Journal of Perinatology (2009) 29,8–12 r 2009 Nature Publishing Group All rights reserved. 0743-8346/09 $32 www.nature.com/jp ORIGINAL ARTICLE Hematologic effects of placental pathology on very low birthweight infants born to mothers with preeclampsia KJ Zook1,2, AB Mackley1, J Kern1 and DA Paul1,2 1Department of Pediatrics, Section of Neonatology, Christiana Care Health System, Newark, DE, USA and 2Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA Introduction Objective: To investigate the effect of placental pathology on neonatal Preeclampsia is a common disorder of pregnancy affecting nearly 5 neutrophils, platelets, hematocrit and nucleated red blood cells in very low to 8% of pregnant women annually in the United States. The NIH birthweight (VLBW) infants born to mothers with preeclampsia. reported in 2000 that preeclampsia had risen by one-third over the Study Design: Retrospective cohort study of infants with birthweight previous decade.1 Preeclampsia is known to be a common cause of < 1500 g born to mothers with preeclampsia from july, 2002 to july, 2006 neonatal neutropenia and thrombocytopenia. It has previously at a single level III neonatal intensive care unit. Placental pathology been postulated that both neonatal neutropenia and was reviewed for the presence of placental infarction and vasculopathy. thrombocytopenia result from decreased production of WBCs and Hematologic parameters from day of life 0, 1 and 2 were obtained. platelets (Plt) from placental insufficiency.2–9 Statistical analysis included repeated-measures analysis of variance Preeclampsia is also known to have associated placental and multivariable analysis using logistic regression. pathology.10 Different placental histopathologies are associated with Result: The study sample included 203 infants with estimated specific clinical features of preterm preeclampsia. Severe maternal gestational age of 28±3 weeks; 45% had placental infarctions and 26% proteinuria is related to placental chronic inflammation, whereas placental vasculopathy. Infants with neutropenia and thrombocytopenia lower maternal antepartum Plt counts are related to placental did not have an increased occurrence of placental infarction or maternal abruption and infarction. Lower birthweight percentiles and lighter vasculopathy but were more likely to be of small gestational age (SGA) placentas are directly associated with uteroplacental vascular 11 and of lower gestational age compared with infants without neutropenia lesions. or thrombocytopenia. After multivariable analysis, gestational age and To date, the link between different placental pathological SGA remained associated with both neutropenia and thrombocytopenia conditions associated with preeclampsia, neonatal neutropenia and whereas placental infarction and vasculopathy did not remain in the thrombocytopenia have not been explored. In this study, we models. hypothesized that there would be specific placental findings associated with neonatal hematologic abnormalities in infants born Conclusion: In our population of VLBW infants born to mothers with to mothers with preeclampsia. preeclampsia, placental pathology was common. There was no association The purpose of this study was to investigate the association of placental infarction or vasculopathy with neonatal neutropenia and between placental pathology and neonatal absolute neutrophil thrombocytopenia. The data suggest that neonatal hematologic effects of count (ANC), Plt, hematocrit (Hct) and nucleated red blood cells maternal preeclampsia, if related to the placenta, are associated with (NRBC) in very low birthweight (VLBW) infants born to mothers factors other than placental histology. with preeclampsia. Journal of Perinatology (2009) 29, 8–12; doi:10.1038/jp.2008.104; published online 18 December 2008 Keywords: placenta; placental insufficiency; neonatal thrombocytopenia and neutropenia Methods The study was a retrospective nested-cohort study of VLBW infants (<1500 gm) born to mothers with preeclampsia at Christiana Care Correspondence: Dr KJ Zook, Christiana Care Health System, Department of Neonatology, Health System. Christiana Care Health System is the single level III 4755 Ogletown-Stanton Road, Newark, DE 19718, USA. regional neonatal intensive care unit serving the state of Delaware. E-mail: [email protected] Received 4 January 2008; revised 28 April 2008; accepted 15 May 2008; published online The study sample included inborn infants cared for between July 18 December 2008 2002 and July 2006. The study sample included only infants born Placental effects in preeclampsia KJ Zook et al 9 to mothers with preeclampsia. The Institutional Board Review at regression. A P-value < 0.05 was considered significant; all data Christiana Care Health Services approved this project. are expressed as mean±s.d. The diagnosis of preeclampsia was made by the attending obstetrician based on ACOG guidelines of elevated blood pressure (>140 systolic or >90 diastolic) and proteinuria (>0.3gm of Results protein in a 24 h urine collection) after 20 weeks of gestation.12 For During the study period, 211 inborn infants were born to mothers the purposes of this study, estimated gestational age was defined by with preeclampsia. The final study sample included 203 infants; best obstetric estimate. Small for gestational age (SGA) was defined 8 infants born to mothers with preeclampsia were excluded, as as birthweight of <10%. Data on prenatal steroid administration they did not have placental pathology results. In the study sample, were collected and mothers were classified as receiving antenatal 30 infants were diagnosed with neutropenia and 48 infants with steroids if they received a minimum of 1 dose of betamethasone or thrombocytopenia during the first 48 h of life. The distribution dexamethasone before the delivery. of the placental pathologies included infarction (45%), maternal Clinical pathology reports were obtained on all infants. The vasculopathy (26%), meconium staining (16%), histologic decision to send the placenta for pathologic evaluation was made chorioamnionitis (13%), calcification (9%) and funisitis (3%). by the attending obstetrician. The placentas were examined by Because of their prevalence, placental infarction, maternal one of nine attending pathologists at Christiana Care Health vasculopathy and placental calcifications were chosen to compare System who were blinded to the clinical and hematologic outcomes with the presence or absence of neutropenia and of the infants. Christiana Care Health System evaluates thrombocytopenia, total NRBCs and Hct values. Although more approximately 1500 placentas per year of the 7000 live births. The prevalent than placental calcifications, histologic chorioamnionitis placentas were systematically reviewed according to the Placental and meconium staining were not considered in relationship to Pathology Practice Guideline Development Task Force.13 These neonatal parameters as they are common comorbid factors for guidelines attempt to create uniformity for analysis of the placenta, many other conditions. which is a relatively subjective process. The reports were reviewed Infants with neutropenia were of lower gestation, lower for placental abnormalities using standard definitions for birthweight and more likely to be SGA compared with infants commonly described placental lesions.14 The guidelines encourage without neutropenia (Table 1). There were no differences in the the reporting of the most significant lesions such as presence occurrence of placental infarction, placental vasculopathy or of chorioamnionitis, villitis, central infarcts (rather than placental weight in infants with neutropenia compared with those marginal infarcts) and vasculopathy and discourage reporting without neutropenia. After multivariable analysis to control for minor findings. Those born to mothers with preeclampsia who potential confounding variables including gestational age, did not have a placental pathology report were excluded from birthweight, race, SGA, multiple gestation, use of prenatal steroids this study. and placental pathology, only gestational age (odds ratio of 1.3, Infants in the study sample had complete blood counts drawn 95% CI 1.1 to 1.6) and SGA (odds ratio of 4.2 (CI 1.3 to 13.5) as per neonatal intensive care unit protocol. This included a complete blood counts on admission and the first two days of life. Complete blood counts were obtained more frequently as clinically Table 1 Univariate analysis of neutropenia and placental pathologies, EGA, BW, indicated. Hematologic parameters investigated included ANC, Plt Race, SGA, multiple gestation, prenatal steroids count, Hct and total NRBC’s. All complete blood counts were Neutropenia Neutropenia P-value analyzed in standard fashion using a Sysmex Model Xe2100 present absent, Coulter Counter (Hialiah, FL, USA). Total NRBCs were calculated (n ¼ 30) (n ¼ 173) by multiplying the total WBC count by the number of NRBC ± ± counted per 100 WBC. EGA (weeks) 27.9 2.1 29.3 2.4 0.02 ± ± Thrombocytopenia was defined as Plt count less than 100 K/ BW (grams) 852 283 1091 267 <0.01 Placental infarction 33% 46% 0.2 mm3.15 Neutropenia was defined by the Mouzhino criteria: ANC Placental calcification 10% 9% 0.85 less than 500 on day of life 0, ANC less than 2000 on day of life 1, Maternal vasculopathy 33% 25% 0.41 16 and ANC less than 1100 on day of life 2. Placental weight (grams) 217±37 245±85 0.17 Race (Caucasian/African American) 31%/68% 50%/40% 0.02 Statistics SGA 37% 15% 0.01 Statistical