Clinical opinionObstetricsThe preterm birth syndrome: issues to consider in creating a classification system
Section snippets
What is the reason for creating this classification system for preterm birth?
There are many reasons to classify preterm births and to consider various systems of classification. In this article, we focus on the decisions involved in creating a classification system for use in both population surveillance and research, so that when specific types of preterm births are discussed, studied, or compared across populations or over time, categories have consistent definitions that are widely understood and accepted.
What should the gestational age boundaries in a classification of preterm births be?
The lower and upper gestational age boundaries for defining preterm birth are variably defined. Although most geographic areas base their preterm birth rates on live births (usually excluding stillbirths), the boundaries at both ends are arbitrary. For example, if a lower gestational age boundary for defining a preterm birth is used at all, the cutoffs range from 200/7 to 22 or even 28 weeks. However, as demonstrated in the first paper in this series, the risk factors, causes, and recurrence
What information will be collected in this preterm birth classification system?
Because the system we envision will be used for research and population surveillance, we propose to classify the preterm birth at some time after delivery, with as much information available as possible. The clinical record should be the primary source of information. This record should include antepartum and intrapartum data, a record of all prior pregnancies, medical history, a patient and physician interview when preterm birth has been scheduled and where the reason for delivery is not
Should a classification system be based on phenotype or cause?
Because the cause of a specific case of preterm birth is rarely known with any degree of certainty, the authors agreed that the optimal classification system should primarily be based on the clinical phenotype, defined in this study as one or more characteristics of the mother, fetus, placenta, and the presentation for delivery. We also agree that more than 1 phenotype may be present in a single case of preterm delivery and that each phenotype present should be recorded so that the choice of a
Should risk factors be part of the classification system?
The next issue is whether risk factors should be part of the classification system. We believe that distal determinants that have no clear causal pathway to preterm birth, such as low socioeconomic status, ethnicity, smoking, or illicit drug use, should be collected in a systematic way, but should not be part of the classification system. Some classification systems include potential causes, like stress, unspecified immune, or allergic pathways, with no clear means of defining how a specific
Should pregnancy terminations and stillbirths be included?
The issue of whether to include pregnancy terminations (live born or stillborn), occurring at or above the lower gestational age limit in the classification, is controversial. Various stillbirth classification systems handle these cases differently, with many systems excluding them.22 An important question in this study is whether the reason for the termination makes a difference. Terminations occur electively but also for diverse reasons, such as severe growth retardation, absence of amniotic
How do we deal with multiple births?
Should multiple births be combined with singletons in the same classification system, or should they be considered separately? And if separately, should twins and higher-order multiples be considered together? If multiples are considered separately, should they be classified using the same system used for singletons? If a single system were used for classifying both singleton and multiple preterm births, multiplicity could be part of a preterm birth phenotype. Thus, there are many questions
What should the definition of indicated and spontaneous births be and how do we draw a distinction between them?
The most common classifications divide all live born preterm births into spontaneous vs indicated deliveries.28, 29, 30, 31, 32, 33 However, review of papers using these categories reveals that these terms are neither well defined nor consistently used. An indicated preterm birth is often defined as one that occurred because continuation of the pregnancy risked the health of the mother and/or fetus, but the degree of risk is variably defined, affected by local circumstances, and may arise from
How do we classify P-PROM, spontaneous dilation, and bleeding?
Classification of preterm (<37 weeks) premature (before the onset of labor) rupture of the fetal membranes (P-PROM) is a particularly difficult issue.31, 34 Most women with confirmed P-PROM enter spontaneous preterm labor within several hours or days, depending on the gestational age and cause of rupture, but some remain undelivered for many days without infection or other complications. In women who do not labor spontaneously, labor might be induced or a cesarean delivery performed for many
How should we define and classify indicated preterm births?
For this classification system, maintenance of the existing terminology related to what are customarily called indicated preterm births, proved confusing.35, 36, 37 Thus, we chose to define a category of (indicated) preterm birth as one in which parturition was initiated by the caregivers. This designation would apply to a preterm birth in which there was no evidence that any part of the parturitional process had begun (ie, little cervical shortening or effacement and no fluid leakage,
Other important issues
At times, signs of spontaneous parturition will occur in pregnancies complicated by preeclampsia, maternal illness, fetal growth restriction, and fetal distress, although these conditions might not be part of another obvious phenotype that led to the preterm birth.40 If preeclampsia is present in a preterm birth that follows spontaneous onset of labor, should this birth be still be classified as a spontaneous preterm birth? We agree that these births should still be classified as having signs
Definitions
For this classification system to achieve its goals, virtually all of the maternal and fetal conditions, presentations at delivery, and placental findings that may comprise a phenotype must be rigorously defined. For example, how much hydramnios must occur and when must it occur for polyhydramnios to be considered a component of the phenotype of a preterm birth?
Moving toward a classification system
From the foregoing discussion, the issues and components of a preterm birth phenotypic classification system are coming more clearly into focus. After much discussion, we agree that a preterm phenotype could be defined as having the following 4 components: (1) the presence of important maternal pregnancy related conditions; (2) important fetal conditions; (3) clinical presentation for delivery, including evidence of spontaneous parturition; and (4) placental findings. Risk factors for preterm
Conclusions
Preterm birth is a syndrome defined by time and clearly is not a distinct clinical phenotype. Births at gestational ages less than 20 weeks and many of those at 37 and 38 weeks share with births at 20-36 weeks several etiologic and prognostic features that suggest these boundaries are artificial and therefore, should be reconsidered.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 42, 43 Because the cause of many preterm births is unknown, we also believe that, at least for the near future,
References (43)
- et al.
Challenges in defining and classifying the preterm birth syndrome
Am J Obstet Gynecol
(2012) - et al.
Care for women with prior preterm birth
Am J Obstet Gynecol
(2010) - et al.
Placental inflammation and viral infection are implicated in second trimester pregnancy loss
Am J Obstet Gynecol
(2006) - et al.
Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis
Am J Obstet Gynecol
(2003) - et al.
First trimester bacterial vaginosis, individual microorganism levels, and risk of second trimester pregnancy loss among urban women
Fertil Steril
(2007) - et al.
Second trimester loss and subsequent pregnancy outcomes: what is the real risk?
Am J Obstet Gynecol
(2007) - et al.
Adverse neonatal outcomes: examining the risks between preterm, late preterm, and term infants
Am J Obstet Gynecol
(2008) Classification and heterogeneity of preterm birth
Br J Obstet Gynaecol
(2003)- et al.
Stillbirth: the way forward in high income countries
Lancet
(2011) - et al.
A placental cause of intra-uterine fetal death depends on the perinatal mortality classification system used
Placenta
(2008)
The placenta in stillbirth
Curr Diag Pathol
Epidemiologic characteristics of preterm delivery: etiologic heterogeneity
Am J Obstet Gynecol
Clinical significance and outcome of preterm prelabor rupture of the membranes: population-based study
Eur J Obstet Gynecol Repro Biol
Medically induced preterm birth: recognizing the importance of the problem
Clin Perinatol
Neonatal and maternal outcomes associated with elective term delivery
Am J Obstet Gynecol
The association between polyhydramnios and preterm delivery
Obstet Gynecol
Pregnancy outcomes following a second trimester loss
Obstet Gynecol
Prior adverse pregnancy outcome and the risk of stillbirth
Obstet Gynecol
Histologic, infectious, and molecular correlates of idiopathic spontaneous abortion and perinatal mortality
Diagn Mol Pathol
Risk factors for 14-21 week abortions: a case-control study in EuropeThe Europop Group
Hum Reprod
Association of bacterial vaginosis with a history of second trimester miscarriage
Hum Reprod
Cited by (169)
Etiologically Based Functional Taxonomy of the Preterm Birth Syndrome
2024, Clinics in PerinatologySmall vulnerable newborns—big potential for impact
2023, The LancetPlacental transcriptomic signatures of spontaneous preterm birth
2023, American Journal of Obstetrics and GynecologyDoes vaginal progesterone prevent recurrent preterm birth in women with a singleton gestation and a history of spontaneous preterm birth? Evidence from a systematic review and meta-analysis
2022, American Journal of Obstetrics and GynecologyCitation Excerpt :There are several reasons why meta-analyses evaluating the efficacy of any proposed intervention to prevent preterm birth in high-risk populations should not group women with different risk factors into a single category. They are as follows: (1) preterm birth is a complex syndrome caused by multiple etiological factors with different mechanisms of disease and significant individual heterogeneity.15–22 This is the rationale for assessing separately the proposed interventions to prevent preterm birth in multiple gestations; (2) the groups of patients with a sonographic short cervix and those with a history of spontaneous preterm birth do not overlap in clinical practice.
A cybernetic framework for predicting preterm and enhancing care strategies: A review
2021, Biomedical Engineering Advances
This project was supported by the Bill and Melinda Gates Foundation and the Global Alliance to Prevent Prematurity and Stillbirth, an initiative of Seattle Children's, and by INTERGROWTH-21st Grant ID 49038 from the Bill and Melinda Gates Foundation to the University of Oxford, for which we are very grateful.
The authors report no conflict of interest.
Reprints not available from the authors.