Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review

BACKGROUND@#There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.@*METHODS@#Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.@*RESULTS@#Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.@*CONCLUSION@#There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.

Hormonal biomarkers for evaluating the impact of fetal growth restriction on the development of chronic adult disease / Biomarcadores hormonais para avaliar o impacto da restrição do crescimento fetal no desenvolvimento de doenças crônicas em adultos

Abstract The hypothesis of fetal origins to adult diseases proposes that metabolic chronic disorders, including cardiovascular diseases, diabetes, and hypertension originate in the developmental plasticity due to intrauterine insults. These processes involve an adaptative response by the fetus to changes in the environmental signals, which can promote the reset of hormones and of the metabolism to establish a "thrifty phenotype". Metabolic alterations during intrauterine growth restriction can modify the fetal programming. The present nonsystematic review intended to summarize historical and current references that indicated that developmental origins of health and disease (DOHaD) occur as a consequence of altered maternal and fetal metabolic pathways. The purpose is to highlight the potential implications of growth factors and adipokines in "developmental programming", which could interfere in the development by controlling fetal growth patterns. These changes affect the structure and the functional capacity of various organs, including the brain, the kidneys, and the pancreas. These investigations may improve the approach to optimizing antenatal as well as perinatal care aimed to protect newborns against long-termchronic diseases.

Resumo A hipótese das origens fetais de doenças em adultos propõe que distúrbios crônicos metabólicos, incluindo doenças cardiovasculares, diabetes e hipertensão, se originam na plasticidade do desenvolvimento devido a insultos intrauterinos. Estes processos envolvem uma resposta adaptativa do feto amudanças nos sinais ambientais que podem promover a redefinição dos hormônios e do metabolismo para estabelecer um "fenótipo poupador". Alteraçõesmetabólicas durante a restrição de crescimento intrauterino podem modificar a programação fetal. A presente revisão não-sistemática pretendeu resumir referências históricas e atuais que indicassem que as origens desenvolvimentistas da saúde e doença (DOHaD, na sigla em inglês) ocorrem como consequência de alterações nas vias metabólicas materna e fetal. O propósito é destacar as potenciais implicações de fatores de crescimento e adipocinas na "programação do desenvolvimento", que poderia interferir no desenvolvimento, controlando os padrões de crescimento fetal. Estas alterações afetam a estrutura e a capacidade funcional de inúmeros órgãos, incluindo o cérebro, os rins e o pâncreas. Estas investigações podemmelhorar a abordagempara otimizar os cuidados prénatais e perinatais, como objetivo de proteger os recém-nascidos contra doenças crônicas em longo prazo.

Contribución del crecimiento prenatal y posnatal temprano en las enfermedades crónicas relacionadas con la nutrición / Contribution of prenatal and early postnatal growth in nutrition related chronic diseases

La transición alimentaria y nutricional en América Latina y los cambios demográficos-epidemiológicos, se presentaron muy rápido en países con "doble carga nutricional", tal como sucede en Venezuela. Las enfermedades crónicas relacionadas con la nutrición (ECRN) y las muertes violentas son las principales causas de muerte y desplazan a la diabetes, sin que exista una política de prevención. Estudios epigenéticos y epidemiológicos de nichos obesogénicos con transmisión intergeneracional: Programación Metabólica (PM)=adaptaciones fisiológicas- metabólicas del feto, en medio ambiente adverso, o aporte exagerado en período crítico, influyen en la respuesta en la vida extrauterina: hipótesis del "fenotipo ahorrador de Barker": hiperlipidemia, hipertensión, obesidad central y resistencia a la insulina, debido a una dieta materna inadecuada antes y durante el embarazo; igual la hipótesis del "crecimiento acelerado" por sobrealimentación, independiente del peso al nacer. Los niños amamantados ganan menor peso-grasa corporal, consumen menos proteínas y la densidad calórica es menor que con fórmulas infantiles. El exceso de proteínas acelera el rebote adiposo. El control de factores de riesgo en adultos atenúa las ECRN, ya que son principales desencadenantes y agravantes. Sin embargo, hay que intervenir tempranamente, ya que la ateroesclerosis es una enfermedad de la infancia. Promover la lactancia materna exclusiva durante los primeros 6 meses, evitar las dietas de alta densidad calórica y vigilar la introducción de nuevos alimentos. El pediatra debería identificar factores de riesgos cardiometabólico en el niño y los obstetras vigilar el estado nutricional pre/postconcepcional y la ganancia de peso gestacional, para controlar los factores de riesgo desde temprana edad(AU)

Food and nutrition transition in Latin America and demographic-epidemiological shifts constitute a rapid process, typical of countries where under and over nutrition coexist: the dual burden of nutrition related diseases. Nutrition related chronic diseases are the main causes of death followed by violence induced deaths and Diabetes. The genetic component of obesity has been overestimated and life styles are less related to mortality rates than the Developmental Origins of Health and Disease (DOHaD). The epidemiological and epigenetic analysis of trans generational- intergenerational transmission: obesogenic environments and Metabolic Intrauterine Programming (MIP): metabolic-physiologic adaptations during fetal life to exposure to restrictions or excesses that relate to Barker´s hypothesis whose outcome includes hyperlipidemia, hypertension, central obesity and insuline resistance due to maternal inadequate pre pregnancy and pregnancy nutrition, plus the hypothesis of acccelerated growth, independent of size at birth. Breastfed infants gain less weight and fat; proteins accelerate adiposity rebound and infant formulas contain 60-70% more and are also richer in calories than human milk. Control of lifestyle’s in adults will not eliminate cardiometabolic risks; it is necessary to intervene at early stages as atherosclerosis is a pediatric problem. The window of opportunity, from preconception to 36 months of age, includes promotion of exclusive breast feeding for the first 6 months, the need to defineoptimal nutrition to prevent under and over nutrition and the awareness of physicians in monitoring weight gain during pregnancy and identifying cardio metabolic risks in children and adolescents(AU)

Early Infantile Growth and Cardiovascular Risks inAdolescent Japanese Women / Journal of Rural Medicine

<b>Objective:</b> Early life events connected with the risk of later disease can occur not only <i>in utero</i>, but also in infancy. In study of the developmental origins of health and disease, the relationship between infantile growth patterns and adolescent body mass index and blood pressure is one of the most important issues to verify.<br><b>Materials and Methods:</b> We analyzed the correlation of current body mass index and systolic blood pressure of 168 female college students with their growth patterns <i>in utero</i> and in infancy.<br><b>Results:</b> Body mass index and systolic blood pressure in adolescence showed positive correlations with changes in weight-for-age z scores between 1 and 18 months but not with those between 18 and 36 months. Stepwise multiple regression analysis showed that both change in weight-for-age z scores from 1 to 18 months and body mass index at 1 month were significantly and independently associated with systolic blood pressure in adolescence. Body mass index at 36 months was positively correlated with body mass index in adolescence, while body mass index at birth was negatively correlated with body mass index in adolescence.<br><b>Conclusion:</b> Our findings shows that restricted growth <i>in utero</i> and accelerated weight gain in early infancy are associated with the cardiovascular risk factors of high systolic blood pressure and high body mass index in adolescence. In Japan, an increasing proportion of low birth weight infants and accelerated catch-up growth after birth have been observed in recent decades. This might be an alarming harbinger of an increase in diseases related to the developmental origins of health and disease in Japan.