Timing and risk factors associated with acute kidney injury in infants with necrotizing enterocolitis.

OBJECTIVE: To evaluate the prevalence, onset, risk factors, and mortality associated with acute kidney injury (AKI) in infants with necrotizing enterocolitis (NEC). DESIGN/METHODS: Retrospective study at 2 centers in infants with NEC, with/without AKI. AKI assessed by serum creatinine and urine output. Statistical tests used included t, Mann-Whitney U, Chi-square, and Fisher Exact tests. RESULTS: Among 80 eligible infants with NEC, 56 (70%) had AKI. Median onset of NEC was day 15, with median AKI onset two days (IQR, -5.75 to 0) prior to NEC onset. Vasopressors were significantly more likely to be used in infants with NEC and AKI (p = 0.009). Increased mortality (p = 0.01) was noted in infants with NEC and AKI. CONCLUSIONS: The onset of AKI mostly precedes NEC onset, with moderate to severe AKI more prevalent than the milder form in infants with NEC. These infants are significantly more likely to be hemodynamically unstable and have increased mortality.

Influence of birth-related maternal and neonatal factors on the levels of energy metabolism mediators in infants born at 32 or fewer weeks of gestation.

BACKGROUND: Energy metabolism mediators, which include the adipokines (leptin, adiponectin, ghrelin) and insulin-like growth factor 1 [IGF-1], are hormone-like proteins, produced and expressed in the placenta and fetal membranes, with properties featuring metabolic adaptation and inflammatory processes. Due to the complexity of the metabolic adaptation of preterm neonates during the transition to extrauterine life, it becomes essential to recognize the factors that influence the alteration of the adipokines and IGF-1 levels in the early postpartum stage.This study assessed the significance of maternal-fetal-neonatal factors in predicting the levels of leptin, adiponectin, ghrelin, and IGF-1 in preterm infants born at 32 or fewer weeks of gestation, during the early stage of postnatal adaptation. METHODS: Energy metabolism mediator levels were measured in urine samples obtained from extremely (less than 28 weeks) and very (28-32 weeks) preterm infants, within 48 h after their birth, and before the initiation of enteral nutrition. The urine samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. The collected data included all birth-related maternal and neonatal factors such as maternal age, race/ethnicity, hypertensive disorders of pregnancy, diabetes, gravidity, parity, type of pregnancy, mode of delivery, and antenatal use of corticosteroids, antibiotics, magnesium sulfate, Apgar scores at 1 and 5 min, gestational age, and birth weight. We investigated the correlation between the levels of the tested mediators, the significance of the differences in their average levels based on the dichotomized maternal and neonatal factors, and the effect of the selected factors, in multiple regression models. Data from the regression models constructed for leptin, adiponectin, ghrelin, and IGF-1 are presented as regression coefficient ß with Standard Error (SE) of ß, coefficient of determination (R2), and adjusted R2. Before including the factor in regression models, we tested for the multicollinearity effect. Two-sided P values <0.05 were considered statistically significant. RESULTS: Among the 70 studied infants, 47.1% were male, 40.6% were white, 28.6% were extremely preterm, and 18.6% were born with a weight <750 grams. Except for a mild interplay between the adiponectin and IGF-1 levels, there was no correlation between the levels of the other studied mediators. Up to 20% variation in the tested energy metabolism mediator levels was dependent on some of the birth-related maternal and neonatal characteristics. For instance, leptin levels were reduced in association with male gender (-0.493 [0.190], p < 0.02) and increased in infants born to primigravids (0.562 [0.215], p < 0.02). Adiponectin levels were increased in infants born to nulliparous as compared to multiparous women (0.400 [0.171], p < 0.03). Ghrelin levels were reduced in males (-0.057 [0.026], p < 0.04). IGF-1 levels were increased in the urine of extremely preterm neonates (0.357 [0.111], p < 0.01) and preterm infants born with an Apgar less than three at 1 min (0. 340 [p < 0.153], p < 0.04). CONCLUSIONS: Nearly one-fifth of the variation in the urinary levels of the adipokines (leptin, adiponectin, ghrelin) and IGF-1 during the early postnatal stage in infants born at 32 or fewer weeks of gestation was predicated on one or more of the maternal and neonatal factors such as the infant's sex, extreme preterm gestation, a low Apgar score at 1 min, or birth to nulliparous women or primigravida mothers. Further studies will be required to explain the role of energy metabolism mediators in the postnatal adaptation of preterm-born infants.

Extreme prematurity-associated alterations of pulmonary inflammatory mediators before and after surfactant administration.

BACKGROUND: The role of prematurity and pulmonary inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD) is very well-defined. However, there is limited knowledge about whether the level of prematurity and surfactant therapy alter the pulmonary cytokines and endothelial growth factor (VEGF). METHODS: This study analyzed the VEGF and cytokines, including interleukin (IL)-1ß, IL-6, IL-8, and IL-10, and tumor necrosis factor α (TNF-α) in the tracheal aspirate (TA) of preterm infants obtained before (within 2 h after birth) and 10-12 h after the administration of the first dose of surfactant. TA was collected from 40 infants of 35 or fewer weeks of gestation, including extremely (Group 1, n = 19), very (Group 2, n = 13), and moderate/late (Group 2, n = 8) preterm neonates. In addition to univariate analysis, controlled regression models estimated the association of perinatal factors with the tested parameters and their role in the development of BPD. RESULT: We recorded significantly lower post-partum levels of VEGF and higher IL-8, IL-1ß, and TNF-α in the TA of Group 1 infants than in Group 2 and 3. Compared to the infants in Group 2 and 3, the post-surfactant increases of pulmonary VEGF, IL-8, IL-10, and TNF-α were more significant in Group 1. All tested parameters in Group 1 and 2 infants, before and after surfactant administration, were comparable. BPD was recorded in nearly 60% of the extremely preterm survivors and was significantly predicted by increased IL-8 before, and elevated TNF-α level after surfactant administration. CONCLUSION: This study indicates the association of birth at extremely preterm gestation with reduction in pulmonary VEGF and exacerbation of pro-inflammatory cytokines followed by greater elevation post-surfactant administration levels of VEGF, IL-8, TNF-α, and IL-10 than in neonates born with gestational age of 28-35 weeks.

Spondylocostal dysplasia and brachydactyly associated with TBX6 and IHH variants: A case report.

We report a preterm male neonate presenting with a short trunk, short neck, low hairline, deformed ears, preauricular skin tag, penoscrotal transposition (PT), palmar crease, short and broad fingers and toes (brachydactyly), hypoplastic and deep-set nails, metatarsal abductus, and cross-fused, small echogenic kidneys. Radiologic findings and genetic studies are consistent with spondylocostal dysostosis (SCD) and autosomal dominant brachydactyly. This is the first case report of spondylocostal dysostosis and brachydactyly associated with TBX6 and IHH variants. We reviewed the literature and compared our patient's phenotype with previously reported cases of SCD.

Prune Belly Syndrome Associated with Interstitial 17q12 Microdeletion.

We report a term male neonate presenting with a "prune belly," bilateral hydronephrosis, hydroureter, posterior urethral obstruction, and bilateral undescended testes. Analysis with the whole genome SNP microarray revealed an interstitial deletion of about 1.49 megabase (MB) at chromosome 17q12. We present a rare association of prune belly syndrome with a chromosomal deletion in this same region.

Multiparametric Magnetic Resonance Imaging in Evaluation of Clinically Significant Prostate Cancer.

Aim In this prospective study, we evaluate the role of multiparametric magnetic resonance imaging (mp-MRI) in the assessment of clinically significant prostate cancer at 1.5 T without endorectal coil (ERC). Materials and Methods Forty-five men with clinical suspicion of prostate cancer (prostate-specific antigen [PSA] level > 4 ng/mL, hard prostate on digital rectal examination, and suspicious area at transrectal ultrasound [TRUS]) were evaluated using the mp-MRI protocol over a period of 24 months. All cases were interpreted using the Prostate Imaging Reporting and Data System (PI-RADS) version 2 guidelines and correlated with histopathology. Statistical Analysis Used A chi-squared test was used for analysis of nominal/categorical variables and receiver operating characteristic (ROC) curve and one-way analysis of variance (ANOVA) test for continuous variables. Results The mean age was 67 years and the mean PSA was 38.2 ng/mL. Eighty percent had prostate cancer and 20% were benign (11% benign prostatic hyperplasia [BPH] and 9% chronic prostatitis). Eighty-six percent of all malignancies were in the peripheral zone. The PI-RADS score for T2-weighted (T2W) imaging showed good sensitivity (81%) but low specificity (67%). The PI-RADS score for diffusion weighted imaging (DWI) with sensitivity of 92% and specificity of 78% had a better accuracy overall than T2W imaging alone. The mean apparent diffusion coefficient (ADC) value (×10 -6 mm 2 /s) was 732 ± 160 in prostate cancer, 1,009 ± 161 in chronic prostatitis, 1,142 ± 82 in BPH, and 663 in a single case of granulomatous prostatitis. Low ADC values (<936) have shown good correlation (area under curve [AUC]: 0.87) with the presence of cancer foci. Inverse correlation was observed between Gleason scores and ADC values. Dynamic contrast-enhanced (DCE) imaging has shown 100% sensitivity/negative predictive value (NPV), but moderate specificity (67%) in predicting malignancy. The final PI-RADS score had 100% sensitivity and NPV with good overall positive predictive value (PPV) of 95%. Conclusions T2W imaging and DWI remain the mainstays in diagnosis of prostate cancer with mp-MRI. DCE-MRI can be a problem-solving tool in case of equivocal findings. Because assessment with mp-MRI can be subjective, use of the newly developed PI-RADS version 2 scoring system is helpful in accurate interpretation.

Direct antiglobulin test in the prediction of hyperbilirubinemia and predischarge bilirubin levels in infants with mother-infant blood type incompatibility.

BACKGROUND: This research evaluated the association between the mother-infant blood type or rhesus (ABO or Rh) incompatibility, the pattern of neonatal jaundice, and serum bilirubin (TSB) values obtained prior to discharge from hospital of healthy born neonates with gestational age >34 weeks and birth weight >2000 g. METHODS: We utilized a laboratory and neonatal database to identify the cord blood ABO/Rh and direct antiglobulin test (DAT) and TSB measured during hospitalization and re-admission with hyperbilirubinemia for phototherapy treatment. We used hour-specific TSB to analyze the TSB levels for ABO/Rh compatibility and isoimmunization using chi-square, analysis of variance, and regression models. RESULTS: Of the 901 infants studied, 158 (17.5%) had ABO/Rh incompatibility, including 27 with positive DAT. Hyperbilirubinemia was diagnosed in 33.3% DAT positive, 6.9% DAT negative, and 4.6% of infants with compatible blood types. Increased predischarge TSB was observed in DAT positive infants at 48-72 h of postnatal age (P < 0.001). After controlling for age at TSB testing and weight loss percentage, multiple regression analysis did not show any impact of ABO/Rh incompatibility and DAT results on the predischarge TSB levels. CONCLUSION: Blood type incompatibility increases the frequency of hyperbilirubinemia only in the DAT-positive infants. Irrespective of the isoimmunization status, it does not significantly affect the level of predischarge TSB.

Role of the Proportional Intake of Fortified Mother's Own Milk in the Weight Gain Pattern of Their Very-Preterm-Born Infants.

Breastfeeding has been recommended for preterm infants as the optimal diet from nutritional, gastrointestinal, immunological, and developmental perspectives. However, the relevance of differing intakes of fortified mother's own milk (MOM) on the growth of their preterm infants is a challenging question because of the potential risk of extrauterine growth impairment, apart from its essential role in the provision of biological and immunological factors, and the reduction of serious morbidities. We aimed to identify the weight gain pattern in very-preterm-born infants with respect to their proportional intake of fortified MOM. The daily and average weight gain, dietary volume, calories, and proportional intake of fortified MOM were studied in a cohort of 84 very-preterm-born infants during the first 2 weeks post initiation of full enteral feeds. Groups 1, 2, and 3 were comprised of infants with a proportional fortified MOM intake of 85% or more, 35% to 84.9%, and 0 to 34.9%, respectively. Data analysis included regression models and a group-based comparison of the number of infants with weight gain that would be considered minimally acceptable for normal intrauterine growth. The infants' weight gain was not found to be associated with the proportional intake of fortified MOM or other feeding parameters. Overall, the intergroup variability in the proportion of infants with weight gain less than the lower limit of normal fetal growth was insignificant. During the first 2 weeks post initiation of full enteral feeds, the weight gain pattern of the studied very-preterm-born infants was not significantly dependent on the proportional intake of fortified maternal milk.

Multiple Congenital Anomalies in a Patient with Interstitial 6q26 Deletion.

We report a preterm male neonate presenting with a lumbosacral meningomyelocele, type II Arnold Chiari malformation, hypoplasia of the aortic arch, bicuspid aortic valve, ventricular septal defect, secundum atrial septal defect, multicystic dysplastic kidney, and hydronephrosis. Analysis with whole genome SNP microarray revealed an interstitial deletion of about 237 kb in chromosome 6q26. Long contiguous stretches of homozygosity (>3 Mb) were seen in 18 chromosomes with a total genomic size of 219 Mb. The phenotype seen in our patient has not been reported in association with the genes in the homozygous regions. However, our patient shares many phenotypic features with other reported cases that have shown a deletion in the same region of chromosome 6.

Pattern of intracranial findings detected on magnetic resonance imaging in surviving infants born before 29 weeks of gestation.

Despite the positive survival trend in infants born prematurely, the risk for development of intracranial lesions has remained unchanged. However, there are limitations to our understanding of the pattern of the magnetic resonance imaging (MRI) -detected brain pathology in the preterm infants surviving to discharge. The present study outlines the type of intracranial lesions and factors allied with the neonatal brain hemorrhage (NBH) and white matter injury (WMI) seen on MRI at term-equivalent age or close to discharge in infants born before 29 weeks of gestation. We obtained demographic and clinical data, and reports of serial cranial ultrasound (CUS) performed during first month of life and qualitative MRI at term-equivalent age or close to discharge. Statistical comparison was conducted with respect to the MRI results that were classified as normal, WMI, and NBH using univariate and logistic regression analysis. One hundred and ninety three infants with MRI at term-equivalent age or close to discharge were included in final analysis. They were less mature and had a higher prevalence of pathological findings on CUS as compared with 249 other survivors born with gestational ages less than 29 weeks during the assigned study period. MRI was normal in 72.5% [95% Confidence Interval (95% CI 65.9%-78.4%)], showed WMI in 9.8% (95%CI 6.4%-14.9%) and NBH in 17.6% (95%CI 12.9-23.6) of the studied infants. Intracranial hemorrhages had also been reported in 42.2% of the infants with WMI. Except for moderate agreement with prior CUS results, no other factors were associated with the MRI detected pathological findings. In general, the likelihood for detection of WMI and NBH on MRI at term-equivalent age or close to discharge was reduced by approximately 80% and 70%, respectively if the serial CUS had not shown any abnormalities during the first month of life.

Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Meningitis and Cerebral Abscess in a Neonate: Therapeutic Challenge.

We report a case of a 12-day-old term neonate with extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli) meningitis and cerebral abscess. The patient received a 7-day course of antibiotics just few days prior to the infection. The incidence of infections from ESBL-producing E. coli is increasingly emerging. Antimicrobial agents must be vigilantly utilized to prevent the new highly resistant bacteria.

8p 11 Microduplication Is Associated with Neonatal Stridor.

We report a term male infant with congenital stridor secondary to tracheomalacia and a mild coarctation of the aorta. Developmental delay was noted upon follow-up. Whole genome SNP microarray analysis showed an ∼846-kb interstitial duplication of the short arm of chromosome 8 (8p11.21p11.1). We report novel clinical findings of this rare genetic condition.

11p15.4 Microdeletion Associates with Hemihypertrophy.

We report a preterm female infant with intrauterine growth retardation, dysmorphic facies, missing rib, small hands and feet, and hemihypertrophy. The results of whole genome SNP microarray analysis showed approximately 77 Kb interstitial deletion of the short arm of chromosome 11 (11p15.4). We report novel clinical findings of this rare genetic condition.

Ventriculomegaly and cerebellar hypoplasia in a neonate with interstitial 11q 24 deletion in Jacobsen syndrome region.

Jacobsen syndrome (JS) is a rare contiguous gene disorder caused by partial deletion of the distal part of the long arm of chromosome 11 ranging in size from 7 to 20 Mb. We report a term male neonate with an interstitial deletion of about 12.3 megabase (Mb) of chromosome 11q24.1qter. Our case is the first reported newborn patient with 11q24 deletion.

Biliary Tract Abnormalities as a Cause of Distal Bowel Gas in Neonatal Duodenal Atresia.

BACKGROUND: The presence of distal bowel gas in an infant does not exclude the diagnosis of duodenal atresia. CASE PRESENTATION: We report a term neonate with Down syndrome. The infant developed vomiting and cyanosis with each feeding soon after birth. Plain film abdominal X-rays showed a nonspecific gas-filled stomach and small bowel. Duodenal atresia and an anomalous common bile were noted on an upper GI study and exploratory laparotomy. CONCLUSION: In the absence of a "double bubble" appearance and intestinal gas distally on a plain radiograph, one must not exclude duodenal atresia as the differential diagnosis.

A Giant Gastroschisis Associated with Pulmonary Hypoplasia and Spinal Anomaly: A Case Report and a Literature Review.

Gastroschisis most often occurs as an isolated anomaly and extragastrointestinal associations are rare. Most commonly, the anomalies associated with gastroschisis are cardiac and central nervous system abnormalities. Respiratory insufficiency has sometimes been reported in association with giant abdominal wall defects. Poor outcomes and prolonged ventilator support have been reported in giant gastroschisis and omphalocele, especially if associated with herniation of the majority of the liver. We report a case of a large gastroschisis that was associated with a kyphoscoliosis and pulmonary hypoplasia.

Congenital second-degree heart block and total anomalous pulmonary venous return associated with microduplication of 1q32.2.

We report a term female infant with congenital heart block and total anomalous of pulmonary venous return. The results of single nucleotide polymorphism oligonucleotide microarray analysis showed an interstitial duplication of approximately 818 Kb, which involved 11 genes, including the entire LAMB3 gene which is known to associate with cardiac conduction defect. Our report adds to the collective knowledge that the cardiac conduction defect is a clinical feature of chromosome 1q32.2 duplication.

Pulmonary Vasculitis and a Horseshoe Kidney in Noonan Syndrome.

We report a term male neonate with congenital myeloproliferative disorder, thrombocytopenia, a horseshoe kidney, feeding difficulty secondary to dysphagia/foregut dysmotility, and respiratory failure. Prenatal molecular genetic analysis revealed a fetus carrying c.184T>G (p.Tyr62Asp) pathogenic variant in PTPN11. The infant eventually succumbed to respiratory failure. Bacterial and viral cultures/studies were all no growth/negative. Pulmonary capillaritis and vasculitis were noted at autopsy. This report presents a new case of Noonan syndrome with unusual associated disorders and a review of the literature.

Cleidocranial Dysplasia with 6p21.1-p12.3 Microdeletion: A Case Report and Literature Review.

OBJECTIVE: The aim of this article is to publish a literature review and report on a new case of cleidocranial dysplasia syndrome with 6p21.1-p12.3 microdeletion. DESIGN: A PubMed search using "cleidocranial dysplasia syndrome (CCD)" or "6p microdeletion" was performed. Articles with information relevant to our case were obtained for review. A new case of cleidocranial dysplasia syndrome is presented to describe and discuss clinical manifestations, pathogenesis, clinical progression of cleidocranial dysplasia syndrome, and management. RESULTS: There were 22 articles with reports of cleidocranial dysplasia syndrome or 6p microdeletion. Cleidocranial dysplasia syndrome, a rare genetic disorder, documented to have an autosomal dominant inheritance pattern and caused by caused by mutations of the transcription factor RUNX2. RUNX2 has been mapped to chromosome 6p21. The anomalies in cleidocranial dysplasia syndrome can involve not only the clavicle and skull but the entire skeleton because the membranous as well as endochondral bone formation may be affected. Upon follow-up, our patient was found to have global developmental delay. CONCLUSIONS: We report a near-term neonate with characteristic features of cleidocranial dysplasia and a 6p21.1-p12.3 microdeletion. Cleidocranial dysplasia syndrome is a rare autosomal dominant skeletal dysplasia. The mutation of the RUNX2 gene results in cleidocranial dysplasia syndrome.

Vessel Perforation and False Tracking Resulting From Umbilical Artery Catheterization: A Case Report and Literature Review.

We report an extremely low-birth-weight neonate who developed umbilical artery perforation and false tracking. There was no life-threatening event relating to the complication. Diagnosis was made at postmortem examination. Little information exists regarding the anatomic and vascular effects of umbilical artery catheterization placement in newborns. We report a new complication of umbilical artery catheterization. We raise the awareness regarding the potential life threat due to this rare but very serious complication.