A Practical Approach, Second Edition=Ronald D. Ho.pdf

818 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONwho are using anticonvulsants. During the last decades, such information has been published fromTeratology Information Services (TIS). Women and doctors can approach such organizations toask for advice when a drug has been used in early pregnancy, and by following up such exposedpregnancies, information on possible hazards can be obtained. The main drawbacks are that onlyrelatively small numbers of exposures are usually identified, that pregnancy outcome is not alwaysknown, and that it is sometimes difficult to get control groups for comparison. A positive characteristicis that exposure data with respect to timing and drug dosage are often precise.During the past few years, there have been further opportunities. Prospective recording of druguse in early pregnancy has become part of the Swedish Medical Birth Registry. This provides agrowing database of prospectively recorded drug information with outcome data that can easily becompared with that of all births. 49 The main drawback is that there are few data on time of exposureand amounts of drug used. Other programs have used linkage between registries of drug prescriptionand birth registries. 50 Exposure information will be crude because it will not be known whetherthe woman actually used the drug during pregnancy, especially if it is not a chronic medication.In one system, prospectively recorded drug exposure data are combined with retrospective data,obtained by interview. 51In studies on drug teratogenesis, various confounders, such as maternal age and parity, subfertility,and smoking habits, should be taken into consideration. The most important confounder, thedisease or complaint for which the drug was used, is difficult to control. One way is to comparedifferent drug categories used for the same condition.3. Information on Occupational ExposureIn many studies on occupational hazards to reproduction, maternal occupation has been used as aproxy for exposure. 52 This will usually give rather crude exposure information, and within thestudied group a subgroup with markedly different exposure conditions that may represent a riskmight be hidden. The more detailed the occupational characterization, the better the study, butusually it is not possible to get accurate actual exposure levels. In some studies (usually designedas nested case control studies), the actual exposure for each involved woman has been evaluatedblindly by an occupational hygienist. In such a situation, the relevant period when the malformationin question could have been formed should also be considered. Direct measurements will furtherincrease exposure precision, but as stressed above, the necessary small number of cases will oftenreduce the study power too greatly.In other studies, exposure information is obtained by retrospective interviews or questionnaires.Except for the risks involved in all retrospective studies (see Section III.C), lack of knowledgeamong the women of their real exposure is a problem.4. Information on General Environmental ExposureIn studies of the impact of the environment on pregnancy outcome, one is usually dealing withrather generalized exposures of large populations (e.g., air pollution, drinking water contamination,radioactive fallout) where very strong effects are not expected. In studies of congenital malformations,the environment for the woman during her early pregnancy is of interest. Often only themother’s address at the time of delivery is available, and a change of address is not uncommonduring pregnancy, especially the first pregnancy. In most studies, a rather crude geographicallocalization is made, e.g., parish or postal code. In more sophisticated studies, the actual coordinatesof the address can be used and perhaps linked to air pollution measurements or information ondrinking water composition.When a source of environmental pollution is studied, the distance between the address of thewoman and the source of pollution is often used as a proxy for exposure. In some studies of airbornepollution, the dominating wind direction has been taken into consideration.© 2006 by Taylor & Francis Group, LLC