Correlation of neonatal nucleated red blood cell counts in preterm infants with histologic chorioamnionitis

doi:10.1016/S0002-9378(97)70433-2

American Journal of Obstetrics and Gynecology

Volume 177, Issue 1, July 1997, Pages 27-30

https://doi.org/10.1016/S0002-9378(97)70433-2 Get rights and content

Abstract

OBJECTIVE: The aim of this study was to compare the neonatal nucleated red blood cell counts in preterm infants in the presence and absence of clinical and histologic chorioamnionitis while controlling for gestational age and birth weight percentile. STUDY DESIGN: Nucleated red blood cell counts were obtained from preterm infants delivered after preterm labor or preterm premature rupture of membranes. Patients were divided on the basis of clinical and histologic chorioamnionitis. Nucleated red blood cell counts between groups were compared, and regression analysis controlling for gestational age and birth weight percentile was performed. RESULTS: Of 359 patients, both measures of infection status were significantly associated with increased nucleated red blood cell counts. In the regression analysis histologic chorioamnionitis retained significance, whereas clinical chorioamnionitis did not. CONCLUSIONS: Histologic chorioamnionitis produces an erythropoietic response in the fetus. Whether fetal erythropoiesis is a direct response to mediators of inflammation or whether it is the result of a rise in erythropoietin is unknown.(Am J Obstet Gynecol 1997;177:27-30.)

Section snippets

Material and methods

The study was conducted in a tertiary care facility with a yearly delivery rate of 1200 neonates and a low birth weight rate (<2501 gm) of 20% to 24%. All inborn neonates with birth weights of 500 to 1750 gm, born between Jan. 1, 1990, and June 30, 1993, with a diagnosis of premature rupture of membranes or preterm labor who had a complete blood cell count (including a nucleated red blood cell count) taken from the infant within 24 hours of birth were candidates for inclusion. Complete blood

Results

Five hundred one consecutive neonates with birth weights >499 gm and <1751 gm delivered between Jan. 1, 1990, and June 30, 1993, were candidates for this study. One hundred forty-two neonates were excluded: 108 were delivered for medical indications other than preterm premature rupture of the membranes or preterm labor and 34 did not have nucleated red blood cell counts. Of the definitive 359 patients, 192 had preterm premature rupture of membranes and 167 had preterm labor. Placental

Comment

Our data confirm that of Salafia et al.,¹⁸ who found an increase in nucleated red blood cell counts in patients with preterm premature rupture of membranes and preterm labor with clinical and histologic chorioamnionitis. We controlled for gestational age and birth weight percentile, factors that are inversely proportional to nucleated red blood cell counts, and demonstrated that histologic chorioamnionitis significantly increased the nucleated red blood cell count. When these factors were

References (23)

U Nicolini et al.
Limited role of fetal blood sampling in prediction of outcome in intrauterine growth retardation
Lancet
(1990)
GK Clemons et al.
Immunoreactive erythropoietin concentrations in fetal and neonatal rats and the effects of hypoxia
Blood
(1986)
LMS Dubowitz et al.
Clinical assessment of the newborn infant
J Pediatr
(1970)
WE Brenner et al.
A standard of fetal growth for the United States of America
Am J Obstet Gynecol
(1976)
MAS. Moore
Clinical implications of positive and negative hematopoietic stem cell regulators
Blood
(1991)
JP Phelan et al.
Nucleated red blood cells: a marker for fetal asphyxia
Am J Obstet Gynecol
(1994)
GS Philip et al.
Nucleated red blood cell counts in small for gestational age infants with very low birthweight
Arch Pediatr Adolesc Med
(1989)
PW Soothill et al.
Prenatal asphyxia, hyperlactiaemia, hypoglycemia and erythroblastosis in growth retarded fetuses
BMJ
(1987)
DW Green et al.
Nucleated erythrocytes in healthy infants and in infants of diabetic mothers
J Pediatr
(1989)
RF Maier et al.
Umbilical venous erythropoietin and umbilical arterial pH in relation to morphologic placental abnormalities
Obstet Gynecol
(1994)

KA Teramo et al.

Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy

Obstet Gynecol

(1987)

Cited by (27)

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications
2020, Seminars in Fetal and Neonatal Medicine
Citation Excerpt :
Affected fetuses have a slightly higher median nucleated red blood cell count (adjusted for gestational age) compared to those without FIRS [29]. An elevated nucleated red blood cell count has also been observed in neonates delivered from patients with prolonged (>24 h) rupture of the fetal membranes [37], histologic chorioamnionitis [38], a high acute placental inflammation score [39], and early-onset neonatal sepsis [40]. Since changes in nucleated red blood cells in FIRS are not associated with a lower pH or PO2 [41], metabolic acidemia/hypoxemia is unlikely to be the cause of the observed changes [42].
The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term “Fetal Inflammatory Response Syndrome” (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur (“rescued by birth”). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.
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 cells in concordant, appropriate-for-gestational age twins
2004, American Journal of Obstetrics and Gynecology
Citation Excerpt :
All infants were Caucasians of Jewish descent. In both groups we excluded infants with other factors associated with a potential increase in ANRBC counts, as described by us and others, such as small-for-gestational age infants,13 infants born to women with gestational or insulin-dependent diabetes9; pregnancy-induced hypertension14; placental abruption or placenta previa; any maternal heart, kidney, lung, or other chronic condition; drug, tobacco, or alcohol abuse10,15; perinatal infections (eg, fever, leukocytosis, signs of chorioamnionitis)16; abnormal electronic intrapartum monitoring17; or infants with low Apgar scores (below 7 at 1or 5 minutes)18; infants delivered with the assistance of forceps or vacuum. We also excluded infants with perinatal blood loss, meconium-stained amniotic fluid,19 hemolysis (blood group incompatibility with positive Coombs' test),20 or chromosomal anomalies.21
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.
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.
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.
Concordant, appropriate-for-gestational age twins have increased nucleated RBCs at birth compared with singleton control infants.
Nucleated red blood cells in infants of mothers with asthma
2003, American Journal of Obstetrics and Gynecology
Citation Excerpt :
The severity of asthma in pregnancy was classified according to National Asthma Education and Prevention Program12: the absence of asthma was given a score of 0, mild intermittent asthma was given a score of 1, mild persistent asthma was given a score of 2, moderate persistent asthma was given a score of 3, and severe persistent asthma was given a score of 4. In both groups we excluded those infants with other factors that were associated with potential increase in absolute nucleated RBC counts, as described by us and others, such as infants born to women with gestational or insulin-dependent diabetes mellitus7; pregnancy-induced hypertension13; abruptio placentae or placenta previa; any maternal heart, kidney, other lung, or other chronic condition; drug, tobacco, or alcohol abuse8,14; perinatal infections (eg, fever, leukocytosis, signs of chorioamnionitis)15; abnormal electronic intrapartum monitoring16; infants with low Apgar scores (||8 at 1 or 5 minutes)17; or infants delivered with the assistance of forceps or vacuum. We also excluded infants with perinatal blood loss, meconium-stained amniotic fluid,18 hemolysis (blood group incompatibility with positive Coombs test),19 or chromosomal anomalies.20
Objective: The purpose of this study was to evaluate whether the absolute nucleated red blood cell and lymphocyte count is elevated in term, appropriate-for-gestational-age infants born to women with asthma. Study design: We compared absolute nucleated red blood cell counts taken during the first 12 hours of life in two groups of term, vaginally delivered, appropriate-for-gestational-age infants; one group was born to mothers with active asthma during pregnancy (n = 28 infants), and the other group was born to control mothers (n = 29 infants). Asthma severity was classified according to the National Asthma Education and Prevention Program. We excluded infants of women with diabetes mellitus, hypertension, alcohol, and tobacco or drug abuse and infants with fetal heart rate abnormalities, hemolysis, blood loss, or chromosomal anomalies. Results: There were no differences between groups in birth weight, gestational age, maternal age, gravidity, parity, maternal analgesia during labor, 1- and 5-minute Apgar scores, and infant sex. The hematocrit level, red blood cell count, absolute nucleated red blood cell count, and corrected leukocyte and lymphocyte counts were significantly higher in the asthma group than in the control group. The platelet count was not significantly different between groups. The absolute nucleated red blood cell count correlated significantly with the asthma severity score (r ² = 28%, P < .001). Backward stepwise multiple regression that included Apgar scores and gestational age showed a significant correlation of absolute nucleated red blood cell count with the presence of asthma and its severity (P < .001). Conclusion: At birth, term appropriate-for-gestational-age infants born to mothers with asthma have increased circulating absolute nucleated red blood cell and lymphocyte counts compared with control infants. (Am J Obstet Gynecol 2003;188:409-12.)
Nucleated red blood cells in polycythemic infants
2003, American Journal of Obstetrics and Gynecology
Citation Excerpt :
We selected only infants with polycythemia (venous hematocrit greater than or equal to 65%) significant enough to require partial dilutional exchange transfusion because of clinical symptoms, hypoglycemia, or because of hematocrit was greater than 70%.2 We excluded from the study infants born to women with gestational or insulin-dependent diabetes7; pregnancy-induced hypertension8; abruptio placentae or placenta previa9; any maternal heart, kidney, other lung, or other chronic condition; drug, tobacco, or alcohol abuse10; perinatal infections (eg, fever, leukocytosis, clinical signs of chorioamnionitis)11; any abnormality in electronic intrapartum monitoring9; or infants with low Apgar scores (below 8 at 1 or 5 minutes).12 We also excluded infants with perinatal blood loss, hemolysis (blood group incompatibility with positive Coombs test or hematocrit below 45%)13 or chromosomal anomalies.14
Objective: This study was undertaken to evaluate whether the absolute nucleated red blood cell (RBC) count is elevated in term, appropriate-for-gestational-age (AGA) polycythemic infants. Study Design: We compared absolute nucleated RBC counts taken during the first 12 hours of life in term, AGA infants with neonatal polycythemia (n = 29), and in control, nonpolycythemic infants (n = 37). We excluded infants of women with diabetes, hypertension, and alcohol, tobacco, or drug abuse, and those with fetal heart rate abnormalities or low Apgar scores, hemolysis, blood loss, or chromosomal anomalies. Results: There were no differences between groups in birth weight, gestational age, or other demographic or perinatal factors. The hematocrit, RBC count, and absolute nucleated RBC counts were significantly higher and the platelet counts significantly lower in the polycythemic group. Regression analysis that included Apgar scores and gestational age showed a significant correlation of absolute nucleated RBC count with the polycythemia status only (P = .017). Conclusion: At birth, term AGA polycythemic infants have increased indices of active erythropoiesis. We speculate that this finding is suggestive of subtle fetal hypoxemia. (Am J Obstet Gynecol 2003;188:193–5.)
Nucleated red blood cells in infants of smoking mothers
1999, Obstetrics and Gynecology
Objective: To evaluate whether the absolute nucleated red blood cell (RBC) count is elevated in term, appropriate for gestational age (AGA) infants born to smoking women.
Methods: We compared absolute nucleated RBC counts taken during the first 12 hours of life in two groups of term, vaginally delivered, AGA infants, one group born to mothers who smoked during pregnancy (n = 30) and the other born to mothers who did not smoke (n = 30). We excluded infants of women with diabetes, hypertension, or alcohol or drug abuse, and infants with heart rate abnormalities, hemolysis, blood loss, or chromosomal anomalies.
Results: There were no differences between the groups in birth weight, gestational age, maternal age, gravidity, parity, maternal analgesia during labor, 1- and 5-minute Apgar scores, corrected white blood cell counts, lymphocyte counts, or hematocrits. The median absolute nucleated RBC count in infants of smoking mothers was 0.5 × 10⁹/L (range 0 to 5.0) versus 0.0005 × 10⁹/L (range 0 to 0.6) in nonsmoking controls (P < .002). Regression analysis that included Apgar scores, gestational age, and number of cigarettes smoked per day showed a significant correlation of absolute nucleated RBC count only with the number of cigarettes smoked per day (P < .001).
Conclusion: At birth, term AGA infants born to smoking mothers have increased circulating absolute nucleated RBC counts compared with controls. The absolute nucleated RBC count in newborns correlates with the number of cigarettes smoked during pregnancy.

View all citing articles on Scopus

^☆: From the Departments of Obstetrics and Gynecology and Health Quantitative Sciences, New York Medical College.

^☆☆: Reprint requests: Enid Leikin, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Westchester County Medical Center/New York College of Medicine, Valhalla, NY 10595.

^★: 6/1/81763

View full text

Correlation of neonatal nucleated red blood cell counts in preterm infants with histologic chorioamnionitis☆,☆☆,★

Abstract

Section snippets

Material and methods

Results

Comment

Lancet

Blood

J Pediatr

Am J Obstet Gynecol

Blood

Nucleated red blood cells: a marker for fetal asphyxia

Am J Obstet Gynecol

Nucleated red blood cell counts in small for gestational age infants with very low birthweight

Arch Pediatr Adolesc Med

Prenatal asphyxia, hyperlactiaemia, hypoglycemia and erythroblastosis in growth retarded fetuses

BMJ

Nucleated erythrocytes in healthy infants and in infants of diabetic mothers

J Pediatr

Umbilical venous erythropoietin and umbilical arterial pH in relation to morphologic placental abnormalities

Obstet Gynecol

Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy

Obstet Gynecol