Sonia Brescianini

Teratogenic effects of antiepileptic drugs : Use of an international database on malformations and drug exposure (MADRE)

Summary: Purpose: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging.

OBJECTIVES: To analyze the relationship between serum total cholesterol (TC) and all‐cause mortality, taking into account various potential confounders.

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors.

Heritability and shared genetic effects of asthma and hay fever: an Italian study of young twins.

A number of studies have provided evidence of a significant familial aggregation for both asthma and hay fever, and have reported a substantial comorbidity between the two conditions. However, far fewer, especially in Italy, have aimed at clarifying the origins of such comorbidity. The main aims of the present study were (a) to estimate heritability of asthma and hay fever, (b) to measure the association between asthma and hay fever at the individual level, and (c) to assess the extent to which genetic and environmental factors, shared by the two conditions, mediate this association. The twin method was used. The study sample was derived from the Italian Twin Registry, and included 392 twin pairs aged 8 to 17 years. Data collection was performed through parent self-administered questionnaire. Bivariate structural equation twin modeling was applied to asthma and hay fever. Genetic factors accounted for 92% and 78% of the variance in liability to asthma and hay fever, respectively, with the remaining contributions due to unique environmental influences. The within-individual association between asthma and hay fever was substantial. The genetic correlation between the two conditions was .58, whereas no evidence of overlapping unique environmental effects was found. In conclusion, this study showed a high heritability of asthma and hay fever in the Italian child and adolescent population. It also indicated that asthma and hay fever share, to a large extent, a common genetic background, and environmental factors are not relevant to explain the comorbidity.

Genetic and Environmental Factors Shape Infant Sleep Patterns: A Study of 18-Month-Old Twins

OBJECTIVE: Between 25% and 30% of children and adolescents experience sleep disorders. These disorders are complex phenotypes that are regulated by many genes, the environment, and gene-environment interactions. The objective of this study was to evaluate the contribution of genetic and environmental factors to sleep behaviors in early childhood and to contribute to the knowledge on appropriate therapeutic approaches, using a twin design. PATIENTS AND METHODS: Data on sleeping behavior were collected from 314 18-month-old twin pairs (127 monozygotic and 187 dizygotic)using a parent-rated questionnaire. We used structural equation modeling to estimate genetic and environmental variance components for different sleep behaviors (cosleeping, sleep duration, and night awakenings). RESULTS: Shared environment explained almost all (98.3%) of the total variance in cosleeping. Sleep duration was substantially influenced by shared environmental factors (64.1% nocturnal sleep and 61.2% diurnal sleep), with a moderate contribution of additive genetic effects (30.8% and 36.3% for nocturnal and diurnal sleep, respectively). For nocturnal waking episodes, we found a shared environmental contribution of 63.2% and a heritability estimate of 35.3%. CONCLUSIONS: Most sleep disturbances during early childhood are explained by common shared environmental factors, and behavioral interventions adopted by parents and focused on modifying sleep behavior could contribute to solving sleep disturbances in this age group. However, the influence of genetic factors should not be underestimated, and research in this area could clarify the physiologic architecture of sleeping and contribute to selecting appropriate personalized therapeutic approaches.

An update on the Italian Twin Register: advances in cohort recruitment, project building and network development.

The Italian Twin Register has been in place for more than 10 years. Since its establishment, it has been focusing, on the one hand, on a continuous update of the existing information, and on the other hand, on new phenotypes and sample collection. Demographic data on about 140,000 twins have been updated using the municipality registries. The Italian Twin Register has been carrying out several new studies during the last few years. A birth cohort of twins, Multiple Births Cohort Study, has been started and the enrollment is ongoing. For this cohort, data on pregnancy and birth are collected, and periodical follow-ups are made. DNA is being collected for the twins and their parents. In the area of behavioral genetics, most efforts have been directed to psychological well being assessed with self-reported tools. Research on age-related traits continues with studies on arteriosclerosis development, early biomarkers in mild cognitive impairment, and the relation between lifestyle habits and mutagen sensitivity. The Italian Twin Register biobanking has grown in its size and in its know-how in terms of both technical issues and ethical procedures implementation. Furthermore, attitudes toward biobank-based research, together with willingness and motivation for donation, are being investigated. A valuable key resource for the Italian Twin Register is the possibility of linking twin data with disease registries. This approach has been yielding several important results, such as the recent study on the heritability of type 1 diabetes.

Prenatal and Perinatal Determinants of Neonatal Seizures Occurring in the First Week of Life

To evaluate prenatal and perinatal risk factors for early neonatal seizures, we conducted a case-control study including 100 newborns with neonatal seizures in the first week of life and 204 controls randomly selected from a list of healthy newborns born in the same hospital during the study period. Generalized tonic seizures were the most common seizures observed (29%), although the majority of newborns (71%) experienced more than one type of seizure. The most frequent presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%). A history of epilepsy in first-degree relatives was found only for cases. Neonatal seizures were found to be associated with maternal disease in the 2 years before pregnancy, mothers weight gain > 14 kg during pregnancy, placental pathology, preeclampsia, low birthweight, low gestational age, and jaundice in the first 3 days of life. The need for cardiopulmonary resuscitation was found only for cases (37%). The causal pathways for neonatal seizures often begin before birth, and some of the factors identified may be preventable. (J Child Neurol 2001;16:651-656).

Association of body mass index with arterial stiffness and blood pressure components: a twin study.

RATIONALE Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. METHODS We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. RESULTS Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). CONCLUSION Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.

Clumsiness and psychopathology: Causation or shared etiology? A twin study with the CBCL 6–18 questionnaire in a general school-age population sample

In a sample of 398 twin pairs aged 8-17 belonging to the Italian Twin Registry we explored the extent to which physical clumsiness/motor problems covary with a broad spectrum of behavioral problems identified by the Child Behavior Checklist 6-18/DSM oriented scales, and the causes of such covariation. Only Anxiety and Attention Deficit Hyperactivity (ADH) Problems maintained significant correlation with Clumsiness after partialling out the effects of the other problem scales. By the co-twin control method we found no indication of clear, direct causal effect of Clumsiness upon Anxiety or ADH Problems, or vice versa. Twin bivariate analyses showed that the co-occurrence of motor problems and Anxiety/ADH Problems is best explained by genetic factors shared between Clumsiness and the behavioral problems phenotypes.