Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies.

PURPOSE: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C27 bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression. Currently, CDCA is contraindicated for use during pregnancy based on animal studies that showed that high-dose CDCA may cause fetal harm when administered to pregnant animals. Data regarding the safety of CDCA treatment in humans are lacking. METHODS: We present a case series of 19 pregnancies in 9 women with CTX who either received CDCA treatment throughout pregnancy or did not. RESULTS: In 11 pregnancies where mothers continued CDCA treatment, no complications were reported, and newborns were born at or near full term, with normal birth weight and Apgar scores. In 8 pregnancies where mothers did not receive CDCA, 2 newborns experienced elevated bilirubin soon after birth. One woman who stopped treatment during her pregnancy deteriorated neurologically while off treatment. CONCLUSION: The data we present support the benefit of continued CDCA treatment in pregnant women with CTX for both the affected women and their offspring.

Ectopic pregnancy: perinatal outcomes of future gestations and long-term neurological morbidity of the offspring.

PURPOSE: To evaluate perinatal outcomes and long-term neurological morbidity of offspring to mothers with a history of ectopic pregnancy. METHODS: In this retrospective study, perinatal outcomes and long-term neurological morbidity of offspring were assessed among mothers with a history of ectopic pregnancy, either medically or surgically treated. The study groups were followed until 18 years of age for neurological-related morbidity. For perinatal outcomes, generalized estimated equation (GEE) models were used to control for confounders. A Kaplan-Meier survival curve was used to compare cumulative neurological morbidity incidence and Cox proportional hazards model was conducted to control for confounders. RESULTS: A total of 243,682 mothers were included; 1424 mothers (0.58%) had a previous ectopic pregnancy, of which 25.6% (n = 365) were treated medically, and 74.3% (n = 1059) were treated surgically. Using GEE models, controlling for confounders, both surgically and medically treated ectopic pregnancies were noted as independent risk factors for preterm delivery in the subsequent pregnancies. Maternal history of surgically treated ectopic pregnancy was also independently associated with cesarean delivery. Offspring to mothers with previous ectopic pregnancy had comparable rates of long-term neurological morbidity. In the Cox proportional hazards model, controlling for confounders, being born to a mother with a history of previous ectopic pregnancy was not found to be independently associated with long-term neurological morbidity of offspring. CONCLUSIONS: Maternal history of ectopic pregnancy is independently associated with preterm delivery. However, offspring of mothers with a history of ectopic pregnancy are not at an increased risk for long-term neurological morbidity.