Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled ß2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled ß2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting ß2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled ß2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting ß2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

Protein-losing enteropathy after the total cavopulmonary connection: impact of intravenous immunoglobulin.

OBJECTIVE: Despite multiple treatment modalities, protein-losing enteropathy remains a serious complication to Fontan-type operations. Observations suggest inflammation to be involved in the pathogenesis of this condition, and immunomodulating treatment with high-dose intravenous immunoglobulin may modify the condition positively. PATIENTS: Four patients with protein-losing enteropathy occurring after the total cavopulmonary connection, presenting with edema, hypoalbuminemia, and hypogammaglobulinemia, received intravenous immunoglobulin replacement therapy. INTERVENTIONS: Standard replacement dose (1 g/kg) was used with intervals between infusions adjusted according to albumin and gamma globulin levels. Treatment periods ranged from 1 year to 5.3 years. RESULTS: Intravenous immunoglobulin treatment was associated with significant increase in plasma albumin and to some extent in immunoglobulin G levels, as well as resolution of edema and the children started to thrive normally. During treatment, no serious infections or serious side effects were seen. Additional follow-up intervals ranged from 2 years to 2.8 years, during which only one episode of clinical relapse was registered and treated. CONCLUSIONS: We find the increase in albumin level and the resolution of protein-losing enteropathy symptoms after treatment with intravenous immunoglobulin of particular interest considering this serious complication to Fontan-type operations.