Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) ¼ 12.2, 95% confidence interval (CI): 2.4 -62.3). A statistically significant association with additional birth defects, female gender and gestational age .40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR ¼ 1.9, 95% CI: 0.7-5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR ¼ 15.7, 95% CI: 0.9-523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease. 153 765-773 European Journal of Endocrinology

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.

Seventy-five percent of the women reported use of at least one drug during pregnancy. Haematological and nutritional drugs are over prescribed. Although hormones have been clearly proven to be ineffective in preventing threatened abortion, the study shows an almost unchanged and out of date prescription pattern of progestational drugs. In order to avoid unnecessary exposure to potential risk, maternity care procedures should be reviewed and strictly related to an "evidence-based" approach.

Most of the interviewed women in this study preferred, or were satisfied with, vaginal birth.

The relative influence of early life events in the development of IgE-mediated allergy is still undetermined. We investigated early life factors in relation to skin-prick test positivity (SPT) and clinical manifestations of atopic disease in a population-based sample of 201 Italian children (3 months-5 years), after considering their interactions with known determinants of allergy. Among them, 143 children had SPT performed to common allergens. Threatened abortions, general anesthesia at delivery, prematurity, birthweight < 2500 g, maternal smoking, dampness and gas heating exposure were all significantly related to an increased risk of frequent rhinitis in the absence of cold (18%). In utero smoking, threatened abortions, fetal health complications, infantile colic, maternal smoking in childhood (satisfactorily correlated with maternal expired CO during the survey) and respiratory infections were all independent determinants of frequent wheezing (23%). Doctor's diagnosis of asthma (3%) was related to in utero smoking, being born in spring, infantile colic and respiratory infections. A simultaneous exposure to in utero smoking and infantile colic put the infants to a fourfold higher risk of frequent wheezing and to a ninefold risk of asthma, respectively. Having a pet and washing blankets at < 60 degrees C were inversely related to frequent wheezing. Data confirmed also that maternal phenotype influences the inheritance of atopic disease. No event, except a low intake of fruit (< 3/week), was significantly associated with positive SPT (20%) or eczema. Besides allergic sensitization, other events, which occur early in life, seem critical to the development of IgE-mediated allergy.