Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVES: Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). METHODS: It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. RESULTS: Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). CONCLUSIONS: Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

Intrapartum cardiotocography in pregnancies with and without fetal CHD.

OBJECTIVES: Congenital heart defects (CHD) are the most common inherited abnormalities. Intrapartum cardiotocography (CTG) is still considered a "gold standard" during labor. However, there is a lack of evidence regarding the interpretation of intrapartum CTG in fetuses with CHD. Therefore, the study aimed to compare intrapartum CTG in normal fetuses and fetuses with CHD and describe the association between CTG and neonatal outcomes. METHODS: The present study is a retrospective analysis of the CTG of 395 fetuses. There were three study groups: Group 1: 185 pregnancies with a prenatal diagnosis of CHD, Group 2: 132 high-risk pregnancies without CHD, and Group 3: 78 low-risk pregnancies without CHD. RESULTS: Abnormal CTG was present statistically OR=3.4 (95%CI: 1.61-6.95) more often in Group 1. The rate of the emergency CS was higher in this group OR=3 (95%CI: 1.3-3.1). Fetuses with CHD and abnormal CTG were more often scored ≤7 Apgar, with no difference in acidemia. The multivariate regression model for Group 1 does not show clinical differences between Apgar scores or CTG assessment in neonatal acidemia prediction. CONCLUSIONS: CTG in fetuses with CHD should be interpreted individually according to the type of CHD and conduction abnormalities. Observed abnormalities in CTG are associated with the fetal heart defect itself. Preterm delivery and rapid cesarean delivery lead to a higher rate of neonatal complications. Health practitioners should consider this fact during decision-making regarding delivery in cases complicated with fetal cardiac problems.

Tetralogy of Fallot in the fetus - from diagnosis to delivery. 18-year experience of a tertiary Fetal Cardiology Center.

BACKGROUND: Tetralogy of Fallot (TOF) is a common congenital heart disease but very heterogeneous in terms of detailed cardiac anatomy, associated malformations, and genetic anomalies, especially when assessed prenatally. AIMS: We aimed to analyze the clinical spectrum of TOF in the prenatal period, including detailed cardiac morphology, coexisting anomalies, and their impact on short-term neonatal outcome. We also assessed changing trends in the prenatal diagnostic workup of TOF. METHODS: A retrospective cohort study including fetuses diagnosed with TOF between 2002 and 2019 was conducted in a tertiary Fetal Cardiology Center. Medical records and echocardiographic examinations were reviewed to collect demographic, sonographic, and genetic data. RESULTS: Among 326 TOF fetuses, 237 (73%) had pulmonary stenosis (TOF-PS), 72 (22%) pulmonary atresia (TOF-PA), and 17 (5%) absent pulmonary valve (TOF-APV). The yearly number of diagnoses increased during the study period, with decreasing fetal age at the time of diagnosis. Extracardiac malformations were found in 172 (53%) fetuses, cardiovascular malformations in 159 (49%), and genetic anomalies in 99 (39% of the tested group). Hypoplastic thymus, right aortic arch, and polyhydramnios were sonographic markers of microdeletion 22q11. Left-to-right ductal flow was predictive of postnatal ductal dependency. The perinatal outcome was dependent on the presence of associated anomalies and disease subtype, with TOF-APV having the worst prognosis. CONCLUSIONS: Extracardiac and genetic anomalies are common in fetuses with TOF, and, together with disease subtype and ductal flow assessment, they impact the perinatal management and outcomes. Genetic testing with array comparative genomic hybridization should be offered in all cases.

Liver herniation into the pericardium mimicking a pericardial tumor: unusual presentation of trisomy 13.

Aim of the study: Trisomy 13 is the third most common autosomal trisomy. The following case report shows an atypical case of trisomy 13, highlighting the usefulness of 3D volume storage and reconstruction, and the necessity of careful interpretation of the first trimester screening results. Case description: The results of the first trimester screening tests were interpreted as normal, and invasive tests were not recommended. At 21 weeks, a bright spot in the left ventricle was noted, and fetal echocardiography was performed at 33 weeks. The scan showed a massive pericardial effusion and a pericardial tumor located in front of the right ventricle. Conclusions: The final diagnosis, made postnatally, revealed an atypical right-sided diaphragmatic hernia. Part of the liver was displaced to the pericardial cavity, mimicking a pericardial tumor in a baby with trisomy 13. Following the diagnosis of the lethal disorder, the baby was discharged under a home-based palliative care program and died on the 49th day of life.

Fetal Cardiac Interventions-Are They Safe for the Mothers?

The aim of fetal cardiac interventions (FCI), as other prenatal therapeutic procedures, is to bring benefit to the fetus. However, the safety of the mother is of utmost importance. The objective of our study was to evaluate the impact of FCI on maternal condition, course of pregnancy, and delivery. 113 mothers underwent intrauterine treatment of their fetuses with critical heart defects. 128 percutaneous ultrasound-guided FCI were performed and analyzed. The patients were divided into four groups according to the type of FCI: balloon aortic valvuloplasty (fBAV), balloon pulmonary valvuloplasty (fBPV), interatrial stent placement (IAS), and balloon atrioseptoplasty (BAS). Various factors: maternal parameters, perioperative data, and pregnancy complications, were analyzed. There was only one major complication-procedure-related placental abruption (without need for blood products transfusion). There were no cases of: procedure-related preterm prelabor rupture of membranes (pPROM), chorioamnionitis, wound infection, and anesthesia associated complications. Tocolysis was only necessary only in two cases, and it was effective in both. None of the patients required intensive care unit admission. The procedure was effective in treating polyhydramnios associated with fetal heart failure in six out of nine cases. Deliveries occurred at term in 89%, 54% were vaginal. The results showed that FCI had a negligible impact on a further course of pregnancy and delivery.

Complete closure of the ductus arteriosus in the foetus with transposition of the great arteries.

Prenatal restriction of the ductus arteriosus can manifest as persistent pulmonary hypertension in the newborn, especially dangerous with the transposition of the great arteries. Its aetiology has long been related to maternal intake of non-steroidal anti-inflammatory drugs; however, some other substances, including polyphenols, may have similar properties. We describe a case of complete prenatal closure of the ductus arteriosus in the foetus with transposition of the great arteries. The newborn presented with pulmonary hypertension unresponsive to pharmacotherapy and died of multi-organ failure.

Spontaneous resolution of prenatally diagnosed isolated pleural effusion: An unusual early sign of a newborn disease.

We present a case report of a fetus with a diagnosed pleural effusion in the first trimester on nuchal translucency scan. The effusion resolved spontaneously by 17 weeks of pregnancy. Toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH) - negative. Array comparative genomic hybridization (aCGH) - normal. Serial Doppler scans normal - no prenatal signs of anemia. Maternal antibodies against red cell antigens - negative. Delivery at term by cesarean section because of macrosomia. Neonate suffered from prolonged jaundice. At 3 weeks of life diagnosed with hereditary spherocytosis. Literature review shows that this may be the first connection between this disease and prenatal life.

Fetal echocardiography gives a clue for the maternal diagnosis of tuberous sclerosis complex.

The detection of multiple cardiac tumors during fetal echocardiography allowed us to make the diagnosis of tuberous sclerosis complex in the mother and establish the reason of her first epileptic seizures.

Echocardiographic analysis of left ventricular function in term and preterm neonates at week 40 of postconceptional life.

BACKGROUND Both gestational and chronological age of the neonate may influence and impair the function of the delicate and immature myocardium. However, the transition from fetal to neonatal circulation in preterm neonates is poorly understood. AIMS This study aimed to compare left ventricular (LV) systolic and diastolic function between premature neonates at expected term and term neonates during the postnatal cardiovascular transitional period. METHODS Using echocardiography, we assessed systolic and diastolic function of the LV in 89 preterm neonates at week 40 of postconceptional age and 29 term neonates after closure of the patent ductus arteriosus (PDA) and on the 28th day of life. Based on M­mode images, we measured myocardial thickness and fractional shortening (FS%). Using pulsed­wave Doppler echocardiography, we estimated cardiac output, myocardial performance index (MPI), and LV diastolic function (E and A waves, E/A ratio). Systolic and diastolic function was also assessed by tissue Doppler imaging. RESULTS Compared with term neonates on the 28th day of life, preterm neonates had reduced myocardial thickness (P ≤0.04), FS% (P = 0.002), and cardiac output (P = 0.01). However, preterm neonates had a lower MPI than term neonates after PDA closure (P <0.001) and on the 28th day of life (P = 0.02). The E/A ratio and S' wave values were similar in preterm and term neonates (P >0.05). CONCLUSIONS Preterm neonates at 40 weeks of postconceptional age have preserved systolic and diastolic function of the LV.

Evaluation of left ventricular function in preterm infants with bronchopulmonary dysplasia using various echocardiographic techniques.

AIM: Echocardiographic evaluation of left ventricular function in preterm infants with and without bronchopulmonary dysplasia. METHODS: In 82 preterm infants (32 in no-bronchopulmonary-dysplasia group, 35 in mild-bronchopulmonary-dysplasia group, and 15 in severe-bronchopulmonary-dysplasia group), echocardiography was performed on the first day of life, at 28 days of life, and at 36 weeks postconceptional age. RESULTS: The mean E/A ratio at 36 PCA was 0.94±0.31 and 0.73±0.12 in the mild- and severe-bronchopulmonary-dysplasia groups, respectively (P=.037). The mean E'-wave velocity was 5.62±1.61 cm/s vs 4.32±1.11 cm/s at 1 day of life (P=.006) and 6.40±1.39 cm/s vs 5.34±1.37 cm/s at 28 days of life (P=.030) in the no-bronchopulmonary-dysplasia and mild-bronchopulmonary-dysplasia groups, respectively. This measure tended to be lower in the severe-bronchopulmonary-dysplasia group compared to the no-bronchopulmonary-dysplasia group (5.25±1.29 cm/s at 28 days of life; P=.081). The E/E' ratio differed between the no-bronchopulmonary-dysplasia (7.21±1.85) and mild-bronchopulmonary-dysplasia groups (9.03±2.56; P=.019) at 1 day of life. The left ventricle myocardial performance index decreased between 1 day of life and 36 postconceptional age in infants without bronchopulmonary dysplasia and those with mild bronchopulmonary dysplasia, but not in those with severe bronchopulmonary dysplasia. CONCLUSION: E/A and E/E' ratios are the most sensitive indicators of impaired left ventricle diastolic function in preterm infants with bronchopulmonary dysplasia.

Echocardiographic evaluation of right ventricular function in preterm infants with bronchopulmonary dysplasia.

AIM: To evaluate right ventricular function in preterm infants with and without bronchopulmonary dysplasia. METHODS: Eighty-nine preterm infants (<32 weeks) were divided into three groups: (1) no-bronchopulmonary dysplasia (n=32); (2) mild-bronchopulmonary dysplasia (n=35); (3) severe-bronchopulmonary dysplasia (n=15). Right ventricular echocardiographic parameters included the following: (1) pulsed-wave Doppler through the tricuspid valve (E/A ratio), pulmonary artery acceleration time, right ventricular ejection time, right ventricular velocity-time integral; (2) tissue Doppler measurements of myocardial velocities and atrioventricular conduction times; (3) pulsed-wave Doppler and tissue Doppler evaluation of myocardial performance index and E/E' ratio; and (4) M-mode detection of right ventricular end-diastolic wall diameter. RESULTS: The severe-bronchopulmonary dysplasia group had higher mean right ventricular myocardial performance index (on the 28th day of life by pulsed-wave Doppler) than the no-bronchopulmonary dysplasia (P=.014) or mild-bronchopulmonary dysplasia (P=.031) groups; no differences were found between no-bronchopulmonary dysplasia and mild-bronchopulmonary dysplasia groups (P=.919). A reduction in right ventricular myocardial performance index at later time points was observed in all three groups (P<.05). We found no differences between preterm infants with differing bronchopulmonary dysplasia severity in other right ventricular echocardiographic parameters. CONCLUSION: Right ventricular myocardial performance index measured by pulsed-wave Doppler indicates impaired right ventricular function in preterm infants with severe bronchopulmonary dysplasia.

Myocardial performance index (Tei index) in term and preterm neonates during the neonatal period.

BACKGROUND: The myocardial performance index (MPI) is a noninvasive method to measure global systolic and diastolic myocardial function. In both term and premature neonates, changes in the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) reflect the degree of neonatal myocardial immaturity and the co-existence of foetal circulation. AIM: To assess MPI (or Tei indices) of both ventricles in term and preterm newborns, and to observe MPI trends throughout the neonatal period. METHODS: Heart ultrasound imaging was performed on the first day of life (DOL), after patent ductus arteriosus (PDA) closure, and on the 28th DOL, in 29 term and 29 preterm newborns. RVMPI and LVMPI were measured within the preterm group at 40 weeks of post-conception age (PCA). RESULTS: A statistically significant reduction in RVMPI was observed in both term and preterm newborns. In term newborns, the RVMPI value on the first DOL was 0.42 ± 14, dropping to 0.29 ± 0.09 after PDA closure, and finally reaching 0.22 ± 0.09 on the 28th DOL. The respective RVMPI values for the preterm newborns were 0.44 ± 0.15, 0.30 ± 0.12, and 0.21 ± 0.08. Little variability in the mean values of LVMPI was observed in both groups throughout the neonatal period. The LVMPI for term neonates in successive measurements was 0.37 ± 0.10, 0.39 ± 0.07, and 0.37 ± 0.11, respectively, and for the preterm neonates it was 0.37 ± 0.10, 0.35 ± 0.09, and 0.36 ± 0.10, respectively. The MPI values from preterm newborns taken at 40 weeks PCA (RVMPI = 0.28 ± 0.09; LVMPI = 0.37 ± 0.05) were comparable to those measured in term newborns after PDA closure. CONCLUSIONS: Observed postnatal changes in RVMPI correspond to changes in ventricular function, reflecting the haemodynamic changes of the transitional circulation. The relatively small postnatal changes in LVMPI in term and preterm newborns may reflect an immature myocardium. The RVMPI and LVMPI values at 40 weeks PCA in preterm newborns correlate best with MPI values in term newborns just after PDA closure.

[Fetal cardiac interventions - are we ready for them?]. / Interwencyjne zabiegi kardiologiczne u plodów - czy jestesmy do nich przygotowani?

OBJECTIVE: The aim of the study was to analyze types and methods of intrauterine fetal cardiac interventions performed between June 2011 and December 2013, and to assess the perinatal management of the neonates. METHODS: The program was developed after analysis of the available literature, practical individual training in Linz, Austria, and simulation of the procedure in a dissecting-room. The rules for anesthesia in pregnant women and their fetuses were developed. The interventions were performed in fetuses with critical cardiac defects, in the operating room, under ultrasonographic control. The protocol was approved by the Local Bioethics Committee at the Centre of Postgraduate Medical Education. MATERIAL: We included fetuses with critical aortic stenosis (n=29), critical pulmonary stenosis (n=2), and closed or extremely restricted foramen ovale (n=7). Between June 2011 and December 2013, the team comprised of JD, MD and AK conducted 42 interventions in 35 fetuses, including 32 balloon aortic valvuloplasties (in 29 fetuses), 2 pulmonary valvuloplasties, 4 balloon atrial septostomies and 4 atrial septal stent placement. Three fetuses required both, aortic valvuloplasty and fenestration of the atrial septum. RESULTS: Out of the 42 procedures, 41 (97%) were technically successful. We recorded 3 cases of fetal demise associated with the intervention. We modulated the protocol of anesthesia given to pregnant women, switching from general to local anesthesia with intravenous sedation. We always provided additional fetal anesthesia with fentanyl and atracurium via the umbilical vein. CONCLUSIONS: Based on our 2.5-year experience, it seems safe to conclude that all types of fetal cardiac interventions may be successfully conducted at Polish centers. The procedures are safe for the pregnant women and improve fetal status. Most of the neonates treated prenatally were referred in good general condition to a tertiary pediatric cardiology and cardiac surgery center

Doppler tissue imaging assessment of myocardial velocities and atrioventricular time intervals in term newborn infants during the neonatal period.

BACKGROUND: In both term and premature neonates, changes in the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) reflect the degree of neonatal myocardial immaturity and the co-existence of foetal circulation as well as the presence of concurrent diseases. AIM: To evaluate the changes in values of systolic and diastolic LV and RV function using pulse tissue Doppler imaging (TDI) in 20 healthy term newborn infants from birth to the 28th day of life. METHODS: Ventricular peak myocardial velocities were recorded during early diastole (Em wave), atrial contraction (Am wave), and systole (Sm wave). TDI derived atrioventricular (AV) intervals were measured as the period from atrial contraction (Am) to isovolumic contraction (IV), from Am to ventricular systole (Sm), from Sm to the following Am, and from IV to the following Am. The first measurements were taken as soon as possible after birth, the second on the third day, and the final one on the 28th day of life. RESULTS: The diastolic myocardial velocities recorded in the RV were higher than those in the LV. Statistically significant differences were observed for time intervals in the RV: Am-IV and Am-Sm (day 1-3), p < 0.02; IV-Am (day 1-28), p < 0.005; Sm-Am (day 1-28), p < 0.01. Statistically significant differences for time intervals were also evident in the LV: Am-IV (day 1-28), p < 0.05; and for Sm-Am (day 1-28), p < 0.01. Mean isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) intervals remained stable for all measurements recorded in the RV. However, a statistically significant difference was evident for both ICT and IRT intervals in the LV between days 1 and 28 of life (p < 0.01). CONCLUSIONS: 1. Cardiac TDI is feasible in the neonate. 2. In neonates, the diastolic and systolic function recorded in the RV was better than that in the LV. This may reflect the 'persistent' foetal status of this ventricle in the first day of life. 3. The differences observed in conduction times also reflect the haemodynamic changes which occur in the circulatory system of the neonate in the first month of life. 4. Further investigation of a larger population of neonates throughout the whole neonatal period is indicated.

[Right ventricular hypertrophic cardiomyopathy in the fetus --may it be caused by chronic oral tocolysis with fenoterol?]. / Kardiomiopatia przerostowa prawej komory u plodu--czy przewlekla doustna tokoliza fenoterolem moze byc jej przyczyna?

The use of fenoterol in the treatment of preterm labor is associated with the risk of many complications in the mother and the fetus. We present a case of a multipara treated with oral fenoterol due to threatening preterm labor 14 weeks. At 35 weeks of gestation the fetus was diagnosed with hypertrophic cardiomyopathy with severe impairment of the right ventricle. The only factor that might have caused such a state of the fetal circulatory system was fenoterol, used from 21 weeks of gestation. After the withdrawal of the fenoterol the fetal right ventricular function improved gradually. However fetal cardiac hypertrophy persisted until the birth at 39 weeks of gestation. Concentric hypertrophy of the right ventricular wall and interventricular septum were confirmed in the newborn.

The Polish National Registry for Fetal Cardiac Pathology: organization, diagnoses, management, educational aspects and telemedicine endeavors.

OBJECTIVE: We describe the National Registry for Fetal Cardiac Pathology, a program under the Polish Ministry of Health aimed at improving the prenatal diagnosis, care, and management of congenital heart disease (CHD). METHODS: An online database was created to prospectively record diagnosis, prenatal care, delivery, follow-up, and still images and video for fetuses with CHD. A certification program in fetal cardiac ultrasound was also implemented. Optimal screening and referral centers were identified by number of fetuses entered in the Registry yearly by each center. RESULTS: From 2004 to 2009, 2910 fetuses with CHD were registered (2473 structural, 437 functional anomalies). The most common reasons for referral for fetal echocardiography were abnormal four-chamber view (56.0%) and extra-cardiac anomalies (8.2% ), while the most common diagnoses were atrioventricular septal defects (10.2%) and hypoplastic left heart syndrome (9.7%). Prenatal diagnosis increased yearly, from 10.0% of neonatal diagnoses in 2003 to 38.0% in 2008. CONCLUSION: From inception of the registry up to 2009 there has been a fourfold increase in the number of neonates referred for cardiac surgery in whom the condition was prenatally diagnosed. Equally important achievements include the establishment of a certification program for fetal echocardiography and the organization of prenatal and neonatal management.

[Quantitative assessment of the right and the left ventricular function using pulsed Doppler myocardial performance index in normal fetuses at 18 to 40 weeks of gestation]. / Ilosciowa ocena funkcji-prawej i lewei komory metoda Dopplera pulsacyjnego z uzyclem wskaznika sprawnosci miesnia serca u zdrowych plodów miedzy 18 a 40 tygodniem ciazy.

OBJECTIVE: To establish the values of the pulsed Doppler myocardial performance index (MPI, Tei index) for the left and the right ventricle in normal fetuses at 18 to 40 weeks gestation. MATERIAL AND METHODS: Echocardiography exams were performed in 140 normal fetuses at 18 to 40 weeks gestation at the tertiary centre for fetal cardiology MPI was calculated in pulsed Doppler using formula: (a-b)/b. The time a was measured from a closure click to the subsequent opening click of the mitral/tricuspid valve and time b from opening to the closure clicks of the aortic/pulmonary valve. RESULTS: The mean MPI for the LV was 0.47 +/- 0.07 and for RV 0.48 +/- 0.1. There was no difference between the Tei index LV and the Tei index RV (p = 0.41). We observed a linear correlation between the Tei index LV and the Tei index RV (p = 0.008; r = 0.22). Fetal heart rate and gestational age had no effect on the MPI for both ventricles. CONCLUSIONS: The assessed normal values of Tei index for the left and the right ventricles in fetuses may be used in comparison of myocardial performance in various clinical settings.

Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex.

BACKGROUND: Epilepsy appears in 70-80% of patients with tuberous sclerosis complex, most commonly in the first year of age. Early manifestation of epilepsy is associated with drug-resistant epilepsy and mental retardation in more than 80% of patients. Clinical epileptic seizures are preceded by deterioration of EEG recording thus infants with high risk of epilepsy can be identified. AIMS: We hypothesized that preventative antiepileptic treatment of infants with multifocal activity on EEG might lower the incidence of drug-resistant epilepsy and mental retardation. METHODS: Forty-five infants with early diagnosis of tuberous sclerosis complex were included in the open-label study. They were divided in two groups: standard (n=31) and preventative one (n=14). In standard group the antiepileptic treatment was launched early, but after the onset of seizures. In preventative group medication was commenced when active epileptic discharges were seen on EEG, but before the onset of clinical seizures. Children were followed till the end of 2 years of age. RESULTS: At 24 months of age mental retardation was significantly more frequent and severe in "standard" vs "preventative" group (48% vs 14%; p=0.031; mean IQ score 68.7 vs 92.3; p<0.05). The "preventative" group was characterized by higher ratio of seizure-free patients (93% vs 35%; p=0.004), lower incidence of drug-resistant epilepsy (7% vs 42%; p=0.021) and lower number of patients requiring polytherapy (21% vs 55%; 0.039) than the "standard group. CONCLUSIONS: Preventative antiepileptic treatment of infants with tuberous sclerosis complex and high risk of epilepsy markedly improves their neurodevelopmental outcome and reduces the incidence of drug-resistant seizures.