Cryptorchidism and maternal alcohol consumption during pregnancy

BACKGROUND: Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys. METHODS: We examined 2,496 boys in a prospective Danish-Finnish birth cohort study for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and at 3 months of age (33/2,215). Quantitative information on alcohol consumption (average weekly consumption of wine, beer, and spirits and number of binge episodes), smoking, and caffeine intake was obtained by questionnaire and/or interview once during the third trimester of pregnancy, before the outcome of the pregnancy was known. For a subgroup (n = 465), information on alcohol consumption was obtained twice during pregnancy by interviews. RESULTS: We investigated maternal alcohol consumption both as a continuous variable and categorized. The odds for cryptorchidism increased with increasing weekly alcohol consumption. After adjustment for confounders (country, smoking, caffeine intake, binge episodes, social class, maternal age, parity, maturity, and birth weight) the odds remained significant for women with a weekly consumption of five or more alcoholic drinks (odds ratio = 3.10; 95% confidence interval, 1.05-9.10). CONCLUSIONS: Regular alcohol intake during pregnancy appears to increase the risk of congenital cryptorchidism in boys. The mechanisms for this association are unknown. Counseling of pregnant women with regard to alcohol consumption should also consider this new finding.     

First-trimester maternal alcohol consumption and the risk of infant oral clefts in Norway: a population-based case-control study

Although alcohol is a recognized teratogen, evidence is limited on alcohol intake and oral cleft risk. The authors examined the association between maternal alcohol consumption and oral clefts in a national, population-based case-control study of infants born in 1996-2001 in Norway. Participants were 377 infants with cleft lip with or without cleft palate, 196 with cleft palate only, and 763 controls. Mothers reported first-trimester alcohol consumption in self-administered questionnaires completed within a few months after delivery. Logistic regression was used to calculate odds ratios and 95% confidence intervals, adjusting for confounders. Compared with nondrinkers, women who reported binge-level drinking (>or=5 drinks per sitting) were more likely to have an infant with cleft lip with or without cleft palate (odds ratio = 2.2, 95% confidence interval: 1.1, 4.2) and cleft palate only (odds ratio = 2.6, 95% confidence interval: 1.2, 5.6). Odds ratios were higher among women who binged on three or more occasions: odds ratio = 3.2 for cleft lip with or without cleft palate (95% confidence interval: 1.0, 10.2) and odds ratio = 3.0 for cleft palate only (95% confidence interval: 0.7, 13.0). Maternal binge-level drinking may increase the risk of infant clefts.     

Moderate maternal and paternal alcohol consumption and the risk of spontaneous abortion.

Maternal alcoholism can lead to the fetal alcohol syndrome in offspring, but the effect of more moderate alcohol consumption during pregnancy remains an issue of concern. Therefore, we analyzed data from a large case-control study of spontaneous abortion (626 cases, 1,300 controls) that ascertained maternal alcohol consumption before and during pregnancy, as well as paternal consumption. Asking when in pregnancy alcohol consumption changed allowed us to calculate a weighted average of the amount consumed weekly during the first trimester. The odds ratio for consumption of seven or more drinks per week was 1.9 [95% confidence interval (CI) = 1.1-3.4] when adjusted for maternal smoking, passive smoking, and maternal age. Data were too sparse to examine higher consumption levels. There was some evidence that cases may have had less opportunity than controls to decrease consumption during their shorter pregnancies, potentially biasing the odds ratio upward. The adjusted odds ratio for any paternal alcohol consumption was 1.2 (CI = 0.93-1.5), with no dose-response effect seen. Among pregnancies in which the mother did not drink, there was no association with paternal drinking.     

Association of Xenobiotic Metabolizing Enzymes Genetic Polymorphisms With Esophageal Cancer in Kashmir Valley and Influence of Environmental Factors

The Kashmir Valley has an elevated incidence rate of esophageal cancer (EC). Several environmental and genetic factors have been suspected for development of EC. A case-control study was performed in 135 EC patients and 195 healthy controls to analyze association of polymorphisms in glutathione S-transferase (GST) mu (GSTM1), GST theta (GSTT1), GST pi (GSTP1), GSTM3, Cytochrome P450 (CYP)1A1, and CYP2E1 genes with susceptibility to EC as well as their interaction with environmental factors such as smoking and high consumption of salted tea in Kashmir valley. All subjects were genotyped through polymerase chain reaction restriction fragment length polymorphism. Data was statistically analyzed using the chi-square test and logistic regression model. Results showed that GSTP1313 val/val and CYP2E1c1c2 genotypes imparted risk for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma [EADC; odds ratio (OR) = 3.24, 95% confidence interval (CI) = 1.30–8.05; OR = 4.20, 95% CI = 1.65–10.70], respectively. GSTM3AB genotype/B allele was found to be associated with low risk for EC. Tobacco smoking through hukka (water pipe) and consumption of salted tea itself were high risk factors for developing EC (OR = 21.44, 95% CI = 11.63–39.54; OR = 14.86, 95% CI = 8.41–26.24), and the risks were modulated through the interaction of GSTM3AB, GSTP1val/val genotypes. In conclusion, GSTP1val/val and CYP2E1c1c2 genotypes/c2 allele increased the risk of ESCC and EADC, respectively, in the Kashmiri population; whereas GSTM3AB genotype imparted lower risk for both ESCC and EADC.     

Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms.

We conducted a population-based case-control study of childhood acute lymphoblastic leukemia (ALL) to evaluate the risk posed by reported exposure to pesticides used in and around the home. We compared 491 cases 0-9 years of age to as many controls. We also conducted a case-only study on a subsample of 123 cases to evaluate gene-environment interaction between child genotype and maternal exposure during pregnancy as well as child exposure after birth. We used the polymerase chain reaction (PCR) approach to analyze polymorphisms in CYP1A1, CYP2D6, GSTT1, and GSTM1 genes, which encode enzymes involved in carcinogen metabolism. Indoor use of some insecticides by the owners and pesticide use in the garden and on interior plants, in particular frequent prenatal use, was associated with increased risks up to severalfold in magnitude. Interaction odds ratios were increased among carriers of the CYP1A1m1 and CYP1a1m2 mutations when mother during pregnancy or the child had been exposed to certain indoor insecticides. No such effects were observed in the presence of other tested polymorphisms.     

Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking

BACKGROUND: Little is known about the role of xenobiotic-metabolizing gene variants as risk factors for small-for-gestational-age (SGA) births or as modifiers for the effects of exposures such as maternal smoking. METHODS: We conducted 2 joint studies: a case-control design including 493 cases (birth weight below the 10th percentile according to gestational age and sex) and 472 controls (at or above the 10th percentile) and a family-based study (mother, father, and newborn) with approximately 250 case trios and a similar number of control trios. Logistic regression and a log-linear model were used to analyze the association between genetic variants such as CYP1A1*2A, CYP1A1*2B, CYP1A1*4, GSTT1, GSTM1, and XRCC3 and SGA. The interaction between genetic variants and maternal smoking was also studied. RESULTS: The odds ratio (OR) for the association of complete maternal GSTT1 deletion with SGA was 0.63 (95% confidence interval = 0.41-0.97), and that for the complete newborn GSTM1 deletion was 0.74 (0.55-0.98). Newborns with the partial GSTT1 deletion had an OR of 1.40 (1.01-1.95), and newborns homozygous for CYP1A1*2A had an OR of 4.28 (1.02-18.0). These results were coherent with the trio-based results. Significant interactions were observed between maternal smoking in the third trimester and CYP1A1*2A (P = 0.03), XRCC3 (P = 0.03), and newborn GSTT1 (P = 0.01). CONCLUSIONS: Certain genetic variants involved in the metabolism of xenobiotics increase the risk of SGA, as well as modify the effects of maternal smoking by increasing or decreasing its risk.     

Metabolic gene polymorphisms and risk of dysmenorrhea

We conducted a molecular epidemiologic study in rural China to investigate the association of the cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase Mu (GSTM1) polymorphisms with dysmenorrhea. This report includes 435 subjects, 129 with and 306 without any history of dysmenorrhea, who did not smoke or drink alcohol. We obtained information on dysmenorrhea and major covariates by questionnaire interview. We used categorical methods and logistic regression models to evaluate the individual and combined associations of CYP2D6 and GSTM1 polymorphisms with dysmenorrhea and its subgroups, occasional (N = 70) and recurrent (N = 59), with adjustment for age, education, occupation, passive smoke exposure, age of menarche, parity, contraceptive method, height, and body mass index. Both variant CYP2D6 and GSTM1 genotypes were associated with increased risk of recurrent dysmenorrhea [for CYP2D6, odds ratio (OR) = 1.7 and 95% confidence interval (95% CI) = 0.9-3.1; for GSTM1, OR = 1.8 and 95% CI = 1.0-3.4). There was no appreciable association between these variant genotypes and occasional dysmenorrhea. When both the CYP2D6 and GSTM1 genotypes were considered together, the highest risk of recurrent dysmenorrhea was found among women with variant genotypes in both CYP2D6 and GSTM1 (OR = 3.1; 95% CI = 1.2-8.0). This study provides evidence of genetic susceptibility to recurrent dysmenorrhea.     

Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic oral clefting: a gene-environment interaction

The importance of maternal smoking in the pathogenesis of oral facial clefts is not clear. Susceptibility to cigarette smoke depends on biotransformation of the toxic compounds by mother and embryo. In a population-based case-control study, we investigated the effects of maternal smoking during the first pregnancy trimester and the interaction with polymorphisms in the biotransformation enzymes cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase theta 1-1 (GSTT1) on the risk of nonsyndromic oral clefting in the offspring. We recruited 113 infants with nonsyndromic oral clefts and their mothers, as well as 104 control infants and their mothers. Maternal smoking habits were collected regarding the period 3 months before through 3 months after conception. Buccal swabs were taken from mothers and infants for genetic analysis. Maternal smoking was not strongly associated with oral clefting (odds ratio = 1.1; 95% confidence interval = 0.6-2.2), nor were CYP1A1 and GSTT1 polymorphisms. Mothers who smoked and carried the GSTT1-null genotype, however, had an increased risk for having a child with oral clefting compared with nonsmokers with the wild type genotype (odds ratio = 3.2; 95% confidence interval = 0.9-11.6). The risk was almost five times greater (odds ratio = 4.9; 95% confidence interval = 0.7-36.9) in mothers and infants both having the GSTT1-null genotype compared with both having the wild genotype. There was no interaction between CYP1A1 and maternal smoking in relation to oral clefting.     

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany.

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the children's parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While the association with maternal use of oral contraceptives or sex hormones was strong for stages I/II (odds ratio 4.5, 95% confidence interval 1.2-16.5), the associations with shorter gestation duration (odds ratio 3.4, 95% confidence interval 1.7-6.7) as well as maternal alcohol consumption during pregnancy (>7 glasses/week odds ratio 5.2, 95% confidence interval 1.3-20.6) were observed only for the unfavourable advanced stages. It is notable that the associations in our study were either observed only for the advanced stages of disease or only for the less advanced stages, but not for both subgroups. This adds to evidence for the hypothesis that neuroblastoma consists of at least two distinct disease entities, which differ in clinical stage at the time of diagnosis.     

CYP1A1, cigarette smoking, and colon and rectal cancer

Cytochrome P-450 (CYP) is involved in the activation and metabolism of polycyclic aromatic hydrocarbons in tobacco products. The authors evaluated the association of two polymorphisms in the CYP1A1 gene--the noncoding Msp I polymorphism in the 3'-untranslated region and the Ile462Val polymorphism in exon 7--with colon and rectal cancer. The authors used data from two incident case-control studies of colon cancer (1,026 cases and 1,185 controls) and rectal cancer (820 cases and 1,036 controls) conducted in California and Utah (1991-2002). CYP1A1 genotype was not associated with colon or rectal cancer. Having GSTM1 present, a CYP1A1 variant allele, and the rapid-acetylator NAT2 imputed phenotype was associated with increased risk of colon cancer (odds ratio = 1.7, 95% confidence interval: 1.2, 2.3). Among men, the greatest colon cancer risk was observed for having any CYP1A1 variant allele and currently smoking (odds ratio = 2.5, 95% confidence interval: 1.3, 4.8; Wald chi(2)test: p < 0.01). Assessment of GSTM1 and CYP1A1 and rectal cancer in men showed a twofold elevation in risk for more than 20 pack-years of smoking, except among those with GSTM1 present who had a variant CYP1A1 allele. These data support the association between smoking and colon and rectal cancer. Smoking may have a greater impact on colorectal cancer risk based on CYP1A1 genotype; this might further be modified by GSTM1 for rectal cancer risk.     

A case-control study of pesticides and fetal death due to congenital anomalies

We examined the association between late fetal death due to congenital anomalies (73 cases, 611 controls) and maternal residential proximity to pesticide applications in ten California counties. A statewide database of all applications of restricted pesticides was linked to maternal address to determine daily exposure status. We examined five pesticide chemical classes. The odds ratios from logistic regression models, adjusted for maternal age and county, showed a consistent pattern with respect to timing of exposure; the largest risks for fetal death due to congenital anomalies were from pesticide exposure during the 3rd-8th weeks of pregnancy. For exposure either in the square mile of the maternal residence or in one of the adjacent 8 square miles, odds ratios ranged from 1.4 (95% confidence interval = 0.8-2.4) for phosphates, carbamates, and endocrine disruptors to 2.2 (95% confidence interval = 1.3-3.9) for halogenated hydrocarbons. Similar odds ratios were observed when a more restrictive definition of nonexposure (not exposed to any of the five pesticide classes during the 3rd-8th weeks of pregnancy) was used. The odds ratios for all pesticide classes increased when exposure occurred within the same square mile of maternal residence.     

Early intrauterine exposure to tobacco-inhaled products and obesity

An association between maternal smoking during pregnancy and offspring obesity has been reported. This study assessed the impact of maternal smoking during the first trimester. Data on 4,974 German children aged 5-6 years were obtained at school entry health examinations in 2001-2002 in Bavaria. Obesity was defined by body mass index using International Obesity Task Force cutpoints. Prevalence of obesity was 1.9% (95% confidence interval (CI): 1.5, 2.4) in offspring of never smokers, 4.5% (95% CI: 2.9, 6.7) for maternal smoking during the first trimester only, and 5.9% (95% CI: 3.8, 8.7) for maternal smoking throughout pregnancy. Unadjusted odds ratios were higher for maternal smoking throughout pregnancy (odds ratio = 3.23, 95% CI: 2.00, 5.21) compared with the first trimester only (odds ratio = 2.41, 95% CI: 1.49, 3.91). Adjusted odds ratios were similar: 1.70 (95% CI: 1.02, 2.87) for maternal smoking throughout pregnancy and 2.22 (95% CI: 1.33, 3.69) for maternal smoking in the first trimester only. When modeled together, no statistically significant difference in obesity risk was found between maternal smoking in the first trimester compared with throughout pregnancy. The effect of intrauterine tobacco exposure on childhood obesity may depend largely on cigarette smoking during the first trimester, whereas the additional impact of smoking throughout pregnancy might be due to confounding by sociodemographics. Women should be encouraged to quit smoking prior to conception.     

Effect of maternal smoking and coffee consumption on the risk of having a recognized Down syndrome pregnancy

To evaluate the possible effects of maternal smoking and caffeine or coffee consumption on the occurrence of a recognized pregnancy with Down syndrome, the authors analyzed data from a case-control study of 997 liveborn infants or fetuses with Down syndrome ascertained in California from 1991 to 1993 and 1,007 liveborn controls without a birth defect. Interviews with mothers covered demographic information, pregnancy, and medical history, with detailed questions on the use of tobacco, alcohol, and caffeinated beverages. All analyses were age-adjusted. High alcohol consumption (> or =4 drinks/week) in the first month of pregnancy was associated with reduced risk for a recognized Down syndrome conceptus (odds ratio (OR) = 0.54; 95% confidence interval (CI): 0.34, 0.85). Maternal smoking during the periconceptional period was not associated with risk of recognized Down syndrome (OR = 1.04; 95% CI: 0.79, 1.37), but maternal consumption of four or more cups of coffee per day was inversely associated (OR = 0.63; 95% CI: 0.41, 0.96). In multivariate analysis, a significant interaction between coffee drinking and smoking was observed. The inverse association remained only for nonsmoking mothers who drank four or more cups of coffee per day (OR = 0.48; 95% CI: 0.28, 0.82). These results suggest that among nonsmoking mothers, high coffee consumption is more likely to reduce the viability of a Down syndrome conceptus than that of a normal conceptus.     

Interaction of soy food and tea consumption with CYP19A1 genetic polymorphisms in the development of endometrial cancer

Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997-2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (p(interaction) < 0.05) but not by soy isoflavone intake. The authors' findings suggest that tea polyphenols may modify the effect of CYP19A1 genetic polymorphisms on the development of endometrial cancer.     

Maternal smoking during pregnancy and limb reduction malformations in Sweden.

OBJECTIVE: This study was undertaken to investigate a possible connection between different types of limb reduction defects and maternal smoking during pregnancy. METHODS: With the use of the Swedish health registries, 610 cases of limb reduction malformations were selected from among 1 109 299 infants born between 1983 and 1993 with known smoking exposure in early pregnancy. Confounders such as maternal age and parity were controlled for with the use of the Mantel-Haenszel technique. RESULTS: The odds ratio for any maternal smoking among all cases of limb reductions was 1.26 (95% confidence interval = 1.06, 1.50). The main subgroups of limb reduction defects showed similar odds ratios, but in longitudinal reduction defect, only unilateral cases showed an association with maternal smoking. CONCLUSIONS: This study supports an association between maternal smoking and limb reduction malformations, but further work is needed before a causal inference can be made.     

Maternal occupational exposure to extremely low frequency magnetic fields during pregnancy and childhood leukemia

BACKGROUND: Pregnancy is a target period for events that could induce childhood leukemia. There has been little attention to possible effects of maternal occupational exposure to extremely low frequency magnetic fields (ELF-MF) during pregnancy. METHODS: We conducted a population-based, case-control study of 491 incident cases of acute lymphoblastic leukemia in children 0-9 years of age, matched on age and sex to 491 healthy controls. Cases were diagnosed in the Province of Québec between 1980 and 1993. Mothers were interviewed to obtain detailed prenatal occupational history; individual exposure to ELF-MF was estimated based on a method we recently developed. We used 3 metrics for analyzing exposure: cumulative, average and maximum levels. Analyses were carried out among all study women and among working women only. RESULTS: Comparing the highest 10% of exposed mothers to the others, the risk of leukemia among offspring was moderately increased by using any metric, in all women and among working women only. The highest odds ratio of 2.5 (95% confidence interval = 1.2-5.0) was found for maximum exposure attained in an occupation (>/=0.4 microtesla). CONCLUSIONS: Our results are compatible with an increased risk of childhood leukemia among children whose mothers were exposed to the highest occupational levels of ELF-MF during pregnancy.     

Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study

The authors investigated a possible association of supplemental folic acid and multivitamin use with placental abruption by using data on 280,127 singleton deliveries recorded in 1999-2004 in the population-based Medical Birth Registry of Norway. Odds ratios, adjusted for maternal age, marital status, parity, smoking, pregestational diabetes, and chronic hypertension, were estimated with generalized estimating equations for logistic regression models. Use of folic acid and/or multivitamin supplements before or any time during pregnancy was reported for 36.4% of the abruptions (0.38% of deliveries) and 44.4% of the nonabruptions. Compared with no use, any supplement use was associated with a 26% risk reduction of placental abruption (adjusted odds ratio = 0.74, 95% confidence interval: 0.65, 0.84). Women who had taken folic acid alone had an adjusted odds ratio of 0.81 (95% confidence interval: 0.68, 0.98) for abruption, whereas multivitamin users had an adjusted odds ratio of 0.72 (95% confidence interval: 0.57, 0.91), relative to supplement nonusers. The strongest risk reduction was found for those who had taken both folic acid and multivitamin supplements (adjusted odds ratio = 0.68, 95% confidence interval: 0.56, 0.83). These data suggest that folic acid and other vitamin supplementation during pregnancy may be associated with reduced risk of placental abruption.     

Parental occupational exposure to pesticides and childhood germ-cell tumors

In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring.     

Alcohol consumption during pregnancy and the risk of early stillbirth among singletons

The purpose of this study is to investigate the association between maternal alcohol intake in pregnancy and the occurrence of early stillbirth using a retrospective cohort analysis of singleton births in Missouri that occurred in the period 1989 through 1997 (N=655,979). We used Cox proportional hazards regression to generate adjusted risk estimates for total, early, and late stillbirth associated with maternal alcohol intake and used the Robust Sandwich Estimator to adjust for intracluster correlations among sibships. Overall, a total of 3,508 counts of stillbirth were identified, yielding a stillbirth rate of 5.3 per 1,000. Among mothers who consumed alcohol during pregnancy, the stillbirth rate was 8.3 per 1,000. Mothers who consumed alcohol while pregnant were 40% more likely to experience stillbirth as compared with nondrinking mothers (adjusted hazards ratio=1.4, 95% confidence interval: 1.2-1.7). A dose-response relationship was evident; mothers who consumed five or more drinks per week during pregnancy experienced a 70% elevated risk of stillbirth compared with nondrinking mothers (adjusted hazards ratio=1.7; 95% confidence interval: 1.0-3.0). The risk of early stillbirth was 80% higher among drinking mothers compared with abstainers (adjusted hazards ratio=1.8; 95% confidence interval: 1.3-2.3). The elevated risks for both early and late stillbirth did not reach statistical significance when broken down by level of alcohol intake. In conclusion, maternal drinking during pregnancy is associated with an increased risk of early stillbirth. These findings underscore the need to reinforce current counseling strategies toward pregnant women and women who intend to conceive on the detrimental effects of alcohol use in pregnancy.     

Does selenium reduce the risk of threatened preterm delivery associated with placental cytochrome P450-1A1 activity?

Selenium (Se), an essential trace element in human nutrition, is thought to have an important role in the prevention of oxygen damage by organic hydroperoxides generated by oxidative metabolism. Epidemiological studies have shown an association between placental cytochrome P450-1A1 (CYP1) activity and threatened preterm delivery (TPD), and other experimental studies have shown alterations in fetal development with CYP1 activity or toxicity. The present study examined the possible protective effect of selenium on the potential toxicity of maternal exposure to polycyclic aromatic hydrocarbons (PAHs) on the normal course of pregnancy. Placental CYP1 activity was used as a risk factor resulting from maternal exposure to PAHs. TPD occurrence was used as a general indicator of troubles in the normal course of pregnancy. A group of TPD patients and a group of controls were selected from 178 pregnant women attending obstetrical care in a maternity hospital. Selenium concentrations in maternal plasma were lower in the TPD group: 63.7 ng/ml (CI 95% confidence bounds = 43.6-82.2) vs 69.2 ng/ml (CI 95% confidence bounds = 49. 3-96.3) (t test, P<0.01). When placental CYP1 was induced, an association between TPD and selenium was found, with an increase of 10 ng/ml for the latter. An adjusted odds ratio of 0.55 (CI 95% confidence bounds = 0.34-0.88; chi(2), P<0.01) was estimated. When placental CYP1 was not activated, the odds ratio was estimated at 0.99 (CI 95% confidence bounds=0.95-1.03; NS). This epidemiologic finding suggests that antioxidant Se status may be a protective factor against the potential toxic effect of PAHs on the normal course of pregnancy. The downward trend that we observed supports the hypothesis that the one-electron pathway metabolism of PAHs may explain a large fraction of TPD and some preterm deliveries.