Risk factors for preterm birth: systematic literature review

Cristina Maria de Jesus Serralha Castanho Pires1, Cátia Sofia Andrade Teixeira2, Maria Otília Brites Zangão3

1,2Unidade Local de Saúde Arco Ribeirinho. Hospital Nossa Senhora do Rosário. Serviço de Urgência Obstétrica e Ginecológica/Bloco de Partos. Barreiro, Portugal. 3Universidade de Évora. Comprehensive Health Research Centre (CHRC). Escola Superior de Enfermagem São João de Deus. Évora, Portugal.

 Introduction

Preterm birth (PPT), which is defined as that which occurs before the 37th week of gestation1, represents one of the main challenges to maternal and neonatal health on a global scale.

The overall prevalence of preterm birth varies significantly across geographic regions, ranging from 5% to 18%, with a higher prevalence in low- and middle-income countries. In developed countries, the rate is between 8–12%, whereas in developing countries, it can reach 15–18%. Socioeconomic factors, such as low educational level (less than a secondary education) and insufficient family income (of less than twice the minimum wage), contribute substantially to this epidemiological variation2.

The significant incidence and adverse impact of preterm birth on neonatal morbidity and mortality prioritize its prevention. This is a problem that transcends biological scope, and it carries profound economic, social and emotional implications for families and health systems2 .

Because it is a multifactorial phenomenon, preterm birth is influenced by a wide range of factors, including the clinical and obstetric conditions of the pregnant woman, sociodemographic aspects, behavioral factors, psychological conditions and environmental exposures.3,5 .

The early and accurate identification of these risk factors is essential for implementing targeted interventions that can prevent or delay preterm birth, thus minimizing its harmful effects1. In this context, prenatal care plays a central role in providing space for personalized surveillance, adequate guidance and early intervention6 .

Among the professionals who make up the multidisciplinary prenatal care team, the Nurse Specialist (we use the term obstetric nurses throughout the text) plays an indispensable role in Maternal and Obstetric Health Nursing. This professional, by combining technical-scientific skills with the ability to establish bonds of trust with pregnant women/families, is strategically positioned for identifying the predictive factors of preterm birth7.

Through continuous and systematic evaluations during prenatal care, an obstetric nurse can recognize warning signs, track risk conditions and provide guidance to pregnant women and families. In addition, obstetric nurses contribute to strengthening health education to promote the active role of women in both their own health and in the healthy development of the fetus7.

However, despite the relevance of the practice of obstetric nurses, there is a gap in the literature regarding the systematization of risk factors for preterm birth on the basis of recent scientific evidence. The systematization of these factors is essential for improving the quality of prenatal care and developing more effective clinical protocols.

This systematic literature review aims to identify the risk factors associated with preterm delivery in the scientific literature.

Method

This systematic review of the literature follows the methodological guidelines of the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) protocol.

The preparation of a systematic literature review should follow a set of rigorous steps, namely, the (1) definition of the research question; (2) development of the research protocol; (3) determination of the inclusion and exclusion criteria for the studies; (4) development of a database search strategy; (5) selection of studies; (6) evaluation of the quality of the studies; (7) data extraction; (8) data synthesis and evidence-quality evaluation; and (10) dissemination of results among the scientific community8.

The review protocol used was PRISMA9. The protocol was recorded on the OSF platform: https://doi.org/10.17605/OSF.IO/UGNXM

Research Question

To prepare this review, defining a research question was essential. As shown in Table 1, the initial question followed the acronym PICo, where P = pregnancies, I = the risk factors for preterm delivery, and Co = prenatal care.

Following topic selection and as a response to the objective of this systematic literature review, the following research question was defined: What are the risk factors for preterm delivery (I) in those pregnancies (P) monitored in prenatal care (Co)?

Table 1 - Criteria For the Formulation of the PICo Question.

PICo

Element

Description

Application

P

I

 

Co

Population

Phenomenon of interest

Context

What is the study population?

What is the phenomenon of interest in the study?

 What is the context of the study?

Pregnant women

The risk factors for preterm delivery

 Prenatal care

Source: Adapted from Vilelas8.

 Eligibility Criteria

In the preparation of a systematic literature review, strict inclusion and exclusion criteria should be previously established so that the most relevant studies to the topic under study can be selected and included8 .

To guide the research and selection of scientific literature for this review, the following inclusion criteria were established: full-text published studies (free access through institutional databases) in English, Spanish and Portuguese, and studies of quantitative methodology published between 2014 and 2024.

The technical inclusion criteria were as follows: studies that investigated the risk factors, predictors or other factors associated with preterm delivery in obstetric populations, including primary studies (cohort, case–control, clinical trials, cross-sectional) and studies with clearly described methodologies.

The exclusion criteria (applied after the initial inclusion) were as follows: studies with incomplete data or inadequate methodology; studies with overlapping or duplicate populations; studies focused exclusively on postdiagnosis therapeutic interventions; studies with exclusively neonatal populations; narrative reviews and opinion articles; and duplicate articles (which were only analyzed once, with the most complete publication selected for inclusion).

Database Search Strategy

Once the study problem was clearly defined and the research question was formulated, the next step was searching for studies using scientific databases such as CINAHL (Cumulative Index of Nursing and Allied Health Literature), MEDLINE (International Literature in Health and Biomedical Sciences), PMC (PubMed Central) and VHL (Virtual Health Library). This study was conducted in December of 2024, and the following Health Sciences Descriptors (DeCS) and indexed terms (MeSH) were applied in English using Boolean equations: (midwives OR nurse midwives) AND (labor, premature OR obstetric labor, premature) AND (risk factors) AND (prenatal care). The search strategy was applied by combining the descriptors with the Boolean operators AND and OR (Table 2).

Table 2 - Database search strategies.

Database

Search Strategy

MEDLINE

 

CINAHL

 

PMC

 

BVS

(MH "Labor, Premature" OR "preterm labor") AND (MH "Risk Factors" OR "predictive factors") AND (MH "Prenatal Care")

(MH "Labor, Premature" OR "preterm labor") AND (MH "Risk Factors" OR "predictive factors") AND (MH "Prenatal Care")

(preterm birth OR premature labor) AND (risk factors OR predictors) AND (prenatal care OR antenatal care)

parto prematuro OR nascimento pré-termo) AND (fatores de risco OR preditores) AND (cuidado pré-natal)

Study Selection Process

The process of identification, screening and selection was independently conducted by two reviewers, who used Rayyan® software for reference management and the removal of duplicates. In cases of disagreement, a third reviewer was introduced for resolution by consensus. Data extraction was performed using a standardized, previously tested form with independent double extraction for 100% of the sampled studies.

Evaluation of Methodological Quality

To assess the methodological quality of the articles sampled in this review, the following checklist from the Joanna Briggs Institute (JBI) was used according to each type of study identified10. Each study was evaluated by answering a series of questions with the options “Yes”, “No”, “Unclear” or “Not Applicable”. Studies that met 75% or more of the criteria presented in the respective grids were included11.

The level of evidence was classified according to the criteria of the Oxford Center for Evidence-Based12, which was used to rank the studies into categories ranging from 1 (strongest evidence) to 5 (weakest evidence).

The data were synthesized in a narrative form because of the methodological heterogeneity of the included studies, which precluded conducting a meta-analysis. The synthesis was focused on the identification and categorization of risk factors, considering the consistency of the findings among the studies.

Figure 1 - Study Selection Diagram (PRISMA).

Results

A total of 272 studies were identified in the databases. After the removal of duplicates (n = 12) and application of the eligibility criteria, 31 eligible studies were retained. After a full reading and evaluation of their methodological quality (> 75% of the JBI criteria), 21 studies were subsequently included in the final analysis.

The study sample included 8 cohort studies (level of evidence 2), 4 cross-sectional studies (level of evidence 4), 3 case–control studies (level of evidence 3), 3 observational studies (level of evidence 4), 2 randomized clinical trials (level of evidence 1), and 1 systematic review with meta-analysis (level of evidence 1). Table 3 presents a summary of the evidence evaluation and methodological quality.

 Table 3. Summary of the evidence evaluation and methodological quality.

Type of Study

N of studies

JBI Average Quality (%)

Level of Evidence

Main Limitations Identified

Randomized Clinical Trials

2

90%

1

Limited sample size

Cohort Studies

8

81%

2

Loss to follow-up, selection bias

Case–Control Studies

3

78%

3

Recall bias, selection of controls

Cross-sectional studies

4

76%

4

Causality cannot be established

Observational Studies

3

79%

4

Absence of a control group

Systematic Review

1

95%

1

Heterogeneity between studies

The included studies originate in 12 different countries: the United Kingdom (n=4), the Netherlands (n=3), Canada (n=3), Ethiopia (n=2), China (n=1), France (n=1), Iran (n=2), South Africa (n=1), Thailand (n=1), Somalia (n=1), Brazil (n=1), and multiple countries (n=1). The sample size ranges from 40 participants (pilot study) to 23,940 participants (meta-analysis).

The main risk factors are as follows: cervical changes (length <25 mm) were identified in 8 studies; a previous obstetric history of prematurity was identified in 12 studies; hypertensive pregnancy complications was identified in 9 studies; urogenital infections were identified in 7 studies; adverse socioeconomic factors (low income, lack of social support, etc.) were identified in 11 studies; late onset of prenatal surveillance was identified in 6 studies; multiple pregnancies were identified in 5 studies; and the premature rupture of membranes was identified in 8 studies.

To provide the reader with a better understanding, the process of collection and selection of studies is represented by the PRISMA flowchart (Figure 1). The entire process was performed by two independent reviewers, and in cases where disagreements occurred, a third reviewer was introduced as a tiebreaker.

 

Source: Adaptation of the PRISMA 2020 model.

Figure 1 - Study Selection Diagram (PRISMA).

Extraction of the Study Data

The data were extracted into a synthetic table to organize the information obtained and to answer the research question. The following data were systematically extracted: authors, study country, methodology design, objective, participants, main results and conclusions (as detailed in Table 4).

Table 4 - Characteristics of Sampled Studies

Title/Authors/Year/Country

Study Design/Main Objective

Participants/Sample

Main Results

Conclusions

The Association Between Unintended Pregnancy and Perinatal Outcomes in Low - Risk Pregnancies. A

Retrospective

Registry Study in the

Netherlands13

(2024, Paises

Low)

 

Design: Retrospective cohort study

Objective: To explore the association between unplanned pregnancies and perinatal outcomes in low-risk pregnancies.

n = 9.803

pregnant women with low-risk pregnancies and unplanned pregnancies

Criteria: Singleton low-risk pregnancies, complete data in the registry

An unplanned pregnancy can increase the risks for the mother and the newborn, emphasizing the importance of providing adequate support to women facing an unplanned pregnancy.

This study concludes that unplanned pregnancies, especially those

that end in birth, are associated with higher risks of adverse outcomes and adverse perinatal conditions, such as prematurity and low birth weight, although their

association with cesarean section is inverted. Unplanned pregnancy was also

associated with the late onset of prenatal surveillance, but the late onset of surveillance

did not mediate the relationship between pregnancy intention and perinatal outcomes.

This study highlights the importance of raising the awareness of health professionals and political leaders to free them from prejudice to offer individualized prenatal care rather than judgement.

Models of antenatal care to reduce and prevent preterm birth: a systematic review and meta-analysis14

(2016, Reino Unido)

Design: Systematic review containing meta-analysis of randomized clinical trials

Objective: To evaluate the effectiveness of prenatal care models that are designed to prevent and reduce preterm birth.

n = 22.437

Pregnant women in 15 clinical trials

Criteria: Randomized trials, prenatal interventions, and reported perinatal outcomes.

Alternative models of prenatal care significantly reduced the probability of preterm birth compared to that under regular specialized care.

This study concludes that more research and evidence is needed to understand the multicausal and complex nature of preterm birth and to support the development of an effective care structure.

Development and validation of a prognosis risk score model for preterm birth among pregnant women who had antenatal care visit, Northwest, Ethiopia, retrospective follow-up15 (2023, United Kingdom)

Design: Retrospective cohort study

Objective: To develop and validate a risk scoring model for preventing preterm birth in pregnant women through prenatal surveillance.

n = 1.132

Pregnant women were selected by simple random sampling

Criteria: At least one prenatal surveillance visit, complete data available.

This study revealed a prevalence of 10.9% for preterm births, identified six main risk factors (age <20 years, late onset of prenatal surveillance, unplanned pregnancy, short interval between pregnancies, pregnancy-induced hypertension and prenatal hemorrhage) of delivery and validated an effective predictive model with an AUC of 0.82.

This study reveals the possibility of predicting preterm delivery using a simple prediction model constructed from maternal characteristics identified through anamnesis and a hemoglobin test.

It also shows that the calculation of risk score on the basis of predictive factors is effective compared to that of more complex models and can be routinely used to improve prenatal care.

Effectiveness of score card-based antenatal risk selection, care pathways, and multidisciplinar consultation in the Healthy Pregnancy 4 All study (HP4ALL): study protocol for a cluster randomized controlled trial16

(2015, Países Baixos)

Design: Cluster-randomized clinical trial

Objective: To evaluate the effectiveness of scorecard-based risk selection (R4U) in conjunction with prenatal care and multidisciplinary consultations.

n = 7.000

Randomly allocated municipalities: intervention (n = 3,500) and control (n = 3,500)

Criteria: Pregnant women in participating municipalities who have given informed consent.

The implementation of risk selection based on the R4U scorecard, in conjunction with personalized care methods and multidisciplinary consultations, has the potential to improve perinatal outcomes in vulnerable populations, although its effectiveness depends on factors such as the adherence and feasibility of the intervention.

This study concludes that the developed model is an effective tool for predicting preterm birth through widely available and easily accessible maternal characteristics. An internal validation and performance analysis shows that the model has excellent discrimination ability and can be used in clinical settings to improve pregnancy management and reduce the risk of preterm delivery. The simplicity of

This model is a viable option for developing countries or locations with limited resources, where advanced diagnostic technologies may not be available. The use of this model can help save lives through the timely identification of women at risk and the provision of adequate care to prevent the neonatal complications associated with preterm birth.

Factors associated with preterm birth at Wachemo University Nigist Eleni Mohammed memorial hospital, Southern Ethiopia: case–control study17

(2021, Etiópia)

Design: Case–control study

Objective: To identify the factors associated with premature birth among women treated at the Memorial Hospital.

n = 213

71 cases (premature births) and 142 controls (term births)

Criteria: Single births, complete data, and informed consent.

The results show that the premature rupture of membranes, pregnancy-induced hypertension and multiple pregnancies increase the risk of preterm birth, while urban residence and adequate prenatal care reduce this risk. In addition, 36.6% of the preterm infants sampled died during the study.

The study identified that the urban residence, prenatal care, the premature rupture of membranes,

pregnancy-induced hypertension and multiple pregnancies are all factors that

increase the risk of premature birth. In addition, neonatal mortality among

prematurity is significant, and respiratory failure is the main cause of death. Prenatal surveillance needs to be improved, access to care needs to be promoted, and complications during pregnancy need to be detected early to reduce the occurrence of preterm birth and improve neonatal outcomes.

The Use of a Brief Antenatal Lifestyle Education Intervention to Reduce Preterm Birth: A Retrospective Cohort Study18

(2022, China)

Design: Retrospective cohort study

Objective: To evaluate the effectiveness of a brief educational intervention on lifestyle during prenatal surveillance to reduce preterm birth.

n = 351

Pregnant women were monitored during prenatal surveillance

Criteria: Participation in an educational program, complete follow-up.

An educational intervention regarding lifestyle (healthy diet, exercise and stress reduction) during prenatal surveillance significantly reduces the rate of preterm birth and improves maternal health and perinatal outcomes.

This study identified that participation in a health education seminar on lifestyle is associated with a reduced risk of preterm birth. Participation

in the first trimester was the most effective. However, for older women

with histories of cesarean section or assisted reproduction techniques, the impact of the seminar was limited. Further exploratory research is needed to better understand these results. This study also suggests that more flexible prenatal care options should be explored for multiparous women to improve adherence and clinical outcomes.

A continuity of care program for women at risk of preterm birth in the UK: Process evaluation of a hybrid randomized controlled pilot trial19

(2023, Reino Unido)

Design: Randomized clinical trial (RCT).

Objective: To evaluate the implementation and processes involved in a continuity of care program for women at risk of preterm birth.

n = 168 Pregnant women who were at risk of premature birth in the United Kingdom.

The continuity of care program was well accepted by women at risk of preterm birth, and it had high adherence and satisfaction. Its implementation was effective, although there were some logistical challenges. The participants reported a positive experience with greater emotional support and confidence in care. Although the study did not focus on health outcomes, it suggested that the proposed intervention could help reduce the risk of preterm birth.

This study concludes that the POPPIE model is effectively implemented in a satisfactory and sustainable manner, with good acceptance among women and health professionals. However, due to the pilot nature of the study and the

limited sample size, there was no significant difference in the results

of preterm birth among the care models. This study highlights the importance of larger-scale trials with more statistical power to better evaluate clinical outcomes, and suggests that future research should explore

continuity models in populations with greater social vulnerability and risk.

Repeated cervical length measurements for the verification of short cervical length20 (2017, Netherlands).

Design: Secondary retrospective cohort study.

Objective: To evaluate whether repeated cervical length measurement improves the identification of pregnant women at increased risk of spontaneous preterm delivery.

n = 12,358 Pregnant women with singleton pregnancies, no history of preterm delivery before the age of 34and with a transvaginal ultrasound to measure cervical length

Repeated measurement of cervical length in pregnant women without a history of preterm birth did not improve the identification of the risk of spontaneous preterm birth before 37 weeks.

The study concludes that a single measurement of cervical length is sufficient to stratify the risk of preterm birth without the need for a second assessment.

The Biomarkers for Preterm Birth Study — A prospective observational study comparing the impact of vaginal biomarkers on clinical practice when used in women with symptoms of preterm labor21

(2019, Reino Unido).

Design: Observational prospective cohort study. Objective: To evaluate the impact of vaginal biomarkers, such as quantitative fetal fibronectin (fFN) and placental α-microglobulin-1 (PAMG-1), in clinical practice, particularly for women with symptoms of preterm labor

n = 128 Women with symptoms of preterm labor between 24 and 34 weeks of gestation.

The use of vaginal biomarkers, especially quantitative fetal fibronectin, may reduce hospital admissions in women with symptoms of preterm labor, but there no significant impact on the use of corticosteroids/magnesium sulfate or on the incidence of preterm delivery was detected, and there were false-negative results when α-microglobulin-1 was used.

This study suggests the adoption of quantitative fFN with adjustments in the admission threshold values and warns about the low sensitivity of PAMG-1, thus highlighting the potential of combining biomarkers with clinical data to improve prenatal monitoring.

Evaluation of the impact of fetal fibronectin test implementation on hospital admissions for preterm labor in Ontario: a multiple baseline time-series design22

(2014, Canadá)

Design: Retrospective cohort study based on a time series analysis.

Objective: To evaluate the impact of the implementation of the fetal fibronectin (fFN) test on the rates of hospital admissions for preterm labor in Ontario.

Pregnant women at risk of preterm labor, whose hospital admissions were recorded in all of the hospitals in Ontario that implemented the fetal fibronectin (fFN) test for detection of risk of preterm birth, between 2002 and 2010.

Reduction in hospital admissions for preterm labor in Ontario. Specifically, the admission rates decreased significantly after the implementation of the test compared to those prior to the implementation of the test, with a reduction of approximately 10% in preterm labor admissions.

In the hospitals that were analyzed individually, approximately 55%

showed a significant reduction in admissions for preterm labor 12

months after the implementation of the fFN test.

This study concluded that the implementation of the fFN test in Ontario resulted in a significant, albeit small, reduction in hospital admissions for preterm delivery. The evaluation suggests that the fFN test can be an effective tool to improve the clinical management of women at risk of preterm birth. However, further studies are needed to evaluate the additional benefits of the program, especially in relation to a more targeted implementation and the consideration of other factors of the health system.

Relationship between Revised Graduated Index (R-GINDEX) of Prenatal Care Utilization and Preterm Labor and Low Birth Weight23 (2014, Canadá)

Design: Retrospective cohort study.

Objective: To evaluate the relationship between the adequacy of prenatal surveillance, as measured via the Revised Graduated Index (R-GINDEX), and the occurrence of preterm birth and low birth weight.

n= 420 Women aged between 18 and 35 years, with a single fetus, an absence of physical and psychological illness and an available clinical record, who gave birth at the Ghaem Hospital, Iran, in 2010. Subjects were classified into three groups based on the Revised Graduated Index (R-GINDEX) for prenatal surveillance:

inadequate care, adequate care and intensive care.

The results of the study revealed that the highest percentage of mothers (51.9%) received adequate care (5-8 visits). On the other hand, compared to the adequate and intensive care groups, the inadequate care group had a 3.93 times higher risk of preterm birth and 2.53 times higher risk of low birth weight.

This study concluded that the amount of prenatal care, as measured by the R-GINDEX, is an important factor in reducing the risk of preterm birth and low birth weight of NBs. Women who received inadequate care (less than 5 prenatal surveillance visits) had a higher risk of adverse outcomes, and those who received adequate care (between 5 to 8 prenatal surveillance visits) or intensive care (more than 8 prenatal -natal) showed significant benefits for maternal and neonatal health.

Accuracy of fetal fibronectin for the prediction of preterm birth in symptomatic twin pregnancies: a pilot study24

(2018, França)

 

Design: Prospective cohort study.

Objective: To evaluate the accuracy of the fetal fibronectin (fFN) test, either alone or in combination with the measurement of cervical length, in the prediction of spontaneous preterm birth in symptomatic twins.

n = 40 Women pregnant with twins, with a gestational age of between 24 and 33 weeks + 6 days and with symptoms of preterm labor

The fetal fibronectin test showed high specificity and a negative predictive value for predicting premature birth within 7 days, while the measurement of the cervical length alone had low predictive accuracy, and its combination with the fFN test did not significantly improve its predictive ability.

 

The study concluded that the fFN test was the best predictor of spontaneous preterm birth in symptomatic twin pregnancies, especially within 7 days, while its combination with the cervical length did not improve the predictive accuracy, which requires confirmation in larger studies.

Combination of selected biochemical markers and cervical length in the prediction of impending preterm delivery in symptomatic patients25

(2016, Canadá)

 

Design: Prospective, observational and analytical study.

Objective: To evaluate the usefulness of different biochemical markers (fetal fibronectin - fFN, phosphorylated insulin-like growth factor binding protein - phIGFBP-1, interleukin 6 - IL-6, soluble interleukin 2 receptor - IL-2R, and protein C-reactive - CRP) in combination with cervical length measurement via transvaginal ultrasonography for the prevention of preterm birth (PTD) in symptomatic women to identify early those at risk of imminent preterm birth

n = 58 Pregnant women with gestational ages of between 24 and 36.6 weeks who presented symptoms of threatened preterm delivery

This study showed that the combination of tests for fetal fibronectin (fFN), interleukin 6 (IL-6), phosphorylated insulin-like growth factor binding protein (phIGFBP-1), C-reactive protein (CRP) and the of the length of the cervix can be used to effectively predict imminent premature birth in symptomatic women.

This study concluded that the predictive model that combines phIGFBP-1, positive fFN, cervical length < 21.5 mm, elevated IL-6 in the cervicovaginal fluid (FVC) and elevated serum CRP was highly effective in predicting preterm birth within 14 days, surpassing the accuracy of individual tests. However, this study was limited by its small sample size and single focus on high-risk women, suggesting the need for future studies on the cost–benefit ratio in low-risk populations.

Risks of preterm labor among women who attend public antenatal care clinics26

(2018, África do Sul)

 

Design: Quantitative study taking an exploratory, retrospective and descriptive approach.

Objective: To identify the causes of preterm birth in women attending public prenatal surveillance clinics in the East London area, in the Buffalo City Metropolitan Health District, and in the Eastern Cape province of South Africa.

n= 50 randomly selected women who had preterm births in 2014 and attended public prenatal surveillance clinics in East London

This study identified the following risk factors for premature birth: unemployment, marital status - single, lack of social support, history of abortion or obstetric complications, tobacco, alcohol, hypertension and untreated urinary tract infections, inadequate weight gain and growth restricted fetus.

This study concluded that the identification of women at risk of preterm birth is crucial for providing high-quality prenatal surveillance to prevent or at least prepare for preterm delivery. However, clinical records indicate that many women did not receive adequate surveillance, and that there were flaws in examinations and documentation. Adequate prenatal surveillance can significantly reduce premature births. It is essential to sensitize nurses to this reality in order to improve care practices and reinforce health education interventions and evidence-based research.

Epidemiology and Related Risk Factors of Preterm Labor as an Obstetrics Emergency27

(2017, Irão)

 

Design: Analytical observational study taking a retrospective approach.

Objective: To identify the epidemiological and clinical risk factors associated with preterm labor.

n= 200 Pregnant women who were admitted with the diagnosis of preterm labor in a reference hospital in Iran.

This study identified significant risk factors for preterm birth, such as sexual intercourse in the previous week, multiparity, a short interval between births, preeclampsia, fetal anomalies, the rupture of membranes, and hypertension. Preventive factors included iron intake, cephalic presentation of the fetus, adequate prenatal surveillance, a history of cesarean section and adequate maternal weight. The multivariate regression analysis highlighted multiparity and recent sexual intercourse as the strongest risk factors, while iron intake and cephalic presentation of the fetus were found to be the most significant preventive factors.

This study concluded that factors such as recent sexual intercourse, multiparity, preeclampsia, hypertension, fetal anomalies and ruptured membranes increase the risk of preterm birth. On the other hand, factors such as iron intake, cephalic presentation of the fetus, controlled systemic diseases, a history of cesarean section, adequate prenatal surveillance and adequate maternal weight decrease this risk. Controlling these factors can help reduce the rate of premature births and their consequences for health and society.

Effectiveness of the Preterm Labor Prevention Program for High-Risk Pregnant Women: A Randomized Controlled Trial28 (2023, Thailand)

Design: Randomized clinical trial (RCT).

Objective: To develop and test the effectiveness of a Premature Labor Prevention Program (PLPP) in high-risk pregnant women.

n= 66 High-risk pregnant women, aged 15 to 49 years, who attended prenatal surveillance clinics in northeastern Thailand.

They were randomly divided into two groups:

n = 32 experimental group and n = 34 control group.

Although there were no statistically significant differences in preterm birth rates, the experimental group showed significant improvements in knowledge, attitudes and self-care practices, suggesting a positive impact of the program in reducing these rates.

This study concludes that the Premature Labor Prevention Program is effective in improving self-care and reducing premature birth in high-risk pregnant women, and it is a valuable tool for health professionals depending on training and future research.

The implementation of this program is a valuable tool for obstetric nurses, and it helps them to identify high-risk women and improve prenatal surveillance.

Maternal Risk Factors Associated with Preterm Births among Pregnant Women in Mogadish29 (2022, Somalia)

 

Design: Case–control study.

To investigate the maternal risk factors for preterm birth in Mogadishu, Somalia.

Objective: To identify target areas for future evidence-based interventions.

 

n = 499 newborns, n = 70 cases of preterm birth and n = 429 full-term controls

Premature birth in Mogadishu, Somalia is associated with factors such as a history of preterm birth, preeclampsia, obstetric complications and female genital mutilation. Adequate prenatal surveillance, vaccination, supplementation and monitoring during pregnancy reduces the risk of preterm birth. FGM was highlighted as an unexplored risk factor requiring further research.

This study highlighted the high prevalence of prematurity in Mogadishu and identifies risk factors such as lack of prenatal surveillance, female genital mutilation (FGM), obstetric complications and anemia. It suggests that improving access to prenatal care, health education and training of health institutions can reduce the rates of preterm birth and improve the capacity of care through the identification and treatment of obstetric complications.

Prevalence and risk factors related to preterm birth in Brazil30

(2016, Brasil)

Design: Analytical cross-sectional study.

Objective: To investigate the rates and factors associated with preterm birth in Brazil, addressing both spontaneous births and those births induced by health professionals.

 

n = 23,940 hospital births in various regions of Brazil.

The preterm birth rate in Brazil was 11.5%, with 60.7% being spontaneous and 39.3% being induced (mainly through elective cesarean sections). The risk factors for spontaneous preterm birth included teenage pregnancy, low educational level and inadequate prenatal care. Other risk factors were previous preterm delivery, multiple pregnancy, placental abruption and infections.

In contrast, preterm birth initiated by health professionals was associated with pregnancy surveillance in private clinics, pregnancy at an advanced age, previous cesarean sections, multiple pregnancies and maternal-fetal complications.

This study concluded that the high rate of prematurity in Brazil is linked to the high rate of cesarean sections and inductions that are conducted without clear indication. To reduce prematurity, it is necessary to reduce unnecessary cesarean sections and improve access to prenatal care, especially for adolescents and women with low educational levels.

Relationship between maternal factors and preterm infant birth: a case-control study31

(2023, Irão)

 

Design: Case–control study.

Objective: To determine the relationship between certain maternal factors and premature birth.

 

n = 216 Pregnant women. n= 108 premature births (case) and n= 108 term births (control).

This study showed that factors such as history of premature birth, hypertension, preeclampsia, cesarean section, premature rupture of membranes, smoking and inadequate prenatal care, a history of abortion, curettage and previous premature births all increase the risk of preterm birth. The prevention and adequate treatment of these factors can reduce the incidence of preterm births.

This study concluded that prematurity is associated with preventable risk factors. Adequate prenatal surveillance, the early identification of pregnant women at risk and education on healthy habits are essential for reducing premature births and improving maternal and neonatal outcomes.

Maternal, reproductive and obstetric factors associated with preterm births in Mulago Hospital, Kampala, Uganda: a case control study32 (2018, Uganda)

Design: Case–control study.

Objective: To identify and describe the risk factors associated with preterm birth among women who gave birth at the Mulago Hospital in Kampala, Uganda.

 

n= 99 women with preterm birth are used as cases and n= 193 women with term birth are used as the control group.

Bivariate analysis identified the associations between preterm birth and maternal height <1.5 m, BMI >25, rural residence, and lack of prenatal surveillance as well as obstetric factors such as preeclampsia/eclampsia, the premature rupture of membranes (PROM), predelivery hemorrhaging and abdominal trauma. In the multivariate analysis, the main independent risk factors were height <1.5 m, rural residence, unemployment, lack of prenatal surveillance, PROM, antepartum hemorrhage and preeclampsia/eclampsia.

The study concluded that women with a height of <1.5 m living in rural areas without prenatal care have a higher risk of preterm birth. Factors such as PRM, antepartum hemorrhage and preeclampsia are also strongly associated. Early identification and adequate control can be used to reduce the incidence of preterm birth.

Cervical pathways for racial disparities in preterm births: the Preterm Prediction Study33 (2019, EUA)

Design: Prospective cohort study.

Objective: To investigate whether differences in cervical characteristics can explain racial disparities in preterm births.

n= 2,920 Women with singleton pregnancies who were followed-up with between 22 and 29 weeks of gestation.

Cervical length, dilatation and score and membrane protrusion were the factors associated with preterm delivery. Mediation indicated that these characteristics explained only 7% to 26% of the increased risk of preterm birth among black women. Even after adjusting for cervical length, black women still had a 55% higher risk of preterm birth compared to white women.

Among social factors, a lower educational level, low income, lack of transportation and residential stability were associated with preterm birth, whereas race and number of residence changes remained its most significant predictors.

This study concluded that black women have a shorter cervical length and greater internal dilation in early pregnancy, which are factors that increase the risk of preterm delivery. Although the socioeconomic factors also influenced cervical characteristics, they did not fully explain the racial differences that were observed. However, cervical characteristics partially mediated the relationship between race and preterm birth, contributing to racial disparities in preterm births.

Discussion

This systematic review identified multiple risk factors for preterm birth that were determined across 21 studies covering 12 countries and various levels of evidence. Among the most consistently identified factors were cervical changes (length <25 mm) identified in 8 studies, a previous obstetric history of prematurity identified in 12 studies, hypertensive complications of pregnancy identified in 9 studies, urogenital infections identified in 7 studies, adverse socioeconomic factors (low income, absence of social support, etc.) identified in 11 studies and inadequate prenatal surveillance (late onset, low adherence, etc.) identified in 6 studies15,17,26,30–33. The factors identified support the multifactorial nature of prematurity. The findings confirm and expand the current knowledge on sociodemographic, clinical, and obstetric determinants as related to the quality of prenatal care and provide information to guide evidence-based preventive strategies.

The analysis reveals significant convergence with the recent international literature, in which the multifactorial nature of preterm birth is highlighted. The organization of factors into categories (sociodemographic, obstetric history, quality of prenatal care and behavioral) allows a systematic approach to the identification and stratification of risk to facilitate targeted interventions by health professionals.

The geographic variations identified in the study reflect structural disparities in the level of access to health care, confirming that the socioeconomic context significantly influences obstetric outcomes. The methodological diversity of the sampled studies enriches the understanding of the phenomenon, although it limits direct comparisons.

Sociodemographic Factors

Sociodemographic determinants play a crucial role in premature birth, and they reflect the structural inequalities in the access to health care. Current evidence demonstrates that regional variations in the percentage of preterm births primarily reflect socioeconomic and environmental differences among other risk factors34-35. These findings are in line with the guidelines for the identification and intervention of risk factors provided by the World Health Organization (WHO)6.

Maternal age serves as a prominent predictor, with teenage pregnancy being associated with biological immaturity and insufficient prenatal care15,30,36-37. Current evidence reinforces the notion that pregnant women under 20 years of age are at increased risk because of nutritional factors, socioeconomic instability and difficulties in accessing health services, and early pregnancy is often associated with a lack of access to adequate care36-37. Furthermore, pregnancy at an advanced age (>35 years) is associated with a higher prevalence of hypertensive and metabolic complications30,38, which are conditions that significantly increase the likelihood of preterm delivery30,38.

A healthy lifestyle, which includes adequate nutrition and physical activity, has a protective effect because it’s early implementation can significantly reduce the incidence of prematurity 18,39-40.

Housing conditions in rural areas, unemployment and single marital status all amplify the risk through psychosocial stress and difficulties in the access to services26,32,39-40. Recent literature41 has emphasized that adverse socioeconomic factors require integrated approaches that transcend the health sector, showing that international recommendations face structural barriers in operationalization, particularly in the context of limited resources.

The identified racial disparities33,42 transcend biological differences, fundamentally reflecting the inequalities in health care access and exposure to cumulative socioeconomic factors throughout reproductive life, which are factors that persist even in developed health systems42-43.

A low level of education limits the level of access to information on health care and promotes risk behaviors30,33, which confirms that education, as recommended by the WHO and DGS, is an essential tool 37,44.

Obstetric History

Previous obstetric history is the most robust predictor of preterm delivery, particularly previous preterm delivery, which is the strongest individual factor38,45. Hypertensive complications, multiple pregnancies17,27 and a previous cesarean section31 all substantially increase the likelihood of premature birth. A comparative analysis between Brazil and Portugal revealed that in Brazil, the prematurity rate is linked to a high rate of cesarean section and induction without proper indication30, and in Portugal, the prevalence of cesarean section is between 34 and 36%44,46. Cesarean rates that are higher than that recommended by the WHO (10–15%) do not reduce maternal or neonatal mortality37,46, which highlights the need for evidence-based practices44,46.

A history of repeated abortions26,31, previous preterm births27,29,31 and short intervals between pregnancies15,27 all confirm international recommendations that highlight obstetric history as a crucial factor38,45. The implementation of targeted preventive strategies, including rigorous monitoring, specialized and individualized prenatal care, maternal education about the necessary intervals between pregnancies and the prevention and early treatment of complications can contribute significantly to the reduction in prematurity rates6,7,44.

Quality of Prenatal Care

Quality prenatal care is a key element in the prevention of prematurity. Evidence shows that structured and multidisciplinary follow-ups significantly reduce perinatal morbidity and mortality37,44,45,47.

The late onset of prenatal surveillance prevents timely interventions, and women who begin monitoring after their first trimester present a higher risk of complications15,17,26,31-32. The DGS recommends starting prenatal surveillance with a minimum of eight consultations in the first trimester44,47.

In addition, educational interventions improve knowledge about warning signs and increase the adherence to follow-up, which results in a lower rate of prematurity18,28,39-40. Models based on personalization and continuity of care promote greater involvement and better perinatal outcomes16,19,45.

Adequate nutritional supplements, particularly iron and folic acid supplements, prevent anemia and associated complications26-27,29,37-38,44,47.

"The adequacy of prenatal surveillance is a consistent protective factor, although there are significant variations in the definition of “adequate surveillance” between contexts"14,23,27, which indicates the need for adaptation to local realities while maintaining quality standards7,37,44-45.

Assessment of Cervical Length

A cervical length of <25 mm, as measured by transvaginal ultrasound conducted between 18 and 24 weeks, is an essential predictor of prematurity and is consistently associated with increased risk20,25,33,38,49-50. The evidence shows that a single measurement is sufficient to stratify the risk in low-risk populations without the need for repeated measurements20,38. The WHO and the DGS recommend incorporating this evaluation into surveillance protocols, particularly for high-risk pregnant women36-37,44.

Biomarkers

Quantitative fetal fibronectin is the most promising biomarker for the prediction of preterm delivery, especially among symptomatic pregnant women21-22,24-25,38, because it allows for early interventions that minimize complications. The implementation of the fetal fibronectin (fFN) test has been shown to reduce unnecessary hospital admissions, thereby enabling better risk stratification and contributing to the more efficient management of hospital resources22,38.

The combination of biochemical markers with cervical length measurement increases predictive accuracy25,38, although the cost–benefit ratio in low-risk populations needs to be evaluated26,38.

Both the WHO and the DGS emphasize the incorporation of biomarkers in surveillance protocols as a clinical decision support strategy44. The current literature suggests that the integrated approach, which combines different biomarkers with detailed clinical evaluation, optimizes the identification of pregnant women at risk21,25,38,45. The incorporation of these strategies in clinical practice on the basis of robust evidence that demonstrates the superiority of a single measurement of cervical length as a risk stratification tool20,38,49 can significantly contribute to a reduction in prematurity rates and their associated complications, thereby ensuring more complete and evidence-based obstetric care45.

This review has important limitations that should be considered when interpreting the results. The predominance of studies from developed countries limits the generalizability of the findings to contexts of limited resources35,43. The methodological heterogeneity precluded a quantitative meta-analysis. The restriction to four databases and the exclusion of qualitative studies may have limited the understanding of contextual and experiential factors. Finally, the 10-year period may not reflect more recent changes in obstetric practices45.

Conclusion

The present systematic review reveals that the risk factors for preterm delivery that are recognized in prenatal care are multifactorial, and they encompass sociodemographic, obstetric, behavioral and clinical determinants as well as aspects inherent to prenatal surveillance and the use of predictive technologies such as biomarkers and cervical length assessments.

The main risk factors identified provide robust evidence for guiding the early identification of high-risk pregnancies in clinical practice. The results highlight the following concrete needs in clinical practice: the implementation of protocols for the systematic screening of the identified factors; the development of evidence-based risk stratification systems; the continuous training of professionals in the early recognition of risk factors; and the integration of predictive technologies (cervical ultrasound, biomarkers, etc.) in the clinical routine and development of targeted interventions for vulnerable populations. Furthermore, the role of the obstetric nurse is central to this preventive approach.

The systematization of evidence regarding the risk factors for preterm birth provides a solid scientific basis for the development of clinical guidelines and prenatal care protocols. The identification of those factors that are most consistently reported in the literature allows for the prioritization of resources and preventive interventions, thereby directing future research toward less studied areas, particularly under contexts of limited resources.

Authors Contributions

Study conception: Cristina Maria de Jesus Serralha Castanho Pires; Cátia Sofia Andrade Teixeira; Maria Otília Brites Zangão. Data collection: Cristina Maria de Jesus Serralha Castanho Pires; Cátia Sofia Andrade Teixeira. Data analysis and interpretation: Cristina Maria de Jesus Serralha Castanho Pires; Cátia Sofia Andrade Teixeira; Maria Otília Brites Zangão. Manuscript writing: Cristina Maria de Jesus Serralha Castanho Pires; Maria Otília Brites Zangão. Critical revision of the manuscript: Maria Otília Brites Zangão. Approval of the final version of the text: Cristina Maria de Jesus Serralha Castanho Pires; Cátia Sofia Andrade Teixeira; Maria Otília Brites Zangão.

Conflict of interest

The authors declared that there is no conflict of interest.

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Corresponding Author

Name: Maria Otília Brites Zangão

E-mail: otiliaz@uevora.pt

The Author(s) 2026.  This work is licensed under Creative Commons Attribution 4.0 International. License text for use: https://creativecommons.org/licenses/by/4.0/deed.pt_BR