Prevalence of neutropenia in US residents: a population based analysis of NHANES 2011–2018 | BMC Public Health

Neutrophil plays a pivotal role in immune response and inflammation. Upon pathogenic invasion, chemokine activation prompts neutrophils to migrate from capillaries to the site of injury, enabling them to engage in pathogen phagocytosis [24]. Concurrently,neutrophils contain a significant quantity of lysosomal enzymes, which can also decompose bacteria and tissue debris phagocytosed into cells, so as to avoid the spread of infection in the body [25]. Neutropenia, characterized by a neutrophil counts below 1.5 × 10⁹ cell/L, heightens the susceptibility to infection. Based on a large multiracial population from NHANES survey in the United States, our results showed that 1.24% population in the United States had neutropenia, approximately 35.5 million nationwide. Besides, the proportion of black individuals with neutropenia were significantly higher than participants from other races. Male participants were more likely to have neutropenia than female participants, and children younger than 5 years had a higher risk of neutropenia than adults.

The underlying mechanisms of congenital neutropenia remain largely elusive [26]. Some researchers have postulated that neutropenia may occur due to a dysfunction in the release of mature granulocytes from the bone marrow. A recent study enrolled 30 patients with congenital neutropenia (14 black participants and 16 white participants) and demonstrated that the bone marrow of black participants released fewer neutrophils than that of white participants through bone marrow biopsies [27]. Interestingly, no disparities were observed in terms of bone marrow cellularity and the degree of myeloid maturation between Black and White individuals following hydrocortisone treatment, suggesting similar bone marrow hematopoietic function. The similar increase in neutrophil count was also observe in black and white participants. On the other hand, Bain et al. demonstrated that the increment of neutrophils was significantly higher in normal individuals compared with individuals with congenital neutropenia after receiving the injection of hydrocortisone, also indicating similar hematopoietic function but decreased marrow response in Yemenite Jews patients with neutropenia [28]. Nevertheless, it is worth emphasizing that ethnicity exerts a significant influence on the prevalence of congenital neutropenia, necessitating further studies investigating neutropenia among diverse racial populations. Dominant mutations of autosomal in ELANE gene is the most common reason of congenital neutropenia [29]. With the development of genomics and sequencing technology, more and more attention has been paid to the correlation between changes in the expression of genes and incidence of neutropenia in recent years [30,31,32]. Studies have also revealed significant alterations in the that expression of genes associated with leukocyte migration and hematopoietic stem cells mobilization significantly changed among individuals with neutropenia [29, 33, 34]. To gain a better understanding of the prevalence characteristics of neutropenia, we enrolled participants from recent four consecutive circles of NHANES (2011–2012, 2013–2014, 2015–2016, 2017–2018) to carry out this population-based cross-sectional study.

As mentioned before, the prevalence of neutropenia in different races are significantly different, in the present study we mainly focus on three major ethnicities in the United States, including non-Hispanic White, non-Hispanic Black, American Mexican. The first report on the difference of neutropenia risk between black and white individuals was 1941, investigators found that residents of African descent in the United States had lower leukocyte counts and firstly thought it was related to nutriture, and then found that was a result of neutropenia [35]. Consequently, Freedman et al. carried out a cross-sectional study and reported that the difference of the neutrophil count was more significant in black male individuals based on a large population in the United States [36]. At the same time, in the United Kingdom, Bain et al. also demonstrated that residents of African descent had lower neutropenia count [28]. In this study, we observed a significant downward shift (approximately 1.0 × 10⁹ cells/L) in distribution of both leukocyte count and neutrophil count among black participants. The leukocyte count and neutrophil count exhibited similar distributions among white participants, American Mexican participants, and participants from other racial backgrounds. Consistent with previous research, the present study observed a higher risk of neutropenia among black participants. Of note, our study revealed a noteworthy incidence of neutropenia in black children, 19.8% of black children (age 1–2 years) and 9.8% of black children (age 3–5 years) had neutropenia.

Leukocyte count and neutrophil count are different at different ages. Investigators have revealed that the leukocyte count were highest at birth, and then decreased rapidly in the first six month, and the prevalence of neutropenia is higher in children younger than 9 years compared with adults [37]. Chronic and severe neutropenia in children can have serious consequences, it has been reported that the incidence of infection in children with neutropenia was 44.2%, and the incidence of severe infection ranged from 9.6 − 11.9% [38]. Children with congenital neutropenia often have other clinical manifestations in addition to neutropenia.

Some children are complicated with abnormal liver function, nephrotic syndrome, hearing loss, ventricular septal defect, iron deficiency anemia, etc. [39]. Consistent with previous studies, results of our study also showed that children younger than 5 years were more like to have neutropenia. Lyall et al. reported that the prevalence of neutropenia in preterm infants is higher than that in full-term infants, which may be related to the imbalance of immune regulation caused by the immature immune system [40]. Therefore, more attention should be paid to neutropenia, especially in children younger than 5 years.

Furthermore, we investigated the influence of smoking on the prevalence of neutropenia and found that smokers had higher leukocyte and neutrophil counts than those of participants who never smoked. This conclusion is consistent with an earlier retrospective study performed by Aghaji et al., they enrolled 5850 Nigerian participants and found that the leukocyte count was higher than nonsmokers [41]. Another study indicated a higher likelihood of neutropenia in male individuals compared to females. Consistent with these findings, we observed difference in leukocyte and neutrophil count between male and female participants, and our multivariable logistic regression analysis confirmed a higher risk of neutropenia among males [42]. Our results suggest that neutropenia is more common in the general population than we thought. The need for a thorough diagnostic evaluation of neutropenia requires consideration of multiple factors such as clinical symptoms, age, sex, race, and smoking status.

There are several advantages and limitations of our study. First, it was adequate to provide reliable conclusion and precise statistical power considering the large-scale sample size included; second, we adopted the most recent data from NHANE survey, and all of the statistical processes were weighted for a more objective and comprehensive study of the prevalence of neutropenia in the United States. However, it is important to acknowledge several limitations of this study. Firstly, the causal associations could not be determined considering the research type of cross-sectional study, more prospective studies are needed to determine the exact risk factors of neutropenia. Secondly, the self-reported covariates obtained from the NHANES database may introduce potential subjective bias. Thirdly, there are large ethnic differences in diet, physical activity, genetic variants, lipid metabolism, and susceptibility to cardiovascular disease. Consequently, whether the conclusion in the present study based on US participants could be applicable to other populations need to be further explored in the future work.