The Assessment of Pentraxin 3: A Novel Biomarker in Early Detection of Infection in Newborns.

INTRODUCTION: As the clinical manifestation of neonatal infection is nonspecific and characterised by varied clinical features, it is highly problematic to establish an early diagnosis. Recently, hopes have been raised by the new acute-phase protein-pentraxin 3 (PTX3). PTX3 belongs to the family of long pentraxins, which is synthesized in numerous cells like endothelial cells, macrophages, and monocytes infiltrating sites of inflammation. Material and Methods. In our research, we have enrolled 29 newborns with infection as the study group and 47 healthy ones as the control group, as well as their mothers. The C-reactive protein (CRP), procalcitonin (PCT), and PTX3 levels were determined in venous blood samples from all investigated neonates and their mothers. Moreover, PTX3 concentrations were assessed in the umbilical cord. RESULTS: There were statistically significant differences in PTX3 levels between healthy and sick newborns both in the umbilical cord (p = 0.02) and venous blood (p = 0.01). The highest PTX3 concentrations were observed in children with infection in the presence of premature rupture of membranes (PROM). PTX3 concentrations in this group were significantly higher compared to those in healthy children without PROM. We observed elevated PCT levels in newborns with infection. No differences in CRP levels in 12 hours of life were noticed between the investigated groups. A comparison of ROC curves for PTX3 and PCT concentrations revealed similar sensitivity and specificity in the prediction of infection in neonates. CONCLUSIONS: Serum PTX3 is an important and specific biomarker of early infection. It is already elevated in the umbilical cord, so measuring PTX3 concentration might be useful in the early prediction of infection in newborns.

Human Epididymis Protein 4 Levels in Neonates with Respiratory Disorder.

RESULTS: There were no differences found in the HE4 levels determined for the mothers' blood samples and umbilical cord blood samples in all investigated groups. In comparison with healthy children, the elevated HE4 levels were observed in neonates with TTN. Significant positive correlation between HE4 and CRP as well as PCT levels was observed in all investigated neonates. The receiver operating characteristic (ROC) curve analysis demonstrated the cut-off value for the serum HE4 in the researched neonates at the level of 318.5 pmol/L, yielding the sensitivity of 73.9% and specificity of 66.7% for the early diagnosis of TTN. CONCLUSIONS: Serum HE4 could be considered as a candidate biomarker for the early diagnosis of pulmonary dysfunction in the newborns.

The External Genitalia Score (EGS): A European Multicenter Validation Study.

CONTEXT: Standardized description of external genitalia is needed in the assessment of children with atypical genitalia. OBJECTIVES: To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs). DESIGN, SETTING: A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018. PATIENTS AND METHODS: EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0-12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0-24 months) and 181 preterm babies, and 111 babies with atypical genitalia. RESULTS: The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6-11.5); in males 28-32 weeks 11.5 (9.2-12); in males 33-36 weeks 11.5 (10.5-12) and in full-term males 12 (10.5-12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia. CONCLUSIONS: EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research.

Abnormal Biomarkers of Homocysteine Metabolism in Neonates with Conotruncal Heart Defects.

OBJECTIVES: The etiology of conotruncal heart defects (CHD) remains unknown; however relation between homocysteine, folate levels, and congenital heart disease was found. With this perspective in mind, the aim of the study was to investigate biomarkers of homosyteine metabolism pathway in mothers and their neonates with CHD. MATERIAL AND METHODS: Forty-three pairs of mothers and their neonates with CHD and forty pairs of mothers and neonates with nonconotruncal heart defects (non-CHD) were enrolled. The control group (CG) consisted of fifty-nine pairs of mothers and their healthy neonates. For estimating the plasma total homocysteine (tHcy), serum folates, and cobalamin levels, mothers' venous blood samples and umbilical cord blood were taken in all groups. RESULTS: We observed higher tHcy levels in newborns with CHD in comparison to their mothers and to neonates with non-CHD. Cobalamin levels were significantly lower in neonates with CHD compared to other children. Folates and cobalamin levels were lower in CHD mothers compared to their children. CONCLUSIONS: Elevated homocysteine levels in neonates with CHD and folate metabolism disturbances in their mothers were noticed. The observed differences in homocysteine and cobalamin levels between neonates with CHD suggest the influence of various agents disturbing homocysteine metabolic pathways.

Serum NGAL and copeptin levels as predictors of acute kidney injury in asphyxiated neonates.

BACKGROUND: Acute kidney injury (AKI) is the most common complication of perinatal asphyxia. Recent research indicates that serum neutrophil gelatinase-associated lipocalin (NGAL) is an early marker for AKI, but there are the lacks of data about its use in term neonates with perinatal asphyxia. METHODS: A prospective cohort study was conducted on 43 term neonates. Umbilical cord blood and 24 h after birth serum NGAL, copeptin, creatinine, and molality were measured in all asphyxiated and controls neonates. RESULTS: During the study period, 8 of asphyxiated nenates (18.6 %) suffered from AKI, while 35 newborns have no signs of AKI and 30 healthy infants. We did not observe any differences in creatinine and copeptin levels, as well as serum osmolality in all three investigated groups (AKI, no-AKI, and controls) in cord blood, and 24 h after birth. Serum NGAL levels in umbilical cord blood were significantly higher in the AKI group (174.3 ng/mL) compared with no-AKI (88.5 ng/mL, p = 0.01) and control groups (28.5 ng/mL, p < 0.001), and 24 h after birth (respectively, AKI 152.5 ng/mL vs no-AKI 74.9 ng/mL, p = 0.02 vs controls 39.1 ng/mL, p < 0.001). NGAL concentration showed a strong negative correlation to umbilical artery pH (Rho = -0.42, p = 0.04), base excess (Rho = -0.31, p = 0.03), and Apgar score in 1st min (Rho = -0.41, p = 0.02) and 5th min of life (Rho = -0.20, p = 0.001). ROC curve analysis demonstrated a good predictive value for NGAL levels (>140.7 ng/mL) which allows to diagnose AKI in asphyxiated patients with 88.9 % sensitivity (95 % CI 75-95 %) and 95.0 % specificity (95 % CI 76-99 %). CONCLUSION: NGAL seems to be a promising marker, even in subclinical AKI in neonates, due to its high specificity, but copeptin did not meet expectations.

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis.

OBJECTIVES: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband's prenatal examination. MARETIAL AND METHODS: Nine family members were tested for TBX5 gene mutation. RESULTS: Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results. The diagnosis allowed to identify a genetic risk family and enabled to provide them with genetic counselling. CONCLUSIONS: Diagnosis of Holt-Oram syndrome is possible as early as in prenatal period and it can be verified by genetic tests.

Umbilical markers of perinatal hypoxia.

OBJECTIVES: The aim of the study was to evaluate activin A and NGAL levels as potential early markers of perinatal hypoxia. MATERIAL AND METHODS: We prospectively studied 58 full-term newborns: 24 with perinatal hypoxia (study group) and 34 healthy controls. Umbilical cord blood samples were obtained from all subjects immediately after delivery for the measurement of activin A and NGAL levels. Both biomarkers were correlated with biochemical indicators od hypoxia and neonatal complications. RESULTS: Activin A levels were significantly higher in hypoxic as compared to non-hypoxic newborns (0.51 vs. 0.22pg/mL; p<0.01). NGAL levels were also higher in asphyxiated babies as compared to controls (99.1 vs. 22.3ng/mL; p<0.001). A correlation between NGAL and activin A levels was detected (R=0.54; p<0.01). NGAL concentration was also correlated with Apgar score at 5 min. and pH value, HCO3, based deficit and lactate levels. ROC curve analysis demonstrated the cutoff value of >33.9ng/ml for NGAL in prediction of perinatal asphyxia in neonates, with a sensitivity of 100% and specificity 78.3%, whereas the cutoff value for activin A was 0.208ng/ml had, with a sensitivity of 93.1% and only 26.7% specificity. CONCLUSIONS: Asphyxiated neonates demonstrate elevated NGAL and activin A levels as compared to controls. The correlation of NGAL with clinical and biochemical signs of neonatal hypoxia, as well as higher sensitivity and specificity for NGAL measurements, have led us to believe that NGAL could be a better marker of perinatal hypoxia than activin A.

Geospatial clustering of gastroschisis in Poland: Data from the Polish Registry of Congenital Malformations (PRCM).

OBJECTIVES: The aims of this study were: to evaluate the prevalence of abdominal wall defects in the Polish population, to analyze temporal trends in the prevalence, to identify areas (clusters) of high risk of abdominal wall defects, and to characterize, with respect to epidemiology, children with abdominal wall defects and their mothers in the area defined as a cluster. MATERIAL AND METHODS: We used isolated congenital malformations (gastroschisis Q79.3 and omphalocele Q79.2 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10, the extended version)) data reported to the Polish Registry of Congenital Malformations (PRCM) over the years 1998- 2008 based on the population of 2 362 502 live births. We analyzed 11 administrative regions of Poland with complete epidemiologic data. RESULTS: Of 11 regions, 2 had a significantly higher standardized prevalence of isolated gastroschisis: Dolnoslaskie (1.7/10 000 live births, p = 0.0052) and Slaskie (1.9/10 000 live births, p < 0.0001). Furthermore, within the region of Dolnoslaskie, we defined a clear prevalence of the isolated gastroschisis cluster (p = 0.023). We comprehensively examined demographic and socio-economic risk factors for abdominal wall defects in this area, and we found that these factors failed to account for the cluster. CONCLUSIONS: We identified a distinct prevalence cluster for isolated gastroschisis, although a precise reason for the disease clustering in this region remains unknown. Cluster identification enables more focused research aimed at identification of specific factors with teratogenic effects.

Can neonates born at 34 weeks be classified as late preterm?

OBJECTIVES: In recent years, much attention has been given to infants born prematurely, at 34 0/7 to 36 6/7 weeks of gestation (WG), which have been classified as 'late preterm'. Neonates from that subgroup are less physiologically and metabolically mature than term infants. The aim of the study was to determine whether infants born at 34WG can be classified as 'late preterm' or 'preterm' newborns. MATERIAL AND METHODS: A total of 141 newborns were included in the study: 25 born ≤ 33WG, 53 late-preterm newborns, and 63 term infants. Cord-blood neutrophil gelatinase-associated lipocalin (NGAL) and creatinine concentrations were measured in all newborns. Also, the incidence of clinical complications in the early adaptive period during hospitalization was evaluated. RESULTS: Higher NGAL concentration was noted among preterm newborns as compared to late-preterm neonates (p < 0.05), and term newborns (p < 0.05), especially in children born at 34WG as compared to 35WG (p < 0.001). However, no differences in NGAL concentration were found between neonates born at 35WG and 36WG, as well as children born at 36WG and term infants. A relationship between umbilical NGAL levels and gestational age was observed. Additionally, a statistically significant difference was found in the incidence of respiratory distress syndrome (p < 0.05) and infections (p < 0.05) among neonates born at 34WG as compared to 35WG. CONCLUSIONS: Late preterm neonates should be defined as 'preterm' between 35 0/7 and 36 6/7 WG. Infants born at 34WG should be included in the preterm group.

Umbilical neutrophil gelatinase-associated lipocalin level as an early predictor of acute kidney injury in neonates with hypoplastic left heart syndrome.

Acute kidney injury (AKI) is a primarily described complication after unbalanced systemic perfusion in neonates with congenital heart defects, including hypoplastic left heart syndrome (HLHS). The aim of the study was to compare the umbilical NGAL concentrations between neonates born with HLHS and healthy infants, as well as to analyze whether the determination of NGAL level could predict AKI in neonates with prenatally diagnosed HLHS. Twenty-one neonates with prenatally diagnosed HLHS were enrolled as study group and 30 healthy neonates served as controls. Perinatal characteristics and postnatal parameters were extracted from the hospital neonatal database. In umbilical cord blood, we determined plasma NGAL concentrations, acid base balance, and lactate and creatinine levels. In neonates with HLHS, complications (respiratory insufficiency, circulatory failure, NEC, IVH, and AKI) were recorded until the day of cardiosurgery. We observed in neonates with HLHS higher umbilical NGAL levels compared to controls. Among 8 neonates with HLHS and diagnosed AKI stage 1, we observed elevated NGAL levels in comparison to those newborns without AKI. Umbilical NGAL could predict, with high sensitivity and specificity, AKI development in study neonates. We suggest that the umbilical blood NGAL concentration may be an early marker to predict AKI in neonates with HLHS.

Umbilical cord blood NGAL concentration as an early marker of perinatal asphyxia in neonates.

INTRODUCTION: Recent reports have revealed increased concentration of neutrophil gelatinase-associated lipocalin (NGAL) in cardiovascular diseases and after episodes of hypoxia. We hypothesized that elevated plasma NGAL levels could be a result of vascular endothelial injury due to perinatal asphyxia. MATERIALS AND METHODS: Ninety-three newborns with a gestational age > or = 37 weeks, of which 32 newborns were asphyxiated (study group), and 61 were healthy children (control group), were enrolled in the study Serum NGAL, lactate and creatinine concentrations, acid-base balance, neutrophil and white blood cell count were measured in the umbilical cord blood. RESULTS: Asphyxiated newborns had a significantly lower pH value (7.0 vs. 7.3, p < 0.001), lower HCO3 (15.8 mmol/L vs. 23.2 mmol/L; p < 0.001) and higher lactate concentrations (7.5 mmol/L vs. 2.3 mmol/L; p < 0.001), as compared to controls. Neutrophil count (10.3 x 109/L vs. 6.5 x 109/L; p = 0.02) and NGAL concentration (122.5 ng/mL vs. 24.3 ng/ mL p < 0.001) were elevated in asphyxiated newborns as compared to healthy children. CONCLUSIONS: The measurement of NGAL in the umbilical blood can be a valuable biomarker of perinatal asphyxia in neonates.

Umbilical activin A concentration as an early marker of perinatal hypoxia.

OBJECTIVE: To evaluate activin A as a potential, early marker of perinatal hypoxia and to analyze factors, other than hypoxia, which influence on activin A concentration. METHODS: Umbilical cord blood samples were collected from 86 newborns with gestational age 30-41. Of the 86 newborns, 26 were regarded as hypoxic. Activin A concentrations were measured by means of specific two-site enzyme immunoassays. Activin A concentrations were correlated with newborns' gender, week gestation, mode of delivery and blood gas measurements. RESULTS: Activin A levels were significantly higher in hypoxic than nonhypoxic newborns (medians, minimum and maximum values: 1.516; 0.149 -1.974 versus 0.368; 0.054 - 1.041 ng/mL, p = 0.0452). Activin A concentration was significantly higher in male newborns (p = 0.0074). Activin A levels were lower in term than preterm babies but the differences were not statistically significant (p = 0.2368 in hypoxic, p = 0.2487 nonhypoxic). Mode of delivery did not influence on activin A concentration (p = 0.8293 hypoxic, p = 0.9458 nonhypoxic). The differences of occurrence of intraventricular hemorrhage (IVH) in both group was not statistically significant (p = 0.61). CONCLUSIONS: Umbilical artery activin A combined with other markers of hypoxia could be a useful marker of perinatal hypoxia. Concentration of activin A is significantly higher in male newborns. The mode and time of delivery have no influence on activin A concentration.

[Late preterm infants--complications during the early period of adaptation]. / Zaburzenia w okresie adaptacyjnym noworodków urodzonych "blisko terminu porodu".

UNLABELLED: A subgroup of more mature preterm infants, so-called "near term" ("late preterm") infants, 34 weeks 0/7 days to 36 weeks 6/7 days, have become the interest of countless research recently OBJECTIVES: the aim of the study is the observation of more frequent occurrence of clinical problems in near-term infants in comparison with term infants. METHODS: A retrospective review, conducted from January 1, 2008 to December 31, 2008, included 1271 neonatal records and subset analyses of 312 near-term infants and 812 full term infants. RESULTS: Late preterm newborns were at higher risk of respiratory distress syndrome (p < 0.01), infections, (p = 0.00012) hyperbilirubinemia (p < 0.001), temperature instability (p < 0.001) and intraventricular hemorrhage (p < 0.001) than term infants. A prolonged infant stay at hospital (beyond 72 hours after vaginal delivery and 96 hours after a cesarean delivery) resulting from specific clinical problems was observed. CONCLUSIONS: Even a little shortened period of pregnancy influences the adaptation period of the infants and increases the occurrence of clinical problems like respiratory distress syndrome, hyperbilirubinemia, infections, temperature instability and intraventricular hemorrhage, when comparing to term infants.

Plasma homocysteine concentrations in mothers and term and preterm newborns.

AIM: To assess the correlation between homocysteine concentrations and gestational age, gender Apgar score, complications in pregnancy delivery modalities and levels of vitamin B12 and foliate. MATERIAL AND METHODS: Concentration of homocysteine, vitamins-B12, foliate were measured in cord blood and mother blood. There were 40 full-term babies and 38 preterm babies and their mothers. RESULT: The homocysteine concentration in newborns correlated with homocysteine level in mothers. There was no difference in homocysteine level regardless of newborns gender. There was no correlation in the homocysteine concentration of mothers blood and cord blood with the levels of vitamin 812 and foliate. In full-term newborns a significant increase in homocysteine levels in comparison with premature babies was observed (7.2 +/- 1.4 micromol/ vs. 6.4 +/- 1.3 micromo/l; p = 0.01). Additionally negative correlation between the mothers' age and homocysteine concentration (r = -0.23; p = 0.04) and positive correlation between homocysteine concentration in cord plasma and gestation age (r = 0.28; p = 0.01) were found. CONCLUSION: Homocysteine concentration depends on gestational age, Apgar score and mother's age. There is no correlation between homocysteine level and hypertension during pregnancy type of delivery levels of vitamin 812 and foliate. Determination of homocysteine level is therefore of no significant importance in newborns pathophysiology.

[Activin A as a possible marker for hypoxia and intraventricular haemorrhage in newborns]. / Aktywina A potencjalnym markerem niedotlenienia okoloporodowego oraz krwawien dokomorowych u noworodków.

The article presents general information about activin A, a glycoprotein that belongs to the transforming growth factor beta superfamily. Structure, mechanism and role of activin as a possible marker of hypoxia and intraventricular haemorrhage were described.

[Congenital cystic adenomatoid lung malformation - diagnosis and treatment - based on literature and own experiences]. / Wrodzona torbielowatosc gruczolakowata pluc - diagnostyka i leczenie - na podstawie literatury oraz wlasnych doswiadczen.

Congenital cystic adenomatoid malformation (CCAM) is an uncommon congenital abnormality of the lung which has a wide spectrum of potential outcomes, ranging from hydrops and severe respiratory distress with pulmonary hypoplasia, to resolution of the lesion either antenatally or postnatally. Most of the babies are asymtomaptic. It is caused by arrest of normal foetal pulmonary maturation. The prognosis is generally good. In cases where the lesion persists, surgery is recommended. CCAM is an important diagnosis and can be suspected on routine antenatal ultrasound. It has implication for both the ongoing pregnancy, at delivery and later in life. The authors present a male newborn with CCAM diagnosed during the neonatal period. The diagnosis was based on CT scan and histopathological examination. Characteristic plural cystic defects in the lungs were found. The patient was referred for surgical treatment.

[The Smith-Lemli-Opitz syndrome--case report, early diagnosis]. / Zespól Smitha, Lemlego i Opitza--opis przypadku, wczesna diagnostyka.

Smith-Lemli-Opitz syndrome (SLOS) is one of the most frequent metabolic disorders in Poland and manifests itself with multiple congenital anomalies, psychomotor delay and intellectual disability. It is caused by mutations in DHCR7 gene, which codes one of the cholesterol biosynthesis enzymes. Clinical diagnosis of the syndrome is difficult due to lack of pathognomonic features and their variable expression. Despite high carrier frequency in Poland, SLO syndrome is rarely suspected and recognized. Its early diagnosis is essential, mainly because of high genetic risk (25%) as well as possibilities of treatment. Authors present a female-newborn, diagnosed with SLOS during the neonatal period. The diagnosis was based on biochemical and molecular tests. Mutations in DHCR7 gene have been found in both, the child and the parents.

[Nitric oxide--doctor or killer?]. / Tlenek azotu--lekarz czy zabójca?

This study shows present knowledge on the role of nitric oxide (NO)--a reactive gas that functions both as a signaling molecule in endothelial cells and nerve cells and as a killer molecule. The article also presents how we can use NO in treatment.

[Leptin concentration in umbilical cord blood and maternal blood]. / Stezenie leptyny w surowicy krwi pepowinowej noworodków i w surowicy krwi ich matek.

We investigated leptin concentration in umbilical cord blood of 51 newborns (mean 5.71 +/- 3.28 ng/ml) and in maternal blood (mean 22.11 +/- 10.95 ng/ml). Leptin concentration in 20 preterm infants (mean 4.73 +/- 2.15 ng/ml) was significantly lower (p < 0.05) than in full-term newborns (mean 6.34 +/- 2.08 ng/ml) and tended to increase according to gestational age and birth weight. We suggested leptin concentration had a role in intrauterine development.

[Do preterm infants differ from healthy newborns by endothelin para/endocrine function?]. / Czy noworodki urodzone przedwczesnie róznia sie czynnoscia parakrynno/endokrynna sródblonka naczyniowego od noworodków donoszonych?

We measured plasma concentration of endothelin-1 (ET-1), nitric oxide metabolites (NOx) and von Willebrand factor (vWF) in maternal and umbilical cord blood in 11 spontaneous (SN), 11 elective cesarean section (CC) and 13 preterm deliveries. Plasma concentrations of ET-1 in umbilical cord blood of preterm infants and systemic blood withdrawn 4 days after birth was higher then in respective healthy infants delivered by natural forces or elective cesarean section. Positive correlation were found between ET-1 and NOx (p < 0.05) and between ET-1 and vWF (p < 0.05) in maternal blood with preterm delivery. In umbilical cord of preterm infants a negative correlation between ET-1 and Apgar score was noticed. Higher concentrations of ET-1, NOx and vWF found in umbilical cord blood of preterm infants as compared with respective values assessed in healthy infants delivered per vaginam or by cesarean section respectively seem to be induced by hypoxia.