Contribution of Environment in Comorbidities in Children with Sickle Cell Disease: A Prospective Observational Study at a Tertiary Care Center in India

Key words -environmental determinants, morbidity, sickle cell disease, children

Sickle cell disease (SCD) presents with highly variable clinical consequences, which are noted even among identical twins residing in different geographical areas, but remain unexplained even after extensive genetic studies. India has 2^nd largest number of births with SCD, only second to Africa. Different regions in India also have variability in climate and environment which also varies from season to season. Therefore, we aimed to study the contribution of environmental determinants associated with morbidity in children with SCD.

We conducted a prospective observational study in hospitalized children diagnosed with SCD in a tertiary care center in Government medical college, Nagpur, Maharashtra in India. Our study included 88 females (41.51%) and 124 males (58.49%) in the age group of 6 months -14 years, but majority were between 5-10 years of age (50.94%). Children living outside a radius of 10 km from the hospital where study is conducted and children with systemic disorders were excluded. Convenience sampling method was used to examine the effect of several environmental factors including temperature, rainfall, relative humidity, wind speed, atmospheric pollutants such as nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone from 1^st January 2020 to 31^st December 2021. We correlated the association of these environmental factors with the severity of morbidity related to the duration of hospital stay, infection, vasoocclusive crises (VOC), intensive care utilization (ICU) & number of blood transfusions.

In our study population maximum duration of hospital stay was 44 days and minimum of 2 days. The cause of admissions included VOCs (54.25%), severe anemia requiring blood transfusion (41.98%), and infections (34.91%). During our 2 years study period, range of maximum and minimum temperature was 22-46.8 and 0 -30.8degree Celsius, relative humidity of 20-100%, wind speed of 0-28 knots, rainfall of 0-100.3 mm, NO2 levels of 0-95 ug/mm³, SO2 levels of 0-39ug/mm³ & 0zone of 0-148ug/mm³. Maximum number of admissions (62.73%) occurred in the months of June - November. High relative humidity (p value =0.0001) was the most important factor leading to an increase in hospital admissions, followed by rainfall (p value =0.0004). Among air pollutants, increase in NO2(p value =0.0002) and SO2(p value =0.0014) levels were associated with higher number of admissions, whereas ozone levels had no significant impact on number of admissions (p value =0.1499). (More statistical analysis will be provided at the time of presentation). Surprisingly COVID-19 pandemic substantially reduced the number of SCD patients seeking medical attention in our tertiary care center. It is also likely that our results may be influenced by a change in the environmental exposure due to the pandemic. Also, the current observations are from a single city. However, our data provide a 'proof of principle' that the environment contributes to the comorbidities of SCD and offer support to undertake larger studies in different geographic regions of tropical countries.

We conclude that environmental factors are important determinants of acute complications in children with SCD. Identification of such environmental factors will help develop strategies to prevent/reduce the comorbidities of SCD and improving the quality of life for children and perhaps adults with SCD.

Gupta:UCI Foundation: Research Funding; Zilker LLC: Research Funding; Grifols: Research Funding; 1910 Genetics: Research Funding; Cyclerion: Research Funding; CSL Behring: Honoraria; Novartis: Honoraria, Research Funding; Tautona Group: Honoraria; SCIRE Foundation: Research Funding.