Effect of Prenatal Diagnosis on Epidemiologic Studies of Birth Defects

Abstract

Prenatal diagnostic technology makes it possible to offer women the option of electively terminating pregnancies affected by birth defects. Excluding these pregnancies from epidemiologic studies may affect study results. We explored this effect using examples from the literature. We calculated the bias in the odds ratio caused by excluding prenatally diagnosed pregnancies when the exposure of interest is not correlated with the likelihood of terminating an affected pregnancy and when it is correlated with an increase or decrease in this likelihood. We assumed that control infants did not have birth defects. When the exposure is not associated with the likelihood of a pregnancy termination, studies excluding terminations suffer a loss of precision. When the exposure is associated with an increase or decrease in this likelihood, the odds ratios are biased toward or away from the null, respectively. The magnitude of the bias will vary according to characteristics of the study population such as the prevalence of the exposure and the frequency with which prenatal diagnosis and elective termination are used. Whenever possible, pregnancies terminated after prenatal diagnosis must be included in epidemiologic studies.

Trends in Congenital Heart Defects in Infants With Down Syndrome

“…28 We can only speculate about underlying mechanisms for the shift in cardiovascular phenotype observed in Sweden, as we had no information on fetuses from terminated pregnancies. 29 In recent years, congenital heart defects are reportedly less common in the general population, but the magnitude of changes observed among Swedish infants with Down syndrome is unlikely to be explained by factors related to such small general trends. 7,12 Instead, it is plausible that we are observing the consequences of selection.…”

Pregnancy termination following prenatal diagnosis of anencephaly or spina bifida: A systematic review of the literature

“…The second did not present results separately for each NTD type (anencephaly, spina bifida, and encephalocele) but found that TOP following prenatal diagnosis of NTDs was more common in older than younger mothers, in Asian compared to white mothers, and in certain areas of their study catchment area in Hawaii (Forrester and Merz, 2000). Because these characteristics are associated with TOP and therefore inclusion in the study, selection bias is possible in studies investigating these factors in relation to NTD etiology (Cragan and Khoury, 2000). Further studies will be needed to evaluate whether these and other maternal and fetal characteristics are associated with TOP following prenatal diagnosis for different NTD subtypes.…”

“…Descriptive studies underestimate the number of pregnancies with recognized NTDs when only live births are included or some proportion of affected pregnancies resulting in TOPs is missed (Roberts et al, 1995;Bower et al, 2001;Cragan and Gilboa, 2009). In etiologic studies, exclusion or incomplete ascertainment of NTDs among TOPs can lead to selection bias when the exposure of interest is associated with likelihood of TOP (Cragan and Khoury, 2000). Clinical studies of long-term outcomes following infants from birth might not be useful for counseling parents with prenatally diagnosed fetuses about prognosis if liveborn infants represent only a small, selected subset of all affected pregnancies.…”

Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states.

“…Although selection of urban counties as referent would have had the advantage of little or no exposure to agricultural herbicides, the disadvantage would have been that other, nonagricultural factors might also be involved in causing a lower level of birth malformations in urban counties. For example, easier access to prenatal care may be associated with elective abortion after prenatal diagnosis of an anomaly (Cragan and Khoury 2000). Underreporting may be more frequent in urban than in rural counties, because in large hospitals information on birth malformations is provided by obstetricians, in contrast to small hospitals, where pediatricians are the source of information (Hexter and Harris 1991).…”