Disease activity and maternal–fetal outcomes in pregnant women with cushing’s syndrome: a systematic review and meta‑analysis

Pregnancy in women with Cushing’s syndrome (CS) is uncommon due to the detrimental effects of hypercortisolism on fertility and is associated with an increased risk of maternal and fetal complications. This systematic review evaluated the natural course and maternal–fetal outcomes of CS during pregnancy. Searches were conducted in MEDLINE, EMBASE and LILACS for observational studies including at least three pregnant women with CS. Twenty-two studies comprising 381 pregnancies were included. Among 200 women with reported etiologies, 54% had Cushing’s disease, 24% had adrenal adenoma, and 11% had adrenal carcinoma. The overall rate of spontaneous miscarriage was 6% (21 studies, 245 pregnancies; 95% CI, 3–13%), and that of preterm birth was 37% (18 studies, 342 pregnancies; 95% CI, 24–52%). Worsening of preexisting diabetes or development of gestational diabetes was reported in 24% (16 studies, 344 pregnancies; 95% CI, 13–39%), whereas hypertensive disorders of pregnancy (HDP) occurred in 39% (19 studies, 362 pregnancies; 95% CI, 23–58%). Among 134 pregnancies, only one thromboembolic event was reported. The perinatal mortality rate was 7% (18 studies, 342 newborns; 95% CI, 3–14%), low birth weight was 26% (11 studies, 113 newborns; 95% CI, 15–43%), and congenital malformations were 1% (11 studies, 306 newborns; 95% CI, 0–7%). A meta-analysis of four studies revealed that uncontrolled hypercortisolism was associated with higher odds of HDP, diabetes, and preterm birth. These findings suggest that pregnancy in women with uncontrolled CS is associated with an increased risk of adverse maternal and fetal outcomes.