Right ventricular function indices and platelet parameters for early prediction value of bronchopulmonary dysplasia: a retrospective study.

BACKGROUND: To examine the value of early echocardiographic indices for the right ventricular function combined with platelet(PLT) parameters for predicting bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This retrospective study included infants with gestational age (GA) below 32 weeks, who were admitted to the neonatal intensive care unit(NICU). The detection rate of tricuspid regurgitation jet velocity (TRVJ), ventricular septal flattening, pulmonary artery widening, right ventricular dilation, and right atrial enlargement on the 7th day of life (DOL 7) were compared between BPD and non-BPD infants. Echocardiographic indices of the right ventricular function including tricuspid annular plane systolic excursion (TAPSE) and right ventricular index of myocardial performance (RIMP) were measured on 1 day of life (DOL 1)、on DOL 7 and on 14 day of life (DOL 14) respectively. The PLT parameters including the PLT count, mean platelet volume (MPV), platelet hematocrit (PCT) level, and platelet distribution width (PDW) were measured on the DOL 1,DOL 7, and DOL 14. Multivariate logistic regression was used to analyze the relationship between these parameters and BPD. Receiver operating characteristic curve analysis was performed to assess the predictive value of the right ventricular function indices and PLT parameters for BPD. RESULTS: A total of 220 preterm infants were included in this study, and of these, 85 infants developed BPD among them. The RIMP of the BPD group on DOL 14 was higher than that of the non-BPD group (P < 0.05). The TAPSE of the BPD group on DOL 14 was lower than that of the non-BPD group (P < 0.05). The PLT count of the BPD group on DOL 1 was lower than that of the non-BPD group (P < 0.05), and the MPV of the BPD group on DOL 1 was higher than that of the non-BPD group (P < 0.05). Using multivariate logistic regression, GA、invasive mechanical ventilation duration ≥ 7 days、 PLT、 MPV、 TAPSE and RIMP were found to be independent risk factors for BPD. The area under the receiver operating characteristic curve was 0.846 (95CI: 0.794∼0.899), which improved when using right ventricular function indices combined with platelet parameters. CONCLUSION: TAPSE and RIMP combined with PLT count and MPV can help identify preterm infants at an increased risk of developing BPD.

Pneumoprotein CC16 in the Umbilical Cord Blood of Preterm Neonates.

OBJECTIVE: We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates. STUDY DESIGN: A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses. RESULTS: In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 320/7 and 336/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p = 0.015), and birth weight. CONCLUSION: Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight. KEY POINTS: · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD..

Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders.

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Fluid status in the first 10 days of life and death/bronchopulmonary dysplasia among preterm infants.

OBJECTIVE: To investigate the association between fluid and sodium status in the first 10 postnatal days and death/bronchopulmonary dysplasia (BPD) among infants born <29 weeks' gestation. STUDY DESIGN: Single center retrospective cohort study (2015-2018) of infants born 23-28 weeks'. Three exposure variables were evaluated over the first 10 postnatal days: cumulative fluid balance (CFB), median serum sodium concentration, and maximum percentage weight loss. Primary outcome was death and/or BPD. Multivariable logistic regression adjusting for patient covariates was used to assess the association between exposure variables and outcomes. RESULTS: Of 191 infants included, 98 (51%) had death/BPD. Only CFB differed significantly between BPD-free survivors and infants with death/BPD: 4.71 dL/kg (IQR 4.10-5.12) vs 5.11 dL/kg (IQR 4.47-6.07; p < 0.001). In adjusted analyses, we found an association between higher CFB and higher odds of death/BPD (AOR 1.56, 95% CI 1.11-2.25). This was mainly due to the association of CFB with BPD (AOR 1.60, 95% CI 1.12-2.35), rather than with death (AOR 1.08, 95% CI 0.54-2.30). CONCLUSION: Among preterm infants, a higher CFB in the first 10 days after delivery is associated with higher odds of death/BPD. IMPACT: Previous studies suggest that postnatal fluid status influences survival and respiratory function in neonates. Fluid balance, serum sodium concentration, and daily weight changes are commonly used as fluid status indicators in neonates. We found that higher cumulative fluid balance in the first 10 days of life was associated with higher odds of death/bronchopulmonary dysplasia in neonates born <29 weeks. Monitoring of postnatal fluid balance may be an appropriate non-invasive strategy to favor survival without bronchopulmonary dysplasia. We developed a cumulative fluid balance chart with corresponding thresholds on each day to help design future trials and guide clinicians in fluid management.

A clinical study on plasma biomarkers for deciding the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia of premature infants.

Objective: The study was designed to investigate some plasma markers which help us to decide the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia (BPD) of premature infants. Methods: Thirty BPD infants were treated by dexamethasone. Among these cases, dexamethasone was significant effective in 10 cases, and no significant effective in 20 cases. These patients were divided into two groups as the significant effect (SE) group (n=10) and the non-significant effect (NE) group (n=20) according to the curative effect of dexamethasone. Fifteen non-BPD infants with gestational age and gender matching were selected as the control group. Plasma samples before and after dexamethasone treatment were collected from three infants chosen randomly from SEG for the data-independent acquisition (DIA) analysis. ELISA was further used to detect the levels of differential proteins LRP1 and S100A8 in all individuals, including SE, NE and control groups. Results: DIA analysis results showed that after dexamethasone treatment, there were a total of 52 plasma proteins that showed significant differences, of which 43 proteins were down-regulated and 9 proteins were up-regulated. LRP1 and S100A8 were two plasma proteins that were significantly changed after dexamethasone treatment. Compared with the control group, plasma LRP1 was significantly increased in BPD. Interestingly, the plasma concentration of LRP1 in the NE group was significantly higher than that in the SE group. S100A8, as an indicator of plasma inflammation, was significantly higher in BPD than the control group. Unlike LRP1, there was no significantly difference between the SE and NE group (P=0.279) before dexamethasone treatment. Conclusion: Elevated plasma LRP1 and S100A8 in BPD infants are two indicators that correlated with the efficacy of dexamethasone, and might be used as biomarkers for deciding the use of adjuvant corticosteroids therapy in the BPD.

An Evaluation to Establish the Acceptable Serum Triglyceride Levels in Neonates Receiving Intravenous Fat Emulsion Infusion in a Multicenter Retrospective Study.

OBJECTIVE: This study aimed to establish neonatal serum triglyceride (TG) level reference ranges during lipid infusion and correlate peak TG with neonatal outcomes. STUDY DESIGN: This is a retrospective review of 356 neonates with 696 TG measures obtained in four neonatal intensive care units between 2015 and 2017. TG was evaluated collectively to establish a reference range and a threshold limit. To analyze the effects of a higher TG threshold, neonates were categorized by their peak TG: <180 (TG<180), 180 to 400 (TG180-400), and > 400 mg/dL (TG>400). Univariable and multivariable regression models were constructed to compare peak TG to patient characteristic and clinical outcomes. RESULTS: The frequency of TG > 400 mg/dL was 5% and found only in neonates weighing < 1.5 kg. Neonates in the TG180-400 (n = 91) group were significantly lower in birth weight and gestational age, had lower 5-minute APGAR scores, and had increased ventilatory requirement when compared with neonates in the TG<180 (n = 240) group (all p < 0.001). The TG180-400 group had increased risk of severe intraventricular hemorrhage (p = 0.02) and bronchopulmonary dysplasia (p = 0.03). Elevated TG was associated with mortality (odds ratio [OR]: 14.4, p < 0.001) in univariable analysis, but the relationship weakened (OR: 4.4, p = 0.05) after adjusting for comorbidities in multivariable logistic regression. CONCLUSION: It is unclear if the adverse outcomes seen in neonates with higher peak TG were due to elevated TG alone, or whether illness severity predicted the increased TG. More prospective studies are needed to further delineate the relationships.

Long non-coding RNA MALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB.

Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non-coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up-regulated in the lung tissue from BPD neonates, hyperoxia-based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down-regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia-treated cells. Subsequently, qRT-PCR, Western blotting and dual-luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.

Proportional assist ventilation (PAV) versus neurally adjusted ventilator assist (NAVA): effect on oxygenation in infants with evolving or established bronchopulmonary dysplasia.

Both proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) provide pressure support synchronised throughout the respiratory cycle proportional to the patient's respiratory demand. Our aim was to compare the effect of these two modes on oxygenation in infants with evolving or established bronchopulmonary dysplasia. Two-hour periods of PAV and NAVA were delivered in random order to 18 infants born less than 32 weeks of gestation. Quasi oxygenation indices ("OI") and alveolar-arterial ("A-a") oxygen gradients at the end of each period on PAV, NAVA and baseline ventilation were calculated using capillary blood samples. The mean "OI" was not significantly different on PAV compared to NAVA (7.8 (standard deviation (SD) 3.2) versus 8.1 (SD 3.4), respectively, p = 0.70, but lower on both than on baseline ventilation (mean baseline "OI" 11.0 (SD 5.0)), p = 0.002, 0.004, respectively). The "A-a" oxygen gradient was higher on PAV and baseline ventilation than on NAVA (20.8 (SD 12.3) and 22.9 (SD 11.8) versus 18.5 (SD 10.8) kPa, p = 0.015, < 0.001, respectively).Conclusion: Both NAVA and PAV improved oxygenation compared to conventional ventilation. There was no significant difference in the mean "OI" between the two modes, but the mean "A-a" gradient was better on NAVA.What is Known:• Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) can improve the oxygenation index (OI) in prematurely born infants.• Both PAV and NAVA can provide support proportional to respiratory drive or demand throughout the respiratory cycle.What is New:• In infants with evolving or established BPD, using capillary blood samples, both PAV and NAVA compared to baseline ventilation resulted in improvement in the "OI", but there was no significant difference in the "OI" on PAV compared to NAVA.• The "alveolar-arterial" oxygen gradient was better on NAVA compared to PAV.

Next-generation sequencing to investigate circular RNA profiles in the peripheral blood of preterm neonates with bronchopulmonary dysplasia.

BACKGROUND: Circular RNAs (circRNAs) are emerging noncoding RNAs that are involved in many biological processes and diseases. The expression profile of circRNAs in preterm neonates with bronchopulmonary dysplasia (BPD) remains unresolved. METHODS: In BPD infants, peripheral venous blood was drawn and circRNAs were extracted and sequenced by next-generation sequencing. The levels of the selected circRNAs were measured by real-time quantitative reverse transcription PCR. RESULTS: Among thousands of circRNAs, 491 circRNAs were significantly changed. Among the top 10 changed circRNAs, hsa_circ_0003122, hsa_circ_0003357, hsa_circ_0009983, hsa_circ_0003037, and hsa_circ_0009256 were significantly increased, while hsa_circ_0014932, hsa_circ_0015109, hsa_circ_0017811, hsa_circ_0020588, and hsa_circ_0015066 were significantly decreased. These altered circRNAs are involved in complicated biological functions and signaling pathways. Additionally, hsa_circ_0005577 (hsa_circ_FANCL), which was significantly increased in the moderate-to-severe BPD subjects, was correlated with oxygenation therapy. CONCLUSION: These results suggest that an aberrant circRNA profile in the peripheral blood of BPD infants might be important in BPD pathogenesis.

Influence of prevention of caffeine citrate on cytokine profile and bronchopulmonary dysplasia in preterm infants with apnea.

BACKGROUND: This study aims to investigate the preventive effects of caffeine citrate on cytokine profile and bronchopulmonary dysplasia (BPD) in preterm infants with apnea. METHODS: Preterm infants with apnea who were born at less than 32 weeks of gestational age and birth weight ≤1500 g were randomly divided into caffeine citrate prevention group and caffeine citrate treatment group. Preterm infants in caffeine citrate prevention group who were at risk of developing recurrent apnea were given to caffeine citrate within 8 h after birth. Those in caffeine citrate treatment group experienced apnea after birth were given to caffeine citrate for treatment. Preterm infants in both groups were treated with the same respiratory management and other conventional therapy. After drug discontinuation, levels of cytokine profile, and incidence of BPD were compared between two groups. RESULTS: A total of 56 preterm infants were enrolled. Differences in gestational age (P=0.11) and birth weight (P=0.251) were not statistically significant. Differences in application time of caffeine citrate (P=0.356), hour of ventilator use (P=0.152), length of stay (P=0.416) and BPD morbidity (P=1.00) between two groups were not statistically significant. At birth, there were no statistically significant in levels of IL-6 (P=0.063) and IL-8 (P=0.125) between two groups. After conventional therapy, levels of IL-6 (P=0.001) and IL-8 (P=0.001) significantly decreased in caffeine citrate prevention group compared with those in caffeine citrate treatment group. CONCLUSIONS: Prevention usage of caffeine citrate in preterm infants with apnea could reduce the level of cytokine profile and the incidence of BPD.

Antioxidative effects of caffeine in a hyperoxia-based rat model of bronchopulmonary dysplasia.

BACKGROUND: While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats. METHODS: Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR. RESULTS: Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response. CONCLUSION: In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.

Oxygen desaturations in the early neonatal period predict development of bronchopulmonary dysplasia.

BACKGROUND: Bradycardia and oxygen desaturation episodes are common among preterm very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU), and their association with adverse outcomes such as bronchopulmonary dysplasia (BPD) is unclear. METHODS: For 502 VLBW infants we quantified bradycardias (HR < 100 for ≥ 4 s) and desaturations (SpO2 < 80% for ≥ 10 s), combined bradycardia and desaturation (BD) events, and percent time in events in the first 4 weeks after birth (32 infant-years of data). We tested logistic regression models of clinical risks (including a respiratory acuity score incorporating FiO2 and level of respiratory support) to estimate the risks of BPD or death and secondary outcomes. We then tested the additive value of the bradycardia and desaturation metrics for outcomes prediction. RESULTS: BPD occurred in 187 infants (37%). The clinical risk model had ROC area for BPD of 0.874. Measures of desaturation, but not bradycardia, significantly added to the predictive model. Desaturation metrics also added to clinical risks for prediction of severe intraventricular hemorrhage, retinopathy of prematurity and prolonged length of stay in the NICU. CONCLUSIONS: Oxygen desaturations in the first month of the NICU course are associated with risk of BPD and other morbidities in VLBW infants.

Increased serum Th2 chemokine levels are associated with bronchopulmonary dysplasia in premature infants.

Bronchopulmonary dysplasia (BPD) is one of the most common chronic inflammatory lung disease of premature infants, with serious short- and long-term consequences. Early identification of premature infants at risk of BPD is critical to preventing the pathogenesis of disease. Thus, in the present study, we recruited 126 premature infants, collected peripheral blood samples at different time points during early life, and measured the concentration of Th1 (MCP-1, IP-10, and MIG) and Th2 (eotaxin-1, eotaxin-2, and MCP-4) chemokines in serum. We found serum eotaxin-2 levels were significantly higher in the BPD group than in the non-BPD group on day 1 [1662 pg/ml vs. 1221 pg/ml, P < 0.05], day 7 [1533 pg/ml vs. 1089 pg/ml, P < 0.05], and day 14 [1246 pg/ml vs. 704 pg/ml, P < 0.05] after birth, and serum MCP-4 levels were also significantly higher in the BPD group than in the non-BPD group on day 1 [186 pg/ml vs. 128 pg/ml, P < 0.05], day 7 [199 pg/ml vs. 101 pg/ml, P < 0.05], and day 14 [238 pg/ml vs. 106 pg/ml, P < 0.05] of life.Conclusions: Increased levels of Th2 chemokines, eotaxin-2, and MCP-4, are associated with BPD in premature infants. What is Known: • The pathogenesis of BPD is multifactorial and it is difficult to predict and prevent. • Previous studies have demonstrated that inflammation plays a major role in the pathogenesis of BPD. What is New: • Increased Th2 chemokines, eotaxin-2 and MCP-4, were associated with BPD in premature infants. • Abnormal Th1/Th2 response in early life maybe associated with the subsequent development of BPD, which provide a new insight to understand the pathogenesis of the disease.

NTproBNP is a useful early biomarker of bronchopulmonary dysplasia in very low birth weight infants.

Bronchopulmonary dysplasia (BPD) is a severe complication of prematurity that impacts survival and neurodevelopment. Currently, no early marker exists which could help clinicians identify which preterm infants will develop BPD. Given the evidence that NTproBNP is elevated in children with BPD, we hypothesized that it could be used as an early marker of BPD development. We conducted a prospective cohort study including very low birth weight infants (VLBWI) admitted to our NICU between January 2015 and January 2017 in which we determined serial NTproBNP levels on days 1 and 3 and then weekly, until 49 days of life. A total of 101 patients were recruited (mean birth weight 1152 g (SD 247.5), mean gestational age 28.9 weeks (SD 1.9)). NTproBNP levels differed among infants who did and did not develop BPD from 14 to 35 days of life with the greatest difference on day 14 of life (non-BPD group (n = 86): 1155 (IQR 852-1908) pg/mL, BPD (n = 15): 9707 (IQR 3212-29,560) pg/mL; p = 0.0003). The presence of HsPDA did not account for higher levels of NTproBNP at day 14 (p = 0.165). We calculated an optimal cutoff point of 2264 pg/mL at 14 days of life (sensitivity 100%, specificity 86% and AUC 0.93).Conclusions: NTproBNP at 14 days of life could be used as an early marker of later BPD development in VLBWI. What is Known: • Children with BPD have elevated NTproBNP levels, which are related to the severity of BPD and the development of pulmonary hypertension. What is New: • NTproBNP at 14 days of life is higher in those who later develop BPD, regardless of the presence of hemodynamically significant patent ductus arteriosus. • A calculated cutoff point of 2264 pg/mL of NTproBNP at 14 days has a sensitivity of 100% and specificity of 86% in the prediction of BPD.

Neonatal hematological parameters and the risk of moderate-severe bronchopulmonary dysplasia in extremely premature infants.

OBJECTIVE: To evaluate the association between hematological parameters at birth and the risk of moderate-severe bronchopulmonary dysplasia (BPD) in a cohort of extremely preterm infants. METHODS: This is a retrospective study of all extremely premature infants admitted to the neonatal intensive care unit, Shenzhen Maternity and Child Healthcare Hospital from January 2016 to May 2018. Extremely prematurity was defined as a delivery at a gestational age ≤ 28 weeks or a birth weight ≤ 1000 g. BPD was diagnosed if oxygen exposure exceeded 28 days and the severity was decided at 36 weeks PMA or discharge. Multivariable analysis was performed to assess the independence of the association between hematological parameters at birth and risk of moderate or severe BPD. RESULTS: A total of 115 extremely premature infants were analyzed in this study. The median platelet count, neutrophil and monocyte count at birth were significantly higher in infants with moderate-severe BPD compared to infants without BPD (228 vs 194*109/l, P = 0.004; 5.0 vs 2.95*109/l, P = 0.023; 0.88 vs 0.63*109/l, P = 0.026, respectively) whereas the mean platelet volume was significantly lower in infants with moderate-severe BPD than those without BPD (9.1 vs 9.4 fl, P = 0.002). After adjusting for covariates, the risk of moderate-severe BPD was independently associated with platelet count≥207*109/l (odds ratio 3.794, 95% confidence interval: 1.742-8.266, P = 0.001). CONCLUSION: Our findings suggest that hematologic parameters at birth are different in extremely preterm infants who will develop moderate-severe BPD. A higher platelet count at birth may increase the risk of moderate-severe BPD after extremely premature birth.

Screening Echocardiography and Brain Natriuretic Peptide Levels Predict Late Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia.

Through this study, we aimed to assess the ability of routine neonatal screening at time of bronchopulmonary dysplasia (BPD) diagnosis to predict the development of late pulmonary hypertension (PHTN). This is a retrospective longitudinal cohort study of 37 premature infants with BPD assessing the utility of screening serum brain natriuretic peptide (BNP) and echocardiograms performed at the time of BPD diagnosis ('early PHTN') to predict 'late PHTN' at the last follow-up. Screening evaluation demonstrated early PHTN in 9/37 patients. At an average follow-up interval of 52.7 ± 38.7 weeks, 4/9 had late PHTN; one patient without early PHT had late PHT. At initial screening, infants with late PHTN were significantly more likely to have demonstrated elevated BNP values (p = 0.003), and echocardiographic evidence of right atrial dilatation (p = 0.01), right ventricular hypertrophy (p = 0.01), lower right ventricular area change percentage (p = 0.03), and larger main pulmonary artery Z-scores (p = 0.02). Serum BNP and echocardiographic evaluation performed at the time of BPD diagnosis can detect patients at increased risk of late PHTN. Large, prospective studies are necessary to further address this question.

Effect of Cord Blood Magnesium Level at Birth on Non-neurologic Neonatal Outcomes.

OBJECTIVE: We examined the effects of magnesium sulfate on non-neurologic neonatal outcomes with respect to cord blood magnesium level. STUDY DESIGN: We conducted a secondary analysis of the Maternal-Fetal Medicine Units Beneficial Effects of Antenatal Magnesium (MFMU BEAM) trial comparing the upper and lower quintiles of cord blood magnesium level. Outcomes included cerebral palsy (CP), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios (aORs) of each outcome, controlling for gestational age (GA), birth weight, and treatment group (TG). RESULTS: A total of 1,254 women of the 2,444 included in the BEAM trial had cord blood magnesium levels recorded. GA and birth weight were lower and TG was more common in the upper quintile cohort (p < 0.001). Neonates in the upper quintile were more likely to have severe NEC (OR, 2.41, 95% confidence interval [CI]: 1.11-5.24), ROP (OR, 1.65, 95% CI: 1.05-2.59), and BPD (OR, 1.70, 95% CI: 1.04-2.73). Adjustment for covariates demonstrated no difference in the NEC, ROP, and BPD rates, although there was a decrease in rates of mental disability index < 70 which was not seen in the unadjusted analysis (aOR, 0.49, 95% CI: 0.25-0.99). CONCLUSION: Higher cord blood magnesium levels do not appear to have adverse non-neurologic effects on the neonate and may demonstrate improvement in neurologic outcomes.

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus.

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

Ginger ( Zingiber officinale ) prevents severe damage to the lungs due to hyperoxia and inflammation

Background/aim: Hyperoxia- and inflammation-induced lung injury is an important cause of the development of bronchopulmonary dysplasia (BPD) in premature infants. We aimed to ascertain the beneficial effects of ginger ( Zingiber officinale ) on rat pups exposed to hyperoxia and inflammation. Materials and methods: Thirty-six newborn Wistar rats were randomly divided into 3 groups as the hyperoxia (95% O 2 ) + lipopolysaccharide (LPS) group, the hyperoxia + LPS + ginger-treated group, and the control/no treatment group (21% O 2 ). Pups in the hyperoxia + LPS + ginger group were administered oral ginger at a dose of 1000 mg/kg daily during the study period. Histopathologic, immunochemical (SMA and lamellar body), and biochemical evaluations including total antioxidant status (TAS), total oxidant status (TOS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and caspase-3 activities were performed. Results: Better weight gain and survival rates were shown in the hyperoxia + LPS + ginger group (P < 0.05). In the histopathologic and immunochemical evaluation, severity of lung damage was significantly reduced in the hyperoxia + LPS + ginger group, as well as decreased apoptosis (ELISA for caspase-3) (P < 0.05). Tissue TAS levels were significantly protected, and TOS, MDA, and MPO levels were significantly lower in the hyperoxia + LPS + ginger group (P < 0.05). Tissue TNF-α, IL-1ß, and IL-6 concentrations were significantly decreased in the ginger-treated group (P < 0.05). Conclusion: Ginger efficiently reduced the lung damage and protected the lungs from severe damage due to hyperoxia and inflammation. Therefore, ginger may be an alternative option for the treatment of BPD.

The Improvement of Respiratory Performance After Phototherapy-Induced EPC Mobilization in Preterm Infants With RDS.

Many infants who develop bronchopulmonary dysplasia (BPD) are born with serious respiratory distress syndrome (RDS), which is associated with impaired vascular and alveolar growth. RDS is a breathing disorder that mostly affects preterm infants and occurs in infants whose lungs have not yet been fully developed. The use of surfactant in RDS treatment does not necessarily prevent BPD. Endothelial progenitor cells (EPCs) may contribute to lung angiogenesis for the prevention and treatment of BPD. The aim of this study was to evaluate the therapeutic efficacy of phototherapy for EPC release in preterm infants born with RDS. Seventy-five RDS preterm infants were divided into two groups: RDS with phototherapy and RDS without phototherapy. Respiratory indices were recorded for each patient. Circulating EPCs were isolated before and after phototherapy and colony forming efficiency, chemotactic, tubulogenic, proliferative, and functional properties of these cells were analyzed. Our results showed that phototherapy increased the release of EPCs into the circulation in RDS preterm infants, with augmentation of cell proliferation, tubulogenic, chemotactic, and proliferative properties of EPCs. Phototherapy-induced EPC release was associated with improved lung function as was recorded by significantly decrease in continuous positive airway pressure (CPAP) days, CPAP plus ventilator days, and PCO2 along with a significant increase in PO2 and PaO2 /FiO2 , resulting in markedly decreased rate of BPD occurrence in preterm infants with RDS. Overall, phototherapy is touted as a promising modality for the amelioration of respiratory performance and prohibition of BPD occurrence in RDS preterm infants. J. Cell. Biochem. 118: 594-604, 2017. © 2016 Wiley Periodicals, Inc.