Previable preterm premature rupture of membranes: 117 cases with neonatal outcomes in light of current research.

BACKGROUND: ppPROM < 24 + 0 weeks of gestation complicates < 1 % of all pregnancies but is responsible for significant maternal and neonatal morbidity. It is associated with 18-20% of perinatal deaths. OBJECTIVE: To evaluate neonatal outcome after expectant management in ppPROM in order to obtain evidence-based information for purposes of future counselling. METHODS: A single-centre, retrospective cohort study of 117 neonates born 1994 to 2012 after ppPROM < 24 weeks of gestation with a latency period > 24 hours and admission to the NICU of the Department of Neonatology, University of Bonn. Data of pregnancy characteristics and neonatal outcome were collected. The results were compared to those found in the literature. RESULTS: The mean gestational age at ppPROM was 20.45±2,9 weeks (range 11 + 2 -22 + 6) with a mean latency period of 44.7±34.8 days (range 1-135). Mean gestational age at birth was 26.77±3.22 weeks (range 22 + 2-35 + 3). 117 newborns were admitted to the NICU, the overall survival rate at discharge was 72.6% (85/117). Non-survivors had a significantly lower gestational age and higher rates of intra-amniotic infections. The most common neonatal morbidities were RDS (76.1%), BPD (22.2%), pulmonary hypoplasia (PH) (14.5%), neonatal sepsis (37.6%), IVH (34.1% all grades, 17.9% grades III/IV), NEC (8.5%) and musculoskeletal deformities (13.7%). Mild growth restriction as a new complication of ppPROM was observed. CONCLUSIONS: Neonatal morbidity after expectant management is similar to that described for infants without ppPROM, but carries a higher risk of pulmonary hypoplasia and mild growth restriction.

Small for gestational age-cognitive performance from infancy to adulthood: an observational study.

OBJECTIVE: To determine whether cognitive performance from infancy to adulthood is affected by being born small for gestational age (SGA), and if this depends on the SGA reference used. Furthermore, to determine SGA's effect while considering the effects of very preterm/very low birthweight (VP/VLBW), socio-economic status (SES) and parent-infant relationship. DESIGN, SETTING AND POPULATION: A total of 414 participants (197 term-born, 217 VP/VLBW) of the Bavarian Longitudinal Study. METHODS: Small for gestational age was classified using neonatal or fetal growth references. SES and the parent-infant relationship were assessed before the infant was 5 months old. MAIN OUTCOME MEASURES: Developmental (DQ) and intelligence (IQ) tests assessed cognitive performance on six occasions, from 5 months to 26 years of age. RESULTS: The fetal reference classified more infants as SGA (<10th centile) than the neonatal reference (n = 138, 33% versus n = 75, 18%). Using linear mixed models, SGA was associated with IQ -8 points lower than appropriate for gestational age, regardless of reference used (95% CI -13.66 to -0.64 and 95% CI -13.75 to -1.98). This difference narrowed minimally into adulthood. Being VP/VLBW was associated with IQ -16 (95% CI -21.01 to -10.04) points lower than term-born participants. Low SES was associated with IQ -14 (95% CI -18.55 to -9.06) points lower than high SES. A poor parent-infant relationship was associated with IQ -10 points lower than those with a good relationship (95% CI -13.91 to -6.47). CONCLUSIONS: Small for gestational age is associated with lower IQ throughout development, independent of VP/VLBW birth, low SES or poor parent-child relationship. Social factors effects on IQ comparable to those of SGA and should be considered for interventions. TWEETABLE ABSTRACT: Small for gestational age is associated with lower cognitive performance from infancy to adulthood.

The association of children's mathematic abilities with both adults' cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals.

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults' IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children's mathematic abilities and adults' fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults' IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children's mathematic abilities may represent potential neurocognitive targets for early intervention.

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

[Stillbirths in Germany: Retrospective Analysis of 168 Cases between 2003 and 2011]. / Totgeburten in Deutschland: Retrospektive Datenanalyse von 168 Fällen zwischen 2003 und 2011.

BACKGROUND: The decline in the incidence of stillbirths in Germany has remained static in recent years. This study aims to analyse the current situation of data documentation and examination of stillbirths. Furthermore, possible stillbirth prevention strategies should be developed. METHODS: Searches in the international peer-reviewed literature, retrospective data collection of 168 stillbirths in 8 hospitals, (in the area of Bonn) with subsequent statistical evaluation (descriptive statistics, t-test and binominal test) were undertaken. RESULTS: This study shows considerable deficits in data documentation, interdisciplinary communication and postmortal examination. Only in 51.8% (87/168) of the cases was a certain or uncertain cause of death found (42.3% placental, 1.2% foetal, 3.6% chromosomal, 4.8% umbilical cord abnormalities). Severe foetal growth restriction (<5(th) percentile) was observed in 29.2%; 44.9% (22/49) of them died at the age of ≥36+0 weeks of gestation. CONCLUSION: The first step to reduce the rate of stillbirths in Germany is to increase the identified causes of foetal death: Therefore, an interdisciplinary case report form was compiled to improve data collection and interdisciplinary collaboration. To standardise and complete postmortal management, an algorithm was created. The long-term aim is the development of a central data register for statistical analysis, to identify goals of research and to organise conferences with interdisciplinary reports of diagnostic findings.

Poor attention rather than hyperactivity/impulsivity predicts academic achievement in very preterm and full-term adolescents.

BACKGROUND: Very preterm (VP) children are at particular risk for attention deficit/hyperactivity disorder (ADHD) of the inattentive subtype. It is unknown whether the neurodevelopmental pathways to academic underachievement are the same as in the general population. This study investigated whether middle childhood attention or hyperactivity/impulsivity problems are better predictors of VP adolescents' academic achievement. METHOD: In a geographically defined prospective whole-population sample of VP (<32 weeks gestation) and/or very low birth weight (<1500 g birth weight) (VLBW/VP; n = 281) and full-term control children (n = 286) in South Germany, ADHD subtypes were assessed at 6 years 3 months and 8 years 5 months using multiple data sources. Academic achievement was assessed at 13 years of age. RESULTS: Compared with full-term controls, VLBW/VP children were at higher risk for ADHD inattentive subtype [6 years 3 months: odds ratio (OR) 2.8, p < 0.001; 8 years 5 months: OR 1.7, p = 0.020] but not for ADHD hyperactive-impulsive subtype (6 years 3 months: OR 1.4, p = 0.396; 8 years 5 months: OR 0.9, p = 0.820). Childhood attention measures predicted academic achievement in VLBW/VP and also full-term adolescents, whereas hyperactive/impulsive behaviour did not. CONCLUSIONS: Attention is an important prerequisite for learning and predicts long-term academic underachievement. As ADHD inattentive subtype and cognitive impairments are frequent in VLBW/VP children, their study may help to identify the neurofunctional pathways from early brain development and dysfunction to attention problems and academic underachievement.

Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health.

The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.

Familial translocation t(6;20)(p21;p13) resulting in partial trisomy 6p and partial monosomy 20p: report of a new case and review of the literature.

Carriers of completely balanced chromosomal translocations have all necessary genetic information. Nevertheless, because of the possibility of maldistribution during gametogenesis, they are at increased risk for infertility, miscarriage, stillbirth or having a child with congenital anomalies including mental retardation. As postnatal clinical reports are infrequent, prediction of clinical course for specific unbalanced karyotypes diagnosed during pregnancy remains difficult. Here, we report the 6th case of partial trisomy 6p and partial monosomy 20p due to an unbalanced adjacent-1 segregation of the rare familial translocation t(6;20)(p21;p13). We give a thorough clinical description of the present case, demonstrating broad phenotypic overlap with the 5 previously published cases reviewed here, providing important data on postnatal outcome.

The coagulation system of extremely preterm infants: influence of perinatal risk factors on coagulation.

OBJECTIVE: Little is known about the influence of preterm delivery and perinatal risk factors on development and expression of the coagulation system in extremely preterm infants. The objective of this study was to determine reference values for the components of the coagulation system at the first day of life in extremely preterm infants. STUDY DESIGN: Components of the coagulation system were examined retrospectively in 132 extremely preterm infants. Patients were grouped according to clinical criteria for preterm delivery: group A: maternal indication; group B: uteroplacental dysfunction; group C: systemic inflammation. RESULT: Levels of coagulation factors VII and X rose with increasing gestational age, whereas fibrinogen and coagulation factors II, V and VIII remained constant. Levels of factors V and VIII were higher than those of vitamin K-dependent factors. If preterm delivery was caused by placental disorder (group B) or chorioamnionitis (group C), levels of factor II, VIII and X were significantly lower, whereas factor V and VII levels did not differ. In group C fibrinogen levels in group C were higher compared with group A. CONCLUSION: Identification of perinatal risk factors may help to define patients at risk of bleeding disorders.

Successful management of an MRSA outbreak in a neonatal intensive care unit.

We report an MRSA outbreak in our 25-bed tertiary neonatal intensive care unit (NICU), which was successfully contained. Methods include a retrospective review of patient files, microbiology records and meeting protocols. During the seven months of outbreak, 27 patients and seven health care workers (HCWs) had positive cultures for MRSA. The outbreak was caused by the epidemic Rhine-Hessen strain; cultured isolates were monoclonal. After a sharp increase of the number of new MRSA-cases the installation of an outbreak management team (OMT) and implementation of comprehensive measures (extensive screening and decolonization strategy including orally applied vancomycin, isolation wards, intensive disinfection regimen) successfully terminated the outbreak within one month. Ten (53%) of 19 patients with completed follow-up and all of the HCWs were decolonized successfully. Gastrointestinal colonization was present in 15 of 27 (56%) neonates, and was associated with poor decolonization success (30% vs. 78% in absence of gastrointestinal colonization). A comprehensive outbreak management can terminate an outbreak in a NICU setting within a short time. Thorough screening of nares, throat and especially stool is necessary for correct cohorting. Gastrointestinal decolonization in neonates seems difficult.

Clinical characteristics of viral intestinal infection in preterm and term neonates.

The clinical presentation of the viral enteric pathogens in newborn infants has not been adequately examined. The aim of this study was to evaluate the clinical characteristics of viral intestinal infections in newborn infants. Clinical data of all term and preterm infants admitted to our tertiary neonatal intensive care unit from 1998 to 2007 with clinical signs of gastroenteritis (GE) or necrotizing enterocolitis (NEC) were retrospectively reviewed and compared between infants with different viral enteric pathogens in stool specimens. In 34 infants with signs of GE or NEC, enteropathogenic viruses were found in stool specimens. Rotavirus was detected in 12 cases, of which two infants had NEC. Compared with infants with rotavirus or norovirus, infants with astrovirus more frequently suffered from NEC (p<0.05). In addition, an acute systemic inflammatory response was significantly more common in patients with astrovirus infection (astrovirus vs. rotavirus and astrovirus vs. norovirus, p < 0.01 and p < 0.05, respectively). Of eight children infected with norovirus, one infant had a systemic acute inflammatory response and NEC. This study demonstrates that in newborn infants, intestinal rotavirus, norovirus, and astrovirus infections may be associated with severe illness such as hemorrhagic enteritis resulting in bloody diarrhea or even NEC.

Growth after intrauterine laser coagulation for twin-twin transfusion syndrome.

OBJECTIVE: The aim of this study was to investigate prenatal and postnatal growth of twins with twin-twin transfusion syndrome (TTTS) after intrauterine laser coagulation. STUDY DESIGN: The weight and length of 54 sets of twins with severe TTTS surviving intrauterine laser coagulation at the intervention (median 20+4 weeks), at birth (median 34+3 weeks) and on the occasion of neurodevelopmental follow-up (median age 3 years 10 months) were investigated. All data were converted to Z scores, and groups were compared by two-tailed paired t test. RESULTS: At all time points, donors are significantly lighter than recipients (p<0.001). After laser treatment the weight Z score of donors until birth remains unchanged (p=0.76), whereas recipients lose weight significantly (p<0.01). Postnatally, both donors and recipients show catch-up growth. CONCLUSION: Intrauterine laser coagulation stops growth acceleration in recipients that leads to a decrease in intertwin discordance. After birth, significant catch-up growth was observed for the donor group (p<0.001).

ARDS as presenting symptom in an infant with CD40L deficiency (Hyper-IgM syndrome Type 1).

We report on a 4 month old male infant with respiratory syncytial virus (RSV) infection leading to acute respiratory distress syndrome (ARDS). A diagnostic algorithm including extended infectiological and immunological work-up revealed absence of CD40-ligand. ARDS was treated successfully with a complex respiratory therapy plus intravenous immunoglobulin substitution. Molecular analysis detected mutations in the CD40L gene (Hyper-IgM syndrome Type 1). The case underlines the importance of an extended diagnostic work-up in an uncommonly severe course of respiratory infection in early infancy.

Pyridoxal phosphate-dependent neonatal epileptic encephalopathy.

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.

Influenza A-associated rhabdomyolysis with acute renal failure.

Rhabdomyolysis induced acute renal failure as a rare complication of influenza A infection has been mainly described in adults. Consideration of this potentially life-threatening complication in pediatric patients presenting with influenza is important as clinical symptoms may be unspecific and early diagnosis leading to prompt treatment is essential to decrease associated morbidity and mortality. We report a 9 year old girl who developed severe rhabdomyolysis with myoglobinuric renal failure associated with influenza A virus infection. Receiving supportive therapy including intensive care management the patient recovered renal function completely.

Pyridoxal phosphate-dependent neonatal epileptic encephalopathy.

Pyridox(am)ine-5'-phosphate oxidase converts pyridoxine phosphate and pyridoxamine phosphate to pyridoxal phosphate, a cofactor in many metabolic reactions, including neurotransmitter synthesis. A family with a mutation in the pyridox(am)ine-5'-phosphate oxidase gene presenting with neonatal seizures unresponsive to pyridoxine and anticonvulsant treatment but responsive to pyridoxal phosphate is described. Pyridoxal phosphate should be considered in neonatal epileptic encephalopathy unresponsive to pyridoxine.

Oral valganciclovir for symptomatic congenital cytomegalovirus infection in an extremely low birth weight infant.

Cytomegalovirus (CMV) infection is the most important congenital viral infection. Intravenous (i.v.) Ganciclovir (GCV) improved outcome in term infants with symptomatic congenital CMV infection. We present data on oral valganciclovir (VGCV) in an extremely low birth weight infant. A male preterm infant was delivered at 28 weeks of gestation because of abnormal fetal perfusion with severe intrauterine growth retardation. The infant developed hepatitis and a severe thrombocytopenia. Serology revealed a positive CMV IgM in maternal serum 3 days after delivery and CMV DNA was detected in plasma and urine samples of the infants. Treatment with i.v. GCV was started at day 4 of life for 35 days and continued with oral VGCV for further 6 weeks. Plasma GCV levels were 1.68 ng ml(-1) (peak) and 0.92 ng ml(-1) (trough) on day 10 of oral treatment. Clinical signs resolved and virus load decreased slowly during therapy. At discharge brain stem-evoked audiometry was normal. Oral treatment with VGCV in an extremely low birth weight preterm infant with congenital CMV infection resulted in adequate GCV plasma levels, reduced effectively the CMV viral load and was well tolerated without apparent adverse effects.