Influence of severity of anemia on clinical findings in infants with sickle cell anemia: Analyses from the BABY HUG study

Abstract

Background Clinical complications of sickle cell anemia begin in infancy. BABY HUG (ClinicalTrials.gov, NCT00006400) was a NHLBI-NICHD supported randomized phase III placebo-controlled trial of hydroxyurea (HU) in infants (recruited at 9–18 months) unselected for clinical severity with sickle cell anemia. This secondary analysis of data from BABY HUG examines the influence of anemia on the incidence of sickle cell related complications, and the impact of hydroxyurea therapy in altering these events by comparing children with lower (<25th percentile) and higher (>75th percentile) hemoglobin concentrations at study entry. Procedure Infants were categorized by: 1) age-adjusted hemoglobin quartiles as determined by higher (Hi) and lower (Lo) hemoglobin concentrations at study entry (9 to12 months old: <8.0 gm/dL and >10.0gm/dL; 12 to 18 months old: <8.1 gm/dL and >9.9gm/dL) and 2) treatment arm (hydroxyurea or placebo). Four subgroups were created: placebo (PL) LoHb (n=25), PL HiHb (n=27), hydroxyurea (HU) LoHb (n=21), and HU HiHb (n=18). The primary and secondary endpoints of BABY HUG were analyzed by subgroup. Results Infants with lower hemoglobin at baseline were more likely to have a higher incidence of clinical events (acute chest syndrome, pain crisis, fever) as well as higher TCD velocities and lower neuropsychological scores at study exit. Hydroxyurea reduced the incidence of these findings. Conclusion Infants with more severe anemia are at risk for increased clinical events that may be prevented by early initiation of hydroxyurea.

Impact of hydroxyurea on clinical events in the BABY HUG trial

“…The impact of hydroxyurea on TCD velocity was previously reported; at baseline, TCD velocity was negatively correlated with hemoglobin level. 8,9 The average increase in TCD velocity during the study was significantly lower in the hydroxyurea group. 1,8,9 Gallbladder disease.…”

“…8,9 The average increase in TCD velocity during the study was significantly lower in the hydroxyurea group. 1,8,9 Gallbladder disease. On abdominal ultrasound at study exit, 8 children in the hydroxyurea group and 6 children in the placebo group had sludge and 5 children in the hydroxyurea group and 5 children in the placebo group had cholelithiasis.…”

Severe anemia early in life as a risk factor for sickle-cell kidney disease

“…11 We assessed risk factors for developing MiA, tested the hypothesis that early severe anemia is a risk factor for developing MiA, and analyzed our cohort based on the KDIGO definition of CKD. 14 We conducted an institutional review board-approved pediatric SCD nephropathy prospective cohort of 152 patients (.5 years) with hemoglobin SS (HbSS) or HbSB 0 thalassemia. We recorded every spot urine albumin/creatinine level obtained since birth (n 5 595) and prospectively collected annual urine measurements along with clinical and laboratory values.…”

“…15 "Early severe anemia" was categorized as Hb ,8.0 g/dL on their earliest complete blood count (CBC) between 12 and 24 months of age. 14 We analyzed age, sex, blood pressure, laboratory variables, and current therapy from the visit that coincided with identification of MiA and an early CBC to identify associations with MiA using t tests and x 2 tests for continuous and categorical variables, respectively. To examine the time to development of MiA and its predictors, we used Weibull parametric survival regression model, which accommodates left, right, and interval censored data.…”

Emerging drugs for sickle cell anemia

“…Last year witnessed the culmination of a decade-long Phase III clinical trial (BABY HUG) involving infants with SCA randomized either to HU (fixed dose 20 mg/kg/day) or placebo. BABY HUG showed that HU did not clearly prevent organ damage in a 2-year treatment period, but significantly decreased pain, ACS, hospitalizations, and transfusions in children [25][26][27][28][29][30].…”