Dose-response associations between maternal smoking during pregnancy and subsequent childhood obesity: effect modification by maternal race/ethnicity in a low-income US cohort

Studies suggest that children exposed to cigarette smoke in utero are at risk of becoming obese. Few researchers have evaluated the dose-response association between maternal smoking during pregnancy and childhood obesity or whether this association varies by maternal race/ethnicity. The authors obtained retrospective cohort data by linking records from the Pregnancy Nutrition Surveillance System and the Pediatric Nutrition Surveillance System on 155,411 low-income children born during 1995-2001 in 9 US states and 2 tribal nations. The authors examined maternal smoking status, duration of smoking, quantity of smoking, and both duration and quantity combined. Childhood obesity was based on a body mass index greater than or equal to the 95th percentile for sex and age, assessed at age 2-4 years. Maternal race/ethnicity modified the association between smoking during pregnancy and childhood obesity. Among non-Hispanic White mothers, both duration and quantity of smoking were positively associated with childhood obesity in a dose-response manner. Among non-Hispanic Black mothers, only heavy smoking was positively associated with childhood obesity. Among Hispanics, American Indians/Alaska Natives, and Asians/Pacific Islanders, smoking was not associated with childhood obesity. The inconsistent association between smoking during pregnancy and childhood obesity across race/ethnicity categories merits further investigation into potential explanations for this variation, which may include confounding, reporting bias, or unexplored biologic mechanisms.     

Fetal growth, maternal prenatal smoking, and risk of invasive meningococcal disease: a nationwide case-control study

BACKGROUND: The prenatal period may be important for susceptibility to infections. We evaluated whether low birthweight, prematurity, and prenatal maternal smoking were associated with increased risk of invasive meningococcal disease. METHODS: We linked the Danish nationwide National Registry of Patients, the Birth Registry, and social registries to obtain data on fetal growth and social factors on 1921 cases of meningococcal disease hospitalized between 1 January, 1980 and 31 December, 1999 (median age 31 months, interquartiles 13-65 months) and 37 451 population controls. The impact of maternal smoking was examined in a subsample of 462 cases and 9240 controls born after 1990, when data on smoking became available in the Birth Registry. RESULTS: The adjusted odds ratios (OR) of meningococcal disease associated with low birthweight (<2500 g) varied between 1.6 (95% CI: 1.1, 2.3) in infants <12 months to 1.5 (95% CI: 1.0, 2.3) in children >60 months of age at hospitalization for meningococcal disease. Premature children had an increased risk of meningococcal disease during the first year of life only (adjusted OR = 1.3, 95% CI: 1.1, 1.9). The effect of low birthweight was very similar among mature and premature children. The adjusted OR for maternal smoking was 1.8 (95% CI: 1.4, 2.2). CONCLUSIONS: Low birthweight is associated with an increased risk of meningococcal disease throughout childhood, while an effect of prematurity persists only for 12 months. Maternal prenatal smoking was associated with the risk of meningococcal disease.     

Fetal and maternal immune responses to methylmercury exposure: a cross-sectional study

Methylmercury (MeHg) is a ubiquitous environmental contaminant with known neurodevelopmental effects. In humans, prenatal exposures primarily occur through maternal consumption of contaminated fish. In this study, we evaluated the association between prenatal exposure to MeHg and titers of total immunoglobulins (Ig) and specific autoantibodies in both mothers and fetuses by analyzing maternal and cord blood serum samples. We examined multiple immunoglobulin isotypes to determine if these biomarkers could inform as to fetal or maternal responses since IgG but not IgM can cross the placenta. Finally, we evaluated serum cytokine levels to further characterize the immune response to mercury exposure.The study was conducted using a subset of serum samples (N=61 pairs) collected from individuals enrolled in a population surveillance of MeHg exposures in the Brazilian Amazon during 2000/2001. Serum titers of antinuclear and antinucleolar autoantibodies were measured by indirect immunofluorescence. Serum immunoglobulins were measured by enzyme-linked immunosorbent assay (ELISA) and BioPlex multiplex assay. Serum cytokines were measured by BioPlex multiplex assay.In this population, the geometric mean mercury level was within the 95th percentile for US populations of women of childbearing age but the upper level of the range was significantly higher. Fetal blood mercury levels were higher (1.35 times) than those in their mothers, but highly correlated (correlation coefficient [r]=0.71; 95% CI: 0.54, 0.89). Total IgG (r=0.40; 95% CI: 0.19, 0.62) and antinuclear autoantibody (odds ratio [OR]=1.05; 95% CI: 1.02, 1.08) levels in paired maternal and fetal samples were also associated; in contrast, other immunoglobulin (IgM, IgE, and IgA) levels were not associated between pairs. Total IgG levels were significantly correlated with both maternal (r=0.60; 95% CI: 0.25, 0.96) and cord blood mercury levels (r=0.61; 95% CI: 0.25, 0.97), but individual isotypes were not. Serum cytokines, interleukin-1β (r=0.37; 95% CI: 0.01, 0.73), interleukin-6 (r=0.34; 95% CI: 0.03, 0.65), and tumor necrosis factor-α (r=0.24; 95% CI: 0.015, 0.47), were positively correlated between maternal and fetal samples. Antinuclear and antinucleolar autoantibody titer and serum cytokine levels, in either maternal or cord blood, were not significantly associated with either maternal or cord blood mercury levels.These data provide further evidence that there are likely IgG biomarkers of mercury-induced immunotoxicity in this population since IgG levels were elevated with increased, and associated with, mercury exposure. However, unlike previous data from adult males and non-pregnant females, we found no evidence that antinuclear and antinucleolar autoantibody titer is a reliable biomarker of mercury immunotoxicity in this population.     

Pregnancy complications and subsequent maternal cerebrovascular events: a retrospective cohort study of 119,668 births

Low birth weight infants are at increased risk of cerebrovascular disease in adulthood. This has been attributed to physiologic programming following inadequate intrauterine nutrition. The authors sought to determine whether mothers who deliver low birth weight infants or who suffer related pregnancy complications are also at increased risk. They used routine data to identify all first singleton livebirths in Scotland (1981-1985) and found that 342 of the 119,668 mothers suffered cerebrovascular events over 14-19 years' follow-up. Compared with women who delivered babies of > or = 3,500 g, women who delivered low birth weight (<2,500 g) infants were at increased risk of cerebrovascular disease (adjusted hazards ratio (HR) = 2.51, 95% confidence interval (CI): 1.71, 3.70) with a consistent trend across birth weight categories. The lowest birth weight quintile (adjusted HR = 1.29, 95% CI: 1.01, 1.65), preterm delivery (adjusted HR = 1.91, 95% CI: 1.35, 2.70), and previous spontaneous abortion (adjusted HR = 1.49, 95% CI: 1.09, 2.03) were all predictive of subsequent maternal cerebrovascular events. The effects were additive. Women who experienced all three complications had a sevenfold risk (adjusted HR = 7.03, 95% CI: 2.24, 22.06). The association with low birth weight in mothers, as well as offspring, is unlikely to be explained by intrauterine programming and suggests that cerebrovascular disease and low birth weight may share common genetic or lifestyle risk factors.     

A case-control study of maternal smoking and congenital malformations

We conducted a population-based case-control study to assess the association between maternal smoking during pregnancy and the risk of giving birth to a child with a congenital malformation. Cases were all singleton livebirths with a congenital malformation recorded on the 1984-1986 Washington State Birth Records (n = 3284). The smoking histories of these mothers were compared to a randomly selected group of mothers with a singleton livebirth of a child without a malformation during these same years (n = 4500). When all malformations were taken as a group, there was no association with maternal smoking (relative risk (RR) = 1.0, 95% CI 0.9-1.1). However, increased risks were observed for a number of specific malformations, including microcephalus (RR = 2.0, 95% CI 1.0-4.0), cleft defects (RR = 1.4, 95% CI 1.0-2.0), and club foot (RR = 1.4, 95% CI 1.0-2.0). We did not find any association with Down's syndrome (RR = 0.8 95% CI 0.5-1.3) or any other malformation. We conclude that maternal smoking during pregnancy may be associated with an increased risk for some malformations.     

A case-control study of maternal smoking and congenital malformations

Summary. We conducted a population-based case-control study to assess the association between maternal smoking during pregnancy and the risk of giving birth to a child with a congenital malformation. Cases were all singleton livebirths with a congenital malformation recorded on the 1984–1986 Washington State Birth Records (n = 3284). The smoking histories of these mothers were compared to a randomly selected group of mothers with a singleton livebirth of a child without a malformation during these same years (n = 4500). When all malformations were taken as a group, there was no association with maternal smoking (relative risk (RR) = l.0, 95% CI 0.9–1.1). However, increased risks were observed for a number of specific malformations, including microcephalus (RR = 2.0, 95% CI 1.0–4.0), cleft defects (RR=1.4, 95% CI 1.0–2.0), and club foot (RR= 1.4, 95% CI 1.0–2.0). We did not find any association with Down's syndrome (RR=0.8, 95% CI 0.5–1.3) or any other malformation. We conclude that maternal smoking during pregnancy may be associated with an increased risk for some malformations.     

Cigarette smoking, obesity, and benign prostatic hypertrophy: a prospective population-based study.

The authors examined the relation of smoking and obesity to surgically treated benign prostatic hypertrophy in a prospective study of white men aged 40-79 years who were first examined in 1972-1974 and were followed for an average of 12 years. After exclusion of those whose surgery preceded assessment of smoking and obesity and those who had prostate cancer, there were 165 cases of benign prostatic hypertrophy among 929 men. Age-adjusted relative risk of benign prostatic hypertrophy in current or previous smokers compared with nonsmokers was 1.1 (95% confidence interval 0.8-1.6). Age-adjusted relative risk of benign prostatic hypertrophy in the most obese tertile (body mass index (kg/m2) greater than 26.75) compared with the remainder showed a relative risk of 0.9 (95% confidence interval 0.6-1.4). Multivariate analysis also failed to show a relation between cigarette smoking or obesity and the development of surgically treated benign prostatic hypertrophy.     

Association of maternal smoking and alcohol consumption with young adults' cannabis use: a prospective study

This 2006 study examined 1) whether maternal use of tobacco and consumption of alcohol when a child is 5 and 14 years of age predict cannabis use in young adults, and 2) whether this association is explained by possible confounding or mediating factors. Data were taken from a prospective birth cohort study of mothers and their children in Brisbane, Australia. This study was based on a cohort of 3,176 young adults who participated at the 21-year follow-up of the study and for whom data were available on maternal smoking and alcohol consumption 5 and 14 years after their birth. After controlling for possible confounders, the authors found that maternal smoking at 14 years was associated with frequent use of cannabis in offspring at 21 years, regardless of maternal smoking at 5 years. Children of mothers who drank more than one glass of alcohol at 5 years and continued at 14 years were more likely to use cannabis in early adulthood. The association between maternal substance use and offspring cannabis use was partially mediated by adolescent externalizing behavior and smoking measured at 14 years. Prevention programs that address maternal and adolescent tobacco use and adolescent externalizing behavior should be considered as strategies to reduce cannabis use by young adults.     

Fetal origins of obesity

The worldwide epidemic of obesity continues unabated. Obesity is notoriously difficult to treat, and, thus, prevention is critical. A new paradigm for prevention, which evolved from the notion that environmental factors in utero may influence lifelong health, has emerged in recent years. A large number of epidemiological studies have demonstrated a direct relationship between birth weight and BMI attained in later life. Although the data are limited by lack of information on potential confounders, these associations seem robust. Possible mechanisms include lasting changes in proportions of fat and lean body mass, central nervous system appetite control, and pancreatic structure and function. Additionally, lower birth weight seems to be associated with later risk for central obesity, which also confers increased cardiovascular risk. This association may be mediated through changes in the hypothalamic pituitary axis, insulin secretion and sensing, and vascular responsiveness. The combination of lower birth weight and higher attained BMI is most strongly associated with later disease risk. We are faced with the seeming paradox of increased adiposity at both ends of the birth weight spectrum-higher BMI with higher birth weight and increased central obesity with lower birth weight. Future research on molecular genetics, intrauterine growth, growth trajectories after birth, and relationships of fat and lean mass will elucidate relationships between early life experiences and later body proportions. Prevention of obesity starting in childhood is critical and can have lifelong, perhaps multigenerational, impact.     

母体孕期主动或被动吸烟与后代多指(趾)畸形的病例对照研究

目的 近年来,临床上所见多指（趾）畸形的患儿数量与日俱增。除了遗传因素外,母体怀孕期间自身行为和环境因素的影响也越显重要;然而,关于这些影响的流行病学数据十分匮乏。方法 采用以医院为基础、以患儿年龄配对的1∶2病例对照研究,对多指（趾）患儿与正常儿的母亲进行问卷调查。采用交互作用分析、协变量筛选和多元logistic回归分析探究母亲孕期吸烟（主动或被动）和后代多指（趾）畸形的危险因素关系。结果 研究对象共纳入病例组143例,对照组286例。孕妇在怀孕期间吸烟,显著增加后代多指（趾）畸形的发病风险（主动吸烟：OR=4.74,95% CI：1.43～15.65,P=0.011;被动吸烟：OR=2.42,95% CI：1.32～4.44,P=0.004）。调整混杂因素后,母亲孕期吸烟对后代多指（趾）畸形的影响仍显著存在（主动吸烟：aOR=7.27,95% CI：1.72～30.72,P=0.007;被动吸烟：aOR=2.41,95% CI：1.11～5.23,P=0.026）。结论 母亲孕期主动或被动吸烟是后代发生多指（趾）畸形的危险因素,显著增加其发病风险。     

Fetal environment and schizophrenia

Schizophrenia and related disorders are adult-onset illnesses with no definitively established risk factors. Several studies report that exposures to infection and nutritional deprivation during early development may elevate the risk of later developing schizophrenia, specifically during the prenatal period. Preliminary evidence implicates lead exposure as well, suggesting that chemical exposures during early development may constitute a new class of risk factors for schizophrenia that has not been adequately investigated. Exposure to lead is given as an example of a chemical agent for which some effects have been described throughout the life course on both general neurodevelopmental outcomes and now on a specific psychiatric diagnosis. Findings from prospectively collected birth cohorts are offered as examples of both innovations in methodology and opportunities for future generations of investigators.     

Brief intervention on maternal smoking: a randomized controlled trial

OBJECTIVES: To determine if mothers receiving a smoking cessation intervention emphasizing health risks of environmental tobacco smoke (ETS) for their children have a higher quit rate than mothers who received routine smoking cessation advice, which focused on their own health, or a control group of mothers. SETTING: Tertiary referral centre. METHODS: Randomized control trial. A total of 363 mothers were randomly assigned to a smoking cessation intervention either aimed at their children's health (n = 111) or their own health (n = 131), or to a control group receiving no smoking cessation advice (n = 121). RESULTS: Provision to mothers of both groups of health risks of tobacco smoke resulted in significantly higher rate of cessation of smoking and smoking location change than those of the control group, with child intervention group having significantly higher rate of cessation of smoking and smoking location change than those of the maternal intervention group (P < 0.05). Post-intervention knowledge scores differed significantly for all groups; however, child intervention group was the only significantly better group than the others (P < 0.05). According to the multivariate analysis results, intervention grouping and presence of smoking friends were independent factors determining smoking cessation (P < 0.05). Intervention grouping, post-intervention knowledge, presence of other household members who smoked and family income were independent factors determining smoking location change (P < 0.05). Family income, intervention grouping and presence of smoking friends were significant independent factors influencing post-intervention knowledge (P < 0.05). CONCLUSION: Discussion during short paediatric visits on effects of smoking on child's or maternal health may result in a significant smoking cessation, smoking location change rate or knowledge change. Those who cannot give up smoking usually change their location of smoking. Provision of information on effects of smoking on child's health, rather than maternal, may result in more significant changes in behaviour or knowledge. Maternal education on smoking should include information on effects of smoking on both child's and maternal health, but should be especially focused on child's health.     

Multiple malformations and maternal smoking

The Swedish health registries were used to investigate a possible effect of maternal smoking on the incidence of multiple malformations. Among 1413811 infants born in 1983-96 and with known smoking exposure in early pregnancy, 26619 with isolated malformations and 1409 with two or more malformations were selected. After controlling for year of birth, maternal age, parity and educational level, a statistically significant association between maternal smoking and multiple malformations was found (OR 1.15; 95% CI 1.02, 1.29). Among isolated malformations, the estimated OR for maternal smoking was close to unity (OR 1.02; 95% CI 0.99, 1.05), but a strong heterogeneity of the magnitude of the association between maternal smoking and the different malformations was found. Among multimalformed, no such heterogeneity was indicated. The ORs for maternal smoking were calculated for all possible pairwise combinations of 44 selected malformations, but no association between maternal smoking and any specific combination could be detected. The ORs for maternal smoking among probable cases of VATER, CHARGE or OEIS non-random associations, respectively, were estimated, but no association was indicated between maternal smoking and any of the malformation complexes. The results of the present study indicate that maternal smoking is associated with a non-specific increased risk of multiple malformations, but further research is needed before such an inference can be made.     

Fetal trisomy 21 and maternal preeclampsia

BACKGROUND: Placental trophoblast shedding into maternal circulation has been hypothesized as a potential cause of preeclampsia. Because pregnancies with a trisomy 21 fetus also have high levels of fetal cells and cell-free fetal DNA in maternal circulation, we examined whether trisomy 21 pregnancies have a higher risk of preeclampsia than euploid pregnancies. METHODS: We used 2 population-based databases. We identified 7763 pregnancies with a singleton trisomy 21-affected fetus and 15,293 matched euploid gestations from the U.S. Natality files for the period 1995-1999. The second database consisted of 665 pregnancies with fetal trisomy 21 and 987 euploid controls in a population-based Down syndrome study in California. In the latter study, women were interviewed by telephone regarding characteristics and pregnancy complications. Gestational hypertension and preeclampsia are the outcomes of this study. RESULTS: The U.S. Natality files showed that in nulliparous women fetal trisomy 21 was associated with a reduced risk of pregnancy-induced hypertension (adjusted relative risk [aRR] = 0.67; 95% confidence interval [CI] = 0.53 to 0.85). Findings from the California study confirmed this association in nulliparous women, and further revealed that the decrease in overall risk of pregnancy-induced hypertension was mainly the result of a large reduction in the risk of preeclampsia (aRR = 0.19; CI = 0.04 to 0.88) rather than in gestational hypertension by itself (0.83; 0.37 to 1.84). Neither dataset showed these effects among multiparous pregnancies. CONCLUSION: Fetal trisomy 21 is associated with a reduced, rather than increased, risk of preeclampsia, specifically in nulliparous women.     

母亲孕前及分娩前超重肥胖对中学生超重肥胖影响的病例对照研究

目的 探讨广州市母亲孕前及分娩前超重肥胖对子代中学时期超重肥胖的影响,为预防中学生肥胖提供科学依据.方法 依托广州市中学生常规体检,抽取3所高中、3所初中共3384名学生,将体检中超重肥胖的中学生纳入超重肥胖组(642名),其余学生纳入对照组(2742名),对学生及家长进行问卷调查.使用倾向性评分匹配(propensi...     

Fetal origins of insulin resistance and obesity

A number of epidemiological studies worldwide have demonstrated a relationship between poor early growth and an increased susceptibility to insulin resistance, visceral obesity, type 2 diabetes and other features of the metabolic syndrome in adulthood. However, the mechanistic basis of this relationship and the relative roles of genes and the environment remain a subject of debate. The 'thrifty phenotype' hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. The maternal reduced-protein rat model has been used to examine the importance of the maternal environment in determining susceptibility to adult disease. Pregnant and lactating rat dams are fed a diet containing 80 g protein/kg as compared with 200 g protein/kg, which leads to growth restriction in utero. Offspring of low-protein dams have increased susceptibility to diabetes, insulin resistance and hypertension when fed a palatable high-fat diet that promotes obesity. Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet. Increased glucocorticoid exposure, particularly during late gestation, has been linked with insulin resistance in adulthood. High levels of fetal glucocorticoids may result from a decreased activity of placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2, which normally protects the fetus from high maternal glucocorticoid levels. Leptin administration to protein-restricted dams inhibits the suppression of 11beta-HSD-2 and may be one mechanism by which the metabolic syndrome is prevented.