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.

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.

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.

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.

Neonatal Sequential Organ Failure Assessment (nSOFA) Score within 72 Hours after Birth Reliably Predicts Mortality and Serious Morbidity in Very Preterm Infants.

The aim of this study was to assess the applicability of the neonatal sequential organ failure assessment score (nSOFA) within 72 h after delivery as a predictor for mortality and adverse outcome in very preterm neonates. Inborn neonates <32 weeks of gestation were evaluated. The nSOFA scores were calculated from medical records in the first 72 h after birth and the peak value was used for analysis. Death or composite morbidity at hospital discharge defined the adverse outcome. Composite morbidity consisted of chronic lung disease, intraventricular haemorrhage ≥grade III, periventricular leukomalacia and necrotizing enterocolitis. Among 423 enrolled infants (median birth weight 1070 g, median gestational age 29 weeks), 27 died and 91 developed composite morbidity. Death or composite morbidity was associated with organ dysfunction as assessed by nSOFA, systemic inflammatory response, and low birthweight. The score >2 was associated with OR 2.5 (CI 1.39−4.64, p = 0.002) for the adverse outcome. Area under the curve of ROC was 0.795 (95% CI = 0.763−0.827). The use of nSOFA seems to be reasonable for predicting mortality and morbidity in very preterm infants. It constitutes a suitable basis to measure the severity of organ dysfunction regardless of the cause.

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.

C-Reactive Protein, Interleukin-6, and Procalcitonin in Diagnosis of Late-Onset Bloodstream Infection in Very Preterm Infants.

BACKGROUND: Late-onset bloodstream infection (LOBSI) is common in very preterm infants. Early and accurate diagnosis is crucial for prognosis and outcome. We aimed to analyze the accuracy of routinely used inflammatory biomarkers in the diagnosis of LOBSI as compared to uninfected controls. METHODS: In this single-center, retrospective case-control study, interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were routinely measured, when infection was clinically suspected. The definition of LOBSI was based on positive blood culture, clinical signs of infection, and onset more than 72 hours after birth. RESULTS: Among 285 enrolled infants, 66 developed LOBSI. IL-6 was superior to other markers, and levels greater than 100 ng/L had a sensitivity of 94% and a specificity of 99% for the presence of LOBSI. Receiver operating characteristic curve of IL-6 had area under the curve of 0.988 (95% CI = 0.975-1.00, P < .001). The negative predictive value of IL-6, CRP, and PCT for optimal cutoff values was 99%, 95%, and 93%, respectively. The logistic regression model of IL-6 > 100 ng/L or CRP > 10 mg/L were successfully predicted LOBSI in 97.9% of cases. CONCLUSIONS: The combination of IL-6 and CRP seems to have great potential in routine rapid diagnosis of LOBSI development. High negative predictive value of all tested markers could encourage the early discontinuation of antibiotic 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).

Corpus Callosum Growth and Neurodevelopmental Outcome Are Negatively Influenced by Systemic Infection in Very Low-Birth-Weight Infants.

Systemic infection may negatively modulate the development of cerebral white matter and long-term outcome of neonates. We analyzed the growth of corpus callosum (using cranial ultrasonography) and neurodevelopment (Bayley Scales of Infant Development, Third Edition) in 101 very low-birth-weight newborns. We observed significantly reduced corpus callosum length at 3 months of corrected age (44.5 mm vs 47.7 mm, P = .004) and diminished corpus callosum growth (0.07 mm/d vs 0.08 mm/d, P = .028) in infants who experienced systemic infection. The subgroup exhibited inferior neurodevelopmental outcomes with predominant motor impairment. The results suggest that length and growth of corpus callosum might be affected by systemic inflammatory response in preterm newborns. The changes in corpus callosum can contribute to adverse neurodevelopment at 2 years of corrected age. Serial ultrasonographic measurements of the corpus callosum may be suitable to identify preterm infants with increased risk of neurodevelopmental impairment.

Cerebral oxygenation reflects fetal development in preterm monochorionic and dichorionic twins.

BACKGROUND: Cerebral oxygenation (crSO2) monitoring is increasingly used in high-risk infants. Monochorionic twins suffer from specific fetal pathologies that can affect cerebral hemodynamics. Limited data are available on crSO2 and blood flow patterns in this population after birth. OBJECTIVE: To evaluate crSO2 changes in preterm monochorionic and dichorionic twins during the first 72 h of life. METHODS: Near-infrared spectroscopy was used to measure crSO2 in 62 infants from 31 twin pregnancies <32 weeks of gestation. The study group was divided into 4 subgroups: donor (1) and recipient (2) monochorionic twins (with twin-twin transfusion syndrome), fetal growth restriction (FGR) infants (3) and twins without fetal compromise (4). RESULTS: There was significant difference in birth weight (p < 0.001) among 4 subgroups. We observed significant variation in crSO2 among the subgroups using mixed model analysis (p < 0.001). The recipient twins exhibited the lowest crSO2 (mean ±â€¯SE) throughout the study period (76 ±â€¯0.3%), whereas the FGR and donor twins presented with the highest values (86 ±â€¯0.3% and 83 ±â€¯0.4% respectively). We found no statistically significant differences in neonatal mortality and morbidity among subgroups. CONCLUSION: Our study revealed significant correlation between crSO2 values postnatally and underlying fetal pathology in monochorionic and dichorionic preterm twins.

Tibial speed of sound changes in preterm infants during the first year of life.

INTRODUCTION: Metabolic bone disease of prematurity (MBD) frequently affects preterm infants. The accurate diagnosis of the MBD remains a challenging issue despite characteristic clinical, laboratory and imaging features. Recently, non-invasive quantitative ultrasound (QUS) measuring speed of sound (SOS) has been applied to assess bone status. Limited data are available on comparison of QUS among preterm infants. OBJECTIVE: To evaluate development of tibial bone SOS values in preterm infants during the first year of life and compare the SOS values among different birth weight categories. METHODS: QUS was used in 153 infants below 34 weeks of gestation. The study group was divided into 3 subgroups based on birth weight (BW): ≤1000 g, 1001-1500 g and >1500 g. SOS measurement was performed at 6 and 12 months of corrected age (CA). RESULTS: Overall, we found significant increase in mean tibial SOS between 6 and 12 months of CA (3004 ±â€¯123 vs 3253 ±â€¯109 m/s, p = 0.001). There were significant differences in SOS among birth weight categories at 6 months of CA (p = 0.045). However, these differences were not statistically significant at 12 months of CA (p = 0.289). The infants ≤ 1000 g scored the highest SOS values at both time points. CONCLUSIONS: Tibial SOS significantly increases during infancy in preterm newborns. Significant variation exists in SOS at 6 months, but not at 12 months of corrected age according to BW. Moreover, inverse correlation between BW and SOS indicating better bone status was revealed in extremely low birth weight infants at both 6 or at 12 months of CA.

Placental Transfusion and Cardiovascular Instability in the Preterm Infant.

Postnatal adaptation in preterm newborn comprises complex physiological processes that involve significant changes in the circulatory and respiratory system. Increasing hemoglobin level and blood volume following placental transfusion may be of importance in enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. The European consensus on resuscitation of preterm infants recommends delayed cord clamping (DCC) for at least 60 s to promote placenta-fetal transfusion in uncompromised neonates. Recently, published meta-analyses suggest that DCC is associated with fewer infants requiring transfusions for anemia, a lower incidence of intraventricular hemorrhage, and lower risk for necrotizing enterocolitis. Umbilical cord milking (UCM) has the potential to avoid some disadvantages associated with DCC including the increased risk of hypothermia or delay in commencing manual ventilation. UCM represents an active form of blood transfer from placenta to neonate and may have some advantages over DCC. Moreover, both methods are associated with improvement in hemodynamic parameters and blood pressure within first hours after delivery compared to immediate cord clamping. Placental transfusion appears to be beneficial for the preterm uncompromised infant. Further studies are needed to evaluate simultaneous placental transfusion with resuscitation of deteriorating neonates. It would be of great interest for future research to investigate advantages of this approach further and to assess its impact on neonatal outcomes, particularly in extremely preterm infants.

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.

Procalcitonin is more likely to be released by the fetus rather than placental tissue during chorioamnionitis.

AIMS: To analyze the relationship between maternal, cord blood and neonatal procalcitonin (PCT) levels in preterm deliveries with and without histologically proven chorioamnionitis (HCA). METHODS: 91 mother-infant pairs from 24+0 to 33+0 gestational weeks were analyzed. Procalcitonin was measured in all mothers within 24 hours before and subsequently in cord blood and in neonates within the first two hours after delivery. PCT levels were analysed in relationship to HCA and clinical outcome. RESULTS: HCA was confirmed in 28 cases (31%). We found no differences in PCT values between HCA positive and negative groups in maternal blood (0.1±0.1 vs 0.09±0.09 ng/L, P = 0.76). PCT values in cord blood and neonates were significantly higher in the HCA positive compared to HCA negative group (0.23±0.1 vs 1.2±2.7 ng/L, P < 0.001 and 0.89±3.4 vs 4.2±9.3 ng/L, P < 0.0001 respectively). PCT values in neonates were significantly higher than those of cord blood. Levels were not influenced by the mode of delivery, gestational age or premature rupture of membranes. Chorioamnionitis was more frequently associated with early onset neonatal sepsis (36% in HCA group vs 5% in non HCA group, P < 0.0001). Comparison of other clinical data revealed no differences between HCA positive and negative groups. CONCLUSION: This study showed higher PCT in cord and neonatal blood in the presence of proven histological chorioamnionitis. The measurement of PCT in mothers' blood is not helpful for diagnosis of HCA. The changes in PCT values shown suggest its production and release by fetal tissue.

Fetal distress and circulatory disturbance in monochorionic twins: Possible risk factors for sialadenitis?

Neonatal sialadenitis is a rare condition. The vast majority of cases are caused by Staphylococcus aureus with predominant involvement of the parotid gland and need for long-term antimicrobial therapy. We reviewed three distinct cases of submandibular sialadenitis in preterm infants from monochorionic pregnancies. The association with neonatal sialadenitis is unproven. We speculate about the role of fetal distress and circulatory compromise in monochorionic twins as a risk factor in the development of this serious condition.