Prenatal Characteristics of Infants with a Neuronal Migration Disorder: A National-Based Study

The development of the central nervous system is complex and includes dorsal and ventral induction, neuronal proliferation, and neuronal migration, organization, and myelination. Migration occurs in humans in early fetal life. Pathogenesis of malformations of the central nervous system includes both genetic and environmental factors. Few epidemiological studies have addressed the impact of prenatal exposures. All infants born alive and included in the Swedish Medical Birth Register 1980–1999 were included in the study. By linkage to the Patient Register, 820 children with a diagnosis related to a neuronal migration abnormality were identified. Through copies of referrals for computer tomography or magnetic resonance imaging of the brain, the diagnosis was confirmed in 17 children. Median age of the mothers was 29 years. At the start of pregnancy, four out of 17 women smoked. Almost half of the women had a body mass index that is low or in the lower range of average. All infants were born at term with normal birth weights. Thirteen infants had one or more concomitant diseases or malformations. Two infants were born with rubella syndrome. The impact of low maternal body mass index and congenital infections on neuronal migration disorders in infants should be addressed in future studies

Perinatal Risk Factors for Childhood Leukemia

The aim of the studies described in this thesis was to assess the association between certain perinatal factors and the risk of childhood lymphatic and myeloid leukemia and infant leukemia. The five studies presented were all conducted in Sweden as population-based case-control studies. All cases were born and diagnosed between 1973-89 with leukemia up to the age of 16 years. A control was individually matched to each case. As Down’s syndrome entails a major risk for childhood leukemia, children with Down’s syndrome were excluded. The studies comprised a total of 652 cases, 47 of whom were diagnosed before the age of one year. Exposure data were extracted blindly from antenatal, obstetric, pediatric and other standardized medical records. No association was found between prenatal exposure to ultrasound or diagnostic x-ray and childhood lymphatic or myeloid leukemia. Infant leukemia was associated with prenatal exposure to x-ray. A history of maternal lower genital tract infection significantly increased the risk of childhood leukemia, especially among children diagnosed at four years or older or in infancy. Factors such as young maternal age, and mothers working with children or in the health sector were associated with infant leukemia. Resuscitation with 100% oxygen with a face-mask and bag directly postpartum was associated with an increased risk of childhood lymphatic leukemia. The oxygen-related risk further increased if the manual ventilation lasted for three minutes or more. There was no association between lymphatic or infant leukemia and supplementary oxygen later in the neonatal period or other birth-related factors. Low Apgar scores at one and five minutes were associated with a non-significantly increased risk of lymphatic leukemia, and were significantly associated with infant leukemia. Previously reported relations between childhood leukemia and exposures such as maternal diagnostic x-ray and birth related factors could not be confirmed by these studies. However, the present studies indicate that events during pregnancy or during the neonatal period are associated with increased risks of childhood and infant leukemia. These events can either be non-specific, such as exposure to maternal lower genital tract infection, or specific, such as the use of supplementary oxygen directly postpartum

Increased risk of pulmonary hypertension following premature birth

Background: Pulmonary hypertension (PAH) among children and adults has been linked to premature birth, even after adjustments for known risk factors such as congenital heart disease and chronic lung disease. The aim of this population-based registry study was to assess the risk of PAH following exposure to premature birth and other factors in the decades when modern neonatal care was introduced and survival rates increased. Methods: Data on pulmonary hypertension and perinatal factors were retrieved from population-based governmental and national quality registers. Cases were adults and children over five years of age with pulmonary hypertension born from 1973 to 2010 and individually matched to six controls by birth year and delivery hospital. Conditional multiple logistic regression was performed to assess the risk of pulmonary hypertension following premature birth and to adjust for known confounding factors for the total study population and for time of birth, grouped into five-year intervals. Results: In total, 128 cases and 768 controls were included in the study group. Preterm birth was over three times more common among cases (21%) than among controls (6%). The overall adjusted risk of pulmonary hypertension was associated with premature birth, OR = 4.48 (95% CI; 2.10–9.53). Maternal hypertension, several neonatal risk factors and female gender were independently associated with PAH when potential confounders were taken into account. For each five-year period, the risk of PAH following premature birth increased several times for children born in the 2000s and later, OR = 17.08 (95% CI 5.60–52.14). Conclusions: Preterm birth, along with other factors, significantly contributes to PAH. PAH following premature birth has increased over the last few decades. Our study indicates that new, yet unknown factors may play a role in the risk of preterm-born infants developing PAH later in life

Risk factors for isolated atrial septal defect secundum morbidity

Abstract Atrial septal defect secundum is a common type of congenital heart defect and even more common among children born premature. The aim of this study was to assess premature birth as a potential associated risk factors for cardiac morbidity in children with isolated ASD II. In this retrospective national registry-based case–control study all children born in Sweden between 2010 and 2015 with an isolated ASD II diagnosis were included. Association between premature birth and cardiac morbidity in children with isolated ASD II was assessed by different outcomes-models using conditional logistic regression and adjustments were made for confounding factors. Overall, 11% of children with an isolated ASD II received treatment for heart failure. Down syndrome was the only independent risk factors for associated with cardiac morbidity in children with ASD II (OR = 2.25 (95%CI 1.25–4.07). Preterm birth in children was not associated with an increased risk of ASD II cardiac morbidity

QTc interval-dependent body posture in pediatrics

Background: Syncope is a common and often benign disorder presenting at the pediatric emergency department. Long-QT syndrome may be presented with syncope, ventricular arrhythmias or sudden death and is vital to exclude as an underlying cause in children presented with syncope. Few studies have assessed QTc in relation to body posture in children. In this study, we assessed the QTc interval while laying down and during active standing in children with known long-QT syndrome compared to healthy controls. Methods: Children aged 1-18 years with long-QT syndrome (N = 17) matched to two healthy controls (N = 34) were included in this case-control study. The ECG standing was performed immediately after the ECG in the supine position. The QTc interval and QTc-difference by changing the body position were calculated. Results: All children with long-QT syndrome were treated with propranolol. QTc was prolonged among long-QT syndrome children while lying down and when standing up, compared to controls. A prolongation of QTc appeared when standing up for both cases and controls. There was no significant difference in QTc increase between the groups. A QTc over 440 ms was observed among four cases lying down and in eight cases while standing, but not in any of the controls. The standing test with a cut-off of 440 ms showed a sensitivity of 47% and a specificity of 100% for case-status in our study. Conclusion: QTc measured on ECG when rapidly rising up is prolonged in both healthy and LQTS children. More importantly, it prolongs more in children with LQTS and increases in pathological levels

Predictors of the Need for an Atrial Septal Defect Closure at Very Young Age

An asymptomatic Atrial Septal Defect (ASD) is often closed at the age of 3-5 years using a transcatheter or surgical technique. Symptomatic ASD or ASD associated with pulmonary hypertension (PHT) may require earlier closure, particularly in combination with other non-cardiac risk factors for PHT, but the indications for early closure and the potential risk for complications are largely unknown. The aim of this study was to assess risk factors for needing ASD closure during the first and second years of life. This case-control study included all children treated with surgical or percutaneous ASD closure between 2000 and 2014 at two out of three pediatric heart centers in Sweden. "Cases" were children with ASD closure at <= 1 or <= 2 years of age. Clinical data were retrieved from medical journals and national registries. Overall, 413 children were included. Of these, 131 (32%) were <= 2 years, and 50 (12%) were <= 1 year. Risk factors associated with a <= 2 years ASD closure were preterm birth, OR = 2.4 (95% CI: 1.5-3.9); additional chromosomal abnormalities, OR = 3.4 (95% CI: 1.8-6.5); pulmonary hypertension, OR = 5.8 (95% CI: 2.6-12.6); and additional congenital heart defects, OR = 2.6 (95% CI: 1.7-4.1). These risk associations remained after adjustments for confounding factors, such as need for neonatal respiratory support, neonatal pulmonary diseases, neonatal sepsis, additional congenital heart defects (CHD) and chromosomal abnormalities. ASD size:body weight ratio of 2.0, as well as a ratio of 0.8 (upper and lower limit of the ASD size:body weight ratios), was associated with increased risk of an early ASD closure. Risk factors such as very premature birth, very low birth weight, congenital, and chromosomal abnormalities, neonatal pulmonary disease and need for ventilation support, as well as pulmonary hypertension, were associated with very early (<1 year of age) ASD closure. Several independent neonatal risk factors were associated with an increased risk of early ASD closure at 2 and at 1 year of age. An ASD size:body weight ratio is a poor predictor for indications for ASD closure

Early Complications After Percutaneous Closure of Atrial Septal Defect in Infants with Procedural Weight Less than 15 kg

Atrial septal defect (ASD) is the most common congenital cardiac lesion accounting for 10-15% of all cardiac malformations. In the majority of cases, the secundum type of the ASD is closed percutaneously in the catheterization laboratory. Although transcatheter closure of ASD is considered safe and effective in pediatric patients, there are limited data regarding the efficacy and safety of device ASD closure in smaller infants. The aim of this study was to determine risk of complications within 72 h following device closure of ASD in children of body weight <15 kg compared to larger children. Overall 252 children who underwent transcatheter closure of ASD at Children's Heart Centre in Lund, Sweden, between 1998 and 2015 were included. Data regarding demographics, comorbidity and complications occurring during and after device procedure until discharge were retrieved from the hospital's databases. Echocardiographic data were obtained from the digital and videotape recordings. Nearly half of the study cohort (n = 112; 44%) had a procedural weight <15 (median 11.3) kg with a median procedural age of 2.02 years. Among this study group, 22 (9%) children had post-procedural in-hospital complications, of which 16 (7%) were considered as major and six (2%) considered as minor. No deaths occurred. There was no significant difference in of the occurrence of major or minor complications between the two groups (p = 0.32). Larger ASD was more often associated with minor complications, OR 1.37 (95% CI 0.99-1.89), which most often consisted of transient arrhythmias during or after the procedure. Percutaneous ASD device closure can be performed safely in low-weight infants with a risk of post-procedural in-hospital complications comparable to larger/older children. Nevertheless, careful considerations of the indications to device closure is needed, particularly in children with larger ASD, as recommended by the current international guidelines for ASD closure

Risk factors for adverse events within one year after atrial septal closure in children : a retrospective follow-up study

Introduction: Secundum atrial septal defect is one of the most common congenital heart defects. Previous paediatric studies have mainly addressed echocardiographic and few clinical factors among children associated with adverse events. The aim of this study was to identify neonatal and other clinical risk factors associated with adverse events up to one year after closure of atrial septal defect. Methods: This retrospective case-control study includes children born in Sweden between 2000 and 2014 that were treated surgically or percutaneously for an atrial septal defect. Conditional logistic regression was used to evaluate the association between major and minor adverse events and potential risk factors, adjusting for confounding factors including prematurity, neonatal sepsis, neonatal general ventilatory support, symptomatic atrial septal defects, and pulmonary hypertension. Results: Overall, 396 children with 400 atrial septal defect closures were included. The median body weight at closure was 14.5 (3.5-110) kg, and the median age was 3.0 (0.1-17.8) years. Overall, 110 minor adverse events and 68 major events were recorded in 87 and 49 children, respectively. Only symptomatic atrial septal defects were associated with both minor (odds ratio (OR) = 2.18, confidence interval (CI) 95% 1.05-8.06) and major (OR = 2.80 CI 95% 1.23-6.37) adverse events. Conclusion: There was no association between the investigated neonatal comorbidities and major or minor events after atrial septal defect closure. Patients with symptomatic atrial septal defects had a two to four times increased risk of having a major event, suggesting careful management and follow-up of these children prior to and after closure