Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children

We review the potential neurodevelopmental and behavioral effects of children's prenatal and/or postnatal exposure to environmental tobacco smoke (ETS). Children's exposure to ETS has been assessed in epidemiologic studies as a risk factor for a variety of behavioral and neurodevelopmental problems including reduced general intellectual ability, skills in language and auditory tasks, and academic achievement, and behavioral problems such as hyperactivity and decreased attention spans. We review 17 epidemiologic studies that have attempted to separate the effects of maternal active smoking during pregnancy from passive ETS smoke exposure by the pregnant mother or the child. Based on the available data, we found that ETS exposure could cause subtle changes in children's neurodevelopment and behavior. However, studies to date are difficult to interpret because of the unknown influence of uncontrolled confounding factors, imprecision in measurements of smoking exposure, and collinearity of pre- and postnatal maternal smoking. Although some evidence suggests that maternal smoking during pregnancy may be associated with deficits in intellectual ability and behavioral problems in children, the impact of prenatal or postnatal ETS exposure remains less clear.     

Sinistrality--a side-effect of prenatal sonography: a comparative study of young men.

Although ultrasound during pregnancy is used extensively, there is little published on adverse fetal effects. We undertook a cohort study including men born in Sweden from 1973 to 1978 who enrolled for military service. We estimated relative risks for being born left-handed according to ultrasound exposure in fetal life using logistic regression analysis. Eligible for the study were 6,858 men born at a hospital that included ultrasound scanning in standard antenatal care (exposed) and 172,537 men born in hospitals without ultrasound scanning programs (unexposed). During the introduction phase (1973 to 1975) there was no difference in left-handedness between ultrasound exposed and unexposed (odds ratio = 1.03, 95% confidence interval (CI) = 0.91 to 1.17). When ultrasonography was offered more widely (1976 to 1978), the risk of left-handedness was higher among those exposed to ultrasound compared with those unexposed (odds ratio = 1.32, 95% CI = 1.16 to 1.51). We conclude that ultrasound exposure in fetal life increases the risk of left-handedness in men, suggesting that prenatal ultrasound affects the fetal brain.     

Pyrethroids: Exposure and health effects – An update

Synthetic pyrethroids are present in numerous commercial insecticide formulations and have extensive indoor and outdoor applications worldwide, including agricultural, public, residential, and veterinary usages for pest control. Pyrethroid use has increased continuously in recent years. The aim of this review is to provide updated and comprehensive information on human exposure and potential hazards associated with this class of pesticides. An initial keyword search in the PubMed database was conducted to identify relevant articles. Were taken into considerations only the studies published in the last decade that have assessed exposure and health effects of pyrethroids in human populations. Literature review shows that exposure evaluations increasingly focus on biomonitoring and that a large number of recent epidemiological studies pertain to the effects of pyrethroids on male fertility and prenatal development.The main metabolites of pyrethroids have frequently been detected in urine samples from the general population, confirming widespread exposure of children and adults to one or more pyrethroids. Non-occupational exposure to pyrethroids mainly occurs through ingestion of residues in food, or ingestion of or dermal contact with contaminated house dust or surface-adhering particles, following domestic use. Although clinical features resulting from acute accidental exposure to pyrethroids are well described (e.g., paraesthesiae, and respiratory, eye and skin irritation), information regarding their chronic effects at low concentrations is both limited and controversial. Several recent epidemiological studies have raised concerns about potentially adverse effects on sperm quality and sperm DNA, reproductive hormones, and pregnancy outcomes. Early neurobehavioural development after in utero exposure is discussed. Further research is needed to clarify the possible risks associated with long-term environmental exposure to pyrethroids.     

Effects of low-frequency magnetic fields on embryonic development and pregnancy

Experimental and epidemiologic studies on the effects of low-frequency magnetic fields on pregnancy are reviewed. The literature suggests that these fields have adverse effects on chick embryo development. The interaction mechanism is not known. The results of experiments with mammals are inconsistent. There is more evidence of effects on mice than on rats, and the data suggest that fetal loss might be increased rather than malformations. Most of the epidemiologic studies related to pregnancy and low-frequency magnetic fields have concerned operators of a video display terminal (VDT). The results do not provide evidence for an association between adverse pregnancy outcome and use of a VDT. Other (stronger) sources of low-frequency magnetic fields have been addressed in only a few studies. It is not yet possible to conclude whether occupational or residential exposure to low-frequency magnetic fields affects human prenatal development. There is an apparent need for further investigation.     

Methamphetamine and Other Substance Use During Pregnancy: Preliminary Estimates From the Infant Development, Environment, and Lifestyle (IDEAL) Study

Objectives: Methamphetamine use is a continuing problem in several regions of the United States and yet few studies have focused on prenatal methamphetamine exposure. The purpose of this study was to estimate the prevalence and correlates of alcohol, tobacco, and other substance use—including methamphetamine—during pregnancy. Methods: The sample consisted of the first 1632 eligible mothers who consented to participate in a large-scale multisite study focused on prenatal methamphetamine exposure. This unselected screening sample included both users and nonusers of alcohol, tobacco, methamphetamine, and other drugs. Substance use was determined by maternal self-report and/or GC/MS confirmation of a positive meconium screen. Results: Overall, 5.2% of women used methamphetamine at some point during their pregnancy. One quarter of the sample smoked tobacco, 22.8% drank alcohol, 6.0% used marijuana, and 1.3% used barbiturates prenatally. Less than 1% of the sample used heroin, benzodiazapenes, and hallucinogens. Multivariate modeling results showed that tobacco smokers and illicit drug users were more likely to be single and less educated, have attended less than 11 prenatal visits, and utilize public financial assistance. Conclusions: This is the first large-scale investigation to report the prevalence of methamphetamine use during pregnancy in areas of the United States where methamphetamine is a notable concern. Follow-up research is ongoing to investigate the outcomes associated with prenatal methamphetamine exposure. Given that this research extends and confirms previous findings showing that high-risk groups of pregnant women can be identified on the basis of basic demographic characteristics, targeted interventions are greatly needed to reduce serious adverse outcomes associated with prenatal alcohol and tobacco use.     

Maternal dental history, child's birth outcome and early cognitive development

Prenatal exposure to high levels of mercury, radiation and inflammation have been associated with adverse reproductive outcomes such as increases in preterm delivery, low birthweight and delayed neurodevelopment. Few data are available to evaluate the potential effects of prenatal low-level exposure to these factors as may occur during dental care. We evaluated maternal dental history prior to and during pregnancy in relation to birth outcomes and early communicative development among offspring in a large cohort (n = 7375) of British children born in 1991-92. Dental history was assessed by questionnaire. The child's communicative development was assessed using the MacArthur Communicative Development Inventory at 15 months of age. Total mercury was measured in umbilical cord tissue for a subset of the children. Overall, dental care, including amalgam fillings, was not associated with birth outcomes or language development. Having X-rays taken during pregnancy was not associated with birthweight measured continuously (b = 14.7, P = 0.4), but was associated with slightly increased odds of having a term, low-birthweight baby (OR 1.9, [95% confidence interval 1.0, 3.4]). More detailed evaluation of the potential adverse effects of elective dental treatment during pregnancy, particularly dental X-rays, may be warranted.     

The influence of season and ambient temperature on birth outcomes: a review of the epidemiological literature

Seasonal patterns of birth outcomes, such as low birth weight, preterm birth and stillbirth, have been found around the world. As a result, there has been an increasing interest in evaluating short-term exposure to ambient temperature as a determinant of adverse birth outcomes. This paper reviews the epidemiological evidence on seasonality of birth outcomes and the impact of prenatal exposure to ambient temperature on birth outcomes. We identified 20 studies that investigated seasonality of birth outcomes, and reported statistically significant seasonal patterns. Most of the studies found peaks of preterm birth, stillbirth and low birth weight in winter, summer or both, which indicates the extremes of temperature may be an important determinant of poor birth outcomes. We identified 13 studies that investigated the influence of exposure to ambient temperature on birth weight and preterm birth (none examined stillbirth). The evidence for an adverse effect of high temperatures was stronger for birth weight than for preterm birth. More research is needed to clarify whether high temperatures have a causal effect on fetal health.     

双胎妊娠的产前筛查与产前诊断

随着近二十年辅助生殖技术的发展及不孕夫妇对不孕症治疗年限较长,双胎及高龄双胎孕妇数量逐年增加。伴随而来的双胎妊娠的产前筛查问题成为当今的一个热点。双胎妊娠较单胎妊娠而言,产前筛查与产前诊断难度更大。近30年来,随着母胎血清学、超声技术及非侵入性产前筛查技术的发展,产前筛查与产前诊断发生了显著的变化。     

The interaction of lead exposure and pregnancy.

The toxic effects of low-level lead exposure have been the subject of a good deal of research and media attention in recent times. In most countries, the acceptable occupational exposure limit for lead is being progressively decreased as the adverse health effects of lead are being identified at levels approaching those found in non-occupational environments. Due to the sensitive nature of the fetus to hazardous substances, the exposure to lead of the unborn child via maternal sources is of critical concern. Preterm delivery, congenital abnormalities and decreases in growth stature have all been associated with prenatal lead exposure at "acceptable" levels. There is an accumulation of evidence which indicates that maternal exposures prior to conception can play an important role in determining blood lead levels during pregnancy. In light of these observations the practice of removing the pregnant woman from lead sources may be of questionable value with regards to providing sufficient protection for the fetus. This article reviews the relevant literature pertaining to the mobilization of lead from bone during pregnancy and the toxicity of low-level lead exposure to the fetus, and briefly discusses some factors which may affect this toxicity.     

Human reproduction and environmental risk factors

Environmental pollution is a great cause of concern, in particular, growing attention is being paid to the potential of many chemicals to affect the reproductive system in humans. The key role of prevention and control of reproductive hazards is recognized world-wide. Many chemicals have been shown to impair fertility and/or prenatal and perinatal development in experimental studies. However, a sufficient evidence of an effect on human reproduction is available for some compounds only. The use of biological markers may improve the assessment of exposure to chemicals, contribute to identify mechanisms of action and put into evidence early, reversible, biological effects. Valid biological markers are also needed in epidemiological studies: without reliable data on the level of current and past exposures it is difficult to establish a causal relationship between a pollutant and the occurrence of adverse health effects. A multidisciplinary approach to risk assessment is required. Priorities for interdisciplinary research on environmental chemicals and reproduction include the identification of susceptible population subgroups and risk assessment of exposure to multiple chemicals.     

The role of gangliosides in brain development and the potential benefits of perinatal supplementation

The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research.     

Effects of binge drinking on infant growth and development in an Inuit sample

Prenatal exposure to an average of 0.5 oz absolute alcohol per day (the equivalent of 7 standard drinks per week) during pregnancy has been found to be associated with numerous adverse effects on pre- and postnatal development. In the animal model, concentrated alcohol exposure has been found to lead to more adverse effects than exposure to the same total quantity of alcohol ingested in smaller doses over a longer period of time. The primary aim of this study is to determine whether, in a population where binge drinking is common but total alcohol consumption across pregnancy is low, prenatal exposure to alcohol is associated with effects on prenatal growth, visual acuity and cognitive development during infancy. The second aim is to determine which of several indicators of alcohol consumption best predicts pre- and postnatal outcomes. Data were collected from 216 Inuit women and their infants living in Nunavik, the northern region of Québec. Maternal interviews were conducted during mid-pregnancy and at 1 and 6 months postpartum. Birth weight, length, and head circumference were assessed at delivery. Visual acuity and cognitive development were assessed at 6 months of age. In this population in which infrequent heavy episodic drinking is common, even occasional binge exposure was associated with reduced prenatal growth and poorer visual acuity at 6 months of age. A simple dichotomous measure of binge drinking during pregnancy provided the best predictor of fetal growth and 6-month acuity. The population studied here is unusual in terms of its pattern of binge alcohol consumption. To our knowledge, this is the first study to observe effects of binge drinking during pregnancy on infant growth and development in a sample where the average daily alcohol intake is low (<0.5 ounces).     

Effects of parental occupational exposures on spontaneous abortion and congenital malformation

Human reproduction is a complex process and can be disturbed in many phases by both host and environmental factors. Therefore, it has been difficult to distinguish the occupational causes of spontaneous abortion and congenital malformations from other factors related to the parents' characteristics and their living environment. The extrapolation of results of animal studies to humans is often complicated because there are structural and functional differences between the species and the mechanisms of harmful effects are seldom known. There is also a lack of conclusive epidemiologic studies on the topic. At present knowledge on the potential reproductive toxicity of even rather common occupational exposures is limited and in many cases only suggestive. Paternal exposure to organic solvents before conception and maternal exposure during pregnancy may have adverse effects on the pregnancy and offspring. Heavy physical work during pregnancy may increase the risk of spontaneous abortion.     

Reproductive and developmental effects of disinfection by-products in drinking water.

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach.     

Alcohol and pregnancy. An epidemiologic perspective.

This article considers maternal use of alcohol during pregnancy, from an epidemiologic perspective. In general, maternal use of alcohol during pregnancy has been associated with a number of effects in offspring including fetal alcohol syndrome, a reduction in birth weight, effects on behavior, and other late effects. It is apparent from the existing literature that the epidemiologic dimensions of these effects are poorly defined and hampered by methodologic problems. Assessment of both outcome and exposure can be difficult, and there is great potential for uncontrolled confounding. Additionally, it is unclear whether the apparent teratogenicity of alcohol results from direct, acute effects of alcohol on the developing fetus, or results from chronic effects of excessive alcohol intake in the mother. This article concludes with recommendations for further research, which may help clarify the complexity of effects associated with maternal use of alcohol during pregnancy.     

Residential mobility during pregnancy

In epidemiological studies of environmental exposures and adverse pregnancy outcomes, maternal residence at delivery is often used to assign an exposure level, based on routinely collected data. In order to examine the potential for exposure misclassification due to residential mobility, we examined maternal mobility according to changes in residence overall, as well as changes in municipality and county. The potential for mobility to be related to pregnancy outcomes was considered by examining the relationship between mobility and risk factors commonly included in investigations of adverse pregnancy outcomes. Previously collected data were studied from 398 population-based control subjects from a case-control study of stillbirths. We compared demographic, lifestyle, medical, pregnancy and environmental factors of women who moved during pregnancy with those who did not. Bivariable and multivariable log binomial regressions were used to identify risk factors that were associated with mobility during pregnancy. Twelve per cent of subjects moved at least once during their pregnancy. Among women who moved, the majority (62%) moved within the same municipality. In bivariable analyses, we found that low family income, lower maternal age, unmarried status and tobacco use were associated with an increased likelihood of moving during pregnancy, whereas women who used folic acid before conception and who had a higher prepregnancy body mass index (BMI) were less likely to move during pregnancy. In multivariable analyses, only family income, age and prepregnancy BMI were independently predictive of mobility. These results indicate that in studies using maternal residence at delivery to assign environmental exposures, mobility during pregnancy is likely to be prevalent enough to introduce exposure misclassification. The potential for differential exposure misclassification should be considered should any of the risk factors for moving identified by this study also be risk factors for the outcome under study.     

A review of studies on maternal occupational exposures and birth defects, and the limitations associated with these studies.

The proportion of pregnant women who work during pregnancy is increasing as more women move into previously male-dominated occupations. With this move, occupational exposure to chemical or physical factors during pregnancy could be further increased. In the last decade, there have been many reports on the causes of birth defects. Unfortunately, most reported associations between occupational exposures and adverse reproductive outcomes in epidemiological studies are equivocal and often controversial. Many reported associations are only suggestive. More information is needed before firm conclusions can be drawn. The major reasons for ambiguous findings are due to limitations of study methodology, e.g. inappropriate endpoints, multiple confounders, low study power and inadequate analysis methods. It must also be noted that maternal work, and therefore exposure, may also differ greatly from country to country.     

Use of meconium in perinatal epidemiology: potential benefits and pitfalls

PurposeMeconium is a biomarker matrix that can be used to assess cumulative exposures in epidemiologic studies of prenatal risk factors. Depending on when meconium is collected, different exposure windows during pregnancy can be measured. However, little guidance exists regarding the extent to which timing of meconium collection will influence resulting effect estimates.MethodsWe performed a simulation study of prenatal tobacco smoke exposure (assessed from meconium nicotine) and birth weight. We discuss four typical meconium collection methods capturing different exposure windows and assess the biases induced by these methods.ResultsIn simulations assuming that exposure to tobacco smoke only during late gestation was of etiologic relevance to birth weight, use of a meconium collection method that captured exposure windows other than late gestation resulted in biased estimates of the true nicotine–birth weight association.ConclusionsUsing meconium collection methods that do not reflect an exposure window of etiologic relevance can lead to biased results and erroneous conclusions regarding the nature of prenatal exposure–outcome associations. Understanding how prenatal exposure patterns vary across the pregnancy and exposure windows of etiologic relevance is essential in determining when and how to collect meconium for use in biomarker studies of prenatal exposure.     

Prenatal alcohol exposure and childhood balance: a systematic review

Humphriss R, Hall A, Macleod J. Prenatal alcohol exposure and childhood balance: a systematic review. Paediatric and Perinatal Epidemiology 2010; 24: 156–165. Balance problems in childhood have known adverse psychosocial associations such as poorer quality of life and lower educational achievement. Previous longitudinal studies have documented an adverse effect of prenatal alcohol exposure on a variety of neurodevelopmental outcomes and so an effect on balance would seem plausible. This is supported by a previous laboratory study that found that rats exposed to ethanol in utero have dysfunctional balance and gait. The present study is a systematic review of the current evidence on the effects of maternal alcohol use during pregnancy on offspring balance in childhood. A search strategy was devised and applied in the CENTRAL database (Cochrane Collaboration). Prospective longitudinal studies were then sought using databases including Medline, EMBASE, PsychInfo, CINAHL and AMED. In addition, citations in relevant published papers and books were followed up and experts in the field were contacted. No relevant human experimental studies were found. Four longitudinal studies were found to have assessed balance in preschool children. Only one of these studies suggested strong or substantial effects of alcohol exposure on balance‐related outcomes. However, this study appeared the most methodologically robust. In conclusion, at present, there is limited evidence on the possible effects of alcohol exposure on childhood balance.     

Effects of psychosocial characteristics of work on pregnancy outcomes: a critical review

Birth outcomes may influence subsequent susceptibility to chronic diseases. With the increased number of women who continue to work during pregnancy, occupational stress has been hypothesized to be a potential contributor to adverse reproductive health outcomes. The Job Demand and Control model has been primarily used in investigating associations between work-related stress and outcomes such as preterm delivery, low birth weight, and spontaneous abortion. A literature review of occupational factors that have been associated with adverse reproductive outcomes was conducted. In studies assessing preterm delivery and low birth weight, some evidence has suggested a modest association with work-related stress but has not been conclusive. In the literature on psychosocial characteristics of work and spontaneous abortion, job strain alone was often not associated with adverse outcomes. However the presence of other risk factors resulted in a synergistic effect which strengthened the odds of an adverse outcome. Future studies should use a prospective design with a large study sample, in which work-related stress exposure data are collected before or in the early stages of the pregnancy. In addition, future research should measure psychosocial characteristics of work both objectively and subjectively.