Published September 3, 2021 | Version v1
Dataset Open

Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset

Description

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10−40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10−7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.

Notes

The data files contain the normalized plasma protein data, expressed as relative fluorescence units (RFU). Please refer to the ReadMe file ('Onset of labor proteomics') for additional information.

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: 2RM1HG00773506

Funding provided by: Doris Duke Charitable Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000862
Award Number: 2018100

Funding provided by: March of Dimes Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000912
Award Number: 22FY19343

Funding provided by: American Heart Association
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000968
Award Number: 18IPA34170507

Funding provided by: Evergreen State College Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100007437
Award Number: STE2757/1-1

Funding provided by: Stanford Maternal and Child Health Research Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100015521

Funding provided by: Deutsche Forschungsgemeinschaft
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100001659
Award Number: STE2757/1-1

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01AG058417

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01HL13984401

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R21DE02772801

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R61NS114926

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R01HL13984403

Funding provided by: Gates Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000865
Award Number: OPP1189911

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: 2RM1HG00773506

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R35GM138353

Funding provided by: NIH
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R35GM137936

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