Maternal Cigarette Smoking Research Articles

Cigarette smoke induces proteasomal-mediated degradation of DNA methyltransferases and methyl CpG-/CpG domain-binding proteins in embryonic orofacial cells.

Orofacial clefts, the most prevalent of developmental anomalies, occur with a frequency of 1 in 700 live births. Maternal cigarette smoking during pregnancy represents a risk factor for having a child with a cleft lip and/or cleft palate. Using primary cultures of first branchial arch-derived cells (1-BA cells), which contribute to the formation of the lip and palate, the present study addressed the hypothesis that components of cigarette smoke alter global DNA methylation, and/or expression of DNA methyltransferases (Dnmts) and various methyl CpG-binding proteins. Primary cultures of 1-BA cells, exposed to 80μg/mL cigarette smoke extract (CSE) for 24h, exhibited a >13% decline in global DNA methylation and triggered proteasomal-mediated degradation of Dnmts (DNMT-1 and -3a), methyl CpG binding protein 2 (MeCP2) and methyl-CpG binding domain protein 3 (MBD-3). Pretreatment of 1-BA cells with the proteasomal inhibitor MG-132 completely reversed such degradation. Collectively, these data allow the suggestion of a potential epigenetic mechanism underlying maternal cigarette smoke exposure-induced orofacial clefting.

Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective cohort study of 8120 assisted reproduction technology cycles.

Is endometrial combined thickness (ECT) measured prior to embryo transfer (ET) associated with ectopic pregnancy (EP)? Following IVF, the risk of EP is 4-fold increased in women with an ECT of <9 mm compared with women with an ECT of >12 mm. Known risk factors for EP include tubal damage, maternal cigarette smoking and endometriosis. EP is also more common following IVF but the underlying causes for this remain unclear. Retrospective cohort study restricted to all IVF cycles leading to a pregnancy (βhCG > 50 IU/l) between January 2006 and December 2014. A total of 6465 patients achieved a pregnancy in 8120 cycles. Cycles using preimplantation genetic screening or donor oocytes were excluded. This cohort consists of 6465 patients achieving a pregnancy in 6920 stimulated cycles with fresh embryo transfers (STIM ET) and 1200 hormone replacement therapy frozen embryo transfers (HRT-FET) cycles at a private IVF unit (Monash IVF, Melbourne, Australia). ECT was the primary independent variable of interest; the primary outcome was a diagnosis of EP. The dataset was analysed using binary logistic general estimating equations (SPSS v22.0) to calculate odds ratio (OR) for EP adjusted for known confounders (aOR). There was no loss to follow-up in the dataset. The study groups did not differ significantly prior to IVF treatment. After adjusting for confounders, ECT remained statistically significant as an independent risk factor for EP. Compared with women with an ECT of <9 mm, women with an ECT of 9-12 mm had an aOR of 0.44 (95% CI 0.29-0.69, P < 0.01) and women with an ECT > 12 mm had an aOR of 0.27 (95% CI 0.10-0.77, P = 0.01). These differences remained statistically significant after performing a sensitivity analysis excluding HRT-FET, smokers and patients with tubal infertility. The study design is retrospective, and it is possible that not all confounders have been accounted for. Measurement of ECT was performed by highly trained sonographers, but some inconsistency between individuals may be present. Our group has previously demonstrated an increased risk of placenta praevia with increased ECT. These new findings suggest that the directionality of the uterine peristalsis waves matters more than their frequency or amplitude. Combining the data from both studies we now hypothesize that increased ECT is a marker for increased fundus-to-cervix uterine peristalsis, explaining both the increased placenta praevia risk and the lower EP risk. Further prospective studies are required to confirm these observations.

The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome.

Nicotine may link maternal cigarette smoking with respiratory dysfunctions in sudden infant death syndrome (SIDS). Prenatal-perinatal nicotine exposure blunts ventilatory responses to hypercapnia and reduces central respiratory chemoreception in mouse neonates at Postnatal Days 0 (P0) to P3. This suggests that raphe neurons, which are altered in SIDS and contribute to central respiratory chemoreception, may be affected by nicotine. We therefore investigated whether prenatal-perinatal nicotine exposure affects the activity, electrical properties, and chemosensitivity of raphe obscurus (ROb) neurons in mouse neonates. Osmotic minipumps, implanted subcutaneously in 5- to 7-day-pregnant CF1 mice, delivered nicotine bitartrate (60 mg kg(-1) d(-1)) or saline (control) for up to 28 days. In neonates, ventilation was recorded by head-out plethysmography, c-Fos (neuronal activity marker), or serotonin autoreceptors (5HT1AR) were immunodetected using light microscopy, and patch-clamp recordings were made from raphe neurons in brainstem slices under normocarbia and hypercarbia. Prenatal-perinatal nicotine exposure decreased the hypercarbia-induced ventilatory responses at P1-P5, reduced both the number of c-Fos-positive ROb neurons during eucapnic normoxia at P1-P3 and their hypercapnia-induced recruitment at P3, increased 5HT1AR immunolabeling of ROb neurons at P3-P5, and reduced the spontaneous firing frequency of ROb neurons at P3 without affecting their CO2 sensitivity or their passive and active electrical properties. These findings reveal that prenatal-perinatal nicotine reduces the activity of neonatal ROb neurons, likely as a consequence of increased expression of 5HT1ARs. This hypoactivity may change the functional state of the respiratory neural network leading to breathing vulnerability and chemosensory failure as seen in SIDS.

Excess placental secreted frizzled-related protein 1 in maternal smokers impairs fetal growth

Maternal cigarette smoking during pregnancy remains one of the most common and preventable causes of fetal growth restriction (FGR), a condition in which a fetus is unable to achieve its genetically determined potential size. Even though epidemiologic evidence clearly links maternal cigarette smoking with FGR, insight into the molecular mechanisms of cigarette smoke-induced FGR is lacking. Here, we performed transcriptional profiling of placentas obtained from smoking mothers who delivered growth-restricted infants and identified secreted frizzled-related protein 1 (sFRP1), an extracellular antagonist of endogenous WNT signaling, as a candidate molecule. sFRP1 mRNA and protein levels were markedly upregulated (~10-fold) in placentas from smoking mothers compared with those from nonsmokers. In pregnant mice, adenovirus-mediated overexpression of sFRP1 led to FGR, increased karyorrhexis in the junctional zone, and decreased proliferation of labyrinthine trophoblasts. Consistent with our hypothesis that placental WNT signaling is suppressed in maternal smokers, we found that exposure to carbon monoxide analogs led to reduced WNT signaling, increased SFRP1 mRNA expression, and decreased cellular proliferation in a trophoblast cell line. Moreover, administration of carbon monoxide analogs to pregnant mice in late gestation led to FGR. In summary, our results indicate that the increased placental expression of sFRP1 seen in smokers impairs fetal growth by inhibiting WNT signaling and trophoblast proliferation.

Early postnatal nicotine exposure disrupts the α2* nicotinic acetylcholine receptor-mediated control of oriens-lacunosum moleculare cells during adolescence in rats

Maternal cigarette smoking during pregnancy and maternal nicotine exposure in animal models are associated with cognitive impairments in offspring. However, the underlying mechanism remains unknown. Oriens-lacunosum moleculare (OLM) cells expressing α2* nicotinic acetylcholine receptors (nAChRs) are an important component of hippocampal circuitry, gating information flow and long-term potentiation (LTP) in the CA1 region. Here we investigated whether early postnatal nicotine exposure alters the normal role of α2*-nAChR-expressing OLM cells during adolescence in rats. We found that early postnatal nicotine exposure significantly decreased not only the number of α2-mRNA-expressing interneurons in the stratum oriens/alveus, but also α2*-nAChR-mediated responses in OLM cells. These effects of nicotine were prevented by co-administration with the nonselective nAChR antagonist mecamylamine, suggesting that nicotine-induced activation, but not desensitization, of nAChRs mediates the effects. α2*-nAChR-mediated depolarization of OLM cells normally triggers action potentials, causing an increase in spontaneous inhibitory postsynaptic currents in synaptically connected pyramidal cells. However, these α2*-nAChR-mediated effects were profoundly reduced after early postnatal nicotine exposure, suggesting altered control of CA1 circuits by α2*-nAChR-expressing OLM cells. Furthermore, these effects were associated with altered excitatory neural activity and LTP as well as the loss of normal α2*-nAChR-mediated control of excitatory neural activity and LTP. These findings suggest the altered function of α2*-nAChR-expressing OLM cells as an important target of further study for identifying the mechanisms underlying the cognitive impairment induced by maternal smoking during pregnancy.

Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy.

It has been postulated that prenatal cigarette smoke exposure (CSE) increases the risk for sudden infant death syndrome. The victims of infant death syndrome suffer from respiratory abnormalities, such as central apnea, diminished chemoreflex and alteration in respiratory pattern during sleep. However, no experimental evidence on CSE model exists to confirm whether prenatal CSE gives rise to reduction of neonatal central chemoreception in in vitro preparations in absence of peripheral sensory feedback. The aim of the present study was to test the hypothesis that maternal CSE during pregnancy depresses central chemoreception of the neonatal rats. The pregnant rats were divided into two groups, control (n = 8) and CSE (n = 8). Experiments were performed on neonatal (0–3days) rat pups. Fictive respiratory activity was monitored by recording the rhythmic discharge from the hypoglossal rootlets of the medullary slices obtained from the neonatal rats. The burst frequency (BF) and integrated amplitude (IA) of the discharge were analyzed. Their responses to acidified artificial cerebrospinal fluid (aCSF) were tested to indicate the change of the central chemosensitivity. Under condition of perfusing with standard aCSF (pH 7.4), no significant difference was detected between the two groups in either BF or IA (P>0.05). Under condition of perfusing with acidified aCSF (pH 7.0), BF was increased and IA was decreased in both groups (P<0.01). However, their change rates in the CSE group were obviously smaller than that in the control group, 66.98 ± 10.11% vs. 143.75 ± 15.41% for BF and −22.38 ± 2.51% vs. −44.90 ± 3.92% for IA (P<0.01). In conclusion, these observations, in a prenatal CSE model, provide important evidence that maternal smoking during pregnancy exerts adverse effects on central chemoreception of neonates.

Altered DNA methylation status (BDNF gene exon IV) associated with prenatal maternal cigarette smoking in borderline patients and healthy controls

Altered DNA methylation status (BDNF gene exon IV) associated with prenatal maternal cigarette smoking in borderline patients and healthy controls

Does maternal race influence the short-term variation of the fetal heart rate? An historical cohort study

ObjectivesThe main aim of this article was to analyze short-term variation (STV) of the fetal heart rate according to maternal race. The secondary aim was to study the baseline fetal heart rate according to this factor. Study designThis single-center historical cohort study covered the period from November 2008 through December 2011 (n=182). The inclusion criteria were: black women from sub-Saharan Africa or white European women, with a singleton pregnancy ≥34 weeks and fetal heart rate recorded by computerized analysis (Oxford Sonicaid System 8002) at a prenatal visit. The exclusion criteria were: medication likely to modify fetal heart rate, abnormal fetal heart rate tracing, and being in labor. A multiple linear regression analysis was used to study the association between maternal race and STV. ResultsSTV was lower by 2.6ms in fetuses of black women (n=55) compared to those of white women (n=127) (8.9±2.1ms vs. 11.4±3.4ms) (p<0.001). The basal fetal heart rate was higher (p=0.001), and the recording criteria were met less often for the black women (p=0.04). After adjustment for maternal age, body mass index at the beginning of pregnancy, maternal cigarette smoking, parity, gestational diabetes, gestational age at the time of the fetal heart rate recording, and the time between the last meal and the recording, mean STV was lower by 3.1±0.6ms in fetuses of black compared with white women (p<0.001). ConclusionSTV is lower in fetuses of black women compared to those of white women in a low-risk population. A study of black and white women with high-risk pregnancies is necessary to assess the impact of medical practices on perinatal outcome after STV analysis.

Intimate partner violence and maternal cigarette smoking before and during pregnancy.

Intimate partner violence and maternal cigarette smoking before and during pregnancy.

Altered placental DNA methylation patterns associated with maternal smoking: current perspectives.

The developmental origins of health and disease hypothesis states that adverse early life exposures can have lasting, detrimental effects on lifelong health. Exposure to maternal cigarette smoking during pregnancy is associated with morbidity and mortality in offspring, including increased risks for miscarriage, stillbirth, low birth weight, preterm birth, asthma, obesity, altered neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy interferes with placental growth and functioning, and it has been proposed that this may occur through the disruption of normal and necessary placental epigenetic patterns. Epigenome-wide association studies have identified a number of differentially methylated placental genes that are associated with maternal smoking during pregnancy, including RUNX3, PURA, GTF2H2, GCA, GPR135, and HKR1. The placental methylation status of RUNX3 and NR3C1 has also been linked to adverse infant outcomes, including preterm birth and low birth weight, respectively. Candidate gene analyses have also found maternal smoking-associated placental methylation differences in the NR3C1, CYP1A1, HTR2A, and HSD11B2 genes, as well as in the repetitive elements LINE-1 and AluYb8. The differential methylation patterns of several genes have been confirmed to also exhibit altered gene expression patterns, including CYP1A1, CYP19A1, NR3C1, and HTR2A. Placental methylation patterns associated with maternal smoking during pregnancy may be largely gene-specific and tissue-specific and, to a lesser degree, involve global changes. It is important for future research to investigate the mechanistic roles that these differentially methylated genes may play in mediating the association between maternal smoking during pregnancy and disease in later life, as well as to elucidate the potential influence of emerging tobacco product use during pregnancy, including the use of electronic cigarettes, on placental epigenetics.

Adverse Impact of Maternal Cigarette Smoking on Preterm Infants: A Population-Based Cohort Study.

The aim of the study is to examine the impact of exposure to maternal cigarette smoking on neonatal outcomes of very preterm infants. A retrospective cohort study examined preterm infants (<33 weeks gestational age) admitted to the Canadian Neonatal Network centers between 2003 and 2011. Mortality and major morbidities (bronchopulmonary dysplasia, severe intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy) were compared between infants exposed and unexposed to maternal smoking during pregnancy after adjusting for confounders. Among 29,051 study infants, 4,053 (14%) were exposed to maternal smoking during pregnancy. Multivariable analysis revealed higher odds of grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia (adjusted odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.04-1.41) and bronchopulmonary dysplasia (adjusted OR: 1.16, 95% CI: 1.02-1.33) in the smoking group, while mortality, severe retinopathy, and necrotizing enterocolitis were not significantly different. Maternal smoking during pregnancy is associated with severe neurological injury and bronchopulmonary dysplasia in preterm infants.

Prenatal smoking and age at menarche: influence of the prenatal environment on the timing of puberty.

Do prenatal exposure to cigarette smoking and birthweight influence age at menarche (AAM) in a cohort of Australian girls? We find that prenatal smoke exposure and lower birthweight increase the chance of earlier menarche in accordance with theoretical predictions as do confounding factors of maternal AAM and higher BMI of the girls. Much prior research focuses on the role of the early childhood environment in determining AAM but fewer studies consider the role of the prenatal environment. Those studies that examine the prenatal period find an acceleration of maturation associated with maternal smoking and low birthweight. Life history theory predicts that early life exposure to stressful environments should promote more rapid maturation and that this timing can be established before birth, making the prenatal environment particularly important. Statistical analysis of longitudinal survey data collected from a large cohort (n = 2446) of Australian children using data from birth to 12-13 years of age. Owing to missing data, 1493 girls were included in the final analysis. Using cox regression, we examine how (i) maternal cigarette smoking during gestation and (ii) birthweight influence girls' AAM. Cox regression was used because not all girls had reached menarche. We find that older maternal AAM (hazards ratio (HR): 0.75, confidence interval (CI) (95%): 0.71-0.79) and higher birthweight (HR: 0.86, CI (95%): 0.75-0.97) lower the chance of earlier menarche; while higher girls' BMI at 8-9 years (HR: 1.12, CI (95%): 1.10-1.15), and maternal cigarette smoking on 'most days' during gestation (HR: 1.40, CI (95%): 1.10-1.79 with 'no smoking' as the reference level) increased the chance of earlier menarche. All factors were statistically significant at P = 0.05. Not all girls had reached menarche, necessitating the use of cox regression. As with other longitudinal studies, there was study sample attrition and some missing data, particularly in reports of maternal smoking. In addition, as the degree of bias in the missing data is unknown, possible inaccurate reporting of maternal smoking may influence the results of birthweight on AAM. Because of the association between younger AAM and higher risk of uterine, endometrial and breast cancer development, our finding adds to the need to consider the stress caused by prenatal smoke exposure as an important health risk. In addition, this study needs to be extended, when the same girls are 14-15 years of age, and on a larger dataset from a younger cohort within the same Australian Government project. No funding was received for this study and there are no competing interests to declare.

Intimate partner violence and maternal cigarette smoking before and during pregnancy.

To determine the association of intimate partner violence with maternal cigarette smoking before and during pregnancy. Data were obtained for 196,391 U.S. mothers who delivered live neonates from 2004-2008 and completed the Pregnancy Risk Assessment Monitoring System survey 2-9 months postpartum. Intimate partner violence was defined as being physically hurt by a current or expartner in the year before or during pregnancy. Weighted descriptive and multivariate analyses were performed. Compared with nonphysically abused women, those who experienced physical abuse were 2.1 times more likely to smoke before pregnancy (44.0% compared with 21.0%, P<.001) and 2.6 times more likely to smoke during pregnancy (29.6% compared with 11.4%, P<.001). Smoking prevalence during pregnancy was highest for abused women who were non-Hispanic white (42.3% smoked) and lowest for nonabused college graduates (2.2% smoked). Smoking rates more than tripled for college graduates in abusive relationships (2.2% compared with 7.1%). After adjusting for potential confounding factors, abused women were significantly more likely to smoke during pregnancy than nonabused women (adjusted odds ratio 1.95, P<.001, 95% confidence interval 1.80-2.12). Women who experienced intimate partner violence had significantly higher rates of smoking before pregnancy and were less likely to quit during pregnancy than women who did not experience intimate partner violence. The American College of Obstetricians and Gynecologists and the U.S. Public Services Task Force recommend routine intimate partner violence screening with appropriate interventions to prevent violence against women, optimize safety, and improve health. Additional and targeted intimate partner violence assessment of women who smoke during pregnancy may prove especially beneficial.

Nuclear and mitochondrial DNA alterations in newborns with prenatal exposure to cigarette smoke.

Newborns exposed to maternal cigarette smoke (CS) in utero have an increased risk of developing chronic diseases, cancer, and acquiring decreased cognitive function in adulthood. Although the literature reports many deleterious effects associated with maternal cigarette smoking on the fetus, the molecular alterations and mechanisms of action are not yet clear. Smoking may act directly on nuclear DNA by inducing mutations or epigenetic modifications. Recent studies also indicate that smoking may act on mitochondrial DNA by inducing a change in the number of copies to make up for the damage caused by smoking on the respiratory chain and lack of energy. In addition, individual genetic susceptibility plays a significant role in determining the effects of smoking during development. Furthermore, prior exposure of paternal and maternal gametes to cigarette smoke may affect the health of the developing individual, not only the in utero exposure. This review examines the genetic and epigenetic alterations in nuclear and mitochondrial DNA associated with smoke exposure during the most sensitive periods of development (prior to conception, prenatal and early postnatal) and assesses how such changes may have consequences for both fetal growth and development.

L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.

Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences.

Prenatal exposure to cigarette smoke interacts with OPRM1 to modulate dietary preference for fat.

Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal cigarette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene-environment interaction. We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip. We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (-1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the "protective" (fat intake-lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (-3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031). A limitation of our study was its cross-sectional design. Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.

Effect of maternal cigarette smoking on newborn iron stores

Maternal smoking has been known to have a negative impact on the well being of the developing fetus. Prenatal smoking has been associated with premature births, low birth weight and with certain birth defects. Small research studies have also found a negative correlation between maternal smoking and neonatal body iron. To study and compare the relationship between maternal and infants' body iron in smokers and non-smokers in a large matched-pair cohort. This was a prospective cohort study involving 144 mothers - 72 smokers and 72 non-smokers and their respective infants. Samples were obtained from maternal and infants' cord blood at delivery for Serum transferrin receptor (sTfR) and ferritin levels. Serum TfR and ferritin were measured by RAMCO ELISA and RIA assays. Total Body Iron (TBI) was calculated using the sTfR/ferritin ratio in a previously described formula by Cook et al. Women who smoked had lower sTfR, higher ferritin and higher body iron compared to nonsmoking women. In contrast to their respective mothers, we found a small, but statistically significant negative correlation between smoking and infants' total body iron. The number of packs per day smoked was also negatively correlated with infants' ferritin and total body iron. Lower birth weight was noted in babies of smokers compared to nonsmokers (mean /- SD =3270 +/-475 vs. 3393 g +/- 475 g, p=0.03). Women who smoked during pregnancy had higher iron stores but their newborn infants had lower iron stores than those of non-smoking mothers. The more packs per day (PPD) and more days smoked during pregnancy led to lower total body iron of the babies. There may be a negative dose-dependent response between fetal smoke exposure and infant iron stores.

Smoking during pregnancy and vision difficulties in children: a systematic review.

Cigarette smoking during pregnancy is a major public health concern. Intra-uterine exposure to maternal cigarette smoking is associated with increased risks of growth and neurodevelopmental problems during childhood and later life. Few studies have focussed on visual difficulties in children in the context of maternal smoking during pregnancy. A systematic search of online databases was carried out between February and May 2013 to examine the trend in visual outcomes in children exposed to maternal cigarette smoking during intra-uterine life. Twenty-four non-randomized studies were identified. Each study was rated for quality using the Newcastle-Ottawa Scale. Most studies (n = 18) reported fetal exposure to active or passive maternal cigarette smoking to be associated with an increased risk of adverse visual outcomes in children. In particular, there were higher rates of strabismus, refractive errors and retinopathy among children of women who smoked during pregnancy. These findings suggest that fetal exposure to cigarette smoke is a significant risk factor for visual problems during later life and that certain visual faculties, such as the intraocular muscles and retinal neurons, are more affected than others. The findings provide evidence in support of public health policies aimed at reducing fetal exposure to smoking by advising both women and their partners to quit smoking during pregnancy.

779: The effect of maternal cigarette smoking on pregnancy outcome in FGR

Maternal cigarette smoking is a leading cause of fetal growth restriction (FGR). This global restriction of growth is thought to be due to intrauterine carbon monoxide and nicotine exposure and direct effects of toxins at a cellular level. Smoking is protective against the development of pre-eclampsia (PET). As abnormal UA and MCA Doppler waveforms are independent predictors of morbidity in FGR we aimed to examine the effect of cigarette smoking on Doppler patterns and perinatal outcome in a large cohort of fetuses with EFW <10th centile.

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.