Anaemia is a common complication of a myriad medical conditions often met in general ward. Its etiology is complex and multifactorial, encompassing intrinsic and extrinsic factors ^{1– 3} . Additionally, large intracardiac defects (cyanotic ventricular septal defects) can cause pulmonary vascular overload, infection and anaemia ² . Further, pulmonay hypertension (PH) due to pulmonary vascular overload can elicit a cascade of events leading to poor quality of life, morbidity and mortality ^{4, 5} . In the developing world with no heart surgery centers, pneumonia (PNA) due to large intracardiac defect(s) (cyanotic VSDs) is responsible for retardation, persistent morbidity and mortality ^{2, 6} .

Nevertheless, the effect(s) of small to moderate VSD’s on the occurrence of both PNA and PH amongst paediatric patients, especially infants has not been fully explored. Adults and older children may tolerate and survive the effects. However, infants with limited iron storage and supply (exclusive breast milk) may not with stand ^{7, 8} . For these reasons, we hypothesize that paediatric patients with solitary acyanotic VSD coexisting with PNA or PH retain a risk of developing anaemia. In this retrospective study, we aim to establish the prevalence of anaemia in patients with solitary acyanotic VSD in comorbid with PNA or PH.

In this case study, we used hemoglobin reference ranges based on age as follow: (I) young children (95–135) and (II) older children were (105–135) gram per liter, as per local protocol. According to data analysis reflected in Table 3, 27 patients (36%) in total had anaemia. Of the anaemia cohort, 16(59.3%) had PNA, 9 (33.3%) PH and 2(7.4%) asymptomatic. Of the cohort, 42 were young children with anaemia prevalence of 19/42(45.2%), while the older children had 24.2%. Hemoglobin Intergroup (ANOVA) independent sample t-test was significant (p<0.05). In addition, intergroup Tukey HSD test for hemoglobin: A/B(p>0.05), A/C(p<0.01), B/C(p<0.01). The mean WBC in PNA was higher and intergroup p-value was significant. Other hematologic and laboratory are reflected in the respective group

Of the cohort, 42 were young children, and of those 19 had anaemia (45.2%), while 24.2% of the older children had anaemia. Haemoglobin intergroup (ANOVA) independent sample t-test was significant (p<0.05). In addition, intergroup Tukey HSD test for haemoglobin: A/B (p>0.05), A/C (p<0.01), B/C (p<0.01). The mean white blood cells in patients with PNA was higher and intergroup p-value was significant (p<0.05).

Anaemia, defined as haemoglobin (Hb) concentration below the 5 ^th percentile for age at sea-level, is a common complication of a myriad medical conditions often met in the general ward ¹ . Its aetiology is complex and multifactorial, encompassing intrinsic and extrinsic factors. Both pneumonia (PNA) and pulmonary hypertension (PH) due to cyanotic congenital heart defect (CHD) have been implicated in the occurrence of anaemia ^{2, 3, 6} . In addition, sporadic reports linking anaemia to PNA or PH amongst patients with acyanotic ventricular septal defect (VSD) have been publish.

VSD is the second commonest CHD after bicuspid aortic valve ^{4, 9} , and solitary cases account for almost 20%. One of the most common defects associated with elevated pulmonary artery pressure is a large VSD. Elevated pulmonary artery pressure in CHD can be due to pulmonary hyper-circulation, pulmonary vasoconstriction, and pulmonary vascular disease, either alone or in combination. In an infant, despite pulmonary pressure being at systemic level, pulmonary vascular resistance is low; therefore, minor shunt easily elicits hyper-circulation ^{2, 4, 6, 10} .

PH, defined as mean pulmonary artery pressure of ≥25mmHg at rest as measured by cardiac catheterization in children aged ≥3months, is a serious disorder with a high morbidity and mortality rate ² . Blood shunt may cause haemolysis due to shear stress and produce free haemoglobin, which in turn depletes nitric oxide leading to endothelial dysfunction, vasoconstriction, pulmonary oedema and hypoxia. Furthermore, haemolysis produces arginase, which converts L-arginine to ornithine; therefore, bypassing nitric oxide production ^{2, 8, 11} .

PNA as defined by Ozdemir and colleagues is a serious reason for morbidity and mortality in children (≤2years) with hemodynamic significant VSD ^{5, 12} . Both PNA and PH share a common interface; inflammation, homostasis, hypoxia, and subsequent upregulation of erythropoiesis ^{7, 13} . Prolonged upregulated erythropoiesis in young children with low iron store and limited iron supplement leads to anaemia ¹ . In addition, microangiopathic hemolytic anaemia in CHD and PH has been reported ³ , a complication commonly observed in primary PH. Unlike in PH, Mycoplasma Pneumonia and Plebsiella are known to cause anaemia in PNA ^{14– 16} .

This study shows that acyanotic VSD within mean sizes: 1.2±0.3 and 0.89±0.2 centimeters, thus, defect measured from the left ventricular septal side are prone to pulmonary vascular infection/dysfunction. Both transthoracic and transoesophageal echocardiography were employed in the diagnosis and delineation of VSD and PH ¹⁷ . Although, right heart catheterization (RHC) is regarded as gold standard, our center favor echocardiography due to less vascular and technical challenges, especially in clinically compromised infants. According to 2018 guidelines issued by British Society of Echocardiography, aforementioned is recommended and RHC superiority is insignificant ¹⁸ . Young infants (3moths old) with small defects were considered for closure if defect(s) showed no trait of spontaneous closure in the presence of symptoms after 2 consective follow-up at 2-month interval. Apical VSDs (Swiss cheese) seldom achieved closure, hence, inclusion.

Although this study is not focused on closure techniques, suffice to mention that surgical and minimally invasive. i.e. 1. perventricular ¹⁹ , 2. peratrial ²⁰ and 3. percutaneous (<10%) device closure were used. Surgical was employed when device implation proved futile, while percutaneous was limited to a small potion due to vascular limitation and possible complications. Recent publication cited small weight and age as recipe for complication during percutaneous intervention ²¹ . In addition, surgical technique was employed with utmost care due to bypass related complication and blood transfusion complications related in PH subjects. Its worthy mentioning that this study does not include prevalence of anaemia post intervention. Symptomatic subjects became asymptomatic at dismissal, and both aforementioned and asymptotic ones progressively improved anthropometric parameters during sequential follow-ups ²² .

Paediatric patients without hematologic disorders, diagnosed with hemodynamic significant acyanotic VSD in comorbid with pneumonia or pulmonary hypertension are 8 and 4 times susceptible to develop anaemia compared to asymptomatic counterparts. Susceptibility is even high amongst young children (3–6 months). However, a long post closure follow-up study is required to exclude possibly missed intrinsic (genetical/gastro-intestinal) and extrinsic (economical) etiologies and validate findings.

The Shandong Provincial Hospital Ethics Committee approved this study, and waived individual patient consent as the study was based on archived data.

Harvard Dataverse: Anaemia in solitary acyanotic ventricular septal defect in comorbid with pneumonia or pulmonary hypertension; a retrospective study of 75 paediatric cases, https://doi.org/10.7910/DVN/2B328D ²² .

Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).