Release of HMGB1 and Toll-like Receptors 2, 4, and 9 Signaling Are Modulated by Bifidobacterium animalis subsp. lactis BB-12 and Salmonella Typhimurium in a Gnotobiotic Piglet Model of Preterm Infants.

Gnotobiotic (GN) animals with defined microbiota allow us to study host-microbiota and microbiota-microbiota interferences. Preterm germ-free (GF) piglets were mono-associated with probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB12) to ameliorate/prevent the consequences of infection with the Salmonella Typhimurium strain LT2 (LT2). Goblet cell density; expression of Toll-like receptors (TLRs) 2, 4, and 9; high mobility group box 1 (HMGB1); interleukin (IL)-6; and IL-12/23p40 were analyzed to evaluate the possible modulatory effect of BB12. BB12 prevented an LT2-induced decrease of goblet cell density in the colon. TLRs signaling modified by LT2 was not influenced by the previous association with BB12. The expression of HMGB1, IL-6, and IL12/23p40 in the jejunum, ileum, and colon and their levels in plasma were all decreased by BB12, but these changes were not statistically significant. In the colon, differences in HMGB1 distribution between the GF and LT2 piglet groups were observed. In conclusion, the mono-association of GF piglets with BB12 prior to LT2 infection partially ameliorated the inflammatory response to LT2 infection.

Abnormal kidney ultrasound and function in a five-year-old boy born prematurely with a birth weight of 370 grams.

It is known that prematurity and low birth weight are associated with chronic kidney disease and hypertension. A positive correlation between kidney volume and birth weight was also described. In our ongoing observational study in 5-year-old children, we perceived highly abnormal kidney ultrasound and functions of a male patient born weighing 370 grams. It was his first nephrology examination since discharge from the hospital. We believe that thorough follow up and timely diagnosis of developing renal insufficiency may help us to initiate proper treatment in high-risk children (Tab. 1, Fig. 1, Ref. 7). Text in PDF www.elis.sk Keywords: prematurity; extremely low birth weight; chronic kidney disease; renal ultrasound; renal function.

A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome.

OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

Bacterial DNA detection in very preterm infants assessed for risk of early onset sepsis.

OBJECTIVES: The aim of this study is to evaluate the diagnostic ability of multiplex real-time polymerase chain reaction (PCR) in very preterm infants assessed for risk of early onset neonatal sepsis (EOS). METHODS: Prospective observational cohort study. Blood samples of preterm neonates ≤32 weeks of gestation were evaluated by commercial multiplex real-time PCR within 2 h after delivery. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection and abnormal neonatal blood count and serum biomarkers. RESULTS: Among 82 subjects analyzed in the study, 15 had clinical or confirmed EOS. PCR was positive in four of these infants (including the only one with a positive blood culture), as well as in 15 of the 67 infants without sepsis (sensitivity 27%, specificity 78%). Out of 19 PCR positive subjects, Escherichia coli was detected in 12 infants (63%). Statistically significant association was found between vaginal E. coli colonization of the mother and E. coli PCR positivity of the neonate (p=0.001). No relationship was found between neonatal E. coli swab results and assessment findings of bacterial DNA in neonatal blood stream. CONCLUSIONS: Multiplex real-time PCR had insufficient diagnostic capability for EOS in high risk very preterm infants. The study revealed no significant association between PCR results and the diagnosis of clinical EOS. Correlation between maternal vaginal swab results and positive PCR in the newborn needs further investigation to fully understand the role of bacterial DNA analysis in preterm infants.

Cerebral oxygen saturation and autoregulation during hypotension in extremely preterm infants.

BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death.  Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

Role of umbilical interleukin-6, procalcitonin and C-reactive protein measurement in the diagnosis of fetal inflammatory response syndrome.

OBJECTIVE: Fetal Inflammatory Response Syndrome (FIRS) is a serious complication accompanied by increased neonatal mortality and morbidity. Early dia-gnosis of FIRS is essential to detect high risk infants. The aim of the study was to evaluate the correlation between interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) in cord blood and histologically proven funisitis;chorioamnionitis in high-risk infants after preterm birth. METHODS: Blood sampling for the measurement of inflammatory bio-markers was performed immediately after placental delivery and umbilical cutting. Umbilical and placental inflammatory changes were assessed using a recently released scoring system (Amsterdam Placental Workshop Group Consensus). RESULTS: One hundred preterm infants (30.5 ± 2.5 gestational week, birth weight 1,443 ± 566 grams) and 21 health term infants were analyzed. Histologic chorioamnionitis was confirmed in 19% cases and chorioamnionitis with funisitis in 7% cases. Thirty-three infants (33%) fulfilled criteria of FIRS (funistis and/ or umbilical IL-6 > 11 ng/ L). The presence of FIRS correlated significantly with maternal leukocytosis (P < 0.001), preterm premature rupture of membrane (P < 0.001) and preterm uterine contraction (P < 0.0001). In comparison to preterm and healthy term infants we found statistically significant higher levels of umbilical inflammatory bio­markers (IL-6, PCT, CRP) in FIRS group (P < 0.0001). Composite mortality and morbidity (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia) was higher in FIRS group (28.1 vs 22.4% in preterm group). However, the difference was not statistically significant (P = 0.53). CONCLUSION: Our study confirmed the correlation of umbilical inflammatory bio­markers levels (IL-6, PCT, CRP) and the presence of FIRS. We did not find significant adverse impact of FIRS on neonatal mortality and morbidity. Nevertheless, our results could be influenced by the size of study group and strict inclusion criteria (only cases after C-section were analyzed).

Complications of planned home births in the Czech Republic between 2016‒2017.

OBJECTIVE: This study aimed to analyze the complications of planned home births treated at healthcare facilities in the Czech Republic. METHODS: This prospective cohort observational study is based on analysis of women hospitalized with complications related to planned home deliveries in the Czech Republic between 2016 and 2017. The data were collected using an online form made accessible to the directors of all maternity hospitals in the Czech Republic. The results were statistically evaluated. RESULTS: We identified 45 complications during planned home deliveries. Complications occurred most often among women living in largely populated cities with higher levels of education. Overall, 40% of patients did not receive routine antenatal care, and 38% of women gave birth after the 41st week of pregnancy. In 60% of cases, no professionals attended the birth. Hospital transfer frequencies were 42% after delivery, 36% at third-stage labour, 11% first-stage labour, 9% second-stage labour, and 2% before delivery. We recorded four neonatal deaths and one severe newborn morbidity. There was one maternal death unrelated to the home-birthing process and six cases of severe maternal haemorrhagic shock requiring intensive care. CONCLUSION: Complications of planned home births occurred more frequently in women living in largely populated cities and with higher education levels. Planned home births were also observed among women who were at a higher risk of complications. Risk factors included nulliparity, postdate pregnancy, and lack of prenatal care. Hospital transfers occurred most often in the third stage of labour and postpartum.

Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers.

To achieve optimal development of a newborn, breastfeeding is extensively recommended, but little is known about the role of non-nutritive bioactive milk components. We aimed to characterize the fatty acid esters of hydroxy fatty acids (FAHFAs), namely palmitic acid hydroxystearic acids (PAHSAs)-endogenous lipids with anti-inflammatory and anti-diabetic properties, in human breast milk. Breast milk samples from 30 lean (BMI=19-23) and 23 obese (BMI>30) women were collected 72h postpartum. Adipose tissue and milk samples were harvested from C57BL/6J mice. FAHFA lipid profiles were measured using reverse phase and chiral liquid chromatography-mass spectrometry method. PAHSA regioisomers as well as other FAHFAs were present in both human and murine milk. Unexpectedly, the levels of 5-PAHSA were higher relative to other regioisomers. The separation of both regioisomers and enantiomers of PAHSAs revealed that both R- and S-enantiomers were present in the biological samples, and that the majority of the 5-PAHSA signal is of R configuration. Total PAHSA levels were positively associated with weight gain during pregnancy, and 5-PAHSA as well as total PAHSA levels were significantly lower in the milk of the obese compared to the lean mothers. Our results document for the first time the presence of lipid mediators from the FAHFA family in breast milk, while giving an insight into the stereochemistry of PAHSAs. They also indicate the negative effect of obesity on 5-PAHSA levels. Future studies will be needed to explore the role and mechanism of action of FAHFAs in breast milk.

For Debate: The Significance of Etiologic Diagnosis in Neonates with Overgrowth Syndromes. Lesson Learned from the Simpson-Golabi-Behmel Syndrome.

Overgrowth syndromes are rare genetic disorders characterized by excessive pre- and postnatal growth accompanied by dysmorphic features and developmental disorders. In addition to other health hazards, the life expectancy of affected children may be compromised due to an increased risk of developing tumors. To demonstrate the need for early recognition, correct diagnostic evaluation and adequate follow-up, we present a family with recurrent Simpson-Golabi-Behmel syndrome (SGBS). SGBS is a X-linked neonatal overgrowth syndrome caused by mutations in the GPC3 or GPC4 genes. All three affected males manifested with congenital diaphragmatic hernia. When fetal overgrowth and congenital diaphragmatic hernia co-occur, the choice for a possible cause is limited among SGBS, Marfan syndrome and Pallister-Killian syndrome. Their different phenotypes allow clinical assessment and correct diagnosis in most cases and should be followed by genetic testing. Regular oncologic screening aimed towards early recognition of malignant tumors may improve long-term outcomes in SGBS as well as in all other overgrowth syndromes.

Prenatally Acquired Multiple Limb Ischemia in a Very Low Birth Weight Monochorionic Twin.

Limb ischemia is an extremely rare event occuring in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). The authors describe a case of TTTS and TAPS treated successfully using amnioreduction and laser ablation. However, severe ischemia of both lower extremities in the recipient twin developed after the fetal treatment. This serious complication was diagnosed on MRI in utero and confirmed postnatally. Elective amputation of the affected limbs was performed. The etiology of the disease remains unclear despite profound clinical and histopathological examinations; although the role of thromboembolism in monochorionic pregnancy seems to be most likely, this unique case of multiple limb ischemia with distinct macroscopic findings has not yet been described.

International survey on diagnosis and management of hypotension in extremely preterm babies.

UNLABELLED: Hypotension is a commonly diagnosed and treated complication of extremely low gestational age newborns (ELGAN), but enormous variation in diagnosis, management and clinical practice has been documented. We sought to evaluate practice regarding the management of hypotension in ELGANs and developed a web-based questionnaire addressing diagnosis, intervention thresholds and modes of treatment of hypotension in ELGANs. We received 216 completed questionnaires from respondents in 38 countries. Most responses (83 %) were from specialist units where, together, over 26,000 very low birth weight (VLBW) infants are cared for annually. The majority (73 %) defined hypotension as a mean blood pressure (BP) in mmHg less than the gestational age in weeks. Sixty percent assessed the circulation with additional methods; echocardiography was the most commonly used (74 %), with left ventricular output and fractional shortening the two most common measurements made. The majority (85 %) used volume administration as the initial intervention. Dopamine was the inotrope most commonly used initially (80 %). If the initial inotrope therapy failed, dobutamine was the most popular second-line treatment (28 %). Delayed cord clamping was used at 51 % of the centres. CONCLUSION: The definition of hypotension in ELGANs continues to follow traditional standards. Functional echocardiography is now used to assess the circulation at many centres. Volume expansion and dopamine remain the most frequently used therapies.

No differences were observed in the prevention of necrotizing enterocolitis and late-onset sepsis among preterm infants who received either single-species or multi-species probiotics.

BACKGROUND: Probiotic prophylaxis has been suggested to reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm newborns. However, choosing the optimal probiotic is difficult due to variations in strain-specific effects and interactions facilitated by the use of combination species. AIMS: To compare clinical outcomes of very preterm infants receiving multi or single-species probiotics. STUDY DESIGN: Retrospective, single-center, cohort study. SUBJECTS: Very preterm infants (<32 weeks' gestation) born between 2019 and 2022 at a tertiary perinatal center received either a multi-species (Lactobacillus rhamnosus 45 %, Lactobacillus casei 15 %, Lactobacillus acidophilus 15 %, Bifidobacterium infantis 15 %, Bifidobacterium bifidum 10 %; n = 228) or a single-species (Bifidobacterium breve BR03 and B632; n = 227) probiotic formulation. MAIN OUTCOME MEASURES: NEC, LOS, and mortality. RESULTS: The overall incidence of NEC and LOS was 3.1 % and 13.8 %, respectively. There were no differences between the multi-species and single-species probiotic groups in the rate of NEC (3.5 % vs 2.6 %; p = 0.787), LOS (15.4 % vs 12.3 %; p = 0.416), mortality (0.9 % vs 1.8 %; p = 0.449), or composite outcome (NEC, LOS and/or death; 16.7 % vs 12.8 %; p = 0.290). CONCLUSION: The clinical outcomes of very preterm newborns receiving multi vs. single-species probiotic formulations were similar in our study. In view of the sample size and low baseline rate of NEC in our unit, further trials are warranted to investigate the effects of specific probiotics for prevention of serious neonatal morbidities.

High protein intake can lead to serious hypophosphatemia and hypokalemia in growth restricted preterm newborns.

Objectives: High protein parenteral nutrition (HPPN) in the early postnatal period is a recommended strategy for very low birth weight (VLBW) infants. However, limited data is available on electrolyte changes when HPPN strategy is utilized. We investigated the impact of HPPN on the development of hypophosphatemia and hypokalemia in preterm VLBW newborns. Methods: A retrospective, single-center study investigated the levels of phosphate and potassium in VLBW infants who received HPPN (amino acids intake up to 3.5 g/kg/day) during the first week of life. Preterm infants were divided into two subgroups: appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. Clinical data were obtained from hospital database and medical records. Results: Overall, 170 VLBW infants were included for the study analysis: 41 SGA (mean birth weight 752 ± 39 g) and 129 AGA infants (mean birth weight 994 ± 23 g). Phosphate and potassium levels were significantly lower in the SGA infants compared to AGA infants (Phosphate: 0.97 ± 0.07 mmol/l vs. 1.44 ± 0.04 mmol/l, p < 0.001; Potassium: 3.0 ± 0.1 mmol/l vs. 3.6 ± 0.1 mmol/l, p < 0.001). Conclusions: Repeated measurement of serum phosphate and potassium is recommended when HPPN strategy is utilized in preterm SGA infants where significant hypophosphatemia and hypokalemia might have serious clinical consequences.

Macular pigment evaluation using dual-wavelength fundus auto-fluorescence imaging.

INTRODUCTION: Macular pigment plays an important role in the reduction of oxidative stress and in preventing retinal diseases. Quick and easy measurements of the macular pigment are essential in both clinical and research settings. Dual wavelength fundus auto-fluorescence seems to be the optimal method. This study aims to investigate changes in fundus autofluorescence in patients taking daily lutein oral supplements and develop image processing methods for follow-up evaluations of the images. METHODS: New devices allow us to examine fundus autofluorescence using both blue and green excitation wavelengths. This allows detection of the amount of macular pigment by subtracting these two images because the yellow pigment particles absorb blue wavelengths. We determined daily dose of 25 mg of lutein and 3 mg of zeaxanthin. Patients were followed up for 15 months at 3-month intervals. RESULTS: During our 15-month study, we observed a positive trend in pixel lightness values, suggesting an increase in macular pigments in the foveal area. In all patients taking daily lutein supplements, the foveal index significantly increased after six months, with a median change of 0.081. We did not observe a significant change after the first three months (0.006) and only a small change between the 6th and 12th-month visits (0.012). CONCLUSION: With appropriate patients and procedures for capturing autofluorescence images, this is a valuable technique for macular pigment evaluation in follow-up examinations using software image post-processing and analysis with commonly available hardware. To put this into everyday practice, developing tools to automate the assessment is necessary.

Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?

Background: Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants. Methods: Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high-grade IVH (grade III-IV according to the classification by Papile) within the first week after birth. Results: The incidence of any IVH was 14.3% (183/1,279); the rate of low-grade (I-II) and high-grade (III-IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high-grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39-0.85; P = .006) and for high-grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20-0.65; P < .001). Conclusion: The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high-risk newborns.

Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals.

PURPOSE: To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. METHODS: The experimental Libechov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. RESULTS: Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. CONCLUSIONS: This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery.

Serial Measurement of Interleukin-6 Enhances Chance to Exclude Early-Onset Sepsis in Very Preterm Infants.

The aim of this retrospective study was to evaluate the reliability of peak interleukin-6 (IL-6) level within 24 hours after delivery as a predictor for early-onset sepsis (EOS) in very preterm neonates. Interleukin-6 was assessed at 2 hours and at 12 to 24 hours after delivery. The highest level was considered a peak value. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection, and C-reactive protein >10 mg/L. Among 445 enrolled infants, 53 developed EOS. A peak IL-6 level of more than 200 ng/L had a sensitivity of 89% and specificity of 77% for the presence of EOS. The negative predictive value was 98%. Receiver operating characteristics curve had area under the curve of 0.92. Peak IL-6 is a reliable marker of systemic inflammatory response and might be useful to exclude EOS within the first 24 hours.

Complications of planned home births in the Czech Republic.

OBJECTIVES: This study evaluated complications that can occur during planned home births that require transfer to the hospital. These factors were assessed to improve the current status of deliveries performed outside health care facilities in the Czech Republic. MATERIALS AND METHODS: This prospective cohort study included data on 105 cases of complicated home births during 2017 to 2021 using an online form accessible to all hospital maternity wards in the Czech Republic. RESULTS: Planned home births were complicated by fetal/neonatal causes, maternal causes, and combined fetomaternal complications in 28 (26.7%), 20 (19%), and 2 (1.9%) cases, respectively. The need for transfer was most often realized after the birth of the fetus (86; 81.9%); however, it was realized during birth in 19 (18.1%) cases. The following complications were noted most often: postpartum hemorrhage (23; 21.9%); neonatal asphyxia (17; 16.2); placental retention (14; 13.3%); birth injury (12; 11.4%); neonatal hypothermia (5; 4.8%); and placental birth (5; 4.8%). Indications for transfer during labor were as follows: labor obstruction (10; 9.5%); fetal hypoxia (5; 4.8%); bleeding during labor (2; 1.9%); preeclampsia (1; 0.9%); and fetal malformation (1; 0.9%). Perinatal death occurred in 8 (7.6%) cases. Permanent neonatal morbidity occurred in 4 (3.8%) cases. CONCLUSIONS: Patients with home birth complications were transferred to the hospital most often after the birth of the fetus. The low proportion of transfers during childbirth is caused by the unprofessional management of planned home births, resulting in a high number of perinatal deaths and high rate of permanent neonatal morbidity.

Machine Learning Detects Intraventricular Haemorrhage in Extremely Preterm Infants.

OBJECTIVE: To test the potential utility of applying machine learning methods to regional cerebral (rcSO2) and peripheral oxygen saturation (SpO2) signals to detect brain injury in extremely preterm infants. STUDY DESIGN: A subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (n = 46). All eligible infants were <28 weeks' gestational age and had continuous rcSO2 measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO2 data were available for 32 infants. The rcSO2 and SpO2 signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II-IV) using a leave-one-out cross-validation approach. RESULTS: The area under the receiver operating characteristic curve (AUC) for the PRD rcSO2 was 0.846 (95% CI: 0.720-0.948), outperforming the rcSO2 threshold approach (AUC 0.593 95% CI 0.399-0.775). Neither the clinical model nor any of the SpO2 models were significantly associated with brain injury. CONCLUSION: There was a significant association between the data-driven definition of PRDs in rcSO2 and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.