Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium

Abstract

Purpose Our objective was to compare observed and expected genotype proportions from newborn screening surveys of structural hemoglobin variants. Methods We conducted a systematic review of newborn screening surveys of hemoglobins S and C in Africa and the Middle-East. We compared observed frequencies to those expected assuming Hardy-Weinberg equilibrium (HWE). Significant deviations were identified by an exact test. The fixation index FIS was calculated to assess excess homozygosity. We compared newborn estimates corrected and uncorrected for HWE deviations using demographic data. Results Sixty samples reported genotype counts for hemoglobin variants in Africa and the Middle-East. Observed and expected counts matched in 27%. The observed number of sickle-cell anemia (SCA) individuals was higher than expected in 42 samples, reaching significance (p<0.05) in 24. High FIS were common across the study regions. The estimated total number of newborns with SCA, corrected based on FIS, were 33,261 annual births instead of 24,958 for the 38 samples across sub-Saharan Africa and 1,109 annual births instead of 578 for 12 samples from the Middle East. Conclusion Differences between observed and expected genotype frequencies are common in surveys of hemoglobin variants in the study regions. Further research is required to identify and quantify factors responsible for such deviations. Estimates based on HWE might substantially underestimate the annual number of SCA affected newborns (up to one third in sub-Saharan Africa and one half in the Middle East).

Prevalence of Sickle Cell Trait and Reliability of Self-Reported Status among Expectant Parents in Nigeria: Implications for Targeted Newborn Screening

“…Specifically, the observed prevalence of SCD in screened newborns is typically much higher than that expected based on HWE [22]. This implies that within the birth cohort represented by the adult, expectant parents in our study, the 1% SCD prevalence expected based on HWE may also be an underestimate.…”

“…Furthermore, a recent analysis of newborn SCD screening surveys throughout Africa determined that deviations from HWE equilibrium are common [22]. Specifically, the observed prevalence of SCD in screened newborns is typically much higher than that expected based on HWE [22].…”

“…A binary logit logistic analysis with Fisher’s scoring was used to determine by an odds ratio assessment whether certain demographic variables were significantly associated with the ability to provide an accurate sickle cell status self-report. Analyses were performed with Statistical Analysis System (SAS), version 9.4.The log-likelihood ratio full-enumeration exact test (“HWxtest” package in R, version 3.3.1) was used to determine if there was a significant difference (P < 0.05) between the number of observed SS individuals and the number of SS individuals expected, assuming Hardy-Weinberg Equilibrium [22]. …”

Newborn screening for sickle cell disease in Europe: recommendations from a Pan‐European Consensus Conference

“…Globally, SCD is among the most commonly inherited disorders. Every year, more than 300Á000 babies are born with SCD, the majority in Sub-Saharan Africa and in India (Piel et al, 2013(Piel et al, , 2016Serjeant, 2017;Ware et al, 2017). Although morbidity and mortality rates in affected children from these regions are very high (Grosse et al, 2011;Makani et al, 2011), outcomes have been dramatically improved in higher income countries by implementation of early preventive measures and improvements in comprehensive care (Gaston et al, 1986;Vichinsky et al, 1988;Quinn et al, 2010;Le et al, 2015;Couque et al, 2016).…”

Evaluation of cardiac function tests in Sudanese adult patients with sickle cell trait

“…6 Persons who are heterozygous and have Hb S usually do not show symptoms but the homozygous patients having Hb S (SS) show symptoms of sickle cell disease (SCD) that includes persistent pain, obstructive blood vessel, and inflammation and these symptoms cause high mortality rates in countries with low-income. 7 The sickle cell trait (SCT) is inherited through a sickle cell gene from either parent while the SCD is inherited from two sickle cell genes, one from each of the parent. The symptoms appear in patients with SCD because they have a kind of Hb S that converts normal red blood cells into sickle shapes, the symptoms do not appear in SCT patients because these patients have both normal Hb A and Hb S. The children of SCT patients can inherit the sickle cell gene.…”