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The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: A multicenter, randomized, controlled trial (the FOREMOST trial)
American Journal of Obstetrics and Gynecology (2006) 194, 606.e1–606.e16
www.ajog.org
The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: A multicenter, randomized, controlled trial (the FOREMOST trial) Christine E. East, MMedSc,a,* Shaun P. Brennecke, DPhil(Oxon),b James F. King, MPH,b Fung Yee Chan, MD,c Paul B. Colditz, DPhil(Oxon),a on behalf of The FOREMOST Study Group Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australiaa; Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women’s Hospital, Melbourne, Victoria, Australiab; Department of Maternal-Fetal Medicine, The University of Queensland, Mater Mothers’ Hospital, Brisbane, Queensland, Australiac Received for publication May 23, 2005; revised August 2, 2005; accepted August 18, 2005
KEY WORDS Fetal pulse oximetry Randomized controlled trial Electronic fetal monitoring
Objective: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. Study design: The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. Results: There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry C cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry C cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. Conclusion: The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal
Supported by grants from the Australian National Health and Medical Research Council (142936, 301050), Queensland Health, The University of Queensland, and TYCO Inc (Nellcor) and loan equipment (fetal pulse oximetry) from TYCO Inc (Nellcor). Supplemental information can be found at: www.ajog.org. * Reprint requests: Ms. C. East, Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Butterfield Street, Herston, Queensland 4029, Australia. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.08.051
606.e2
East et al status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes. Ó 2006 Mosby, Inc. All rights reserved.
Conventional cardiotocography (CTG) methods of fetal assessment are limited by a high false-positive rate, resulting in an unnecessarily high operative delivery rate for nonreassuring fetal status.1 A safe, reliable, and accurate test of fetal well-being in labor is an important and urgent need in contemporary obstetrics. Fetal pulse oximetry (FPO) may improve the assessment of fetal well-being in labor.2-7 On the basis of human and animal data, fetal oxygen saturation (FSpO2) values 30% or greater are reassuring in the human fetus and FSpO2 values greater than 30% for 10 minutes require further assessment or intervention.3,8-11 We recently conducted a systematic review to compare outcomes for fetuses with presumed compromise during labor, whose well-being was monitored with and without fetal oximetry.12 At the time of the review, the only published randomized controlled trial (RCT) reported a lower rate of operative deliveries for nonreassuring fetal status in the FPO with CTG group than the CTG-only group.13 The review recommended that further RCTs address dystocia in labors monitored with FPO, maternal satisfaction, long-term neurodevelopmental outcome of infants who exhibited nonreassuring fetal status in labor, and cost effectiveness of FPO. More recently a further RCT (n = 146) also reported a reduction in operative delivery for nonreassuring fetal status.14 The issue of dystocia has been explored in a cohort study by Porreco et al.15 They reported cesarean section rates for prospectively defined and managed dystocia of 8% and 22% for those with mildly nonreassuring and moderate or severely nonreassuring CTGs, respectively, despite the presence of normal FSpO2 values and consistent with the cesarean rates for dystocia in the RCT reported by Garite et al.13 The use of a new technology in different obstetric environments justifies a number of RCTs, and metaanalysis of such RCT findings improves power and precision of estimates of effects.16 Additionally, we considered a further study necessary to further document the incidence of dystocia in labors monitored with and without FPO. We have therefore conducted a RCT to compare operative delivery rates for nonreassuring fetal status between 2 groups: those having CTG monitoring and those having CTG monitoring plus FPO.
Material and methods Participants Women were informed about the trial during antenatal visits/classes, at induction of labor, and/or during labor.
Women were approached to consider trial participation during labor only when clinicians considered it appropriate to do so. Many women eligible for trial participation were therefore not approached (Figure). Women qualified for trial participation if there was a nonreassuring CTG during labor (Table I) and they met the remaining criteria listed in the Figure. The trial was conducted in the birth and delivery suites of 4 Australian maternity hospitals, each with more than 4000 births a year: the Royal Brisbane and Women’s Hospital, Brisbane (co-ordinating center); the Royal Women’s Hospital, Melbourne; the Mater Mothers’ Hospital, Brisbane; and the Royal Hospital for Women, Sydney. Investigators at the first 3 hospitals had prior experience with fetal oximetry.2,4,6
Procedures Women were randomized to continue with conventional CTG monitoring (CTG-only, control group) or the addition of FPO to CTG monitoring (FPOCCTG, intervention group). In the intervention group, the FPO sensor (Nellcor OxiFirst, TYCO Inc, Pleasanton, CA) was placed during a vaginal examination by a research midwife or medical staff/midwives who had received instruction in sensor placement. The FSpO2 was displayed on the oximeter and printed on the CTG paper. Monitoring continued from the time of sensor placement until as close as possible to birth, with minor sensor adjustments during labor to achieve a signal, usually performed externally by withdrawing or advancing the sensor in 1-cm increments.7 The CTG following randomization could become reassuring, continue to be nonreassuring, or develop an ominous pattern. Clinical management of the control and intervention arms of the study were: (1) if the CTG subsequently became reassuring, labor was continued unless otherwise indicated; (2) in the control group, a nonreassuring CTG prompted evaluation and management of the fetal heart rate (FHR) pattern. In the FPOCCTG group, when FSpO2 values were reassuring (30% or greater) in the presence of a nonreassuring CTG, labor continued unless otherwise indicated. If the FSpO2 values were less than 30% for 10 minutes or not recording, evaluation and management of the FHR pattern were recommended. Evaluation and management of the nonreassuring CTG or FSpO2 could include maternal position change, supplemental O2 administration, hydration, correction of hypotension, discontinuation of oxytocin infusion, or delivery; and (3) ominous FHR patterns (prolonged decelerations to less than 70 beats/min for more than
East et al
Figure
606.e3
Numbers of women assessed for trial eligibility, randomized, and included in intention-to-treat analysis.
606.e4 Table I
East et al Nonreassuring fetal heart rate patterns at study entry
Pattern (may have more than one) Persistent late decelerations (O50% of contractions) O15 min Sinusoidal pattern O15 min Variable decelerations with 1 or more of the following O15 min Relative drop of R70 beats/min or an absolute drop to %70 beats/min for O60 s Persistent slow return to baseline Baseline variability !5 beats/min Tachycardia O160 beats/min with decreased baseline variability !5 beats/min Recurrent prolonged decelerations (2 or more below 70 beats/m for O90 s) O15 min Persistent decreased baseline variability (!5 beats/min for O60 min) Tachycardia O160 beats/min with decreased baseline variability !5 beats/min O60 min Supraventricular tachycardia or heart block any length of time Other
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
59 (19.3%) 0 (0%)
61 (20.7%) 0 (0%)
63 (20.7%)
67 (22.7%)
61 (20.0%) 23 (7.5%) 12 (3.9%)
70 (23.7%) 33 (11.2%) 10 (3.4%)
24 (7.9%)
13 (4.4%)
61 (20.0%) 14 (4.6%)
45 (15.3%) 10 (3.4%)
0 (0%) 39 (12.8%)
0 (0%) 42 (14.2%)
Data for the 2 study groups are number (%) of patients.
7 minutes) prompted delivery, regardless of group allocation. Fetal blood sampling was available to both study groups without restriction. The study did not seek to regulate management based on fetal scalp pH or lactate values. It was considered that the stratification by center at randomization and randomization per se would compensate for any institutional differences in management based on fetal blood samples. The decision to intervene and documentation of indication for operative delivery remained the responsibility of the attending clinicians. The following hypotheses were tested. The first was the primary hypothesis. In the presence of a nonreassuring CTG, the use of intrapartum FPO plus CTG monitoring, compared with CTG monitoring alone, would result in a 33% reduction in the operative delivery rate for nonreassuring fetal status. In addition were the secondary hypotheses including the following: (1) there would be no difference in operative delivery rate for dystocia; (2) there would be no difference in fetal/neonatal outcomes (umbilical arterial pH, Apgar score, admission to the neonatal intensive care unit) between the 2 groups; and (3) there would be no difference in women’s satisfaction with fetal monitoring or their labor, delivery, and outcome between the 2 groups. This manuscript provides data outcomes related to the primary hypothesis and the first 2 components of the secondary hypothesis. Data outcomes from the third component of the secondary hypothesis and the economic evaluation will be described in separate manuscripts. The primary end point was operative birth (cesarean section, forceps, or vacuum) for nonreassuring fetal status. Secondary end points included overall operative
delivery for all indications and fetal/neonatal variables. Because of the low prevalence of poor neonatal outcomes such as hypoxic-ischemic encephalopathy or death, the study had insufficient power to reliably identify any differences between groups for these outcomes. The nature of the trial meant that it was not possible to blind the participants, clinicians, or research midwives to group allocation. The chief investigators remained blinded to group allocation until data collection, entry, and tabulation were completed. Data were presented to the data monitoring committee for the interim analysis in 2 unlabeled study groups. The research protocol was approved by The University of Queensland Human Research Ethics Committee and all relevant hospital ethics committees. Serious adverse events (SAEs)17 were reported to the ethics committees and the data monitoring committee.
Statistical analysis The sample size was dictated by the operative delivery rate for nonreassuring fetal status in fetuses demonstrating a nonreassuring CTG, defined in Table II. Intrapartum CTG monitoring is performed in approximately 50% of women at term at the Royal Women’s Hospital, Melbourne.18 Of these, 15% of CTGs are nonreassuring and 34% of these undergo operative delivery for nonreassuring fetal status.18 Unpublished data from the other participating centers were similar during the planning phase of the trial. A sample size of 281 women in each arm of the trial was therefore required to test the hypothesis that operative delivery rates for nonreassuring fetal status would be reduced by 33%, from 34%
East et al Table II
606.e5 Baseline demographics Intervention (FPO+CTG) (n = 305)
Maternal age (y) Hospital status Public Private Nulliparous Cervical dilatation on first vaginal examination (VE) (cm) Station on first VE Previous cesarean, overall Previous cesarean for dystocia/failure to progress Previous cesarean for nonreassuring fetal status Previous cesarean for nonreassuring fetal status C dystocia/failure to progress Maternal risk factors R1* Fetal risk factors R1y Birth weight (g) Birth weight O4000 g Induction of labor Prostaglandin Oxytocin infusion Artificial rupture of membranesz Meconium liquor Epidural analgesia Epidural at cervical dilatation !5 cm
29.72 (5.806)
Control (CTG-only) (n = 295) 28.92 (5.620)
288 17 247 3 2 19 3 8 0
(94.4%) (5.6%) (81.0%) (2, 3.9) (0.8) (6.2%) (1.0%) (2.6%) (0%)
276 19 226 3 2 16 3 5 2
(93.6%) (6.4%) (76.6%) (2, 4) (0.8) (5.4%) (1.0%) (1.7%) (0.7%)
110 84 3435.3 33 140 86 254 162 116 274 54
(36.1%) (27.5%) (500.88) (10.8%) (45.9%) (28.2%) (83.3%) (53.1%) (38.0%) (89.8%) (17.7%)
117 86 3440.9 35 144 88 238 171 115 254 53
(39.7%) (29.2%) (510.27) (11.9%) (48.8%) (29.8%) (80.7%) (58.0%) (39.0%) (86.1%) (18.0%)
Data for the 2 study groups are mean (SD), number of patients (%), or median (IQR). * One or more of: chronic hypertension, pregnancy-induced hypertension, eclampsia, prepregnancy diabetes, glucose intolerance in pregnancy, no prenatal care, maternal cardiac disease, maternal renal disease. y One or more of: small for dates/intrauterine growth restriction, polyhydramnios, oligohydramnios, O42 weeks’ gestation, !37 weeks’ gestation, maternal substance use (alcohol, drugs, smoking). z All were prerandomization.
in the control group to 23% in the intervention group (power 80%, alpha 0.05) (EpiInfo, version 6, Centers for Disease Control and Prevention, Atlanta, GA). We aimed to recruit 300 into each group to allow for withdrawals. An interim analysis was planned and conducted when 50% of the subjects had been enrolled and their outcomes known, with the data monitoring committee blinded to group allocation. A recommendation to the trial investigators to consider stopping the trial was to be made if: (1) the probability of finding the prespecified difference in operative delivery for nonreassuring fetal status between the 2 groups was less than 0.01 or (2) the frequency of SAEs was significantly worse in 1 group than the other (P ! .05) or would have reached that level of significance had the trial continued until its full sample size had been reached. The committee recommended continuation of the trial to full recruitment. After the first 14 recruits, when randomization was by use of numbered, sealed, opaque envelopes opened sequentially by the research midwife, a central telephone randomization system became available and was
employed (Voiceguide, versions 3 and 4, Katalina Technologies, Sydney, Australia). Researchers and clinicians were unaware of the randomization sequence prior to group allocation. The location and spread of baseline demographic and outcome data were summarized using proportions, mean and SD, median and interquartile range (IQR), or relative risks and 95% confidence intervals, as appropriate. Outcomes were compared using c2/Fisher’s exact test, Student t tests, Mann-Whitney U, or KaplanMeier (log rank) time-to-event analysis, as appropriate. Binary outcomes of operative delivery, labor complications, and fetal/neonatal outcomes were predicted from possible covariates (hospital, obstetric history of previous cesarean section, maternal age, parity, preeclampsia, intrauterine growth restriction, onset of labor [spontaneous/induced], meconium, hematuria, prolonged rupture of membranes, and maternal/neonatal infection), as appropriate, using logistic regression. The level of statistical significance for comparison was P ! .05 (2 sided). Data were analyzed using STATA (Intercooled STATA 8, Stata Corp, College Station, TX) and SPSS (version 11.5, SPSS Inc, Chicago, IL).
606.e6 Table III
East et al Delivery route and indication
Operative delivery For nonreassuring fetal status For dystocia/failure to progress Other indications Total Spontaneous vaginal birth Assisted vaginal birth (vacuum/forceps) For NRFS For dystocia/failure to progress For combined indication NRFS and dystocia/failure to progress For all other indications Total Cesarean section For NRFS For dystocia/FTP For NRFS/FTP All other indications Total
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
Relative risk (FPO+CTG: CTG-only) 95% CI
76 74 74 224
95 46 68 209
(32.2%) (15.6%) (23.1%) (70.8%)
.048 .008 .727 .478
0.77 1.56 1.05 1.04
81 (26.6%)
86 (29.2%)
.478
0.91 (0.70, 1.18)
34 (11.1%) 30 (9.8%) 13 (4.3%)
36 (12.2%) 14 (4.7%) 12 (4.1%)
.687 .017 .905
0.91 (0.59, 1.42) 2.07 (1.12, 3.83) 1.05 (0.49, 2.26)
7 (2.3%) 84 (27.5%)
5 (1.7%) 67 (22.7%)
.600 .173
1.35 (0.43, 4.22) 1.21 (0.92, 1.60)
.042 .188 .689 .246 .584
0.69 1.33 0.92 1.77 0.95
42 44 43 11 140
(24.9%) (24.3%) (24.3%) (73.4%)
(13.8%) (14.4%) (14.1%) (3.6%) (45.9%)
59 32 45 6 142
(20.0%) (10.8%) (15.3%) (2.0%) (48.1%)
(0.599, 0.999) (1.12, 2.17) (0.79, 1.40) (0.94, 1.15)
(0.48, (0.87, (0.63, (0.66, (0.80,
0.99) 2.04) 1.36) 4.73) 1.13)
Data for the 2 study groups are number of patients (%). NRFS, Nonreassuring fetal status; FTP, failure to progress. * By c2.
Results Of more than 50,000 women assessed for trial eligibility, 601 were randomized: 306 to the intervention group and 295 to the control group (Figure) between July 1999 and September 2004. Following randomization to the intervention group, 1 patient revoked consent at the request of her partner, so no data were collected and she was excluded from further analysis. Baseline demographics, clinical characteristics and nonreassuring CTG features that allowed for study entry were similar for each group (Tables I and II). Analysis was by intention to treat and included all except the 1 participant who revoked consent. There was a statistically significant 23% reduction in operative delivery for nonreassuring fetal status in those allocated to FPOCCTG (n = 76, 25%), compared with those in the CTG-only group (n = 95, 32%) (relative risk [RR] 0.77, 95% confidence interval [CI] 0.599, 0.999, P = .048) (Table III). Cesarean section was performed for nonreassuring fetal status in 42 of the FPOCCTG group (14%) and 59 of the CTG-only group (20%) (RR 0.69, 95% CI 0.48, 0.99, P = .042). There was no difference in overall operative delivery (FPOCCTG group, n = 224, 73%; CTG-only group, n = 209, 71%, RR 1.04, 95% CI 0.94, 1.15, P = .478) (Table III). There were no overall between-group differences for spontaneous or assisted vaginal birth or cesarean section
(Table III). Women in the FPOCCTG group were more likely to have an operative birth for dystocia/failure to progress than those in the CTG-only group (RR 1.56, 95% CI 1.12, 2.17, P = .008). This increase was statistically significant for assisted vaginal births (RR 2.07, 95% CI 1.12, 3.83, P = .017) but not for cesarean births (RR 1.33, 95% CI 0.87, 2.04, P = .188) (Table III). There were no differences in neonatal outcomes between the 2 groups (Table IV). Neonatal SAEs were identified in 8 of the FPOCCTG group (2.6%) and 7 of the CTG-only group (2.4%). Details are available on the FOREMOST Web site.17 The data monitoring committee reviewed each event and did not consider that the SAEs raised issues affecting the continuation of the trial. Labor interventions were similar for the 2 groups following randomization (Table V). Fetal scalp blood sampling was performed more often in the CTG-only group (n = 157, 53%) than the FPOCCTG group (n = 41, 13%). Fetal heart rate patterns after randomization were similar for the 2 groups (Table VI). There was a longer time from randomization to birth for women in the FPOCCTG group, compared with those in the CTG-only group (Table VII). Prespecified logistic regression analyses were undertaken but did not alter the finding that women in the FPOCCTG group were statistically significantly less likely to have an operative delivery for nonreassuring
East et al Table IV
606.e7 Neonatal outcomes Intervention (FPO+CTG) (n = 305 unless otherwise stated)
1-min Apgar !4 5-min Apgar !7 Apgar score 1 min 5 min Cord arterial pH (FPO+CTG, n = 272; CTG-only, n = 240) !7.15 !7.00 Cord arterial BE (FPO+CTG, n = 257; CTG-only, n = 224) !–10 !–16 Cord arterial lactate (mmol/L) (FPO+CTG, n = 216; CTG-only, n = 194) Bag and mask IPPV Admission to NICU Admission to SCN Congenital sepsis (blood culture positive) Neonatal injuryk Time to neonatal discharge (d)
Control (CTG-only) (n = 295 unless otherwise stated)
P value*
12 (3.9%) 5 (1.6%)
9 (3.1%) 6 (2%)
.556 .719
8 (7, 9) 9 (9, 9)
9 (7, 9) 9 (9, 9)
.344 .802
39 (14.3%) 2 (0.7%)
35 (14.6%) 2 (0.8%)
.937 1.000y
24 (9.4%) 2 (0.7%)
18 (8.1%) 0 (0%)
.615 .501y
4.2 61 9 73 1 5 3.50
(2.9, 6.1) (20.0%) (3%) (23.9%) (0.3%) (1.4%) (2.74, 4.55)
4.2 42 11 60 1 4 3.49
(2.7, 5.9) (14.2%) (3.7%) (20.3%) (0.3%) (1.5%) (2.69, 4.72)
.605z .061 .596 .289 1.000y 1.000y .621x
Relative risk (FPO+CTG: CTG-only) 95% CI 1.29 (0.55, 3.02) 0.81 (0.25, 2.61)
0.98 (0.64, 1.50) 0.89 (0.13, 6.26)
1.16 (0.72, 2.33) Unable to calculate
1.40 0.79 1.18 0.97 1.21
(0.98, (0.33, (0.87, (0.06, (0.33,
2.01) 1.88) 1.59) 15.39) 4.46)
Data for the 2 study groups are number of patients (%) or median (IQR). IPPV, Intermittent positive pressure ventilation; NICU, neonatal intensive care unit; SCN, special care nursery. * By c2 unless otherwise noted. y Fisher’s exact test. z Mann-Whitney U test. x Log rank test. Medians are provided for interest only. k CTG-only group: bruising/torn skin following vacuum/forceps (n = 4); FPO+CTG group: torn skin following vacuum (n = 1), bruising to arm and scalp (shoulder dystocia) (n = 1), left-sided facial palsy (resolved) C right arm weakness (n = 1), scalp lesion at site of fetal scalp electrode (n = 1), cephalhematoma C facial edema (n = 1).
Table V
Postrandomization labor interventions and fetal evaluations
Oxytocin admin change Maternal oxygen administered Maternal position adjustment Intravenous hydration Fetal stimulation Correction of hypotension Fetal scalp pHz pH % 7.20 pH O 7.20 ! 7.25 Scalp lactatex R4.8 mmol/L
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
114 80 163 39 20 2
108 66 153 37 23 3
(37.4%) (26.3%) (53.6%) (12.9%) (6.6%) (0.7%)
(36.6%) (22.4%) (51.9%) (12.5%) (7.8%) (1.0%)
P value* .846 .261 .667 .904 .564 .682y
Relative risk (FPO+CTG: CTG-only) 95% CI 1.02 1.17 1.03 1.02 0.84 0.65
(0.83, (0.88, (0.89, (0.67, (0.47, (0.11,
1.26) 1.56) 1.20) 1.55) 1.50) 3.86)
4 (1.3%) 8 (2.6%)
3 (1.0%) 10 (3.4%)
1.000y .582
1.29 (0.29, 5.71) 0.77 (0.31, 1.93)
7 (2.3%)
21 (7.1%)
.005
0.32 (0.14, 0.75)
Data for the 2 study groups are number of patients (%). Admin, Administration. * c2 unless otherwise indicated. y Fisher’s exact test. z The lowest pH value was used in which more than 1 sample was taken. x The highest lactate recorded was used if more than 1 sample was taken.
606.e8 Table VI
East et al Fetal heart rate patterns after randomization
Reassuring (no features of nonreassuring or ominous FHR patterns) Nonreassuring (may have more than one) Persistent late decelerations (O50% of contractions) O15 min Sinusoidal pattern O15 min Variable decelerations with 1 or more of the following O15 min Relative drop of R70 beats/min or an absolute drop to %70 beats/min for O60 s Persistent slow return to baseline Baseline variability !5 beats/min Tachycardia O160 beats/min with decreased baseline variability !5 beats/min Recurrent prolonged decelerations (2 or more below 70 beats/min for O90 s) O15 min Persistent decreased baseline variability (!5 beats/min for O60 min) Tachycardia O160 beats/min with decreased baseline variability !5 beats/min O60 min Supraventricular tachycardia or heart block any length of time Other Ominous Prolonged decelerations to !70 beats/min for O7 min
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
51 (16.7%)
28 (15.3%)
.428
51 (16.7%) 0 (0%)
45 (15.3%) 0 (0%)
.624
89 (29.2%)
78 (26.4%)
.451
79 (25.9%) 44 (14.4%) 26 (8.5%)
93 (31.5%) 34 (11.5%) 14 (4.7%)
.128 .291 .064
16 (5.2%)
15 (5.1%)
.929
39 (12.8%)
31 (10.5%)
.385
12 (3.9%)
9 (3.1%)
.556
0 (0%) 30 (9.8%)
0 (0%) 36 (12.2%)
.354
0 (0%)
0 (0%)
Data for the 2 study groups are number of patients (%). * By c2 test.
Table VII
Length of time from randomization to birth
All births (min) SVD (min) Assisted vaginal (min) Assisted vaginal for nonreassuring fetal status (min) Assisted vaginal for failure to progress (min) Cesarean (min) Cesarean for nonreassuring fetal status (min) Cesarean for failure to progress (min)
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
186 146 190 116 300 212 118 330
147 133 161 144 191 154 100 327
.010 .624 .041 .366 .049 .084 .016 .838
(109, 306) (76, 248) (114, 314) (71, 175) (181, 376) (121, 330) (72, 166) (226, 436)
(94, 248) (73, 199) (95, 256) (62, 239) (131, 308) (103, 280) (68, 141) (184, 457)
Data for the 2 study groups are median (IQR). SVD, Spontaneous vaginal delivery. * Log rank testing was used to calculate significance for all time-to-event variables. The medians, representing the time when 50% of women had given birth, are provided for interest.
fetal status than those in the CTG-only group. More detailed analyses of the data set are available on the Web site.17 Successful FPO sensor placement with FSpO2 values recorded occurred for 94% of FPO cases. Fetal SpO2 values were returned for a median of 83% (IQR 69%, 91%) of recording time, with FSpO2 values less than 30% recorded a median of 14% (IQR 5%, 28%) of recording time. Sensor placement was attempted at mean (SD, range) cervical dilatation of 6.9 cm (2.29 cm, 2.5 to 10 cm) and fetal station at mean (SD, range) of –0.9 (1.26, –3 to C2) cm relative to the maternal ischial spines.
There were 4 cases (1.3%) of endometritis in the intervention group and 1 (0.3%) in the control group (P = .192). Postpartum maternal temperature higher than 37.5(C was recorded for 84 women in the intervention group (30.8%) and 88 women in the control group (29.8%) (P = .792).
Comment The 2 study groups were well matched at study entry, both in terms of baseline demographics and nonreassuring CTGs qualifying their participation. The
East et al high proportion of nulliparas was representative of the population of nonparticipants with a nonreassuring CTG in the 4 hospitals during the study period (unpublished data) but higher than the overall Australian figure of 41%.19 The high epidural rate was in contrast to the 29% epidural rate for all women giving birth.20 We postulate that researchers and clinicians were more likely to seek consent for participation in the trial when women had adequate analgesia. The use of epidural analgesia is not a prerequisite to FPO, however. The primary aim of adding FPO was to reduce operative delivery for nonreassuring fetal status. A statistically significant reduction of 23% was found, with narrow relative risk confidence intervals, suggesting adequate power to demonstrate this difference. The difference is in the same direction as the other published RCTs.13,14 Operative delivery is a clearly definable end point, which is important in its own right. Routine costs of cesarean section are substantially greater than for an uncomplicated vaginal birth.21 Maternal morbidity and mortality are greater from cesarean than vaginal birth, with an excess of pulmonary embolism, wound infection, and aspiration pneumonitis.22 Forceps delivery is usually accompanied by greater use of general and regional anesthesia than vacuum or spontaneous delivery, and women are more likely to sustain significant genital tract injury.23 Operative vaginal birth is also associated with a higher incidence of cephalhematoma and facial injury to the baby.23 Operative birth for nonreassuring fetal status was selected as the primary outcome, rather than overall operative delivery for the following reasons: (1) FPO is intended to discern fetal well-being; and (2) the indication for intervention is important, rather than simply the intervention itself. For example, the likelihood of a successful vaginal birth after cesarean in a subsequent pregnancy is improved for those whose previous cesarean was performed for nonreassuring fetal status, compared with those in which the indication was dystocia.24 There are also resource implications from the indication for operative birth: for example, an emergency cesarean section for nonreassuring fetal status is performed a median 42 minutes from the decision for intervention in Australian maternity hospitals,25 comparable with those in which this RCT was conducted. This may have a greater impact on staffing levels and operating room availability than a less urgent cesarean section, which may be expected to occur a median 67 minutes from the decision for intervention.25 Despite the statistically significant reduction in operative delivery for nonreassuring fetal status in the intervention group, compared with the control group, there were no differences in overall spontaneous or assisted vaginal birth or cesarean section rates between the 2 groups. The rate of cesarean section performed for
606.e9 dystocia in the control group was similar to both the control group rate in another reported RCT13 and the rate for the mildly nonreassuring group of a cohort study monitored with FPO.15 The rate of cesarean section performed for dystocia in the intervention group was lower than that reported in either the intervention group of the RCT reported by Garite et al13 or for the moderate or severely nonreassuring group of the cohort study reported by Porreco et al15 and was not statistically significantly different between groups. Progress to a vaginal birth may be viewed as precluding a diagnosis of dystocia.15 However, clinicians frequently documented the indication for assisted vaginal birth as failure to progress in our trial (Table III). Our finding of a relative risk of 2.07 (intervention/control) for assisted vaginal birth for failure to progress/dystocia during the second stage of labor has not been described in previous reports of FPO and dystocia13,15 and may suggest that FPO allowed the decision to intervene to be delayed from first to second stage. Data in Table VII support this explanation, insofar as there was an increased interval between randomization and delivery in the intervention group, compared with the control group. This delay may result in lower maternal morbidity because a cesarean section may be avoided in favour of operative vaginal birth.22 It may thereby also impact positively on resource use.21 Whereas FPO provides reassurance of fetal wellbeing, it does not address other indications influencing delivery mode, such as dystocia/failure to progress, fetal malposition, and/or maternal exhaustion. Our trial design does not permit reliable analysis of the impact of these factors on the overall delivery mode. Further trials are required to address ways of reducing operative birth for such indications. Study participants, with nonreassuring fetal status during labor, constitute a subgroup of child-bearing women overall. Within this subgroup the overall assisted vaginal birth and caesarean section rates (Table III) were considerably higher than the rates of 11% and 27% for assisted vaginal birth and cesarean section for Australian women overall.19 Our reported rates for each mode of birth were, however, consistent with those for nonparticipants with nonreassuring CTGs at the 4 study sites during the study period (unpublished data). There were no differences in neonatal outcomes between the 2 groups, despite finding that, compared with the control group, the intervention group had fewer operative deliveries for nonreassuring fetal status; more operative vaginal births for dystocia/failure to progress; and longer time from randomization to birth. We therefore conclude the decision not to intervene did not result in worse outcomes for those babies. There were few SAEs in either group and the study was not adequately powered to detect significant differences in these events. An ideal study would be able to
606.e10 examine long-term neurological outcomes. However, because there is a low prevalence of poor outcomes of this type, such a study would need to be much larger and better resourced than the current one to identify any differences. The majority of postrandomization interventions to assess fetal well-being or correct nonreassuring CTGs were similar for the 2 groups. More fetal blood samples (FBS) were performed in the CTG group, although there had been no between-group differences in nonreassuring CTGs, suggesting that FPO provided the reassurance otherwise sought by performing FBS. Those in the FPOCCTG group were 68% less likely to have a scalp lactate sample 4.8 mmol/L or greater than those in the CTG-only group, suggesting that FSpO2 values less than 30% may have prompted action earlier, ranging from a simple change in maternal position through to delivery. In hospitals in which FBS is not commonly performed to augment CTG monitoring, the rate of operative intervention for nonreassuring fetal status may be higher than that observed in our control group: the reduction in operative delivery for nonreassuring fetal status we observed when FPO was added to CTG monitoring may be even greater in such circumstances. Fetal SpO2 values were recorded for a median of 83% of monitoring time, consistent with our previous observational study5 and greater than that reported in a previous RCT.13 We recorded FSpO2 values less than 30% for a median 14% of monitored time. This is higher than our previous report of 3.9% in fetuses with and without nonreassuring CTGs,5 as would be expected with a nonreassuring CTG being required for study entry. The addition of FPO to the CTG to monitor fetal wellbeing during labor resulted in a significant decrease in operative intervention for nonreassuring fetal status, compared with use of conventional monitoring alone. This decrease was achieved with no significant difference in neonatal outcomes. The place of FPO in contemporary maternity care may now be evaluated by incorporating the findings of the FOREMOST trial into the systematic review of FPO12 and considering our economic analysis and maternal perceptions of their experience in the FOREMOST trial, yet to be published. Further studies may address ways of reducing operative birth for indications other than nonreassuring fetal status.
Acknowledgments We thank the child-bearing women and their babies who participated in this trial and the midwifery and medical staff at the respective birth/delivery suites who actively assisted in recruitment to and conduct of the trial. We also thank the data monitoring committee (J.F. King, chair, C. Crowther, D. Henderson-Smart, R. Hockey) for conducting the interim analysis and reviewing serious adverse events.
East et al Following are members of the FOREMOST Study Group: K. Andrews, Research Midwife, Mater Mothers’ Hospital Brisbane; K. Barr, Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane; R. Aziz, Research Midwife, Mater Mothers’ Hospital Brisbane; E. Beller, Statistician, final analysis; K. Cleary, Research Midwife, Mater Mothers’ Hospital Brisbane; C. Crowther, Data Monitoring Committee member; J. Davies, Research Midwife, Mater Mothers’ Hospital Brisbane; K. Dunster, Establishment and maintenance of the randomization system; D. Everding, Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane; G. Healy, Data management; D. Henderson-Smart, Data Monitoring Committee member; R. Hockey, Statistician, interim analysis; Data Monitoring Committee member; L. Leader, Collaborator, Royal Hospital for Women, Sydney; N. Henshall, Research Midwife, Royal Hospital for Women, Sydney; L. Moroney, Research Midwife, Royal Brisbane and Women’s Hospital; M. Stewart, Research Midwife, Royal Women’s Hospital, Melbourne.
References 1. Thacker SB, Stroup D, Chang M. Continuous electronic fetal heart monitoring for fetal assessment during labor. Cochrane Database System Rev 2001;(2):CD000063. 2. Colditz PB, Begg LM, East CE. Fetal pulse oximetry: instrumentation and recent clinical experience. Clin Perinatol 1999;26: 869-80. 3. Kuhnert M, Seelbach-Gobel B, Di Renzo GC, Howarth E, Butterwegge M, Muray JM. Guidelines for the use of fetal pulse oximetry during labor and delivery. Prenat Neonatal Med 1998;3:432-3. 4. Begg LM, East CE, Chan FY, Brennecke SP. Intrapartum fetal oxygen saturation monitoring in congenital fetal heart block. Aust N Z J Obstet Gynaecol 1998;38:271-4. 5. East CE, Dunster KR, Colditz PB. Fetal intrapartum oxygen saturation monitoring: an analysis of 118 cases. Aust N Z J Obstet Gynaecol 1997;37:397-401. 6. East CE, Colditz PB, Begg LM, Brennecke SP. Update on intrapartum fetal pulse oximetry. Aust N Z J Obstet Gynaecol 2002; 42:119-24. 7. East CE, Colditz PB, Dunster KR, Khoo SK. Human fetal intrapartum oxygen saturation monitoring: agreement between readings from two sensors on the same fetus. Am J Obstet Gynecol 1996;174:1594-8. 8. Nijland R, Jongsma HW, Crevels J, Menssen J, Nijhuis JG, van den Berg PP, et al. The ductus arteriosus, pre- and post-ductal oxygen saturation measurements in fetal lambs. Eur J Obstet Gynecol Reprod Biol 1994;55:135-40. 9. Nijland R, Jongsma HW, Nijhuis JG, van den Berg PP, Oeseburg B. Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs. Am J Obstet Gynecol 1995;172:810-9. 10. Dildy GA, Thorp JA, Yeast JD, Clark SL. The relationship between oxygen saturation and pH in umbilical blood: implications for intrapartum fetal oxygen saturation monitoring. Am J Obstet Gynecol 1996;175:682-7. 11. Kuhnert M, Seelbach-Gobel B, Butterwegge M. Predictive agreement between the fetal arterial oxygen saturation and fetal scalp pH: results of the German multicenter study. Am J Obstet Gynecol 1998;178:330-5.
East et al 12. East CE, Chan FY, Colditz PB. Fetal pulse oximetry for fetal assessment in labour. Cochrane Database System Rev 2004;(4): CD004075. 13. Garite TJ, Dildy GA, McNamara H, Nageotte MP, Boehm FH, Dellinger EH, et al. A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns. Am J Obstet Gynecol 2000;183:1049-58. 14. Kuhnert M, Schmidt S. Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry. Am J Obstet Gynecol 2004;191:1989-95. 15. Porreco RP, Boehm FH, Dildy GA, Miller HS, Wickstrom EA, Garite TJ, et al. Dystocia in nulliparous patients monitored with fetal pulse oximetry. Am J Obstet Gynecol 2004;190:113-7. 16. Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med 1997;126: 376-80. 17. East CE, Brennecke SP, King JF, Chan FY, Colditz PB, on behalf of the FOREMOST Study Group. The FOREMOST Study. Available from: http://152.98.230.3/som/women_foremosttrial. shtml. 2005. 18. Umstad MP. The predictive value of abnormal fetal heart rate patterns in early labour. Aust N Z J Obstet Gynaecol 1993;33:145-9. 19. Laws PJ, Sullivan EA. Australia’s mothers and babies 2002. AIHW cat no PER 28. Sydney: AIHW National Perinatal Statistics Unit (Perinatal Statistics series no 15); 2004. 20. Centre for Epidemiology and Research New South Wales Department of Health. New South Wales Mothers and Babies 2001. Sydney: NSW Public Health Bulletin; 2002;20:3(S4). 21. Henderson J, McCandlish R, Kumiega L, Petrou S. Systematic review of economic aspects of alternative modes of delivery. BJOG 2004;108:149-57. 22. Lomas J, Enkin M, Pearson J, Rees G. Caesarean section. In: Enkin M, Keirse MJNC, Renfrew M, Neilson J, editors. A guide to effective care in pregnancy and childbirth. 2nd ed. Oxford (UK): Oxford University Press; 1995. p. 318-22. 23. Vacca A, Keirse MJNC. Instrumental vaginal delivery. In: Chalmers I, Enkin M, Keirse MJNC, editors. Effective care in pregnancy and childbirth. Oxford (UK): Oxford University Press; 1989. 24. Grinstead J, Grobman WA. Induction of labor after one prior cesarean: predictors of vaginal delivery. Obstet Gynecol 2004; 103:534-8. 25. Spencer MK, MacLennan A. How long does it take to deliver a baby by emergency caesarean section? Aust N Z J Obstet Gynaecol 2001;41:7-11.
606.e11 Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australiaa; Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women’s Hospital Melbourne, Victoria, Australiab; Royal Women’s Hospital Melbourne, Victoria, Australiac; Maternal Fetal Medicine, The University of Queensland, Mater Mothers’ Hospital Brisbane, Queensland, Australiad The FOREMOST Study Groupe:
K. Andrews R. Aziz K. Barr E. Beller K. Cleary C. Crowther J. Davies K. Dunster D. Everding G. Healy D. HendersonSmart R. Hockey L. Leader N. Henshall L. Moroney M. Stewart
Research Midwife, Mater Mothers’ Hospital, Brisbane Research Midwife, Mater Mothers’ Hospital, Brisbane Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane Statistician Research Midwife, Mater Mothers’ Hospital, Brisbane Data Monitoring Committee member Research Midwife, Mater Mother’s Hospital, Brisbane Establishment and maintenance of the randomization system Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane Data Management Data Monitoring Committee member Statistician, interim analysis; Data Monitoring Committee member Collaborator, Royal Hospital for Women, Sydney Research Midwife, Royal Hospital for Women, Sydney Research Midwife, Royal Brisbane and Women’s Hospital Research Midwife, Royal Women’s Hospital, Melbourne
Appendix* The FOREMOST Trial (Fetal Intrapartum Pulse Oximetry: a Multicenter Randomized Controlled Trial) Statement of purpose. Information provided on this Web site is intended to complement results published in the peer-reviewed literature. Details of publications and additional data will be added to this site as they become available. Investigators: C. E. Easta, S. P. Brenneckeb, J. F. Kingc, F. Y. Chand, P. B. Colditza, for the FOREMOST Study Groupe
* The full results of the FOREMOST trial can be found at: http:// www.som.uq.edu.au/som/women_foremosttrial.shtml.
Project synopsis Aims To compare obstetric outcomes (specifically the rates of operative deliveries performed for the indication of nonreassuring fetal status) between 2 groups of patients: those having conventional cardiotocography (CTG) monitoring and those having CTG monitoring plus fetal oxygen saturation monitoring. To compare neonatal outcome of the 2 study groups including cord blood gases, Apgar scores, requirements for resuscitation, and admission to a neonatal intensive care unit.
606.e12 To evaluate the impact of the new technology by conducting a cost analysis and assessing maternal satisfaction with fetal monitoring, labor, and delivery. The following hypotheses were tested: 1. Primary hypothesis In the presence of nonreassuring CTG tracings, the use of fetal intrapartum oxygen saturation monitoring and CTG monitoring, compared with CTG monitoring alone, would result in a 33% reduction in operative delivery rates for nonreassuring fetal status. 2. Secondary hypotheses There would be no difference in operative delivery rate for dystocia. There would be no difference in fetal/neonatal outcomes (umbilical arterial pH, Apgar scores, admission to the neonatal intensive care unit) between the 2 groups. There would be no difference in women’s satisfaction with fetal monitoring or their labor, delivery, and outcome between the 2 groups.
Background synopsis The FOREMOST trial was an Australian multicenter, randomized, controlled trial to evaluate the effect of fetal intrapartum pulse oximetry, in the presence of nonreassuring CTG tracings, on operative delivery rates at the Royal Brisbane and Women’s Hospital, Brisbane; the Mater Mother’s Hospital, Brisbane; the Royal Women’s Hospital, Melbourne; and the Royal Hospital for Women, Sydney. Women whose fetuses displayed a nonreassuring CTG pattern in labor at term, who gave informed consent and did not meet any of the exclusion criteria, were randomized to either the control group (conventional CTG monitoring) or the experimental group (CTG plus fetal oximetry). Clinical management in the control and intervention arms of the study followed a protocol.
Results The information on this Web site is designed to complement the published data. Findings currently include details, expanded from the published data, for the following:
Baseline demographics. Neonatal outcomes. Logistic regression analyses. Serious adverse events. Trial management issues of interest.
East et al Baseline demographics Experimental (FPOCCTG) (n = 305) Indigenous 9 (3.0%) Parity 0 247 (81.0%) 1 36 (11.8%) 2 17 (5.6%) 3 1 (0.3%) O3 4 (1.3%) Maternal risk factors None 195 (63.9%) One or more of risk factors Chronic hypertension 4 (1.3%) PIH/PE 35 (11.5%) Eclampsia 0 (0%) Prepregnancy diabetes 0 (0%) Glucose intolerance in 14 (4.6%) pregnancy No prenatal care 2 (0.7%) Maternal cardiac disease 5 (1.6%) Maternal renal disease 5 (1.6%) Fetal risk factors None 221 (72.5%) One or more of risk factors Small for dates/IUGR 11 (3.6%) Polyhydramnios 3 (1.0%) Oligohydramnios 1 (0.3%) Postdates O42 wk 1 (0.3%) Preterm labor !37 wk 6 (2.0%) Maternal substance use 52 (17.0%) Alcohol 19 (6.2%) Drugs 10 (3.3%) Smoking 39 (12.8%)
Control (CTG-only) (n = 295) 11 (3.8%) 226 42 13 7 7
(76.6%) (14.2%) (4.4%) (2.4%) (2.4%)
178 (60.3%) 3 38 0 3 14
(1.0%) (12.9%) (0%) (1.0%) (4.7%)
0 (0%) 9 (3.1%) 2 (0.7%) 209 (70.8%) 10 1 3 2 11 55 19 15 41
(3.4%) (0.3%) (1.0%) (0.7%) (3.7%) (18.6%) (6.4%) (5.1%) (13.9%)
Study group data are number of patients (%). PIH, Pregnancy; IUGR, intrauterine growth restriction.
Logistic regression Covariates entered into the logistic regression models included: Hospital B Royal Women’s Hospital, Brisbane (RWH Bris) B Mater Mothers’ Hospital, Brisbane (MMH Bris) B Royal Women’s Hospital, Melbourne (RWH Melb) B Royal Hospital for Women, Sydney (RHW Syd)
Group (FPO or CTG) Previous cesarean Maternal age Parity (0, R1) Pregnancy induced hypertension/pre-eclampsia Intrauterine growth restriction Labor induced Meconium stained amniotic fluid
East et al
606.e13
Neonatal outcomes
Cord arterial pH (FPO, n = 272; CTG, n = 240) Mean (SD) !7.15 !7.10 !7.05 !7.00 Cord arterial BE (FPO, n = 257; CTG, n = 224) Median (IQR) !10 !12 !16 Skin impression from FPO sensor (n = 294 attempted)k Resuscitation None One or more of risk factors Suction Facial oxygen Aspiration of meconium above cords ETT intubation for asp of meconium below cords Bag and mask (IPPV) Bag and mask (IPPV) C naloxone Naloxone IPPV via ETT IPPV via ETT C naloxone Cardiac massage Routine well-baby care
Experimental (FPOCCTG) (n = 305 unless otherwise stated)
Control (CTG-only) (n = 295 unless otherwise stated)
P value*
Relative risk (FPOCCTG: CTG-only) 95% CI
7.236 39 13 5 2
7.236 35 12 4 2
.987y .937 .908 1.000z 1.000z
0.98 0.96 1.10 0.89
(0.770) (14.3%) (4.8%) (1.8%) (0.7%)
4.0 (6.3, 2.2) 24 (9.4%) 10 (3.9%) 2 (0.7%) 30 (10.2%)
71 (23.3%)
(0.0756) (14.6%) (5.0%) (1.7%) (0.8%)
3.6 (6.1, 1.9) 18 (8.1%) 6 (2.7%) 0 (0%)
83 (28.1%)
(0.64, (0.42, (0.30, (0.13,
1.50) 2.05) 4.06) 6.26)
.336x .615 .466 .501z
1.16 (0.72, 2.33) 1.45 (0.53, 3.91) Unable to calculate
.173
0.83 (0.63, 1.09)
213 110 22 4
(69.8%) (36.1%) (7.2%) (1.3%)
186 85 14 10
(63.1%) (28.8%) (4.7%) (3.4%)
.078 .058 .203 .092
1.11 1.25 1.52 0.39
(0.99, (0.99, (0.79, (0.12,
1.24) 1.58) 2.91) 1.22)
61 0 0 1 0 0 214
(20%) (0%) (0%) (0.3%) (0%) (0%) (70.2%)
42 0 1 6 0 0 216
(14.2%) (0%) (0.3%) (2.0%) (0%) (0%) (73.2%)
.061
1.40 (0.98, 2.01)
.492z .065z
Not able to calculate 0.16 (0.02, 1.33)
.406
0.96 (0.87, 1.06)
Study group data are number of patients (%), mean (SD), or median (IQR). BE, Base excess; ETT, endotracheal tube; IPPV, intermittent positive pressure ventilation. * c2 unless otherwise stated. y Student t test. z Fisher’s exact test. x Mann-Whitney U test. k Sensor placement not attempted as bleeding commenced (n = 2), commenced pushing or gave birth (n = 3), or decision made for cesarean or forceps (n = 6).
Maternal temperature in labor O37.5(C Rupture of amniotic membranes (ROM) O18 hours Group B Streptococcus (GBS) Antibiotics for maternal temperature, ROMO18 hours, GBS Cervical dilatation !5 cm at epidural placement Rise in blood pressure during labor Hematuria Only the significant findings are presented here. We also tested for group and hospital effect modification but found none (ie, the hospital still made a difference regardless of group allocation but not because FPO was managed differently in each hospital).
Summary: After adjusting for hospital, group allocation remained a significant predictor of operative delivery for nonreassuring fetal status. Multiple regression: operative delivery for nonreassuring fetal status
Group (CTG:FPO) Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
P value
Odds ratio
95% confidence intervals
.043 .000 .000 .000 .010
0.686
(0.476, 0.988)
2.742 3.434 2.061
(1.730, 4.347) (2.040, 5.782) (1.184, 3.585)
606.e14
East et al
Multiple regression: cesarean section for dystocia/failure to progress
Hematuria Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
P value
Odds ratio
95% confidence intervals
0.000 0.030 0.032 0.030 0.075
3.396
1.953, 5.904
0.493 0.426 0.481
0.257, 0.942 0.196, 0.922 0.215, 1.077
Summary: After adjusting for hospital, women with hematuria during labor were more than 3 times more likely to have a cesarean section for dystocia/failure to progress that those without. Univariate regression: umbilical arterial pH !7.15
Hospital Hospital Hospital Hospital
(RWH Bris) (MMH Bris) (RWH Melb) (RHW Syd)
P value
Odds ratio
95% confidence intervals
0.004 0.335 0.728 0.004
0.711 1.137 2.525
0.355, 1.422 0.551, 2.346 1.354, 4.709
Summary: Hospital was the only significant covariate to predict umbilical arterial pH !7.15. Univariate regression: bag and mask intermittent positive pressure ventilation
GBS
P value
Odds ratio
95% confidence intervals
0.050
1.967
0.999, 3.874
Summary: The clinical significance of this finding is uncertain. Multiple regression: maternal post partum temperature O37.5(C 95% confidence P value Odds ratio intervals Temp in labor O37.5(C Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
.000 .009 .001 .481 .037
4.027
2.710, 5.986
2.177 1.236 1.839
1.348, 3.514 0.685, 2.229 1.039, 3.256
Summary: After adjusting for hospital differences, elevated maternal temperature during labor predicted elevated maternal temperature postpartum. Logistic regression was also undertaken to determine whether the mode of birth or indication for operative birth influenced neonatal outcomes.
Multiple regression: Selected neonatal outcomes Odds P value ratio
95% confidence intervals
Cord arterial pH !7.10 Spontaneous vaginal birth .629 Assisted vaginal birth For nonreassuring fetal status .297 0.491 (0.129, 1.871) For all other indications .533 0.588 (0.111, 3.120) Cesarean section For nonreassuring fetal status .725 0.769 (0.178, 3.318) For dystocia/failure to progress .707 1.263 (0.373, 4.277) For all other indications .599 1.408 (0.393, 5.047) Cord arterial pH !7.15 Spontaneous vaginal birth .274 Assisted vaginal birth For nonreassuring fetal status .060 2.080 (0.971, 4.457) For all other indications .088 2.167 (0.892, 5.262) Cesarean section For nonreassuring fetal status .388 1.493 (0.601, 3.710) For dystocia/failure to progress .927 1.044 (0.415, 2.626) For all other indications .997 0.000 (0.000) Cord arterial base excess !10 Spontaneous vaginal birth .667 Assisted vaginal birth For nonreassuring fetal status .114 2.492 (0.804, 7.723) For all other indications .336 1.942 (0.503, 7.501) Cesarean section For nonreassuring fetal status .177 2.389 (0.674, 8.459) For dystocia/failure to progress .326 1.880 (0.533, 6.630) For all other indications .640 1.403 (0.340, 5.795) Cord arterial base excess !12 Spontaneous vaginal birth .723 Assisted vaginal birth For nonreassuring fetal status .234 2.591 (0.540, 12.445) For all other indications .997 0.000 (0.000) Cesarean section For nonreassuring fetal status .793 1.304 (0.180, 9.460) For dystocia/failure to progress .622 1.577 (0.258, 9.638) For all other indications .761 0.687 (0.061, 7.713) Bag and mask intermittent positive pressure ventilation Spontaneous vaginal birth .247 Assisted vaginal birth For nonreassuring fetal status .213 0.651 (0.331, 1.279) For all other indications .229 1.567 (0.754, 3.254) Cesarean section For nonreassuring fetal status .941 1.029 (0.486, 2.176) For dystocia/failure to progress .895 1.049 (0.519, 2.121) For all other indications .519 0.766 (0.341, 1.721)
Summary: Mode of birth or indication for operative birth did not result in differences in neonatal outcomes. Serious adverse events Mothers and babies were monitored for serious adverse events from the time of study entry until transfer to another hospital, discharge from hospital, or in-hospital death.
East et al Serious adverse events could include:
Death Events that prolonged hospitalisation Congenital abnormalities Placental abruption requiring surgical intervention Any event of sufficient concern to researchers or clinicians
Serious adverse events were reviewed by the Data Monitoring Committee and the relevant Human Research Ethics Committee.
Abbreviations BE: CPAP: C/S: EEG: ETT: IPPV: O2: PROM: UA: UV:
base excess continuous positive airway pressure cesarean section electroencephalogram endotracheal tube intermittent positive pressure ventilation oxygen prelabor rupture of membranes umbilical arterial umbilical venous
606.e15 5. Baby: pneumothorax
C/S failure to progress and nonreassuring fetal status ETT suction of meconium below cords, then IPPV by ETT Apgars 31, 85 UA pH 7.312 UA BE 2.0 mmol/L Pneumothorax diagnosed at age 45 min IPPV 14 h, intercostal catheter 4 d intensive care nursery Home at day 7 6. Mother and baby No maternal temperature O37.5(C septic during labor C/S nonreassuring fetal status Mother: profuse Staphylococcus aureus on high vaginal swab day 2 after C/S– antibiotics. Discharged home day 8 Baby: Staphylococcus aureus on blood cultures, antibiotics 7 d Discharged home day 8 7. Hyaline membrane C/S failure to progress and disease nonreassuring fetal status Apgars 71, 95 UV pH 7.25 UA BE 6 mmol/L Total hospitalisation 13 d
Experimental group (fetal pulse oximetry with CTG)
Control group (CTG) Serious adverse event Relevant clinical details 1. Death
Hemolytic disease of the newborn presenting with jaundice at 7 h of age (at which time the hemoglobin was 89 g/L) due to homozygous mutation of pyruvate kinase gene 2. Meconium Meconium seen at artificial rupture of aspiration membranes, 75 min prior to study syndrome entry C/S nonreassuring fetal status Apgars 91, 105 UA pH 7.23 UA BE 0.5mmol/L CPAP 24 h, antibiotics Transferred to a children’s hospital for ongoing care Apgars 71, 85 3. Mild respiratory distress UA pH 7.202 syndrome and UA BE 4.3 mmol/L pneumomediastinum Facial O2 at birth Head box O2 4. Baby: prolonged Growth restricted length of stay Gastric tube feeds 4 d Discharged home at 12 d
Serious adverse event
Relevant clinical details
1. Neonatal encephalopathy (Sarnat stage 1) (not hypoxic-ischemic encephalopathy)
Mother used cannibas Growth restriction
2. Neonatal encephalopathy (Sarnat stage 1) (not hypoxic-ischemic encephalopathy)
3. Acute tubular necrosis
4. Meconium aspiration syndrome
Spontaneous vaginal birth Apgars 11, 65 UA pH 7.21 UA BE 10 mmol/L Irritability for 24 h No seizures noted Spontaneous vaginal birth Growth restriction Central brain disorder Hypertonicity Poor ability to suck/swallow Apgars 61, 85 UA pH 7.234 UA BE 5.2 mmol/L Possible subtle seizures not confirmed by EEG C/S nonreassuring fetal status Apgars 41, 85 UA pH 7.104 UA BE 11.1 mmol/L Baby discharged home day 8 PROM, labor induced after developed meconium staining of liquor.
606.e16
5. Erb’s palsy and Facial palsy 6. FPO sensor placement not attempted Mother: 800 mL hemorrhage
7. Lateral uterine tear during cesarean
8. Baby: atrioventricular canal (AVC)
East et al C/S for slow progress, thick meconium, nonreassuring fetal status ETT for aspiration of meconium Apgars 61, 95 UA pH 7.146 UA BE 10.2 mmol/L Mechanical ventilation not necessary O2 ! 24 hours Forceps delivery for insufficient progress and malposition Facial palsy resolved by discharge Immediately after randomization, bleed occurred and shoulder presentation diagnosed; emergency C/S No further hemorrhage occurred and no maternal blood transfusion required Apgars 51, 95 UV pH 7.215 UV BE 5.4 mmol/L C/S for nonreassuring fetal status Converted from epidural to general anesthesia during cesarean Estimated blood loss 2000 mL No blood transfusion Diagnosed antenatally Allowed into trial because obstetrician confident the abnormality would not affect well-being until after birth Postnatal echo: AVC and large ventricular septal defect, and atrioseptal defects Home day 6 with hospital follow-up arranged
Trial management details of interest: The research midwife was in attendance for a median (IQR) of 16 min (0, 82 min) in the CTG-only group and 97 min (0, 195 min) for the CTGCFPO group.
www.ajog.org
The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: A multicenter, randomized, controlled trial (the FOREMOST trial) Christine E. East, MMedSc,a,* Shaun P. Brennecke, DPhil(Oxon),b James F. King, MPH,b Fung Yee Chan, MD,c Paul B. Colditz, DPhil(Oxon),a on behalf of The FOREMOST Study Group Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australiaa; Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women’s Hospital, Melbourne, Victoria, Australiab; Department of Maternal-Fetal Medicine, The University of Queensland, Mater Mothers’ Hospital, Brisbane, Queensland, Australiac Received for publication May 23, 2005; revised August 2, 2005; accepted August 18, 2005
KEY WORDS Fetal pulse oximetry Randomized controlled trial Electronic fetal monitoring
Objective: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. Study design: The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. Results: There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry C cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry C cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. Conclusion: The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal
Supported by grants from the Australian National Health and Medical Research Council (142936, 301050), Queensland Health, The University of Queensland, and TYCO Inc (Nellcor) and loan equipment (fetal pulse oximetry) from TYCO Inc (Nellcor). Supplemental information can be found at: www.ajog.org. * Reprint requests: Ms. C. East, Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Butterfield Street, Herston, Queensland 4029, Australia. E-mail: [email protected] 0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.08.051
606.e2
East et al status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes. Ó 2006 Mosby, Inc. All rights reserved.
Conventional cardiotocography (CTG) methods of fetal assessment are limited by a high false-positive rate, resulting in an unnecessarily high operative delivery rate for nonreassuring fetal status.1 A safe, reliable, and accurate test of fetal well-being in labor is an important and urgent need in contemporary obstetrics. Fetal pulse oximetry (FPO) may improve the assessment of fetal well-being in labor.2-7 On the basis of human and animal data, fetal oxygen saturation (FSpO2) values 30% or greater are reassuring in the human fetus and FSpO2 values greater than 30% for 10 minutes require further assessment or intervention.3,8-11 We recently conducted a systematic review to compare outcomes for fetuses with presumed compromise during labor, whose well-being was monitored with and without fetal oximetry.12 At the time of the review, the only published randomized controlled trial (RCT) reported a lower rate of operative deliveries for nonreassuring fetal status in the FPO with CTG group than the CTG-only group.13 The review recommended that further RCTs address dystocia in labors monitored with FPO, maternal satisfaction, long-term neurodevelopmental outcome of infants who exhibited nonreassuring fetal status in labor, and cost effectiveness of FPO. More recently a further RCT (n = 146) also reported a reduction in operative delivery for nonreassuring fetal status.14 The issue of dystocia has been explored in a cohort study by Porreco et al.15 They reported cesarean section rates for prospectively defined and managed dystocia of 8% and 22% for those with mildly nonreassuring and moderate or severely nonreassuring CTGs, respectively, despite the presence of normal FSpO2 values and consistent with the cesarean rates for dystocia in the RCT reported by Garite et al.13 The use of a new technology in different obstetric environments justifies a number of RCTs, and metaanalysis of such RCT findings improves power and precision of estimates of effects.16 Additionally, we considered a further study necessary to further document the incidence of dystocia in labors monitored with and without FPO. We have therefore conducted a RCT to compare operative delivery rates for nonreassuring fetal status between 2 groups: those having CTG monitoring and those having CTG monitoring plus FPO.
Material and methods Participants Women were informed about the trial during antenatal visits/classes, at induction of labor, and/or during labor.
Women were approached to consider trial participation during labor only when clinicians considered it appropriate to do so. Many women eligible for trial participation were therefore not approached (Figure). Women qualified for trial participation if there was a nonreassuring CTG during labor (Table I) and they met the remaining criteria listed in the Figure. The trial was conducted in the birth and delivery suites of 4 Australian maternity hospitals, each with more than 4000 births a year: the Royal Brisbane and Women’s Hospital, Brisbane (co-ordinating center); the Royal Women’s Hospital, Melbourne; the Mater Mothers’ Hospital, Brisbane; and the Royal Hospital for Women, Sydney. Investigators at the first 3 hospitals had prior experience with fetal oximetry.2,4,6
Procedures Women were randomized to continue with conventional CTG monitoring (CTG-only, control group) or the addition of FPO to CTG monitoring (FPOCCTG, intervention group). In the intervention group, the FPO sensor (Nellcor OxiFirst, TYCO Inc, Pleasanton, CA) was placed during a vaginal examination by a research midwife or medical staff/midwives who had received instruction in sensor placement. The FSpO2 was displayed on the oximeter and printed on the CTG paper. Monitoring continued from the time of sensor placement until as close as possible to birth, with minor sensor adjustments during labor to achieve a signal, usually performed externally by withdrawing or advancing the sensor in 1-cm increments.7 The CTG following randomization could become reassuring, continue to be nonreassuring, or develop an ominous pattern. Clinical management of the control and intervention arms of the study were: (1) if the CTG subsequently became reassuring, labor was continued unless otherwise indicated; (2) in the control group, a nonreassuring CTG prompted evaluation and management of the fetal heart rate (FHR) pattern. In the FPOCCTG group, when FSpO2 values were reassuring (30% or greater) in the presence of a nonreassuring CTG, labor continued unless otherwise indicated. If the FSpO2 values were less than 30% for 10 minutes or not recording, evaluation and management of the FHR pattern were recommended. Evaluation and management of the nonreassuring CTG or FSpO2 could include maternal position change, supplemental O2 administration, hydration, correction of hypotension, discontinuation of oxytocin infusion, or delivery; and (3) ominous FHR patterns (prolonged decelerations to less than 70 beats/min for more than
East et al
Figure
606.e3
Numbers of women assessed for trial eligibility, randomized, and included in intention-to-treat analysis.
606.e4 Table I
East et al Nonreassuring fetal heart rate patterns at study entry
Pattern (may have more than one) Persistent late decelerations (O50% of contractions) O15 min Sinusoidal pattern O15 min Variable decelerations with 1 or more of the following O15 min Relative drop of R70 beats/min or an absolute drop to %70 beats/min for O60 s Persistent slow return to baseline Baseline variability !5 beats/min Tachycardia O160 beats/min with decreased baseline variability !5 beats/min Recurrent prolonged decelerations (2 or more below 70 beats/m for O90 s) O15 min Persistent decreased baseline variability (!5 beats/min for O60 min) Tachycardia O160 beats/min with decreased baseline variability !5 beats/min O60 min Supraventricular tachycardia or heart block any length of time Other
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
59 (19.3%) 0 (0%)
61 (20.7%) 0 (0%)
63 (20.7%)
67 (22.7%)
61 (20.0%) 23 (7.5%) 12 (3.9%)
70 (23.7%) 33 (11.2%) 10 (3.4%)
24 (7.9%)
13 (4.4%)
61 (20.0%) 14 (4.6%)
45 (15.3%) 10 (3.4%)
0 (0%) 39 (12.8%)
0 (0%) 42 (14.2%)
Data for the 2 study groups are number (%) of patients.
7 minutes) prompted delivery, regardless of group allocation. Fetal blood sampling was available to both study groups without restriction. The study did not seek to regulate management based on fetal scalp pH or lactate values. It was considered that the stratification by center at randomization and randomization per se would compensate for any institutional differences in management based on fetal blood samples. The decision to intervene and documentation of indication for operative delivery remained the responsibility of the attending clinicians. The following hypotheses were tested. The first was the primary hypothesis. In the presence of a nonreassuring CTG, the use of intrapartum FPO plus CTG monitoring, compared with CTG monitoring alone, would result in a 33% reduction in the operative delivery rate for nonreassuring fetal status. In addition were the secondary hypotheses including the following: (1) there would be no difference in operative delivery rate for dystocia; (2) there would be no difference in fetal/neonatal outcomes (umbilical arterial pH, Apgar score, admission to the neonatal intensive care unit) between the 2 groups; and (3) there would be no difference in women’s satisfaction with fetal monitoring or their labor, delivery, and outcome between the 2 groups. This manuscript provides data outcomes related to the primary hypothesis and the first 2 components of the secondary hypothesis. Data outcomes from the third component of the secondary hypothesis and the economic evaluation will be described in separate manuscripts. The primary end point was operative birth (cesarean section, forceps, or vacuum) for nonreassuring fetal status. Secondary end points included overall operative
delivery for all indications and fetal/neonatal variables. Because of the low prevalence of poor neonatal outcomes such as hypoxic-ischemic encephalopathy or death, the study had insufficient power to reliably identify any differences between groups for these outcomes. The nature of the trial meant that it was not possible to blind the participants, clinicians, or research midwives to group allocation. The chief investigators remained blinded to group allocation until data collection, entry, and tabulation were completed. Data were presented to the data monitoring committee for the interim analysis in 2 unlabeled study groups. The research protocol was approved by The University of Queensland Human Research Ethics Committee and all relevant hospital ethics committees. Serious adverse events (SAEs)17 were reported to the ethics committees and the data monitoring committee.
Statistical analysis The sample size was dictated by the operative delivery rate for nonreassuring fetal status in fetuses demonstrating a nonreassuring CTG, defined in Table II. Intrapartum CTG monitoring is performed in approximately 50% of women at term at the Royal Women’s Hospital, Melbourne.18 Of these, 15% of CTGs are nonreassuring and 34% of these undergo operative delivery for nonreassuring fetal status.18 Unpublished data from the other participating centers were similar during the planning phase of the trial. A sample size of 281 women in each arm of the trial was therefore required to test the hypothesis that operative delivery rates for nonreassuring fetal status would be reduced by 33%, from 34%
East et al Table II
606.e5 Baseline demographics Intervention (FPO+CTG) (n = 305)
Maternal age (y) Hospital status Public Private Nulliparous Cervical dilatation on first vaginal examination (VE) (cm) Station on first VE Previous cesarean, overall Previous cesarean for dystocia/failure to progress Previous cesarean for nonreassuring fetal status Previous cesarean for nonreassuring fetal status C dystocia/failure to progress Maternal risk factors R1* Fetal risk factors R1y Birth weight (g) Birth weight O4000 g Induction of labor Prostaglandin Oxytocin infusion Artificial rupture of membranesz Meconium liquor Epidural analgesia Epidural at cervical dilatation !5 cm
29.72 (5.806)
Control (CTG-only) (n = 295) 28.92 (5.620)
288 17 247 3 2 19 3 8 0
(94.4%) (5.6%) (81.0%) (2, 3.9) (0.8) (6.2%) (1.0%) (2.6%) (0%)
276 19 226 3 2 16 3 5 2
(93.6%) (6.4%) (76.6%) (2, 4) (0.8) (5.4%) (1.0%) (1.7%) (0.7%)
110 84 3435.3 33 140 86 254 162 116 274 54
(36.1%) (27.5%) (500.88) (10.8%) (45.9%) (28.2%) (83.3%) (53.1%) (38.0%) (89.8%) (17.7%)
117 86 3440.9 35 144 88 238 171 115 254 53
(39.7%) (29.2%) (510.27) (11.9%) (48.8%) (29.8%) (80.7%) (58.0%) (39.0%) (86.1%) (18.0%)
Data for the 2 study groups are mean (SD), number of patients (%), or median (IQR). * One or more of: chronic hypertension, pregnancy-induced hypertension, eclampsia, prepregnancy diabetes, glucose intolerance in pregnancy, no prenatal care, maternal cardiac disease, maternal renal disease. y One or more of: small for dates/intrauterine growth restriction, polyhydramnios, oligohydramnios, O42 weeks’ gestation, !37 weeks’ gestation, maternal substance use (alcohol, drugs, smoking). z All were prerandomization.
in the control group to 23% in the intervention group (power 80%, alpha 0.05) (EpiInfo, version 6, Centers for Disease Control and Prevention, Atlanta, GA). We aimed to recruit 300 into each group to allow for withdrawals. An interim analysis was planned and conducted when 50% of the subjects had been enrolled and their outcomes known, with the data monitoring committee blinded to group allocation. A recommendation to the trial investigators to consider stopping the trial was to be made if: (1) the probability of finding the prespecified difference in operative delivery for nonreassuring fetal status between the 2 groups was less than 0.01 or (2) the frequency of SAEs was significantly worse in 1 group than the other (P ! .05) or would have reached that level of significance had the trial continued until its full sample size had been reached. The committee recommended continuation of the trial to full recruitment. After the first 14 recruits, when randomization was by use of numbered, sealed, opaque envelopes opened sequentially by the research midwife, a central telephone randomization system became available and was
employed (Voiceguide, versions 3 and 4, Katalina Technologies, Sydney, Australia). Researchers and clinicians were unaware of the randomization sequence prior to group allocation. The location and spread of baseline demographic and outcome data were summarized using proportions, mean and SD, median and interquartile range (IQR), or relative risks and 95% confidence intervals, as appropriate. Outcomes were compared using c2/Fisher’s exact test, Student t tests, Mann-Whitney U, or KaplanMeier (log rank) time-to-event analysis, as appropriate. Binary outcomes of operative delivery, labor complications, and fetal/neonatal outcomes were predicted from possible covariates (hospital, obstetric history of previous cesarean section, maternal age, parity, preeclampsia, intrauterine growth restriction, onset of labor [spontaneous/induced], meconium, hematuria, prolonged rupture of membranes, and maternal/neonatal infection), as appropriate, using logistic regression. The level of statistical significance for comparison was P ! .05 (2 sided). Data were analyzed using STATA (Intercooled STATA 8, Stata Corp, College Station, TX) and SPSS (version 11.5, SPSS Inc, Chicago, IL).
606.e6 Table III
East et al Delivery route and indication
Operative delivery For nonreassuring fetal status For dystocia/failure to progress Other indications Total Spontaneous vaginal birth Assisted vaginal birth (vacuum/forceps) For NRFS For dystocia/failure to progress For combined indication NRFS and dystocia/failure to progress For all other indications Total Cesarean section For NRFS For dystocia/FTP For NRFS/FTP All other indications Total
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
Relative risk (FPO+CTG: CTG-only) 95% CI
76 74 74 224
95 46 68 209
(32.2%) (15.6%) (23.1%) (70.8%)
.048 .008 .727 .478
0.77 1.56 1.05 1.04
81 (26.6%)
86 (29.2%)
.478
0.91 (0.70, 1.18)
34 (11.1%) 30 (9.8%) 13 (4.3%)
36 (12.2%) 14 (4.7%) 12 (4.1%)
.687 .017 .905
0.91 (0.59, 1.42) 2.07 (1.12, 3.83) 1.05 (0.49, 2.26)
7 (2.3%) 84 (27.5%)
5 (1.7%) 67 (22.7%)
.600 .173
1.35 (0.43, 4.22) 1.21 (0.92, 1.60)
.042 .188 .689 .246 .584
0.69 1.33 0.92 1.77 0.95
42 44 43 11 140
(24.9%) (24.3%) (24.3%) (73.4%)
(13.8%) (14.4%) (14.1%) (3.6%) (45.9%)
59 32 45 6 142
(20.0%) (10.8%) (15.3%) (2.0%) (48.1%)
(0.599, 0.999) (1.12, 2.17) (0.79, 1.40) (0.94, 1.15)
(0.48, (0.87, (0.63, (0.66, (0.80,
0.99) 2.04) 1.36) 4.73) 1.13)
Data for the 2 study groups are number of patients (%). NRFS, Nonreassuring fetal status; FTP, failure to progress. * By c2.
Results Of more than 50,000 women assessed for trial eligibility, 601 were randomized: 306 to the intervention group and 295 to the control group (Figure) between July 1999 and September 2004. Following randomization to the intervention group, 1 patient revoked consent at the request of her partner, so no data were collected and she was excluded from further analysis. Baseline demographics, clinical characteristics and nonreassuring CTG features that allowed for study entry were similar for each group (Tables I and II). Analysis was by intention to treat and included all except the 1 participant who revoked consent. There was a statistically significant 23% reduction in operative delivery for nonreassuring fetal status in those allocated to FPOCCTG (n = 76, 25%), compared with those in the CTG-only group (n = 95, 32%) (relative risk [RR] 0.77, 95% confidence interval [CI] 0.599, 0.999, P = .048) (Table III). Cesarean section was performed for nonreassuring fetal status in 42 of the FPOCCTG group (14%) and 59 of the CTG-only group (20%) (RR 0.69, 95% CI 0.48, 0.99, P = .042). There was no difference in overall operative delivery (FPOCCTG group, n = 224, 73%; CTG-only group, n = 209, 71%, RR 1.04, 95% CI 0.94, 1.15, P = .478) (Table III). There were no overall between-group differences for spontaneous or assisted vaginal birth or cesarean section
(Table III). Women in the FPOCCTG group were more likely to have an operative birth for dystocia/failure to progress than those in the CTG-only group (RR 1.56, 95% CI 1.12, 2.17, P = .008). This increase was statistically significant for assisted vaginal births (RR 2.07, 95% CI 1.12, 3.83, P = .017) but not for cesarean births (RR 1.33, 95% CI 0.87, 2.04, P = .188) (Table III). There were no differences in neonatal outcomes between the 2 groups (Table IV). Neonatal SAEs were identified in 8 of the FPOCCTG group (2.6%) and 7 of the CTG-only group (2.4%). Details are available on the FOREMOST Web site.17 The data monitoring committee reviewed each event and did not consider that the SAEs raised issues affecting the continuation of the trial. Labor interventions were similar for the 2 groups following randomization (Table V). Fetal scalp blood sampling was performed more often in the CTG-only group (n = 157, 53%) than the FPOCCTG group (n = 41, 13%). Fetal heart rate patterns after randomization were similar for the 2 groups (Table VI). There was a longer time from randomization to birth for women in the FPOCCTG group, compared with those in the CTG-only group (Table VII). Prespecified logistic regression analyses were undertaken but did not alter the finding that women in the FPOCCTG group were statistically significantly less likely to have an operative delivery for nonreassuring
East et al Table IV
606.e7 Neonatal outcomes Intervention (FPO+CTG) (n = 305 unless otherwise stated)
1-min Apgar !4 5-min Apgar !7 Apgar score 1 min 5 min Cord arterial pH (FPO+CTG, n = 272; CTG-only, n = 240) !7.15 !7.00 Cord arterial BE (FPO+CTG, n = 257; CTG-only, n = 224) !–10 !–16 Cord arterial lactate (mmol/L) (FPO+CTG, n = 216; CTG-only, n = 194) Bag and mask IPPV Admission to NICU Admission to SCN Congenital sepsis (blood culture positive) Neonatal injuryk Time to neonatal discharge (d)
Control (CTG-only) (n = 295 unless otherwise stated)
P value*
12 (3.9%) 5 (1.6%)
9 (3.1%) 6 (2%)
.556 .719
8 (7, 9) 9 (9, 9)
9 (7, 9) 9 (9, 9)
.344 .802
39 (14.3%) 2 (0.7%)
35 (14.6%) 2 (0.8%)
.937 1.000y
24 (9.4%) 2 (0.7%)
18 (8.1%) 0 (0%)
.615 .501y
4.2 61 9 73 1 5 3.50
(2.9, 6.1) (20.0%) (3%) (23.9%) (0.3%) (1.4%) (2.74, 4.55)
4.2 42 11 60 1 4 3.49
(2.7, 5.9) (14.2%) (3.7%) (20.3%) (0.3%) (1.5%) (2.69, 4.72)
.605z .061 .596 .289 1.000y 1.000y .621x
Relative risk (FPO+CTG: CTG-only) 95% CI 1.29 (0.55, 3.02) 0.81 (0.25, 2.61)
0.98 (0.64, 1.50) 0.89 (0.13, 6.26)
1.16 (0.72, 2.33) Unable to calculate
1.40 0.79 1.18 0.97 1.21
(0.98, (0.33, (0.87, (0.06, (0.33,
2.01) 1.88) 1.59) 15.39) 4.46)
Data for the 2 study groups are number of patients (%) or median (IQR). IPPV, Intermittent positive pressure ventilation; NICU, neonatal intensive care unit; SCN, special care nursery. * By c2 unless otherwise noted. y Fisher’s exact test. z Mann-Whitney U test. x Log rank test. Medians are provided for interest only. k CTG-only group: bruising/torn skin following vacuum/forceps (n = 4); FPO+CTG group: torn skin following vacuum (n = 1), bruising to arm and scalp (shoulder dystocia) (n = 1), left-sided facial palsy (resolved) C right arm weakness (n = 1), scalp lesion at site of fetal scalp electrode (n = 1), cephalhematoma C facial edema (n = 1).
Table V
Postrandomization labor interventions and fetal evaluations
Oxytocin admin change Maternal oxygen administered Maternal position adjustment Intravenous hydration Fetal stimulation Correction of hypotension Fetal scalp pHz pH % 7.20 pH O 7.20 ! 7.25 Scalp lactatex R4.8 mmol/L
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
114 80 163 39 20 2
108 66 153 37 23 3
(37.4%) (26.3%) (53.6%) (12.9%) (6.6%) (0.7%)
(36.6%) (22.4%) (51.9%) (12.5%) (7.8%) (1.0%)
P value* .846 .261 .667 .904 .564 .682y
Relative risk (FPO+CTG: CTG-only) 95% CI 1.02 1.17 1.03 1.02 0.84 0.65
(0.83, (0.88, (0.89, (0.67, (0.47, (0.11,
1.26) 1.56) 1.20) 1.55) 1.50) 3.86)
4 (1.3%) 8 (2.6%)
3 (1.0%) 10 (3.4%)
1.000y .582
1.29 (0.29, 5.71) 0.77 (0.31, 1.93)
7 (2.3%)
21 (7.1%)
.005
0.32 (0.14, 0.75)
Data for the 2 study groups are number of patients (%). Admin, Administration. * c2 unless otherwise indicated. y Fisher’s exact test. z The lowest pH value was used in which more than 1 sample was taken. x The highest lactate recorded was used if more than 1 sample was taken.
606.e8 Table VI
East et al Fetal heart rate patterns after randomization
Reassuring (no features of nonreassuring or ominous FHR patterns) Nonreassuring (may have more than one) Persistent late decelerations (O50% of contractions) O15 min Sinusoidal pattern O15 min Variable decelerations with 1 or more of the following O15 min Relative drop of R70 beats/min or an absolute drop to %70 beats/min for O60 s Persistent slow return to baseline Baseline variability !5 beats/min Tachycardia O160 beats/min with decreased baseline variability !5 beats/min Recurrent prolonged decelerations (2 or more below 70 beats/min for O90 s) O15 min Persistent decreased baseline variability (!5 beats/min for O60 min) Tachycardia O160 beats/min with decreased baseline variability !5 beats/min O60 min Supraventricular tachycardia or heart block any length of time Other Ominous Prolonged decelerations to !70 beats/min for O7 min
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
51 (16.7%)
28 (15.3%)
.428
51 (16.7%) 0 (0%)
45 (15.3%) 0 (0%)
.624
89 (29.2%)
78 (26.4%)
.451
79 (25.9%) 44 (14.4%) 26 (8.5%)
93 (31.5%) 34 (11.5%) 14 (4.7%)
.128 .291 .064
16 (5.2%)
15 (5.1%)
.929
39 (12.8%)
31 (10.5%)
.385
12 (3.9%)
9 (3.1%)
.556
0 (0%) 30 (9.8%)
0 (0%) 36 (12.2%)
.354
0 (0%)
0 (0%)
Data for the 2 study groups are number of patients (%). * By c2 test.
Table VII
Length of time from randomization to birth
All births (min) SVD (min) Assisted vaginal (min) Assisted vaginal for nonreassuring fetal status (min) Assisted vaginal for failure to progress (min) Cesarean (min) Cesarean for nonreassuring fetal status (min) Cesarean for failure to progress (min)
Intervention (FPO+CTG) (n = 305)
Control (CTG-only) (n = 295)
P value*
186 146 190 116 300 212 118 330
147 133 161 144 191 154 100 327
.010 .624 .041 .366 .049 .084 .016 .838
(109, 306) (76, 248) (114, 314) (71, 175) (181, 376) (121, 330) (72, 166) (226, 436)
(94, 248) (73, 199) (95, 256) (62, 239) (131, 308) (103, 280) (68, 141) (184, 457)
Data for the 2 study groups are median (IQR). SVD, Spontaneous vaginal delivery. * Log rank testing was used to calculate significance for all time-to-event variables. The medians, representing the time when 50% of women had given birth, are provided for interest.
fetal status than those in the CTG-only group. More detailed analyses of the data set are available on the Web site.17 Successful FPO sensor placement with FSpO2 values recorded occurred for 94% of FPO cases. Fetal SpO2 values were returned for a median of 83% (IQR 69%, 91%) of recording time, with FSpO2 values less than 30% recorded a median of 14% (IQR 5%, 28%) of recording time. Sensor placement was attempted at mean (SD, range) cervical dilatation of 6.9 cm (2.29 cm, 2.5 to 10 cm) and fetal station at mean (SD, range) of –0.9 (1.26, –3 to C2) cm relative to the maternal ischial spines.
There were 4 cases (1.3%) of endometritis in the intervention group and 1 (0.3%) in the control group (P = .192). Postpartum maternal temperature higher than 37.5(C was recorded for 84 women in the intervention group (30.8%) and 88 women in the control group (29.8%) (P = .792).
Comment The 2 study groups were well matched at study entry, both in terms of baseline demographics and nonreassuring CTGs qualifying their participation. The
East et al high proportion of nulliparas was representative of the population of nonparticipants with a nonreassuring CTG in the 4 hospitals during the study period (unpublished data) but higher than the overall Australian figure of 41%.19 The high epidural rate was in contrast to the 29% epidural rate for all women giving birth.20 We postulate that researchers and clinicians were more likely to seek consent for participation in the trial when women had adequate analgesia. The use of epidural analgesia is not a prerequisite to FPO, however. The primary aim of adding FPO was to reduce operative delivery for nonreassuring fetal status. A statistically significant reduction of 23% was found, with narrow relative risk confidence intervals, suggesting adequate power to demonstrate this difference. The difference is in the same direction as the other published RCTs.13,14 Operative delivery is a clearly definable end point, which is important in its own right. Routine costs of cesarean section are substantially greater than for an uncomplicated vaginal birth.21 Maternal morbidity and mortality are greater from cesarean than vaginal birth, with an excess of pulmonary embolism, wound infection, and aspiration pneumonitis.22 Forceps delivery is usually accompanied by greater use of general and regional anesthesia than vacuum or spontaneous delivery, and women are more likely to sustain significant genital tract injury.23 Operative vaginal birth is also associated with a higher incidence of cephalhematoma and facial injury to the baby.23 Operative birth for nonreassuring fetal status was selected as the primary outcome, rather than overall operative delivery for the following reasons: (1) FPO is intended to discern fetal well-being; and (2) the indication for intervention is important, rather than simply the intervention itself. For example, the likelihood of a successful vaginal birth after cesarean in a subsequent pregnancy is improved for those whose previous cesarean was performed for nonreassuring fetal status, compared with those in which the indication was dystocia.24 There are also resource implications from the indication for operative birth: for example, an emergency cesarean section for nonreassuring fetal status is performed a median 42 minutes from the decision for intervention in Australian maternity hospitals,25 comparable with those in which this RCT was conducted. This may have a greater impact on staffing levels and operating room availability than a less urgent cesarean section, which may be expected to occur a median 67 minutes from the decision for intervention.25 Despite the statistically significant reduction in operative delivery for nonreassuring fetal status in the intervention group, compared with the control group, there were no differences in overall spontaneous or assisted vaginal birth or cesarean section rates between the 2 groups. The rate of cesarean section performed for
606.e9 dystocia in the control group was similar to both the control group rate in another reported RCT13 and the rate for the mildly nonreassuring group of a cohort study monitored with FPO.15 The rate of cesarean section performed for dystocia in the intervention group was lower than that reported in either the intervention group of the RCT reported by Garite et al13 or for the moderate or severely nonreassuring group of the cohort study reported by Porreco et al15 and was not statistically significantly different between groups. Progress to a vaginal birth may be viewed as precluding a diagnosis of dystocia.15 However, clinicians frequently documented the indication for assisted vaginal birth as failure to progress in our trial (Table III). Our finding of a relative risk of 2.07 (intervention/control) for assisted vaginal birth for failure to progress/dystocia during the second stage of labor has not been described in previous reports of FPO and dystocia13,15 and may suggest that FPO allowed the decision to intervene to be delayed from first to second stage. Data in Table VII support this explanation, insofar as there was an increased interval between randomization and delivery in the intervention group, compared with the control group. This delay may result in lower maternal morbidity because a cesarean section may be avoided in favour of operative vaginal birth.22 It may thereby also impact positively on resource use.21 Whereas FPO provides reassurance of fetal wellbeing, it does not address other indications influencing delivery mode, such as dystocia/failure to progress, fetal malposition, and/or maternal exhaustion. Our trial design does not permit reliable analysis of the impact of these factors on the overall delivery mode. Further trials are required to address ways of reducing operative birth for such indications. Study participants, with nonreassuring fetal status during labor, constitute a subgroup of child-bearing women overall. Within this subgroup the overall assisted vaginal birth and caesarean section rates (Table III) were considerably higher than the rates of 11% and 27% for assisted vaginal birth and cesarean section for Australian women overall.19 Our reported rates for each mode of birth were, however, consistent with those for nonparticipants with nonreassuring CTGs at the 4 study sites during the study period (unpublished data). There were no differences in neonatal outcomes between the 2 groups, despite finding that, compared with the control group, the intervention group had fewer operative deliveries for nonreassuring fetal status; more operative vaginal births for dystocia/failure to progress; and longer time from randomization to birth. We therefore conclude the decision not to intervene did not result in worse outcomes for those babies. There were few SAEs in either group and the study was not adequately powered to detect significant differences in these events. An ideal study would be able to
606.e10 examine long-term neurological outcomes. However, because there is a low prevalence of poor outcomes of this type, such a study would need to be much larger and better resourced than the current one to identify any differences. The majority of postrandomization interventions to assess fetal well-being or correct nonreassuring CTGs were similar for the 2 groups. More fetal blood samples (FBS) were performed in the CTG group, although there had been no between-group differences in nonreassuring CTGs, suggesting that FPO provided the reassurance otherwise sought by performing FBS. Those in the FPOCCTG group were 68% less likely to have a scalp lactate sample 4.8 mmol/L or greater than those in the CTG-only group, suggesting that FSpO2 values less than 30% may have prompted action earlier, ranging from a simple change in maternal position through to delivery. In hospitals in which FBS is not commonly performed to augment CTG monitoring, the rate of operative intervention for nonreassuring fetal status may be higher than that observed in our control group: the reduction in operative delivery for nonreassuring fetal status we observed when FPO was added to CTG monitoring may be even greater in such circumstances. Fetal SpO2 values were recorded for a median of 83% of monitoring time, consistent with our previous observational study5 and greater than that reported in a previous RCT.13 We recorded FSpO2 values less than 30% for a median 14% of monitored time. This is higher than our previous report of 3.9% in fetuses with and without nonreassuring CTGs,5 as would be expected with a nonreassuring CTG being required for study entry. The addition of FPO to the CTG to monitor fetal wellbeing during labor resulted in a significant decrease in operative intervention for nonreassuring fetal status, compared with use of conventional monitoring alone. This decrease was achieved with no significant difference in neonatal outcomes. The place of FPO in contemporary maternity care may now be evaluated by incorporating the findings of the FOREMOST trial into the systematic review of FPO12 and considering our economic analysis and maternal perceptions of their experience in the FOREMOST trial, yet to be published. Further studies may address ways of reducing operative birth for indications other than nonreassuring fetal status.
Acknowledgments We thank the child-bearing women and their babies who participated in this trial and the midwifery and medical staff at the respective birth/delivery suites who actively assisted in recruitment to and conduct of the trial. We also thank the data monitoring committee (J.F. King, chair, C. Crowther, D. Henderson-Smart, R. Hockey) for conducting the interim analysis and reviewing serious adverse events.
East et al Following are members of the FOREMOST Study Group: K. Andrews, Research Midwife, Mater Mothers’ Hospital Brisbane; K. Barr, Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane; R. Aziz, Research Midwife, Mater Mothers’ Hospital Brisbane; E. Beller, Statistician, final analysis; K. Cleary, Research Midwife, Mater Mothers’ Hospital Brisbane; C. Crowther, Data Monitoring Committee member; J. Davies, Research Midwife, Mater Mothers’ Hospital Brisbane; K. Dunster, Establishment and maintenance of the randomization system; D. Everding, Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane; G. Healy, Data management; D. Henderson-Smart, Data Monitoring Committee member; R. Hockey, Statistician, interim analysis; Data Monitoring Committee member; L. Leader, Collaborator, Royal Hospital for Women, Sydney; N. Henshall, Research Midwife, Royal Hospital for Women, Sydney; L. Moroney, Research Midwife, Royal Brisbane and Women’s Hospital; M. Stewart, Research Midwife, Royal Women’s Hospital, Melbourne.
References 1. Thacker SB, Stroup D, Chang M. Continuous electronic fetal heart monitoring for fetal assessment during labor. Cochrane Database System Rev 2001;(2):CD000063. 2. Colditz PB, Begg LM, East CE. Fetal pulse oximetry: instrumentation and recent clinical experience. Clin Perinatol 1999;26: 869-80. 3. Kuhnert M, Seelbach-Gobel B, Di Renzo GC, Howarth E, Butterwegge M, Muray JM. Guidelines for the use of fetal pulse oximetry during labor and delivery. Prenat Neonatal Med 1998;3:432-3. 4. Begg LM, East CE, Chan FY, Brennecke SP. Intrapartum fetal oxygen saturation monitoring in congenital fetal heart block. Aust N Z J Obstet Gynaecol 1998;38:271-4. 5. East CE, Dunster KR, Colditz PB. Fetal intrapartum oxygen saturation monitoring: an analysis of 118 cases. Aust N Z J Obstet Gynaecol 1997;37:397-401. 6. East CE, Colditz PB, Begg LM, Brennecke SP. Update on intrapartum fetal pulse oximetry. Aust N Z J Obstet Gynaecol 2002; 42:119-24. 7. East CE, Colditz PB, Dunster KR, Khoo SK. Human fetal intrapartum oxygen saturation monitoring: agreement between readings from two sensors on the same fetus. Am J Obstet Gynecol 1996;174:1594-8. 8. Nijland R, Jongsma HW, Crevels J, Menssen J, Nijhuis JG, van den Berg PP, et al. The ductus arteriosus, pre- and post-ductal oxygen saturation measurements in fetal lambs. Eur J Obstet Gynecol Reprod Biol 1994;55:135-40. 9. Nijland R, Jongsma HW, Nijhuis JG, van den Berg PP, Oeseburg B. Arterial oxygen saturation in relation to metabolic acidosis in fetal lambs. Am J Obstet Gynecol 1995;172:810-9. 10. Dildy GA, Thorp JA, Yeast JD, Clark SL. The relationship between oxygen saturation and pH in umbilical blood: implications for intrapartum fetal oxygen saturation monitoring. Am J Obstet Gynecol 1996;175:682-7. 11. Kuhnert M, Seelbach-Gobel B, Butterwegge M. Predictive agreement between the fetal arterial oxygen saturation and fetal scalp pH: results of the German multicenter study. Am J Obstet Gynecol 1998;178:330-5.
East et al 12. East CE, Chan FY, Colditz PB. Fetal pulse oximetry for fetal assessment in labour. Cochrane Database System Rev 2004;(4): CD004075. 13. Garite TJ, Dildy GA, McNamara H, Nageotte MP, Boehm FH, Dellinger EH, et al. A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns. Am J Obstet Gynecol 2000;183:1049-58. 14. Kuhnert M, Schmidt S. Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry. Am J Obstet Gynecol 2004;191:1989-95. 15. Porreco RP, Boehm FH, Dildy GA, Miller HS, Wickstrom EA, Garite TJ, et al. Dystocia in nulliparous patients monitored with fetal pulse oximetry. Am J Obstet Gynecol 2004;190:113-7. 16. Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: synthesis of best evidence for clinical decisions. Ann Intern Med 1997;126: 376-80. 17. East CE, Brennecke SP, King JF, Chan FY, Colditz PB, on behalf of the FOREMOST Study Group. The FOREMOST Study. Available from: http://152.98.230.3/som/women_foremosttrial. shtml. 2005. 18. Umstad MP. The predictive value of abnormal fetal heart rate patterns in early labour. Aust N Z J Obstet Gynaecol 1993;33:145-9. 19. Laws PJ, Sullivan EA. Australia’s mothers and babies 2002. AIHW cat no PER 28. Sydney: AIHW National Perinatal Statistics Unit (Perinatal Statistics series no 15); 2004. 20. Centre for Epidemiology and Research New South Wales Department of Health. New South Wales Mothers and Babies 2001. Sydney: NSW Public Health Bulletin; 2002;20:3(S4). 21. Henderson J, McCandlish R, Kumiega L, Petrou S. Systematic review of economic aspects of alternative modes of delivery. BJOG 2004;108:149-57. 22. Lomas J, Enkin M, Pearson J, Rees G. Caesarean section. In: Enkin M, Keirse MJNC, Renfrew M, Neilson J, editors. A guide to effective care in pregnancy and childbirth. 2nd ed. Oxford (UK): Oxford University Press; 1995. p. 318-22. 23. Vacca A, Keirse MJNC. Instrumental vaginal delivery. In: Chalmers I, Enkin M, Keirse MJNC, editors. Effective care in pregnancy and childbirth. Oxford (UK): Oxford University Press; 1989. 24. Grinstead J, Grobman WA. Induction of labor after one prior cesarean: predictors of vaginal delivery. Obstet Gynecol 2004; 103:534-8. 25. Spencer MK, MacLennan A. How long does it take to deliver a baby by emergency caesarean section? Aust N Z J Obstet Gynaecol 2001;41:7-11.
606.e11 Perinatal Research Centre, The University of Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australiaa; Department of Obstetrics and Gynaecology, The University of Melbourne, Royal Women’s Hospital Melbourne, Victoria, Australiab; Royal Women’s Hospital Melbourne, Victoria, Australiac; Maternal Fetal Medicine, The University of Queensland, Mater Mothers’ Hospital Brisbane, Queensland, Australiad The FOREMOST Study Groupe:
K. Andrews R. Aziz K. Barr E. Beller K. Cleary C. Crowther J. Davies K. Dunster D. Everding G. Healy D. HendersonSmart R. Hockey L. Leader N. Henshall L. Moroney M. Stewart
Research Midwife, Mater Mothers’ Hospital, Brisbane Research Midwife, Mater Mothers’ Hospital, Brisbane Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane Statistician Research Midwife, Mater Mothers’ Hospital, Brisbane Data Monitoring Committee member Research Midwife, Mater Mother’s Hospital, Brisbane Establishment and maintenance of the randomization system Research Midwife, Royal Brisbane and Women’s Hospital, Brisbane Data Management Data Monitoring Committee member Statistician, interim analysis; Data Monitoring Committee member Collaborator, Royal Hospital for Women, Sydney Research Midwife, Royal Hospital for Women, Sydney Research Midwife, Royal Brisbane and Women’s Hospital Research Midwife, Royal Women’s Hospital, Melbourne
Appendix* The FOREMOST Trial (Fetal Intrapartum Pulse Oximetry: a Multicenter Randomized Controlled Trial) Statement of purpose. Information provided on this Web site is intended to complement results published in the peer-reviewed literature. Details of publications and additional data will be added to this site as they become available. Investigators: C. E. Easta, S. P. Brenneckeb, J. F. Kingc, F. Y. Chand, P. B. Colditza, for the FOREMOST Study Groupe
* The full results of the FOREMOST trial can be found at: http:// www.som.uq.edu.au/som/women_foremosttrial.shtml.
Project synopsis Aims To compare obstetric outcomes (specifically the rates of operative deliveries performed for the indication of nonreassuring fetal status) between 2 groups of patients: those having conventional cardiotocography (CTG) monitoring and those having CTG monitoring plus fetal oxygen saturation monitoring. To compare neonatal outcome of the 2 study groups including cord blood gases, Apgar scores, requirements for resuscitation, and admission to a neonatal intensive care unit.
606.e12 To evaluate the impact of the new technology by conducting a cost analysis and assessing maternal satisfaction with fetal monitoring, labor, and delivery. The following hypotheses were tested: 1. Primary hypothesis In the presence of nonreassuring CTG tracings, the use of fetal intrapartum oxygen saturation monitoring and CTG monitoring, compared with CTG monitoring alone, would result in a 33% reduction in operative delivery rates for nonreassuring fetal status. 2. Secondary hypotheses There would be no difference in operative delivery rate for dystocia. There would be no difference in fetal/neonatal outcomes (umbilical arterial pH, Apgar scores, admission to the neonatal intensive care unit) between the 2 groups. There would be no difference in women’s satisfaction with fetal monitoring or their labor, delivery, and outcome between the 2 groups.
Background synopsis The FOREMOST trial was an Australian multicenter, randomized, controlled trial to evaluate the effect of fetal intrapartum pulse oximetry, in the presence of nonreassuring CTG tracings, on operative delivery rates at the Royal Brisbane and Women’s Hospital, Brisbane; the Mater Mother’s Hospital, Brisbane; the Royal Women’s Hospital, Melbourne; and the Royal Hospital for Women, Sydney. Women whose fetuses displayed a nonreassuring CTG pattern in labor at term, who gave informed consent and did not meet any of the exclusion criteria, were randomized to either the control group (conventional CTG monitoring) or the experimental group (CTG plus fetal oximetry). Clinical management in the control and intervention arms of the study followed a protocol.
Results The information on this Web site is designed to complement the published data. Findings currently include details, expanded from the published data, for the following:
Baseline demographics. Neonatal outcomes. Logistic regression analyses. Serious adverse events. Trial management issues of interest.
East et al Baseline demographics Experimental (FPOCCTG) (n = 305) Indigenous 9 (3.0%) Parity 0 247 (81.0%) 1 36 (11.8%) 2 17 (5.6%) 3 1 (0.3%) O3 4 (1.3%) Maternal risk factors None 195 (63.9%) One or more of risk factors Chronic hypertension 4 (1.3%) PIH/PE 35 (11.5%) Eclampsia 0 (0%) Prepregnancy diabetes 0 (0%) Glucose intolerance in 14 (4.6%) pregnancy No prenatal care 2 (0.7%) Maternal cardiac disease 5 (1.6%) Maternal renal disease 5 (1.6%) Fetal risk factors None 221 (72.5%) One or more of risk factors Small for dates/IUGR 11 (3.6%) Polyhydramnios 3 (1.0%) Oligohydramnios 1 (0.3%) Postdates O42 wk 1 (0.3%) Preterm labor !37 wk 6 (2.0%) Maternal substance use 52 (17.0%) Alcohol 19 (6.2%) Drugs 10 (3.3%) Smoking 39 (12.8%)
Control (CTG-only) (n = 295) 11 (3.8%) 226 42 13 7 7
(76.6%) (14.2%) (4.4%) (2.4%) (2.4%)
178 (60.3%) 3 38 0 3 14
(1.0%) (12.9%) (0%) (1.0%) (4.7%)
0 (0%) 9 (3.1%) 2 (0.7%) 209 (70.8%) 10 1 3 2 11 55 19 15 41
(3.4%) (0.3%) (1.0%) (0.7%) (3.7%) (18.6%) (6.4%) (5.1%) (13.9%)
Study group data are number of patients (%). PIH, Pregnancy; IUGR, intrauterine growth restriction.
Logistic regression Covariates entered into the logistic regression models included: Hospital B Royal Women’s Hospital, Brisbane (RWH Bris) B Mater Mothers’ Hospital, Brisbane (MMH Bris) B Royal Women’s Hospital, Melbourne (RWH Melb) B Royal Hospital for Women, Sydney (RHW Syd)
Group (FPO or CTG) Previous cesarean Maternal age Parity (0, R1) Pregnancy induced hypertension/pre-eclampsia Intrauterine growth restriction Labor induced Meconium stained amniotic fluid
East et al
606.e13
Neonatal outcomes
Cord arterial pH (FPO, n = 272; CTG, n = 240) Mean (SD) !7.15 !7.10 !7.05 !7.00 Cord arterial BE (FPO, n = 257; CTG, n = 224) Median (IQR) !10 !12 !16 Skin impression from FPO sensor (n = 294 attempted)k Resuscitation None One or more of risk factors Suction Facial oxygen Aspiration of meconium above cords ETT intubation for asp of meconium below cords Bag and mask (IPPV) Bag and mask (IPPV) C naloxone Naloxone IPPV via ETT IPPV via ETT C naloxone Cardiac massage Routine well-baby care
Experimental (FPOCCTG) (n = 305 unless otherwise stated)
Control (CTG-only) (n = 295 unless otherwise stated)
P value*
Relative risk (FPOCCTG: CTG-only) 95% CI
7.236 39 13 5 2
7.236 35 12 4 2
.987y .937 .908 1.000z 1.000z
0.98 0.96 1.10 0.89
(0.770) (14.3%) (4.8%) (1.8%) (0.7%)
4.0 (6.3, 2.2) 24 (9.4%) 10 (3.9%) 2 (0.7%) 30 (10.2%)
71 (23.3%)
(0.0756) (14.6%) (5.0%) (1.7%) (0.8%)
3.6 (6.1, 1.9) 18 (8.1%) 6 (2.7%) 0 (0%)
83 (28.1%)
(0.64, (0.42, (0.30, (0.13,
1.50) 2.05) 4.06) 6.26)
.336x .615 .466 .501z
1.16 (0.72, 2.33) 1.45 (0.53, 3.91) Unable to calculate
.173
0.83 (0.63, 1.09)
213 110 22 4
(69.8%) (36.1%) (7.2%) (1.3%)
186 85 14 10
(63.1%) (28.8%) (4.7%) (3.4%)
.078 .058 .203 .092
1.11 1.25 1.52 0.39
(0.99, (0.99, (0.79, (0.12,
1.24) 1.58) 2.91) 1.22)
61 0 0 1 0 0 214
(20%) (0%) (0%) (0.3%) (0%) (0%) (70.2%)
42 0 1 6 0 0 216
(14.2%) (0%) (0.3%) (2.0%) (0%) (0%) (73.2%)
.061
1.40 (0.98, 2.01)
.492z .065z
Not able to calculate 0.16 (0.02, 1.33)
.406
0.96 (0.87, 1.06)
Study group data are number of patients (%), mean (SD), or median (IQR). BE, Base excess; ETT, endotracheal tube; IPPV, intermittent positive pressure ventilation. * c2 unless otherwise stated. y Student t test. z Fisher’s exact test. x Mann-Whitney U test. k Sensor placement not attempted as bleeding commenced (n = 2), commenced pushing or gave birth (n = 3), or decision made for cesarean or forceps (n = 6).
Maternal temperature in labor O37.5(C Rupture of amniotic membranes (ROM) O18 hours Group B Streptococcus (GBS) Antibiotics for maternal temperature, ROMO18 hours, GBS Cervical dilatation !5 cm at epidural placement Rise in blood pressure during labor Hematuria Only the significant findings are presented here. We also tested for group and hospital effect modification but found none (ie, the hospital still made a difference regardless of group allocation but not because FPO was managed differently in each hospital).
Summary: After adjusting for hospital, group allocation remained a significant predictor of operative delivery for nonreassuring fetal status. Multiple regression: operative delivery for nonreassuring fetal status
Group (CTG:FPO) Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
P value
Odds ratio
95% confidence intervals
.043 .000 .000 .000 .010
0.686
(0.476, 0.988)
2.742 3.434 2.061
(1.730, 4.347) (2.040, 5.782) (1.184, 3.585)
606.e14
East et al
Multiple regression: cesarean section for dystocia/failure to progress
Hematuria Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
P value
Odds ratio
95% confidence intervals
0.000 0.030 0.032 0.030 0.075
3.396
1.953, 5.904
0.493 0.426 0.481
0.257, 0.942 0.196, 0.922 0.215, 1.077
Summary: After adjusting for hospital, women with hematuria during labor were more than 3 times more likely to have a cesarean section for dystocia/failure to progress that those without. Univariate regression: umbilical arterial pH !7.15
Hospital Hospital Hospital Hospital
(RWH Bris) (MMH Bris) (RWH Melb) (RHW Syd)
P value
Odds ratio
95% confidence intervals
0.004 0.335 0.728 0.004
0.711 1.137 2.525
0.355, 1.422 0.551, 2.346 1.354, 4.709
Summary: Hospital was the only significant covariate to predict umbilical arterial pH !7.15. Univariate regression: bag and mask intermittent positive pressure ventilation
GBS
P value
Odds ratio
95% confidence intervals
0.050
1.967
0.999, 3.874
Summary: The clinical significance of this finding is uncertain. Multiple regression: maternal post partum temperature O37.5(C 95% confidence P value Odds ratio intervals Temp in labor O37.5(C Hospital (RWH Bris) Hospital (MMH Bris) Hospital (RWH Melb) Hospital (RHW Syd)
.000 .009 .001 .481 .037
4.027
2.710, 5.986
2.177 1.236 1.839
1.348, 3.514 0.685, 2.229 1.039, 3.256
Summary: After adjusting for hospital differences, elevated maternal temperature during labor predicted elevated maternal temperature postpartum. Logistic regression was also undertaken to determine whether the mode of birth or indication for operative birth influenced neonatal outcomes.
Multiple regression: Selected neonatal outcomes Odds P value ratio
95% confidence intervals
Cord arterial pH !7.10 Spontaneous vaginal birth .629 Assisted vaginal birth For nonreassuring fetal status .297 0.491 (0.129, 1.871) For all other indications .533 0.588 (0.111, 3.120) Cesarean section For nonreassuring fetal status .725 0.769 (0.178, 3.318) For dystocia/failure to progress .707 1.263 (0.373, 4.277) For all other indications .599 1.408 (0.393, 5.047) Cord arterial pH !7.15 Spontaneous vaginal birth .274 Assisted vaginal birth For nonreassuring fetal status .060 2.080 (0.971, 4.457) For all other indications .088 2.167 (0.892, 5.262) Cesarean section For nonreassuring fetal status .388 1.493 (0.601, 3.710) For dystocia/failure to progress .927 1.044 (0.415, 2.626) For all other indications .997 0.000 (0.000) Cord arterial base excess !10 Spontaneous vaginal birth .667 Assisted vaginal birth For nonreassuring fetal status .114 2.492 (0.804, 7.723) For all other indications .336 1.942 (0.503, 7.501) Cesarean section For nonreassuring fetal status .177 2.389 (0.674, 8.459) For dystocia/failure to progress .326 1.880 (0.533, 6.630) For all other indications .640 1.403 (0.340, 5.795) Cord arterial base excess !12 Spontaneous vaginal birth .723 Assisted vaginal birth For nonreassuring fetal status .234 2.591 (0.540, 12.445) For all other indications .997 0.000 (0.000) Cesarean section For nonreassuring fetal status .793 1.304 (0.180, 9.460) For dystocia/failure to progress .622 1.577 (0.258, 9.638) For all other indications .761 0.687 (0.061, 7.713) Bag and mask intermittent positive pressure ventilation Spontaneous vaginal birth .247 Assisted vaginal birth For nonreassuring fetal status .213 0.651 (0.331, 1.279) For all other indications .229 1.567 (0.754, 3.254) Cesarean section For nonreassuring fetal status .941 1.029 (0.486, 2.176) For dystocia/failure to progress .895 1.049 (0.519, 2.121) For all other indications .519 0.766 (0.341, 1.721)
Summary: Mode of birth or indication for operative birth did not result in differences in neonatal outcomes. Serious adverse events Mothers and babies were monitored for serious adverse events from the time of study entry until transfer to another hospital, discharge from hospital, or in-hospital death.
East et al Serious adverse events could include:
Death Events that prolonged hospitalisation Congenital abnormalities Placental abruption requiring surgical intervention Any event of sufficient concern to researchers or clinicians
Serious adverse events were reviewed by the Data Monitoring Committee and the relevant Human Research Ethics Committee.
Abbreviations BE: CPAP: C/S: EEG: ETT: IPPV: O2: PROM: UA: UV:
base excess continuous positive airway pressure cesarean section electroencephalogram endotracheal tube intermittent positive pressure ventilation oxygen prelabor rupture of membranes umbilical arterial umbilical venous
606.e15 5. Baby: pneumothorax
C/S failure to progress and nonreassuring fetal status ETT suction of meconium below cords, then IPPV by ETT Apgars 31, 85 UA pH 7.312 UA BE 2.0 mmol/L Pneumothorax diagnosed at age 45 min IPPV 14 h, intercostal catheter 4 d intensive care nursery Home at day 7 6. Mother and baby No maternal temperature O37.5(C septic during labor C/S nonreassuring fetal status Mother: profuse Staphylococcus aureus on high vaginal swab day 2 after C/S– antibiotics. Discharged home day 8 Baby: Staphylococcus aureus on blood cultures, antibiotics 7 d Discharged home day 8 7. Hyaline membrane C/S failure to progress and disease nonreassuring fetal status Apgars 71, 95 UV pH 7.25 UA BE 6 mmol/L Total hospitalisation 13 d
Experimental group (fetal pulse oximetry with CTG)
Control group (CTG) Serious adverse event Relevant clinical details 1. Death
Hemolytic disease of the newborn presenting with jaundice at 7 h of age (at which time the hemoglobin was 89 g/L) due to homozygous mutation of pyruvate kinase gene 2. Meconium Meconium seen at artificial rupture of aspiration membranes, 75 min prior to study syndrome entry C/S nonreassuring fetal status Apgars 91, 105 UA pH 7.23 UA BE 0.5mmol/L CPAP 24 h, antibiotics Transferred to a children’s hospital for ongoing care Apgars 71, 85 3. Mild respiratory distress UA pH 7.202 syndrome and UA BE 4.3 mmol/L pneumomediastinum Facial O2 at birth Head box O2 4. Baby: prolonged Growth restricted length of stay Gastric tube feeds 4 d Discharged home at 12 d
Serious adverse event
Relevant clinical details
1. Neonatal encephalopathy (Sarnat stage 1) (not hypoxic-ischemic encephalopathy)
Mother used cannibas Growth restriction
2. Neonatal encephalopathy (Sarnat stage 1) (not hypoxic-ischemic encephalopathy)
3. Acute tubular necrosis
4. Meconium aspiration syndrome
Spontaneous vaginal birth Apgars 11, 65 UA pH 7.21 UA BE 10 mmol/L Irritability for 24 h No seizures noted Spontaneous vaginal birth Growth restriction Central brain disorder Hypertonicity Poor ability to suck/swallow Apgars 61, 85 UA pH 7.234 UA BE 5.2 mmol/L Possible subtle seizures not confirmed by EEG C/S nonreassuring fetal status Apgars 41, 85 UA pH 7.104 UA BE 11.1 mmol/L Baby discharged home day 8 PROM, labor induced after developed meconium staining of liquor.
606.e16
5. Erb’s palsy and Facial palsy 6. FPO sensor placement not attempted Mother: 800 mL hemorrhage
7. Lateral uterine tear during cesarean
8. Baby: atrioventricular canal (AVC)
East et al C/S for slow progress, thick meconium, nonreassuring fetal status ETT for aspiration of meconium Apgars 61, 95 UA pH 7.146 UA BE 10.2 mmol/L Mechanical ventilation not necessary O2 ! 24 hours Forceps delivery for insufficient progress and malposition Facial palsy resolved by discharge Immediately after randomization, bleed occurred and shoulder presentation diagnosed; emergency C/S No further hemorrhage occurred and no maternal blood transfusion required Apgars 51, 95 UV pH 7.215 UV BE 5.4 mmol/L C/S for nonreassuring fetal status Converted from epidural to general anesthesia during cesarean Estimated blood loss 2000 mL No blood transfusion Diagnosed antenatally Allowed into trial because obstetrician confident the abnormality would not affect well-being until after birth Postnatal echo: AVC and large ventricular septal defect, and atrioseptal defects Home day 6 with hospital follow-up arranged
Trial management details of interest: The research midwife was in attendance for a median (IQR) of 16 min (0, 82 min) in the CTG-only group and 97 min (0, 195 min) for the CTGCFPO group.