Nucleated red blood cells in cord blood of singleton term neonates

doi:10.1016/S0002-9378(97)70328-4

American Journal of Obstetrics and Gynecology

Volume 176, Issue 6, June 1997, Pages 1149-1156

Presented at the Sixty-fourth Annual Meeting of The Central Association of Obstetricians and Gynecologists, Houston, Texas, October 17-19, 1996.

https://doi.org/10.1016/S0002-9378(97)70328-4 Get rights and content

Abstract

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.)

Section snippets

Methods

This study was approved by the Institutional Review Board of Sinai-Samaritan Medical Center, Milwaukee, Wisconsin. We prospectively studied pregnant women delivered of singletons at our institution between Feb. 1 and July 31, 1995. All were ≥37 weeks of gestation and had birth weights ≥2500 gm.¹² After delivery blood was drawn from the umbilical vein into an ethylenediaminetetraacetic acid tube for hematologic analysis. Samples from gestations of ≥37 weeks were labeled “NRBC STUDY” and sent to

Results

A total of 1609 singletons weighing ≥2500 gm at ≥37 weeks' gestation were delivered at our institution during the study period. Four hundred ninety-seven cases were not analyzed because of clotting or mislabeling of specimen, leaving 1112 cases in which nucleated red blood cells were studied. No significant differences in maternal age, race, gravidity, gestational age, neonatal birth weight, Apgar scores, or cord pH were found between cases in which nucleated red blood cells were studied and

Comment

In this study we set out to establish normative data for nucleated red blood cells in cord blood of term neonates. This has not previously been described in a large series. Early investigators attempted to define variations in the normal nucleated red blood cell counts by studying blood cells inside vessels on fixed histologic placental specimens.3, 4 Others have evaluated hematologic data obtained by venipuncture of neonates after varying periods of time.¹⁴ Hematologic data obtained after

Acknowledgements

We thank Judy Klingbeil, Chris Van Mullem, and Jerri Walters for their excellent technical assistance.

References (33)

GW. Anderson
Studies on the nucleated red cell count in the chorionic capillaries and the cord blood of various ages of pregnancy
Am J Obstet Gynecol
(1941)
IAL Groenenberg et al.
Relationship between fetal cardiac and extra-cardiac Doppler flow velocity waveforms and neonatal outcome in intrauterine growth retardation
Early Hum Dev
(1991)
JP Phelan et al.
Nucleated red blood cells: a marker for fetal asphyxia?
Am J Obstet Gynecol
(1995)
GR Alexander et al.
A United States national reference for fetal growth
Obstet Gynecol
(1996)
DW Green et al.
Nucleated erythrocytes in healthy and in infants of diabetic mothers
J Pediatr
(1990)
GB Merenstein et al.
Nucleated red-cells in the newborn
Lancet
(1970)
EM Ostrea et al.
Detection of prenatal drug exposure in the pregnant woman and her newborn
Clin Perinatol
(1991)
AC Halstead et al.
Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns
Clin Biochem
(1988)
L Pijpers et al.
Acute effect of maternal smoking on the maternal and fetal cardiovascular system
Early Hum Dev
(1984)
SN MacGregor et al.
Cocaine use during pregnancy: adverse perinatal outcome
Am J Obstet Gynecol
(1987)

DR Salvesen et al.

Fetal plasma erythropoietin in pregnancies complicated by maternal diabetes mellitus

Am J Obstet Gynecol

(1993)

SD Richey et al.

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid

Am J Obstet Gynecol

(1995)

GW. Anderson

Studies on the nucleated red cell count in the chorionic capillaries and the cord blood of various ages of pregnancy

Am J Obstet Gynecol

(1941)

JP Phelan et al.

Nucleated red blood cells: a marker for fetal asphyxia?

Am J Obstet Gynecol

(1995)

RL Naeye et al.

Determining the time before birth when ischemia and hypoxemia initiated cerebral palsy

Obstet Gynecol

(1995)

E. Neumann

Studies on the nucleated red cell count in the chorionic capillaries and the cord blood of various ages of pregnancy

Am J Obstet Gynecol

(1941)

Cited by (70)

Nucleated red blood cell: a feasible quality parameter of cord blood units
2023, Hematology, Transfusion and Cell Therapy
Umbilical cord blood is an alternative source of hematopoietic progenitor cells for bone marrow transplantation; however, it is associated with a higher graft failure rate. The presence of a high rate of nucleated red blood cells (NRBCs) seems to be related to a greater capacity for engraftment, although is also associated with fetal distress conditions. We analyzed the correlation of the NRBC with quality parameters and its association with the utilization score of a cord blood unit.
Data of 3346 units collected in a public cord blood bank from May 2010 to December 2017 were analyzed, retrospectively, to identify factors associated with an increased number of nucleated red blood cells and its correlation with the engraftment capacity measured through total nucleated cells (TNCs) and CD34 positive cells. We also evaluated the utilization score of these units and identified an NRBC cutoff associated with a higher score.
The median volume collected was 104 mL (42–255), the pre-processing TNC count was 144.77 × 10⁷ (95.46–477.18), the post-processing TNC count was 119.44 × 10⁷ (42.7–477.18), the CD34 count was 4.67 × 10⁶ (0.31–48.01), the NRBC count was 5 (0–202) and the utilization score was 0.0228 (0.00143–0.9740). The NRBC showed a correlation with the collected volume, TNC and CD34 positive cells and a higher utilization score and the receiver operating characteristic (ROC) curve analysis identified the five NRBC/100 leukocytes cutoff that correlates better with the probability of use. No association with pathological conditions and the NRBC rate was observed.
The NRBC is a feasible parameter for the screening of the cord blood unit (CBU) and the minimum cutoff of five NRBC/100 leukocytes can be a strategy in conjunction with the TNC to identify better units for cord blood bank sustainability.
Skewed fate and hematopoiesis of CD34<sup>+</sup> HSPCs in umbilical cord blood amid the COVID-19 pandemic
2022, iScience
Umbilical cord blood (UCB) is an irreplaceable source for hematopoietic stem progenitor cells (HSPCs). However, the effects of SARS-CoV-2 infection and COVID-19 vaccination on UCB phenotype, specifically the HSPCs therein, are currently unknown. We thus evaluated any effects of SARS-CoV-2 infection and/or COVID-19 vaccination from the mother on the fate and functionalities of HSPCs in the UCB. The numbers and frequencies of HSPCs in the UCB decreased significantly in donors with previous SARS-CoV-2 infection and more so with COVID-19 vaccination via the induction of apoptosis, likely mediated by IFN-γ-dependent pathways. Two independent hematopoiesis assays, a colony forming unit assay and a mouse humanization assay, revealed skewed hematopoiesis of HSPCs obtained from donors delivered from mothers with SARS-CoV-2 infection history. These results indicate that SARS-CoV-2 infection and COVID-19 vaccination impair the functionalities and survivability of HSPCs in the UCB, which would make unprecedented concerns on the future of HSPC-based therapies.
Reference values for nucleated red blood cells and serum lactate in very and extremely low birth weight infants in the first week of life
2017, Early Human Development
Citation Excerpt :
Moreover several studies proved the association between NRBC counts and intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), cerebral palsy, periventricular leukomalacia (PVL) and retinopathy of prematurity (ROP) [3,4,9–13]. It is important to know that NRBCs may be influenced by a number of different factors during pregnancy including pregnancy-induced hypertension, gestational diabetes, rhesus immunization, chorioamnionitis or maternal nicotine consumption [31–36]. Undoudtedly, this is one of the limitations of our study because we did not exclude patients who were exposed to intra uterine risk factors such as pregnancy-induced hypertension, gestational diabetes or maternal nicotine consumption etc.
To provide reference values for nucleated red blood cells and serum lactate concentrations in very and extremely low birth weight (VLBW/ELBW) infants in the first week of life.
Retrospective data analysis of serial, daily measurements of NRBC counts and serum lactate during the first 6 days of life in VLBW and ELBW infants.
In total, 250 infants < 1500 g were included in this study. Intrauterine growth retardation (IUGR) was seen in 87 (34.8%) patients. Gestational age (GA) ranged from 23 to 35 weeks (mean 29.0 weeks) and birth weight (BW) was 320– 1499 g (mean 1047.9 g). During hospital stay, 55 (22%) patients developed IVH and 55 children (22%) BPD. PVL was seen in 12 (4.8%) cases, ROP in 93 (37.2%) and NEC in only 1 (0.4%) patient.
NRBC counts as well as serum lactate concentrations depended significantly on birth weight (p < 0.01) and presence respectively absence of IUGR (p < 0.01). Both NRBC counts and serum lactate concentrations declined constantly during the 6-day period (p < 0.01), and both were highly inter-correlated (p < 0.01).
This is one of only a very few studies that systematically and serially evaluated both NRBC counts and serum lactate concentration in VLBW and ELBW infants in the first 6 days of life. Both parameters were significantly dependent on birth weight and the presence of IUGR. Moreover, a significant correlation between NRBC counts and serum lactate concentrations in this early period of life could be demonstrated. In future studies, the role of these readily available biomarkers in predicting important neonatal outcome parameters needs to be evaluated in a prospective manner.
Nucleated red blood cell counts: An early predictor of brain injury and 2-year outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling-based treatment
2014, Brain and Development
Citation Excerpt :
NRBCs are commonly seen in healthy term neonates at birth. The value is rarely >10 NRBC/100WBC, and they are quickly cleared from circulation within the first few days after birth [15,16]. Previous reports have suggested that NRBCs increase in response to an asphyxial event [7–10].
Background: Raised nucleated red blood cell (NRBC) counts in neonates may indicate in utero hypoxia and brain damage. Objective: The study aimed to examine the use of NRBC counts as a predictor of brain injury and neurodevelopmental outcomes in neonates with hypoxic–ischemic encephalopathy (HIE) treated under current cooling-based strategy. Methods: Forty-three neonates with asphyxia between 2004 and 2010 were retrospectively investigated. Twenty neonates with moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated in normothermia (NT). Neonates were divided into groups according to the presence of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks after birth. All patients were followed-up neurologically for ⩾24 months. NRBC counts during the first 3 days were compared between groups. Results: Eleven HT (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L) neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT-N: 502 [0–3060]/mm³ vs HT-L: 2765 [496–6192]; 0 [0–3417] vs NT-L: 4384 [3978–4789], median [range]). Neonates with /100 white blood cells ⩾6/mm³ and absolute NRBC counts ⩾1324/mm³ within 6 hours of birth had high risks of abnormal MRIs and 2-year outcomes. Conclusions: NRBC counts can predict brain injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.
Comparison of the umbilical artery blood gas, nucleated red blood cell, C-reactive protein, and white blood cell differential counts between neonates of diabetic and nondiabetic mothers
2011, Taiwanese Journal of Obstetrics and Gynecology
The aim of this study was to compare the neonatal umbilical artery blood gas values, C-reactive protein (CRP) levels, nucleated red blood cells (NRBCs), and white blood cells (WBCs) differential counts between offspring’s of the diabetic mothers who needed insulin during pregnancy and normal mothers after cesarean delivery.
A prospective study was performed involving 68 pregnant diabetic women who needed insulin during pregnancy and 410 healthy pregnant women and their neonates with gestational ages between 35 weeks and 41 weeks. Arterial blood was analyzed for pH and blood gas values and venous blood was analyzed for CRP level, NRBC, and WBC differential counts.
The mean NRBC count in the neonates of diabetic mothers and healthy mothers was 560 ± 985/μL and 202 ± 281/μL, respectively (p < 0.001). The umbilical arterial blood gas showed a lower pH (7.22 ± 0.07 vs. 7.24 ± 0.04, p = 0.004) and a higher pCO₂ (49.33 ± 10.08 vs. 47 ± 8.67, p = 0.045) in neonates of diabetic mothers compared with the controls. Values of pO₂, HCO₃⁻, base excess, WBC differential counts, and CRP levels were almost similar in the two groups.
Lower pH, higher pCO₂, and elevated NRBC counts were found in the neonates of diabetic mothers that may be suggestive of chronic intrauterine acidosis.
Nucleated Red Blood Cells and early EEG: Predicting Sarnat stage and two year outcome
2011, Early Human Development
Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24 h.
Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24 h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24 h was recruited.
44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3/100 WBC [range of 0–11] vs 12.3/100 WBC [0–240]) (p < 0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate/severe HIE than mild (16/100 WBC [range of 0–240] vs 8/100 WBC [1–23]) (p = 0.016), and among infants with abnormal outcome compared to normal (21.3/100 WBC [1–239.8] vs 8.3/100 WBC [0–50])(p = 0.03).
The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24 h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12 h: r = 0.661 vs r = 0.622), (24 h: r = 0.645 vs r = 0.598), and with outcome at 2 years (12 h: r = 0.756 vs r = 0.652), (24 h: r = 0.802 vs r = 0.746).
Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.

View all citing articles on Scopus

^☆: From the University of Wisconsin Medical School Milwaukee Clinical Campus and the Department of Obstetrics and Gynecology, Sinai-Samaritan Medical Center.

^☆☆: Reprint requests: Kathleen M. Hanlon-Lundberg, MD, Department of Obstetrics and Gynecology, Sinai-Samaritan Medical Center West Campus, 2000 W. Kilbourn Ave., P.O. Box 342, Milwaukee, WI 53201-0342.

^★: 0002-9378/97 $ 5.00 + 0 6/6/80789

View full text

Nucleated red blood cells in cord blood of singleton term neonates☆,☆☆,★

Abstract

Section snippets

Methods

Results

Comment

Acknowledgements

Am J Obstet Gynecol

Early Hum Dev

Am J Obstet Gynecol

Obstet Gynecol

J Pediatr

Lancet

Clin Perinatol

Clin Biochem

Early Hum Dev

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Studies on the nucleated red cell count in the chorionic capillaries and the cord blood of various ages of pregnancy

Am J Obstet Gynecol