Perinatal factors affecting platelet parameters in late preterm and term neonates

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates.

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Introduction
Platelets parameters are associated with various physiological and pathological functions in various disease diseases (1,2,3). Platelet production is a complex process arising from the proliferation and differentiation of megakaryocytes under the stimulating influence of thrombopoietin. Platelet function in premature neonates is immature. Previous research indicated that low birth weight infants were at almost 2.5-fold increased risk for thrombocytopenia (4). On the other hand, elevated mean platelet volume (MPV), platelet distribution width (PDW), and increased plateletcrit (PCT) are associated with neonatal disease such as sepsis, fungal infection and intraventricular hemorrhage (5, 6, 7, 8). Among extremely low birth weight neonates born to mothers with preeclampsia, the MPV/platelet count (PLT) ratio at birth significantly correlated with mortality (9). Also, changes of PDW during the neonatal period were associated with thrombocytopenia with neonatal sepsis in very low birth weight infants (10). However, few studies have addressed whether perinatal factors may be associated with platelet parameters (PCT, PLT, MPV and PDW) at birth in a large cohort of late preterm and term neonates. The objective of this study was to investigate the factors affecting platelet parameters at birth in late preterm and term neonates.  Why was analysis on preterm babies not performed? That data is discussed in the introduction, but you do not provide a rationale for why it is not included in this study. Why did yo limit to term and late preterm?

Platelet parameter measurements
Blood samples were collected through umbilical cord or peripheral venipuncture to measure PLT, PCT, MPV and PDW of each newborn. Complete blood counts were measured using a Sysmex CS-5100 coagulation analyzer (Sysmex, Kobe, Japan) on admission. Therefore it is important to note what the exposure to resucitation and epinephrine is in these subjects.

Prenatal and postnatal risk factors
Platelet parameters were compared with demographic variables including gender, birth weight (BW), and gestational age (GA).
Furthermore, we considered pregnancy-induced hypertension (PIH), chorioamnionitis (CAM), premature rupture of membranes (PROM), and placental abruption (PA) as possible prenatal risk factors, and small for gestational age (SGA, birth weight <10 th percentile), appropriate for gestational age (AGA, birth weight >10 th percentile), respiratory distress syndrome (RDS), and Apgar score as factors possibly associated with platelet parameters.

Statistical analysis
Platelet parameters from medical records were rendered as medians of non-normally distributed continuous variables. The Mann-Whitney U-test was performed to analyze nonparametric data. Likewise, correlations between BW, GA, and Apgar score versus 1 It would have been nice if platelet morphology was examined via microscopy on peripheral smears platelet parameters were also investigated using Spearman's rank correlation (r). Moreover, the variables at P < 0.05 in univariate analysis were entered into a multiple regression analysis to identify independent prognostic factors.
SPSS for Mac, release 25.0 (SPSS, Chicago, IL) was used for statistical analyses with P < 0.05 considered to be statistically significant. Table 1 shows platelet parameters in late preterm and term neonates. There are no significant differences in platelet parameters between late preterm and term neonates. Figures 1A and 1B show significant correlation between BW and PLT, but none between GA and PLT. Likewise, Figures 1C and 1D show significant correlation between BW and PCT, but none between GA and PCT.

Tables 2 and 3 outline the results of univariate and multivariate analyses for the correlation between perinatal factors and platelet
parameters in preterm and term neonates, respectively.
As shown in Table 2 As shown in Table 3, univariate analysis revealed that PDW was correlated with PIH in late preterm neonates (PIH=10.4 fl vs. no PIH=11.3 fl, P = 0.038). Multivariate analysis revealed that PLT and PCT were associated with SGA, whereas no factors associated with PDW and MPV were found in late preterm neonates.  Multivariate analysis showed that SGA was associated with PCT and PDW. Furthermore, SGA (β＝-0.252, P<0.001) and Apgar score at 5 min. (β＝0.096, P=0.031) were associated with PLT (

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Next, we compared the differences of platelet parameters between SGA and AGA ( Table 5). Table 5 showed that PLT, and PCT were significantly decreased and PDW was significantly increased in SGA neonates compared with AGA neonates. PCT, plateletcrit; PDW, platelet distribution width; MPV, mean platelet volume; PLT, platelet count; GA, gestational age; BW, birth weight; RDS, respiratory distress syndrome; SGA, small for gestational age; AP1, Apgar score at 1 min; AP5, Apgar score at 5 min; PROM, premature rupture of membranes; CAM, chorioamnionitis; PA, placental abruption; PIH, pregnancy-induced hypertension. Significant correlation between GA, BW, Apgar score and platelet parameters were analyzed using Spearman's rank correlation (r). β means standardized regression coefficient.

Discussion
This large cohort showed no differences in platelet parameters at birth between late preterm and term neonates. Previous reports indicated that PLT and PCT were lower in late preterm neonates compared with term neonates (11,12). Furthermore, they suggested that GA was significantly correlated with PLT, however, in our study, GA did not correlate with PLT (11). Instead, there was positive  Click here to download Figure Figure1 PLT.pdf