Response of leukocytes and nucleated red blood cells in very low-birth weight preterm infants after exposure to intrauterine inflammation

Objectives.?To test the hypothesis if very immature preterm infants exposed to chorioamnionitis would exhibit increased numbers of leukocytes, neutrophils, and nucleated red blood cells (NRBC) in peripheral blood.

Study design.?Preterm infants with birth weight <1500?g were prospectively evaluated. Blood cells were counted within the first hour of life in infants exposed to histological chorioamnionitis and controls.

Results.?Birth weight, gestational age, and sex did not differ between the groups (n?=?71). Seventeen infants who were exposed to chorioamnionitis had significantly higher counts of leukocytes, neutrophils, and immature neutrophils after birth. However, there was no difference in the number of circulating NRBCs between both groups. In contrast, there was a tendency towards an increased NRBC count in the control group.

Conclusion.?Preterm infants exposed to chorioamnionitis elicited a strong inflammatory response as reflected by increased numbers of leukocytes and neutrophils. However, chorioamnionitis did not induce an increase in numbers of NRBC.     

Cord blood erythropoietin and cord blood nucleated red blood cells for prediction of adverse neonatal outcome associated with maternal obesity in term pregnancy: prospective cohort study

Objective: To determine the adverse pregnancy outcomes associated with maternal pre-pregnancy overweight and obesity and we measure cord blood erythropoietin and NRBC count as indices of hypoxia and predictors of neonatal outcome.

Study design: This prospective cohort study was done in Minia University Hospital, carried out from May 2015 to April 2016. Two hundred and seventy full-term neonates born to mothers of various body mass indices were included. Excluded were neonates with major factors known to be associated with a potential increase in fetal erythropoiesis. Pre-pregnancy maternal BMI was calculated from maternally reported weight and height. Cord blood erythropoietin and nucleated red blood cells were measured.

Results: There is a significant increase of various adverse pregnancy outcomes as cesarean section. Postpartum hemorrhage and macrosomia with the increase of maternal pre-pregnancy BMI. Significant positive correlations between cord blood erythropoietin and nucleated red blood cells with maternal BMI.

Conclusion: The increase in the maternal pre-pregnancy BMI is associated with poor pregnancy outcomes. Cord blood erythropoietin and nucleated red blood cells can predict the poor neonatal outcome.     

Comparison of maternal and cord blood nucleated red blood cell count between pre-eclamptic and healthy women

AIM: The aim of this study was to evaluate the influence of pre-eclampsia on the cord and maternal nucleated red blood cell (NRBC) count. METHODS: Immediately after delivery, 1 mL of maternal venous blood and 1 mL of cord blood from 50 pre-eclamptic and 150 healthy pregnant women were collected separately in tubes containing 1.5 mg ethylene diamine tetra-acetic acid. Blood smears were prepared and stained using the Giemsa method. The number of NRBC per 100 leukocytes in maternal and cord blood was counted and compared between the two groups using SPSS software package for Windows. Any correlation of the NRBC count in maternal and umbilical cord blood was also evaluated. P-values < 0.05 were considered significant. RESULTS: The mean (+/-SD) NRBC per 100 white blood cell (WBC) level in cord blood of newborns in the pre-eclamptic group (18.2 +/- 31.8, range 0-142) was significantly greater than in the control group (6.2 +/- 8.1, range 0-36). Low birth weight and intrauterine growth restriction showed a statistically significant relationship with abnormal NRBC count in pre-eclamptic patients. A significant correlation was found between the maternal and cord blood NRBC count in the pre-eclamptic group. CONCLUSION: Fetal response to utero-placental insufficiency in pre-eclampsia leads to elevated NRBC in the cord blood, particularly in the presence of low birth weight and intrauterine growth restriction. The positive correlation between maternal and cord blood NRBC counts in pre-eclamptic patients indicates that maybe the hypoperfused placenta plays a role in the correlated alteration of the maternal and fetal NRBC count.     

Ongoing issues in the intensive care for the periviable infant—Nutritional management and prevention of bronchopulmonary dysplasia and nosocomial infections

The focus of this paper is to describe the following: (1) the benefits of implementing feeding guidelines, (2) management practices associated with the prevention of BPD, and (3) management practices associated with prevention of nosocomial infection.     

Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns.

OBJECTIVE: To determine normal level of nucleated red blood cells (NRBC) per 100 white blood cells (WBC) in cord blood of term non-asphyxiated newborns and to investigate variations in NRBC counts in perinatal asphyxia. METHODS: A total of 75 cases were studied. Levels of NRBC per 100 WBC in umbilical venous blood were compared between 26 asphyxiated newborns (group I) and 49 non-asphyxiated newborns (group II). Correlation with neonatal outcome was also evaluated. RESULTS: The mean (+/-S.D.) NRBC per 100 WBC level in umbilical blood of newborns in group I was 16.5+/-6.4, range 3-25; whereas that in group II was 8.6+/-7.01, range 1-26. This difference was statistically significant (P<0.001). A statistically significant negative correlation existed between NRBC level and markers of acute intrapartum asphyxia, Apgar score and umbilical arterial pH (r=-0.50, P<0.001 and r=-0.48, P<0.001, respectively). Positive correlation was demonstrated with evidence of chronic antepartum asphyxia, presence of pregnancy induced hypertension and intrauterine growth restriction (r=2.66, P=0.02). A high NRBC count in umbilical blood correlated with poor early neonatal outcome. CONCLUSIONS: The level of NRBC per 100 WBC correlates both with acute as well as chronic antepartum asphyxia. Further, it can be used as a reliable index of early neonatal outcome.     

Fetal "nonreassuring status" is associated with elevation of nucleated red blood cell counts and interleukin-6

OBJECTIVE: Previous studies have established the association between fetal hypoxia and elevated nucleated red blood cells (NRBCs). Animal studies have demonstrated that a rise in plasma erythropoietin (EPO) is not detectable until 4 to 6 hours after the initiation of hypoxia. In contrast, interleukin-6 (IL-6) has the capacity to directly induce erythroid maturation. Therefore, we set forth to evaluate the role of EPO and IL-6 as potential mediators of elevated fetal NRBCs in response to acute hypoxia. STUDY DESIGN: Low-risk pregnancies with a normal fetal heart rate at admission to labor and delivery were eligible for participation. Deliveries for "nonreassuring fetal status" comprised the study group. All other deliveries served as controls. Umbilical cord blood was prospectively collected for blood gas analysis, NRBC counts, EPO, and IL-6. RESULTS: One hundred women participated in the study. Nonparametric univariate analysis demonstrated a significant association between elevated NRBC counts and Apgar scores, arterial cord blood pH, base excess, EPO, and IL-6 levels (all P values <.01). Stepwise regression analysis identified only pH, IL-6, and EPO as independent variables associated with elevated NRBC counts at birth (all P values <.0001 with R2 of 0.27, 0.42, and 0.46, respectively). A significant increase in NRBC counts was noted in study patients. IL-6 was significantly increased in study patients, whereas there was no difference in EPO between groups. CONCLUSION: The fact that NRBC counts were elevated in fetuses who were delivered for "nonreassuring fetal status" with EPO being normal and IL-6 being elevated implies that IL-6 may have a unique, short-term role in elevating fetal NRBC counts.     

Nucleated red blood cells in cord blood of singleton term neonates

OBJECTIVE: This study aims to establish normal values for nucleated red blood cells in term singletons and factors associated with their elevation.STUDY DESIGN: Cord blood was prospectively collected from term singleton gestations from Feb. 1 to July 31, 1995. Umbilical vein white blood cells and nucleated red blood cells were counted and umbilical arterial pH was determined. Medical records provided maternal and neonatal information.RESULTS: Cord blood from 1112 cases was obtained and evaluated for nucleated red blood cells per 100 white blood cells. Nine outliers were censored (nucleated red blood cells per 100 white blood cells = 126 to 830); five cases were excluded because of missing data. The mean value of nucleated red blood cells per 100 white blood cells was 8.55, the SD was 10.27, and the range was 0 to 89. The value did not vary by maternal tobacco or drug use, anemia, fetal presentation, or mode of delivery. Both maternal diabetes and meconium were associated with elevated values, p < 0.01. Apgar scores and cord pHs showed trends toward inverse proportionality to the number of nucleated red blood cells per 100 white blood cells.CONCLUSION: The mean number of nucleated red blood cells per 100 white blood cells was 8.55, with a wide range and SD. Elevated values may be associated with markers of intrauterine hypoxia such as meconium, lower Apgar scores, and lower pH values. (Am J Obstet Gynecol 1997;176:1149-56.)     

The correlation between automated hematology and manually read smears for the determination of nucleated red blood cells in umbilical cord blood

Objective.?To determine the correlation between automated hematology nucleated red blood cell counts and manual counts in umbilical cord blood.

Methods.?Umbilical cord venous blood was obtained after cord clamping at the time of delivery. The number of nucleated red blood cells per one hundred white blood cells was measured using an automated hematology analyzer and compared with direct microscopic visualization of prepared slides by experienced hematology technicians.

Results.?The umbilical cord blood from 128 women was studied. The mean, median and standard deviations of nucleated red blood cell counts were not significantly different between the automated reading and the manual reading (mean 9.3?±?11.2 versus 9.1?±?13.1, respectively, P?=?0.76; median 5.9 versus 5.0, P?=?0.95; range 0–77, 0–105). Automated derived nucleated red blood cell counts and manual numbers were highly correlated with a correlation coefficient of 0.794.

Conclusion.?The automated hematology analyzer readings of nucleated red blood cell counts correlate well with readings by laboratory hematologists.     

The relationship between nucleated red blood cell counts and early-onset neonatal seizures

OBJECTIVE: This study was undertaken to better define the timing of neurologic insult in neonates with early-onset seizures through evaluation of neonatal nucleated red blood cell levels. STUDY DESIGN: Medical records and the International Classification of Diseases, Ninth Revision codes were used to identify all term neonates with neonatal convulsions who were delivered at our institution (January 1, 1990-December 31, 1995). Each neonate with early-onset seizures was matched to the next 3 neonates who met the following criteria: gestational age > or =37 weeks, no early-onset seizures, birth weight > or =800 g, umbilical artery pH > or =7.25, and a 5-minute Apgar score >7. Demographic characteristics, clinical factors, and mean initial nucleated red blood cell counts were compared between groups. RESULTS: During the 6-year study period, there were a total of 36, 490 singleton term deliveries of infants who were alive at birth. Forty-five (0.1%) of these neonates had early-onset seizures. Thirty neonates with early-onset seizures met the inclusion criteria. Mean nucleated red blood cell counts (number of nucleated red blood cells per 100 white blood cells) for neonates with early-onset seizures were significantly increased compared with those of control neonates (18.4 +/- 22.0 vs 4.6 +/- 4.5; P <.0008). CONCLUSIONS: Our findings are suggestive of the hypothesis that neurologic injury leading to early-onset seizures often occurs before the intrapartum period.     

Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates

Objective: Nucleated-red-blood-cells (NRBC) count in umbilical cord of newborns is been suggested as a sign of birth asphyxia. The present study was conducted to explore the value of NRBC count in prognosis of asphyxiated neonates.

Methods: Sixty-three neonates with asphyxia were followed up for two years. Maternal and neonatal information was recorded follow by clinical and laboratory evaluation. NRBC-level was determined per 100 white-blood-cells (WBC). After discharge, follow-up of asphyxiated infants was performed using Denver II test at 6, 12, 18 and 24 months. Neonates were divided into two groups, with favorable and unfavorable outcome based on developmental delay or death.

Results: We observed that NRBC count with more than 11 per 100 WBC, had sensitivity of 85% and specificity of 90% in predicting complications of asphyxia, while in absolute NRBC count with more than 1554, the sensitivity and specificity were 85% and of 87%, respectively. Combination of NRBC?+?HIE (hypoxic ischemic encephalopathy) grade had a high-predictive power for determining the prognosis of asphyxia in neonates.

Conclusion: We demonstrate that NRBC/100 WBC and absolute NRCB count can be used as prognostic marker for neonatal asphyxia, which in combination with the severity of asphyxia could indicate high infant mortality, and complications of asphyxia. Further studies in a larger and multi center setting trail are warranted to investigate the value of NRBC and HIE in asphyxiate term infants.     

Nucleated red blood cells in concordant, appropriate-for-gestational age twins

OBJECTIVES: The purpose of this study was to test the hypothesis that neonatal nucleated red blood cell (RBC) counts are elevated in nondiscordant twins compared with singletons. STUDY DESIGN: We compared absolute nucleated RBC counts taken after birth in 2 groups of term, appropriate-for-gestational age infants; 74 concordant twins, and 29 singleton control infants. We excluded infants with factors associated with a potential increase in absolute nucleated RBC counts. RESULTS: Birth weight and gestational age were significantly lower in twins than in singletons (P < .01). Hematocrit, absolute nucleated RBC count, and corrected lymphocyte counts were significantly higher in twins (P < .01). In multiple regression, the significantly higher absolute nucleated RBC count in twins remained significantly higher even after taking into account gestational age and Apgar scores. CONCLUSION: Concordant, appropriate-for-gestational age twins have increased nucleated RBCs at birth compared with singleton control infants.     

Vitamin A supplementation in late pregnancy can decrease the incidence of bronchopulmonary dysplasia in newborns

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infancy which is associated with prematurity and early lung injury resulting from mechanical ventilation. Oxygen toxicity, barotrauma, and volutrauma play key roles in its pathogenesis. Parenteral administration of Vitamin A to the newborn is the current recommended preventive therapy for BPD. Vitamin A has been found to upregulate genes necessary for fetal lung growth and increase surfactant production in animal models. Supplementation of Vitamin A in late pregnancy increases the cord blood vitamin A levels proportionately. Hence, we hypothesize that Vitamin A supplementation during late pregnancy can decrease the incidence of BPD in newborns. This can be an effective adjunct to postnatal preventive therapy. Vitamin A supplementation in late pregnancy carries no risk of teratogenicity unlike in early pregnancy. Moreover, vitamin A deficiency in pregnancy is associated with depressed immune function leading on to increased infectious morbidity and can cause intrauterine growth retardation, low birth weight and anemia in newborns. Combining antenatal Vitamin A supplementation to the mother with postnatal supplementation to the newborn can effectively prevent BPD better than the traditional postnatal preventive therapy alone. It will also treat the highly prevalent vitamin A deficiency in pregnant mothers and newborns of the developing world.     

Nucleated red blood cell and platelet counts in asphyxiated neonates sufficient to result in permanent neurologic impairment

Objective.?Recent research has suggested that a nucleated red blood cell (NRBC) count ≥26 per 100 white blood cells (%) or the development of a platelet count ≤100 000 per mm³ within five days of birth is characteristic of neonates who have experienced acute birth asphyxia.

Study design.?Study cases were from the population defined in a prior publication (Prenat Neonat Med 1997;2:286). The impaired neonates were separated into three groups: group 1, persistent non-reactive fetal heart rate (FHR) pattern from admission until delivery; group 2, reactive FHR pattern on admission followed by a tachycardia, non-reactivity, repetitive variable or late decelerations, and usually a loss of variability; group 3, cases with a reactive FHR pattern on admission followed by a sudden, rapid and sustained deterioration of the FHR usually in response to a hypoxic sentinel event that lasted until delivery or a bradycardia on admission. The FHR pattern in group 3 is considered most consistent with acute birth asphyxia. We then examined these FHR groups with respect to the presence of hematologic injury. Chi-square testing was used to describe differences among the study populations.

Results.?Of the original 52 cases, sufficient hematologic data were available for 47. Of these, the proportion of cases with NRBC ≥26% was: group 1, 10/21 (47.6%); group 2, 0/14 (0%); group 3, 0/12 (0%). Those with a platelet count ≤100 000 per mm³: group 1, 11/21 (52.4%); group 2, 2/14 (14.3%); group 3, 0/12 (0%). Group 1 was significantly more likely to have an NRBC count ≥26% than group 3 (p = 0.0135). A platelet count ≤100 000 per mm³ within five days of birth was also significantly more likely to be encountered in group 1 as compared with group 3 (p = 0.0072).

Conclusion.?In cases of acute birth asphyxia, hematologic injury was infrequently encountered. Our findings suggest that a neonatal NRBC count ≥26% and/or a platelet count ≤100 000 per mm³ within five days of birth is inconsistent with acute birth asphyxia.     

Fetal origin of single nucleated erythroblasts and free DNA in the peripheral blood of pregnant women.

OBJECTIVES: To investigate the feasibility of using single fetal nucleated erythroblasts (FNRBCs) and free DNA in maternal blood for non-invasive prenatal diagnosis. METHODS: Single FNRBCs were isolated from 51 of 116 samples of maternal blood analyzed by micromanipulation after density gradient centrifugation. Furthermore, the nested polymerase chain reaction (PCR) method was used to amplify the SRY gene of single FNRBCs. Primer extension pre-amplification and nested PCR were used to amplify the SRY gene of the plasma DNA extracted from 65 samples of maternal blood. RESULTS: The detection rate of single FNRBCs was 90.20% (46/51). The concordance rates between real fetal sex and sex determined by amplification of the SRY gene from single cells and from free DNA analysis were 82.61% (38/46) and 90.77% (59/65), respectively. CONCLUSIONS: Single nucleated erythroblasts and free DNA in maternal blood are of fetal origin and can be valuable fetal material sources for non-invasive prenatal diagnosis.     

Preclinical evaluation of cell-based strategies to prevent or treat bronchopulmonary dysplasia in animal models: a systematic review

Bronchopulmonary dysplasia (BPD) remains the most common complication of extreme prematurity as no effective treatment is available to date. This calls for the exploration of new therapeutic options like cell therapy, which is already effective for various human (lung) disorders. We systematically searched the MEDLINE, Embase, and Web of Science databases from the earliest date till January 2017 and included original studies on the perinatal use of cell-based therapies (i.e. cells and/or cell-derivatives) to treat BDP in animal models. Fourth publications describing 47 interventions were retrieved. Newborn mice/rats raised in a hyperoxic environment were studied in most interventions. Different cell types – either intact cells or their conditioned medium – were administered, but bone marrow and umbilical cord blood derived mesenchymal stem cells were most prevalent. All studies reported positive effects on outcome parameters including alveolar and vascular morphometry, lung function, and inflammation. Cell homing to the lungs was demonstrated in some studies, but the therapeutic effects seemed to be mostly mediated via paracrine modulation of inflammation, fibrosis and angiogenesis.

Conclusion: Multiple rat/mouse studies show promise for cell therapy for BPD. Yet careful study of action mechanisms and side effects in large animal models is imperative before clinical translation can be achieved.