Preterm Birth Prevention: Effectiveness of Current Strategies

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OBSTETRICS

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PRETERM BIRTH PREVENTION: EFFECTlVENESS OF CURRENT STRATEGIES Moutquin, MD, MSc, FRCSC,l Valerie Milot~ Roy, MSc, 2 Olivier Irion, MD,3

Jean~Marie

1Professor,

Department of Obstetrics and Gynaecology, Centre de recherche, Hopital Saint~Fran~ois d'Assise, Faculty of Medicine , Laval University, 2 Medical Student, Recipient of a Summer Research Studentship from the Division of Research and Development, Wyeth Ayerst Canada, 30bstetrician~Gynaecologist , Invited Professor at Laval University, Hopital Cantonal, Universitaire de Geneve, Switzerland

ABSTRACT

Objective: to describe the current state of preterm birth in Canada and to ascertain the effectiveness of published preventive strategies . Data sourees: a literature review including Statistics Canada 1991 and peer reviewed articles using preterm birth as the primary medical subject heading. The Cochrane Database of Systematic Reviews also was studied. Study selection: randomized controlled trials , quasi-experimental trials , and analytic studies (including retrospective and prospective cohort studies) .

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, , , Data extraction: the following infcmnation was rwm1ed about each preventive intervention: population type, sample size, study design, type of intervention, and whether interventions or programmes were carried out in high risk pregnant women or using a populationoriented approach. Data synthesis: high risk strategy tested nine various single interventions and three programmes of multiple interventions in almost 35,000 pregnancies, all in randomized controlled trials. The population-oriented strategy was applied in almost 500,000 pregnancies, although onIy three interventions in less chan 6,000 pregnancies were tested by randomized clinical trials. ConcIusion: preterm birth rates have not decreased in Canada fOT at least thirry years. High risk screening and interventions are not effective in reducing preterm birth rates. There is promising potential fOT effectiveness with population-oriented strategies OOt these have to be tested in appropriately designed randomized controlled trials. RESUME

Objectif: Decrire I' etat des connaissances sur les naissances prematurees au Canada et evaluer I' efficaciti reelle des stratigies preventives pub/iees. Source des dannees: Revue de la littirature incIuant le registre des naissances de Statistiques Canada 1991, ainsi que les publications dans /es journaux dotis de comiti de lecrnre en utilisant le terme accouchement prerruuure comme principale rubrique. La base de dannees Cochrane de revues systimatiques a aussi eti consultie. Selection d'etudes: Essais cliniques contröles et randomises, etudes quasi-experimentales et etudes analytiques (incIuant ecudes retrospectives et prospectives de cohortes). Extraction de dannees: L' infcmnation suivante a eti consignee: type de population, taille de I' echantillon, architecture de l' etude, type d'intervention et si I'intervention a eti testie chez une population arisque eleve de prematuriti ou par une approche incIuant toute la population enceinte . Synthese des donnees: La stratigie visant les femmes arisque eleve a evalue neuf interventions et trois programmes comprenant plusieurs interventions chez pres de 35 000 grossesses . T outes ces etudes etaient des essais contröles randomises. Les stratigies orienties vers toute la population enceinte ont enröle pres de 500 000 femmes mais seulement trois etudes contrölees ont eti reaJisees chez moins de 6 000 femmes. ConcIusion: Le taux d' accouchement premature n' a pas diminue au Canada depuis 30 ans. Les interventions visant la detection et la prevention du travail premature chez les grossesses arisques eleves n' ont pas demontre leur efficaciti. L' efficaciti areduire la prematuriti semble s'orienter vers une approche offerte a toute la population enceinte. Certains de ces programmes devraient cependant etre evalues par des etudes contrölees randomisees avant leur app1ication.

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KEY WORDS

Preterm birth, preterm birth prevention, high risk pregnancy, population-oriented prevention, self-manitoring.

INTRODUCTION

BURDEN OF SUFFERING

IMPORTANCE OF THE CONDITION

More than 75 percent of neonatal mortality is attributed to preterm delivery.2 Premature infants are more likely to place a burden on specialized neonatal intensive care resources for resuscitation, severe respiratory disorders, patent ductus arteriosus, sepsis, necrotizing enterocolitis, intraventricular haemorrhage or bronchopulmonary dysplasia. In the Uni ted States, this accounts for five million hospital days per year at a cost of five billion dollars. 1 Among the survivors, 12 to 18 percent suffer from major neuro-developmental handicaps (including cerebral palsy) and learning disabilitiesY Twenty-five percent of children born before 37 weeks and 48 percent of those born at less than 32 weeks also will require special education during the first year of primary schoo1. 6 Neonates with a birthweight ::; 1,OOOg are significantly disadvantaged

Preterm birth is defined as a birth occurring before 37 weeks of pregnancy « 259 days). Preterm delivery is the most frequent complication of pregnancy. The incidence of preterm delivery in Canada is 6.64 percent: 26,334 births in 1991. 1In almost all industrialized countries, including the Uni ted States, the rate of preterm birth has changed little in the last thirty years, despite improvements in standards of living and health care and a great deal of research, together with extensive development of diagnostic and therapeutic technologies. In Canada, the relative frequency (percent) of preterm delivery according to various gestational age strata are 1.40 (20 to 23 weeks), 4.00 (24 to 27 weeks), 9.31 (28 to 31 weeks), 42.12 (32 to 35 weeks), and 43.17 (36 weeks).1

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in regard to cognitive ability and school performance at eight years of age 7 and use significantly more resources with a much lower health related quality of life. 8 An intervention which would reduce the crude rate of preterm births by one to two percent would have a major effect on perinatal mortality and morbidity, as well as on the health of the general population, while drastically reducing health care costs. A conservative estimate based on Canadian data shows that lifetime costs for every surviving preterm infant with a birthweight of less than 2,500g (low birthweight) averages more than $600,000. This estimate takes into account the use of neonatal intensive care, rehospitalization during the first year, and averaged lifetime costs of handicapped survivors. 9

who by screening were shown to be positive for known risks factors for preterm deliveries. METHODS

The literature review included da ta extracted from Statistics Canada l and the Cochrane Database of Systematic Reviews of randomized clinical trials on prevention of preterm birth. A medline search (1981 to 1995), using preterm birth as the primary medical subject heading, identified English and French peer reviewed articles reporting randomized clinical trials, quasi-experimental trials, and analytic studies (including retrospective and prospective cohort studies). Criteria to select studies included a description of interventions, a defined outcome, description of the population studied, withdrawals and exclusion rates, appropriate analysis, and identification of potential bias. The following information was recorded about each preventive intervention: population type, sampie size, study design, type of intervention, and whether interventions or programmes were carried out on high risk pregnant women or by using a population-oriented approach.

CATEGORIES OF PRETERM DELIVERIES

Preterm delivery results from three clinical conditions. Prematurity may occur because of such medical indications as severe pre-eclampsia, abruptio placentae, intra-uterine growth restriction, or fetal distress. This accounts for about 25 percent of cases (range 18.7 to 35.2 percent).9,IO

PREVENTION STRATEGIES

Preterm premature rupture of membranes is usually followed by preterm delivery for another 25 percent (range 7.1 to 51.2 percent),IO,11 occurring more often in the disadvantaged population, especially among black Americans. Although infection is usually regarded as the main cause of this condition,1,9,10 other cases are preceded by spontaneous preterm labour. 1 Spontaneous or "idiopathic" preterm delivery accounts for at least 50 percent of preterm deliveries (range 23.2 to 64.1 percent),IO,11 being more frequent in the population without any established risk factors where it represents 50 to 75 percent of all preterm deliveriesY lt is preceded by spontaneous preterm labour which cannot be stopped in 70 to 80 percent of casesy,Il

A variety of strategies has been proposed to prevent preterm delivery. The therapeutic approach, using tocolytic agents, has predominated in medical practice over the last few decades. No benefit has been shown in clinical trials in terms of rate of preterm delivery or perinatal mortality and morbidity.14 An excess of potentially severe maternal side effects has been observed. 14 Another approach, also based on secondary prevention, is risk screening. Various interventions were proposed for women who screened positive (high risk strategy). Finally, primary prevention programmes have been proposed which target the entire obstetrical population (population-oriented approach).

OBJECTIVE

RISK FACTORS SCREENING

The purpose of this mview is to assess the relative effectiveness of various preventive interventions or programmes. Two different strategies have been tested: a secondary prevention aimed at high risk pregnancies (those screened with established risk factors for preterm deliveries) and a population-oriented approach performed at the level of the entire population (mainly primary prevention), including a small fraction of women

Since the initial "coefficient de risque d'accouchement premature" by Papiernik in 1969,15 numerous studies have highlighted the aetiologic heterogeneity of preterm delivery, emphasizing its multifactorial origins. Il ,16 However, if exposure to a single variable is a strong risk factor for only spontaneous "idiopathic" preterm labour, but is studied in relation to all preterm births, the strength of association is weakened and may

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, , , not be apparent. Finally, there is a fraction of preterm births wh ich cannot be explained by any apparent cause. II ,17 Arecent epidemiological studyl8 found only 13 well established risk factors: prior preterm delivery, second trimester aborti on, uterine and cervical anomalies, in vitra fertilization, multiple pregnancy, matemal medical complications, obstetrical haemorrhage, abnormal placentation, urinary tract infection, Afro-American ethnic origin, low socio-economic status, social isolation, and smoking. Other factors are still being debated including infertility, heredity, matemal age and height, drug abuse, work outside horne, sexual activity, and stressful events.

incompetency.24 This condition however, is rare in high risk patients (less than 2%). BED REST

Hospital bed rest prescribed for approximately 1,000 twin pregnancies worsened the outcome (Table 1 ).25 There is little information on the effectiveness of bed rest in other pregnancy conditions, however, health hazards in the non-pregnant state have been described since 1929. 26,27 ROUTINE CERVICAL EXAMINATION

Routine cervical examination carried out in 5,000 women did not show any benefit in terms of reduction in prematurity (Table 1).28 Another recent multinational trial confirmed this. 29

HIGH RISK PREVENTIVE STRATEGIES

In addition to the risk screening, many interventions relied on detecting precocious increased uterine activity, usually quiescent at least until32 to 34 weeks in pregnancies delivering at term,19 and maturational cervical changes (dilatation, effacement). Observation al studies from the Haguenau experiment have shown that increased preterm uterine activity perceived by women and early cervical changes can be attributed respectively to 15.9 and 17.6 percent of preterm deliveries. 20 These observations along with the modified Papiemik risk scoring system20 have been used as a basis for the development of a strategy of screening for high risk pregnancies. Approximatively 12 talS percent of the pregnant population can be identified as being at high risk for preterm delivery.21,22 The rationale was that screening will identify a proportion of pregnancies where early recognition of premature uterine activity or cervical changes will allow effective interventions to prevent preterm delivery.23 An overview of single or multiple interventions carried out in high risk pregnancies and tested by randomized controlled trials (RCfs) is illustrated in Table 1.

M EDICATIONS

Intravenous tocolytics 14 ,30 or even oral tocolytics either after preterm labour has been diagnosed31 or as prophylaxis 32 ,33 have been proven to be ineffective. Antibiotics also have been shown ta be ineffective. 34 Other agents including medroxyprogesterone acetate showed some efficacy35 although this was abandoned because of its potentially harmful effects on the fetus. Calcium and magnesium, although effective, did not address preterm delivery as the target outcome. 36,37 MULTI PLE INTERVENTIONS PROGRAMMES

The high risk strategies include the organization of specialized high risk clinics, frequent antenatal visits, routine cervical assessment, education sessions advising rest, and recording of uterine activity either by selfpalpation or during hospital visits. Three categories of strategies have been tested: comprehensive education and surveillance, horne uterine activity monitoring, and psychosocial support. COMPREHENSIVE EDucATloN AND SURVEILLANCE

SINGLE INTERVENTIONS

In addition to screening and education, this type of programme included routine cervical examination with uterine activity monitoring by the woman herself or at hospital, and a frequent recourse to hospital admission. The first report of such a programme was most promising in that the preterm delivery rate was reduced by half compared to historical controls. 38 A collaborative clinical

CERVICAL CERCLAGE

Whether performed in high or moderate risk women, this intervention was not effective in more than 2,000 women (Table 1).24 In one trial (MRC/RCOG), there was some suggestion ofbenefit in high risk patients with previous cerclage success or suspected cervical

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, , , TABLE 1 EFFECTIVENESS OF INTERVENTIONS TO PREVENT PRETERM DELIVERY IN A HIGH RISK POPULATION (RANDOMIZED CLiNICAL TRIALS) NO. TRIALS

NO. WOMEN

OR

CI

A. Interventions • cervical cerclage (Grant, 1993)24

4

2,040

0.87

0.70, 1.07

- high risk (Grant, 1993)

2

1,051

0.79

0.61, 1.03

- moderate risk (Grant, 1993)

2

775

0.90

0.57, 1.43

• hospital bed rest in twins (Crowther, 1993)25

4

955

• routine cervix exam. (Kaufman, 1994)28

1

5,067

1.39 0.93

0.74, 1.17

1.02, 1.78

Medications 16

1,500

0.82

0.66, 1.02

• tocolytics, oral after preterm labour (Keirse, 1993)30

3

208

0.66

0.38, 1.13

• tocolytics, oral in twins (Keirse, 1993)33

7

611

0.84

• progestogens (Prendeville, 1993)35

5

328

0.50

0.61, 1.18 0.30, 0.85

• tocolytics, I.V. (Keirse, 1994)30

• magnesium (Keirse, 1993)36

3

1,738

0.67

0.47, 0.97

• calcium (Duley, 1994)37

5

1,509

0.66

0.45, 0.97

• antibiotics (Crowley, 1994)34

4

625

0.79

0.57, 1.09

1

132

1.05

0.48, 2.27

1

4,595

1.06

-

1

969

1.12

0.83, 1.51

B. Programmes • high risk evaluation, cervix exam., increased antenatal visits, rest· Main, 198541 Mueller-Huebach, 198942 Goldenberg, 199040 Collaborative Group (1993)39

1

2,395

1.04

0.86, 1.26

Hobel, 199443

1

2,654

0.81

0.62, 1.06

• home uterine activity monitoring (Keirse, 1993; f n i dings not valid)44

7

1,422

0.67

0.49,

• psychosocial support from caregivers (Hodnett, 1994)49

9

8,067

0.92

0.80, 1.05

0.91

• Calculations on primary data in Relative Risk ± 95% Confidence Interval OR, CI: Odds Ratios ± 95% Confidence Interval

delivery.44 A meta-analysis however, suggests that because of multiple methodological flaws in clinical trials, there "is at the present time no convincing evidence of effectiveness."44 This was confirmed by Grimes and SchulzY Further multivariate analysis established that such risk factors as twin pregnancies and previous preterm delivery are so determinant that they cannot be modified by this intervention. 46

trial however, sponsored by the March of Dimes did not provide any evidence of effectiveness (Table 1).39 Apart of this trial was reported by Goldenberg. 40 Neither Main using a similar approach,41 nor Mueller-Heubach42 found evident beneHt. Hobel's programme wh ich placed emphasis on the reduction of psychological stress was unable to reduce preterm deliveryY After evidence of ineffectiveness in more than 10,000 high risk pregnaneies, no further study is needed.

PSYCHOSOCIAL SUPPORT HOME UTERINE ACTIVITY MONITORING

Psychosocial support with an educational component has been apart of all multiple interventions trials. It was specifically addressed in large trials in Australia47 and Latin America. 48 A meta-analysis showed no evidence of a reduetion in preterm births in the high risk population,49 despite inereased knowledge of risk faetors among women reeeiving the intervention. 48

In the 1980s, a mobile microcircuit device was developed for the measurement of uterine activity at horne, monitoring twice daily. The tracings were transmitted by telephone for evaluation. In addition, patients were given both comprehensive surveillance and education. This expensive technology added to nursing feedback seemed to be effective in reducing preterm

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, , , improvement in her group of women in Brooklyn, NY, when education was appropriate for the woman's reading abilities, cultural background, and intellectual capabilities. 59 In the Province of Quebec, a survey carried out in 1986 among obstetricians and ob-gyn residents has shown that if risk factors were not present, one obstetrician out of five and one resident out of three would not discuss methods of prevention to achieve a term pregnancy.60 Conversely, among 800 middle-class pregnant women questioned in that province, knowledge of preterm delivery was poor: 50 percent did not know at what gestational age an infant was considered to be at term and 33 percent ignored the fact that preterm infants might encounter problems,61 confirming others' observations. 6Z

HOME VISITS

Horne visits by midwives to women at high risk for threatened preterm labour did not result in a reduction of preterm delivery in three randomized controlled trials. 50 POPULATION-ORIENTED PREVENTIVE STRATEGIES

I NTRODUCTION

The ineffectiveness of the high risk strategy in reducing preterm birth has been suggested for many years 51 .5Z and it was recently confirmed. 53 ,54 Many authors agree that efforts should be directed towards populationoriented prevention strategies. 53 ,54 Such strategies hypothesized that it was better to have a modest effect on a large number of individuals than a substantial effect on obviously a restricted number of people. As yet, there is only circumstancial evidence that some interventions or programmes are effective in preventing preterm delivery (Table 2).

WORKING CONDITIONS

Several studies using uni varia te analyses reported that some employees working under certain conditions are at increased risk of preterm birth, especially health care professionals and unskilled workers. 63 An index of professional fatigue including working long ho urs (> 40h), standing up for more than two hours at a time, shift hours, humid and cold environments, repetitive and unstimulating tasks was associated with an increased risk of preterm birth in a prospective cohort studyY Using a multivariate analysis, adjusting for socio-economic confounders, the only factor still associated with preterm delivery was standing for more than two hours. One retrospective64 and another prospective65 cohort study of work leave in high risk ergonomic conditions confirmed this observation (Table 2). However, the evidence is weak that withdrawal from work is effective. In Canada, there is no national policy of paid work leave on medical prescription as in France. 5Z In Quebec, a policy of paid "Retrait preventif de la femme enceinte" in risky working conditions since 1980 did not reduce the preterm delivery rate. z

RELATIVE EVIDENCE OF EFFECTIVENESS USE OF PRENATAL CARE

In France55 and the United States,56 studies with historical controls or retrospective assessments showed that the use of intensive prenatal services was associated with preterm birth reduction. Inadequate attendance had the worst outcome (Table 2).57 However, this evidence is of poor quality due to the research design used (historical controls) and selection biases (compliers). EDUCATION

Education on preterm birth risk factors was not tested by RCT in a population-oriented strategy. A retrospective cohort study comparing participants and non-participants showed a non-significant reduction of prematurity (Table 2).58 The educational programme included a videotape for expectant mothers of 24 to 32 weeks, nurse discussions with pregnant women about the universal risk of preterm birth, and education for care providers. In another study, women who were educated about preterm labour had a 95 percent chance ofbeing candidates for tocolytic therapy when they presented in preterm labour compared to 57 percent before the educational intervention. 59 Freda showed significant

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CARRYING OWN CASE NOTES

Two RCTs assessed the effectiveness of this intervention in preventing preterm delivery in 552 women (Table 2).66 Although it was not effective, the metaanalysis' author urged the need for more trials on this issue as no harmful effects were observed. In addition, this intervention showed an increased sense of self-control in women during their pregnancy (OR: 1.51; CI 1.08,2.18)

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, , , TABLE2

POPULATION-ORIENTED STRATEGIES TO PREVENT PRETERM DELIVERY. RELATIVE EVIDENCE OF EFFECTIVENESS POPULATION TYPE

STUDY DESIGN

NO. WOMEN

OR

CI

Bouyer, 198955

population oriented

historical control

12,000

0.86

0.45, 0.97

Alexander, 1987 56

population oriented

retrospective cohort

430,349

0.50

0.49, 0.51

low risk

retrospective cohort

6,176

0.60

0.51, 0.71

ordinary risk

retrospective cohort

2,326

0.80

0.57, 1.12

Teitelman, 199064

ordinary risk

retrospective cohort

1,206

2.72

1.24, 5.95

Launer, 199065

ordinary risk

retrospective cohort

15,786

1.56

1.04, 2.60

population oriented

RCT (n2)

552

0.92

0.80, 1.05

population oriented

RCT (n4)

4,852

0.81

0.65, 1.01

population oriented

RCT(n1)

547

0.44

0.21, 0.90

INTERVENTION Prenatal care utilization

Hulsey, 1991 57 Education Anderson, 1989 58 Working position (standing vs. sitting)

Carrying own case-notes Hodnett, 199400 Smoking cessation strategies Lumley, 199467 Energy and protein intake Kramer, 199470 Programmes Risk, education, training Konte, 198871 Yawn, 198922 (2 more minutes)

rural

historical control

9,296

0.85

0.67, 1.07

population oriented

historical control

2,041

0.40

0.20, 0.80

population oriented

historical control

16,143

0.69

0.58, 0.82

lowand medium risk

quasiexperimental

2,172

0.58

0.36, 0.94

French programme Papiernik, 1985 72 Prenatal surveillance for preterm labour Breart, 1981 73 OR, CI: Odds Ratios ± 95% Confidence Interval

ENERGY AND PROTEIN INTAKE INTERVENTION

and more women would prefer similar care in the future (OR: 4.76; CI 3.33,7.14).66

Nutritional intake was tested in Greece in one RCT.70 In addition to increased birthweight, a significant reduction of preterm delivery was observed (T able 2). Further study in our population is needed.

SMOKING CESSATION STRATEGIES

Four RCTs tested this behaviourial intervention with an almost significant reduction of the preterm birth rate when tested on 4,852 pregnancies (Table 2).67 Another recent study showed that quitting rates were significantly increased in the intervention group compared to usual care (I4.5 versus 2.5 percent).68 Individualized counselling had a similar effect on the intervention group when the intervention started before 25 weeksY Interventions varied from a self-help booklet with a 10- to 30-minute teaching session for smoking cessation to frequent dinic visits, phone calls or letter reinforcements.69

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UNIVERSAL RISK ASSESSMENT, SELFTRAINING, AND PROVIDER'S EDUCATION

A community-wide programme induded: 1) assessing all pregnant women for their risk of developing preterm labour; 2) providing education, training, and support to high risk women; and 3) offering education and consultation for health providers regarding recognition and treatment of preterm labour. This was carried out in the rural population of Northem California but was found to be ineffective (Table 2).71

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, , , discomfort but not necessarily pain. The goal of the programme was to modify women's attitudes, lifestyles, and daily activities according to self-recognition and selfmanagement of what initiates preterm uterine contractions, by modifying these daily activities to avoid uterine activity. Liberal use of work leave and hospital selfadmission were encouraged. The preterm birth rate decreased from 5.4 to 4.1 percent and then to 3.7 percent for the three four-year periods.68 The overall 30 percent reduction was associated with a conspicuous decrease of 66 percent in the very preterm birth rates « 33 weeks), from 1.5 to 0.5 percent. Conversely, no reduction occurred in high risk women with a history of a previous preterm labour (12.7%,12.5%,12.3%), respectively, for the periods studied. 72

Yawn used a programme of community risk screening together with several additional interventions. 22 An educational programme adding on average an extra two more minutes to each antenatal visit was provided repeatedly by the physician. This was followed up by one individualized educational session with a nurse. The programme also included a patient education pamphlet given at the first antenatal visit increasing patient awareness, together with instructions to all health care personnel (emergency room, receptionists, nurses) on how to handle any phone calls from pregnant women, with the message that preterm labour cannot be diagnosed over the phone but only in hospital. A 24-hour hotline was available. Within two years, the matemal admission rate increased by a third but there was a 30 percent reduction in preterm deliveries (Table 2).22 Further analysis showed that potentially preventable preterm deliveries were reduced by 60 percent. 22 Cost savings in terms of neonatal care less matemal admission costs was estimated to be close to half a million dollars within the two-year study period.

SPECIFIC PRENATAL SURVEILLANCE

A quasi-experimental study compared two polieies of antenatal supervision in two different matemity units in the Paris area. 71 Usual care was compared to intensive surveillance induding quest ions regarding preterm uterine activity at each antenatal visit, refraining from physical exertion, liberal self-admission to hospital, and bi-weekly visits from 26 weeks in women with increased preterm uterine activity. The preterm birth rate was 4.02 percent compared to 7.05 percent in the control unit (p < 0.025; Table 2) while the preterm delivery below 35 weeks was 2.19 percent as compared to 3.02 percent (p< 0.05). Low birthweight « 2,500g) occurred in 4.06 percent and 6.50 percent (p < 0.05) in the intensive and control groups, respectively. Variations were seen more in the "average risk" group, excluding married women of upper social dass (low risk). This weil designed nonrandomized study was carried out from 1974 to 1976/ 3 but could not be confirmed by RCT in France due to national ongoing prematurity prevention policy and has not been repeated elsewhere.

FRENCH PROGRAMMES

In the early seventies, a national perinatal poliey was enforced. 52 There were changes in the organization of medical care services regarding continuity of antenatal care. Financial compensation to women was an incentive to start their antenatal care in their first trimester. Other social measures included recommendations to reduce daily physical efforts with liberal use of paid work leave when needed, and horne visits to advise rest in high risk women, reinforcing the educational message to both the woman and her family and horne domestic assistance as determined by a social worker. The national preterm birth rate fell by 30 percent berween 1971 and 1981 (6.8 to 5.0%) with a further reduction of 20 percent in 1991 (4.0%).52 A prospective study was carried out in an industrial region for 12 years (1971 to 1982): the Haguenau Experiment. 72 The basic principle relied on the concept that physical effort, in professional or daily activities, causes uterine contractions which increase the risk of preterm delivery among predisposed women. The assessment of uterine contractions, especially by nulliparous women, was expressed as an abnormal sensation that their abdomen was becoming hard, or even as asensation of heaviness in the lower abdomen or cyclic lower back

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SUMMARY There is some evidence to suggest that a communityoriented approach may be an effective strategy for reducing preterm birth. Most promising interventions for a programme of prevention of preterm birth may include the following: 1. Perinatal care utilization with increased preventive content may be a key element. 7l The average duration of a prenatal visit in North America, however, is five

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What would a major advanceme nt • mean tn the treatment of osteoporosis?

, , , minutes compared to 20 minutes in France SI where the health care provider must complete a pregnancy booklet (with a list of specific points). The booklet puts emphasis on health promotion rather than complications. Asking specifically about "tightenings" or abnormal sensations at each antenatal visit required only two more minutes in the Yawn Study.22 This would allow for appropriate counselling and further investigation if needed. Free accessibility to health care resources is mandatory, together with a hotline access. 22 Risk screening, periodically reassessed, applied to the general population (to ascertain the normal evolution of pregnancy) was apart of the Haguenau experiment. 72 Women carrying their own pregnancy booklet was assessed favourably by expectant mothers. 66 2. Education of pregnant women about preterm birth is lacking. This can be improved by the use of a simple pamphlet and own-case pregnancy notes compiled by the attending physician and a nurse educator. At each antenatal visit, counselling towards achieving a term pregnancy together with advice on healthy pregnancy habits seemed to have an effect. The importance of an individualized teaching session provided by a nurse educator was stressed in several effective interventions. 22 ,S8 3. Self-control and self-management are the only ways of changing attitudes and behaviours in pregnant women and will raise awareness of what causes preterm uterine activity in their daily lives. Trials based on efficacy expectations of behaviour changes including performance accomplishments (behaviour), vicarious experience (MD), verbal persuasion (MD, nurse educator), emotional arousal (attribution), and self efficacy (pregnant woman, spouse) have been described. 74 The well-informed woman who accepts responsibility for her own actions is more likely to accept lifestyle modifications, especially smoking cessation and healthy nutritional habits. 74 Lifestyle modifications are possible, and measures of the effects of change are available. 7s A sense of self-control and self-management are the starting points of any health promotion programme and based on this, compliance is increased in pregnant women. 76 Demographic variables associated significantly with behavioural changes included previous contact with a physician and being married. Matemal age, income, and education were not. These observations were made in a programme which included lifestyle assessment, physician prescriptions of lifestyle change, and educational materia1. 75

JOURNAL SOGC

DISCUSSION

The lack of effectiveness ofhigh risk strategies raises several issues. Was the intervention inappropriate or was it simply that it was applied to the wrong segment of the population? Indeed, there is some evidence that high risk factors cannot be modified, emphasizing the concept of dichotomy between identification and prevention by modifying permanent and non-preventable risk factors including previous preterm delivery, twins, and uterine anomaliesYI.51 Furthermore, as there are still as yet unknown risk factors, the majority of preterm births still cannot be predicted.),18 As such, sensitivity of screening processes ranged from 14 to 48 percent) and was assessed to be only seven percent in nulliparas. 21 MuellerHeuback reported that more than 60 percent of preterm births were from the so-called low risk population. 41 Finally, an intervention aimed at the reduction of preterm birth in a high risk population would have to decrease dramatically the preterm delivery rate in the high risk group if it were to produce a significant effect on the overall preterm birth rate of a country (estimated rate reduction from 13 to 3% by Bouyer, in France, for obtaining a crude risk reduction rate of 1% in the total population with a prematurity rate of 5.8%).51 This avenue of prevention is impossible with the current state of knowledge and available interventions. CONCLUSION

The preterm birth rate in Canada has not decreased for decades and is the cause of increased use of health care resources and societal costs, with devastating social implications for survivors and their families. The actual curative approach (tocolytics) cannot improve pregnancy duration. The secondary preventive strategy used in high risk women has established its ineffectiveness mainly due to a still unknown causal pathway of preterm delivery. A programme of primary prevention intervention applied to the entire population, including education and giving responsibility for their health to pregnant women, has circumstantial potential to reduce preterm delivery, although its effectiveness has not yet been demonstrated in a randomized controlled trial. Such a study directed to sampIes of the entire pregnant population should be undertaken as soon as possible for the benefit of future Canadian generations.

582

JUNE 1996

New PrFOSAMAX®

increases bone mass in

postmenopausal women

8.8% increase in BMD at the spine 1·••.t.t

7.8%

3.1%

increase in BMD* at the hip l.t.t

increase in BMD at the wrist

(ultradistal forearm) 2 ·t·*

20% of bone mass has been lost by the average postmenopausal woman

FOSAMAX* is a bone metabolism regulator FOSAMAX• is indicated for the treatment of osteoporosis in postmenopausal women • Bone Mineral Density •• In clinical studies. over 96% of patients studied for up to three years had a measured increase in spine BMD I t FOSAMAX* 10 mg daily produced statistically significant and clinically important increases in BMD at the hip. spine. and wrist (ultradistal forearm) relative to placebo at three years (p:!>O.OOI )-'' t Combined data from two large. identically designed. double-blind placebo-controlled. three-year multicenter studies in 994 women with osteoporosis. defined as low bone mass. 397 received placebo and 196 of whom received FOSAMAX• 10 mglday. To ensure an adequate calcium intake. all patients were supplemented with 500 mg of calcium per day 1 I Liberman UA et al Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl I Med 1995;333(22) 1437-43 2 Data on file. Merck Frosst Canada Inc .. 1\vo double-blind. randomized . placebo-controlled. parallelgroup. multicenter studies to evaluate the safety and effect on bone density of daily oral MK-217 for two years in osteopenic postmenopausal women . with a one-year open treatment extension !Protocol No. 035 (US) and 037 (lnternationai)I-Three Year Data

Builds bone to build independence *Trademark Merck & Co . Inc.. Merck Frosst Canada Inc .. licensed user

olendronote sodium

, , , 15. Papiernik E. Coefficient de risque d'accouchement premature. Presse Medicale 1969;77:793. 16. Papiernik E, Kaminski M. Multifactorial study of the risk of prematurity at 32 weeks of gestation: a study of the frequency of 30 predictive characteristics. J Perinat Med 1974;2:30-6. 17. Lettieri L, Vintzileos A, Rodis J, Albini M, Salafia e. Does "idiopathic" preterm labor resulting in preterm birth exist? Am J Obstet GynecoI1993;168:1480-5. 18. Berkowitz G, Papiernik E. Epidemiology of preterm birth. Epidemiol Rev 1993;15:41443. 19. Germain A, Valerzuela G, Ivankovic M, Ducsay CA, Gabella C, Seron-Ferre M. Relationship of circadian rhythms of uterine activity with term and preterm delivery. Am J Obstet GynecoI1993;168:1271-7. 20. Bouyer J, Papiernik E. Risk factors identified during prenatal consultation. In: Papiernik E, Keith LG, Bouyer J, Dreyfus J, Lazar P (Eds). Effective Prevention of Preterm Birth: The French Experience Measured at Haguenau. March of Dimes. Birth Defects, Original Article Series. White Plains, New York, Vol 25, no 1, 1989:39-72. 21. Creasy RK, Gummer BA, Liggins Ge. A system for predicting spontaneous preterm birth. Obstet Gynecol 1980;55:692-5. 22. Yawn BP, Yawn RA. Preterm birth prevention in rural practice. JAMA 1989;262:230-3. 23. Katz M, Goodyear K, Creasy RK. Early signs and symptoms of preterm labor. Am J Obstet Gynecol 1990;162:1150-3. 24. Grant AM. Cervical cerclage (all trials). In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 04135, 4 October, 1993. High risk, review no. 03279, 4 October, 1993; Moderate risk, Review no. 03281, 4 October, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1993, Disk Issue 2. 25. Crowther CA. Hospitalisation for bed rest in twin pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 03376,5 October, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 26. Cuthbertson DP. The influence of prolonged muscular rest on metabolism. Biochem J 1929;23:1328-45. 27. Deitriek JE, Whedon GD, Shorr E. Effect of immobilization upon various metabolie and physiologie functions of normal men. Am J Med 1948;4:3-26. 28. Kaufman K. Weekly vaginal examinations. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of System atic Reviews:' Review No. 06818, 25 March, 1994. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1.

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JUNE 1996

New FOSAMAX® reduces the risk of vertebral fractures

48%

reduction in the proportion of patients treated with FOSAMAX® experiencing one or more vertebral fractures relative to those treated with placebo in pooled analysis (5~20 mg) (p=0.034) 1''1

Low bone mass is a major predictor of increased risk of osteoporotic fractures 3

'I Vertebral fractures occurred in 6.2% (22/355) of patients who received placebo and 3.2% ( 17/526) of patients who received FOSAMAX® (5 or 10 mg for 3 years or 20 mg for 2 years followed by 5 mg for I year) .' 3. Consensus Development Conference: Diagnosis. prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-9.

Builds bone to build independence alendronate sodium

, , , 29. Buekens P, Alexander S, Boutsen M, Blondel B, Kaminski M, Reid M and European Community Collaborative Study Group on Prenatal Screening. Randomized controlled trial of routine cervical examinations in pregnancy. Lancet 1994;344:841-3. 30. Kierse MJNC. Betamimetic tocolytics in preterm labour. In: Enkin MW, Keirse MJ, Renfrew MJ, Neilson JP (Eds). 'Cochrane Database of Systematic Reviews.' Pregnancy and Childbirth Module. Review no. 03237,17 February, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 31. Keirse MJNC. Oral betamimetics for maintenance after preterm labour. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 04380,2 April, 1992. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 32. Moutquin JM. The limits of medical actions: oral betamimetics. In: E Papiernik, G Breart, N Spira (Eds). Prevention de la naissance prematuree. INSERM, Paris, 1986:69-82. 33. Keirse MJNC. Prophylactic oral betamimetics in twin pregnancies. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 03462, 24 March, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 34. Crowley P. Antibiotics in preterm labour with intact membranes. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 05531,5 May, 1994. Published through 'Cochrane Updates on Disk,' Oxford: Update Software, 1994, Disk Issue 1. 35. Prendiville WJ. 17alpha-hydroxyprogesterone caproate in pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 04399, 2 April, 1992. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1993, Disk Issue 2. 36. Keirse MJNC. Routine magnesium supplementation in pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 04008,16 June, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1993, Disk Issue 2. 37. Duley L. Routine calcium supplementation in pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 05938, 23 June, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 38. Herron MA, Katz M, Creasy RK. Evaluation of apreterm prevention program: preliminary report. Obstet Gynecol 1982;59:452-6.

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39. Collaborative Group on Preterm Birth Prevention. Multicenter randomized controlled trial of apreterm prevention program. Am J Obstet GynecoI1993;169:352-66. 40. Goldenberg R. The Alabama preterm birth prevention project. Obstet GynecoI1990;75:933-9. 41. Main DM, Gabbe SG, Richardson D, Strong S. Can preterm deliveries be prevented? Am J Obstet Gynecol 1985;151 :892-8. 42. Mueller-Heubach E, Reddick D, Barnett B, Bente R. Preterm birth prevention: evaluation of a prospective controlled randomized trial. Am J Obstet Gynecol 1989;160:1172-8. 43. Hobel CJ, Ross MG, Bemis RL, Bragonier JR, Nessim S, Sandhu M, Bear MB, Mori B. The West Los Angeles Preterm Birth Project. Am J Obstet Gynecol 1994;170:54-62. 44. Keirse MJNC. Home uterine activity monitoring for preventing preterm delivery. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 06656, 2 April, 1992. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1993, Disk Issue 2. 45. Grimes DA, Schulz KF. Randomized controlled trials of home uterine activity monitoring: a review and critique. Obstet GynecoI1992;79:137-42. 46. Moutquin JM, Bernard PM, Turcot L, Fraser WD, Bastide A. Is uterine activity monitoring in high risk women effective to prevent preterm delivery? Proc 39th SOGC AGM Calgary, June 24-29,1995. 47. Bryce RL, Stanley FJ, Garner JB. Randomized controlled trial of antenatal social support to prevent preterm birth. Br J Obstet Gynaecol 1991 ;98: 1001-8. 48. Vilar J, Farnot V, Barros F, Victoria C, Langer A. Belizan JM. A randomized trial of psychosocial support during high risk pregnancies. N Engl J Med 1992;327:1266-7. 49. Hodnett ED. Support from caregivers during at-risk pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds). Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 04169, 27 April, 1994. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1. 50. Blondel B, Breart G. Home visits for pregnancy complications and management of antenatal care: an overview of three randomized controlled trials. Br J Obstet Gynaecol 1992;99:283-6. 51. Bouyer J, Papiernik E. The dichotomy between prediction and prevention. In: E. Papiernik, LG Keith, J Bouyer, J Dreyfus, P Lazar (Eds). Effective Prevention of Preterm Birth: The French Experience Measured at Haguenau. Birth Defects Original Article Series Vol 25, March of Dimes 1989:167-73. 52. Papiernik E. Community wide approaches to preventing preterm birth. In: Beyond individual risk assessment: community wide approaches to promoting the health and the

586

JUNE 1996

New FOSAMAX® generally well tolerated nonhonnonaltherapy

Adapted from the product monograph

.... FOSAMAX® has been evaluated for safety in clinical studies in 994 postmenopausa l patients . .... The overall safety profiles of FOSAMAX® I 0 mg per day and placebo were similar. .... Adverse events were usually mild and generally did not require discontinuation of therapy. As with other bisphosphonates. caution should be used when FOSAMAXG> is given to patients with active upper gastrointestinal problems. such as dysphagia . symptomatic esophageal diseases. gastritis. duodeniti s. or ulcers FOSAMAX® is contraindicated in patients who are hypersensitive to any component of this product. patients who are hypocalcemic. or patients who suffer from renal insufficiency (creatinine clearance < 35 mUmin)

Builds bone to build independ ence alendronate

0

sodium

MERCK FROSST

MERCK SHARP & DOH ME CANADA DIV. OF MERCK FROSST CANADA INC. KIRKLAND, QUEBEC

BEFORE PRESCRIBING. PLEASE CONSULT THE PRESCRIBING INFORMATION .

FSM-96-CDN-941 0-JA

, , , development of families and children. Washington. U.S.

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Department of Health and Human Services, 1988:145-75. 53. Alexander GR, Weiss J, Hulsey TC, Papiernik E. Preterm birth prevention: an evaluation of programs in the United States. Birth 1991;18:160-9.

base of Systematic Reviews:' Review No. 03312, 2 October, 1993. Published through 'Cochrane Updates on

54. Yawn BP. Preterm prevention: a physieian's perspective. Minn Med 1990;73:31-4.

Disk: Oxford: Update Software, 1994, Disk Issue 1. 68. Seeker-Walker RH, Solomon U, Flynn BS, Skelly JM, Lepage S, Goodwin GD, Mead PB. Individualized smoking

55. Bouyer J, Guegen S. The effectiveness of modifying prenatal care. In: Papiernik E, Keith LG, Bouyer J, Dreyfus J and Lazar P (Eds). Effective Prevention of Preterm Birth: The French Experience Measured at Haguenau. Birth Defects Original artide series. Vol 25, no. 1, March of Dimes. White Plains, NewYork,1989:159-65.

cessation counselling during prenatal and early postnatal care. Am J Obstet Gyneco11994;171 ;1347-55. 69. Dolan-Mullen P, Ramirez G, Groff JY. A meta-analysis of randomized dinical trials of prenatal smoking cessation interventions. Am J Obstet Gyneco11994;171 :1328-34. 70. Kramer MS. Nutritional advice in pregnancy. In: Enkin

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plicated pregnaneies? Birth 1991;18:146-50. 58. Anderson HF, Freda MC, Damus K, Brustrnan L, Merkata IR. Effectiveness of patient education to reduce preterm delivery arnong ordinary risk patients. Am J Perinatol 1989;6:214-7. 59. Comerford Freda M, Damus K, Merkatz I. The urban

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1985;76:154-8. 73. Breart G, Goujard J, Blondel B, Maillard F, Sureau C, Rumeau-Rouquette C. A comparison of two polieies of ante-natal supervision for the prevention of prematurity. Int J Epidemiol1981 ;10:241-4. 74. Comerford Freda M, Andersen H, Damus K, Poust D, Brustman L, Merkatz I. Lifestyle modification as an intervention for inner city women at high risk for preterm birth. J Adv Nurs 1990;15:264-72. 75. Kelly RB. Controlled trial of a time-effieient method of health promotion. Am J Prev Med 1988;4:200-7. 76. Stewart DE, Buchegger M, Lickrish GM, Sierra S. The effect of educational brochures on follow-up compliance in women with abnormal Papanicolaou smears. Obstet Gynecol 1994;83:583-5.

60. Moutquin JM, Desgranges MF. A survey on prevention of prematurity among obstetrieians and residents in Quebec Province. Proc SOGC Meeting, Vancouver BC, June 2225,1988. 61. Labrecque M, Martin J, Moutquin JM, Marcoux S, Gingras S. Connaissance des femmes enceintes sur la prematurite. Un Med Can 1993;122:347-52. 62. Cormerford Freda M, Damus K, Meikatz I. What do pregnant women know about preventing preterm birth? J Obstet Gynecol Neonatal Nurs 1990;20:140-5. 63. Mamelle N, Laumon B, Munoz F, Collin D. Mode de vie pendant la grossesse et prematurite. In: Bouyer J, Dreyfus S, Guengen P, Lazar E, Papiernik (Eds). La Prematurite: Enquete perinatale de Haguenau. INSERM, Paris, 1987:59-73. 64. Teitelbaum AM, Welch LD, Hellenbrand KG, Bracken MB. Effect of maternal work activity on preterm birth and low birthweight. Am J EpidemioI1990;131: 104-13. 65. Launer U, Villar J, Kestler E, Mercedes DO. The effect of maternal work on fetal growth and duration of pregnancy: a prospective study. Br J Obstet Gynaecol 1990;97:62-70. 66. Hodnett ED. Women carrying their own case-notes during pregnancy. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP (Eds).Pregnancy and Childbirth Module. 'Cochrane Database of Systematic Reviews:' Review No. 03776,12 May, 1993. Published through 'Cochrane Updates on Disk: Oxford: Update Software, 1994, Disk Issue 1.

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