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Biomedical subjects

A A Mitchell

Publications and source records attributed to A A Mitchell.

At least 19 recordsLinked to original sources
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

The safety of acetaminophen and ibuprofen among children younger than two years old.

BACKGROUND: Recently ibuprofen has been introduced as a nonprescription analgesic/antipyretic for use in children. OBJECTIVE: To compare the incidence of serious adverse clinical events among children <2 years old given ibuprofen and acetaminophen to control fever. STUDY DESIGN: A practitioner-based, randomized clinical trial. A total of 27 065 febrile children were randomized to receive acetaminophen (12 mg/kg), ibuprofen (5 mg/kg), or ibuprofen (10 mg/kg). Rates of hospitalization for acute gastrointestinal bleeding, acute renal failure, anaphylaxis, Reye's syndrome, asthma, bronchiolitis, and vomiting/gastritis were compared by randomization group. RESULTS: The risk of hospitalization with any diagnosis in the 4 weeks after enrollment was 1.4% (95% confidence interval, 1. 3%-1.6%) and did not vary by antipyretic assignment. No children were hospitalized for acute renal failure, anaphylaxis, or Reye's syndrome. Three children were hospitalized with gastrointestinal bleeding; all 3 had been assigned to treatment with ibuprofen. The risk of hospitalization with gastrointestinal bleeding among children randomized to ibuprofen was 17 per 100 000 (95% confidence interval, 3.5-49 per 100 000) but was not significantly greater than the risk among children given acetaminophen. The risk of hospitalization with asthma, bronchiolitis, or vomiting/gastritis did not differ by antipyretic assignment. CONCLUSIONS: The risk of serious adverse clinical events among children <2 years old receiving short-term treatment with either acetaminophen or ibuprofen suspension was small and did not vary by choice of medication. These data do not provide any information on the safety of these medications when used for prolonged periods or when used together, regardless of duration.

Acetaminophen↗
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↗
PubMed1999

Selection bias and the use of controls with malformations in case-control studies of birth defects.

We compared four methods of control selection to assess the effect of using infants with malformations as controls in case-control studies of birth defects. We identified cases and controls using data from the Slone Epidemiology Unit Births Defect Study for the years 1976-1992. Cases were defined as infants with cleft lip and palate and no other malformations (N = 494). Controls (N = 8356) were chosen from infants with other malformations, excluding other oral cleft conditions or syndromes associated with clefts. Maternal smoking during the first 13 weeks of pregnancy was the exposure of interest. We then assessed the measures of association resulting from using controls with varying restrictions. When we excluded all defects potentially associated with maternal smoking (based on reports in the literature), the crude odds ratio for smoking and oral cleft risk was 1.6 (1.3-1.9). When we eliminated all defect groups with a smoking prevalence that was one or more standard deviations above or below the total control group mean, the odds ratio was 1.5 (1.2-1.8); with controls restricted to infants with Mendelian-inherited disorders (with presumably no causal effect of smoking), the odds ratio was 1.6 (1.1-2.7); and when selection was unrestricted, the crude odds ratio was 1.5 (1.2-1.8). When used selectively, infants with malformations other than the anomaly of interest can be a suitable source of controls.

Boston↗
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↗
PubMed1997

Renal function after short-term ibuprofen use in infants and children.

OBJECTIVE: To test the hypothesis that short-term use of ibuprofen increases the risk of impaired renal function in children. STUDY DESIGN: Randomized, double-blind acetaminophen-controlled clinical trial. Children with a febrile illness were enrolled from outpatient pediatric and family medicine practices and randomly assigned to receive either acetaminophen suspension or one of two dosages of ibuprofen suspension (5 mg/kg or 10 mg/kg) for fever control. RESULTS: Mean blood urea nitrogen levels on admission among children admitted to hospital and assigned ibuprofen 5 mg/kg (n = 96), ibuprofen 10 mg/kg (n = 102), and acetaminophen 12 mg/kg (n = 87) were 4.1, 3.8, and 3.9 mmol/L, respectively. The corresponding creatinine levels were 43, 41, and 43 micromol/L, respectively. The prevalence of a creatinine level >62 micromol/L was 9.5% overall and did not vary by antipyretic assignment. Among 83 children hospitalized with dehydration, the mean creatinine level was 44 micromol/L, and the prevalence of an elevated creatinine was 14%; neither measure varied by antipyretic assignment. CONCLUSION: Although renal failure in children has been reported after ibuprofen use, these data suggest that for short-term use the risk of less severe renal impairment, as reflected by blood urea nitrogen and creatinine levels, is small and not significantly greater than that after acetaminophen use.

Acetaminophen↗