Analysis of preterm delivery risk factors - a literature review

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1 JOURNAL OF OF PUBLIC HEALTH, NURSING AND AND MEDICAL RESCUE No.4/2013 (9-15) 9 Analysis of preterm delivery risk factors - a literature review (Analiza czynników ryzyka porodu przedwczesnego przegląd piśmiennictwa) M Sulima 1 A,D, M Lewicka 1 E,F, K Wiktor 2 C, H Wiktor 1 C Author Affiliations: Abstract A preterm birth is defined as delivery between pregnancy weeks 22 and 37. It is the case for 6-15% of pregnant women. It constitutes one of the fundamental problems of modern perinatology, as prematurity and low birth weight are the causes of approximately 70% of perinatal mortality.despite considerable progress in medical science in recent years, an increase in the frequency of preterm births has been observed. At the moment, the possibilities of reducing the frequency of preterm births are associated primarily with the identification of risk factors, primary prophylaxis, the intensification of secondary prophylaxis and regionalization of perinatal care. Defining preterm delivery risk factors allows one to identify groups of pregnant women who are at greater risk of premature birth and to apply appropriate preventive measures in time. Key words - premature birth, risk factors, pregnant women. Streszczenie Poród przedwczesny definiowany jest jako poród pomiędzy 22. a 37. tygodniem ciąży i dotyczy 6 15% kobiet ciężarnych. Stanowi jeden z podstawowych problemów współczesnej perinatologii, ponieważ wcześniactwo i mała masa urodzeniowa noworodka warunkują około 70% przypadków śmiertelności okołoporodowej. Mimo postępu w naukach medycznych w ostatnich latach zaobserwowano zwiększenie częstości występowania porodów przedwczesnych. W chwili obecnej możliwości zmniejszenia częstości występowania porodów przedwczesnych związane są przede wszystkim z identyfikacją czynników ryzyka, profilaktyką pierwotną, intensyfikacją profilaktyki wtórnej, oraz regionalizacją opieki okołoporodowej.identyfikacja czynników ryzyka porodu przedwczesnego umożliwia wyodrębnienie grup ciężarnych zwiększonego ryzyka wystąpienia porodu przedwczesnego i wczesne zastosowanie odpowiedniej profilaktyki w tej grupie kobiet ciężarnych. Słowa kluczowe - poród przedwczesny, czynniki ryzyka, kobiety ciężarne. 1. Department of Obstetrics, Gynecology and Obstetrical - Gynecological Nursing, Faculty of Nursing and Health Sciences, Medical University, Lublin. 2. Department of Gynecology and Gynecological Endocrinology, Faculty of Nursing and Health Sciences, Medical University, Lublin; Authors contributions to the article: A. The idea and the planning of the study B. Gathering and listing data C. The data analysis and interpretation D. Writing the article E. Critical review of the article F. Final approval of the article Correspondence to: Magdalena Sulima MD, PhD Department of Obstetrics, Gynecology and Obstetrical - Gynecological Nursing, Faculty of Nursing and Health Sciences, Medical University, Chodźki 6 Str., PL Lublin, Poland, msulima13@wp.pl I I. INTRODUCTION n the course of the last 20 years, an increase in the frequency of preterm deliveries was observed across the world [1,2,3,4]. Delivering in the due date is a result of physiologically activated processes of the so-called common pathway, defined as a range of anatomical, physiological, biochemical, immunological, endocrinlogical and clinical occurrences in the organism of the mother or/and the foetus during childbirth. On the other hand, a preterm delivery results from incorrect processes which cause a temporary activation of one or more elements of the common pathway, the final and common element of

2 JOURNAL OF PUBLIC HEALTH, NURSING AND MEDICAL RESCUE No.4/ which is premature end of pregnancy and the birth of a premature baby [4,5,6,7]. Direct causes of preterm delivery are: spontaneous premature systolic function of the uterus muscle (around 50.0% of preterm deliveries), premature leak of amniotic fluid (accounting for around 30.0% of preterm deliveries) and premature completion of pregnancy for medical reasons (around 20% of preterm deliveries) [8]. The risk factors for preterm birth are: history of obstetric abnormalities, sociodemographic factors, intrauterine infections, pregnancy-related irregularities, genetic factors, environmental factors and using stimulants [9,10]. The purpose of this paper is to present a review of literature on the factors influencing premature deliveries. II. THE CHARACTERISTICS OF PRETERM DELIVERY RISK FACTORS One of the main risk factors of preterm delivery is a prior preterm birth in the past [4,11]. It is estimated that after one premature delivery, the risk of another is three times as high. If there have been two preterm births, the risk is six times higher. Furthermore, if there has been a delivery before the pregnancy week 28, the risk of another preterm birth is times as high [12]. Other authors have concluded that a preterm delivery increases the risk of another by 2.5 times, with the risk being inversely proportional to the gestational age at which the previous pregnancy was completed [9]. The study by Karwan- Płońska [13] showed that 48.0% of women who had preterm deliveries had a history of obstetric abnormalities (a miscarriage or preterm birth). Goldenberg et al. [14] observed the following correlation: the more preterm deliveries a woman had, the greater the risk of her having another. These authors also noted that while women who had a spontaneous delivery in the past face increased risk of the reoccurrence of a spontaneous preterm birth, women who gave birth prematurely for medical reasons also are in the risk group of possible premature birth for medical reasons. Similarly, Rouget et al. [15] observed a higher percentage of preterm deliveries in the group who had abnormalities in the past. Sociodemographic factors that increase the risk of premature birth include, among others, the age of the mother, her marital status, education, professional career, nutritional status and stress [16]. Women who are pregnant before they are 18 or after they are 35 years old are also threatened by the risk of premature completion. The increased risk of premature delivery pertaining to very young women is related to the fact that their reproductive organs are not yet fully developed. In the case of women over 35 years of age, the trouble is related to the aging of the vasculature, which leads to higher likelihood of placenta insufficiency. Smith et al. [17] reported that the mother s age below 18 and over 40 increase the risk of preterm completion of pregnancy. The study by Piekarska et al. [16] showed that among women under 18 and over 35, the percentage of preterm birth was significantly the largest. Rouget et al. [15] noted that a large percentage of preterm deliveries pertained to women over 35, yet the age of below 20 was not synonymous with the risk of preterm birth. Anholcer et al. [18], Chazan [19] and Borkowski & Mielniczuk [6] showed that single mothers give preterm births more often. Similar observations were made by Smith et al. [17]. What is more, women with lower education are in the risk group of preterm delivery [17,20]. Preterm birth migh also be related to poor housing conditions. This was pointed to by Etitler et al. [21] and Bucholc & Oleszczuk [22]. The factor that determines delivering prematurely may also be professional career. The multicentre research by Saurel- Cubizolles et al. [23] conducted in European countries showed that remaining in a standing position for over 6 hours, over 42 weekly working hours and no satisfaction with one s work increase the risk of premature births. Similarly, Bonzini et al. [24] concluded that long working hours, shift work system, remaining in standing positions for extended periods of time and being overburdened with work are all related to premature birth. The meta-analysis by Palmer et al. [25] showed that pregnant women who worked over 40 hours a week, remained in a standing position for over 4 hours daily and worked in shifts face an increased risk of preterm delivery. The literature on the subjects also makes references to the correlation between the body weight of pregnant women and the preterm delivery risk. Ehrenberg et al. [26] showed that low pre-pregnancy body weight influences earlier completion of pregnancy. Similar observations were made by Koplan et al. [27] as well as Borkowski & Mielniczuk [6], who showed that the ones to give most premature births were underweight pregnant women. In their study, Hendler et al. [28] showed that the frequency of spontaneous preterm deliveries significantly decreased along with the BMI (with BMI under 19 the frequency of preterm births was 16.6%, BMI between 19 and 24.9% %, BMI between 25 and 29.9% - 8.1%, BMI 30 to %, BMI over %). What is more, Torloni et al. [29] and McDonald et al. [30] reported the decrease in the risk of spontaneous preterm delivery among obese and very obese women. However, a crucial fact is that obese pregnant women are more frequently observed to have: foeti with congenital defects, preeclampsia, hypertension and diabetes, which leads to a premature completion of pregnancy for medical reasons [28,31]. Stress is a widely acknowledged risk factor of premature birth [4,32]. Two mechanisms of the impact of stress on the duration of pregnancy have been defined; namely a direct and indirect one. Direct (physiological) mechanism consists in a

3 JOURNAL OF PUBLIC HEALTH, NURSING AND MEDICAL RESCUE No.4/ stressful situation triggering a specific reaction, activating the structures of nervous, immune and endocrine system. Indirect (behavioural) mechanism causes the pregnant woman to, as a result of stress, engage in various health-related behaviours (diet, stimulants) [33]. As Copper et al. [34] reported, stress doubles the risk of premature delivery. Similarly, Biernacka & Hanke [35], Goldenberg et al. [36], Kramer et al. [37] and Cardwell [38] observed increased risk of premature completion of pregnancy resulting from the stress experienced by the mother. A significant part in the etiopathogenesis of premature births is played by infections. The main reason for premature deliveries is an intrauterine infection, which may be contracted vaginally from peritoneal cavity via Fallopian tubes, haematogenously via placenta or iatrogenically. Infections via ascending tracts are most common, which may lead to premature systolic function of the uterus or rupture of foetal membranes, as a consequence of which a premature birth may occur [39]. Gomez et al. [40] analysed the results of 13 studies on the impact of amniotic fluid on pregnant women threatened by a premature delivery. The results of a bacteriological examination of amniotic fluid were positive in the cases of pregnant women who showed no clinical symptoms of infection during examination. Later on, larger percentages of chorioamnionitis (42.2%), spontaneous rupture of membranes (19.6%) and decreased effectiveness of tocolytic treatment (62.0%) were observed among those women. Reroń et al. [41] quoted Divers and Lilford [42] saying that infections may cause as many as 40.0% of premature deliveries. The occurrence of inflammatory lesions was recorded in 19.0%-74.0% of the placentas from premature births. The study by Ville et al. [43] showed that the inflammation of foetal membranes was the case in 75.0% of the premature deliveries. However, the study by Reroń et al. [41] showed increased percentage of pathogenic bacterial flora in the cervix of the pregnant women threatened by a premature birth with a ruptured amnion in comparison to those whose amnion remained in proper condition. Bacterial vaginosis is a significant independent risk factor of premature births [44]. The study by Mikhov et al. [45] showed 2.5 times as frequent bacterial vaginosis in the group of women who had premature deliveries as in the group of those giving birth in a due date. Other infections which do not affect reproductive organs and still are suggested to shorten the duration of pregnancy are: pyelonephritis, asymptomatic bacteriuria, appendicitis, pneumonia and periodontal diseases [15,36]. Cervical incompetence, placental pathology and systemic diseases suffered by the mother are also among the factors that increase the risk of premature birth. Each change in the length or width of cervix is related to the risk of premature delivery. The causes of cervical incompetence include congenital disorders, cervical trauma and functional disorders. If the cervix of a pregnant woman in her 24 th gestational week is found to be less than 25 mm long during an ultrasound test, the risk of premature pregnancy is increased [4]. Ochędalski [46] reported that if the cervix length is below 10 percentile of the gestational age, the risk of premature completion before pregnancy week 35 is increased 6 times. Bleeding related to placenta praevia or placental abruption signifies a very high risk of premature delivery [47]. A mother s illnesses also affect the course and duration of a pregnancy. Murphy et al. [48] claimed a disease of the mother has an influence on premature birth in 25.0% of cases. Karwan-Płońska [13] studied 392 women whose pregnancies concluded in a premature delivery and showed that there was a connection between preterm birth and a mother s systemic disease such as: heart conditions, hypertension, kidney diseases, gestosis (oedema and proteinuria), anaemia, lung diseases and diabetes. Goldenberg et al. [49] observed more frequent preterm births in women suffering from diabetes and hypertension. Köck et al. [50] showed there was a significant relationship between pregnant women s diabetes and preterm completion of pregnancy. Dennis [51] emphasised a significant risk of shorter pregnancy duration because of preeclampsia, whereas Rouget et al. [15] pointed to asthma, hypertension and diabetes of the mother. Other factors increasing the risk of preterm delivery include oligohydramniosis, polihydramniosis, abdominal surgeries, thyroid diseases and depression [36,52,53]. Factors related to the foetus, such as Intrauterine Growth Restriction (IUGR) and congenital defects also increase the risk of preterm delivery [4]. Multiple pregnancy is also a significant risk factor of preterm delivery. The mechanism of early completion of pregnancy is related to excessive uterus stretching, spontaneous systolic function of the uterus as well as deciding to complete the pregnancy before week 34 [4,54]. Goldenberg et al. [36] reported that 50,0% of twin pregnancies and multiple pregnancies end in premature birth. Similarly, Stock & Norman [55] claimed that the risk of preterm completion in cases of multiple pregnancies is increased. Another crucial problem is the increased preterm delivery risk in cases of implementing assisted reproductive technologies. The risk of preterm delivery in cases of IVF pregnancies is related to more frequent multiple pregnancies and greater risk of obstetric complications such as diabetes, gestational hypertension and urinary tract infections [56]. The study by Perri et al. [57] also showed increased risk of preterm delivery in cases of singleton assisted reproductive technology pregnancies. Marianowski et al. [56] claimed that the percentage of preterm births among IVF pregnancies is comparable to the percentage observed among multiple pregnancies after natural insemination. In the study by Zamłyński et al. [58], preterm

4 JOURNAL OF PUBLIC HEALTH, NURSING AND MEDICAL RESCUE No.4/ deliveries in twin pregnancies were the case in 85,0% of the studied women; the percentage related to natural pregnancies was comparable with that among assisted reproductive technology pregnancies. Preterm birth is a complex condition which occurs as a result of mutual correlation of genes and environmental factors. The result of that correlation is lower or increased risk of preterm delivery [4]. There are many pieces of indirect evidence that genetic factors do impact the pathomechanism of premature delivery. It has been observed that women who were born prematurely are in the risk group of preterm delivery. The lower the gestational age the mother was born in is, the higher the risk. Also, the risk is higher in the cases of women whose sisters delivered prematurely. What is more, preterm deliveries are more common among black women as compared to white women [4,59]. The impact of genetic factors on intrauterine infection-related preterm births has been best explored. Certain inter-individual, qualitative and quantitative differences in the expression of proteins regulating an inflammatory process may contribute to the increase is preterm birth risk (inter-individual differences may stem from, among others, the polymorphism of protein-coding genes). Genetic polymorphism consists in the co-existence of different allelic forms of a given gene in the population [4]. The literature on the subject reports studies on the impact of the polymorphism of both a mother s and a foetus s genes on the risk of preterm delivery. Arbour et al. [60] showed that carrier-state of the polymorphic allele TLR4 gene is related to decreased response to lipopolysaccharide stimulation. The study by Lorenz et al. [61] showed that the foetal carrier-state of this allele increased preterm delivery risk. A lot of attention in literature is paid to the polymorphism of IL-1 (IL-1ra) receptor antagonist-coding gene and its impact on shorter duration of pregnancy. The study by Chaves et al. [62] showed that the carrier-state of allele 2 of this gene (IL1RN*) is related to the increased preterm delivery risk. Kalinka & Bitner [63] observed that when a mother is a carrier of the polymorphic allele 2 of IL-1 (IL1RN*) receptor antagonist-coding gene, the risk of shorter gestation is increased. What is more, that study showed that coincident mother s carrier-state of at least one polymorphic IL-1ra allele and at least one polymorphic IL-6 allele causes further significant increase in the risk of premature birth (the occurrence of gene-gene interaction). Apart from the interaction between two genes, the interaction between genes and environment has also been observed to shorten gestation. Macones et al. [64] showed there is increased risk of preterm birth in case of coincidence of TNF-α gene polymorphism and bacterial vaginosis during pregnancy. Nukui et al. [65] discussed the relation between the existence of polymorphic allele of GSSTT1 glutathione S- transferase-coding gene and the risk of preterm delivery in the case of being exposed to tobacco smoke. Environmental factors penetrating the placenta may also cause a premature delivery [66]. Epidemiological tests point to the possible impact of air pollution on premature pregnancy completion. Gregoraszczuk et al. [67] discussed the role of environmental xenoestrogens as a cause of preterm deliveries. Hanke & Kalinka [68] reported that total suspended dust, nitrogen oxides, carbon monoxide and sulphur monoxide all impact the increase of preterm birth risk. Also stimulants mainly smoking and drinking alcohol have impact on preterm delivery risk. In her study, Karwan-Płońska [13] confirmed that smoking influences the frequency of preterm deliveries. Similarly, Windham et al. [69] showed that mothers who smoked over 10 cigarettes a day delivered before gestation week 35. The risk of premature delivery related to smoking was also confirmed by Burguet et al. (2004) and Resende et al. [70]. Parazzini et al. [71] showed that having more than 2 drinks a day is related to preterm delivery. Albertsen et al. [72] observed that future mothers who had 7 or more drinks a week face 3 times as high a risk of preterm birth as pregnant women who do not drink alcohol. Nevertheless, Rougetet al. [15] saw no connection between smoking or drinking alcohol and the risk of preterm delivery. III. CONCLUSIONS Defining preterm delivery risk factors allows one to identify groups of pregnant women who are at greater risk of premature birth and to apply appropriate preventive measures in time. 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