The Clinical Significance of Extreme Leukocytosis among Newborns: A Retrospective Cohort Study.

OBJECTIVE: The aim of the study is to examine the clinical significance of extreme leukocytosis (>40,000 cells/µL) at birth among neonates. STUDY DESIGN: Data were retrospectively collected on 208 infants with leukocytosis >40,000 cells/µL and on matched normal controls as determined in complete blood counts obtained on the first day of life. RESULTS: There were no significant group differences in birth weight, Apgar's score, timing of respiratory support, hospitalization in special care units or rehospitalization during the first month of life. All neonates with leukocytosis received antibiotics. The blood cultures of both groups were negative. A multivariate analysis showed that leukocytosis did not predict either the presence of symptoms associated with sepsis among neonates or hospitalization in a neonatal special care unit. CONCLUSION: Extreme leukocytosis on the first day of life is a poor predictor of infection. Clinicians should decide upon treatment according to risk factors and symptoms but not according to the degree of leukocytosis. KEY POINTS: · Extreme leukocytosis on the first day of life is a poor predictor of infection.. · Clinicians should decide upon treatment according to risk factors and symptoms.. · Leukocytosis was not predictive of a higher risk of morbidity in neonates..

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

OBJECTIVE: The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. STUDY DESIGN: This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. RESULTS: During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). CONCLUSION: The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. KEY POINTS: · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

Do Serial Sonographic Assessments of Fetuses with Isolated Congenital Diaphragmatic Hernia Help Us Predict Survival?

OBJECTIVE: The aim of this study was to assess the ability of serial prenatal sonographic measurements, and specifically changes in the observed-to-expected lung-to-head ratio (O/E LHR) throughout gestation and to predict survival in congenital diaphragmatic hernia (CDH). METHODS: Retrospective study of CDH fetuses evaluated prenatally and treated postnatally in a single tertiary center, 2008-2020. Sonographic evaluations included side of herniation, liver involvement, and O/E LHR. All data were calculated to assess ability to predict survival. RESULTS: Overall, 94 fetuses were evaluated prenatally and delivered in our medical center. Among them, 75 had isolated CDH and 19 nonisolated. CDH was categorized as left (n = 76; 80.8%), right (n = 16; 17.0%), or bilateral (n = 2; 2.2%). Overall perinatal survival rate was 57% for all live-born infants, 68% in isolated CDH, and 40% in nonisolated (excluding 2 cases that underwent fetoscopic endoluminal tracheal occlusion and did not survive). The O/E LHR was lower in cases with perinatal death compared to survivors. In cases with multiple evaluations, the minimal O/E LHR was the most accurate predictor of survival and need for perinatal extracorporeal membrane oxygenation (ECMO) support. This remained significant when excluding twin pregnancies or when evaluating only isolated left CDH. In addition to disease severity, the side of herniation and liver position was associated with preoperative mortality. CONCLUSION: O/E LHR is associated with perinatal survival. In cases with multiple evaluations, the minimal O/E LHR is the most accurate and significant predictor of perinatal mortality and need for ECMO support.

Increased risk for early hypertriglyceridemia in small for gestational age preterm infants.

Small for gestational age preterm are at increased risk for future metabolic syndrome. Early indication for the disrupted metabolism may be found in the perinatal period. We aimed to evaluate whether small for gestational age preterm infants are at increased risk for hypertriglyceridemia when treated with lipid emulsions, and to investigate the association between triglyceride levels and morbidity. Small for gestational age infants ≤ 34 weeks' gestation age born during 2013-2016 were matched and compared with appropriate for gestational age counterparts. Triglyceride concentration > 250 mg/dL during treatment with parenteral nutrition was considered high. The study included 71 pairs of preterm infants. Hypertriglyceridemia was documented among 22.5% of the small for gestational age infants vs. 5.6% of the appropriate for gestational age infants (p = 0.007). Mean triglyceride levels were 194.4 ± 192.3 mg/dL and 99.9 ± 82.8 mg/dL, respectively (p < 0.001). Small for gestational age was predictive of hypertriglyceridemia (OR = 6.41; 95% CI 1.8-22.9). No significant association was found between triglyceride levels and morbidities in multivariate analysis.Conclusion: Small for gestational age preterm infants receiving lipid emulsions might be at a higher risk for hypertriglyceridemia. Routine monitoring of triglyceride levels will enable identification of the necessity for a slower increase in lipid emulsion therapy. What is Known: • Moderate and very preterm infants are routinely treated with lipid emulsions. • Small for gestational age (SGA) infants may have different metabolism, as they demonstrate higher risk for metabolic syndrome. What is New: • • SGA infants had a higher mean triglyceride level and more commonly had early hypertriglyceridemia (triglycerides > 250 mg/dL) compared with appropriate for gestational age infants treated with the same intravenous lipid dose. Small for gestational age was predictive of hypertriglyceridemia. • No significant association was found between triglyceride levels and morbidities in multivariate analysis.

[NECROTIZING ENTEROCOLITIS - AN ONGOING CHALLENGE].

INTRODUCTION: Necrotizing enterocolitis (NEC) is a major cause for morbidity and mortality among neonates, especially among low birth weight premature infants. Even though NEC has been highly investigated during the last few decades, understanding of the pathogenesis is still relatively poor. Throughout the years protective measures, as well as risk factors, were identified, but there is still no clear prevention strategy, and the percentage of neonates suffering of NEC was not changed. Moreover, the treatment approach is controversial in many circumstances other than a few clear surgical indications. The decision between conservative and surgical treatment in many situations is in the hands of the medical staff. Herein we present the story of a premature infant who suffered from feeding intolerance since birth, with major clinical deterioration after receiving packed red blood cells (PRBCs) transfusion. She was diagnosed with NEC and was treated conservatively, with clinical improvement and worsening alternately, until a colonic stricture was identified and treated surgically. We will provide a short review on risk factors, preventive measures, as well as the research regarding PRBCS transfusion and NEC development.

Pre-term delivery, optimism and initial personal growth as predictors of mothers' long-term personal growth.

Introduction: Positive outcomes in the aftermath of childbirth have increasingly been studied in the last decade. However, most of the studies concentrate on short-term outcomes. The current study examined the perceived personal growth of mothers four years after childbirth, investigating the contribution of the event characteristics (full-term/pre-term birth), internal resources (optimism, self-esteem) and personal growth as measured one year after the birth. Methods: Mothers (n=259) participated in the study by completing a set of self-report questionnaires one and four years following the birth of their child/ren. Results: Personal growth after four years was found to be higher among mothers of pre-terms than of full-terms, and higher four years after the birth than it had been three years earlier. Furthermore, regression analysis indicated the significant contributions of being a mother to pre-term baby/ies, optimism and personal growth one year after the birth to women's personal growth three years later. Discussion: The results highlight the potential long-term effects of giving birth to a pre-term baby on personal growth, as well as the contribution of optimism as an important internal resource. They also indicate the development of personal growth over time. Explanations for the findings are offered and their practical implications are discussed.

A Proposed Role of Surfactant in Platelet Function and Treatment of Pulmonary Hemorrhage in Preterm and Term Infants.

BACKGROUND: We evaluated the effect of surfactant on platelet function as a potential contributing mechanism to the pathogenesis of pulmonary hemorrhage (PHEM) in term and preterm infants. METHODS: Cord blood samples were collected from neonates following delivery. Complete blood count and platelet function were measured using a cone and platelet analyzer (CPA). Increasing surfactant concentrations were added to platelets in vitro, and the adhesion molecule P-selectin and the monoclonal antibody PAC-1 were evaluated following platelet activation by flow cytometry. RESULTS: Forty-one infants (11 preterm and 30 term) were studied. CPA revealed a significant decrease in the average size of the aggregates and in platelet adhesion when surfactant was added. In term infants, the addition of surfactant to native platelets yielded an increased binding capacity of PAC-1 but did not affect P-selectin expression. In preterm infants, platelet activation with adenosine diphosphate in the presence of a high surfactant concentration (0.5 mg/mL) resulted in increased PAC-1 binding and no change in P-selectin expression. CONCLUSIONS: The platelets of preterm infants are less active (hyporesponsive) than those of term infants, both in their native state as well as after stimulation with various agonists. Surfactant may play an important role in treating PHEM in preterm infants.

Feeding Imprinting: The Extreme Test Case of Premature Infants Born With Very Low Birth Weight.

Feeding imprinting, considered a survival-enabling process, is not well understood. Infants born very preterm, who first feed passively, are an effective model for studying feeding imprinting. Retrospective analysis of neonatal intensive care unit (NICU) records of 255 infants (Mgestational age  = 29.98 ± 1.64) enabled exploring the notion that direct breastfeeding (DBF) during NICU stay leads to consumption of more mother's milk and earlier NICU discharge. Results showed that DBF before the first bottle feeding is related to shorter transition into oral feeding, a younger age of full oral feeding accomplishment and earlier discharge. Furthermore, the number of DBF meals before first bottle feeding predicts more maternal milk consumption and improved NICU outcomes. Improved performance in response to initial exposure to DBF at the age of budding feeding abilities supports a feeding imprinting hypothesis.

Infants Born with Esophageal Atresia with or without Tracheo-Esophageal Fistula: Short- and Long-Term Outcomes.

BACKGROUND: The estimated incidence of esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is 1:3500 live births. During childhood these patients have various co-morbidities, but the overall quality of life among adults is similar to that of the general population. OBJECTIVES: To evaluate short- and long-term co-morbidities and quality of life among infants born with EA ± TEF at a large single medical center. METHODS: Medical records of 65 children born over a 21 year period were reviewed for short- and long-term medical data. Telephone interviews were conducted with 46 of their parents regarding medical problems and quality of life after home discharge. RESULTS: The main long-term co-morbidities during the first 2 years of life, 4-6 years of age, and during adolescence (12-16 years) included gastro-esophageal reflux disease (GERD) in 56.5%, 35.8%, and 18.7%, respectively; stridor in 84.8%, 45.2%, and 12.5%, respectively; hyper-reactive airway disease (HRAD) in 43.5%, 35.5%, and 36.5%, respectively; recurrent pneumonia in 43.5%, 32.3%, and 18.8%, respectively; and overall recurrent hospitalizations in 87%, 41.9%, and 25%, respectively. The quality of life was reportedly affected among 100%, 75%, and 33.3% respectively. CONCLUSIONS: Long-term follow-up of patients with EA ± TEF indicates a high burden of co-morbidities during the first 6 years of life, with a gradual decrease in symptoms thereafter. Nevertheless, HRAD continued to impact the daily life of about one-third of the older adolescents, and GERD one-fifth. A long-term multidisciplinary follow-up should be conducted to prevent late onset complications that may affect the quality of life.

Short-Term Perinatal Outcome among Term Infants with Prenatal Diagnosis of Large Abdominal Circumference.

Background Measuring fetal abdominal circumference (AC) prenatally is an effective tool for predicting neonatal weight and macrosomia. Data are lacking regarding the outcome of newborn infants with prenatal diagnosis of large AC. Aim The aim of this study was to evaluate early short-term neonatal outcome among term singleton newborn infants with prenatal diagnosis of large AC. Methods Retrospective data were collected on 501 term infants with prenatal diagnosis of large AC (≥ 360 mm) and on matched controls, including information on maternal condition and on infant perinatal complications. Results In compare with controls, the study group had higher incidence of macrosomia (188 [37.5%] vs. 18 [3.6%], p < 0.001), hypoglycemia (48 (9.6%) vs. 25 [5%], p = 0.007), and significant morbidity (49 [9.8%] vs. 28 [5.6%], p = 0.017) but without increased incidence of congenital malformations or other perinatal complications. Only among the macrosomic, study subgroup and their controls differences were recorded including hypoglycemia (17.6 vs. 4.8%, p < 0.001), need for oral glucose (11.2 vs. 2.7%, p = 0.002), significant morbidity (10.1 vs. 3.7%, p = 0.024), and hospitalization in special care unit (11.7 vs. 4.3%, p = 0.012). Conclusion Prelabor diagnosis of large AC mostly reflects the infant's high birth weight and macrosomia with the associated perinatal complications. Large AC by itself was not predictive of any congenital malformations or perinatal and postnatal complications.

Indication of Mild Hemolytic Reaction Among Preterm Infants With ABO Incompatibility.

BACKGROUND: Among term infants, ABO incompatibility is a leading cause of hemolytic disease and neonatal jaundice. With respect to preterm infants, data are lacking. OBJECTIVE: To evaluate the incidence and severity of ABO incompatibility hemolytic disease among preterm infants with respect to hemolytic and jaundice parameters. DESIGN: Clinical and laboratory data were collected retrospectively from the medical records of 118 ABO-incompatible preterms born at gestational age (GA) 29-34 weeks, as well as 118 controls matched for GA, birth weight, and multiplicity. All infants were born at the Sheba Medical Center Tel-Hashomer between 2009 and 2012. RESULTS: The study and control groups were similar on all maternal and neonatal outcome parameters. No differences between the groups were recorded throughout hospitalization regarding hematocrit levels or the need for blood transfusion. Bilirubin levels were higher among the study (ABO-incompatible) group during the first 10 days of life; however, no significant differences were found regarding the need for phototherapy. Upon evaluating subgroups divided by GA, we found no differences on any hematological and jaundice factors among preterms of 29-31 weeks, whereas among preterms of 32-34 weeks higher positive direct antiglobulin test (DAT) results (7% vs. 0% in the control, P = 0.014) as well as higher bilirubin levels were documented. CONCLUSIONS: Among ABO-incompatible preterm infants with GA 29-34 weeks, there is no evidence of significant hemolytic reaction derived from placental transfer of antibodies. With increasing GA, antibody transfer becomes more significant, resulting in more positive DAT results and greater incidence of neonatal jaundice.

Assessment of Functional Fibrinolysis in Cord Blood Using Modified Thromboelastography.

BACKGROUND: The fibrinolytic system in newborns is immature and probably impaired. The aim of this study was to prospectively evaluate functional fibrinolytic capacity of newborn's cord blood using a new thromboelastometry (rotational thromboelastogram, ROTEM®) test. METHODS: Infants born at Sheba Medical Center were studied prospectively. Cord blood was obtained immediately after clumping, and ROTEM parameters were assessed applying non-activated TEM (NATEM) assay with increasing concentration of tissue plasminogen activator (tPA, 0-200 U/ml). Baseline clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) were compared among infants versus adults. Each infant's demographic information was prospectively followed up until discharge. RESULTS: One hundred one newborns were tested. CT and CFT values were lower and alpha angles were higher among neonate's cord blood compared to adults (n = 23; P = 0.001, 0.03, and 0.02, respectively). The addition of tPA significantly shortened CT and CFT, and reduced alpha angles and MCF in both groups. The lysis index at 30 min (LI30) and lysis onset time (LOT) decreased significantly, and fibrinolysis was more rapid in the newborns. Hematocrit and platelet counts in neonates correlated with LI30 (P = 0.035 and 0.037, respectively) and LOT (P = 0.02) when higher tPA concentrations were used. ROTEM values were unrelated to the occurrence of postnatal complications. CONCLUSIONS: This first report of functional fibrinolysis in cord blood demonstrated that neonatal fibrinolysis may be augmented as compared to adult values. Further studies are required to validate this test and assess its predictive value and clinical relevance.

Gestational weight gain and body mass indexes have an impact on the outcomes of diabetic mothers and infants.

AIM: This study evaluated mothers with diabetes to determine whether prepregnancy body mass index (BMI), BMI on delivery or gestational weight gain (GWG) had the greatest impact on maternal and neonatal outcomes. METHODS: We retrospectively examined the medical charts of 634 full-term infants born to mothers with gestational diabetes mellitus not requiring insulin (n = 476), gestational diabetes mellitus requiring insulin (n = 140) and insulin-dependent diabetes mellitus (n = 18). Data regarding maternal BMI before pregnancy and on delivery were recorded, as well as maternal and neonatal complications. RESULTS: Infants born to women who gained more than the recommended weight during pregnancy had higher birthweights, higher rates of meconium-stained amniotic fluid and neonatal hypoglycaemia. Using logistic regression, Caesarean section delivery was predicted by gestational diabetes requiring insulin, with an odds ratio (OR) of 1.76, maternal hypertension (OR 2.4), infants born large for gestational age (OR 2.78) and maternal BMI ≥ 30 on delivery (OR 1.06). Neonatal complications were predicted by maternal insulin-dependent diabetes (OR 5.21), lower gestational age (OR 0.8) and GWG above the recommended amount (OR 1.56). CONCLUSION: Women with diabetes should be made aware that higher GWG can lead to Caesarean section delivery, infant macrosomia and other neonatal complications.

Bone density among infants of gestational diabetic mothers and macrosomic neonates.

Decreased bone density has been found among infants of diabetic mothers and among large-for-gestational-age newborns. To evaluate which etiologies (physical or metabolic effect) have the greatest impact on neonatal bone density. A case-control study was conducted that included two study groups: one comprising 20 appropriate-for-gestational-age (AGA) infants of gestational diabetic mothers (IGDM) and matched controls, and the other comprising 20 macrosomic infants (birth weight > 4 kg) and matched controls. Bone density was examined along the tibia bone using quantitative ultrasound that measured speed of sound. Bone density among the group of macrosomic infants was significantly lower than among the control group (2,976 vs. 3,120 m/s respectively, p < 0.005). No differences in bone density were found between infants of diabetic mothers and their controls (3,005 vs. 3,043 m/s respectively, p = 0.286). Low bone density was predicted only by birth weight (for every increase of 100 g) (OR 1.148 [CI 1.014-1.299], p = 0.003). Bone density was found to be low among macrosomic newborn infants, whereas among AGA-IGDM infants bone density was similar to that of the control group. These findings strengthen the hypothesis that reduced fetal movements secondary to fetal macrosomia constitute the mechanism for reduced bone density.

Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia--A Tertiary Center's Experience.

Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2-16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management.

Waterhouse Friderichsen syndrome complicating fulminant Enterobacter cloacae sepsis in a preterm infant: the unresolved issue of corticosteroids.

Bilateral adrenal hemorrhage can complicate severe sepsis in the neonate and is most commonly attributed to meningococcal disease; however, it can be caused by other etiologic agents as well. We report herein a fatal case of Enterobacter cloacae sepsis in a preterm infant, resulting in massive adrenal hemorrhages. This is the first documented case of adrenal hemorrhage following infection with this pathogen.

Establishing healthy longevity clinics in publicly funded hospitals.

Healthy longevity medicine integrates geroscience and other disciplines into clinical settings, aiming to optimize health throughout one's lifespan. Multiple factors have led to increased consumer engagement, with private clinics currently meeting the demand for guidance to improve healthy longevity. The establishment of healthy longevity clinics in publicly funded hospitals is a significant development, making longevity-focused healthcare more accessible. These clinics rely on multidisciplinary teams of physicians and allied health professionals. Diagnostics involve comprehensive evaluations of medical history, physical examinations, and various clinical tests to detect early signs of age-related functional decline. Interventions in healthy longevity medicine encompass lifestyle modifications, supplements, repurposed drugs, and social and environmental interventions. Collaboration with research institutions and industry partners is crucial for advancing healthy longevity medicine and creating standardized protocols. In this article, we review the process of creating healthy longevity clinics in public hospitals to ensure the best possible care for individuals pursuing healthy longevity.

The impact of genetic and environmental factors on homocysteine levels in preterm neonates.

BACKGROUND: Hyperhomocysteinemia may be associated with vascular complications in adults. Whereas pediatric thrombosis risk peaks in neonates, data on homocysteine (Hcy) levels assessed in term and preterm infants during the perinatal period are scarce. In the present study, we aimed to establish Hcy reference values for preterm infants and study their potential associations with the early post-natal health status. Plasma Hcy and hematocrit levels and MTHFR polymorphisms (C677T and A1298C substitution) were studied in a large cohort of preterm infants in a tertiary referral medical center during an 18-month period. Data were collected on maternal history and delivery as well as on post-natal complications. RESULTS: The study cohort included 167 infants whose mean gestational age was 30.98 ± 2.34 weeks (range: 26-36 weeks), mean birth weight 1327.6 ± 327 g, and mean Hcy level 7.99 ± 3.27 (range: 2.2-21.2) µmol/L. Maternal intake of folic acid was inversely associated with the babies' Hcy levels (P = 0.0001). Increased Hcy levels positively correlated with birth weight, gestational age (P < 0.005), total number of pregnancies (P = 0.012), and presence of MTHFR polymorphism. Higher Hcy levels were associated with feeding (P = 0.008), especially total parenteral nutrition (P = 0.0001). There was no correlation between Hcy levels and any vascular post-natal complications. CONCLUSIONS: During their post-natal hospitalization, preterm infants may have relatively high, that is, within the adult normal range, Hcy levels which are influenced by genetic and environmental factors. Despite the fact that no correlation was found between Hcy levels and post-natal complications, these associations should be further studied.