The phenotype of spontaneous preterm birth: application of a clinical phenotyping tool
Open accessAbstract
Objective Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible causes. We hypothesized that a comprehensive classification system appropriately could group women with similar STPB causes and could provide an explanation, at least in part, for the disparities in SPTB that are associated with race and gestational age at delivery.Study design This was a planned analysis of a multicenter, prospective study of singleton SPTBs. Women with SPTB at <34 weeks' gestation were included. We defined 9 potential SPTB phenotypes based on clinical data: infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman's condition was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0-27.9 weeks' gestation) SPTB vs those with early SPTB (28.0-34.0 weeks' gestation) and between African American and white women. Statistical analysis was by t test and χ(2) test, as appropriate.Results The phenotyping tool was applied to 1025 women with SPTBs who delivered at a mean 30.0 ± 3.2 (SD) weeks' gestation. Of these, 800 women (78%) had ≥2 phenotypes. Only 43 women (4.2%) had no phenotypes. The 281 women with early SPTBs were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all P ≤ .001). African American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared with white women (all P < .05). Gestational age at delivery decreased as the number of phenotypes that were present increased.Conclusion Precise SPTB phenotyping classifies women with SPTBs and identifies specific differences between very early and early SPTB and between African American and white women.
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Among women who gave birth before 34 weeks, 56.6% had some maternal stress or distress during pregnancy.
“In fact, some form of maternal stress or distress (i.e., stressor exposure, financial strain, perceived stress, symptoms of depression or anxiety, maladaptive coping behaviors) was present during the current pregnancy among 56.6% of women giving birth before 34 weeks (Manuck et al., 2015).”
From Childhood stress and birth timing among African American women: cortisol as biological mediator (2017) · cites this paper as Manuck et al., 2015
Maternal psychosocial stress is the most frequent phenotype underlying spontaneous preterm birth.
“A recent study examining nine diverse potential PTB phenotypes (e.g., inflammation, decidual hemorrhage) among 1,025 women identified maternal psychosocial stress as the most common phenotype underlying spontaneously-initiated PTB (Manuck et al., 2015).”
From Childhood stress and birth timing among African American women: cortisol as biological mediator (2017) · cites this paper as Manuck et al., 2015
The findings support prior work linking stress and distress to birth timing and add to work implicating childhood stress specifically.
“Findings lend support to a large literature linking various forms of stress and distress to birth timing (e.g., Manuck et al., 2015) and add to a small literature implicating childhood stress in particular (Christiaens et al., 2015; Smith et al., 2016).”
From Childhood stress and birth timing among African American women: cortisol as biological mediator (2017) · cites this paper as Manuck et al., 2015
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- Authors
- Manuck, T. A., Esplin, M. S., Biggio, J., Bukowski, R., Parry, S., Zhang, H., Huang, H., Varner, M. W., Andrews, W., Saade, G., Sadovsky, Y., Reddy, U. M., & Ilekis, J.
- Affiliations
- Intermountain Healthcare (US)
- University of Alabama at Birmingham (US)
- The University of Texas Medical Branch at Galveston (US)
- University of Pennsylvania (US)
- Yale University (US)
- University of Pittsburgh (US)
- National Institutes of Health (US)
- Corresponding author
- Manuck, Tracy A.
- ORCID
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 212
- Issue
- 4
- Pages
- 487.e1-487.e11
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC4456184
- OpenAlex
- W2092576140
- Cited by
- 132
- References
- 22
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 6 · 2021: 18 · 2020: 19 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 11 · 2015: 7
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD050062, U01HD050078, U01HD050088, K23HD067224, U01HD050094, U01HD050080)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Development and Preterm Care
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Keywords
- spontaneous preterm birth, very preterm birth, early preterm birth, gestational age at delivery, racial disparities, African American women, maternal stress, cervical incompetence, infection and inflammation, placental insufficiency, premature rupture of membranes, maternal comorbidities, family risk factors
- MeSH terms
- Adult, Female, Gestational Age, Humans, Phenotype, Pregnancy, Prospective Studies, Risk Factors, United States, Case-Control Studies, Premature Birth
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