Malia S.Q. Murphy

Postnatal Prediction of Gestational Age Using Newborn Fetal Hemoglobin Levels

Introduction In many parts of the developing world procurement of antenatal gestational age estimates is not possible, challenging provision of appropriate perinatal care. This study aimed to develop a model for postnatal gestational age estimation utilizing measures of the newborn hemoglobin levels and other metabolic analyte data derived from newborn blood spot samples. Methods We conducted a retrospective cohort analysis of 159,215 infants born January 2012–December 2014 in Ontario, Canada. Multivariable linear and logistic regression analyses were used to evaluate the precision of developed models. Results Models derived from a combination of hemoglobin ratios and birthweight were more precise at predicting gestational age (RMSE1·23 weeks) than models limited to birthweight (RMSE1·34). Models including birthweight, hemoglobin, TSH and 17-OHP levels were able to accurately estimate gestational age to ± 2 weeks in 95·3% of the cohort and discriminate ≤ 34 versus > 34 (c-statistic, 0·98). This model also performed well in small for gestational age infants (c-statistic, 0·998). Discussion The development of a point-of-care mechanism to allow widespread implementation of postnatal gestational age prediction tools that make use of hemoglobin or non-mass spectromietry-derived metabolites could serve areas where antenatal gestational age dating is not routinely available.

Risks and trends of red blood cell transfusion in obstetric patients: a retrospective study of 45,213 deliveries using administrative data.

Transfusion data for obstetric patients are scarce. Identifying characteristics associated with red blood cell transfusion (RBCT) is of importance to better identify patients who would benefit from blood conservation strategies as the risk of alloimmunization from RBCT has the potential to affect the fetus and newborn.

Risk of exposure to blood products during pregnancy: guidance for Zika and other donor deferral policies: VIRAL TRANSMISSION RISK IN PREGNANCY

Exposure to blood products during pregnancy carries a potential risk of transfusion transmission of infectious agents. Blood agencies have historically sought optimal deferral and testing strategies to protect blood supplies in part to ensure the protection of pregnant women and their unborn infants. The Zika virus outbreak of 2016 has heightened attention to these concerns. In the current context of the recent Zika outbreak, and also more broadly, data are needed to shed light on the likelihood of exposure to blood products throughout pregnancy to inform policy.

T-cell receptor excision circle levels and safety of paediatric immunization: A population-based self-controlled case series analysis

ABSTRACT T-cell receptor excision circle levels are a surrogate marker of T-cell production and immune system function. We sought to determine whether non-pathological levels of infant T-cell receptor excision circles were associated with adverse events following immunization. A self-controlled case series design was applied on a sample of 231,693 children who completed newborn screening for severe combined immunodeficiency in Ontario, Canada between August 2013 and December 2015. Exposures included routinely administered pediatric vaccines up to 15 months of age. Main outcomes were combined health services utilization for recognized adverse events following immunization. 1,406,981 vaccination events were included in the final dataset. 103,007 children received the Pneu-C-13 or Men-C-C vaccine and 97,998 received the MMR vaccine at 12 months of age. 67,725 children received the varicella immunization at 15 months. Our analysis identified no association between newborn T-cell receptor excision circle levels and subsequent health services utilization events following DTa-IPV-Hib, Pneu-C-13, and Men-C-C vaccinations at 2-month (RI 0.94[95%CI 0.87-1.02]), 4-month (RI 0.82[95%CI 0.75-0.9]), 6-month (RI 0.63[95%CI 0.57-0.7]) and 12-month (RI 0.49[95%CI 0.44-0.55]). We also found no trends in health services utilization following MMR (RI 1.43[95%1.34-1.52]) or varicella (RI 1.14[95%CI 1.05-1.23]) vaccination. Our findings provide further support for the safety of pediatric vaccinations.

Problems with precaution: the transfusion medicine experience

Abstract The precautionary principle is a dominant paradigm governing risk-based decision-making. Today, there are increasing pressures to re-examine aggressive precautionary approaches, and to assess how the principle should be applied in the modern system. In this paper, we examined three key applications of precautionary approaches in the field of transfusion medicine to provide insight into the risks and benefits of these approaches. The three case studies examined were the donor deferral policies to safeguard against transfusion transmission of human immunodeficiency virus, variant Creutzfeldt–Jacob disease, and, lastly, xenotropic murine leukemia virus-related virus. Characterization of precautionary applications was conducted using an embedded case study design. Our findings indicate that transfusion transmission mitigation strategies have become increasingly aggressive in the face of theoretical risks. In contrast, the review processes for implementation and reversal of precautionary policies have been slow, and historical donor deferral policies are still in place today. Application of precautionary approaches has proved challenging with both benefits and pitfalls. In light of emerging threats to the blood system, policy-makers should consider the implementation of frameworks to guide the appropriate application of precaution in transfusion medicine in the future.

Performance of a postnatal metabolic gestational age algorithm: a retrospective validation study among ethnic subgroups in Canada

Objectives Biological modelling of routinely collected newborn screening data has emerged as a novel method for deriving postnatal gestational age estimates. Validation of published models has previously been limited to cohorts largely consisting of infants of white Caucasian ethnicity. In this study, we sought to determine the validity of a published gestational age estimation algorithm among recent immigrants to Canada, where maternal landed immigrant status was used as a surrogate measure of infant ethnicity. Design We conducted a retrospective validation study in infants born in Ontario between April 2009 and September 2011. Setting Provincial data from Ontario, Canada were obtained from the Institute for Clinical Evaluative Sciences. Participants The dataset included 230 034 infants born to non-landed immigrants and 70 098 infants born to immigrant mothers. The five most common countries of maternal origin were India (n=10 038), China (n=7468), Pakistan (n=5824), The Philippines (n=5441) and Vietnam (n=1408). Maternal country of origin was obtained from Citizenship and Immigration Canada’s Landed Immigrant Database. Primary and secondary outcome measures Performance of a postnatal gestational age algorithm was evaluated across non-immigrant and immigrant populations. Results Root mean squared error (RMSE) of 1.05 weeks was observed for infants born to non-immigrant mothers, whereas RMSE ranged from 0.98 to 1.15 weeks among infants born to immigrant mothers. Area under the receiver operating characteristic curve for distinguishing term versus preterm infants (≥37 vs <37 weeks gestational age or >34 vs ≤34 weeks gestational age) was 0.958 and 0.986, respectively, in the non-immigrant subgroup and ranged from 0.927 to 0.964 and 0.966 to 0.99 in the immigrant subgroups. Conclusions Algorithms for postnatal determination of gestational age may be further refined by development and validation of region or ethnicity-specific models. However, our results provide reassurance that an algorithm developed from Ontario-born infant cohorts performs well across a range of ethnicities and maternal countries of origin without modification.

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

Introduction Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. Methods We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD) or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. Results CKD occurred in 2086 (0.16%, median time 612 days) and dialysis in 641 (0.05%, median time 99 days) infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09). This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. Conclusion Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors.

Immunization and technology among newcomers: A needs assessment survey for a vaccine-tracking app

ABSTRACT Objectives: Newcomers experience unique challenges with respect to vaccination. These challenges are compounded by the need to navigate complex vaccination catch-up schedules upon arrival in their new home countries. Our group has pioneered the development of CANImmunize, a free, bilingual, pan-Canadian digital application designed to empower individuals to manage their vaccination records. To inform how a vaccine tracking app such as CANImmunize might be tailored to meet the unique needs of newcomers, this study sought to determine commonly spoken languages, technology use, and current methods of vaccine tracking among recent newcomers to Canada. Methods: Government-assisted refugees attending a health clinic in Ottawa, Canada were invited to complete a 17-question needs assessment survey. The survey captured data on household demographics, spoken languages, country of origin, technology use and methods used to track vaccination history. Results: 50 newcomers completed the needs assessment survey. Arabic was the predominant language spoken by surveyed individuals. Although 92% of participants owned a smartphone, the majority did not actively use digital health applications. 18 (36%) participants reported being vaccinated before arriving in Canada. 27 (54%) participants were parents, 23 of whom reported that their children were vaccinated prior to arrival in Canada. 38 (76%) participants indicated that they would use a vaccine tracking app such as CANImmunize if it were translated into their primary language of communication. Conclusions: The results of our study indicate that mobile technology may be a useful tool to help newcomer families stay on track with provincial and territorial immunization schedules.

Healthcare provider perspectives on the uptake of the human papillomavirus vaccine among newcomers to Canada: a qualitative study

ABSTRACT Human papillomavirus is among the most common sexually transmitted infections in the world. Newcomers, defined in Canada as foreign-born individuals who are either immigrants or refugees, but may also include students and undocumented migrants, face numerous barriers to HPV vaccination. This study sought to understand, from the perspective of healthcare providers, barriers and facilitators to HPV vaccination, and recommendations to improve HPV vaccine uptake among newcomers. Semi-structured interviews were conducted with 10 healthcare providers between March and April 2018. Data were analyzed at the manifest level using a Qualitative Content Analysis approach. Categories of barriers to vaccination included: access, communication, knowledge, culture, and provider-related factors. Facilitators included targeted health promotion; understanding the relevance of HPV vaccination; trusting the healthcare system; and cultural sensitivity. Two overarching recommendations were to publicly fund the HPV vaccine, and enhance language- and culturally-appropriate health promotion activities. Further research should explore informational desires and needs from the perspective of newcomers to inform strategies to promote equitable HPV vaccine coverage.

Metabolic profiles derived from residual blood spot samples: A longitudinal analysis

Background: Secondary use of newborn screening dried blood spot samples include use for biomedical or epidemiological research. However, the effects of storage conditions on archival samples requires further examination. The objective of this study was to determine the utility of residual newborn samples for deriving reliable metabolic gestational age estimates. Methods: Residual newborn dried blood spot samples that had been stored for 2-, 4-, 6-, or 12-months in temperature controlled (21°C) conditions were re-analyzed for the full panel of newborn screening analytes offered by a provincial newborn screening lab in Ottawa, Canada. Data from re-analyzed samples were compared to corresponding baseline newborn screening values for absolute agreement, and Pearson and intraclass correlation. Performance of a gestational age estimation algorithm originally developed from baseline newborn screening values was then validated on data derived from stored samples. Results: A total of 307 samples were used for this study. 17-hydroxyprogesterone and newborn hemoglobin profiles measured by immunoassay and high-performance liquid chromatography, respectively, were among the most stable markers across all time points of analysis. Acylcarnitines exhibited the greatest degree of variation in stability upon repeat measurement. The largest shifts in newborn analyte profiles and the poorest performance of metabolic gestational age algorithms were observed when samples were analyzed 12-months after sample collection. Conclusions: Duration of sample storage, independent of temperature and humidity, affects newborn screening profiles and gestational age estimates derived from metabolic gestational dating algorithms. When considering use of dried blood spot samples either for clinical or research purposes, care should be taken when interpreting data stemming from secondary use.