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The Effect of Prolonged Rupture of Membranes on Circulating Neonatal Nucleated Red Blood Cells

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The Effect of Prolonged Rupture of Membranes on Circulating Neonatal Nucleated Red Blood Cells Original Article The Effect of Prolonged Rupture of Membranes on Circulating Neonatal Nucleated Red Blood Cells Dror Mandel, MD, MHA INTRODUCTION Tal Oron, MD Prolonged rupture of membranes (PROM) is usually defined as Galit Sheffer Mimouni, MD rupture of membranes more than 24 hours prior to delivery.1 A Yoav Littner, MD major concern for fetuses exposed to PROM is maternal–fetal Shaul Dollberg, MD infection,2 but other risks include placental abruption,3 fetal lung Francis B. Mimouni, MD, FAAP hypoplasia,4 fetal distress due to cord compression and/or cord prolapse,1 and fetal deformation syndrome.1,5 A recent review of the significance of elevated neonatal nucleated red blood cells (NRBC) in the fetus and the neonate included chorioamnionitis as a OBJECTIVES: ‘‘known’’ risk factor of elevation;6 this article suggests that ‘‘acute To test the hypothesis that absolute nucleated red blood cells (ANRBC) chorioamnionitis’’ may lead to increased levels of erythropoietin, counts are higher at birth in infants who were born after prolonged and increased newborn NRBC, but does not relate the finding of rupture of membranes (PROM, >24 hours). elevated NRBC counts with the occurrence or not of PROM. As mentioned earlier, PROM may lead to cord compression1 and STUDY DESIGN: subsequently to fetal hypoxia;1,7 a well-described consequence of Retrospective study of 31 infants admitted to the neonatal intensive care intrauterine hypoxia is increased compensatory erythropoiesis due 8–10 unit who were born after PROM, and pair matched for gestational age to increased erythropoietin secretion. In situations associated and Apgar scores with 31 no PROM controls. Venous ANRBC counts were with intrauterine hypoxia, such as intrauterine growth restriction, obtained within 1 hour of life. maternal pregnancy-induced hypertension, or maternal diabetes or smoking, there is an elevation of the NRBC at birth, presumably RESULTS: due to increased compensatory erythropoiesis.9 Groups did not differ in birthweight, gestational age, Apgar scores, and The aim of this study was to examine circulating NRBC in platelets counts. The ANRBC counts and hematocrit were significantly infants born after PROM compared to suitable controls. We higher in infants who were born after PROM than in controls. hypothesized that higher neonatal absolute NRBC (ANRBC) counts CONCLUSIONS: would be found in infants born after PROM, compared to control infants. Infants born after PROM have higher ANRBC counts at birth than control infants. We suggest that increased fetal erythropoiesis exists in infants who are delivered after PROM. If correct, our interpretation supports the theory that fetal hypoxia and/or ischemia may result from PROM. MATERIAL AND METHODS Journal of Perinatology (2005) 25, 690–693. doi:10.1038/sj.jp.7211389; Patients published online 13 October 2005 We retrospectively analyzed the charts of all infants born at the Lis Maternity Hospital, Tel Aviv Sourasky Medical Center from January 1, 2003 to February 29, 2004, who were admitted to our neonatal intensive care unit, and were delivered after prolonged (at least 24 hours prior to delivery) rupture of membranes. Each infant born after PROM was pair matched with the infant without PROM admitted immediately after it, with the same gestational age (±1 week), and 1- and 5-minute Apgar scores (±1 point). In an Department of Neonatology (D.M., T.O., Y.L., S.D., F.B.M.), Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel; Department of Pediatrics (T.O.), Tel Aviv-Sourasky Medical Center, Tel Aviv, Israel; attempt to control for the various variables known to affect NRBC Department of Obstetrics and Gynecology (G.S.M.), Tel Aviv Sourasky Medical Center, Tel Aviv, counts, we excluded from the study infants born to women with Israel; and Sackler Faculty of Medicine (D.M., Y.L., S.D., F.B.M.), Tel Aviv University, Tel Aviv, 11 Israel. gestational or insulin-dependent diabetes; pregnancy-induced hypertension;12 placental abruption or placenta previa;13 any Address correspondence and reprint requests to Dror Mandel, MD, MHA, Department of Neonatology, Lis Maternity Hospital, Tel Aviv-Sourasky Medical Center, 6 Weizman Street, Tel Aviv maternal heart, kidney, lung, or other chronic condition; drug, 14 64239, Israel. tobacco (active and passive) or alcohol abuse; perinatal Journal of Perinatology 2005; 25:690–693 r 2005 Nature Publishing Group All rights reserved. 0743-8346/05 $30 690 www.nature.com/jp Premature Rupture of Membrane and Nucleated Red Blood Cells Mandel et al. infections (e.g., fever, leukocytosis, clinical signs of Table 1 depicts demographic and clinical characteristics of infants chorioamnionitis);15 any significant abnormality in electronic with PROM and controls. There were no significant differences intrapartum monitoring, such as decreased variability, fetal between groups for all clinical or demographic parameters tachycardia, variable decelerations or fetal bradycardia;13 or infants considered. By design, infants with PROM did not differ from controls with low Apgar scores (below 7 at 1 or 5 minutes).16 We also in terms of gestational age, birthweight and Apgar scores. excluded infants with perinatal blood loss, hemolysis (blood group Table 2 depicts the hematologic data obtained for both groups. incompatibility with positive Coombs test or hematocrit below There were no differences between the two groups in terms of 45%)17 or chromosomal anomalies.6 lymphocyte counts and platelet counts. ANRBC count at birth and hematocrit were significantly higher in infants with PROM than in Hematologic Methods control infants. In our institution, all admitted infants undergo a routine complete In backward stepwise regression analysis, taking into account blood count, with differential count and NRBC count within the gestational age (GA), the 1- or 5-minute Apgar scores, mode of first hour of life. Venous blood samples for complete blood cell delivery and the PROM status as independent variables and the counts were analyzed according to laboratory routine using a ANRBC count as the dependent variable, only PROM (p<0.001) GEN-S counter (Beckman-Coulter Inc., Switzerland). Differential and gestational age (p<0.01) were predictors of increased ANRBC cell counts were performed manually and NRBC counts were counts. We conducted an additional backward stepwise regression counted per 100 white blood cells (WBC). We showed previously analysis taking into account GA, 1- or 5-minute Apgar scores, 18 that leukocyte counts correlate inversely with ANRBC numbers. mode of delivery, and the duration of ruptured membranes as Thus, the traditional expression of NRBC as their number per 100 independent variables, and the NRBC counts as the dependent WBC might introduce a significant bias. Therefore, we expressed variables. In this analysis, only the rupture of membrane duration the number of NRBCs as an absolute number (ANRBC) rather than predicted significantly the NRBC counts (Figure 1) (R2 ¼ 0.24, per 100 leukocytes, and the WBC count was expressed as corrected p<0.001). for the presence of NRBC. Statistical Analysis SIGNIFICANCE Data are reported as mean±standard deviation (SD), n (%), or, for non-normally distributed variables (such as NRBCs or Apgar We found that infants born after PROM have increased ANRBC scores) as median and range. Statistical analysis included two- counts compared with suitable controls. In our study, we excluded 19 tailed paired t-test for normally distributed variables and paired SGA infants, an important confounding variable. We excluded Wilcoxon test for ANRBC or Apgar scores and w2 test or Fisher’s exact test for discrete demographic and clinical variables. Backward stepwise regression analysis was used to assess the effect of Table 1 Demographic and Perinatal Characteristics of Infants with gestational age, 1- or 5-minute Apgar scores and the PROM status PROM and Matched Controls as independent variables, with the ANRBC count as the dependent PROM* Controls* variable. A p-value <0.05 was considered significant. (n ¼ 31) (n ¼ 31) Our local Institutional Review Board approved the study. Since all infants in our institution receive a routine complete blood count Administration of prenatal betamethasone 10 (32.3) 9 (29.0) including NRBC count after birth, the requirement for informed Birthweight (g) 2347±707 2444±650 consent was waived. Gestational age (weeks) 34.0±2.9 34.2±2.7 1-minute Apgar score 8 (7–9) 8 (7–9) 5-minute Apgar score 9 (9–10) 9 (8–10) RESULTS Presence of UVC 5 (16.1) 5 (16.1) Duration of UVC (days) 1±1.5 1±1.6 A total of 58 infants were eligible for the study in the PROM group. Presence of UAC 6 (20.1) 5 (16.1) In all, 27 of them were excluded because of at least one of the Duration of UAC (days) 2±1.8 1.7±1.6 exclusion criteria described in the Methods section. The 31 Infants requiring mechanical ventilation 8 (25.8) 7 (22.8) remaining infants were matched with 31 appropriate controls. Duration of ventilation (days) 3±2 3±2 Whenever an eligible control was found to meet one of the Number diagnosed with patent ductus arteriosus 6 (20) 5 (16.7) exclusion criteria, it was replaced by the next eligible control *Data are expressed as mean±SD, or n (%) except for Apgar scores, which are without exclusion criteria. A total of 13 control infants were expressed as median (range). The two groups did not differ significantly for any of the replaced in manner such that six of the infants in each group were variables considered. UVC ¼ 3D umbilical vein catheter; UAC ¼ 3D umbilical artery catheter. born at term and 25 were preterm. Journal of Perinatology 2005; 25:690–693 691 Mandel et al. Premature Rupture of Membrane and Nucleated Red Blood Cells The mechanism by which PROM is associated with increased Table 2 Hematological Characteristics of Infants with PROM and Matched Controls circulating neonatal ANRBC counts is unknown.
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