Neonatal outcome following metformin-treated gestational diabetes mellitus: A population-based cohort study.

INTRODUCTION: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth. MATERIAL AND METHODS: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models. RESULTS: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. CONCLUSIONS: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.

Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: A longitudinal, placebo-controlled study.

OBJECTIVE: To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls. DESIGN: Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls). SETTING: Eleven Norwegian, Swedish, and Icelandic hospitals. POPULATION: Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15). METHODS: Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters. MAIN OUTCOME MEASURES: Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels. RESULTS: The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (P < 0.001), and lower third trimester allopregnanolone levels (P = 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2-0.8, P = 0.005). FLI decreased during pregnancy in PCOS-M (P = 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy. CONCLUSION: Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS. TWEETABLE ABSTRACT: Metformin counteracts excessive weight gain and leptin resistance in pregnant women with polycystic ovary syndrome.

Characteristics and short-term obstetric outcomes in a case series of 67 women test-positive for SARS-CoV-2 in Stockholm, Sweden.

INTRODUCTION: The Stockholm region was the first area in Sweden to be hit by the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The national guidelines on the care of women with a positive test for SARS-CoV-2 (detection with polymerase chain reaction [PCR]) recommend individualized antenatal care, mode of delivery based on obstetric considerations, and no routine separation of the mother and the newborn. Breastfeeding is encouraged, and although there is no specific recommendation regarding wearing a face mask to prevent viral transmission to the newborn while nursing, instructions are given to keep high hygiene standards. All studies based on cases tested on hospital admission will capture more women with pregnancy complications than in the general population. Our aim was to describe the clinical characteristics of SARS-CoV-2-positive women and their neonates, and to report short-term maternal and neonatal outcomes. MATERIAL AND METHODS: A retrospective case series with data from medical records including all test-positive women (n = 67) who gave birth to 68 neonates from 19 March to 26 April 2020 in Stockholm, Sweden. Means, proportions and percentages were calculated for clinical characteristics and outcomes. RESULTS: The mean age was 32 years, 40% were nulliparous and 61% were overweight or obese. Further, 15% had diabetes and 21% a hypertensive disease. Seventy percent of the women had a vaginal birth. Preterm delivery occurred in 19% of the women. The preterm deliveries were mostly medically indicated, including two women who were delivered preterm due to severe coronavirus disease 19 (COVID-19), corresponding to 15% of the preterm births. Four women (6%) were admitted to the intensive care unit postpartum but there were no maternal deaths. There were two perinatal deaths (one stillbirth and one neonatal death). Three neonates were PCR-positive for SARS-CoV-2 after birth. CONCLUSIONS: In this case series of 67 women testing positive for SARS-CoV-2 with clinical presentations ranging from asymptomatic to manifest COVID-19 disease, few women presented with severe COVID-19 illness. The majority had a vaginal birth at term with a healthy neonate that was negative for SARS-CoV-2.