Estradiol, estriol, progesterone, prolactin, and human chorionic gonadotropin in pregnant women with alcohol abuse.

Serum estradiol, estriol, progesterone, PRL, and hCG concentrations were measured at 4-week intervals in 40 pregnant women who chronically abused alcohol and in 20 abstinent pregnant women. Sixteen alcohol users gave birth to infants with the fetal alcohol syndrome (FAS), whereas the remaining 24 infants of alcohol users and all infants of the abstinent women were healthy. The women whose infants had the FAS had decreased estradiol and estriol levels throughout pregnancy. Progesterone levels also tended to be low. In contrast, the alcohol users had increased PRL levels during the 16-24th weeks of pregnancy compared with those in the abstinent women, but this rise was not related to the FAS. The concentrations of hCG fluctuated widely, without any consistent difference between alcohol users and abstinent women. Thus, heavy maternal abuse of alcohol resulting in FAS is accompanied, primarily or secondarily, by reduced estrogen concentrations throughout pregnancy and increased PRL levels during the 16-24th weeks of pregnancy.

Minor anomalies in children of mothers with epilepsy.

Minor anomalies are small, structural deviations that result from alterations in morphogenesis during gestation. Multiple minor anomalies are clinically significant, because they are associated with an increased risk of major developmental defects in the affected individuals. Children of mothers with epilepsy have an excess of minor and major anomalies as compared with the incidence in children of parents without epilepsy. Of the typical minor anomalies described in offspring of mothers with epilepsy, most features appear to be genetically linked with epilepsy. Only distal digital hypoplasia seems to be a specific marker for phenytoin teratogenicity. In most children, distal digital hypoplasia is not associated with serious developmental disorders. Genetic defects in the mechanisms of drug detoxification in the fetus and treatment of the mother with more than one antiepileptic drug during pregnancy increase the risk of severe teratogenic effects in offspring.

Psychomotor development in children of mothers with epilepsy.

The risk of psychomotor retardation and the prevalence of mental subnormality are slightly increased in offspring of mothers with epilepsy. The prevalence rates of mental deficiency observed in population-based studies have been lower than those in reports of hospital-based studies. In addition to use of antiepileptic drugs (AEDs), several other factors associated with maternal epilepsy, such as seizures during pregnancy, inherited brain disorders, and nonoptimal psychosocial environment, can affect the child's psychomotor development. None of the major AEDs carries any special risk for mental retardation. However, polytherapy and inherited deviations in AED metabolism in the fetus probably do increase the risk for mental retardation.

Focal and global cortical hypometabolism in patients with newly diagnosed infantile spasms.

OBJECTIVE: To evaluate the occurrence and prognostic importance of focal defects in cerebral cortical glucose metabolism in infants with newly diagnosed symptomatic and cryptogenic infantile spasms. PATIENTS AND METHODS: Ten children with symptomatic and seven with cryptogenic infantile spasms underwent MRI, video-EEG, and PET using fluorodeoxyglucose as a tracer within 2 weeks of diagnosis. PET was repeated at 1 year of age in 12 patients. RESULTS: Cortical hypometabolic foci were found in 13 children (77%) with newly diagnosed spasms (six cryptogenic and seven symptomatic). The hypometabolic foci disappeared in seven of nine reexamined at age 1. The occipital foci disappeared in all (n = 6). Focal findings on PET correlated well with focal findings on video-EEG. There was no difference in quantitative cortical or subcortical glucose metabolic rate at the onset of infantile spasms between children with cryptogenic and symptomatic etiology of spasms. The glucose metabolic rate at the onset of spasms or focal lesions in glucose metabolism did not have prognostic value for seizure outcome. CONCLUSIONS: Infantile spasms are often associated with transient cortical, especially occipital, hypometabolic foci that are not necessarily associated with structural lesions and do not indicate a poor prognosis.

Apparent asynchrony between interictal electric and magnetic spikes.

We recorded simultaneous multichannel electroencephalogram (EEG) and magnetoencephalogram (MEG) in four children with partial epilepsy. Sources of averaged spikes were modelled with current dipoles. Of 10 spike averages obtained, three peaked simultaneously in MEG and EEG, and in seven averages, the MEG peak preceded the main EEG peak by 9-40 ms. A small positive early EEG signal coincided with the MEG peak in six asynchronous spikes. The simultaneous MEG and EEG spikes originated within 5-23 mm, while sources of asynchronous peaks were 12-67 mm apart. We conclude that non-identical neurone currents underlie the MEG and EEG signals, and emphasize the importance of modelling early phases of EEG spikes when localizing interictal epileptic zones.

Landau-Kleffner syndrome: epileptic activity in the auditory cortex.

The Landau-Kleffner syndrome (LKS) is characterized by electroencephalographic spike discharges and verbal auditory agnosia in previously healthy children. We recorded magnetoencephalographic (MEG) spikes in a patient with LKS, and compared their sources with anatomical information from magnetic resonance imaging. All spikes originated close to the left auditory cortex. The evoked responses were contaminated by spikes in the left auditory area and suppressed in the right--the latter responses recovered when the spikes disappeared. We suggest that unilateral discharges at or near the auditory cortex disrupt auditory discrimination in the affected hemisphere, and lead to suppression of auditory information from the opposite hemisphere, thereby accounting for the two main criteria of LKS.

Parietal epileptic mirror focus detected with a whole-head neuromagnetometer.

Whole-head magnetoencephalographic recordings revealed two parietal epileptic foci in homotopic areas of the hemispheres. The discharges occurred 17-20 ms later on the left than on the right hemisphere, implying the existence of a left-sided mirror focus. The foci were about 1 cm posterior to the hand primary somatosensory area, identified by evoked response measurements, and thus suggested epileptic activity at the parietal association cortex, in agreement with the observed callosal conduction time.

A transient retardation of early postnatal growth in drug-exposed children of epileptic mothers.

Increase of length and weight during the first 6 months of life, and height at 1 and 5.5 years of age were investigated in 132 children of epileptic mothers (the study group) and 103 control children born after 37 completed gestational weeks. One hundred and seventeen children had been exposed to antiepileptic drugs in utero: 48 to phenytoin monotherapy, 16 to carbamazepine monotherapy, 24 to barbiturates (23 in combination with other drugs), 27 to drug combinations including phenytoin and/or carbamazepine but not barbiturates, and 2 to other drugs. There was no evidence of intrauterine drug exposure causing prenatal growth retardation. The mean length increment in the first postnatal month was significantly smaller in the drug-exposed children than in the non-exposed study children or controls. The drug-exposed children also gained significantly less weight during the first postnatal month than non-exposed study group children. A normal growth rate was already resumed in the drug-exposed group in the second postnatal month. Sedative drug effects on the neonate probably partly explain the transient weight lag, especially in the barbiturate-exposed subgroup. The marked delay in length gain suggests that a hormonal mechanism, perhaps a reversible suppression of thyroid function, might also be involved. The transient growth retardation was not associated with an excess of minor anomalies or impaired intelligence at 5.5 years of age. As only 1 drug-exposed child had persistent postnatal growth deficiency combined with other signs suggesting a prenatal disorder, the risk of teratogenic growth deficiency caused by antiepileptic drug exposure seems to be very low.

Head circumference in children of epileptic mothers: contributions of drug exposure and genetic background.

Head circumference after the first year of life was investigated in 144 children of epileptic mothers ('study group'). Fifty-two children had been exposed to phenytoin monotherapy, 19 to carbamazepine monotherapy, 27 to drug combinations including barbiturates, 29 to other drug combinations, and 17 children had not been exposed to antiepileptic drugs (AEDs) during pregnancy. The prevalence of microcephaly (2.1%) was no higher than that in the general population. Head circumference was measured at 5.5 years in 121 of the study group children, in 105 control children, and in the majority of their parents (118 mothers and 89 fathers in the study group, and 103 mothers and 65 fathers in the control group). The sex-adjusted head circumferences of the children showed a significant variation according to exposure subgroup, with the barbiturate and carbamazepine monotherapy exposed children having the lowest mean values. This result is similar to our previous findings in the same children at birth and at 18 months of age. Paternal head circumference was also below average in the same subgroups. After further adjustment for parental head circumference, the significant variation between the subgroups of children disappeared, even though the barbiturate exposed children continued to have the lowest mean value. Genetic causes may thus contribute to the relatively small head circumference in some AED exposed children of epileptic mothers. However, a mild drug effect in the barbiturate and carbamazepine exposed children cannot be excluded.

Oxcarbazepine in the treatment of early childhood epilepsy.

Very little data are available on the usefulness of oxcarbazepine in young children with epilepsy. From January 1991 through October 1994, we treated 53 children under age 7 years with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 13 months. Etiology was symptomatic in 39, cryptogenic in 12, and idiopathic in 2 children. Forty-three children had previously been intractable to one or more antiepileptic drugs (including carbamazepine in 30 patients) and two had carbamazepine hypersensitivity. The age at onset of oxcarbazepine therapy ranged from 0.6 to 6.9 years (mean, 3.9 yr). The mean maximum oxcarbazepine dose was 50 mg/kg/day (range, 21-86 mg/kg/day). Of the children with localization-related epilepsy, 12 of 44 (27%) became seizure free and an additional 16 of 44 (36%) had an at least 50% reduction of seizures. Five of nine children with generalized epilepsy also had some benefit but none became seizure free. In the 33 children with at least 50% seizure reduction, the mean effective dose and trough serum level of the active metabolite monohydroxycarbazepine were 47 mg/kg/day (range, 21-75 mg/kg/day) and 91 micromol/L (range, 42-130 micromol/L), respectively. Efficacy was transient in 4 children; side effects were observed in 17 children (32%); in 9 (17%) of whom, they led to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for localization-related early childhood epilepsy. Young children need a higher dose per body weight than adults.

Monitoring of concentrations of clobazam and norclobazam in serum and saliva of children with epilepsy.

Clobazam was added to the previous antiepileptic drug therapy of 90 children suffering from drug resistant epilepsy. Ten patients became seizure free, although four of these later developed tolerance. Thirty-three patients experienced a decrease in seizure frequency, and 24 of these, too, developed tolerance. Forty-four patients showed no change in seizure frequency, and three experienced an increase. The best results were experienced by patients with myoclonic seizures, whereas patients with complex partial seizures usually developed tolerance. The concentrations of clobazam and its active metabolite norclobazam were measured in 251 serum and 57 saliva samples. The group of seizure-free patients had the lowest clobazam and norclobazam concentrations; tolerance was associated with the highest concentrations. Beneficial side effects were associated with low, and adverse effects with high, concentrations of norclobazam. The concentrations of clobazam and norclobazam in saliva correlated with concentrations in serum. Monitoring of serum and salivary concentrations of clobazam and norclobazam is of limited value only, and no therapeutic target range can be given.

Development of children with early cytomegalovirus infection.

To find out whether cytomegalovirus (CMV) infection during the first months of life influences child development, developmental assessment at the age of 2 years was performed on 116 Finnish children chosen at random in a maternity hospital and followed from birth for the occurrence of CMV infection. Two of the children had congenital infection and 39 were infected after birth but before the age of 6 months. Another five children were infected between the ages of 6 and 12 months, and 70 remained non-infected. The developmental assessment, based principally on the Denver Development Screening Test (DDST), included 7 items for gross motor skills, 6 items for fine motor skills, and 4 items for language development. Significantly more perinatally infected children (7/39) were delayed in speech, compared with the non-infected children (3/70). Furthermore, some items assessing fine motor development were passed better by the non-infected than the perinatally infected children, but the difference in total score was not significant. The performance of the two children with congenital CMV infection did not differ from that of the non-infected children.

Illnesses during the first two years of life and their association with perinatal cytomegalovirus infection.

In order to find out whether perinatal cytomegalovirus (CMV) infection causes clinical symptoms or signs or influences the general morbidity of a child, a prospective study was performed on 147 children during their first year of life. 48 infants were infected with CMV perinatally. Reports of clinical infections during the second year were available from a total of 108 infants, and serum samples for viral antibody screening at the age 24 months from 111. No specific symptoms or signs could be attributed to perinatal CMV infection. None of the symptoms previously described in connection with CMV infection in childhood were observed. Urinary tract infections were, however, noticed in the group of perinatally infected children. Judging from the prevalence of illnesses and the frequency of elevated antibody titres against different agents, perinatal CMV infection does not seem to influence the general morbidity of a child. In general, the frequency and distribution of illnesses were the same as previously reported by Finnish authors. Breast-feeding did not protect against infection. The children of CMV seronegative mothers were not resistant to other infections, although all of them escaped perinatal CMV infection.

The effect of intrauterine alcohol exposition in various durations on early cognitive development.

Fifty-three children exposed to alcohol of various duration were examined at 18 to 19 months of age. No significant difference was found in developmental outcome between non-exposed (n = 56) and during the I trimester exposed children (n = 21). Exposure until the III trimester (n = 19) or continuous exposure (n = 13) caused significantly lower scores in language and total mental assessment. The procentual numbers of children with possible developmental risk (failure or pass at acceptance limit) in various developmental fields grew with increasing duration of intrauterine alcohol exposure. Failures in gross or fine motor items differed significantly between the non-exposed and the two long exposed children but in language items only between the non-exposed and the children exposed until the III trimester. A high number of exposed children scored just the limit values indicating a milder form of developmental delay. In comparison with the developmental results of one year of age an increase in delay in cognitive development was seen. The incidences of other teratogenic effects (pre- or postnatal growth retardation, facial dysmorphia) of fetal alcohol exposure were highest in the continuous exposed group. Five (38%) of the continuous exposed children had typical fetal alcohol syndrome and only 1 (5%) of the children exposed until the III trimester.