Low incidence of acute kidney injury in VLBW infants with restrictive use of mechanical ventilation.

BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.

Human preterm colostrum stimulates outgrowth in neurogenic tissue.

BACKGROUND: The olfactory bulb has a key role for nasal delivery of drugs to the brain by its access from the nasal mucosa and its connection to the subventricular zone. The aim of this study was to investigate the neuromodulatory capacity of human milk of premature infants on the olfactory bulb. METHODS: Olfactory bulbs from P1 mice were embedded in a collagen I gel and incubated with DMEM supplemented with the aqueous phase of human colostrum (Col) of five mothers after very preterm birth, mature milk (Mat) of the same mothers or without supplement (Ctrl). After 7 days, the neurite outgrowth was quantified. Proteome analysis of the milk samples was performed using unlabeled mass spectrometry. RESULTS: Outgrowth increased significantly in bulbs exposed to Col but not when exposed to Mat. Mass spectrometry revealed profound differences in the proteome of Col versus Mat. Among 21 upregulated proteins in Col were proteins involved in neurite outgrowth, axon guidance, neuromodulation and longevity. CONCLUSIONS: A high bioactivity of human preterm colostrum on murine neonatal neurogenic tissue is demonstrated to be associated with a proteome profoundly differing from mature milk. IMPACT: The hypothesis has been raised that neonatal brain damage in a preterm infant could potentially be ameliorated by intranasal application of maternal breast milk. In an in-vitro model using neonatal murine olfactory bulb explants a significant stimulatory effect by human preterm colostrum is observed. Proteomics reveals upregulated neuroactive proteins in human colostrum compared to mature milk. A confirmation of this exploratory study would indicate that preterm colostrum stimulates neurogenic tissue. Early intranasal colostrum application might attenuate perinatal loss of neurogenic tissue thereby contributing to reducing complications such as cerebral palsy.

Diseases associated with prematurity in correlation with N-terminal pro-brain natriuretic peptide levels during the early postnatal life.

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values.    Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known: • Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New: • Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life. • Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmonary dysplasia are important factors in the increase in NT-proBNP levels in preterm infants at approximately 1 month of age.

High rate of insecure attachment patterns in preterm infants at early school age.

AIM: In preterm infants, insecure attachment is associated with behavioural and emotional problems but data on attachment beyond toddler age are scarce. This study assessed attachment security at 6-8 years in very and moderate or late preterm infants. The results were compared to a non-clinical full-term sample. METHODS: Attachment security of 38 very and 20 moderate or late preterm infants was assessed during a home visit with the German version of the Attachment Story Completion Task. Attachment patterns of 28 full-term controls were taken from a previous study. Primary outcomes were attachment security and attachment security score. Secondary outcomes for the preterm groups were infant behavioural problems, parental stress, perceived social support, maternal depressive symptoms, and infant development. RESULTS: Very preterm infants had the highest rate of insecure attachment (81%) compared to moderate or late preterm infants (60%) and full-term infants (47%); (p = 0.013). Attachment security scores differed significantly between very preterm and full-term infants (p = 0.001). Secondary outcomes were similar in very and moderate or late preterm cohorts. CONCLUSION: Prematurity was associated with an increased risk of insecure attachment at early school age. Interventions targeting attachment security are reasonable considering the high rate of behavioural problems following premature birth.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

Ultra-rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours.

Genetic diseases are a major cause of neonatal morbidity and mortality. The clinical differential diagnosis in severely ill neonates, especially in premature infants, is challenging. Next generation sequencing (NGS) diagnostics is a valuable tool, but the turnaround time is often too long to provide a diagnosis in the time needed for clinical guidance in newborn intensive care units (NICU). To minimize turnaround time, we developed an ultra-rapid whole genome sequencing pipeline and tested it in clinical practice. Our pilot case, was a preterm infant presenting with several crises of dehydration, hypoglycaemia and hyponatremia together with nephrocalcinosis and hypertrophic cardiomyopathy. Whole genome sequencing was performed using a paired-end 2x75bp protocol. Sequencing data were exported after 50 sequencing cycles for a first analysis. After run completion, the rapid-sequencing protocol, a second analysis of the 2 x 75 paired-end run was performed. Both analyses comprised read-mapping and SNP-/indel calling on an on-site Edico Genome DRAGEN server, followed by functional annotation and pathogenicity prediction using in-house scripts. After the first analysis within 17 h, the emergency ultra-rapid protocol identified two novel compound heterozygous variants in the insulin receptor gene (INSR), pathogenic variants in which cause Donohue Syndrome. The genetic diagnosis could be confirmed by detection of hyperinsulinism and patient care adjusted. Nonetheless, we decided to pursue RNA studies, proving the functional effect of the novel splice variant and reduced expression levels of INSR in patients skin fibroblasts.

Reference values for N-terminal Pro-brain natriuretic peptide in premature infants during their first weeks of life.

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277-5200) during the first week of life, 463 ng/l (n = 26, IQR: 364-704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714-1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750-8972) than infants born ≥ 28 + 0-31 weeks GA (n = 18, median: 1528, IQR: 838-3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups.Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life. What is Known: • Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life. What is New: • This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life. • In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

Primary anastomosis as a valid alternative for extremely low birth weight infants with spontaneous intestinal perforation.

The aim was to assess the results of primary anastomosis (PA) compared to enterostomy (ES) in infants with spontaneous intestinal perforation (SIP) and a weight below 1000 g. Between 2014 and 2016, enterostomy was routinely carried out on extremely low birth weight (ELBW) patients with SIP. From 2016 until 2019, all patients underwent anastomosis without stoma formation. We compared outcome and complications in both groups. Forty-two patients with a median gestational age of 24.3 weeks and a birth weight of 640 g with SIP were included. Thirty patients underwent PA; ES was performed in 12 patients. Overall in-hospital mortality was 11.9% (PA: 13.3%, ES: 8.3%). Reoperations due to complications became necessary in 10/30 patients with PA and 4/12 patients with ES. Length of stay was 110.5 days in the PA group and 124 days in the ES group. Median weight at discharge was higher in the PA group (PA: 2258 g, ES: 1880 g, p = .036).Conclusion: Primary anastomosis is a feasible treatment option for SIP in infants < 1000 g and may have a positive impact on weight gain and length of hospitalization. However, further studies on selection criteria for PA are necessary. What is Known: • Enterostomy (ES) and primary anastomosis (PA) are feasible treatment options in preterm infants with spontaneous intestinal perforation (SIP). • Stomal complications or failure to thrive due to poor food utilization can pose significant problems. What is New: • Primary anastomosis in case of SIP is equal to enterostomy in terms of mortality and revision rate; however, length of stay and weight gain can be presumably positively influenced. • Primary anastomosis is a valid treatment option even for patients weighing less than 1000 g.

Developmental outcome of extremely preterm infants is improved after less invasive surfactant application: Developmental outcome after LISA.

AIM: The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age. METHODS: Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors. RESULTS: In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008). CONCLUSION: At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior.

Privacy, Early Colostrum, and Gestational Age are Associated with Exclusive Breastfeeding in Preterm and Sick Term Infants.

Our study was designed to assess the rates of exclusive breastfeeding (defined as direct breastfeeding) and the use of mother's own milk (MOM) in preterm infants and sick term infants at discharge and to identify potential influencing factors such as gestational age, early colostrum, and privacy. The study was conducted at a German level III neonatal department. All preterm and sick term infants admitted to the neonatal intensive care unit, the pediatric intensive care unit, the intermediate care unit, and the low care ward were included in the study. Infants were recruited between March and October 2015 (phase 1) and April to July 2016 (phase 2). Due to an emergency evacuation, privacy was limited during the first phase. Breastfeeding and the use of MOM were assessed daily using a self-designed score. In total, 482 infants of 452 mothers were included. More than 90% initiated breastfeeding and one-third were exclusively breastfed at discharge. Extremely immature infants and late preterm infants were less likely to be exclusively breastfed at discharge. Privacy (p<0.001) and early colostrum (p=0.002) significantly increased exclusive breastfeeding. Conclusion Extremely immature and late preterm infants were least likely to be exclusively breastfed at discharge and need special support. Interventions such as privacy and early colostrum should be promoted to increase breastfeeding.

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study.

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment.Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect. What is Known: • LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation. What is New: • Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment.

Delivery room skin-to-skin contact for preterm infants-A randomized clinical trial.

AIM: To investigate the effects of 60 minutes delivery room skin-to-skin contact (DR-SSC) compared with 5 minutes visual contact (VC) on mother-child interaction (MCI), salivary cortisol, maternal depression, stress and bonding at 6 months corrected age. METHODS: A single-centre randomized controlled trial conducted in a German level III NICU. Eighty-eight preterm infants (25-32 weeks of gestational age) were randomized after initial stabilization to either 60 minutes DR-SSC or 5 minutes VC. Forty-five infants were allocated to DR-SSC, 43 to VC. RESULTS: Delivery room skin-to-skin contact dyads showed a higher quantity of maternal motoric (18 vs 15, P = .030), infant's vocal (7 vs 5, P = .044) and motoric (20 vs 15, P = .032) responses. Moreover, the combined score of maternal and infant responsive behaviour was higher (86 vs 71, P = .041) in DR-SSC dyads. DR-SSC mothers had lower risk of both, early postpartum depression (15% vs 45%, P = .003) and impaired bonding (Score 3 vs 5, P = .031). CONCLUSION: In addition to regular intermittent kangaroo mother care, DR-SSC promotes MCI and decreases risk of maternal depression and bonding problems. Thus, DR-SSC may have positive effects on preterm development.

Use of whole exome sequencing in the NICU: Case of an extremely low birth weight infant with syndromic features.

Single gene (Mendelian) disorders are one of the leading causes of neonatal morbidity and mortality. However, in the setting of preterm birth phenotypic features of genetic diseases are often undifferentiated and are clinically very difficult to interpret based on the wide range of differential diagnoses. We report an extremely low birth weight infant (ELBW) born prematurely at 23 + 0 gestational weeks after twin pregnancy with a novel clinical manifestation with persistent hyperglycaemia as well as the known manifestations of disease-associated hypokinesia, renal salt wasting, and multifocal atrial tachycardia. The patient died of heart failure on the 72nd day of life. Whole exome sequencing (WES) revealed a previously well established, disease-causing heterozygous likely pathogenic variant in the Harvey rat sarcoma viral oncogene homolog (HRAS)-gene (c.35G > C, p. G12A, rs104894230), which implied the clinical diagnosis of Costello syndrome (CS; OMIM#190020.0004). The twin brother merely had complications related to preterm birth and did not show any CS symptoms. In conclusion, our case illustrated that CS should be considered in ELBW infants showing a life-threatening combination of complex cardiac arrhythmia and hypokinesia. If a syndromic disorder is suspected in the neonatal intensive care unit (NICU) setting, rapid WES is a useful, non-invasive diagnostic tool in critically ill ELBW infants.

Intranasal breast milk for premature infants with severe intraventricular hemorrhage-an observation.

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants.

Prenatal parental decision-making and postnatal outcome in renal oligohydramnios.

BACKGROUND: Previous studies on renal oligohydramnios (ROH) report highly variable outcome and identify early onset of ROH and presence of extrarenal manifestations as predictors of adverse outcome in most cases. Data on termination of pregnancy (TOP) and associated parental decision-making processes are mostly missing, but context-sensitive for the interpretation of these findings. We provide here a comprehensive analysis on the diagnosis, prenatal decision-making and postnatal clinical course in all pregnancies with ROH at our medical centre over an 8-year period. METHODS: We report retrospective chart review data on 103 consecutive pregnancies from 2008 to 2015 with a median follow-up of 554 days. RESULTS: After ROH diagnosis, 38 families opted for TOP. This decision was associated with onset of ROH (p < 0.001), underlying renal disease (p = 0.001) and presence of extrarenal manifestations (p = 0.02). Eight infants died in utero and 8 cases were lost to follow-up. Of the 49 liveborn children, 11 received palliative and 38 underwent active care. Overall survival of the latter group was 84.2% (n = 32) corresponding to 31% of all pregnancies (32 out of 103) analysed. One third of the surviving infants needed renal replacement therapy during the first 6 weeks of life. CONCLUSIONS: Over one third of pregnancies with ROH were terminated and the parental decision was based on risk factors associated with adverse outcome. Neonatal death was rare in the actively treated infants and the overall outcome promising. Our study illustrates that only careful analysis of the whole process, from prenatal diagnosis via parental decision-making to postnatal outcome, allows sensible interpretation of outcome data.

Treatment and outcome data of very low birth weight infants treated with less invasive surfactant administration in comparison to intubation and mechanical ventilation in the clinical setting of a cross-sectional observational multicenter study.

The aim of this study was to contribute further to existing randomized controlled trials and meta-analyses showing advantages in the outcome of less invasive surfactant administration (LISA)-treated infants and add new aspects concerning treatment and outcome data collected in the routine clinical setting. Four hundred seven very low birth weight infants who received surfactant via either LISA or intubation methods were enrolled in the observational cross-sectional multicenter study. To compare infants in terms of surfactant administration, we used an exact matching procedure (the same gestational age, severe perinatal depression (pH < 7.10), birth weight < 10th percentile, antenatal steroid treatment, and the same gender). To check for robustness, we performed repeated matching. LISA-treated infants required significantly less mechanical ventilation during hospital stay (p < 0.001) and days with supplemental oxygen (p = 0.03). Analgesics and sedatives were used less often during the stay (p < 0.001). Infants treated with LISA had significantly lower rates of bronchopulmonary dysplasia (p = 0.003). LISA failure infants were identified as more likely to be small for gestational age and more immature. CONCLUSION: Our study complements former results with advantages for LISA-treated infants in mechanical ventilation and bronchopulmonary dysplasia in the clinical routine. TRIAL REGISTRATION: DRKS00004589 What is Known: • According to existing literature, LISA-treated infants seem to have some favors in terms of treatment and outcome data. Observational studies in routine clinical setting are missing. What is New: • Data of 407 VLBW infants collected in routine clinical setting showed that LISA-treated infants needed less mechanical ventilation and fewer days with supplemental oxygen and less analgesics and sedatives. A reduced risk of BPD could be showed. SGA infants seem to have higher risks of LISA failure.

Peritoneal drainage in pneumoperitoneum in extremely low birth weight infants.

The aim was to determine if peritoneal drainage (PD) is a suitable treatment for pneumoperitoneum in extremely low birth weight (ELBW) infants. A retrospective chart review of 42 ELBW infants with pneumoperitoneum at the University Hospital of Cologne between November 2014 and April 2017 was performed. Forty-two infants with a median birth weight of 645 g (interquartile range (IQR) 550, 806) and a median gestational age of 24.3 weeks (IQR 23.2, 25.6) were treated for pneumoperitoneum. Twenty-six (62%) received PD, and in ten (38%), the drain could be removed without further intervention. Infants in the PD group were of significantly lower birth weight (622g vs. 750 g), age (4.5 vs. 10.0 days), and weight at diagnosis (538 vs. 778 g). The mortality in the PD group was 15% at 90 days of life, but no patient deceased in the primary laparotomy group. CONCLUSION: We suggest PD with close evaluation of drainage and clinical course as an alternative treatment for pneumoperitoneum in ELBW infants allowing bridging the vulnerable first days of life until these infants are in a more stable condition. Despite not reaching statistical significance in our series, PD showed the trend towards higher mortality. What is known: • Pneumoperitoneum is traditionally treated with laparotomy, but placement of peritoneal drainage (PD) is a valuable treatment option. • Previous randomized controlled trials have shown no significant differences in mortality for PD versus laparotomy. What is new: • In our cohort, 38% of the infants with PD could be saved from secondary laparotomy, but in the PD group there was a trend towards higher mortality. • PD allows bridging the vulnerable first days of life until ELBW infants are in a more stable condition for possible laparotomy.

The flexion withdrawal reflex increases in premature infants at 22-26 weeks of gestation due to changes in spinal cord excitability.

AIM: Our aim was to study the development of the cutaneous flexion withdrawal reflex among premature infants admitted to the neonatal intensive care unit of the Children's Hospital, University of Cologne, in 2013. METHODOLOGY: This longitudinal cohort study explored the development of spinal cord excitability of 19 premature infants born at 22-26 weeks of gestation. We performed five investigations per subject and studied changes in the reflex threshold with increasing postnatal age at different behavioural states. The premature infants were stimulated with von Frey filaments on the plantar surface of the foot near the first metatarsophalangeal joint during the first 3 days of life and at postnatal ages of 10-14 days, 21-28 days, 49-59 days and a corrected gestational age of 37-40 weeks. RESULTS: The mean gestational age of the premature infants included in the study was 24 weeks. Premature infants with a gestational age of less than 26 weeks presented a flexion withdrawal reflex with a low threshold (0.5-2.85 milli-Newton) in the first 72 hours of life. CONCLUSION: The flexion withdrawal reflex among premature infants born at less than 26 weeks showed a continuous threshold increase with increasing postnatal age, reflecting changes in spinal cord excitability.