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Prediction and Prevention of Preterm Birth: A Prospective, Randomized Intervention TrialFunding This study was funded by Sera Prognostics, Inc., Salt Lake City, UT.
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.
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.
Received: 22 December 2020
Accepted: 17 June 2021
Article published online:
16 August 2021
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- 1 Prediction and prevention of preterm birth. Practice bulletin no. 130. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012; 120: 964-973
- 2 Manuck TA, Rice MM, Bailit JL. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort. Am J Obstet Gynecol 2016; 215 (01) 103.e1-103.e14
- 3 Boyle EM, Poulsen G, Field DJ. et al. Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study. BMJ 2012; 344: e896-e896
- 4 Iams JD. Clinical practice. Prevention of preterm parturition. N Engl J Med 2014; 370 (03) 254-261
- 5 Birth P. Causes, consequences, and prevention. In: Behrman RE, Bulter AS. eds. Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes. Washington, DC: National Academies Press; 2007
- 6 Ferrero DM, Larson J, Jacobsson B. et al. Cross-country individual participant analysis of 4.1 million singleton births in 5 countries with very high human development index confirms known associations but provides no biologic explanation for 2/3 of all preterm births. PLoS One 2016; 11 (09) e0162506
- 7 Salihu H, Mbah AK, Alio AP. et al. Nulliparity and preterm birth in the era of obesity epidemic. J Matern Fetal Neonatal Med 2010; 23 (12) 1444-1450
- 8 Esplin MS, Elovitz MA, Iams JD. et al; nuMoM2b Network. Predictive accuracy of serial transvaginal cervical lengths and quantitative vaginal fetal fibronectin levels for spontaneous preterm birth among nulliparous women. JAMA 2017; 317 (10) 1047-1056
- 9 Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008; 371 (9606): 75-84
- 10 Smith GCS, Shah I, White IR, Pell JP, Crossley JA, Dobbie R. Maternal and biochemical predictors of spontaneous preterm birth among nulliparous women: a systematic analysis in relation to the degree of prematurity. Int J Epidemiol 2006; 35 (05) 1169-1177
- 11 Dekker GA, Lee SY, North RA, McCowan LM, Simpson NAB, Roberts CT. Risk factors for preterm birth in an international prospective cohort of nulliparous women. PLoS One 2012; 7 (07) e39154
- 12 Bastek JA, Elovitz MA. The role and challenges of biomarkers in spontaneous preterm birth and preeclampsia. Fertil Steril 2013; 99 (04) 1117-1123
- 13 Mercer BM, Goldenberg RL, Das A. et al. The preterm prediction study: a clinical risk assessment system. Am J Obstet Gynecol 1996; 174 (06) 1885-1893 , discussion 1893–1895
- 14 Schaaf JM, Ravelli ACJ, Mol BWJ, Abu-Hanna A. Development of a prognostic model for predicting spontaneous singleton preterm birth. Eur J Obstet Gynecol Reprod Biol 2012; 164 (02) 150-155
- 15 Saade GR, Boggess KA, Sullivan SA. et al. Development and validation of a spontaneous preterm delivery predictor in asymptomatic women. Am J Obstet Gynecol 2016; 214 (05) 633.e1-633.e24
- 16 Hassan SS, Romero R, Vidyadhari D. et al; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38 (01) 18-31
- 17 Markenson GR, Saade GR, Laurent LC. et al. Performance of a proteomic preterm delivery predictor in a large independent prospective cohort. Am J Obstet Gynecol MFM 2020; 2 (03) 100140
- 18 American College of Obstetricians and Gynecologists. Committee opinion no 700: Methods for estimating the due date. Obstet Gynecol 2017; 129 (05) e150-e154
- 19 Broglio KR, Connor JT, Berry SM. Not too big, not too small: a goldilocks approach to sample size selection. J Biopharm Stat 2014; 24 (03) 685-705
- 20 Fay MP, Proschan MA, Brittain E. Combining one-sample confidence procedures for inference in the two-sample case. Biometrics 2015; 71 (01) 146-156
- 21 R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Accessed 2013 at: http://www.R-project.org/
- 22 Chan ISF, Zhang Z. Test-based exact confidence intervals for the difference of two binomial proportions. Biometrics 1999; 55 (04) 1202-1209
- 23 Carroll AE. The high costs of unnecessary care. JAMA 2017; 318 (18) 1748-1749