Induction of labour or expectant management for suspected macrosomia in term pregnancies: a randomised controlled trial

Macrosomia is defined as a birthweight above 4000 g, 4200 g or 4500 g, depending on the authors. In our institution, 8% of newborns have a birthweight above 4000. The delivery of these large infants is associated with high maternal and perinatal morbidity and mortality. Maternal complications of macrosomia include caesarean section, perineal, anal sphincter and cervical tears, vaginal lacerations, uterine atonia and postpartum haemorrhage. Neonatal complications include shoulder dystocia and its dramatic consequences, brachial plexus palsy, bone fracture and asphyxia.

One possible strategy to reduce the risk of morbidity associated with the delivery of a macrosomic fetus is to induce labour in case of suspected large-for-dates fetus. The goal of induction of labour is to reduce the duration of pregnancy and thus fetal growth. This may reduce the risk of a difficult vaginal delivery, with the associated maternal and neonatal morbidity. The risk of caesarean section, mainly indicated by cephalopelvic disproportion, increases with birthweight. On the other hand, induction of labour may be associated with a higher risk of dysfunctional labour and of caesarean section. Only two randomised trials, including a total of 313 women, were found by a systematic review of the literature. The results of these two studies do not provide sufficient evidence to guide clinical practice. Antenatal detection either clinically or by ultrasound scanning of a large-for-dates fetus is difficult. It is unclear whether a policy of induction of labour for women with a fetus suspected to be large-for-dates could reduce the risk of neonatal and maternal morbidity.

Some clinicians perform induction of labour when the fetus is suspected to be large-for-dates, while others prefer to wait until the onset of spontaneous labour. We propose to conduct a multicentre randomised controlled clinical trial to compare these two management options in the case of suspected large-for-dates fetus at term.

The proposed study will include 1600 women with a singleton pregnancy in vertex presentation at 37 to 38 weeks of pregnancy, presenting with a suspicion of large-for-dates fetus diagnosed clinically and confirmed by ultrasound. Consenting women will be randomly allocated to induction of labour at 37 to 38 weeks or expectant management until spontaneous onset of labour. The main outcome measures will be shoulder dystocia, neonatal trauma, birth asphyxia, maternal perineal trauma and caesarean section. Sequelae of perineal trauma, including fecal, urinary incontinence and dyspareunia will be assessed by a postal questionnaire 3 months and one year after delivery. Disease specific, the incontinence impact (IIQ7) and the general health (SF-12) questionnaires will be submitted to the participants to detect and measure the severity of symptoms and to evaluate their impact on self-perceived general health. Sequelae of neonatal trauma will also be evaluated.

The results of this study will provide clinicians and women with valid evidence to guide decision-making in the case of term pregnancy with suspected macrosomia.

Keywords: obstetrics, neonatology, induction of labour, macrosomia, large-for-dates, maternal morbidity, perinatal morbidity, caesarean section, incontinence.

	Boys		Girls
Week	p90	p95	p90	p95
36	3354	3534	3225	3405
37	3555	3727	3416	3588
38	3731	3896	3584	3748
39	3884	4044	3729	3887
40	4017	4076	3854	4009
41	4131	4296	3958	4117
42	4227	4408	4042	4212

Etiologic factors of macrosomia

The growth and development of the fetus are regulated by and dependent on numerous factors that includes genetic and hormonal factors, uterine environment, placenta function and the availability of nutrients to mother and fetus.

The initial drive for growth is genetic. By mechanisms that remain poorly defined, there is a genetic control of cell growth and differentiation that is the basic determinant of species size at birth. Male gender contributes approximately 150-200 g of increased birthweight, compared with female infants at term. Macrosomia as part of genetic syndrome accounts for only a small portion of cases. Specific syndromes, including Beckwith-Wiedemann, Sotos and others rare syndromes are associated with fetal macrosomia.

Maternal weight before pregnancy is an important determinant of fetal weight19. Parous women are two to three times more likely than nulliparous women to have macrosomic infants20. Multiparity and age over 35 years are also significant risk factors for macrosomia21. Some authors showed that birthweight has increased over time.

The difference in fetal size becomes apparent in the third trimester. Fetal growth in late gestation can be considered the result of the interrelation between the genetic cause of growth and constraining influences that inhibit growth. The balance between genetic and exogenous influences (maternal nutrition, placental factors) is probably controlled by fetal hormones. Clinical and experimental evidence has indicated that insulin can be considered as the true fetal growth hormone22. Nesidioblastosis, an autosomal recessive genetic disorder, is a diffuse or disseminated proliferation of pancreatic islet cells associated with macrosomia. Chronic fetal hyperglycaemia accelerates the development of insulin secretory mechanisms, predisposing infants of mothers with diabetes to have higher levels of insulin and macrosomia.

Consequences of macrosomia

Cephalopelvic disproportion and maternal morbidity

Cephalopelvic disproportion is defined as a disparity between the size of the fetal head and the size of the maternal pelvis, precluding vaginal delivery. Clinically, CPD is diagnosed when labour is prolonged.

A large fetal weight is associated with an increased risk of cephalopelvic disproportion, dysfunctional labour, and failure of engagement of the fetal head. As a consequence, the risk of caesarean section and instrumental delivery is increased. Long-term complications, including perineal trauma, urinary and fecal incontinence are more frequent when the fetus is large23,24.

The risk of caesarean section is increased 2 to 3 times when the fetus is macrosomic.25 Maternal morbidity associated with caesarean section includes thromboembolism, haemorrhage, wound complications, endometritis and urinary tract infection2. The risk of complications is higher when the caesarean section is performed as an emergency, compared to elective procedures26. Prolonged first and second stage of labour is more frequent when the fetus is macrosomic27. Use of oxytocin for labour augmentation may cause uterine hyperstimulation, with the attendant risk of fetal heart rate abnormalities. Prolonged second stage of labour leads to instrumental delivery, which is associated with maternal morbidity (uterine rupture, cervico-vaginal, perineal and anal sphincter tears, and haemorrhage). A large study conducted in Switzerland showed that prolonged first and second stage of labour, caesarean section and operative delivery are significantly more frequent when birthweight is more than 4500 g28.

Shoulder dystocia and neonatal morbidity

Shoulder dystocia is a dramatic emergency with devastating consequences for both the mother and the neonate. The cause of the dystocia is the impaction of the anterior shoulder on the symphysis pubis29. Shoulder dystocia is defined as a delivery of the shoulders requiring manoeuvres in addition to downward traction and episiotomy. A specific duration between the delivery of the fetal head and the completion of the delivery, i.e. more than 60 seconds, was also proposed to define shoulder dystocia30,31. The incidence of shoulder dystocia in the general obstetric population was estimated to be between 1% and 4% of vaginal births in vertex presentation17. The estimate depends on the population and the criteria used to define shoulder dystocia. The retrospective nature of most of the studies may also underestimate the incidence of this accident31.

The risk of shoulder dystocia is associated with higher fetal weight32. Diabetes during pregnancy is a significant risk factor, because of the risk of large-for-dates fetus and of a larger biacromial diameter. Other risk factors include prolonged first and second stage of labour, instrumental delivery and past history of shoulder dystocia33. When birthweight is above 4000 g, the risk of shoulder dystocia was estimated to be 10 times higher than with lower birthweight34. The relative risk when birthweight is above 4500 g is about 20, compared to average weight infants.28

Maternal and neonatal morbidity following shoulder dystocia are severe. Among 98 women with shoulder dystocia, 19% had severe perineal tears, 14% had postpartum haemorrhage and 1% had uterine rupture, compared to 0.5%, 0.4% and 0.06%, respectively, in the general obstetric population of the same hospital35. Shoulder dystocia was found to be significantly associated with perineal morbidity, in a study including 390 women with 4th degree perineal tear36.

Neonatal complications in case of shoulder dystocia include brachial plexus injury, bone fracture, asphyxia and death. In the case of shoulder dystocia, 12% are complicated by brachial plexus palsy, 4% by severe asphyxia and 0.3% by neonatal death37. Erb-Duchenne palsy, the most frequent trauma of the brachial plexus (80%), results from injury of C5-C6 roots38. Affected neonates have adducted arm, with internal rotation, extension of the elbow and pronation of the forearm. This palsy improves in 80% of the cases after 3 to 6 months39.Klümpke palsy involves the lower roots (C7-T1) of the brachial plexus. The prognosis is poorer, as only 40% recover after 6 months. A combination of both palsies has an even worse prognosis. The clavicle is the bone which is the most frequently fractured during a traumatic delivery. This occurs in 0.4% to 1.1% of all deliveries, and a relative risk of 5 was reported with high birthweight28. The incidence may be underestimated, as some fractures are not diagnosed. These fractures usually heal spontaneously without sequelae, but are cause of concern for both the medical staff and the parents. Perinatal death following shoulder dystocia is rare. A total of 56 deaths were reported voluntarily in the UK, which gives an incidence of 2/100 000 births40. In Kuwait, a mortality of 7% among 96 cases of shoulder dystocia was observed35.

Prompt diagnosis and treatment of shoulder dystocia are important to minimise the consequence of this dramatic emergency. Birth asphyxia is a consequence of delay, with cord blood pH decreasing by 0.04 units per minute after the delivery of the head. In macrosomic fetuses, severe neonatal asphyxia is reported in 1.4% after a delivery without shoulder dystocia and in 14.3% with shoulder dystocia. Shoulder dystocia was shown to be a significant and independent risk factor for the occurrence of neonatal seizures41.

In a decision analysis model, Rouse and Goldenberg estimated the cost-effectiveness of elective caesarean section for the prevention of morbidity related to the delivery of large-for-dates fetuses42. The risk of shoulder dystocia was estimated to be 7% when birthweight is between 4000 to 4499 g in non-diabetic women and 14% in diabetic women. With a birthweight of more than 4500 g, the risk increased to 15% and 50%, respectively. Because of the difficulties in estimating fetal weight and the risks and costs associated with caesarean section, their conclusions were that an elective caesarean section to prevent shoulder dystocia is not recommended when fetal weight is below 4500 g, or 4200 g in diabetic women. Given the low cost-effectiveness ratio of elective caesarean section, induction of labour might be an alternative strategy to prevent the occurrence of shoulder dystocia and its consequences.

Detection of macrosomia

For a policy of induction of labour to be effective, large for gestational age fetuses must be reliably identified before they become macrosomic. Clinical estimation based on manual palpation of the uterus or uterine height measurements, as well as ultrasound scanning are currently used methods to attempt at predicting the fetal weight. The predictive value of such tests, especially for large fetuses, is controversial.10 Maternal estimates of fetal weight, compared to that of a previous pregnancy, are as reliable as the estimation made by clinicians43. The limitation of this approach is that it is not applicable to nulliparous women.

Clinical estimates of birthweight

Clinical estimates of fetal weight are usually based on Leopold manoeuvres or on symphysis fundus height measurement.44 These estimates were said to be less precise at the extremes of birthweight45. Reported sensitivity and specificity of clinical estimates of fetal weight, based on Leopold manoeuvres, vary greatly. When clinical estimates of fetal weight were assessed in comparison with a birthweight 4000 g or more, sensitivities ranged from 24 to 97% with specificities ranging from 98 to 82%. Clinical estimates were analysed with the use of ROC curve. The area under the curve for clinical estimates was 0.84, significantly greater than 0.50, which is the area under the curve of a useless test46. The authors of a recent review conclude that clinical estimation of fetal weight is a useful test for predicting birthweight47.

Other authors estimated the prediction of birthweight above 4000 g based on symphysis fundus height measurement 48,49. A height of more than 38 cm was shown to be accurate in the prediction of birthweight above 4000 g.

Sonographic estimates of birthweight

Ultrasound is the most commonly used and widely studied method for fetal weight estimation. Sonographic methods for the diagnosis of macrosomia were developed to improve clinical estimates. Most sonographers use fetal biparietal diameter, abdominal circumference and femur length to estimate fetal weight. These parameters are combined using data-derived formulas, which best fit the specific population from which the method was developed. Using any of the formulas with other populations yield errors of 7 to 10%. Benacerraf reported the prediction of birthweight in 1301 fetuses, of which 324 were greater than 4000 g, by sonographic estimated fetal weight based on abdominal diameter and biparietal diameter. The sensitivity was 65% and the specificity was 90% for predicting a birthweight greater than 4000 g. In the same group of women, the sensitivity improved to 82% and the specificity decreased to 79% when a cut-off off 3800 g was used for the estimated fetal weight instead of 4000 g.

Comparison between clinical and sonographic estimates of fetal weight

A meta-analysis of studies in which both clinical and sonographic estimates were performed showed that 67% of clinical estimates and 66% of sonographic estimates were within 10% of the actual birthweight.47 The mean absolute error of clinical and sonographic estimates of birthweight was 300 g. Among reports of comparison between clinical and sonographic estimates, three reported the accuracy of clinical estimates when the birthweight was ³4000 g. In these studies, 58% of clinical estimates were within 10% of birthweight, compared with 51% of sonographic estimates46,50,51.

When clinical estimates of fetal weight were compared with sonographic estimates in parallel samples, clinical estimates performed favourably. A large study compared clinical and sonographic suspicion of macrosomia (fetal weight at or above 4000 g), with actual macrosomia, defined as birthweight at or above 4000 g. Clinical diagnosis had a sensitivity of 54% and a positive predictive value of 60%, while sonographic diagnosis had a slightly higher sensitivity (71%), but lower positive predictive value (55%). ROC curves for both clinical and sonographic predictions of macrosomia subsume areas between 0.81 and 0.95, significantly larger than the area of 0.5 that indicates a useless test. Thus, these tests are defined as useful from a statistical point of view. Prediction of macrosomia by clinical techniques and ultrasound is limited by false positives and false-negatives cases, but, nevertheless, these tests identify a population with high risk of macrosomia.

Induction of labour for suspected macrosomia

Many obstetricians induce labour at term when the fetus is estimated to be either large for gestational age or macrosomic. The purpose of labour induction in case of suspected fetal macrosomia is to reduce the likelihood of Caesarean section and of difficult operative delivery, possibly resulting in maternal or perinatal morbidity. Observational studies cast doubts on the effectiveness of such a policy6,52. For a policy of induction to be effective, large for gestational age fetuses must be reliably identified before they become macrosomic. This may be one of the limitations of a policy of induction of labour for suspected macrosomia.

Two randomised controlled trials comparing induction of labour to expectant management when the fetus is suspected to be macrosomic were included in this review7.8. Women were included when fetal weight, estimated by ultrasound examination, was between 4000 g and 4500 g7 or between 4000 g and 4750 g8. Diabetic women were excluded from both trials. A computer-generated table of random numbers was used in both studies. The method for concealment of the allocation was by sealed, sequentially numbered, opaque envelopes in one of the trials8, while the method was not described in the other report7. The method used for labour induction was dependent on the cervical status (prostaglandins for cervical ripening in the case of an unfavourable cervix, otherwise oxytocin infusion). In one of the trials7, elective Caesarean section was performed when estimated fetal weight was greater than 4500 g and women in the expectant management group underwent induction of labour upon completion of 42 weeks of gestation.

A total of 313 women were included in the two studies. Compared to expectant management, induction of labour for suspected macrosomia did not reduce the risk of caesarean section (Odds ratio 0.85, 95% confidence interval 0.50 to 1.46) or instrumental delivery (OR 0.98, 95%CI 0.48 to 1.98). Shoulder dystocia was similar between groups (OR 1.07, 95%CI 0.41 to 2.81). Perinatal morbidity was infrequent and similar between groups. Two cases of brachial plexus injury and 4 cases of fracture were reported in the expectant management group. Three and two cases of intracranial haemorrhage were diagnosed by sonography in the induced and expectant group, respectively.7 No information is available regarding mother’s views on their care, urinary and fecal incontinence, and sexual dysfunction or on other long-term morbidity. There is presently no evidence that induction of labour for suspected fetal macrosomia modifies the risk of caesarean section or instrumental delivery. The studies were however of too small sample size to exclude even large effects on these outcomes. There is also very limited evidence to quantify the effect on maternal and neonatal morbidity9.

Risks associated with induction of labour

The results of numerous observational studies suggested that induction of labour is associated with an increased risk of caesarean section14,53-57. Two other observational studies, conducted in contexts of very high rates of labour induction (35 and 50% respectively), reported a 30% reduction in the risk of caesarean section associated with labour induction58,59. It is likely that residual confounding by the indication may bias the above estimates of risk associated with labour induction.

In contrast with the results of observational studies, randomised controlled trials evaluating labour induction do not show an increased morbidity associated with the intervention. A systematic review of randomised controlled trials showed elective induction of labour before 41 weeks to be associated with more use of non-epidural analgesia, more operative vaginal deliveries and a reduction of meconium stained amniotic fluid, but there was no difference in caesarean section between groups11. A large trial, including women with post-term pregnancy (>41 weeks), showed a reduction in the risk of caesarean section when induction of labour was performed, compared to expectant management12.A systematic review of the randomised controlled trials suggested that routine induction of labour after 41 weeks reduced perinatal mortality (OR 0.2, 95%CI 0.1 to 0.9) and the risk of caesarean section (OR 0.9, 95%CI 0.8 to 1.0). In women with prelabour rupture of membranes, induction of labour was shown to decrease the risk of infection, of perinatal mortality without increase in caesarean section, when compared to expectant management13. For pregnant diabetic women treated with insulin, a relatively small trial suggested that induction of labour at 38 weeks do not increase the risk of caesarean section60,61.

There is at present no valid evidence that induction of labour for specific indications increases the risk of caesarean section or of other maternal or neonatal morbidity.

Objectives

The objectives of this randomised controlled trial are, in pregnancies at term with a fetus suspected to be large-for-dates at 37 to 38 weeks
1. To evaluate the effectiveness of induction of labour to reduce neonatal trauma,
2. To evaluate the effectiveness of induction of labour to reduce the risk of maternal morbidity,
3. To evaluate the risk of caesarean section associated with a policy of induction of labour, compared to expectant management.


Hypotheses

Induction of labour for suspected large-for-dates fetuses decreases the risk of maternal morbidity and neonatal trauma associated with the delivery of a macrosomic neonate. The risk of caesarean section with either policy is similar, as a possible increase of caesarean section for dysfunctional labour may be compensated by a reduction of caesarean section for cephalopelvic disproportion.


Type of study

This study will be a multicentre randomised controlled trial comparing induction of labour at 37 (259 days) to 38 weeks (272 days) of gestation with expectant management in women with a large-for-dates fetus.


Study population

Women will be recruited at the antenatal clinic at 36 to 38 weeks of gestation. The obstetrician in charge will inform the eligible woman on the study. Written informed consent will be obtained.

Inclusion criteria

· Reliable estimation of gestational age (clinical and ultrasound before 22 weeks)

· Singleton pregnancy, cephalic presentation

· Fetal weight estimated to be large-for-dates. To identify large-for-dates fetuses, we will first evaluate the fetal weight clinically (1st column). The cut-offs correspond to the 90th percentile for a male fetus and to the 95th percentile for a female fetus. We aim at including in the trial fetuses at high risk of having a birthweight higher than 4000 g, should delivery occur at 40 weeks. This birthweight is the 90th percentile of the distribution for males and the 95th percentile for females.18 If fetal weight is large clinically, we will perform an ultrasound scanning, to verify the clinical estimate. If the estimate is at or above the limits of the 2nd column, the women will be eligible for the trial.

Exclusion criteria

· Maternal diabetes (gestational, type I or type II) treated with insulin

· Previous history of anal sphincter tear or of severe fecal or urinary incontinence

· Shoulder dystocia or neonatal trauma in a previous delivery

· Previous caesarean section or other uterine scar

· Contraindications to induction of labour or vaginal delivery


Intervention

Consenting women will be randomly allocated to one of the following two groups:

· Induction of labour between 37+0 and 38+ 6 weeks gestation. Labour will be induced within 72 hours of randomisation. Women with unfavourable cervix (Bishop score <6) will have cervical ripening using vaginal prostaglandins E2 or Misoprostol, depending of hospital policy. Women with favourable cervix will be induced by intravenous oxytocin with or without artificial rupture of membranes

· Expectant management until spontaneous onset of labour. Labour induction will be performed in the absence of spontaneous labour at 41 weeks (290 days).

Central randomisation will be performed by a telephone call or via the Internet, without communication of nominal data. Randomisation will be stratified by centre and by parity (nulliparous and multiparous women).


Outcome measures

Obstetrical outcome measures

· Neonatal trauma will be defined as any of the following: shoulder dystocia (see definition), bone fracture, brachial plexus palsy or intracranial haemorrhage

· Birth asphyxia, defined as arterial cord blood pH less than 7.10 or Apgar score less than 7 at 5 minutes

· Maternal trauma: 3rd or 4th degree perineal tear or cervical tear or vaginal laceration involving the upper third of the vagina

· Caesarean section

· Other outcome measures will include instrumental delivery, haemorrhage, blood transfusion, icterus respiratory distress and admission to the neonatal intensive care unit.

The definition of shoulder dystocia will be a difficult delivery of the shoulders requiring manœuvres in addition to downward traction and episiotomy and a delay of more than 60 seconds after delivery of the head before completing the delivery.30

Long-term outcome measures (3 and 12 months postpartum)

· Fecal incontinence: assessed by a specific questionnaire and the incontinence impact questionnaire (IIQ7)

· Urinary incontinence: assessed by a specific questionnaire and the incontinence impact questionnaire (IIQ7)

· Dyspareunia and other symptoms of sexual dysfunction

· Self-perceived general health and emotional well-being, assessed by the SF-12 questionnaire74

· Sequelae of neonatal trauma


Data collection

Data will be collected at 4 specific times. Baseline characteristics will be collected after informed consent. Obstetric data will be recorded at delivery and during the hospital stay. Questionnaires evaluating incontinence and general health will be submitted to the participants 3 months and 1 year after delivery. The questionnaires will be sent by post, together with a self-addressed pre-paid envelope. In previous studies conducted in our unit in a similar population, more than 95% of participants completed and returned the questionnaires.


Data analysis

All the analysis will be performed on an intention to treat basis. This means that the outcome for women in the induction of labour group having spontaneous labour or women in the expectant management group being induced for other reasons will be analysed according to the group allocated by randomisation. Blinding to women or to the medical team will not be feasible. Charts will be reviewed by an obstetrician and a neonatologist unaware of the study group to verify the occurrence of outcomes related to perinatal morbidity (assessor blinding). The analysis will be conducted without knowing the group (group X and Y), to ensure blinding at the analysis level.

The two groups will be compared to determine if they differ with respect to baseline characteristics. These characteristics will include age, smoking status and socio-economic factors. Next we will assess the extent to which the protocol was respected in the two groups, i.e. the proportion of women having induction of labour and the difference in mean birthweight. It is likely that some women in the experimental group will start labour before the date set for induction of labour and that some women in the control group will have induction of labour for other reasons. A subgroup analysis by parity (primiparas and multiparas) will be reported, as this variable will likely be an important effect modifier.

Results for the main outcome measures will be reported as relative risks and their 95% confidence intervals. These estimates will be adjusted for study centre by the Mantel-Haenszel method. Statistical significance of the difference in proportions will be evaluated by the Fisher exact test. Logistic regression will be used to adjust the estimate for important predictors. Continuous measures will be compared between groups using the t-test, or non-parametric statistics if data are not normally distributed.


Sample size

The sample size calculation is based on differences between groups in the frequency of neonatal and maternal trauma. The goal of the proposed study is to test the null hypothesis that the risk of neonatal or maternal trauma is similar in the two groups. Neonatal morbidity occurs in 10% or less of deliveries of macrosomic infants. Maternal morbidity occurs in 10 to 20% of these deliveries.

The criterion for significance (alpha, 2-tailed) has been set at 0.05. With a sample size of 800 women per group, we will have a power of 80% or more to show a significant and clinically important risk reduction in a range of incidence in the control group from 5 to 20%. The risk differences for neonatal outcomes (3 to 4%) mean that 25 to 33 women need to have induction of labour to avoid one additional morbidity (number needed-to-treat, NNT). The NNT for maternal outcomes (risk difference 5 to 6%) is 17 to 20.

An additional objective of this study is to test the equivalence in the risk of caesarean section. In this case, the null hypothesis is that the difference between groups is superior to a pre-specified delta (5%). The proposed sample size (800 per group) is of sufficient power (80%) to reject this null hypothesis, if the risk of caesarean section is 20% in both groups. Also, the 95% confidence interval for the risk difference will exclude a 5% difference.


Feasibility

Theoretically, about 5% of pregnant women will be eligible for the study. Taking into account that the agreement between clinical assessment and ultrasound is not perfect and that some women will decline to participate, we estimate that 40% of eligible women will be included. To recruit 1600 women, hospitals delivering a total of 80 000 women during the study period are needed. We plan the study duration to be 2 years, with 3 extra-months as a run-in period of progressively increasing recruitment. Hospitals in Switzerland, France, Belgium and Canada where more than 40 000 deliveries take place each year will participate to the study.


Ethical considerations

Women delivering for large babies at high risk of long term perineal morbidity and their fetuses may suffer from a traumatic delivery. Thus, it is important to evaluate an intervention to prevent such complications. Some clinicians may feel that induction of labour results in a higher rate of caesarean section. However two large trials of induction at or after term for other reasons than suspicion of fetal macrosomia did not show any increase in caesarean section rates in the induced group12,13. On the other hand, a potential risk in the control group would be to allow the fetuses to grow further, with a difficult delivery at a result. However, there is currently no evidence that induction of labour can prevent such an outcome9. Given the current uncertainty, a trial should be conducted to determine whether induction of labour for suspected foetal macrosomia could prevent maternal or neonatal morbidity75.

The study protocol will be submitted to the Ethics Committee of the Hôpitaux Universitaires de Genève, and of all the participating institutions. The protocol of the study will comply with the “Directives pour les recherches expérimentales sur l’être humain” of the “Académie Suisse des Sciences Médicales” and with all the recommendation the Ethics Committees may suggest. Women will be informed of the potential advantages and the possible risks of the intervention. They will be free to participate or not to the trial. Participants will be free to remove their consent at any time. Data will be identified by a study number and kept confidential. In a separate database, stored in each institution and protected by a password, the link between the name and the number will be recorded only for administrative purposes.

Safety of the participating women will be assessed periodically by using a “Safety Monitoring” form and severe maternal or neonatal complications will be reviewed by a panel of independent experts. If these experts consider that there is a significant imbalance in the occurrence of significant complications between the experimental and control group, a meeting with the investigators and with members of the Ethics Committee will be organised. Consensus on either continuing or stopping the study will be reached.

1st Year 2002-2003

2nd Year 2003-2004

3rd Year 2004-2005

Trimester

2nd

3rd

4th

1st

2nd

3rd

4th

1st

2nd

3rd

4th

1st

General organisation

Questionnaire design & testing

Preparation of the database

Recruitment of subjects & data collection

Completion of data entry

Analysis

Report writing

Dissemination

Induction of labour is a frequently performed intervention. The proportion of women whose labour is induced varies between hospitals and over time. Despite the frequency of the intervention, very few randomised controlled trials have been conducted to evaluate the indications for this intervention. Post-term pregnancy and premature rupture of membranes were the only indications for which practice can be based on the results of at least one properly conducted large trial. For other frequent indications for induction of labour, including suspected large-for-dates fetus, there is insufficient information for evidence-based decision-making.

Despite the fact that suspected macrosomia or suspected large-for-dates fetus is a frequent indication for labour induction, only two randomised controlled trials of small sample size were conducted to evaluate this policy. Previous studies failed to show a benefit of a policy of labour induction. However, as discussed above, the contrast between the two groups was very small, resulting in very similar birthweight in both groups. Our study will include women with large-for-dates fetuses detected earlier in pregnancy (37 to 38 weeks), thus increasing the difference between groups in birthweight. This approach may reduce the risks associated with the delivery of a macrosomic baby, but may increase the risks associated with induction of labour. To determine the balance between those two concurrent risks will help in deciding what is the best option for term women with a suspected large-for-dates fetus. Guidelines recently issued by the Royal College of Obstetricians and Gynaecologists stress the need for conducting a valid evaluation of this important clinical question70.

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10. Johnstone FD, Prescott RJ, Steel JM, Mao JH, Chambers S, Muir N. Clinical and ultrasound prediction of macrosomia in diabetic pregnancy. Br J Obstet Gynaecol 1996;103:747-54.

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