Maternal residential atrazine exposure and risk for choanal atresia and stenosis in offspring.

OBJECTIVE: To assess the relationship between estimated residential maternal exposure to atrazine during pregnancy and the risk for choanal atresia or stenosis in offspring. STUDY DESIGN: Data for 280 nonsyndromic cases and randomly selected, population-based controls delivered between 1999 and 2008 were obtained from the Texas Birth Defects Registry. County-level estimates of atrazine levels obtained from the US Geological Survey were assigned to cases and controls based on maternal county of residence at delivery. Unconditional logistic regression was used to assess the relationship between maternal residential atrazine exposure and the risk for choanal atresia or stenosis in offspring. RESULTS: Compared with offspring of mothers with low levels of estimated residential atrazine exposure, those with high levels had nearly a 2-fold increase in risk for choanal atresia or stenosis (aOR, 1.79; 95% CI, 1.17-2.74). A significant linear trend was also observed with increasing levels of atrazine exposure (adjusted P = .002). CONCLUSION: A link between maternal exposure to endocrine disruptors, such as atrazine, and the risk of choanal atresia is plausible based on previous findings. Our results lend further support to this hypothesis.

Pharmacologic treatment of hyperthyroidism during pregnancy.

Clinical hyperthyroidism has been associated with an increased risk of maternal, fetal, and neonatal complications. The available antithyroid drugs are methimazole/carbimazole and propylthiouracil. Several case reports and some epidemiologic studies suggest that methimazole/carbimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations, including ectodermal anomalies, choanal atresia, esophageal atresia, and omphalocele. However, the absolute risk appears to be very small, and it remains unclear whether the association is driven by the maternal disease, the medication, or the combination of both factors. Propylthiouracil exposure has not been associated with an increased risk of congenital malformations and is the recommended drug during the first trimester of pregnancy. Since propylthiouracil-induced hepatotoxicity has been reported in approximately 0.1% of exposed adults and the number of case-reports of severe liver injury is increasing, treatment with low dose methimazole during the second and third trimesters should be considered. Until now, there has been no evidence that children prenatally exposed to methimazole/carbimazole or propylthiouracil have an increased risk of neurodevelopmental delay.

Choanal atresia associated with tracheoesophageal fistula: the spectrum of carbimazole embryopathy.

This article focuses on the case of a newborn infant boy with bilateral choanal atresia, tracheoesophageal fistula, and bilateral fifth-finger clinodactyly. This infant had been exposed to carbimazole in utero during the treatment of maternal Graves disease. Teratogenic defects caused by carbimazole were recently recognized, and their phenotypes have been defined. Choanal atresia, esophageal atresia, athelia or hypothelia, developmental delay, hearing loss, and dysmorphic facial features have all been reported. To our knowledge, this is the first documented case of tracheoesophageal fistula without esophageal atresia (H type). Knowledge of the teratogenic potential of carbimazole is important when managing Graves disease in women of childbearing age.

Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.

OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.

Choanal atresia associated with maternal hyperthyroidism treated with methimazole: a case-control study.

Thyrotoxicosis affects 0.2% of pregnant women and antithyroid drugs are the treatment of choice during pregnancy. Several case reports have suggested a relationship between the prenatal use of methimazole (MMI) and choanal atresia in the offspring. However, two epidemiological studies did not find an increased teratogenic risk for MMI. This multicenter case-control study compared the frequency of maternal hyperthyroidism treated with MMI during pregnancy, in children with choanal atresia (cases) and a control group randomly selected (three matched controls according to maternal age for each case). Mothers of cases (N = 61) and controls (N = 183) were interviewed for socio-demographic questions, obstetrical and genetic history, and exposure during pregnancy to different agents; specifically detailed information regarding hyperthyroidism and MMI intake was obtained. Prenatal exposure to maternal hyperthyroidism treated with MMI was identified in 10/61 cases (16.4%) compared to 2/183 (1.1%) in the control group (OR = 17.75; CI95% = 3.49-121.40). Cases and controls did not differ in their parental degree of education, paternal occupation, twinning, maternal parity, and other exposures during pregnancy. Facial features in exposed cases showed some similarities. Our data suggest that prenatal exposure to maternal hyperthyroidism treated with MMI is associated with choanal atresia. In addition, based on our cases and a critical literature review, we propose that the mother's disease might be the causal factor and not the MMI treatment.

Carbimazole embryopathy-bilateral choanal atresia and patent vitello-intestinal duct: a case report and review of literature.

BACKGROUND: In utero exposure to carbimazole for maternal hyperthyroidism has been reported to cause choanal atresia. There are case reports of patent vitello-intestinal duct and Meckel's diverticulum in similar association. CASE: We report another such instance of an infant who was exposed to carbimazole in utero, presenting with bilateral choanal atresia and patent vitello-intestinal duct. CONCLUSIONS: As there seems to be no reports of a possible association between propylthiouracil and congenital malformations, it may be safer to use propylthiouracil instead of carbimazole.

Antenatal carbimazole and choanal atresia: a new embryopathy.

Carbimazole embryopathy is a recently recognized and defined phenotype. Choanal atresia; gastrointestinal anomalies, particularly esophageal atresia; athelia or hypothelia; developmental delay; hearing loss; aplasia cutis; and dysmorphic facial features all can occur after exposure to the antithyroid drugs carbimazole or methimazole during gestation. Although full expression of this phenotype appears to be an uncommon sequelae of antenatal carbimazole exposure, infants with less overt manifestations may remain with the condition undiagnosed. It is clearly important when an infant with choanal atresia is assessed to take an adequate drug history and consider this embryopathy as a potential causative factor.

Choanal atresia - a recurrent feature of foetal carbimazole syndrome.

Choanal atresia is described as a feature of several congenital anomaly phenotypes. Most cases of choanal atresia arises as an isolated clinical finding. In utero exposure to carbimazole for maternal hyperthyroidism has been reported in five cases of choanal atresia. We report another instance of this teratogenic cause of choanal atresia. Maternal drug history is an important aspect of assessment in cases of choanal atresia.

Choanal atresia associated with prenatal methimazole exposure: three new patients.

We report three patients with bilateral choanal atresia in children prenatally exposed to methimazole (MMI) in order to define a MMI embryopathy clinical pattern. The combination of choanal atresia and other specific malformations strongly resembles previously reported patients exposed to MMI in utero. At present, propylthiouracil is considered the best treatment in pregnancies. However in Argentina and some other countries MMI is the only antithyroid drug, possibly posing a significant risk to the unborn fetus.

Choanal atresia: the result of maternal thyrotoxicosis or fetal carbimazole?

We present the fourth published case of a child affected with choanal atresia following maternal treatment with carbimazole. The mother was receiving her highest dose of carbimazole at the crucial period for development of the choanae, between days 35 and 38.

Methimazole embryopathy: delineation of the phenotype.

We report on a further case of congenital anomalies in a child exposed to methimazole during the first trimester of pregnancy (from first to seventh gestational week), and define a specific malformation pattern related to prenatal methimazole exposure and consisting of choanal and esophageal atresia, scalp defects, minor facial anomalies and psychomotor delay.

Choanal atresia and hypothelia following methimazole exposure in utero: a second report.

We report on a 3-year-old boy with bilateral choanal atresia, hypoplastic nipples, and developmental delay who had been exposed to carbimazole in utero because of maternal Graves disease. His combination of abnormalities and facial appearance strongly resembles that of a previously reported child exposed to methimazole (which is the active metabolite of carbimazole) in utero. We suggest that this represents a rare but distinct syndrome of methimazole teratogenicity, probably related to first-trimester exposure. Recognition of such teratogenic effects is clearly important for genetic counselling and for management of subsequent pregnancies.

Choanal atresia and athelia: methimazole teratogenicity or a new syndrome?

An infant girl with choanal atresia, athelia, minor anomalies, and mild to moderate mental retardation was born to a woman treated for hyperthyroidism throughout pregnancy with methimazole and propranolol. The patient's defects may be due to methimazole teratogenicity or could represent a previously undescribed syndrome affecting ectodermal structures.