Environmental and individual exposure and the risk of congenital anomalies: a review of recent epidemiological evidence

INTRODUCTION Congenital anomalies (CAs) represent one of the main cause of foetal death, infant mortality and morbidity, and long-term disability. CAs have been object of systematic registration activity for a long-time in many geographical areas in Europe and worldwide. CAs are often associated with disabilities of different types and severity, including the developed Countries worldwide. According to the World Health Organization (WHO), each year approximately 3,2 million of children worldwide are born with a CA and approximately 300,000 newborns with a diagnosis of birth defect die within the first 28 days of life. In Europe, CAs are the leading cause of perinatal mortality: the European Surveillance of Congenital Anomalies (EUROCAT) network estimated a perinatal mortality associated with CAs of 9.2 per 10,000 births in 2008-2012. In Italy, the Ministry of Health estimates that, on the average of 500,000 births each year, about 25,000 present at least one CA. Moreover, approximately 25% of infant mortality is due to CAs and about 50% of infant mortality is attributable to perinatal morbidity, almost always of prenatal origin. Regarding long-term survival, a recent population study conducted between 1985 and 2003 in the UK estimated a 20.5-year survival of 85.5% of children born with at least one CA. According to the Centre for Disease Control and Prevention, approximately 3.3% of live births in the United States have a severe birth defect. Since CAs represent a significant public health issue, an effective primary prevention strategy should be a priority for public policies and healthcare system. Regarding aetiology, although in many cases the cause is still unknown, it has been hypothesized that CAs may be developed during the first trimester of pregnancy as a result of hereditary polygenic defects or of a gene-environment interaction. The aetiology is predominantly multifactorial, caused by complex interactions between genes and environment, which modify the normal embryo-foetal development, especially during the organogenesis phase. In particular, environmental factors (e.g., chemical toxicants, infection agents, maternal disease, and exogenous factors) can have preconceptional mutagenic action, postconceptional teratogenic effects, periconceptional endocrine disruption or epigenetic action. Regarding genetic causes, there are geneticchromosomal aberrations or dysgeneses. Furthermore, socioeconomic factors affect reproductive health by differentiating the exposure to the other risk factors as well as the access to prevention measures. In recent years, the importance of the environment as a major factor of reproductive risk has been highlighted. An individual may be exposed to pollutants present in the workplace and the population may be exposed to multiple sources of environmental contamination of water, soil, and air matrices. Pregnant women and the developing foetus are particularly sensitive to the effects of environmental exposure. OBJECTIVE The aim of the present working paper is to produce an updated review of the epidemiological evidence on the risk of CAs associated with environmental exposures, socioeconomic, and main individual risk factors, such as cigarette smoking and alcohol consumption, according to the approach proposed by Pirastu et al. 2010 in the framework of the SENTIERI Project (the Italian Epidemiological Study of Residents in National Priority Contaminated Sites). DESIGN AND METHODS Literature search was carried out in PubMed, following the SENTIERI project criteria to evaluate evidence, by selecting articles in English or Italian language published from 2011 to 2016 regarding human studies. For this review, descriptive and analytical epidemiological studies (cohort, case-control, cross-sectional, and