Impact of postnatal steroids on peripheral avascular retina and severity of retinopathy of prematurity.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

Characteristics of Newborns Born to SARS-CoV-2-Positive Mothers: A Retrospective Cohort Study.

OBJECTIVE: The novel virus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to a terrifying pandemic. The range of illness severity among children is variable. This study aims to assess the characteristics of newborns born to SARS-CoV-2-positive women compared with those mothers who tested negative. STUDY DESIGN: This was a retrospective cohort study performed at Brookdale Hospital Medical Center in New York City from March to May 2020. Electronic medical records of mother-baby dyads were reviewed. RESULTS: Seventy-nine mothers tested for SARS-CoV-2 were included, out of which 18.98% of mothers tested SARS-CoV-2 positive. We found a significant association between symptoms and SARS-CoV-2 status. We observed a significant association between newborns of SARS-CoV-2 positive and SARS-CoV-2 negative mothers regarding skin-to-skin contact (p < 0.001). Both groups showed significant differences regarding isolation (p < 0.001). Interestingly, regarding SARS-CoV-2 infection in newborns, only one newborn tested SARS-CoV-2 positive and was unstable in the neonatal intensive care unit (NICU). With the multivariable logistic regression model, babies of SARS-CoV-2 positive mothers were three times as likely to have desaturations in comparison to newborns from negative mothers. Also, newborns of SARS-CoV-2-positive mothers were four times more likely to have poor feeding, compared with newborns of SARS-CoV-2-negative mothers. Finally, babies of SARS-CoV-2-positive mothers were ten times more likely to be symptomatic at the 2-week follow-up. CONCLUSION: SARS-CoV-2 has caused major morbidity and mortality worldwide. Neonates born to mothers with confirmed or suspected SARS-CoV-2 are most of the time asymptomatic. However, neonatal critical illness due to SARS-CoV-2 is still a possibility; thus, isolation precautions (such as avoiding skin-to-skin contact and direct breastfeeding) and vertical transmission should be studied thoroughly. In addition, testing these newborns by nasopharyngeal swab at least at 24 hours after birth and monitoring them for the development of symptoms for 14 days after birth is needed. KEY POINTS: · For SARS-CoV-2-positive mothers, reducing transmission of infection to newborns is crucial.. · Newborns of SARS-CoV-2-positive mothers are usually asymptomatic and may not be easily infected.. · Critical illness in the newborn may still happen, so monitoring is needed..

Hospital Factors Associated with the Survival of Infants Born at Periviable Gestation: The USA National Database.

Background: Reports on the survival of infants born at periviable gestation (GA of ≤24 weeks and birth weight of <500 gm) vary significantly. We aimed to determine hospital factors associated with their survival and to assess the trend for the timing of postnatal mortality in these periviable infants. Methods: We utilized the de-identified National Inpatient Sample (NIS) dataset of the Healthcare Cost and Utilization Project (HCUP) from the Agency for Healthcare Research and Quality (AHRQ). National data were analyzed for the years 2010-2018. Hospitals were categorized according to delivery volume, USA regions, and teaching status. Results: We identified 33,998,014 infants born during the study period; 76,231 infants were ≤24 weeks. Survival at birth and first 2 days of life was greatest in urban teaching hospitals in infants <24 weeks and those who completed 24 weeks, respectively. The Northeast region has the lowest survival rate. There was a significant delay in the postnatal day of mortality in periviable infants. Conclusions: Hospital factors are associated with increased survival rates. Improved survival in large teaching hospitals supports the need for the regionalization of care in infants born at the limits of viability. There was a significant delay in the postnatal mortality day.

Characteristics of fecal calprotectin as an early marker for suspected necrotizing enterocolitis in newborns exclusively fed maternal breast milk: a case-control study.

Objective: Numerous studies have proposed using fecal calprotectin among many biomarkers associated with necrotizing enterocolitis (NEC) diagnosis. This study aimed to evaluate fecal calprotectin as an early marker for suspected NEC (stage 1) in infants fed exclusively breast milk. Methods: We collected 20 stool samples from newborns admitted to the neonatal intensive care unit at Aswan University Hospital diagnosed with stage I NEC. We compared them with 20 samples from matched healthy newborns. Fecal calprotectin level was measured by enzyme-linked immunosorbent assay. Results: Fecal calprotectin level was higher in cases than in the control group (P < 0.001). Also, there was a positive correlation between fecal calprotectin and C-reactive protein in the studied cases (P = 0.001). However, there were no correlations between fecal calprotectin and sex or postnatal age. Conclusion: Fecal calprotectin levels increase in newborns with stage I NEC. Although not specific, its sensitivity suggests a role as a potential biomarker in the evaluation of suspected NEC.

Placental abruption and risk for intraventricular hemorrhage in very low birth weight infants: the United States national inpatient database.

OBJECTIVE: To examine the association of placental abruption with intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. METHODS: We examined the National Inpatient Sample (NIS) datasets. Preterm infants <1500 g birth weight (BW) were included. The odds ratios (OR) of developing IVH and severe IVH in association with placental abruption were calculated. Adjusted OR (aOR) were calculated using logistic regression models. RESULTS: The study included 113,445 VLBW infants. IVH occurred in 18.7% in the infants who were born to mothers with history of placental abruption versus 14.7% in infants without placental abruption, aOR 1.25 (95%CI: 1.13-1.38), p < 0.001. Severe IVH occurred in 6.4% in infants born to mothers with history of placental abruption versus 4.0% in those without placental abruption, aOR 1.53 (95%CI: 1.30-1.78), p < 0.001. CONCLUSION: Placental abruption is associated with increased prevalence of IVH and severe IVH in VLBW infants.

Glucose instability and outcomes of neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia.

BACKGROUND: To investigate the prevalence and associated outcomes of glucose abnormalities in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Glucose values were reviewed in all HIE infants. Pearson's correlation was used to assess the association of hypo- and hyperglycemic episodes with neonatal brain MRI and neurodevelopmental outcomes (NDO) at 12 & 24 months. RESULTS: Of 153 infants included, 31, 56 and 43 had episodes of hypo-, hyperglycemia and combined, respectively. Hyperglycemia and combined hypo/hyper had higher mortality (p = 0.035), seizures (p = 0.009), and longer hospitalization (p = 0.023). Hypo- and hyperglycemia were associated with parenchymal hemorrhages (p = 0.028 & p = 0.027, respectively). Hypoglycemia was associated with restricted diffusion (p = 0.014), while hyperglycemia was associated with cortical injuries (p = 0.045). Each hour of hyper- or hypoglycemia was associated with 5.2-5.8 times unfavorable outcomes (p < 0.001). CONCLUSION: Blood glucose aberrations were detrimental in HIE infants treated with TH. Optimizing glucose management is crucial in this setting.

The accessibility and safety of inserting proximal basilic and axillary veins central lines in neonates.

Objectives: to evaluate the accessibility, success rate, and attributable complications and to describe the maneuver for central line insertion via proximal basilic or axillary veins in neonates. Methods: This retrospective study included all infants admitted to the neonatal intensive care unit and had an axillary central line inserted or attempted. Success rate, complications, and outcomes were reviewed. Results: Axillary central line was attempted in 85 infants and was successful in 78 infants with a success rate of 91.7%. The median postnatal age of patients was 8 days (2 days-92 days), and the median weight of patients at the procedure was 2600 g (590 g-3900 g). The median corrected gestational age of patients at the procedure was 36 weeks (23 weeks-46 weeks). No serious complication was observed in any of the 85 infants. Conclusion: This study demonstrated a high success rate for insertion of proximal basilic and axillary veins central lines in neonates with difficult vascular access. This procedure was feasible in very low birth and extremely low birth preterm infants, especially in those who failed previous central line attempts.

Intracranial hemorrhages in infants of diabetic mothers: A national cohort study.

OBJECTIVE: To assess the association of maternal diabetes mellitus (DM) with intraventricular hemorrhage (IVH) and other intracranial hemorrhages (ICH) in newborns. STUDY DESIGN: We analyzed the National Inpatient Sample dataset and compared prevalence of IVH and other subtypes of ICH in infants of diabetic mothers (IDMs) vs. those born to mothers without DM. Regression models were used to control for demographic and clinical confounding variables. RESULT: A total of 11,318,691 infants were included. Compared to controls, IDMs had increased prevalence of IVH (aOR = 1.18, CI: 1.12-1.23, p < 0.001) and other ICH (aOR = 1.18, CI: 1.07-1.31, p = 0.001). Severe IVH (grades 3 & 4) was encountered less frequently in IDMs (aOR = 0.75, CI: 0.66-0.85, p < 0.001) than controls. Gestational DM was not associated with increased IVH after controlling for the demographic, clinical and perinatal confounders in the logistic regression model (aOR = 1.04, CI: 0.98-1.11, p = 0.22). CONCLUSION: Chronic maternal DM is associated with increased neonatal IVH and other ICH but not severe IVH. This association needs to be confirmed in further studies.

Chorioamnionitis, Cesarean Deliveries, and Racial Disparities in the USA.

BACKGROUND: Studies showed disparities in management and outcomes of African American when compared to Caucasian population. The presence of chorioamnionitis may affect the decision to have a cesarean delivery (CD); however, it is not known if such a decision is affected by the mothers' race/ethnicity. OBJECTIVE: To assess the interaction between African American race/ethnicity and CD in women with chorioamnionitis. METHODS: Utilizing the National Inpatient Sample dataset, we examined the association of CD with chorioamnionitis in the overall population and within Caucasian and African American. Logistic regression models were used to control for confounders. RESULTS: The study included 6,648,883 women who delivered 6,925,920 infants. The prevalence of chorioamnionitis was 0.78 and 1.1 in Caucasian and African American, respectively. CD with and without chorioamnionitis was 41.2% and 32.4%, respectively (aOR 1.46 (1.43-1.49), p < 0.001), in Caucasian population and 45.0% and 36.6% in African American population aOR 1.42 (1.37-1.47), p < 0.001. African American population had significantly higher CD after controlling for chorioamnionitis and other confounding variables (aOR of 1.18 (1.17-1.18), p < 0.001). CONCLUSION: Chorioamnionitis is associated with increased rate of CD. Ethnic disparities exist in CD rates regardless of the chorioamnionitis status. Such findings warrant further investigation to explore factors associated with this discrepancy.

Survival of infants born at periviable gestation: The US national database.

Background: Substantial differences exist in the approach to resuscitating infants born at periviable gestation. Evaluation of current survival may help guide prenatal counselling and provide accurate expectations of clinical outcomes. We aimed to assess the US national survival trends in periviable infants born at gestational age (GA) ≤24 weeks. Methods: We used de-identified patient data obtained from the US Healthcare Cost and Utilization Project (HCUP) from 2007 to 2018. All infants with documented GA ≤24 weeks were included. The Cochran-Armitage test was used for trend analyses. Regression analyses were conducted for variables associated with survival. Findings: A total of 44,628,827 infant records were identified with 124,345 (0.28%) infants born ≤24 weeks; of those, 77,050 infants <24 weeks and 47,295 infants had completed 24 weeks. Survival rates for infants <24 weeks and with completed 24 weeks were 15.4% and 71.6%, respectively, with higher survival over the years (Z = 9.438, P<0.001 & Z = 3.30, P<0.001, respectively). Survival was lower in males compared to females (aOR = 0.96, CI: 0.93-0.99 & aOR = 0.94, CI: 0.92-0.96, respectively) and with private insurance compared to public insurance (aOR = 0.74, CI: 0.71-0.77 & aOR = 0.67, CI: 0.65-0.69, respectively). Survival was higher when birth weight was >500 g compared to ≤500 g (aOR = 4.62, CI:3.23-5.02 & aOR = 5.44, CI: 4.59-5.84, respectively). Black (aOR = 1.33, CI: 1.31-1.36 & aOR = 1.24, CI: 1.20-1.32, respectively) and Hispanic (aOR = 1.29, CI: 1.27-1.32 & aOR = 1.27, CI: 1.22-1.30, respectively) had higher survival than White. Interpretation: There is a national increase in survival over the years in infants born at periviable GA. BW >500 is associated with >4 folds higher survival compared to ≤500 g. The results of this study should be cautiously interpreted as long-term outcomes are unknown. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Association of IL-10 gene polymorphisms and susceptibility to Juvenile Idiopathic Arthritis in Egyptian children and adolescents: a case-control study.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children worldwide. Among anti-inflammatory cytokines, interleukin-10 (IL-10) is a key immunosuppressive cytokine involved in the pathogenesis of JIA. To date, only a few studies concerned the association of interleukin-10 gene polymorphisms with JIA. In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -1082(G/A), -819(C/T), and -592(C/A) in the promoter region of the IL-10 gene to determine whether this polymorphism could be a marker of susceptibility to JIA in Egyptian children and adolescents. We also measured the serum level of IL-10 to assess its relation to such polymorphism. METHODS: This was a case-control study included 100 patients diagnosed with JIA, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-10 -1082(G/A), -819(C/T), and -592(C/A) polymorphisms were genotyped by amplification refractory mutation system- polymerase chain reaction (ARMS)-PCR methodology, while the serum IL10 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of IL-10- AA genotype and A allele at the -1082 position were overrepresented in patients with JIA (OR = 2.7; 95% CI: 1.1-6.4 for the AA genotype; P <0.05 and OR: 1.5; 95% CI: 1.03-2.3 for the A allele; P <0.05 respectively). On the other hand, no significant differences were found between the 2 groups in the genotype or allele frequencies for the -819 and -592 positions. Of note, we found a significant positive association between the IL-10 (-1082) AA genotype and susceptibility to polyarticular JIA (OR: 4.3; 95% CI: 1.5-12.7; P <0.01). We observed that patients with the IL-10 (-1082) AA genotype had significantly lower serum IL-10 levels (2.3 ± 0.9 pg/ml) compared to those with AG genotype (7.6 ± 1.5 pg/ml) and GG genotype (9.5 ± 1.2 pg/ml); P < 0.01, respectively. CONCLUSION: We demonstrate for the first time, to the best of our knowledge, that the presence of an A allele or AA gene variant at the -1082 position of the promoter region of the interleukin-10 gene may constitute risk factors for developing JIA in Egyptian children and adolescents. Moreover, we observed a significant positive association between the IL10 -1082 AA gene variant and susceptibility to polyarticular JIA.

Interleukin-1ß and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.

Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31 (C/T), and -511 (C/T) of interleukin-1beta (IL-1ß) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1ß to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1ß promoter at positions -31 (C/T), -511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1ß levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1ß-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; P = 0.001and OR: 1.73; 95% CI: 1.24-2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1ß compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1ß promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.

Vitamin D receptor gene BsmI polymorphisms in Egyptian children and adolescents with systemic lupus erythematosus: A case-control study.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. To date, only a few studies concerned the association of the VDR gene polymorphisms with childhood-onset SLE.In this study, we aimed to investigate the BsmI polymorphisms in the VDR gene, for the first time in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a marker of susceptibility to or severity of SLE and we also measured the serum level of 25-hydroxyvitamin D (25[OH] D) to assess its relation to such polymorphism.This was a case-control study including 100 patients with SLE and matched with age, sex, and ethnicity and 100 healthy controls. All subjects were genotyped for the VDR gene BsmI polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), whereas the serum 25(OH) D levels were measured by enzyme-linked immunosorbent assay method.Compared to the contros subjects, the VDR BsmI BB genotype and B allele were overrepresented among SLE patients (odda ratio [OR]: 5.5; 95% confidence interval [CI]: 1.9-15.9; P = 0.002 and OR: 1.84; 95% CI: 1.21-2.80; P = 0.003; respectively). We found a significant association between VDR BsmI BB genotype with lupus nephritis (OR: 6.8; 95% CI: 1.18-50.5; P = 0.001). However, we did not observe any significant association of studied polymorphisms with other clinical manifestations, laboratory profiles of SLE, or disease activity score. Our data revealed no association between VDR BsmI genotypes or alleles and serum 25-hydroxyvitamin D levels among studied patients with SLE (all P > 0.05).We demonstrate for the first time, to the best of our knowledge, that the VDR BsmI gene polymorphisms may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, we found that the BB genotype constituted a risk factor for the development of nephropathy among studied patients with SLE. However, we did not find any significant association of the VDR BsmI gene variants with other clinical manifestations, laboratory profiles of SLE, disease activity index score, or serum 25-hydroxyvitamin D levels.