Maternal dietary intake of vitamin A and risk of orofacial clefts: a population-based case-control study in Norway

A population-based case-control study was carried out in Norway between 1996 and 2001. The aim was to evaluate the association between maternal intake of vitamin A from diet and supplements and risk of having a baby with an orofacial cleft. Data on maternal dietary intake were available from 535 cases (188 with cleft palate only and 347 with cleft lip with or without cleft palate) and 693 controls. The adjusted odds ratio for isolated cleft palate only was 0.47 (95% confidence interval: 0.24, 0.94) when comparing the fourth and first quartiles of maternal intake of total vitamin A. In contrast, there was no appreciable association of total vitamin A with isolated cleft lip with or without cleft palate. An intake of vitamin A above the 95th percentile was associated with a lower estimated risk of all isolated clefts compared with the 40th-60th percentile (adjusted odds ratio = 0.48, 95% confidence interval: 0.20, 1.14). Maternal intake of vitamin A is associated with reduced risk of cleft palate only, and there is no evidence of increased risk of clefts among women in our study with the highest 5% of vitamin A intake.     

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.     

Genetic variants in IRF6 and the risk of facial clefts: single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway

Mutations in the gene encoding interferon regulatory factor 6 (IRF6) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996-2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the 'a'-allele at rs4844880 had an increased risk of having a child with CL/P (RR=1.85, 95% confidence interval: 1.04-3.25; P=0.036). An RR of 0.38 (95% confidence interval: 0.16-0.92; P=0.031) was obtained when the child carried a single-dose of the 'a'-allele at rs2235371 (the p.V274I polymorphism). The P-value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test (P=0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population.     

Risk factors for oral clefts: a population-based case-control study in Shenyang, China

Shenyang in Northern China has one of the highest reported prevalence rates of oral clefts in the world. To explore the risk factors for oral clefts in Shenyang, we carried out a population-based case-control study. A total of 360 990 births in 2000 to 2007 were screened for oral clefts; the overall prevalence was 1.76 per 1000. The ratio of cleft lip with or without cleft palate (CL ± P) : cleft palate only (CP) was 5.60:1. The overall male : female ratio was 2.02:1. CLP and CL were more common in males than in females with a sex ratio (SR) of 2.88:1 and 1.86:1 respectively, whereas CP was more common in females with an SR of 0.71:1.
Using a multivariable conditional logistic regression model, 586 oral clefts cases were compared with 1172 control mothers. Maternal factors significantly associated with increased risk for oral clefts were history of a fever or cold (adjusted OR 2.34, 95% CI 1.06, 5.60); use of analgesic and antipyretic drugs (adjusted OR 3.10, 95% CI 1.41, 6.86); poor ventilation during heating (adjusted OR 2.25, 95% CI 1.10, 4.60); and consumption of pickled vegetables >6 per week (adjusted OR 3.86, 95% CI 1.11, 13.47) during pregnancy. Factors which appeared to be protective were meat consumption ≥4 times per week (adjusted OR 0.43, 95% CI 0.28, 0.67); and legume consumption >6 times per week (adjusted OR 0.60, 95% CI 0.41, 0.89). Differences in risk were found between the two most common phenotypes, CL ± P and CP only. Most of the environmental factors had stronger associations with risk for CL ± P rather than CP, whereas history of oral clefts, as well as legume consumption, were more strongly associated with the risk for CP than for CL ± P. The findings suggest that aetiological heterogeneity may exist between CL ± P and CP.     

Maternal employment status and isolated orofacial clefts in Hungary

AIMS: To study the role of maternal employment status as indicator of socioeconomic status in the origin of isolated orofacial clefts (OFC) and in the use of periconceptional folic acid/multivitamin supplementation. METHODS: 1,975 cases with OFC (1,374 cases with cleft lip +/- palate and 601 cases with posterior cleft palate), 38,151 population controls without any defects and 20,868 patient controls with other isolated defects were compared in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996. RESULTS: The proportion of professionals and managerials was lower, while the proportion of unskilled workers, housewives and others was higher in the mothers of cases with OFC compared with the population control group. However, the comparison of OFC and patient control groups did not show any difference in the employment status of mothers. A lower level of folic acid supplementation occurred in the professional and skilled worker mothers of cases with OFC compared with the population control group. This difference was confirmed by the comparison of folic acid used by mothers of cases with OFC compared with patient controls. An infrequent multivitamin use was displayed in the studied groups. CONCLUSIONS: The prevalence of OFC at birth shows a slightly lower maternal employment status as indicator of socioeconomic status than in the population control group. The higher level of maternal education does not imply a higher rate of folic acid supplementation in the group of OFC.     

A population-based case-control study of occupation and renal cell carcinoma risk in Iowa

A case-control study involving 406 incident cases and 2,434 controls was conducted in Iowa to examine the association between occupational exposures and renal cell carcinoma risk. After adjusting for major confounders, an increased risk was observed for men among mechanics and repairers (odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.2-2.9); assemblers (OR 2.5, 95% CI = 0.8-7.6); automotive dealership and service station employees (OR 1.9, 95% CI = 0.9-3.9); wholesale traders of durable goods (OR 1.5, 95% CI = 0.7-3.2); farm product vendors (OR 4.4, 95% CI = 1.3-15.5); service organization managers (OR 2.2, 95% CI = 1.0-5.1); financial specialists (OR 2.7, 95% CI = 1.0-7.6); sales occupation supervisors (OR 1.8, 95% CI = 1.0-3.3); guards (OR 5.4, 95% CI = 1.4-20.7); and general farm workers (OR 1.9, 95% CI = 1.0-3.7). Among women, an increased risk was found for employees in depository institutions (OR 3.6, 95% CI = 1.1-11.3); colleges and universities (OR 7.6-95% CI = 2.3-25.6); and retail, including those in grocery stores (OR 2.2, 95% CI = 1.0-4.7). Our results indicate that occupational exposures may increase the risk of renal cell carcinoma.     

Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: a large population-based pooling study

Using individual participant data from six population-based case–control studies, we conducted pooled analyses to examine maternal alcohol consumption and the risk of clefts among >4600 infants with cleft lip only, cleft lip with cleft palate, or cleft palate only and >10,000 unaffected controls. We examined two first-trimester alcohol measures: average number of drinks/sitting and maximum number of drinks/sitting, with five studies contributing to each analysis. Study-specific odds ratios (ORs) were estimated using logistic regression and pooled to generate adjusted summary ORs. Across studies, 0.9–3.2 % of control mothers reported drinking an average of 5+ drinks/sitting, while 1.4–23.5 % reported drinking a maximum of 5+ drinks/sitting. Compared with non-drinkers, mothers who drank an average of 5+ drinks/sitting were more likely to deliver an infant with cleft lip only (pooled OR 1.48; 95 % confidence intervals 1.01, 2.18). The estimate was higher among women who drank at this level 3+ times (pooled OR 1.95; 1.23, 3.11). Ever drinking a maximum of 5+ drinks/sitting and non-binge drinking were not associated with cleft risk. Repeated heavy maternal alcohol consumption was associated with an increased risk of cleft lip only in offspring. There was little evidence of increased risk for other cleft types or alcohol measures.     

A population-based case-control study of isolated congenital cataract

BACKGROUND: To detect the possible etiological factors in the origin of isolated congenital cataracts. METHOD: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contained 111 cases with isolated congenital cataract and their 111 matched control pairs without defect, 22744 patient controls with other non-ocular abnormalities and 37837 population controls without any defects. Exposure data and family history were based on (i) medical records, (ii) retrospective maternal information and (iii) information obtained by regional nurses at home visit of nonrespondent families. RESULTS: Positive family history indicated autosomal dominant origin in 9,9% of the cases. Rubella infections occurred more frequently in case mothers than in control mothers before the vaccination against rubella virus. A higher prevalence of influenza/common cold (55.9% in the case and 18.5% in the population control group, adjusted OR with 95% CI: 5.8, 4.0-8.4 and 21.7% in the malformation control group: 4.7, 3.2-6.9) and acute infectious diseases of respiratory system (26.1% in the case and 9.1% in the population control group: 3.8, 2.5-5.8 and 9.3% in the malformation control group: 3.4, 2.2-5.3) related with fever was found during the pregnancy of the case mothers. In addition the higher risk of isolated congenital cataract was prevented by antifever therapy. CONCLUSIONS: Some part of isolated congenital cataract is preventable by rubella vaccination and probably by influenza vaccination in the epidemic period, in addition it is worth using an effective antifever therapy of fever related respiratory diseases to restrict the teratogenic risk of fever.     

Sinonasal cancer and occupation: a multicenter case-control study

A case-control study was conducted to examine occupational risk factors for sinonasal cancer. 207 cases and 409 controls (323 cancer hospital controls and 86 controls selected from lists provided by the cases) were included in the study. All cases and controls were interviewed by specially trained physicians. Detailed information on occupational history was collected, in addition to other potential risk factors for nasal cancer. Results are presented for two histologic types: adenocarcinoma and squamous cell carcinoma. Among males, the risk of adenocarcinoma was significantly elevated for carpenter and joiners (OR = 17.7) and other woodworkers (OR = 26.9). A significant increase in risk of squamous cell cancer (OR = 2.5) and a moderate increase in risk of adenocarcinoma (OR = 1.7; NS) were noted for construction workers. Among females, an excess risk of squamous cell carcinoma was associated with employment in textile industry (OR = 2.9). Elevated risks of squamous cell cancer were observed for farm workers of both sexes (males: OR = 2.2; females OR = 4.9).     

Maternal occupation and congenital heart defects: a case-control study

Summary This paper reports a Swedish analysis of the possible effect of maternal occupation on the occurrence of congenital heart defects. The analysis included 3324 infants (1108 cases and 2216 controls) born during the period 1982–1986. Information on maternal occupation was retrieved using two sources: the 1985 census and the Medical Birth Registry. A comparison between these two sources using the information on mothers of 756 infants born in 1986 showed a good concordance although 11% of the women were reported with a different employment status. No association appeared between the type of maternal occupation and the occurrence of infant congenital heart defects although some odds ratios were slightly above 1.     

Melanoma and occupation: results of a case-control study.

OBJECTIVES: Associations between occupational exposures and the occurrence of cutaneous melanoma were examined as part of a large population based case-control study of 19 cancer sites. METHODS: Cases were men aged 35 to 70 years old, resident in Montreal, Canada, with a new histologically confirmed cutaneous melanoma (n = 103). There were two control groups, a randomly selected population control group (n = 533), and a cancer control group (n = 533) randomly selected from among subjects with other types of cancer in the large study. Odds ratios for the occurrence of melanoma were calculated for each exposure circumstance for which there were more than four exposed cases (85 substances, 13 occupations, and 20 industries) adjusting for age, ethnicity, and number of years of schooling. RESULTS: Significantly increased risk of melanoma was found for exposure to four substances (fabric dust, plastic dust, trichloroethylene, and a group containing paints used on surfaces other than metal and varnishes used on surfaces other than wood), three occupations (warehouse clerks, salesmen, and miners and quarrymen), and two industries (clothing and non-metallic mineral products). CONCLUSIONS: Most of the occupational circumstances examined were not associated with melanoma, nor is there any strong evidence from previous research that any of those are risk factors. For the few occupational circumstances which were associated in our data with melanoma, the statistical evidence was weak, and there is little or no supporting evidence in the scientific literature. On the whole, there is no persuasive evidence of occupational risk factors for melanoma, but the studies have been too small or have involved too much misclassification of exposure for this conclusion to be definitive.     

Maternal cigarette smoking and oral clefts: a population-based study.

Analyses of 1984 data from the Maryland Birth Defects Reporting and Information System indicate that mothers of infants with oral clefts (cleft lip with or without cleft palate; and cleft palate) smoked more during pregnancy than mothers of infants with other defects (odds ratio OR of 2.56 and 2.39, respectively). There was a dose-response relation between the daily amount smoked and the risk of clefting. Adjustment for available confounding variables did not account for the association between smoking and oral clefts.     

Occupation and asthma: a population-based incident case-control study

The authors assessed the relations between occupation and risk of developing asthma in adulthood in a 1997-2000 population-based incident case-control study of 521 cases and 932 controls in south Finland. The occupations were classified according to potential exposure to asthma-causing inhalants. Asthma risk was increased consistently for both men and women in the chemical (adjusted odds ratio (OR) = 5.69, 95% confidence interval (CI): 1.08, 29.8), rubber and plastic (OR = 2.61, 95% CI: 0.92, 7.42), and wood and paper (OR = 1.72, 95% CI: 0.71, 4.17) industries. Risk in relation to occupation was increased only for men-for bakers and food processors (OR = 8.62, 95% CI: 0.86, 86.5), textile workers (OR = 4.70, 95% CI: 0.29, 77.1), electrical and electronic production workers (OR = 2.83, 95% CI: 0.82, 6.93), laboratory technicians (OR = 1.66, 95% CI: 0.17, 16.6), and storage workers (OR = 1.57, 95% CI: 0.40, 6.19). Of the predominantly men's occupations, metal (OR = 4.52, 95% CI: 2.35, 8.70) and forestry (OR = 6.00, 95% CI: 0.96, 37.5) work were the strongest determinants of asthma. For women, asthma risk increased for waiters (OR = 3.03, 95% CI: 1.10, 8.31), cleaners (OR = 1.42, 95% CI: 0.81, 2.48), and dental workers (OR = 4.74, 95% CI: 0.48, 46.5). Results suggest an increased asthma risk both in traditional industries and forestry and in several nonindustrial occupations.     

Infertility and breast cancer: a population-based case-control study

To investigate whether a history of infertility affects a woman's risk of developing breast cancer, the authors analyzed case-control data collected between 1980 and 1982 as part of the Cancer and Steroid Hormone Study. The 4,730 cases were women aged 20-54 years with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women randomly selected from the general population of these same eight areas. After controlling for age, age at first birth, and parity, the odds ratio (OR) for breast cancer associated with infertility was 1.01 (95% confidence interval (CI) 0.89-1.15) among gravid women. Controlling for age, the odds ratio was 0.82 (95% CI 0.59-1.14) among nulligravid women. Women who reported that the reason for their infertility was a problem with their ovaries had a risk similar to that for women without a history of infertility (OR = 0.75, 95% CI 0.48-1.24). Women whose physicians reported that the reason for their infertility was anovulation or Stein-Leventhal syndrome also had risks similar to those for women without a history of infertility (OR = 1.26 (95% CI 0.67-2.34) and OR = 1.13 (95% CI 0.46-2.78), respectively). Menopausal status, age at menarche, history of spontaneous abortions, drinking or smoking behavior, use of exogenous hormones, or family history of breast cancer did not appreciably alter the observed odds ratios. If infertility has an effect on breast cancer that is independent of age at first birth, then the effect is small.     

Parent's age and the risk of oral clefts

BACKGROUND: Some malformations are clearly associated with older maternal age, but the effect of older age of the father is less certain. The aim of this study is to determine the degree to which maternal age and paternal age independently influence the risk of having a child with oral clefts. METHODS: Among the 1,489,014 live births in Denmark during 1973-1996, there were 1920 children with nonsyndromic cleft lip with or without cleft palate and 956 children with nonsyndromic cleft palate. We used logistic regression to assess the impact of parental age on the occurrence of cleft lip with or without cleft palate and cleft palate. Interaction between mother's and father's age was included in the analysis. RESULTS: Separate analyses of mother's and father's age showed that older age was associated with increased risk of both cleft lip with or without cleft palate and cleft palate only. In a joint analysis, both maternal and paternal ages were associated with the risk of cleft lip with or without cleft palate, but the contribution of each was dependent on the age of the other parent. In the analysis of cleft palate only, the effect of maternal age disappeared, leaving only paternal age as a risk factor. CONCLUSION: Both high maternal age and high paternal age were associated with cleft lip with or without cleft palate. Higher paternal age but not maternal age increased the risk of cleft palate only.     

Oral and pharyngeal cancer and occupation: a case-control study.

We studied the relation between occupation and oral and pharyngeal cancer with a population-based case-control study conducted in four areas of the United States. The study group included 1,114 incident male and female cases and 1,268 frequency-matched controls. After adjustment for age, race, smoking, alcohol, and study location, an analysis of lifetime occupational histories revealed a small number of noteworthy associations. Risk was increased among male carpet installers (23 cases, 4 controls), with an adjusted odds ratio of 7.7 [95% confidence interval (CI) = 2.4-24.9], and tended to rise with longer duration of employment. A decreased risk was found among male and female textile mill workers (odds ratio 0.48, 95% CI = 0.27-0.88). Previously reported increases in oral cancer risks among printing workers, electrical and electronics workers, and workers other than carpet installers who were possibly exposed to formaldehyde were not found in this study. For several employment groups, including male machinists, primary metal industry workers, petroleum industry workers, painters, furniture and fixture industry workers, woodworking machine operators, and workers with inferred exposure to fossil fuel combustion, odds ratios were approximately 2.0 for cancers of pharyngeal sites.     

Familial ovarian cancer: a population-based case-control study

Data from a multicenter population-based case-control study were analyzed to assess the degree of aggregation of ovarian cancer in families. Included as cases were 493 women aged 20-54 who had been newly diagnosed with epithelial ovarian cancer. The frequency with which cases reported a family history of ovarian cancer was compared with the frequency for a group of 2,465 controls selected by random digit dialing. The odds ratios for ovarian cancer in first- and second-degree relatives were 3.6 (95% confidence interval (Cl) 1.8-7.1) and 2.9 (95% Cl 1.6-5.3), respectively, compared with women with no family history of ovarian cancer. The null hypothesis of no association was excluded on both the maternal and paternal sides of the families studied. Ovarian cancer in relatives was reported by women with malignant lesions but not by women with borderline lesions. These results did not seem to be attributable to the possible confounding effects of any of several covariates or to errors in reporting family history of ovarian cancer.