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Original research
Umbilical cord interleukin-6 predicts outcome in very low birthweight infants in a high HIV-burden setting: a prospective cohort study
  1. Cheryl Anne Mackay1,
  2. James Stephanus Smit2,
  3. Farhaad Khan2,
  4. Fazana Dessai3,
  5. Catherine Connolly3,
  6. Refiloe Masekela4
  1. 1 Paediatrics Department, Dora Nginza Hospital, Port Elizabeth, South Africa
  2. 2 Paediatrics Department, Dora Nginza Hospital, Port Elizabeth, Eastern Cape, South Africa
  3. 3 University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
  4. 4 Paediatrics and Child Health, University of KwaZulu-Natal College of Health Sciences, Durban, South Africa
  1. Correspondence to Dr Cheryl Anne Mackay, Paediatrics Department, Dora Nginza Hospital, Port Elizabeth 6059, South Africa; cmackay{at}


Objectives South Africa has a double burden of high neonatal mortality and maternal HIV prevalence. Common to both is a proinflammatory in utero and perinatal milieu. The aim of this study was to determine cytokine profiles in HIV exposed (HE) and HIV unexposed (HU) very low birthweight (VLBW) infants and to determine whether these were associated with predischarge outcomes.

Design Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019.

Patients Inborn infants with birth weight of <1500 g were enrolled and cord blood was collected for interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) assays. Participants provided informed consent and ethics approval was obtained.

Outcome measures The primary outcome was umbilical cord cytokine levels according to maternal HIV status. Secondary outcomes included death and/or serious neonatal infection, necrotising enterocolitis, intraventricular haemorrhage, periventricular leucomalacia, chronic lung disease and haemodynamically significant patent ductus arteriosus before discharge.

Results A total of 279 cases were included with 269 cytokine assays performed on 122 HEs and 147 HUs. Median IL-6 levels were 53.0 pg/mL in HEs and 21.0 pg/mL in HUs (p=0.07). Median TNF-α levels were 7.2 pg/mL in HEs and 6.5 pg/mL in HUs (p=0.6). There was significantly more late-onset sepsis in the HE group compared with the HU group (41.2% vs 27.9%) (p=0.03). IL-6 levels were significantly higher for those with any adverse outcome (p=0.006) and death and/or any adverse outcome (p=0.0001). TNF-α levels did not differ according to predischarge outcomes.

Conclusion There is no significant difference in IL-6 and TNF-α levels in cord blood of HE compared with HU VLBWs. However, IL-6 levels are significantly higher in VLBWs with adverse predischarge outcomes, and VLBW HEs are at increased risk of adverse predischarge outcomes compared with HUs, particularly late-onset sepsis.

  • HIV
  • mortality
  • neonatology
  • outcomes research
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  • Contributors CAM: protocol development, data collection and writing of the manuscript. RM: protocol development and writing/revision of the manuscript. JSS: data collection and review of the manuscript. FK: data collection. FD: data collection, responsible for cytokine assays, manuscript review and revision. CC: statistical analysis.

  • Funding The study was funded by the University of KwaZulu-Natal, the Discovery Foundation and the South African Medical Research Council.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethics approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BE632/16), the Human Research Ethics Committee of Walter Sisulu University (003/2017) and the Eastern Cape Department of Health (EC_2017RP58_14).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Original data, in the form of deidentified participant data, are available upon reasonable request from the primary corresponding author (Dr Cheryl Mackay; email

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