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ObjectiveTo clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters.MethodsClinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons.ResultsEleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons.ConclusionsAnti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons.

This study examined whether physical activity is associated with better mental health and well-being among very preterm (≤32 weeks) and term born (≥37 weeks) adolescents alike or whether the associations are stronger in either of the groups. Physical activity was measured with accelerometry in children born very preterm and at term in two cohorts, the Basel Study of Preterm Children (BSPC, 40 adolescents born ≤32 weeks of gestation and 59 term born controls aged 12.3 years) and the Millennium Cohort Study (MCS, 45 adolescents born ≤32 weeks of gestation and 3137 term born controls aged 14.2 years on average). In both cohorts, emotional and behavioral problems were mother-reported using the Strengths and Difficulties Questionnaire. Subjective well-being was self-reported using the Kidscreen-52 Questionnaire in the BSPC and single items in the MCS. Hierarchical regressions with ‘preterm status × physical activity’-interaction effects were subjected to individual participant data (IPD) meta-analysis. IPD meta-analysis showed that higher levels of physical activity were associated with lower levels of peer problems, and higher levels of psychological well-being, better self-perception/body image, and school related well-being. Overall, the effect-sizes were small and the associations did not differ significantly between very preterm and term born adolescents. Future research may examine the mechanisms behind effects of physical activity on mental health and wellbeing in adolescence as well as which type of physical activity might be most beneficial for term and preterm born children.

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

Objectives\ud To assess the association of gestational age groups (VP

Objective: To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/Bifidobacterium infantis probiotics on the outcomes of preterm infants &lt, 29 weeks of gestation that receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit from probiotics in terms of sepsis prevention and growth. Methods: We performed an observational study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013 and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm infants &lt, 29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727). The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted in linear/logistic regression models. Results: 5954 (76.5%) infants received L. acidophilus/B. infantis prophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size B = 0.224, 95% CI: 2.82&ndash, 4.35, p &lt, 0.001) but not in the F group (effect size B = &minus, 0.06, 95% CI: &minus, 3.05&ndash, 0.28, p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation proved to be protective against clinical sepsis (OR 0.69, 95% CI: 0.59&ndash, 0.79, 0.001). Conclusion: Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive effect, probiotics seem to require human milk.

ObjectivePostnatal vitamin D supplementation is standard of care in neonates and preterm infants. Despite routine supplementation of vitamin D, a wide range of complications related to vitamin D deficiency has been described in the literature. Since standard vitamin D supplementation might be not sufficient in preterm infants with a genetic predisposition for vitamin D deficiency, we investigated the outcome of preterm infants with regard to their genetic estimated vitamin D levels.MethodsPreterm infants with a birth weight below 1500 grams were included in the German Neonatal Network at the time of their birth and tested at the age of five. The vitamin D level was genetically calculated based on three single nucleotide polymorphisms (SNPs: rs12794714, rs7944926 and rs2282679) which alter vitamin D synthesis pathways. Specific alleles of these polymorphisms are validated markers for low plasma vitamin D levels. Outcome data were based on baseline data at the time of birth, typical complications of prematurity, body measurements at the age of five and occurrence of bone fractures. T-test and Fisher's exact test were used for statistical comparison.ResultsAccording to their genetic predisposition, 1,924 preterm infants were divided into groups of low (gsVitD < 20. Percentile), intermediate and high vitamin D level estimates. Low genetic vitamin D level estimates could not be shown to be associated with any adverse outcome measures examined. The analyses covered data on aforementioned determinants.ConclusionLow genetic vitamin D level estimates could not be shown to be associated with previously described adverse outcome in preterm infants.

Eine Fruhfordermasnahme mit Schwerpunkt Eltern-Kind-Interaktion im ersten Lebensjahr ist bei sehr kleinen Fruhgeborenen (VLBW) mit einem besseren kognitiven Outcome im Schulalter assoziiert. Wie die Verordnung von Fruhforderung bei VLBW-Kindern in Deutschland gehandhabt wird, wurde noch nicht systematisch untersucht. Folgende Fragen sollten untersucht werden: Welche Angebote machen Fruhforderstellen bei VLBW-Fruhgeborenen? Welche Barrieren bestehen fur die Inanspruchnahme einer Fruhfordermasnahme bei VLBW-Fruhgeborenen? Welche VLBW-Fruhgeborenen erhalten eine Fruhfordermasnahme im ersten Lebensjahr? Im Rahmen eines strukturierten Interviews befragten wir Fruhforderstellen (N = 81) in Deutschland zu den von ihnen eingesetzten Therapeuten und Therapieformen. Gleichzeitig ermittelten wir Barrieren fur die Inanspruchnahme einer Fruhfordermasnahme. Wir erhoben mithilfe einer Onlinebefragung von VLBW-Nachsorge-Einrichtungen (N = 44) deren Empfehlungen zu Fruhfordermasnahmen im ersten Lebensjahr sowie Barrieren. Wir analysierten anhand von quantitativen Daten einer Fruhgeborenenkohorte (German Neonatal Network [N = 1387]) die Inanspruchnahme von Fruhforderung. Einen Forderschwerpunkt im Bereich der Eltern-Kind-Interaktion gaben 38/81 Fruhforderstellen zusatzlich zu einer Entwicklungsforderung des Kindes an. Barrieren fur die Initiierung einer Fruhfordermasnahme im ersten Lebensjahr waren eine fehlende Information bzw. ein fehlendes Verstandnis des Nutzens aufseiten der Eltern und der niedergelassenen Kinderarzte; ein fordernder Faktor war eine sozialmedizinische Nachsorge. Eine Fruhfordermasnahme im ersten Lebensjahr erhielten 346 (25 %) der sehr kleinen Fruhgeborenen uberwiegend therapeutisch nach neonatalen Komplikationen wie einer intraventrikulare Hamorrhagie (OR [95%-KI]: 1,35 [1,17–1,55]), bronchopulmonalen Dysplasie (1,75 [1,20–2,55]) oder bei einem geringeren Gestationsalter (0,77 [0,62–0,95]). Eine generelle Empfehlung der Klinik/Nachsorge zu einer Fruhfordermasnahme fur alle sehr kleinen Fruhgeborenen wurde als der wichtigste Faktor im Zugang zur Fruhforderung identifiziert (OR [95%-KI]: 5,70 [2,78–11,69]). Der evidenzbasierte Einsatz von Fruhforderung mit dem Schwerpunkt Eltern-Kind-Interaktion wird bislang in Deutschland nicht in die Versorgung ubertragen und zeigte eine ausgepragte regionale Variation. Eine Fruhforderung in Deutschland erfolgt meist im Sinne einer Tertiarpravention, die Moglichkeiten der Gesundheitsforderung/Sekundarpravention auch im Hinblick auf die sozial-emotionale Entwicklung und die Inklusion werden dagegen zu selten genutzt.

Outcomes after extremely preterm birth (28 weeks gestation) have been studied intensely, and follow-up into adulthood is well-established. Following the introduction of the International Classification of Functioning, Disability and Health, participation has been recognized to be a relevant outcome in rehabilitation research. During adolescence, participation is crucial to adapting to new social roles. The aim of our study was to investigate participation in the domains Autonomy, Relationships and Community Recreation.Participation was assessed as part of a cross-sectional, population-based study in a German federal state examining all adolescents born between January 1997 and December 1999 at under 27 weeks gestation. Of the surviving 90 adolescents, 72 (80%) were followed-up at age 14 to 17. Frequency of participation was assessed using the short form of the Questionnaire of Young People's Participation and compared to matched peers. Associations with physical, cognitive, and psychological functioning and contextual factors were examined using multivariate regression.Frequency of participation in Autonomy, Relationships, and Community Recreation in adolescents born extremely preterm was significantly lower than that of matched peers from the general population (p 0,001). Lower frequency of participation in Autonomy and Relationships was associated with severe physical and cognitive impairment, and psychological problems. Fifty-seven percent of the adjusted variance in Autonomy and 31% of the adjusted variance in Relationships was explained by our regression models.Further research is warranted to investigate additional factors associated with the restricted frequency of participation of adolescents born preterm to design suitable interventions for improving participation.

Aim\ud 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.\ud \ud Methods\ud 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.\ud \ud Results\ud 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.\ud \ud Conclusion\ud 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.

(1) Background: We aimed to evaluate the effect of proposed &ldquo, microbiome-stabilising interventions&rdquo, i.e., breastfeeding for &ge, 3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5&ndash, 6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding &ge, 3 months was associated with lower conduct disorders (B (95% confidence intervals (CI)): &minus, 0.25 (&minus, 0.47 to &minus, 0.03)) and inattention/hyperactivity (&minus, 0.46 (&minus, 0.81 to &minus, 0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development.

Background There are only few data on medical problems and utilization of health services of former very low birth weight (VLBW) children at preschool age. Study design At five years of age parents of a cohort of VLBW children ( N = 862) received questionnaires, a medical interview and examination. The results were compared to the KIGGS cohort (Deutscher-Kinder-und Jugendgesundheitssurvey, N = 777). Results Parents of the VLBW and KIGGS cohort reported a very good or good health in 95% in their children. When compared to the KIGGS cohort, families in the VLBW cohort had a lower social economic status. The VLBW cohort suffered more frequently from disabilities (9.6% vs. 1.4%), from chronic bronchitis (45% vs. 17%) and from recurrent pain (headaches (20% vs. 7%), ear (16% vs. 6%), throat (23% vs. 8%), tooth (10% vs. 3%)). The VLBW cohort received more specialized care (ophthalmologist, ENT, orthopaedics, paediatric neurologist). Conclusion Families of VLBW children report a good health status in their children, but they utilized more specialized care. Higher rates of pain are reported in the VLBW cohort. Chronic bronchitis and various upper respiratory infections cause an increased morbidity in former VLBW children. Follow up programs are needed to develop optimal treatment and prevention strategies for these problems.

Objective\ud \ud 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.\ud \ud Study design\ud \ud 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).\ud \ud Results\ud \ud 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.\ud \ud Conclusions\ud \ud 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.

Nicotine and alcohol consumption have been associated with premature delivery and adverse neonatal outcome. We wanted to analyze the influence of self-reported nicotine and alcohol consumption on outcome of VLBW infants.In an ongoing multicenter study 2475 parents of former very low birth weight (VLBW) infants born between January 2009 and December 2011 answered questionnaires about maternal smoking habits and alcohol consumption during pregnancy. 2463 (99.5%) completed questions on alcohol consumption and 2462 (99.5%) on smoking habits. These infants were stratified to reported maternal smoking and alcohol consumption during pregnancy. We compared the reasons for premature delivery, neonatal outcome and parental reports on bronchitis during the first year of life, as well as growth and development at age 2 years to pregnancy exposure.In nicotine exposed infants intrauterine growth restriction (31 vs. 21%, p0.01), a birth weight below the 10th percentile (26 vs. 17%, p0.01) and placenta abruption (9.2 vs. 5.8%, p0.05) was seen more often. Premature rupture of membranes (24 vs. 30%, p0.05) or HELLP syndrome (6 vs. 11%, p0.01) was less frequent. A birth weight below the 3rd percentile was seen more frequently in mothers with reported alcohol consumption (13 vs. 6%, p0.05). We noted an increased rate of BPD and ROP if mothers reported smoking during pregnancy (p0.05). Growth parameters and scores on Bayley Sscales of infant development at age 2 years did not differ.Smoking during pregnancy results in a high rate of growth restricted VLBW infants. Prenatal exposition to nicotine seems to increase postnatal complications such as BPD und ROP.

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. 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. 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. Premature birth seems to be correlated to gestational hypertension and associated problems in about ¼ of VLBW infants. Further studies should focus on preventing and treating gestational hypertension to avoid premature delivery and associated neonatal morbidity.

We performed an observational study with very-low-birth weight infants (VLBWI) ≤33 weeks of gestation born in centers of the German Neonatal Network (GNN; (total n = 8534, n = 6229 received probiotics). The primary objectives of our study were (a) to assess the effect of Lactobacillus acidophilus/Bifidobacterium infantis probiotics on growth in VLBWI during primary stay in hospital and (b) to determine whether this effect is modified by antibiotic exposure. In linear regression models the administration of probiotics was independently associated with improved weight gain [g/d; effect size B = 0.62 (95% CI: 0.37–0.87), p

Recently, exome sequencing has extended our knowledge of genetic causes of developmental delay through identification of de novo, germline mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) in 13 patients with neurodevelopmental disability and a wide range of additional symptoms and signs including hypotonia in 11 and seizures in 10 of the patients. Limb/arm dystonia was found in 2 patients.(1).

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.

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 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.

A 31-year-old 2 G 1 P was referred to our unit of prenatal medicine at 35+3 weeks of gestation with a spontaneously conceived singleton pregnancy of a female fetus without detectable anomalies. Maternal hematological evaluation revealed an Evans-syndrome-related thrombocytopenia based on a lupus erythematosus. The former delivery was aggravated by a severe hemorrhage several years before. Anti-autoimmunologic therapy was started and maternal platelets count increased to physiological values. Uneventful ceasarean section was performed at 37 weeks of gestation with favourable outcome for mother and child. This case is the first report of a successful therapy in maternal Evans syndrome in pregnancy combined with a lupus erythematosus.

Background: In very low birth weight (VLBW) infants, obstructive bronchitis is a frequent cause of hospital re-admission. For VLBW infants, early vaccinations starting at 2 months after birth have been recommended. Objective: To analyze risk factors for bronchitis during the first year after discharge and the effects of in-hospital standard vaccination (hexavalent/pneumococci) and/or RSV immunoprophylaxis with palivizumab. Methods: A standardized questionnaire was sent to the parents of VLBW infants 7 month after discharge. The reported episodes of bronchitis were correlated with clinically recorded parameters including risk factors for pulmonary morbidity. The effects of in-hospital vaccination were assessed in a subgroup discharged after day 60. Results: A sample of 1 967 responses of infants born 2009–2011 was analyzed. Risk factors for bronchitis were male gender and older siblings. 24% of the population had episodes of bronchitis. In the subgroup discharged after day 60, episodes of bronchitis were reported for 31% of infants who were not vaccinated in-hospital. A significant reduction of the bronchitis rate was found in infants who received palivizumab±standard vaccination (17% bronchitis, p=0.003). Interestingly, in-hospital standard vaccination without RSV immunoprophylaxis was protective (20% bronchitis; p=0.037) as well. Conclusions: Non-vaccinated male VLBW infants with older siblings are at increased risk for bronchitis during the first year after discharge. Vaccination according to schedule seems to have protective effects, while underlying mechanisms are unknown. The rate of timely vaccination in preterm infants should be increased.

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. 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. 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. 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.

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.

We analysed at what age parents start complementary food in very low birth weight infants, determined risk factors for early introduction of complementary food (post-term age) and analysed whether the age at introduction of complementary food influences height or weight at 2 years of age.Parents of premature infants born in 2009-2011 answered questionnaires regarding introduction of complementary food in the first year of life (N=2262) and were followed up at a post-term age of 2 years (N=981). Length and weight were compared with full-term infants from the KiGGs study. Logistic and linear regression analyses were conducted to study predictors for early introduction of complementary food and the influence of age at introduction of complementary food on later height and weight.Average age at introduction of complementary food was 3.5 months post-term age. The lower the gestational age at birth, the earlier (post-term age) vegetables and meat were introduced. Age at introduction of complementary food was influenced by intrauterine growth restriction, gestational age at birth, maternal education and a developmental delay perceived by the parents. Length and weight at a post-term age of 2 years was not negatively influenced by early introduction of complementary food.VLBW infants are introduced to complementary food on average before a post-term age of 4 months. There was no negative effect of early introduction of complementary food on height and weight at 2 years of age.

BACKGROUNDThe FTO gene, located on chromosome 16q12.2, and the MAF gene, located on chromosome 16q22-23, were identified as genes harboring common variants with an impact on obesity predisposition. We studied the association of common variants with birth weight, gain of body weight, body mass index (BMI), Ponderal index and relevant neonatal outcomes in a large German cohort of infants with a birth weight below 1500 grams.METHODSThe single nucleotide polymorphisms rs9939609 (FTO gene) and rs1424233 (MAF gene) were genotyped using allelic discrimination assays in a prospective multicenter cohort study conducted in 15 neonatal intensive care units in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols.RESULTS1946 infants were successfully genotyped at FTO and 2149 infants at MAF. Allele frequencies were not significantly different from other European cohorts. The polymorphisms were in Hardy-Weinberg equilibrium. The polymorphisms did not show associations with birth weight, BMI and Ponderal Index at discharge, and weight gain, neither testing for a dominant, additive nor for a recessive model.DISCUSSIONSince an association of the polymorphisms with weight gain has been demonstrated in multiple populations, the lack of association in a population of preterm infants with regular tube feeding after birth and highly controlled feeding volumes provides evidence for the hypothesis that these polymorphisms affect food intake behavior and hunger rather than metabolism and energy consumption.

Background Morbidity and mortality in Very Low Birth Weight (VLBW) infants during their hospital stay have been well described. However, there are insufficient data regarding health problems after discharge. Study design In a multicenter study performed between January 2009 and December 2010 including 2493 VLBW infants, questionnaires were sent out to all participating parents in the first year of life. We compared the parental reported health of VLBW infants with a national cohort (KIGGS). Results The reported health of VLBW infants born after 29 weeks of gestation was identical to term infants. Even in the group of infants born before 24 weeks of gestation health was regarded as very good or good in > 70% of cases. However, parents described a delayed development in > 50% increasing to > 70% with lower gestational age. In the first year of life VLBW infants have an increased risk of visual and hearing problems. Bronchitis was more frequent in VLBW infants but there were no differences in other infections typical for that age group. VLBW infants had less sleeping problems. No gender differences were described. Conclusion VLBW infants in our study require slightly more medical care compared to their peers. However, medical problems are relatively small compared to the developmental needs as perceived by their parents. Therefore, close follow-up and advice by specialists in infant development are needed.

Congenital insensitivity to pain with anhidrosis is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene, which encodes the receptor for nerve growth factor. We report the clinical and radiological pitfalls in the diagnosis and treatment of two brothers, aged 5 and 8 years, with congenital insensitivity to pain with anhidrosis, the older brother having a proven NTRK1 mutation. In the neonatal period, both presented with recurrent episodes of fever of unknown origin, but their clinical problems changed later. In addition to severe mental retardation and self-harming behaviour, the older brother developed recurrent nonbacterial destructive infections of both the calcaneus and later the talus. No immunodeficiency was found. The younger brother had three complex fractures with a long history of healing problems: overwhelming production of callus, osteomyelitis and movement restrictions. He has less mental retardation than his older brother and shows no self-mutilation.

Objective To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia. Design Case reports, literature review, and video presentation. Setting University of Lubeck, Lubeck, Germany. Patients Two boys from a consanguineous family. Main Outcome Measures Physical and mental development as a function of replacement initiation. Results The older sibling presented with typical features of AR GTPCH deficiency due to a homozygous mutation in the GCH1 gene with proven pathogenicity. Levodopa treatment was initiated at age 10 months and resulted in a distinct motor improvement. However, mental development was delayed. In the younger sibling, prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH deficiency was made. At age 17 months, both motor and mental development were normal for his age. Conclusions This report highlights the importance of an early diagnosis, including prenatal diagnosis, of complex dopa-responsive extrapyramidal syndromes. Prenatally initiated dopaminergic replacement therapy is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of significant impairment of mental abilities.

Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder. AHS is caused by homozygous or compound heterozygous mutations in the nuclear gene encoding mitochondrial DNA polymerase gamma (POLG, chromosome 15q25). Most patients become symptomatic before the age of 2 years. We report 3 patients who were treated in our clinic between 2007 and 2010. All patients suffered from myoclonic seizures and had at least one refractory convulsive status which led to the diagnosis. All of them had varying degrees of developmental delay, 2 of them additionally ataxia. Gastrointestinal motility problems were severe in all patients despite only mildly deranged liver function. While in most aspects our patients present with typical AHS features, they also share intestinal problems, a feature that has not been recognized as typical for AHS before. AHS is a multisystem disorder that does affect all cell systems. Liver and brain are organs with the highest energy demand and are therefore usually affected early in the disease course of AHS. However, constipation and bowel obstruction should be regarded as typical complications in AHS and patients should be monitored and treated to improve quality of life. Regarding treatment options for epilepsy in AHS ketogenic diet as well as lacosamide might be considered.

Background: The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE-ins/del) and the angiotensin II type 1 receptor 1166A/C polymorphism (ATR1166A/C) were reported to be associated with several unfavorable outcome parameters in preterm infants like bronchopulmonary dysplasia, persistent ductus arteriosus and impaired insulin sensitivity. Objective: To confirm the above-mentioned associations in a large cohort of very-low-birthweight (VLBW) infants. Method: Clinical data of VLBW infants were prospectively recorded. The ACE-ins/del polymorphism and the ATR1166A/C polymorphism were determined by polymerase chain reaction in 1,209 and 1,168 infants, respectively. Results: There was no significant association between ACE-ins/del or ATR1166A/C genotype and outcome parameters (death, intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, ventilation, supplemental oxygen at discharge, postnatal treatment with insulin, surgery for intestinal perforation/necrotizing enterocolitis/retinopathy of prematurity/persistent ductus arteriosus. Conclusion: Both known functional polymorphisms of the renin-angiotensin system do not seem to be associated with the outcome of VLBW infants.