SEARCH

SEARCH BY CITATION

Keywords:

  • Antenatal corticosteroids;
  • preterm birth

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

Please cite this paper as: Mahony R, McKeating A, Murphy T, McAuliffe F, O’Herlihy C, Foley M. Appropriate antenatal corticosteroid use in women at risk for preterm birth before 34 weeks of gestation. BJOG 2010;117:963–967.

Objective  To determine the utilisation of antenatal corticosteroid administration in women presenting at risk of preterm birth (PTB) in a centre where tocolytics are not prescribed.

Design  A prospective cohort study.

Setting  Tertiary referral centre, Dublin, Ireland.

Population  Four hundred and fourteen consecutive women presenting at risk of PTB.

Methods  Clinical details were collated prospectively on all booked patients who presented at risk of PTB (i.e. at <34 weeks of gestation) during 2008.

Main outcome measure  Rate of administration of antenatal corticosteroids in PTB.

Results  Of 8985 deliveries, 414 women (5%) presented at <34 weeks of gestation with a clinical potential for PTB, of whom 277 (67%) received antenatal corticosteroids. Amongst women delivering at <34 weeks of gestation, 93% (80/86) received any corticosteroids and 76% (65/86) received a complete course. The ratio of women given a complete course of corticosteroids to the number who actually delivered before 34 weeks of gestation was 4:1 overall. Analysis by indication for PTB revealed this ratio to be 15:1 in suspected preterm labour (PTL), 8:1 in antepartum haemorrhage (APH), and 2:1 in both preterm prelabour rupture of membranes (PPROM) and medically indicated PTB (MIPTB). Seven of ten multiparae (70%) who delivered prematurely during the study period following PTL had a history of previous PTL before 34 weeks of gestation.

Conclusion  The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at <34 weeks of gestation was high in categories such as PTL and substantial APH, whereas selection in PPROM and MIPTB approached 100%. There should be a low threshold for single course therapy for women with prior PTL before 34 weeks of gestation.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

In the context of preterm birth (PTB) before 34 weeks of gestation, antenatal maternal treatment with corticosteroids has been associated with an overall reduction in a range of adverse neonatal outcomes, including neonatal death, intraventricular haemorrhage, necrotising enterocolitis, need for respiratory support, admission to neonatal intensive care and systemic infection.1,2 Whereas a single course of antenatal corticosteroid is generally considered to be safe, concerns have recently been expressed regarding the safety and additional benefit of multiple course therapy.3,4 Other controversies include optimal dose to delivery interval, optimal steroid type and long-term effects of use.5 Nonetheless, current opinion certainly supports the use of a single course of antenatal steroid to improve neonatal outcome following PTB.6,7 Indeed, guidelines for the administration of antenatal steroids have been issued by a large number of obstetric institutions globally, and it has been suggested that it is possible to achieve an administration rate of a completed course of antenatal steroid of 85% or greater in infants delivering before 34 weeks of gestation.8 Such a target figure may be achievable in medically indicated PTB (MIPTB), where some degree of anticipation exists, but can be more difficult to attain in spontaneous PTB, when the onset of labour can be subtle and precipitous. The potential ability to administer antenatal steroids appropriately is further hampered by the fact that many women who present with symptoms or potential indication for PTB do not, in fact, deliver early. In order to address this issue, our aim was to study prospectively all women presenting before 34 weeks of gestation with potential precursors of preterm delivery, and to evaluate the specificity of administration of maternal antenatal steroids relative to subsequent delivery outcome.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

This is a prospective cohort study. Data were collated prospectively on all women with singleton pregnancies admitted to the National Maternity Hospital, Dublin, with potential precursors for delivery between 24 + 0 and 33 + 6 weeks of gestation. Patients with known fetal anomalies, multiple pregnancy and those transferred from other units were excluded. Gestational age was determined from the date of the last menstrual period, and was confirmed with information from a routine dating ultrasound scan, carried out between 18 and 20 weeks of gestation. Potential precursors for delivery were categorised as: (i) suspected spontaneous preterm labour (PTL), (ii) preterm prelabour rupture of membranes (PPROM), (iii) MIPTB delivery, for either fetal or maternal reasons and including all cases of antepartum haemorrhage (APH). APH was further classified, based on history and physical evidence of bleeding, into those with minor painless blood loss, i.e. non-substantial APH, and those with significant APH. Patients were identified on admission to the hospital and their subsequent antenatal course was followed prospectively. In addition, a previous history of preterm delivery was recorded in the case of multiparous women. Patients presenting with suspected PTL were admitted to the labour ward for vaginal digital examination, and the diagnosis of labour was accepted or rejected on the basis of a history of pains and a ‘show’ or ruptured membranes, corroborated by evidence of cervical effacement and cervical dilation of 1 cm or greater. The diagnosis of labour was rejected in the absence of cervical effacement and dilatation. Fetal fibronectin tests were not used to assist the diagnosis of labour. Spontaneous rupture of membranes in the absence of pains did not constitute a diagnosis of labour. Patients presenting with suspected PPROM were encouraged to collect a specimen of fluid for examination, or underwent sterile speculum examination, to identify pooling of liquor amnii in the posterior fornix. In doubtful cases amniotic fluid was confirmed by the ferning test. When membrane rupture was confirmed, low vaginal, rectal and midstream urine cultures were performed to rule out group B streptococcus or any other pathogens. Patients were then treated for 7 days with erythromycin, or an alternative broad spectrum antibiotic was prescribed in the event of known erythromycin allergy, and managed expectantly until at least after 34 weeks of gestation. According to hospital policy between 24 + 0 and 33 + 6 weeks of gestation, patients deemed to be at risk of preterm delivery were administered antenatal steroids (12 mg betamethasone intramuscularly in two doses 12 hours apart, for a complete course of antenatal corticosteroids). Women who received just one course were classified as having had a partial course or ‘any’ antenatal corticosteroids. Women were usually retained in hospital for 24 hours for observation and to facilitate the administration of antenatal corticosteroids. Women with PPROM were retained in hospital until delivery. Tocolytic agents were not administered to any patient during the course of the study.

The study was deemed exempt from ethical approval by the hospital Ethics Committee Board.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

Of 8985 deliveries, 414 women (5%) presented with a clinical potential for PTB at <34 weeks of gestation, and 86 (1%) actually delivered before 34 weeks of gestation. The clinical presentation of the 414 cases was suspected preterm labour (218; 52.7%), maternal or fetal complications (55; 13.3%), significant APH (55; 13.3%), minor painless APH (45; 10.9%) and PPROM (41; 9.9%) (Table 1). Overall, 277 (67%) of those presenting received antenatal steroids. Of those who delivered, 93% (80/86) received any course of antenatal corticosteroids, and 76% (65/86) received a complete course. The ratio of women treated with steroids to those who were treated and subsequently delivered was 4:1 (277:80). Overall, 328 (79%) of 414 women presenting at risk of PTM in fact delivered after 34 weeks of gestation, 211 (64%; ratio 2:1) of whom received a full course of corticosteroids.

Table 1.   Cohort of 414 women presenting at risk of PTB, and the percentage treated with steroids. The ratio of treated to delivered, and the percentage receiving a complete course of steroids (two doses of betamethasone 12 mg, 12 hours apart) or any steroids (a single intramuscular injection), among the categories of PTB who delivered before 34 weeks of gestation
Preterm delivery aetiologyNumber presenting at risk of PTBNumber treated with corticosteroidsNumber who deliveredNumber who completed a course of steroids Ratio of treated to deliveredNumber who received any steroids Ratio of treated to delivered
  1. PTL, Preterm labour; APH, antepartum haemorrhage; PPROM, preterm prelabour rupture of the membranes.

  2. A footnote on the abbreviations used in this table is required here.

Suspected PTL218117 (55%)178 (47%) 15:115 (88%) 8:1
Maternal fetal indication5551 (93%)3127 (87%) 2:131 (100%) 2:1
Significant APH5546 (82%)146 (43%) 8:110 (71%) 5:1
Minor, painless APH4527 (58%)000
PPROM4136 (84%)2424 (100%) 2:124 (100%) 2:1
Total414277 (67%)8665 (76%) 4:180 (93%) 4:1

The individual results for each of the PTB precursor categories for completed or any steroid treatment are presented in Table 1. The ratio for treated (complete course) to delivered cases was 2:1 for both PPROM and maternal fetal complications, and was 8:1 for clinically significant APH. The highest ratios were for minor, painless APH (none of whom delivered) and for suspected PTL (15:1) (Table 1).

Maternofetal indications (n = 45) included: pre-eclampsia (21 cases); placental abruption and placenta praevia (14); intrauterine growth retardation (IUGR), with absent or reversed end-diastolic Doppler flow (8); maternal cardiomyopathy, requiring early delivery in the maternal interest (1); and early delivery indicated prior to the commencement of chemotherapy for breast cancer (1).

Among 86 women who delivered before 34 weeks of gestation, 65 completed a course of antenatal corticosteroids, six did not receive any steroids and 15 received a partial dose. Of the six women who did not receive steroids there were four cases of placental abruption, one cord prolapse on admission in PTL and one admission at 1-cm cervical dilation with major haemorrhage: all were delivered within 45 minutes of admission to the hospital. Among the 15 who received a partial dose of steroid, there were eight medically indicated cases for APH or pre-eclampsia, who were delivered within 4 hours. Four presented in advanced labour (10-cm cervical dilatation in two cases, and 4-cm cervical dilatation in another two cases). Three cases presented with pains and a show, a substantial APH, and spontaneous rupture of the membranes without pains, respectively: these cases were delivered at 3, 6 and 6 hours from the time of admission. Two patients returned in labour, whereas another woman (the first case) was delivered by emergency caesarean section for a transverse lie following spontaneous rupture of the membranes.

Of 176 multiparae presenting at risk of PTB, 22 (12.5%) had a history of prior PTL (<37 weeks of gestation), 30% (7/22; ratio 3:1) of whom delivered before 34 weeks of gestation. Ten (6%) had a history of PTL before 34 weeks of gestation, 70% (7/10; ratio 2:1) of whom delivered before 34 weeks.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

This prospective cohort study of antenatal corticosteroid administration prior to 34 weeks of gestation demonstrates that a high rate of antenatal corticosteroid administration can be achieved among those delivering before 34 weeks in a centre where tocolytics are not used, in line with Royal College of Obstetricians and Gynaecologists (RCOG) guidelines,9 and where the diagnosis of labour is based on history and clinical assessment of the cervix. Relatively few studies have examined the accuracy of selecting women for appropriate antenatal steroid administration, based on clinical criteria;6 this cannot be achieved unless the obstetric contexts are taken into account. Obstetric events such as placental separation, cord prolapse, or even rapidly advancing PTL are impossible to anticipate, so that it would prove very difficult to increase the percentage of delivered infants who completed a course of steroids beyond our rate of 76%. A similar rate was reported for ‘any’ steroid use in California prior to their concerted effort to promote the administration of antenatal corticosteroids,8 resulting in an increase in usage to 85%, which they proposed as a benchmark; however, if we report on ‘any’ antenatal steroid administration (partial or complete), our percentage increased to 94%.

In selected categories such as APH and suspected PTL, the ratio of steroid-treated women to those who actually delivered at <34 weeks of gestation was high. No woman presenting with a painless minor APH delivered early. Overall, however, at least half of the women presenting with potential PTB delivered after 34 weeks, and received a course of antenatal corticosteroids, suggesting that our case selection for antenatal steroid administration could be more specific, and while it could be argued that a single course of antenatal corticosteroids causes no long term demonstrable risk,10 it would not constitute ‘best practice’, and administration of two doses 12 hours apart can represent a major inconvenience to the patient and the hospital.

Arguably the most difficult subgroup in terms of selection for antenatal corticosteroids is the cohort with suspected PTL. While the ratio of treated to delivered cases of 15:1 might be considered acceptable, or indeed unavoidable, previous studies from this centre has demonstrated that a very high accuracy in clinical diagnosis of PTL can be achieved,11 yet it is clear from this current study that reluctance remains within the institution to rely on clinical judgment alone. The adjunct of fetal fibronectin screening to enhance the diagnosis of PTL is currently under review, and will be studied prospectively. The introduction of such additional screening may lead to a reduction in the number of women presenting with suspected PTL being treated unnecessarily with maternal antenatal corticosteroids. Conversely, in categories such as MIPTB and PPROM, delivery was more likely to be planned or anticipated in time to administer a complete course of steroids, resulting in a low ratio of women treated to delivered women.

Following a review of perinatal deaths in this hospital in 1985,12 showing that the perinatal mortality rate attributed to spontaneous PTL had improved dramatically over a 15-year period when tocolytic therapy was not used, a decision was made not to use tocolytic therapy in any circumstances in this hospital, particularly as it was judged that tocolytics would not have prevented any of the deaths. The Royal College Guidelines and Cochrane reviews recommend that tocolytics are a possible option to facilitate the transfer of a woman in suspected labour and to postpone labour for long enough to prescribe a full course of antenatal corticosteroids.9,13 Atosiban, an oxytocin antagonist is the only licenced tocolytic agent available in Ireland, and the exclusion criteria for its use include cervical dilatation of greater than 3 cm, ruptured membranes, fever and major haemorrhage.14 Certainly none of the five cases of PTL who did not receive corticosteroids, and only one of seven cases who received a partial dose, could have been considered for tocolytic therapy.

The importance of previous history in predicting subsequent PTB is now well established, and has been reported by numerous authors.15,16 Seven of ten women presenting with a combination of symptoms of suspected PTL and a history of previous PTL before 34 weeks delivered before 34 weeks of gestation again. In this study period there were 4770 multiparas, and given our background rate for spontaneous PTL and delivery before 34 weeks of gestation, of 0.2%, it can be extrapolated that ten multiparas will present annually with a history of previous spontaneous preterm delivery. If all had been offered prophylactic antenatal corticosteroids, seven of the ten multiparas who delivered before 34 weeks of gestation would have been included – a ratio of 1.4:1 (10:7), a specificity comparable to our best value; careful consideration should therefore be given to at least this select group. Further studies and a possible randomised controlled trial aimed at answering this question appears to be desirable.

This study is limited by relatively small numbers, and examines the use of maternal administration of antenatal steroids for PTB in only one institution. In addition, we do not provide any neonatal outcome to determine if steroid administration made any difference within the categories of PTB discussed – PTL, PPROM and MIPTB – because our sample size is too small to draw conclusions in relation to perinatal mortality and morbidity, in particular.

In conclusion, some obstetric precursors such as minor haemorrhage were over-treated, whereas our selection in other categories, e.g. PPROM and maternal fetal indications, approached 100%. The finding that 70% of multiparae gave a history of a prior PTB before 34 weeks of gestation suggests that prophylactic steroids might be indicated in this cohort of patients, provided these findings are confirmed with prospective studies.

Contribution to authorship

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

RM wrote the paper. AMcK, a medical student, helped with data collection during a summer project. TM is the chief midwife who assessed many of the cases on admission to the delivery ward. FMcA and CO’H helped design and review the paper. MF helped conceive, design, and review the paper.

Details of ethics approval

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References

The study was exempt from ethical approval as there was no change in hospital policy, and it was an analysis of existing hospital data.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Disclosure of interests
  8. Contribution to authorship
  9. Details of ethics approval
  10. Funding
  11. References
  • 1
    Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol 1995;173:32235.
  • 2
    Roberts D, Dalziel S Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane database syst rev 2006, Art. No.:CD004454. DOI: 10.1002/14651858. CD004454.pub2.
  • 3
    Murphy KE, Hannah ME, Willan AR, Hewson SA, Ohlsson A, Kelly EN, et al. Multiple courses of antenatal corticosteroids for preterm birth (MACS): A randomised control trial. Lancet 2008;372:214351.
  • 4
    Wapner RJ, Sorokin Y, Mele L, Johnson F, Dudley DJ, Spong CY, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Eng J Med 2007;357:11908.
  • 5
    Brownfoot FC, Crowther CA, Middleton P. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev, 2008;CD006764.
  • 6
    Crane J, Armson A, Brumer M, De La Ronde S, Farine D, Keenan-Lindsay L, et al. Executive Committee of the Society of Obstetricians and Gynaecologists of Canada. Antenatal corticosteroid therapy for fetal maturation. J Obstet Gynaecol Can 2003;25:4552.
  • 7
    Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet 2008;371:16475.
  • 8
    Wirtschafter DD, Danielsen BH, Main EK, Korst LM, Gregory KD, Wertz A, et al. Promoting antenatal steroid use for fetal maturation: results from the California Perinatal Quality Care Collaborative. J Pediatr 2006;148:60612.
  • 9
    Royal College of Obstetricians and Gynaecologists. Tocolytic Drugs for Women in Preterm Labour. Clinical guidelines No.1(B) London:RCOG;2002
  • 10
    Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A, et al. Cardiovascular risk factors after antenatal exposure to betamethasone: 30 year follow-up of a randomized controlled trial. Lancet 2005;365:185662.
  • 11
    Robson M, Murphy T. Should every unit have a 24-hour transvaginal ultrasound available? BJOG 2006;113(suppl. 3):579.
  • 12
    Boylan P, O’Driscoll K. Improvement in perinatal mortality attributed to spontaneous preterm labor without the use of tocolytic agents. Am J Obstet Gynecol 1983;145:7813.
  • 13
    Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2002;4:CD000065.
  • 14
    The worldwide Atosiban versus beta-agonists study group. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG 2001;108:13342.
  • 15
    Spong CY. Prediction and prevention of spontaneous recurrent preterm birth. Obstet Gynecol 2007;110:40515.
  • 16
    Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:7584.