Hair analysis--a biological marker for passive smoking in pregnancy and childhood.

Passive smoking has been shown to adversely affect the health of infants and children. We used hair analysis for nicotine and its metabolite cotinine as a biological marker for exposure to smoking in these two groups. Using radioimmunoassay we measured maternal and fetal hair concentrations of nicotine and cotinine in the mother-infant pairs belonging to three different groups based on the mother's smoking habits. The three groups were: active smokers, passive smokers and nonsmokers. There was a significant correlation between maternal and neonatal hair concentration for both, nicotine and cotinine. Mothers and infants in the smoking groups, both active and passive, had significantly higher hair concentrations of both, nicotine and cotinine than in the control, nonsmoking group. In an older cohort, we compared two groups: 78 asthmatic children were compared to 86 healthy children exposed to similar degrees of passive smoking. By using objective, biological markers, our study aimed at verifying whether asthmatic children are different from nonasthmatic children in the way their bodies handle nicotine. Our results show, that, despite the fact that parents of asthmatic children tend to smoke a lower number of cigarettes per day, their children had an average twofold higher concentrations of cotinine in their hair then the control, nonasthmatic children. These studies document the importance of hair analysis as a tool for measuring exposure to cigarette smoke.     

Visuospatial memory deficits emerging during nicotine withdrawal in adolescents with prenatal exposure to active maternal smoking.

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents. We examined visuospatial and verbal memory in 35 adolescent tobacco smokers with prenatal exposure to active maternal smoking and 26 adolescent tobacco smokers with no prenatal exposure to maternal smoking who were similar in age, educational attainment, general intelligence, and baseline plasma cotinine. Subjects were studied during ad libitum smoking and after 24 h of abstinence from smoking. A subset of subjects from each group also underwent functional magnetic resonance imaging while performing a visuospatial encoding and recognition task. Adolescent tobacco smokers with prenatal exposure experienced greater nicotine withdrawal-related deficits in immediate and delayed visuospatial memory relative to adolescent smokers with no prenatal exposure. Among adolescent smokers with prenatal exposure, nicotine withdrawal was associated with increased activation of left parahippocampal gyrus during early recognition testing of visuospatial stimuli and increased activation of bilateral hippocampus during delayed recognition testing of visuospatial stimuli. These findings extend prior preclinical work and suggest that, in human adolescent tobacco smokers, prenatal exposure to active maternal smoking is associated with alterations in medial temporal lobe function and concomitant deficits in visuospatial memory.     

From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action.

The objective of the present work is to critically summarize published studies and reassess the state of knowledge on a highly controversial topic: the potential association between prenatal exposure to passive smoking as well as maternal active smoking and postnatal exposure to environmental tobacco smoke (ETS) and enhanced incidence of childhood cancer. Elements to be considered include the substantial proportion of pregnant women who remain smokers, the widespread nature of exposure to ETS during pregnancy as well as during childhood, the known toxicology of tobacco smoke, and in particular sidestream smoke, characterized by a rich carcinogen content, the specific metabolism of foetuses and new-borns and finally the amount of epidemiologic data already available. We conducted a thorough review of the literature to identify studies either exclusively dealing with the effects of passive smoking on the occurrence of childhood cancers or more generally etiologic studies of cancer, be it overall or site-specific. We identified close to 50 publications presenting pertinent results from epidemiological investigations and about 50 more on mechanisms and metabolism, smoking in pregnancy and exposure to ETS as well as selected reviews and commentaries. Collaborative epidemiological studies were conducted in the United Kingdom (UK), USA, Sweden, Netherlands and internationally (France, Italy). In addition, other studies were also available from the USA, UK, Canada, Australia, Sweden, Italy, Denmark and People's Republic of China. The vast majority were case-control studies dealing with all cancers, leukaemia and lymphomas, central nervous system (CNS) tumours, Wilms' tumour, retinoblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, bone and soft tissues tumours, germ cell tumours, as well as specific histological types of leukaemias, lymphomas or CNS tumours. No strong association between maternal smoking in pregnancy and/or exposure to ETS and childhood cancer is found. Yet, several studies found slightly increased relative risks, generally smaller than 1.5, i.e. the order of magnitude associated with some recognized hazards of exposure to ETS (1.2 to 1.3 for adult lung cancer and cardiovascular diseases). Tumours most often found associated with maternal smoking in pregnancy or ETS exposure are childhood brain tumours and leukaemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies coupled with demonstration of genotoxic effects on the foetus of exposure to metabolites of tobacco smoke, and demonstrable presence of adducts should lead to strong recommendations aiming at fully protecting foetuses, new-borns and infants from tobacco smoke.     

Impact of smoking on the concentration and activity of alpha-1-antitrypsin in serum in relation to the urinary excretion of hydroxyproline

The impact of active and passive smoking on the serum levels of alpha 1-AT, the trypsin inhibitory capacity (TIC), the trypsin inhibitory activity (TIA) and the urinary hydroxyproline to creatinine ratio (HOP-ratio) was studied. The subjects used in the study on active smoking were 167 healthy adult men and in the study on passive smoking 189 healthy primary school children. Serum levels of alpha 1-AT in active smokers were significantly higher than those in non-smokers. The TIC as well as the TIA in active smokers decreased with increasing number of cigarettes smoked. The urinary HOP-ratio increased significantly with increasing number of cigarettes smoked. On the other hand, in the case of passive smokers a significant difference was obtained only for the HOP-ratio. The correlations between all markers in active smokers were significant. Less significant correlations were found in the case of passive smokers. These results suggest that the urinary excretion of hydroxyproline can be considered as a marker for the imbalance between proteases and anti-proteases as a result of smoking.     

Psychosocial differences between smokers and non-smokers during pregnancy

Despite the well-established adverse birth and childhood health outcomes associated with maternal smoking, smoking rates among pregnant women remain high. Psychosocial health attributes, including anxiety, depression, perceived stress, self-efficacy, and personality characteristics, have especially important roles in smoking behavior. Understanding who smokes during pregnancy and what factors influence this behavior choice may be key to improving the effectiveness of smoking cessation intervention programs. We use data from a prospective cohort study of pregnant women to understand the psychosocial health profiles of women who choose to smoke during pregnancy compared to the profiles of women who do not smoke or successfully quit smoking during pregnancy. Multinomial logistic regression analyses on 1518 non-Hispanic black and non-Hispanic white women assessed the association between smoking status and psychosocial health while controlling for demographic characteristics. Higher levels of perceived stress, depression, neuroticism, negative paternal support, and perceived racism among non-Hispanic blacks were associated with higher odds of being a smoker than a non-smoker (p < 0.05). Higher levels of self-efficacy, extraversion, agreeableness, conscientiousness, interpersonal support, positive paternal support, and perceived social standing were associated with lower odds of being a smoker than a non-smoker (p < 0.05). Our analysis indicates that women who smoked during pregnancy experienced a more negative constellation of psychosocial adversities than women who did not smoke. Given the psychosocial needs and personality profiles experienced by smokers, more attention to the psychosocial strengths and weaknesses of these women may allow for more tailored smoking cessation programs, enhancing both the short- and long-term effectiveness of such interventions.     

Passive and active exposure to cigarette smoke in a smoking experiment

Six volunteer female habitual smokers were exposed during a 2-wk experimental period to cigarette smoke, both actively and passively, in an exposure chamber (volume 10 m3, average air exchange rate 6.8 times/h), where the ambient carbon monoxide, particle, and aldehyde concentrations were monitored. Three of the six subjects were smoking at the time, 2 cigarettes (filtered, self-burning low tar brand) per person per hour, 30 cigarettes altogether during each of the 5-h experimental days in the chamber. Samples of blood and urine were taken from each subject after 3 nonsmoking days and after each day of active or passive smoking. Among the parameters tested, blood carboxyhemoglobin, plasma cotinine, and urinary mutagenicity were higher in samples taken after active smoking than after nonsmoking periods. Although the exposure conditions were similar for all subjects, the parameters measured showed quite high interindividual variation. Thioethers and thiocyanates were not significantly elevated in the active smoking samples; neither were there any differences during this short experimental period in the sister chromatid exchange frequencies. The only parameters showing an increasing trend after passive exposure, as compared with nonsmoking samples, were urinary mutagenicity and plasma cotinine, the main metabolite of nicotine.     

Examining characteristics associated with quitting smoking during pregnancy and relapse postpartum

IntroductionSmoking during pregnancy is a significant public health concern that can cause adverse health outcomes for both the mother and fetus. Studies have shown only 40% of women quit smoking during pregnancy, with more than half relapsing within 6 months, and up to 90% relapsing within one year. This study investigates differences in demographics and smoking-related symptomatology between pregnant smokers and pregnant quitters, as well as factors associated with postpartum relapse.MethodsData on pregnant smokers and pregnant quitters were obtained from two separate parent studies. Data on smoking demographics and smoking-related symptomatology were collected at screening visits.ResultsCompared to pregnant smokers, pregnant quitters had more favorable smoking characteristics (e.g., smoked fewer cigarettes per day, reported higher motivation for abstinence and less dependency). They also had more favorable relationship characteristics (e.g., were more likely to be married, less likely to have a significant other who smokes) and had less reproductive liability (e.g., fewer pregnancies, fewer children). In terms of symptomatology, pregnant quitters reported more positive affect, negative affect, physical symptoms and withdrawal but less craving. Predictors of postpartum relapse included increased maternal age, having a significant other who smokes and an increased likelihood of returning to smoking after pregnancy (self-reported prior to delivery).ConclusionsSeveral demographics and smoking-related symptomatology were significantly different between pregnant quitters and pregnant smokers. In addition, multiple factors predicting postpartum relapse were identified. This information can inform personalized interventions for high risk pregnant smokers and pregnant quitters at risk for postpartum relapse.     

Nicotine downregulates the l-selectin system that mediates cytotrophoblast emigration from cell columns and attachment to the uterine wall

Here we show that maternal smoking downregulated, in a dose-dependent manner, cytotrophoblast expression of l-selectin and its TRA-1-81-reactive carbohydrate ligands. Cell islands -- cell columns that fail to make uterine attachments, often more numerous in the placentas of smokers -- exhibited an even greater downregulation of the l-selectin adhesion system. These effects were attributable to nicotine, since exposure of explanted villi to this drug in vitro reproduced the effects observed in situ. Videomicroscopy showed that the downstream consequences included inhibition of all stages of cytotrophoblast outgrowth from columns, including rolling adhesion within columns and generation of invasive cells at the distal ends. These results suggest that nicotine, acting through the l-selectin adhesion system, impairs the development of cell columns that connect the fetal portion of the placenta to the uterus, one possible reason why women who smoke have a much harder time achieving and sustaining pregnancy than their nonsmoking counterparts.     

Ecological Momentary Assessment of Antecedents and Consequences of Smoking in Adults with Attention-Deficit/Hyperactivity Disorder

The current study assessed antecedents and consequences of ad lib cigarette smoking in smokers diagnosed with attention-deficit/hyperactivity disorder (ADHD) using ecological momentary assessment (EMA). Adult smokers with ADHD (n = 17) completed 870 smoking and 622 nonsmoking electronic diary entries over a 7-day observation period of their naturalistic smoking behavior. Data collection occurred from 2011 to 2012. Generalized estimating equations indicated that ADHD smokers were more likely to smoke when urge to smoke, negative affect, boredom, stress, worry, and restlessness were elevated. In addition, participants were more likely to smoke in situations that elicited higher levels of nervousness and frustration. ADHD symptoms, in general, did not differ between smoking and nonsmoking contexts, though hyperactive–impulsive ADHD symptoms were elevated prior to smoking in frustrating situations. Additional situational antecedent variables were associated with smoking, including being in the presence of others smoking, being in a bar or restaurant, while outside, and while consuming caffeinated or alcoholic beverages. Participants also reported a significant improvement in urge to smoke, negative affect, stress, hunger, and ADHD symptoms after smoking a cigarette. Findings suggest certain contextual factors that may maintain ad lib cigarette smoking in smokers with ADHD and identify potential treatment targets in smoking cessation interventions for this at-risk group. Clinical implications and future research directions are discussed. Funding for this study was provided by the National Institute on Drug Abuse.     

Effects of cigarette smoking on lipid peroxidation

We monitored serum malondialdehyde (MDA), an indicator of lipid peroxidation, to determine whether active cigarette smoking causes oxidative damage. The results revealed that the concentration of serum MDA was higher in cigarette smokers than in nonsmoking control subjects. No relation was found between lipid peroxidation and the number of cigarettes smoked by an individual. This finding supports the hypothesis that oxidative damage in smokers is due to the number of hours of active exposure to cigarette smoke.     

Differential effect of cigarette smoking on antipyrine oxidation versus acetaminophen conjugation

The effect of cigarette smoking on drug oxidation and conjugation was studied using antipyrine and acetaminophen as marker compounds. For the antipyrine study, healthy cigarette smokers (n = 30) and nonsmoking controls (n = 53) received a single 1.0-gram intravenous dose of antipyrine. For the acetaminophen study, 14 smokers and 15 nonsmokers received a 650-mg intravenous dose of acetaminophen. The clearance of antipyrine was significantly increased (0.93 vs. 0.60 ml/min/kg, p less than 0.0001) and elimination half-life was correspondingly reduced (8.9 vs. 13.0 h, p less than 0.0001) in smokers compared to nonsmoking controls. Total recovery of antipyrine and metabolites excreted in urine did not differ between groups, but there was a significantly increased fractional clearance of antipyrine via formation of 4-hydroxyantipyrine and 3-hydroxymethyl metabolites in smokers. Fractional clearance via formation of norantipyrine did not differ significantly between groups. Comparison of acetaminophen kinetics between smokers and nonsmokers indicated no significant differences in elimination half-life, clearance or volume of distribution. Thus, cigarette smoking is more likely to induce drug oxidation rather than drug conjugation. However, not all oxidative pathways are equally influenced; induction effects of smoking are highly substrate selective and pathway specific.     

孕期被动吸烟对注意缺陷多动障碍患儿认知和行为的影响

目的研究孕期被动吸烟对注意缺陷多动障碍（ADHD）患儿认知和行为的影响。方法选取伴孕期被动吸烟ADHD患儿92例、不伴孕期被动吸烟ADHD患儿99例及正常儿童100例,通过智力测定、Stroop测验和威斯康星卡片分类评估研究对象的认知和行为能力。结果ADHD患儿言语智商（VIQ）、操作智商（HQ）和总智商（FIQ）均较较正常儿童低,其中有孕期被动吸烟史的患儿更低。ADHD患儿的A、B、C卡片耗时均较对照组患儿长,而B、C卡片正确数均较对照组患儿低,有孕期被动吸烟史的ADHD患儿更为显著。ADHD患儿的错误应答数、持续性应答数、持续性错误数、持续性错误百分数和非持续性错误数均较正常儿童高,而概念化水平均较正常儿童低,且有孕期被动吸烟史的患儿更为明显。结论孕期被动吸烟损害能加重缺陷多动障碍患儿的认知和行为的缺陷。     

The effect of passive and active exposure to tobacco smoke on lipid profile parameters and the activity of certain membrane enzymes in the blood of women in the first trimester of pregnancy

The effect of tobacco smoke on lipid peroxidation, the lipid profile and membrane-bound enzymatic activity in the first trimester of pregnancy was investigated.In the plasma of women with active exposure to tobacco smoke, we have found increased lipid peroxidation and higher total concentrations of cholesterol, triglycerides and low-density lipoproteins in the blood, as well as a decreased concentration of high-density lipoproteins. A higher concentration of low-density lipoproteins and a lower concentration of high-density lipoproteins were also found in the plasma of passive smokers. In contrast, women who smoked before pregnancy had only a higher low-density lipoprotein concentration. In the group of active and passive smoking women, lower arylesterase and phosphotriesterase activities of paraoxonase were observed, while the lactonase activity of paraoxonase decreased only in the group of active smoking women. In women with active exposure to tobacco smoke, a higher activity level of alanine aminopeptidase and γ-glutamyltransferase in the plasma was found.It is important to monitor the lipid profile during pregnancy, especially when exposure to tobacco smoke occurs.     

Interactive effect of combined exposure to active and passive smoking on cardiovascular system

A great number of observations show that cardiovascular damage from smoking may be a consequence of both active and passive smoking exposure. Some findings identify an increase in cardiovascular events in active smokers as well as in non-smokers exposed to passive smoking. The type and extension of damage seem to be similar qualitatively either in active smokers or in exposed never smokers. Artery vessels and myocardium feel particularly the effects of smoking. Ischaemic heart disease and atherosclerosis progression are the common alterations observed. Individuals exposed to both active and passive smoking feel the adverse effects of smoking. Result of the interaction consists primarily of increased rate of clinical events whereas the type of anatomical alterations is similar to those which characterize respectively isolated exposure to active or passive smoking. However, the extension of cardiovascular damage may vary even if, usually, in the same location of pre-existing lesions. The article also presents some of the patents regarding the effects of smoking on cardiovascular system.     

Smoking during pregnancy as a possible risk factor for pediatric neoplasms in the offspring: A population-based cohort study

ObjectiveThe aim of this study was to evaluate the association between maternal smoking during pregnancy and future risk of childhood neoplasm risk.Study designA population based cohort analysis comparing the risk for long-term childhood neoplasms in children born (1991–2014) to mothers that smoked during pregnancy vs. those that did not. Childhood neoplasms were pre-defined based on ICD-9 codes, as recorded in the hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative oncological morbidity over time. Cox proportional hazards model was used to control for confounders.Results241,273 infants met the inclusion criteria; out of those 2841 were born to mothers that smoked during pregnancy. Offspring to smoking mothers had higher incidence of benign (OR 1.6, 95%CI 1.02–2.58; p value = .038) but not malignant tumors. Total cumulative neoplasm incidence was significantly higher in smoking women (Log Rank = 0.001) but no significant difference in the incidence of malignant tumors was noted (Log Rank = 0.834). In a Cox regression model controlling for maternal confounders; a history of maternal smoking during pregnancy remained independently associated only with increased risk for benign tumors (adjusted HR 2.5, 95%CI 1.57–3.83, p = .001).ConclusionMaternal smoking during pregnancy is associated with increased long-term risk for benign but not malignant tumors. This is important when counseling mothers regarding potential future risks and recommended lifestyle modifications. Despite this large population study with long follow-up, childhood malignancies are rare, and clarifying the possible association may require further studies.     

Psychosocial mediators of abstinence, relapse, and continued smoking: a one-year follow-up of a minimal intervention

This study investigates the relationship of health locus of control, health beliefs, social support, use of nonsmoking areas, and objecting to another person's smoking to long-term abstinence and relapse following a minimal intervention for smoking cessation. Subjects participated in a single session group hypnosis treatment for smoking cessation. Questionnaires were completed by participants pretreatment and at a 1-year follow-up. Ex-smoker, recidivist, and continuing smoker groups were defined using follow-up data from 219 participants (70 males and 149 females). The data were analyzed using univariate and multiple discriminant analysis techniques. The results show that the three smoking status groups could be discriminated. Ex-smokers actively coped with smokers in their environment, avoided other smokers in public places, and received considerable support from spouses and friends. In contrast, recidivists prior to treatment had been unable to quit smoking for extended periods of time and placed greater responsibility on powerful others for their health. Following treatment, recidivists did not actively cope with smokers, were more likely to participate in additional hypnosis, and placed less responsibility on either powerful others or themselves for their own health. It was concluded that posttreatment factors appear to be more important for long-term maintenance of nonsmoking than entry characteristics of participants. Recommendations include incorporation of coping skills training into cessation programs and restrictions on smoking in the ex-smokers' environments to prevent relapse.     

Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study

Using ambulatory methods for 1 day of monitoring, the authors of this study investigated the association between smoking and situational cues in 63 smokers with posttraumatic stress disorder (PTSD) and 32 smokers without PTSD. Generalized estimating equations contrasted 682 smoking and 444 nonsmoking situations by group status. Smoking was strongly related to craving, positive and negative affect, PTSD symptoms, restlessness, and several situational variables among PTSD smokers. For non-PTSD smokers, the only significant antecedent variables for smoking were craving, drinking coffee, being alone, not being with family, not working, and being around others who were smoking. These results are consistent with previous ambulatory findings regarding mood in smokers but also underscore that, in certain populations, mood and symptom variables may be significantly associated with ad lib smoking.     

DNA methylation alterations in response to prenatal exposure of maternal cigarette smoking: A persistent epigenetic impact on health from maternal lifestyle?

Despite increased awareness, maternal cigarette smoking during pregnancy continues to be a common habit causing risk for numerous documented negative health consequences in the exposed children. It has been proposed that epigenetic mechanisms constitute the link between prenatal exposure to maternal cigarette smoking (PEMCS) and the diverse pathologies arising in later life. We here review the current literature, focusing on DNA methylation. Alterations in the global DNA methylation patterns were observed after exposure to maternal smoking during pregnancy in placenta, cord blood and buccal epithelium tissue. Further, a number of specific genes exemplified by CYP1A1, AhRR, FOXP3, TSLP, IGF2, AXL, PTPRO, C11orf52, FRMD4A and BDNF are shown to have altered DNA methylation patterns in at least one of these tissue types due to PEMCS. Investigations showing persistence and indications of trans-generational inheritance of DNA methylation alterations induced by smoking exposure are also described. Further, smoking-induced epigenetic manifestations can be both tissue-dependent and gender-specific which show the importance of addressing the relevant sex, tissue and cell types in the future studies linking specific epigenetic alterations to disease development. Moreover, the effect of paternal cigarette smoking and second-hand smoke exposure is documented and accordingly not to be neglected in future investigations and data evaluations. We also outline possible directions for the future research to address how DNA methylation alterations induced by maternal lifestyle, exemplified by smoking, have direct consequences for fetal development and later in life health and behavior of the child.     

Assessment of prenatal smoke exposure by determining nicotine and its metabolites in maternal and neonatal urine

Urine specimens were collected from 75 pregnant women before childbirth and from their newborns within 48 postnatal hours. A high-performance liquid chromatography (HPLC) method was used to determine urinary nicotine and its metabolites, cotinine and trans-3'-hydroxycotinine (OH-cotinine) to objectivise prenatal smoke exposure. Using the sum of nicotine metabolites as a marker, 34 women were classed as not exposed to smoke ( < 15 nmol/l), 18 as passive smokers (15-400 nmol/l), and 23 as active smokers ( > 400 nmol/1). The newborns of active smokers exhibited significantly (P < 0.001) higher nicotine metabolite concentrations than did those of either non-exposed women or passive smokers. A close correlation was found to exist between maternal and neonatal nicotine and cotinine concentrations (r=0.8968 and r=0.9205, respectively). For OH-cotinine, this correlation was particularly close when maternal, but not neonatal, OH - cotinine was adjusted to creatinine (r=0.9792). The neonatal/maternal urine concentration ratios for cotinine and OH-cotinine were noted to not significantly depend on the time of postpartal urine collection. Within the first two postnatal days, the extent of current prenatal smoke exposure attributable to active smoking of the mother was best reflected by the urinary concentrations of cotinine plus OH-cotinine without adjustment to creatinine.     

Maternal smoking during pregnancy and long-term neurological morbidity of the offspring

ObjectiveTo evaluate the long-term pediatric neurological morbidity of children born to mothers who reported smoking during pregnancy as compared with children born to non-smoking mothers.Study designA population-based cohort analysis was performed comparing all deliveries of mothers who reported smoking during pregnancy and non-smoking mothers between 1991 and 2014 at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving neurological morbidities were evaluated according to a predefined set of ICD-9 codes, including autism, development and movement disorders, cerebral palsy and more. A Kaplan-Meier survival curve was used to compare cumulative hospitalization rate in exposed and unexposed offspring and a Cox proportional hazards model was used to control for confounders.ResultsDuring the study period, 242,342 deliveries met the inclusion criteria. Of them, 2861 (1.2%) were children of smoking mothers. Neurological-related hospitalizations were significantly higher in children born to smoking mothers, as compared with the non-smoking group (5.3% vs. 3.1%, p < 0.01). Specifically, these children had higher rates of movement, eating and developmental disorders as well as attention deficit hyperactive disorder. The Kaplan-Meier survival curve demonstrated a significant higher cumulative incidence of neurological-related hospitalizations in the smoking group (log rank p < 0.01). Using a Cox proportional hazards model, controlling for potential confounders, maternal tobacco use was found to be independently associated with long-term neurological morbidity of the offspring (adjusted HR = 1.58, CI 1.33–1.89, p value < 0.01).ConclusionMaternal smoking during pregnancy is an independent risk factor for long-term neurological morbidity of the offspring.