Maternal preconception and first trimester exposure to PM10 and the risk of oral clefts in offspring: a population-based, case-control study.

BACKGROUND: Current literature describes limited and controversial evidence on the associations between maternal preconception and first trimester exposure to particulate matter with a diameter ≤10 µm (PM10) and the risk of oral cleft (OC). METHODS: We conducted a case-control study involving 3086 OC cases and 7950 controls, registered in the Maternal and Child Health Certificate Registry in Liaoning Province between 2010 and 2015. PM10 concentrations were obtained from the Environment Protection Bureau. The exposure windows included the 3 months before pregnancy, the first trimester and the individual months. Unconditional logistic regression model was performed to estimate the OR and 95% CI for the association between PM10 exposure and the risk of OC, cleft lip only (CLO), cleft palate only (CPO), and cleft lip and palate (CLP). RESULTS: Maternal PM10 exposure was positively associated with an increased risk for OC during the 3 months preconception (per 10 µg/m3 increment: OR=1.04, 95% CI 1.01 to 1.07; highest vs lowest quartile: OR=1.23, 95% CI 1.04 to 1.45) and the first trimester (per 10 µg/m3 increment: OR=1.05, 95% CI 1.02 to 1.08; highest vs lowest quartile: OR=1.37, 95% CI 1.15 to 1.64). Analyses based on individual months presented similar positive associations, particularly in the second month of pregnancy (OR=1.77, 95% CI 1.51 to 2.09) for highest versus lowest quartile. In the subtype analysis, stronger associations were observed for CLO, whereas there was negligible evidence for CPO and CLP. Sensitivity analyses using propensity score matching generated similar findings. CONCLUSIONS: Our study provides evidence that PM10 exposure during the 3 months preconception and the first trimester increases the risk of OC.

The "First 1,000 Days+" as Key Contributor to the Double Burden of Malnutrition.

Growth from conception through age 2 years, the "First 1,000 days," is important for long-term health of the growing fetus and child and is influenced by several factors including breastfeeding and complementary feeding. Low- and middle-income countries face a complicated array of factors that influence healthy growth, ranging from high food insecurity, poor sanitation, limited prenatal or neonatal care, and high levels of poverty that exacerbate the "vicious cycle" associated with intergenerational promotion of growth retardation. It is now well recognized that the period prior to conception, both maternal and paternal health and diet, play an important role in fetal development, giving rise to the concept of the "First 1,000 Days+". Breastfeeding and complementary feeding practices can be improved through a combination of interventions such as baby-friendly hospitals, regulations for marketing of foods and beverages to children, adequate counseling and support, and sound social and behavior change communication, but continued research is warranted to make such programs more universal and fully effective. Thus, improving the overall understanding of factors that influence growth, such as improved breastfeeding and age-appropriate and adequate complementary feeding, is critical to reducing the global prevalence of the double burden of malnutrition.

Intergenerational Effects of Alcohol: A Review of Paternal Preconception Ethanol Exposure Studies and Epigenetic Mechanisms in the Male Germline.

While alcohol use disorder (AUD) is a highly heritable psychiatric disease, efforts to elucidate that heritability by examining genetic variation (e.g., single nucleotide polymorphisms) have been insufficient to fully account for familial AUD risk. Perhaps not coincidently, there has been a burgeoning interest in novel nongenomic mechanisms of inheritance (i.e., epigenetics) that are shaped in the male or female germ cells by significant lifetime experiences such as exposure to chronic stress, malnutrition, or drugs of abuse. While many epidemiological and preclinical studies have long pointed to a role for the parental preconception environment in offspring behavior, over the last decade many studies have implicated a causal relationship between the environmentally sensitive sperm epigenome and intergenerational phenotypes. This critical review will detail the heritable effects of alcohol and the potential role for epigenetics.

Childhood asthma and smoking exposures before conception-A three-generational cohort study.

BACKGROUND: Some human and animal studies have recently shown that maternal grandmother's smoking during pregnancy increases the risk of asthma in the grandchildren. We have investigated whether sex of the exposed parent and/or grandchild modifies the association between grandmaternal smoking and grandchild asthma. METHODS: We formed a cohort study based on linkage of national registries with prospectively collected data over three generations. Smoking habits in early pregnancy were registered since 1982 and purchases of prescribed medication since 2005. In all, 10 329 children born since 2005 had information on maternal and grandmaternal smoking on both sides and were followed from birth up to 6 years of age. Ages when medication was purchased were used to classify the cohort into never, early transient (0-3 years), early persistent (0-3 and 4-6 years), and late-onset (4-6 years) phenotypes of childhood asthma. RESULTS: Maternal grandmother's smoking was associated with an increased odds of early persistent asthma after adjustment for maternal smoking and other confounders (odds ratio 1.29, 95% confidence interval 1.10-1.51). Grandchild sex did not modify the association. Paternal grandmother's smoking was not associated with any of the asthma phenotypes. CONCLUSION: Maternal but not paternal exposure to nicotine before conception was related to an increased risk of early persistent childhood asthma, but not other asthma phenotypes. Our findings are possibly consistent with a sex-specific mode of epigenetic transfer.

Investigating paternal preconception risk factors for adverse pregnancy outcomes in a population of internet users.

BACKGROUND: Paternal preconception risk factors such as smoking, exposure to environmental substances, medication use, overweight and advanced age correlate with the occurrence of malformations and birth defects in the offspring. Nonetheless, the prevalence of risk factors for adverse pregnancy outcomes in the male population has been scarcely investigated and no report on preconception interventions targeting prospective fathers is available. We conducted a web-based survey to measure the prevalence of paternal preconception risk factors for adverse pregnancy outcomes in an Italian population of Internet users. METHODS: Prospective or expectant fathers were enrolled during a four-week period through two of the main Italian web-sites dedicated to preconception, pregnancy, childhood and family care. Participants filled in a web questionnaire regarding preconception risk factors for adverse pregnancy outcomes. Logistic regression analysis was used to explore the predictors of paternal preconception risk factors. RESULTS: We enrolled 131 prospective and 205 expectant fathers. More than half of the total participants used medications during the preconception period, 35% were smokers and 8% were obese. Exposure to environmental substances was declared by almost 20% of the participants, with the group including pesticides/herbicides/professional paints being the most prevalent. More than a half of the study sample included men aged over 35 years. According to the multivariate analysis, smoking and exposure to environmental toxics were less frequent among individuals with a university degree (respectively: OR = 0.52; 95% CI 0.32-0.84; OR = 0.52; 95% CI 0.29-0.93). Paternal obesity and medication use in the preconception period were not associated with any of the independent variables. CONCLUSIONS: The prevalence of preconception risk factors among male population should not be neglected when planning preconception interventions, confirming that preconception health must be focused on the couple, rather than on women only.

[Impact of maternal overnutrition on the periconceptional period]. / Impacto de la sobrenutrición materna sobre el periodo de periconcepción.

Overnutrition may lead to obesity. Maternal obesity may affect fertility not only via anovulation, but also through direct effects on oocytes and preimplantation embryos, indicating that the periconceptional period is sensitive to conditions of overnutrition. The periconceptional period includes from folliculogenesis to implantation. Animal model studies suggest that oocytes derived from obese females usually have a small size and mitochondrial abnormalities. These disruptions are probably induced by changes in the components of the ovarian follicular fluid. Experimental evidence also suggests that obesity may affect the microenvironment in oviducts and uterus, resulting in development of preimplantation embryos with reduced cell numbers and up-regulation of proinflammatory genes. However, further research is needed for in-depth characterization of the effects of maternal obesity during the periconceptional period.

[SYNERGISM OF PRECONCEPTIVE RADIATION EXPOSURE AND PARENTS' ONCO-PATHOLOGY IN THE RISE OF CARCINOGENIC RISK IN THE OFFSPRINGS OF PROFESSIONAL EMPLOYEES].

The problem of carcinogenic risk in offsprings of individuals exposed to radiation is challenging and insufficiently studied. In that there are no evaluations of the interaction between radiation and non-radiation factors. The aim of the study was the analysis of interaction of preconceptive radiation exposure and parents' onco-pathology in cancer mortality in offsprings (F1) of workers (fathers) of the Mayak Production Association exposed to a wide range of doses of radiation over a year prior conception. The number of offspring is 8191 individuals (4180 men and 4011 women). The analysis was performed with the use of fourfold table and eightfold tables. The interaction offactors was estimated on the base of the additive and multiplicative models. The studied factors were independent. The odds ratio (OR) of cancer mortality in the offspring with parents' oncopathology (1.43) was insignificant. OR of cancer mortality in preconceptive radiation exposure in a dose over 110 mGy and without parents' onco-pathology was 2.61 (1.52-4.49), and in their combination--3.86 (1.93-7.71). Index of synergism of preconceptive radiation exposure and parents' onco-patholog in the rise of carcinogenic risk in the offspring was 1.34 and the character of their interaction was multiplicative. Thus, for the first time there was established the interaction between radiation and non-radiation factors in the synergism sort in the increase of carcinogenic risk in the offspring of people exposed to radiation.