Infants of mothers with epilepsy (IME), are at greater risk for a variety of adverse outcomes of pregnancy. To date most research has focused on congenital malformations. Neonatal and infant mortality rates have been found to be elevated as well. Some of the excess of mortality has been associated with low birth weight, the lower socioeconomic status of many persons with epilepsy has so far been considered a significant confounding factor. We studied fetal death, neonatal and infant mortality rates in 484 infants of mothers with epilepsy (IME), 250 infants of mothers who had convulsions during the pregnancy (IMC), 543 infants whose mothers had post partum convulsions (PPC), 62 infants of mothers with eclampsia (E), and 112,813 controls living in Washington State delivering between 1988 - 1992. All were Medicaid clients, therefore of similar socioeconomic status. Infants of Mothers with epilepsy were three times as likely to have a fetal death as were infants of control mothers. Post neonatal mortality rates were slightly higher for IME (0.6% vs. 0.4% for controls), and even higher for those with post partum convulsions (3% if the child also had seizures vs... 2.1% if the child did not). It appears as though gestational seizures not simply maternal epilepsy is associated with an increased risk for post neonatal death. Infants of mothers with epilepsy are at significantly greater risk for fetal death which cannot simply be explained by differences in socioeconomic status or access to medical care.

The pregnancy outcomes of six groups of women Medicaid clients were compared. All of whom delivered in the State of Washington between 1988 and 1992. They were divided into 6 groups.

The first group were 484 children of 477 women with a diagnosis of epilepsy.

The second 62 infants of 61 women with eclampsia.

The third 250 children of 247 women with no diagnosis of epilepsy but who were diagnosed as having a convulsion during their pregnancy.

The fourth group was 164 children of 162 women with post partum convulsions whose children also had seizures in the postpartum period. These women had no diagnosis of epilepsy.

The fifth group, 379 infants of 373 women with post partum convulsions in which the children were free of seizures.

The sixth group 112,813 children of 11,598 control women without diagnosis of epilepsy, eclampsia or convulsions. The outcomes are listed in table 1.

Washington State's First Steps Database (FSDB) was used to identify women with epilepsy who gave birth between July 1988 and December 1992. The FSDB contains information from (1) birth and death certificates collected by the Center for Health Statistics of the Department of Health and (2) Medicaid claims and eligibility files maintained by the Medical Assistance Administration of the Department of Social and Health Services. The database includes maternal claims for nine months of pregnancy and two months postpartum and infant claims for the first twelve months of life.

Non-Medicaid women were excluded from this study since it was not possible to ascertain their seizure history because no claims records were available for non medicaid women.

Adverse birth outcomes studied included low birth weight, fetal deaths, neonatal and postneonatal mortality. Birthweight was obtained from the birth certificate. Multiple birth and fetal deaths were excluded from calculations of the low birth weight rate. The low birthweight was defined as the percentage of singleton liveborn infants weighting less than 2500 grams. Fetal deaths were identified from death certificates matched to birth certificates. Neonatal mortality rates were reported as the number of neonatal deaths (death of an infant within the first 27 days of life) per 1000 liveborn infants. Postneonatal mortality rates were reported as the number of postneonatal deaths (death of an infant between days 28 and 365 of life) per 1000 liveborn infants.

Maternal characteristics: Maternal age, marital status, race, smoking history, and month prenatal care began were obtained from the birth certificate. Medicaid women included those matched to birth certificates with medicaid funding for prenatal care and/or delivery.

Selected diagnostic codes (ICD-9) from Medicaid claims (291, 292, 303, 304, 305, excluding 305.1, for mothers and 760.71, -.72, -.73, -.75, -.79, and 779.5 for infants) were used to identify women as substance abusers.

Death outcomes were defined as: Fetal Death, a child born dead after 20 weeks gestation; Neonatal Death, a live born child who died between 1 and 28 days of life; Post Neonatal Death, a child who died between 29 and 365 days of life. Women with epilepsy were at greater risk for having a fetal death regardless of their seizure control. Their children were also at greater risk for neonatal and post neonatal death. Women without epilepsy or eclampsia but with gestational convulsions were also at greater risk for fetal death, neonatal and post neonatal death. Maternal substance abuse alone is associated with increased risks of fetal, neonatal and post neonatal death. When WWE also suffer from substance abuse the risk of these outcomes is higher than with maternal epilepsy or substance abuse alone.

The effect of potential confounding factors: maternal gestational seizures and maternal substance abuse was examined for the outcomes birth weight and death. Birth weight was stratified into: very low birth weight (VLBW) < 1500gr.; medium low birth weight (MLBW) 1500 - 2499gr.; normal birth weight (NBW) > 2500gr. Mothers were stratified into: Maternal Epilepsy no convulsions, 1 - 3 convulsions, 3 - 5 convulsions, or > 6 convulsions during the pregnancy. Women without a diagnosis of epilepsy but with gestational convulsions were stratified into similar categories.

For WWE substance abuse independent of maternal seizures increased the risk of low and very low birthweight. Women with maternal convulsions without a diagnosis of epilepsy or eclampsia are at significantly greater risk for bearing low and very low birthweight babies.

A disturbing potential confounder is substance abuse. Fourteen point four percent of women with epilepsy and women presenting with gestational convulsions were felt by their physicians to abuse alcohol drugs or both. This compares unfavorably with control women of whom only 6% were diagnosed as substance abusers.

The causes of death for the children in the various groups are listed. Of note is the higher than expected occurrence of sudden infant death syndrome (SIDS) in the infants of mothers with epilepsy (0.61%) compared to controls (0.17%). In fact 21% (3 of 14) of the deaths in infants of mothers with epilepsy were due to SIDS.

Previous studies demonstrating increased death rates for infants of mothers with epilepsy failed to control for socioeconomic status. When this is done we find no increased risk of neo or post neonatal death for infants of mothers with epilepsy compared to controls. We do however find that women with convulsions during pregnancy or the post partum period have significantly higher rates of postneonatal death and low birthweight.

While there is a potential for misclassification among these groups with some women with gestational or post partum convulsions actually having epilepsy we feel this risk is low. We know that none of the women with convulsions in pregnancy had a previous diagnosis of epilepsy despite the fact that they had been receiving medical care. This group was more likely to smoke and had higher marital rates than other groups. Their rates of offspring with low birth weight and gestational age of 28 - 37 weeks is similar to that of women with eclampsia. These women also had a rate of substance abuse significantly higher than that of the controls (14.4% vs.. 6%). This group may therefore consist of persons with a variety of diagnoses with some possibly having eclampsia.

The proportion of women with epilepsy (14.4%) abusing drugs or alcohol is significantly higher than controls (6%). This is particularly discouraging in light of the fact that such use can worsen epilepsy. One would hope that persons with epilepsy would be counseled against such activities.

Convulsions have long been recognized as hazardous to patients. It is therefore not difficult to accept the observation of a higher mortality rate among children exposed to convulsions in than those who are not even if their mother has epilepsy. What is more difficult to explain is why women with postpartum convulsions should also have children with higher mortality rates. We attempted to eliminate systemic effects by segregating out women with eclampsia, but interestingly enough none of these 61 eclamptic women had a neonatal or post neo natal death.

The marked increase in the risk of SIDS in IME (0.6%) is a new observation. Sudden death has been well described in persons with epilepsy. Previous studies have suggested that the risk of a child

whose mother has epilepsy, developing epilepsy themselves is approximately 3% compared to 1% in the general population. It is possible that SIDS is a manifestation of a neurological disorder.

Infants of Women with epilepsy are at greater risk for adverse pregnancy outcomes even after controlling for socioeconomic status and access to prenatal care. In particular they have an increased risk of fetal death, (1.7%). When causes of neonatal and post neonatal death are evaluated for this population a three fold increase in the rate of sudden infant death syndrome is found accounting for 21% of the deaths in this group of children.

Infants of mothers who have convulsions during gestation or post partum have higher rates of post neonatal death,(1.2 - 2.1%). The death rates are higher if the child also had convulsive seizures (3.0%).

Both maternal epilepsy and convulsive seizures during pregnancy appear to contribute to an increase in the rates of fetal and post neonatal death respectively. Most previous research has concentrated on congenital malformations as the most important adverse outcome of pregnancy for women with epilepsy. This study suggests that the increased magnitude of fetal loss and infant mortality is as significant as the problem of malformations.

Mark S. Yerby M.D., M.P.H.
North Pacific Epilepsy Research
Mother Joseph Plaza
9427 SW Barnes Road - Suite 595
Phone: 503-291-5300
Fax: 503-291-5303

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