Statistical model for fetal death, fetal weight, and malformation in developmental toxicity studies. 1993

P J Catalano, and D O Scharfstein, and L M Ryan, and C A Kimmel, and G L Kimmel
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.

The purpose of this paper is to present a statistical model for analyzing the joint effects of exposure on fetal death, fetal weight, and malformation in a developmental toxicity study. In addition to allowing for the usual litter effect, the model allows for correlations between different outcomes measured on the same fetus. Fitting the model requires first focusing on non-live outcomes by modeling the probability of fetal death or resorption as a function of dose. Then outcomes among live fetuses are modeled using a two-stage regression approach. The first stage models fetal weight as a function of dose and the second stage models fetal malformation as a function of dose, as well as residuals from the weight model. The regression coefficients from the malformation model have intuitive interpretations in terms of correlations between littermates and between different outcomes measured within the same fetus. Not only does the approach provide a useful way to investigate the relationship between adverse fetal outcomes, it also yields a natural framework for conducting quantitative risk assessment. A procedure is proposed for quantifying overall risk by incorporating the three outcomes in order to estimate safe dose levels and corresponding lower confidence limits. The method is illustrated using data from an experiment in mice conducted through the National Toxicology Program.

UI MeSH Term Description Entries
D008738 Methyl Ethers A group of compounds that contain the general formula R-OCH3. Ethers, Methyl
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011256 Pregnancy Outcome Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; or SPONTANEOUS ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO. Outcome, Pregnancy,Outcomes, Pregnancy,Pregnancy Outcomes
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005026 Ethylene Glycols An ethylene compound with two hydroxy groups (-OH) located on adjacent carbons. They are viscous and colorless liquids. Some are used as anesthetics or hypnotics. However, the class is best known for their use as a coolant or antifreeze. Dihydroxyethanes,Ethanediols,Glycols, Ethylene
D005260 Female Females
D005313 Fetal Death Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH. Fetal Mummification,Fetal Demise,Death, Fetal,Deaths, Fetal,Demise, Fetal,Fetal Deaths,Mummification, Fetal
D005327 Fetal Resorption The disintegration and assimilation of the dead FETUS in the UTERUS at any stage after the completion of organogenesis which, in humans, is after the 9th week of GESTATION. It does not include embryo resorption (see EMBRYO LOSS). Fetal Resorptions,Resorption, Fetal,Resorptions, Fetal

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