Search

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42–0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18–0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34–0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27–0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.

Background: In low-income countries, including the east African region, a third of neonatal deaths are due to infections. A substantial proportion of these have been attributed to sepsis, which can result from umbilical cord infections. Evidence from Asia suggests that chlorhexidine application to the neonatal umbilical cord reduces mortality, but no data from Africa are available. We aimed to assess the effect of umbilical cord cleansing with 4% chlorhexidine solution on neonatal mortality and omphalitis in rural settings of sub-Saharan Africa. Methods: We did a community-based randomised controlled trial on Pemba Island, Zanzibar, Tanzania. All eligible babies (aged 1 h to 48 h, without congenital malformations) from hospital-based and community-based deliveries on Pemba Island were enrolled. Participants were randomly assigned to either 4% free chlorhexidine for cord care or to dry cord care using a computer-generated random sequence. For babies allocated to the chlorhexidine group, mothers or caretakers were advised to apply the solution to the cord every day until 3 days after the cord had dropped off. Cord stumps were examined for redness, pus, swelling, and foul odour on day 0, 1, 4, 10, and 28. The primary outcome for this study was mortality until day 28 on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, number NCT01528852. Findings: Between May 19, 2011, and Aug 31, 2014, 36 911 newborn babies were enrolled into the chlorhexidine (n=18 015) and dry cord care study (n=18 896) groups. 17 468 (96·9%) of 18 015 neonates in the chlorhexidine group were available for complete follow-up (28 days) compared with 18 384 (97·3%) of 18 896 neonates in the dry cord care group. Mortality rate in the chlorhexidine group (10·5 deaths per 1000 livebirths) was not significantly lower than that in the dry cord care group (11·7 per 1000 livebirths; relative risk 0·90, 0·74–1·09; p=0·27). Interpretation: Our findings do not support the use of chlorhexidine for reduction of neonatal mortality in this east African setting, which might not justify a change in the WHO policy. To inform global policy, a detailed meta-analysis and pooled analysis needs to be undertaken using data from both African and Asian settings. Funding: Bill & Melinda Gates Foundation.