A Higher Amount of Nutritional Intake as a Possible Cause of Hyperglycemia in Extremely Premature Infants in Parenteral and Enteral Nutrition at the Tertiary Neonatal Intensive Care Unit.

BACKGROUND: This study aimed to find an association between infants who had hyperglycemia and those who did not, those treated with insulin or not and several prenatal and postnatal variables or the suboptimal prescription of parenteral nutrition. METHODS: We conducted a retrospective study, which included extremely premature infants (<28 weeks of gestation) admitted to the tertiary NICU, University Medical Centre Ljubljana, between 1 January 2021 and 31 December 2021. Blood glucose measurements, insulin treatment, general characteristics, nutritional data and complications of prematurity were obtained retrospectively from hospital data. RESULTS: There were 21 infants included in the study who did not receive insulin and 17 who were treated with insulin. Infants receiving insulin were younger and lighter compared to the non-insulin treatment group (mean gestational age 178 vs. 188 days; median birth weight 680 g vs. 990 g). The younger insulin group of infants received the same daily number of total macronutrients per kg per day compared to the older non-insulin group, i.e., glucose, lipids and amino acids, as recommended for the gestational age and birth weight. After adjusting for gestational age, no significant association with complications of prematurity was found. CONCLUSIONS: The postulated explanation (with the prescription of a higher amount of macronutrients during the first seven days) for hyperglycemia and treatment with insulin in the less mature and lighter infants cannot be supported by the data given.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Ethical Dilemmas in Neonatal Care at the Limit of Viability.

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.

Comparison of Neonatal Morbidity and Mortality Following Spontaneous and Medically Indicated Preterm Births: A Retrospective Population-Based Study Using Data from the Slovenian National Perinatal Information System 2013-2018.

BACKGROUND This retrospective population-based study analyzed data from the Slovenian National Perinatal Information System (NPIS) between 2013 and 2018 to compare neonatal morbidity and mortality following spontaneous and medically indicated preterm births. MATERIAL AND METHODS Retrospective population-based cohort. Entries to the NPIS database were searched by gestational age (GA) <37 weeks in Slovenia between 2013 and 2018. Of 9200 (6252 following spontaneous birth, 2948 following medically indicated) neonates included, 1358 were born at extremely to very preterm GA (998 following spontaneous birth, 360 following medically indicated). Logistic regression analysis was used to examine the association between neonatal mortality and composite severe neonatal morbidity and preterm birth type (spontaneous vs medically indicated) controlling for potential confounding variables. Analysis was first performed for all preterm births (GA 22 0/7 to 36 6/7) and later only for extremely to very preterm births (GA 22 0/7 to 31 6/7). RESULTS Neonatal mortality was significantly lower following spontaneous preterm birth at extremely to very preterm GA (odds ratio [OR] 0.34; 95% confidence interval [CI] [0.14, 0.81]), while there was no association in all preterm births group (OR 0.56; 95% CI [0.26, 1.20]). No significant correlation between preterm birth type and neonatal morbidity was found (OR 0.76; 95% CI [0.54, 1.09] for all preterm births and OR 0.71; 95% CI [0.47, 1.07] for extremely to very preterm births). CONCLUSIONS In this population study from Slovenia between 2013 and 2018, medically indicated preterm births at <32 weeks of GA were associated with significantly increased neonatal mortality but not neonatal morbidity.

Postnatal CMV Infection and Antiviral Treatment in Extremely Premature Infants: A 12-Year Retrospective Analysis.

BACKGROUND: The impact and outcomes of postnatal cytomegalovirus (CMV) infection are not entirely clear. We aimed to determine the associations between treatment outcomes of postnatal CMV infection and its antiviral treatment. METHODS: Retrospective study in a tertiary center. Infants of < 29 weeks gestational age who were tested for postnatal CMV infection were included. CMV-infected infants were compared to uninfected infants (control group). CMV-infected infants were either treated with ganciclovir and/or valganciclovir (CMVPT group) or not (CMVPNT group). Demographic, clinical, laboratory, treatment, and outcome data were collected. Primary outcomes were the length of stay, death before discharge and hearing impairment, cognitive and motor development as assessed by the Denver Developmental Screening Test II, and neurologic impairment at the corrected age of 1.5-2 years. RESULTS: We included 103 extremely premature infants. The Median (interquartile range [IQR]) length of stay was 94 (69-112) days in control, 85 (70-102) days in CMVPNT, and 100 (88-137) days in the CMVPT group. Mortality before discharge was 6% in control, 3.8% in CMVPNT, and 3.7% in the CMVPT group. Normal hearing at follow-up was found in 30/37 infants in control (81.1%), 13/13 infants in CMVPNT (100%), and 17/20 infants in the CMVPT group (85%). Denver Developmental Screening Test II results did not differ among the three groups. Neurologic impairment was found in 21/37 infants (56.8%) in control, 9/13 infants in CMVPNT (69.2%), and 14/20 infants in CMVPT group (70%). CONCLUSIONS: The associations between antiviral treatment of postnatal CMV infection and better treatment outcomes were nonsignificant.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.

OBJECTIVE: To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone. DESIGN: Multicentre, multinational, randomised controlled phase 3 trial. SETTING: 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. PARTICIPANTS: 1121 pregnant women (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group. INTERVENTION: Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation. MAIN OUTCOME MEASURE: The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge. RESULTS: Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70). CONCLUSION: Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166722.

Risk Factors for Feeding and Swallowing Disorders in Very Low Birth Weight Infants in Their Second Year of Life.

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.

No increase in GFAP and S-100B in very preterm infants with mild periventricular leukomalacia or intraventricular hemorrhage: a pilot study.

AIM: To determine the serum levels of glial fibrillary acidic protein (GFAP) and S-100B in very preterm infants with and without periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH). METHODS: The study enrolled preterm infants born between 23 and 32 weeks of gestation admitted to the Neonatal Intensive Care Unit, University Medical Center Ljubljana. PVL and IVH were determined with cranial ultrasound. Peripheral blood was collected in the first 24 hours after delivery and once between days 4 to 7. GFAP and S-100B concentrations were measured in serum samples. Infants with PVL or IVH were compared with infants without PVL or IVH. RESULTS: Of 40 patients (mean gestational age 29.4 weeks), 7 had IVH and/or PVL. S-100B was detectable in peripheral blood in all patients at every measurement. In the group with IVH or PVL, the median S-100B at the first sampling was 0.43 (IQR 0.29-0.60) ng/mL, and 0.40 (IQR 0.33-1.01) ng/mL at the second sampling. In the group without PVL or IVH, it was 0.40 (IQR 0.29-0.6) ng/mL at the first sampling and 0.43 (IQR 0.34-0.62) ng/mL at the second sampling. The median GFAP was 0 regardless of the group and sampling time. The groups did not significantly differ in serum GFAP or S-100B levels. CONCLUSION: Peripheral blood levels of GFAP and S-100B were not significantly increased in very preterm infants that developed PVL or IVH. The predictive value of GFAP and S-100B as biomarkers of neonatal brain injury should be further explored in a larger cohort of neonates with more extensive IVH or PVL.

Association between latency period and perinatal outcomes after preterm premature rupture of membranes at 32-37 weeks of gestation: a perinatal registry-based cohort study.

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.

Perinatal outcomes in women with severe acute respiratory syndrome coronavirus 2 infection: comparison with contemporary and matched pre-COVID-19 controls.

OBJECTIVES: To compare perinatal outcomes in women with vs. without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Perinatal outcomes in SARS-CoV-2 positive pregnant women who delivered at our institution between October 27th 2020 and January 31st 2021 were compared to SARS-CoV-2 negative pregnancies (contemporary controls) and historical 2019 controls matched by maternal age, pre-pregnancy body mass index and parity. Testing was performed based on symptoms or close contact at any time during pregnancy and as part of universal screening at hospital admission. Multivariable log-linear regression models were used adjusting for potential confounders (p < 0.05 statistically significant). RESULTS: One thousand three hundred seventeen women delivered at our institution during the study period. 1,124 (85%) tested negative and 193 (15%) positive for SARS-CoV-2. 189 (98%) were infected during third trimester. 19 (10%) were asymptomatic, 171 (89%) had mild to moderate coronavirus disease 2019 (COVID-19), and 3 (2%) were critically ill with one case of maternal death. There were no significant differences in preterm birth, small-for-gestational-age birth weight, congenital anomalies, operative delivery, intrapartum hypoxia, and perinatal mortality in SARS-CoV-2 positive pregnancies compared to contemporary reference group or historical controls from pre-COVID-19 period. Labor was more commonly induced in SARS-CoV-2 positive women compared to reference SARS-CoV-2 negative group (68 [35%] vs. 278 [25%], adjusted odds ratio 1.62; 95% confidence interval 1.14-2.28). CONCLUSIONS: SARS-CoV-2 infection in pregnancy was not strongly associated with adverse perinatal outcomes. While the majority of SARS-CoV-2 positive women had no or mild/moderate symptoms, 2% were critically ill, with one case of maternal death.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Serum hepcidin and ferritin as markers of iron deficiency in premature infants born at less than 32 weeks of gestation: prospective observational study.

BACKGROUND: Preterm infants born at less than 32 weeks of gestation are at higher risk of low total iron stores (iron deficiency). Serum ferritin is used as a valid total iron stores and iron deficiency biomarker, usually as a combination of ferritin and red blood cell counts. METHODS: Serum hepcidin and ferritin values and red blood cell counts were obtained from 37 of 40 included premature infants born at less than 32 weeks of gestation at risk of iron deficiency. The first sample was obtained in the first week of life, and the second at transfer from the Neonatal intensive care unit to the maternity ward, when serum ferritin level below 25 µg/L has been defined as very low total iron stores (iron deficiency). RESULTS: Ferritin median levels decreased from a median value of 152 µg/L at the first measurement to 54 µg/L at the second measurement. Hepcidin median levels also decreased from 30.1 µg/L to 2.1 µg/L. We found a positive and statistically significant correlation between levels of ferritin and hepcidin at both measurements (r = 0.57; p < 0.001 and r = 0.72; p < 0.001, respectively). Compared to serum hepcidin, ferritin at the first measurement has not statistically significant higher power in predicting children with iron deficiency before discharge from the hospital. CONCLUSIONS: We found a correlation between ferritin and hepcidin levels. Nevertheless, hepcidin does not have a worse power in predicting children with iron deficiency compared to ferritin.

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes. CONCLUSION: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001-2018.

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.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): an investigator-initiated, randomized, multi-center, multi-national, clinical trial on additional cerebral tissue oxygen saturation monitoring combined with defined treatment guidelines versus standard monitoring and treatment as usual in premature infants during immediate transition: study protocol for a randomized controlled trial.

BACKGROUND: 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). METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017.

Pregnancy complicated by influenza A ARDS requiring consecutive VV-ECMO treatment with successful vaginal delivery.

A 29-year-old woman presented with influenza A ARDS at 23+0 weeks of gestation. Mechanical ventilation failed and VV-ECMO was started in a non-ECMO hospital. Transportation was performed on ECMO. Within 5 days ECMO weaning was successful. Fetal condition was stable, and decision to continue pregnancy was taken. However, second VV-ECMO was needed due to ventilator-associated pneumonia. At 25+6 weeks, the patient spontaneously delivered a neonate vaginally. Patient's condition improved, and ECMO could be removed 10 days postpartum. 2-year follow-up showed no severe consequences in the mother and the child.

Lipopolysaccharide-binding protein as marker of fetal inflammatory response syndrome after preterm premature rupture of membranes.

BACKGROUND: Intra-amniotic inflammation with preterm premature rupture of membranes (PPROM) is a risk factor for fetal inflammatory response syndrome (FIRS) and adverse neonatal outcome. OBJECTIVES: To evaluate the diagnostic accuracy of lipopolysaccharide-binding protein (LBP) for detecting FIRS in preterm neonates born after PPROM. METHODS: This was a prospective study in the level III neonatal intensive care unit (42 neonates; 23 + 6 to 31 + 6 weeks' gestation) of mothers with PPROM. Umbilical cord blood concentrations of LBP, C-reactive protein (CRP), interleukin (IL)-6 and white blood cell count with differential were measured at delivery and 24 h after birth. Neonates were classified into FIRS (n = 22) and no FIRS (n = 20) groups according to clinical criteria and IL-6 level (≥17.5 pg/ml). Histological examination of the placenta and umbilical cord was performed. Neurological examination at 12 months' corrected age was performed. RESULTS: Umbilical cord blood concentration of LBP was significantly higher in the FIRS group than in the no FIRS group at delivery (median 21.6 mg/l vs. median 2.3 mg/l; p < 0.0001) and 24 h after birth (median 17.2 mg/l vs. median 20.0 mg/l; p < 0.001). The area under the ROC curve for FIRS at delivery was 0.98 (95% CI 0.88-1.0) for LBP, 0.92 (95% CI 0.80-0.99) for CRP and 0.82 (95% CI 0.64-0.94) for immature to total neutrophil ratio. Similar results were obtained if FIRS was defined by funisitis. Umbilical cord blood concentration of LBP at delivery was significantly higher in neonates with abnormal neurological exam at 12 months than in those with normal exam (median 19.5 mg/l vs. median 3.75 mg/l; p < 0.015). CONCLUSIONS: In preterm neonates born to asymptomatic women with PPROM, LBP in cord blood at delivery is an excellent diagnostic biomarker of FIRS/funisitis with prognostic potential.

Neutrophil defensins but not interleukin-6 in vaginal fluid after preterm premature rupture of membranes predict fetal/neonatal inflammation and infant neurological impairment.

OBJECTIVE: To determine whether neutrophil defensins (HNP1-3) and interleukin-6 (IL-6) in vaginal fluid after preterm premature rupture of membranes predict fetal inflammatory response syndrome (FIRS), neurological impairment or chorioamnionitis. DESIGN: Prospective study. SETTING: Tertiary referral university hospital. POPULATION: Forty-two patients with preterm premature rupture of membranes at <32 weeks. METHODS: Levels of HNP1-3 and IL-6 were measured in vaginal fluid obtained by swabs. Mann-Whitney U-test was used to compare HNP1-3 and IL-6 levels in groups with vs. without FIRS, infant death or neurological impairment, and chorioamnionitis (p<0.05 significant). Logistic regression was used to control for potential confounders. Diagnostic accuracies of HNP1-3 and IL-6 were determined by receiver operator characteristics analysis. MAIN OUTCOME MEASURES: Fetal inflammatory response syndrome was defined as neonatal inflammation within 72 hours postpartum. Neurological impairment was defined as motor and/or tone abnormalities at one year of corrected age. Chorioamnionitis was diagnosed histologically. RESULTS: Levels of HNP1-3, but not IL-6, were higher in 12 cases of FIRS (p=0.019 and p=0.256, respectively). Levels of HNP1-3, but not IL-6, were higher in 14 cases of infant death or neurological impairment (p=0.015 and p=0.100, respectively) and, when only survivors were analyzed, in nine cases of neurological impairment (p=0.030 and p=0.187, respectively). Levels of HNP1-3 and IL-6 were higher in 29 cases of chorioamnionitis (p=0.005 and p=0.003, respectively). The differences remained significant after adjustment for gestational age. Levels of HNP1-3 predicted FIRS, infant death or neurological impairment and chorioamnionitis with an area under the curve of 0.75, 0.79 and 0.78, respectively. CONCLUSIONS: Elevated vaginal fluid HNP1-3 and IL-6 levels are associated with histological chorioamnionitis. Elevated HNP1-3 can also identify FIRS and predict infant death or neurological impairment.

A comparison of respiratory patterns in healthy term infants placed in car safety seats and beds.

OBJECTIVE: The purpose of this work was to compare the incidence of apnea, hypopnea, bradycardia, or oxygen desaturation in healthy term newborns placed in hospital cribs, infant car safety beds, or infant car safety seats. METHODS: A consecutive series of 200 newborns was recruited on the second day of life. Each subject was studied while placed in the hospital crib (30 minutes), car bed (60 minutes), and car seat (60 minutes). Physiologic data, including oxygen saturation, frequency, and type of apnea, hypopnea, and bradycardia were obtained and analyzed in a blinded manner. RESULTS: The mean oxygen saturation level was significantly different among all of the positions (97.9% for the hospital crib, 96.3% for the car bed, and 95.7% for the car seat; P < .001). The mean minimal oxygen saturation level was lower while in both safety devices (83.7% for the car bed and 83.6% for the car seat) compared with in the hospital crib (87.4%) (P < .001). The mean total time spent with an oxygen saturation level of <95% was significantly higher (P = .003) in both safety devices (car seat: 23.9%; car bed: 17.2%) when compared with the hospital crib (6.5%). A second study of 50 subjects in which each infant was placed in each position for 120 minutes yielded similar results. CONCLUSIONS: In healthy term newborns, significant desaturations were observed in both car beds and car seats as compared with hospital cribs. This study was limited by lack of documentation of sleep stage. Therefore, these safety devices should only be used for protection during travel and not as replacements for cribs.

Intrauterine inflammation and the onset of peri-intraventricular hemorrhage in premature infants.

BACKGROUND: Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants. METHODS: A prospective study included 125 infants with gestational age 23-29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late. RESULTS: Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH. CONCLUSIONS: These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.