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Jointly modelling longitudinally measured urinary human chorionic gonadotrophin and early pregnancy outcomes

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journal contribution
posted on 20.05.2020, 11:50 by NB Ashra, L Marriott, S Johnson, KR Abrams, MJ Crowther
Human chorionic gonadotrophin (hCG) is largely used to confirm pregnancy. Yet evidence shows that longitudinal hCG profiles are distinguishable between healthy and failing pregnancies. We retrospectively fitted a joint longitudinal-survival model to data from 127 (85 healthy and 42 failing pregnancies) US women, aged 18–45, who were attempting to conceive, to quantify the association between longitudinally measured urinary hCG and early miscarriage. Using subject-specific predictions, obtained uniquely from the joint model, we investigated the plausibility of adaptively monitoring early pregnancy outcomes based on updating hCG measurements. Volunteers collected daily early morning urine samples for their menstrual cycle and up to 28 days post day of missed period. The longitudinal submodel for log hCG included a random intercept and slope and fixed linear and quadratic time terms. The survival submodel included maternal age and cycle length covariates. Unit increases in log hCG corresponded to a 63.9% (HR 0.36, 95% CI 0.16, 0.47) decrease in the risk of miscarriage, confirming a strong association between hCG and miscarriage. Outputted conditional survival probabilities gave individualised risk estimates for the early pregnancy outcomes in the short term. However, longer term monitoring would require a larger sample size and prospectively followed up data, focusing on emerging extensions to the joint model, which allow assessment of the specificity and sensitivity.

Funding

This was a diagnostic accuracy study on a sample bank collected from a multicentre, prospective study, conducted by Radiant Research (USA) on behalf of the sponsor SPD Development Company Ltd. (UK). The study was approved by Quorum Review Committee on 30th November 2009; clinical trial number NCT01077583. This analysis was conducted by N.B.A as part of a doctoral training programme jointly funded by MRC IMPACT and SPD Development Company Ltd.

History

Citation

Ashra, N.B., Marriott, L., Johnson, S. et al. Jointly modelling longitudinally measured urinary human chorionic gonadotrophin and early pregnancy outcomes. Sci Rep 10, 4589 (2020). https://doi.org/10.1038/s41598-020-61461-w

Version

VoR (Version of Record)

Published in

SCIENTIFIC REPORTS

Volume

10

Issue

1

Pagination

4589 (9)

Publisher

NATURE PUBLISHING GROUP

issn

2045-2322

eissn

2045-2322

Acceptance date

26/02/2020

Copyright date

2020

Available date

12/03/2020

Notes

The datasets analysed during the current study are not publicly available due to confidentiality restrictions in place between SPD Development Company Ltd. and the University of Leicester. Stata code written/used to perform the analysis are available from the corresponding author on reasonable request.

Spatial coverage

US

Language

English