Clinical Characteristics, and Outcomes of Severe Neonatal Thrombocytopenia: a Retrospective Cohort Study in China

doi:10.21203/rs.3.rs-4877481/v1

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Clinical Characteristics, and Outcomes of Severe Neonatal Thrombocytopenia: a Retrospective Cohort Study in China

https://doi.org/10.21203/rs.3.rs-4877481/v1

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Background: Severe neonatal thrombocytopenia, as a rare but life-threatening disease with multiple etiologies, has limited relevant reports in China. The single-center study was performed in a severe thrombocytopenic cohort to improve the prognosis of this disease.

Methods: We included all the patients diagnosed with severe thrombocytopenia (platelet counts £ 50×10³/μL) in our institution between October 2016 and February 2021, and retrospectively reviewed their electronic records. Comparisons were made according to etiology and outcome.

Results: Among the 5819 inpatients, 194 with severe thrombocytopenia were included in this study, with 64.4% of the cases occurring within 72 hours of life. The highest incidence was recorded among extremely low birth weight neonates (6.5%). The main etiologies included sepsis (22.2%), genetic syndromes (14.4%), perinatal asphyxia (9.8%), necrotizing enterocolitis (NEC; 8.8%), and cytomegalovirus infection (6.7%). The mean (SD) platelet nadir was 26.0 (14.0) × 10³/μL, and 112 patients developed very severe thrombocytopenia (platelet counts £ 30×10³/μL), of which 21.4% were caused by late-onset sepsis. In 45 culture-positive cases, the gram-negative group had a lower level of platelets (mean [SD]: 28 [11]×10³/μL) as compared to the gram-positive group (mean [SD]: 39 [12]×10³/μL). A total of 120 cases (61.9%) exhibited evidence of hemorrhage, with patients diagnosed with NEC demonstrating the highest incidence of hemorrhage at 58.8%. The platelet counts took a median of 10 days to recover: 11 and 7 days for early and late-onset cases; 15 days without and 21 days with platelet transfusions, respectively. The overall mortality rate was 26.8%. The causes of severe thrombocytopenia in 32.7%, 19.2%, and 17.3% of patients who died were identified as sepsis, birth asphyxia, and NEC, respectively. The levels of PT (P = 0.025), APTT (P = 0.046), and lactate (P = 0.028) were lower among surviving patients.

Conclusions:

Sepsis, genetic syndromes, and perinatal asphyxia are the predominant etiologies of severe neonatal thrombocytopenia in China. The overall prognosis of severe neonatal thrombocytopenia is poor, but its severity and short-term prognosis can be determined by relevant laboratory tests and the etiology.

Thrombocytopenia

Neonates

Platelet transfusion

Hemorrhage

Thrombocytopenia, defined as a platelet count < 150×10³/µL, occurs in 20 to 35% of patients admitted to the neonatal intensive care unit (NICU) [1]. A small minority (2.1–10%) developed severe neonatal thrombocytopenia (platelet count ≤ 50×10³/µL), but such patients are at increased risks of severe consequences, such as intraventricular hemorrhage (IVH) and death, compared to those with mild or moderate thrombocytopenia, making it a common concern for neonatologists [2, 3]. Additionally, the severity of neonatal thrombocytopenia significantly influences platelet transfusion decisions. However, most of the published reports of neonatal thrombocytopenia include mild to severe patients, with limited data for severe thrombocytopenic neonates.

The aim of this study was to describe the etiological spectrum, clinical features and outcomes of severe neonatal thrombocytopenia in a mono-centric cohort. Additionally, we explored risk factors for prolonged thrombocytopenia and death. The results of this study could contribute to early diagnosis and effective treatment to improve the outcomes of severe thrombocytopenic patients in NICU.

All neonates with a diagnosis of severe thrombocytopenia adimitted to the NICU of the Children’s Hospital of Fudan University, a tertiary care center in China, from October 2016 to the end of February 2021 were included retrospectively for analysis. Local ethical approval for the study was obtained.

Patients

Neonates with at least one episode of severe thrombocytopenia (defined as a platelet count ≤ 50×10³/µL, confrmed by a peripheral blood smear) during their hospital stay were incorporated into the cohort. We excluded inpatients: (i) whose platelet count was suspicious, (ii) undergoing exchange transfusion, and (iii) whose clinical data were missing.

Data collection

Maternal data included mode of delivery, aids in delivery, and maternal diseases such as diabetes mellitus, pre-eclampsia, immune thrombocytopenic purpura, and systemic lupus erythematosus. The following perinatal and neonatal characteristics were collected: multiple births; Apgar score at 1 and 5 min; history of premature rupture of the membrane; sex; GA in weeks, categorized as term (≥ 37 weeks), moderate to late preterm (32-37weeks), very preterm (< 32 weeks); and BW in grams, categorized as normal (≥ 2500 g), low (1500–2499 g), very low (VLBW; 1000–1499 g), and extremely low (ELBW; < 1000 g). In addition, various types of hemorrhage, coagulation disorders, sepsis, chromosomal disorders, NEC, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, platelet counts, time of onset, treatment (platelet transfusions and mechanical ventilation), durations of hospital stay and thrombocytopenia, and outcomes were collected. Data from all patients were collected until they were transferred to other hospitals, discharged, or deceased.

Definitions

Severe thrombocytopenia was classified as early-onset (presenting within the first 72 h of life) and late-onset (after 72 h of life). The severity of thrombocytopenia was further categorized into severe (platelet count 31–50×10³/µL) and very severe (platelet count ≤ 30×10³/µL) subgroups based on the platelet nadir. PMI (platelet mass index) is the product of platelet count and mean platelet volume. Neonatal sepsis was defined as (I) positive blood culture; (II) non-specific clinical signs of infection with abnormal hematological tests. Sepsis was divided into early-onset sepsis (EOS; onset within the first 72 h of life) and late-onset sepsis (LOS; onset after 72 h of life). An Apgar score < 7 at 1 and 5 min was considered a low Apgar score. Neonatal asphyxia was diagnosed with an Apgar score < 7 at 1 and 5 min without establishing spontaneous respiration and an umbilical artery pH < 7.2. Severe neonatal asphyxia was diagnosed with an Apgar score ≤ 3 at 1 min or an Apgar score ≤ 5 at 5 min and an umbilical artery pH < 7.0. IVH was detected using cranial ultrasonography or magnetic resonance imaging and graded according to Papile et al [4]. We used the following guidelines for administering platelet transfusions in our unit: (I) platelet count < 50×10³/µL, unstable, and (or) overt bleeding; (II) platelet count < 30×10³/µL, preterm or unstable (mechanical ventilation or vasopressors); (III) platelet count < 20×10³/µL. Normalization of thrombocytopenia was defned as at least twoconsecutive episodes of platelet count > 150×10³/µL.

Statistical analysis

Data were analyzed using SPSS Statistics (version 20.0; SPSS, Chicago, Illinois, USA). Quantitative data are represented as mean and standard deviation (SD), or median and interquartile range (IQR, P₂₅-P₇₅). Data were compared using Student’s t-test or one-way ANOVA. Qualitative data are presented as numbers and percentages and were compared using either the chi-square test or Fisher’s exact test. The Mann-Whitney test and Fisher’s exact test were used to compare outcomes. A P-value < 0.05 in all statistical tests was judged to be significant.

Patient and Public Involvement statement

Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.

Total patient population

In total, 5819 neonates were admitted to our NICU during the study period and 194 (3.3%) neonates with severe thrombocytopenia were utimately enrolled in this study (Fig. 1), of whom 125 (64.4%) were diagnosed within the first 72h of life and 69 (35.6%) after 72h. And very severe thrombocytopenia were found in 82 (42.3%) cases. As shown in Table 1, of the 194 included neonates, 95 (49.0%), 44 (22.7%) and 21 (10.8%) weighed < 2500, < 1500 and < 1000 g, respectively. The median birth weight (BW) was 2560 (IQR: 1610–3200) g, and the median gestational age (GA) of life was 37.1 (IQR: 35.4–39.0) weeks. In total, 93 (47.9%) patients were born preterm, among which 45 (23.2%) and 13 (6.7%) were born at less than 32 and 28 weeks of gestational age, respectively. The incidence of severe thrombocytopenia was 6.5% (21/325) in ELBW neonates and 3.1% (173/5494) in neonates with BW ≥ 1000 g (P = 0.001). By doing comparative analysis by applying ANOVA, it was noted that the lower the birth weight, the lower the platelet level (P = 0.018). However, the other parameters were not statistically significant: gender, P = 0.255; gestational age, P = 0.068; and mode of delivery, P = 0.501.

Table 1

Baseline maternal and neonatal characteristics.
Variables	Summary
Mother’s age/year	30.4 ± 4.9
Multifetation	35(18.0%)
Caesarean section	118(60.8%)
PROM > 24 h	22(11.3%)
Maternal diabetes	33(17.0%)
Maternal preeclampsia	18(9.3%)
Maternal ITP/SLE	9(4.6%)
Birth weight/g	2560(1610–3200)
VLBW	44(22.7%)
ELBW	21(10.8%)
Gestational age/week	37.1(35.4–39.0)
<32 weeks	45 (23.2%)
< 28 weeks	13 (6.7%)
Male	128(66.0%)
5 min Apgar score	8.4 ± 2.0

PROM preterm ruption of membrane; ITP immune thrombocytopenic purpura; SLE systemic lupus erythematosus;VLBW very low birth weight; ELBW extremely low birth weight.

Etiologies

The etiology of severe neontal thrombocytopenia was identified in 190 (98.0%) patients. Sepsis was the most commonly identified etiology, occurring in 37.6% (73/194, [43 EOS, 30 LOS]) of the patients, followed by genetic defects (28/194, 14.4%) and neonatal asphyxia (19/194, 9.8%) (Table 2). The sepsis group included 45 (45/73, 61.6%) neonates with positive blood culture. The top three organisms in the culture-positive cases were E.coli (n = 8), Klebsiella (n = 6), and Enterobacter cloacae (n = 5). In the cases of gram-negative organisms, the level of platelets (mean: 28×10³/µL, SD: 11×10³/µL) was lower as compared to gram-positive organisms (mean: 39×10³/µL, SD: 12×10³/µL), with a p value of 0.030. Very severe neonatal thrombocytopenia was significantly associated with sepsis and predominantly with LOS (P = 0.006). Wiskott-Aldrich syndrome (WAS) accounted for 25.0% (7/28) of the genetic defect group, and other gene mutations included vWF (n = 5, 17.9%), GATA1 (n = 3, 10.7%), PTPN11 (n = 3, 10.7%), UNC13D (n = 2, 7.1%), TUBB1 (n = 2, 7.1%), ANKRD26 (n = 2, 7.1%), PCCB (n = 2, 7.1%), SLFN14 (n = 1, 3.6%) and ITGA2B (n = 1, 3.6%). The asphyxia group in our series included nineteen patients, of whom fifteen had severe neonatal asphyxia. NEC (n = 17) and congenital cytomegalovirus (CMV) infection (n = 13) accounted for 8.8% and 6.7% of the patients, respectively. In addition, the etiology could not be determined in 2.1% (4/194) of the patients, and they did not undergo trio whole exome sequencing (trio-WES) or bone marrow puncture due to critical condition or family member refusal.

Table 2

Explanations for severe thrombocytopenia in different subgroups categorized by onset time and platelet nadir.
Diagnosis	Summary (n = 194)	Date of onset			Platelat nadir(×10⁹/L)				P value
	Summary (n = 194)	≤ 72 hours (n = 125)	> 72 hours (n = 69)		< 30 (n = 112)		30–50 (n = 82)		P value
Early onset sepsis	43 (22.2)	30 (24.0)	13 (18.8)	.408	25 (22.3)	18 (22.0)		0.951
Late onset sepsis	30 (15.5)	12 (9.6)	18 (26.1)	.003	24 (21.4)	6 (7.3)		0.007
CMV infection	13 (6.7)	9 (7.2)	4 (5.8)	.941	7 (6.3)	6 (7.3)		0.769
Asphyxia	19 (9.8)	17 (13.6)	2 (2.9)	.016	10 (8.9)	9 (11.0)		0.636
NEC	17 (8.8)	3 (2.4)	14 (20.3)	.000	11 (9.8)	6 (7.3)		0.542
Post-surgery	2 (1.0)	2 (1.6)	0 (0)	.539	0 (0)	2 (2.4)		0.346
Hemolytic disease	6 (3.1)	5 (4.0)	1 (1.4)	.425	1 (0.9)	5 (6.1)		0.099
Genetic	28 (14.4)	21 (16.8)	7 (10.1)	.207	21 (18.8)	7 (8.5)		0.046
Chromosomal anomalies	3 (1.5)	2 (1.6)	1 (1.4)	1.000	1 (0.9)	2 (2.4)		0.785
Metabolic disorders	9 (4.6)	4 (3.2)	5 (7.2)	.354	4 (3.1)	5 (6.1)		0.631
KMP	8 (4.1)	6 (4.8)	2 (2.9)	.714	3 (2.7)	5 (6.1)		0.414
Alloimmune	12 (6.2)	10 (8.0)	2 (2.9)	.219	4 (3.6)	8 (9.8)		0.077
Idiopathic	4 (2.1)	4 (3.2)	0 (0)	.299	1 (0.9)	3 (3.7)		0.408

CMV cytomegalovirus, NEC necrotizing enterocolitis, KMP Kasabach-Merritt phenomenon.

Clinical features and laboratory data

Cases were first recognized at a median age of 5 (IQR: 2–16) days, with 50% detected by day 5, 75% by day 16, and 95% by day 40 after birth (Fig. 2). Patients with birth asphyxia were diagnosed at the youngest age (median: 1 day, IQR: 1–3.5 days). In contrast, patients with NEC were diagnosed at the oldest age (median: 6 day, IQR: 4–15 days). Family history of repeated miscarriages, neonatal death was most common among the genetic defect group (35.7%, 10/28); and maternal diabetes was most common among the sepsis group (27.4%, 20/73).

Hemorrhage was detected in 120 (61.9%) cases, including the skin (62.5%, 75/120), gastrointestinal tract (20.0%, 24/120), lungs (15.0%, 18/120), intracranial space (45.0%, 54/120), and umbilicus (9.2%, 11/120). Neonates with very severe thrombocytopenia had a higher incidence rate of hemorrhage (77.8%) than those with the platelet nadir between 30 and 50 × 10³/µL (53.5%). Among neonates with different etiologies, the rate of hemorrhage was highest in patients with NEC (n = 10, 58.8%) and lowest in those with congenital CMV infection (n = 2, 15.4%). Patients with LOS had the most IVH of all grades (30.0%, 9/30). In eighteen cases (60.0%, 18/30) of neonates with IVH, thrombocytopenia developed during the subsequent course of haemorrhage.

Table 3 shows the hematological and infective markers of the neonates. The mean (SD) platelet nadir in this cohort was 26.0 (14.0) × 10³/µL. The platelet level was lower in the sepsis group [mean (SD) 21.5 (18.6) × 10³/µL], and the LOS subgroup had lower platelet nadir than the EOS subgroup [mean (SD) 23.3 (13.4)×10³/µL vs. 27.7 (13.5)×10³/µL; P = 0.032]. By doing the comparative analysis of hematological and infective parameters, it was found that the higher the C-reactive protein level, the lower the platelet level (F = 4.545, P = 0.010).

Table 3

Mean hematological and infective markers of the neonates admitted to the NICU (n = 194).
Parameters	PLT (×10³/µL)	Hemoglobin (g/dL)	MPV (fL)	PT (s)	APTT (s)	CRP (mg/dL)	Lac (mmol/L)
Mean	26	12.3	11.8	21.4	55.1	13.5	2.1
SD	14	2.1	4.5	13.2	34.6	8.7	1.4
Minimum	1	4.9	9	11.7	23.5	0.5	0.2
Maximum	50	20.3	17	120	180	160	5.5

SD Standard deviation, PLT platelet, MPV mean platelet volume, PT prothrombin time, APTT activated partial thromboplastin time, CRP C-reactive protein, Lac lactate.

Treatment and Outcomes

Over one third (n = 69, 35.6%) of the patients received more than one platelet transfusion (median: 1 [range: 1–10]). Among those with a lowest platelet count between 30 and 50 × 10³/ µL, only 6 (5.4%) neonates received platelet transfusions due to critical conditions. Over three quarters (n = 63, 76.8%) of those with very severe thrombocytopenia received a transfusion. Among the different etiological groups, neonates with NEC received the highest number of platelet transfusions (IQR: 1–3 [range: 0–10]. And the rate of platelet transfusions was higher in early-onset cases (44.9%, 31/69) than in late-onset cases (30.4%, 38/125) with a p value of 0.043. Mechanical ventilatory support was ordered in 85 (43.8%) patients, including all of the 18 patients with pulmonary hemorrhage.

The platelet counts took a median (IQR) of 10 (4.5–30.5) days to recover; 11 (6–25.5) days for early-onset and 7 (5–16) days for late-onset cases (P = 0.046). The median duration of thrombocytopenia was 15 days without platelet transfusions versus 21 days with platelet transfusions, respectively. However, the decreased platelet nadir did not increase the duration of thrombocytopenia (P = 0.187). Thrombocytopenia persisted in 50 patients at discharge and 45 patients at death. Of the 95 unrecovered patients, 42 (44.2%), 37 (38.9%), and 16 (16.8%) still had mild, moderate, and severe thrombocytopenia, respectively.

The overall mortality rate was 26.8% (52/194) at the last follow-up: 14 and 38 with early- and late-onset severe thrombocytopenia, respectively. Most of the deaths were from sepsis (32.7%, 17/52), birth asphyxia (19.2%, 10/52) and NEC (17.3%, 9/52) groups (Fig. 3). The NEC group had the highest mortality rate (52.9%, 9/17) among different etiological groups. Compared with the death group, the survival group had a significantly smaller number of platelet transfusions (P = 0.032). Coagulation data were also collected from both groups. The values of prothrombin time (PT), activated partial thromboplastin time (APTT) and lactate in the deceased patients were significantly higher than those in the patients who survived. Other characteristics were not significantly different between patients who survived and patients who died (all p values < 0.05) (Table 4).

Table 4

Patients and laboratory features of diferent outcomes.
	Survival	Death	P value
Birth weight (g)	2860(2310–3350)	2350 (1520–3100)	0.564
Gestational age (weeks)	37.8 (35.4–39.1)	35.9 (33.4–38.1)	0.134
Age at diagnosis (days)	3 (2-9.5)	4 (2-11.5)	0.728
PLT (×10³/µL)	32 (25.7–40.1)	29 (22.9–37.3)	0.124
PT (s)	24.5 (12.4–31.4)	34.2 (24.6–48.9)	0.025
APTT (s)	51.2 (36.8–53.6)	61.3 (49.6–86.7)	0.046
CRP (mg/dL)	9 (5.6–12.4)	12 (6.2–15.8)	0.164
Lac (mmol/L)	0.9 (0.2–1.8)	2.5 (1.1–4.5)	0.028

PLT platelet, PT prothrombin time, APTT activated partial thromboplastin time, CRP

C-reactive protein, Lac lactate.

Severe neonatal thrombocytopenia is a rare but fatal disease in NICU, however, it is rarely reported and examined in detail, particularly in the Chinese population. This study was conducted at a large tertiary pediatric hospital in China. Our data indicated that the overall incidence rate of severe neonatal thrombocytopenia was 3.3% in our NICU over the last 5 years, which was comparable to the rates reported in the literature. We discovered that lower birth weight was correlated with lower platelet counts in this cohort. Furthermore, severe thrombocytopenia at anytime during the NICU stay was more common in the smallest patients, with the prevalence in ELBW neonates more than twice as high as in patients weighing over 1,000 g at birth. Biological differences observed between fetal, neonatal, and adult megakaryocytes are likely involved in the marked susceptibility of ELBW neonates to develop thrombocytopenia [5].

Our data showed sepsis, especially early-onset sepsis, predominated among the etiologies of severe neonatal thrombocytopenia, which was consistent with the findings of Ree et al. [6]. The increased incidence of severe thrombocytopenia may be attributable to a partial response in terms of platelet and thrombopoietin production during sepsis with diminished energy reserves in the host [7]. Furthermore, we explore the pathogenic organisms in culture-positive cases, indicating that gram-negative bacteria was the most common pathogen isolated from blood culture samples and was shown to be associated with a lower nadir platelet count. Arabdin et al. [8] reported that neonatal thrombocytopenia was independently associated with gram-negative sepsis. In animal models, the likely mechanisms of thrombocytopenia associated with gram-negative sepsis include cell-free extracts comprising lipopolysaccharide and a constituent of gram-negative bacteria’s cell wall [9]. Furthermore, it was discovered that an elevated CRP level, an infective marker, was associated with decreased platelet counts. This finding was also supported by Rabindran et al. [10] and Arabdin et al. [8].

Genetic defect was the second most common etiology in our series. Trio-WES was performed for neonates with a suspected genetic disease or an unknown cause of severe thrombocytopenia, resulting in the diagnosis of 28 patients, including seven cases caused by WAS gene mutation, which has been highlighted in previous studies. We analyzed the records of these patients to look for any commonality of features among this group and found that congenital thrombocytopenia needs to be considered when unexplained severe or very severe thrombocytopenia occurs in term or normal birth weight neonates within three days after birth, especially in those with congenital malformations or a family history of thrombocytopenia.

In our study, perinatal asphyxia, especially severe asphyxia, also played an important role in severe neonatal thrombocytopenia. The findings revealed that the incidence of early-onset severe thrombocytopenia was significantly higher in neonates following perinatal asphyxia in comparison to late-onset severe thrombocytopenia. The mechanism by which perinatal asphyxia causes early-onset thrombocytopenia remains unclear. Several studies have shown that acute severe hypoxia may play a role in the pathogenesis of neonatal thrombocytopenia: reducing platelet survival time and impairing platelet production by altering the structural and functional characteristics of megakaryocytes [11, 12]. The results in these studies also suggest a correlation between the severity of perinatal asphyxia and thrombocytopenia, and are thus in agreement with our study.

The prevalence of hemorrhage in thrombocytopenic neonates was approximately 20–30% according to the literature and thus markedly lower than our rate of 61.9% in severe thrombocytopenia [13]. The higher incidence of total hemorrhage in neonates with very severe thrombocytopenia discovered in our study was similar to that reported in the literature [4]. The risk of hemorrhage was found to be associated with definite causes of thrombocytopenia in this study. NEC and sepsis have been identified as the most common diagnoses in the hemorrhage and IVH group, respectively, as shown in our data. And a similar result was observed in Robert et al.’s study [14]. However, pathological hemorrhage in neonates is multifactorial and unlikely to be attributable solely to a lower platelet count. We recorded over half of the neonates who have developed IVH become thrombocytopenic during the subsequent course of bleeding, as opposed to thrombocytopenia being the cause of IVH, which was in line with several studies [13, 15, 16], and whether there was a causal link between severe thrombocytopenia and IVH requires a deeper inquiry.

In line with previous reports, platelet transfusions did not shorten the duration of thrombocytopenia, which may be explained, in part, by the fact that severely ill patients receive more platelet transfusions; but may also be explained by adverse effects of platelet transfusions [17]. We recorded a comparable overall mortality rate of 26.8%, which was positively correlated with the number of platelet transfusions, but not with the platelet nadir. This finding was in line with several studies [16, 18, 19]. Neonates with late-onset severe thrombocytopenia had a higher mortality rate than those with early-onset severe thrombocytopenia (26.1% vs. 11.2%), and the highest mortality rate was attributable to severe thrombocytopenia secondary to NEC. We speculate that this increase in mortality rate can be explained by the fact that severe thrombocytopenia secondary to NEC occurs more commonly after 72 h of life and has more serious and life-threatening conditions.

The great majority (62.3%) of deaths were ascribed to cardiopulmonary failure and 10 (5.2%) cases eventually progressed to mutiple organ dysfunction syndrome. DIC was recorded in 10 (5.2%) episodes of discharge diagnosis and coagulopathy in 56 (28.9%). The prolongation of both PT and APTT in deceased patients indicated a correlation between death from severe thrombocytopenia and coagulation disorders [20]. The production and accumulation of lactate in blood occur after asphyxia due to poor tissue perfusion following anaerobic metabolism [21]. Given the elevated lactate levels observed in deceased patients, it is plausible that perinatal asphyxia was more prevalent and severe in this cohort compared to those who survived.

A limitation of this study is that it was conducted at a single centre with a relatively small sample size due to the rarity of the disease and the diversity of its aetiologies. Multicentre studies are required to address the limitations of the sample size and the discrepancies in the results due to regional specificity. In addition, intrauterine growth restriction and antenatal steroid administration were not included in the analysis, as several patients were initially treated in the outer court and subsequently transferred to our specialized children’s hospital.

In conclusion, the incidence of severe neonatal thrombocytopenia was described, and it was found that sepsis, genetic syndromes, and birth asphyxia are the predominant causes of severe neonatal thrombocytopenia in the Chinese population. The severity and short-term prognosis of severe thrombocytopenia are dependent on the underlying etiology. Further research is needed to improve the accuracy and accessibility of diagnostic tests, such as trio-WES, bone marrow aspiration and blood culture, in order to achieve accurate and timely diagnoses and improve outcomes.

BW: Birth weight; ELBW: Extremely low birth weight; VLBW: very low birth weight; GA: Gestational age; LOS: Late-onset sepsis; EOS: Early-onset sepsis; CMV: Cytomegalovirus; PT: prothrombin time; APTT: activated partial thromboplastin time; IQR: Interquartile range; IVH: Intraventricular hemorrhage; NEC: Necrotizing enterocolitis; NICU: Neonatal intensive care unit; NRDS: Neonatal respiratory distress syndrome; PDA: Patent ductus arteriosus; DIC: disseminated intravascular coagulation.

Acknowledgements

We would like to thank all the nursing staff, physicians, and residents who cared for the infant patients. We would also like to express our gratitude to the parents for their cooperation and consent.

Authors’ contribution

YY Shan, P Zhang, and GQ Cheng designed the study. YY Shan and T Peng collected the data. YY Shan was involved in data cleaning, mortality follow-up, and verification. YY Shan, T Peng, and P Zhang analyzed the data. YY Shan interpreted the results and drafted the manuscript. GQ Cheng contributed to critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript.

Funding

No applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

This study obtained ethical approval from the Ethics Committee of the Children’s Hospital of Fudan University (Number 251, 2022). Informed consent was not applicable because the data were anonymized. Ethics Committee of the Children’s Hospital of Fudan University waived the need for patient informed consent due to retrospective analysis of medical records.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

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Clinical Characteristics, and Outcomes of Severe Neonatal Thrombocytopenia: a Retrospective Cohort Study in China

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Introduction

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Patients

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Results

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Etiologies

Clinical features and laboratory data

Treatment and Outcomes

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