Can serum periostin predict bronchopulmonary dysplasia in premature infants?

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD. METHODS: A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006). CONCLUSIONS: Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants. IMPACT: This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.

Biomarker Potential of the Soluble Receptor for Advanced Glycation End Products to Predict Bronchopulmonary Dysplasia in Premature Newborns.

Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants. The soluble receptor for advanced glycation end products (sRAGE) is implicated in the development of various pulmonary diseases. The objectives of the current study were to investigate perinatal factors associated with serum sRAGE levels at birth and to establish whether serum sRAGE could be a biomarker for BPD. This retrospective single-center study was conducted at Fukushima Medical University Hospital's Department of Pediatrics Neonatal Intensive Care Unit from April 2014 to September 2020. Mechanically ventilated or oxygenated neonates born at <32 weeks gestational age and healthy control neonates were included in this study. Serum sRAGE levels in cord blood were measured using an enzyme-linked immunosorbent assay. Eighty-four preterm infants born at <32 weeks and 40 healthy infants were identified. The 84 born at <32 weeks were categorized as BPD (n = 34) or non-BPD (n = 50) neonates. The median gestational age (GA) and birthweight (BW) were significantly lower in BPD vs. non-BPD neonates (24.4 vs. 27.6 weeks, P < 0.001, 634 vs. 952 g, P < 0.001, respectively). Serum sRAGE at birth in all 124 preterm and term infants significantly correlated with BW (r = 0.417, P < 0.0001) and GA (r = 0.415, P < 0.0001). Among those born at <32 weeks, median serum sRAGE levels at birth were significantly lower in infants with BPD than without (1,726 vs. 2,797 pg/mL, P = 0.0005). Receiver operating characteristic analysis for sRAGE levels at birth in infants with and without BPD revealed that the area under the curve was 0.724 (95% confidence interval 0.714-0.834, P = 0.001). However, serum RAGE levels were not associated with severity of BPD. Serum sRAGE levels at birth were significantly correlated with BW and GA. Furthermore, serum sRAGE levels at birth could serve as a biomarker for predicting BPD, but not its severity.

Red cell distribution width as a predictor for bronchopulmonary dysplasia in premature infants.

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at < 30 weeks were included in this study. They were categorized into BPD (n = 85) and non-BPD (n = 91) infants. RDW at birth and 14 days and 28 days of life (DOL 14, DOL 28) were measured. Clinical data were obtained from all subjects at Fukushima Medical University (Fukushima, Japan). The mean RDW at birth, DOL 14 and DOL 28 were 16.1%, 18.6%, 20.1%, respectively. Small for gestational age (SGA), chorioamnionitis (CAM), hypertensive disorders of pregnancy (HDP), gestational age and birth weight were significantly associated with RDW at birth. SGA, BPD and red blood cell (RBC) transfusion before DOL 14 were associated with RDW at DOL 14. BPD and RBC transfusion before DOL 14 were associated with RDW at DOL 28. Compared with non-BPD infants, mean RDW at birth DOL 14 (21.1% vs. 17.6%, P < 0.001) and DOL 28 (22.2% vs. 18.2%, P < 0.001) were significantly higher in BPD infants. Multivariate analysis revealed that RDW at DOL 28 was significantly higher in BPD infants (P = 0.001, odds ratio 1.63; 95% CI 1.22-2.19). Receiver operating characteristic analysis for RDW at DOL 28 in infants with and without BPD yielded an area under the curve of 0.87 (95% CI 0.78-0.91, P < 0.001). RDW at DOL 28 with mild BPD (18.3% vs. 21.2%, P < 0.001), moderate BPD (18.3% vs. 21.2%, P < 0.001), and severe BPD (18.3% vs. 23.9%, P < 0.001) were significantly higher than those with non-BPD, respectively. Furthermore, there are significant differences of RDW at DOL 28 between mild, moderate, and severe BPD. In summary, we conclude that RDW at DOL 28 could serve as a biomarker for predicting BPD and its severity. The mechanism by which RDW at DOL 28 is associated with the pathogenesis of BPD needs further elucidation.

Perinatal factors affecting platelet parameters in late preterm and term neonates.

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (ß = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (ß = -0.135, P = 0.026) and male sex (ß = -0.185, P = 0.002). PLT was associated with SGA (ß = -0.186, P = 0.002), PIH (ß = -0.137, P = 0.024) and male sex (ß = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates.

Risk factors and treatments for disseminated intravascular coagulation in neonates.

BACKGROUND: Although disseminated intravascular coagulation (DIC) is a critical disease, there is few gold standard interventions in neonatal medicine. The aim of this study is to reveal factors affecting neonatal DIC at birth and to assess the effectiveness of rTM and FFP for DIC in neonates at birth. METHODS: We retrospectively evaluated DIC score on the first day of life in neonates with underlying conditions associated with DIC. DIC in neonates was diagnosed according to Japan Society of Obstetrical, Gynecological & Neonatal Hematology 2016 neonatal DIC criteria. RESULTS: Comparing neonates with DIC scores of ≥3 (n = 103) to those < 3 (n = 263), SGA, birth asphyxia, low Apgar score, hemangioma, hydrops, PIH, and PA were statistically increased. Among 55 neonates underwent DIC treatment, 53 had birth asphyxia and 12 had intraventricular hemorrhage. Forty-one neonates received FFP or a combination of FFP and antithrombin (FFP group), while 14 neonates received rTM or a combination of rTM, FFP, and antithrombin (rTM group). DIC score before treatment in the rTM group was significantly higher than in the FFP group (4.7 vs 3.6, P < 0.05). After treatment, DIC scores in both groups were significantly reduced on Day 1 and Day 2 (P < 0.05). CONCLUSIONS: Among various factors associated with DIC in neonates at birth, birth asphyxia is particularly significant. Furthermore, rTM in combination with FFP therapy was effective for neonatal DIC at birth.

Using Platelet Parameters to Anticipate Morbidity and Mortality Among Preterm Neonates: A Retrospective Study.

Background: Platelets participate in many physiological and pathological functions and some platelet parameters predict adult diseases. However, few studies report whether platelet parameters may reflect neonatal disease and mortality in a large cohort. Objective: We aimed to investigate whether platelet parameters could predict bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and NICU mortality. Study Design and Methods: This retrospective cohort study examined records from 2006 to 2017 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. We retrospectively investigated platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on the first day of life in preterm newborns born <32 weeks' gestation admitted to our NICU from 2006 to 2017. Receiver operating characteristic (ROC) and multiple regression analyses, along with Cox proportional hazard modeling, identified independent predictors of morbidities and mortality in preterm newborns. Results: Of 1,501 neonates admitted to our NICU, a total of 305 preterm newborns were included in this study. Gestational age, birth weight, and Apgar score were significantly lower in non-survivors than in survivors. Platelet count, PCT, PDW and PMI did not differ significantly between the two groups, whereas mean MPV in non-survivors was significantly higher than in survivors (10.5 fl vs. 10.0 fl, p = 0.001). Multivariate Cox hazard modeling showed that shorter GA [HR: 0.628, 95% CI: 0.464-0.840, p = 0.003], male sex [HR: 0.269, 95% CI: 0.113-0.640, p = 0.001], and MPV [HR: 1.469, 95% CI: 1.046-2.063, p = 0.026] independently predicted overall survival. Per receiver operating curve, an MPV threshold of 10.2 fl. MPV predicts prognosis in neonates with a sensitivity of 72.4% and a specificity of 58.6% (AUC = 0.685, 95% CI: 0.600-0.789, p = 0.001). Furthermore, multivariate analysis revealed that platelet parameters were not associated with BPD and NEC, whereas small for gestational age (SGA), Apgar score at 5 min, and low PCT were associated with intraventricular hemorrhage (IVH). Conclusion: This study demonstrates that low PCT predicts IVH, and MPV ≥ 10.2 fL correlates with mortality among infants born after <32 weeks' gestation.

Perinatal Factors Affecting Coagulation Parameters at Birth in Preterm and Term Neonates: A Retrospective Cohort Study.

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time-international normalized ratio correlated with intraventricular hemorrhage (p = 0.000; ß = 0.180) and placental abruption (PA; p = 0.000; ß = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p = 0.000; ß = - 0.217), gestational age (GA; p = 0.000; ß = - 0.282), and PA (p = 0.000; ß = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome (p = 0.007; ß = - 0.114), pregnancy-induced hypertension (p = 0.000; ß = - 0.141), and Apgar score at 1 minute (p = 0.043; ß = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes (p = 0.049). Finally, antithrombin III levels positively correlated with GA (p = 0.000) and BW (p = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates.

Neonatal meningitis and recurrent bacteremia with group B Streptococcus transmitted by own mother's milk: A case report and review of previous cases.

This article reports a case of neonatal meningitis and recurrent bacteremia caused by group B Streptococcus (GBS) transmitted via the mother's milk. A 3-day-old neonate suffered early-onset meningitis due to GBS, from which he recovered after antibiotic treatment for 4 weeks. GBS was not detected in the vaginal or stool cultures of the neonate's mother before delivery. However, 4days after treatment of GBS meningitis, the neonate developed GBS bacteremia. As the mother repeatedly showed signs of mastitis after the delivery, bacterial culture tests were performed on her breast milk, in addition to vaginal and stool culture tests. GBS was exclusively detected in the mother's breast milk. The GBS strains detected in the cerebrospinal fluid of the neonate and the mother's breast milk were both serotype III, and were confirmed to be identical through pulsed-field gel electrophoresis analysis. As horizontal GBS transmission between the mother and neonate was indicated, breastfeeding was ceased and replaced with formula milk. No recurrence of bacterial meningitis or bacteremia due to GBS was observed thereafter. Physicians need to consider culturing breast milk in cases of recurrent neonatal GBS infections, even in mothers without prior detection of GBS in conventional vaginal or stool cultures before delivery.

Neonatal and maternal serum creatinine levels during the early postnatal period in preterm and term infants.

We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman's test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born <29 weeks, pregnancy-induced hypertension (PIH) (p = 0.000, ß = 0.20) and mSCr (p = 0.000, ß = 0.73) were significantly associated with nSCr. In term infants, maternal magnesium administration (p = 0.000, ß = 0.25), respiratory distress syndrome (p = 0.013, ß = 0.16), PIH (p = 0.005, ß = 0.19), and mSCr (p = 0.000, ß = 0.33) were significantly associated with nSCr. nSCr reflected mSCr at all gestational ages. The correlation between nSCr and mSCr in preterm infants (p = 0.000, ß = 0.74) was stronger than in term infants (p = 0.000, ß = 0.34).

Volumetric Analysis of Gallbladder in Extremely Premature Infants.

BACKGROUND: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants. METHODS: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W. RESULTS: Intotal, 30 infants were included. Themediangestationalageoftheinfantswas 26 weeks 5 days (range, 23 weeks 1 day-28 weeks 6 days), and the median birth weight was 731 g (range, 398-1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05 -0.59) in infants on admission and constantly < 0.05 in those between Day 10 and Day 56 after birth. There was no correlation of GV/W with clinical variables after birth. CONCLUSION: It is considered that GB volume is not affected by serial changes without nonfavor-able course of enteral nutrition.