We found significant variation in prevalences of stunting and underweight by sickle cell status, and these were markedly high among children with SCD. Prevalences varied significantly by socio-demographic characteristics as well. Stunting prevalence exceeded 50% among children from the poorest households. Mean z-scores of all three anthropometric indices were notably lower among children with SCD. Regression analyses revealed significant association of SCD with stunting and underweight. Hb level emerged as a statistically significant mediator in the association of SCD with all three anthropometric indices. The extent of mediation by Hb level was markedly high for SCD-HAZ association. To the best of our knowledge, this is one of the first analyses of association of SCD with nutritional status accounting for biological and socioeconomic correlates in a nationally representative sample.
The negative impact of SCD on anthropometric measures of nutritional status has been persistently captured in studies from Nigeria  and elsewhere [7, 19–24]. Proposed mechanisms fall into three broad categories: elevated resting energy expenditure (REE), reduced dietary intake, and metabolic and endocrine alterations [4, 25, 26]. A combination of increased protein turnover due to accelerated erythropoiesis and increased cardiac workload secondary to anemia and consequent hypoxia results in a higher REE among children with SCD . Dietary intake is postulated to reduce from appetite suppression by high blood level of inflammatory mediators, particularly interleukin-6 , and during episodes of acute complications and hospitalization . Dietary intake that is nutritionally adequate for children without SCD is unlikely to be sufficient for children with the condition because of the increased REE . This may have driven growth faltering disproportionately among under-five children with SCD in Nigeria, where children´s dietary and feeding practices remain suboptimal and compounded by poverty and food insecurity [28, 29]. The extent to which suboptimal diet may amplify the impact of SCD on nutritional status in sub-Saharan Africa needs to be explored in future.
The magnitude of SCD´s association with stunting and underweight in our analyses was high with OR surpassing two. As the 2018 Nigeria DHS is the first DHS to implement SCD genotyping in a nationally representative sample , we could not find nation-wide studies to compare the effect sizes with. In their prospective study involving a hospital-based cohort (n = 1618) in Tanzania, Cox et al. reported OR for stunting and underweight of 1.82 (95% CI: 1.43–2.32) and 2.61 (95% CI: 2.06–3.31), respectively, at enrolment. The mean age of the cohort was 10.1 years (range 0.5–48 years) . Considering the older age distribution of participants, the lower OR for stunting versus our analyses (1.82 vs. 2.39) may reflect a survivor cohort effect . The OR for stunting and underweight among children under 12 years of age were 4.87 (95% CI: 2.94–8.06) and 4.74 (95% CI: 2.96–7.60), respectively, in a cross-sectional study from the Democratic Republic of the Congo (DRC; n = 455) . The higher OR compared to our analyses could be a manifestation of difference in HbS gene haplotype ; as Bantu haplotype predominates in DRC, whereas Benin haplotype is pre-eminent in Nigeria .
Interestingly, we did not find a statistically significant association between SCD and wasting. This contradicts some of the previous studies [7, 23]. Pooled analyses show that the trajectory of mean WHZ in the first five years of life is different from that of mean HAZ and WAZ. Faltering in WHZ is concentrated between 3–15 months of age, and thereafter, it recovers steadily . We posit that wasting could be an adaptive response to redirect energy and nutrients for maintaining essential metabolic processes , and it begins to accelerate as children with SCD live beyond the first five years. Of note, both studies [7, 23] finding significant SCD-wasting association had higher age distribution of participants with smaller number in the under-five category. Alternatively, the SCD-wasting non-association in this study may be a reflection of phenotypic difference owing to distinct HbS haplotypes .
The mean HAZ, WHZ, and WAZ of children with SCD in this study were significantly lower than their peers with HbAA genotype. The most severe deficit was observed for mean HAZ of children with SCD (-2.17, SD 1.47). This is appreciably lower than mean HAZ from children with SCD in Ilesa, Nigeria (− 0.52, SD 1.33) ; Enugu, Nigeria (− 0.50, SD 1.57) ; Ghana (− 0.86, SD 1.40) ; and Kenya (–1·10, SD 1·00) . However, in the Kenyan SCD cohort (n = 128) with median age of 21.1 months, mean HAZ and WAZ did not significantly differ from those of non-sickle cell children . No significant difference in mean HAZ was reported also in the study from Enugu, Nigeria  that recruited outpatient cases and controls from a tertiary hospital (n = 116). The mean age of cases in that study was 40.6 months (SD 16.79). The mean WAZ of -1.63 (SD 1.16) among children with SCD found in our study is suggestive of a drastic left shift in weight-for-age trajectory compared with the WHO Child Growth Standards. An unitary increase in WAZ reduces hospitalization risk among children with SCD by 13% . Besides, mortality risk for sickle children with WAZ below − 3 can be threefold higher (adjusted hazard ratio 3.42; 95% CI: 2.50–4.68) . The low mean WAZ in our study, therefore, signals increased likelihood of adverse prognosis for community-dwelling Nigerian children with SCD lacking definitive care. Moreover, the better anthropometric indices recorded among facility-recruited children with SCD indicates that early diagnosis and access to care can minimize growth faltering to a large extent.
The mean Hb level of sickle children in our study (8.04 gm/dL, SD 1.65) was similar to that found in a multi-country (Mali, Senegal, Cameroon, Gabon, and the Ivory Coast) analysis , and in studies from Ghana  and Brazil ; but higher than that of Kenyan cohorts [36, 39]. We captured a significant mediating role of Hb in SCD-nutritional status association. While this is unsurprising as chronic hemolytic anemia lies at the core of pathophysiologic alterations in SCD , the extent of mediation has enormous public health implication. Robust studies show Hb concentration to positively correlate with z-scores of height, weight, and BMI as well as growth velocity in SCD [10, 20]. Our mediation analysis corroborates this by pinpointing the extent of SCD´s impact on conventional anthropometric indices mediated through Hb level. Approximately 93% of the impact on HAZ, 37% of that on WHZ, and 66% of that on WAZ was mediated through Hb level. Hence, improved Hb level could prevent deterioration of nutritional status to a large extent. Furthermore, low Hb is a consistent predictor of stroke and mortality among children with SCD [12, 40]. This mediation analysis, therefore, highlights the critical need for interventions to optimize Hb level among under-five children with SCD; including universal point-of-care screening in early infancy, hydroxyurea therapy, and judicious use of blood transfusion . The pitfalls of blood transfusion in African settings concern unavailability of transfusable blood, transmission of infections, and alloimmunization. Local trials are needed to guide context-appropriate use of blood transfusion for under-five children with SCD in Nigeria and to examine its impact on nutritional status and mortality .
Some limitations of this study must be acknowledged for allowing careful interpretation of the findings. Because of the cross-sectional design, causal inferences cannot be drawn. Nevertheless, it is noteworthy that although clinical presentation takes time to fully develop, the genetic changes underlying SCD are present at birth. The rapid diagnostic test (SickleSCAN) used for SCD genotyping in the DHS showed diagnostic sensitivity and specificity of 85% and 98%, respectively, when compared with high-performance liquid chromatography . We did not have data on energy intake, blood nutrient levels and HbF concentration, which could have made the analysis comprehensive. We adjusted for age, sex, and SES in the statistical model, but residual confounding could not be ruled out. Generalizability of the results to other countries in sub-Saharan Africa could be limited by phenotypic variation in SCD and difference in socio-demographic attributes.