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Parental alcohol consumption before and during pregnancy has been linked to adverse outcomes in the offspring including leukemogenesis. We, therefore, aimed to systematically assess and quantitatively synthesize published data on the association of paternal consumption during preconception and maternal consumption during pregnancy with leukemia risk in childhood (0-14 years). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed (until February 2016) and the reference lists of the relevant studies. Observational studies examining the association between parental alcohol consumption and childhood leukemia were considered eligible. Data extracted from 39 case-control studies (over 16 000 leukemia cases and 30 000 controls) were pooled and summary-effect estimates were calculated. Subgroup analyses were carried out by main acute leukemia type [lymphoblastic or myeloid), cytogenetics/genetic polymorphisms, and specific alcohol beverages. We found a statistically significant dose-response association of any level of maternal alcohol consumption compared with nondrinking during pregnancy exclusively with acute myeloid leukemia (AML) [odds ratio (OR)moderate consumption: 1.64, 95% confidence intervals (CIs): 1.23-2.17 and ORhigh consumption: 2.36, 95% CI: 1.60-3.49]. In contrast, no association of paternal preconception consumption with any leukemia type was noted. In beverage-specific analyses, only a positive association of maternal wine drinking with childhood AML was found, which was more pronounced in analyses including only studies on infant leukemia (ORwine: 2.12, 95% CI: 1.16-3.90). The largest ever meta-analysis shows a sizeable, statistically significant dose-response association of maternal alcohol consumption during index pregnancy with AML risk. Future research exploring the role of genetic polymorphisms is anticipated to shed light on the underlying pathophysiology.

Background: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype., Methods: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child's age, sex, ethnicity, parental education, and study center., Results: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78-0.92) for vitamin use and 0.80 (0.71-0.89) for folic acid use. The reduced risk was more pronounced in children whose parents' education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75-1.14) and 0.68 (0.48-0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester)., Conclusions: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.

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.

Background: The relationship between thrombophilic polymorphisms and intrauterine growth restriction remains unclear. Whereas a subset of these polymorphisms have received some attention, others have not., Methods: We conducted a case-control study of 493 cases of intrauterine growth restriction (birthweight less than the 10th percentile for gestational age and sex) and 472 controls (greater than the 10th percentile). We also conducted a family study including approximately 250 case trios (affected newborn, mother, and father) for each studied gene. Plasminogen activator inhibitor-1(PAI-1) 4G/5G and Factor XIII Val134Leu variants were compared between maternal and newborn cases and controls. Relative risks for newborn and maternal PAI-1 and Factor XIII genotypes in case trios were estimated using a log-linear model. Transmission of MTHFR C677T and 1298C haplotypes was analyzed in case trios, and the estimated haplotype distribution compared between cases and controls. Finally, we explored pairwise gene-gene interactions between all measured polymorphisms, including Factor V Leiden G1691A and Prothrombin G20210A., Results: PAI-1 and Factor XIII polymorphisms were not associated with an increased risk of intrauterine growth restriction in the case-control analysis, and the case-parent analysis showed no newborn or maternal excess genotype relative risk. No excess transmission of the MTHFR haplotypes was observed in case newborns, and the distribution of MTHFR haplotypes was similar between cases and controls. Some results were suggestive of interactions between genes., Conclusions: Overall, there seems to be little or no indication that thrombophilic genes, at least individually, have an effect on intrauterine growth restriction.

Objective: Most developed countries have medical surveillance programs for some of the workers (typically miners) exposed to silica, but the impact of these programs is not documented., Methods: Clinical data from 1388 compensated silicotic workers in Quebec, Canada, were used. The severity of disease at compensation was compared between workers in the surveillance program and those who were not., Results: Predicted vital capacity at less than 80% at compensation was less likely among workers under surveillance than among those who were not (odds ratio = 0.59; 95% confidence interval 0.44-0.80); the occurrence of a radiological image with large opacities and profusion of category 1/1 or more was also less likely in the group with surveillance (odds ratio = 0.60; 95% CI = 0.39-0.92)., Conclusions: The data indicate a benefit from medical surveillance but alternative explanations are discussed.

A model for childhood leukemia proposes that characteristic chromosomal translocations can arise in utero and that for most cases a second hit occurring postnatally will be necessary. Possible causal mechanisms for leukemias are environmental factors such as ionizing radiation from x rays and inherited susceptibility from polymorphisms in DNA repair genes. We performed a case-control study of childhood acute lymphoblastic leukemia measuring reported postnatal x rays in 701 cases aged 0-14 y and in as many population-based controls matched on age and sex. In addition we performed a case-only study in 207 cases to evaluate the interaction between x ray exposure and polymorphisms in DNA repair genes. There was an increase in risk of leukemia with number of x rays: the adjusted odds ratio for two or more x rays vs. none was 1.48 (95% confidence interval: 1.11-1.97). That risk was slightly higher among girls (odds ratio = 1.67). A polymorphism in the APE gene (ex 5) involved in the base excision repair system was suggestive of an increased risk among boys and a reduced risk among girls. HMLH1 (ex 8), a mismatch repair gene, was associated with reduction of risk among girls. Results from the genetic data are still preliminary and must be interpreted with caution especially because of the relatively small number of genotyped cases. However, ionizing radiation from x rays as well as polymorphisms in DNA repair genes are plausible risk factors for childhood leukemia and should be studied more.

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.

Background: Limited information is available on the association of parental consumption of alcohol prior to and during pregnancy with the risk of childhood leukemia, as well as for the potentially modifying role of genetic polymorphisms., Methods: We conducted a population-based, case-control study of 491 incident cases of acute lymphoblastic leukemia age 0-9 years and matched on age and sex to 491 healthy controls. Cases were identified at tertiary care centers in the Province of Québec between 1980 and 1993. Each parent was interviewed separately about alcohol consumption habits. We also used a case-only design with 186 cases to estimate interaction odds ratios between prenatal exposure and child DNA variants in the GSTM1 and CYP2E1 genes., Results: The adjusted odds ratio for any maternal consumption during pregnancy was 0.7 (95% confidence interval = 0.5-0.9). The interaction odds ratios for the GSTM1 null genotype during third pregnancy trimester was 2.4 (95% confidence interval = 1.1-5.4); the interaction odds ratio for CYP2E1 variant G-1295C (or allele *5) during the nursing period was 4.9 (95% confidence interval = 1.5-16.7)., Conclusions: The observed association with maternal alcohol consumption during pregnancy could be due to the potential chemopreventive effects of flavonoids found in wine and beer. These possible effects of alcohol may be at least partially genetically determined, although data are preliminary.

Objective: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL., Data Sources: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field., Study Selection: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal., Data Extraction: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers., Data Synthesis: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL., Conclusion: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.

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.

The relation between past induced abortions and subsequent fetal loss is still unclear. We report a case-control study with 331 cases of first spontaneous abortion and 993 controls with no previous spontaneous abortion and a normal pregnancy at the same period of pregnancy. In comparison with primigravid women, the odds ratio for a fetal loss in the current one was 1.41 [95% confidence interval (CI) = 0.81-2.43] among women with one previous pregnancy ending in induced abortion, 4.43 (95% CI = 1.46-13.36) among those with two previous induced abortions out of two pregnancies, and 1.35 (95% CI = 0.64-2.82) among women with three or more previous pregnancies ending in one or more induced abortions.

Some studies indicate that children born to younger mothers are at higher risk for wheezing or asthma. I conducted a case-control study that included 457 new cases of asthma in 3- and 4-year-old children and an equal number of controls. I found that, in comparison with children of mothers 30 years of age or older, children of mothers age 26-30 years had an adjusted odd ratio (OR) of 1.16 [95% confidence interval (CI) = 0.73-1.85] of developing asthma; children of mothers between 21 and 25 years of age had an OR of 1.25 (95% CI = 0.76-2.07), and those whose mothers were 20 years of age or younger had an OR of 3.48 (95% CI = 1.08-11.22).

Data collected during postnatal visits were used to study the risk of low birth weight (LBW) among unmarried women living alone and among unmarried women living with a partner or another adult, using married women living with their husbands as the reference group. Information on 1,627 singleton live births was included in a binomial regression, controlling for seven potential confounding variables: mother's age, education, gestational weight gain, parity, smoking status, and presence of medical problems preceding or during pregnancy. Unmarried women living alone were at greater risk of bearing a LBW infant than married women living with their husbands (RR = 2.0, 95% Cl = 1.2-3.4). Unmarried women living with a partner had a slightly lower risk of LBW than married women (RR = 0.6, 95% Cl = 0.3-1.3) and unmarried women living with another adult had a slightly increased risk (RR = 1.3, 95% Cl = 0.6-3.0), although neither of these results was statistically significant. On the basis of these findings, we suggest that public health interventions should target women according to their household structure rather than their marital status.

Emergency portacaval shunt for variceal bleeding is associated with a high operative mortality, particularly if used as a last resort. Because of this, a strong case has been made against emergency shunt. This report describes an experience with emergency portacaval shunt for the treatment of variceal bleeding when used systematically after hemodynamic stabilization and control of the bleeding episode with balloon tamponade, if necessary, in patients with mild or moderate liver disease. The population studied comprised 62 consecutive patients who rebled from varices while participating in a controlled trial of propranolol for the prevention of rebleeding. Of the 62 patients, nine died of massive hemorrhage and 53 survived the hemorrhage. Of the 53 survivors, 11 had severe liver disease and were not considered for shunt surgery. Of the remaining 42 patients with mild or moderate liver disease, 36 had emergency central portacaval shunt. The interval between endoscopic diagnosis of variceal bleeding and surgery averaged 19 +/- 3 hours (mean +/- SE). The operative mortality rate, defined as in-hospital mortality, was 19%. One- and 2-year survival rates were 78% and 71%, respectively. The incidence of postoperative hepatic encephalopathy was 36%; all patients responded favorably to protein restriction and lactulose. Thus, under specific conditions, emergency portacaval shunt results in an acceptable long-term survival rate. In patients with mild or moderate liver disease, emergency portacaval shunt should be considered when other forms of treatment for the prevention of variceal rebleeding have failed.