<p>  </p> <p>Maternal smoking during pregnancy (MSDP) is still occurring in the United States, as of 2021, at an average rate of 6% (CDC, WONDER). This proximal exposure to MSDP has been associated with decreased fetal head size, increased risk of SIDS, and increased risk for low birthweight (Abraham et al., 2017, Avsar et al., 2021; Knopik et al., 2016b) in infants exposed to MSDP compared to infants not exposed to MSDP. Additionally, MSDP has been associated with epigenetics in the form of differential DNA methylation (DNAm) in children and adolescents who were exposed to MSDP. Among these studies, there has been consistency in gene-specific findings of differential methylation in global DNAm (across the genome), <em>AHRR, CYP1A1, CNTNAP2, MYOIG, </em>and<em> GFI1 </em>(Ladd-Acosta et al., 2015; Lee et al., 2015; Richmond et al., 2015; Rzehak et al., 2016)<em>.</em> Using the frameworks of the Developmental Origins of Health and Disease, as well as Ecological Systems Theory, the current study aims to (1) test the effect of MSDP on global DNAm (across the genome) cross-sectionally in 8-17 y/o children and adolescents, (2) attempt to replicate and analyze the MSDP impacts on <em>AHRR, CYP1A1, CNTNAP2, MYOIG, </em>and<em> GFI1, </em>and (3) adjust for several prenatal and postnatal covariates (second-hand smoke and particulate matter (PM2.5), specifically) in an attempt to isolate the MSDP exposure on DNAm analysis. In a sample of 325 8-17 y/o children whose sibling was exposed to more or less MSDP compared to them, it was found that higher child-specific MSDP was associated with more global methylation and less <em>CNTNAP2</em> methylation, possibly suggesting evidence for a partially causal pathway between MSDP and DNAm for these genetic outcomes. Both child-specific and family-average MSDP were associated with<em> CYP1A1</em> and <em>MYO1G</em> methylation. There were also various findings related to child sex and age covariates, as well as postnatal PM2.5. Future studies focused on replication of these findings in a longitudinal genetic design could further confirm the associations found in the current study.</p>

Introdução: A exposição do feto a grandes quantidades de componentes tóxicos decorrente do consumo de tabaco e álcool durante a gestação pode acarretar problemas tais como prematuridade, baixo peso ao nascer, aborto e distúrbios no desenvolvimento infantil. Essa associação tem sido recentemente objeto de diversos estudos, porém os resultados são contraditórios devido aos métodos e amostras distintos. Objetivo: Estudar a associação entre o consumo de tabaco e/ou álcool pela gestante e o desenvolvimento infantil entre 13 e 30 meses de idade. Método: Estudo descritivo e analítico, prospectivo, de uma coorte de conveniência iniciada no pré-natal (2010), avaliada no nascimento e a partir do início do segundo ano de vida (2011/2013) no município de Ribeirão Preto, SP. A variável dependente foi o escore médio do desempenho dos filhos nas cinco subescalas da Bayley Scales of Infant and Toddler Development ® third edition - screening test (Bayley - III®). A variável exploratória foi o consumo de tabaco e/ou álcool na gestação, classificado como nenhum consumo, consumo isolado de tabaco ou álcool e consumo concomitante das substâncias. As diferenças entre as médias nos escores das cinco subescalas foram comparadas por meio de regressão linear, em quatro modelos: ajustado pelas faixas etárias de aplicação do teste, propostas no manual técnico da escala (modelo 1); ajustado pelas faixas etárias, por consumo de tabaco e/ou álcool na gestação e características da mãe, da gestação e do parto (modelo 2); ajustado pelas faixas etárias, por consumo de tabaco e/ou álcool na gestação e variáveis do seguimento das crianças (modelo 3); ajustado por todas as variáveis dos modelos anteriores (modelo 4). Resultados: Foram estudadas 998 mulheres, das quais 121 (12,1%) fumaram e 246 (24,6%) referiram ter consumido bebida alcoólica na gravidez. O consumo isolado de álcool foi três vezes maior (18,6%) do que o consumo apenas de tabaco (6,1%). O consumo combinado de tabaco e álcool durante a gestação foi de 6,0%, sem diferença segundo a faixa etária das crianças avaliadas (p>0.05). Não houve diferença nas médias do escore cognitivo segundo o consumo das substâncias em nenhum modelo. Consumo concomitante foi associado a menor média dos escores em ambas as subescalas de comunicação (diferença de 1,12 pontos para comunicação receptiva, IC95% 0,45 a 1,79; 1,19 pontos para comunicação expressiva, IC95% 0,31 a 2,07) e motoras (diferença de 1,20 pontos na subescala motora fina, IC95% 0,55 a 1,85; 0,70 pontos para subescala motora grossa, IC95% 0,13 a 1,28), em torno de um ponto em média, comparado com nenhum consumo de tabaco e álcool. Conclusão: Consumo concomitante de tabaco e álcool teve efeito significativo, porém pequeno, na média dos escores de comunicação e motores, mas não na subescala cognitiva. / Introduction: Fetal exposure to large amounts of toxic compounds resulting from the consumption of tobacco and alcohol during pregnancy can lead to problems such as preterm birth, low birth weight, miscarriage and disorders in child development. This association has recently been the subject of several studies, but the results are contradictory due to differences in methods and samples. Objective: To study the association between the consumption of tobacco and/or alcohol by pregnant women and child development between 13 and 30 months of age. Methods: This is a descriptive and analytical, prospective study of a cohort of convenience initiated prenatally (2010), assessed at birth and from the beginning of the second year of life (2011-2013) in the city of Ribeirão Preto, Brazil. The dependent variable was the mean score of the performance of children in the five subscales of the Bayley Scales of Infant and Toddler Development ® third edition - screening test (Bayley - III®). The explanatory variable was the use of tobacco and/or alcohol during pregnancy rated as no consumption, isolated consumption of tobacco and alcohol and concomitant consumption of the substances. The differences between the mean scores in the five subscales were compared using linear regression in four models: adjusted for age of test application proposed in the technical manual of the scale (model 1); adjusted by age groups, for tobacco and/or alcohol use during pregnancy and maternal characteristics of pregnancy and childbirth (model 2); adjusted by age groups, for tobacco and/or alcohol use during pregnancy and variables related to children in the follow-up (model 3); adjusted for all the variables of the previous models (model 4). Results: 998 women were studied, 121 of them (12.1%) smoked and 246 (24.6%) reported having consumed alcohol in pregnancy. The isolated alcohol consumption was three times higher (18.6%) than the consumption of tobacco only (6.1%). The combined use of tobacco and alcohol during pregnancy was 6.0%, with no difference according to the child\'s age group (p> 0.05). There was no difference in mean cognitive score based on consumption of substances in any model. Concomitant intake was associated with lower mean scores in both communication subscales (1.12 points difference for receptive communication, 95% CI 0.45 to 1.79; 1.19 points for expressive communication, 95% CI 0.31 to 2.07) and motor subscale (1.20 points difference in the fine motor subscale, 95% CI 0.55 to 1.85; 0.70 points for gross motor subscale, 95% CI 0.13 to 1.28), around a point on average compared with no consumption of tobacco and alcohol. Conclusion: concomitant consumption of tobacco and alcohol had a significant effect, however small, in the mean score of the communication and motor subscales, but not in the cognitive subscale.

Introdução: A exposição do feto a grandes quantidades de componentes tóxicos decorrente do consumo de tabaco e álcool durante a gestação pode acarretar problemas tais como prematuridade, baixo peso ao nascer, aborto e distúrbios no desenvolvimento infantil. Essa associação tem sido recentemente objeto de diversos estudos, porém os resultados são contraditórios devido aos métodos e amostras distintos. Objetivo: Estudar a associação entre o consumo de tabaco e/ou álcool pela gestante e o desenvolvimento infantil entre 13 e 30 meses de idade. Método: Estudo descritivo e analítico, prospectivo, de uma coorte de conveniência iniciada no pré-natal (2010), avaliada no nascimento e a partir do início do segundo ano de vida (2011/2013) no município de Ribeirão Preto, SP. A variável dependente foi o escore médio do desempenho dos filhos nas cinco subescalas da Bayley Scales of Infant and Toddler Development ® third edition - screening test (Bayley - III®). A variável exploratória foi o consumo de tabaco e/ou álcool na gestação, classificado como nenhum consumo, consumo isolado de tabaco ou álcool e consumo concomitante das substâncias. As diferenças entre as médias nos escores das cinco subescalas foram comparadas por meio de regressão linear, em quatro modelos: ajustado pelas faixas etárias de aplicação do teste, propostas no manual técnico da escala (modelo 1); ajustado pelas faixas etárias, por consumo de tabaco e/ou álcool na gestação e características da mãe, da gestação e do parto (modelo 2); ajustado pelas faixas etárias, por consumo de tabaco e/ou álcool na gestação e variáveis do seguimento das crianças (modelo 3); ajustado por todas as variáveis dos modelos anteriores (modelo 4). Resultados: Foram estudadas 998 mulheres, das quais 121 (12,1%) fumaram e 246 (24,6%) referiram ter consumido bebida alcoólica na gravidez. O consumo isolado de álcool foi três vezes maior (18,6%) do que o consumo apenas de tabaco (6,1%). O consumo combinado de tabaco e álcool durante a gestação foi de 6,0%, sem diferença segundo a faixa etária das crianças avaliadas (p>0.05). Não houve diferença nas médias do escore cognitivo segundo o consumo das substâncias em nenhum modelo. Consumo concomitante foi associado a menor média dos escores em ambas as subescalas de comunicação (diferença de 1,12 pontos para comunicação receptiva, IC95% 0,45 a 1,79; 1,19 pontos para comunicação expressiva, IC95% 0,31 a 2,07) e motoras (diferença de 1,20 pontos na subescala motora fina, IC95% 0,55 a 1,85; 0,70 pontos para subescala motora grossa, IC95% 0,13 a 1,28), em torno de um ponto em média, comparado com nenhum consumo de tabaco e álcool. Conclusão: Consumo concomitante de tabaco e álcool teve efeito significativo, porém pequeno, na média dos escores de comunicação e motores, mas não na subescala cognitiva. / Introduction: Fetal exposure to large amounts of toxic compounds resulting from the consumption of tobacco and alcohol during pregnancy can lead to problems such as preterm birth, low birth weight, miscarriage and disorders in child development. This association has recently been the subject of several studies, but the results are contradictory due to differences in methods and samples. Objective: To study the association between the consumption of tobacco and/or alcohol by pregnant women and child development between 13 and 30 months of age. Methods: This is a descriptive and analytical, prospective study of a cohort of convenience initiated prenatally (2010), assessed at birth and from the beginning of the second year of life (2011-2013) in the city of Ribeirão Preto, Brazil. The dependent variable was the mean score of the performance of children in the five subscales of the Bayley Scales of Infant and Toddler Development ® third edition - screening test (Bayley - III®). The explanatory variable was the use of tobacco and/or alcohol during pregnancy rated as no consumption, isolated consumption of tobacco and alcohol and concomitant consumption of the substances. The differences between the mean scores in the five subscales were compared using linear regression in four models: adjusted for age of test application proposed in the technical manual of the scale (model 1); adjusted by age groups, for tobacco and/or alcohol use during pregnancy and maternal characteristics of pregnancy and childbirth (model 2); adjusted by age groups, for tobacco and/or alcohol use during pregnancy and variables related to children in the follow-up (model 3); adjusted for all the variables of the previous models (model 4). Results: 998 women were studied, 121 of them (12.1%) smoked and 246 (24.6%) reported having consumed alcohol in pregnancy. The isolated alcohol consumption was three times higher (18.6%) than the consumption of tobacco only (6.1%). The combined use of tobacco and alcohol during pregnancy was 6.0%, with no difference according to the child\'s age group (p> 0.05). There was no difference in mean cognitive score based on consumption of substances in any model. Concomitant intake was associated with lower mean scores in both communication subscales (1.12 points difference for receptive communication, 95% CI 0.45 to 1.79; 1.19 points for expressive communication, 95% CI 0.31 to 2.07) and motor subscale (1.20 points difference in the fine motor subscale, 95% CI 0.55 to 1.85; 0.70 points for gross motor subscale, 95% CI 0.13 to 1.28), around a point on average compared with no consumption of tobacco and alcohol. Conclusion: concomitant consumption of tobacco and alcohol had a significant effect, however small, in the mean score of the communication and motor subscales, but not in the cognitive subscale.