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Biomedical subjects

M M Werler

Publications and source records attributed to M M Werler.

At least 19 recordsLinked to original sources
PubMed2001

Neural tube defects in relation to use of folic acid antagonists during pregnancy.

Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTDs). To determine whether periconceptional exposure to folic acid antagonists (FAAs) might therefore increase the risk of NTDs, the authors examined data from an ongoing case-control study of birth defects (1979-1998) in the United States and Canada. They compared data on 1,242 infants with NTDs (spina bifida, anencephaly, and encephalocele) with data from a control group of 6,660 infants with malformations not related to vitamin supplementation. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors and about medication use. The adjusted odds ratios of NTDs related to exposure to FAAs (including carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, triamterene, and trimethoprim) during the first or second months after the last menstrual period, compared with no use in either month, were 2.8 (95% confidence interval: 1.7, 4.6) for FAAs as a group, 4.8 (95% confidence interval: 1.5, 16.1) for trimethoprim (based on five exposed cases), and 6.9 (95% confidence interval: 1.9, 25.7) for carbamazepine (six exposed cases). These results are adjusted for region, interview year, periconceptional folic acid supplementation, maternal age, weight, education, and infections early in pregnancy. These findings suggest that a number of FAAs may increase NTD risk, and they provide estimates of risk for selected drugs.

Adult↗
PubMed2000

Folic acid antagonists during pregnancy and the risk of birth defects.

BACKGROUND: Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations. METHODS: We compared data on exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs for 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects with data for 8387 control infants with malformations the risk of which is not reduced after vitamin supplementation. Mothers were interviewed within six months after delivery about their medication use. RESULTS: The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to 6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5 (95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs. CONCLUSIONS: Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.

Abnormalities, Drug-Induced↗
PubMed2000

Use of a job-exposure matrix to assess occupational exposures in relation to birth defects.

Accurate exposure assessment remains a challenge in occupational epidemiology. We evaluated one approach, use of a job-exposure matrix (JEM), by applying the National Institute for Occupational Safety and Health (NIOSH) JEM to a large case-control birth defects study that included parental occupation information. We investigated the JEM exposure predictions in several ways and found that for a substantial proportion of the parents in the birth defects study, the JEM yielded either no exposure data or nonsense predictions. Among exposure predictions that were plausible, most were of low probability. The high probability exposure predictions were statistically unstable, and neither low nor high probability exposure predictions were reliable. There was considerable discrepancy between the JEM predictions and expert assessments for five exposures of interest. Application of the NIOSH JEM to the birth defects study database (and probably other databases as well) does not provide a useful means of assessing occupational exposures.

Case-Control Studies↗
PubMed2000

Comparison of alternative survey methods for sensitive self-reported behaviours in a follow-up study of isotretinoin.

BACKGROUND: Responses to questions on sensitive behaviours can be affected by when and how questions are asked. METHODS: Using data from an ongoing survey of women taking isotretinoin (a teratogenic drug used to treat acne), we compared answers to questions on contraceptive use during therapy among 126966 women who had begun treatment in 1990-93. 20503 were randomly assigned to a group which was surveyed by telephone at the start of treatment, during treatment and 6 months after treatment ended (DAT group). 106463 received a mail survey 6 months after treatment ended (AT group). Women who could not be contacted during treatment, along with the non-respondents in the AT group, received follow-up surveys by US mail, air courier and, if necessary, were called by telephone. RESULTS: The response rate was higher in the DAT group (96.4%) than in the AT group (84.8%). Among respondents, the odds of reported contraceptive use in the AT group compared with the DAT group (asked at 6 months after treatment) was 1.41 [95% confidence interval (CI): 1.36-1.46]. However, rates of oral contraceptive (OC) use were virtually identical in the two groups. In both groups, women surveyed by telephone reported lower rates of contraceptive use than women surveyed by mail. In the AT group, a late response was associated with a significantly lower rate of contraceptive use. CONCLUSIONS: Both mode of data collection (phone versus mail) and time to response affected reported rates of contraceptive use. Reasonable assumptions about the effect of non-response could not account for the difference between the AT and DAT groups. We found that contacting women during their treatment did not increase their reported use of contraceptives.

Acne Vulgaris↗
PubMed1999

Multivitamin supplementation and risk of birth defects.

It is widely accepted that supplementation with folic acid, a B vitamin, reduces the risk of neural tube defects (NTDs). This case-control study tested the hypothesis that multivitamins reduce risks of selected birth defects other than NTDs. Infants with and without birth defects and aborted fetuses with birth defects were ascertained in the greater metropolitan areas of Boston, Philadelphia, and Toronto during 1993-1996. Mothers were interviewed within 6 months after delivery about a variety of factors, including details on vitamin use. Eight case groups were included: cleft lip with or without cleft palate, cleft palate only, conotruncal defects, ventricular septal defects, urinary tract defects, limb reduction defects, congenital hydrocephaly, and pyloric stenosis (n's ranged from 31 to 186). Controls were 521 infants without birth defects (nonmalformed controls) and 442 infants with defects other than those of the cases (malformed controls). Daily multivitamin supplementation was evaluated according to gestational timing categories, including periconceptional use (28 days before through 28 days after the last menstrual period). Odds ratios (ORs) below 1.0 were observed for all case groups except cardiac defects, regardless of control type. For periconceptional use, ORs with 95% confidence intervals that excluded 1.0 were estimated for limb reduction defects using both nonmalformed controls (OR = 0.3) and malformed controls (OR = 0.2) and for urinary tract defects using both nonmalformed controls (OR = 0.6) and malformed controls (OR = 0.5). Statistically significant ORs for use that began after the periconceptional period were observed for cleft palate only and urinary tract defects. These data support the hypothesis that periconceptional vitamin supplementation may extend benefits beyond a reduction in NTD risk. However, other than folic acid's protecting against NTDs, it is not clear what nutrient or combination of nutrients might affect risk of other specific defects.

Adult↗
PubMed1999

Achieving a public health recommendation for preventing neural tube defects with folic acid.

OBJECTIVES: This study examined 3 approaches to achieving the public health recommendation that all women of child-bearing age ingest 0.40 mg of folic acid per day to reduce the occurrence of neural tube defects (NTDs). METHODS: A total of 1136 mothers of infants with major malformations from the Boston and Philadelphia areas, whose pregnancies began from 1993 to 1995, were interviewed within 6 months of delivery about vitamin supplementation, dietary intakes, and other factors. RESULTS: Seventy-one percent of the 1136 women in the study did not take folic acid--containing supplements daily before conception, but the proportion decreased over the years of the study. Women not taking supplements consumed an average of 0.25 mg of naturally occurring folates daily. On the basis of dietary intakes reported by women not taking folic acid supplements, a simulation of cereal grain fortification with folic acid at the level required by the US Food and Drug Administration showed that an average of only 0.13 mg of folic acid would be ingested daily. CONCLUSIONS: With consumption of folic acid only through dietary intake, sizeable portions of the childbearing population would receive less than the level of folic acid recommended for preventing NTDs. Even with food fortification, women of childbearing age should be advised to take folic acid--containing supplements on a daily basis.

Adult↗
PubMed1997

Multivitamin supplementation and multiple births.

It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: "periconceptional" use--before through at least the third month after conception; "early" use--beginning in the first month and continuing through at least the third month after conception; and "later" use--beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for "early" and "later" use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects.

Congenital Abnormalities↗
PubMed1996

Case-control study of periconceptional folic acid supplementation and oral clefts.

There is consistent evidence that the risk of neural tube defects is decreased by periconceptional supplementation with folic acid. A similar protective effect has been postulated for oral clefts. A case-control study was conducted in greater metropolitan Boston; Massachusetts; Philadelphia, Pennsylvania; and southeastern Ontario, Canada, from 1988 through 1991 to test the hypothesis that folic acid supplementation during the periconceptional period reduces the risk of oral clefts. Crude and multivariate-adjusted relative risks were calculated for all oral clefts (n = 303), cleft palate (n = 108), and cleft lip with or without cleft palate (n = 195). Controls (n = 1,167) were liveborn or stillborn infants less than age 6 months who had various congenital anomalies other than oral clefts, neural tube defects, or other "midline defects." Adjusted relative risks and 95 percent confidence intervals for daily folic acid supplementation during the periconceptional period were: oral clefts, 1.1 (95% confidence interval (CI) 0.8-1.7), cleft palate, 0.9 (95% CI 0.5-1.6), and cleft lip with or without cleft palate, 1.3 (95% CI 0.8-2.1). These findings do not support a protective association between the periconceptional use of folic acid supplements and the risk of oral clefts.

Case-Control Studies↗
PubMed1996

Prepregnant weight in relation to risk of neural tube defects.

OBJECTIVE: To examine the relation between prepregnant weight and the risk of neural tube defects (NTDs). DESIGN: Data were collected from 1988 to 1994 in a case-control surveillance program of birth defects. SETTING: Study subjects were ascertained at tertiary care centers and birth hospitals in the greater metropolitan areas of Boston, Mass, and Philadelphia, Pa, and in southeastern Ontario. PARTICIPANTS: Cases were 604 fetuses or infants with an NTD identified within 6 months of delivery. Controls were 1658 fetuses or infants with other major malformations identified within 6 months of delivery. For 1992 to 1994, there were 93 control infants without major malformations. MAIN OUTCOME MEASURE: Relative risk of NTDs in infants or fetuses for different maternal weights. RESULTS: Relative to women who weighed 50 to 59 kg, risk of NTDs increased from 1.9 (95% confidence interval [CI], 1.2 to 2.9) for women weighing 80 to 89 kg to 4.0 (95% CI, 1.6 to 9.9) for women weighing 110 kg or more. When women were classified according to daily intake above or below the recommended level of 400 micrograms of folate, approximate threefold increases in risk were estimated for the heaviest weights in both groups. Intakes of 400 micrograms of folate or more reduced risk of NTDs by 40% among women weighing less than 70 kg, but no risk reduction was observed among heavier women. CONCLUSION: The risk of NTDs increased with increasing prepregnant weight, independent of the effects of folate intake.

Adult↗
PubMed1994

Ovulation induction and risk of neural tube defects.

The relation between use of ovulation-inducing drugs and risk of neural tube defects (NTDs) was studied in a case-control surveillance programme. The frequency of any use of such drugs during the 6 months before the last menstrual period or during pregnancy was 3.0% for 1034 mothers of infants and fetuses with NTDs (cases) and 2.8% for 4081 mothers of those with other major congenital malformations (controls) (relative risk 1.1, 95% CI 0.8-1.7). Relative risks for clomiphene and for hormones were 0.8 (0.5-1.3) and 1.5 (0.7-3.4), respectively. These data suggest that use of ovulation-inducing drugs before conception does not increase the risk of NTDs.

Case-Control Studies↗