Vein of Galen Aneurysmal Malformation Presenting As Persistent Pulmonary Hypertension in a Newborn: A Case Report.

We present a case of a newborn infant with a vein of Galen aneurysmal malformation (VOGM) who was admitted to our neonatal intensive care unit (NICU) with the diagnosis of persistent pulmonary hypertension of the newborn (PPHN). Further work-up at our institution, which included an echocardiogram and cranial ultrasound revealed VOGM. The patient was transferred to a children's center for further management of the vascular malformation where the patient subsequently died from high cardiac output heart failure. This study highlights the importance of considering a VOGM as a rare cause of PPHN in an infant.

Impact of severity and age with variable definitions of bronchopulmonary dysplasia on neurodevelopmental outcomes.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental impairment (NDI). METHODS: To compare the ability of NICHD 2001 and Jensen 2019 definitions of BPD and respiratory support at 40 weeks postmenstrual age (PMA) to predict NDI, a retrospective study (1/2010-12/2020) was conducted in infants with gestational age <32 weeks and birth weight <1500 g. The primary outcome measure was NDI at 18-24 months corrected age. RESULTS: Of 1119 infants, 227 (20.7%) met the inclusion criteria and had adequate follow-up data. Multivariate regression analysis showed that the NICHD 2001 definition was not predictive of NDI. Infants with Grade 2 or 3 BPD (Jensen 2019) had 4.75 (95% CI: 1.282-17.563) times greater odds of having NDI than infants without BPD. Infants requiring respiratory support at 40 weeks PMA had 4.95 (95% CI: 1.490-16.47) times greater odds of having NDI. Receiver operating characteristic curves demonstrated that the 2 definitions of BPD and the need for respiratory support at 40 weeks PMA were similar in their ability to predict NDI. CONCLUSION: There is no significant difference in the ability of the NICHD 2001 and Jensen 2019 BPD definitions, as well as the need for respiratory support at 40 weeks, for predicting NDI. IMPACT STATEMENT: Current bronchopulmonary dysplasia (BPD) definitions may not effectively predict neurodevelopmental impairment (NDI) in preterm infants. Grades 2/3 BPD (Jensen 2019 criteria) significantly associate with NDI. Infants requiring respiratory support at 40 weeks post-menstrual age (PMA) have 5 times higher odds of NDI than those on room air at 40 weeks PMA. The NICHD 2001, Jensen 2019 definitions, and the requirement for respiratory support at 40 weeks PMA, do not differ in their ability to predict NDI. Future studies should include multiple centers, with level III-IV NICUs, catering to socioeconomic, culturally, and racially diverse populations.

Hepatitis C Exposure Diagnosis and Testing in Infants Born to Hepatitis C Virus-infected Mothers.

BACKGROUND: There has been a 5-fold increase in the number of cases of hepatitis C virus (HCV) infection among pregnant women, which is potentially associated with the increase in opioid use. METHODS: This study was a retrospective review of infants born at a tertiary urban hospital in New Jersey, from January 1, 2011 to January 1, 2021, who were born to mothers with a prenatal diagnosis of HCV. RESULTS: Of the 142 mothers with a prenatal diagnosis of HCV, 114 (80%) infants had a diagnosis of HCV exposure in the electronic health records. Of the HCV-exposed infants with follow-up data at 24 months of age, 52 (46%) were tested, with 34 of 52 (65%) receiving adequate testing. Infants documented as HCV exposed were more likely to be born to a mother with nonopioid drug use in pregnancy ( P = 0.01) and have a higher birth weight ( P = 0.03). Of tested infants, those with a higher number of well-child pediatrician visits ( P = 0.01) were more likely to receive adequate testing. Trends showed more polymerase chain reaction testing than antibody testing for those who were inadequately tested. CONCLUSIONS: A significant proportion of infants born to HCV-infected mothers were either not identified at birth (20%) or did not receive adequate testing on follow-up (35%). Further work needs to be done to improve documentation of HCV exposure at birth and follow-up testing to avoid missing congenitally acquired HCV.

Iron Deficiency Prior to Discharge in Very Low Birth Weight Infants: Screening with Reticulocyte Hemoglobin Content.

OBJECTIVE: This study aimed to assess the iron status prior to discharge in very low birth weight (VLBW) infants utilizing reticulocyte hemoglobin content (CHr) and evaluate the impact of delayed cord clamping (DCC) on iron status. STUDY DESIGN: This is a retrospective analysis of VLBW infants from two tertiary level of care Neonatal Intensive Care Units. The primary outcome was the proportion of VLBW infants with low CHr (<29 pg) prior to discharge. Hematologic parameters were also compared between infants who received or did not receive DCC. Infants with a positive newborn screen for hemoglobin Bart's were excluded. RESULTS: Among the 315 infants included, 99 infants (31.4%) had low CHr prior to discharge. The median (interquartile range) CHr prior to discharge was 30.8 pg (28.4-39 pg). DCC was performed in 46.7% of infants. Hemoglobin at birth, discharge, and CHr prior to discharge were higher and the need for blood transfusion and the number of infants with low CHr prior to discharge were lower in the DCC group. CONCLUSION: Approximately 31.4% of VLBW infants had low CHr near the time of discharge suggesting they were iron deficient. DCC improved hematological parameters prior to discharge in VLBW infants. CHr content can be used to guide iron supplementation in VLBW infants to potentially improve their iron status and long-term neurocognitive outcomes. KEY POINTS: · DCC was associated with an improved hemoglobin and iron status at discharge in VLBW infants.. · CHr is an early and reliable marker for iron deficiency.. · Approximately one in three VLBW infants can be iron deficient at the time of discharge..

Delayed Cord Clamping for 45 Seconds in Very Low Birth Weight Infants: Impact on Hemoglobin at Birth and Close to Discharge.

OBJECTIVE: To assess the impact of delayed cord clamping (DCC) for 45 seconds on hemoglobin at birth and close to discharge in very low birth weight (VLBW) infants and to compare modes of delivery in infants who received DCC. STUDY DESIGN: In a retrospective study, 888 VLBW infants (≤1,500 g) who survived to discharge and received immediate cord clamping (ICC) were compared with infants who received DCC. Infants who received DCC and born via Cesarean section (C-section) were compared with those born via vaginal birth. RESULTS: A total of 555 infants received ICC and 333 DCC. Only 188 out of 333 VLBW infants (56.5%) born during the DCC period received DCC. DCC was associated with higher hemoglobin at birth (15.9 vs. 14.9 g/dL, p = 0.001) and close to discharge (10.7 vs. 10.1 g/dL, p < 0.001) and reduced need for blood transfusion (39.4 vs. 54.9%, p < 0.001). In the DCC group, hemoglobin at birth and close to discharge was similar in infants born via C-section and vaginal birth. CONCLUSION: DCC for 45 seconds increased hemoglobin at birth and close to discharge and reduced need for blood transfusion in VLBW infants. DCC for 45 seconds was equally effective for infants born by C-section and vaginal delivery. Approximately 44% of VLBW infants did not receive DCC even after implementing DCC guidelines. KEY POINTS: · Studies to date have shown that DCC improves mortality and short- and long-term outcomes in VLBW infants.. · No consistent guidelines for the duration of DCC in preterm and term neonates.. · DCC for 45 seconds increased hemoglobin at birth and close to discharge in VLBW infants..

Does Neonatal Sepsis Independently Increase Neurodevelopmental Impairment?

Editorial Comment on: Short- and long- term neurodevelopmental outcomes of very preterm infants with neonatal sepsis: a systematic review and meta-analysis [...].

Stopping caffeine in premature neonates: how long does it take for the level of caffeine to fall below the therapeutic range?

BACKGROUND: Caffeine is routinely used in preterm infants for apnea of prematurity. Preterm infants are usually monitored for 5 days after discontinuation of caffeine to assess for possible recurrence of apnea. Our objective was to determine if the serum concentration of caffeine decreases to a subtherapeutic level 5 days after its discontinuation. METHODS: This is a retrospective analysis of caffeine levels after the drug was discontinued in preterm neonates (birth weight ≤1500 g) born between January 2010 and June 2017. The primary outcome was the proportion of infants with therapeutic levels of caffeine 5 days after the drug was stopped. RESULTS: Caffeine levels were measured in 353 samples from 280 infants (birth weight 1246 ± 390 g and gestational age 29.2 ± 2.4 weeks) after discontinuation of the drug. Five and more days after discontinuation of caffeine, 29.3% (82/280) of the infants had caffeine levels ≥5 mg/L. Approximately 41% (75/181) of the caffeine levels measured between 5 and 7 days and 18% (17/95) between 8 and 10 days were ≥5 mg/L. A caffeine dose of >5 mg/kg/day when discontinued was associated with the caffeine level of ≥5 mg/L (OR 2.3, 95% CI 1.28-4.13, p = .005). CONCLUSIONS: Preterm infants treated with caffeine frequently had therapeutic levels of caffeine 5-10 days after discontinuation of the drug. The infants receiving higher doses were more likely to have a therapeutic level of caffeine 5 days after stopping the medication. Preterm infants should be monitored for recurrence of apnea for more than 5 days after stopping caffeine or levels should be monitored prior to discharge.

Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families.

Isolated Microspherophakia (MSP) is an autosomal recessive disorder characterized by a smaller than normal spherical lens. Till date, LTBP2 is the only gene shown to cause MSP. We used homozygosity mapping and whole-exome sequencing and identified a homozygous mutation, c.1148C > T (p.Pro383Leu), in the WDR8 (or WRAP73) gene in two Indian MSP families. In vitro experiments showed that the missense mutation renders the protein unstable. WDR8 is a centriolar protein that has important roles in centrosomal assembly, spindle pole formation and ciliogenesis. Co-immunoprecipitation experiments from HeLa cells indicated that the mutation interferes with the interaction of WDR8 with its binding partners. In zebrafish, both morpholino-mediated knockdown and CRISPR/Cas knockout of wdr8 resulted in decreased eye and lens size. The lack of wdr8 affected cell cycle progression in the retinal cells, causing a reduction in cell numbers in the retina and lens. The reduction in eye size and the cell cycle defects were rescued by exogenous expression of the human wild-type WDR8. However, the human mutant WDR8 (p.Pro383Leu) was unable to rescue the eye defects, indicating that the missense mutation abrogates WDR8 protein function. Thus, our zebrafish results suggested that WDR8 is the causative gene for MSP in these Indian families.

Gastroschisis: A State-of-the-Art Review.

Gastroschisis, the most common type of abdominal wall defect, has seen a steady increase in its prevalence over the past several decades. It is identified, both prenatally and postnatally, by the location of the defect, most often to the right of a normally-inserted umbilical cord. It disproportionately affects young mothers, and appears to be associated with environmental factors. However, the contribution of genetic factors to the overall risk remains unknown. While approximately 10% of infants with gastroschisis have intestinal atresia, extraintestinal anomalies are rare. Prenatal ultrasound scans are useful for early diagnosis and identification of features that predict a high likelihood of associated bowel atresia. The timing and mode of delivery for mothers with fetuses with gastroschisis have been somewhat controversial, but there is no convincing evidence to support routine preterm delivery or elective cesarean section in the absence of obstetric indications. Postnatal surgical management is dictated by the condition of the bowel and the abdominal domain. The surgical options include either primary reduction and closure or staged reduction with placement of a silo followed by delayed closure. The overall prognosis for infants with gastroschisis, in terms of both survival as well as long-term outcomes, is excellent. However, the management and outcomes of a subset of infants with complex gastroschisis, especially those who develop short bowel syndrome (SBS), remains challenging. Future research should be directed towards identification of epidemiological factors contributing to its rising incidence, improvement in the management of SBS, and obstetric/fetal interventions to minimize intestinal damage.

Genetic analysis of ATP7B in 102 south Indian families with Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ATP7B. We report here the genetic analysis of 102 WD families from a south Indian population. Thirty-six different ATP7B mutations, including 13 novel ones [p.Ala58fs*19, p.Lys74fs*9, p.Gln281*, p.Pro350fs*12, p.Ser481*, p.Leu735Arg, p.Val752Gly, p.Asn812fs*2, p.Val845Ala, p.His889Pro, p.Ile1184fs*1, p.Val1307Glu and p.Ala1339Pro], were identified in 76/102 families. Interestingly, the mutation analysis of affected individuals in two families identified two different homozygous mutations in each family, and thus each affected individual from these families harbored two mutations in each ATP7B allele. Of 36 mutations, 28 were missense, thus making them the most prevalent mutations identified in the present study. Nonsense, insertion and deletion represented 3/36, 2/36 and 3/36 mutations, respectively. The haplotype analysis suggested founder effects for all the 14 recurrent mutations. Our study thus expands the mutational landscape of ATP7B with a total number of 758 mutations. The mutations identified during the present study will facilitate carrier and pre-symptomatic detection, and prenatal genetic diagnosis in affected families.

Pharmacological Inhibition of Serine Palmitoyl Transferase and Sphingosine Kinase-1/-2 Inhibits Merkel Cell Carcinoma Cell Proliferation.

The majority of Merkel cell carcinoma, a highly aggressive neuroendocrine cancer of the skin, is associated with Merkel cell polyomavirus infection. Polyomavirus binding, internalization, and infection are mediated by glycosphingolipids. Besides receptor function, bioactive sphingolipids are increasingly recognized as potent regulators of several hallmarks of cancer. Merkel cell polyomavirus+ and Merkel cell polyomavirus- cells express serine palmitoyl transferase subunits and sphingosine kinase (SK) 1/2 mRNA. Induced expression of Merkel cell polyomavirus-large tumor antigen in human lung fibroblasts resulted in upregulation of SPTLC1-3 and SK 1/2 expression. Therefore, we exploited pharmacological inhibition of sphingolipid metabolism as an option to interfere with proliferation of Merkel cell polyomavirus+ Merkel cell carcinoma cell lines. We used myriocin (a serine palmitoyl transferase antagonist) and two SK inhibitors (SKI-II and ABC294640). In MKL-1 and WaGa cells myriocin decreased cellular ceramide, sphingomyelin, and sphingosine-1-phosphate content. SKI-II increased ceramide species but decreased sphingomyelin and sphingosine-1-phosphate concentrations. Aberrant sphingolipid homeostasis was associated with reduced cell viability, increased necrosis, procaspase-3 and PARP processing, caspase-3 activity, and decreased AKTS473 phosphorylation. Myriocin and SKI-II decreased tumor size and Ki-67 staining of xenografted MKL-1 and WaGa tumors on the chorioallantoic membrane. Our data suggest that pharmacological inhibition of sphingolipid synthesis could represent a potential therapeutic approach in Merkel cell carcinoma.

A short-term in vivo model for Merkel Cell Carcinoma.

In vivo tumor models are essential for studying the biology of cancer, identifying tumor targets and evaluating antitumor drugs. Considering the request for the minimisation of animal experiments and following the "3R"-rule ("replacement," "refinement," "reduction"), it has become crucial to develop alternative experimental models in cancer biology. Several studies have already described the avian chorioallantoic membrane (CAM) model as an alternative to rodents, suitable to investigate growth, progression and metastasis of various types of cancer. In the present work, we grafted three Merkel cell carcinoma (MCC) cell lines onto the avian CAM and monitored tumor growth and development of solid tumor nodules. Morphology of xenograft was characterised histologically and immunohistochemically. Our results demonstrate CAM assay as a useful tool to study MCC pathophysiology.

A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

Anencephaly (APH) is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to APH. APH shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of APH has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C > A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive APH in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silico analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared with cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to APH.

Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex.

Mutations in PLA2G6 were identified in patients with a spectrum of neurodegenerative conditions, such as infantile neuroaxonal dystrophy (INAD), atypical late-onset neuroaxonal dystrophy (ANAD) and dystonia parkinsonism complex (DPC). However, there is no report on the genetic analysis of families with members affected with INAD, ANAD and DPC from India. Therefore, the main aim of this study was to perform genetic analysis of 22 Indian families with INAD, ANAD and DPC. DNA sequence analysis of the entire coding region of PLA2G6 identified 13 different mutations, including five novel ones (p.Leu224Pro, p.Asp283Asn, p.Arg329Cys, p.Leu491Phe, and p.Arg649His), in 12/22 (54.55%) families with INAD and ANAD. Interestingly, one patient with INAD was homozygous for two different mutations, p.Leu491Phe and p.Ala516Val, and thus harboured four mutant alleles. With these mutations, the total number of mutations in this gene reaches 129. The absence of mutations in 10/22 (45.45%) families suggests that the mutations could be in deep intronic or promoter regions of this gene or these families could have mutations in a yet to be identified gene. The present study increases the mutation landscape of PLA2G6. The present finding will be useful for genetic diagnosis, carrier detection and genetic counselling to families included in this study and other families with similar disease condition.

Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an Indian family with Weill-Marchesani syndrome.

PURPOSE: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder, characterized by short stature, microspherophakic lens, and stubby hands and feet (brachydactyly). WMS is caused by mutations in the FBN1, ADAMTS10, and LTBP2 genes. Mutations in the LTBP2 and ADAMTS17 genes cause a WMS-like syndrome, in which the affected individuals show major features of WMS but do not display brachydactyly and joint stiffness. The main purpose of our study was to determine the genetic cause of WMS in an Indian family. METHODS: Whole exome sequencing (WES) was used to identify the genetic cause of WMS in the family. The cosegregation of the mutation was determined with Sanger sequencing. Reverse transcription (RT)-PCR analysis was used to assess the effect of a splice-site mutation on splicing of the ADAMTS17 transcript. RESULTS: The WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in a known WMS-like syndrome gene, ADAMTS17, in the family. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. CONCLUSIONS: The mutation in the WMS-like syndrome gene ADAMTS17 also causes WMS in an Indian family. The present study will be helpful in genetic diagnosis of this family and increases the number of mutations of this gene to six.

Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin.

The TSC2 gene, mutated in patients with tuberous sclerosis complex (TSC), encodes a 200 kDa protein TSC2 (tuberin). The importance of TSC2 in the regulation of cell growth and proliferation is irrefutable. TSC2 in complex with TSC1 negatively regulates the mTOR complex 1 (mTORC1) via RHEB in the PI3K-AKT-mTOR pathway and in turn regulates cell proliferation. It shows nuclear as well as cytoplasmic localization. However, its nuclear function remains elusive. In order to identify the nuclear function of TSC2, a whole-genome expression profiling of TSC2 overexpressing cells was performed, and the results showed differential regulation of 266 genes. Interestingly, transcription was found to be the most populated functional category. EREG (Epiregulin), a member of the epidermal growth factor family, was found to be the most downregulated gene in the microarray analysis. Previous reports have documented elevated levels of EREG in TSC lesions, making its regulatory aspects intriguing. Using the luciferase reporter, ChIP and EMSA techniques, we show that TSC2 binds to the EREG promoter between -352 bp and -303 bp and negatively regulates its expression. This is the first evidence for the role of TSC2 as a transcription factor and of TSC2 binding to the promoter of any gene.

Clinical phenotype and the lack of mutations in the CHRNG, CHRND, and CHRNA1 genes in two Indian families with Escobar syndrome.

The objective of this study was to report the clinical phenotype and genetic analysis of two Indian families with Escobar syndrome (ES). The diagnosis of ES in both families was made on the basis of published clinical features. Blood samples were collected from members of both families and used in genomic DNA isolation. The entire coding regions and intron-exon junctions of the ES gene CHRNG (cholinergic receptor, nicotinic, gamma), and two other related genes, CHRND and CHRNA1, were amplified and sequenced to search for mutations in both families. Both families show a typical form of ES. Sequencing of the entire coding regions including the intron-exon junctions of the three genes did not yield any mutations in these families. In conclusion, it is possible that the mutations in these genes are located in the promoter or deep intronic regions that we failed to identify or the ES in these families is caused by mutations in a different gene. The lack of mutations in CHRNG has also been reported in several families, suggesting the possibility of at least one more gene for this syndrome.

Detection of pepsin in mouth swab: correlation with clinical gastroesophageal reflux in preterm infants.

OBJECTIVE: To study the relationship between pepsinogen/pepsin in a mouth swab and clinical gastroesophageal reflux (GER) in preterm infants. METHODS: Preterm infants (birth weight ≤ 2000 g) on full enteral feeds were enrolled. Mouth swabs from cheek and below the tongue were collected one, two and three hours after feeding. An enzymatic assay with substrate fluorescein isothiocyanate-casein was used to detect pepsin A and C activities with further confirmation by western blot. Blinded investigators reviewed the infant's medical record to clinically diagnose GER. RESULTS: A total of 101 premature infants were enrolled. Pepsinogen/pepsin was detected in 45/101 (44.5%) infants in at least one sample. A clinical diagnosis of GER was made in 36/101 (35.6%) infants. Mouth swabs were positive in 26/36 (72%) infants with clinical GER and only 19/65 (29%) infants without GER (p < 0.001). Similarly, the levels of pepsinogen/pepsin A and C were higher in the mouth swabs of infants with clinical GER. CONCLUSION: The detection of pepsinogen/pepsin in a mouth swab correlates with clinical GER in premature infants.

IFN-γ and IP-10 in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia.

BACKGROUND: Interferon-gamma (IFN-γ) and interferon-inducible protein of 10 kDa (IP-10) are potent inflammatory mediators and contribute to acute lung injury in adults. Recently, a potential role for IFN-γ and IP-10 in the pathogenesis of bronchopulmonary dysplasia (BPD) has been reported in animal models. OBJECTIVE: To study the association between IFN-γ and IP-10 in tracheal aspirate (TA) and the development of BPD in premature infants. DESIGN/METHODS: TA samples collected within 48 hr after birth from 79 mechanically ventilated premature neonates [gestational age (GA) <30 weeks (w), birth weight (BW) <1,250 g (g)] were analyzed. IFN-γ was measured in a subgroup of 38 infants by using a biochip multi-analyte immunoassay. The level of IP-10 was determined using a commercially available ELISA kit. Total protein in TA was measured by Bradford assay to correct for sampling related dilution. BPD was defined as the need of supplemental oxygen at 36 weeks postmenstrual age (PMA). RESULTS: Twenty infants (GA 26.4 ± 1.9w, BW 860 ± 201 g) survived without BPD at 36 weeks PMA and 59 infants (GA 25.5 ± 1.5w, BW 751 ± 163 g) died before 36 weeks PMA or developed BPD. The mean IFN-γ level was higher in infants who died or developed BPD (9.7 ± 2.8 vs. 3.1 ± 1.1 pg/ml, P = 0.03). Similarly, the mean IP-10 level was higher in infants who died or developed BPD (63.4 ± 17.5 pg/ml) compared to those who survived without BPD (18.5 ± 7.5 pg/ml, P = 0.02). CONCLUSIONS: Higher IFN-γ and IP-10 levels in TA samples are associated with the development of BPD or death in premature infants.