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]

Background and Aims Compared to those without inflammatory bowel disease [IBD], women with IBD may have increased healthcare utilization during pregnancy and postpartum, though this remains to be confirmed. We aimed to characterize this healthcare use between these groups. Methods Administrative databases were accessed to identify women [aged 18–55 years] with and without IBD who had a live, singleton pregnancy between 2003 and 2018. Differences in emergency department [ED] visits, hospitalizations and prenatal care during 12 months preconception, pregnancy and 12 months postpartum were characterized. Multivariable negative binomial regression was performed to report incidence rate ratios [IRRs] with 95% confidence intervals [95% CIs]. Covariates included maternal age at conception, location of residence, socioeconomic status and maternal comorbidity. Results In total, 6163 women with IBD [9158 pregnancies] and 1091 013 women without IBD [1729 411 pregnancies] were included. Women with IBD were more likely to visit the ED [IRR 1.13, 95% CI 1.08–1.18] and be hospitalized [IRR 1.11, 95% CI 1.01–1.21] during pregnancy, and visit the ED [IRR 1.21, 95% CI 1.15–1.27] and be hospitalized [IRR 1.18, 95% CI 1.05–1.32] during postpartum. On unadjusted analysis, women with IBD were more likely to be hospitalized for venous thromboembolic events. There was no difference in healthcare use in preconception. Finally, women with IBD also had a greater number of prenatal visits during pregnancy and were more likely to receive a first-trimester prenatal visit. Conclusion Women with IBD have increased healthcare utilization during pregnancy and postpartum. Efforts should be made to increase ambulatory care access during this period, which in turn may reduce this health-services utilization. [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]