Risk factors for spontaneous preterm birth: results of a clinicalepidemiological study

Preterm birth (PB) is one of the most significant clinical problems facing contemporary obstetrics. The incidence of PB in developed countries is estimated to affect between 5% and 7% of all pregnancies and does not tend to decrease [1]. According to the Rosstat estimates, the incidence of PB in the Russian Federation in 2017 was 4.3%. PB is also a challenging problem for perinatal medicine due to increased risk for neonatal morbidity associated with PB.

To date, risk factors for PB are described in detail in numerous clinical guidelines, including Russian ones. So, the “Preterm birth” clinical guidelines describe 23 risk factors [2]. The MAYO Clinic guidelines contain information on 12 factors [3], there are 7 [4] of them on the Medscape medical information resource, and 27 on the US National Institute of Health website [5].

PB risk factors have been extensively investigated. To date, PubMed contains more than 7 thousand articles that mention risk factors for PB. Moreover, a large number of articles published in the last five years. However, most of them had problems with study design. For example, there was a case-control [6] or population cohort study with a cohort of only 127 women [7].

It should be noted that, as a rule, guidelines include all types of PB risk factors. This means that part of these factors is associated with other types of pregnancy complications (for example, placental abruption, severe preeclampsia, etc.). However, the current literature is lacking sufficient coverage of the evidence regarding risk factors for spontaneous PB (SPB).

However, the problem of PB risk factors is an urgent scientific issue that needs to be continued since risk factors can vary depending on socio-economic, climatic and geographical conditions, ethnic and genetic characteristics, changes in the infectious landscape, the availability of primary and specialized medical care, etc.

This study aimed to determine risk factors for spontaneous preterm birth in contemporary conditions based on a longitudinal clinical-epidemiological study.

Material and methods

This is a population longitudinal clinical-epidemiological study of 1361 pregnant women residing in the Ivanovo region, who were surveyed in 2013-2018 at early gestational ages. All study participants gave their informed consent before their inclusion in the study when registering for antenatal care in early pregnancy and were interviewed using a specially designed questionnaire. The questionnaire included assessment of social, professional, material conditions, obstetric, gynecological, and somatic history, and basic health awareness.

Pregnancy outcomes were followed, and a group of women with SPB was identified (study group; n = 73). The control group consisted of 1288 women who had a normal pregnancy and full-term birth.

Statistical analysis The rates were compared using the chi-square test, and the results were considered statistically significant at p <0.05. To quantify the various risk factors, we calculated odds ratios (OR) using the OpenEpi system: Open Source Epidemiologic Statistics for Public Health (Version 3.03, www.OpenEpi.com).

Results and Discussion

The results of the study showed that the incidence rate of SPB in the Ivanovo region was 5.36%, which was significantly higher than the average level for all PB in Russia.

The age of future parents was found to play an important role as an SPB risk factor. The age of pregnant women who developed SPB often was above 25 years (table). The father’s age beginning from the age of 30 also was a significant risk factor for SPB (Fig. 1). Thus, in contemporary conditions, the maternal age threshold was lower than it was reported in previous studies and clinical guidelines [2]. The association of increased PB risk with the age of the father has not been described in clinical guidelines [2], although some researchers have observed this relationship [8].

Some social and occupational factors increasing the risk of SPB were identified (Fig. 2). The role of smoking as a risk factor for PB has been confirmed (Fig. 2) [2].

A lower maternal educational level (secondary education) was also found to be a risk factor for SPB. Women of the study group were more likely to have secondary education. Several studies have also reported a higher risk of SPB in women with a lower educational level [8, 9].

The impact of occupational hazards on pregnancy outcomes has been repeatedly noted in various studies, but the published evidence is extremely contradictory. This is probably because countries and regions differ significantly in terms of the intensity of anthropogenic pressure and the environmental situation. So, in the Ivanovo region, the only occupational risk factor for SPB was vibration, since this is the main hazardous exposure in textile production.

Of the clinical and anamnestic risk factors for SPB (Fig. 3), a history of induced abortion was more common among pregnant women in the study group than in the control group. Women with SPB were 1.9 times more likely to have a history of vaginitis than women who had a full-term birth. Women in the study group reported a history of threatened PB 2.9 times more often than women in the control group. The same pattern was observed in a history PB. Pregnancy as a result of IVF was associated with a 5.9-fold higher risk of SPB.

One of the most important risk factors for SPB is a uterine leiomyoma. This disease is not mentioned in clinical guidelines [2]. An increased risk for PB in patients with uterine leiomyoma, which persists even after myomectomy, [11] has been described in the literature [10].

Not using contraceptives before pregnancy was demonstrated to be a PB risk factor. According to some authors [12], the use of combined oral contraceptives before pregnancy, on the contrary, was associated with an increased risk of PB.

It is important to take into account the information that the pregnant woman was born prematurely (Fig. 4). The role of this factor is confirmed by some studies [13].

The analysis of the current pregnancy course showed that some complications are risk factors for SPB (Fig. 5).

These include a threatened miscarriage in the current pregnancy, fetal hypoxia, and fetal growth restriction. The most significant risk factor for SPB is a previous episode of threatened PB.

Conclusion

Based on a population longitudinal clinical-epidemiological study of pregnant women residing in the Ivanovo region and surveyed at early gestational ages, we identified risk factors for SPB.

Our study confirmed several known PB risk factors specified in clinical guidelines [2] such as induced pregnancy, a history of PB, and smoking. Some identified factors in contemporary conditions look somewhat different. For example, the risk factor for SPB is a maternal age beginning from the age of 25, which may be due to deterioration in the health of young women of reproductive age.

Some of the factors described in the literature were not confirmed in our study, for example, low socio-economic standards of living, stressful situations, and alcohol consumption.

At the same time, new factors that increase the risk of SPB have been identified, including maternal secondary education, non-use of contraceptives before pregnancy, uterine leiomyoma and maternal history of being born prematurely.

The study findings suggest the need for continuous monitoring of PB risk factors, including using monitoring programs. An example of such a program is “Monitoring the health and quality of medical support for pregnant women and women who have completed pregnancy” (state registration certificate of computer software No. 20100614816 of 07.23.2010). Continuous updating of risk factors may be utilized to adjust antenatal care programs to correct modifiable factors.

The results of the studies can be used to develop regional reproductive health programs.