabetes.

Evidenced-Based Nutrition for Gestational Diabetes Mellitus.

PURPOSE OF REVIEW: To review the latest evidence for dietary interventions for treatment of gestational diabetes (GDM). RECENT FINDINGS: High-quality systematic reviews demonstrate no major advantages between the low-carbohydrate or calorie-restricted diets. However, the low glycemic index (GI) diet, characterized by intake of high-quality, complex carbohydrates, demonstrated lower insulin use and reduced risk of macrosomia in multiple reviews. Recent evidence suggests the Mediterranean diet is safe in pregnancy, though trials are needed to determine its efficacy over conventional dietary advice. Currently, there are insufficient data to support the safety of the ketogenic diet for the treatment of GDM. The low GI diet may improve maternal and neonatal outcomes in GDM. The liberalized carbohydrate intake is less restrictive, culturally adaptable, and may improve long-term maternal adherence. Further research is needed to establish the optimal, most sustainable, and most acceptable medical nutrition therapy for management of women with GDM.

Neurocognitive and behavioural outcomes in offspring exposed to maternal pre-existing diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring. METHODS: We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle-Ottawa scale. Meta-analyses of summary measures were performed using random-effects models. RESULTS: Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference -3.07 [95% CI -4.59, -1.55]; I2 = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I2 = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I2 = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias. CONCLUSIONS/INTERPRETATION: There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings.