Hepatic extravasation of total parenteral nutrition following umbilical venous catheter insertion: A rare complication.

Umbilical venous catheters are commonly inserted in critically ill newborns and can lead to severe complications when misplaced. We report a preterm female with a prenatal diagnosis of duodenal atresia who presented 2 days after the surgical repair with abdominal distension, hemodynamic instability, elevated liver enzymes with severe cholestatic jaundice, and a hepatic collection on abdominal sonography. An urgent explorative laparotomy demonstrated a large amount of white, milky-appearing fluid in the abdominal cavity. Together with the sonographic findings, this led to the diagnosis of hepatic total parenteral nutrition extravasation. Upon removal of the umbilical venous catheter line, the infant's clinical state rapidly improved; however, cholestasis continued for months, with a very slow resolution. During follow-up, the liver enzymes normalized, and a complete resolution of the liver collection was observed, without drainage.

Perinatal and neonatal risk factors for retinopathy of prematurity in very low birthweight, very preterm twins: a population-based study.

OBJECTIVE: To determine the effect of perinatal and neonatal risk factors on retinopathy of prematurity (ROP) and to examine the association of fertility treatments on the risk for ROP in very low birth weight (VLBW) preterm twins. METHODS: The population-based observational study consisted of VLBW twins born at 24-29 weeks gestational age (GA). Data from the Israel national database (1995-2020) were applied. Univariate and multivariable logistic regression using the General Estimating Equation were used for assessment of risk factors. RESULTS: The study population comprised 4092 infants of whom 2374 (58%) were conceived following fertility treatments. ROP was diagnosed in 851 (20.8%) infants. The odds for ROP approximately doubled with each week decrease in GA: at 24 weeks, Odds Ratio (OR) 58.00 (95% confidence interval (CI) 31.83-105.68); 25 weeks, OR 25.88 (95% CI 16.76-39.96); 26 weeks, OR 12.69 (95% CI 8.84-18.22) compared to 29 weeks GA. Each decrease in one birthweight z-score was associated with 1.82-fold increased risk for ROP (OR, 1.82, 95% CI 1.59-2.08). Infertility treatments were not associated with ROP. Neonatal morbidities significantly associated with ROP were surgical necrotizing enterocolitis (NEC) (OR, 2.04, 95% CI 1.31-3.19); surgically treated patent ductus arteriosus (PDA) (OR, 1.63, 95% CI 1.12-2.37); sepsis (OR, 1.43, 95% CI 1.20-1.71) and bronchopulmonary dysplasia (OR, 1.52, 95% CI 1.22-1.90). CONCLUSION: Among preterm VLBW twins, poor intrauterine growth and surgical interventions for NEC and PDA were associated with high odds for ROP. This study does not support an association of fertility treatments with increased risk for ROP.

Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.

BACKGROUND: The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population. OBJECTIVE: To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. STUDY DESIGN: This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. RESULTS: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001). CONCLUSION: Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

[THE CHILDREN OF TODAY- ADULTS OF TOMORROW].

INTRODUCTION: According to a recent publication in the Lancet, infants who are born today will live to be up to 100 years of age. Neonatology is a medical specialty with great and grave responsibility. The way we administer the treatment of infants today and their subsequent neurodevelopmental outcome will affect not only their own lives but the lives of their families as well, in addition to impacting society, for many decades. Challenges encountered in neonatology subspecialties are enormous. We treat various systems in the human body that are not yet fully developed, taking upon ourselves the onus of directing the most optimal development. We are committed to address the physical challenges and the complex emotional burdens of the whole family unit. Indeed, the new parents and the baby-parents dyad are in our hands alone. We recognize that these infants deserve the best head start that we can provide. We treat a variety of conditions, including term newborns who are born with congenital malformations as well as those who sustain major injury through delivery complications, and provide 24-hour care during the long-term hospitalizations of very preterm infants. In this journal, we will share the very broad spectrum of challenges that will be described in case studies and original reports, and highlight the various approaches that reflect the versatility of our profession, from the baby's first breath to diagnosis, to choosing the therapeutic management most suitable for the infant and the family.

Factors associated with early phosphate levels in preterm infants.

To investigate perinatal factors and early morbidities associated with early serum phosphate (sPhos) levels in a cohort of preterm infants. Retrospective data were obtained from the medical records of a cohort of 454 infants born at < 32 weeks gestational age. Serum phosphate levels were directly associated with gestational age, body weight z-score, and Apgar scores and inversely associated with timing of enteral nutrition initiation and diet consisting of mostly breast milk. Maternal hypertension, lactate levels, early symptomatic hypotension, and total protein supplemented on days 1 to 3 were also inversely associated with sPhos. Morbidities that were found to be associated with sPhos did not persist after adjustment for confounding factors.Conclusions: We report a novel association between early sPhos and timing and content of enteral nutrition, as well as with the early neonatal hemodynamic condition of preterm infants. This information may help identify infants at risk for low sPhos and aid in the nutritional strategy utilized in these patients. This study did not identify early morbidities associated with sPhos. What is Known: • High initial amino acid intake is associated with increased risk of Refeeding like syndrome and hypophosphatemia, among preterm infants. What is New: • Early enteral nutrition, starting within the first 72 h of life, is associated with higher serum phosphate (sPhos) compared to nothing per os (NPO). • sPhos was not associated with early adverse neonatal outcomes.

Postnatal Growth Disadvantage of the Small for Gestational Age Preterm Twins.

In this study, we examined early growth characteristics among small-for-gestational-age (SGA) preterm twins compared to their appropriate-for-gestational-age (AGA) counterparts. A retrospective study evaluated all consecutive twins born between 2008 and 2015 at a tertiary referral center whose gestational age ranged from 30.0 to 34.86 weeks. Included were twins in which one twin was AGA and the other SGA at birth. Changes of ≥2, 1-1.99, and 0-0.99 in z-score between births and 36 weeks post menstrual age (PMA) were respectively defined as severe, moderate, and mild postnatal growth failure (PNGF) in weight or head circumference (HC). Early neonatal morbidities were documented. Multiple logistic regression analysis was applied to determine conditions associated with PNGF and its severity. Out of 666 sets of twins, 83 met the inclusion criteria. Weight PNGF was similar and mild among the SGA and the AGA groups (0.9 ± 0.46 vs. 0.96 ± 0.44 z-score, respectively, p = 0.24). At 36 weeks PMA, a significantly larger proportion of SGAs were below -2 z-scores in weight (84.3%) compared to birth (31.3%) or to the AGAs (8.4%). In both groups, weight PNGF correlated with the time needed to regain birth weight. HC PNGF was mild among both groups, yet significantly more prominent among the AGAs (0.39 ± 0.72 z-score) vs. SGAs (0.75 ± 0.65 z-score, p = 0.001). We suggest that among preterm SGA infants, the absolute z-score should be used to assess the severity of weight PNGF. Individual nutritional strategies to decrease time to regain birth weight may mitigate severe malnutrition among SGAs.

Direct Feeding at the Breast Is Associated with Breast Milk Feeding Duration among Preterm Infants.

BACKGROUND: In spite of high rates of initiating breast milk feeding (BMF) among preterm infants, a significant rate of discontinuation occurs shortly after discharge. AIM: To investigate the effect of mode (direct feeding at the breast vs. expressing) and exclusivity (breast milk combined with formula vs. breast milk only) as well as maternal perceptions on the duration of BMF among preterm infants. METHODS: The study included mothers whose infants were born before 32 weeks gestation, between January 2012 and August 2015 at Sheba Medical Center (SMC). Perinatal data were collected retrospectively from infants' computerized charts. Mothers were approached >12 months postpartum and were asked to complete a questionnaire. Those who agreed to participate were asked (during their visit to the follow-up clinic or by phone or mail) to complete a questionnaire regarding mode and duration of BMF as well as reasons for its discontinuation. Mothers were also asked about their pre-partum intentions to feed directly at the breast. RESULTS: Out of 162 eligible mothers, 131 (80.8%) initiated BMF during their intensive care unit (ICU) hospitalization. Of these, 66 (50.3%) discontinued BMF earlier than six months postpartum. BMF ≥ 6 months was significantly associated with direct feeding at the breast, duration of exclusive BMF, and singleton birth. Regression analysis revealed that direct feeding at the breast (any or only) and duration of BMF exclusivity were the only significant variables associated with BMF duration (Odds ratio (OR) 5.5 and 95% confidence interval (CI) 2.00-15.37; OR 1.5 and 95% CI 1.25-1.88, respectively). Milk supply (inadequate or nonexistent) was the most commonly reported cause for BMF discontinuation <6 months. Direct feeding at the breast was significantly associated with BMF duration and was more common among singletons. CONCLUSIONS: Direct feeding at the breast and duration of exclusive BMF are associated with duration of BMF among infants born <32 weeks of gestational age (GA). These findings suggest that targeting these two factors may play a key role in prolonging BMF duration among preterm infants.

A man-made disease: Fetal neonatal alloimmune thrombocytopenia due to incompatibility between oocyte donor and gestational mother.

The incompatibility causing fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from a fetus inheriting a paternal human platelet antigen (HPA), which is different from the maternal HPA. We present a unique case of FNAIT in a pregnancy involving an oocyte recipient mother with Turner syndrome. This is the first report of FNAIT in which the suggested mechanism involves antibodies produced by a gestational mother against the incompatible HPA of the oocyte donor.

Short-term morbidities and neurodevelopmental outcomes in preterm infants exposed to magnesium sulphate treatment.

AIM: The aim of the study is to examine whether baseline serum Mg concentration has an impact on short-term and long-term outcomes in preterm infants exposed antenatally to MgSO4. METHODS: Participants included all infants admitted to the neonatal intensive care unit at <32 weeks of gestational age. Infant serum Mg concentration (iMgC) was examined immediately after birth in those exposed to maternal MgSO4. Data for short-term outcomes were collected from the infants' computerised charts. Neurodevelopmental outcomes at 6-12 months corrected age were assessed using the Griffiths Mental Developmental Scales. RESULTS: Of 197 eligible infants, 145 were exposed to MgSO4. Baseline iMgC was available for 88 infants. Mean iMgC was 3.5 ± 0.88 mg/dL (1.6-5.7 mg/dL). Baseline iMgC was not associated with an increased risk for neither early morbidities nor adverse long-term outcome. However, iMgC above the mean (>3.5 mg/dL) was associated with significantly lower scores on locomotor (P = 0.016) and personal-social (0.041) scales in the first year of life. CONCLUSIONS: In a cohort of preterm infants antenatally exposed to MgSO4, elevated baseline iMgC (>3.5 mg/dL) was associated with lower locomotor scores. Further research is needed in order to study the relationship between supra-physiologic iMgC and its effect on the developing brain.

Factors Associated with Breast Milk Feeding of Very Preterm Infants from Birth to 6 Months Corrected Age.

OBJECTIVES: To investigate factors that may affect breast milk feeding (BMF) practices among very preterm infants. MATERIALS AND METHODS: This retrospective study included infants born before 32 weeks gestational age (GA) and monitored up to 6 months corrected age (CA). Feeding method was assessed at day 14 of life, 36 weeks GA, 6 weeks after home discharge, and 6 months CA. Multivariable logistic regression analysis was used to examine which factors were associated with BMF initiation at cessation. RESULTS: Of 181 infants who qualified for the study, 146 (81%) initiated BMF. Of these, 80% were mainly BMF (≥75% of daily nutrition volume). At 36 weeks GA, 6 weeks postdischarge, and 6 months CA, 130 (71.8%), 87 (48%), and 36 (19.9%) infants, respectively, continued to receive some BMF. Multivariate analysis revealed that initiation of BMF was more common with younger GA and higher level of maternal education. Infants whose mothers failed to supply ≥75% of daily nutrition as BMF at day 14 were more likely to be exclusively formula fed 6 weeks after discharge. Cessation of BMF at 6 months CA was associated with birth at >28 weeks. CONCLUSIONS: Successful BMF can be commenced and maintained throughout hospitalization in the majority of very preterm infants. Despite a significant dropout rate occurring within several weeks after discharge, in this select cohort, infants with lower GA were more likely to be breastfed after discharge.

Point of care testing in children undergoing cardiopulmonary bypass.

BACKGROUND: Excessive hemorrhage is a major complication after cardiac surgery requiring cardiopulmonary bypass (CPB). The aim of this study was to define the potential role of the cone and platelet analyzer (CPA) and the rotating thromboelastogram (ROTEM) point of care tests in children undergoing CPB. PROCEDURE: We prospectively studied 15 pediatric patients aged 1 month to 10 years. Blood count, blood coagulation tests (prothrombin time [PT], activated partial thromboplastin time, fibrinogen, thrombin time), CPA and ROTEM parameters were measured before and after CPB. Demographic and surgical data were recorded as were those on perioperative blood loss and blood product transfusion. RESULTS: Low body weight, longer duration on CPB and lower core body temperature were associated with an increased bleeding risk. The ROTEM test showed a significant prolongation of clotting time and decreased maximal clot firmness (MCF) postoperatively in children with increased bleeding. The coagulation parameters associated with increased bleeding were: prolonged PT, lower fibrinogen levels, prior to surgery, and lower MCF after surgery. CPA test findings were not associated with postoperative bleeding in our patients. CONCLUSIONS: CPA did not serve as a prognostic tool for predicting bleeding risk in children undergoing CPB. The change in ROTEM's post-CPB results associated with bleeding tendency, and they may predict for poorer clot formation and stability.

Childhood outcomes of neonates diagnosed with portal vein thrombosis.

AIM: The study aims to determine childhood outcomes of neonates diagnosed with portal vein thrombosis (PVT). METHODS: A retrospective chart review of neonates diagnosed with PVT who had documented follow up (physical examination, laboratory tests or ultrasonographic examination) at the age of 2 years or beyond was conducted. RESULTS: Data were available for 70 children (71% of eligible neonates) at a median age of 5 years (range 2-8 years). Physical examination was unremarkable in all who were examined (n= 68). Twenty-five children had liver functions assessed and only mild abnormalities were detected in nine children. Six of 25 patients tested for thrombophilia showed abnormalities. Thirty-seven children had ultrasonographic follow up. Left lobar atrophy (LLA) was noted in 20 children (16 had isolated LLA, two had LLA and splenomegaly, and two had LLA and portal hypertension). Five children who had normal ultrasound examinations at discharge had splenomegaly (two with additional finding of LLA) at follow up. Two children with portal hypertension diagnosed during neonatal period needed porta-caval shunting. CONCLUSION: Our results show that among patients, who had PVT as neonates, 28% still had asymptomatic LLA in childhood, 7% had slowly progressive splenomegaly and 3% required shunting because of progression of portal hypertension. Ultrasonographic follow up was the most sensitive method in detecting progression associated with neonatal PVT. Until more data are available, periodic long-term ultrasonographic follow up should be considered for neonates diagnosed with PVT.

Factor v Leiden and antiphospholipid antibodies in either mothers or infants increase the risk for perinatal arterial ischemic stroke.

BACKGROUND AND PURPOSE: The objective was to investigate the role of infant and maternal thrombophilia in a cohort of mothers and infants presenting with perinatal arterial ischemic stroke. METHODS: Forty-seven infants with clinically and radiologically confirmed perinatal arterial ischemic stroke underwent thrombophilia workup: factor V Leiden (FVL), PII20210A mutation, Methylene-tetrahydrofolate reductase 677T polymorphism, protein C, protein S, antithrombin, FVIII, and antiphospholipid antibodies. Thrombophilia data were available for 23 mother-infant pairs and compared with control populations to evaluate the risk for PAS. RESULTS: Thirty of 47 (64%) infants and 15 of 22 mothers (68%) had evidence of thrombophilia. In 18 of 23 (78%) mother-infant pairs, there was at least 1 thrombophilic risk factor, but 15 pairs were mismatched in pathology. Among infants, FVL, protein C deficiency, and presence of antiphospholipid antibodies prevailed (OR, 4.2; 95% CI, 1.5-11.3; OR, 12.2; 95% CI, 2.5-59.9; OR, 4.1; 95% CI, 1.4-12.2, respectively). Interestingly FVL prevailed in almost one-third of mothers (OR, 8.5; 95% CI, 4.1-17.5) and 18% of mothers had antiphospholipid antibodies (OR, 3.8l; 95% CI, 1.5-10.0). CONCLUSIONS: Maternal and neonatal thrombophilia, especially presence of FVL or antiphospholipid antibodies, may be important in the pathogenesis of perinatal arterial ischemic stroke. The nature of thrombophilic mother-infant risk potential interactions warrants further investigation.

Hemostasis and thrombosis in critically ill children.

Patients in the pediatric intensive care unit (PICU) often suffer from a variety of pathophysiologic conditions that are associated with abnormal hemostasis. Bleeding is a major complication of any surgery or trauma, thus patients with inherited or acquired coagulopathies or those experiencing massive trauma or undergoing major (especially cardiac) operations present a special challenge to the ICU experts as well as to the hematologist. Awareness of thromboembolic events in the pediatric population has been increasing in the past few years mainly due to improvement in diagnostic tools, advances in new therapy and procedures, together with an increased index of suspicion. Young infants are at greater risk for either bleeding or thromboembolic events, due to lower concentration of vitamin K-dependent procoagulant clotting factors, reduced thrombin potential, and altered fibrinolytic pathway with low levels of the coagulation inhibitors. The combination of infection, hypotension, acidosis, and release of activated substances, such as tumor necrosis factor, is common after severe trauma or in seriously ill ICU patients and often leads to disseminated intravascular coagulation, which may be complicated either by bleeding or thrombosis. The conditions, risk factors, and therapeutic options available for critically ill PICU patients are discussed in this review.