Developmental effects of maternal smoking during pregnancy on the human frontal cortex transcriptome

AbstractCigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N=33; 16 smoking-exposed) as well as adult (N=207; 57 active smokers) human post-mortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only 2 genes showed significant differential expression (FDR<10%). Moreover, 1,315 genes showed significantly different exposure effects between maternal smoking during pregnancy and direct exposure in adulthood (FDR<10%) – these differences were largely driven by prenatal differences that were enriched for pathways previously implicated in addiction and synaptic function. Furthermore, prenatal and age-dependent differentially expressed genes were enriched for genes implicated in non-syndromic autism spectrum disorder (ASD) and were differentially expressed as a set between patients with ASD and controls in post-mortem cortical regions. These results underscore the enhanced sensitivity to the biological effect of smoking exposure in the developing brain and offer novel insight into the effects of maternal smoking during pregnancy on the prenatal human brain. They also begin to address the relationship between in utero exposure to smoking and the heightened risks for the subsequent development of neuropsychiatric disorders.One Sentence SummaryMaternal smoking during pregnancy alters the expression of genes within the developing human cortex and these changes are enriched for genes implicated in neuropsychiatric disorders.

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A Meta-Analysis of Maternal Smoking during Pregnancy and Autism Spectrum Disorder Risk in Offspring

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph120910418 ◽

2015 ◽

Vol 12 (9) ◽

pp. 10418-10431 ◽

Cited By ~ 21

Author(s):

Shiming Tang ◽

Ying Wang ◽

Xuan Gong ◽

Gaohua Wang

Keyword(s):

Autism Spectrum Disorder ◽

Maternal Smoking ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Smoking During Pregnancy ◽

Autism Spectrum Disorder Risk ◽

Maternal Smoking During Pregnancy ◽

Disorder Risk

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BrainEXP-NPD: a database of transcriptomic profiles of human brains of six neuropsychiatric disorders

10.1101/2021.05.30.446363 ◽

2021 ◽

Author(s):

Cuihua Xia ◽

Teng Ma ◽

Chuan Jiao ◽

Chao Chen ◽

Chunyu Liu

Keyword(s):

Bipolar Disorder ◽

Differential Expression ◽

Differentially Expressed Genes ◽

Neuropsychiatric Disorders ◽

Brain Regions ◽

Autism Spectrum ◽

Differentially Expressed ◽

Sequencing Data ◽

Network Analyses ◽

Gene Differential Expression

Background: Spatio-temporal gene expression has been widely used to study gene functions and biological mechanisms in diseases. Numerous microarray and RNA sequencing data focusing on brain transcriptomes in neuropsychiatric disorders have accumulated. However, their consistency, reproducibility has not been properly evaluated. Except for a few psychiatric disorders, like schizophrenia, bipolar disorder and autism, most have not been compared to each other for cross-disorder comparisons. Methods: We organized 48 human brain transcriptome datasets from six sources. The original brain donors include patients with schizophrenia (SCZ, N=427), bipolar disorder (BD, N=312), major depressive disorder (MDD, N=219), autism spectrum disorder (ASD, N=53), Alzheimer's disease (AD, N=765), Parkinson's disease (PD, N=163) as well as controls as unaffected by such disorders (CTRL, N=6,378), making it a total of 8,317 samples. Raw data included multiple brain regions of both sexes, with ages ranging from embryonic to seniors. After standardization, quality control, filtering and removal of known and unknown covariates, we performed comprehensive meta- and mega- analyses, including gene differential expression and gene co-expression network. Results: A total of 6922, 3011, 2703, 4389, 3507, 4279 significantly differentially expressed genes (FDR q < 0.05) were detected in the comparisons of 6 brain regions of SCZ-CTRL, 5 brain regions of BD-CTRL, 6 brain regions of MDD-CTRL, 4 brain regions of ASD-CTRL, 7 brain regions of AD-CTRL, and 6 brain regions of PD-CTRL, respectively. Most differentially expressed genes were brain region-specific and disease-specific. SCZ and BD have a maximal transcriptome similarity in striatum (ρ=0.42) among the four brain regions, as measured by Spearman's correlation of differential expression log2 FC values. SCZ and MDD have a maximal transcriptome similarity in hippocampus (ρ=0.30) among the five brain regions. BD and MDD have a maximal transcriptome similarity in frontal cortex (ρ=0.45) among the five brain regions. Other disease pairs have a less transcriptome similarity (ρ<0.1) in all brain regions. PD is negatively correlated with SCZ, BD, and MDD in cerebellum and striatum. We also performed coexpression network analyses for different disorders and controls separately. We developed a database named BrainEXP-NPD (http://brainexpnpd.org:8088/BrainEXPNPD/), to provide a user-friendly web interface for accessing the data, and analytical results of meta- and mega-analyses, including gene differential expression and gene co-expression networks between cases and controls on different brain regions, sexes and age groups. Discussion: BrainEXP-NPD compiled the largest collection of brain transcriptomic data of major neuropsychiatric disorders and presented lists of differentially expressed genes and coexpression modules in multiple brain regions of six major disorders.

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Maternal Smoking during Pregnancy and the Prevalence of Autism Spectrum Disorders, Using Data from the Autism and Developmental Disabilities Monitoring Network

Environmental Health Perspectives ◽

10.1289/ehp.1104556 ◽

2012 ◽

Vol 120 (7) ◽

pp. 1042-1048 ◽

Cited By ~ 41

Author(s):

Amy E. Kalkbrenner ◽

Joe M. Braun ◽

Maureen S. Durkin ◽

Matthew J. Maenner ◽

Christopher Cunniff ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Developmental Disabilities ◽

Maternal Smoking ◽

Monitoring Network ◽

Autism Spectrum ◽

Smoking During Pregnancy ◽

Maternal Smoking During Pregnancy ◽

Spectrum Disorders ◽

Using Data

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Maternal smoking status before and during pregnancy and bronchial asthma at 3 years of age: a prospective cohort study from the Japan Environment and Children's Study (JECS)

10.21203/rs.3.rs-966835/v1 ◽

2021 ◽

Author(s):

Kunio Miyake ◽

Megumi Kushima ◽

Ryoji Shinohara ◽

Sayaka Horiuchi ◽

Sanae Otawa ◽

...

Keyword(s):

Bronchial Asthma ◽

Maternal Smoking ◽

Smoking Status ◽

Multivariate Logistic Regression Analysis ◽

Smoking During Pregnancy ◽

Established Risk Factor ◽

Smoking Exposure ◽

Increased Risk ◽

Maternal Smoking During Pregnancy ◽

Prenatal Maternal Smoking

Abstract Background Maternal smoking exposure during pregnancy is an established risk factor for childhood asthma, but the association between maternal pre-pregnancy smoking status and asthma risk is not well understood. This study examined the association between maternal smoking status before and during pregnancy and bronchial asthma at 3 years of age. Methods The data of 75,411 mother-child pairs, excluding the missing data of exposure and outcomes from the Japan Environment and Children's Study (JECS) were used. The association between prenatal maternal smoking status and the risk of bronchial asthma at 3 years of age was determined using multivariate logistic regression analysis. Results The percentage of 3-year-old children with doctor-diagnosed bronchial asthma was 7.2%. The distribution of maternal smoking status before childbirth was as follows: Never = 60.0%, Quit before recognizing current pregnancy = 24.1%, Quit after finding out current pregnancy = 12.3%, and Still smoking = 3.6%. Maternal smoking during pregnancy was significantly associated with an increased risk of bronchial asthma at 3 years of age even after adjusting for pre- and postnatal covariates (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.16–1.57). Furthermore, mothers who quit before recognizing current pregnancy (aOR 1.10, 95% CI 1.02–1.18) or who quit after finding out about current pregnancy (aOR 1.11, 95% CI 1.01–1.23) were also significantly associated. Conclusions This study suggested that not only maternal smoking during pregnancy but also maternal smoking exposure of pre-pregnancy or early pregnancy may be associated with an increased risk of bronchial asthma in children.

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Maternal smoking during pregnancy and offpsring's psychiatric morbidity in early adulthood. Findings from the Finnish Family Competence Birth Cohort Study

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.008 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S73-S73

Author(s):

S. Niemelä ◽

S. Mikola ◽

A. Sourander ◽

P. Rautava ◽

M. Sillanpää

Keyword(s):

Maternal Smoking ◽

Psychiatric Morbidity ◽

Early Adulthood ◽

Education Level ◽

Birth Cohort Study ◽

Prenatal Smoking ◽

Psychiatric Diagnoses ◽

Smoking During Pregnancy ◽

Smoking Exposure ◽

Maternal Smoking During Pregnancy

IntroductionPrenatal smoking exposure is one of the most common insults during the fetal period prevalence varying from 5 to 19% in the European countries [1].ObjectivesPrenatal smoking exposure increases the risk of psychiatric morbidity in the offspring, externalizing disorders in particular. However, less is known whether maternal smoking during pregnancy increases the risk for anxiety disorders [1].AimsTo study the associations between maternal smoking during pregnancy and offspring psychiatric morbidity in early adulthood in a Finnish birth cohort study.MethodsA prospective data collection from 10th gestational week (GW10) to early adulthood (n = 475, 37% from the original sample). Information on self-reported smoking during pregnancy was collected using questionnaires at GW10 and GW28. Offspring psychiatric diagnoses and clinically relevant symptoms were assessed using Development and Well-being Assessment (DAWBA)-interviews at age 18 to 20 years. Information on parental alcohol use, depressive mood, anxiety, and education level, as well as offspring's gender, education level, and birth weight were used as covariates.ResultsMaternal smoking during pregnancy associated independently associated with PTSD (OR = 6.9, 95% CI 1.3–35.6, P = 0.021), and conduct disorder (OR = 2.7, 95% CI 1.02–6.9, P = 0.046) in a multivariate analysis after adjusting for other psychiatric diagnoses, offspring and parental variables (OR = 1.9, 95% CI 0.5–6.9, P = 0.359).ConclusionsIn addition to conduct problems, prenatal nicotine exposure may increase the offspring's risk for posttraumatic stress disorder (PTSD). This relationship may be explained, in part, by effects on nicotinic acetylcholine receptors and uteroplacental mechanisms [1].Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Association between Smoking during Pregnancy and Short Root Anomaly in Offspring

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182111662 ◽

2021 ◽

Vol 18 (21) ◽

pp. 11662

Author(s):

Yuki Sagawa ◽

Takuya Ogawa ◽

Yusuke Matsuyama ◽

Junka Nakagawa Kang ◽

Miyu Yoshizawa Araki ◽

...

Keyword(s):

Public Schools ◽

Passive Smoking ◽

Maternal Smoking ◽

Population Based ◽

Short Root ◽

Population Based Study ◽

Smoking During Pregnancy ◽

Smoking Exposure ◽

Maternal Smoking During Pregnancy ◽

Exposure During Pregnancy

Short root anomaly (SRA) is a dental anomaly with short dental roots and its pathogenesis is poorly understood. This study investigated the association between maternal smoking during pregnancy and SRA in offspring. A survey was conducted on 558 children aged 8–16 years from two public schools in Ulaanbaatar, Mongolia. SRA was diagnosed using cases with a root-crown ratio of maxillary central incisors of ≤1.0. A questionnaire survey was conducted to assess maternal lifestyle habits. Multiple logistic regression was used to analyse the association between maternal smoking during pregnancy and SRA in offspring after adjusting for possible confounders. The prevalence of SRA in these children was 14.2%. Children whose mothers smoked from pregnancy to date were found to be 4.95 times (95% confidence interval [CI]: 1.65–14.79) more likely to have SRA than those whose mothers never smoked, after adjusting for possible confounders. Additionally, children whose mothers had been exposed to passive smoking during pregnancy were found to be 1.86 times (95% CI: 1.02–3.40) more likely to have SRA than those whose mothers had not been exposed to passive smoke. Our population-based study suggests that maternal and passive smoking exposure during pregnancy can affect tooth root formation in children.

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Maternal Smoking and Orofacial Clefts

The Cleft Palate-Craniofacial Journal ◽

10.1597/1545-1569_1997_034_0011_msaoc_2.3.co_2 ◽

1997 ◽

Vol 34 (1) ◽

pp. 11-16 ◽

Cited By ~ 24

Author(s):

Karin Källén

Keyword(s):

Cleft Palate ◽

Odds Ratio ◽

Maternal Smoking ◽

Maternal Age ◽

Cleft Lip ◽

Orofacial Clefts ◽

Oral Clefts ◽

Smoking During Pregnancy ◽

Smoking Exposure ◽

Maternal Smoking During Pregnancy

To investigate a possible association between maternal smoking during pregnancy and oral clefts, a study was conducted using Swedish health registries. Infants with oral clefts (N = 1834) were selected among 1,002,742 infants born between 1983 and 1992 with known smoking exposure in early pregnancy. Confounders such as maternal age and parity were controlled for by using the Mantel-Haenszel technique. A statistically significant association with maternal smoking was found. The odds ratio (OR) for any maternal smoking among cases of cleft lip with or without cleft palate [CL(P)] was 1.16 (95%CI: 1.02–1.32). For cases of cleft palate alone (CP), the corresponding OR was 1.29 (95%CI: 1.08–1.54). The results of the present study, based on the largest series of oral cleft cases published to date, indicate that cigarette smoking during pregnancy is associated with increased risks of CL(P) and CP.

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