Pregnancy outcomes in women exposed to cancer chemotherapy.

PURPOSE: There is little data on the effects of cancer chemotherapy in pregnant women. The objective of this study was to describe pregnancy outcomes of women exposed to cancer chemotherapy, recorded in the French Terappel database. METHODS: We performed a descriptive, prospective study of the pregnancies of women exposed to cancer chemotherapy recorded in Terappel between June 1984 and December 2016. Terappel is a French database that has recorded questions of health professionals and/or individuals at the Regional Pharmacovigilance Centres about drugs and pregnancy. For each question, pregnancies are monitored and the outcome is recorded in the database. RESULTS: In total, 75 questions about "anti-cancer drugs and pregnancy" received by 16 Regional Pharmacovigilance Centres between 1997 and 2016 were recorded in Terappel. Breast cancer accounted for 62.7% of the cases, followed by leukaemia (13.3%) and lymphoma (9.3%). Cyclophosphamide is the leading anti-cancer drug with 40.0% of exposed pregnant women, followed by 5-fluorouracil (34.7%), epirubicin (32.0%), tamoxifen (26.7%), and doxorubicin (16.0%). Among the 75 pregnancies, we observed 55 births with 57 children (73.3%) (two cases of twins), nine medical terminations of pregnancy (12.0%), six voluntary terminations of pregnancy (8.0%), three intrauterine foetal deaths (4.0%), and two miscarriages (2.7%). We found a malformation rate of 7.8%. Sixteen of 57 (28.1%) newborns developed one or more neonatal pathologies. CONCLUSION: Pregnancy of women taking anti-cancer drugs resulted in birth in 73% of cases. Nevertheless, pregnant women exposed to cancer chemotherapy remains at risk of malformations and neonatal conditions related to prematurity and drugs.

Möbius syndrome in a neonate after mifepristone and misoprostol elective abortion failure.

OBJECTIVE: To report a case of a child born with Möbius syndrome following exposure in utero to mifepristone and misoprostol for elective abortion. CASE SUMMARY: In the seventh week of pregnancy, a woman was administered mifepristone 600 mg and, 2 days later, misoprostol 400 mug for abortion. One month later, despite significant metrorrhagia, an ultrasound examination showed ongoing gestation. At 33 weeks and 3 days of gestation, the woman gave birth to a male with left facial palsy, microretrognathia, and axial hypotonia related to Möbius syndrome. DISCUSSION: Möbius syndrome is characterized by unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal [XII]), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Möbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia (particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Möbius syndrome has been suggested. The critical period for the development of Möbius syndrome following teratogen exposure appears to be 5-8 weeks of gestation. To date, mifepristone alone does not appear to have induced Möbius syndrome. In contrast, oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow. CONCLUSIONS: Ineffective use of mifepristone and misoprostol in the first trimester of pregnancy may be associated with a risk of Möbius syndrome, primarily due to misoprostol activity. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk.

Fetal toxic effects of angiotensin II receptor antagonists: case report and follow-up after birth.

OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 microg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high beta2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and beta2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.