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CC BY-NC-ND 4.0 · Am J Perinatol 2023; 40(10): 1071-1080
DOI: 10.1055/s-0041-1732339
Original Article

Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention Trial

D. Ware Branch
1   Department of Obstetrics and Gynecology, Intermountain Healthcare Maternal-Fetal Medicine and University of Utah Health, Murray, Utah
,
John M. VanBuren
2   Division of Pediatric Critical Care, Department of Pediatrics, University of Utah Health, Murray, Utah
,
T. Flint Porter
1   Department of Obstetrics and Gynecology, Intermountain Healthcare Maternal-Fetal Medicine and University of Utah Health, Murray, Utah
,
Calla Holmgren
1   Department of Obstetrics and Gynecology, Intermountain Healthcare Maternal-Fetal Medicine and University of Utah Health, Murray, Utah
,
Richard Holubkov
2   Division of Pediatric Critical Care, Department of Pediatrics, University of Utah Health, Murray, Utah
,
Kent Page
2   Division of Pediatric Critical Care, Department of Pediatrics, University of Utah Health, Murray, Utah
,
Julja Burchard
3   Sera Prognostics, Inc., Department of Research & Development, Salt Lake City, Utah
,
Garrett K. Lam
4   High Risk Pregnancy Center, Las Vegas, Nevada
,
M. Sean Esplin
1   Department of Obstetrics and Gynecology, Intermountain Healthcare Maternal-Fetal Medicine and University of Utah Health, Murray, Utah
› Author Affiliations Funding This study was funded by Sera Prognostics, Inc., Salt Lake City, UT.
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Abstract

Objective The study aimed to determine if a program of mid-trimester serum proteomics screening of women at low risk for spontaneous preterm birth (sPTB) and the use of a PTB risk-reduction protocol in those whose results indicated an increased risk of sPTB would reduce the likelihood of sPTB and its sequelae.

Study Design Prospective comparison of birth outcomes in singleton pregnancies with mid-trimester cervical length ≥2.5 cm and at otherwise low risk for sPTB randomized to undergo or not undergo mid-trimester serum proteomics screening for increased risk of sPTB (NCT 03530332). Screen-positive women were offered a group of interventions aimed at reducing the risk of spontaneous PTB. The primary outcome was the rate of sPTB <37 weeks, and secondary outcomes were gestational age at delivery, total length of neonatal stay, and NICU length of stay (LOS). Unscreened and screen-negative women received standard care. The adaptive study design targeted a sample size of 3,000 to 10,000 women to detect a reduction in sPTB from 6.4 to 4.7%. Due to limited resources, the trial was stopped early prior to data unblinding.

Results A total of 1,191 women were randomized. Screened and unscreened women were demographically similar. sPTB <37 weeks occurred in 2.7% of screened women and 3.5% of controls (p = 0.41). In the screened compared with the unscreened group, there were no between-group differences in the gestational age at delivery, total length of neonatal stay, and NICU LOS. However, the NICU LOS among infants admitted for sPTB was significantly shorter (median = 6.8 days, interquartile range [IQR]: 1.8–8.0 vs. 45.5 days, IQR: 34.6–79.0; p = 0.005).

Conclusion Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB compared with women not screened, though the trial was underpowered thus limiting the interpretation of negative findings. Infants in the screened group had a significantly shorter NICU LOS, a difference likely due to a reduced number of infants in the screened group that delivered <35 weeks.

Key Points

  • Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB, though the trial was underpowered.

  • NICU LOS following sPTB was significantly shortened among women who underwent screening and risk-reduction management.

  • The use of serum biomarkers may contribute to a practical strategy to reduce sPTB sequelae.

Keywords

spontaneous preterm birth - serum proteomics screening - neonatal length of stay

Supplementary Material



Publication History

Received: 22 December 2020

Accepted: 17 June 2021

Article published online:
16 August 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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