Mean Glucose and Gestational Weight Gain as Predictors of Large-for-Gestational-Age Infants in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitoring.

Aims/hypothesis: To compare glycemic metrics during pregnancy between women with type 1 diabetes (T1D) delivering large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants, and to identify predictors of LGA infants. Materials and Methods: A cohort study including 111 women with T1D using intermittently scanned continuous glucose monitoring from conception until delivery. Average sensor-derived metrics: mean glucose, time in range in pregnancy (TIRp), time above range in pregnancy, time below range in pregnancy, and coefficient of variation throughout pregnancy and in pregnancy intervals of 0-10, 11-21, 22-33, and 34-37 weeks were compared between women delivering LGA and AGA infants. Predictors of LGA infants were sought for. Infant growth was followed until 3 months postdelivery. Results: In total, 53% (n = 59) delivered LGA infants. Mean glucose decreased during pregnancy in both groups, with women delivering LGA infants having a 0.4 mmol/L higher mean glucose from 11-33 weeks (P = 0.01) compared with women delivering AGA infants. Mean TIRp >70% was obtained from 34 weeks in women delivering LGA infants and from 22-33 weeks in women delivering AGA infants. Independent predictors for delivering LGA infants were mean glucose throughout pregnancy and gestational weight gain. At 3 months postdelivery, infant weight was higher in infants born LGA compared with infants born AGA (6360 g ± 784 and 5988 ± 894, P = 0.04). Conclusions/interpretations: Women with T1D delivering LGA infants achieved glycemic targets later than women delivering AGA infants. Mean glucose and gestational weight gain were independent predictors for delivering LGA infants. Infants born LGA remained larger postdelivery compared with infants born AGA.

Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Faster-acting insulin aspart (faster aspart) is considered safe for use during pregnancy and breastfeeding but has not been evaluated in this population. We aimed to evaluate the effect of faster aspart versus insulin aspart on fetal growth, in women with type 1 or type 2 diabetes during pregnancy and post-delivery. METHODS: This open-label, single-centre, superiority trial was conducted at Rigshospitalet, Copenhagen, Denmark. Participants aged 18 years or older with type 1 or type 2 diabetes were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump), randomly assigned 1:1 to faster aspart or insulin aspart, from 8 weeks and 0 days (8+0) of gestation to 13+6 weeks of gestation, and followed up until 3 months post-delivery. Primary outcome was infant birthweight SD score. Secondary outcomes included HbA1c as well as maternal and fetal outcomes in all participants during the trial. This trial is registered with ClinicalTrials.gov, NCT03770767. FINDINGS: Between Nov 11, 2019 and May 10, 2022, 109 participants were included in the faster aspart group and 107 in the insulin aspart group. Primary outcome data were available in 203 (94%) of 216 participants, and no participants discontinued treatment during the trial. Mean birthweight SD score was 1·0 (SD 1·4) in the faster aspart group versus 1·2 (1·3) in the insulin aspart group; estimated treatment difference -0·22 [-0·58 to 0·14]; p=0·23. At 33 weeks of gestation, mean HbA1c was 42 mmol/mol (SD 6 mmol/mol; 6·0% [SD 0·9%]) versus 43 mmol/mol (SD 7 mmol/mol; 6·1% [SD 1·2%]); estimated treatment difference -1·01 (-2·86 to 0·83), p=0·28. No additional safety issues were observed with faster aspart compared with insulin aspart. INTERPRETATION: Treatment with faster aspart resulted in similar fetal growth and HbA1c, relative to insulin aspart, in women with type 1 or type 2 diabetes. Faster aspart can be used in women with type 1 or type 2 diabetes during pregnancy and post-delivery with no additional safety issues. FUNDING: Novo Nordisk. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Falling Insulin Requirement in Pregnant Women With Diabetes Delivering Preterm: Prevalence, Predictors, and Consequences.

CONTEXT: Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated. OBJECTIVE: To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity. METHODS: A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded. RESULTS: In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34 + 5 (33 + 6-35 + 4) weeks + days and delivery occurred 3 (1-9) days later. Gestational age at delivery, prevalence of suspected fetal asphyxia, and neonatal morbidity were similar in women with and without falling insulin requirements. Neither glycemic control, nausea, or preeclampsia was associated with falling insulin requirement. CONCLUSION: Falling insulin requirements often preceded preterm delivery in women with type 1 diabetes, foremost when preterm delivery was indicated, but was not related to fetal asphyxia or neonatal morbidity. Whether falling insulin requirements in late pregnancy are a warning sign of placental insufficiency or mainly reflects variations in normal physiology needs further investigation.

Unchanged Prevalence of Preeclampsia After Implementation of Prophylactic Aspirin for All Pregnant Women With Preexisting Diabetes: A Prospective Cohort Study.

OBJECTIVE: To evaluate the prevalence of preeclampsia after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes compared with the prevalence in a previous risk-based prophylaxis. RESEARCH DESIGN AND METHODS: A prospective observational cohort study of 410 consecutive pregnant women with preexisting diabetes categorized according to aspirin prophylaxis strategy, with the prevalence of preeclampsia as primary outcome. In total, 207 women were included after implementation of prophylactic aspirin for all pregnant women with preexisting diabetes in February 2018 (all-cohort). The 203 women included before this date, where aspirin prophylaxis was risk based and only prescribed to selected women (selected-cohort), were studied for comparison. RESULTS: Aspirin was prescribed at ∼10 gestational weeks for 88% (all-cohort) compared with 25% (selected-cohort). HbA1c, parity, chronic hypertension, home blood pressure, microalbuminuria/diabetic nephropathy, and smoking were similar in the two cohorts in early pregnancy. In the all-cohort, fewer women had type 2 diabetes (32% vs. 42%, respectively; P = 0.04) and BMI tended to be lower (P = 0.05). The prevalence of preeclampsia was similar (12% vs. 11%, P = 0.69) in the two cohorts, and this was also the case with stratification for diabetes type. Prevalence of preterm delivery <37 weeks (23% vs. 27%, P = 0.30), preterm preeclampsia (7% vs. 7%, P = 0.96), and infants large (40% vs. 32%, P = 0.07) and small (7% vs. 6%, P = 0.88) for gestational age was similar in the two cohorts. CONCLUSIONS: Implementation of prophylactic aspirin for all pregnant women with diabetes did not reduce the prevalence of preeclampsia compared with the previous risk-based prophylaxis in this cohort study.

The impact of restricted gestational weight gain by dietary intervention on fetal growth in women with gestational diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to investigate the impact of maternal gestational weight gain (GWG) during dietary treatment on fetal growth in pregnancies complicated by gestational diabetes (GDM). METHODS: This was a retrospective cohort study of 382 women consecutively diagnosed with GDM before 34 weeks' gestation with live singleton births in our centre (Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark) between 2011 and 2017. The women were stratified into three groups according to restricted (53%), appropriate (16%) and excessive (31%) weekly GWG during dietary treatment (using the Institute of Medicine guidelines) to estimate compliance with an energy-restricted 'diabetes diet' (6000 kJ/day [1434 kcal/day], with approximately 50% of energy intake coming from carbohydrates with a low glycaemic index, and a carbohydrate intake of 175 g/day). Insulin therapy was initiated if necessary, according to local clinical guidelines. RESULTS: Glucose tolerance, HbA1c, weekly GWG before dietary treatment (difference between weight at GDM diagnosis and pre-pregnancy weight, divided by the number of weeks) and SD score for fetal abdominal circumference were comparable across the three groups at diagnosis of GDM at 276 ± 51 weeks (gestation time is given as weeksdays). The women were followed for 100 ± 51 weeks, during which 54% received supplementary insulin therapy and the average (mean) GWG during dietary treatment was 0 kg, 3 kg and 5 kg in the three groups, respectively. Excessive weekly GWG during dietary treatment, reflecting poor dietary adherence was associated with increasing HbA1c (p = 0.014) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.59 ± 1.6. In contrast, restricted weekly GWG during dietary treatment, reflecting strict dietary adherence, was associated with decreasing HbA1c (p = 0.001) from diagnosis of GDM to late pregnancy and infants with a birthweight-SD score of 0.15 ± 1.1, without increased prevalence of infants born small for gestational age. Excessive GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score (p = 0.02 for both variables) after correction for confounders. CONCLUSIONS/INTERPRETATION: Restricted GWG during dietary treatment was associated with healthier fetal growth in women with GDM. GWG during dietary treatment and late-pregnancy HbA1c were identified as potentially modifiable clinical predictors of infant birthweight-SD score.