Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China

Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China Dongyan Cui, Yan Hou, Ling Feng, Guo Li, Chi Zhang, Yanli Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-32762/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Oct, 2020 Read the published version in BMC Pediatrics → Version 2 posted 2 You are reading this latest preprint version Show more versions Abstract Background : No consensus has been reached on capillary blood reference intervals for platelet parameters in full-term neonates. We aimed to establish neonatal capillary blood reference intervals for platelet parameters and evaluate influences of sex, gestational age and postnatal age on platelet parameters. Methods : This study was a prospective investigation and implemented in 594 healthy full-term neonates from 12 to 84 hours of age, using SYSMEX XN-9000 haematology automatic analyser by means of capillary blood. Reference intervals for platelet parameters were defined by an interval of 2.5th –97.5th percentiles. Results : Capillary reference interval for platelet count was (152 - 464) ×109/L. No significance was found between sex-divided reference intervals for platelet parameters. The values of platelet count changed minimally across gestational age (37-41 weeks) and postnatal age (12-84 hours). Reference intervals for other platelet parameters were affected by these factors to a different extent. Conclusions : We established capillary blood reference intervals for platelet parameters in the first days after birth of full-term neonates in China. Pediatrics Neonates Capillary blood Platelet count Platelet parameters Reference intervals Figures Figure 1 Background Reference intervals (RIs) play a critical role in clinical practice. Appropriate RIs for platelet parameters ensure clinical laboratories provide reliable information and enable clinicians to correctly interpret results and further determine whether transfusions are needed for neonates [1, 2]. However, few normative data are available in RIs for platelet parameters in full-term neonates [3]. Neonates are in a crucial period of rapid development, and platelet parameters are significantly affected by these physiological changes[4]. Moreover, RIs for platelet parameters have often been derived from haematological results of both inpatient and outpatient neonates[4, 5], or blood samples are leftover material from the donated blood for a specific use in a pre-term (delivered at less than 37 weeks of gestation) or full-term neonate population [6, 7], which may be inaccurate and unreliable for full-term neonates. It is hard for neonatal health care providers to provide standard-of-care health services as a lack of appropriate RIs for haematology may impede diagnostics for neonates [8]. The study of RIs for platelet parameters in neonates is highly restricted due to the ethical limitations and difficulties to obtain sufficient blood samples. Capillary sampling by the automated incision device spends a shorter time for blood collection with reduced haemolysis [9], and is increasingly used in clinical practice nowadays in China. Capillary blood for haematology tests is as small as necessary in volumes and as non-invasively as possible with a very low frequency of local infection and decreased extent of bruising [10]. Although capillary blood is used to develop RIs for other biologic markers [11-13], studies have not been carried out to evaluate its clinical utility in neonatal capillary blood RIs for platelet parameters. Ideally, RIs for platelet parameters are established in a healthy full-term neonate population and more than 120 specimens are required by the Clinical and Laboratory Standards Institute (CLSI). [14] The objectives of the present study were to determine capillary blood RIs for platelet count (PLT) and related parameters in 594 healthy full-term neonates from 12 to 84 hours of age, and furthermore to evaluate influences of sex, gestational age and postnatal age on platelet parameters. Methods Study populations The study commenced after obtaining Institutional Ethical Committee approval (TJ-IRB20190308). The subjects were prospectively enrolled into this study, and all of them were healthy full-term (259 to 293 days (37 to 41 weeks) of gestation) neonates born at two hospitals from November 2018 to April 2019. Major inclusion/exclusion criteria are listed as follows. As listed in Chang et al.[6] for mothers, maternal age ranged from 20 to 40 years old and they had a normal health check-up without unfavourable past history during pregnancy, such as smoking, infectious diseases (hepatitis B/C, HIV, syphilis infections), idiopathic thrombocytopenic purpura, malignancies and chronic diseases (diabetes mellitus, autoimmune disease, immunodeficiencies and thrombotic disorders); mothers did not receive aspirin during pregnancy; a vaginal delivery or caesarean section was event-free. Professional obstetricians were responsible for the data of this part. As listed in Chang et al.[6] and Wasiluk [15] for neonates, they fitted all clinical state criteria for full-term neonates; they were born with normal birth weight (2500-4000g) appropriate for gestational age and normal Apgar score (8-10 points at 1-5 minutes of life); physical examinations of the subjects were normal without any signs of infection or congenital anomalies at the time of sampling. And we excluded all neonates with an unfavourable perinatal history of premature rupture of membrane more than 24 hours, abnormal placenta, placenta abruption, chorioamnionitis or meconium stain, or with a medical history of hospitalizing in the neonatal intensive care unit. All subjects are Han ethnicity. Blood sampling After written informed consent was obtained from a parent or guardian for all subjects, we collected about 70μL capillary whole blood of the subjects during the first four days of life (12 to 84 hours old), by heel prick with the automated incision device into BD Microtainer tubes (spec, 0.5mL; Becton Dickinson and Company, USA) containing K2-ethylenediaminetetraacetic acid (EDTA) as an anticoagulant. Samples were obtained by experienced technicians at the same time of blood sampling for the screening of congenital hypothyroidism and phenylketonuria or the routine serum bilirubin in morning hours (1-2 hours later after last food intake). The first-second drop of blood was discarded and each collection time was less than 1 minute. Samples were stored at ambient temperature for a maximum of four hours before the assay was performed. Laboratory analyses All capillary blood samples were analysed by SYSMEX XN-9000 haematology automatic analyser (Sysmex Corporation, Kobe, Japan) in the pre-dilution mode (dilution ratio, complete blood: PK dilution = 1:6) to measure PLT (´ 10 9 /L) and related parameters, including mean platelet volume (MPV, fL), plateletcrit level (PCT, %), platelet size distribution width (PDW, fL) and platelet large cell ratio (P-LCR, %). As listed in Kaito et al. [16] for the detection principle of platelet parameters, MPV was calculated by a formula (PCT / PLT ´ 10 4 ), and PDW and P-LCR were analysed from a histogram of platelet size distribution. Quality controls were run during every shift. Statistical analysis Data management and analyses were performed using SPSS 25.0 software (SPSS Inc., Chicago, USA). The data distribution was evaluated using Q-Q plots, histograms and Shapiro-Wilk test. We built Box plot (with Tukey variation) to identify the outliers using GraphPad Prism 8.2.1 (GraphPad software, La Jolla, CA, USA). An outlier was defined as a value Q 3 + 1.5 × IQR (Q 3 : 75 th percentiles). Quantitative data were expressed as either mean (± standard deviation, SD) for normally distributed data or median (IQR) for data not normally distributed. RIs for platelet parameters were defined by an interval of 2.5 th – 97.5 th percentiles. We performed Student’s t -test or Mann-Whitney U test as appropriate in order to evaluate influence of sex on platelet parameters. Pearson’s or Spearman’s correlation coefficients was performed as appropriate to evaluate correlations between platelet parameters and correlation factors. Two-tailed P values of less than 0.05 were set as statistical significance. Results Platelet parameters reference intervals Totally 594 neonates were enrolled in present study. Demographic data are shown in Table 1. Several values were identified as outliers in platelet parameters and we excluded cases test-by-test in data analyses (see Figure 1). Except for PLT, other platelet indices were not normally distributed. RIs for platelet parameters represent the central ninety-five percent out of all data (Table 2). As a result, capillary blood RI of PLT ranged from 152 to 464 (´ 10 9 /L). Correlation factors Female neonates had higher capillary blood PLT values (310 (±77) ´ 10 9 /L) than male neonates (299 (±77) ´ 10 9 /L) but this difference was not statistically significant ( p-value = 0.082). Expectedly, other platelet parameters were not significantly affected by sex (all p-values > 0.05) (Table 2). In order to evaluate correlations between platelet parameters and gestational age (259 to 293 days of gestation) and postnatal age (12 to 81 hours old), we performed Pearson’s correlation coefficient in PLT and Spearman’s correlation coefficient in platelet indices (Table 3). Significant negative correlations between gestational age and platelet parameters were observed ( p-value <0.05). However, in view of the low coefficients of correlation in PLT and PDW across gestational age, a biologic relationship between them is likely absent. Moreover, correlations between postnatal age and platelet parameters (except for PCT) were significant but very mild as all of absolute values of correlation coefficients were below 0.2. Discussion RIs for platelet parameters are of great value in diagnosis and monitoring of various diseases in the neonatal period, particularly in the first days of life. [17-19] Previous studies on developing RIs for platelet parameters provided important information [8, 20-26]. However, the RIs were based on cord blood or venous blood in pre-term or term neonates [4-6, 27]. In present study, we presented the first RIs for platelet parameters using capillary blood in healthy term neonates. Unfortunately, due to the difficulty to persuade parents to obtain venous blood samples from their healthy babies, we did not determine difference among various sampling sites. Early studies [20, 28] reported that significantly lower PLT values were found in capillary blood than venous blood. Their data proved the fact that capillary MPV values were higher than venous MPV values. Not surprisingly, PCT values were positively correlated strongly with PLT values, while other platelet indices remained unchanged basically and did not obviously fluctuate along with PLT values [22]. Thus, a higher PCT value was also observed in venous blood compared with capillary blood. These data confirmed the effect of different sampling sites on platelet parameters in the neonatal period. Venous blood collection in neonates is full of challenges and time-consuming, which may make platelets relatively more likeness to activate and aggregate. Composition of capillary blood may be affected by local metabolic state as well as perfusion. Moreover, various extent of stress about extrusion on heel sampling sites may disturb the microcirculation and microenvironment and also affect the composition of capillary blood for that the samples may be mixed with an undetermined proportion of interstitial and intracellular fluids.[27] And in clinical practice, we should take neonatal sampling sites into consideration when choosing RIs for platelet parameters. A recent study showed that neonatal age had a significant effect on the parameters regarding coagulation. [29] And we found a slight variation in PLT in the first days of life. Of note, a multicentre study recruiting a large neonate cohort [4] reported that PLT values changes with two peak sinusoids at 2-3 weeks and 6-7 weeks of postnatal age. On the other hand, in our current study, a very mild negative correlation was observed between PLT values and term gestational age (Pearson's correlation coefficient, r = -0.143), which may reflect a true absence of a biologic relationship. The multicentre study above and other previous studies [26, 30] reported that PLT values increased linearly with advancing gestational age. However, these studies[4, 31] are heterogeneous in nature because of both pre-term and term babies included and using variable blood samples, which may potentially lead to multiple confounding factors influencing their results and further resulting in a different observation with us. The present study has some limitations. First, our cohort did not precisely determine the difference between various sampling sites because of the difficulty to obtain venous blood samples from healthy babies as described above. Secondly, as the neonates in our reference population aged from 12 to 84 hours, we cannot extrapolate how the RIs vary in the first 12 hours of life or after postnatal age of 84 hours. Moreover, when the population is divided according to gestational age and postnatal age, the size of our study population does not meet the CLSI recommendation and therefore, we chose to report RIs for the combined population. Conclusions In conclusion, for the first time, the current study established capillary blood RIs for platelet parameters in the first days after birth in China. Furthermore, sex difference was of little clinical significance and therefore RIs for platelet parameters were combined for male and female neonates. And our findings showed values of platelet parameters changed with advancing gestational and postnatal age, which might provide clues for further multicentre investigations aimed at offering more accurate RIs for haematological parameters, in a larger population study. Abbreviations RIs: Reference intervals; CLSI: Clinical and Laboratory Standards Institute; EDTA: K2-ethylenediaminetetraacetic acid; PLT: platelet count; MPV: platelet volume; PCT: plateletcrit level; PDW: platelet size distribution width; P-LCR: platelet large cell ratio; SPSS: Statistical Product and Service Solutions; SD: standard deviation; IQR: interquartile range. Declarations Ethics approval and consent to participate Written informed consent was obtained from a parent or guardian for all subjects. The study was approved by The Human Ethics Committees of the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20190308). Consent for publication We have received informed consent from all subjects’ parents or suitable proxies for publication of this paper and the written consent is held by our institution. Availability of data and materials All data generated or analysed during this study are included in this published article. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests We have no conflicts of interest to disclose. Funding The authors declare that they have no funding for the research reported. Authors’ contributions QH conceived and designed the research study, and reviewed the manuscript. LF and YH made contributions to the conception of the work and selected the qualified subjects. GL, CZ and JF analysed the neonatal blood samples. DC and YH analysed the data and wrote the manuscript. All authors (DC, YH, LF, GL, CZ, YH, JF and QH) have substantively revised the work and approved the final manuscript and submission. Acknowledgements We would like to thank all the subjects and their parents very much for their support and dedication, and the staff members of participating hospitals for their valuable cooperation in this research. References Jung B, Adeli K. Clinical laboratory reference intervals in pediatrics: the CALIPER initiative. CLIN BIOCHEM 2009; 42 : 1589-95. https://doi.10.1016/j.clinbiochem.2009.06.025 Alnor AB, Vinholt PJ. Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples. EUR J PEDIATR 2019; 178 : 963-71. https://doi.10.1007/s00431-019-03377-w Andres O, Schulze H, Speer CP. Platelets in neonates: central mediators in haemostasis, antimicrobial defence and inflammation. Thromb Haemost 2015; 113 : 3-12. https://doi.10.1160/TH14-05-0476 Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J PERINATOL 2009; 29 : 130-6. https://doi.10.1038/jp.2008.141 Grecu DS, Paulescu E. Quality assurance in the laboratory testing process: indirect estimation of the reference intervals for platelet parameters in neonates. CLIN BIOCHEM 2014; 47 : 33-7. https://doi.10.1016/j.clinbiochem.2014.07.002 Chang YH, Yang SH, Wang TF, Lin TY, Yang KL, Chen SH. Complete blood count reference values of cord blood in Taiwan and the influence of gender and delivery route on them. PEDIATR NEONATOL 2011; 52 : 155-60. https://doi.10.1016/j.pedneo.2011.03.007 Zierk J, Arzideh F, Rechenauer T, Haeckel R, Rascher W, Metzler M , et al. . Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. CLIN CHEM 2015; 61 : 964-73. https://doi.10.1373/clinchem.2015.239731 Henry E, Christensen RD. Reference Intervals in Neonatal Hematology. CLIN PERINATOL 2015; 42 : 483-97. https://doi.10.1016/j.clp.2015.04.005 Paes B, Janes M, Vegh P, LaDuca F, Andrew M. A comparative study of heel-stick devices for infant blood collection. Am J Dis Child 1993; 147 : 346-8. Krleza JL. Nationwide survey of policies and practices related to capillary blood sampling in medical laboratories in Croatia. Biochem Med (Zagreb) 2014; 24 : 350-8. https://doi.10.11613/BM.2014.037 Gallo S, Comeau K, Sharma A, Vanstone CA, Agellon S, Mitchell J , et al. . Redefining normal bone and mineral clinical biochemistry reference intervals for healthy infants in Canada. CLIN BIOCHEM 2014; 47 : 27-32. https://doi.10.1016/j.clinbiochem.2014.07.012 Bell KJ, Gray R, Munns D, Petocz P, Howard G, Colagiuri S , et al. . Estimating insulin demand for protein-containing foods using the food insulin index. EUR J CLIN NUTR 2014; 68 : 1055-9. https://doi.10.1038/ejcn.2014.126 Iijima S, Baba T, Ueno D, Ohishi A. International normalized ratio testing with point-of-care coagulometer in healthy term neonates. BMC PEDIATR 2014; 14 : 179. https://doi.10.1186/1471-2431-14-179 Clinical and Laboratory Standards Institute CLSI. CLSI document C28-A3 (2008) Defining, Establishing, and Veryfying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. C28–A3. Wasiluk A. Thrombocytopoiesis in healthy term newborns. J PERINAT MED 2005; 33 : 252-4. https://doi.10.1515/JPM.2005.046 Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E , et al. . Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol 2005; 128 : 698-702. https://doi.10.1111/j.1365-2141.2004.05357.x Coller BS. Historical perspective and future directions in platelet research. J THROMB HAEMOST 2011; 9 Suppl 1 : 374-95. https://doi.10.1111/j.1538-7836.2011.04356.x Christensen RD, Henry E, Del VA. Thrombocytosis and thrombocytopenia in the NICU: incidence, mechanisms and treatments. J Matern Fetal Neonatal Med 2012; 25 Suppl 4 : 15-7. https://doi.10.3109/14767058.2012.715027 Andres O, Schulze H, Speer CP. Platelets in neonates: central mediators in haemostasis, antimicrobial defence and inflammation. Thromb Haemost 2015; 113 : 3-12. https://doi.10.1160/TH14-05-0476 Kayiran SM, Ozbek N, Turan M, Gurakan B. Significant differences between capillary and venous complete blood counts in the neonatal period. Clin Lab Haematol 2003; 25 : 9-16. https://doi.10.1046/j.1365-2257.2003.00484.x Melioli G, Risso FM, Sannia A, Serra G, Bologna R, Mussap M , et al. . Reference values of blood cell counts in the first days of life. Front Biosci (Elite Ed) 2011; 3 : 871-8. https://doi.10.2741/e295 Hoffmann JJ, van den Broek NM, Curvers J. Reference intervals of reticulated platelets and other platelet parameters and their associations. ARCH PATHOL LAB MED 2013; 137 : 1635-40. https://doi.10.5858/arpa.2012-0624-OA Effiong CE, Usanga EA, Mellits ED. Platelet count in healthy full-term Nigerian neonates. Trop Geogr Med 1976; 28 : 329-32. Ozyurek E, Cetintas S, Ceylan T, Ogus E, Haberal A, Gurakan B , et al. . Complete blood count parameters for healthy, small-for-gestational-age, full-term newborns. Clin Lab Haematol 2006; 28 : 97-104. https://doi.10.1111/j.1365-2257.2006.00767.x Biino G, Santimone I, Minelli C, Sorice R, Frongia B, Traglia M , et al. . Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data. PLOS ONE 2013; 8 : e54289. https://doi.10.1371/journal.pone.0054289 Glasser L, Sutton N, Schmeling M, Machan JT. A comprehensive study of umbilical cord blood cell developmental changes and reference ranges by gestation, gender and mode of delivery. J PERINATOL 2015; 35 : 469-75. https://doi.10.1038/jp.2014.241 Proytcheva MA. Issues in neonatal cellular analysis. AM J CLIN PATHOL 2009; 131 : 560-73. https://doi.10.1309/AJCPTHBJ4I4YGZQC Ozbek N, Gurakan B, Kayiran SM. Complete blood cell counts in capillary and venous blood of healthy term newborns. Acta Haematol 2000; 103 : 226-8. https://doi.10.1159/000041056 Liu Q, Xu C, Chen X, Wang J, Ke Z, Hu H. Establishing a reference range for thromboelastograph parameters in the neonatal period. INT J LAB HEMATOL 2019. https://doi.10.1111/ijlh.13043 Van den Hof MC, Nicolaides KH. Platelet count in normal, small, and anemic fetuses. AM J OBSTET GYNECOL 1990; 162 : 735-9. https://doi.10.1016/0002-9378(90)90997-l Rolim A, Lambert MA, Borges J, Abbas SA, Bordin JO, Langhi JD , et al. . BLOOD CELLS PROFILE IN UMBILICAL CORD OF LATE PRETERM AND TERM NEWBORNS. Rev Paul Pediatr 2019; 37 : 264-74. https://doi.10.1590/1984-0462/;2019;37;3;00008 Tables Tables Table 1 Demographic data of the subjects Sex Total Male Female N 594 323 271 Gestational age, days 273 (266 - 278) 271 (265 - 278) 274 (268 - 279) Postnatal age, hours 29 (22 - 49) 29 (22 - 49) 30 (22 - 49) Quantitative data were expressed as median (interquartile range, IQR). Table 2 Capillary blood reference intervals for platelet parameters in healthy term neonates Platelet parameters Percentiles Demographic data 2.5th 97.5th Total Male Female PLT, ´10 9 /L 152 464 304 (± 77) 299 (± 77) 310 (± 77) PCT, % 0.18 0.46 0.30 (0.26-0.36) 0.30 (0.25-0.36) 0.31 (0.26-0.37) MPV, fL 8.3 12.6 10.9 (10.1-11.4) 10.9 (10.2-11.4) 10.8 (10.0-11.4) PDW, fL 9.4 17.1 12.5 (11.1-15.8) 12.5 (11.2-15.8) 12.3 (11.0-15.9) P-LCR, % 15.4 42.8 30.0 (25.0-34.7) 30.5 (25.2-35.2) 29.5 (24.7-34.0) Abbreviations: PLT, platelet count; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet size distribution width; P-LCR, platelet-large cell ratio. Data were expressed as either mean (± standard deviation, SD) or median (interquartile range, IQR). Table 3 Correlations between platelet parameters and gestational age and postnatal age in healthy term neonates Factor PLT PCT MPV PDW P-LCR Gestational age r* -0.143 -0.237 -0.255 -0.161 -0.206 p 0.001 <0.001 <0.001 <0.001 <0.001 Postnatal age r* -0.085 0.027 0.094 0.196 0.105 p 0.041 0.509 0.023 <0.001 0.011 Abbreviations: PLT, platelet count; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet size distribution width; P-LCR, platelet-large cell ratio. *. Pearson's correlation coefficient was performed in PLT, and Spearman's correlation coefficient was performed in other platelet indices. Cite Share Download PDF Status: Published Journal Publication published 10 Oct, 2020 Read the published version in BMC Pediatrics → Version 2 posted Submission checks completed at journal 05 Oct, 2020 Editorial decision: Accept 01 Oct, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-32762","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":3094304,"identity":"363d7284-c9cc-427c-b6ef-b4983cd9b710","order_by":0,"name":"Dongyan Cui","email":"","orcid":"","institution":"Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dongyan","middleName":"","lastName":"Cui","suffix":""},{"id":3094305,"identity":"6c1971de-f8a0-4ef0-a430-b7285e6eaa1d","order_by":1,"name":"Yan Hou","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Hou","suffix":""},{"id":3094306,"identity":"d9258373-53ef-4ef1-af31-bc8985971982","order_by":2,"name":"Ling Feng","email":"","orcid":"","institution":"Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Feng","suffix":""},{"id":3094307,"identity":"46ec19e1-fd5d-4044-86c6-8bcb4ed480fc","order_by":3,"name":"Guo Li","email":"","orcid":"","institution":"Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guo","middleName":"","lastName":"Li","suffix":""},{"id":3094308,"identity":"f040ce84-9d38-4ea1-ae69-0d22501ec533","order_by":4,"name":"Chi Zhang","email":"","orcid":"","institution":"Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chi","middleName":"","lastName":"Zhang","suffix":""},{"id":3094309,"identity":"cfef861f-a84b-4142-99e2-8f0471853e2b","order_by":5,"name":"Yanli Huang","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yanli","middleName":"","lastName":"Huang","suffix":""},{"id":3094310,"identity":"f6c08eee-301e-455c-af3b-558c1e4dd292","order_by":6,"name":"Jiubo Fan","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiubo","middleName":"","lastName":"Fan","suffix":""},{"id":3094311,"identity":"319c0632-0eef-4e80-827b-c3a926fd7f6b","order_by":7,"name":"Qun Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYHACNgaGCgkeefbGxocfiNdyxkbGsOdws7EE0VoY29JsGG6ktwnwEKOe70buscc8bId5GGc+bGOQYLCT020goEXyRl66MQ/PYR526cS2BwUMycZmBwhoMbiRYybNIwG0ZXZiu4EEw4HEbcRpMTjMw3DzYJsED/FaEtJ4GG4wEqlF8swbM8k5B2x4DHsSgYFsQIRf+I7nmEm8/SdhL89+/OHDDxV2cgS1MKAqMCCkHFPLKBgFo2AUjAIsAAAjYT/BKeYOoAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-1508-2796","institution":"Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Qun","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2020-05-30 22:48:49","currentVersionCode":2,"declarations":"","doi":"10.21203/rs.3.rs-32762/v2","doiUrl":"https://doi.org/10.21203/rs.3.rs-32762/v2","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-020-02373-6","type":"published","date":"2020-10-10T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2957767,"identity":"58593215-275b-4135-8d05-26f230aa8646","added_by":"auto","created_at":"2020-10-13 20:36:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11017,"visible":true,"origin":"","legend":"The Box plot for platelet parameters data. The centre, the variability and the outliers are displayed. The following number of outliers was found: 11 for PLT, 9 for PCT, 3 for MPV, 3 for PDW, and 7 for P-LCR. \nAbbreviations: PLT, platelet count; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet size distribution width; P-LCR, platelet-large cell ratio. \n","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-32762/v2/6f2474c6ec71d5bd3655ff9d.png"},{"id":13602025,"identity":"d52375ef-40db-4fd3-b080-90af9fea6b49","added_by":"auto","created_at":"2021-09-17 05:50:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":361469,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-32762/v2/e1c8b93b-db81-475c-98fe-e7f8978433e4.pdf"}],"financialInterests":"","formattedTitle":"Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China","fulltext":[{"header":"Background","content":"\u003cp\u003eReference intervals (RIs) play a critical role in clinical practice. Appropriate RIs for platelet parameters ensure clinical laboratories provide reliable information and enable clinicians to correctly interpret results and further determine whether transfusions are needed for neonates [1, 2]. However, few normative data are available in RIs for platelet parameters in full-term neonates [3].\u003c/p\u003e\n\u003cp\u003eNeonates are in a crucial period of rapid development, and platelet parameters are significantly affected by these physiological changes[4]. Moreover, RIs for platelet parameters have often been derived from haematological results of both inpatient and outpatient neonates[4, 5], or blood samples are leftover material from the donated blood for a specific use in a pre-term (delivered at less than 37 weeks of gestation) or full-term neonate population [6, 7], which may be inaccurate and unreliable for full-term neonates. It is hard for neonatal health care providers to provide standard-of-care health services as a lack of appropriate RIs for haematology may impede diagnostics for neonates [8]. The study of RIs for platelet parameters in neonates is highly restricted due to the ethical limitations and difficulties to obtain sufficient blood samples. Capillary sampling by the automated incision device spends a shorter time for blood collection with reduced haemolysis [9], and is increasingly used in clinical practice nowadays in China. Capillary blood for haematology tests is as small as necessary in volumes and as non-invasively as possible with a very low frequency of local infection and decreased extent of bruising [10]. Although capillary blood is used to develop RIs for other biologic markers [11-13], studies have not been carried out to evaluate its clinical utility in neonatal capillary blood RIs for platelet parameters.\u003c/p\u003e\n\u003cp\u003eIdeally, RIs for platelet parameters are established in a healthy full-term neonate population and more than 120 specimens are required by the Clinical and Laboratory Standards Institute (CLSI). [14] The objectives of the present study were to determine capillary blood RIs for platelet count (PLT) and related parameters in 594 healthy full-term neonates from 12 to 84 hours of age, and furthermore to evaluate influences of sex, gestational age and postnatal age on platelet parameters.\u003c/p\u003e"},{"header":"Methods","content":"\n\u003ch2\u003eStudy populations\u003c/h2\u003e\n\u003cp\u003eThe study commenced after obtaining Institutional Ethical Committee approval (TJ-IRB20190308). The subjects were prospectively enrolled into this study, and all of them were healthy full-term (259 to 293 days (37 to 41 weeks) of gestation) neonates born at two hospitals from November 2018 to April 2019. Major inclusion/exclusion criteria are listed as follows. As listed in Chang et al.[6] for mothers, maternal age ranged from 20 to 40 years old and they had a normal health check-up without unfavourable past history during pregnancy, such as smoking, infectious diseases (hepatitis B/C, HIV, syphilis infections), idiopathic thrombocytopenic purpura, malignancies and chronic diseases (diabetes mellitus, autoimmune disease, immunodeficiencies and thrombotic disorders); mothers did not receive aspirin during pregnancy; a vaginal delivery or caesarean section was event-free. Professional obstetricians were responsible for the data of this part. As listed in Chang et al.[6] and Wasiluk [15] for neonates, they fitted all clinical state criteria for full-term neonates; they were born with normal birth weight (2500-4000g) appropriate for gestational age and normal Apgar score (8-10 points at 1-5 minutes of life); physical examinations of the subjects were normal without any signs of infection or congenital anomalies at the time of sampling. And we excluded all neonates with an unfavourable perinatal history of premature rupture of membrane more than 24 hours, abnormal placenta, placenta abruption, chorioamnionitis or meconium stain, or with a medical history of hospitalizing in the neonatal intensive care unit. All subjects are Han ethnicity.\u003c/p\u003e\n\u003ch2\u003eBlood sampling\u003c/h2\u003e\n\u003cp\u003eAfter written informed consent was obtained from a parent or guardian for all subjects, we collected about 70\u0026mu;L capillary whole blood of the subjects during the first four days of life (12 to 84 hours old), by heel prick with the automated incision device into BD Microtainer tubes (spec, 0.5mL; Becton Dickinson and Company, USA) containing K2-ethylenediaminetetraacetic acid (EDTA) as an anticoagulant. Samples were obtained by experienced technicians at the same time of blood sampling for the screening of congenital hypothyroidism and phenylketonuria or the routine serum bilirubin in morning hours (1-2 hours later after last food intake). The first-second drop of blood was discarded and each collection time was less than 1 minute. Samples were stored at ambient temperature for a maximum of four hours before the assay was performed.\u003c/p\u003e\n\u003ch2\u003eLaboratory analyses\u003c/h2\u003e\n\u003cp\u003eAll capillary blood samples were analysed by SYSMEX XN-9000 haematology automatic analyser (Sysmex Corporation, Kobe, Japan) in the pre-dilution mode (dilution ratio, complete blood: PK dilution = 1:6) to measure PLT (\u0026acute; 10\u003csup\u003e9\u003c/sup\u003e/L) and related parameters, including mean platelet volume (MPV, fL), plateletcrit level (PCT, %), platelet size distribution width (PDW, fL) and platelet large cell ratio (P-LCR, %). As listed in Kaito et al. [16] for the detection principle of platelet parameters, MPV was calculated by a formula (PCT / PLT \u0026acute; 10\u003csup\u003e4\u003c/sup\u003e), and PDW and P-LCR were analysed from a histogram of platelet size distribution. Quality controls were run during every shift. \u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eData management and analyses were performed using SPSS 25.0 software (SPSS Inc., Chicago, USA). The data distribution was evaluated using Q-Q plots, histograms and Shapiro-Wilk test. We built Box plot (with Tukey variation) to identify the outliers using GraphPad Prism 8.2.1 (GraphPad software, La Jolla, CA, USA). An outlier was defined as a value \u0026lt; Q\u003csub\u003e1\u003c/sub\u003e \u0026ndash; 1.5 \u0026times; IQR (Q\u003csub\u003e1\u003c/sub\u003e: 25\u003csup\u003eth\u003c/sup\u003e percentiles, IQR: interquartile range), or \u0026gt; Q\u003csub\u003e3\u003c/sub\u003e + 1.5 \u0026times; IQR (Q\u003csub\u003e3\u003c/sub\u003e: 75\u003csup\u003eth\u003c/sup\u003e percentiles). Quantitative data were expressed as either mean (\u0026plusmn; standard deviation, SD) for normally distributed data or median (IQR) for data not normally distributed. RIs for platelet parameters were defined by an interval of 2.5\u003csup\u003eth\u003c/sup\u003e \u0026ndash; 97.5\u003csup\u003eth\u003c/sup\u003e percentiles. We performed Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or Mann-Whitney U test as appropriate in order to evaluate influence of sex on platelet parameters. Pearson\u0026rsquo;s or Spearman\u0026rsquo;s correlation coefficients was performed as appropriate to evaluate correlations between platelet parameters and correlation factors. Two-tailed P values of less than 0.05 were set as statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003ePlatelet parameters reference intervals\u003c/h2\u003e\n\u003cp\u003eTotally 594 neonates were enrolled in present study. Demographic data are shown in Table 1. Several values were identified as outliers in platelet parameters and we excluded cases test-by-test in data analyses (see Figure 1). Except for PLT, other platelet indices were not normally distributed. RIs for platelet parameters represent the central ninety-five percent out of all data (Table 2). As a result, capillary blood RI of PLT ranged from 152 to 464 (\u0026acute; 10\u003csup\u003e9\u003c/sup\u003e/L).\u003c/p\u003e\n\u003ch2\u003eCorrelation factors\u003c/h2\u003e\n\u003cp\u003eFemale neonates had higher capillary blood PLT values (310 (\u0026plusmn;77) \u0026acute; 10\u003csup\u003e9\u003c/sup\u003e/L) than male neonates (299 (\u0026plusmn;77) \u0026acute; 10\u003csup\u003e9\u003c/sup\u003e/L) but this difference was not statistically significant (\u003cem\u003ep-value\u003c/em\u003e = 0.082). Expectedly, other platelet parameters were not significantly affected by sex (all \u003cem\u003ep-values\u003c/em\u003e \u0026gt; 0.05) (Table 2). In order to evaluate correlations between platelet parameters and gestational age (259 to 293 days of gestation) and postnatal age (12 to 81 hours old), we performed Pearson\u0026rsquo;s correlation coefficient in PLT and Spearman\u0026rsquo;s correlation coefficient in platelet indices (Table 3). Significant negative correlations between gestational age and platelet parameters were observed (\u003cem\u003ep-value\u003c/em\u003e \u0026lt;0.05). However, in view of the low coefficients of correlation in PLT and PDW across gestational age, a biologic relationship between them is likely absent. Moreover, correlations between postnatal age and platelet parameters (except for PCT) were significant but very mild as all of absolute values of correlation coefficients were below 0.2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRIs for platelet parameters are of great value in diagnosis and monitoring of various diseases in the neonatal period, particularly in the first days of life. [17-19] Previous studies on developing RIs for platelet parameters provided important information [8, 20-26]. However, the RIs were based on cord blood or venous blood in pre-term or term neonates [4-6, 27]. In present study, we presented the first RIs for platelet parameters using capillary blood in healthy term neonates.\u003c/p\u003e\n\u003cp\u003eUnfortunately, due to the difficulty to persuade parents to obtain venous blood samples from their healthy babies, we did not determine difference among various sampling sites. Early studies [20, 28] reported that significantly lower PLT values were found in capillary blood than venous blood. Their data proved the fact that capillary MPV values were higher than venous MPV values. Not surprisingly, PCT values were positively correlated strongly with PLT values, while other platelet indices remained unchanged basically and did not obviously fluctuate along with PLT values [22]. Thus, a higher PCT value was also observed in venous blood compared with capillary blood. These data confirmed the effect of different sampling sites on platelet parameters in the neonatal period. Venous blood collection in neonates is full of challenges and time-consuming, which may make platelets relatively more likeness to activate and aggregate. Composition of capillary blood may be affected by local metabolic state as well as perfusion. Moreover, various extent of stress about extrusion on heel sampling sites may disturb the microcirculation and microenvironment and also affect the composition of capillary blood for that the samples may be mixed with an undetermined proportion of interstitial and intracellular fluids.[27] And in clinical practice, we should take neonatal sampling sites into consideration when choosing RIs for platelet parameters.\u003c/p\u003e\n\u003cp\u003eA recent study showed that neonatal age had a significant effect on the parameters regarding coagulation. [29] And we found a slight variation in PLT in the first days of life. Of note, a multicentre study recruiting a large neonate cohort [4] reported that PLT values changes with two peak sinusoids at 2-3 weeks and 6-7 weeks of postnatal age. On the other hand, in our current study, a very mild negative correlation was observed between PLT values and term gestational age (Pearson's correlation coefficient, r = -0.143), which may reflect a true absence of a biologic relationship. The multicentre study above and other previous studies [26, 30] reported that PLT values increased linearly with advancing gestational age. However, these studies[4, 31] are heterogeneous in nature because of both pre-term and term babies included and using variable blood samples, which may potentially lead to multiple confounding factors influencing their results and further resulting in a different observation with us.\u003c/p\u003e\n\u003cp\u003eThe present study has some limitations. First, our cohort did not precisely determine the difference between various sampling sites because of the difficulty to obtain venous blood samples from healthy babies as described above. Secondly, as the neonates in our reference population aged from 12 to 84 hours, we cannot extrapolate how the RIs vary in the first 12 hours of life or after postnatal age of 84 hours. Moreover, when the population is divided according to gestational age and postnatal age, the size of our study population does not meet the CLSI recommendation and therefore, we chose to report RIs for the combined population.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, for the first time, the current study established capillary blood RIs for platelet parameters in the first days after birth in China. Furthermore, sex difference was of little clinical significance and therefore RIs for platelet parameters were combined for male and female neonates. And our findings showed values of platelet parameters changed with advancing gestational and postnatal age, which might provide clues for further multicentre investigations aimed at offering more accurate RIs for haematological parameters, in a larger population study.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRIs: Reference intervals; CLSI: Clinical and Laboratory Standards Institute; EDTA: K2-ethylenediaminetetraacetic acid; PLT: platelet count; MPV: platelet volume; PCT: plateletcrit level; PDW: platelet size distribution width; P-LCR: platelet large cell ratio; SPSS: Statistical Product and Service Solutions; SD: standard deviation; IQR: interquartile range.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from a parent or guardian for all subjects. The study was approved by The Human Ethics Committees of the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20190308).\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eWe have received informed consent from all subjects\u0026rsquo; parents or suitable proxies for publication of this paper and the written consent is held by our institution.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eWe have no conflicts of interest to disclose.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no funding for the research reported.\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003eQH conceived and designed the research study, and reviewed the manuscript. LF and YH made contributions to the conception of the work and selected the qualified subjects. GL, CZ and JF analysed the neonatal blood samples. DC and YH analysed the data and wrote the manuscript. All authors (DC, YH, LF, GL, CZ, YH, JF and QH) have substantively revised the work and approved the final manuscript and submission.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eWe would like to thank all the subjects and their parents very much for their support and dedication, and the staff members of participating hospitals for their valuable cooperation in this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJung B, Adeli K. Clinical laboratory reference intervals in pediatrics: the CALIPER initiative. \u003cem\u003eCLIN BIOCHEM\u003c/em\u003e 2009; 42\u003cstrong\u003e: \u003c/strong\u003e1589-95. https://doi.10.1016/j.clinbiochem.2009.06.025\u003c/li\u003e\n\u003cli\u003eAlnor AB, Vinholt PJ. Paediatric reference intervals are heterogeneous and differ considerably in the classification of healthy paediatric blood samples. \u003cem\u003eEUR J PEDIATR\u003c/em\u003e 2019; 178\u003cstrong\u003e: \u003c/strong\u003e963-71. https://doi.10.1007/s00431-019-03377-w\u003c/li\u003e\n\u003cli\u003eAndres O, Schulze H, Speer CP. Platelets in neonates: central mediators in haemostasis, antimicrobial defence and inflammation. \u003cem\u003eThromb Haemost\u003c/em\u003e 2015; 113\u003cstrong\u003e: \u003c/strong\u003e3-12. https://doi.10.1160/TH14-05-0476\u003c/li\u003e\n\u003cli\u003eWiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. \u003cem\u003eJ PERINATOL\u003c/em\u003e 2009; 29\u003cstrong\u003e: \u003c/strong\u003e130-6. https://doi.10.1038/jp.2008.141\u003c/li\u003e\n\u003cli\u003eGrecu DS, Paulescu E. Quality assurance in the laboratory testing process: indirect estimation of the reference intervals for platelet parameters in neonates. \u003cem\u003eCLIN BIOCHEM\u003c/em\u003e 2014; 47\u003cstrong\u003e: \u003c/strong\u003e33-7. https://doi.10.1016/j.clinbiochem.2014.07.002\u003c/li\u003e\n\u003cli\u003eChang YH, Yang SH, Wang TF, Lin TY, Yang KL, Chen SH. Complete blood count reference values of cord blood in Taiwan and the influence of gender and delivery route on them. \u003cem\u003ePEDIATR NEONATOL\u003c/em\u003e 2011; 52\u003cstrong\u003e: \u003c/strong\u003e155-60. https://doi.10.1016/j.pedneo.2011.03.007\u003c/li\u003e\n\u003cli\u003eZierk J, Arzideh F, Rechenauer T, Haeckel R, Rascher W, Metzler M\u003cem\u003e, et al.\u003c/em\u003e. Age- and sex-specific dynamics in 22 hematologic and biochemical analytes from birth to adolescence. \u003cem\u003eCLIN CHEM\u003c/em\u003e 2015; 61\u003cstrong\u003e: \u003c/strong\u003e964-73. https://doi.10.1373/clinchem.2015.239731\u003c/li\u003e\n\u003cli\u003eHenry E, Christensen RD. Reference Intervals in Neonatal Hematology. \u003cem\u003eCLIN PERINATOL\u003c/em\u003e 2015; 42\u003cstrong\u003e: \u003c/strong\u003e483-97. https://doi.10.1016/j.clp.2015.04.005\u003c/li\u003e\n\u003cli\u003ePaes B, Janes M, Vegh P, LaDuca F, Andrew M. A comparative study of heel-stick devices for infant blood collection. \u003cem\u003eAm J Dis Child\u003c/em\u003e 1993; 147\u003cstrong\u003e: \u003c/strong\u003e346-8.\u003c/li\u003e\n\u003cli\u003eKrleza JL. Nationwide survey of policies and practices related to capillary blood sampling in medical laboratories in Croatia. \u003cem\u003eBiochem Med (Zagreb)\u003c/em\u003e 2014; 24\u003cstrong\u003e: \u003c/strong\u003e350-8. https://doi.10.11613/BM.2014.037\u003c/li\u003e\n\u003cli\u003eGallo S, Comeau K, Sharma A, Vanstone CA, Agellon S, Mitchell J\u003cem\u003e, et al.\u003c/em\u003e. Redefining normal bone and mineral clinical biochemistry reference intervals for healthy infants in Canada. \u003cem\u003eCLIN BIOCHEM\u003c/em\u003e 2014; 47\u003cstrong\u003e: \u003c/strong\u003e27-32. https://doi.10.1016/j.clinbiochem.2014.07.012\u003c/li\u003e\n\u003cli\u003eBell KJ, Gray R, Munns D, Petocz P, Howard G, Colagiuri S\u003cem\u003e, et al.\u003c/em\u003e. Estimating insulin demand for protein-containing foods using the food insulin index. \u003cem\u003eEUR J CLIN NUTR\u003c/em\u003e 2014; 68\u003cstrong\u003e: \u003c/strong\u003e1055-9. https://doi.10.1038/ejcn.2014.126\u003c/li\u003e\n\u003cli\u003eIijima S, Baba T, Ueno D, Ohishi A. International normalized ratio testing with point-of-care coagulometer in healthy term neonates. \u003cem\u003eBMC PEDIATR\u003c/em\u003e 2014; 14\u003cstrong\u003e: \u003c/strong\u003e179. https://doi.10.1186/1471-2431-14-179\u003c/li\u003e\n\u003cli\u003eClinical and Laboratory Standards Institute CLSI. CLSI document C28-A3 (2008) Defining, Establishing, and Veryfying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. C28\u0026ndash;A3.\u003c/li\u003e\n\u003cli\u003eWasiluk A. Thrombocytopoiesis in healthy term newborns. \u003cem\u003eJ PERINAT MED\u003c/em\u003e 2005; 33\u003cstrong\u003e: \u003c/strong\u003e252-4. https://doi.10.1515/JPM.2005.046\u003c/li\u003e\n\u003cli\u003eKaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E\u003cem\u003e, et al.\u003c/em\u003e. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. \u003cem\u003eBr J Haematol\u003c/em\u003e 2005; 128\u003cstrong\u003e: \u003c/strong\u003e698-702. https://doi.10.1111/j.1365-2141.2004.05357.x\u003c/li\u003e\n\u003cli\u003eColler BS. Historical perspective and future directions in platelet research. \u003cem\u003eJ THROMB HAEMOST\u003c/em\u003e 2011; 9 Suppl 1\u003cstrong\u003e: \u003c/strong\u003e374-95. https://doi.10.1111/j.1538-7836.2011.04356.x\u003c/li\u003e\n\u003cli\u003eChristensen RD, Henry E, Del VA. Thrombocytosis and thrombocytopenia in the NICU: incidence, mechanisms and treatments. \u003cem\u003eJ Matern Fetal Neonatal Med\u003c/em\u003e 2012; 25 Suppl 4\u003cstrong\u003e: \u003c/strong\u003e15-7. https://doi.10.3109/14767058.2012.715027\u003c/li\u003e\n\u003cli\u003eAndres O, Schulze H, Speer CP. Platelets in neonates: central mediators in haemostasis, antimicrobial defence and inflammation. \u003cem\u003eThromb Haemost\u003c/em\u003e 2015; 113\u003cstrong\u003e: \u003c/strong\u003e3-12. https://doi.10.1160/TH14-05-0476\u003c/li\u003e\n\u003cli\u003eKayiran SM, Ozbek N, Turan M, Gurakan B. Significant differences between capillary and venous complete blood counts in the neonatal period. \u003cem\u003eClin Lab Haematol\u003c/em\u003e 2003; 25\u003cstrong\u003e: \u003c/strong\u003e9-16. https://doi.10.1046/j.1365-2257.2003.00484.x\u003c/li\u003e\n\u003cli\u003eMelioli G, Risso FM, Sannia A, Serra G, Bologna R, Mussap M\u003cem\u003e, et al.\u003c/em\u003e. Reference values of blood cell counts in the first days of life. \u003cem\u003eFront Biosci (Elite Ed)\u003c/em\u003e 2011; 3\u003cstrong\u003e: \u003c/strong\u003e871-8. https://doi.10.2741/e295\u003c/li\u003e\n\u003cli\u003eHoffmann JJ, van den Broek NM, Curvers J. Reference intervals of reticulated platelets and other platelet parameters and their associations. \u003cem\u003eARCH PATHOL LAB MED\u003c/em\u003e 2013; 137\u003cstrong\u003e: \u003c/strong\u003e1635-40. https://doi.10.5858/arpa.2012-0624-OA\u003c/li\u003e\n\u003cli\u003eEffiong CE, Usanga EA, Mellits ED. Platelet count in healthy full-term Nigerian neonates. \u003cem\u003eTrop Geogr Med\u003c/em\u003e 1976; 28\u003cstrong\u003e: \u003c/strong\u003e329-32.\u003c/li\u003e\n\u003cli\u003eOzyurek E, Cetintas S, Ceylan T, Ogus E, Haberal A, Gurakan B\u003cem\u003e, et al.\u003c/em\u003e. Complete blood count parameters for healthy, small-for-gestational-age, full-term newborns. \u003cem\u003eClin Lab Haematol\u003c/em\u003e 2006; 28\u003cstrong\u003e: \u003c/strong\u003e97-104. https://doi.10.1111/j.1365-2257.2006.00767.x\u003c/li\u003e\n\u003cli\u003eBiino G, Santimone I, Minelli C, Sorice R, Frongia B, Traglia M\u003cem\u003e, et al.\u003c/em\u003e. Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data. \u003cem\u003ePLOS ONE\u003c/em\u003e 2013; 8\u003cstrong\u003e: \u003c/strong\u003ee54289. https://doi.10.1371/journal.pone.0054289\u003c/li\u003e\n\u003cli\u003eGlasser L, Sutton N, Schmeling M, Machan JT. A comprehensive study of umbilical cord blood cell developmental changes and reference ranges by gestation, gender and mode of delivery. \u003cem\u003eJ PERINATOL\u003c/em\u003e 2015; 35\u003cstrong\u003e: \u003c/strong\u003e469-75. https://doi.10.1038/jp.2014.241\u003c/li\u003e\n\u003cli\u003eProytcheva MA. Issues in neonatal cellular analysis. \u003cem\u003eAM J CLIN PATHOL\u003c/em\u003e 2009; 131\u003cstrong\u003e: \u003c/strong\u003e560-73. https://doi.10.1309/AJCPTHBJ4I4YGZQC\u003c/li\u003e\n\u003cli\u003eOzbek N, Gurakan B, Kayiran SM. Complete blood cell counts in capillary and venous blood of healthy term newborns. \u003cem\u003eActa Haematol\u003c/em\u003e 2000; 103\u003cstrong\u003e: \u003c/strong\u003e226-8. https://doi.10.1159/000041056\u003c/li\u003e\n\u003cli\u003eLiu Q, Xu C, Chen X, Wang J, Ke Z, Hu H. Establishing a reference range for thromboelastograph parameters in the neonatal period. \u003cem\u003eINT J LAB HEMATOL\u003c/em\u003e 2019. https://doi.10.1111/ijlh.13043\u003c/li\u003e\n\u003cli\u003eVan den Hof MC, Nicolaides KH. Platelet count in normal, small, and anemic fetuses. \u003cem\u003eAM J OBSTET GYNECOL\u003c/em\u003e 1990; 162\u003cstrong\u003e: \u003c/strong\u003e735-9. https://doi.10.1016/0002-9378(90)90997-l\u003c/li\u003e\n\u003cli\u003eRolim A, Lambert MA, Borges J, Abbas SA, Bordin JO, Langhi JD\u003cem\u003e, et al.\u003c/em\u003e. BLOOD CELLS PROFILE IN UMBILICAL CORD OF LATE PRETERM AND TERM NEWBORNS. \u003cem\u003eRev Paul Pediatr\u003c/em\u003e 2019; 37\u003cstrong\u003e: \u003c/strong\u003e264-74. https://doi.10.1590/1984-0462/;2019;37;3;00008\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\n\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch1\u003eTables\u003c/h1\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" width=\"100%\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"100%\"\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Demographic data of the subjects\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"32%\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"32%\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e594\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e323\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e271\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"32%\"\u003e\n\u003cp\u003eGestational age, days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e273 (266 - 278)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e271 (265 - 278)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e274 (268 - 279)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"32%\"\u003e\n\u003cp\u003ePostnatal age, hours\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e29 (22 - 49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e29 (22 - 49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"22%\"\u003e\n\u003cp\u003e30 (22 - 49)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"100%\"\u003e\n\u003cp\u003eQuantitative data were expressed as median (interquartile range, IQR).\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Capillary blood reference intervals for platelet parameters in healthy term neonates\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"100%\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"27%\"\u003e\n\u003cp\u003ePlatelet parameters\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"20%\"\u003e\n\u003cp\u003ePercentiles\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" width=\"52%\"\u003e\n\u003cp\u003eDemographic data\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e2.5th\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e97.5th\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"27%\"\u003e\n\u003cp\u003ePLT,\u003c/p\u003e\n\u003cp\u003e\u0026acute;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e152\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e464\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e304 (\u0026plusmn; 77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e299 (\u0026plusmn; 77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e310 (\u0026plusmn; 77)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"27%\"\u003e\n\u003cp\u003ePCT, %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e0.18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e0.46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e0.30\u003c/p\u003e\n\u003cp\u003e(0.26-0.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e0.30\u003c/p\u003e\n\u003cp\u003e(0.25-0.36)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e0.31\u003c/p\u003e\n\u003cp\u003e(0.26-0.37)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"27%\"\u003e\n\u003cp\u003eMPV, fL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e8.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e12.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e10.9\u003c/p\u003e\n\u003cp\u003e(10.1-11.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e10.9\u003c/p\u003e\n\u003cp\u003e(10.2-11.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e10.8\u003c/p\u003e\n\u003cp\u003e(10.0-11.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"27%\"\u003e\n\u003cp\u003ePDW, fL\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e9.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e17.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e12.5\u003c/p\u003e\n\u003cp\u003e(11.1-15.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e12.5\u003c/p\u003e\n\u003cp\u003e(11.2-15.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e12.3\u003c/p\u003e\n\u003cp\u003e(11.0-15.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"27%\"\u003e\n\u003cp\u003eP-LCR, %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"9%\"\u003e\n\u003cp\u003e15.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"11%\"\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e30.0\u003c/p\u003e\n\u003cp\u003e(25.0-34.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e30.5\u003c/p\u003e\n\u003cp\u003e(25.2-35.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"17%\"\u003e\n\u003cp\u003e29.5\u003c/p\u003e\n\u003cp\u003e(24.7-34.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: PLT, platelet count; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet size distribution width; P-LCR, platelet-large cell ratio. Data were expressed as either mean (\u0026plusmn; standard deviation, SD) or median (interquartile range, IQR).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Correlations between platelet parameters and gestational age and postnatal age in healthy term neonates\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\"\u003e\n\u003cp\u003eFactor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003ePLT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003ePCT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003eMPV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003ePDW\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003eP-LCR\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\"\u003e\n\u003cp\u003eGestational age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003er*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.237\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.255\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.161\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.206\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\"\u003e\n\u003cp\u003ePostnatal age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003er*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e-0.085\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.094\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.196\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.105\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.041\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.509\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd\u003e\n\u003cp\u003e0.011\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e\n\u003cp\u003eAbbreviations: PLT, platelet count; PCT, plateletcrit; MPV, mean platelet volume; PDW, platelet size distribution width; P-LCR, platelet-large cell ratio. *. Pearson's correlation coefficient was performed in PLT, and Spearman's correlation coefficient was performed in other platelet indices.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neonates, Capillary blood, Platelet count, Platelet parameters, Reference intervals","lastPublishedDoi":"10.21203/rs.3.rs-32762/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-32762/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: No consensus has been reached on capillary blood reference intervals for platelet parameters in full-term neonates. We aimed to establish neonatal capillary blood reference intervals for platelet parameters and evaluate influences of sex, gestational age and postnatal age on platelet parameters.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This study was a prospective investigation and implemented in 594 healthy full-term neonates from 12 to 84 hours of age, using SYSMEX XN-9000 haematology automatic analyser by means of capillary blood. Reference intervals for platelet parameters were defined by an interval of 2.5th –97.5th percentiles.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Capillary reference interval for platelet count was (152 - 464) ×109/L. No significance was found between sex-divided reference intervals for platelet parameters. The values of platelet count changed minimally across gestational age (37-41 weeks) and postnatal age (12-84 hours). Reference intervals for other platelet parameters were affected by these factors to a different extent.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: We established capillary blood reference intervals for platelet parameters in the first days after birth of full-term neonates in China.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Capillary blood reference intervals for platelet parameters in healthy full-term neonates in China","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2020-10-13 20:36:35","doi":"10.21203/rs.3.rs-32762/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-10-05T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-10-01T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-06-08 19:55:45","doi":"10.21203/rs.3.rs-32762/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-07-20T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-07-03T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-03T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nReview BMC Pediatrics\n\nThis study aimed at obtaining normative data for platelet parameters in a large population of healthy term infants (n = 594), aged 12 to 84 hours.\nThe methodology based on capillary blood samples is interesting because this method of sampling is increasingly used by neonatology and maternity teams, unlike direct venous samples, which are more difficult to obtain in babies.\nHowever, I would like to make a few comments;\nAbstract:\nIt is indicated that there is no consensus on RI for platelets with full-term new-borns, but several bibliographic references (4. 8. … cited elsewhere in this text) show that many authors have already made the effort to propose standards for this age group.\nThe first and main substantive question is therefore that of the novelty of such an article ... authors should clarify how this data is innovative.\n\nMethod:\nThe exclusion criteria for new-borns with risk factors for thrombocytopenia are not clearly listed:\n- Fetomaternal incompatibility by maternal allo-immunization\n- Idiopathic thrombocytopenic purpura by maternal auto-immunization (in this case, the mother is thrombocytopenic)\n- Maternal autoimmune disease (lupus)\n- Infectious bacterial or viral aetiology of the mother (chorioamniotitis) or of the new-born (neonatal sepsis?)\nIn addition, children with growth restriction do not seem to have been excluded in this cohort. Or certain birth weights suggest a foetal growth restriction (2500g at term ...)\nIn this area, placental vascular data or nicotinic fœtal exposure during pregnancy that may explain such growth restriction are not known and have to be describe\n\nBlood sampling:\nThe usual sampling time for neonatal screening for hypothyroidism and phenylketonuria is rather between 60 and 84 postnatal hours, to move away from the physiological peak of TSH in the first hours of life, for healthy new-borns.\nSo, can you specify the average time of these systematic screening samples and those of the jaundice monitoring samples (which may actually be earlier)?\n\nStatistical analysis:\nUse a multivariate analysis to ensure that the parameters \"growth restriction\" and \"infection\" are not secondary factors influencing the normative data of such a population.\n\nTable 2: What were the criteria chosen to define the outliers?\n\nFinally, this article is rather well constructed and the authors wanted to clearly define the problem.\nDetails on the selection of the population are nevertheless essential, in order to be able to attest that this population is \"normal\" without any confounding risk factor.\nFurthermore, the contribution of new standards concerning only the platelets of healthy new-borns does not seem very relevant in light of what is already published in the literature.\nIt would be beneficial for the authors to bring together in one article all the blood parameters of the automated count.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **NONE**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-03T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-03T12:00:00+00:00","index":3,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThe submission by Cui et al. reports platelet metrics from a Sysmex XN-9000 from 594 term neonates in their first 3 ½ days after birth. The report adds important information to the neonatal hematology literature. Perhaps the authors would address the two major and several minor issues listed below.\nMAJOR\n1. The Sysmex XN-9000 also quantifies the \"immature platelet fraction\" (both as an absolute number and as a percentage of platelets). Perhaps this data is available on these 594 patients and could be included in the tables. If so, it would add yet another important platelet metric reference interval.\n2. It is not clear whether this study was a prospective investigation or a retrospective analysis of existing data. The Discussion, second paragraph on Page 5, line 50, reads as if this were prospective (\"…difficulty to persuade parents to obtain venous blood samples…\"). However, there is no mention of parental consent or an institutional review board approval (the latter is typically needed for either prospective or retrospective data analysis). Please clarify this issue.\nMINOR\n1. Abstract. Results, line 26. Is the word \"significantly\" correct? I believe it gives the wrong impression, and suggest it be replaced by \"minimally\". Also consider, after \"gestational age\" on line 26, add in parentheses (37-41 weeks) and after \"postnatal age\" on line 27 add in parenthesis (12-81 hours). This way, readers of the abstract will know the very narrow range of gestational age and post-natal age studied. In the Abstract Conclusion, line 33, consider deleting \"early phases\" and inserting \"first days\". Also consider deleting \"for the first time\".\n2. Methods. Page 4, the paragraph labeled, \"Laboratory analysis\". Consider providing a small table defining the new platelet metrics, with which many readers may be unfamiliar. Consider referencing Kaito et al. Brit J Haematol 2005:128-689-702, which explains these metrics clearly. The names used by the authors for two of these parameters differ somewhat from the Sysmex names. Specifically, PDW is platelet size distribution width, and P-LCR is platelet large cell ratio (it is not a rate but is a ratio).\n3. Results. Page 5, first paragraph, lines 1 and 2. Identifying \"outliers\" and removing them from the reference interval data-set is a critical step in creating a report such as this. The authors should be more specific about what they considered to be an \"outlier\".\n4. Discussion.\nPage 5, line 52. Consider deleting \"in the real world\".\nPage 5, line 1. Consider a better way to state, \"…on behalf of the quantity of platelets...\"\nPage 5. Middle paragraph, from line 24 thorough 38. The authors show no difference in platelet counts of male vs female neonates, but devote this entire paragraph discussing this issue as if there was a difference. Please consider deleting this entire paragraph.\nPage 5, last paragraph, line 42. Consider changing, \"We found a slight fluctuation...\" Fluctuation is not what was found, but variation.\nDiscussion. Page 7, Conclusion, line 27. Consider changing, \"open a new cue\".\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-06-28T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThe authors are commended on completing this important study in the neonatal population, which represents a setting that, as authors accurately point out, is a difficult one for research to be undertaken. The number of participants and statistical approach chosen is something that the authors should also be commended on.\n\n\nDuring my review process I identified three major concerns:\n\n1. There is no mention of the ethics approval that was obtained BEFORE this study was undertaken. Approval institution, ethics committee, approval number and any other relevant details are not provided.\n2. The use of capillary blood renders the results of this study applicable only to this blood collection approach, which is not used in the majority of settings worldwide.\n3. The quality of written english needs to be improved significantly.\n\n\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewersInvited","content":"","date":"2020-06-21T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-06-21T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-06-02T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-06-01T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-06-01T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-06-01T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":"","date":"2020-06-08 19:55:45","doi":"","editorialEvents":[{"type":"decision","content":"Minor revision","date":"2020-09-25T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-08-04T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-07-30T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-07-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-07-29T12:00:00+00:00","index":"","fulltext":""},{"type":"notPreprinted","content":""}],"status":"timeline","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a69ce76-3279-4067-a076-5760154f13b4","owner":[],"postedDate":"October 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":691334,"name":"Pediatrics"}],"tags":[],"updatedAt":"2020-10-11T15:02:01+00:00","versionOfRecord":{"articleIdentity":"rs-32762","link":"https://doi.org/10.1186/s12887-020-02373-6","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2020-10-10 12:00:00","publishedOnDateReadable":"October 10th, 2020"},"versionCreatedAt":"2020-10-13 20:36:35","video":"","vorDoi":"10.1186/s12887-020-02373-6","vorDoiUrl":"https://doi.org/10.1186/s12887-020-02373-6","workflowStages":[]},"version":"v2","identity":"rs-32762","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-32762","identity":"rs-32762","version":["v2"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}