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This study aimed to describe the pattern and immediate outcome of severe childhood anaemia requiring blood transfusion at a secondary level of care in Nigeria. A cross-sectional survey of children hospitalized in a secondary health facility in Ogun State, Nigeria, with packed cell volume <20% and who received blood transfusion was done. Of the 253 children admitted between March 2013 and June 2014, 79 (31.2%) had severe anaemia and were transfused with blood. Two-thirds had multiple transfusions. Higher rates of blood transfusion were obtained among underweight children. Fever (98.7%), hypoglycaemia (65.8%) and tender liver (54.4%) were the leading co-morbidities. The case fatality rate was 21.5%. Respiratory distress, convulsions and altered sensorium were significantly associated with mortality. In conclusion, severe anaemia was associated with major morbidities and mortality at the secondary level of paediatric care in Nigeria.
The health care delivery system in Nigeria uses the three-tier system via the primary (primary and comprehensive health centres), secondary (general and state hospitals) and tertiary (university-teaching and specialist hospitals) health facilities [1, 2]. Sick children are usually referred from the primary level of care and from private clinics to the secondary health care facilities. Beside health care services, some amount of research takes place at the secondary facilities. Therefore, the bulk of epidemiological data on most of the major health challenges of children reflects the pattern of disease occurrence documented at the tertiary level of care [3–6].
In most cases, the secondary level of care in Nigeria is only equipped to provide emergency paediatric services because of limited facilities. Other conditions requiring more advanced care are usually referred to better-equipped tertiary facilities. Blood transfusion is a common intervention in a paediatric emergency room in the developing world . Severe anaemia requiring blood transfusion is a common condition accounting for a bulk of emergency room admissions in most parts of Nigeria [7–9]. The bulk of the available data on severe childhood anaemia and paediatric blood transfusion in Nigeria were obtained from the tertiary facilities. Therefore, this study aimed to examine the pattern and immediate outcome of severe childhood anaemia requiring blood transfusion at a secondary level of care in Nigeria.
The descriptive cross-sectional survey was conducted between March 2013 and June 2014. All consecutive children from birth to the age of 15 years admitted to the Iye Subomi Child Care Centre (ISCCC), the Paediatric Unit of the State Hospital, Ijebu-Ode, Ogun State, Nigeria (a secondary health facility), with a packed cell volume (PCV) of 20% were recruited into the survey following ethical approval obtained from the State Ministry of Health and informed parental consent. Children who had been transfused in other facilities before admission at the ISCCC were also included in the study.
The ISCCC is manned by a full complement of physicians led by a Consultant Paediatrician. This secondary health facility receives sick children from all socio-economic background, who were referred from the various primary health centres and private clinics within the locality, as the latter lacked the required expertise and equipment for managing paediatric emergencies. Blood transfusion is prescribed for severe haemorrhages or severe anaemia (defined as PCV <14% or higher PCV values of 15–20%, coexisting with congestive cardiac failure or encephalopathy ). Severe anaemia is managed with the transfusion of partially packed cells or sedimented red cells (at a dose of 15ml/kg) because of lack of facilities to pack red cells in the laboratory.
The basic data obtained from every child enrolled into the study at the point of transfusion included the age in months, sex, weight in kilograms, nutritional status (Weight-for-Age Z-score <−2 SD on the World Health Organization (WHO) chart ) and maternal factors such as age, highest educational attainment and socio-economic classes (I–V). . The co-morbidities present in each child were also recorded. The outcome of hospitalization and duration of hospitalization were also recorded. The case fatality rates (CFRs) were determined for each group of children studied.
The data were processed with SPSS 17.0 version statistical software (SPSS Inc., Chicago, IL, USA) using descriptive and inferential statistics [Student's t-test, risk ratio (RR), 95% confidence interval (CI) and Fisher's Exact test]. Statistical significance was established when CI excluded unity or p-values were <0.05.
Two hundred and fifty-three children comprising 154 (60.8%) males and 99 (39.1%) females (1.6 : 1) were surveyed. They were aged 15 days–146 months, with a mean age of 32.7±31.5 months.
Eighty children had severe anaemia (PCV<20% and requiring blood transfusion), but 79 children were transfused with blood, giving a transfusion rate of 31.2%. Seventy-four were transfused at the site of study, while five had received blood at the referring private clinics. One child with a PCV level of 9% was not transfused because the parents refused transfusion on religious grounds, and the child eventually died. The age range of children who had blood transfusion was 15 days–144 months, with a mean of 29.7±25.9 months. Children aged ≤59 months constituted 96.2% (76/79). The sex distribution of the children who had blood transfusion showed 47 males and 32 females, giving a male-to-female ratio of 1.5 : 1.
All the 79 children who were transfused with blood had severe anaemia of haemolytic origin. There was none with trauma or other forms of haemorrhagic anaemia. Ten (12.6%) children had PCV <10%, while 42 (53.2%) and 27 (34.2%) children had a PCV level of 10–13% and 14–20%, respectively. The 15day old infant had cephalohaematoma with severe anaemia, necessitating blood transfusion but without Exchange Blood Transfusion. Blood film staining was positive for asexual forms of Plasmodium falciparum among 75 (94.9%) children; 29 (36.7%) children had varying degrees of microcytosis and hypochromia on blood film appearance, suggestive of iron deficiency anaemia, while 9 (11.4%) had clinical and laboratory features of sepsis. Nineteen of the 60 (31.7%) children on whom haemoglobin electrophoresis had been performed had sickle cell anaemia. The remaining 19 children did not undergo haemoglobin electrophoresis before transfusion for logistic reasons. Some children had multiple clinical conditions associated with severe anaemia. The glucose-6-phosphate dehydrogenase (G6PD) statuses were not subsequently determined because of lack of facilities.
Twenty-five (31.6%) children had a single session of blood transfusion, while the remaining 54 (68.4%) had two to four sessions of blood transfusion. The mean age of children who received single or multiple transfusions was not statistically significantly different (27.9±17.7 months vs. 30.5±28.5 months; t=0.42, p=0.67). The mean pre-transfusion PCV of children who received single blood transfusion was significantly higher than the PCV of children who received multiple blood transfusions (13.2±3.1% vs. 11.2±3.6%; t=2.40, p=0.019). The post-transfusion PCV for children who received single transfusion was 24.6±3.3% compared with 26.7±3.2% for children with multiple transfusions (t=2.69; p=0.009). All the 25 children who received single blood transfusion had demonstrable malaria parasitaemia compared with 92.6% (50/54) of the children who received multiple blood transfusions.
Table 1 shows similarities in the age, sex, maternal education and family socio-economic status patterns of the comparison groups, but underweight was significantly more common among the transfused children (p=0.02). Table 2 shows that the blood transfusion rates increased with age from infancy to preschool age, while underweight children, children of teenage mothers and children in the lower socio-economic classes had higher transfusion rates compared with children in the comparison groups.
Seventy-eight (98.7%) of the children who had severe anaemia presented with fever. The other morbidities included underweight (43; 54.4%), hypoglycaemia (52; 65.8%), heart failure (43; 54.4%), respiratory distress (38; 48.1%), haemoglobinuria (37; 46.8%), convulsions (35; 44.3%), altered sensorium (28; 35.4%), jaundice (18; 22.8%) and oliguria (13; 16.4%).
Forty-two (80.8%) of the 52 children with PCV<14% received multiple blood transfusion compared with 12 (44.4%) of the 27 children with PCV≥14% (RR=0.34; CI 0.18–0.66; p=0.002). Tables 3 and and44 show that similar proportions of children who had PCV levels of <14% or ≥14% were aged ≤12 months, were males, underweight, with low maternal education and belonged to family socio-economic classes IV and V. The prevalence of convulsions, heart failure, oliguria and jaundice were comparable among children in both groups. However, the prevalence of respiratory distress, haemoglobinuria, altered sensorium and hypoglycaemia was significantly higher (p=0.018, p=0.02, p<0.001 and p<0.001, respectively) among children with PCV<14%.
Of the 79 children who had blood transfusion, 60 (75.9%) were discharged home, 17 (21.5%) died, while the remaining 2 (2.5%) were prematurely discharged from the hospital against medical advice; thus, the CFR was 21.5%. The two children who were prematurely discharged against medical advice were included in the analysis of the morbidities on the basis of Intention-To-Treat. The 17 children who died in the transfusion group represented 48.6% (17/35) of the overall deaths recorded at the centre during the survey. The CFR was higher among children with PCV<10% (6/10; 60%) compared with children with a PCV level of 10–13% (10/42; 23.8%). There was no death among children with PCV≥14%. The CFR among children who had single transfusion was 10/25 (40.0%) compared with 7/54 (12.9%) among children who had multiple transfusions. The mean age of the fatalities and the survivors was comparable (28.5±20.6 months vs. 30.0±27.0 months; t=0.22, p=0.83). On the other hand, the mean PCV was significantly higher among the survivors compared with the fatalities (12.9±2.6% vs. 9.9±1.7%; t=4.71, p<0.001). Overall, the mean duration of hospital stay of the children who were transfused with blood was 4.4±2.3 days; the fatalities had significantly shorter duration of hospital stay compared with the survivors (1.7±1.2 days vs. 5.3±1.9 days; t=7.76, p<0.001).
Tables 5 and and66 show that age≤12 months, male sex, low family socio-economic status and jaundice occurred with the same frequencies among the survivors and the fatalities, whereas respiratory distress, convulsions, heart failure, altered sensorium and hypoglycaemia were significantly more frequent among the fatalities (p<0.0001, p<0.0001, p=0.003, p<0.0001 and p=0.013, respectively).
The overall transfusion rate of 31.2% in the present study implied that one of every three children admitted into the Nigerian secondary-level paediatric centre required blood transfusion for severe anaemia. The researchers are constrained to make comparison with only data reported from the tertiary facilities. The prevalence of severe anaemia and the transfusion rate observed in the present study were >2.7, 9.7 and 17.9% as previously reported from tertiary health facilities in Ado-Ekiti, Sokoto and Abakaliki in southwest, northwest and southeast Nigeria, respectively,[8, 13, 14] reflecting the general pattern of admission at the secondary and tertiary ends.
A significant proportion of the transfused children in the present study were <5 years of age. This is in keeping with a previous report obtained from another part of southwestern Nigeria . The predominance of children <5 years may be linked to the pivotal role of severe malaria in the aetiology of severe childhood anaemia in this part of the world . This is not surprising as >95% of the children in the present study had fever and demonstrable malaria parasitaemia similar to Nigerian reports of 62.9% in Sokoto, , 90.7% in Ado-Ekiti  and 83.1% in Umuna . The strong association between severe malaria-related anaemia and paediatric blood transfusion had previously been observed among Zambian children . Although, the scope of the present study did not include the pattern of pre-hospitalization treatment of malaria, it is plausible that incomplete or inappropriate home treatment of malaria, which had previously been documented in southwest Nigeria, , might have contributed to the severe degree of anaemia associated with falciparum malaria in this study.
There had been no community-based study of the burden of falciparum malaria or iron deficiency anaemia among children in Ijebu-Ode community; hence, it is difficult to relate the findings among children hospitalized with severe anaemia to the situation within the same community. Nevertheless, a previous tertiary hospital-based study at Ibadan in southwest Nigeria had suggested that severe malaria accounted for 11.3% of all children emergency room admissions . Similarly, the prevalence of iron deficiency anaemia in the present study (36.7%) was relatively >14.9% reported among children aged <24 months in Lagos, southwest Nigeria . The difference may be attributed to the fact that the Lagos study did not specifically focus on children hospitalized with severe anaemia. Although, haemoglobin electrophoresis could not be determined among 19 of the 79 children studied, 31.7% of those who were tested had sickle cell anaemia. This observation highlights the burden of sickle cell anaemia in severe childhood anaemia as well as the limitations practitioners encounter in a resource-poor setting.
The children of teenage mothers recorded remarkably higher blood transfusion rates in the present study. This observation may be related to poor access to quality health care arising from relative inexperience about child care, poor finances and inadequate supports. The association between low maternal education and higher proportion of children with PCV<14% in the present study may reflect, among other known factors, poor understanding of health instructions, poor utilization of health interventions and poor health care-seeking behaviour as earlier suggested .
More than two-thirds of the transfused children in the present study required two to four sessions of blood transfusion. This evidently reflects the severity of anaemia but may also be a consequence of the use of sedimented cells in place of packed cells. The children who required multiple blood transfusions had significantly lower mean pre-transfusion PCV but higher post-transfusion PCV. Malaria prevalence did not appear to differ between children who required single or multiple blood transfusions. The lower mortality rate among children who had multiple transfusions in the present study may also be an advantage as previously observed .
The association of severe anaemia with morbidities such as heart failure, altered sensorium and hypoglycaemia were consistent with previous findings . The association of severe anaemia with falciparum malaria in almost all the children in the cohort studied would suggest that most of the children had severe falciparum malaria in conformity with the WHO definition of severe malaria as earlier suggested . Immunologic studies have indicated that the risk of severe anaemia among malarious children becomes 7-fold when increased parasite biomass (by way of sequestration in tissues) coexists with expanded CD8+T-cells population . Although immunologic studies were not included in the present survey, the major role of severe falciparum malaria is strengthened by the high prevalence of hypoglycaemia, heart failure and altered sensorium in agreement with previous studies [19, 25, 26].
In the present study, children with lower PCV (<14%) tended to be more ill with life-threatening morbidities, which reflects severe degrees of tissue hypoxia with deranged metabolism and higher risk of mortality. Therefore, children presenting with low PCV should be routinely screened for these life-threatening morbidities, and these should prompt anticipatory management to minimize mortality.
The overall CFR among children who had severe anaemia in the present study was 21.5%. This figure also represented 48.6% of total deaths in the unit during the study period and lent credence to the prime position of severe anaemia in childhood mortality in Nigeria. Compared with the tertiary centres with CFR 9.3–15.7%, [7, 8, 13] the higher CFR at this secondary health facility may be attributed, by speculation, to inadequate supportive care. All the fatalities in the present study occurred among children with PCV<14%, and they all had more co-morbidities compared with the survivors. This observation might be because of late presentation in the hospital and, therefore, more severe illness.
The inability to carry out haemoglobin electrophoresis and assay G6PD deficiency in all the children is acknowledged as a limitation to this study, but this has not reduced the observed role of severe anaemia as a major cause of childhood morbidity and mortality in a Nigerian secondary level of care with limited facilities.
In conclusion, it is attractive to suggest that children presenting with PCV<14% in resource-poor settings should be considered for multiple transfusions for better outcome. Adherence to standard treatment guidelines for severe malaria is likely to contribute to improved outcome of children with severe anaemia in this setting. More efforts should be geared at educating the public on the importance of malaria control, and early presentation of children with fever to the nearest secondary or tertiary levels of care should be encouraged, particularly among teenage and poorly supported mothers. Although multiple transfusions improved the outcome of the severely anaemic children in the present study, the known risks of multiple transfusions should justify a search for safer and more efficient methods of transfusion, which would not deplete the blood bank and further improve the outcome of children with low PCV. Further studies are also required to explore the role of nutrition in the susceptibility of Nigerian children to severe malarial anaemia as well as the role of the synergy between the membranopathies, haemoglobinopathies and falciparum malaria in the severity and outcome of severe childhood anaemia in Nigeria.
The medical interns who worked at the Iye-Subomi Child Care Centre, State Hospital, Ijebu-Ode, Nigeria, during the period of study are appreciated for meticulous data collection.