Membrane stripping in group B streptococcus carriers does not impede adequate intrapartum antibiotic prophylaxis: a retrospective study.

Objective: Membrane stripping in group B streptococcus (GBS) carriers poses an increased risk of inadequate antibiotic prophylaxis, potentially due to accelerated labor, thereby potentially impacting the management of GBS colonization during delivery. We compared the adequacy of intrapartum antibiotic prophylaxis between pregnant women colonized with GBS, who underwent membrane stripping and those who did not. The study aimed to determine whether the performance of membrane stripping, by potentially shortening labor duration, increases the risk of inadequate antibiotic prophylaxis dispensation. Study design: A retrospective cohort study was conducted on GBS screen-positive women with a full-term singleton pregnancy in cephalic presentation, who were eligible for vaginal delivery. The exposed group consisted of women who underwent membrane stripping, while the unexposed group consisted of women who did not undergo membrane stripping. The primary outcome was defined as inadequate duration of antibiotic prophylaxis during labor, wherein less than 4 h of beta-lactam antibiotics were administered prior to delivery. Neonatal outcome was compared between the groups. Results: This retrospective cohort study comprised 1,609 women, with 129 in the exposed group (stripping group) and 1,480 in the unexposed group (no stripping group). Adequate intrapartum antibiotic prophylaxis was received by 64.3% (83/129) of the exposed group, compared to 46.9% (694/1,480) of the unexposed group (p = 0.003). Membrane stripping was associated with increased odds of receiving adequate prophylaxis (OR 1.897, 95% CI 1.185-3.037, p = 0.008). After excluding women who presented to the labor ward in active labor and delivered in less than 4 h, both the exposed and unexposed groups had similarly high rates of adequate intrapartum antibiotic prophylaxis (87.5% vs. 85.8%, respectively). No significant difference was observed in adverse neonatal outcomes between the groups. Conclusion: The provision of membrane stripping did not impede adequate intrapartum antibiotic prophylaxis and was correlated with a higher rate of sufficient prophylaxis in comparison to non-swept patients. These observations suggest that membrane stripping can be considered a safe option for ensuring adequate antibiotic prophylaxis in women colonized with GBS.

Implementation of pooled saliva tests for universal screening of cCMV infection.

Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to neurodevelopmental disabilities. Universal newborn infant screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test, which can identify all infected newborn infants, the development of an accurate and efficient testing strategy has remained an ongoing challenge. Here we assessed the implementation of pooled saliva polymerase chain reaction (PCR) tests for universal screening of cCMV, in two hospitals of Jerusalem from April 2022 through April 2023. During the 13-month study period, 15,805 infants (93.6% of all live newborn infants) were screened for cCMV using the pooled approach that has since become our routine screening method. The empirical efficiency of the pooling was six (number of tested newborn infants per test), thereby sparing 83% of the saliva tests. Only a minor 3.05 PCR cycle loss of sensitivity was observed for the pooled testing, in accordance with the theoretical prediction for an eight-sample pool. cCMV was identified in 54 newborn infants, with a birth prevalence of 3.4 per 1,000; 55.6% of infants identified with cCMV were asymptomatic at birth and would not have been otherwise targeted for screening. The study demonstrates the wide feasibility and benefits of pooled saliva testing as an efficient, cost-sparing and sensitive approach for universal screening of cCMV.

Cumulative Dose of Prostaglandin E1 Determines Gastrointestinal Adverse Effects in Term and Near-Term Neonates Awaiting Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to assess the association between treatment characteristics of prostaglandin E1 including initiation time and duration, maximal and cumulative doses, and adverse effects. DESIGN: A retrospective cohort study in which medical records of neonates with duct-dependent lesions were studied for treatment parameters and adverse effects. Multivariable logistic regression model was applied for testing the effect PGE1 variables on outcomes. MAIN OUTCOME MEASURES: The primary outcomes of this study were association of adverse effects of PGE1 treatment with maximal dose, cumulative dose, and treatment duration. The secondary outcomes included safety of feeding in infants treated with PGE1. RESULTS: Eighty-two infants with duct-dependent lesions receiving PGE1 were included. Several infants who received early PGE1 treatment required ventilation support. Feeds were ceased more often as the cumulative dose and duration of PGE1 treatment increased. Gastrointestinal adverse effects were significantly associated with the cumulative dose of PGE1 and treatment duration. Apneas, hyperthermia, and tachycardia were associated with maximal dose. Our data did not demonstrate a difference in the incidence of NEC associated with characteristics of PGE1 treatment. CONCLUSION: Cumulative PGE1 dose is associated with gastrointestinal adverse effects in neonates. Lower doses should be considered in neonates expecting prolonged PGE1 treatment.

Serious Bacterial Infections in Preterm Infants: Should Their Age Be "Corrected"?

Adjusting the chronological age of preterm infants according to their gestational age is a widely accepted practice in the field of neurodevelopment. It has been suggested for the assessment of preterm infants with suspected infection, but has been poorly validated. Correcting for chronological age is especially critical in infants with a chronological age above 3 months, but a corrected age below 3 months due to the differences in assessment protocols. This study assessed the difference in incidence of serious bacterial infection (SBI) according to chronological and corrected age in preterm infants. A retrospective analysis of pediatric emergency department (PED) presentations was conducted for all 448 preterm infants born in between January 2010 and August 2019. Of the 448 preterm infants, 204 (46%) presented at one of 3 PEDs in Jerusalem, Israel, during their first year of life. Overall, 141 (31.4%) presented with fever and were included in the study. The infants were divided into 3 age groups: 1-corrected age >3 months; 2-chronological age >3 months, but corrected age <3 months; 3-chronological and corrected age <3 months. SBI was diagnosed in 2.6%, 16.7%, and 33.3% of the infants in groups 1, 2 and 3, respectively; (p < 0.01, p = 0.17, p < 0.001). The incidence of SBI in the control group of 300 term infants <3 months presenting to the PED due to fever was 15.3%. Preterm infants with a corrected age <3 months are at increased risk for SBI, similarly to term infants <3 months of age. Age correction should thus be considered for preterm infants presenting with fever.

Acute Kidney Injury in Very Low Birth Weight Infants: A Major Morbidity and Mortality Risk Factor.

BACKGROUND AND OBJECTIVES: Very low birth weight (VLBW) infants are at high risk of developing acute kidney injury (AKI), presumably secondary to low kidney reserves, stressful postnatal events, and drug exposures. Our study aimed to identify the prevalence, risk factors, and outcomes associated with AKI in VLBW infants. STUDY DESIGN: Records of all VLBW infants admitted to two medical campuses between January 2019 and June 2020 were retrospectively reviewed. AKI was classified using the modified KDIGO definition to include only serum creatinine. Risk factors and composite outcomes were compared between infants with and without AKI. We evaluated the main predictors of AKI and death with forward stepwise regression analysis. RESULTS: 152 VLBW infants were enrolled. 21% of them developed AKI. Based on the multivariable analysis, the most significant predictors of AKI were the use of vasopressors, patent ductus arteriosus, and bloodstream infection. AKI had a strong and independent association with neonatal mortality. CONCLUSIONS: AKI is common in VLBW infants and is a significant risk factor for mortality. Efforts to prevent AKI are necessary to prevent its harmful effects.

Early Enteral Feeding of the Preterm Infant-Delay until Own Mother's Breastmilk Becomes Available? (Israel, 2012-2017).

AIM: To consider the question of whether to initiate trophic feeds with formula in the absence of own mother's breastmilk or to wait for breastmilk to be available. METHODS: A retrospective study of infants born prior to 32 weeks of gestation during the period 2012-2017 at a single tertiary center in Tel Aviv, Israel. Three TF groups were defined: exclusive breastmilk, mixed, and exclusive formula. Univariate and multivariate analyses were conducted. Logistic regression was used, and adjusted odds ratio and 95% interval were reported. RESULTS: Univariate analysis demonstrated that infants in the exclusive breastmilk group were born earlier, had lower birth weights and lower Apgar scores, were given lower volumes of TF, and were more likely to have a longer hospital stay. Poor composite outcome was more common among the exclusive breastmilk group. Multivariate regression analysis revealed no differences in incidence of early neonatal morbidities between the groups, except for longer duration of parenteral nutrition in the exclusive breastmilk group. CONCLUSION: In our cohort, exclusive formula TF was not associated with increased risk of any of the studied morbidities. Clinicians should consider this finding in deciding between early TF or fasting while waiting for own mother's breastmilk.

Neonatal morbidities and postnatal growth failure in very low birth weight, very preterm infants.

AIM: To assess postnatal growth in infants with and without major neonatal morbidities. METHODS: This study is based on analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 2009 to 2018. Postnatal growth was assessed in two 5 years epochs: 2009-2013 (n = 4583) and 2014-2018 (n = 4558). Outcome was considered as severe, mild and no postnatal growth failure (PNGF). Morbidities included respiratory distress syndrome, bronchopulmonary dysplasia, necrotising enterocolitis, patent ductus arteriosus and grades 3-4 intraventricular haemorrhage. Multinomial logistic regression analyses with the generalised estimating equation approach were applied. RESULTS: The study population composed 9141 infants. Of them, 2089 had at least one major morbidity and 7052 infants had none. In infants with no morbidities, 2.1% had severe PNGF, 23.7% mild PNGF and 74.2% had no PNGF, as compared to 13.6%, 43.9% and 42.5%, respectively, in infants with any major neonatal morbidity (p < 0.0001). CONCLUSION: Despite enormous advances in neonatal care, postnatal growth remains a challenge in VLBW infants, particularly in infants with major neonatal morbidities. Along with efforts to decrease morbidity, a more personalised plan and follow-up may be required in infants with major morbidities, given their high risk for diminished growth and potentially, adverse neurodevelopmental outcomes.

The role of sonographic head circumference in the occurrence of subgaleal hemorrhage following vacuum delivery.

OBJECTIVE: Subgaleal hemorrhage (SGH) is a severe neonatal morbidity that is associated with vacuum-assisted delivery (VAD). Large sonographic head circumference (sHC) was previously associated with complicated VAD. Nevertheless, the association of large sHC with SGH formation following VAD is underreported. We aim to evaluate the role of sonographic head circumference (sHC) with SGH formation following attempted VAD. METHODS: A retrospective case-control study. Cases comprised singleton pregnancies for whom attempted VAD resulted in SGH with an sHC measured within 2 weeks from delivery. Controls were VAD deliveries which not resulted in SGH, with an sHC measured within 2 weeks from delivery. We matched controls in a 1:1 ratio by gestational age, parity and year of delivery. RESULTS: Overall, 118 women were included in the SGH study group and were matched to 118 controls. Baseline maternal and fetal characteristics were similar between the groups except for higher neonatal birth weight in the SGH group (median 3422 vs. 3195 grams, p = .001). sHC did not vary between groups (median 336 mm in SGH groups vs. 333, p = .08). Rate of sHC >90th and >95th percentile did not significantly differ between the groups (13.6% vs. 8.5%, 6.8% vs. 3.4%, p = .21, p = .37, for SGH vs. controls, respectively). In multivariate regression analysis, sHC was not found to be independently associated with SGH - aOR (95% CI) 1.004 (0.97-1.03). Receiver operating characteristic curves of sHC for SGH formation underlined an area under the curve of 0.58 (95% CI) (0.51-0.65). CONCLUSIONS: sHC is not associated with SGH formation following VAD.

Predictors of Developmental and Respiratory Outcomes Among Preterm Infants With Bronchopulmonary Dysplasia.

Objectives: To examine the importance of perinatal and postnatal environmental factors on developmental and respiratory outcomes among preterm infants with bronchopulmonary dysplasia (BPD). Methods: Preterm infants (<32 weeks of gestation) born at a single tertiary medical center between 2012 and 2015 were included. Development was assessed at 12 months corrected age. Parents retrospectively completed a health and lifestyle questionnaire reviewing their child's health during the first 2 years of life. A linear regression model was applied to assess the effect of various perinatal and postnatal factors on development. A machine-learning algorithm was trained to assess factors affecting inhaler use. Results: Of 398 infants meeting the inclusion criteria, 208 qualified for the study: 152 (73.1%) with no BPD, 40 (19.2%) with mild BPD, and 16 (7.7%) with moderate-severe BPD. Those in the moderate-severe group were more likely to be male, have mothers who were less educated, and require longer ventilation periods and less time to regain birth weight. They were also more likely to have mothers with asthma/allergies and to have a parent who smoked. Those in the moderate-severe BPD group exhibited significantly lower developmental scores (85.2 ± 16.4) than the no-BPD group (99.3 ± 10.9) and the mild BPD group (97.8 ± 11.7, p < 0.008) as well as more frequent inhaler use (p = 0.0014) than those with no or mild BPD. In addition to perinatal factors, exposure to breast milk, income level and daycare attendance positively affected development. Exposure to cigarette smoke, allergies among family members and daycare attendance proved to be important factors in inhaler use frequency. Conclusions: Postnatal environmental factors are important in predicting and modifying early childhood outcomes among preterm infants.

NKX2-2 Mutation Causes Congenital Diabetes and Infantile Obesity With Paradoxical Glucose-Induced Ghrelin Secretion.

CONTEXT: NKX2-2 is a crucial transcription factor that enables specific ß-cell gene expression. Nkx2-2(-/-) mice manifest with severe neonatal diabetes and changes in ß-cell progenitor fate into ghrelin-producing cells. In humans, recessive NKX2-2 gene mutations have been recently reported as a novel etiology for neonatal diabetes, with only 3 cases known worldwide. This study describes the genetic analysis, distinctive clinical features, the therapeutic challenges, and the unique pathophysiology causing neonatal diabetes in human NKX2-2 dysfunction. CASE DESCRIPTION: An infant with very low birth weight (VLBW) and severe neonatal diabetes (NDM) presented with severe obesity and developmental delay already at age 1 year. The challenge of achieving glycemic control in a VLBW infant was unexpectedly met by a regimen of 3 daily doses of long-acting insulin analogues. Sanger sequencing of known NDM genes (such as ABCC8 and EIF2AK3) was followed by whole-exome sequencing that revealed homozygosity of a pathogenic frameshift variant, c.356delG, p.P119fs64*, in the islet cells transcription factor, NKX2-2. To elucidate the cause for the severe obesity, an oral glucose tolerance test was conducted at age 3.5 years and revealed undetectable C-peptide levels with a paradoxically unexpected 30% increase in ghrelin levels. CONCLUSION: Recessive NKX2-2 loss of function causes severe NDM associated with VLBW, childhood obesity, and developmental delay. The severe obesity phenotype is associated with postprandial paradoxical ghrelin secretion, which may be related to human ß-cell fate change to ghrelin-secreting cells, recapitulating the finding in Nkx2-2(-/-) mice islet cells.

Risk factors for cesarean delivery and adverse neonatal outcome in twin pregnancies attempting vaginal delivery.

INTRODUCTION: Twin vaginal delivery presents a unique clinical challenge for obstetricians. The Twin Birth Study demonstrated the safety of planned vaginal delivery regarding neonatal outcomes. However, that study lacked a description of the risk factors associated with and the outcome of unplanned cesarean section. The aim of this study is to identify potential risk factors for cesarean section and delivery related neonatal morbidity and mortality in women with twin pregnancy attempting vaginal delivery. MATERIAL AND METHODS: A retrospective cohort study including 1070 women with twin pregnancy that underwent a trial of labor between 2003 and 2015. The study population was divided according to the mode of delivery: vaginal delivery, combined vaginal-cesarean and intrapartum cesarean delivery of both twins. Several risk factors and neonatal outcomes were examined by both univariate analysis and multinomial logistic regression analysis. RESULTS: The rate of vaginal delivery of both twins was 88.3%, whereas the rates of combined vaginal cesarean and unplanned cesarean delivery were 4.6% and 7.1%, respectively. Nulliparity and nonvertex presentation of twin B were found to be independently associated with cesarean delivery for both twins. Additionally, nonvertex presentation of twin B was independently associated with combined vaginal-cesarean delivery. The proportion of neonates with Apgar score <7 at 5 min was increased for both twins in the combined vaginal-cesarean group compared with those delivered by the vaginal route alone. CONCLUSION: Nulliparity and nonvertex presentation of twin B were found to be associated with intrapartum cesarean delivery in twin pregnancies.

[PREDICTION OF LATE ONSET SEPSIS IN VERY LOW BIRTH WEIGHT INFANTS BY A SOFTWARE APPLICATION--ARE WE THERE YET?].

INTRODUCTION: Early prediction of late onset sepsis is imperative in order to improve survival and reduce long-term complications. Since clinical deterioration is detrimental, empiric antibiotic treatment is initiated once sepsis is suspected. Symptoms that may indicate invasive infection are non-specific. Previous risk scores offered to improve clinical decision-making but provided low predictive values. AIMS: To evaluate the quantitative early alert of software application compared to clinical judgment by the treating physician, and the "gold standard" of positive blood and/or positive cerebrospinal fluid. METHODS: Weight, heart and respiratory rates, episodes of bradycardia and desaturation, and temperature were collected for each neonate and loaded daily into the system for a period of 30 days by a registered nurse. The medical team and the registered nurse were blind to the system alerts. Analysis of the correlation between the software alerts, the clinical suspicion of sepsis and bacteremia was conducted. RESULTS: Forty-five very low birth weight consecutively born infants who did not have early onset sepsis and survived, were evaluated, of whom 17 infants had culture proven bloodstream infection. The software positive predictive value was 6%, 23%, 31%, at 12, 24, 48, hours respectively for alerts approximately to positive cultures. The positive predictive value of clinical suspicion of LOS was 28% but increased from 25% with low levels of clinical suspicion to 34% with high levels of clinical suspicion. DISCUSSION: The software application did not improve sepsis prediction. However, further trials may develop a more accurate algorithm that will alert the physician to be more attentive to infants in special cases.

Inflammatory injury to the neonatal brain - what can we do?

Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory, or both. This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1 receptor antagonists, erythropoietin, caffeine, estradiol, insulin-like growth factor, and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long-term morbidity among term and pre-term infants.

Population-based study shows improved postnatal growth in preterm very-low-birthweight infants between 1995 and 2010.

AIM: To assess whether the postnatal growth of preterm very-low-birthweight (VLBW) infants, as determined by measures of postnatal growth failure (PNGF), improved during the period 1995-2010 and to evaluate postnatal growth by gestational age (GA) and intrauterine growth groups. METHODS: The study was based on the Israel national VLBW infant database and comprised 13 531 VLBW infants of 24-32 weeks' GA, discharged at a postmenstrual age of ≤40 weeks. Z-scores were determined for weight at birth and discharge. Severe and mild PNGF was defined as a decrease >2 and 1-2 z-scores, respectively. Three time periods were considered: 1995-2000, 2001-2005 and 2006-2010. Multinomial logistic regression was used to assess the independent effect of time period on PNGF. RESULTS: Severe PNGF decreased from 11.7% in 1995-2000 to 7.2% in 2001-2005 and 5.2% in 2006-2010. Infants born in 2006-2010 had sixfold lower odds for severe PNGF than babies born in 1995-2000 (adjusted odds ratio 0.17, 95% confidence interval 0.14-0.21) and

Umbilical venous catheter position: evaluation by ultrasound.

OBJECTIVE: Umbilical venous catheter (UVC) insertion is frequently performed in critically ill neonates, with catheter position evaluated by an abdominal radiograph. The position of the catheter can be difficult to assess based on supine film alone. We aimed to determine whether ultrasound enables precise evaluation of the catheter tip position. METHODS: We prospectively evaluated UVC position in 75 neonates by ultrasound and supine abdominal radiograph. Distance from the catheter tip to the diaphragm was measured for both modalities. Anatomical location of the catheter was recorded for both studies. The Student's t-test was used to compare the means of the differences in catheter position on radiograph and ultrasound. RESULTS: In 46 patients there was no difference in the distance between the catheter tip and the diaphragm on ultrasound and radiograph. In 29 babies there was a difference of 1-to-7 mm. Ultrasound identified malposition of the catheter in three cases in which the position of the catheter on the plain film was deemed acceptable. CONCLUSIONS: Our study suggests that ultrasound is reliable and may replace plain radiograph for the identification of the UVC position, preventing complications from malposition, and reducing exposure to ionizing radiation.

Neonatal sepsis following maternal amnionitis by Edwardsiella tarda: a case report and a review of the literature.

Edwardsiella tarda, a gram-negative bacterium, is a rare pathogen in the neonatal period. We present a term newborn that developed E. tarda septicemia following maternal amnionitis. The severe neurological outcome in this case, as well as in all other reported cases, highlights the need for meticulous neurological evaluation in neonates presenting with E. tarda septicemia even in the absence of bona fide meningitis.