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.

Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature.

OBJECTIVE: Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome. CASE REPORT: We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP. CONCLUSION: We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis.

Long term ophthalmic complications of distal arthrogryposis type 5D.

BACKGROUND: Distal Arthrogryposis type 5D (DA5D) is a rare genetic disease, expressed phenotypically by skeletal and ocular abnormalities. MATERIALS AND METHODS: Two sisters, ages 42 and 46 years old, were ascertained, both diagnosed with arthrogryposis and unusual ophthalmic late expressions of the disease. They were examined and followed up by both ophthalmologists and medical geneticists. Molecular analysis was performed and population screening followed among healthy individuals of the same ethnic background who reside in the same village. RESULTS: The two sisters expressed myogenic ptosis with poor levator palpebrae function, limitation in up gaze, lagophthalmos, refractive errors, corneal scarring and vascularization along with severe distal arthrogryposis. The newly reported features were: significant lower lid retraction, causing inferior scleral show. Sanger sequencing of the coding regions of ECEL1 gene revealed a homozygous deletion of 46 bps. The carrier frequency is 1:24 (4.2% carriers) in the probands' village. CONCLUSIONS: We diagnosed two patients with DA5D carrying a homozygous pathogenic genetic variant previously reported only once. We report the late ophthalmologic manifestations of this rare disorder and emphasize the importance to recognize possible long-term ophthalmic complications. Measures are needed to diagnose this rare disorder at a younger age and to address ophthalmic and orthopedic complications that might be prevented. We revealed the causative genetic variant and a carrier frequency of 1:24 for DA5D, in the probands' village, thus enabling accurate genetic counselling and justifying genetic testing to the residents of this village as a diagnostic and preventive measure.

Differences in outcomes between cesarean section in the second versus the first stages of labor.

OBJECTIVE: We aimed to compare maternal morbidity and mortality of cesarean sections (CS) in the second versus first stage of labor. STUDY DESIGN: Retrospective study of all CS at a single, university-affiliated medical center, between January 2010 and December 2014. Eligibility was limited to term, singleton pregnancies with cephalic presentation. Maternal outcomes of second-stage CS were compared to those of first-stage CS. The primary outcome was defined as estimated blood loss >1000 ml. RESULTS: Overall, 1004 women met the inclusion criteria, of which 290 (29%) had a second-stage CS and 714 (71%) had a first-stage CS. Women in the second-stage CS group had a higher nulliparity and hypertensive disorders rates and a lower rate of previous CS. Second-stage CS was associated with more than double the rate of estimated blood loss >1000 ml (9.7% versus 3.8%, p<.001), and more prone to unintentional uterine incision extension, uterine atony, hemoglobin decrease >2 g/l and antibiotic treatment for suspected endometritis. In a multivariable logistic regression model, second-stage CS was found to be independently associated with unintentional uterine incision extension (OR 6.8, 95% CI 4.1-11.2), uterine atony (OR 3.3, 95% CI 1.4-8.0) and antibiotic treatment for suspected endometritis (OR 2.6, 95% CI 1.4-5.1), but not with excessive blood loss (OR 1.5, 95% CI 0.8-2.8). Additionally, failed assisted vaginal delivery prior to second-stage CS was not associated with a higher rate of complications. CONCLUSION: Second-stage CS is associated with higher rates of adverse maternal outcomes, mainly unintentional uterine incision extension, uterine atony, and suspected endometritis.

When should repeat cesarean delivery be scheduled, after two or more previous cesarean deliveries?

BACKGROUND: The optimal gestational age for a planned high-order cesarean delivery (CD) reflects the balance between the risk of neonatal morbidity and the risk of unscheduled cesarean delivery prior to the scheduled date. METHODS: A retrospective cohort study of 656 women with ≥2 previous CDs were divided in two groups of women based on the gestational age at which the CD was scheduled: "38 group" and "39 group". Medical records were reviewed for demographic, medical and obstetrical history, and for adverse maternal and neonatal outcomes. RESULTS: The rate of unscheduled CDs was significantly higher among the 39 group (23.2% vs. 12.7%). There were no significant differences in the rate of maternal or neonatal composite adverse outcome between the two groups. The rate of neonatal respiratory morbidity, however, was higher among the 38 group (5.8% vs. 2.1%).Compared with planned CD, unscheduled CD was associated with a similar rate of maternal composite adverse outcome, but with increased rate of neonatal composite adverse outcome (23.3% vs. 8%, respectively). In a multivariable logistic regression analysis we found that this latter association was due to the earlier actual gestational age at delivery in cases of unscheduled versus planned CD. CONCLUSIONS: Planned CD at 39 weeks, rather than at 38 weeks, is associated with more unscheduled CDs, a similar rate of maternal and neonatal composite morbidity, but a decreased rate of neonatal respiratory morbidity.