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Biomedical subjects

M M Werler

Publications and source records attributed to M M Werler.

34 records · Page 2Linked to original sources
PubMed1993

Periconceptional folic acid exposure and risk of occurrent neural tube defects.

OBJECTIVES: A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs. DESIGN: Case-control study. SETTING: Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario. PARTICIPANTS: Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations. MAIN OUTCOME MEASURES: The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls. RESULTS: The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid-NTD hypothesis and were excluded from further analysis. For daily use of a multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake (P for trend = .02). CONCLUSION: These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk.

Case-Control Studies↗
PubMed1992

Demographic, reproductive, medical, and environmental factors in relation to gastroschisis.

To identify risk factors for gastroschisis other than drug use in pregnancy, an analysis of data collected in a case-control surveillance program of birth defects (1976-1990) was conducted. Drug use is considered in Werler et al., Teratology, 45:361-367, 1992. Maternal demographic, reproductive, and medical factors, and first trimester environmental exposures, were compared between 76 gastroschisis cases and 2,581 malformed controls. A strong inverse association was found for maternal age: relative to women 30 years or older, relative risks for 25-29, 20-24, and less than 20-year-old women were 1.7, 5.4, and 16, respectively. Multivariate relative risks (and 95% confidence intervals) for alcohol use were as follows: for 1-5 drinks per week, 1.6 (0.7-3.4); for greater than or equal to 6 drinks per week, 2.5 (0.9-6.8); for a maximum of 1-4 drinks at any one time, 0.8 (0.4-1.6); and for a maximum of greater than or equal to 5 drinks, 2.8 (1.2-6.5). With the effect of age taken into account, no associations were identified for cigarette smoking, consumption of caffeinated or decaffeinated coffee, unplanned pregnancy, 12 or less years of education, or a parity of two or more. Other medical and reproductive factors, including weight gain, vaginal bleeding, nausea or vomiting, influenza, "other" infection, and history of spontaneous abortion or elective abortion did not increase the risk.

Abdominal Muscles↗
PubMed1992

First trimester maternal medication use in relation to gastroschisis.

In a case-control surveillance program, first trimester medication use was studied in relation to gastroschisis. There were 76 cases of gastroschisis which were compared with 2,142 controls with other major malformations. For pseudoephedrine use, we found a significantly elevated relative risk of 3.2 (95% confidence interval, 1.3-7.7), with adjustment for confounding. Multivariate relative risks for analgesic/antipyretics and another decongestant were as follows: salicylates, 1.6 (0.9-2.7); acetaminophen, 1.7 (1.0-2.9); ibuprofen, 1.3 (0.4-3.7); and phenylpropanolamine, 1.5 (0.4-5.4). No increases in risk were identified for use of antihistamines, antibiotics, oral contraceptives, or spermicides. Because salicylates, pseudoephedrine, and phenylpropanolamine are vasoactive, the elevated risks for these drugs support the hypothesis of vascular disruption in the etiology of gastroschisis. We therefore examined maternal use of vasoactive medications in relation to a second case group of 416 infants with hetereogeneous defects suspected to have a vascular etiology. Relative risks for salicylates, ibuprofen, pseudoephedrine, phenylpropanolamine, and other decongestants approximated unity. These positive associations must be considered tentative. They have not been reported previously and should be confirmed independently. Also, acetaminophen, which may be taken for the same indications as salicylates and decongestants, but is not thought to be vasoactive, was associated with gastroschisis, suggesting that identified associations may be due to an underlying maternal illness.

Abdominal Muscles↗
PubMed1991

Maternal alcohol use in relation to selected birth defects.

The hypothesis that maternal alcohol consumption affects the development of structures possibly derived from a common embryonic cell population, the cranial neural crest, was explored using data collected by a case-control surveillance program of birth defects in greater Boston, Philadelphia, and Toronto, Ontario, Canada, and in five counties in Iowa from 1983 through 1987. Maximum and average alcohol consumption during the first four lunar months of pregnancy were compared between the mothers of 1,464 infants with malformations of the ear, face, anterior neck, and upper heart (cranial neural crest cases) and 1,427 infants with other malformations (controls). For maximum number of drinks in a day and average number of drinking days per week, relative risks approximated unity across levels of exposure. For average number of drinks per drinking day, the relative risk (and 95% confidence interval) for heavy intake (5 or more drinks) was 1.8 (0.8-4.4). When the largest defect subgroup of cases, infants with cleft lip with or without cleft palate, was considered separately, the relative risk for an average of 5 or more drinks per drinking day was 3.0 (1.1-8.5). These findings suggest that maternal alcohol use is less related to overall malformations derived from cranial neural crest cell than to one specific defect among them--cleft lip with or without cleft palate. However, the latter association has not been reported previously in humans and remains to be confirmed in other studies.

Abnormalities, Drug-Induced↗
PubMed1990

Maternal vitamin A supplementation in relation to selected birth defects.

High doses of vitamin A cause birth defects in animals. Concern over vitamin A teratogenicity in humans has been prompted by reports of teratogenic effects of the vitamin A analogue, isotretinoin. The pattern of defects observed among isotretinoin- and vitamin A-exposed infants and animals suggests a possible mechanism involving cranial neural crest cell activity. Data from a case-control study were used to assess maternal use of vitamin A supplements alone and vitamin A-containing multivitamin supplements in relation to the occurrence of certain birth defects involving structures derived, at least in part, from cranial neural crest cells. Cases were 2,658 infants with such defects (primarily craniofacial and cardiac malformations). Controls were 2,609 infants with other malformations. Vitamin A supplementation was defined as daily use for at least 7 days of retinol alone or with vitamin D, or of fish oils. Information on vitamin A dose and nutrition was not available. The mothers of six controls used vitamin A supplements in each of the first three lunar months of pregnancy in comparison to the mothers of 15, 14, and 10 cases in lunar months 1, 2, and 3, respectively. Relative risk estimates and 95% confidence intervals were 2.5(1.0-6.2) for lunar month 1, 2.3(0.9-5.8) for lunar month 2, and 1.6(0.6-4.5) for lunar month 3. These findings should be considered tentative because no dose information was available, small numbers of cases and controls were exposed to vitamin A supplements, and relative risk estimates were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1990

Diazepam use in relation to breast cancer: results from two case-control studies.

The relation between diazepam use and breast cancer was explored in two case-control studies. The first (1981-1987) was a hospital-based study in the United States of 3,078 cases of breast cancer, 1,259 controls with other malignancies, and 672 controls with nonmalignant conditions. The relative risk estimates for regular diazepam use (at least 4 days per week for at least 6 months) that antedated the diagnosis of breast cancer by at least 12 months were 1.0 (95% confidence interval (CI) 0.6-1.7) using the cancer controls and 0.8 (95% CI 0.4-1.8) using the noncancer controls. Risk factors for breast cancer were taken into account in the estimates. There was no association for regular use lasting at least 5 years or for regular use that took place exclusively in the recent or more distant past. The second study (1982-1986), conducted in Toronto, Ontario, Canada, was community-based, and included 607 cases of breast cancer and 1,214 neighbor controls selected from municipal voting and census records. After control of confounding, the relative risk estimate for regular diazepam use was 0.8 (95% CI 0.5-1.3). Again, there was no association for long-term, past, or recent regular use. The results of both studies suggest that regular diazepam use does not increase the risk of breast cancer. The findings are strengthened by the similarity of the results using three different control groups--women with cancer, women with nonmalignant conditions, and neighbors.

Adolescent↗
PubMed1990

Maternal cigarette smoking during pregnancy in relation to oral clefts.

Studies on maternal smoking in relation to oral cleft defects have yielded inconsistent findings, with results ranging from no association to sixfold increases in risk. The authors examined this relation in a case-control study conducted in Boston, Massachusetts, Philadelphia, Pennsylvania, Toronto, Ontario, Canada, and the state of Iowa during the years 1983-1987, in which mothers of malformed infants were interviewed within 6 months after delivery about prenatal events and exposures. Maternal cigarette smoking during pregnancy for 400 infants with cleft lip with or without cleft palate and for 215 infants with cleft palate alone was compared with that for 2,710 infants with other malformations (controls). Relative risks (and 95% confidence intervals) were estimated for smokers of 1-14, 15-24, and greater than or equal to 25 cigarettes per day relative to never smokers; the respective estimates for cleft lip with or without cleft palate were 1.2 (95% confidence interval (CI) 0.9-1.6), 1.4 (95% CI 1.0-2.1), and 0.7 (95% CI 0.3-1.6), and for cleft palate alone, estimates were 1.0 (95% CI 0.7-1.5), 0.9 (95% CI 0.5-1.5), and 0.8 (95% CI 0.3-2.2). Relative risks were also close to unity for case subgroups divided according to the presence or absence of an associated malformation. Multivariate control of several potential confounders did not alter these estimates. Based on this large series of cases, maternal smoking during pregnancy does not appear to increase the risk of oral clefts.

Canada↗
PubMed1989

The relation of aspirin use during the first trimester of pregnancy to congenital cardiac defects.

It has been hypothesized that the ingestion of aspirin by women during pregnancy increases their infants' risk of certain congenital heart defects. Using data from a large program of case-control surveillance of congenital malformations, we evaluated this hypothesis. The case groups were made up of infants with any structural cardiac defect (n = 1381) and five selected cardiac defects (the subgroups were not mutually exclusive): aortic stenosis (n = 43), coarctation of the aorta (n = 123), hypoplastic left ventricle (n = 98), transposition of the great arteries (n = 210), and conotruncal defects (n = 791). First-trimester aspirin use among the mothers of these infants was compared with that among the mothers of a control group of infants with other malformations (n = 6966). The prevalence of any maternal aspirin use was similar for cases (25 to 33 percent) and controls (27 percent). The relative risks (and 95 percent confidence interval) among infants whose mothers were aspirin users as compared with those whose mothers did not use aspirin, adjusted for potential confounding factors, were 0.9 (0.8 to 1.1) for any cardiac defect, 1.2 (0.6 to 2.3) for aortic stenosis, 1.0 (0.6 to 1.4) for coarctation, 0.9 (0.6 to 1.4) for hypoplastic left ventricle, 0.9 (0.6 to 1.2) for transposition of the great arteries, and 1.0 (0.8 to 1.2) for conotruncal defects. Furthermore, no dose-effect pattern was identified. The findings of this study indicate that aspirin use during the first trimester of pregnancy does not increase the risk of congenital heart defects in relation to that of other structural malformations.

Abnormalities, Drug-Induced↗
PubMed1989

Reporting accuracy among mothers of malformed and nonmalformed infants.

The potential for recall bias in case-control studies is a common concern. The authors assessed whether recall bias was present in exposure information reported at postpartum interview by mothers of malformed and nonmalformed infants who delivered at Brigham and Women's Hospital, Boston, during 1984. Accuracy of exposure reporting was measured by comparing interview data with exposure information documented during pregnancy in obstetric records. The authors' measure of recall bias, relative sensitivity (RS), is the ratio of exposure-reporting accuracy for mothers of malformed infants to that of mothers of nonmalformed infants. Relative sensitivity estimates that are greater than 1.0 indicate that mothers of malformed infants are more accurate reporters than mothers of nonmalformed infants. Relative sensitivity was estimated for eight exposure factors: antibiotic or antifungal drug use (RS = 1.2), urinary tract or yeast infection (RS = 2.7), history of infertility (RS = 1.4), use of birth control after conception (RS = 7.6), elective abortion history (RS = 1.1), any over-the-counter drug use (RS = 1.0), spotting or bleeding (RS = 1.2), and nausea or vomiting (RS = 0.8) These data suggest the presence of recall bias for some exposure factors. The authors advise the use of malformed controls to reduce potential recall bias in case-control studies of selected malformations and many etiologic factors.

Abortion, Induced↗
PubMed1989

The risks of cancers of the colon and rectum in relation to coffee consumption.

To assess whether recent coffee consumption is related to the incidence of large bowel cancer, the authors analyzed data from a multipurpose hospital-based case-control study of several cancers, conducted from 1978 to 1986 in Boston, Massachusetts, New York, New York, Philadelphia, Pennsylvania, and Baltimore, Maryland: 717 cases of colon cancer and 538 cases of rectal cancer were compared with 3,883 controls admitted for nonmalignant and malignant illnesses unrelated to coffee use. Relative risks were estimated by multiple logistic regression with allowance for age, sex, cigarette smoking, alcohol consumption, and several other potential confounding factors. Overall, relative to the consumption of one cup of coffee per day, the estimated relative risk of colon cancer for consumption of up to four cups per day in the period before admission was close to 1.0; for consumption of five or more cups per day, it was 0.6 (95% confidence interval 0.4-0.8). The results were consistent in men and women, and similar results were obtained whether the measure of consumption was use in the year before admission or use three years before admission. For rectal cancer, some relative risk estimates were elevated, particularly in men, but there was no consistent pattern of association, nor was there a trend of increasing risk with increasing consumption. The data suggest that recent coffee consumption is not related to an increased risks of large bowel cancer and that heavy coffee consumption may reduce the risk of colon cancer. A biologic rationale for such a reduction has not been established.

Adult↗
PubMed1987

Maternal exposure to spermicides in relation to certain birth defects.

Several studies have found no increase in the overall frequency of birth defects in association with the use of spermicides, but the possibility of an increase in specific defects remains. We evaluated this possibility in a large case-control study. Infants with certain malformations (265 with Down's syndrome, 396 with hypospadias, 146 with limb reduction defects, 116 with neoplasms, and 215 with neural-tube defects) were compared with 3442 control infants with a wide variety of other defects. Exposure to spermicides was assessed for three periods: use during the periconceptional period (one month before through one month after the last menstrual period), use during the first trimester (the first four lunar months of pregnancy), and any use during the lifetime. For the five groups of cases and for each interval, the odds ratios were close to 1.0 (range, 0.7 to 1.3); the upper 95 percent confidence bounds were 2.2 or lower. Risks did not increase with the duration of exposure. When each of the active ingredients in currently available spermicides was considered separately, no differences in odds ratios were apparent between the types of spermicides. With the possible exception of a subgroup of cases (limb reduction defects of unknown cause), these results suggest that risks for the five specific birth defects evaluated are not increased by exposure to spermicides.

Abnormalities, Drug-Induced↗
PubMed1987

Predictive value of minor anomalies. I. Association with major malformations.

We examined 4305 white newborn infants for 114 minor physical features and major malformations to evaluate the hypothesis that the presence of three or more minor anomalies is highly predictive of a major malformation. We confirmed that the infant with three or more minor anomalies is at increased risk for a major malformation. However, this risk (19.6%) was much lower than the risk of 90% popularized by Smith and based on the study of Marden et al. (J Pediatr 1964;64:357). Analysis of the findings in the two studies showed that the lower predictive value was probably related to differences in study design. Nevertheless, some minor anomalies remain essential to the early recognition of several serious malformation syndromes.

Abnormalities, Multiple↗