The effect of gestational age on the initial neonatal platelet count

Thrombocytopenia in the Neonatal Intensive Care Unit (NICU) is common, usually occurring in the first three days of life [1]. This presentation is referred to as early-onset thrombocytopenia. Causes of early-onset thrombocytopenia include growth restriction, aneuploidy, sepsis, congenital infection, and immune-mediated processes such as fetal and neonatal alloimmune thrombocytopenia (FNAIT) [2].

Our previous research investigated the relationship between maternal hypertension and early-onset neonatal thrombocytopenia [3]. We found that maternal hypertension did not increase the risk of neonatal thrombocytopenia on the first day of life. In that manuscript, we did not measure the effect of gestational age on the neonatal platelet count, which other authors have associated with neonatal thrombocytopenia [4–6]. Here, we aim to investigate the impact of gestational age on the initial platelet count and risk of thrombocytopenia using our original cohort of patients.

This study utilized the cohort of infants from our previous work [3]. That study was a retrospective cohort study performed at a single level III NICU over a 30-month period. Infants were eligible for inclusion in the original study if they had a complete blood count (CBC) obtained in the first 24 hours of life and did not have a condition classically associated with early-onset thrombocytopenia (such as infection or birth asphyxia). The study only considered an infant’s initial platelet count. The electronic medical record was used to obtain clinical and demographic data on mother-infant dyads. 

The variables of interest for this project included gestational age, presence of maternal preeclampsia with severe features (as defined by the American College of Obstetricians and Gynecologists [7]), infant sex, infant race, mode of delivery, prolonged rupture of membranes (>18 hrs), maternal fever (intrapartum temperature >100.4 F), and small for gestational age status (birthweight for gestational age <10% using the Fenton Preterm Growth Chart). Thrombocytopenia was defined as an initial platelet count <150,000/mL. All statistical analyses were performed using SAS 9.4 for Windows (SAS Institute Inc., Cary, North Carolina, USA). Multivariable negative binomial regression (NBR) was used to model the effect of different variables on the initial platelet count. Multivariable logistic regression assessed potential risk factors of an initial platelet count < 150,000/mL. 

Our cohort included 224 infants born to mothers with preeclampsia with severe features and an equal number of infants born to normotensive mothers matched for gestational age (plus or minus one week). Seventy-four of the 448 study participants (17%) had an initial platelet count <150,000/μL. The mean gestational age of study participants was 34 weeks, with a mean birthweight of 2112 g. The mode of delivery was a cesarian section in 265 infants (59%).

Multivariable NBR showed that gestational age has a statistically significant positive effect on the initial platelet count (p=0.002). Our results demonstrated the initial platelet count increased by 9% with every five-week increase in gestational age (count ratio=1.09, 95% confidence interval (CI) (1.03, 1.15)). Multivariable NBR also showed vaginal delivery (p=0.004) and prolonged rupture of membranes (p=0.01) were associated with a higher initial platelet count.

Logistic regression showed that gestational age has a statistically significant positive effect on the risk of an initial platelet count < 150,000/mL (p=0.013). Our model predicts with every five-week increase in gestational age, we expect to see a 43% decrease in the odds of thrombocytopenia (odds ratio (OR) 0.57, 95% CI (0.37, 0.89)). The odds of thrombocytopenia were positively affected by cesarian delivery (p=0.045) and SGA status (p=0.02). That is, thrombocytopenia was more likely in the setting of cesarian delivery and SGA status. 

Our data suggests that gestational age statistically significantly impacts an infant’s first platelet count and risk of thrombocytopenia positively (i.e., more mature infants are expected to have higher initial platelet counts and lower odds of early thrombocytopenia). This finding corroborates other authors’ conclusions [4–6].

Our results have meaningful, practical implications. Namely, neonatal providers should expect a lower initial platelet count and a higher likelihood of thrombocytopenia in the least mature infants. This is an important consideration, as thrombocytopenia can be a sign of congenital or early-onset infection [2]. A short course of antibiotics may be warranted in thrombocytopenic infants, especially those born extremely prematurely; however, a low platelet count should not be the sole justification for prolonged antibiotic treatment since some degree of thrombocytopenia is common in this population. Additionally, neonatal providers should be judicious when treating premature infants with antibiotics, as antibiotic exposure early in life has been associated with later adverse outcomes [8,9]. An important caveat to this consideration is when the platelet count is < 50,000/µL (severe thrombocytopenia). In our cohort, only one infant (<1%) had severe thrombocytopenia. If severe thrombocytopenia is present, it is less likely to be related to prematurity alone, and other etiologies should be investigated.

We thank Andrew Chapple, Cornelius Rosenbaum, Maria Velez, and Asha Heard, who contributed to our previous work on early neonatal thrombocytopenia. We have no conflicts of interest to disclose.

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