Early daycare is associated with an increase in airway symptoms in early childhood but is no protection against asthma or atopy at 8 years.

RATIONALE: Daycare exposes young children to more infections early in life and may thereby prevent the development of asthma and allergy. OBJECTIVES: To prospectively study the effect of daycare on the development of asthma and allergic sensitization during the first 8 years of life. METHODS: In the Prevention and Incidence of Asthma and Mite Allergy birth cohort 3,963 newborn children were followed prospectively for 8 years. Daycare use and respiratory health were assessed yearly by questionnaires. At 8 years, sensitization to airborne allergens and airway responsiveness were measured. Daycare was defined as early (aged 0-2 yr), late (aged 2-4 yr), or none (no daycare before age 4 yr). Associations of daycare and/or older siblings with asthma symptoms (wheezing, shortness of breath, and inhaled steroids taken in the last year), airway responsiveness, and allergic sensitization were assessed in a longitudinal repeated-event analysis. MEASUREMENTS AND MAIN RESULTS: Children with early daycare had more wheezing in the first years of life, but less wheezing and steroid use between 4 and 8 years of age. At the age of 8 years, early daycare was not protective for asthma symptoms (adjusted odds ratio [aOR], 0.99; 95% confidence interval [CI], 0.74-1.32), allergic sensitization (aOR 0.86; 95% CI, 0.63-1.18), or airway hyperresponsiveness (aOR, 0.80; 95% CI, 0.57-1.14). The transient reduction in airway symptoms between age 4 and 8 years was only observed in children without older siblings. CONCLUSION: Early daycare is associated with an increase in airway symptoms until the age of 4 years, and fewer symptoms between the ages of 4 and 8 years. We found no protection against asthma symptoms, hyperresponsiveness, or allergic sensitization at the age of 8 years.

Polymorphisms in the mannan-binding lectin gene are not associated with questionnaire-reported respiratory tract infections in children.

BACKGROUND: Low mannan-binding lectin (MBL) levels, caused by MBL2 polymorphisms, are suggested to contribute to susceptibility to respiratory tract infections (RTIs), particularly early in life. Large-scale replication of previous associations is needed, however. We investigated the association between MBL2 polymorphisms and the frequency of RTI in a large population-based birth cohort of white children. METHODS: The frequency of RTI was prospectively assessed by annual parental questionnaires until children were 4 years of age. Thirteen polymorphisms in MBL2 were determined in 987 Dutch children. Haplotypes, previously shown to be associated with functional levels of MBL, were constructed, and their associations with the frequency of RTI during year 1, year 2, and the first 4 years of life were assessed. High-producing, intermediate-producing, and deficient MBL2 genotypes were defined on the basis of exon 1 and Y/X promoter polymorphisms. RESULTS: No differences were found between investigated polymorphisms and haplotype frequencies in the population as a whole or between the groups with frequent, moderately frequent, or no RTIs reported. Deficient MBL2 genotypes were not associated with an increased risk of RTI (odds ratio, 0.71 [95% confidence interval, 0.25 to 2.05]) during years 1-4 of life. This was also true when year 1 and year 2 were studied separately. CONCLUSION: These results suggest that, at the population level, MBL2 polymorphisms do not contribute to the risk of questionnaire-reported RTI in white children.

Mannose-binding lectin and upper respiratory tract infections in children and adolescents: a review.

OBJECTIVE: To review the literature on mannose-binding lectin (MBL) polymorphisms and susceptibility for upper respiratory tract infection (URI) in children and adolescents. DATA SOURCES: We searched PubMed from 1966 and EMBASE from 1974 to July 2005, using the terms respiratory tract infection, respiratory infection, upper respiratory infection, MBL, and mannose-binding lectin. STUDY SELECTION: Initially, 110 studies were identified. Two reviewers independently screened identified titles and abstracts. Potentially relevant studies were obtained and the full text examined. Inclusion criteria were human subjects, 18 years or younger, URI, and MBL polymorphisms. Seven of the initially identified studies met the inclusion criteria. DATA EXTRACTION: Information was gathered for each study on study design, population, possible confounders, and outcomes measured. DATA SYNTHESIS: Because there was significant heterogeneity between the identified studies, we had to describe the identified studies separately. The largest case-control studies (n = 3) as well as the cohort study (n = 1) suggest an association between MBL polymorphisms and URI, especially in young children. Results of the smaller studies (n = 3) are inconsistent. CONCLUSIONS: The association between MBL polymorphisms and URI in children remains controversial. Large prospective cohort studies with regular documentation of URI and possible confounders such as atopy and environmental factors are required to establish the role of MBL polymorphisms in susceptibility for URI.

Treatment of fetal tachycardia with sotalol: transplacental pharmacokinetics and pharmacodynamics.

OBJECTIVES: The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of sotalol in the treatment of fetal tachycardia. BACKGROUND: Maternally administered, intrauterine therapy of fetal tachycardia is dependent on the transplacental passage of the antiarrhythmic agent. METHODS: In a prospective study of patients treated for fetal tachycardia with sotalol, concentrations of sotalol were determined in maternal and umbilical blood and in amniotic fluid, and the relationship between these concentrations and the occurrence of conversion to sinus rhythm was investigated. RESULTS: Eighteen fetal patients were studied, nine with atrial flutter and nine with supraventricular tachycardia. Fourteen were treated with sotalol; 13 converted to sinus rhythm, of whom 2 relapsed. There was one intrauterine death. Four patients were treated with sotalol and digoxin, of whom two were treated successfully. Mean birth weight was 3,266 g. The daily maternal sotalol dose was linearly related to the maternal plasma concentration. The mean fetal/maternal sotalol plasma concentration was 1.1 (range 0.67 to 2.87, SD 0.63), and the mean amniotic fluid/fetal blood ratio of sotalol was 3.2 (range 1.28 to 5.8, SD 1.4). The effectiveness of sotalol therapy could not be extrapolated from maternal blood levels. CONCLUSIONS: Sotalol is a potent antiarrhythmic agent in the treatment of fetal tachycardia. The placental transfer is excellent. Sotalol accumulates in amniotic fluid but not in the fetus itself. Therefore it seems that renal excretion in the fetus is efficient and greater than the oral absorption by fetal swallowing. The maternal blood level is not a reliable predictor of the chances of success of therapy. Sotalol is not associated with fetal growth restriction.

Drug treatment of fetal tachycardias.

The pharmacological treatment of fetal tachycardia (FT) has been described in various publications. We present a study reviewing the necessity for treatment of FT, the regimens of drugs used in the last two decades and their mode of administration. The absence of reliable predictors of fetal hydrops (FH) has led most centers to initiate treatment as soon as the diagnosis of FT has been established, although a small minority advocate nonintervention. As the primary form of pharmacological intervention, oral maternal transplacental therapy is generally preferred. Digoxin is the most common drug used to treat FT; however, effectiveness remains a point of discussion. After digoxin, sotalol seems to be the most promising agent, specifically in atrial flutter and nonhydropic supraventricular tachycardia (SVT). Flecainide is a very effective drug in the treatment of fetal SVT, although concerns about possible pro-arrhythmic effects have limited its use. Amiodarone has been described favorably, but is frequently excluded due to its poor tolerability. Verapamil is contraindicated as it may increase mortality. Conclusions on other less frequently used drugs cannot be drawn. In severely hydropic fetuses and/or therapy-resistant FT, direct fetal therapy is sometimes initiated. To minimize the number of invasive procedures, fetal intramuscular or intraperitoneal injections that provide a more sustained release are preferred. Based on these data we propose a drug protocol of sotalol 160 mg twice daily orally, increased to a maximum of 480 mg daily. Whenever sinus rhythm is not achieved, the addition of digoxin 0.25 mg three times daily is recommended, increased to a maximum of 0.5 mg three times daily. Only in SVT complicated by FH, either maternal digoxin 1 to 2mg IV in 24 hours, and subsequently 0.5 to 1 mg/day IV, or flecainide 200 to 400 mg/day orally is proposed. Initiating direct fetal therapy may follow failure of transplacental therapy.