Search

OBJECTIVE: Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardiometabolic disorders, but there is scant evidence regarding the association between glycemic level during pregnancy and these long-term offspring outcomes. RESEARCH DESIGN AND METHODS: We conducted a population-based, cohort study of deliveries in Ontario between April 1991 and March 2018. Women had preexisting diabetes, gestational diabetes, or no diabetes. We applied a Cox proportional hazard model to examine the risk of developing attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and cardiometabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders. RESULTS: A total of 3,407,961 mother-infant pairs were followed up to 29 years. Using a Cox proportional hazard model, offspring of women with type 1 diabetes had the highest risk of ADHD (adjusted hazard ratio [aHR] 1.43 [95% CI 1.36–1.49]), ASD (aHR 1.94 [1.80–2.09]), diabetes (aHR 4.73 [4.34–5.16]), hypertension (aHR 2.32 [2.07–2.61]), and cardiovascular disease (CVD) (aHR 1.72 [1.56–1.90]), followed by offspring of women with type 2 diabetes and gestational diabetes compared with those unexposed. Among women with preexisting diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22 [95% CI 1.12–1.32]), hypertension (aHR 1.42 [1.29–1.57]), and CVD (aHR 1.20 [1.11–1.29]) but no statistically significant association with neurobehavioral outcomes. CONCLUSIONS: In utero exposure to maternal diabetes was associated with an increase in ADHD, ASD, and cardiometabolic outcomes in offspring, with differences seen across diabetes subtypes. Pregnancy glycemia was associated with cardiometabolic outcomes, but not neurobehavioral outcomes, and provides a potentially modifiable risk factor to decrease cardiometabolic outcomes in offspring. [ABSTRACT FROM AUTHOR]

Aims: Our aims were, in the setting of type 2 diabetes mellitus (T2DM) in pregnancy, to investigate the association of polycystic ovary syndrome (PCOS) with perinatal outcomes and to examine whether treatment with metformin had a differential effect in those with and without PCOS. Materials and Methods: We performed a retrospective cohort study using the metformin in women with type 2 diabetes in pregnancy (MiTy) trial data. We examined differences in maternal and neonatal outcomes among MiTy participants with and without PCOS using linear and logistic regression to adjust for potential confounders. We additionally examined the relative difference in the effect of metformin treatment on pregnancy outcomes among MiTy participants with PCOS versus those without PCOS. Results: Among women with T2DM in pregnancy, PCOS was significantly associated with higher excess gestational weight gain (unadjusted 12.0 vs. 11.4 kg, adjusted mean difference 2.1 kg [0.3, 3.9], p = 0.021) and higher total insulin dose at 34–36 weeks (unadjusted 172 vs. 124 units per day, adjusted mean difference 44 units [15, 73], p = 0.004), but no difference was seen in neonatal outcomes. Unlike the non‐PCOS subgroup, metformin treatment versus placebo in the PCOS subgroup was associated with an increase in extremely large‐for‐gestational‐age infants (28.6 vs. 14.0%, p = 0.008 for interaction) and an increase in worsened pre‐existing maternal hypertension (16.7 vs. 4.5%, p = 0.046 for interaction). Conclusions: Clinicians should be alerted to the potential for high insulin requirements and excess weight gain in pregnant patients with T2DM and comorbid PCOS. Moreover, metformin may not be as beneficial in this population as previously understood. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 1 diabetes in pregnancy is associated with suboptimal pregnancy outcomes, attributed to maternal hyperglycaemia and offspring hyperinsulinism (quantifiable by cord blood C-peptide). We assessed metabolomic patterns associated with risk factors (maternal hyperglycaemia, diet, BMI, weight gain) and perinatal complications (pre-eclampsia, large for gestational age [LGA], neonatal hypoglycaemia, hyperinsulinism) in the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT). Methods: A total of 174 CONCEPTT participants gave ≥1 non-fasting serum sample for the biorepository at 12 gestational weeks (147 women), 24 weeks (167 women) and 34 weeks (160 women) with cord blood from 93 infants. Results from untargeted metabolite analysis (ultrahigh performance LC-MS) are presented as adjusted logistic/linear regression of maternal and cord blood metabolites, risk factors and perinatal complications using a modified Bonferroni limit of significance for dependent variables. Results: Maternal continuous glucose monitoring time-above-range (but not BMI or excessive gestational weight gain) was associated with increased triacylglycerols in maternal blood and increased carnitines in cord blood. LGA, adiposity, neonatal hypoglycaemia and offspring hyperinsulinism showed distinct metabolite profiles. LGA was associated with increased carnitines, steroid hormones and lipid metabolites, predominantly in the third trimester. However, neonatal hypoglycaemia and offspring hyperinsulinism were both associated with metabolite changes from the first trimester, featuring triacylglycerols or dietary phenols. Pre-eclampsia was associated with increased abundance of phosphatidylethanolamines, a membrane phospholipid, at 24 weeks. Conclusions/interpretation: Altered lipid metabolism is a key pathophysiological feature of type 1 diabetes pregnancy. New strategies for optimising maternal diet and insulin dosing from the first trimester are needed to improve pregnancy outcomes in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). Methods: This retrospective population‐based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long‐term residents and immigrants—overall, by time since immigration and by region of—using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). Results: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long‐term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13–1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long‐term residents were found for immigrants from Sub‐Saharan Africa (HR 1.63, 95% CI 1.40–1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28–1.62) and South Asia (HR 1.34, 95% CI 1.25–1.44). Conclusions: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low‐ and middle‐income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions. [ABSTRACT FROM AUTHOR]

The article focuses on two clinical trials investigating the role of metformin during pregnancy for improving outcomes in women with gestational diabetes and type 2 diabetes. Topics discussed include the results of the EMERGE trial, which explored the early use of metformin in gestational diabetes, and the MOMPOD trial, which examined the effects of adding metformin to insulin in individuals with type 2 diabetes during pregnancy.

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. [ABSTRACT FROM AUTHOR]

Women with gestational diabetes (GD) have reduced antioxidant capacity; however, the relationship between maternal diet, maternal biochemical capacity, breast milk concentration, and infant intake has not been adequately explored in the literature. An exploration of underlying mechanism(s) is warranted, particularly for nutrient antioxidants impacted by maternal intake. These nutrients may provide a means for modifying maternal and infant antioxidant capacity. Oxygen radical absorbance capacity (ORAC), alpha-tocopherol, ascorbic acid, and beta-carotene concentrations were measured in breast milk of women with and without GD. Plasma, three-day diet records, and breast milk were collected at 6 to 8 weeks postpartum. Student's t-test was used to compare breast milk ORAC, nutrient antioxidant concentration and plasma ORAC between women with and without GD. Pearson correlations were used to determine associations among antioxidant concentrations in breast milk and dietary antioxidant intake. Breast milk antioxidant concentrations were associated with maternal intake of beta-carotene (r = 0.629, p = 0.005). Breast milk and plasma ORAC and antioxidant vitamin concentrations were not significantly different between GD and NG women. Breast milk ORAC associated with breast milk alpha-tocopherol for NG (r = 0.763, p = 0.010), but not GD women (r = 0.385, p = 0.35), and with breast milk ascorbic acid for GD (r = 0.722, p = 0.043) but not NG women (r = 0.141, p = 0.70; interaction p = 0.041). In GD participants, breast milk ORAC was significantly associated with plasma ORAC (r = 0.780, p = 0.039). ORAC and antioxidant vitamin concentrations in breast milk in women with GD were comparable to women with NG; however, the relationships between breast milk ORAC and vitamin concentrations differed in GD versus NG women for alpha-tocopherol and ascorbic acid. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: As an indicator of maternal cardiometabolic health, newborn birthweight may be an important predictor of maternal type 2 diabetes mellitus (diabetes). We evaluated the relation between offspring birthweight and onset of maternal diabetes after pregnancy. Methods: This retrospective cohort study used linked population‐based health databases from Ontario, Canada. We included women aged 16–50 years without pre‐pregnancy diabetes, and who had a live birth between 2006 and 2014. We used Cox proportional hazard regression to evaluate the association between age‐ and sex‐standardized offspring birthweight percentile categories and incident maternal diabetes, while adjusting for maternal age, parity, year, ethnicity, gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). Results were further stratified by the presence of GDM in the index pregnancy. Results: Of 893,777 eligible participants, 14,329 (1.6%) women were diagnosed with diabetes over a median (IQR) of 4.4 (1.5–7.4) years of follow‐up. There was a continuous positive relation between newborn birthweight above the 75th percentile and maternal diabetes. Relative to a birthweight between the 50th and 74.9th percentiles, women whose newborn had a birthweight between the 97th and 100th percentiles had an adjusted hazards ratio (aHR) of diabetes of 2.30 (95% CI 2.16–2.46), including an aHR of 2.01 (95% CI 1.83–2.21) among those with GDM, and 2.59 (2.36–2.84) in those without GDM. Conclusions: A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes. [ABSTRACT FROM AUTHOR]

The field of diabetes in pregnancy has witnessed tremendous changes over the past 30 years, with an explosive growth in case numbers along with new and exciting opportunities to affect outcomes. Type 1 diabetes in pregnancy has increased by 40%, but type 2 diabetes in pregnancy, rarely seen 30 years ago, has more than doubled and, in some cases, tripled in prevalence. Compared with women with type 2 diabetes, women with type 1 diabetes have higher HbA1c, more large-for-gestational-age infants, and more preterm births. Women with type 2 diabetes have more chronic hypertension, more socioeconomic deprivation, and higher rates of perinatal mortality. Large randomized trials in women with diabetes in pregnancy have helped us understand the effectiveness of new technologies (i.e., continuous glucose monitoring) in women with type 1 diabetes, and the addition of metformin to insulin in women with type 2 diabetes, in improving pregnancy outcomes. Future endeavors, including artificial pancreas systems in women with type 1 diabetes and the use of continuous glucose monitoring, a better understanding of nutrition during pregnancy, and approaches to improve preconception and pregnancy self-care in women with type 2 diabetes, may lead to further improved outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine gestational weekly changes in continuous glucose monitoring (CGM) metrics and 24-h glucose profiles and their relationship to infant birth weight in pregnant women with type 1 diabetes.Research Design and Methods: An analysis of >10.5 million CGM glucose measures from 386 pregnant women with type 1 diabetes from two international multicenter studies was performed. CGM glucose metrics and 24-h glucose profiles were calculated for each gestational week, and the relationship to normal (10-90th percentile) and large (>90th percentile) for gestational age (LGA) birth weight infants was determined.Results: Mean CGM glucose concentration fell and percentage of time spent in the pregnancy target range of 3.5-7.8 mmol/L (63-140 mg/dL) increased in the first 10 weeks of pregnancy and plateaued until 28 weeks of gestation, before further improvement in mean glucose and percentage of time in range until delivery. Maternal CGM glucose metrics diverged at 10 weeks of gestation, with significantly lower mean CGM glucose concentration (7.1 mmol/L; 95% CI 7.05-7.15 [127.8 mg/dL; 95% CI 126.9-128.7] vs. 7.5 mmol/L; 95% CI 7.45-7.55 [135 mg/dL; 95% CI 134.1-135.9]) and higher percentage of time in range (55%; 95% CI 54-56 vs. 50%; 95% CI 49-51) in women who had normal versus LGA. The 24-h glucose profiles were significantly higher across the day from 10 weeks of gestation in LGA.Conclusions: Normal birth weight is associated with achieving significantly lower mean CGM glucose concentration across the 24-h day and higher CGM time in range from before the end of the first trimester, emphasizing the need for a shift in clinical management, with increased focus on using weekly CGM glucose targets for optimizing maternal glycemia from early pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article focuses on the transformative impact of continuous glucose monitoring (CGM) on managing diabetes during pregnancy, emphasizing the association between various CGM metrics and maternal and neonatal outcomes. It discusses research findings that suggest specific CGM targets for women with type 1 diabetes in pregnancy, underscoring the importance of achieving optimal time in range and minimizing time above and below certain glucose levels for improved perinatal outcomes.

Aims: To examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia. Methods: A pre‐planned sub‐study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS‐II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS‐II score. The role of continuous glucose monitoring (CGM) use was examined. Results: Overall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12–34 weeks gestation) and scored higher on the HFS‐II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS‐II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39–2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS‐II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06–3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49–1.15; p = 0.18). Conclusions: In pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: Thyroid hormones play a crucial role in foetal growth and neurocognitive development. Our aim was to compare a weight‐based dosing method of starting thyroxine to a fixed‐dose method in newly diagnosed women with subclinical hypothyroidism during pregnancy. Design: We performed a retrospective cohort study of consecutive women with newly diagnosed subclinical hypothyroidism during pregnancy seen at Mount Sinai Hospital and Women's College Hospital, Toronto, Canada 2015–2018. Patients: We identified women that were treated based on pre‐pregnancy weight and those that were given a fixed dose of 50 mcg/day. Measurements: The percent of women who reached the target TSH of <2.5 mIU/L within 4–8 weeks was compared using a chi‐squared test and a logistic regression model, adjusting for age, initial TSH and gestational age treatment was started. Results: 393 women were included: 252 treated using a fixed‐dose approach; 141 treated based on pre‐pregnancy weight. In the unadjusted analysis, there was no difference between the groups in the percentage of women in the target range within 4–8 weeks (89.6% in the fixed‐dose group vs 88.8% in the weight‐based group (p =.954)). However, after adjustment for between‐group differences in age, initial TSH and gestational age treatment was started, there was a significantly greater odds of achieving the target range using the weight‐based dosing (OR 4.26 (1.60–11.7), p =.004). Conclusions: Treating women with newly diagnosed subclinical hypothyroidism during pregnancy with a weight‐based strategy increased the odds of reaching the target TSH range within 4–8 weeks. Clinicians caring for these women should consider this approach when starting treatment during pregnancy. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the risk of adverse fetal outcomes after exposure to angiotensin converting enzyme inhibitors (ACE‐Is) or angiotensin receptor blockers (ARBs) in first trimester of pregnancy, by conducting a systematic review and meta‐analysis. Materials and Methods: A systematic literature search was conducted using Medline, Embase, Cochrane and PubMed from inception to 25 November 2019. Studies were included if they evaluated pregnancies exposed to ACE‐Is or ARBs, reported fetal outcomes, and compared these outcomes with a control group. Pooled odds ratios (ORs) were estimated using inverse variance‐weighted random effects model. The protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42020160566). Results: Studies reporting on 6234 pregnancies exposed to ACE‐Is or ARBs, 4104 pregnancies exposed to other oral antihypertensives, and 1,872,733 pregnancies without exposure were included in the meta‐analysis. ACE‐I or ARB exposed pregnancies, compared to non‐exposed controls, had higher risk of major congenital malformations (OR 1.82; 95% confidence interval [CI]: 1.42–2.34), cardiovascular malformations (OR 2.50; 95% CI: 1.62–3.87) and stillbirths (OR 1.75; 95% CI: 1.21–2.53). There was no difference in congenital malformations observed between pregnancies exposed to other antihypertensives compared to non‐exposed controls (OR 0.96; 95% CI: 0.69–1.33). Conclusions: Women exposed to ACE‐Is or ARBs during early pregnancy had higher risk of adverse fetal outcomes, including malformations and stillbirths, than non‐exposed controls. This increased risk was independent of underlying maternal hypertension, as those exposed to other antihypertensives did not exhibit a higher risk than healthy controls. Women planning for pregnancy using these medications, including those with diabetic nephropathy, should be counselled appropriately. [ABSTRACT FROM AUTHOR]

Objective: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of β-cell regeneration in pregnancy with type 1 diabetes.Research Design and Methods: C-peptide was measured on maternal serum samples from 127 participants (12, 24, and 34 weeks) and cord blood during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). C-peptide was measured using a highly sensitive direct and solid-phase competitive electrochemiluminescent immunoassay.Results: Three discrete patterns of maternal C-peptide trajectory were identified: pattern 1, undetectable throughout pregnancy, n = 74 (58%; maternal C-peptide <3 pmol/L); pattern 2, detectable at baseline, n = 22 (17%; maternal C-peptide 7-272 pmol/L at baseline); and pattern 3, undetectable maternal C-peptide at 12 and 24 weeks, which first became detectable at 34 weeks, n = 31 (24%; maternal C-peptide 4-26 pmol/L at 34 weeks). Baseline characteristics and third trimester glucose profiles of women with pattern 1 and pattern 3 C-peptide trajectories were similar, but women in pattern 3 had suboptimal glycemia (50% time above range) at 24 weeks' gestation. Offspring of women with pattern 3 C-peptide trajectories had elevated cord blood C-peptide (geometric mean 1,319 vs. 718 pmol/L; P = 0.007), increased rates of large for gestational age (90% vs. 60%; P = 0.002), neonatal hypoglycemia (42% vs. 14%; P = 0.001), and neonatal intensive care admission (45% vs. 23%; P = 0.023) compared with pattern 1 offspring.Conclusions: First maternal C-peptide appearance at 34 weeks was associated with midtrimester hyperglycemia, elevated cord blood C-peptide, and high rates of neonatal complications. This suggests transfer of C-peptide from fetal to maternal serum and is inconsistent with pregnancy-related β-cell regeneration. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. Methods: This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. Results: Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation (p = 0.003). With optimal maternal glycaemia (HbA1c < 48 mmol/mol [6.5%]/ or continuous glucose monitoring time above range ≤ 30%), birthweight z scores were reduced towards zero (normal weight) with increasing PlGF values (representing a healthy placenta), and increased with decreasing PlGF values. With suboptimal glycaemic status (HbA1c ≥ 48 mmol/mol [6.5%] or time above range > 30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. Conclusions/interpretation: In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently 'normal' birthweight. [ABSTRACT FROM AUTHOR]

Background: The Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial (CONCEPTT) found improved health outcomes for mothers and their infants among those randomized to self-monitoring of blood glucose (SMBG) with continuous glucose monitoring (CGM) compared with SMBG alone. In this study, we evaluated whether CGM or standard SMBG was more or less costly from the perspective of a third-party payer. Methods: We conducted a posthoc analysis of data from the CONCEPTT trial (Mar. 25, 2013, to Mar. 22, 2016). Health care resource data from 215 pregnant women, randomized to CGM or SMBG, were collected from 31 hospitals in 7 countries. We determined resource costs posthoc based on prices from hospitals in 3 Canadian provinces (Ontario, British Columbia, Alberta). The primary outcome was the difference between groups in the mean total cost of care for mother and infant dyads, paid by each government (i.e., the third-party payer) from randomization to hospital discharge (time horizon). The secondary outcome included CGM and SMBG costs not paid by governments (e.g., glucose monitoring devices and supplies). Results: The mean total cost of care was lower in the CGM group compared with the SMBG group in each province (Ontario: $13 270.25 v. $18 465.21, difference in mean total cost [DMT] −$5194.96, 95% confidence interval [CI] −$9841 to −$1395; BC: $13 480.57 v. $18 762.17, DMT −$5281.60, 95% CI −$9964 to −$1382; Alberta: $13 294.39 v. $18 674.45, DMT −$5380.06, 95% CI −$10 216 to −$1490). There was no difference in the secondary outcome. Interpretation: Government health care costs are lower when CGM is paid by the patient, driven by lower costs from reduced use of the neonatal intensive care unit in the CGM group; however, when governments pay for CGM equipment, there is no overall cost difference between CGM and SMBG. Governments should consider paying for CGM, as it results in improved maternal and neonatal outcomes with no added overall cost. Trial registration: ClinicalTrials.gov, no. NCT01788527 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to examine how BMI influences the association between Asian ethnicity and risk of gestational diabetes (GDM). Methods: This population-based cohort study included pregnant women without pre-existing diabetes mellitus in Ontario, Canada between 2012 and 2014. Women of Chinese and South Asian ethnicity were identified using a validated surname algorithm. GDM was ascertained using hospitalisation codes. The relationship between ethnicity and GDM was modelled using modified Poisson regression, adjusted for maternal age, pre-pregnancy BMI, parity, previous GDM, long-term residency status, income quintile and smoking status. An interaction term between ethnicity and pre-pregnancy BMI was tested. Results: Of 231,618 pregnant women, 9289 (4.0%) were of South Asian ethnicity and 12,240 (5.3%) were of Chinese ethnicity. Relative to women from the general population, in whom prevalence of GDM was 4.3%, the adjusted RR of GDM was higher among those of South Asian ethnicity (1.81 [95% CI 1.64, 1.99]) and Chinese ethnicity (1.66 [95% CI 1.53, 1.80]). The association between GDM and Asian ethnicity remained significant across BMI categories but differed according to BMI. The prevalence of GDM exceeded 5% at an estimated BMI of 21.5 kg/m2 among South Asian women, 23.0 kg/m2 among Chinese women and 29.5 kg/m2 among the general population. Conclusions/interpretation: The risk of GDM is significantly higher in South Asian and Chinese women, whose BMI is lower than that of women in the general population. Accordingly, targeted GDM prevention strategies may need to consider lower BMI cut-points for Asian populations. [ABSTRACT FROM AUTHOR]

Objective: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.Research Design and Methods: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).Results: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c.Conclusions: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR). [ABSTRACT FROM AUTHOR]

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT).Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome.Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes.Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes.Trial Registration: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013. [ABSTRACT FROM AUTHOR]

Thyroid disease is common in women of childbearing age and can have significant effects on the development of the fetus and perinatal outcomes. Maternal thyroid hormone is critical for proper fetal neurodevelopment, and the fetus relies on thyroid hormone from its mother for the first half of pregnancy. Both overt maternal hypothyroidism and overt maternal hyperthyroidism have been shown to be associated with adverse effects on central nervous system gray matter and neurocognitive development of offspring as well as increased obstetrical risks. Treatment of overt thyroid conditions improves outcomes. Subclinical maternal hypothyroidism may increase adverse neurocognitive and obstetrical outcomes although data are conflicting. To date, treatment of subclinical hypothyroidism has not shown benefit. Subclinical hyperthyroidism is well tolerated in pregnancy. Thyroid autoantibodies alone may also affect neurodevelopment and obstetrical outcomes; however, recent data have shown no improvement with levothyroxine treatment. Several rare maternal genetic thyroid conditions can affect the fetus including a thyroid-stimulating hormone receptor mutation leading to hypersensitivity to human chorionic gonadotropin and thyroid hormone resistance. The thyroid plays a crucial role in fetal health and understanding it is important for optimal care. [ABSTRACT FROM AUTHOR]

Objective: To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).Research Design and Methods: Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.Results: FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L [7-14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L [7-16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks.Conclusions: FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article offers information on a study related to the use of metformin for gestational diabetes mellitus (GDM). It is noted that metformin has a safe record and have some benefits compared with insulin or glyburide when used for the treatment of GDM. It mentions the challenges such as rising costs of insulin, and safe prescription of insulin.

Objective: To compare glycemic control, quality of life, and pregnancy outcomes of women using insulin pumps and multiple daily injection therapy (MDI) during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).Research Design and Methods: This was a prespecified analysis of CONCEPTT involving 248 pregnant women from 31 centers. Randomization was stratified for pump versus MDI and HbA1c. The primary outcome was change in HbA1c from randomization to 34 weeks' gestation. Key secondary outcomes were continuous glucose monitoring (CGM) measures, maternal-infant health, and patient-reported outcomes.Results: At baseline, pump users were more often in stable relationships (P = 0.003), more likely to take preconception vitamins (P = 0.03), and less likely to smoke (P = 0.02). Pump and MDI users had comparable first-trimester glycemia: HbA1c 6.84 ± 0.71 vs. 6.95 ± 0.58% (51 ± 7.8 vs. 52 ± 6.3 mmol/mol) (P = 0.31) and CGM time in target (51 ± 14 vs. 50 ± 13%) (P = 0.40). At 34 weeks, MDI users had a greater decrease in HbA1c (-0.55 ± 0.59 vs. -0.32 ± 0.65%, P = 0.001). At 24 and 34 weeks, MDI users were more likely to achieve target HbA1c (P = 0.009 and P = 0.001, respectively). Pump users had more hypertensive disorders (P = 0.011), mainly driven by increased gestational hypertension (14.4 vs. 5.2%; P = 0.025), and more neonatal hypoglycemia (31.8 vs. 19.1%, P = 0.05) and neonatal intensive care unit (NICU) admissions >24 h (44.5 vs. 29.6%; P = 0.02). Pump users had a larger reduction in hypoglycemia-related anxiety (P = 0.05) but greater decline in health/well-being (P = 0.02).Conclusions: In CONCEPTT, MDI users were more likely to have better glycemic outcomes and less likely to have gestational hypertension, neonatal hypoglycemia, and NICU admissions than pump users. These data suggest that implementation of insulin pump therapy is potentially suboptimal during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Cold-induced thermogenesis is known to improve insulin sensitivity, which may become increasingly relevant in the face of global warming. The aim of this study was to examine the relation between outdoor air temperature and the risk of gestational diabetes mellitus.Methods: We identified all births in the Greater Toronto Area from 2002 to 2014 using administrative health databases. Generalized estimating equations were used to examine the relation between the mean 30-day outdoor air temperature before the time of gestational diabetes mellitus screening and the likelihood of diagnosis of gestational diabetes mellitus based on a validated algorithm using hospital records and physician service claims.Results: Over the 12-year period, there were 555 911 births among 396 828 women. Prevalence of gestational diabetes mellitus was 4.6% among women exposed to extremely cold mean outdoor air temperatures (≤ -10°C) in the 30-day period before screening and increased to 7.7% among those exposed to hot mean 30-day temperatures (≥ 24°C). Each 10°C increase in mean 30-day temperature was associated with a 1.06 (95% confidence interval [CI] 1.04-1.07) times higher odds of gestational diabetes mellitus, after adjusting for maternal age, parity, neighbourhood income quintile, world region and year. A similar effect was seen for each 10°C rise in outdoor air temperature difference between 2 consecutive pregnancies for the same woman (adjusted odds ratio 1.06, 95% CI 1.03-1.08).Interpretation: In our setting, there was a direct relation between outdoor air temperature and the likelihood of gestational diabetes mellitus. Future climate patterns may substantially affect global variations in the prevalence of diabetes, which also has important implications for the prevention and treatment of gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Ivanisevic and Djelmis publishing descriptions of the cohort of pregnant women with type 1 diabetes (T1D) (2). Topics include suboptimal glycemia and higher cord C-peptide, consistent with fetal hyperinsulinemia, and striking rates of neonatal morbidity; and fetal C-peptide crossing the placenta into maternal circulation in late pregnancy.

Background: The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high. Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes. We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. Our aim is to compare the effectiveness of the addition of metformin to insulin, to standard care (insulin plus placebo) in women with type 2 diabetes in pregnancy.Methods: The MiTy trial is a multi-centre randomized trial currently enrolling pregnant women with type 2 diabetes, who are on insulin, between the ages of 18-45, with a gestational age of 6 weeks 0 days to 22 weeks 6 days. In this randomized, double-masked, parallel placebo-controlled trial, after giving informed consent, women are randomized to receive either metformin 1,000 mg twice daily or placebo twice daily. A web-based block randomization system is used to assign women to metformin or placebo in a 1:1 ratio, stratified for site and body mass index. The primary outcome is a composite neonatal outcome of pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age, cord blood gas pH < 7.0, congenital anomalies, hyperbilirubinemia, sepsis, hyperinsulinemia, shoulder dystocia, fetal fat mass, as well as maternal outcomes: maternal weight gain, maternal insulin doses, maternal glycemic control, maternal hypoglycemia, gestational hypertension, preeclampsia, cesarean section, number of hospitalizations during pregnancy, and duration of hospital stays. The trial aims to enroll 500 participants.Discussion: The results of this trial will inform endocrinologists, obstetricians, family doctors, and other healthcare professionals caring for women with type 2 diabetes in pregnancy, as to the benefits of adding metformin to insulin in this high risk population.Trial Registration: ClinicalTrials.gov Identifier: no. NCT01353391 . Registered February 6, 2009. [ABSTRACT FROM AUTHOR]

Background: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy.Methods/design: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes.Discussion: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes.Trial Registration: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012. [ABSTRACT FROM AUTHOR]

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. [ABSTRACT FROM AUTHOR]

Objective Post-partum thyroiditis ( PPT) is a common phenomenon in the general population. To date there have been few studies examining the incidence of PPT in women with hypothyroidism antedating pregnancy. This study aimed to assess the incidence and potential predictors of PPT in women with treated hypothyroidism antedating pregnancy. Design Retrospective cohort study. Patients and Methods We compiled a cohort of 97 women with previous hypothyroidism antedating pregnancy seen in the Endocrinology in Pregnancy clinic from 1999 to 2011, collecting data on thyroid function, antibodies and levothyroxine doses post-partum. The incidence of PPT and its predictors were analysed. Results A total of 66 (68%) women had fluctuations in thyroid function consistent with PPT. Of these, 22 (33%) had a hyperthyroid phase alone, 22 (33%) had a hypothyroid phase alone and 22 (33%) had both a hyper and hypo phase. The majority of women had their dose of thyroid medication adjusted during the PPT episode. Women who were on a full dose of thyroxine post-partum were significantly less likely to have a hypothyroid phase. In multivariable analysis, the only predictor of PPT was the presence of thyroid antibodies, with 83% of antibody positive women having PPT compared to 44% of antibody negative women ( P = 0·0001). Conclusions In our cohort, 2/3 of women had fluctuations in thyroid function consistent with PPT and most required adjustment of their thyroid dose. Women with hypothyroidism antedating pregnancy are at high risk for PPT and should be closely monitored during the first year post-partum. [ABSTRACT FROM AUTHOR]

OBJECTIVE Women with diabetes in pregnancy have high rates of pregnancy complications. Our aims were to explore trends in the incidence of diabetes in pregnancy and examine whether the risk of serious perinatal outcomes has changed. RESEARCH DESIGN AND METHODS We performed a population-based cohort study of 1,109,605 women who delivered in Ontario, Canada, between 1 April 1996 and 31 March 2010. We categorized women as gestational diabetes (GDM) (n = 45,384), pregestational diabetes (pre-GDM) (n = 13,278), or no diabetes (n = 1,050,943). The annual age-adjusted rates of diabetes in pregnancy were calculated, and rates of serious perinatal outcomes were compared between groups and by year using Poisson regression. RESULTS The age-adjusted rate of both GDM (2.7-5.6%, P < 0.001) and pre-GDM (0.7-1.5%, P < 0.001) doubled from 1996 to 2010. The rate of congenital anomalies declined by 23%, whereas the rate of perinatal mortality did not change significantly. However, compared with women with no diabetes, women with pre-GDM and GDM faced an increased risk of congenital anomalies (relative risk 1.86 [95% CI 1.49-2.33] and 1.26 [1.09-1.45], respectively), and perinatal mortality remained elevated in women with pre-GDM (2.33 [1.59-3.43]). CONCLUSIONS The incidence of both GDM and pre-GDM in pregnancy has doubled over the last 14 years, and the overall burden of diabetes in pregnancy on society is growing. Although congenital anomaly rates have declined in women with diabetes, perinatal mortality rates remain unchanged, and the risk of both remains significantly elevated compared with nondiabetic women. Increased efforts are needed to reduce these adverse outcomes. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives To determine whether demographic, community or health status disparities in cardioprotective medication utilization by diabetes patients exist under a universal drug insurance programme, and whether they narrow or widen during periods of increasing drug utilization. Methods We examined all prescriptions filled by all people with diabetes aged ≥65 years in Ontario, Canada in annual cohorts from 1996 ( n = 175 345) to 2010 ( n = 504 093). We ascertained whether any disparities in use of three classes of cardioprotective medication (statins, all antihypertensives and renin-angiotensin-aldosterone system inhibitors) existed, and whether disparities changed over time. Results Utilization of all three cardioprotective medication classes increased substantially over time, particularly statins (rate ratio per year: 1.13, 95% confidence interval 1.11-1.15). We found no disparities associated with many of the demographic or community characteristics examined (including sex, income or rural residence). Use of statins was lower in those aged ≥80 compared with younger age groups, although this disparity narrowed during the study. Persistently lower use of antihypertensives by minorities and by recent immigrants may be due to lower quality of care, barriers to access, or other patient or provider factors, which highlights the need for ongoing monitoring for disparities even in populations with universal drug insurance. Differences in medication utilization based on health status characteristics such as previous cardiovascular disease were medically indicated. Conclusions Although a universal drug insurance programme was reasonably successful in ensuring few disparities in cardioprotective medication use by older patients with diabetes, disparities persisted for some subpopulations, so additional interventions continue to be needed to ensure equitable care. [ABSTRACT FROM AUTHOR]

Background: Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes. Methods and Findings: We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97-2.19) and GH alone (HR = 1.95; 95% CI 1.83-2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44-13.10); however, the co-presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52-17.07, and HR = 18.49; 95% CI 17.12-19.96, respectively). Data on obesity were not available. Conclusions: Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. [ABSTRACT FROM AUTHOR]

Pregnancy in the setting of type 1 diabetes is associated with an increased risk of adverse outcomes for both mother and fetus. Adequate glycaemic control has been shown to result in improved outcomes, but the strict glycaemic targets required in pregnancy are often difficult to achieve. The development of novel technologies for insulin delivery aim to assist in achieving excellent glycaemic control, while attempting to minimize the significant risk of hypoglycaemia that exists in pregnancy. This review will discuss the use of insulin pump therapy, continuous glucose monitoring and closed loop insulin delivery in the setting of pregestational diabetes, highlighting some of the potential advantages of these technologies. Novel insulin delivery devices have been shown to be safe in the setting of pregnancy, but proper randomized controlled trials are still needed to determine if they are superior to traditional insulin delivery mechanisms. [ABSTRACT FROM AUTHOR]