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Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term
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Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term Martina Murphy, BNS; Michelle Butler, PhD; Barbara Coughlan, PhD; Donal Brennan, PhD; Colm O’Herlihy, PhD; Michael Robson, MD OBJECTIVE: We sought to assess amniotic fluid lactate (AFL) at
diagnosis of spontaneous labor at term (37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN: This was a single-institution, prospective cohort study
of 905 singleton, cephalic, term (37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n ¼ 118), 5.0-9.9 mmol/L (n ¼ 707), and 10.0 mmol/L (n ¼ 80).
Increasing AFL was associated with higher total oxytocin dose (P ¼ .001), labor disorders (P ¼ .005), and CD (P .001). Multivariable regression analysis demonstrated that women with AFL 5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06e2.39) and AFL 10.0 mmol/L (OR, 1.72; 95% CI, 1.01e2.93) were independent predictors of a labor disorder. AFL 5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL 10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73e6.46). AFL 5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL 10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION: AFL at diagnosis of labor in spontaneously laboring
single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol. Key words: active management of labor, amniotic fluid lactate, cesarean delivery, labor disorder (dystocia)
Cite this article as: Murphy M, Butler M, Coughlan B, et al. Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term. Am J Obstet Gynecol 2015;213:673.e1-8.
C
esarean delivery (CD) rates have increased significantly over the last 3 decades whereby it is now the most commonly performed surgical procedure in developed countries.1 There is no
consensus on the appropriate rate or indications.2,3 Repeat CD remains the largest contributor to the overall CD rate. In nulliparous women, labor disorders (dystocia), defined as abnormal
From the Departments of Midwifery (Ms Murphy) and Obstetrics and Gynecology (Drs Brennan, O’Herlihy, and Robson), National Maternity Hospital, and Departments of Health Sciences (Ms Murphy and Dr Coughlan) and Obstetrics and Gynecology (Drs Brennan and O’Herlihy), University College Dublin, Dublin, Ireland, and School of Midwifery, University of British Columbia, Vancouver, British Columbia, Canada (Dr Butler). Received March 25, 2015; revised May 17, 2015; accepted June 15, 2015. This study was funded by the medical fund at the National Maternity Hospital, Dublin, Ireland. The authors report no conflict of interest. Presented as a poster at the 34th annual meeting of the Society for Maternal-Fetal Medicine, New Orleans, LA, Feb. 3-8, 2014. Corresponding author: Martina Murphy, BNS. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2015.06.035
or difficult labor, are the most common indication for the first CD.4 CD is rare in women who have had a previous vaginal delivery. More focus should be placed on preventing primary CD, particularly on those women in spontaneous labor. The main causes of a labor disorder (dystocia) are inefficient uterine action, malposition, and cephalopelvic disproportion.5 Inefficient uterine action, also described as dysfunctional uterine action or incoordinate uterine action, refers to the frequency, duration, and force of the uterine contractions and is the most common cause of a labor disorder in nulliparous women.6 Uterine muscle metabolism and muscle fatigue contribute to labor disorders and subsequent CD.7
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FIGURE 1
Flowchart classification of cesarean deliveries
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
Myometrial fatigue causes a switch from aerobic to anaerobic metabolism,8 resulting in an accumulation of intramuscular lactic acid and a subsequent increase in both intracellular and extracellular lactate levels.9 Increased amniotic fluid lactate (AFL) levels have previously been associated with labor disorders (dystocia), but this study was relatively small and AFL was measured when rupture of membranes occurred during labor and not at the diagnosis of labor.10 The purpose of this study was to measure the AFL at the diagnosis and at each assessment of progress in the first stage of labor with last sample measured prior to delivery in an adequately powered cohort of spontaneously laboring single cephalic nulliparous at term cases and to examine labor events
and outcomes so as to assess the relationship between AFL and both labor disorders and CD. This prospective cohort study was carried out in an institution where a uniform approach to management of spontaneous nulliparous labor has been used over 4 decades.
M ATERIALS
AND
M ETHODS
Population The study was conducted over 9 months in 2011 through 2012. Approval from the National Maternity Hospital Ethics Committee and human subject exemption from University College Dublin was obtained. Inclusion criteria were single cephalic nulliparous term (37 weeks’ gestation) women in spontaneous labor (group 1, Ten-Group Classification System).11 All participants signed an
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informed consent form. Women were recruited to the study immediately following the vaginal examination confirming the diagnosis of labor.
Management of labor Labor was diagnosed when the cervix was fully effaced and at least 1 cm dilated. Amniotomy was performed at the diagnosis of labor if spontaneous rupture of the membranes had not already occurred. In single cephalic nulliparous at term women, vaginal examinations were carried out every 2 hours to assess progress in labor. Criteria for diagnosis of labor arrest were dilation of the cervix at <1 cm/h over 2 hours in the first stage of labor and in the second stage of labor was assessed by descent and rotation of the presenting part in the
ajog.org pelvis. Early diagnosis of labor arrest and inadequate descent were treated with oxytocin according to hospital protocol. Oxytocin was administered with a dose of 5 mU/min increasing to a maximum dose of 30 mU/min. The oxytocin was increased or decreased at 15-minute intervals and by 5 mU/min according to uterine activity. A maximum of 7 contractions per 15-minute interval was permitted and midwifery staff palpated and recorded the number of contractions. Increased duration of first stage of labor is associated with increased maternal and neonatal morbidity.12 Duration of the first stage of labor was recorded for AFL groups. Prolonged labor was defined as duration of labor lasting >720 minutes.
Data collection Demographic and clinical data were collected from the clinical labor record and neonatal records of all women recruited to the study. All indications for CD were recorded according to a standard defined classification for intrapartum CD13 (Figure 1). This classification differentiates between suspected fetal distress without oxytocin as opposed to suspected fetal distress after oxytocin was started, but when the primary problem was a labor disorder. It also attempts to differentiate between different subtypes of labor disorders related to the rate of progress in labor, irrespective of the definitions and guidelines for managing labor used in different institutions. These are listed under variables, which means that it can be used universally. Quantification of AFL levels Amniotic fluid samples were collected at each vaginal examination to assess labor progress, including the last sample before delivery, in a clean clear tube. The samples were collected by catching the amniotic fluid sample flowing onto a sterile glove. We needed 1 mL of amniotic fluid to perform the test. All samples were immediately labeled with patient name, identification number, and the date and time of collection. Samples were stored and tested according to guidelines from
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FIGURE 2
Flowchart recruitment process Total PopulaƟon Robson Group 1 (n 1764)
Excluded prior to diagnosis of labour medical or ethical reason (n 105)
Excluded no liquor sample obtained (n 79)
Excluded no reason recorded (n 466) Total populaƟon recruited (n 1,114)
Intrapartum exclusion incomplete data / sample collecƟon (n 187)
Declined to parƟcipate in study (n 22)
Final Study PopulaƟon (n 905)
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
the manufacture of the point-of-care device (LMU061, ObsteCare; Stockholm, Sweden). This instrument is built on patented technology and is currently the only system on the market for point-ofcare use that is tailored for the measurement of lactate in amniotic fluid during labor (US patent no. US 7,318,809).
Statistical analysis Statistical analysis was performed using software (SPSS 20; IBM Corp, Armonk, NY). Unsupervised decision tree analysis with a 10-fold cross-validation was used to identify AFL thresholds. A series of cross-tabulations and analyses of variance were performed to explore the relationships and differences between clinical characteristic variables and lactate levels. Univariate and multivariable binary logistic regression analysis were used to
identify predictors of labor disorders and CD. Variables found to be significant in univariate analysis were included in the multivariable analysis. An alpha level of P < .05 was set for all statistical tests.
Power calculations Power calculation was based on the incidence of labor disorders from the National Maternity Hospital clinical report.13 The assumptions (based on analysis of outcomes obtained from the clinical report) were a level of significance of .05 that 20% of the patients would present with elevated AFL and the rate of operative delivery would be 3 times higher in the AFL 10.0 mmol/L group. A sample of 575 patients in the study could detect a difference in CD rates between 14.2% in the elevated
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TABLE 1
Clinical characteristics of cohort Characteristic
Value
Age, y Mean (minimum-maximum)
30 (16e44)
2
BMI, kg/m
Mean (minimum-maximum)
R ESULTS 24.2 (16.9e50.6)
Gestation at delivery, wk Mean completed (minimum-maximum)
40 (37e42)
Amniotic fluid lactate at diagnosis of labor, mmol/L Mean (minimum-maximum)
7.25 (1.0e20.9)
Amniotomy Spontaneous
278 (31)
Artificial
627 (69)
Cervical dilatation at diagnosis, cm Median (range)
1 (1e10)
Epidural anesthesia No
161 (18)
Yes
744 (82)
Electronic fetal monitoring No
168 (19)
Yes
737 (81)
Labor disorder (dystocia) None
368 (40)
First stage
441 (49)
Second stage
96 (11)
Oxytocin dose, mU Median (range)
650 (0e18,7500)
Duration of oxytocin infusion, min Median (range)
75 (0e737)
Delivery Spontaneous vaginal
609 (67)
Instrumental vaginal
235 (26)
Cesarean
61 (7)
Duration of first stage of labor, min Mean (SD)
300 (213.6)
Duration of second stage of labor, min Mean (range)
51 (0e231)
Infant birthweight, g Median (range)
3550 (2470e5220)
Values in parenthesis are percentages unless otherwise stated. BMI, body mass index. Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
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group and 4.7% in the control group with a power of 90% at a level of significance of .05. A sample size of 500 patients was required for the initial analysis. In all, 905 patients were recruited to the study.
Recruitment process to this study is presented in Figure 2. The study cohort (n ¼ 905) comprised 25 nationalities with native Irish women representing 66.3% (n ¼ 600) of the population and Eastern European women contributing 20.7% (n ¼ 188); other European women, 4.0% (n ¼ 37); Asian women, 3.0% (n ¼ 27); Chinese women, 2.7% (n ¼ 25); US women, 2.0% (n ¼ 19); and other nationalities, 1% (n ¼ 9). Clinical characteristics are described in Table 1. To examine any relationship between AFL levels and delivery outcomes, unsupervised decision tree analysis was used to divide AFL into 3 groups: 0-4.9 mmol/L (n ¼ 118), 5.0-9.9 mmol/L (n ¼ 707), and 10.0 mmol/L (n ¼ 80). Delivery outcomes for the 3 groups are presented in Table 2. The rates of labor disorders (dystocia), spontaneous vaginal delivery, and CD were significantly different among the 3 groups with levels of AFL 0-4.9 mmol/L associated with a higher spontaneous delivery rate, less labor disorder, and a lower CD rate. The CD rate in the AFL 10.0 mmol/L group was 17.5%, almost 3 times that of the 0-4.9 mmol/L group (Table 2). The mean duration of the first stage of labor was 276 minutes in the AFL 0-4.9 mmol/L group and was 77 minutes longer in the AFL 10.0 mmol/L group. Mean birthweight in the AFL 0-4.9 mmol/L group was 3564 g (SD 422), in AFL 5.0-9.9 mmol/L group was 3597 g (SD 468), and in the AFL 10.0 mmol/L group was 3585 g (SD 431). A series of Pearson correlations were performed to explore if a relationship exists among birthweight, labor disorder, and AFL at diagnosis of labor within each AFL group. There were no significant relationships found in AFL 0-4.9 mmol/L group or the AFL 5.0-9.9 mmol/L group. A significant relationship between birthweight and labor disorder (r ¼ 0.263, n ¼ 80) was
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TABLE 2
Labor disorder and delivery methods in amniotic fluid lactate groups AFL 0-4.9 mmol/L (n [ 118)
Variable
AFL ‡5.0-9.9 mmol/L (n [ 707)
AFL ‡10.0 mmol/L (n [ 80)
P value
Mean maternal age, y (SD)
30.1 (4.8)
29.6 (5.1)
29.9 (5.1)
.546
Mean gestation at delivery, wk (SD)
39.4 (0.9)
39.7 (1.0)
40.0 (1.0)
.046
Mean cervical dilation at diagnosis, cm (SD) 2
Mean BMI, kg/m (SD)
2 (1.6)
1.8 (1.63)
1.63 (1.06)
23.7 (3.6)
24.1 (4.0)
25.5 (4.4)
Yes
27.0%
32.4%
27.5%
No
63.0%
37.6%
73.5%
None
61 (52)
286 (41)
21 (26)
Dystocia diagnosed first stage
46 (39)
344 (49)
51 (64)
Dystocia diagnosed second stage
11 (11)
77 (11)
8 (10)
87 (74)
474 (67)
48 (60)
< .001 .001
SROM
Labor disorder (dystocia) .005a
Delivery method Spontaneous vaginal Forceps
8 (7)
77 (11)
6 (8)
Ventouse
19 (16)
113 (16)
12 (15)
Yes
4 (3)
43 (6)
14 (18)
No
114 (97)
664 (94)
66 (82)
No intervention
87 (73)
476 (67)
49 (61)
Fetal reason
10 (9)
50 (7)
5 (6)
Dystocia
21 (18)
181 (26)
26 (33)
.052a
Cesarean delivery < .001a
Reason for operative intervention .027a
Values in parenthesis are percentages unless otherwise stated. AFL, amniotic fluid lactate; BMI, body mass index; SROM, spontaneous rupture of membranes. a
Pearson correlation coefficient.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
found. There was also a significant relationship between birthweight and CD (r ¼ 0.227, n ¼ 80) found in the AFL 10.0 mmol/L. Having demonstrated an association among increased AFL at diagnosis of labor, labor disorders (dystocia), and subsequent CD, we sought to further investigate the relationship between AFL and labor disorders. Univariate predictors of labor disorders included body mass index, gestational age, and cervical dilatation at presentation (Table 3). AFL measured as a continuous variable was associated with a labor disorder (odds
ratio [OR], 1.09; 95% confidence interval [CI], 1.02e1.16). To ascertain if AFL was an independent predictor of a labor disorder (dystocia), a multivariable binary logistic regression model using body mass index >25 or <25, gestational age, and cervical dilatation at diagnosis was employed. Multivariable analysis demonstrated that AFL, when measured as a continuous variable, was an independent predictor of a labor disorder (OR, 1.08; 95% CI, 1.01e1.16). Using the same multivariable model demonstrated that with AFL >5.0-9.9 mmol/L (OR, 1.6; 95% CI, 1.06e2.39)
and AFL 10.0 mmol/L (OR, 1.72; 95% CI, 1.01e2.93) were independent predictors of a labor disorder (dystocia). Predictive values of AFL 5.0-9.9 mmol/L to predict dystocia showed (positive predictive value [PPV] 61, negative predictive value [NPV] 52, overall accuracy 60), AFL 10.0 mmol/L (PPV 74, NPV 42, overall accuracy 45). AFL >5 mmol/L did not predict CD but multivariable analysis confirmed AFL 10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73e6.46). AFL >5.0-9.9 mmol/L did not predict CD (OR, 2.22; 95% CI,
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TABLE 3
Logistic regression analysis of labor disorder (dystocia) Multivariatea
Univariate Variable
P value OR (95% CI)
OR (95% CI)
Multivariatea P value OR (95% CI)
Multivariatea P value OR (95% CI)
P value
Age (continuous)
905 1.02 (0.99e1.04)
BMI (continuous)
862 1.07 (1.03e1.11) < .001 1.06 (1.02e1.10)
.257 .001 1.06 (1.03e1.10) .001
1.06 (1.03e1.10)
.002
Gestation (continuous)
905 1.17 (1.03 e1.34)
.028 1.17 (1.02e1.34) .03
1.15 (1.01e1.32)
.046
Cervical dilatation at diagnosis (continuous)
905 0.25 (0.16e0.40) < .001 0.26 (0.16e0.42) < .001 0.26 (0.16e0.42) < .001 0.26 (0.16e0.42) < .001
Lactate (continuous)
905 1.09 (1.02e1.16)
.01
0-4.9 mmol/L
118 1
.31
1
5 mmol/L
787 1.67 (1.14e2.47)
.009
1.60 (1.06e2.39) .024
0-9.9 mmol/L
825 1
.14
1
.15
.005
1.72 (1.01e2.93)
.046
.017 1.17 (1.02e1.34)
1.08 (1.01e1.16)
.024
Lactate
10 mmol/L
80 2.04 (1.22e3.42)
.23
BMI, body mass index; CI, confidence interval; OR, odds ratio. a
Controls for all other variables in analysis.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
0.79e6.25), but multivariable analysis confirmed AFL >10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 0.73e6.46) (Table 3). AFL 5.0-9.9 mmol/L had a sensitivity of 89% in predicting dystocia and a sensitivity of 14% in predicting CD. AFL
10.0 mmol/L has a sensitivity of 23% and specificity of 92% (PPV 18, NPV 94, overall accuracy 88) and is highly specific but lacks sensitivity for CD. Within the 3 AFL groups, the indication for CD was classified according to the National Maternity Hospital intrapartum
classification for CD.14 Fetal intolerance and overcontracting (tachysystole) after treatment with oxytocin were both the most common reason for delivery (Table 4). Of the operative interventions, 21% occurred as a result of fetal intolerance, 7.6% in the AFL 5.0-9.9 mmol/L
TABLE 4
Classification of indication for cesarean delivery within amniotic fluid lactate groups Classification of operative intervention
AFL <4.9 mmol/L (n [ 118)
AFL 5.0-9.9 mmol/L (n [ 707)
AFL >10.0 mmol/L (n [ 80)
None
87 (73.7)
482 (68.2)
47 (58.6)
Fetal/no dystocia
10 (8.5)
43 (6.0)
5 (6.3)
Dystocia/ITT/FI
9 (7.6)
93 (13.1)
11 (13.8)
Dystocia/ITT/OC
7 (5.9)
38 (5.4)
9 (11.3)
Dystocia/PR
4 (3.4)
40 (5.7)
5 (6.3)
Dystocia/no oxytocin
1 (0.8)
3 (0.4)
1 (1.3)
CPD/malposition
0 (0)
8 (1.1)
2 (2.5)
393.6 (8.2)
400.8 (5.6)
417.5 (14.3)
3 (2.5)
38 (5.4)
8 (10)
Mean (SEM) Admission to NICU
P value .005a
.005b
Values in parenthesis are percentages unless otherwise stated. AFL, amniotic fluid lactate; CPD, cephalopelvic disproportion; FI, fetal intolerance; ITT, inability to treat; NICU, neonatal intensive care unit; OC, overcontracting; PR, poor response (slow/no dilatation of cervix). a
Pearson correlation coefficient; b Analysis of variance.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
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ajog.org group compared with 13.8% in the AFL 10.0 mmol/L group. Consistent with these findings, AFL 10.0 mmol/L was associated with increased electronic fetal monitoring and a need for at least 1 fetal blood sample. Likewise pyrexia and the need for antibiotics were increased in AFL 10.0 mmol/L group. AFL 10.0 mmol/L was also associated with an increase in admissions to the neonatal intensive care unit. Uterine activity was monitored in all cases when labor disorders were treated with oxytocin. Inability to treat labor disorders as a result of the uterus overcontracting occurred in 5.9% of cases in the AFL 5.0-9.9 mmol/L group compared to 11.3% in the AFL 10.0 mmol/L group. Taken together these data demonstrate that the 2 major indications for CD in patients with an increased AFL were fetal intolerance and overcontracting of the uterus. No serious maternal complications were recorded in 800 cases (88.4%). The overall incidence of shoulder dystocia was 0.8% and third-degree tear was 1.3% with no significant differences between the AFL groups. Maternal blood loss of >500 mL was recorded in 11.3% of the AFL 10.0 mmol/L group compared to 6.6% in the AFL 0-4.9 mmol/L group and 5.8% in the AFL 5.0-9.9 mmol/L group. This was associated with the increased CD rate in the AFL 10.0 mmol/L group. In all, 49 infants (5.4%) were admitted to the neonatal unit. Short-term admission for septic screen accounted for 18 (37%) of these infants. Infants in the AFL 10.0 mmol/L were more likely to be admitted with transient tachypnea of the newborn, but the incidence of low cord pH (<7.1) at delivery was 0.8% in both the AFL 0-4.9 mmol/L and the AFL 5.0-9.9 mmol/L groups and was 1.3% in the AFL 10.0 mmol/L group. Two infants developed hypoxic ischemic encephalopathy (defined as seizures, with or without abnormal consciousness, difficulty maintaining respiration, abnormal tone accompanied by evidence of metabolic acidosis pH >7.1 base excess 12 mmol/L).15 Both were in the AFL 5.0-9.9 mmol/L group and received therapeutic hypothermia followed by neurological assessment using magnetic resonance imaging (MRI). One infant had a normal MRI
Obstetrics scan and is achieving normal milestones. The second infant displayed changes on MRI and has a guarded prognosis.
C OMMENT Labor disorders and CD This prospective cohort study is the first to use a point-of-care device to measure AFL at diagnosis of spontaneous labor in single cephalic nulliparous at term women. Herein we demonstrate that increased AFL at diagnosis is an independent predictor of labor disorders and CD. The finding that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol is significant. We have previously demonstrated that the greatest contributor to interinstitutional variability in CD rates is in the management of single cephalic nulliparous at term cohort.13,16 Furthermore, we demonstrate that the main indications for CD in women with elevated AFL were fetal intolerance and tachysystole (overcontracting). This suggests that in women with an elevated AFL (10.0 mmol/L) at diagnosis, oxytocin must be used carefully. Strengths of this study Strengths of this study include the fact that it was a prospectively designed, adequately powered cohort study. Indications for CD were prospectively defined and women were managed using a standard model of care. Active management of labor17 is the standard philosophy of care at our institution. This philosophy aims to prevent prolonged labor and includes clear criteria for the diagnosis of labor (cervix fully effaced at least 1 cm dilated, diagnosis made by a senior midwife). This philosophy of care is applied to all women and not just those diagnosed with labor disorder (dystocia). Our labor management is based on direct clinical observations aimed at achieving safe vaginal delivery.18 Efficient uterine action is considered to be the key to normality. The early diagnosis of labor and rupture of the membranes allows a clear picture of progress to emerge within the first few hours of labor. This in turn facilitates the early diagnosis and treatment of labor disorders. Inefficient
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uterine contractions are reflected clinically by failure of the cervix to dilate. Contemporary studies cite a progress rate of cervical dilation of 0.5-0.7 cm/h as the norm in nulliparous women.19 Based on our data, early correction of inefficient uterine action with the use of oxytocin, before the level of AFL rises to 10.0 mmol/L, may help to reduce the CD rate in single cephalic nulliparous at term women. Our philosophy of care provided a standard treatment to perform the study and reduced the risk that the management of labor influenced the lactate value. A repeat study using the same methodology in a center with a different approach to care in labor would provide useful information.
Study weakness The application of a standard model of care such as active management of labor may also be viewed as a weakness of the study; however the prospective nature of this study we believe reduces selection bias. Variation in practices in other delivery units may make it difficult to repeat this study in other settings. A second potential weakness of the study is the routine practice of rupture of membranes at the diagnosis of labor, which remains controversial. Spontaneous rupture of membranes prior to diagnosis of labor occurred in 30% of cases in this study. Advantages of early amniotomy include examination of the amniotic fluid and ability for direct measurement of the fetal heart; disadvantages are cited as possible fetal distress due to cord compression and potential infection risks.20 Many centers view this practice as an unnecessary intervention and delay amniotomy until a labor disorder is diagnosed.21 Recent evidence suggests that amniotomy during labor enhances electrical uterine activity reinforcing the claim that amniotomy augments labor.22 Artificial rupture of the membranes would however be necessary if we wish to measure AFL at the diagnosis of labor. This provides a baseline recording of AFL as a measure of uterine muscle metabolism and has the benefit of visualization of the amount and color of AFL draining allowing for accurate fetal monitoring practices.
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Myometrial fatigue Increased AFL may reflect myometrial fatigue and a switch from aerobic to anaerobic metabolism resulting in inefficient contractions. The molecular basis for this has been described in previous studies.23 Over time continued reduction in oxygenation of the myometrium leads to impaired fetal oxygenation and fetal acidosis. The role of AFL in the detection of labor disorders has been investigated in previous studies.10 These studies found an association between AFL and labor disorders (dystocia). The women studied were in labor, however the parity and labor onset are not reported. It is not clear how long labor had been diagnosed before AFL samples were taken. We specifically focused on the spontaneously laboring single cephalic nulliparous at term cohort for this study as we had previously demonstrated significant international variation in this group24 and that a high CD rate or an increased CD rate within the single cephalic nulliparous at term cohort was associated with an increase in overall CD rates.24,25 The most common indication for CD in single cephalic nulliparous at term cases is a labor disorder (dystocia). Inefficient uterine action is considered to be the largest contributor to labor disorders (dystocia) in single cephalic nulliparous at term women.14 A better understanding of labor disorders (dystocia) leading to a prompt and accurate diagnosis followed by appropriate management could therefore have a significant effect on CD rates.25 Conclusion Whether or not AFL at the diagnosis of labor will be useful in managing labor and in particular whether it may affect CD is unclear at the moment. A randomized controlled trial study may be able to answer this issue. We believe that in the meantime further studies on AFL using the classification described for intrapartum CD may help explain more about the role of
AFL in the physiology and pathology of labor, in particular how the AFL may vary in women delivering in institutions where the management of labor is different. However, this study has been useful in explaining some of the possible physiological benefits of the principles involved in active management of labor in particular the early diagnosis of labor, early amniotomy, and early diagnosis of inefficient uterine action in single cephalic nulliparous at term cases. There is a clear relationship between AFL at the diagnosis of labor with labor disorders and CD. Women with an AFL of 10.0 mmol/L are almost 3 times more likely to have a CD compared to those with AFL value of <10 mmol/L. Measurement of AFL at the diagnosis of spontaneous labor may be useful in the intrapartum management of single cephalic nulliparous at term (37 weeks’ gestation) cases. REFERENCES 1. Delbare I, Cammu H, Martens E, et al. Limiting the cesarean section rate in low risk pregnancies is key to lowering the trend of increased abdominal deliveries: an observational study. BMC Pregnancy Childbirth 2012;12:3. 2. Ovostar R, Rashidian A, Pourreza A, et al. Developing criteria for cesarean section using the RAND appropriateness method. BMC Pregnancy Childbirth 2010;10:52. 3. Lumbiganon P, Laopaiboon M, Gulmezoglu AM, et al. Method of delivery and pregnancy outcomes in Asia; the WHO global survey on maternal and perinatal health 2007-08. Lancet 2010;375:440-2. 4. Zhu B, Grigorescu V, Le T, et al. Labor dystocia and its association with interpregnancy interval. Am J Obstet Gynecol 2006;85:810-4. 5. Betran AP, Meraldi M, Lauer JA, et al. Rates of cesarean section: analysis of global, regional and national estimates. Paediatr Perinat Epidemiol 2007;21:98-113. 6. Quenby S, Matthew A, Zhang J, et al. In vitro myometrial contractility reflects indication for cesarean section. Br J Obstet Gynaecol 2011;118:1499-506. 7. Quenby S, Pierce S, Brigham S, Wray S. Dysfunctional labor and myometrial lactic acidosis. Obstet Gynecol 2004;103:718-23. 8. Wray S, Jones K, Kuppittanants S, et al. Calcium signaling and uterine contractility. J Soc Gynaecol Investig 2003;10:252-64.
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9. Brooks GA. The lactate shuttle during exercise and recovery. Med Sci Sports Exerc 1986;18:360-8. 10. Wilberg-Itzel E, Petterson H, Cnattingus S, Nordstrom L. Association between lactate concentration in amniotic fluid and dysfunctional labor. Acta Obstet Gynecol 2008;87:924-92. 11. Robson MS. Classification of cesarean sections. Fetal Matern Med Rev 2001;12:23-39. 12. Harper LM, Caughey AB, Roehl KA, et al. Defining an abnormal first stage of labor based on maternal and neonatal outcomes. Am J Obstet Gynecol 2014;210:536.e1-7. 13. Robson M. National Maternity Hospital Clinical Report for the year 2010. Dublin, Ireland: National Maternity Hospital. 14. Robson M, Hartigan L, Murphy M. Methods of achieving and maintaining an appropriate cesarean section rate. Best Pract Res Clin Obstet Gynaecol 2013;27:297-308. 15. Twomey A. National Maternity Hospital Neonatal Clinical report 2010. Dublin, Ireland: National Maternity Hospital. 16. Zhang J, Troendle J, Reddy U, et al. Contemporary cesarean delivery practice in the United States. Am J Obstet Gynecol 2010;203: 326.e1-10. 17. O’Driscoll K, Meagher D, Robson M. Active management of labor. Philadelphia, PA: Elsevier Sciences Limited; 2003. 18. Cohen W, Friedman A. Perils of the new labor management guidelines. Am J Obstet Gynecol 2015;212:420-7. 19. Caughey A, Cahill A, Guise JM, et al. Safe prevention of the primary cesarean delivery. Am J Obstet Gynecol 2014;123:693-711. 20. Mercer B, McNanley T, O’Brien J, et al. Early versus late amniotomy for labor induction: a randomized trial. Am J Obstet Gynecol 1995;173:1321-5. 21. Stewart P, Kennedy JH, Calder A. Spontaneous labor: when should the membranes be ruptured? Br J Obstet Gynaecol 1982;95: 105-6. 22. Rosen H, Hiersh L, Saltzer L, et al. Amniotomy: does artificial rupturing of membranes in the active phase enhance myometrial electrical activity? A common practice still in controversy. Am J Obstet Gynecol 2013;208:S140. 23. Mittal P, Romero R, Tarca AL, et al. A molecular signature of an arrest of descent in human parturition. Am J Obstet Gynecol 2011;204:177.e15-33. 24. Brennan D, Robson M, Murphy M, O’Herlihy C. Comparative analysis of international cesarean delivery rates using 10-group classification identifies significant variation in spontaneous labor. Am J Obstet Gynecol 2009;201:308.e1-8. 25. Stewart P, Dulberg C, Chapman A, Elmslie T, Hall PF. Diagnosis of dystocia and management with cesarean section among primiparous women in Ottawa-Carleton. CMAJ 1990;142:459-63.
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Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term Martina Murphy, BNS; Michelle Butler, PhD; Barbara Coughlan, PhD; Donal Brennan, PhD; Colm O’Herlihy, PhD; Michael Robson, MD OBJECTIVE: We sought to assess amniotic fluid lactate (AFL) at
diagnosis of spontaneous labor at term (37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD). STUDY DESIGN: This was a single-institution, prospective cohort study
of 905 singleton, cephalic, term (37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds. RESULTS: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n ¼ 118), 5.0-9.9 mmol/L (n ¼ 707), and 10.0 mmol/L (n ¼ 80).
Increasing AFL was associated with higher total oxytocin dose (P ¼ .001), labor disorders (P ¼ .005), and CD (P .001). Multivariable regression analysis demonstrated that women with AFL 5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06e2.39) and AFL 10.0 mmol/L (OR, 1.72; 95% CI, 1.01e2.93) were independent predictors of a labor disorder. AFL 5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL 10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73e6.46). AFL 5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL 10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method. CONCLUSION: AFL at diagnosis of labor in spontaneously laboring
single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol. Key words: active management of labor, amniotic fluid lactate, cesarean delivery, labor disorder (dystocia)
Cite this article as: Murphy M, Butler M, Coughlan B, et al. Elevated amniotic fluid lactate predicts labor disorders and cesarean delivery in nulliparous women at term. Am J Obstet Gynecol 2015;213:673.e1-8.
C
esarean delivery (CD) rates have increased significantly over the last 3 decades whereby it is now the most commonly performed surgical procedure in developed countries.1 There is no
consensus on the appropriate rate or indications.2,3 Repeat CD remains the largest contributor to the overall CD rate. In nulliparous women, labor disorders (dystocia), defined as abnormal
From the Departments of Midwifery (Ms Murphy) and Obstetrics and Gynecology (Drs Brennan, O’Herlihy, and Robson), National Maternity Hospital, and Departments of Health Sciences (Ms Murphy and Dr Coughlan) and Obstetrics and Gynecology (Drs Brennan and O’Herlihy), University College Dublin, Dublin, Ireland, and School of Midwifery, University of British Columbia, Vancouver, British Columbia, Canada (Dr Butler). Received March 25, 2015; revised May 17, 2015; accepted June 15, 2015. This study was funded by the medical fund at the National Maternity Hospital, Dublin, Ireland. The authors report no conflict of interest. Presented as a poster at the 34th annual meeting of the Society for Maternal-Fetal Medicine, New Orleans, LA, Feb. 3-8, 2014. Corresponding author: Martina Murphy, BNS. [email protected] 0002-9378/$36.00 ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2015.06.035
or difficult labor, are the most common indication for the first CD.4 CD is rare in women who have had a previous vaginal delivery. More focus should be placed on preventing primary CD, particularly on those women in spontaneous labor. The main causes of a labor disorder (dystocia) are inefficient uterine action, malposition, and cephalopelvic disproportion.5 Inefficient uterine action, also described as dysfunctional uterine action or incoordinate uterine action, refers to the frequency, duration, and force of the uterine contractions and is the most common cause of a labor disorder in nulliparous women.6 Uterine muscle metabolism and muscle fatigue contribute to labor disorders and subsequent CD.7
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FIGURE 1
Flowchart classification of cesarean deliveries
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
Myometrial fatigue causes a switch from aerobic to anaerobic metabolism,8 resulting in an accumulation of intramuscular lactic acid and a subsequent increase in both intracellular and extracellular lactate levels.9 Increased amniotic fluid lactate (AFL) levels have previously been associated with labor disorders (dystocia), but this study was relatively small and AFL was measured when rupture of membranes occurred during labor and not at the diagnosis of labor.10 The purpose of this study was to measure the AFL at the diagnosis and at each assessment of progress in the first stage of labor with last sample measured prior to delivery in an adequately powered cohort of spontaneously laboring single cephalic nulliparous at term cases and to examine labor events
and outcomes so as to assess the relationship between AFL and both labor disorders and CD. This prospective cohort study was carried out in an institution where a uniform approach to management of spontaneous nulliparous labor has been used over 4 decades.
M ATERIALS
AND
M ETHODS
Population The study was conducted over 9 months in 2011 through 2012. Approval from the National Maternity Hospital Ethics Committee and human subject exemption from University College Dublin was obtained. Inclusion criteria were single cephalic nulliparous term (37 weeks’ gestation) women in spontaneous labor (group 1, Ten-Group Classification System).11 All participants signed an
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informed consent form. Women were recruited to the study immediately following the vaginal examination confirming the diagnosis of labor.
Management of labor Labor was diagnosed when the cervix was fully effaced and at least 1 cm dilated. Amniotomy was performed at the diagnosis of labor if spontaneous rupture of the membranes had not already occurred. In single cephalic nulliparous at term women, vaginal examinations were carried out every 2 hours to assess progress in labor. Criteria for diagnosis of labor arrest were dilation of the cervix at <1 cm/h over 2 hours in the first stage of labor and in the second stage of labor was assessed by descent and rotation of the presenting part in the
ajog.org pelvis. Early diagnosis of labor arrest and inadequate descent were treated with oxytocin according to hospital protocol. Oxytocin was administered with a dose of 5 mU/min increasing to a maximum dose of 30 mU/min. The oxytocin was increased or decreased at 15-minute intervals and by 5 mU/min according to uterine activity. A maximum of 7 contractions per 15-minute interval was permitted and midwifery staff palpated and recorded the number of contractions. Increased duration of first stage of labor is associated with increased maternal and neonatal morbidity.12 Duration of the first stage of labor was recorded for AFL groups. Prolonged labor was defined as duration of labor lasting >720 minutes.
Data collection Demographic and clinical data were collected from the clinical labor record and neonatal records of all women recruited to the study. All indications for CD were recorded according to a standard defined classification for intrapartum CD13 (Figure 1). This classification differentiates between suspected fetal distress without oxytocin as opposed to suspected fetal distress after oxytocin was started, but when the primary problem was a labor disorder. It also attempts to differentiate between different subtypes of labor disorders related to the rate of progress in labor, irrespective of the definitions and guidelines for managing labor used in different institutions. These are listed under variables, which means that it can be used universally. Quantification of AFL levels Amniotic fluid samples were collected at each vaginal examination to assess labor progress, including the last sample before delivery, in a clean clear tube. The samples were collected by catching the amniotic fluid sample flowing onto a sterile glove. We needed 1 mL of amniotic fluid to perform the test. All samples were immediately labeled with patient name, identification number, and the date and time of collection. Samples were stored and tested according to guidelines from
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FIGURE 2
Flowchart recruitment process Total PopulaƟon Robson Group 1 (n 1764)
Excluded prior to diagnosis of labour medical or ethical reason (n 105)
Excluded no liquor sample obtained (n 79)
Excluded no reason recorded (n 466) Total populaƟon recruited (n 1,114)
Intrapartum exclusion incomplete data / sample collecƟon (n 187)
Declined to parƟcipate in study (n 22)
Final Study PopulaƟon (n 905)
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
the manufacture of the point-of-care device (LMU061, ObsteCare; Stockholm, Sweden). This instrument is built on patented technology and is currently the only system on the market for point-ofcare use that is tailored for the measurement of lactate in amniotic fluid during labor (US patent no. US 7,318,809).
Statistical analysis Statistical analysis was performed using software (SPSS 20; IBM Corp, Armonk, NY). Unsupervised decision tree analysis with a 10-fold cross-validation was used to identify AFL thresholds. A series of cross-tabulations and analyses of variance were performed to explore the relationships and differences between clinical characteristic variables and lactate levels. Univariate and multivariable binary logistic regression analysis were used to
identify predictors of labor disorders and CD. Variables found to be significant in univariate analysis were included in the multivariable analysis. An alpha level of P < .05 was set for all statistical tests.
Power calculations Power calculation was based on the incidence of labor disorders from the National Maternity Hospital clinical report.13 The assumptions (based on analysis of outcomes obtained from the clinical report) were a level of significance of .05 that 20% of the patients would present with elevated AFL and the rate of operative delivery would be 3 times higher in the AFL 10.0 mmol/L group. A sample of 575 patients in the study could detect a difference in CD rates between 14.2% in the elevated
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TABLE 1
Clinical characteristics of cohort Characteristic
Value
Age, y Mean (minimum-maximum)
30 (16e44)
2
BMI, kg/m
Mean (minimum-maximum)
R ESULTS 24.2 (16.9e50.6)
Gestation at delivery, wk Mean completed (minimum-maximum)
40 (37e42)
Amniotic fluid lactate at diagnosis of labor, mmol/L Mean (minimum-maximum)
7.25 (1.0e20.9)
Amniotomy Spontaneous
278 (31)
Artificial
627 (69)
Cervical dilatation at diagnosis, cm Median (range)
1 (1e10)
Epidural anesthesia No
161 (18)
Yes
744 (82)
Electronic fetal monitoring No
168 (19)
Yes
737 (81)
Labor disorder (dystocia) None
368 (40)
First stage
441 (49)
Second stage
96 (11)
Oxytocin dose, mU Median (range)
650 (0e18,7500)
Duration of oxytocin infusion, min Median (range)
75 (0e737)
Delivery Spontaneous vaginal
609 (67)
Instrumental vaginal
235 (26)
Cesarean
61 (7)
Duration of first stage of labor, min Mean (SD)
300 (213.6)
Duration of second stage of labor, min Mean (range)
51 (0e231)
Infant birthweight, g Median (range)
3550 (2470e5220)
Values in parenthesis are percentages unless otherwise stated. BMI, body mass index. Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
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group and 4.7% in the control group with a power of 90% at a level of significance of .05. A sample size of 500 patients was required for the initial analysis. In all, 905 patients were recruited to the study.
Recruitment process to this study is presented in Figure 2. The study cohort (n ¼ 905) comprised 25 nationalities with native Irish women representing 66.3% (n ¼ 600) of the population and Eastern European women contributing 20.7% (n ¼ 188); other European women, 4.0% (n ¼ 37); Asian women, 3.0% (n ¼ 27); Chinese women, 2.7% (n ¼ 25); US women, 2.0% (n ¼ 19); and other nationalities, 1% (n ¼ 9). Clinical characteristics are described in Table 1. To examine any relationship between AFL levels and delivery outcomes, unsupervised decision tree analysis was used to divide AFL into 3 groups: 0-4.9 mmol/L (n ¼ 118), 5.0-9.9 mmol/L (n ¼ 707), and 10.0 mmol/L (n ¼ 80). Delivery outcomes for the 3 groups are presented in Table 2. The rates of labor disorders (dystocia), spontaneous vaginal delivery, and CD were significantly different among the 3 groups with levels of AFL 0-4.9 mmol/L associated with a higher spontaneous delivery rate, less labor disorder, and a lower CD rate. The CD rate in the AFL 10.0 mmol/L group was 17.5%, almost 3 times that of the 0-4.9 mmol/L group (Table 2). The mean duration of the first stage of labor was 276 minutes in the AFL 0-4.9 mmol/L group and was 77 minutes longer in the AFL 10.0 mmol/L group. Mean birthweight in the AFL 0-4.9 mmol/L group was 3564 g (SD 422), in AFL 5.0-9.9 mmol/L group was 3597 g (SD 468), and in the AFL 10.0 mmol/L group was 3585 g (SD 431). A series of Pearson correlations were performed to explore if a relationship exists among birthweight, labor disorder, and AFL at diagnosis of labor within each AFL group. There were no significant relationships found in AFL 0-4.9 mmol/L group or the AFL 5.0-9.9 mmol/L group. A significant relationship between birthweight and labor disorder (r ¼ 0.263, n ¼ 80) was
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TABLE 2
Labor disorder and delivery methods in amniotic fluid lactate groups AFL 0-4.9 mmol/L (n [ 118)
Variable
AFL ‡5.0-9.9 mmol/L (n [ 707)
AFL ‡10.0 mmol/L (n [ 80)
P value
Mean maternal age, y (SD)
30.1 (4.8)
29.6 (5.1)
29.9 (5.1)
.546
Mean gestation at delivery, wk (SD)
39.4 (0.9)
39.7 (1.0)
40.0 (1.0)
.046
Mean cervical dilation at diagnosis, cm (SD) 2
Mean BMI, kg/m (SD)
2 (1.6)
1.8 (1.63)
1.63 (1.06)
23.7 (3.6)
24.1 (4.0)
25.5 (4.4)
Yes
27.0%
32.4%
27.5%
No
63.0%
37.6%
73.5%
None
61 (52)
286 (41)
21 (26)
Dystocia diagnosed first stage
46 (39)
344 (49)
51 (64)
Dystocia diagnosed second stage
11 (11)
77 (11)
8 (10)
87 (74)
474 (67)
48 (60)
< .001 .001
SROM
Labor disorder (dystocia) .005a
Delivery method Spontaneous vaginal Forceps
8 (7)
77 (11)
6 (8)
Ventouse
19 (16)
113 (16)
12 (15)
Yes
4 (3)
43 (6)
14 (18)
No
114 (97)
664 (94)
66 (82)
No intervention
87 (73)
476 (67)
49 (61)
Fetal reason
10 (9)
50 (7)
5 (6)
Dystocia
21 (18)
181 (26)
26 (33)
.052a
Cesarean delivery < .001a
Reason for operative intervention .027a
Values in parenthesis are percentages unless otherwise stated. AFL, amniotic fluid lactate; BMI, body mass index; SROM, spontaneous rupture of membranes. a
Pearson correlation coefficient.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
found. There was also a significant relationship between birthweight and CD (r ¼ 0.227, n ¼ 80) found in the AFL 10.0 mmol/L. Having demonstrated an association among increased AFL at diagnosis of labor, labor disorders (dystocia), and subsequent CD, we sought to further investigate the relationship between AFL and labor disorders. Univariate predictors of labor disorders included body mass index, gestational age, and cervical dilatation at presentation (Table 3). AFL measured as a continuous variable was associated with a labor disorder (odds
ratio [OR], 1.09; 95% confidence interval [CI], 1.02e1.16). To ascertain if AFL was an independent predictor of a labor disorder (dystocia), a multivariable binary logistic regression model using body mass index >25 or <25, gestational age, and cervical dilatation at diagnosis was employed. Multivariable analysis demonstrated that AFL, when measured as a continuous variable, was an independent predictor of a labor disorder (OR, 1.08; 95% CI, 1.01e1.16). Using the same multivariable model demonstrated that with AFL >5.0-9.9 mmol/L (OR, 1.6; 95% CI, 1.06e2.39)
and AFL 10.0 mmol/L (OR, 1.72; 95% CI, 1.01e2.93) were independent predictors of a labor disorder (dystocia). Predictive values of AFL 5.0-9.9 mmol/L to predict dystocia showed (positive predictive value [PPV] 61, negative predictive value [NPV] 52, overall accuracy 60), AFL 10.0 mmol/L (PPV 74, NPV 42, overall accuracy 45). AFL >5 mmol/L did not predict CD but multivariable analysis confirmed AFL 10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73e6.46). AFL >5.0-9.9 mmol/L did not predict CD (OR, 2.22; 95% CI,
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TABLE 3
Logistic regression analysis of labor disorder (dystocia) Multivariatea
Univariate Variable
P value OR (95% CI)
OR (95% CI)
Multivariatea P value OR (95% CI)
Multivariatea P value OR (95% CI)
P value
Age (continuous)
905 1.02 (0.99e1.04)
BMI (continuous)
862 1.07 (1.03e1.11) < .001 1.06 (1.02e1.10)
.257 .001 1.06 (1.03e1.10) .001
1.06 (1.03e1.10)
.002
Gestation (continuous)
905 1.17 (1.03 e1.34)
.028 1.17 (1.02e1.34) .03
1.15 (1.01e1.32)
.046
Cervical dilatation at diagnosis (continuous)
905 0.25 (0.16e0.40) < .001 0.26 (0.16e0.42) < .001 0.26 (0.16e0.42) < .001 0.26 (0.16e0.42) < .001
Lactate (continuous)
905 1.09 (1.02e1.16)
.01
0-4.9 mmol/L
118 1
.31
1
5 mmol/L
787 1.67 (1.14e2.47)
.009
1.60 (1.06e2.39) .024
0-9.9 mmol/L
825 1
.14
1
.15
.005
1.72 (1.01e2.93)
.046
.017 1.17 (1.02e1.34)
1.08 (1.01e1.16)
.024
Lactate
10 mmol/L
80 2.04 (1.22e3.42)
.23
BMI, body mass index; CI, confidence interval; OR, odds ratio. a
Controls for all other variables in analysis.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
0.79e6.25), but multivariable analysis confirmed AFL >10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 0.73e6.46) (Table 3). AFL 5.0-9.9 mmol/L had a sensitivity of 89% in predicting dystocia and a sensitivity of 14% in predicting CD. AFL
10.0 mmol/L has a sensitivity of 23% and specificity of 92% (PPV 18, NPV 94, overall accuracy 88) and is highly specific but lacks sensitivity for CD. Within the 3 AFL groups, the indication for CD was classified according to the National Maternity Hospital intrapartum
classification for CD.14 Fetal intolerance and overcontracting (tachysystole) after treatment with oxytocin were both the most common reason for delivery (Table 4). Of the operative interventions, 21% occurred as a result of fetal intolerance, 7.6% in the AFL 5.0-9.9 mmol/L
TABLE 4
Classification of indication for cesarean delivery within amniotic fluid lactate groups Classification of operative intervention
AFL <4.9 mmol/L (n [ 118)
AFL 5.0-9.9 mmol/L (n [ 707)
AFL >10.0 mmol/L (n [ 80)
None
87 (73.7)
482 (68.2)
47 (58.6)
Fetal/no dystocia
10 (8.5)
43 (6.0)
5 (6.3)
Dystocia/ITT/FI
9 (7.6)
93 (13.1)
11 (13.8)
Dystocia/ITT/OC
7 (5.9)
38 (5.4)
9 (11.3)
Dystocia/PR
4 (3.4)
40 (5.7)
5 (6.3)
Dystocia/no oxytocin
1 (0.8)
3 (0.4)
1 (1.3)
CPD/malposition
0 (0)
8 (1.1)
2 (2.5)
393.6 (8.2)
400.8 (5.6)
417.5 (14.3)
3 (2.5)
38 (5.4)
8 (10)
Mean (SEM) Admission to NICU
P value .005a
.005b
Values in parenthesis are percentages unless otherwise stated. AFL, amniotic fluid lactate; CPD, cephalopelvic disproportion; FI, fetal intolerance; ITT, inability to treat; NICU, neonatal intensive care unit; OC, overcontracting; PR, poor response (slow/no dilatation of cervix). a
Pearson correlation coefficient; b Analysis of variance.
Murphy. Amniotic fluid lactate levels, labor disorders (dystocia), and cesarean. Am J Obstet Gynecol 2015.
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ajog.org group compared with 13.8% in the AFL 10.0 mmol/L group. Consistent with these findings, AFL 10.0 mmol/L was associated with increased electronic fetal monitoring and a need for at least 1 fetal blood sample. Likewise pyrexia and the need for antibiotics were increased in AFL 10.0 mmol/L group. AFL 10.0 mmol/L was also associated with an increase in admissions to the neonatal intensive care unit. Uterine activity was monitored in all cases when labor disorders were treated with oxytocin. Inability to treat labor disorders as a result of the uterus overcontracting occurred in 5.9% of cases in the AFL 5.0-9.9 mmol/L group compared to 11.3% in the AFL 10.0 mmol/L group. Taken together these data demonstrate that the 2 major indications for CD in patients with an increased AFL were fetal intolerance and overcontracting of the uterus. No serious maternal complications were recorded in 800 cases (88.4%). The overall incidence of shoulder dystocia was 0.8% and third-degree tear was 1.3% with no significant differences between the AFL groups. Maternal blood loss of >500 mL was recorded in 11.3% of the AFL 10.0 mmol/L group compared to 6.6% in the AFL 0-4.9 mmol/L group and 5.8% in the AFL 5.0-9.9 mmol/L group. This was associated with the increased CD rate in the AFL 10.0 mmol/L group. In all, 49 infants (5.4%) were admitted to the neonatal unit. Short-term admission for septic screen accounted for 18 (37%) of these infants. Infants in the AFL 10.0 mmol/L were more likely to be admitted with transient tachypnea of the newborn, but the incidence of low cord pH (<7.1) at delivery was 0.8% in both the AFL 0-4.9 mmol/L and the AFL 5.0-9.9 mmol/L groups and was 1.3% in the AFL 10.0 mmol/L group. Two infants developed hypoxic ischemic encephalopathy (defined as seizures, with or without abnormal consciousness, difficulty maintaining respiration, abnormal tone accompanied by evidence of metabolic acidosis pH >7.1 base excess 12 mmol/L).15 Both were in the AFL 5.0-9.9 mmol/L group and received therapeutic hypothermia followed by neurological assessment using magnetic resonance imaging (MRI). One infant had a normal MRI
Obstetrics scan and is achieving normal milestones. The second infant displayed changes on MRI and has a guarded prognosis.
C OMMENT Labor disorders and CD This prospective cohort study is the first to use a point-of-care device to measure AFL at diagnosis of spontaneous labor in single cephalic nulliparous at term women. Herein we demonstrate that increased AFL at diagnosis is an independent predictor of labor disorders and CD. The finding that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol is significant. We have previously demonstrated that the greatest contributor to interinstitutional variability in CD rates is in the management of single cephalic nulliparous at term cohort.13,16 Furthermore, we demonstrate that the main indications for CD in women with elevated AFL were fetal intolerance and tachysystole (overcontracting). This suggests that in women with an elevated AFL (10.0 mmol/L) at diagnosis, oxytocin must be used carefully. Strengths of this study Strengths of this study include the fact that it was a prospectively designed, adequately powered cohort study. Indications for CD were prospectively defined and women were managed using a standard model of care. Active management of labor17 is the standard philosophy of care at our institution. This philosophy aims to prevent prolonged labor and includes clear criteria for the diagnosis of labor (cervix fully effaced at least 1 cm dilated, diagnosis made by a senior midwife). This philosophy of care is applied to all women and not just those diagnosed with labor disorder (dystocia). Our labor management is based on direct clinical observations aimed at achieving safe vaginal delivery.18 Efficient uterine action is considered to be the key to normality. The early diagnosis of labor and rupture of the membranes allows a clear picture of progress to emerge within the first few hours of labor. This in turn facilitates the early diagnosis and treatment of labor disorders. Inefficient
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uterine contractions are reflected clinically by failure of the cervix to dilate. Contemporary studies cite a progress rate of cervical dilation of 0.5-0.7 cm/h as the norm in nulliparous women.19 Based on our data, early correction of inefficient uterine action with the use of oxytocin, before the level of AFL rises to 10.0 mmol/L, may help to reduce the CD rate in single cephalic nulliparous at term women. Our philosophy of care provided a standard treatment to perform the study and reduced the risk that the management of labor influenced the lactate value. A repeat study using the same methodology in a center with a different approach to care in labor would provide useful information.
Study weakness The application of a standard model of care such as active management of labor may also be viewed as a weakness of the study; however the prospective nature of this study we believe reduces selection bias. Variation in practices in other delivery units may make it difficult to repeat this study in other settings. A second potential weakness of the study is the routine practice of rupture of membranes at the diagnosis of labor, which remains controversial. Spontaneous rupture of membranes prior to diagnosis of labor occurred in 30% of cases in this study. Advantages of early amniotomy include examination of the amniotic fluid and ability for direct measurement of the fetal heart; disadvantages are cited as possible fetal distress due to cord compression and potential infection risks.20 Many centers view this practice as an unnecessary intervention and delay amniotomy until a labor disorder is diagnosed.21 Recent evidence suggests that amniotomy during labor enhances electrical uterine activity reinforcing the claim that amniotomy augments labor.22 Artificial rupture of the membranes would however be necessary if we wish to measure AFL at the diagnosis of labor. This provides a baseline recording of AFL as a measure of uterine muscle metabolism and has the benefit of visualization of the amount and color of AFL draining allowing for accurate fetal monitoring practices.
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Myometrial fatigue Increased AFL may reflect myometrial fatigue and a switch from aerobic to anaerobic metabolism resulting in inefficient contractions. The molecular basis for this has been described in previous studies.23 Over time continued reduction in oxygenation of the myometrium leads to impaired fetal oxygenation and fetal acidosis. The role of AFL in the detection of labor disorders has been investigated in previous studies.10 These studies found an association between AFL and labor disorders (dystocia). The women studied were in labor, however the parity and labor onset are not reported. It is not clear how long labor had been diagnosed before AFL samples were taken. We specifically focused on the spontaneously laboring single cephalic nulliparous at term cohort for this study as we had previously demonstrated significant international variation in this group24 and that a high CD rate or an increased CD rate within the single cephalic nulliparous at term cohort was associated with an increase in overall CD rates.24,25 The most common indication for CD in single cephalic nulliparous at term cases is a labor disorder (dystocia). Inefficient uterine action is considered to be the largest contributor to labor disorders (dystocia) in single cephalic nulliparous at term women.14 A better understanding of labor disorders (dystocia) leading to a prompt and accurate diagnosis followed by appropriate management could therefore have a significant effect on CD rates.25 Conclusion Whether or not AFL at the diagnosis of labor will be useful in managing labor and in particular whether it may affect CD is unclear at the moment. A randomized controlled trial study may be able to answer this issue. We believe that in the meantime further studies on AFL using the classification described for intrapartum CD may help explain more about the role of
AFL in the physiology and pathology of labor, in particular how the AFL may vary in women delivering in institutions where the management of labor is different. However, this study has been useful in explaining some of the possible physiological benefits of the principles involved in active management of labor in particular the early diagnosis of labor, early amniotomy, and early diagnosis of inefficient uterine action in single cephalic nulliparous at term cases. There is a clear relationship between AFL at the diagnosis of labor with labor disorders and CD. Women with an AFL of 10.0 mmol/L are almost 3 times more likely to have a CD compared to those with AFL value of <10 mmol/L. Measurement of AFL at the diagnosis of spontaneous labor may be useful in the intrapartum management of single cephalic nulliparous at term (37 weeks’ gestation) cases. REFERENCES 1. Delbare I, Cammu H, Martens E, et al. Limiting the cesarean section rate in low risk pregnancies is key to lowering the trend of increased abdominal deliveries: an observational study. BMC Pregnancy Childbirth 2012;12:3. 2. Ovostar R, Rashidian A, Pourreza A, et al. Developing criteria for cesarean section using the RAND appropriateness method. BMC Pregnancy Childbirth 2010;10:52. 3. Lumbiganon P, Laopaiboon M, Gulmezoglu AM, et al. Method of delivery and pregnancy outcomes in Asia; the WHO global survey on maternal and perinatal health 2007-08. Lancet 2010;375:440-2. 4. Zhu B, Grigorescu V, Le T, et al. Labor dystocia and its association with interpregnancy interval. Am J Obstet Gynecol 2006;85:810-4. 5. Betran AP, Meraldi M, Lauer JA, et al. Rates of cesarean section: analysis of global, regional and national estimates. Paediatr Perinat Epidemiol 2007;21:98-113. 6. Quenby S, Matthew A, Zhang J, et al. In vitro myometrial contractility reflects indication for cesarean section. Br J Obstet Gynaecol 2011;118:1499-506. 7. Quenby S, Pierce S, Brigham S, Wray S. Dysfunctional labor and myometrial lactic acidosis. Obstet Gynecol 2004;103:718-23. 8. Wray S, Jones K, Kuppittanants S, et al. Calcium signaling and uterine contractility. J Soc Gynaecol Investig 2003;10:252-64.
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