Risk Of Neonatal Seizures Research Articles

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children.

Background and ObjectivesTo evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.MethodsWe used Swedish register-based data to examine associations between maternal reported use of selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs) in pregnancy and diagnosis of neonatal seizures or epilepsy in >1.2 million children. To account for systematic differences between exposed and unexposed children, we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression or anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, comorbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).ResultsCompared with all other children, children of women who reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR] 1.41, 95% CI 1.03–1.94; hazard ratio [HR] 1.21, 95% CI 1.03–1.43, respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR 1.30, 95% CI 0.94–1.80; HR 1.13, 95% CI 0.95–1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR 1.10, 95% CI 0.79–1.53; HR 0.96, 95% CI 0.81–1.14).DiscussionWe found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.Classification of EvidenceThis study provides Class II evidence that exposure to SSRIs/SNRIs in the first trimester of pregnancy is not associated with an increased incidence of neonatal seizures/epilepsy.

Drug-Induced Hyperprolactinemia and Hyponatremia - Biological Markers of Unfavorable Evolution in Schizophrenia

Adverse reactions to psychotropic medication can be considered as risk indicators for an unfavorable evolution of patients with schizophrenia, based on particular pathogenic mechanisms that can be used in the personalized therapeutic approach. The combination of antidepressants with antipsychotic drugs in schizophrenia has a risk of synergistic action of excessive blockade of dopamine receptors, which causes hyperprolactinemia. Primary hyponatremia occurs during pregnancy and can be an important marker for signaling neurodevelopmental abnormalities, while secondary hyponatremia has a major clinical dimension and is induced by psychotropic drugs. The pathogenic mechanisms presented can be objectified by neuroimaging examinations that bring benefits in the diagnostic accuracy and re-evaluation of the therapeutic approach, especially in correlation with the severity of biological markers such as prolactin and sodium. The persistence of high prolactin and low sodium levels is an alarm signal that announces a negative evolution of the patient or a major risk of severe cardiac, metabolic, vascular or renal comorbidities. Recognition of pathogenic mechanisms of neurodevelopment, including ventriculomegaly, hyponatremia, focal cortical dysplasia, hippocampal or temporal lobe lesions, in association with a positive history of neonatal or febrile seizures, requires prophylaxis due to high risk of onset of schizophrenia in childhood. Fetal cortical dysplasia is associated with the risk of neonatal seizures. This vulnerability favors the appearance of febrile convulsions or enuresis with changes in brain structure. Enuresis may be an important marker of neurodevelopmental potential for schizophrenia. Neonatal seizures are correlated with hyponatremia and severe hypertension, which appeared in the third trimester of pregnancy, can trigger eclampsia. Neuroimaging monitoring in patients with neurodevelopmental abnormalities, hyperprolactinemia and primary or secondary hyponatremia, acquires a major importance, being able to delimit the boundary between a functional lesion, potentially reversible, with an irreversible lesion.

Impact of labor induction at 39 weeks gestation compared with expectant management on maternal and perinatal morbidity among a cohort of low-risk women

Objective To determine maternal and perinatal outcomes after induction of labor (IOL) at 39 weeks compared with expectant management. Methods This is a retrospective national cohort study from the National Center for Health Statistics birth database. The study included singleton, low-risk pregnancies with a non-anomalous fetus delivered at 39–42 weeks gestation between 2015 and 2018. Maternal outcomes available included chorioamnionitis (Triple I), blood transfusion, intensive care unit (ICU) admission, uterine rupture, cesarean delivery (CD), and cesarean hysterectomy. Fetal and infant outcomes included stillbirth, 5-min Apgar ≤3, prolonged ventilation, seizures, ICU admission, and death within 28 days. We compared women undergoing IOL at 39 weeks to those managed expectantly. Non-adjusted and adjusted relative risks (aRRs) were estimated using multivariate log-binomial regression analysis. Results There were 15,900,956 births available for review of which 5,017,524 met inclusion and exclusion criteria. For the maternal outcomes, the IOL group was less likely to require a CD (aRR 0.880; 95% CI [0.874–0.886]; p value < .01) or develop Triple I (aRR 0.714; 95% CI [0.698–0.730]; p value < .01) but demonstrated a small increase in the cesarean hysterectomy rate (aRR 1.231; 95% CI [1.029–1.472]; p value < .01). Among perinatal outcomes, the stillbirth rate (aRR 0.195; 95% CI [0.153–0.249]; p value < .01), 5-min Apgar ≤3 (aRR 0.684; 95% CI [0.647–0.723]; p value < .01), prolonged ventilation (aRR 0.840; 95% CI [0.800–0.883]; p value < .01), neonatal intensive care (NICU) admission (aRR 0.862; 95% CI [0.849–0.875]; p value < .01) were lower after 39 week IOL compared with expectant management. There were no differences in risk for neonatal seizures (aRR 0.848; 95% CI [0.718–1.003]; p value 0.011) or death (aRR 1.070; 95% CI [0.722–1.586]; p value 0.660). Conclusions IOL at 39 weeks of gestation in a low-risk cohort is associated with a lower risk of CD and maternal infection, stillbirth, and lower neonatal morbidity. There was no effect on the risk for neonatal seizures or death.

The Use of Antidepressant Medications During Pregnancy and the Risk of Neonatal Seizures: A Systematic Review.

This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures. PubMed was searched for English language reports published between January 1, 1996, and October 31, 2018, by using combinations of the following key words: pregnancy, neonatal outcome, neonatal convulsion, neonatal seizure, SSRI, selective serotonin norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), antidepressants, sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, duloxetine, bupropion, amitriptyline, imipramine, and clomipramine. A total of 9 relevant studies that met the review criteria were examined. The prevalence rates of neonatal seizures in the antidepressant groups and control groups were 0.30% to 0.91% and 0.10% to 0.30%, respectively. The use of selective serotonin reuptake inhibitors was associated with up to 5-fold increase in the risk of neonatal seizures. Compared with the controls, higher risks were reported in newborns of pregnant women using any antidepressant or tricyclic antidepressants albeit in a limited number of studies. Exposure to antidepressants in the third trimester of pregnancy appeared to be associated more with neonatal seizures compared with earlier exposure. Although an increased risk of neonatal seizures in newborns antenatally exposed to antidepressants especially selective serotonin reuptake inhibitors may be suggested, the available studies have severe methodological limitations to enable any firm conclusion.

Calcium Channel Blocker Exposure in Late Pregnancy and the Risk of Neonatal Seizures.

To assess whether maternal calcium channel blocker exposure during late pregnancy is independently associated with neonatal seizures after carefully controlling for confounding factors. Data were derived from the Medicaid Analytic eXtract for the years 2000-2007 and included 2,529,636 completed pregnancies. We compared the risk of neonatal seizures among neonates who were born to women who took calcium channel blockers in the final month of pregnancy to the risk in neonates born to women who did not use calcium channel blockers. Confounding was addressed through the use of propensity score matching. A total of 22,908 (0.91%) pregnancies included exposure to calcium channel blockers during the final month of pregnancy. Neonatal seizures occurred in 53 (0.23%) neonates born to mothers exposed to calcium channel blockers and in 4,609 (0.18%) neonates of unexposed women (unadjusted odds ratio [OR] 1.26, 95% confidence interval [CI] 0.96-1.65). After accounting for confounders, there was no increase in risk of neonatal seizures associated with calcium channel blocker exposure (OR 0.95, 95% CI 0.70-1.30). This null finding was robust across multiple sensitivity analysis. In this large, carefully controlled, population-based cohort study, there was no significant increase in the risk of neonatal seizures in neonates attributable to maternal calcium channel blocker exposure in late pregnancy. The results suggest that calcium channel blockers can be used by obstetricians in late pregnancy without excess concern about this neonatal complication. II.

P38 – 2768: Neonatal seizures in preterm infants

Objective Neonatal seizures are the most prominent feature of neonatal neurologic dysfunction, and the lifespan risk for seizures is highest in the neonatal period, especially in preterm infants. This study was aimed to find and analyze the risk factors and clinical profiles of seizures in preterm infants. Methods Sixteen cases of preterms with seizures were retrospectively reviewed between Mar. 2009 and Feb. 2012. Results The average gestational age was 30.3±4.1 weeks and 11 patients (68.7%) experienced seizures within 1 week after the birth. Eight cases (50%) had a perinatal asphyxia during the delivery and 7 cases (43.8%) had a history of perinatal maternal illness. Various types of seizures were observed of which subtle seizures were the most common (50%). Electroecephalographies were performed in 12 cases, which showed abnormal findings in 9 cases (75%). Neuroimaging studies were performed in 16 cases and showed abnormal findings in 10 cases (62.5%). Thirteen patients were discharged in the improved state and 3 patients expired. Eight cases had normal outcome, while 3 cases showed developmental delay. Conclusion Neonatal asphyxia is the most important risk factor. Furthermore, infants with a history of perinatal maternal illness appear to be at risk for neonatal seizures. EEG is a sensitive method for assessing seizure activity and prognosis. Monitoring high risk infants with asphyxia and a history of perinatal maternal illness, and early postnatal tracing with EEG is required to detect and manage high risk preterms.

EEG background as predictor of electrographic seizures in high-risk neonates.

Experience with continuous EEG monitoring in 29 consecutive infants at risk of neonatal seizures demonstrated that background abnormalities on the initial EEG were strongly associated with electrographic seizures in the subsequent 18-24 h. To test this association prospectively, we examined the relationship between EEG background and the presence of electrographic seizures in the next 22 at-risk infants monitored for seizures. A standard EEG was recorded for each infant at risk for seizures. Based on specific criteria, the background was graded as normal; immature for age; or mildly, moderately, or severely abnormal. The EEG was then monitored continuously until no electrographic seizures were recorded for 18-24 h. Findings in the retrospective group of 29 infants and the prospective group of 22 infants did not differ. For the combined 51 infants, a normal or immature initial EEG background predicted the absence of seizures in the subsequent 18-24 h with a sensitivity of 96% [confidence interval (CI) 0.88, 1.0] and specificity of 81% (CI 0.67, 0.96). Administration of antiepileptic drugs (AEDs) before the start of the EEG recording did not affect this association. In 51 consecutively monitored infants at risk for neonatal seizures, a normal or immature EEG background strongly predicted the absence of electrographic seizures in the subsequent 18-24 h; background abnormalities strongly predicted the occurrence of electrographic seizures concomitantly or in the subsequent 18-24 h of recording. Screening infants at risk for neonatal seizures with a routine EEG allows identification of infants at highest risk for seizures, thus conserving resources required for continuous EEG monitoring and facilitating early intervention for seizures.

Asphyxiated Infants at Risk for Neonatal Seizures

Asphyxiated Infants at Risk for Neonatal Seizures

Can Asphyxiated Infants at Risk for Neonatal Seizures Be Rapidly Identified by Current High-risk Markers?

Markers currently used to identify infants at highest risk for perinatal hypoxic-ischemic cerebral injury are insensitive in predicting the subsequent occurrence of neonatal seizures and/or neurodevelopmental sequelae, ie, cerebral palsy. To facilitate therapeutic strategies, early identification of the infant at highest risk for developing seizures secondary to hypoxia ischemia or asphyxia is critical, particularly if novel but potentially toxic therapies currently under experimental investigation become available for clinical use. Ninety-six inborn term infants considered at high risk for having neonatal seizures secondary to hypoxia ischemia or asphyxia and admitted to the neonatal intensive care unit directly after labor and delivery were prospectively evaluated. Markers of high risk included the presence of moderate to thick meconium-stained amniotic fluid (MSAF), fetal heart rate (FHRT) abnormalities abruptio placentae, intubation and positive pressure ventilation in the delivery room (DR), chest compressions and epinephrine administration as part of resuscitation, a 5-minute Apgar score of 5 or less, umbilical cord arterial pH of 7.00 or less, and/or a base deficit of -14 mEq/L or more negative. Seizures developed in 5 (5.2%) of the 96 infants. High-risk markers included FHRT abnormalities only (n=36), FHRT abnormalities and MSAF (n=20), MSAF only (n=23), abruptio placentae (n=6), intubation in the DR (n=44), intubation in the neonatal intensive care unit (n=22), chest compressions (n=2), 5-minute Apgar scores of 5 or less (n=21), umbilical cord arterial pH of 7.00 or less (n=21), and base deficits of -14 mEq/L or more negative (n=19). By univariate analysis, significant relationships with seizures were found with Apgar scores, the need for intubation in the DR, umbilical cord arterial pH, and base deficit. Combinations of the identified risk markers showed a strong relationship with seizures with the following odds rations (ORs), 95% confidence limits, sensitivity, specificity, and positive predictive values (PPVs): (1) low cord pH and intubation, OR, 163 (confidence limits, 7.9 and 3343.7); sensitivity, 100%; specificity 94%; and PPV, 50%; (2) low cord pH and low 5-minute Apgar score, OR, 39 (confidence limits, 3.9 and 392.5); sensitivity, 80%; specificity, 91%; and PPV, 33.3%; and (3) low pH, intubation, and low 5-minute Apgar score, OR, 340 (confidence limits, 17.8 and 6480.6); sensitivity, 80%; specificity, 98.8%; and PPV, 80%. A combination of high-risk postnatal markers, specifically, a low 5-minute Apgar score and intubation in the DR in association with severe fetal acidemia, facilitates the identification within the first hour of life of term infants at highest risk for developing seizures secondary to perinatal asphyxia.

Neonatal Seizures in the United States: Results of the National Hospital Discharge Survey, 1980–1991

We present nationally representative estimates of neonatal seizure risk by gender, race and geographic region of the United States. National Hospital Discharge Survey data were analyzed for the period 1980-1991. Birth-weight-adjusted risks of neonatal seizures were calculated by the direct method for each gender or race group and for each census region by 4-year intervals. The overall risk of neonatal seizures was 2.84 per 1,000 live births. Risk estimates were consistently higher in low-birth-weight infants (relative risk 3.9). Unadjusted risks were similar across race and gender groups; birth weight adjustment had very little effect. No clear temporal trend was apparent over the 12-year study period. National Hospital Discharge Survey data provide reasonable, although conservative, estimates of neonatal seizure risks nationwide. Underascertainment of neonatal seizures, particularly among sick low-birth-weight infants, is likely due to data collection limitations of the National Hospital Discharge Survey.