Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study

Reference intervals for clinical laboratory parameters are important for assessing eligibility, toxicity grading and management of adverse events in clinical trials. Nonetheless, haematological and biochemical parameters used for clinical trials in sub-Saharan Africa are typically derived from industrialized countries, or from WHO references that are not region-specific. We set out to establish community reference values for haematological and biochemical parameters amongst children aged 4 weeks to 17 months in Kilifi, Kenya. We conducted a cross sectional study nested within phase II and III trials of RTS, S malaria vaccine candidate. We analysed 10 haematological and 2 biochemical parameters from 1,070 and 423 community children without illness prior to experimental vaccine administration. Statistical analysis followed Clinical and Laboratory Standards Institute EP28-A3c guidelines. 95% reference ranges and their respective 90% confidence intervals were determined using non-parametric methods. Findings were compared with published ranges from Tanzania, Europe and The United States. We determined the reference ranges within the following age partitions: 4 weeks to <6 months, 6 months to less than <12 months, and 12 months to 17 months for the haematological parameters; and 4 weeks to 17 months for the biochemical parameters. There were no gender differences for all haematological and biochemical parameters in all age groups. Hb, MCV and platelets 95% reference ranges in infants largely overlapped with those from United States or Europe, except for the lower limit for Hb, Hct and platelets (lower); and upper limit for platelets (higher) and haematocrit(lower). Community norms for common haematological and biochemical parameters differ from developed countries. This reaffirms the need in clinical trials for locally derived reference values to detect deviation from what is usual in typical children in low and middle income countries

Characteristics of study participants.

<p>Characteristics of study participants.</p

Dynamics of cord titres by time and transmission intensity.

<p>The Red diamond symbols denote individual cord titres by date of birth for RSV A2 strain, Blue diamond symbols denote individual cord titres by date of birth for RSV A Kilifi local strain, Maroon circle markers denote the mean cord titre by quarter (95% CI denoted by Brown whiskers) for RSV A2 strain, Navy blue circle markers denote the mean cord titre by quarter (95% CI denoted by Green whiskers) for RSV A Kilifi local strain. The Grey vertical bars (RSVA) and Orange vertical bars (RSV B) show the number of RSV IFAT positive paediatric severe or very severe pneumonia admissions to Kilifi County Hospital 2002–2005.</p

The estimated rate of decay of RSV specific antibodies from birth to 6 months of life among cases and controls.

<p>The estimated rate of decay of maternally transferred RSV specific antibodies (log₂ transformed PRNT titres) over the first 6 months of life for infants (30 RSV cases and 60 controls) from a birth cohort, Kilifi, Kenya, with best fit linear decay models for samples from cases and controls. Grey symbols denote individual cord titres of cases while black symbols denote individual cord titres of controls.</p

Relationship between Odds of RSV disease and the levels of Cord blood antibody titres.

<p>A scatter plot showing the odds of RSV associated hospitalization against maternally transferred RSV specific antibodies (log₂PRNT titres) from cord blood samples of infants (both cases and controls) born in Kilifi, Kenya; 2002–2007. Black symbols denote individual cord titres for all 90 infants.</p

A box plot of the mean concentration of cord blood titres of cases and controls by age categories.

<p>Differences in the mean concentration of maternally transferred respiratory syncytial virus (RSV) specific antibodies (log₂PRNT titres) from cord blood samples (with P values shown), between cases and controls at age categories in months of first RSV infection; 1–2 and 3–5. Cases were matched to controls in a ratio of 1:2. P values generated using a two sample paired t-test.</p