Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.5 mL of blood was drawn to obtain S1 levels, measured via ELISA. Placentas were examined and classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with inflammation of the umbilical cord (funisitis). S1 levels were compared between preterm newborns without exposure to CA verus newborns with exposure to CA (including with and without funisitis). Preterm newborns exposed to CA were found to have significantly elevated S1 levels compared to those unexposed. Although S1 levels could not differentiate fetal exposure to CA from exposure to CA with funisitis, the combined CA groups had significantly higher S1 levels compared to those not exposed to CA. S1 level has the potential to become a clinically useful biomarker that could assist in the management of mothers and preterm newborns with CA and funisitis. Furthermore, S1 level could aid in the diagnosis and treatment of early-onset neonatal sepsis.

Neonatal serial creatinine levels as an adjunct biomarker in timing of fetal neurologic injury.

Objective: To investigate the rise and clearance of newborn creatinine in perinatal asphyxia as an adjunct biomarker to support or refute allegations of acute intrapartum asphyxia. Study design: In this retrospective chart review, newborns > 35 weeks gestational age were evaluated from closed medicolegal cases of confirmed perinatal asphyxia and reviewed for causation. Data collected included newborn demographic data, patterns of hypoxic ischemic encephalopathy, brain magnetic resonance imaging, Apgar scores, cord and initial newborn blood gases, and serial newborn creatinine levels during the first 96 h of life. Newborn serum creatinine values were collected at 0-12, 13-24, 25-48, and 49-96 h. Newborn brain magnetic resonance imaging was used to define 3 patterns of asphyxial injury: acute profound, partial prolonged, or Both. Results: Two hundred and eleven cases of neonatal encephalopathy from multiple institutions were reviewed from 1987 to 2019 with only 76 cases having serial creatinine values during the first 96 h of life. A total of 187 creatinine values were collected. Partial prolonged and Both had significantly greater degree of metabolic acidosis in the first newborn arterial blood gas in comparison to acute profound. Acute profound and Both had significantly lower 5- and 10- minute Apgar scores in comparison to partial prolonged. Newborn creatinine values were stratified by asphyxial injury. Acute profound injury showed minimally elevated creatinine trends with rapid normalization. Partial prolonged and Both demonstrated higher creatinine trends with delayed normalization. Mean creatinine values were significantly different between the three types of asphyxial injuries within 13-24 h of life at the time when creatinine values peaked (p = 0.01). Conclusion: Serial newborn serum creatinine levels taken within the first 96 h of life can provide objective data of timing and duration of perinatal asphyxia.

FIRS: Neonatal considerations.

Fetal Inflammatory Response Syndrome (FIRS) is the fetal counterpart of systemic inflammatory response syndrome (SIRS) described in adults. When the fetus is directly exposed to inflammation of the fetal membranes or the placental-fetal circulation, and organs are adversely affected, the disorder is known as FIRS. This syndrome can significantly affect multiple organs with significant short and long term implications for the newborn. In cases of neonatal encephalopathy when no obvious etiology is identified, FIRS needs to be considered. Based on the significant incidence of chorioamnionitis and its potential effects on the newborn, any evidence of maternal, fetal, or neonatal infection should mandate further evaluation of the placenta and membrane histopathology.

ABO blood group and procoagulant factors: the hypercoagulation hypothesis ABO and Procoagulant Factors.

BACKGROUND: The correlation between procoagulant levels-factor VIII (FVIII), von Willebrand factor (vWF), and fibrinogen-and risk of thrombosis has been well documented in adult populations. We hypothesize that interaction of passively transferred isoagglutinins in premature neonates with a compromised immune system may trigger an immune response that can target the immature gastrointestinal tract. The objective of this study is to evaluate if there are procoagulant level differences in preterm newborns stratified by ABO blood group. METHODS: VWF, FVIII, and fibrinogen levels were analyzed in neonates ≤32 weeks and/or birthweight ≤1500 g over the first 6 weeks of life. Demographic, blood type, and transfusion data were collected. RESULTS: Elevations in vWF and FVIII were found to be statistically significant in the third week of life in non-O neonates vs. type O neonates. FVIII was also found to be significantly elevated in week 1. Transfused neonates also showed elevations between weeks 0 and 3. CONCLUSION: There appears to be a time-dependent variation in procoagulant factor levels in preterm newborns. Although the clinical significance remains unclear, prothrombotic factors vWF and FVIII are significantly higher in non-O blood-type preterm neonates in the third week of life.

Influence of perinatal factors in short- and long-term outcomes of infants born at 23 weeks of gestation.

OBJECTIVE: Investigate the influence of perinatal factors on short- and long-term outcomes for infants born at 23 weeks of gestation. STUDY DESIGN: This is a retrospective study over a 25-year period (1987-2011) of 87 successfully resuscitated infants at 23 weeks of gestation. We investigated the effects of poor prenatal care, race, gender, chorioamnionitis, antenatal corticosteroids, delivery route/location, low 5-minute Apgar score, birth weight, and multiple births on short- and long-term outcomes. RESULTS: The mortality rate was 43% (37/87). A total of 88% (44/50) of the survivors were followed at 2 years corrected age with 66% (29/44) diagnosed with a moderate-to-severe neurological impairment. Outborn and multiple birth infants had significantly higher mortality (p-value 0.042 and 0.006, respectively). Lack of exposure to antenatal steroids and lower birth weight significantly increased the disability score (p-value 0.042 and 0.003, respectively). CONCLUSION: Multiple perinatal factors significantly influence outcomes at the threshold of viability.

Measurement of the glucocorticoid receptor: relevance to the diagnosis of critical illness-related corticosteroid insufficiency in children.

Diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in children continues to remain difficult and controversial in that no consensus for either exists among pediatric critical care physicians. Critical illness-related corticosteroid insufficiency is defined as a corticosteroid response that is inadequate for the severity of the illness experienced by the patient. Critical illness-related corticosteroid insufficiency manifests as an insufficient corticosteroid mediated down-regulation of proinflammatory cytokines, due to either corticosteroid tissue resistance and/or inadequate circulating levels of cortisol. The tissue resistance is likely due to alterations in the functionality of the intracellular receptor for corticosteroids, the glucocorticoid receptor (GR). This article details the role of the GR during critical illness with a focus upon the measurement of the GR, as a potentially important means by which to clinically assess the level of corticosteroid tissue-resistant in patients suspected of CIRCI. Measurement of the GR may be particularly useful as a means by which to determine the judicious administration of steroids, maximizing their therapeutic potential, whereas minimizing the morbidity that can be associated with their use.

The relationship between reticulated platelets, intestinal alkaline phosphatase, and necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP). METHODS: Infants born ≤ 32 weeks and/or ≤ 1500 g were prospectively enrolled from 2009 to 2012. Starting within 72 hours of birth, 5 weekly whole blood specimens were collected to measure RP and serum iAP. Additional specimens were obtained at NEC onset (Bell stage II or III) and 24 hours later. Dichotomous cut-points were calculated for both biomarkers. Non-parametric (Mann-Whitney) and Chi-square tests were used to test differences between groups. Differences in Kaplan-Meier curves were examined by log-rank test. The Cox proportional hazards model estimated hazard ratios. RESULTS: A total of 177 infants were enrolled in the study, 15 (8.5%) of which developed NEC (40% required surgery and 20% died). 14 (93%) NEC infants had "low" (≤ 2.3%) reticulated platelets, and 9 (60%) had "high" iAP (>0 U/L) in at least one sample before onset. Infants with "low" RP were significantly more likely to develop NEC [HR=11.0 (1.4-83); P=0.02]. Infants with "high" iAP were at increased risk for NEC, although not significant [HR=5.2 (0.7-42); P=0.12]. Median iAP levels were significantly higher at week 4 preceding the average time to NEC onset by one week (35.7 ± 17.3 days; P=0.02). CONCLUSION: Decreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.

Long-term follow-up of 2 newborns with a combined birth weight of 540 grams.

Long-term growth and developmental data are presented for the smallest and third smallest surviving newborns in the world literature to 5 and 20 years of age, respectively. Both patients exhibited normal motor and language development. Although head circumference for both newborns demonstrated catchup growth, significant differences in height and weight growth velocities persisted.

Congenital anomalies and rhabdoid tumor associated with 22q11 germline deletion and somatic inactivation of the SMARCB1 tumor suppressor.

The most common microdeletion in humans involves the 22q11 region. Congenital anomalies associated with 22q11 loss include cardiac and facial defects. Less frequent is the co-presentation of malignant rhabdoid tumors that are highly aggressive childhood malignancies typically found in renal or extra-renal soft tissues and central nervous system. A newborn patient presented with multiple congenital anomalies consistent with 22q11 deletion syndrome including cleft lip and palate, ear tags and ventricular septal defects co-presenting with an axillary rhabdoid tumor. Comparative genomic hybridization revealed a 2.8 Mb germline deletion in the 22q11.2 region containing genes required for normal fetal development and the SMARCB1 tumor suppressor gene. Analysis of tumor DNA revealed a somatic deletion of exon 7 in the second allele of SMARCB1. Expression of SMARCB1 was absent, while tumor markers including MYC, GFAP, and CLAUDIN-6 were upregulated. The presence of tandem oriented BCRL modules located within interspersed low copy repeat elements throughout the 22q11 distal region may predispose this area for microdeletions through nonalleleic homologous recombination.

Does the International Classification of Disease (ICD-9) code accurately identify neonates who clinically have hypoxic-ischemic encephalopathy?

BACKGROUND/AIMS: Hypoxic-ischemic encephalopathy (HIE) refers to neonatal neurological signs and symptoms of hypoxia and/or ischemia. Our aim was to determine the accuracy of ICD-9 codes to identify newborns with HIE confirmed by umbilical cord blood analysis. METHODS: ICD-9 codes in the newborn chart for birth trauma, birth asphyxia, intrauterine hypoxia, and fetal distress were used to identify newborns with suspected HIE by neonatal personnel. Maternal charts were reviewed for umbilical cord gases meeting the HIE clinical criteria. RESULTS: There were 21,008 deliveries at center I and 17,540 at center II. ICD-9 codes identified 172 neonates, 49 infants (2.3‰ births) at center I and 123 neonates (7‰) at center II. Only 3 neonates (6%) were ≥34 weeks and none met ACOG criteria [umbilical artery pH <7.00 or base excess (BE) ≥12 mmol/l at center I]. At center II, 80 infants were ≥34 weeks but only 5/123 (4%) met the ACOG clinical criteria for HIE (pH <7.00, BE ≥12 mmol/l, and Apgar ≤3 at 5 min). CONCLUSIONS: ICD-9 codes are unreliable in identifying birth asphyxia and cannot identify newborns meeting the clinical criteria for intrapartum HIE.

A proposed evidence-based neonatal work-up to confirm or refute allegations of intrapartum asphyxia.

OBJECTIVE: To propose a clinical work-up in term and near-term newborns to address the nine American College of Obstetricians and Gynecologists (the College) and American Academy of Pediatrics criteria to define an acute intrapartum event sufficient to cause cerebral palsy. METHODS: We examined our experience as neonatal expert witnesses in 103 closed claims of alleged intrapartum asphyxia with poor newborn outcome over a 21-year period from 1987 to 2008. We estimated how often the clinical components of this proposed work-up were not obtained or recorded in the medical record. RESULTS: Cord arterial blood gases and placental pathology were not obtained or sent in 38% and 32% of the 103 cases, respectively. Routine neonatal laboratory tests, including a complete blood count with differential, nucleated red blood cells, electrolytes, calcium, coagulation profile, and renal and liver function tests, were frequently absent. Cranial imaging in ultrasonograms, computed tomography, and magnetic resonance imaging were absent in more than 50% of the cases reviewed and were often not scheduled at optimal times. CONCLUSION: The medical record of newborns with poor outcomes frequently has a paucity of objective, evidence-based data. This leads to speculation and unethical expert testimony. The protocol will assist in confirming or refuting allegations of intrapartum asphyxia. LEVEL OF EVIDENCE: III.

Pericardial effusion in a preterm infant resulting from umbilical venous catheter placement.

Pericardial effusion in neonates is a rare occurrence associated with malpositioning of central venous catheters. This report describes a case of pericardial effusion in which echocardiographic determination of line position, typically considered one of the most reliable means of placement verification, was misleading. The infant ultimately did well after pericardiocentesis, with complete resolution of symptoms and no further complications.

Old school.

In the last decade, the American Board of Pediatrics has reduced the number of required intensive care rotations. The Accreditation Council for Graduate Medical Education has established guidelines that limit on-call nights to 24 h and the work week to 80 h. This has had a positive impact on housestaff training and patient safety. Inadequate experience can reduce proficiency, especially in the acute management of a sick newborn. New guidelines and evidence-based standards need to assure competency without compromising work hours and broad-based exposure. Times change, but the passion and privilege of caring for sick newborns does not.

Characteristic sonographic findings of hepatic erosion by umbilical vein catheters.

OBJECTIVE: The purpose of this series is to describe findings seen on abdominal sonography in neonates with erosion into the liver by umbilical vein catheters (UVCs). METHODS: Four neonates with erosion of the UVC into hepatic parenchyma within a 2-year period were identified. A retrospective case analysis was performed to determine the symptoms and clinical scenario of presentation. Plain radiographs were examined to establish the location of the UVC placement, and abdominal sonograms were reviewed. RESULTS: All 4 neonates had abdominal distension within 9 days of UVC placement, and in all of them, the UVC tip was located below the hemidiaphragm and superimposed over the liver. Sonographic examination of all patients showed intraparenchymal liver lesions with an echogenic rim and hypoechoic center. Two neonates also had subcapsular fluid collections. Complex ascites was seen in all 4 patients. The fluid was proven to be total parenteral nutrition by paracentesis in 2 patients. Treatment consisted of removal of the UVC. All patients were followed for a period of 2 to 18 months and showed clinical resolution of symptoms or sonographic improvement of the liver lesions. CONCLUSIONS: A characteristic liver lesion can be seen on sonography with hepatic erosion by UVCs. Our study shows the importance of a high index of suspicion of UVC erosion into the liver in neonates with catheters positioned in the liver. When such neonates have abdominal distension, prompt abdominal sonograms should be obtained.

Annular pancreas in identical twin newborns.

Annular pancreas is a rare congenital anomaly occurring in 1 of every 12,000 to 15,000 live births [Nerwich N, Shi E. Neonatal duodenal obstruction: a review of 30 consecutive cases. Pediatr Surg Int 1994;9:47-50]. It may remain asymptomatic throughout life, present in adulthood, or present in infancy as a high intestinal obstruction. Review of the literature demonstrates only 8 cases of familial annular pancreas and no case of twins exhibiting the disease. We will describe a case of identical (monochorionic diamniotic) female twins with neonatal presentation of duodenal obstruction and annular pancreas, and discuss data supportive of a genetic etiology.

Orthopaedic implications of multiple gestation pregnancy with triplets.

Intrauterine crowding has been implicated as a risk factor in several orthopaedic conditions, such as developmental dysplasia of the hip (DDH), metatarsus adductus, and torticollis. The goal of this study was to see whether orthopaedic conditions associated with intrauterine crowding were more frequent in multiple gestation pregnancies, specifically in triplets. The authors reviewed their experience over a 10-year period with 261 children who were products of triplet pregnancies. They surveyed 13 orthopaedic conditions and found only one condition, torticollis, that had a greater incidence than that reported in single gestation pregnancies. A 0% incidence of DDH was found in these patients. Routine ultrasound screening cannot be recommended in these patients based on these results.

Special relationships between fetal inflammatory response syndrome and bronchopulmonary dysplasia in neonates.

OBJECTIVE: To confirm previous known relationships between Fetal Inflammatory Response Syndrome (FIRS) and neonatal bronchopulmonary dysplasia (BPD) and to present information on previously unknown special relationships between inflammatory variables and BPD. STUDY DESIGN: At delivery, we obtained biological specimens including umbilical cord venous blood for plasma interleukin-6 levels, as well as placental histology and bacteriology. Among other neonatal outcomes, we collected prospective information on BPD. RESULTS: Of 141 newborns in the study, 16 had BPD; 79% of these had antecedent FIRS, 27% of those without FIRS had BPD. By multivariable regression, only very low birth weight (adjusted [adj] odds ratio [OR] 32.0, 95% Confidence Interval [CI] 5.0 to positive infinity) and FIRS (adj OR 5.7, 95% CI 1.1 to 42.3) remained significant risk factors. Escherichia coli, perhaps due to its pyogenic nature (strongly elicits inflammatory responses), may have had a special relationship with BPD. CONCLUSIONS: In our data, FIRS and neonatal BPD are highly associated. It is possible that certain pyogenic bacteria in the chorioamnion space may be implicated more often than others. CONDENSATION: Neonates having Fetal Inflammatory Response Syndrome at delivery may later develop BPD. Pyogenic bacteria, such as Escherichia coli, may be implicated more frequently.