Increased prevalence of negative pregnancy and fetal outcomes in women with primary adrenal insufficiency. A systematic review and meta-analysis

Maternal primary adrenal insufficiency (PAI) during pregnancy, due to either Addison disease (AD) or congenital adrenal hyperplasia (CAH), is rare. Only few studies have examined the subsequent important outcomes of maternal glucocorticoid and mineralocorticoid deficiencies during pregnancy upon the fetus and the neonate. Therefore, this systematic review and meta-analysis evaluated the impact of these deficiencies, with data from PubMed/Medline, Cochrane/CENTRAL, and Google Scholar. A total of 31 studies were included for qualitative analysis and 11 for quantitative analysis. Studies examining the prevalence of spontaneous abortion, preterm birth, the occurrence of small for gestational age (SGA) neonates, as well as the neonatal birth weight were included. The systematic review revealed a substantial number of spontaneous abortions, preterm births and SGA neonates in pregnant women with PAI. The meta-analysis showed a mean spontaneous abortion prevalence of 18%, 18% and 17% in women with PAI, AD or CAH, respectively. The mean preterm birth prevalence was 11% when women with AD or CAH were analyzed together, and 13% and 9% in women with AD or CAH, respectively, when these women were analyzed separately. The mean prevalence of SGA neonates was 8% when women with AD or CAH were analyzed together, and 5% and 10% in women with AD or CAH, respectively, when these women were analyzed separately. The mean fetal birth weight was within normalcy in all women with PAI, as well as in women with AD or CAH. In conclusion the executed systematic review of 31 studies followed by a meta-analysis of 11 studies in pregnant women with PAI has shown a greater prevalence of pregnancies with negative outcome (spontaneous abortion, preterm birth) and of negative fetal outcome (SGA) in women with either AD or CAH, as compared to control pregnant women.