Analysis of preterm deliveries below 35 weeks' gestation in a tertiary referral hospital in the UK. A case-control survey
© Bernal et al; licensee BioMed Central Ltd. 2010
Received: 6 April 2010
Accepted: 28 April 2010
Published: 28 April 2010
Preterm birth remains a major public health problem and its incidence worldwide is increasing. Epidemiological risk factors have been investigated in the past, but there is a need for a better understanding of the causes of preterm birth in well defined obstetric populations in tertiary referral centres; it is important to repeat surveillance and identify possible changes in clinical and socioeconomic factors associated with preterm delivery. The aim of this study was to identify current risk factors associated with preterm delivery and highlight areas for further research.
We studied women with singleton deliveries at St Michael's Hospital, Bristol during 2002 and 2003. 274 deliveries between 23-35 weeks' gestation (preterm group), were compared to 559 randomly selected control deliveries at term (37-42 weeks) using standard statistical procedures. Both groups were >80% Caucasian. Previous preterm deliveries, high maternal age (> 39 years), socioeconomic problems, smoking during pregnancy, hypertension, psychiatric disorders and uterine abnormalities were significantly associated with preterm deliveries. Both lean and obese mothers were more common in the preterm group. Women with depression/psychiatric disease were significantly more likely to have social problems, to have smoked during pregnancy and to have had previous preterm deliveries; when adjustments for these three factors were made the relationship between psychiatric disease and pregnancy outcome was no longer significant. 53% of preterm deliveries were spontaneous, and were strongly associated with episodes of threatened preterm labour. Medically indicated preterm deliveries were associated with hypertension and fetal growth restriction. Preterm premature rupture of the membranes, vaginal bleeding, anaemia and oligohydramnios were significantly increased in both spontaneous and indicated preterm deliveries compared to term controls.
More than 50% of preterm births are potentially preventable, but remain associated with risk factors such as increased uterine contractility, preterm premature rupture of the membranes and uterine bleeding whose aetiology is unknown. Despite remarkable advances in perinatal care, preterm birth continues to cause neonatal deaths and long-term morbidity. Significant breakthroughs in the management of preterm birth are likely to come from research into the mechanisms of human parturition and the pathophysiology of preterm labour using multidisciplinary clinical and laboratory approaches.
Preterm birth remains a major cause of perinatal mortality and morbidity and efforts to predict and prevent its occurrence are difficult because of our lack of understanding of the biochemical mechanism of labour and the multiplicity of medical and socioeconomic factors associated with preterm delivery . The incidence of preterm birth (deliveries before 37 weeks' gestation) ranges from 6-8% in Europe, Australia and Canada [2, 3], to 9-12% in Asia, Africa and the United States [4, 5]. Preterm birth is recognised as a worldwide problem responsible for more than 80% of neonatal deaths and more than 50% of long term morbidity in the surviving infants [6, 7]. The incidence of preterm birth has remained relatively constant over the past three decades and there are worrying trends that it is on the increase [5, 8]. It is important to know whether risk factors have changed over the years and to look for new clinical and socioeconomic risks. This information is necessary to guide further research in this area. Epidemiological studies have identified a clear association between preterm birth and previous preterm delivery , preterm premature rupture of the membranes  and maternal smoking during pregnancy . However the association between preterm birth and other maternal and fetal complications of pregnancy is less consistent, due to social, ethnic and demographic differences amongst the populations studied . In this study we have carried out a detailed comparison of preterm and term deliveries in a relatively homogeneous obstetric population attending a tertiary referral maternity hospital, to highlight areas where further research or intervention is needed in order to prevent preterm birth and improve perinatal outcome.
This survey was done at St Michael's Hospital, Bristol. This is a tertiary referral maternity centre with approximately 5500 deliveries a year; preterm deliveries (under 37 weeks' gestation) accounted for approximately 8% of all births during 2002 and 2003. In this survey we have focused on deliveries between 23-35 weeks' gestation (3% of all births) because these account for most of the perinatal mortality and morbidity and so improvements in management are likely to have a strong impact on neonatal outcome. We obtained lists of all deliveries below 35 weeks gestation from the hospital database for two complete years 2002 and 2003 (n = 274). We used computer generated random numbers to draw separate samples from lists of all term babies delivered within each of the 2 years, using term: preterm ratios of 2:1 to increase power; 559 out of 8204 term babies were included. Gestational age was based either on certain dates or a dating scan. Antenatal care was undertaken by an obstetrician or community midwife or a combination of the two professionals and followed standard UK practice.
This study was approved by the Central & South Bristol Research Ethics Committee.
Initial maternal and newborn information was taken from the hospital computer databases (STORK and Vermont Oxford Network). The hospital medical records of each delivery were retrieved and analysed in detail by a trained research midwife (AMD) using a structured proforma. Information recorded was anonymised by assigning a unique project number to each delivery. Data on maternal and fetal characteristics at birth were recorded, including maternal age and gestational age at delivery, ethnicity, gestational age at booking, complications of pregnancy and delivery, birth weight, Apgar score and baby gender. A wide range of potential risk factors - smoking and drinking status before and during pregnancy, history of drug use, socioeconomic status, past obstetric history (including previous history of termination, miscarriage and preterm birth) were recorded. Maternal body mass index (BMI) at booking was calculated using weight (kg)/height (m)2. The definition of lean was BMI <20 kg/m2 and obese BMI ≥ 30 kg/m2. Data was entered into a Microsoft excel 2003 database and imported into STATA version 10 for analysis.
Comparisons between cases and controls were made using standard statistical procedures. Continuous variables were summarised by mean (SD) except for gestational age, which was not normally distributed, where the median (range) was used instead. Means were compared using unpaired Student's t-tests. For categorical variables Chi-squared tests were used and two-tailed Fisher's Exact tests for 2 × 2 tables where expected frequencies were small. A 5% level of significance was used throughout. Multiple logistic regression was used to adjust for confounding factors and compute odd-ratios.
General characteristics of the study groups.
Control (≥ 37 weeks'
Preterm (<35 weeks'
Number of deliveries
Gestational age at delivery
Median 40 (Range 37 - 42)
Median 33 (Range 23 - 34)
Mean maternal age (years)
28.8 (SD 6.04)
29.7 (SD 6.46)
Distribution of births
Maternal age and BMI
Demographic and socioeconomic parameters in singleton pregnancies.
Control (≥ 37 weeks' gestation)
Preterm (<35 weeks' gestation)
Number of deliveries
Median gestational age at delivery (completed weeks) and range
40 (Range 37-42)
33 (Range 23 - 34)
Mean maternal age at delivery (years)
28.8 (SD 6.04)
29.4 (SD 6.69)
≤ 18 years
(Comparison of proportions of mothers >39 years P < 0.001)
Body mass index
Mean BMI at booking (kg/m2)
25.03 (SD 5.29)
(n = 531)
25.8 (SD 6.71)
(n = 195)
Normal 20 - 29.9
With social problems
Smoking during pregnancy
Drinking Alcohol during pregnancy
Using drugs during pregnancy
The proportion of women with at least one social problem (low income; poor housing; unsupported or single parent) was significantly higher in the preterm than in the control group (Table 2). Smoking before conception was not associated with preterm birth (data not shown); however the proportion of women who smoked during pregnancy was significantly higher in the preterm than in the control group. The proportion of smokers in women with and without social problems was 58.2% and 19.6%, respectively. The proportions of women who consumed alcohol or admitted using any recreational drugs (cannabis, amphetamines, barbiturate, crack, cocaine, heroin, methadone, ecstasy) during pregnancy were similar in the control and preterm groups.
History of previous pregnancies
Control (≥37 weeks' gestation)
Preterm (<35 weeks' gestation)
Number of deliveries
Number of women with previous preterm delivery (≥ 20 and <37 weeks' gestation).
Termination of pregnancy (< 20 weeks' gestation)
Spontaneous miscarriage (< 20 weeks' gestation)
Pre-existing medical conditions
Pre-existing medical conditions.
Control (≥37 weeks'
Preterm (<35 weeks'
Number of deliveries
Sexually transmitted diseases
Cervical incompetence/cervical suture
Complications of pregnancy
Complications of pregnancy.
Control (≥37 weeks'
Preterm (<35 weeks'
Number of deliveries
Threatened preterm labour
Hypertension with proteinuria
Hypertension without proteinuria
Urinary tract infection
HVS B Strep.
HVS Other organisms
High Down's Risk
Reduced fetal movements
76/224 (33. 9%)
Fetal growth restriction
Large for dates
Preterm premature rupture of membranes
Prolonged rupture of membranes
Fetal complications were more frequent in the preterm group, especially oligohydramnios, followed by fetal growth restriction and fetal abnormalities (including both structural and chromosomal abnormalities) (Table 5). Preterm premature rupture of the membranes (PPROM) and prolonged rupture (> 48 hours) of the membranes were significantly more common in the preterm group.
Multivariable analysis indicated that women with pre-eclampsia were more likely to have fetal growth restriction; moreover each of the two factors was an effect modifier for the other (supported by significant interaction in logistic regression P = 0.026). For example, the association of fetal growth restriction with preterm birth was much greater in the presence of pre-eclampsia than in its absence (OR 45.4 [95% CI 5.8-354.6] versus 3.71 [1.65-8.33], respectively). Women with both premature and prolonged rupture of the membranes were the most likely to have oligohydramnios (P < 0.001). Finally, women with vaginal bleeding were more likely to have PPROM or episodes of threatened preterm labour (P < 0.001 for both).
Labour and delivery
Metabolic complications including jaundice, hypoglycaemia and hypothermia were relatively common in both control and preterm groups, although the incidence was significantly higher in the latter (data not shown). Severe complications of prematurity such as respiratory distress (56%), patent ductus arteriosus (11%), intracerebral damage (9%) and necrotising enterocolitis (4.5%) were diagnosed almost exclusively in the preterm group. There were 15 stillbirths, 21 neonatal deaths (deaths within 28 days of birth) and 6 postneonatal deaths (after 28 days) in the preterm group compared to only 2 stillbirths, 2 neonatal deaths and 1 postneonatal death in the control group. The main causes of death in the preterm group were severe prematurity, infection and congenital abnormalities; in the control group deaths were associated with congenital abnormalities.
This manuscript provides information on clinical factors associated with preterm delivery in a tertiary referral hospital in the UK. The study benefits from its relatively homogeneous ethnic population and its setting in a maternity hospital with unified management guidelines in the central delivery suite. Moreover, it highlights the main risk factors that remain associated with preterm birth, and emphasizes the need to promote research into the basic mechanisms of parturition as the best way to develop effective management for spontaneous preterm labour.
In our predominantly Caucasian population, teenage pregnancies were not significantly associated with preterm birth; however, our data confirm that older mothers have an increased risk of preterm delivery [12, 13]. A low BMI is associated with increased risk of spontaneous preterm birth  and this was reflected in our population. Previous preterm delivery is a strong risk factor for subsequent preterm birth, with a five fold higher rate of previous preterm delivery in the preterm compared to the control group; this indicates that maternal factors are important, however the mechanism remains unclear. A history of preterm delivery has long been recognised as a strong risk factor for subsequent preterm birth  and is the basis for most risk scoring systems . Moreover, our data confirm that hypertension and fetal growth restriction are major predisposing factors for elective preterm delivery [7, 16].
Episodes of threatened preterm labour were strongly associated with spontaneous preterm deliveries. Thus, spontaneous preterm labour is characterised by remarkable uterine hyperactivity. The mechanism requires further investigation but it probably results from increased sensitivity of the uterus to stimulatory agonists such as oxytocin, prostaglandins or other endogenous mediators , as well as a premature loss of inhibitory pathways involving myometrial ion channels . We have recently shown that spontaneous preterm labour is associated with increased GTP bound RHO proteins in myometrial tissue, a pathway for enhanced uterine contractility through 'calcium sensitization'. Uterine contractions are the most common presenting sign of preterm labour but in a high percentage of women the contractions stop without the need for tocolytic treatment. Separating imminent spontaneous preterm labour from recurrent but transient episodes of uterine contractions remains a major clinical challenge.
Bleeding in pregnancy was strongly associated with both spontaneous and elective preterm deliveries. Women with vaginal bleeding have an increased risk of induction of labour and caesarean section and the condition is associated with other pregnancy complications such as PPROM, oligohydramnios and fetal growth restriction . The mechanism by which intrauterine bleeding may lead to spontaneous preterm labour is not known, but it has been proposed that thrombin activation in the decidua leads to uterine contractions [20, 21]. Moreover thrombin increases matrix metalloproteinase activity in the fetal membranes providing a link between intrauterine bleeding and rupture of the membranes [21, 22].
Anaemia is one of the most common nutritional problems in pregnant women throughout the world and, after smoking, is the most important preventable risk factor for preterm birth. Our data show that even moderate anaemia (< 10.5 g/dl) in pregnancy is associated with preterm birth and this agrees with observations in other tertiary referral hospitals . Ascending intrauterine infection is often quoted as a pathogenic mechanism for preterm labour , however in our survey the proportion of women with bacterial pathogens in high vaginal swabs was similar in the control and preterm groups.
Preterm babies continue to die in the perinatal period or have severe neonatal complications which predispose to a high incidence of neurodevelopmental impairments and sensory deficits. The early administration of glucocorticoids to the mother and impressive advances in neonatal care have steadily improved neonatal survival rates over the past three decades; however it is unrealistic to expect that improvements in neonatal intensive care will decrease neonatal mortality and the sequelae of prematurity much further . The onus is now on understanding the causes and mechanisms of parturition, so that spontaneous preterm labour can be prevented and preterm birth is only allowed to happen electively for the benefit of the mother and her baby . The proportion of elective preterm deliveries in our survey is considerably higher than in similar UK and European hospital populations in the 1970s and 1980s [6, 26]. This reflects a growing confidence among young obstetricians that justified intervention in preterm pregnancies results in good obstetric and neonatal outcome, but significant morbidity should not be forgotten.
This study has limitations because it has surveyed a population of several hundred women in a single tertiary hospital. The factors associated with preterm birth would be better addressed through prospective study of a very large geographical cohort. Furthermore, we believe that over the next decade epidemiological data will be supplemented by advances in uterine physiology and materno-fetal endocrinology which will improve our understanding of human parturition and help devise successful strategies to prevent preterm labour.
The data from this study show that more than 50% of preterm births follow spontaneous preterm labour and further research to clarify the mechanism by which risk factors such as increased uterine contractility, premature rupture of the membranes and uterine bleeding result in preterm labour will be clearly beneficial. Moreover, it is important to address the major causes of elective preterm delivery, namely hypertensive disorders and intrauterine growth restriction. This may be achieved through the discovery of the aetiology of pre-eclampsia and a better understanding of the control of fetal growth and placental function. The reduction of spontaneous preterm labour is a realistic aim; however our lack of knowledge of the process of labour is a major handicap in devising effective strategies. It is essential to promote research into the physiological and physiopathological pathways that increase uterine activity during pregnancy. The combination of laboratory and clinical research will provide the necessary breakthroughs to improve the prevention of preterm birth.
WY: MSc. PhD student, Department of Clinical Science at South Bristol (Obstetrics and Gynaecology). University of Bristol. AMD: Registered Midwife, Department of Obstetrics and Gynaecology, St Michael's Hospital, Bristol. LC: MSc. Research associate, Department of Social Medicine, University of Bristol. LPH: PhD, CStat, Senior Lecturer in Medical Statistics, Dept of Clinical Sciences at South Bristol. University of Bristol. SMS, MD, FRCOG, Consultant Obstetrician, University Hospitals Bristol, Obstetrics and Gynaecology, St Michael's Hospital. ALB, MD, D Phil, Professor of Human Reproductive Biology, Department of Clinical Science at South Bristol (Obstetrics and Gynaecology). University of Bristol.
The authors are members of the European Parturition Group http://www.bris.ac.uk/clinicalsciencesouth/eupg/.
This research was supported through a SAFE Network of Excellence Bursary (WY) and by Wellbeing of Women.
- López Bernal A: Mechanisms of labour--biochemical aspects. Bjog. 2003, 110 (Suppl 20): 39-45.PubMedGoogle Scholar
- Tucker J, McGuire W: Epidemiology of preterm birth. Bmj. 2004, 329: 675-678. 10.1136/bmj.329.7467.675.PubMed CentralPubMedView ArticleGoogle Scholar
- Wen SW, Smith G, Yang Q, Walker M: Epidemiology of preterm birth and neonatal outcome. Semin Fetal Neonatal Med. 2004, 9: 429-435. 10.1016/j.siny.2004.04.002.PubMedView ArticleGoogle Scholar
- Martin JA, Kung HC, Mathews TJ, Hoyert DL, Strobino DM, Guyer B, Sutton SR: Annual summary of vital statistics: 2006. Pediatrics. 2008, 121: 788-801. 10.1542/peds.2007-3753.PubMedView ArticleGoogle Scholar
- Beck S, Woijdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF: The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010, 88: 31-38. 10.2471/BLT.08.062554.PubMed CentralPubMedView ArticleGoogle Scholar
- Rush RW, Keirse MJ, Howat P, Baum JD, Anderson AB, Turnbull AC: Contribution of preterm delivery to perinatal mortality. British medical journal. 1976, 2: 965-968. 10.1136/bmj.2.6042.965.PubMed CentralPubMedView ArticleGoogle Scholar
- Goldenberg RL, Culhane JF, Iams JD, Romero R: Epidemiology and causes of preterm birth. Lancet. 2008, 371: 75-84. 10.1016/S0140-6736(08)60074-4.PubMedView ArticleGoogle Scholar
- Langhoff-Roos J, Kesmodel U, Jacobsson B, Rasmussen S, Vogel I: Spontaneous preterm delivery in primiparous women at low risk in Denmark: population based study. Bmj. 2006, 332: 937-939. 10.1136/bmj.38751.524132.2F.PubMed CentralPubMedView ArticleGoogle Scholar
- Bakketeig LS, Hoffman HJ, Harley EE: The tendency to repeat gestational age and birth weight in successive births. Am J Obstet Gynecol. 1979, 135: 1086-1103.PubMedGoogle Scholar
- Iams JD, Stilson R, Johnson FF, Williams RA, Rice R: Symptoms that precede preterm labor and preterm premature rupture of the membranes. Am J Obstet Gynecol. 1990, 162: 486-490.PubMedView ArticleGoogle Scholar
- Burguet A, Kaminski M, Abraham-Lerat L, Schaal JP, Cambonie G, Fresson J, Grandjean H, Truffert P, Marpeau L, Voyer M: The complex relationship between smoking in pregnancy and very preterm delivery. Results of the Epipage study. Bjog. 2004, 111: 258-265.PubMedView ArticleGoogle Scholar
- Schempf AH, Branum AM, Lukacs SL, Schoendorf KC: Maternal age and parity-associated risks of preterm birth: differences by race/ethnicity. Paediatric and perinatal epidemiology. 2007, 21: 34-43. 10.1111/j.1365-3016.2007.00785.x.PubMedView ArticleGoogle Scholar
- Hall MH, Danielian P, Lamont RL: The importance of preterm birth. Preterm labor. Edited by: Elder MG, Romero R, Lamont RL. 1997, New York: Churchill Livingstone, 1-28.Google Scholar
- Hendler I, Goldenberg RL, Mercer BM, Iams JD, Meis PJ, Moawad AH, MacPherson CA, Caritis SN, Miodovnik M, Menard KM: The Preterm Prediction Study: association between maternal body mass index and spontaneous and indicated preterm birth. Am J Obstet Gynecol. 2005, 192: 882-886. 10.1016/j.ajog.2004.09.021.PubMedView ArticleGoogle Scholar
- Creasy RK: Preventing preterm birth. N Engl J Med. 1991, 325: 727-729. 10.1056/NEJM199109053251009.PubMedView ArticleGoogle Scholar
- Steer P: The epidemiology of preterm labour. Bjog. 2005, 112 (Suppl 1): 1-3.PubMedGoogle Scholar
- Sanborn BM: Relationship of ion channel activity to control of myometrial calcium. J Soc Gynecol Investig. 2000, 7: 4-11. 10.1016/S1071-5576(99)00051-9.PubMedView ArticleGoogle Scholar
- Lartey J, Smith M, Pawade J, Strachan B, Mellor H, Lopez Bernal A: Up-Regulation of Myometrial RHO Effector Proteins (PKN1 and DIAPH1) and CPI-17 (PPP1R14A) Phosphorylation in Human Pregnancy Is Associated with Increased GTP-RHOA in Spontaneous Preterm Labor. Biol Reprod. 2007, 76: 971-982. 10.1095/biolreprod.106.058982.PubMedView ArticleGoogle Scholar
- Chan CC, To WW: Antepartum hemorrhage of unknown origin--what is its clinical significance?. Acta Obstet Gynecol Scand. 1999, 78: 186-190. 10.1080/j.1600-0412.1999.780303.x.PubMedView ArticleGoogle Scholar
- Elovitz MA, Baron J, Phillippe M: The role of thrombin in preterm parturition. Am J Obstet Gynecol. 2001, 185: 1059-1063. 10.1067/mob.2001.117638.PubMedView ArticleGoogle Scholar
- Erez O, Espinoza J, Chaiworapongsa T, Gotsch F, Kusanovic JP, Than NG, Mazaki-Tovi S, Vaisbuch E, Papp Z, Yoon BH: A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor. J Matern Fetal Neonatal Med. 2008, 21: 732-744. 10.1080/14767050802361807.PubMed CentralPubMedView ArticleGoogle Scholar
- Stephenson CD, Lockwood CJ, Ma Y, Guller S: Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes. J Matern Fetal Neonatal Med. 2005, 18: 17-22. 10.1080/14767050500123632.PubMedView ArticleGoogle Scholar
- Lone FW, Qureshi RN, Emanuel F: Maternal anaemia and its impact on perinatal outcome. Trop Med Int Health. 2004, 9: 486-490. 10.1111/j.1365-3156.2004.01222.x.PubMedView ArticleGoogle Scholar
- Saigal S, Doyle LW: An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008, 371: 261-269. 10.1016/S0140-6736(08)60136-1.PubMedView ArticleGoogle Scholar
- Iams JD, Romero R, Culhane JF, Goldenberg RL: Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet. 2008, 371: 164-175. 10.1016/S0140-6736(08)60108-7.PubMedView ArticleGoogle Scholar
- Di Renzo GC, Roura LC: Guidelines for the management of spontaneous preterm labor. J Perinat Med. 2006, 34: 359-366. 10.1515/JPM.2006.073.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.