Incidence, Risk Factors, Short-term Outcomes, and Microbiome of Ventilator-associated Pneumonia in Very-low-birth-weight Infants: Experience at a Single Level III Neonatal Intensive Care Unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in neonates on invasive mechanical ventilation, resulting in high morbidity and mortality. The objective of this study is to determine the incidence, risk factors, short-term outcomes and microbiome associated with VAP in very-low-birth-weight (VLBW) infants born at <32 weeks of gestational age (GA). METHODS: Retrospective study of intubated VLBW infants born at <32 weeks of GA admitted to the Los Angeles General Medical Center neonatal intensive care unit from July 2015 to July 2021 who had routine tracheal aspirate cultures obtained. Neonates were retrospectively classified into 3 groups, confirmed VAP, suspected VAP and no VAP, for comparison of risk factors, outcomes and airway microbial colonization. RESULTS: Eighty-seven infants met inclusion criteria with a mean GA of 26.1 ± 1 weeks and mean birth weight of 812 ± 281 g. The incidence of VAP was 7.8 per 1000 ventilator days, and the most common causative organisms were Gram-positive organisms (39%), predominantly coagulase-negative Staphylococcus. Duration of postnatal dexamethasone exposure predicted VAP compared to no VAP (coefficient, 0.31; 95% CI 0.03-0.59; P = 0.03) after adjusting for duration of intubation, surfactant use and antenatal steroid exposure. Infants with VAP had higher rate of grade 2/3 bronchopulmonary dysplasia (P = 0.03) and longer hospital stay (P = 0.04). CONCLUSIONS: VAP occurs at a high rate in VLBW infants who are exposed to prolonged dexamethasone use. It is predominantly caused by Gram-positive organisms.

Economic and Clinical Impact of Using Human Milk-Derived Fortifier in Very Low Birth Weight Infants.

Background: Implementation of exclusive human milk (EHM) feeding defined as mother's own milk or donor human milk fortified with human milk-derived fortifiers can place an economic burden on institutions. Methods: Retrospective study of very low birth weight (VLBW) infants before and after the implementation of EHM feedings. Neonatal demographics and clinical outcomes including necrotizing enterocolitis, severe retinopathy of prematurity, bronchopulmonary dysplasia, late-onset sepsis, days on parenteral nutrition (PN), and length-of-stay were collected. The net cost to the institution was estimated using published data. Results: Sixty-four infants in the pre-EHM period and 57 infants in the post-EHM period were enrolled. Net product acquisition cost in 2020 and 2021 was $884,823. The EHM feeding guideline led to a reduction in the mean length of stay and mean days of PN use by 6.3 and 6.8 days per infant, respectively. This led to a cost saving of $1,813,444 ($31,815 per infant). No significant difference in incidence of short-term morbidities was observed. Combining the cost avoidance from clinical outcomes, the estimated financial impact over 2 years excluding insurance reimbursement was an estimated $ 913,840 ($16,032 per infant). Conclusion: Implementation of EHM-based feeding in VLBW infants is a cost-effective option for neonatal intensive care units that can result in reduced length of stay and days on PN without adversely impacting short-term morbidities.

Effect of Maternal Preeclampsia on Cardiac Structure and Function in Very Low Birth Weight Infants.

OBJECTIVE: We aimed to determine whether exposure to severe maternal preeclampsia (PE) in very low birth weight (VLBW) infants is associated with hypertrophic cardiac changes and altered hemodynamics. STUDY DESIGN: Case-control study of VLBW infants born at Los Angeles General Medical Center from May 2015 to August 2023, who had an echocardiogram within the first 7 days of life. Cases were infants exposed to maternal PE and controls were infants not exposed to maternal PE matched by birth weight (BW) 1:1. Laboratory, placental pathology results, hemodynamic data and clinical outcomes were collected and compared between cases and control infants. RESULTS: A total of 43 cases matched by BW with control infants were studied. There were no significant anatomical cardiac changes by echocardiography between cases and control infants. Cases had significantly higher blood pressure within the first 72 hours of life and lower ejection fraction (EF), fractional shortening, and peak systolic flow velocity through their patent ductus arteriosus (PDA) within the first week of life. Cases were more likely to be smaller despite being born at a later gestational age (GA), as well as small for GA with placental weight less than 10th percentile compared to control infants. CONCLUSION: Our findings indicate that infants born to mothers with PE have higher systemic vascular resistance as evidenced by elevated blood pressure, and lower EF and shortening fraction and higher pulmonary vascular resistance as evidenced by lower peak flow velocity through the PDA. We did not observe hypertrophic cardiac changes in exposed infants. These findings should be considered in clinical decision-making during management of these infants. KEY POINTS: · VLBW infants exposed to severe PE have higher rate of Small for gestational age and smaller placentas.. · VLBW infants exposed to severe PE have higher systemic vascular resistance during transitional period and lower EF and fractional shortening.. · VLBW infants exposed to severe PE have higher pulmonary vascular resistance..

Transient Hypoglycemia and Biochemical Differences in Infants Less Than 1,250 G at Birth Fed Human Milk with Human Milk-Derived Fortifier versus Cow Milk-Derived Fortifier.

OBJECTIVE: Fortification of human milk (HM) with either human milk-derived fortifier (HMDF) or cow milk-derived fortifier (CMDF) is important in preterm infants. The objective is to compare the incidence of hypoglycemia, and biochemical values in infants less than 1,250 g at birth fed HMDF versus CMDF. STUDY DESIGN: It is a retrospective cohort study on infants less than 1,250 g at birth who were fed with HMDF or CMDF. Hypoglycemia was defined as blood glucose (BG) level equal to or less than 60 mg/dL within 72 hours of full enteral feeds when off total parenteral nutrition and intravenous fluids. RESULTS: Ninety infants were enrolled (HMDF = 61, CMDF = 29). HMDF group had a higher rate of hypoglycemia (46 vs. 24%; p = 0.048) after achievement of full enteral feeding. The median minimum BG was lower (61 vs. 71; p ≤ 0.01), while blood urea nitrogen (12 vs. 6; p ≤ 0.01) and albumin (3.1 vs. 2.7; p ≤ 0.01) were higher in HMDF group compared with CMDF. CONCLUSION: At full enteral feedings in infants less than 1,250 g at birth, an HMDF diet may predispose to hypoglycemia needing intervention. Close monitoring of BG levels once off parenteral nutrition is recommended. KEY POINTS: · Exclusive human milk (EHM) feeding results in better nutritional indices.. · EHM feeding at higher calorie/ounce improves growth.. · Blood glucose needs to be monitored when off TPN during EHM feeding..

Effect of assessing velocity time integral at different locations across ventricular outflow tracts when calculating cardiac output in neonates.

This study aims to evaluate the effect of assessing velocity time integral at different locations across ventricular outflow tracts for calculating cardiac output (CO) in neonates. Velocity time integral (VTI) and CO were measured at 3 different locations across right and left ventricular outflow tracts using transthoracic echocardiography in healthy term neonates without any major congenital heart disease. ANOVA with Bonferroni correction was used to determine the differences between the VTI and CO sampled at these three locations. Forty-one neonates met inclusion criteria with mean gestational age of 38.6 ± 1 weeks and mean birth weight of 3155 ± 463 g. The median hours after birth when echocardiography was obtained was 23 h (range 11-68 h after birth). Left CO were 121 ± 30 mL/kg/min, 155 ± 38 mL/kg/min, and 176 ± 36 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. Right CO were 197 ± 73 mL/kg/min, 270 ± 83 mL/kg/min, and 329 ± 104 mL/kg/min measured below the valve, hinges of the valve, and tip of the valve, respectively. A statistically significant difference (P < 0.001) was found in the VTI and CO measured at the 3 different locations across both left and right ventricular outflow tracts.     Conclusions: There is a significant difference in measurements of VTI and CO depending on the location of Doppler gate sampling across the ventricular outflow tracts. Consistency and precision in Doppler gate location are essential for measuring VTI and calculating CO while assessing changes in hemodynamic status in critically ill infants. What is Known: • Targeted Neonatal Echocardiography is increasingly applied to measure cardiac output in critically ill neonates and serial assessments are performed to assess the trend in changes in cardiac output. • Noninvasive measurement using velocity time integral to calculate cardiac output is commonly performed. However, location of Doppler sample gate to measure ventricular outflow tract velocity time integral is not consistent. What is New: • Statistically significant changes in measured velocity time integral and cardiac output are noted based on the location of Doppler gate sampling. • To monitor the cardiac output for trending, it is important to be consistent with regards to the location of the Doppler sample gate to assess changes in cardiac output in critically ill newborns.

Outcomes of patent foramen ovale greater than 3 mm at birth in extremely low birthweight infants.

BACKGROUND: Foramen ovale (FO) is an obligate fetal shunt that typically resolves after birth, although patency throughout life is not uncommon. The natural history of patent FO (PFO) is known in term infants, but less is known about its course in extremely preterm infants. We describe the echocardiographic changes in FO size from birth to discharge in extremely low birth weight (ELBW) infants in this retrospective study. METHODS: Cohort was divided based on size of FO at birth. Size of FO at discharge was measured and evaluated relative to postnatal weight gain. Demographics and clinical outcomes were compared between the two groups. RESULTS: Of the 54 ELBW infants, 50 were born with FO less than 3 mm in diameter (small), and 4 were born with FO greater than 3 mm (large). Of small defects, the majority (44/50, 88%) did not increase in size with weight gain, and minority (6/50, 12%) increased in size, and three of these 6 patients, FO grew to be slightly larger than 3 mm. In contrast, all large defects (4 of 4, 100%) nearly doubled in size with postnatal growth. These 4 ELBW infants with enlargement of FO had a flap valve evident on echocardiogram obtained prior to discharge, and subsequently closed on outpatient follow-up echocardiograms, although time to resolution was variable (6 months - 3 years). One infant had presumptive resolution because of the presence of flap valve. CONCLUSION: No maternal or neonatal demographic characteristics were predictive of FO enlargement, although, demonstrable flap valve on discharge echocardiogram correlated with resolution of FO on outpatient follow-up echocardiogram. Therefore, based on our data, we recommend that ELBW infants born with large FO should have echocardiographic re-evaluation of the atrial septal opening prior to discharge, to specify the presence of a flap valve or lack thereof, which is an important detail that can help a neonatologist determine the need for outpatient cardiac follow-up.

Pulmonary hemorrhage in extremely low birth weight infants: Significance of the size of left to right shunting through a valve incompetent patent foramen ovale.

OBJECTIVE: Pulmonary hemorrhage is a rare but severe complication of extremely low birth weight (ELBW) infants. The association of hemodynamically significant patent ductus arteriosus (hsPDA) and the diameter of the foramen ovale (FO) with pulmonary hemorrhage has not been reported. STUDY DESIGN: Case control study of ELBW infants with and without pulmonary hemorrhage. Each ELBW infant with an echocardiogram within 48 h of pulmonary hemorrhage was analyzed. RESULT: 16 infants with pulmonary hemorrhage were matched with 32 controls by birth weight and gestational age. Echocardiogram showed hsPDA in all infants and those with pulmonary hemorrhage had significantly smaller patent FO [PFO] (1 vs 2.4 mm, p < 0.01) (OR 0.007; 95% CI 0.00007, 0.67 p = 0.03). Incidence of pulmonary hemorrhage was 8.9%. CONCLUSION: ELBW infants with hsPDA who experienced pulmonary hemorrhage had a significantly restricted or closed FO. Evaluation of FO should be considered with serial echocardiograms when evaluating for hsPDA.

Association between blood carboxyhemoglobin level and bronchopulmonary dysplasia in extremely low birthweight infants.

Carboxyhemoglobin (CO-Hb) can be endogenously formed in the presence of oxidative stress and may be elevated in inflammatory lung disease. There is lack of evidence of its relationship with the development of bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW) infants. The objective of the study is to evaluate the relationship between blood CO-Hb levels in the first 14 days of life (DOL) in ELBW infants and the development of BPD at 36 weeks postmenstrual age (PMA). This is a retrospective cohort study of 58 ELBW infants born at LAC-USC Medical Center between June 2015 and and June 2019 who survived to 36 weeks PMA. CO-Hb values were collected daily from DOL 1 to DOL 14. BPD definition using the recent 2019 NICHD criteria was used. Multivariate logistic regression was performed to determine the association between blood CO-Hb levels and BPD. Receiver operator curve was used to evaluate the ability of the median fraction of inspired oxygen (FiO2) level used at DOL 11-14 in discriminating absent to mild BPD versus moderate to severe BPD. 58 ELBW infants were included in the study. 24 (41%) were diagnosed with moderate to severe BPD, while 34 (59%) were diagnosed with no to mild BPD. Severity of BPD was fairly discriminated by FiO2 at DOL 11-14, but not with CO-Hb levels at any point within the first 14 DOL. The role and mechanism of CO-Hb production in this population need to be further studied.

Nasal high-frequency jet ventilation (NHFJV) as a novel means of respiratory support in extremely low birth weight infants.

OBJECTIVE: Describe our experience of successfully using nasal high-frequency jet ventilation (NHFJV) in extremely low birth weight infants with respiratory failure. STUDY DESIGN: A retrospective review was conducted on 16 infants with birth weights <1000 g who received NHFJV from 2015 to 2019. Successful use was defined as avoiding intubation for at least 72 hours and demonstrating tolerance after being placed on NHFJV. RESULTS: Median gestational age was 24.5 weeks (IQR 24, 25), and weight at the start of NHFJV 1090 g (IQR 905, 1250). NHFJV was used successfully in 13/16 (81%) infants with a median duration of 7 days (IQR 3, 12). Days on invasive (30 vs. 186) and noninvasive (46 vs. 81) ventilation were shorter when compared to those who failed the use of NHFJV. CONCLUSION: This is the first reported case series for the successful use of NHFJV. Our study highlights the feasibility of a potential new mode of noninvasive respiratory support.

Systemic to Pulmonary Collaterals in Extremely Low Birth Weight Infants: Incidence, Clinical Significance, and Hemodynamic Features.

OBJECTIVE: This study aimed to determine the incidence of systemic to pulmonary collaterals (SPCs) in extremely low birth weight infants and to assess its clinical and hemodynamic significance beyond the neonatal period. STUDY DESIGN: Retrospective cohort study was conducted on 61 infants with echocardiogram performed at the time of discharge to determine the presence of SPC and to measure the right and left ventricular outputs and left atrium to aortic ratio. We compared two groups: small or no SPC (Group 1) to moderate or large SPC (Group 2) on demographics, clinical outcomes, and echocardiographic parameters. RESULTS: Sixty-one infants were included. The incidence of SPC was 57%; 21% of infants had moderate or large shunts and 31% had small SPC. Demographics, clinical outcomes, and echocardiographic parameters were not significantly different between small or no SPC and moderate to large SPC. CONCLUSION: More than half of the infants had SPC. The size of the shunt did not affect the clinical outcomes nor the echocardiographic parameters measured. All infants had cardiac output above the normative mean.

Proportion of Retinopathy of Prematurity That Was Treated across Regions in the United States.

OBJECTIVES: Retinopathy of prematurity (ROP) is the leading preventable cause of blindness in children worldwide. Major eye and visual problems are strongly linked to ROP requiring treatment. Objectives of the study are to: (1) evaluate the trends and regional differences in the proportion of treated ROP, (2) describe risk factors, and (3) examine if treated ROP predicts mortality. STUDY DESIGN: Retrospective data analysis was conducted using the Kids' Inpatient Database from 1997 to 2012. ROP was categorized into treated ROP (requiring laser photocoagulation or surgical intervention) and nontreated ROP. Bivariate and multivariate logistic regression analyses were performed. RESULTS: Out of 21,955,949 infants ≤ 12 months old, we identified 70,541 cases of ROP and 7,167 (10.2%) were treated. Over time, the proportion of treated ROP decreased (p = < 0.001). While extremely low birth weight infants cared for in the Midwest was associated with treated ROP (adjusted odds ratio [aOR] = 29.05; 95% confidence interval [CI]: 10.64-79.34), black race (aOR = 0.57; 95% CI: 0.51-0.64) care for in the birth hospital (aOR = 0.44; 95% CI: 0.41-0.48) was protective. Treated ROP was not associated with mortality. CONCLUSION: The proportion of ROP that is surgically treated has decreased in the United States; however, there is variability among the different regions. Demographics and clinical practice may have contributed for this variability.

Early postnatal weight gain as a predictor for the development of retinopathy of prematurity.

OBJECTIVE: The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). STUDY DESIGN: Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g. Weekly weights to 36 weeks post-menstrual age or discharge if earlier were entered into the WINROP tool. This tool generated alarm and risk indicator for developing ROP. The infants with type 1 ROP requiring treatment as well as all stages of ROP were compared with the alarms and risks generated by WINROP tool. RESULTS: A total of 492 infants were entered into the WINROP tool. The infants who developed type 1 ROP requiring treatment, the WINROP tool detected 80/89 (90%) at less than 32 weeks gestation. Nine infants developed type 1 ROP were classified as low risk and did not alarm. CONCLUSIONS: Postnatal weight gain alone, in predominantly Hispanic US population, predicted type 1 ROP requiring treatment before 32 weeks of gestation in infants with a sensitivity of 90%. The tool appeared to identify majority of affected infants much earlier than the scheduled screening.

High unbound bilirubin for age: a neurotoxin with major effects on the developing brain.

Neonatal hyperbilirubinemia is one of the most frequent diagnoses made in neonates. A high level of unconjugated bilirubin that is unbound to albumin is neurotoxic when the level exceeds age-specific thresholds or at lower levels in neonates with neurotoxic risk factors. Lower range of unbound bilirubin results in apoptosis, while moderate-to-high levels result in neuronal necrosis. Basal ganglia and various brain stem nuclei are more susceptible to bilirubin toxicity. Proposed mechanisms of bilirubin-induced neurotoxicity include excessive release of glutamate, mitochondrial energy failure, release of proinflammatory cytokines, and increased intracellular calcium concentration. These mechanisms are similar to the events that occur following hypoxic-ischemic insult in neonates. Severe hyperbilirubinemia in term neonates has been shown to be associated with increased risk for autism spectrum disorders. The neuropathological finding of bilirubin-induced neurotoxicity also includes cerebellar injury with a decreased number of Purkinje cells, and disruption of multisensory feedback loop between cerebellum and cortical neurons which may explain the clinical characteristics of autism spectrum disorders. Severe hyperbilirubinemia occurs more frequently in infants from low- and middle-income countries (LMIC). Simple devices to measure bilirubin, and timely treatment are essential to reduce neurotoxicity, and improve outcomes for thousands of neonates around the world.

Chorioamnionitis and Management of Asymptomatic Infants ≥35 Weeks Without Empiric Antibiotics.

BACKGROUND AND OBJECTIVE: Management of asymptomatic infants ≥35 weeks' gestation born to mothers with chorioamnionitis remains controversial, with many clinicians considering the need for changes to the current guidelines. The study objective was to evaluate the outcomes of asymptomatic chorioamnionitis-exposed neonates without the use of immediate empirical antibiotics. METHODS: A retrospective data review was conducted from May 2008 to December 2014, including asymptomatic infants ≥35 weeks' gestation with a maternal diagnosis of clinical chorioamnionitis. RESULTS: A total of 240 asymptomatic infants with chorioamnionitis exposure were identified. The majority of asymptomatic chorioamnionitis-exposed infants, 162 (67.5%), remained well in the mother-infant unit with a median stay of 2 days. There were 78 (32.5%) infants admitted to the NICU and exposed to antibiotics due to abnormal laboratory data or development of clinical symptoms. Of those infants admitted to the NICU, 19 (24%) received antibiotics for <72 hours, 47 (60%) were treated for culture-negative clinical sepsis, and 12 (15%) for culture-positive sepsis, with a median NICU stay of 7 days. CONCLUSIONS: Nonroutine use of empirical antibiotics in asymptomatic newborns ≥35 weeks' gestation with maternal chorioamninonitis prevented NICU admission in two-thirds of these infants. This prevented unnecessary antibiotic exposure, increased hospitalization costs, and disruption of mother-infant bonding and breastfeeding. Laboratory evaluation and clinical observation without immediate antibiotic administration may be incorporated into a management approach in asymptomatic chorioamnionitis-exposed neonates. Additional studies are needed to establish the safety of this approach.

Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally.

Graded oxygen saturation targets and retinopathy of prematurity in extremely preterm infants.

BACKGROUND: We compared the incidence of severe retinopathy of prematurity (ROP) and need for laser treatment before and after implementing graded pulse oximeter oxygen saturation (SpO2) targets in extremely preterm infants. Mortality and other secondary outcomes were compared. METHODS: Before 2002, we used 90-94% as the SpO2 target in infants 24(0/7)-27(6/7)wk gestation and birth weight <1,000 g until 35(6/7) wk postmenstrual age (PMA). We implemented graded SpO2 targets based on vaso-obliterative and vaso-proliferative phases of ROP in 2002. Group 1 (1995-2001) before, and Group 2 (2003-2010) after implementation of graded SpO2 targets based on PMA (83-89% until 32(6/7) wk, 90-94% until 35(6/7) wk and >94% at ≥ 36 wk PMA). RESULTS: There were 267 patients in Group 1 and 220 in Group 2. There was no significant difference in birth weight or gestational age. Severe ROP (adjusted OR: 0.18, 95% CI: 0.11, 0.30; P < 0.001) and laser surgery rates (adjusted OR: 0.31, 95% CI: 0.18, 0.52; P < 0.001) decreased significantly in Group 2. There was no difference in mortality (adjusted OR: 0.74, 95% CI: 0.37, 1.49; P = 0.40). CONCLUSION: In this retrospective cohort study, implementation of graded SpO2 targets decreased severe ROP and need for laser therapy, without increasing mortality.

Lung inflammation and pulmonary function in infants with meconium aspiration syndrome.

OBJECTIVE: To evaluate the relationship between inflammation and pulmonary function, we quantified changes in inflammatory cellular profile, pro-inflammatory cytokines, and pulmonary function in intubated neonates with meconium aspiration syndrome (MAS). METHODS: Sixteen term infants were studied. Tracheal aspirate fluids, obtained within the first 6, 24, 48, and 96 hr of life were used for measurements of: (1) cellular profile changes; (2) mRNA and protein levels for pro-inflammatory cytokines, IL-1beta, IL-6, IL-8, and TNF-alpha, using RT-PCR and ELISA. Using the same time points as above, we determined mean airway pressure, oxygenation index (OI), alveolar-arterial oxygen gradient, and arterial/alveolar oxygen ratio. Baseline tidal volume and pulmonary compliance were obtained. RESULTS: Birth weight was 3,820 +/- 656 g, gestational age 39.8 +/- 1.4 weeks. Mean airway pressure and OI significantly decreased from the first 6-96 hr of age (P = 0.01, P = 0.027). Cell counts were elevated in the first 6 hr compared to 96 hr (17.4 x 10(6)/ml vs. 1.5 x 10(6)/ml, P < 0.05). Pro-inflammatory cytokines decreased from the first 6-96 hr: IL-1beta (187 vs. 37 pg/ml, P < 0.05); IL-6 (3,469 vs. 150 pg/ml, P < 0.05); IL-8 (16,230 vs. 6,334 pg/ml, P = 0.01). CONCLUSIONS: MAS is associated with an inflammatory response characterized by the presence of elevated cell count and pro-inflammatory cytokines which significantly decreased by 96 hr of life. This decrease in lung inflammation has a positive correlation with corresponding decreases in mean airway pressure and oxygenation index, two parameters associated with improved pulmonary function.

Constitutive IL-10 expression by lung inflammatory cells and risk for bronchopulmonary dysplasia.

Expression of IL-10 is decreased in lungs of preterm infants. We determined the constitutive and lipopolysaccharide (LPS)-induced IL-10 synthesis by lung inflammatory cells from preterm and term infants and examined their relationship to gestational age and/or incidence of bronchopulmonary dysplasia (BPD). A total of 37 infants; preterm neonates at gestational ages of 23-27 wk (group 1); 28-34 wk (group 2), and four full-term infants with meconium aspiration (group 3) were enrolled. One sample of lung inflammatory cells, obtained during postnatal d 1-3, and another during postnatal d 4-7 were cultured in vitro in presence or absence of 100 mug/mL of LPS. Secreted IL-10 was measured by ELISA. A positive relationship was found between gestational age and LPS-induced, but not constitutive IL-10 production within 1-3 d of life; group 1 on d 1-3 had a significant number of IL-10 nonresponders compared with group 2. All term neonates in group 3 had positive LPS-induced IL-10 response. Thus, in utero maturation of IL-10 gene expression is due to acquisition of inducibility. In contrast, constitutive IL-10 production within d 1-3 of life correlated with, and predicted the incidence of BPD in the highly vulnerable very premature infants.