TNF-α as a predictive factor of pulmonary hypertension in children with Down syndrome with and without congenital heart disease

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Paediatrica Indonesiana, Vol. 62, No. 1, January 2022

TNF-α as a Predictive Factor of Pulmonary Hypertension in Children with Down Syndrome with and without Congenital Heart Disease

Latifah Rahmi Hariyanti, Sri Lilijanti Widjaja, Dwi Hidayah

Abstract

Background. Down syndrome (DS) is a chromosomal disorder due  to trisomy 21 that may involve congenital heart disease (CHD).  Pulmonary  hypertension  (PH)  may  be  present  in  DS  with  and  without CHD. TNF-α is a cytokine involved in the pathogenesis  of inflammation in PH.

Objective. To determine the association between TNF-α and the risk of PH in children with DS with and without congenital heart disease.

Methods. This observational study was conducted in DS children aged  two  months  to  five  years  who  visited  the  outpatient  clinic of  a  regional  referral  hospital  in  Indonesia. Subjects underwent echocardiography and were classified into four groups (CHD-PH, CHD-no PH, no CHD-PH, no CHD-no PH). Serum TNF-α was measured  in  all  subjects.  We  used  the  ANOVA  test  to  compare  mean  TNF-α between  the  groups  and  to  determine  the  optimal TNF-α cut-off point. We compared the risk of PH in subjects with TNF-α above and below the cut-off point.

Results. We included 36 DS children in this study. Mean TNF-α in the CHD-PH, CHD-no PH, no CHD-PH, and no CHD-no PH  groups  was  2,564.44  (SD  177.00)  pg/mL,  2,112.89  (SD  382.00) pg/mL, 2,211.56 (SD 330.70) pg/mL, and 1,118.89 (SD 1056.65) pg/mL, respectively (P<0.001). The optimal TNF-α cut-off point was 2,318 pg/mL. DS children with TNF-α ≥2,318 pg/mL had a higher risk of CHD (RR=2.6; 95%CI 1.17 to 5.78; P=0.008) and PH (RR=3.5; 95%CI 1.43 to 8.60; P=0.001).

Conclusions. DS  children  with  CHD  accompanied  by  PH  have significantly  higher  TNF-α levels  than  those  without  PH  and  those without CHD. In children with DS, an elevated TNF-α level  (≥2,318 pg/mL) is associated with a higher risk of CHD and PH.

[Paediatr  Indones.  2022;62:61-5;  DOI: 10.14238/pi62.1.2022.61-5 ].

Keywords: Down syndrome; pulmonary hypertension; TNF-α

From Department of Child Health, Universitas Sebelas Maret Medical School/Dr. Moewardi Hospital, Surakarta, Central Java, Indonesia.

Corresponding author: Latifah Rahmi Hariyanti. Department of Child Health, Universitas Sebelas Maret Medical School/Dr. Moewardi Hospital. Jalan Kolonel Sutarto No. 132, Surakarta, Indonesia. Email: latifahrh15@ gmail.com. Submitted May 5, 2021. Accepted February 21, 2022