Interactions between fetal HLA-DQ alleles and maternal smoking influence birthweight

Maternal smoking during pregnancy inhibits fetal growth, and is a major cause of childhood and adult morbidity, including increased risks of cardiovascular disease and diabetes. However, the use of birthweight as a proxy for future smoking-related morbidity is hindered by its wide variability, suggesting a role for other birthweight-modifying factors. We report here, for the first time, that interactions between specific fetal HLA-DQA1 and DQB1 alleles and maternal smoking can influence birthweight. We compared mean birthweights of a series of term, HLA-DQ typed white UK newborns (n = 552) whose mothers had either smoked (n = 211) or not smoked (n = 341) during pregnancy. Maternal smoking during pregnancy resulted in an average birthweight reduction of 244 g, but the combined effects of maternal smoking and fetal DQA1*0101 or DQB1*0501 alleles resulted in a 230 and 240 g further reduction in mean birthweight, respectively, resulting from interactions between smoking and these DQ types. Other fetal DQ allele-specific interactions with maternal smoking are suggested by a "protective" effect on smoking-associated birthweight reduction in newborns typing for DQA1*0201 and DQB1*0201. Our results suggest biological interactions between maternal cigarette smoking during pregnancy and specific fetal DQ alleles that affect fetal growth. The precise nature of these interactions merits further investigation, as knowledge of fetal HLA-DQ type may be useful in refining risk estimates of severe fetal growth restriction because of maternal smoking during pregnancy.     

Low birthweight, preterm births and intrauterine growth retardation in relation to maternal smoking

The association between the intensity and duration of cigarette smoking during pregnancy and the frequency of low birthweight, preterm births and intrauterine growth retardation was investigated in a historical cohort. All 5166 livebirths occurring in the city of Pelotas, Brazil, during 1993 were identified and mothers interviewed soon after delivery. Children whose mothers smoked during pregnancy had a birthweight 142 g lower than those of non-smoking mothers. The odds ratio for low birthweight among children of smokers was 1.59 [95% CI 1.30–1.95]. There was no association between smoking and preterm delivery assessed by the Dubowitz score. In relation to intrauterine growth retardation, smoking was associated with an odds ratio of 2.07 [95% CI 1.69–2.53]. There was a direct dose–response association between the number of cigarettes smoked and the risk of growth retardation. Women whose partner smoked were also at higher risk of having a child with growth retardation. All the above results were adjusted for confounding factors. The effect of maternal smoking on low birthweight seems to be attributable to intrauterine growth retardation rather than preterm delivery.     

Reinterpreting the effects of maternal smoking on infant birthweight and perinatal mortality: a multivariate approach to birthweight standardization.

Infants of women who smoke during pregnancy have lower birthweights and have been observed to have higher rates of perinatal mortality than infants of non-smokers. It is not clear whether this increased risk of mortality is due to an excess of small births among smokers or to an independent effect of smoking. Although infants of smokers have overall higher mortality rates than non-smokers, low birthweight (< 2500 g) infants of smokers have lower mortality rates than low birthweight infants of non-smokers. However, comparison of birthweight-specific mortality between two groups is problematic when there are differences in the birthweight distributions. Methods that have been developed to standardize for these differences by comparing mortality rates relative to their own mean do not allow for simultaneous control of confounding variables. Using data from over 13,000 births of women who participated in a prepaid health care plan we present a method to standardize for birthweight while adjusting for variables that may confound the relationship between maternal smoking and perinatal mortality. After controlling for race, maternal age, education, parity, and number of cigarettes smoked, we found that 85% of the increased mortality due to smoking was attributable to an excess of small births in the birthweight distribution of offspring of smoking mothers, while 15% was due to higher birthweight-specific mortality at almost all standardized birthweights. Contrary to previous reports, we found that low birthweight infants of smoking mothers are at higher risk of perinatal mortality if a population-specific standard for birthweight is used.     

Neonatal hair nicotine levels and fetal exposure to paternal smoking at home

Exposure to environmental tobacco smoke (ETS) is a major risk to human health, and the home is the greatest single source of ETS for children. The authors investigated fetal exposure to paternal smoking at home during pregnancy. Korean families were included as trios of fathers, mothers, and neonates identified in 2005-2007. Sixty-three trios were finally enrolled in this study after exclusion of those in which the mother was a smoker or was regularly exposed to ETS at places other than the home. Nicotine and cotinine concentrations in hair were measured by using liquid chromatography-tandem mass spectrometry to determine long-term exposure to ETS. The difference between neonatal nicotine concentrations in the smoker and nonsmoker groups was not statistically significant. However, in the indoor-smoker group, neonatal nicotine concentrations were significantly higher than in the outdoor and nonsmoker groups (P < 0.05). Furthermore, neonatal nicotine concentrations in the outdoor-smoker group were not different from those in the nonsmoker group. These findings indicate that paternal smoking inside the home leads to significant fetal and maternal exposure to ETS and may subsequently affect fetal health. Conversely, findings show that paternal smoking outside the home prevents the mother and her fetus from being exposed to ETS.     

Effect of maternal age, smoking and deprivation on birthweight

Low birthweight is often used as a health indicator. This paper reports the findings of a cohort study, which were analysed to determine the relationship, if any, between the age of the mother and birthweight given the mother's smoking habits and the level of social deprivation of the mother's place of residence. The data used were extracted from those data routinely collected by the Information and Statistics Division of the National Health Service, Scotland. Information on 178,801 singleton live births occurring between 1992 and 1994 was used in the analysis. The factors considered were those available directly from the official records. The level of social deprivation was measured using Carstairs index based on the postcode sector. Although younger and older mothers have lighter babies, on average, it was found that this effect can be largely explained by differences in the smoking habits and level of deprivation of the mothers. Birthweight, adjusted for gestational age, sex of the baby and parity of the mother, was significantly lower for babies born to mothers who smoked during pregnancy. It is clear, however, that the detrimental effect of smoking increases with the age of the mother. Although adjusted birthweight was lower for those in areas of high deprivation, this effect is small compared with the effect of smoking. Any attempt to decrease the percentage of low-birthweight babies must focus on reducing the percentage of mothers who smoke.     

Measures of maternal tobacco exposure and infant birth weight at term

This study was undertaken to determine the relation between self-reported number of cigarettes smoked per day and urine cotinine concentration during pregnancy and to examine the relations between these two measures of tobacco exposure and birth weight. Data were obtained from the Smoking Cessation in Pregnancy project, conducted between 1987 and 1991. Cigarette smoking information and urine cotinine concentration were collected for 3,395 self-reported smokers who were receiving prenatal care at public clinics in three US states (Colorado, Maryland, and Missouri) and who delivered term infants. General linear models were used to quantify urine cotinine variability explained by the number of cigarettes smoked per day and to generate mean adjusted birth weights for women with different levels of tobacco exposure. Self-reported number of cigarettes smoked per day explained only 13.9% of the variability in urine cotinine concentration. Birth weight declined as tobacco exposure increased; however, the relation was not linear. The sharpest declines in birth weight occurred at low levels of exposure. Furthermore, urine cotinine concentration did not explain more variability in birth weight than did number of cigarettes smoked. These findings should be considered by researchers studying the effects of smoking reduction on birth outcomes.     

Passive and active maternal smoking as measured by serum cotinine: the effect on birthweight.

To determine how maternal exposure to environmental tobacco smoke affects birthweight, maternal sera obtained from 3529 pregnant women around 27 weeks gestation were analyzed for cotinine, a metabolite of nicotine. Based on cotinine levels, nonsmokers were divided into those exposed to environmental tobacco smoke (2-10 ng/mL) and those unexposed (< 2 ng/mL), and smokers were divided into tertiles. Compared with unexposed nonsmokers' infants, infants of exposed nonsmokers averaged 45 g less (P = .28) after adjustment for confounders, and smokers' infants averaged 78, 191, and 233 g less for the first, second, and third cotinine tertiles, respectively. Birthweight decreased 1 g for every nanogram per milliliter of cotinine increase (P < .001).     

Maternal exposure to ambient PM2.5 and term low birthweight in the State of Georgia

A growing body of evidence suggests that ambient air pollution could be associated with low birthweight (LBW). In this study, we examined pregnancy exposure to ambient PM_2.5 and the risk of LBW in the State of Georgia. The study population consisted of 48,172 full-term live births between 1 January 2004 and 31 December 2004 in nine counties of Georgia, which was obtained from the national natality dataset. County-level air quality index data obtained from the U.S. Environmental Protection Agency was used to estimate exposure to ambient levels of PM_2.5. Multivariate logistic regression revealed that infants with maternal exposure to PM_2.5 falling within 75 to < 95th percentiles were at increased risk of LBW (OR: 1.36; 95 % CI: 1.03, 1.79), after adjusting for potential confounders. This study provided more evidence on the role of PM_2.5 in LBW. Reducing exposure for pregnant women would be necessary to improve the health of infants.     

Paternal smoking and birthweight in Shanghai.

OBJECTIVES. Although maternal active smoking has been established to be associated with fetal growth retardation, evidence of an effect of environmental tobacco smoke exposure on birthweight is still limited and inconclusive. This study addressed the relationship between prenatal environmental tobacco smoke exposure and birthweight and fetal growth retardation in Shanghai, China. METHODS. Data on 1785 full-term live-born normal infants of nonsmoking mothers were used from the Shanghai Birth Defects and Perinatal Death Monitoring conducted between October 1986 and September 1987. Environmental tobacco smoke exposure was defined as exposure to paternal smoking. RESULTS. Infants with environmental tobacco smoking exposure were, on average, 30 g lower in birthweight than nonexposed infants, after adjustment for gestational age, parity, maternal age, and occupation. CONCLUSION. Consistent with previous research, this study suggests that environmental tobacco smoking exposure may have a modestly adverse effect on birthweight.     

Influence of maternal active and passive smoking during pregnancy on birthweight in newborns

Many studies have documented a strong association of active smoking during pregnancy with fetal growth retardation. Increasing interest has also been focused on whether there is an association between exposure of pregnant women to environmental tobacco smoke (ETS) and low birthweight of their babies. In the intervention controlled study "Healthy Pregnancy--Healthy Child", mothers after delivery were interviewed by medical students who collected data about their smoking and nutrition. Students were also trained to stimulate non-smoking behaviour and to explain the risks related to smoking and exposure to ETS. Data from 1147 mothers after delivery were collected but only single births were included in the analysis of birthweight. In our study, 63.4% women never smoked and 32.2% women reported they had stopped smoking either before pregnancy or during the first trimester. Only 4.4% of mothers (n = 50) smoked during the whole pregnancy. Women with the history of smoking were exposed to ETS more often than mothers who never smoked (51.6% vs 17.4%; p < 0.001). The number of heavily exposed both at home and workplaces was more than twice higher among former smokers compared with never smokers (22.4% versus 9.4%, p < 0.01). The average birthweight of babies born to women who had stopped smoking was higher than that born to never smokers. The average birthweight of babies born to women who smoked during pregnancy was lower by 119 g and 171 g than that of the babies born to never smokers and former smokers, respectively. When pre-term neonates were excluded, differences in birthweight between babies born to never smokers and either formerly smoking or still smoking mothers were slightly lower. The greatest effect of ETS exposure on birthweight was recorded in never smoking mothers; an average reduction in birthweight was 88 g. A strong dose-effect was observed; in mothers heavily exposed to ETS both at home and at work, the babies' birthweight was lower by 189 g in comparison with the group of non-exposed, never smoking mothers and even by 70 g compared with mothers smoking during pregnancy.     

The effect of maternal smoking on the relationship between maternal and fetal zinc status and infant birth weight.

We have previously reported a trapping of zinc in the placenta directly related to circulating cadmium that comes from cigarette smoke. The purpose of this study was to examine in detail the effect of smoking on (a) the relationship between maternal and fetal zinc status and (b) the relationship between zinc status and birth weight. One hundred and eighteen smokers and 172 nonsmokers without any medical complications during pregnancy were studied. Atomic absorption spectroscopy was used to assess zinc status in maternal and cord vein plasma and red blood cells. Plasma alkaline phosphatase was also determined as an index of zinc status. Thiocyanate was used as an index of smoking status. The data were analyzed using univariate correlations and repeated measures analysis of variance. Infants of smokers had a statistically significant decrease in plasma zinc (5%), alkaline phosphatase (13%), and in cord vein RBC zinc (12%). Furthermore, the results showed an altered relationship between maternal and fetal indices of zinc status and zinc status and birth weight due to maternal smoking. The infant of the nonsmoking mother appears to be able to maintain adequate zinc status due to depletion of maternal zinc. However, it appears that the infant of the smoking mother may be marginally zinc deficient. These findings support studies of zinc supplementation in the pregnancy complicated by smoking.     

Children's exposure to smoking.

Exposure to smoking and the attitudes of other people have, in many studies, been associated with an increase in smoking through childhood and adolescence. Previous studies which have examined the relative influence of parents, siblings and friends on young people smoking do not show the same pattern of results, indicating that parents and siblings who smoke may or may not have an influence above or beyond that of friends. In this study, the extent to which these sources of exposure influence young people is examined. A related hypothesis which is tested in this study is that the amount of exposure to smoking may be a factor which influences young people to smoke independent of the particular source of the influence. The pattern of results suggests that the source of the influence is more important than the extent of influence among friends and family members. In particular, the influence of friends' smoking was evident at ages 9 to 15 years to the exclusion of the parental example of smoking. Parental smokers may lead their children to try smoking but it seems unlikely that this is related to them smoking at a later age. While peer influence may result in smoking, the influence of parents or older people smoking may be becoming a disincentive in this time of changing attitudes to smoking.     

The effects of maternal smoking on fetal and infant mortality

Although maternal cigarette smoking has been shown to reduce the birth weight of an infant, previous findings on the relation between smoking and fetal and infant mortality have been inconsistent. This study used the largest data base ever available (360,000 birth, 2,500 fetal death, and 3,800 infant death certificates for Missouri residents during 1979-1983) to assess the impact of smoking on fetal and infant mortality. Multiple logistic regression was used to estimate the joint effects of maternal smoking, age, parity, education, marital status, and race on total mortality (infant plus fetal deaths). Compared with nonsmoking women having their first birth, women who smoked less than one pack of cigarettes per day had a 25% greater risk of mortality, and those who smoked one or more packs per day had a 56% greater risk. Among women having their second or higher birth, smokers experienced 30% greater mortality than nonsmokers, but there was no difference by amount smoked. The prevalence of smoking in this population was 30%. It was estimated that if all pregnant women stopped smoking, the number of fetal and infant deaths would be reduced by approximately 10%. The higher rate of mortality among blacks compared with whites could not be attributed to differences in smoking or the other four maternal characteristics studied. In fact, the black-white difference was greater among low-risk women (e.g., married multiparas aged 20 and over with high education) than among high-risk women (e.g., unmarried teenagers with low education).     

Acute effect of maternal smoking on fetal blood circulation

The authors examined the acute effects of cigarette smoking on maternal and fetal cardiovascular system in 22 healthy voluntary pregnant smoker women. All examined patients were chronic cigarette smokers who smoked more than 5 cigarettes per day before and during pregnancy. All of the pregnancies subsequently had normal outcomes. Maternal heart rate, and blood pressure, fetal heart rate, resistance indices of fetal descending aorta, those of umbilical artery, middle cerebral artery and uterine artery were measured immediately before and after cigarette smoking. It was found that smoking was associated with increase in maternal and fetal heart rate and an increase in umbilical artery resistance indices was also observed. These changes might be considered as a reaction improving fetal oxygen supply.     

Declining maternal smoking prevalence did not change low birthweight prevalence in Massachusetts from 1989 to 2004

Background: Maternal smoking is associated with low birthweight(LBW). LBW prevalence is increasing in the US. However, it isunclear whether a fall in maternal smoking has any impact onthe LBW prevalence in Massachusetts, a state with a comprehensivetobacco control program since 1993. Methods: Temporal patternsin prenatal maternal smoking and in LBW prevalence were quantifiedbetween 1989 and 2004, using Massachusetts Community HealthInformation Profile database. Yearly population-attributable-risk(PAR %) of singleton LBW live-births among pregnant smokingmothers were estimated based on a summary relative risk. Theexpected number of LBW babies attributable to reductions inmaternal smoking in 2004 relative to 1989 was compared to theactual number of LBW babies in 2004. Results: Of 88 929 and74 554 singleton live-births, 4297 and 4004 LBW births occurredin 1989 and 2004, respectively. Between 1989 and 2004, maternalsmoking prevalence significantly declined yearly by 6% (from19.9% to 6.8%) but overall LBW prevalence increased yearly by<1% (from 4.8% to 5.4%), with a significant yearly increase(<1%) in moderately LBW (1500–2499 g) prevalence. YearlyPAR % declined from 20.3% (n = 872) to 8.0% (n = 320), withan expected total of 3745 [4297 – (872 – 320)] LBWbabies in 2004 relative to 1989. However, actual LBW babiesnumbered 4004 in 2004. The 259 above predicted (4004 –3745) LBW babies born in 2004 being attributed to factors otherthan prenatal maternal smoking. Conclusions: Massachusetts experienceda decline in prenatal maternal smoking prevalence, but an increasein moderately LBW prevalence has offset the potential gainsapparently achieved due to reductions in maternal smoking prevalence.     

Impact of maternal seafood diet on fetal exposure to mercury, selenium, and lead.

Umbilical cord blood from 1,023 consecutive births in the Faroe Islands showed a median blood-mercury concentration of 121 nmol/l (24.2 micrograms/l); 250 of those samples (25.1%) had blood-mercury concentrations that exceeded 200 nmol/l (40 micrograms/l). Maternal hair mercury concentrations showed a median of 22.5 nmol/g (4.5 micrograms/g), and 130 samples (12.7%) contained concentrations that exceeded 50 nmol/g (10 micrograms/g). Frequent ingestion of whale meat dinners during pregnancy and, to a much lesser degree, frequent consumption of fish, and increased parity or age were associated with high mercury concentrations in cord blood and hair. Blood-mercury levels were slightly lower if the mother had occasionally ingested alcoholic beverages. Mercury in blood correlated moderately with blood selenium (median, 1.40 mumol/l). Increased selenium concentrations were associated with intake of whale meat, alcohol abstention, delivery after term, and high parity. Lead in cord blood was low (median, 82 nmol/l), particularly if the mothers had frequently had fish for dinner and had abstained from smoking.     

Very low birthweight in African American infants: the role of maternal exposure to interpersonal racial discrimination

OBJECTIVES: We determined whether African American women's lifetime exposure to interpersonal racial discrimination is associated with pregnancy outcomes. METHODS: We performed a case-control study among 104 African American women who delivered very low birthweight (<1500 g) preterm (<37 weeks) infants and 208 African American women who delivered non-low-birthweight (>2500 g) term infants in Chicago, Ill. RESULTS: The unadjusted and adjusted odds ratio of very low birthweight infants for maternal lifetime exposure to interpersonal racism in 3 or more domains equaled 3.2 (95% confidence intervals=1.5, 6.6) and 2.6 (1.2, 5.3), respectively. This association tended to persist across maternal sociodemographic, biomedical, and behavioral characteristics. CONCLUSIONS: The lifelong accumulated experiences of racial discrimination by African American women constitute an independent risk factor for preterm delivery.     

The effects on fetal development of high alpha-fetoprotein and maternal smoking

OBJECTIVES: This study determined the risk of impaired fetal growth resulting from the interaction between maternal smoking during pregnancy and unexplained elevated concentrations of maternal serum alpha-fetoprotein (MSAFP). METHODS: This observational study involved 123 pregnant smokers with unexplained second-trimester elevated concentrations of MSAFP, 827 smokers with normal levels, and 471 nonsmokers with raised levels. RESULTS: By logistic regression, coincident smoking and elevated MSAFP levels were found to be associated with increases in the low basic risks of prematurity, small-for-gestational-age births, low birthweight, and need for neonatal care. CONCLUSIONS: Maternal smoking has an adverse effect on fetal development in pregnancies with unexplained elevated MSAFP concentrations. Such pregnancies merit close surveillance.