From peril to new reality: scientific advances transform pregestational diabetes in pregnancy care and outcomes.

For hundreds of years, pregestational diabetes mellitus was a life-limiting, devastating diagnosis managed by extreme caloric restriction, but with the inevitable outcome of wasting and death within months to a few years. The maternal mortality rate was unacceptably high (over 50%), and although many women desired to have children, or even the chance despite the extremely high rates of pregnancy loss, fetal death, and neonatal death, women were universally discouraged from pregnancy due to high maternal risk. This was accompanied by depression and even suicide in some instances. When insulin was discovered in 1921, pregnancy became possible but associated with high maternal and perinatal morbidity and mortality. Over the past several decades, remarkable discoveries in the pathophysiology of diabetes and innovations in management have been made. The discovery of hyperglycemia as a teratogen, and thus blood glucose levels as a modifiable risk factor for congenital anomalies, has highlighted the importance of preconception care. Advances in fetal ultrasound and echocardiography have led directly to improved neonatal care and a reduction in perinatal mortality. Continuous glucose monitoring and automated insulin delivery systems have improved maternal glycemic stability, subsequently decreasing rates of large for gestational age infants, neonatal intensive care unit admissions, and neonatal hypoglycemia. However, risks remain, including preeclampsia, preterm birth, large for gestational age infants, congenital anomalies, cesarean delivery, neonatal morbidity, and long-term offspring health consequences. While ongoing advances in prenatal imaging and screening protocols continue to improve diagnosis and management, disparities in access to preconception care and diabetes technologies remain major obstacles to optimal outcomes worldwide. We review the scientific discoveries and clinical advances that have shaped modern care and discuss the persistent challenges and future directions in the management of pregestational diabetes in pregnancy.