Correspondence
Paternal and Maternal Components of the Predisposition to Preeclampsia
N Engl J Med 2001; 345:149-150July 12, 2001
- Article
To the Editor:
Esplin and colleagues (March 22 issue)1 found evidence of both paternal and maternal components of the predisposition to preeclampsia. However, their methods raise some issues of concern. First, this association was adjusted for 15 possible confounding variables. Nevertheless, several maternal factors well known to be associated with preeclampsia, such as body-mass index before pregnancy,2 cigarette smoking,3 a change of partner,4 a history of preeclampsia in multiparous women,5 and type of birth (single or multiple),2 were not taken into account as confounding variables. The authors should demonstrate that the inclusion of these factors in the logistic-regression models would not alter the results. Moreover, information about preeclampsia in the mothers of the female partners of the men in the study group and the control group should be available for all the men.
Second, the authors used only birth-certificate records to identify pregnancies complicated by preeclampsia. We wonder how many of these women in fact had gestational hypertension. To address this question, the authors should have obtained medical records to verify the diagnosis of preeclampsia.
5 ReferencesAgustin Conde-Agudelo, M.D.
Fundación Clìnica Valle del Lili, Cali, Colombia
condeagu@uniweb.net. co 1
Esplin MS ,Fausett MB ,Fraser A , et al. Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med 2001;344:867-872
Full Text | Web of Science | Medline2
Conde-Agudelo A ,Belizan JM . Risk factors for pre-eclampsia in a large cohort of Latin American and Caribbean women. BJOG 2000;107:75-83
CrossRef | Web of Science | Medline3
Conde-Agudelo A ,Althabe F ,Belizan JM ,Kafury-Goeta AC . Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am J Obstet Gynecol 1999;181:1026-1035
CrossRef | Web of Science | Medline4
Trupin LS ,Simon LP ,Eskenazi B . Change in paternity: a risk factor for preeclampsia in multiparas. Epidemiology 1996;7:240-244
CrossRef | Web of Science | Medline5
Lie RT ,Rasmussen S ,Brunborg H ,Gjessing HK ,Lie-Nielsen E ,Irgens LM . Fetal and maternal contributions to risk of pre-eclampsia: population based study. BMJ 1998;316:1343-1347
CrossRef | Web of Science | Medline
To the Editor:
Esplin and colleagues suggest that the maternal and paternal components of the predisposition to preeclampsia are mediated by the fetal genotype. The apparent maternal component, at least, may simply reflect the inheritability of hypertension. Preeclampsia is often misdiagnosed in women with chronic (or gestational) hypertension; the distinction is often not apparent when birth certificates are completed, because a diagnosis of preeclampsia can be made with certainty only if the blood pressure is normal for several weeks or longer after delivery. Women with chronic hypertension are more likely to deliver daughters who are genetically predisposed to chronic hypertension; in both groups of women, preeclampsia may be misdiagnosed during pregnancy. Clinically, the simplest way to improve diagnostic accuracy is to restrict the diagnosis of preeclampsia to nulliparous women.1 What is the magnitude of the maternal and paternal components of the predisposition to preeclampsia if only gestations in nulliparous women (in both generations) are included?
1 ReferencesKent Heyborne, M.D.
Swedish Medical Center, Englewood, CO 80110
heyborne@hotmail.com 1
Chesley LC . Diagnosis of preeclampsia. Obstet Gynecol 1985;65:423-425
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: The associations described in our article were based on diagnoses recorded on birth certificates between 1947 and 1957 and on the birth certificates of the subsequent generation, born between 1970 and 1992. We excluded subjects with any recorded predisposition to preeclampsia (e.g., chronic hypertension or diabetes mellitus) but were unable to evaluate factors such as body-mass index before pregnancy because these data were not systematically recorded during this era. Likewise, information about the mothers of the female partners of the men in the study was not available if the births of the female partners had not been recorded in Utah. The recorded incidence of tobacco use in this population was too low to have an effect. Neither the total nor an unbiased sample of the actual medical records was available because of the varied locations of the records and because of issues relating to patients' privacy and the policies of institutional review boards.
We agree that the accuracy of aggregate birth-certificate data should be considered suspect. However, our study provides internal evidence supporting the accuracy of the recorded diagnoses of preeclampsia and our methods. The effect of nulliparity and the intergenerational mother-to-mother risk of preeclampsia have been characterized in other studies.1,2 The fact that we identified these variables as risk factors supports our definition of the study groups. We did perform analyses in which only nulliparous women or women with eclampsia were included. Although the trends remained, the comparisons were not statistically significant (except in the case of the risk of preeclampsia in the offspring of women with eclampsia [relative risk, 3.9; 95 percent confidence interval, 1.8 to 8.7]). To control for the effect of parity, we matched study subjects and control subjects according to birth order in the population born between 1947 and 1957. Maternal parity and birth order were significant variables in the comparisons in the population born between 1970 and 1992 and were included in the final regression analyses.
Finally, we concede that some women with chronic or gestational hypertension could have been classified incorrectly and included in the study groups born between 1947 and 1957. However, there is no reason to suspect that the aggregate birth-certificate data in the generation born between 1970 and 1992 were biased toward either the study group or the control group. Since chronic hypertension is a preexisting condition, a fetus cannot possibly cause maternal chronic hypertension. Thus, any bias introduced would only “dilute” the study groups born between 1947 and 1957 and favor the finding of no difference.
The important observation of this study remains the independent existence of a paternal contribution to the development of preeclampsia.
2 ReferencesM. Bardett Fausett, M.D.
Keesler Medical Center, Keesler AFB, MS 39534M. Sean Esplin, M.D.
Michael W. Varner, M.D.
University of Utah Health Sciences Center, Salt Lake City, UT 84132
mesplin@hsc.utah. edu 1
Arngrimsson R ,Bjornsson S ,Geirsson RT ,Bjornsson H ,Walker JJ ,Snaedal G . Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population. Br J Obstet Gynaecol 1990;97:762-769
CrossRef | Medline2
Chesley LC ,Cooper DW . Genetics of hypertension in pregnancy: possible single gene control of pre-eclampsia and eclampsia in the descendants of eclamptic women. Br J Obstet Gynaecol 1986;93:898-908
CrossRef | Medline
- Citing Articles (1)
Citing Articles
1
Gabriella Pridjian, Jules B. Puschett. (2002) Preeclampsia. Part 2: Experimental and Genetic Considerations. Obstetrical & Gynecological Survey 57:9, 619-640
CrossRef
