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Mean Platelet Volume in Asymptomatic Chorioamnionitis-Exposed Infants www.jpnim.com Open Access eISSN: 2281-0692 Journal of Pediatric and Neonatal Individualized Medicine 2021;10(1):e100132 doi: 10.7363/100132 Received: 2019 Aug 22; revised: 2020 Jan 26; accepted: 2020 Feb 02; published online: 2020 Dec 28 Original article Mean platelet volume in asymptomatic chorioamnionitis- exposed infants. A retrospective case-control study Atef Alshafei, Moustafa Hassan, Yaser El saba, Anwar Khan, Mahmoud Ahmed Neonatology Section, Pediatric Department, Dubai Hospital, Dubai, UAE Abstract Introduction: Maternal chorioamnionitis (CA) is a serious condition causing several neonatal morbidities and long-term neurodevelopmental sequelae in exposed infants. Current guidelines still recommend admission, laboratory evaluation, and antibiotic administration to all CA-exposed infants. The incidence of early-onset neonatal sepsis (EOS) is currently low, owing to the routine intrapartum antibiotic administration to mothers identified to be at risk of developing CA. New diagnostic tools for early diagnosis of sepsis in apparently healthy infants exposed to maternal CA are needed. Previous studies showed that mean platelet volume (MPV) is evolving as a potential inflammatory marker of neonatal sepsis. We aimed to study whether MPV can be used as an adjuvant diagnostic tool for EOS in asymptomatic CA-exposed infants. Objective: To evaluate the role of MPV as an adjuvant biomarker of EOS in cases of asymptomatic CA-exposed infants. Design: Retrospective case-control study. Setting: A tertiary care Neonatal Intensive Care Unit (NICU). Patients: Asymptomatic CA-exposed infants 37-40 weeks of gestation admitted between May 2016 and April 2019 to the NICU of Dubai Hospital, UAE. Results: A total of 1,300 infants were admitted to NICU during the study period. Fifty-eight infants were included in the CA-exposed group and met the inclusion criteria, and 63 infants were matched as controls. No statistically significant differences were found in the MPV between the CA-exposed infants’ group and the control group. Similarly, no significant differences were noted in total white blood cell count, platelet count, and absolute neutrophil count between the two study groups. Inflammatory markers were significantly elevated in the CA-exposed group; however, blood cultures were sterile in all included infants. 1/8 www.jpnim.com Open Access Journal of Pediatric and Neonatal Individualized Medicine • vol. 10 • n. 1 • 2021 Conclusions: MPV is not a sensitive marker all asymptomatic term infants exposed to maternal of EOS in asymptomatic CA-exposed infants CA [9-11]. Close clinical monitoring would whose mothers received intrapartum antibiotic potentially reduce the unnecessary administration prophylaxis. of empiric antibiotics, mother-infant separation, health care costs, and prevent longer hospital stays. Keywords However, delayed administration of antibiotics to apparently healthy asymptomatic infants who are Chorioamnionitis, mean platelet volume, sepsis, actually infected could have deleterious short- and neonate. long-term outcomes. Blood culture and C-reactive protein (CRP) are the tools currently used for Corresponding author neonatal EOS diagnosis. The sensitivity of blood cultures is reduced, and they are commonly Atef Alshafei, MRCPCH, NICU, Dubai Hospital, Dubai, UAE; postal negative in those infants with the current IAP address: NICU, Pediatrics Department, Dubai Hospital, Dubai, PO routine use. Platelet indices, especially increased Box: 7272, UAE; e-mail: [email protected]. mean platelet volume (MPV), have been studied before, as a promising sensitive neonatal sepsis How to cite marker [12-15]. With the development of invasive sepsis, the production of larger and younger Alshafei A, Hassan M, El saba Y, Khan A, Ahmed M. Mean platelet platelets in the peripheral circulation precedes the volume in asymptomatic chorioamnionitis-exposed infants. A subsequent development of thrombocytopenia, retrospective case-control study. J Pediatr Neonat Individual Med. secondary to bone marrow suppression [16]. 2021;10(1):e100132. doi: 10.7363/100132. This study aimed to evaluate MPV as a sensitive marker of EOS in CA-exposed infants in order to Introduction help determine whether these infants need to be treated or simply monitored in maternity wards. Chorioamnionitis (CA) – or intrauterine in- flam mation, infection, or both (Triple I) – refers Materials and methods to inflammation of the fetal membranes (chorion and amnion), mostly secondary to ascending Study design, setting, and participants bacterial infection through the maternal genital tract [1, 2]. CA is commonly associated with We conducted a retrospective case-control premature rupture of membranes, preterm de- study of consecutive neonates admitted to the liveries, early-onset neonatal sepsis (EOS), and Neonatal Intensive Care Unit (NICU) of the Dubai possible long-term neurodevelopmental disorders Hospital, UAE, between May 2016 and April 2019. and cerebral palsy [3]. Because of these adverse Ethical approval was obtained from the Dubai neonatal outcomes, the American Academy of Scientific Research Ethics Committee (DSREC). Pediatrics (AAP) and the Centers for Disease A total of 121 term infants were included in the Control and Prevention (CDC) guidelines for the study, of whom 58 were admitted to the NICU prevention of perinatal group B streptococcal due to suspected maternal CA and were classified (GBS) disease, have recommended that all CA- as cases, and 63 matched healthy term infants exposed asymptomatic term infants should be delivered by mothers with uneventful pregnancies admitted, evaluated, and treated with broad- were classified into the control group. spectrum antibiotics [4-6]. These guidelines were based on studies conducted before the era Study protocol of widespread intrapartum antibiotics prophylaxis (IAP) implementation, in cases of suspected CA, CA-exposed infants were asymptomatic term prolonged rupture of membranes (PROM), or infants (37-40 weeks of gestation) and were maternal GBS colonization. At present, the risk admitted and received antibiotics, as per hospital of culture-positive EOS in asymptomatic CA- protocol that follows the current AAP and CDC exposed infants whose mothers received IAP is guidelines. Gestational age was determined by extremely low [7, 8]. Accordingly, this strategy ultrasound and the first day of the last normal has been called into question based on the recent menstrual period. Diagnosis of suspected CA was data that only address close clinical monitoring of made by the obstetrician, either before delivery or 2/8 Alshafei • Hassan • El saba • Khan • Ahmed Journal of Pediatric and Neonatal Individualized Medicine • vol. 10 • n. 1 • 2021 www.jpnim.com Open Access within 4-6 hours after labor. Maternal CA diagnosis apnea, poor perfusion, need for ventilation support, was clinically suspected in cases of intrapartum hypotonia, feeding intolerance, bradycardia (< 100/ fever of 38.0°C or higher, and one of the following min), tachycardia (> 200/min), or hypotension, signs: purulent or foul-smelling uterine discharge, requiring inotropic support. fundal tenderness, fetal or maternal tachycardia, or maternal leukocytosis. Full blood count (FBC) data, Statistical analysis including platelet count, white blood cell (WBC) count, absolute neutrophil count (ANC), and MPV Data analysis was done using the IBM® were collected for all included infants. In the CA- SPSS® Statistics 23.0. The quantitative data were exposed infants, additional blood culture results on presented as mean and standard deviations (SD). admission and CRP at 24 hours of age were also The qualitative data were presented as count and recorded. Three days after admission, FBC and percentages. Student’s t-test was used to compare CRP data were collected again, for comparison. quantitative data between the two groups, while a The FBC was performed using an automated chi-square test was used to compare the qualitative hematology analyzer (DxH800; Beckman Coulter, data. Paired samples t-test was used to compare the USA) with ethylenediaminetetraacetic acid quantitative data at two different time points for the (EDTA) anticoagulated whole blood samples. same group, and McNemar’s test was used for the Blood culture was performed by a sample of 1 ml of qualitative data. Receiver-operating characteristics venous blood, transferred into a BACTEC culture (ROC) curve was used to measure the MPV validity vial (BACTEC FX/VIRTUE BacT/ALERT). CRP in the diagnosis of neonatal sepsis, and the area was measured by an immunoturbidimetric method, under the curve (AUC) was calculated. P-value < using the Roche Cobas C501/502 CRP L3 clinical 0.05 was considered statistically significant. chemistry analyzer, according to the operator’s manual for operating instructions, mainte- Results nance, and troubleshooting (Roche Diagnostics, Indianapolis, IN, USA). All infants admitted to the During the study period, a total of 1,300 infants NICU received ampicillin and gentamicin, shortly were admitted to the NICU, of whom 58 (0.4%) after a full clinical and laboratory sepsis evalua- were healthy CA-exposed infants. There were no tion. Antibiotics were discontinued after 48 hours statistically significant differences between the if the infant remained asymptomatic and blood study and control groups in Apgar score, gender, culture and CRP were negative. However, the and maternal age (p > 0.05). However, gestational treatment duration would be extended to 5-7 days, age and birth weight were higher in
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