Women and Birth
Volume 24, Issue 4 , Pages 141-147, December 2011

The effectiveness of medical interventions aimed at preventing preterm birth: A literature review

School of Nursing and Midwifery, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia

Received 27 July 2010; received in revised form 13 December 2010; accepted 13 December 2010. published online 20 June 2011.

Article Outline

Abstract 

Background

Preterm birth is a significant global health problem with serious short and long term consequences. This paper reviews the research literature to answer the question how effective are the medical interventions that aim to reduce the rates of preterm birth?

Methods

A systematic search was carried out in CINAHL, Cochrane, Medline and Embase in relation to following medical treatments aimed at preventing preterm births: anti-infective medications, tocolytics, progesterone and cervical cerclage. The research underpinning each type of intervention is critically analysed in order to establish the validity of knowledge claims that are made for each type of intervention.

Findings

In relation to reducing the rates of preterm births, anti-infectives are only effective in the presence of known infection. Screening for infections during pregnancy is ineffective. Tocolytic agents are not effective in decreasing the preterm birth rates. Progesterone seems to be effective in a select group of pregnant women at higher risk of preterm birth. Cervical cerclage plays a small and an occasional role in preventing some preterm births.

Conclusions

This literature review demonstrates that medical interventions aimed at preventing, not just delaying, preterm birth, are not effective at a population level. Providing holistic, antenatal midwifery care for women living in socio-economic disadvantage and/or with an increased risk of preterm birth seems to be a promising strategy to address the negative effects of the social determinants of disease and thus to reduce the rate of preterm births at an individual and a population level.

Keywords: Preterm birth, Cervical cerclage, Infections, Tocolysis, Progesterone, Meta-analysis

 

This review was undertaken as part of a study seeking to find ways to reduce the preterm birth rate in Thailand where the rate is 11.4% of all births.1 This rate is high by world standards where the average is preterm birth rate is 9.6%.2 Preterm birth is recognized by WHO3 as one of the top 10 causes of death worldwide. Preterm birth is defined as one that occurs after 20 weeks and before 37 completed weeks’ gestation.4, 5

A starting assumption of this study has been that Thailand probably needs to make the medical treatments for preterm labour more widely available as a way of reducing the rate of preterm birth. A review of the epidemiological evidence unsettled this assumption because in Western countries, despite the increasing availability and variety of medical treatments, the rates of preterm birth have not declined over the past 30 years. Worse, in some countries, the rates are actually increasing.6, 7, 8, 9, 10 Along with rising preterm birth rates, survival rates for preterm babies have also gone up; approximately 75% of perinatal morbidity is related to preterm birth.11, 12, 13, 14 In developing countries, the rise in the numbers of neonatal intensive care units has led to many more babies surviving with deficits that are associated with prematurity and blindness, neurological impairment and chronic respiratory disease are becoming more common.7, 15 Preterm birth is, therefore, a significant cause of short and long term morbidity. Preterm birth is expensive for the country, both in terms of health costs and lost working capacity of the survivors and their carers.

The question guiding this review is: how effective are the medical interventions that aim to reduce the rates of preterm birth? This paper begins with a description of the systematic search of the literature. Then the research evidence for the four main categories of medical therapies that are used to prevent preterm birth, i.e. (1) anti-infective medications, (2) tocolytic agents, (3) progesterone and (4) cervical cerclage are presented and discussed. We acknowledge that there are sometimes benefits in using these therapies for particular women in specific circumstances. However, in this paper we argue that medical interventions aimed at preventing, not just delaying, preterm birth, are not effective at a population level. The discussion section of the paper considers the idea of primary prevention by focusing on the modification of known risk factors for preterm birth (see Table 1 for risk factors). These risk factors are widely accepted within the obstetric and midwifery literature. The risk factors are mostly socio-economic, which suggests that a primary health care strategy may be more promising than medical interventions in reducing preterm birth rates.16, 17, 18, 19 In conclusion, we briefly discuss the benefits of midwife-led, woman-centred, group-based, interactive antenatal models of care/education. There is some evidence that these models of care provide an effective primary health care preventative strategy. Further, these midwife-led models could be made widely available to virtually all childbearing women at a fraction of the cost of medical interventions.

Table 1. Risk factors for preterm birth.
History of previous preterm birth or low birth weight
History of recurrent miscarriage in the second trimester
History of multiple terminations of pregnancy
History of cervical incompetence
Immune system dysfunction
Low pre-pregnancy weight or low body mass index
Urogenital infections
Low socioeconomic status
Single status
Age under 19 years or over 35 years
Unhealthy behaviors such as smoking and drinking alcohol
Non-Caucasian race; with the most socio-economically disadvantaged women and babies being the most at risk of preterm birth

Back to Article Outline

Literature search strategy 

The search was conducted from 1998 to 2008 and updated in 2010 for this paper. The databases searched were CINAHL, Cochrane, Medline and Embase. The search terms were derived from the keywords in the question guiding this review. MeSH terms, synonyms and variants spellings were used. The search key terms were research OR clinical trial OR random* OR ‘review’; ‘labour, preterm’ including threatened preterm labour; ‘cervical cerclage’, ‘cervical incompetence’, ‘short cervix’; ‘antibiotics’ OR ‘tocolysis’ OR ‘progesterone’ OR ‘periodontitis’. Articles were selected only if they were meta-analyses or randomised controlled trials (RCTs), written in English, and published after a peer reviewed process. Thirty-two articles fulfilled the criteria for selection: 13 were single RCTs and 19 were systematic reviews which incorporated 183 RCTs. This means that a total of 196 RCTs have contributed findings that are incorporated in this review. For the systematic reviews, we only returned to the original RCTs if there was confusion or discrepancy noted in our reading of the systematic review. Methodological quality for most of the studies was assessed by the reviewers who conducted the 19 systematic reviews. For the remaining 13 studies we used some simple questions based on the Cochrane Collaboration's recommendations about quality scores. The questions were: (1) Was a control group present? (2) Were appropriate randomisation procedures used? (3) Did the study involve more than 30 subjects? (4) Was the reviewed paper published within the last 10 years? All the included studies met these criteria.20

Back to Article Outline

Findings 

Four types of medical and surgical intervention are currently used to prevent preterm birth and/or treat preterm labour. When discussing the findings from RCTs and meta-analyses odd ratios (OR) or relative risk (RR) is used along with confidence intervals (CI). See Table 2 for definitions and discussion of the statistical terms and how to interpret them.

Table 2. How to interpret the statistics in the paper.
Statistical conceptMeaning and application
Relative risk (also called risk ratio and reported as RR)“An association between exposure to a factor and the development of a particular outcome; usually a disease. It is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group”.62 “A relative risk of 1 shows that no association; a value of>1 shows a positive association (possibly causal); a value of <1 shows a negative association (possibly protective)” (62, p.179). In the case of treatments for preterm birth, a relative risk means the risk of giving birth prematurely in that group of women who were exposed to a specific treatment compared with those women in the other group who were not exposed to the treatment (or were exposed to a different treatment).

Odds ratio (reported as OR)The proportion of the cases that were exposed to a treatment and the proportion of the controls that was not exposed to the treatment or was exposed to a different treatment. “Odds ratio is used in a case-control study as an estimate of the relative risk when the risk of disease is low” (62, p. 182). An odds ratio of 1 show that there is no association between two groups in terms of the effect of a treatment on an outcome. A value of >1 shows a positive association (possibly causal); a value of<1 shows a negative association (possibly protective) (62, p. 184).

Confidence interval (reported as CI)The CI comprises two numbers which represents the boundary within which the sample means fall. The CI equates to a range of values where the true population value really lies. The mean is always in the centre of the confidence interval which is set at 95% confidence.

How to interpret OR, RR and CI within this paperHere is example of an OR and CI which is statistically significant (OR 0.48; CI 0.28–0.81). The numeral ‘1’ does not fall between the two boundaries of the CI which means that there is a significant difference in the OR between the two groups. If the numeral ‘1’ occurs; for instance (OR 0.48; CI 0.28–1.02) this CI includes the numeral ‘1’ which indicates that there was ‘no difference’ between the two groups. There is one further piece of information which will aid the interpretation of statistics in this paper; if the sample mean accurately represents the true mean, then the CI will be narrow, e.g. CI 0.28–0.81 ranges from which is only 0.53 in range. Conversely, if the CI is wide then the sample mean could be very different from the true mean, indicating that we are quite uncertain about where the true population mean lies.63 For example (CI 1.21–24.86) indicates a significant finding because the numeral 1 is not within the boundaries of 5.21–24.86 however the range is wide at 19.65 meaning we are less sure of where the population mean lies.

Back to Article Outline

Anti-infective medications 

Ascending infections from the urinary and genital tract are strongly associated with preterm birth.21, 22 Scores of studies have examined the effectiveness of anti-infective drugs for these infections on reducing the rate of preterm birth. The main antibiotics tested have been erythromycin, clindamycin and amoxicillin. Metronidazole has been the most tested anti-fungal agent. Thinkhamrop et al.23 found antibiotic treatment was effective in reducing the rate of preterm birth but only in women with previous preterm birth who also have bacterial vaginosis in the current pregnancy (OR 0.48; 95% CI 0.28–0.81). A meta-analysis involving 14 RCTs by Okun et al.24 evaluated the effectiveness of clindamycin, and metronidazole for bacterial or trichomonas vaginosis during pregnancy for reducing the risk of preterm birth. Neither metronidazole nor clindamycin were effective in reducing preterm birth rates. A later meta-analysis of 17 RCTs by Simcox et al.25 evaluated antibiotic treatment in pregnant women at risk abnormal flora (12 trials, e.g. trichomonas vaginalis, group B Streptococcus, ureaplasma urealyticum and Gardnerella vaginalis and/or bacterial vaginosis), previous preterm birth (3 trials), positive fetal fibronectin (2 trails). No significant association between antibiotic treatment and reduced rates of subsequent preterm birth were found (RR 1.03; 95% CI 0.86–1.24).25 In 2008, a meta-analysis of 7 RCTs found no benefit in screening and treating women with low or moderate risk pregnancies.26 Another 2008 meta-analysis assessed the effects of the use of anti-infectives. Women were treated for actual or possible vaginosis regardless of whether the women actually had vaginosis.27 The reviewers found that anti-infective treatment was not effective in reducing preterm birth rates (15 trials involving 5888 women; OR 0.91; 95% CI 0.78–1.06).27 However, when women with vaginosis were treated with anti-infectives before 20 weeks gestation, preterm birth rates were reduced (5 RTCs, 2387 women; OR 0.72; 95% CI 0.55–0.95).27

A more recent meta-analysis involving 14 trials by Morency and Bujold28 evaluated the effect of second trimester anti-infectives, i.e. one or more of: erythromycin; clindamycin; metronidazole, in women with high risk of preterm birth. Metronidazole alone was found to increase preterm birth rates, however, erythromycin and clindamycin in mid-trimester were both related to lower rates of preterm births in women at high risk (3 trials; OR 0.72; 95% CI 0.56–0.93) (5 trials; OR 0.68; 95% CI 0.49–0.95), respectively.28 The meta-analysis did not distinguish between RCTs that used anti-infective (erythromycin and metronidaozole) for women who had vaginosis and those trials for women who did not have any infection. RCTs using anti-infectives were included in the meta-analysis, but did not differentiate between women with or without infection.

Periodontal disease is correlated with preterm birth and low birth weight.29, 30, 31, 32, 33, 34, 35, 36, 37 There are so many confounding variables in the studies that the effect of periodontal disease is difficult to discern.38 If periodontal disease was a cause of preterm birth, then treating periodontal disease early in pregnancy would reduce preterm birth rates. A systematic review of the evidence by the European Academy of Periodontology concluded that treating periodontal disease does not reduce preterm birth rates.39 Treating periodontal disease, as early in pregnancy as possible, is safe, and contributes to the woman's general good health.40 Treating periodontal disease is therefore recommended for all pregnant women but not as a way to reduce preterm birth rates.39, 40, 41

Back to Article Outline

Tocolytic agents 

Nifidipine (Calcium Channel Blocker) is commonly used to delay preterm births. A meta-analysis of the effectiveness of Nifidipine (12 trials; 1029 women) for inhibiting preterm birth was conducted by King et al.42 Nifidipine does reduce the rate of preterm birth prior to 34 weeks (RR 0.83; 95% CI 0.69–0.99)42 but does not prevent preterm births (as defined prior to 37 weeks) overall. The administration of a Calcium Channel Blocker does reduce the number of births within seven days after treatment (RR 0.76; 95% CI 0.60–0.97).42 This delay is beneficial because it allows time to mature the babies’ lungs and get the women to units which have high level neonatal intensive care facilities.

Betamimetic effectiveness was assessed by a systematic review of 11 trials involving 1320 women.43 Betamimetics are effective in stopping preterm labour for a short time (RR 0.63; 95% CI 0.53–0.75) but do not reduce the preterm birth rate (RR 0.95; 95% CI 0.88–1.03).43 More adverse effects for the woman, such as: chest pain, dyspnea, hyperglycemia, hypokalaemia, headaches, nausea, palpitation, tachycardia, and tremor, were found with the use of betamimetics, compared to the use of a placebo (RR 11.38; 95% CI 5.21–24.86).43 A meta-analysis of oral betamimetics for maintenance of uterine quiescence after threatened preterm labour by Dodd et al.44 reviewed 11 RCTs involving 1238 women. The key findings were that oral betamimetics for preventing preterm birth did not reduce the rate of preterm birth after threatened preterm labour. Whitworth and Quenby45 produced similar results.

Magnesium sulfate (MgSO4) effectiveness in threatened preterm birth was evaluated by a systematic review of 23 RCTs involving 2000 women.46 The trials compared MgSO4 with other tocolytic agents. No difference in effectiveness was seen in the rate of preterm birth within 48h of treatment (RR 0.85; 95% CI 0.58–1.25).46 There was a high risk of fetal and neonatal death for the group having MgSO4 (RR 2.82; 95% CI 1.2–6.62).46 Crowther and Moore47 reported similar results from systematic review of 3 trials involving 303 women. There is no beneficial effect of MgSO4 for preventing preterm birth after threatened preterm labour compared with placebo or no treatment (RR 0.85; 95% CI 0.47–1.51).47

Indomethacin (a cyclo-oxygenase (COX) inhibitor) has been used as a treatment aimed at preventing preterm birth. A meta-analysis, involving 13 RCTs and 713 women was conducted to examine the effectiveness of Indomethacin.48 Only one of the reviewed trials, involving only 36 women, actually reported on preterm birth rates and found that COX inhibitors were effective in reducing preterm birth rates (RR 0.21; 95% CI 0.07–0.62).49 COX inhibitors, however, have many unwanted and serious effects for women and babies including the premature closure of the baby's ductus arterious. This use of Indomethicin in women can lead to a bleeding disorder, hepatic or renal dysfunction, gastrointestinal ulcerative disease and/or asthma.49

In summary, the use of tocolytic agents does seem to delay preterm birth for several days. These extra days enable the administration of glucocorticosteroids to stimulate surfactant production in the lungs of the fetus. Also, the extra time is valuable for transferring women to hospitals that can provide neonatal intensive care.

Back to Article Outline

Progesterone 

A recent meta-analysis of 11 RCTs (intramuscular progesterone (7 RCTs) and intravaginal progesterone (4 RCTs) involving 2714 women and 3452 babies by Dodd et al.50 evaluated the benefits and harm of progesterone for preventing preterm birth in women considered to be at increased risk of preterm birth. In women with a history of spontaneous preterm birth, progesterone was effective in decreasing in the risk of preterm birth (4 RCTs; RR 0.80; 95% CI 0.70–0.92) and low birth weight (2 RCTs; RR 0.64; 95% CI 0.49–0.83).50 In women following presentation with threatened preterm labour, progesterone reduced the preterm birth rate (1 RCT; RR 0.29; 95% CI 0.12–0.69), and low birth weight (1 RCT; RR 0.52; 95% CI 0.28–0.98).50 The meta-analysis of progesterone treatment confirmed that progesterone reduces the rate of preterm birth, but cautioned that the potential for harm from the treatment is unknown.50, 51 ACOG52 recommends the use of progesterone and emphasizes that the treatment be restricted to women with a very high risk including those women who have had a previous preterm birth. Further studies need to be done to determine dosage and route of administration including indication for use of progesterone.52 Research on the long term effects and safety for both women and infants of using progesterone for prevention of preterm birth is greatly needed.

Back to Article Outline

Cervical cerclage 

Cervical cerclage is traditionally used in the second and third trimester for women with a short cervix and when cervical insufficiency has been diagnosed.53 A systematic review (6 RTCs involving 2190 women) was conducted to determine the effectiveness of cerclage compared with expectant management in preventing preterm birth.54 The main finding was that cerclage is able to prevent preterm birth <34 weeks (OR 0.77; 95% CI 0.59–0.99) (p=.049) but not preterm birth rates between 34 and 37 weeks. In addition, the poor quality of the research undermines confidence in the findings. Another systematic review studied the effectiveness of cerclage. The review involved 7 RCT's and 2354 women.55 Cerclage was effective in preventing preterm birth before 34 weeks’ gestation; however, this finding was limited to one study (ORs 0.72; 95% CI 0.53–0.97).55 Four studies in this review reported unwanted effects associated with the use of cerclage, i.e. increased rates of perinatal death, premature rupture of membranes, chorioamnionitis and puerperal pyrexia.55 In 2005, a meta-analysis evaluated the use of cerclage for preventing preterm birth for women with a short cervix.56 Four RCTs (607 women with mixture of singleton and twin pregnancies) were included. Cerclage is effective in preventing preterm births only for women with singleton gestations and a history of prior preterm birth (RR 0.61; 95% CI 0.40–0.92). Cerclage does not prevent preterm birth in the total population (RR 0.84; 95% CI 0.67–1.06).56 There was a significant increase in preterm birth in twin gestations suggesting that cerclage should not be used in multiple pregnancies (RR 2.15; 95% CI 1.15–4.01). Therefore, the effectiveness of cerclage was not confirmed by Drakeley et al.57 in this review of six RCTs. There was no reduction in preterm delivery in the group treated only with the cerclage (RR 0.88; 95% of CI 0.76–1.03).57

Back to Article Outline

Discussion 

In spite of 30 years of medical research and multiple modes of intervention aimed at reducing preterm birth rates, the rates are increasing worldwide. The vast amount of contemporary literature on the medical treatments aimed at preventing preterm birth is summarized below.

Anti-infective medications have been extensively studied and the findings are nuanced. Firstly, giving anti-infective drugs to a healthy group of women and no risk of preterm birth does not reduce preterm birth rates. Secondly, screening all women and treating those who are found to have vaginosis is not effective in reducing preterm birth rates. However, giving erythromycin with metronidazole is effective in reducing preterm birth rate for a small and select group of women who have a previous of preterm birth and/or whose pre-pregnancy weight is less than 50kg.58 One trial found that, for women diagnosed with bacterial vaginosis, treatment with intravaginal erythromycin daily for 6 weeks is effective in reducing the preterm birth rate.28

Treating periodontal disease is recommended for all pregnant women, but evidence does not support the claim that preterm birth rates will be reduced by doing so. The delay in birth that accompanies the use of tocolytic drugs is beneficial because it improves neonatal mortality and morbidity rates. Tocolytic medications, however, are not effective in reducing preterm births rates. There is no beneficial effect of betamimetics and MgSO4 in preventing preterm birth. Nifidipine (Calcium Channel Blocker) does reduce the number of births within seven days after treatment. Indomethacin (COX inhibitors) is effective in reducing preterm birth rates but they have unwanted and serious effects. In selected high-risk cases, progesterone may be of some benefit in preventing preterm births, however, the unwanted effects for the woman and baby are not known. The research concerning the effectiveness and unwanted effects of cerclage shows mixed results; perhaps due mainly to poor design of the studies. What is clear is that cerclage has only a small and occasional role to play in preventing preterm birth. Cerclage is not recommended for the prevention of preterm births at the population level.

As shown in this review, medical treatments aimed at preventing preterm births are of limited effectiveness. Medical treatments usually only commence once a woman has a history of multiple miscarriages and/or previous preterm birth: thus the first preterm birth is generally not prevented.59 In addition, the medical treatments, largely do not address the socio-economic risk factors for preterm birth (see Table 1). These socio-economic risk factors are widely accepted within the obstetric and midwifery literature.16, 17, 18, 19 The causes of preterm birth are mainly socio-economic, they are multiple and interactional. Many of these causes are modifiable, including: poverty, education, nutrition, smoking, weight, exercise, stress levels and immune system functioning.

Medical treatments are secondary or tertiary responses that usually require specialised hospital care. In addition, they are very expensive therefore out of the reach of developing nations. Medical treatments are never going to be the answer to this common, widely distributed, health care problem. A much less expensive, midwife-provided primary health care strategy seems to be hold some potential for reducing preterm birth rates. Recent midwifery research, aimed at primary prevention of preterm birth for all pregnant women has provided some promising evidence of effectiveness in terms of decreases in perinatal morbidity. In the United States a matched cohort study, involving 458 racially and socially disadvantaged women found that there was no difference in the rate of preterm births between the groups (9% in both groups). However, preterm babies born to women in the intervention group had higher birth weights due to the increased gestational age of babies: 2397.8g versus 1989.9g, a difference of 407.9g (F=5.66, p=.05).60 In a 5-year RCT involving 1047 women (drawn from the same population as the Ickovics et al. study)60 the researchers found that preterm births were fewer for women who were assigned to group care compared to standard care (9.8% versus 13.8%) (OR 0.67; 95% CI 0.44–0.99, p=.045).61 As the CenteringPregnancy research and practice has been conducted in the US with a focus on particular racial groups it cannot be unproblematically implemented in other contexts; thus additional research in other countries is needed.

Back to Article Outline

Conclusion 

This review has answered the guiding question: How effective are the medical interventions which aim to prevent preterm births? This paper demonstrates that the medical interventions aimed at preventing preterm birth, are not very effective at the level of the individual woman and not effective at all at a population level because the rates of preterm births are rising in Western countries. The causes of preterm birth are mainly socio-economic, they are multiple and interactional. Many of these causes are modifiable, including: poverty, education, nutrition, smoking, weight, exercise, stress levels and immune system functioning. A holistic, woman-centred reconceptualisation of how to prevent preterm birth is consistent with both midwifery philosophy and primary health care. Community-based, woman-centred antenatal care/education holds great promise to reduce preterm birth rates at the population level and in a way that is economically sustainable.

Back to Article Outline

Conflicts of interest 

There are no conflicts of interest.

Back to Article Outline

References 

  1. Number and percentage of livebirth by birth weight [database on the Internet]. Health Information Unit, Bureau of Health Policy and Strategy; 2009;Available from: http://bps.ops.moph.go.th/2.1.7-50.pdf [cited November, 2nd 2010]
  2. In:  Howson CP,  Merialdi M,  Lawn JE,  Requejo JH,  Say L editor. March of dimes: white paper on preterm birth: the global and regional toll, based on data from the World Health Organisation. New York: March of Dimes; 2009;
  3. The top 10 causes of death [database on the Internet]. WHO; 2008;Available from: http://www.who.int/mediacentre/factsheets/fs310/en/ [cited June, 22nd 2010]
  4. UNICEF and WHO . In: Statistic and monitoring Dopap  editors. Low birth weight country, regional and global estimates. UNICEF and WHO; 2004;p. 27
  5. Tucker J, McGuire W. Epidemiology of preterm birth. BMJ. 2004;329:675–678
  6. Behrman RE, Butler AS. Causes consequences and prevention committee on understanding premature birth and assuring healthy outcomes. 1st ed.. Washington, DC: Institute of Medicine of the Academies; 2007;
  7. Mangham LJ, Petrou S, Doyle LW, Draper ES, Marlow N. The cost of preterm birth throughout childhood in England and Wales. Pediatrics. 2009;123(2):e312–e327
  8. Day P, Sullivan E, Ford J, Lancaster P. Australia's mothers and babies 1997. AIHW Cat. no. PER 12 (Perinatal statistics series 140. No. 9). Sydney: AIHW National Perinatal Statistics Unit; 1999;
  9. Laws P, Sullivan E. Australia's mothers and babies 2007. Perinatal statistics series no. 23. Cat. no. PER 48. Sydney: AIHW National Perinatal Statistics Unit; 2009;
  10. Martin JA, Osterman MJK, Sutton PD. Are preterm births on the decline in the United States? Recent data from the national vital statistics system. National Center for Health Statistics; 2010;[NCHS data brief, no. 39]
  11. WHO . Health and the millennium development goals, France. 2005;
  12. Goldenberg RL, Culhane JF, Iams JD, Romero R. Preterm birth: epidemiology and causes of preterm birth. Lancet. 2008;371:75–84
  13. Myers E, Ment LR. Long-term outcome of preterm infants and the role of neuroimaging. Clinics in Perinatology. 2009;36(4):773–789
  14. WHO . Perinatal and neonatal mortality: global, regional and country estimates. 2001;
  15. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Harris Requejo J, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bulletin of the World Health Organization. 2010;88(1):31–38
  16. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Williams obstetrics. 22nd ed.. New York: McGraw-Hill; 2010;
  17. Gilbert ES. Manual of high risk pregnancy & delivery. 5th ed.. Maryland Heights: Mosby Elsevier; 2010;
  18. Fraser DM, Cooper MA. Myles’ textbook for midwives. 15th ed.. Edinburgh: Churchill Livingstone; 2009;
  19. Pairman S, Tracy SK, Thorogood C, Pincombe J. Midwifery: preparation for practice. 2nd ed.. Chatswood: Elsevier Australia; 2010;
  20. The Cochrane Collaboration . Quality score [database on the Internet]. The Cochrane Collaboration. 2010;Available from: http://www.cochrane.org/glossary/5#letterq [accessed 1st October, 2010]
  21. Goldenberg R, Hauth J, Andrews W. Intrauterine infection and preterm delivery. New England Journal of Medicine. 2000;342:1500–1507
  22. Morrison J, Ravikumar N. Prevention of preterm labour. In:  Norman J,  Greer I editor. Preterm labour managing risk in clinical practice. 1st ed.. The United Kingdom: Cambridge University Press; 2005;p. 153–170
  23. Thinkhamrop J, Hofmeyr GJ, Adetoro O, Lumbiganon P. Prophylactic antibiotic administration in pregnancy to prevent infectious morbidity and mortality [database on the Internet]. Cochrane Data of Systematic Reviews. 2004;[cited 2008]
  24. Okun N, Gronau KA, Hannah ME. Antibiotics for bacterial vaginosis or trichomonas vaginalis in pregnancy: a systematic review. The American College of Obstetricians and Gynecologists. 2005;105(4):857–867
  25. Simcox R, Sin W-TA, Seed PT, Briley A, Shennan AH. Prophylactic antibiotic for the prevention of preterm birth in women at risk: a meta-analysis. Australian and New Zealand Journal of Obstetrics and Gynecology. 2007;47:368–377
  26. Nygren P, Fu R, Freeman M, Bougatsos C, Guise J. Screening and treatment for bacterial vaginosis in pregnancy: systematic review to update the 2001 U.S. preventive services task force recommendation. Evidence Synthesis. 2008;57
  27. McDonald H, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy (review) [database on the Internet]. Cochrane Data of Systematic Reviews. 2008;Available from: http://www.thecochranelibrary.com [cited 2007]
  28. Morency A-M, Bujold E. The effect of second-trimester antibiotic therapy on the rate of preterm birth. Journal of Obstetrics & Gynecology Canada: JOGC. 2007;29(1):35–44Jan
  29. Lopez NJ, Da Silva I, Ipinza J, Gutierrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. Journal of Periodontology. 2005;76(November (11 Suppl.)):2144–2153
  30. Jared H, Boggess K. Periodontal diseases and adverse pregnancy outcomes: a review of the evidence and implications for clinical practice. Journal of Dental Hygiene. 2008;82(3 Suppl.):2–20
  31. Jeffcoat M, Geurs N, Reddy M, Clive S, Goldenberg R, Hauth J. Periodontal infection and preterm birth: results of a prospective study. Journal American Dental Association. 2001;132(7):875–880
  32. Khader YS, Ta’ani Q. Periodontal diseases and the risk of preterm birth and low birth weight: a meta-analysis. Journal of Periodontology. 2005;76(February (2)):161–165
  33. Lopez N, Smith P, Gutierrez J. Higher risk of preterm birth and low birth weight in women with periodontal disease. Journal of Dental Research. 2002;81(1):58–63
  34. Márta R, István G, Edit U, József E, Tibor N, Attila P. Possible association between mother's periodontal status and preterm delivery. Journal of Clinical Periodontology. 2006;33(11):791–796
  35. Offenbacher S, Boggess K, Murtha A. Progressive periodontal disease and risk of very preterm delivery. Journal Obstetrics and Gynecology. 2006;107(1):29–36
  36. Santos-Pereira SA, Giraldo PC, Saba-Chujfi E, Amaral RLG, Morais SS, Fachini AM, et al. Chronic periodontitis and pre-term labour in Brazillian pregnant woman association to be analysed. Journal Clinical Periodontology. 2007;34(3):209–213
  37. Xiong X, Buekens P, Vastardis S, Pridjian G. Periodontal disease and gestational diabetes mellitus. American Journal Obstetrics and Gynecology. 2006;195(4):1086–1089
  38. Wimmer G, Pihlstrom BL. A critical assessment of adverse pregnancy outcome and periodontal disease. Journal Clinical Periodontology. 2008;35(Suppl. 8):380–397
  39. Kinane D, Bouchard P. Periodontal diseases and health: consensus report of the sixth European workshop on periodontology. Journal of Clinical Periodontology. 2008;35(Suppl. 8):333–337
  40. Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, et al. Treatment of periodontal disease and the risk of preterm birth. New England Journal of Medicine. 2006;355(November (18)):1885–1894
  41. Vergnes J-N, Sixou M. Preterm low birth weight and maternal periodontal status: a meta-analysis. American Journal Obstetrics and Gynecology. 2007;196(135):e1–e7
  42. King J, Flenady V, Papatsonis D, Dekker G, Carbonne BJT. Calcium channel blockers for inhibiting preterm labour. Cochrane Database of Systematic Reviews. 2010;2003:[Issue 1. Art. No.: CD002255]
  43. Anotayanonth S, Subhadar N, Neilson J, Harigopal S. Betamimetics for inhibiting preterm labour (review). Cochrane Data of Systematic Reviews. 2004;
  44. Dodd J, Crowther C, Dare M, Middleton P. Oral betamimetics for maintenance therapy after threatened preterm labour (review). Cochrane Data of Systematic Reviews. 2006;
  45. Whitworth M, Quenby S. Prophylactic oral betamimetics for preterm labour in singleton pregnancies. Cochrane Data of Systematic Reviews. 2007;
  46. Crowther C, Hiller J, Doyle L. Magnesium sulfate for preventing preterm birth in threatened preterm labour [data base on the Internet]. Cochrane Database of Systematic Reviews. 2009;4:[Art. No.: CD001060]
  47. Crowther C, Moore V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour [data base on the Internet]. Cochrane Database of Systematic Reviews. 2009;1:[Art. No.: CD000940]
  48. King J, Flenady V, Cole S, Thornton S. Cyclo-oxygenase (COX) inhibitors for treating preterm labour (Review). Cochrane Database of Systematic Reviews. 2010;[2005, Issue 2. Art. No.: CD001992]
  49. Zuckerman H, Shalev E, Gilad G, Katzuni E. Further study of the inhibition of premature labor by indomethacin. Part II. Double-blind study. Journal of Perinatal Medicine. 1984;12(1):9–25
  50. Dodd JM, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database of Systematic Reviews. 2009;[4]
  51. Sanchez-Ramos L, Kaunitz AM, Delke I. Progestational agents to prevent preterm birth: a meta-analysis of randomised controlled trials [see comment]. Obstetrics & Gynecology. 2005;105(February (2)):273–279
  52. ACOG . ACOG Committee on Obstetric Practice Number 419, October 2008: use of progesterone to reduce preterm birth. Obstetrics Gynecology. 2008;1–3
  53. Chandiramani M, Shennan AH. Cervical insufficiency: prediction, diagnosis and prevention. The Obstetrician & Gynecologist. 2008;10:99–106
  54. Odibo AO, Elkousy M, Ural SH, Macones GA. Prevention of preterm birth by cervical cerclage compared with expectant management: a systematic review. Obstetrical and Gynecological Survey. 2003;58(2):130–136
  55. Bachmann LM, Coomarasamy A, Honest H, Khan KS. Elective cervical cerclage for prevention of preterm birth: a systematic review. Acta Obstetricia Et Gynecologica Scandinavica. 2003;82:398–404
  56. Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short cervix on ultrasonography: meta-analysis of trials using individual patient-level data. Obstetrics & Gynecology. 2005;106(July (1)):181–189
  57. Drakeley A, Roberts D, Alfirevic Z. cervical cerclage for prevention of preterm delivery: meta-analysis of randomized trials. Obstetrics & Gynecology. 2003;102:621–627
  58. Hauth J, Goldenberg L, Andrews W, DuBard M, Copper R. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. New England Journal of Medicine. 1995;333:1732–1736
  59. Shellhaas CS, Iams JD. Ambulatory management of preterm labor. In:  Hill WC editors. Ambulatory obstetrics. Philadelphia: Lippincott Williams & Wilkins; 2002;p. 13–33
  60. Ickovics JR, Kershaw TS, Westdahl C, Rising SS, Klima C, Reynolds H, et al. Group prenatal care and preterm birth weight: results from a matched cohort study at public clinics. Obstetrics & Gynecology. 2003;102(5):1051–1057
  61. Ickovics JR, Kershaw ST, Westdahl C, Magriples U, Massey Z, Reynolds H, et al. Group prenatal care and perinatal outcomes. Obstetrics & Gynecology. 2007;110:330–339
  62. Gordis L. Epidemiology. 3rd ed.. Philadelphia: Elsevier Saunders; 2004;
  63. Field A. Discovering statistics using SPPS. 2nd ed.. London: SAGE Publications; 2005;

PII: S1871-5192(10)00085-5

doi:10.1016/j.wombi.2010.12.002

Women and Birth
Volume 24, Issue 4 , Pages 141-147, December 2011

Article Tools