De novo variants in RNF213 are associated with a clinical spectrum ranging from Leigh syndrome to early-onset stroke.

PURPOSE: RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations. METHODS: Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts. RESULTS: We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect. CONCLUSION: De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.

Participation in club sport in childhood is associated with mental health in preterm and term born adolescents.

Preterm born individuals have an increased risk for mental health problems. Participation in club sport is associated with better mental health but the causal direction is unclear. It is not known whether this association could also be found in preterm children. Data from term born (N = 10,368), late preterm (N = 630), and very to moderately preterm born (N = 243) children from the Millennium Cohort Study at the ages of 3, 5, 7, 11, and 14 years were used. Longitudinal associations between the parent-reported Strengths and Difficulties questionnaire (SDQ) and club sport participation (days per week) were analysed using multigroup structural equation modelling, adjusting for gender, maternal depression, parental education; motor problems and attrition were controlled for. Multi-group structural equation modelling showed that children with more peer relationship problems, emotional symptoms, conduct problems or hyperactivity-inattention were less likely to participate in club sport at subsequent assessment time points. More days with club sport participation was associated with lower levels of emotional symptoms and peer relationship problems but not conduct problems or hyperactivity-inattention at subsequent ages. Results were similar in all gestational age groups. Club sport participation predicts lower levels of peer relationship and emotional problems in subsequent waves while it is also predicted by lower levels of emotional problems, peer relationship problems, conduct problems and hyperactivity-inattention in preceding waves. Since no differences in the relationship between SDQ subscales and club sport participation were seen with regard to gestational age groups, club sport should be encouraged in all children.

[The biopsychosocial understanding of health disorders and impairments in children with a focus on developmental neurological relationships]. / Das biopsychosoziale Verständnis von Gesundheitsstörungen und Beeinträchtigungen bei Kindern mit Fokus auf entwicklungsneurologische Zusammenhänge.

The distinction between mental (spiritual and psychological) and physical health disorders is particularly difficult due to the special features of neurobiological development in children and adolescents. In this review article, the basics of developmental neurology are briefly described. On the basis of some congenital or early acquired neurological diseases, it is then shown to what extent mental processes can be impaired in interactions with the social context. Taking these aspects into account plays an important role in child and family-oriented counseling and support. The common occurrence of physical, mental, and psychological development disorders, which is also very variable between individuals and fluctuates over the course of a person's life, requires good interdisciplinary cooperation between conservative and surgical child and adolescent medicine and child and adolescent psychiatry.

Extremely and very preterm-born children <1500 g show different weight development in childhood compared to their peers.

AIM: To develop reference growth charts for body mass index (BMI), weight, length and head circumference in children born extremely preterm (EPT) or very preterm (VPT) with a birth weight <1500 g. METHODS: We analysed EPT and VPT children from the German Neonatal Network born between 2009 and 2013 without chronic diseases or medications influencing growth. These data of EPT and VPT datasets were split into a training dataset and a validation dataset. In the validation dataset, data from 385 EPT and 491 VPT children from birth to age 6 years were analysed to calculate growth charts. RESULTS: The percentiles of length of EPT and VPT children were comparable to German reference percentiles. The BMI peak in infancy was attenuated, and BMI was lower in all the EPT and VPT children analysed. From 2 years until 6 years of age, head circumference was lower in EPT and VPT boys and girls. CONCLUSION: Deficits in height described in EPT cohorts born during the 1980 s and 1990 s were not seen in our cohort. However, EPT and VPT born children showed growth patterns that differed from national reference curves for BMI. The growth charts provided here can be used to judge the growth of EPT and VPT born children.

Prospective Study of Physical Activity of Preterm Born Children from Age 5 to 14 Years.

OBJECTIVE: To investigate whether level of prematurity (very, moderate, late preterm, vs full term) is associated with physical activity from childhood to adolescence and to identify factors in childhood that predict moderate-vigorous physical activity in early adolescence. STUDY DESIGN: Parents reported on physical activity at the age 5, 7, and 11 years (n = 12 222-14 639) and adolescents self-reported on moderate-vigorous physical activity at 14 years (n = 10 974). At age 14 years, a subgroup was also assessed by wrist accelerometer (n = 4046). RESULTS: Prematurity was associated with a small or no difference in physical activity at each time point. At age 14 years, moderate-vigorous physical activity in self-report and accelerometer was higher in male adolescents, those of white ethnicity, or higher parental education, having been taken to live sport events at age 5 or 7 years or having taken part in organized physical activity at 5 or 7 years. CONCLUSIONS: In this representative national cohort study in the United Kingdom, preterm birth was not found to be associated with physical activity between 5 and 14 years. Organized physical activity and watching sport events early in life may increase moderate to vigorous physical activity in adolescents.

Association of physical activity and cardiorespiratory function or BMI and body composition in preterm-born individuals: a systematic review.

AIM: To evaluate the association of physical activity (PA) and forced expiratory volume in one second (FEV1), peak oxygen consumption (pVO2), body mass index (BMI) and body composition in preterm-born individuals. METHODS: Cochrane Library, EMBASE, MEDLINE, AMED, ERIC, Web of Science and PsycInfo were searched with no restriction on language and date of publication from inception to January 2018. Data were extracted comparing preterm-born individuals with different frequencies of PA and the outcome of interest. RESULTS: One randomized controlled, two longitudinal and thirteen cross-sectional studies comprising 1922 preterm-born individuals aged 5-25 were included. Assessment varied from a PA program to accelerometer data, interviews and self-report questionnaires. In preterm-born children, more PA was associated with better cardiorespiratory function in those groups with impaired lung function or with lower BMI in those groups with increased risk factors, but no association was found in unimpaired children. In preterm-born adults, more PA was associated with higher pVO2 and lower BMI. CONCLUSION: Only tentative conclusions can be drawn, especially regarding differences of the association of PA between preterm- and term-born populations. Further studies are needed to analyse the association of PA in preterm-born individuals with reduced cardiorespiratory function.

Alternating Hemiplegia of Childhood as a New Presentation of Adenylate Cyclase 5-Mutation-Associated Disease: A Report of Two Cases.

Mutations in the adenylate cyclase 5 (ADCY5) gene recently have been identified as the cause of a childhood-onset disorder characterized by persistent or paroxysmal choreic, myoclonic, and/or dystonic movements. The 2 novel mutations we identified expand the clinical spectrum of ADCY5 mutations to include alternating hemiplegia of childhood.

Does Breastmilk Influence the Development of Bronchopulmonary Dysplasia?

OBJECTIVE: To assess whether breastmilk feeding is associated with a reduced risk of bronchopulmonary dysplasia (BPD). Secondary outcome measures analyzed were retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). STUDY DESIGN: In an ongoing multicenter cohort study, the data of 1433 very low birth weight infants born before 32 weeks of gestation and discharged in 2013 were analyzed. We compared growth and neonatal complications of infants who received breastmilk exclusively (N = 223) with those who received formula feedings exclusively (N = 239). Logistic regression models were estimated for BPD, ROP, and NEC using nutrition as an independent variable. The Firth logistic regression model and Lasso were used for sensitivity analyses. RESULTS: Exclusively breastmilk-fed infants gained less weight compared with formula-fed infants. SDS for weight decreased between birth and discharge (median (Q1-Q3): formula -0.9 (-1.4 to [-0.5]) vs breastmilk -1.1 (-1.7 to [-0.6])). Exclusive formula feeding of very low birth weight infants was associated with increased risks of BPD (OR 2.6) as well as NEC (OR 12.6) and ROP (OR 1.80) after controlling for known risk factors. CONCLUSIONS: Exclusive breastmilk feeding was associated with lower growth rates and a reduced risk of BPD as well as NEC and ROP.

Maternal super-obesity.

PURPOSE: Pregnant women with a body-mass-index (BMI) above 50 are referred to as "super-obese". For these women adverse pregnancy outcome and a higher risk of fetal congenital defects are major issues. This report focuses on the ratio development of super-obesity in pregnant women, as well as on prenatal ultrasound and pregnancy outcome in the super-obese gravida. METHODS: We reviewed data of all women with a BMI above 30 who delivered at our unit in a 15-year period between January 2000 and December 2014. Data of obese but not super-obese mothers were evaluated in comparison. RESULTS: Final evaluation comprised 69/20,711 pregnancies of super-obese mothers. Forty out of 69 women suffered from a preexisting condition requiring medical treatment. Fetal ultrasound evaluation revealed severe congenital defects in four cases. There were no missed and no false positive diagnoses. Elective cesarean section (c-section) took place in 26/69 cases, 21/69 had a secondary c-section. Twenty-two out of 69 women delivered vaginally. Mean gestational age at delivery was 38(+6) gestational weeks. Pregnancy was complicated by macrosomia in 17/69 pregnancies. Severe neonatal hypoglycemia occurred in 6/69 cases. The number of deliveries by super-obese mothers showed no marked variation during the study period. In contrast the rate of deliveries by obese, but not super-obese, mothers showed an increase. CONCLUSIONS: Maternal super-obesity poses a high-risk situation for mother and child which generally demands a higher amount of perinatal care. The number of deliveries by super-obese mothers remained stable over the study period. Primary c-section was the most frequent mode of delivery. Of the parturients who opted for vaginal delivery nearly half of the deliveries had to be completed by secondary c-section. Over-all peripartal maternal complications did not exceed average.

Perinatal Outcomes of Immigrant Mothers and Their Infants Born Very Preterm across Germany.

BACKGROUND: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes. METHODS: The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 (n = 1738 female) children were assessed, and 919 (n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable. RESULTS: Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers. CONCLUSIONS: Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants.

Pregnancy risk factors for very premature delivery: what role do hypertension, obesity and diabetes play?

PURPOSE: Very premature delivery is a major cause of infant morbidity and mortality. Obesity, diabetes and pregnancy hypertension are known risk factors for pregnancy complications. The study aimed to scrutinize differences of pregnancy complications in a cohort of very premature deliveries compared to a national group. METHODS: In a multicenter study performed between January 2009 and December 2010 including 1,577 very low birth weight (VLBW) infants, we compared parental reported pregnancy problems of VLBW infants with a national cohort (KIGGS). We compared reported pregnancy complications to reasons for premature delivery and neonatal outcome within the group of VLBW infants. RESULTS: While parents of the national cohort reported pregnancy-induced hypertension in 8 %, parents of VLBW infants reported this complication more frequently (27 %). Mothers of the national cohort were significantly younger (1 year), suffered less from obesity, anaemia, diabetes. Regression analysis showed that hypertension (OR = 5.11) and advanced maternal age (OR = 1.03) increased the risk for premature birth. Women with hypertension were likely to experience a clinically indicated premature delivery, had more VLBW infants with a moderate growth restriction, but less multiples and their infants had less intraventricular haemorrhages grade 3 or 4. Otherwise, neonatal outcome was correlated with gestational age but not with the pregnancy complications diabetes, hypertension or obesity. CONCLUSION: Premature birth seems to be correlated to gestational hypertension and associated problems in about » of VLBW infants. Further studies should focus on preventing and treating gestational hypertension to avoid premature delivery and associated neonatal morbidity.

Association of Birth Weight Centiles and Gestational Age With Cognitive Performance at Age 5 Years.

Importance: Birth weight percentiles (BWPs) are often dichotomized at the 10th percentile and show statistically significant association with later cognitive performance, for both preterm and term-born children. However, research testing nonlinear associations between BWPs and cognitive performance is scarce. Objective: To investigate culturally invariant, nonlinear associations of BWPs and gestational age with later cognitive performance. Design, Setting, and Participants: In this cohort study, participants with valid neonatal and cognitive data were combined from 4 observational cohorts, including the Millennium Cohort Study, the National Longitudinal Survey of Youth 1979 Child and Young Adult cohort, Growing Up in Ireland, and the Longitudinal Study of Australian Children, with children born between 2000 and 2002, 1980 and 2010, 2007 and 2008, and 2003 and 2004, respectively. Neonatal data were parent reported before age 1 year. At approximately 5 years of age, multiple cognitive tests were performed. Follow-up at 5 years of age was the predominant focus. Data were analyzed July 17, 2023. Exposure: The parent-reported neonatal data were used to calculate BWPs according to the Fenton growth chart. Main Outcome and Measure: Scores for IQ were created from multiple measures of cognition, which were z standardized separately within each cohort. Results: Of 30 643 participants (50.8% male), 7.5% were born preterm (before 37 weeks gestation) and 92.5% were term born (between 37 and 42 weeks gestation). In the pooled data using multivariate adaptive regression splines, IQ linearly increased by 4.2 points as BWPs increased from the first to the 69th percentile before completely plateauing. For gestational age, IQ linearly increased by 1.3 points per week up until 32 weeks, with the association reducing to 0.3 points per week after 32 weeks. The association of BWP with IQ was not moderated by gestational age. For term-born infants, the estimated IQ score was only clinically meaningfully lower than average when birth weight was below the third percentile. Consistent results were found when instead using multivariable regression where gestational age and BWPs were categorized into groups. Conclusions and Relevance: In this cohort study, lower BWPs and gestational age were independently associated with lower IQ. For term-born infants, a cutoff of the third percentile would be more appropriate than the traditionally used 10th percentile when the aim is estimating meaningful cognitive differences.

Timing of Ketogenic Dietary Therapy (KDT) Introduction and Its Impact on Cognitive Profiles in Children with Glut1-DS-A Preliminary Study.

The aim of this research was to characterize cognitive abilities in patients with Glut1-Deficiency syndrome (Glut1DS) following ketogenic diet therapy (KDT). METHODS: The cognitive profiles of eight children were assessed using the Wechsler Intelligence Scale (WISC-IV). The effect of ketogenic diet therapy (KDT) on individual subareas of intelligence was analyzed considering the potential influence of speech motor impairments. RESULTS: Patients with Glut1DS showed a wide range of cognitive performance levels. Some participants showed statistically and clinically significant discrepancies between individual subdomains of intelligence. Both variables, KDT initiation as well as duration, had a positive effect on the overall IQ score. Significant correlations were partially found between the time of KDT initiation and the level of IQ scores, depending on the presence of expressive language test demands of the respective subtests of the WISC-IV. Accordingly, the participants benefited les in the linguistic cognitive domain. The discrepancies in cognitive performance profiles of patients with Glut1DS can be attributed to the possibility of a negative distortion of the results due to the influence of speech motor impairments. CONCLUSIONS: The individual access skills of test persons should be more strongly considered in test procedures for the assessment of intelligence to reduce the negative influence of motor deficits on test performance. Specific characterization and systematization of the speech disorder are indispensable for determining the severity of speech motor impairment in Glut1DS. Therefore, a stronger focus on dysarthria during diagnosis and therapy is necessary.

Indomethacin Prophylaxis Is Associated with Reduced Risk of Intraventricular Hemorrhage in Extremely Preterm Infants Born in the Context of Amniotic Infection Syndrome.

BACKGROUND: Amniotic infection syndrome (AIS) with perinatal inflammation may increase the susceptibility to intraventricular hemorrhage (IVH) in preterm infants. Given its anti-inflammatory and ductus arteriosus constricting capacities, we hypothesized that prophylactic administration of indomethacin reduces the incidence, severity, and consequences of IVH in the context of perinatal inflammation. METHODS: We evaluated data of infants born between 2009 and 2020 of 22 + 0-25+6 weeks of gestation from 68 German Neonatal Network centers. The effect of indomethacin prophylaxis on outcomes was analyzed in univariate analyses and multivariate regression models including a subgroup of infants with available data on 5-year follow-up. RESULTS: 4760 infants were included with a median gestational age of 24.6 SSW [interquartile range (IQR) 24.1w-25.2w] and a birth weight of 640 g [IQR 550-750 g]. 1767/4760 (37.1%) preterm infants were born in the context of AIS and 527/4760 (11.1%) received indomethacin prophylaxis. AIS infants receiving prophylactic indomethacin had lower rates of IVH (32.7% vs. 36.9%, p = 0.04), IVH III/IV (9.7% vs. 16.0%, p = 0.02) and the combined outcome of severe IVH or death (15.9% vs. 23.2%, p = 0.01) as compared to infants without prophylaxis. Multivariate logistic regression analyses confirmed our observations. In a subgroup analysis of 730 preterm infants at 5 years of age, we did not find any correlation between prophylactic indomethacin and intelligence quotient <70 or cerebral palsy. CONCLUSIONS: Our observational data demonstrate that prophylactic indomethacin is associated with a reduced risk of IVH in the highly vulnerable subgroup of preterm infants <26 weeks of gestation born from AIS.

Causes of delivery and outcomes of very preterm twins stratified to zygosity.

The increasing rates of preterm birth among twins implicate that solid data on associated risks and outcomes are required. Assessment of zygosity is often based on clinical criteria (evaluation of placenta; same gender, birth weight discordance as surrogate criteria for monochorionic/monozygotic twins). The aim of this study was to compare clinical versus genetic assessment of zygosity and to compare causes of preterm delivery as well as outcome data of very-low-birth-weight (VLBW; birth weight <1,500 g) twins stratified to zygosity. In a multicenter study, we selected n=176 sets of same gender twins and determined zygosity genetically. In a subgroup of 123 sets of twins, the attending physicians at the study centers were asked to document the parameter 'zygosity' (monozygotic/dizygotic) on the basis of their clinical judgment. Concordance between genetic and clinical assessment was 62.7% for monozygotic twins and 88.9% for dizygotic twins, respectively. Outcome parameters (death, BPD, ROP, NEC, IVH) were comparable in both groups. Genetically dizygotic twins were significantly more often born due to intrauterine infection (33% vs. 20% in monozygotic twins, p<.01) and antenatal antibiotics were more frequently given to mothers of dizygotic twins (62% vs. 47% in monozygotic twins, p<.01). Obstetric complications such as twin-twin-transfusion-syndrome were only seen in monozygotic twins as expected. The unexpected increase of antenatal antibiotic treatment and birth due to intrauterine infection in dizygotic twins should be confirmed in additional VLBW twin-cohorts.

Progressive Respiratory Insufficiency in a Teenager with Diaphragmatic Hypomotility Due to a Novel Combination of Gliomedin Gene Variants.

Lethal congenital contracture syndrome 11 (LCCS11) is a form of arthrogryposis multiplex congenita (AMC) which is associated with mutations in the gliomedin gene (GLDN) and has been known to be severely life-shortening, mainly due to respiratory insufficiency. Patients with this condition have been predominantly treated by pediatricians as they usually do not survive beyond childhood. In this case report, we present a young adult who developed severe progressive respiratory insufficiency as a teenager due to diaphragmatic hypomotility and was diagnosed with LCCS11 following the discovery of compound heterozygous pathogenic variants in GLDN. This case demonstrates the importance of screening for neuromuscular diseases in well-child visits and follow-ups of patients at risk for gross and fine motor function developmental delay. It also underscores the significance of including LCCS11 and other axonopathies in the differential diagnosis of juvenile onset of respiratory insufficiency, highlights that patients with this condition may present to adult practitioners and questions whether the nomenclature of this condition with various phenotypes should be reconsidered due to the stigmatizing term 'lethal'.

Early Skin-to-Skin Contact Does Not Affect Cerebral Tissue Oxygenation in Preterm Infants <32 Weeks of Gestation.

AIM: It was the aim of our study to determine the regional cerebral tissue oxygenation saturation (rcSO2) as an additional monitoring parameter during early skin-to-skin contact (SSC) in preterm infants with a gestational age of <32 gestational weeks. METHODS: We conducted two observational convenience sample studies using additional monitoring with near-infrared spectroscopy (NIRS) in the first 120 h of life: (a) NIRS 1 (gestational age of 26 0/7 to 31 6/7 weeks) and (b) NIRS 2 (gestational age of 24 0/7 to 28 6/7 weeks). The rcSO2 values were compared between resting time in the incubator (period I), SSC (period II) and handling nursing care (period III). For the comparison, we separated the sequential effects by including a "wash-out phase" of 1 h between each period. RESULTS: During the first 120 h of life 38/53 infants in NIRS 1 and 15/23 infants in NIRS 2 received SSC, respectively. We found no remarkable differences for rcSO2 values of NIRS 1 patients between SSC time and period I (95% confidence interval (CI) for the difference in %: SSC vs. period I [1; 3]). In NIRS 2, rcSO2 values during SSC were only 2% lower compared with period I [median [1. quartile; 3. quartile] in %; 78 [73; 82] vs. 80 [74; 85]] but were similar to period III [78 [72; 83]]. In a combined analysis, a small difference in rcSO2 values between SSC and resting times was found using a generalized linear mixed model that included gender and gestational age (OR 95% CI; 1.178 [1.103; 1.253], p < 0.0001). Episodes below the cut-off for "hypoxia"; e.g., <55%, were comparable during SSC and periods I and III (0.3-2.1%). No FiO2 adjustment was required in the vast majority of SSC episodes. CONCLUSIONS: Our observational data indicate that rcSO2 values of infants during SSC were comparable to rcSO2 values during incubator care and resting time. This additional monitoring supports a safe implementation of early SSC in extremely preterm infants in NICUs.

Recurrent Late-Onset Sepsis in Extremely Low Birth Weight Infants Is Associated with Motor Deficits in Early School Age.

INTRODUCTION: Sepsis is regarded as a risk factor for brain injury in preterm infants. We herein hypothesize that extremely low birth weight infants (ELBWI, birth weight <1,000 g) having survived recurrent blood culture-proven late-onset sepsis (LOS) episodes are more likely to have an adverse long-term neurologic outcome. METHODS: In a large multicenter observational study of ELBWI ≤28 6/7 weeks, we evaluated the impact of recurrent LOS (blood culture-proven, after day 7 of life) on development at 5-6 years. Neurodevelopment, behavior, and motor qualities were tested by blinded investigators. Univariate and logistic regression analyses were performed. RESULTS: The cohort consisted of 1343 ELBWI including 1,080 infants without LOS, 186 infants with one LOS, and 77 with recurrent LOS, i.e., 55 infants with two and 22 infants with three LOS episodes. After Bonferroni-Holm correction, multiple logistic regression analysis revealed recurrent sepsis to be significantly associated with adverse motor development (critical MABC-2 testing: 3.3 [1.5-7.3], p = 0.003, pB = 0.012), whereas no significant impact of recurrent LOS was found on intelligence quotient and behavioral difficulties. Odds of having critical motor testing results for infants with recurrent LOS were 1.7 times (95% confidence interval 1.4-2.3) that of infants with one LOS. CONCLUSION: Recurrent sepsis in preterm infants is associated with adverse long-term motor development. However, infants with recurrent infections are also more likely to have preterm-related complications, and reasons for a worse neurodevelopmental outcome remain to be elucidated.

Sleep problems in infancy and early school age in very preterm infants.

BACKGROUND: Sleep plays an important role for psychological and physical health, especially in infants at high risk for long-term neurodevelopmental impairment such as preterm infants. OBJECTIVE: Our study aimed at determining risk factors for long-term sleep impairment in very-preterm (VPT; <32 weeks of gestation) infants. METHODS: Sleep problems were analyzed in an observational study in infants of the German Neonatal Network born between January 1st 2009 and December 31st 2014. Parental questionnaires of n = 2928 VPT children were evaluated regarding the child's sleep behavior at five years of age. Univariate and logistic regression analyses were used to identify risk factors for delayed sleep onset and hyperactivity/inattention (Strength and Difficulties Questionnaire). In a second cohort of n = 342 VPT infants, sleep habits were evaluated at toddlers age via the Infant Sleep Questionnaire. RESULTS: In our cohorts, 424/2928 (14.5 %) preterm children were diagnosed with delayed sleep onset at early school age while 57/342 (16.7 %) had sleep impairment in early infancy. Gestational age was not independently associated with sleep problems (i.e., early school age: OR 0.97, 95 % CI 0.9-1.1, p = 0.15). Notably, in both our cohorts, neonatal exposure to analgesics and sedatives was associated with a higher risk for sleep problems, i.e., early school age: exposure to sedatives: OR 1.31, 95%CI 1.02-1.7, p = 0.03. Sleep problems and drug exposure were both associated with hyperactivity/inattention. CONCLUSION: Sleep problems of VPT children are unrelated to gestational age which suggests rather individual risk factors. The significant neonatal exposure to analgesics and sedatives may contribute to long-term sleep impairment.