Published online October 31, 2008
PEDIATRICS Vol. 122 No. 5 November 2008, pp. 1072-1078 (doi:10.1542/peds.2007-3666)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, C. S.
Right arrow Articles by Olsen, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, C. S.
Right arrow Articles by Olsen, J.
Related Collections
Right arrow Neurology & Psychiatry
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

Preeclampsia and Risk for Epilepsy in Offspring

Chun Sen Wu, MDa,b, Yuelian Sun, MD, PhDa, Mogens Vestergaard, MD, PhDa,c, Jakob Christensen, MD, PhDd, Roberta B. Ness, MD, PhDe, Catherine L. Haggerty, MD, PhDe and Jørn Olsen, MD, PhDa,f

Departments of a Epidemiology
c General Practice, Institute of Public Health, University of Aarhus, Aarhus, Denmark
b Center of Disease Prevention and Control of Jiexiu, Shanxi, China
d Department of Neurology and Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
e Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
f Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, California


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. Eclampsia has been found to be a strong risk factor for epilepsy in the offspring, but it is unclear whether the risk also applies to the preceding condition, preeclampsia.

METHODS. We conducted a population-based cohort study of 1537860 singletons born in Denmark (1978–2004). Information on preeclampsia (mild, severe, and unspecified), eclampsia, and epilepsy was obtained from the Danish National Hospital Register. Information on gestational age, birth weight, and Apgar score was obtained from the Danish Medical Birth Registry. We used Cox proportional hazard models to estimate the incidence rate ratio of epilepsy for children who were exposed to preeclampsia or eclampsia in prenatal life.

RESULTS. We identified 45288 (2.9%) children who were exposed to preeclampsia (34823 to mild, 7043 to severe, and 3422 to unspecified preeclampsia) and 654 (0.04%) to eclampsia during their prenatal life. We identified 20260 people who received a diagnosis of epilepsy during up to 27 years of follow-up in the entire cohort. Prenatal exposure to preeclampsia was associated with an increased risk for epilepsy among children with a gestational age at birth of at least 37 weeks. For mild preeclampsia, the incidence rate ratios were 1.16 among children born at term and 1.68 for children born postterm; for severe preeclampsia, the incidence rate ratios were 1.41 among children born at term and 2.57 among children born postterm. No associations between preeclampsia and epilepsy were found among children who were born preterm. Eclampsia was associated with epilepsy with an incidence rate ratio of 1.29 for children born at term and 5.03 for children born postterm.

CONCLUSIONS. Prenatal exposure to both preeclampsia and eclampsia was associated with an increased risk of epilepsy in children born after 37 weeks of gestation.

Key Words: eclampsia • epilepsy • pregnancy • preeclampsia • cohort studies

Abbreviations: ICD—International Classification of Diseases • SGA—small for gestational age • IRR—incidence rate ratio • CI—confidence interval • ACOG—American College of Obstetricians and Gynecologists

Preeclampsia is a common condition that affects ~2% to 8% of all pregnancies.1 It is a multisystem disorder that is clinically characterized by hypertension and proteinuria.2 Preeclampsia is an important risk factor for perinatal morbidity and mortality2,3 and may lead to eclampsia, a severe complication of preeclampsia with hyperreflexia, seizures, and coma. Pathophysiologic changes of preeclampsia, such as reduced placental perfusion, present before the appearance of clinical symptoms.4

A few studies have found that children of women with eclampsia have an increased risk for epilepsy.5,6 One cohort study from Canada even showed a 14-fold higher risk for epilepsy among children who were born to mothers with eclampsia;7 however, it is unclear whether this high risk is real and whether it also applies to the underlying precursor disease, preeclampsia. If this excess risk for epilepsy is a consequence of brain lesions that are induced by eclamptic seizures, then we would not expect to see any association with preeclampsia, because seizures are not part of this condition. Previous studies have shown an association between preeclampsia and neonatal encephalopathy, cerebral palsy, febrile seizures, and neurologic impairment.8–13 We evaluated the association between preeclampsia and eclampsia and the risk for epilepsy by taking intrauterine growth restriction and gestational age into account.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Study Population
We used data from the Danish Civil Registration System14 to identify all singletons born in Denmark between January 1, 1978, and December 2, 2004 (N = 1614039). All live-born children and new residents in Denmark are assigned a unique civil registration number, which we used to link information from national registries at an individual level.14 The Danish National Hospital Register15 contains information on almost all patients who have been admitted to Danish hospitals in Denmark since 1977, and outpatients have been included since 1995. The diagnostic information is based on the Danish version of the International Classification of Diseases, Eighth revision (ICD-8) from 1977 to 1993 and 10th revision (ICD-10) from 1994 onward. The Danish Medical Birth Registry has registered all births since 1973.16 We excluded children who were adopted (n = 6895), died or emigrated in the neonatal period (n = 8078), or had a missing value on gestational age (n = 60968) or parity (n = 238), leaving 1537860 children for the final analysis.

Preeclampsia and Eclampsia
In the Danish National Hospital Register,15 we obtained information on mild preeclampsia (ICD-8: 637.03; ICD-10: O14.0), severe preeclampsia (ICD-8: 637.04; ICD-10: O14.1), unspecified preeclampsia (ICD-8: 637.09; ICD-10: O14.9), and eclampsia (ICD-8: 637.1; ICD-10: O15). When there were >1 types of diagnosis for the same individual, we categorized them according to the following hierarchical order: eclampsia, severe preeclampsia, mild preeclampsia, and unspecified preeclampsia.

Epilepsy
Information on hospitalization with epilepsy was obtained from the Danish National Hospital Register.15 Cohort members (newborns in the period of recruitment) and their mothers were coded as having epilepsy when they were hospitalized or in hospital outpatient care with a diagnosis of epilepsy (ICD-8: 345; ICD-10: G40–G41). The onset of epilepsy in this study was defined as the first day of hospital contact that resulted in an epilepsy diagnosis.

Potential Confounding Factors
Information on gestational age, birth weight, maternal age at birth, parity, gender of the child, and Apgar score at 5 minutes after birth was obtained from the Danish Medical Birth Registry.16 During the recent 15 years, ultrasound as a measurement has been increasingly used to estimate the gestational age recorded in the Medical Birth Registry together with data on last menstrual period. Information on cerebral palsy (ICD-8: 343, 344; ICD-10: G80) and congenital malformation (ICD-8: 740–759; ICD-10: Q00–Q99) was obtained from the Danish National Hospital Register.15 We coded children as small for gestational age (SGA) when they had a birth weight below the 10th percentile of birth weight distribution according to each gestational week at birth and gender in the population we studied.17,18

Statistical Analysis
Children were followed from day 29 after birth (to exclude neonatal seizures) until the onset of epilepsy; death; emigration; or December 31, 2004, whichever came first. We used Cox proportional hazard models to assess incidence rate ratios (IRRs) for epilepsy and 95% confidence intervals (CIs) for children who were prenatally exposed to preeclampsia or eclampsia. We adjusted for gender of the child, gestational age in weeks, parity (1, 2, ≥3), maternal age (<25, 25, 30, 35, ≥40 years), maternal history of epilepsy (yes, no), and calendar year (1978–1981, 1982–1985, 1986–1989, 1990–1993, 1994–1997, 1998–2001, 2002–2004). First, we estimated the IRRs of epilepsy for children prenatally exposed to preeclampsia or eclampsia in the total population. Then we repeated the analysis after excluding children with cerebral palsy, congenital malformations, and an Apgar score <7 at 5 minutes after birth. We estimated the associations between preeclampsia (mild, severe, and unspecified) and the risk for epilepsy according to onset age of epilepsy to determine whether age modified the associations. Subsequently, we examined the associations between preeclampsia and the risk for epilepsy in the first 5 years of life according to calendar year of birth (4-year interval) to determine whether the association changed with time. We also evaluated the associations between preeclampsia and the risk for epilepsy according to gestational week at birth (20–32, 33–36, 37–41, ≥42 gestational weeks) and SGA and provided P value for interaction between preeclampsia (yes, no) and gestational age (preterm, nonpreterm). Finally, we repeated the analysis stratifying by parity to check whether the associations were different between children who were born to nulliparous mothers and those who were born to multiparous mothers.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Among 1537860 singletons, 45288 (2.94%) children were prenatally exposed to preeclampsia (34823 to mild, 7043 to severe, and 3422 to unspecified) and 654 (0.04%) to eclampsia. During up to 27 years of follow-up, we identified 20260 people with epilepsy.

Table 1 shows characteristics of the study population according to their exposure status. Children who were prenatally exposed to preeclampsia and eclampsia were more often born preterm and SGA than unexposed children.


View this table:
[in this window]
[in a new window]

  		TABLE 1 Characteristics of the Study Population according to Prenatal Exposure to Preeclampsia, Denmark, 1978–2004

 
The crude analyses revealed a higher risk for epilepsy among children who were exposed to preeclampsia and eclampsia. Although the estimates of IRR decreased when potential confounders were adjusted for, including gender of the child, gestational age in weeks, parity, maternal age, maternal history of epilepsy, and calendar year, the largest group, mild preeclampsia, remained statistically associated with epilepsy (IRR: 1.20 [95% CI: 1.10–1.32]). The IRRs for epilepsy changed slightly when children with cerebral palsy, congenital malformations, and low Apgar score (<7) were excluded (Table 2). The IRR between preeclampsia and epilepsy was not modified by time since birth (Fig 1).


View this table:
[in this window]
[in a new window]

  		TABLE 2 IRRs for Epilepsy in Children Exposed to Preeclampsia or Eclampsia, Denmark, 1978–2004

 

Figure 1
View larger version (10K):
[in this window]
[in a new window]

  		FIGURE 1 IRRs of epilepsy among children who were exposed to preeclampsia (mild and severe) according to age, Denmark, 1978–2004. Adjusted for gender of child, gestational age in weeks, parity (1, 2, ≥3), maternal age (<25, 25, 30, 35, ≥40 years), maternal history of epilepsy, and calendar year.

 
Preeclampsia was associated with an increased risk for epilepsy only among children who were born at term and postterm (P = .023 for interaction; Table 3). The associations between preeclampsia and the risk for epilepsy in the first 5 years among children who were born at term and postterm followed the same pattern over time (Fig 2).


View this table:
[in this window]
[in a new window]

  		TABLE 3 IRRs for Epilepsy in Children Exposed to Preeclampsia (Mild and Severe) or Eclampsia Stratifying by Gestational Age, Denmark, 1978–2004

 

Figure 2
View larger version (13K):
[in this window]
[in a new window]

  		FIGURE 2 IRRs of epilepsy in the first 5 years among term- and postterm-born children who were exposed to preeclampsia according to calendar year. Adjusted for gender, gestational age in weeks, parity (1, 2, ≥3), maternal age (<25, 25, 30, 35, ≥40 years), and maternal history of epilepsy.

 
Table 4 shows that both preeclampsia and SGA were independent risk factors for epilepsy. Among children who were born at ≥37 weeks of gestation, the highest IRR was found among children who were prenatally exposed to SGA as well as preeclampsia (Table 4). The associations between preeclampsia and the risk for epilepsy were similar between children who were born to nulliparous mothers and those who were born to multiparous mothers (data not shown).


View this table:
[in this window]
[in a new window]

  		TABLE 4 IRRs for Epilepsy in Children Exposed to Mothers With Preeclampsia (Mild and Severe) or Eclampsia Stratified by SGA, Denmark, 1978–2004

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Preeclampsia and eclampsia both were associated with an increased risk for epilepsy but only in children who were born after 37 weeks of gestation. Because preeclampsia seems to be as strong a risk indicator for epilepsy as eclampsia, the increased risk for epilepsy seems not to be only entirely induced by seizures. Our findings on eclampsia are in keeping with some5,19–21 but not all previous studies.6,7 A case-control study indicated a two-fold increased risk for epilepsy among children who were born to mothers with eclampsia.5 Rocca et al19–21 found that children of mothers with eclampsia had a two-fold higher risk for generalized tonic-clonic seizures, partial seizures, and absence seizures than those nonexposed, but the associations were not statistically significant. Degen6 found that 9 of 100 children with epilepsy had been exposed to eclampsia as compared with 0 of 100 children without epilepsy. Whitehead et al7 found a 14-fold higher risk for epilepsy among children who were born to mothers with eclampsia compared with children who were born to mothers without eclampsia, but the sample size was small and <5 children with epilepsy were identified. Bias and confounding may explain the difference of the findings. None of these studies5–7,19–21 accounted for gestational age at birth, although the risk for epilepsy tends to increase with decreasing gestational age.22

The effect measure modification by gestational age on the risk for epilepsy is similar to what has been found for cerebral palsy.23,24 The biological explanation for this remains unknown but could reflect that other causes of preterm birth outweigh the effect of preeclampsia23–25 or indicate that the pathology related to preeclampsia needs gestational time to increase the susceptibility to epilepsy, or the fetal brain may be more susceptible later in pregnancy. Preeclampsia with an early onset may also be a different disease26 that need not be related to the risk for epilepsy. It is important to try to disentangle these different options, because they have different consequences for clinical management.

Early-onset and late-onset preeclampsia have different characteristics and perhaps different causes.26,27 Early-onset preeclampsia is often associated with an abnormal placental morphology, intrauterine growth restriction, and a family history of preeclampsia.26,27 We did not have data on onset date of preeclampsia. We had data only on the time of hospitalization that need not correspond with onset dates for preeclampsia; therefore, we cannot explore whether the associations differed between early-onset and late-onset preeclampsia, although the lack of association among children who were born preterm suggests that early-onset preeclampsia may not have a strong effect on epilepsy at least comparing with other risk factors that lead to preterm delivery, or early induction of birth eliminates the association.

The mechanisms underlying the associations between preeclampsia and epilepsy are unknown. Preeclampsia may cause fetal brain ischemia and vascular fetal brain lesions. Preeclampsia has been shown to be an important risk factor for newborn encephalopathy.28 The associations may be mediated by placental dysfunction, which the modifying effect of SGA may suggest. If the associations that we found were mediated by biological changes induced by preeclampsia, then one would not expect to see any increased risk among siblings who were themselves unexposed to preeclampsia. Conversely, if time-stable factors underlying causes such as genetic or lifestyle factors played a role, then we would expect to find higher risks for epilepsy even among unexposed siblings, which can be studied. Previous studies showed that cerebral palsy, congenital malformations, and low Apgar scores were associated with an increased risk for epilepsy,7,29,30 but our findings remained when we excluded these risk factors from the analysis.

A major strength of our study is the use of a population-based cohort that included all children who were born in Denmark and had up to 27 years of almost complete follow-up. Bias as a result of selection of study participants or nonresponses cannot explain our findings. Our ability to adjust for potential confounders, however, was limited.

There are 2 Danish guidelines for diagnosing preeclampsia.31,32 The criteria for diagnosing of mild preeclampsia in both are similar to that used by the American College of Obstetricians and Gynecologist (ACOG; diastolic blood pressure ≥90 mm Hg or systolic blood pressure ≥140 mm Hg and proteinuria with total loss of protein in a 24-hour urine specimen ≥0.3 g).33 For the criteria of severe preeclampsia, 180 mm Hg was used as a cut point for systolic blood pressure rather than 160 mm Hg as used in the ACOG, and 3 g loss of protein in a 24-hour urine specimen was used in 1 of the guidelines rather than 5 g in the ACOG. In practice, however, the criteria of the ACOG are also used in Denmark to diagnose severe preeclampsia.34 Use of >1 set of criteria for diagnosing preeclampsia will probably generate some misclassification between mild and severe types of the disorder.

Information on preeclampsia and eclampsia was obtained from the Danish National Hospital Register. The positive predictive value of a preeclampsia diagnosis in the register has been estimated to be 74%, but the positive predictive value for severe preeclampsia diagnosis was almost 100%.35 The sensitivity of the preeclampsia diagnosis in the register is ~70%.35 Because the registration of preeclampsia took place before the outcome (epilepsy) in this study, the misclassification of diagnosis of preeclampsia is expected to be nondifferential, which often attenuates effect measures.36 We expect that the quality of an unspecified preeclampsia diagnosis is lower, but we have no validation studies on which to rely.

Data on gestational age are not always accurate. Gestational age that is based on last menstrual period may be biased by early pregnancy bleeding, irregular periods, use of contraceptive pills, and recall problems.37 Gestational age that is based on ultrasound may be biased by exposures that impair early fetal growth.38 Because preeclampsia is associated with an increased risk for intrauterine growth restriction,39 children who are born to mothers with preeclampsia may be more likely to be recorded with a lower gestational age if the estimate was based on ultrasound examination, which may inflate the incidence of preterm birth.

The positive predictive value of an epilepsy diagnosis in the Danish Hospital Register has been assessed according to International League Against Epilepsy criteria40 and found to be 81% (95% CI: 75%–87%).41 The true validity of the epilepsy diagnosis may be higher because 40% of those who did not fulfill the criteria for epilepsy (at least 2 unprovoked seizures on separate days) had experienced a single unprovoked seizure.41 Unfortunately, we do not have data on the completeness of the register for epilepsy cases, and it is likely that some children are not hospitalized. We expect the numbers of unregistered epilepsy cases to be small, because hospitalization is tax paid and free of charge for patients in Denmark. We do not expect that the completeness of epilepsy registration was different for children who were exposed to preeclampsia than for those who were not exposed. Thus, any bias is likely to be small; however, our study was limited by a lack of clinical data on subtypes of epilepsy, and the associations that we found in this study may be different for specific subtypes of epilepsy.


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Preeclampsia and eclampsia were associated with an increased risk for epilepsy in children who were born after 37 weeks of gestation. Preeclampsia or its related pathologies may increase the susceptibility to epilepsy later in life, or preeclampsia and epilepsy may also share common causative factors.


   ACKNOWLEDGMENTS
 
This study was supported by grants from the National Institutes of Health (1 R01 AI071386-01 [111536–4]) and the Danish Medical Research Council (271-05-0518).


   FOOTNOTES
 
Accepted Mar 3, 2008.

Address correspondence to Chun Sen Wu, MD, Department of Epidemiology, University of Aarhus, Vennelyst Boulevard 6, Aarhus, 8000 C, Denmark. E-mail: cw{at}soci.au.dk

The authors have indicated they have no financial relationships relevant to this article to disclose.


What's Known on This Subject

A few studies have found that children of women with eclampsia have an increased risk for epilepsy; however, it is unclear whether the risk also applies to the underlying disease, preeclampsia.

 

What This Study Adds

Preeclampsia was associated with an increased risk for epilepsy in the offspring, but the association was modified by the child's gestational age at birth. The increased risk for epilepsy was found only among children who were born after 37 weeks of gestation.

 


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Duley L, Meher S, Abalos E. Management of pre-eclampsia. BMJ. 2006;332 (7539):463 –468[Free Full Text]
  2. Villar J, Say L, Gulmezoglu M, et al. Eclampsia and pre-eclampsia: a worldwide health problem for 2000 years. In: Critchley H, Maclean A, Poston L, Walter J, eds. Pre-eclampsia. London, England: PCOG Press; 2003:189–207
  3. Walker JJ. Pre-eclampsia. Lancet. 2000;356 (9237):1260 –1265[CrossRef][Web of Science][Medline]
  4. Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. 2005;46 (6):1243 –1249[Abstract/Free Full Text]
  5. Lilienfeld AM, Pasamanick B. Association of maternal and fetal factors with the development of epilepsy: I—abnormalities in the prenatal and paranatal periods. J Am Med Assoc. 1954;155 (8):719 –724[Abstract/Free Full Text]
  6. Degen R. Epilepsy in children: an etiological study based on their obstetrical records. J Neurol. 1978;217 (3):145 –158[CrossRef][Web of Science][Medline]
  7. Whitehead E, Dodds L, Joseph KS, et al. Relation of pregnancy and neonatal factors to subsequent development of childhood epilepsy: a population-based cohort study. Pediatrics. 2006;117 (4):1298 –1306[Abstract/Free Full Text]
  8. Impey L, Greenwood C, Sheil O, MacQuillan K, Reynolds M, Redman C. The relation between pre-eclampsia at term and neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2001;85 (3):F170 –F172[Abstract/Free Full Text]
  9. Baud O, Zupan V, Lacaze-Masmonteil T, et al. The relationships between antenatal management, the cause of delivery and neonatal outcome in a large cohort of very preterm singleton infants. BJOG. 2000;107 (7):877 –884[Medline]
  10. Martikainen MA, Airaksinen EM, Heinonen KM, Castren ML. The neurological condition of the newborn infant with maternal hypertension, examined at term. Early Hum Dev. 1988;16 (2–3):107 –118[CrossRef][Web of Science][Medline]
  11. Spinillo A, Iasci A, Capuzzo E, Egbe TO, Colonna L, Fazzi E. Two-year infant neurodevelopmental outcome after expectant management and indicated preterm delivery in hypertensive pregnancies. Acta Obstet Gynecol Scand. 1994;73 (8):625 –629[Web of Science][Medline]
  12. Thorngren-Jerneck K, Herbst A. Perinatal factors associated with cerebral palsy in children born in Sweden. Obstet Gynecol. 2006;108 (6):1499 –1505[CrossRef][Web of Science][Medline]
  13. Vestergaard M, Basso O, Henriksen TB, Ostergaard J, Secher NJ, Olsen J. Pre-eclampsia and febrile convulsions. Arch Dis Child. 2003;88 (8):726 –727[Abstract/Free Full Text]
  14. Pedersen CB, Gøtzsche H, Møller JØ, Mortensen PB. The Danish Civil Registration System: a cohort of eight million persons. Dan Med Bull. 2006;53 (4):441 –449[Medline]
  15. Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH. The Danish National Hospital Register: a valuable source of data for modern health sciences. Dan Med Bull. 1999;46 (3):263 –268[Web of Science][Medline]
  16. Knudsen LB, Olsen J. The Danish Medical Birth Registry. Dan Med Bull. 1998;45 (3):320 –323[Web of Science][Medline]
  17. Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol. 1996;87 (2):163 –168[CrossRef][Web of Science][Medline]
  18. Bamberg C, Kalache KD. Prenatal diagnosis of fetal growth restriction. Semin Fetal Neonatal Med. 2004;9 (5):387 –394[CrossRef][Medline]
  19. Rocca WA, Sharbrough FW, Hauser WA, Annegers JF, Schoenberg BS. Risk factors for complex partial seizures: a population-based case-control study. Ann Neurol. 1987;21 (1):22 –31[CrossRef][Web of Science][Medline]
  20. Rocca WA, Sharbrough FW, Hauser WA, Annegers JF, Schoenberg BS. Risk factors for absence seizures: a population-based case-control study in Rochester, Minnesota. Neurology. 1987;37 (8):1309 –1314[Abstract/Free Full Text]
  21. Rocca WA, Sharbrough FW, Hauser WA, Annegers JF, Schoenberg BS. Risk factors for generalized tonic-clonic seizures: a population-based case-control study in Rochester, Minnesota. Neurology. 1987;37 (8):1315 –1322[Abstract/Free Full Text]
  22. Sun Y, Vestergaard M, Pedersen CB, Christensen J, Basso O, Olsen J. Gestational age, birth weight, intrauterine growth, and the risk of epilepsy. Am J Epidemiol. 2008;167 (3):262 –270[Abstract/Free Full Text]
  23. Collins M, Paneth N. Preeclampsia and cerebral palsy: are they related? Dev Med Child Neurol. 1998;40 (3):207 –211[Web of Science][Medline]
  24. Greenwood C, Yudkin P, Sellers S, Impey L, Doyle P. Why is there a modifying effect of gestational age on risk factors for cerebral palsy? Arch Dis Child Fetal Neonatal Ed. 2005;90 (2):F141 –F146[Abstract/Free Full Text]
  25. Kuban KC, Leviton A. Cerebral palsy. N Engl J Med. 1994;330 (3):188 –195[Free Full Text]
  26. Egbor M, Ansari T, Morris N, Green CJ, Sibbons PD. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006;113 (5):580 –589[CrossRef][Web of Science][Medline]
  27. Oudejans CB, van Dijk M, Oosterkamp M, Lachmeijer A, Blankenstein MA. Genetics of preeclampsia: paradigm shifts. Hum Genet. 2007;120 (5):607 –612[CrossRef][Web of Science][Medline]
  28. Badawi N, Kurinczuk JJ, Keogh JM, et al. Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study. BMJ. 1998;317 (7172):1549 –1553[Abstract/Free Full Text]
  29. Sun Y, Vestergaard M, Pedersen CB, Christensen J, Olsen J. Apgar scores and long-term risk of epilepsy. Epidemiology. 2006;17 (3):296 –301[CrossRef][Web of Science][Medline]
  30. Wallace SJ. Epilepsy in cerebral palsy. Dev Med Child Neurol. 2001;43 (10):713 –717[CrossRef][Web of Science][Medline]
  31. Lange AP. Obstetric Guidelines in Coding and Definitions. Copenhagen, Denmark: DSOG; 1996
  32. Johansen M, Kjaergaard N, Legarth J, Salvig JD, Skajaa K, Wilken-Jensen C. Hypertension in pregnancy. Sandbjerg guidelines. Available at: www.dsog.dk/files/Praeeklampsi%202001.htm; 2001
  33. ACOG. National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 1990;163 (5 pt 1):1691 –1712[Web of Science][Medline]
  34. Klemmensen ÅK, Olsen SF, Wengel CM, Tabor A. Diagnostic criteria and reporting procedures for pre-eclampsia: a national survey among obstetrical departments in Denmark. Eur J Obstet Gynecol Reprod Biol. 2005;123 (1):41 –45[CrossRef][Web of Science][Medline]
  35. Klemmensen ÅK, Olsen SF, Osterdal ML, Tabor A. Validity of preeclampsia-related diagnoses recorded in a national hospital registry and in a postpartum interview of the women. Am J Epidemiol. 2007;166 (2):117 –124[Abstract/Free Full Text]
  36. Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia, PA: Lippincott-Raven Publisher; 1998
  37. DiPietro JA, Allen MC. Estimation of gestational age: implications for developmental research. Child Dev. 1991;62 (5):1184 –1199[CrossRef][Web of Science][Medline]
  38. Henriksen TB, Wilcox AJ, Hedegaard M, Secher NJ. Bias in studies of preterm and postterm delivery due to ultrasound assessment of gestational age. Epidemiology. 1995;6 (5):533 –537[Web of Science][Medline]
  39. Ødegård RA, Vatten LJ, Nilsen ST, Salvesen KÅ, Austgulen R. Preeclampsia and fetal growth. Obstet Gynecol. 2000;96 (6):950 –955[CrossRef][Web of Science][Medline]
  40. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1989;30 (4):389 –399[Web of Science][Medline]
  41. Christensen J, Vestergaard M, Olsen J, Sidenius P. Validation of epilepsy diagnoses in the Danish National Hospital Register. Epilepsy Res. 2007;75 (2–3):162 –170[CrossRef][Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Am J EpidemiolHome page
V. Ehrenstein, K. J. Rothman, L. Pedersen, E. E. Hatch, and H. T. Sorensen
Pregnancy-associated Hypertensive Disorders and Adult Cognitive Function Among Danish Conscripts
Am. J. Epidemiol., October 15, 2009; 170(8): 1025 - 1031.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, C. S.
Right arrow Articles by Olsen, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, C. S.
Right arrow Articles by Olsen, J.
Related Collections
Right arrow Neurology & Psychiatry
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?