Potentially modifiable risk factors of preterm delivery in women with type 1 and type 2 diabetes.

AIMS/HYPOTHESIS: We aimed to identify potentially modifiable risk factors and causes for preterm delivery in women with type 1 or type 2 (pre-existing) diabetes. METHODS: A secondary analysis of a prospective cohort study of 203 women with pre-existing diabetes (117 type 1 and 86 type 2 diabetes) was performed. Consecutive singleton pregnancies were included at the first antenatal visit between September 2015 and February 2018. RESULTS: In total, 27% (n = 55) of the 203 women delivered preterm at median 36 + 0 weeks. When stratified by diabetes type, 33% of women with type 1 diabetes delivered preterm compared with 20% in women with type 2 diabetes (p = 0.04). Women delivering preterm were characterised by a higher prevalence of pre-existing kidney involvement (microalbuminuria or diabetic nephropathy) (16% vs 3%, p = 0.002), preeclampsia (26% vs 5%, p < 0.001), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (2.7% vs -1.6% from the mean, p = 0.008), higher gestational weight gain (399 g/week vs 329 g/week, p = 0.01) and similar HbA1c levels in early pregnancy (51 mmol/mol [6.8%] vs 49 [6.6%], p = 0.22) when compared with women delivering at term. Independent risk factors for preterm delivery were pre-existing kidney involvement (OR 12.71 [95% CI 3.0, 53.79]), higher gestational weight gain (per 100 g/week, OR 1.25 [1.02, 1.54]), higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks (% from the mean, OR 1.07 [1.03, 1.12]) and preeclampsia (OR 7.04 [2.34, 21.19]). Two-thirds of preterm deliveries were indicated and one-third were spontaneous. Several contributing factors to indicated preterm delivery were often present in each woman. The main indications were suspected fetal asphyxia (45%), hypertensive disorders (34%), fetal overgrowth (13%) and maternal indications (8%). Suspected fetal asphyxia mainly included falling insulin requirement and abnormal fetal haemodynamics. CONCLUSIONS/INTERPRETATIONS: Presence of preeclampsia, higher positive ultrasound estimated fetal weight deviation at 27 gestational weeks and higher gestational weight gain were independent potentially modifiable risk factors for preterm delivery in this cohort of women with pre-existing diabetes. Indicated preterm delivery was common with suspected fetal asphyxia or preeclampsia as the most prevalent causes. Prospective studies evaluating whether modifying these predictors will reduce the prevalence of preterm delivery are warranted.

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.