Differences in brain changes between adults with childhood-onset epilepsy and controls: A prospective population-based study.

PURPOSE: To determine the impact of childhood-onset uncomplicated epilepsy (COE) on brain aging over 50-year prospective follow-up. METHODS: A population-based cohort of 41 aging subjects with COE and their 46 matched controls participated in a detailed in-person prospective assessment in 2012 and 2017 to characterize ongoing changes in the aging brain. RESULTS: The mean age of the COE participants was 63.2 years (SD 4.14, median 63.2, range 55.8-70.6) and 63.0 years (mean, SD 4.13, median 63.3, range 56.0-69.9) years for controls. Neurologic signs were significantly more common in COE participants not in remission (p = .015), and the most frequent abnormalities were cerebellar signs (p < .001). Neurologic signs in general (p = .008) and cerebellar signs in particular (p = .018) were significantly more common in focal than in generalized epilepsies. MRI white matter abnormalities were significantly associated with absence of vocational education (p = .011), and MRI hippocampal atrophy in COE subjects was associated with arterial hypertension versus normal blood pressure (p = .017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and in the controls from the 2012 to 2017 study. CONCLUSIONS: At ultra-long-term follow-up, clinical and neuroimaging findings show tendencies to brain aging that is more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy.

Parental distress rating at the child's age of 15 years predicts probable mental diagnosis: a three-year follow-up.

BACKGROUND: Mental health in adolescence is an increasing global public health concern. Over half of all mental disorders debut by 14 years of age and remain largely untreated up to adulthood, underlining the significance of early detection. The study aimed to investigate whether parental distress rating at the child's age of 15 predicts a probable mental diagnosis in a three-year follow-up. METHODS: All data was derived from the Finnish Family Competence (FFC) Study. The analysis focused on whether parental CBCL (Child Behavior Checklist) rating (n = 441) at the child's age of 15 years predicted the outcome of the child's standardised DAWBA (Development and Well-Being Assessment) interview at offspring's 18 years. RESULTS: Multivariable analysis showed that a one-unit increase in the total CBCL scores increased the relative risk of a DAWBA-based diagnosis by 3% (RR [95% CI] 1.03 [1.02-1.04], p < 0.001). CONCLUSIONS: Parental CBCL rating in a community sample at the adolescent's age of 15 contributes to early identification of adolescents potentially at risk and thus benefitting from early interventions.

Neurocognition in childhood epilepsy: Impact on mortality and complete seizure remission 50 years later.

OBJECTIVE: To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission. METHODS: A population-based cohort of 245 subjects with childhood onset epilepsy was followed up for 50 years (median = 45, range = 2-50). Childhood NC before age 18 years was assessed as a combination of formal intelligence quotient scores and functional criteria (school achievement, working history, and psychoneurological development). Impaired NC was categorized with respect to definitions of intellectual functioning in International Classification of Diseases, 10th revision (R41.83, F70-F73). The outcome variables, defined as all-cause mortality and 10-year terminal remission with the 5 past years off medication (10YTR), were analyzed with Cox regression models. RESULTS: Of the 245 subjects, 119 (49%) had normal childhood NC, whereas 126 (51%) had various degrees of neurocognitive impairment. During the 50-year observation period, 71 (29%) of the subjects died, 13% of those with normal and 44% of those with impaired NC. The hazard of death increased gradually in line with more impaired cognition, reaching significance in moderate, severe, and profound impairment versus normal NC (hazard ratio [Bonferroni corrected 95% confidence interval] = 3.3 [1.2-9.2], 4.2 [1.2-14.2], and 5.5 [2.4-12.3], respectively). The chance for 10YTR was highest among subjects with normal NC (61%), whereas none of those with profound impairment reached 10YTR. In the intermediate categories, the chance was, however, not directly related to the increasing severity of impairment. SIGNIFICANCE: The severity of neurocognitive impairment during childhood shows a parallel increase in the risk of death. In comparison with normal NC, subjects with lower childhood NC are less likely to enter seizure remission. However, normal NC does not guarantee complete remission or prevent premature death in some individuals with childhood onset epilepsy.

Overrepresentation of epilepsy in children with type 1 diabetes is declining in a longitudinal population study in Finland.

AIM: The aim was to determine temporal changes in increased risk of epilepsy among children with type 1 diabetes. METHODS: The incidence of epilepsy up to age 15 in children with prior type 1 diabetes was analysed regarding the general Finnish child population using data from the Finnish nationwide hospital register. Type 1 diabetes and epilepsy were identified by the International Classification of Diseases 9th and 10th revision codes. Epilepsy was defined according to ILAE guidelines. The analyses were done using negative binomial regression models. RESULTS: Preceding type 1 diabetes was diagnosed in 6162 (0.91%) of the 679 375 general children population. Incidence rate of new-onset epilepsy among children with type 1 diabetes was higher than in controls (140 vs 82 per 100 000 person-years at risk, respectively). The excess incidence diminished with time (P = 0.033 for diabetes to birth cohort interaction), from over twofold in birth cohort 1990-1993 [incidence rate ratio 2.2 (95% CI 1.7-2.9)] to 40% in birth cohort 1998-2000 [1.4 (95% CI 1.001-1.9)]. CONCLUSION: In a population study setting, children with type 1 diabetes had an increased, but slowly declining risk of developing epilepsy. Future research may elucidate the underlying mechanisms.

Long term outcome of childhood onset headache: A prospective community study.

Purpose To examine prevalence, course, and long-term outcome of childhood migraine and other headaches. Method Using questionnaires, 1185 children were followed for recurrent headaches at ages seven, 14 and 32 years, respectively. Results At age seven years, 4.0% of the 1185 children (girls 3.7%, boys 4.3%) had migraine and 24% (25%/23%) had nonmigrainous headache. In adulthood, 16% (22%/8%) had migraine and 60% (64%/54%) nonmigrainous headache. Childhood migraine persisted into adulthood in 65% of females and 21% of males, and nonmigrainous headache in 62% and 59%, respectively. After childhood, 17% of females and 7% of males started to have episodes of migraine. No recurrent headache during the follow-up was reported by 11% (6%/16%). In a multivariate analysis, compared with no childhood headache, childhood migraine increased the risk of adulthood migraine by 3.36-fold (95% CI 1.94-5.82) and that of nonmigrainous headache by 1.72-fold (1.14-2.60). Discussion and conclusions Headaches are generally as common in preschool girls as boys. From early school years, headaches steadily increase up to young adulthood, but among boys the prevalence levels off after adolescence. About two thirds of children experienced changes in their headache status during a 25-year follow-up. Any kind of recurrent headache at school entry predicts an increased risk of headache in young adulthood. Special attention should be paid to girls and particularly those girls who have recurrent headache when they start school.

Remission in epilepsy: How long is enough?

OBJECTIVE: The International League Against Epilepsy (ILAE) has proposed to expand the definition of remission to 10 years seizure-free with the last 5 years off antiepileptic drugs (AEDs). We examined if a 10-year remission is needed to predict the lowest recurrence risk. METHODS: The population-based study cohort consisted of 148 patients with new-onset childhood epilepsy living in the catchment area of Turku University Hospital. They were prospectively followed for 44 years (median). Patients in first remission were prospectively followed for the duration of remission or possible relapse at 2 years in remission with the last year without antiepileptic drugs (AEDs), at 5 years in remission with the last 2 years without AEDs, and at 10 years with the last 5 years without AEDs. For comparison of the proportions of relapsed patients within each remission category exact Clopper Pearson 95% confidence intervals were used. RESULTS: The magnitude of the relapse rate estimates off AEDs did not significantly improve when remission increased from 2 years (2YR) to 5 years (5YR) and further to 10 years (10YR). However, 10YR was a more sensitive measure of no relapse than 2YR. Among patients with remission on or off AEDs, the ability to predict lower relapse rate increased markedly from 2 to 5 years, and again from 5 to 10 years. The risk of relapse was virtually the same estimated after 2YR off AEDs as after 10YR on or off AEDs, except for patients with generalized epilepsy whose 2YR off AEDs was a weaker predictor than 10YR on or off AEDs. SIGNIFICANCE: Given the modest differences in relapse rates between the 5 years seizure-free with last 2 years off medications definition and the 10 years seizure-free with last 5 years off medications, and the adverse impact of not being considered in remission, we propose that a return to the 5-year definition may be warranted.

Long-term changes in the incidence of childhood epilepsy. A population study from Finland.

BACKGROUND: The incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased. METHODS: Changes in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤15years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000person-years in each calendar year during 1968 to 2012. RESULTS: The annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000person-years in the 1990s and decreased thereafter to 61 per 100,000person-years. Since 1996, the incidence density decreased 1-2% per year in children aged <1, 1-5, or 6-10years (all 95% confidence intervals within 0.3%-3%), while no substantial change was seen in older children. CONCLUSION: The incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.

Teenagers' mental health problems predict probable mental diagnosis 3 years later among girls, but what about the boys?

BACKGROUND: The prevalence of mental disorders is increasing, and there seems to be a gender difference in prevalence, with girls reporting more mental health problems than boys, especially regarding internalizing problems. Most mental disorders debut early but often remain untreated into adulthood. Early detection of mental disorders is essential for successful treatment, which is not always happening. The study aimed to estimate to what extent teenagers' self-reports predict probable mental diagnosis as they enter adulthood, particularly regarding gender differences. METHODS: Self-reported mental health problems, Youth Self-Report (YSR) at 15 years (range 3-110, n = 504) from the ongoing Finnish family competence study (FFC) using modified multivariable Poisson regression analysis for prediction of DAWBA (Development and Wellbeing Assessment) interview outcomes 3 years later. RESULTS: One unit's increase in YSR was estimated to correspond to an increase in the relative risk of a probable DAWBA-based diagnosis by 3.3% [RR (95% CI) 1.03 (1.03-1.04), p < 0.001]. In gender-specific analysis, the findings applied, particularly to girls. CONCLUSIONS: Youth Self-Report (YSR) scores at pubertal age predicted the risk of a probable mental diagnosis at the onset of adulthood, particularly in girls. Further research is needed to explain the lower sensitivity of YSR among boys.

Metabolic trajectories in childhood and adolescence: Effects on risk for schizophrenia.

Abnormal glucose and lipid metabolism is common in antipsychotic-naive first-episode patients with schizophrenia, but it is unclear whether these changes can already be seen in premorbid or prodromal period, before the first psychotic episode. We examined insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride trajectories in children and adolescents (9-18 years old), who were later diagnosed with schizophrenia, any non-affective psychosis (NAP) or affective disorder (AD). The study population consisted of a general population-based cohort "The Cardiovascular Risk in Young Finns Study", started in 1980 (n = 3596). Psychiatric diagnoses were derived from the Health Care Register up to the year 2018. Multivariate statistical analysis indicated no significant differences in insulin or lipid levels in children and adolescents who later developed schizophrenia (n = 41) compared to the cohort control group (n = 3202). In addition, no changes in these parameters were seen in the NAP (n = 74) or AD (n = 156) groups compared to the controls, but lower triglyceride levels in childhood/adolescence associated with earlier diagnosis of psychotic disorder in the NAP group. Taken together, our results do not support any gross-level insulin or lipid changes during childhood and adolescence in individuals with later diagnosis of schizophrenia-spectrum disorder. Since changes in glucose and lipid metabolism can be observed in neuroleptic-naive patients with schizophrenia, we hypothesize that the more marked metabolic changes develop during the prodrome closer to the onset of the first psychotic episode. The findings have relevance for studies on developmental hypotheses of schizophrenia.

Child neurology services for children with epilepsy in Finland.

OBJECTIVE: The aim of the study was to describe healthcare organization, training of and needs for child neurologists, patient accessibility to services, and treatment paths of children with epilepsy in Finland. METHODS: Data were collected from all geographic healthcare areas over Finland on training capacity in child neurology, number and density of child neurologists, and availability and accessibility of child neurological services. Data sources included the National Physician Register, Central Register of Healthcare Professionals of National Supervisory Authority for Welfare and Health, and phone and email inquiries to the heads of public healthcare units. RESULTS: The overall density of child neurologists in Finland was 11.9/100 000 children aged 0-15 years or 8402 children per child neurologist (in 2018). There is a remarkable geographic variation, from 7.1 in northern Finland to 15.6 in the metropolitan area. However, waiting times for the treatment are virtually the same all over the country. According to the Finnish current practice recommendation from the year 2013 and again 2020, children with any first nonfebrile or complicated febrile epileptic seizure are invariably admitted to hospital for evaluation. Children with simple febrile seizures are recommended to be treated as outpatients by general practitioners or by experienced pediatricians. SIGNIFICANCE: Child neurology services are today well provided and organized in Finland. While there is geographic variation in the number of child neurologists, the accessibility is virtually the same all over the country. A gap between the numbers of specialists at near-to-retire age and those in training is a challenge.

Sense of coherence predicts adolescent mental health.

BACKGROUND: Strong sense of coherence (SOC) has been shown to predict good mental health among adults whereas its predictive value in adolescence is unclear. This life-course oriented prospective study explores whether SOC predicts mental health in a three-year follow-up. METHODS: The data is part of the ongoing 'Finnish Family Competence Study' launched in 1986 in southwestern Finland (baseline n = 1287). The outcome variable was adolescent's mental health at 18 years of age, measured on the Development and Well-Being Assessment (DAWBA) scale. The main predictor was Antonovsky's SOC score (1987) measured at the age of 15. A total of 498 adolescents were included in the present analyses. Poisson regression was used by univariate and multivariable models using the parents' age and socioeconomic status and adolescents' gender as covariates. RESULTS: Multivariable analysis showed that a one-unit increase in SOC decreased the relative risk of a DAWBA-based diagnosis by 4 % (RR [95% CI] 0.96 [0.94-0.98], p < 0.001). LIMITATIONS: Typical of very long follow-up, as in our study of nearly two decades, a substantial proportion of the original population-based cohort was lost to follow-up weakening the representability of our cohort. CONCLUSIONS: Sense of coherence is a useful and clinically sensitive tool to predict mental health in adolescence. The easily administered, coping-oriented SOC questionnaire is an appropriate instrument in screening for adolescents who would benefit from supportive measures to strengthen their mental well-being.

Body mass index trajectories in childhood and adolescence - Risk for non-affective psychosis.

BACKGROUND: Underweight in early adulthood increases risk for schizophrenia, but the effect of early childhood underweight on psychosis risk is not well known. METHODS: We studied whether underweight or overweight in childhood and adolescence increases risk for non-affective psychosis or other psychiatric disorders in a population-based cohort study 'Cardiovascular Risk in Young Finns'. Body mass index (BMI) trajectories were recorded in the years 1980, 1983 and 1986 (in 3-18 years of age), before the first hospitalization due to a psychiatric disorder. BMI was categorized as underweight, normal weight or overweight, using the BMI classification for children and adolescents. We formed DSM-IV based diagnostic groups of non-affective psychosis (n = 69, including a schizophrenia subgroup, n = 41) and affective disorders (i.e. mood and anxiety disorders, n = 112) based on the Care Register for Health Care. Groups were compared with subjects with no psychiatric diagnoses (n = 3310). Sex, age, low birthweight and mother's mental disorders were included in the analyses. RESULTS: Underweight, but not overweight, independently predicted later development of non-affective psychosis. The risk of psychosis was over two-fold (relative risk (RR) [95% CI] 2.31 [1.2-4.4]) and of schizophrenia nearly 2.5-fold (RR 2.44 [1.03-5.8]) after underweight in childhood/adolescence. Underweight or overweight in childhood and adolescence was not associated with mood or anxiety disorders. CONCLUSIONS: These results support the hypothesis of non-affective psychosis as a neurodevelopmental disorder with somatic manifestations throughout childhood and adolescence.

Inflammatory Bowel Disease Incidence is on the Continuous Rise Among All Paediatric Patients Except for the Very Young: A Nationwide Registry-based Study on 28-Year Follow-up.

BACKGROUND AND AIMS: The burden of inflammatory bowel disease [IBD] in health care is high. We conducted research on the temporal changes in the incidence of paediatric IBD [PIBD] using nationwide registry-based data in Finland. METHODS: All PIBD cases diagnosed at less than 20 years of age during 1987-2014 [in total, 5415 patients] were retrieved from a database documenting reimbursements for drug costs. Incidence rates were calculated by dividing the number of annual new PIBD cases by the size of the paediatric population at risk during each calendar year. Temporal trends in the incidences of PIBD and its subtypes, ulcerative colitis [UC] and Crohn's disease [CD], were estimated using Poisson regression analyses. RESULTS: The mean annual incidence of PIBD increased from 7/100000 for the years 1987-1990 to 23/100000 for the years 2011-2014. The average rate of increase was 4.1% (95% confidence interval [CI]: 3.6-4.5) per annum. In the period 2000-2014, the increase rate in the annual incidence of UC [3.8%; 95% CI: 2.7-5.0], was steeper than for CD [2.5%; 95% CI: 1.0-3.8]. The most pronounced increase occurred in UC among adolescents aged 16-19 years [4.8%; 95% CI: 2.9-6.7]. For children less than 10 years of age, the rate of change remained low. Approximately 0.17% of the birth cohort for the years 1999-2000 was diagnosed with PIBD by the age of 14 years. CONCLUSION: The incidence of PIBD is primarily increasing among adolescents, challenging the identification of the possible environmental triggers for the disease.

Effects of childhood and adolescence physical activity patterns on psychosis risk-a general population cohort study.

Schizophrenia spectrum disorders are associated with high morbidity and mortality in somatic diseases. The risk factors of this excess mortality include, e.g., obesity, dietary factors, and physical inactivity, especially after the onset of psychosis, but there are limited early developmental data on these factors in individuals who later develop psychosis. A population-based cohort study "Cardiovascular Risk of Young Finns" started in 1980 with 3596 children and adolescents from six different age groups (3, 6, 9, 12, 15, and 18 years). Cardiovascular health parameters, including questionnaire of physical activity before first hospitalization (≤18 years), were studied in 1980, 1983, and 1986. All psychiatric diagnoses of the participants were derived from the Finnish Hospital Discharge Register up to the year 2012. We identified diagnostic groups of non-affective psychosis (n = 68, including a schizophrenia subgroup, n = 41), personality disorders (n = 43), affective disorders (n = 111), and substance-related disorders (n = 49), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Groups were compared with controls with no psychiatric diagnoses (n = 3325). Sex, age, body mass index, birth weight, non-preterm birth, and mother's mental disorders were included in the statistical model. Low physical activity in childhood and adolescence (9-18 years) independently predicted later development of non-affective psychosis. Lower physical activity index (relative risk 1.26 [1.1-1.5]), lower level of common activity during leisure time (relative risk 1.71 [1.2-2.5]), and non-participation in sports competitions (relative risk 2.58 [1.3-5.3]) were associated with a higher risk for later non-affective psychosis (expressed as increase in relative risk per physical activity unit). The findings were even stronger for schizophrenia, but no such link was observed for other diagnoses. The cause of low physical activity in premorbid/prodromal phase is likely to be multifactorial, including deviant motor and cognitive development. The results provide a rationale for including exercise and physical activity interventions as a part of psychosis prevention programs.

Long-term mortality of patients with West syndrome.

Objective: To study long-term survival and mortality among patients with West syndrome. Methods: The study population included all children born in 1960-1976 and treated for West syndrome in three tertiary care hospitals in Helsinki, Finland. The participants were prospectively followed for five decades for survival. Death data were derived from the National Causes of Death Register of the Population Register Center of Statistics Finland. Results: During follow-up, 102 (49%) of 207 patients had died at the mean age of 19 years. The mean overall annual mortality rate was 15.3 per 1,000 patient-years. The rates ranged from 18.2 per 1,000 after 10 years to 17.2 per 1,000 after 20 years and 15.4 per 1,000 patient-years after 40 years of follow-up. One fourth (25%) had died by 17.2 (95% CI 11.8-22.7) years and 50% by 48.6 (95% CI 38.5-NA) years of follow-up. Etiology at onset was symptomatic in 87% patients and cryptogenic in 13%; 6 of the latter 26 patients later turned out to be symptomatic. The mean annual mortality rate was 3.7 per 1,000 for 4 patients with cryptogenic etiology and 17.6 per 1,000 for those with symptomatic etiology. The hazard of death was fivefold in patients with symptomatic etiology versus cryptogenic etiology. The overall autopsy rate was 73%. Pneumonia was the most frequent cause of death (46%). All patients who died of pneumonia had symptomatic etiology. SUDEP occurred in 10 patients and was the most common epilepsy-related cause of death (10%). Significance: Risk of excess death of participants with West syndrome is not limited to early age but continues into adulthood, particularly in those with symptomatic etiology, and leads to death in half the cases at around 50 years of age. Measures should be directed to prevent pneumonia, the most common overall cause, and SUDEP, the most frequent seizure-related cause, of death.

Gender differences in actual and preferred nocturnal sleep duration among Finnish employed population.

OBJECTIVE: Sufficient sleep is essential for health and working capacity. Shorter sleep duration on workdays is often compensated by sleeping longer during leisure days. Gender dissimilarities in sleep quality are acknowledged. Our aim was to study the less known gender differences in sleep duration. METHODS: A population based study with a total of 1049 middle-aged regularly working women (n=524) and men (n=525). A questionnaire of sleep durations on workdays and leisure days, preferred sleep duration, with health-related quality of life and health behavior. RESULTS: Women slept 14min longer on workdays (p<0.002) and 27min longer on leisure days (p<0.002) and had 32min longer preferred sleep duration (p<0.001) than men. Compared to workdays, women slept 1h 57minutes longer and men 1h 42min longer on leisure days (gender p<0.001). On workdays, both women and men slept less than their preferred sleep duration and again, with more extensive difference in women (gender-interaction p<0.001). On leisure days the excessive sleep time did not differ between genders (p=0.346). None of the explanatory variables explained the gender differences in sleep durations. CONCLUSIONS: Sleep loss on workdays is presumably more pronounced in women, since despite their longer sleep on workdays, the gender differences persist in both sleep duration on leisure days and in preferred sleep duration.

Prenatal diagnosis improves the postnatal cardiac function in a population-based cohort of infants with hypoplastic left heart syndrome.

BACKGROUND: Prenatal diagnosis of hypoplastic left heart syndrome (HLHS) enables planning of perinatal care and is known to be associated with more stable preoperative hemodynamics. The impact on postnatal myocardial function is poorly known. The aim of this study was to determine the impact of prenatal diagnosis of HLHS on postnatal myocardial function. METHODS: A consecutively encountered cohort of 66 infants with HLHS born between 2003 and 2010 in Finland was retrospectively reviewed. Twenty-five infants had prenatal diagnoses. Postnatal global and segmental right ventricular fractional area change, strain rate, and myocardial velocity were analyzed from the apical four-chamber view using Velocity Vector Imaging. Preoperative hemodynamic status and end-organ damage measurements were the lowest arterial pH, highest lactate, alanine aminotransferase, and creatinine. Early mortality was studied until 30 days after Norwood procedure. RESULTS: Prenatally diagnosed infants had better cardiac function (fractional area change, 27.9 ± 7.4% vs 21.1 ± 6.3%, P = .0004; strain rate, 1.1 ± 0.6/1.3 ± 1.0 vs 0.7 ± 0.2/0.7 ± 0.3 1/sec, P = .004/.003; myocardial velocity, 1.6 ± 0.6/2.0 ± 1.1 vs 1.3 ± 0.4/1.4 ± 0.4 cm/sec, P = .0035/.0009). Mechanical dyssynchrony was similar in both groups (P > .30). Infants diagnosed prenatally had less acidosis (pH = 7.30 vs 7.25, P = .005) and end-organ dysfunction (alanine aminotransferase, 33 ± 38 vs 139 ± 174 U/L, P = .0001; creatinine, 78 ± 18 vs 81 ± 44 mmol/L, P = .05). No deaths occurred among the prenatally diagnosed infants, but four deaths were recorded among postnatally diagnosed infants (P = .15). CONCLUSIONS: A prenatal diagnosis of HLHS is associated with improved postnatal right ventricular function, reduced metabolic acidosis, and end-organ dysfunction.