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Biomedical subjects

K J Rothman

Publications and source records attributed to K J Rothman.

At least 19 recordsLinked to original sources
PubMed1992

Maternal heat exposure and neural tube defects.

OBJECTIVE: To determine if exposure to hot tub, sauna, fever, or electric blanket during early pregnancy was associated with an increased risk for neural tube defects (NTDs). DESIGN: Prospective follow-up study. SETTING: Mostly private obstetric practices, primarily in New England. PARTICIPANTS: A cohort of 23,491 women having serum alpha-fetoprotein screening or an amniocentesis were identified. Complete exposure and outcome information was available for 97% of these women. OUTCOME MEASURES: Relative risks (RRs) were used to compare incidence of NTD in those exposed to heat with those who were not exposed to any heat. Crude RRs were calculated directly from the data. Unconfounded RRs were calculated using logistic regression. RESULTS: Women reporting any heat exposure (sauna, hot tub, fever, or electric blanket) in early pregnancy had a crude risk of their fetuses developing NTD of 1.6 (95% CI [confidence interval], 0.9 to 2.9). Women reporting exposure to sauna, hot tub, or fever in early pregnancy had a crude risk of their fetuses developing NTD 2.2 times that of women without heat exposure (95% CI, 1.2 to 4.1). For hot tub use, the crude RR was 2.9 (95% CI, 1.4 to 6.3); for sauna, 2.6 (95% CI, 0.7 to 10.1); for fever, 1.9 (95% CI, 0.8 to 4.1); and for electric blanket, 1.2 (95% CI, 0.5 to 2.6). Multivariate adjusted RRs for individual heat sources, after controlling for maternal age, folic acid supplements, family history of NTD, and exposure to other heat sources, were for hot tub use, 2.8 (95% CI, 1.2 to 6.5); sauna, 1.8 (95% CI, 0.4 to 7.9); fever, 1.8 (95% CI, 0.8 to 4.1); and electric blanket, 1.2 (95% CI, 0.5 to 2.6). When only hot tub, sauna, and fever were considered and the women's exposure to each tallied, compared with no heat exposure, the RR for NTDs increased from 1.9 (95% CI, 0.9 to 3.7) after one type of heat exposure to 6.2 (95% CI, 2.2 to 17.2) after two types of heat exposure. CONCLUSIONS: Exposure to heat in the form of hot tub, sauna, or fever in the first trimester of pregnancy was associated with an increased risk for NTDs. Hot tub exposure appeared to have the strongest effect of any single heat exposure. Exposure to electric blanket was not materially associated with increased risk for NTDs.

Cohort Studies↗
PubMed1992

Maternal zinc and fetal neural tube defects.

Among the factors implicated in the heterogeneous etiology of neural tube defects (NTDs) is the trace element zinc (Zn). In a case-control study, we collected midtrimester maternal toenail samples for multiple trace element analyses, including Zn, which were assayed by neutron activation analysis. We studied 17 women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7). These results were not materially affected when adjustment was made for folic acid supplementation. An overall increased risk for NTD associated with increasing toenail Zn was also evident. A matched subset of 17 cases and 73 controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched analyses controlling for folic acid supplements, family history of NTD, assay batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6). This study reveals an association between increased toenail Zn in the second trimester of pregnancy and the risk of having a child with an NTD. Whether Zn sequestration has resulted in relative Zn deficiency at the site of neural tube closure remains uncertain.

Case-Control Studies↗
PubMed1992

Rats.

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Animals↗
PubMed1991

The ethics of research sponsorship.

Growing concern regarding ethics in science has prompted calls for reform. These proposals include the mandatory identification of funding source and prohibition of any financial connection between an investigator and a company whose product is being studied. Such reforms imply that scientific work supported by industry should not be considered reliable, that any potential for fraud or subconscious alteration of the work should be considered damning in itself. This thinking will promote an ad hominem evaluation of science, rather than an evaluation based on merits. The reality is that no scientist is impartial. To focus on the circumstances of the work rather than the work itself has the ironic effect of detracting from overall objectivity. Scientific objectivity does not arise through cultivation in the minds of individual scientists, none of whom can lay claim to this pinnacle of rationality, but by the process of open, rational criticism itself. Those who encourage that work be judged in respect to the funding source are slighting honest industry scientists and stifling rational discourse.

Conflict of Interest↗
PubMed1991

Mortality from cancer of the colon or rectum among workers exposed to ethyl acrylate and methyl methacrylate.

Mortality from colon and rectum cancer has been reviewed in three cohorts working in 1933-1982 in two plants manufacturing and polymerizing acrylate monomers. The two cohorts with later dates of hire showed no excess mortality. In the earliest cohort, excess colon cancer seemed restricted to men employed extensively in the early 1940s in jobs entailing the highest exposures to vapor-phase ethyl acrylate (EA) and methyl methacrylate (MMA) monomer and volatile by-products of the EA/MMA polymerization process. The excess mortality appeared only some two decades after the equivalent of three years' employment in jobs with the most intense exposures. A smaller elevation in colon cancer mortality also appeared in a low-exposure group in the early cohort. Rectal cancer mortality was elevated in the same categories that showed excess rates of colon cancer death. Because of the lower rates, the rectal cancer results are more imprecise.

Acrylates↗
PubMed1990

Tampon absorbency, composition and oxygen content and risk of toxic shock syndrome.

Tampon use has been identified as a major risk factor for toxic shock syndrome, although the etiologic role of tampons is not clearly understood. Two epidemiologic studies conducted to date have reported an association between tampon absorbency and risk of toxic shock syndrome. This finding is not corroborated by laboratory studies, however, which have suggested that absorbency may be a marker for other characteristics that create an environment conductive to the elaboration of toxic shock syndrome toxin 1. We used data from the previously reported Tri-state study to estimate simultaneously the effects of tampon oxygen content, absorbency and chemical composition. Although the data are sparse, oxygen content was more strongly associated with risk of toxic shock syndrome than either absorbency or chemical composition. The results suggest that it may be possible to develop a highly absorbent tampon that is not associated with a high risk of toxic shock syndrome.

Acrylates↗
PubMed1990

Bromocriptine and puerperal seizures.

Case reports have prompted concern that the use of bromocriptine mesylate to prevent lactation in the puerperium increases the risk of postpartum seizure. We conducted a record-based case-control study of postpartum seizures in three data bases to evaluate this relation. We identified 43 women who had a postpartum seizure, and we matched 319 controls individually by hospital of delivery, quinquenium of age, and time of delivery. Overall, women taking bromocriptine had a 22% lower risk for seizures, that is, the relative risk estimate was 0.78, with a 90% confidence interval of 0.29 to 1.87. A reduction in seizure risk is consistent with reports of antiseizure activity for bromocriptine in various species, including humans. We found a small positive association between bromocriptine use and seizures occurring more than 72 hours after delivery, with a relative risk estimate of 1.6 after controlling for seizure history. This association was offset by a strong negative association between bromocriptine use and early-occurring seizures. The pattern of an initial reduced risk followed by an increase to normal or above-normal levels of risk could result from an antiseizure activity of bromocriptine, with a rebound in risk when bromocriptine is withdrawn.

Adolescent↗
PubMed1990

No adjustments are needed for multiple comparisons.

Adjustments for making multiple comparisons in large bodies of data are recommended to avoid rejecting the null hypothesis too readily. Unfortunately, reducing the type I error for null associations increases the type II error for those associations that are not null. The theoretical basis for advocating a routine adjustment for multiple comparisons is the "universal null hypothesis" that "chance" serves as the first-order explanation for observed phenomena. This hypothesis undermines the basic premises of empirical research, which holds that nature follows regular laws that may be studied through observations. A policy of not making adjustments for multiple comparisons is preferable because it will lead to fewer errors of interpretation when the data under evaluation are not random numbers but actual observations on nature. Furthermore, scientists should not be so reluctant to explore leads that may turn out to be wrong that they penalize themselves by missing possibly important findings.

Bias↗
PubMed1979

Replacement estrogens and endometrial cancer.

We examined the incidence of endometrial cancer in a large prepaid group practice in the Seattle area. From July, 1975, to July, 1977, there was a sharp downward trend in the incidence of endometrial cancer that paralleled a substantial reduction in prescriptions for replacement estrogens. Incidence rates were estimated for estrogen users and nonusers among women 50 to 64 years of age with intact uteri; current long-term users had an annual risk for endometrial cancer between 1 and 3 per cent, whereas nonusers had a risk less than 1/10th as great. These incidence rates remained fairly constant over time among users and nonusers; the drop in overall incidence soon after estrogen use declined suggests that the increased risk associated with estrogens falls quickly after discontinuation. The reduction in incidence of endometrial cancer in this group practice was part of a general decline in the United States after 1975.

Estrogens↗
PubMed1979

Exogenous hormones and other drug exposures of children with congenital heart disease.

A history of oral contraceptive use, hormonal pregnancy tests, prescribed hormones and other drugs was obtained from 390 mothers of infants with congenital heart disease and 1254 mothers of normal infants in Massachusetts. The data show a small positive association between estrogen/progesterone exposure and cardiac malformation, the prevalence ratio estimate of exposed to non-exposed being 1.5 (90 per cent confidence limits are 1.0, 2.1). No association was evident, however, between hormones and trunco-conal or any other class of defect among the cases, an observation which casts doubt on a causal relationship betweem hormones and cardiovascular malformations. Several other drugs were reported more frequently by cases' mothers. These include: ampicillin; aspirin; a combined anti-nausea agent (doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride); chlordiazopoxide, codeine, diazepam, diphenylhydantoin; insulin; phenobarbital; phenothiazine; phenylephrine; and tetracycline.

Estrogens↗
PubMed1979

Lung cancer in young women.

A comparison was made between cigarette smoking histories of 31 women below age 50 years who had a diagnosis of lung cancer on hospital discharge and smoking histories of 124 women below age 50 years who had been hospitalized for other conditions. Of the women with lung cancer, 28 (90%) were current or former cigarette smokers; 72 (58%) of the comparison women were smokers. The relative risk estimate for lung cancer among smokers as compared with nonsmokers is 6.7, with 90% confidence limits of 4.0 and 11. Risk of lung cancer increased with the amount that the women smoked. The smokers with lung cancer had been smoking for longer periods than the smokers with other conditions. Assuming that the association is causal, cigarette smoking was responsible for about 77% of the lung cancer of young women in this survey.

Adult↗
PubMed1978

A show of confidence.

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Clinical Trials as Topic↗
PubMed1978

Myocardial infarction and other vascular diseases in young women. Role of estrogens and other factors.

We studied 83 women younger than 46 years with acute myocardial infarction (MI) and 154 controls. There was a strong positive association between MI and the following: (1) age, (2) both oral contraceptive and noncontraceptive estrogen use, (3) cigarette smoking, and (4) the presence of predisposing medical conditions, eg, past MI, hypertension, and diabetes. ABO blood type and family history of arterial disease were also positively associated with MI. Whereas the risks for idiopathic stroke and venous thromboembolism have also been shown to be increased among oral contraceptive users, there is comparatively little correlation between these two illnesses and age or smoking in young women. The present study, taken together with previously published work, provides reasonable estimates of the vascular risks associated with oral contraceptive use.

ABO Blood-Group System↗
PubMed1978

Correcting a bias?

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Epidemiologic Methods↗
PubMed1978

Oral contraceptives and birth defects.

We reviewed the birth certificates and hospital records of 7723 infants those mothers had reported using oral contraceptives. The overall frequency of malformation was 4.3 per cent for infants whose mothers terminated use of oral contraceptives shortly before conception, as compared with 3.3 per cent for infants whose mothers did not take oral conceptives diring the three years before conception. The 90 per cent confidence limits for the prevalence ratio were 1.0 and 1.7. No difference was apparent for major malformations. For specific malformations the most notable difference was for undescented testis, but this excess, like the overall excess, could be explained by sampling variability. Despite the slightly greater rate of minor malformations in the short-interval group, a reasonable interpretation of these data would be that oral contraceptives present no major teratogenic hazard.

Abnormalities, Drug-Induced↗