Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia–ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO2) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO2) and heart rate (HR). COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO2, SpO2, and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO2 and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities. crSO2 monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO2 with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury. ClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017.

Advances in neonatal care have pushed the limit of viability to incrementally lower gestations over the last decades. However, surviving extremely premature neonates are prone to long-term neurodevelopmental handicaps. This makes ethics a crucial dimension of periviable birth management. At 22 weeks, survival ranges from 1 to 15%, and profound disabilities in survivors are common. Consequently, there is no beneficence-based obligation to offer any aggressive perinatal management. At 23 weeks, survival ranges from 8 to 54%, and survival without severe handicap ranges from 7 to 23%. If fetal indication for cesarean delivery appears, the procedure may be offered when neonatal resuscitation is planned. At a gestational age ≥24 weeks, up to 51% neonates are expected to survive the neonatal period. Survival without profound neurologic disability ranges from 12 to 38%. Beneficence-based obligation to intervene is reasonable at these gestations. Nevertheless, autonomy of parents should also be respected, and parental consent should be sought prior to any intervention. Optimal counselling of parents involves harmonized cooperation of obstetric and neonatal care providers. Every fetus/neonate and every pregnant woman are different and have the right to be considered individually when treatment decisions are being made.

Background: Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. Methods: GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. Results: Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. Conclusions: A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

Background and Objectives: This study aimed to identify the prevalence of feeding and swallowing disorders (FSD) in very low birth weight (VLBW, 1500 g or less) infants in the first two years after discharge from the maternity hospital, their possible risk factors, and the consequences of them. Materials and Methods: A total of 117 preterm children with VLBW born between 2013 and 2015 were included. The data concerning possible FSD after discharge from the hospital were obtained through accessible medical documentation for the child and a short parental questionnaire. Results: FSD was reported in 32 (27.4%) infants following discharge from the hospital but in only five children (4.3%) at a mean age of four years. Four variables (birth gestational age less than 28 weeks, birth weight equal to or less than 1000 g, birth length below 33 cm, and start of oral feeding after the 34th gestational week) were identified as risk factors for FSD after discharge. However, only birth length remained a significant predictor after being included in a binary logistic regression model (p = 0.000). Abnormal oral sensitivity and a decrease in weight to under the 10th percentile were significantly more common in the FSD group at follow-up visits at the age of about 2 years. Conclusions: FSD was still present in more than one-quarter of VLBW infants after discharge from the maternity hospital but mostly disappeared within four years. A birth gestational age under 28 weeks, weight up to 1000 g, the late beginning of per oral feeding, and a birth length below 33 cm were determined to be significant predictive factors for FSD. Having a birth length below 33 cm was associated with an almost 6.5-fold increase in the odds of having persistent FSD after discharge from the hospital. FSD in the first years of life may have an impact on the child’s further growth and development.

Background: Significant improvement in neonatal care has enabled increasing survival of preterm infants. Metabolic bone disease of prematurity is often overlooked due to other comorbidities of preterm birth. The best approach is screening and prevention of the disease in high-risk infants such as preterm infants. Aim: We followed up the clinical, radiological, and serum biochemical markers of metabolic bone disease in extremely preterm infants (<28 weeks of gestation). The clinical applicability and validation of C-terminal telopeptide of type I collagen (CTX-I) as a novel bone turnover marker were assessed. Standard and novel biochemical bone turnover markers and quantitative ultrasound were compared. Method: Patients’ data were collected from medical records. Assessments of calcium, phosphate, alkaline phosphatase, bone-alkaline phosphatase, CTX-I, and quantitative ultrasound were prospectively performed twice in 42 extremely preterm infants at postmenstrual ages of 30–32 weeks and 36–40 weeks. Bone mineral density was measured by quantitative ultrasound. Conclusion: Phosphate, alkaline phosphatase, bone alkaline phosphatase, calcium, or ionized calcium are not related to gestational age, but bone mineral density, measured by quantitative ultrasound, is related. There is no correlation between standard and novel biochemical markers and quantitative ultrasound for the identification of metabolic bone disease.

Objectives: To investigate association between latency after preterm premature rupture of membranes (PPROM) and perinatal outcomes at moderately and late preterm gestation. Methods: National perinatal registry-based cohort study using data for the period 2013–2018. Singleton pregnancies with non-malformed fetuses in cephalic presentation complicated by PPROM at 32⁺⁰–36⁺⁶ weeks were included. Associations between latency period and perinatal mortality, neonatal respiratory distress syndrome (RDS), early onset neonatal infection (EONI), and cesarean section were assessed using multiple logistic regression, adjusting for potential confounders (labor induction, maternal body-mass-index, maternal age, antenatal corticosteroids, and small-for-gestational-age). p<0.05 was considered statistically significant. Results: Of 3,017 pregnancies included, 365 (12.1%) had PPROM at 32⁺⁰–33⁺⁶ weeks and 2,652 (87.9%) at 34⁺⁰–36⁺⁶ weeks. Among all cases, 2,540 (84%) had latency <24 h (group A), 305 (10%) 24–47 h (group B), and 172 (6%) ≥48 h (group C). Longer latency was associated with higher incidence of EONI (adjusted odds ratio [aOR] 1.350; 95% confidence interval [CI] 0.900–2.026 for group B and aOR 2.500; 95% CI 1.599–3.911 for group C) and higher rate of caesarean section (aOR 2.465; 95% CI 1.763–3.447 for group B and aOR 1.854; 95% CI 1.172–2.932 for group C). Longer latency was not associated with rates of RDS (aOR 1.160; 95% CI 0.670–2.007 for group B and aOR 0.917; 95% CI 0.428–1.966 for group C). Conclusions: In moderately to late PPROM, increased latency is associated with higher risk of EONI and cesarean section with no reduction in RDS.