Longitudinal analysis of carotenoid content in preterm human milk.

To describe the variability in carotenoid content of human milk (HM) in mothers of very to extremely low birth weight preterm infants throughout lactation and to explore the relationship between lutein in HM and the occurrence of retinopathy of prematurity (ROP) in preterm infants. We recruited healthy mothers along with their preterm infants that were born at gestational age 24 + 2 to 29 + 6 weeks or with a birth weight under 1500 g and were exclusively breastfed HM. Each participant provided up to 7 HM samples (2-10 ml) on day 0-3 and once a week until 6 weeks. Additionally, when possible, a blood sample was collected from the infant at week 6. Concentrations of the major carotenoids (lutein, zeaxanthin, beta-carotene, and lycopene) in all HM and blood samples were assessed and compared. Thirty-nine mother-infant dyads were included and 184 HM samples and 21 plasma samples were provided. Mean lutein, zeaxanthin, beta-carotene, and lycopene concentration decreased as lactation progressed, being at their highest in colostrum samples (156.9 vs. 66.9 vs. 363.9 vs. 426.8 ng/ml, respectively). Lycopene (41%) and beta-carotene (36%) were the predominant carotenoids in colostrum and up to 2 weeks post-delivery. Inversely, the proportion of lutein and zeaxanthin increased with lactation duration to account for 45% of the carotenoids in mature HM. Lutein accounted for 58% of the carotenoids in infant plasma and only 28% in HM. Lutein content of transition and mature HM did not differ between mothers of ROP and non-ROP infants.Conclusion Carotenoid content of HM was dynamic and varied between mothers and as lactation progressed. Infant plasma displayed a distinct distribution of carotenoids from HM.

Ultra-processed food (UPF) intake in pregnancy and maternal and neonatal outcomes.

PURPOSE: Ultra-processed food (UPF), as defined by the NOVA classification, is related to lower diet quality, which may adversely affect maternal health and neonatal outcomes. This study aims to describe nutrient intake of pregnant women by the share of UPF in the diet and to identify associations between UPF intake and maternal and neonatal outcomes. METHODS: In this cross-sectional study, pregnant women (n = 206) were recruited upon arrival to the obstetrics ward for delivery, and asked to complete a Food Frequency Questionnaire (FFQ), and questionnaires regarding environmental exposures, and socio-demographic characteristics. Neonatal measurements and clinical data were obtained following delivery. UPF energy intake was expressed as absolute and in terms of percent from total energy. Women with high intake of energy from UPF were compared to those with low intake. RESULTS: Among 206 pregnant women, dietary intake of UPF ranged from 15.6% to 43.4% of total energy in the first and fourth quartiles of UPF consumption, respectively. Women in the fourth quartile of energy from UPF had lower intakes of vitamin C, beta-carotene, vitamin B6, and potassium, which is indicative of inferior diet quality. Percent energy from UPF was associated with maternal obesity (BMI ≥ 30) (OR = 1.06, 95% CI: 1.06, 1.10, p = 0.008) and shorter male infant ano-genital distance (AGD) (B = -1.9, 95% CI: -3.5, -0.24, p = 0.02). CONCLUSIONS: UPF intake during pregnancy is associated with undesirable maternal and neonatal outcomes and more research is needed to confirm these findings.

Upper gastrointestinal series in healthy neonates with bilious vomiting-is it still obvious? A retrospective observational study.

AIM: Demand for upper gastrointestinal contrast series (UGI) to investigate bilious vomiting (BV) has increased in recent years, mostly due to greater awareness of the need to rule out malrotation and midgut volvulus (MGV). We aimed to examine predictive value of clinical parameters in the management of healthy neonates presenting with BV and re-assess the role of UGI in their management. METHODS: A retrospective cohort study including medical, imaging and surgical data of neonates who underwent UGI due to BV. RESULTS: A total of 157 term neonates, eight neonates (5.1%) had confirmed surgical diagnosis of malrotation, five of them had malrotation with MGV, including two neonates who underwent extensive intestinal resection due to necrosis. Neonates with a combination of abnormal plain radiograph and abdominal distention had 10 times higher odds of malrotation diagnosis, adjusting for age at first BV (p = 0.017). Neonates with a combination of abnormal plain radiograph, abdominal distention and abdominal tenderness had 25 times higher odds of MGV (p = 0.002). CONCLUSION: This study reaffirms the role of UGI as the current main diagnostic tool for malrotation and MGV. Physical examination and plain radiograph findings can help but cannot substitute UGI study.

Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study.

OBJECTIVE: The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. STUDY DESIGN: Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. RESULTS: Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R 2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R 2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. CONCLUSION: Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. KEY POINTS: · Hepcidin levels were significantly higher in anemic premature infants.. · A positive correlation was found between hepcidin and ferritin.. · Negative correlation was found between 25(OH)D and CRP..

Weaning Strategy of Diuretics in Outpatient Preterm Infants with Bronchopulmonary Dysplasia: A National Survey.

OBJECTIVE: Long-term diuretic treatment in patients with bronchopulmonary dysplasia (BPD) is common despite lack of data that support its use. We aimed to characterize the commonly used diuretics weaning strategies for outpatient clinically stable preterm infants with BPD. STUDY DESIGN: We conducted a cross-sectional web-based survey among all pediatric pulmonologists and neonatologists in Israel. Questionnaire included data regarding practitioners' different diuretics-weaning practice in this population. RESULTS: The response rate for pulmonologists and neonatologists were 35/50 (70%) and 36/120 (30%), respectively. When both oxygen and diuretics are used, 59% wean oxygen first and 32% wean diuretics first. If patients are solely on diuretics, 27% discontinue instantly, 34% decrease the dosage gradually, and 34% outgrow the discharge dosage. Significantly more pulmonologists decrease the dosage gradually, while more neonatologists discontinue at once (p < 0.001). Most participants (94%) reported being unsatisfied with the existing data and guidelines regarding these issues. CONCLUSION: Our results showed a wide range of practice patterns in the weaning strategy of diuretics in outpatient preterm infants with BPD. Pulmonologists and neonatologists differ significantly in their weaning strategy. A prospective larger controlled study to explore the outcome of gradual tapering versus discontinuation without weaning is warranted. KEY POINTS: · Diuretic treatment in patients with BPD is common despite lack of data that support its use.. · We demonstrated a wide range of practice patterns in the weaning strategy of diuretics in outpatients' BPDs.. · Pulmonologists and neonatologists differ significantly in their weaning strategy.. · Most participants are unsatisfied with the existing data and guidelines regarding these issues..

The role of orotic acid measurement in routine newborn screening for urea cycle disorders.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.

Higher C-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment.

The aim of the study was to characterize factors that may serve as clinical tools to identify neonates with transient neonatal hyperinsulinism hypoglycemia (HH) who may benefit from diazoxide treatment. This retrospective study included 141 neonates with transient HH (93 males) of whom 34 (24%) were treated with diazoxide. Diazoxide treatment was started at median age of 13 days (range 5-35) and discontinued at median age of 42 days (range 14-224). The maximal dose was 7.1 ± 2.3 mg/kg/day. Diazoxide-treated neonates required a higher glucose infusion rate (GIR) compared with non-treated neonates (16.6 ± 3.4 vs. 10.4 ± 4.0 mg/kg/min, respectively, P < .01), had a longer duration of intravenous fluids (15.9 ± 9.3 vs. 7.8 ± 6.5 days, P < .01), a longer hospitalization (32.8 ± 22.7 vs. 20.4 ± 13.4 days, P < .01), a longer duration of carbohydrate supplementation (38.9 ± 40.4 vs. 17.8 ± 21.4 days, P < .01), and higher mean C-peptide levels on "critical sample" (1.4 ± 0.9 vs. 0.8 ± 0.5 ng/ml, P < .01). Their insulin levels also tended to be higher (3.5 ± 2.9 vs. 2.2 ± 3.8 µU/ml, P = .07). A stepwise logistic regression model revealed that significant predictors of prolonged HH were maximal GIRs (odds ratio (OR) 1.56, 95%; confidence interval (CI) 1.3-1.88, P < .001) and C-peptide levels (OR 3.57, 95%; CI 1.3-12.1, P = .005).Conclusion: Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.What is Known:• Neonates with transient hyperinsulinism usually do not require treatment beyond glucose supplementation due to its self-limited clinical course, but some may benefit from diazoxide treatment.What is New:• Higher C-peptide levels and higher GIR requirements may serve as clinical tools to identify neonates with transient HH who may benefit from diazoxide treatment.• The incidence of prolonged neonatal HH is higher than the currently accepted figures.

Risk factors for readmission for phototherapy due to jaundice in healthy newborns: a retrospective, observational study.

BACKGROUND: The guidelines of the American Academy of Pediatrics (AAP) for monitoring neonatal jaundice recommend universal postnatal screening for hyperbilirubinemia within 48 h from discharge. We observed that neonate with low-risk jaundice were more likely to be readmitted to hospital for phototherapy compared to neonate with high-risk jaundice. The aim of this study was to identify additional factors that increase the risk for jaundice-related readmission. METHODS: This observational case-control study was performed on 100 consecutive neonates with jaundice who were readmitted to hospital for phototherapy treatment and were compared to 100 neonates with jaundice during hospitalization who were not readmitted after discharge. The data retrieved from the medical records of all participants included maternal characteristics, delivery type and noteworthy events, gestational age at delivery, birth weight and weight loss, neonate physical findings, Apgar scores, laboratory findings, length of hospital stay, and administration of phototherapy during hospitalization. The length of time since discharge and readmission for jaundice was also recorded. RESULTS: The risk of readmission decreased by 48% [odds ratio (OR) =0.52; 95% confidence interval (CI) 0.341-0.801] with every day added to the original hospitalization stay, and by 71% (OR = 0.29; 95% CI 0.091-0.891) if phototherapy had been administered during postnatal hospitalization. In contrast, the risk increased by 28% (OR = 1.28; 95% CI 1.164-1.398) with every elevation by 1% in hematocrit, and by 2.78 time (95% CI 1.213-6.345; p = 0.0156) when the delta in infant weight was > 5% (the difference between birth weight and weight at discharge during the postnatal hospitalization). CONCLUSIONS: The risk factors for readmission, such as substantial weight loss (> 5% difference between birth and discharge) and elevated hematocrit should be taken into account in the decision to discharge neonate with low-risk jaundice. The AAP guidelines for decreasing readmission rates of neonatal jaundice by postnatal screening for hyperbilirubinemia alone may be more appropriate for neonate with high-risk jaundice.

[THE EFFECT OF MUSIC IN PRETERM ON RESTING ENERGY EXPENDITURE - A PROSPECTOVE RANDOMIZED CLINICAL TRIAL].

BACKGROUND: We have recently showed that Wolfgang Amadeus Mozart's music significantly lowers resting energy expenditure (REE) in preterm infants. Whether or not this effect is specific to Mozart is unknown. OBJECTIVES: To study whether familiar ("ethnic") music has the same effect on REE in preterm infants as music by Mozart. METHODS: A prospective, randomized clinical trial with cross-over was conducted in 9 healthy, appropriate weights for gestational age, gavage fed, preterm infants. Infants were randomized to be exposed to a 30-minute period of Mozart music or "ethnic" music or no music over 3 consecutive days. Metabolic measurements were performed by indirect calorimetry. RESULTS: A total of 27 REE measurements were performed. On average REE was lower in preterm infants who were exposed to "ethnic" music compared to preterm infants who were exposed to music by Mozart (p=0.388). REE was lower in preterm infants who didn't listen to music at all compared to Mozart (p=0.014) or to "ethnic" (p=0.134). CONCLUSIONS: Exposure to music by Mozart significantly elevated REE in healthy preterm infants compared to preterm infants who didn't listen to music at all. Nevertheless a trend of lower REE was demonstrated when preterm infants listened to "ethnic" music compared to Mozart. DISCUSSION: We were unable to demonstrate a significant decrease in REE by exposure of preterm infants to Mozart- or "familiar" music. At this time point we cannot recommend music therapy for preterm infants in order to lower the REE. We speculate that a larger study sample might show a definite effect.

Retrospective study showed that bacterial gastroenteritis was an important cause of bloody stools in newborn infants.

AIM: Acute bacterial gastroenteritis is a major cause of morbidity and mortality, especially in the developing countries. We examined the incidence, clinical features and outcomes in the first week of life. METHODS: This was a retrospective study of culture-proven bacterial gastroenteritis in newborn infants that were diagnosed between January 2011 and September 2018 in a tertiary centre in Israel. RESULTS: There were 10 cases of culture-proven bacterial gastroenteritis, detected out of 91 stool cultures. All infants were born vaginally and nine were full-term infants. The annual incidence was 0.096 per 1000 live births. The responsible pathogen was Campylobacter in six patients, Salmonella in two and Shigella sonnei in two. The mean age of disease onset was two days of life. Antibiotics were given to five patients, but were inappropriate in two cases. Only one patient with the Shigella sonnei infection required respiratory support. All patients fully recovered. CONCLUSION: One in ten newborn infants with bloody stools had bacterial gastroenteritis, contradicting the low rates found in other studies and indicating the importance of considering this diagnosis. Antimicrobials active against Salmonella or Shigella should be given to newborn infants who have bloody stools and look ill.

The interrelationship between hepcidin, vitamin D, and anemia in children with acute infectious disease.

BACKGROUND: Hepcidin is a master regulator of iron metabolism. Recently, it has been shown that vitamin D suppresses hepcidin expression. Our hypothesis was that hepcidin levels inversely correlate with vitamin D levels in anemic children during acute infection. METHODS: A prospective study was performed on 90 patients (45 females, 45 males, mean age 7.3 ± 5 years) who were admitted to the pediatric ward. Sixty-two patients had infectious disease (32 with coexisting anemia, 30 without anemia), and 28 patients were hospitalized for noninfectious causes. Blood samples for IL-6, hepcidin, iron status parameters, and 25-hydroxyvitamin D (25-OHD) were obtained within 72 h after admission. RESULTS: Serum concentrations of IL-6 and hepcidin were significantly higher and 25-OHD, iron, and transferrin were significantly lower in anemic children with infectious disease compared with controls. Children with a serum 25-OHD level < 20 ng/ml had significantly increased odds of having anemia than those with a level > 20 ng/ml (OR: 6.1, CI: 1.15-32.76). Correlation analyses found positive associations between hepcidin levels and ferritin (R2 = 0.47, P < 0.001) and negative associations between hepcidin and transferrin (R2 = 0.57, P < 0.001). CONCLUSION: Higher IL-6 and lower 25-OHD levels may lead to higher hepcidin levels and subsequently to hypoferremia and anemia in children with acute infection.

Homozygous mutation, p.Pro304His, in IDH3A, encoding isocitrate dehydrogenase subunit is associated with severe encephalopathy in infancy.

Mitochondrial encephalopathies are a heterogeneous group of disorders which generally carries a grave prognosis. Using exome sequencing, we identified a homozygous mutation, Pro-304-His in the IDH3A gene, in a patient suffering from infantile encephalopathy with peripheral and autonomic nervous system involvement. Mammalian isocitrate dehydrogenase (IDH) 3 is a heterotetramer of 2alfa, 1beta, and 1gamma subunits, and IDH3A encodes the alfa subunit of the mitochondrial NAD+-dependent IDH. Here we show that in contrast to wild-type human IDH3A, the human IDH3A which harbor the p.Pro304His mutation does not complement the yeast Δidh1/Δidh2 growth defect on ethanol-acetate. We therefore propose that homozygosity for the p.Pro304His mutation is deleterious for mitochondrial NAD+-specific IDH3A activity in human. IDH3A now joins the list of TCA cycle-related proteins, which includes ACO2, DLD, SLC25A19, FH, and succinate dehydrogenase subunits, all associated with neurological disorders.

Is There a Role for Placental Cultures in Cases of Clinical Chorioamnionitis Complicating Preterm Premature Rupture of Membranes?

Objective To assess the role of placental cultures in cases of preterm premature rupture of membranes (PPROM) complicated by chorioamnionitis and to determine the effect of positive cultures on short-term neonatal outcomes. Design A retrospective single-center study. The medical records of all women with PPROM between January 1, 2011, and December 31, 2015, were reviewed. Cases were divided into placental culture positive (group A) and placental culture negative (group B) groups. Maternal and pregnancy characteristics as well as short-term neonatal outcomes were compared between groups. Results During the 5-year study period, 61 cases of clinical chorioamnionitis complicating PPROM were diagnosed: 25 cases were culture positive (group A) and 36 were culture negative (group B). Neonatal outcome measures, including Apgar score at 5 minutes (p = 0.028; odds ratio [OR]: 5.27; confidence interval [CI]: 1.19-23.34), respiratory distress syndrome (p = 0.026; OR: 4.11; CI: 1.18-14.25), and neonatal infection (p < 0.0001; OR: 11.59; CI: 3.37-39.87) were significantly more common in group A newborns, regardless of gestational age at delivery as was the composite neonatal outcome (p = 0.017; OR: 7.35: CI: 1.42-37.79). Placental isolates were primarily Streptococci and Escherichia coli. Conclusion Placental cultures may be an essential predictor of neonatal morbidity in PPROM and may contribute to the modification of neonatal treatment.

Vitamin D Status among Israeli Medical Residents.

BACKGROUND: Israel is a country with a sunny climate; however, vitamin D deficiency and insufficiency are common findings in certain populations whose exposure to sunlight is limited. Medical residency is known for long indoor working hours, thus theoretically limiting the opportunities for sun exposure. OBJECTIVES: To evaluate whether the vitamin D status among residents in a single medical center in Tel Aviv is below the normal range. METHODS: Forty-six residents (28 females, 18 males, average age 33.9 ± 2.8 years) in three residency programs (internal medicine, general surgery/obstetrics and gynecology, pediatrics) were recruited. Demographic data, personal lifestyle, physical activity details and sun exposure duration were obtained by a questionnaire. Serum levels for 25(OH)D were analyzed by a radioimmunoassay. RESULTS: The mean serum 25(OH)D concentration was 29.8 ± 5.8 ng/ml. According to Institute of Medicine definitions, none of the residents were vitamin D deficient and only two residents (4%) were vitamin D insufficient (15 ng/ml each). The level of 25(OH)D was similar among the various medical specialties. The 25(OH)D levels correlated with the duration of sun exposure and the number of offspring (regression analysis: R2 = 9.2%, P < 0.04 and R2 = 8.9%, P < 0.04, respectively), but not with nutritional data, blood chemistry, or extent of physical activity. CONCLUSIONS: Most of the residents maintained normal or near normal 25(OH)D levels, indicating that the residency program itself did not pose a significant risk for vitamin D deficiency.

TIMP-1 inhibition of occludin degradation in Caco-2 intestinal cells: a potential protective role in necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC), a common intestinal disease affecting premature infants, is a major cause of morbidity and mortality. Previous reports indicate an upregulation of intestinal matrix metalloproteinases (MMPs) activity that may play key roles on the higher permeability of the intestinal barrier, typical to NEC. Recently, TIMP-1, a natural inhibitor of MMP's, was found to be over expressed in preterm human breast milk (HBM). Previous studies have shown that infants fed with HBM have a significant reduction in the incidence of NEC. The aim of the present study was to investigate the possible role that TIMP-1 may play on the maintenance of tight junctions and therefore the gut barrier integrity. METHODS: Timp-1-treated Caco-2 intestinal cells were tested for MMP-2 enzymatic activity and cell junction integrity. RESULTS: TIMP-1 inhibited MMP-2 activity, which induced a significant increase in the expression of occludin but not of claudin-4. TIMP-1 did not affect apoptosis. CONCLUSION: One of the putative mechanisms associated with HBM protection against NEC is mediated by TIMP-1, which downregulates MMP-2 activity, inhibits the degradation of occluding, and preserves tight junctions and gut barrier integrity.

Electroencephalographic characteristics in preterm infants born with intrauterine growth restriction.

OBJECTIVE: To determine the impact of fetal growth on postnatal amplitude-integrated electroencephalography (aEEG) and power spectrum electroencephalography (EEG) data in preterm infants born with intrauterine growth restriction (IUGR). STUDY DESIGN: We defined IUGR as birth weight <10th percentile, and control as birth weight appropriate for gestational age (GA). We performed single-channel (C3-C4) EEG during the first 48 hours of life and measured the upper and lower margins of the aEEG trace width. EEG readings were analyzed by spectral analysis, and the relative power of the frequency bands was calculated. The Lacey Assessment of the Preterm Infant was administered before discharge. RESULTS: We enrolled 14 infants with IUGR (mean GA, 34.3 ± 1.8 weeks; mean birth weight 1486 ± 304 g) and 16 appropriate for GA controls (mean GA, 33.7 ± 2 weeks; mean birth weight, 1978 ± 488 g). There were no significant between-group differences in perinatal complications. The mean aEEG trace width was 20.8 ± 1.4 µv in the infants with IUGR versus 17.3 ± 1.6 µv in controls (P < .001). The infants with IUGR also had significantly greater delta frequency activity and decreased theta, alpha, and beta frequency activities compared with controls. Delta frequency activity decreased with increasing GA (r = -0.8; P = .001 for infants with IUGR and r = -0.9; P < .001 for controls). The Lacey Assessment of the Preterm Infant developmental score was significantly lower in the infants with IUGR (P < .02) and was correlated with aEEG trace width (r = -0.6; P = .002) and with delta activity (r = -0.5; P = .02). CONCLUSION: Preterm infants with IUGR have delayed EEG maturation associated with delayed neuromotor development. The predictive value of these alterations regarding developmental deficits associated with IUGR remains undetermined, however.

Time of Birth and the Risk of Adverse Maternal and Neonatal Outcomes-A Retrospective Cohort Study.

Objectives: To determine whether in a labor floor housed continuously by senior physicians the risk of adverse maternal and neonatal outcome is affected by time of delivery. Methods: This retrospective cohort study, conducted at a tertiary medical center, assessed singleton term deliveries from 1 January 2011 to 30 January 2020. Participants were categorized based on delivery timing, correlating with nursing shifts, to evaluate perinatal outcomes. The primary endpoint included adverse maternal outcomes such as emergency Cesarean section, anal sphincter injuries, blood product transfusions, and postpartum surgeries (laparotomy/laparoscopy). Secondary outcomes focused on neonatal health indicators, including low Apgar scores, ICU admissions, respiratory issues, extended hospital stays, and neurological complications. Results: 87,863 deliveries were available for analysis with equal distribution during the day. The risk of adverse composite maternal outcome was highest during the evening (aOR 1.25, 95% CI 1.18-1.32) and lowest during the night (aOR 0.94, 95% CI 0.88-0.99) compared to daytime deliveries. This difference was primarily driven by the highest rate of emergency CD in the evening. Neonatal outcomes were comparable, except for length of stay > 5 days, which was more frequent among newborns delivered during the evening and night shifts compared to the morning shift (aOR 1.19, 95% CI 1.07-1.33 and aOR 1.17, 95% CI 1.05-1.31, respectively). Conclusions: In term pregnancies, the evening shift is associated with the highest risk of adverse maternal and neonatal outcomes despite physician seniority.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Newborn oxygen saturation at mild altitude versus sea level: implications for neonatal screening for critical congenital heart disease.

AIM: To determine the normal SpO2 in healthy term newborns at mild altitude (MA, 780 metres) compared with sea level (SL), within the context of universal screening for critical congenital heart disease (CCHD). METHODS: We studied 199 (119 at MA and 80 at SL) consecutively born healthy newborns. SpO2 recordings were at 24-72 h using Masimo SET Radical-7 on the right hand and left foot. RESULTS: Mean SpO2 was lower at MA compared with SL in the right hand (97.86 ± 1.58 vs 98.28 ± 1.41, p = 0.05) and left foot (98.49 ± 1.35 vs 98.90 ± 1.16, p = 0.03). No infant with SpO2 <95% had CCHD. Extrapolating with predicted regression lines set at 95% CI, a SpO2 cut-off of 95% would result in up to 3.5 times more false-positive screens at MA compared with SL. CONCLUSIONS: At MA, SpO2 is approximately 0.4% lower compared with SL. Our study supports the AAP recommendation suggesting algorithm cut-offs may need adjustment in high-altitude nurseries and suggest broadening it to MA as well.

Blood Glucose, Lactate and Platelet Count in Infants with Spontaneous Intestinal Perforation versus Necrotizing Enterocolitis-A Pilot Study.

The incidence of spontaneous intestinal perforation (SIP) increases up to 10% with decreasing gestational age (GA). We aimed to explore early biomarkers for predicting SIP in preterm infants. In this case-control study, neonates born at ≤34 weeks GA diagnosed with SIP were compared with GA and/or birth-weight-matched neonates diagnosed with necrotizing enterocolitis (NEC). Laboratory markers assessed prior and adjacent to the day of SIP or NEC diagnosis were evaluated. The cohort included 16 SIP and 16 matched NEC infants. Hyperlactatemia was less frequent in SIP than in NEC infants (12% vs. 50%, p = 0.02). The platelets count was lower in SIP than in NEC infants (p < 0.001). Glucose levels strongly correlated with lactate levels (p = 0.01) only in the NEC group. The odds of being diagnosed with SIP decreased as lactate levels increased (OR = 0.607, 95% CI: 0.377-0.978, p = 0.04). Our results suggest that a combination of laboratory markers, namely glucose and lactate, could help differentiate SIP from NEC at early stages so that, in the presence of an elevated blood glucose, an increase in blood lactate was associated with a decrease in the odds of being diagnosed with SIP.