The impact of baseline proteinuria in pregnant women with pregestational diabetes mellitus

BACKGROUND: The incidence of diabetes in pregnancy has increased dramatically with the rising rates of obesity. Because there are a number of recognized adverse maternal and fetal outcomes associated with diabetes, there have been several attempts to classify this disorder for perinatal risk stratification. One of the first classification systems for pregnancy was developed by White nearly 70 years ago. More recently, efforts to stratify diabetic disease severity according to vasculopathy have been adopted. Regardless of classification system, vasculopathy-associated effects have been associated with worsening pregnancy outcomes. Defining vasculopathy within an organ system, however, has not been consistent. For example, definitions of diabetic kidney disease differ from the previously used threshold of >= 500 mg/d by White for pregnancy to varying thresholds of albuminuria by the American Diabetes Association. OBJECTIVE: To evaluate a proteinuria threshold that was a relevant determinant of perinatal risk in a cohort of women with type 2 diabetes. MATERIALS AND METHODS: This was a retrospective cohort study of women with pregestational diabetes delivered of nonanomalous, singleton, liveborn infants. All women were assessed for baseline maternal disease burden with a 24-hour proteinuria quantification performed before 20 weeks' gestation. Women with <500 mg/d on 24-hour urine collections were included. Perinatal outcomes were analyzed according to the following protein excretion values: 50-100, 101-200, 201-300, and 301-499 mg/d. Based on trends noted in these results and using the prior definition of the American Diabetes Association of 300 mg/d of albumin for diabetic kidney disease, women were then analyzed according to 24-hour urine collections of <= 300 or >300 mg/d. RESULTS: Between 2009 and 2016, a total of 594 women with pregestational diabetes were found to meet study criteria. When analyzed according to protein excretion values 50-100, 101-200, 201-300, and 301-499 mg/d, there were no differences in maternal demographics. The rate of preeclampsia with severe features (P for trend = .02), preterm birth at <37 weeks (P for trend <.001), and birthweight <10th percentile (P for trend = .02) were significantly associated with increasing proteinuria excretion, with the highest rates in the >300 mg/d group. Perinatal outcomes were then examined in the context of 24-hour urine protein excretion values of <= 300 or >300 mg/d, with no differences in maternal demographics. Protein excretion values >300 mg/d were significantly associated with preterm birth <37 weeks (P = .003), preeclampsia with severe features (P = .002), and birthweight <10th percentile (P = .048). CONCLUSION: White's classification in 1949 was developed to stratify perinatal risks based on maternal disease burden, and it was found that urinary protein excretion of >500 mg/d was associated with adverse pregnancy outcomes. In a contemporary cohort of pregnant women, proteinuria >300 mg/d was associated with preterm birth, preeclampsia with severe features, and birthweight <10th percentile.