Original Article
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Effect of Growth Restriction on Fetal Heart Rate Patterns in the Second Stage of Labor Kristina A. Epplin, MD1 Methodius G. Tuuli, MD, MPH1 Anthony O. Odibo, MD, MSCE2 Kimberly A. Roehl, MPH1 George A. Macones, MD, MSCE1 Alison G. Cahill, MD, MSCI1 1 Department of Obstetrics and Gynecology, Washington University in
St. Louis, St. Louis, Missouri 2 Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida
Address for correspondence Kristina A. Epplin, MD, Department of Obstetrics and Gynecology, Washington University in St. Louis, Campus Box 8064, 660 S. Euclid Avenue, St. Louis, MO 63110 (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
fetal monitoring fetal heart rate growth restriction IUGR
Objective We aimed to estimate the effect of intrauterine growth restriction (IUGR) on electronic fetal monitoring (EFM) patterns in the second stage of labor. Study Design We performed a 5-year retrospective cohort study of consecutive singleton, nonanomalous, term gestations. We compared IUGR infants, those with a birth weight less than the 10th percentile, with non-IUGR infants, those greater than or equal to the 10th percentile. Our primary outcome was the EFM patterns in the 30 minutes before delivery. A secondary analysis was performed excluding infants with composite morbidity. Logistic regression was used to adjust for body mass index, race, nulliparity, induction, and protracted labor. Results Out of the 5,388 infants, 652 (12.1%) were IUGR. IUGR fetuses had less accelerations (29.0 vs. 35.9%, p < 0.01), even among apparently normal infants (29.0 vs. 36.4%, p < 0.01). IUGR fetuses had a higher risk of decelerations, and in all, IUGR accounted for 6% of late decelerations (attributable risk 0.06, 95% confidence interval 0.02–0.10). There was no significant association between IUGR and bradycardia or minimal variability. Conclusion Growth restriction at term confers an increased risk of late decelerations, even in the absence of neonatal morbidity. EFM patterns may require different interpretations based on a priori risk and clinical factors.
Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality, and is associated with a higher incidence of intrapartum acidemia.1,2 During normal fetal development, fetal behavior and variation of the fetal heart rate become increasingly sophisticated with increasing gestation. In growth-restricted fetuses with chronic hypoxemia and placental dysfunction, there is a delay in all aspects of central nervous system (CNS) maturation.3,4 Small previous studies on electronic fetal monitoring (EFM) in growthrestricted fetuses have suggested that there is an increase in the baseline fetal heart rate (FHR) due to a delay in CNS
maturation.5 These studies have also suggested that there is diminished FHR variation in response to growth restriction and chronic hypoxemia.6 However, there is limited data on intrapartum FHR patterns, a time during which obstetricians rely on EFM to guide management decisions. Intrapartum EFM is used by obstetric providers with common nomenclature endorsed by the American College of Obstetricians and Gynecologists, the Society of Maternal-Fetal Medicine, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) since a 2008 consensus conference.7 However, despite differences in a priori
received August 17, 2014 accepted after revision December 2, 2014 published online January 21, 2015
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1543954. ISSN 0735-1631.
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Am J Perinatol 2015;32:873–878.
Effect of IUGR on EFM Patterns in the Second Stage of Labor risk of acidemia with specific clinical conditions, nurses and providers still use the same system for nomenclature and interpretation. At present, data are lacking to identify differences in intrapartum EFM patterns that are specifically attributable to a variation in clinical characteristics. We aimed to estimate differences in intrapartum EFM patterns between term IUGR infants and non-IUGR infants in the second stage of labor, and their relationship to adverse neonatal outcomes.
Materials and Methods We conducted a 5-year retrospective cohort study, from 2004 through 2008, of consecutive term deliveries at a single, large, tertiary care medical center in the Midwest. The aim of the parent study was to estimate the correlation between FHR patterns in the second stage of labor and acidemia at birth.8 Women included in the cohort had term ( 37 weeks), cephalic, nonanomalous, singleton gestations who reached the second stage of labor. All included participants had at least 10 minutes of EFM in the 30 minutes before birth, and had available umbilical cord gases. There is an institutional policy of universal EFM use and obtaining umbilical cord gases. Those excluded were women who did not labor and women who delivered by cesarean delivery before complete dilation. The study was conducted with the approval of the institutional review board. Detailed maternal sociodemographic information, obstetric and medical history, intrapartum course, complications data, and neonatal characteristics were collected from the medical record by trained research personnel. The active phase of labor was determined from the medical record and was considered as the time for which a patient had a documented cervical examination of 6 to 10 cm. IUGR was defined as birth weight less than the 10th percentile for gestational age at delivery defined by the Alexander birth weight reference curves.9 These infants were compared with all infants greater than or equal to the 10th percentile. Pregnancies were dated by last menstrual period (LMP) if known and concordant with ultrasound (7 days of firsttrimester ultrasound or 14 days of second-trimester ultrasound). If the LMP was unknown or discordant the earliest available ultrasound was used. The FHR tracing in the 30 minutes before delivery was interpreted prospectively by two formally trained and credentialed obstetric research nurses blinded to all clinical and outcome data using NICHD criteria. The 30 minutes of EFM data before delivery were divided into three 10-minute periods and analyzed individually. The average baseline for each of these 10-minute periods was calculated and rounded to the nearest 5 beats per minute (bpm). Baseline heart rate characteristics were determined such as ever bradycardia < 110 bpm, ever < 120 bpm, or ever tachycardia > 160 bpm, if that was the predominant pattern in at least one of three 10-minute periods. Variability was classified as ever absent or minimal, or ever marked if that was the predominant pattern in one of the three 10-minute periods. The descriptor “mostly” was used if a pattern was predominant in two of the three periods. American Journal of Perinatology
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“Always” was used if a pattern was predominant in all three 10-minute periods, such as always absent or minimal, or always moderate. For example, if a fetal heart tracing had moderate variability predominating in two periods it was deemed “mostly moderate.” If the moderate variability was predominant in all three it was deemed as “always moderate.” If only one 10-minute period was available, the predominant pattern was categorized as “ever.” If only two 10-minute periods were available, the predominant pattern was categorized as “mostly.” Accelerations and decelerations were described as present if they occurred in any of the three periods. The absolute number of each were calculated, and decelerations were further classified as early, variable, late, or prolonged according to NICHD guidelines.7 EFM patterns before delivery were compared between IUGR and non-IUGR infants. A sensitivity analysis was performed, comparing IUGR to non-IUGR infants among only those apparently normal infants, excluding those with composite morbidity: arterial cord pH < 7.20, 5 minute Apgar < 7, or neonatal intensive care unit admission. Baseline characteristics were compared between groups using a chisquare and Fisher exact tests for categorical variables, and Student t-test or Mann-Whitney U test for continuous variables. Normality was determined by the Shapiro–Wilk test. Attributable risks (AR), adjusted odds ratios (aOR), and 95% confidence intervals (CIs) were calculated to estimate the association of growth restriction and specific EFM patterns. Stepwise backward multivariable logistic regression was used to adjust estimates of risk for potentially confounding factors. Differences between hierarchical explanatory models were assessed using the Wald test. The final models adjusted for obesity (body mass index 30 kg/m2), maternal race, prior vaginal delivery, smoking, prolonged first stage of labor, and labor induction. Model fit for the final models was assessed with the Hosmer–Lemeshow goodness-of-fit test. All statistical analyses were completed using STATA software package, version 12, special edition (StataCorp LP., College Station, TX).
Results The initial study population included 8,622 deliveries. All multiple gestations, anomalous infants, infants who delivered preterm, infants who delivered via first stage cesarean deliveries, and incarcerated mothers were excluded from this study. Only infants who had sufficient EFM and available umbilical cord gases were included (►Fig. 1). Of 5,388 pregnancies included in this study, 652 (12.1%) were IUGR. Maternal demographics and clinical characteristics are presented in ►Table 1. Labor type and use of regional anesthesia did not differ significantly among groups. Mothers of IUGR infants were more likely to be younger, nulliparous, of black race, use tobacco and alcohol, have a lower body mass index, and be of a lower gravidity. They were more likely to have an operative delivery, and were less likely to deliver via cesarean. They were less likely to have had a prior vaginal delivery, and were more likely to have had a prior cesarean. Growthrestricted infants were more likely to be born at a statistically younger gestational age as compared with non-IUGR infants.
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Fig. 1 Study population including all available cases, and all excluded cases.
IUGR infants had a shorter total time of active labor, and had a shorter second stage of labor. Baseline heart rate characteristics between IUGR and non-IUGR fetuses were compared in ►Table 2. There was no statistical difference between the two groups in regards to ever bradycardia or ever baseline < 120 bpm. Growthrestricted fetuses were less likely to have tachycardia (aOR 0.67, 95% CI 0.50–0.90). IUGR accounted for 4% of the lower rate of tachycardia (AR 0.4, 95% CI 0.07 to 0.02). There was no difference between IUGR and non-IUGR fetuses in regards to absent or minimal, moderate, or marked variability. Growth-restricted fetuses had less accelerations than their non-IUGR counterparts (aOR 0.63, 95% CI 0.63–0.93), accounting for 7% of reduction in accelerations (AR 0.07, 95% CI 0.11 to 0.03). IUGR fetuses had a higher rate of late decelerations (aOR 1.29, 95% CI 1.07 1.55), with a 6% increased frequency accounted for by growth restriction (AR 0.06, 95% CI 0.02 0.08). However, there was no difference between the total number of decelerations, and no difference between early, variable, or prolonged decelerations. Differences in intrapartum EFM patterns attributable to IUGR persisted when we excluded women with adverse neonatal outcomes (►Table 3). Growth-restricted fetuses without adverse neonatal outcomes were less likely to have tachycardia in the 30 minutes before delivery (aOR 0.74, 95% CI 0.55–0.99), with a 3% reduction attributable to IUGR (AR 0.03, 95% CI 0.06 to 0.01). There continued to be no difference between the groups in regards to ever bradycardia, ever < 120 bpm, or variability patterns.
When women with adverse neonatal outcomes were excluded, the FHR differences in the rates of accelerations and decelerations attributed to IUGR remained (►Table 3). IUGR fetuses were less likely to have accelerations (aOR 0.75, 95% CI 0.62–0.91), with a 7% reduction attributed to IUGR (0.0.7, 95% CI 0.11 to 0.04). Among the apparently normal infants, growth restriction still conferred a 6% increased risk of late decelerations (AR 0.6, 95% CI 1.06 1.55) without a statistical difference in the other NICHD categories of decelerations.
Conclusion We found that there are differences in the FHR patterns of IUGR fetuses compared with non-IUGR fetuses, and that these differences persist in the absence of neonatal morbidity in term infants. We found a modest increase in the rate of late decelerations attributable to IUGR. There was also a small reduction in fetal tachycardia and a decrease in the rate of accelerations. There were no differences in variability patterns. The fetus develops multiple systemic responses to growth restriction. The fetal cardiovascular responses to placental insufficiency can be categorized into early and late responses.2 Early adaptive responses result in preferential nutrient shunting to essential organs, and late responses occur once these redistributive responses fail.3 Late adaptive responses result in elevations in placental blood flow resistance and progressive placental insufficiency. These American Journal of Perinatology
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Table 1 Maternal demographics and clinical characteristics
Maternal age (y)
IUGR (n ¼ 652)
No IUGR (n ¼ 4736)
p-Value
23.6 6.0
24.5 5.9
< 0.01
BMI
29.5 6.6
31.9 6.9
< 0.01
Gravidity (median, IQ range)
2 (1–3)
2 (1–4)
< 0.01
Prior vaginal delivery
319 (48.9%)
2,873 (60.7%)
< 0.01
Nulliparous
307 (47.1%)
1,686 (35.6%)
< 0.01
Prior cesarean delivery
55 (8.4%)
292 (6.2%)
0.03
Gestational age (wk)
38.8 1.1
39.0 1.2
< 0.01
Black race
544 (83.4%)
3,380 (71.4%)
< 0.01
Induction
226 (34.6%)
1,427 (30.1%)
0.06
Augmentation
193 (29.6%)
1,527 (32.2%)
Labor
233 (35.7%)
1,782 (37.6%)
Length of active labor (min) (median, IQ range)
Spontaneous
205 (102–365)
245 (130–425)
< 0.01
Length of second stage (min) (median, IQ range)
20 (9–40)
25 (12–57)
< 0.01
Regional anesthesia
548 (84.1%)
3,969 (83.8%)
0.87
Vaginal, spontaneous
554 (85.0%)
4,064 (85.8%)
0.03
Vaginal, operative
94 (14.4%)
588 (12.4%)
Cesarean
Mode of delivery
4 (0.6%)
84 (1.8%)
Tobacco use
168 (25.8%)
812 (17.1%)
< 0.01
Alcohol use
17 (2.6%)
67 (1.4%)
0.03
Diabetes mellitus
26 (4.0%)
53 (1.1%)
0.12
Gestational diabetes
42 (6.5%)
128 (2.7%)
0.08
Abbreviations: BMI, body mass index; IQ, interquartile range; IUGR, intrauterine growth restriction.
responses can potentially lead to myocardial dysfunction and fetal demise.10 In normal fetal development, advancing gestation coincides with an increase in vagal tone which results in a decrease in baseline heart rate, and an increase in shortand long-term variability, FHR variation, and the amplitude of accelerations.2,3 When placental insufficiency disrupts normal development, the fetus adapts via many systemic responses which impact fetal behavioral responses and FHR characteristics. The 2008 NICHD report discussed the need for further EFM research given its highly prevalent use in obstetric practice.7 There are limited data regarding specific maternal or fetal conditions and their potential impact on FHR tracings. Currently, there are small observational studies and case reports regarding growth restriction and FHR patterns.5,6,11 One study suggested that IUGR infants have a higher proportion of “lower amplitude” accelerations, and a lower amount of total accelerations altogether.5 Another small study examining 27 growth-restricted fetuses, found that there was a higher baseline FHR in IUGR fetuses.6 Multiple studies have found that there is a lower rate of FHR variation in IUGR fetuses as compared with non-IUGR controls.6,11 These were small observational studies that were limited by their sample American Journal of Perinatology
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size, and they did not examine fetuses in the absence of neonatal morbidity which we believe assists in best approximating the attributable risk of IUGR for specific FHR patterns. Our findings supported prior data that growth-restricted fetuses had a reduced rate of accelerations, and a decreased risk of fetal tachycardia. Our study did not find a difference in FHR variation among IUGR fetuses and controls. Our study offers several advantages over previous studies. We analyzed a large cohort of women, which allowed us to adjust for potentially confounding factors. Our data also included markers of neonatal morbidity. This allowed us to exclude those infants in a secondary analysis to determine that the differences we found were due to IUGR and not due to confounders associated with IUGR. Another strength of our study is that all FHR tracings were interpreted prospectively by two formally trained research nurses who were blinded to clinical data using the 2008 NICHD guidelines and previously demonstrated to have a high rate of reproducibility. This confers generalizability to our study given that human interpretation is how EFM is used in clinical practice. Our study is not without limitations to consider. We excluded all preterm and anomalous gestations from our cohort, which could potentially limit the ability to generalize
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Table 2 Unadjusted and adjusted risk estimates of fetal heart rate characteristics overall IUGR (n ¼ 652)
No IUGR (n ¼ 4736)
Attributable risk (95% CI)
Adjusted ORa (95% CI)
Baseline Ever bradycardia < 110 bpm
12 (1.8%)
71 (1.5%)
0.00 (0.01 to 0.01)
1.10 (0.58–1.07)
Ever baseline < 120 bpm
77 (11.8%)
436 (9.2%)
0.03 (0.00 to 0.05)
1.19 (0.91–1.56)
Ever tachycardia > 160 bpm
60 (9.2%)
642 (13.6%)
0.04 (0.07 to 0.02)
0.67 (0.50–0.90)
Ever absent or minimal
289 (44.3%)
2,047 (43.2%)
0.01 (0.03 to 0.05)
1.04 (0.87–1.24)
Mostly absent or minimal
182 (27.9%)
1,186 (25.1%)
0.03 (0.01 to 0.07)
1.17 (0.96–1.42)
Always absent or minimal
91 (14.0%)
585 (12.4%)
0.02 (0.01 to 0.04)
1.14 (0.89–1.48)
Mostly moderate
445 (68.3%)
3,356 (70.9%)
0.03 (0.06 to 0.01)
0.88 (0.73–1.06)
Always moderate
313 (48.0%)
2,303 (48.6%)
0.01 (0.05 to 0.03)
0.99 (0.83–1.17)
Ever marked
28 (4.3%)
238 (5.0%)
0.01 (0.02 to 0.01)
0.77 (0.51–1.16)
Accelerations present
189 (29.0%)
1,699 (35.9%)
0.07 (0.11 to 0.03)
0.77 (0.63–0.93)
Number of accelerations (median, IQ range)
0 (0–1)
0 (0–1)
p < 0.01
–
Decelerations present
630 (96.6%)
4,526 (95.6%)
0.01 (0.00 to 0.03)
1.25 (0.76 2.03)
Number of decelerations (median, IQ range)
7 (4–9)
6 (3–9)
p ¼ 0.02
–
Early decelerations
18 (2.8%)
126 (2.7%)
0.00 (0.01 to 0.01)
1.08 (0.65–1.81)
Accelerations
Decelerations
Variable decelerations
590 (90.5%)
4,199 (88.7%)
0.02 (0.01 to 0.04)
1.23 (0.91–1.66)
Late decelerations
447 (68.6%)
2,971 (62.8%)
0.06 (0.02–0.10)
1.29 (1.07–1.55)
Prolonged decelerations
332 (50.9%)
2,280 (48.2%)
0.03 (0.01 to 0.07)
1.10 (0.92–1.31)
Abbreviations: bpm, beats per minute; CI, confidence interval; IUGR, intrauterine growth restriction; IQ, interquartile; OR, odds ratio. a Adjusted for obesity, race, prior vaginal delivery, smoking, prolonged first stage of labor, and induction.
Table 3 Unadjusted and adjusted risk estimates of fetal heart rate characteristics, excluding women with composite of adverse neonatal outcomes IUGR (n ¼ 641)
No IUGR (n ¼ 4570)
Attributable risk (95% CI)
Adjusted ORa (95% CI)
Ever bradycardia < 110 bpm
12 (1.9%)
70 (1.5%)
0.00 (0.01 to 0.01)
1.09 (0.58–2.05)
Ever baseline < 120 bpm
75 (11.7%)
427 (9.3%)
0.02 (0.00 to 0.05)
1.15 (0.88–1.52)
Ever tachycardia > 160 bpm
58 (9.1%)
568 (12.4%)
0.03 (0.06 to 0.01)
0.74 (0.55–0.99)
Ever absent or minimal
284 (44.3%)
1,974 (43.2%)
0.01 (0.03 to 0.05)
1.04 (0.87–1.24)
Mostly absent or minimal
181 (28.2%)
1,146 (25.1%)
0.03 (0.01 to 0.07)
1.18 (0.97–1.44)
Baseline
Variability
Always absent or minimal
91 (14.2%)
558 (12.2%)
0.02 (0.01 to 0.05)
1.18 (0.91 1.53)
Mostly moderate
435 (67.9%)
3,247 (71.1%)
0.03 (0.07 to 0.01)
0.86 (0.71–1.03)
Always moderate
308 (48.1%)
2,235 (48.9%)
0.01 (0.05 to 0.03)
0.97 (0.82–1.16)
Ever marked
28 (4.4%)
225 (4.9%)
0.01 (0.02 to 0.01)
0.81 (0.53–1.22) (Continued)
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Table 3 (Continued) Attributable risk (95% CI)
Adjusted ORa (95% CI)
1,661 (36.4%)
0.07 (0.11 to 0.04)
0.75 (0.62–0.91)
0 (0–1)
p < 0.01
–
619 (96.6%)
4,364 (95.5%)
0.01 (0.00 to 0.03)
1.26 (0.77–2.05)
Number of decelerations (median, IQ range)
7 (4–9)
6 (3–9)
p ¼ 0.01
–
Early decelerations
17 (2.7%)
122 (2.7%)
0.00 (0.01 to 0.01)
1.02 (0.60–1.72)
Variable decelerations
579 (90.3%)
4,048 (88.6%)
0.02 (0.01 to 0.04)
1.21 (0.90–1.64)
Late decelerations
438 (68.3%)
2,860 (62.6%)
0.06 (0.02–0.10)
1.28 (1.06–1.55)
Prolonged decelerations
323 (50.4%)
2,188 (47.9%)
0.03 (0.02 to 0.07)
1.08 (0.91–1.29)
IUGR (n ¼ 641)
No IUGR (n ¼ 4570)
Accelerations present
186 (29.0%)
Number of accelerations (median, IQ range)
0 (0–1)
Decelerations present
Accelerations
Decelerations
Abbreviations: bpm, beats per minute; CI, confidence interval; IUGR, intrauterine growth restriction; IQ, interquartile; OR, odds ratio. a Adjusted for obesity, race, prior vaginal delivery, smoking, prolonged first stage of labor, induction.
our data for all IUGR fetuses. However, by excluding these infants, we eliminated the possible confounding factors that could have been introduced into our cohort. Another potential limitation is that we evaluated EFM patterns in the 30 minutes before delivery. This could have caused us to miss differences in FHR patterns between IUGR and non-IUGR fetuses earlier in labor. However, we chose to evaluate this time period given that the 30 minutes before delivery are most proximate to the outcomes measured and represent a critical time for clinical decision-making. Since the 2008 National Consensus Conference, practitioners have had universal guidelines for the interpretation of FHR patterns. These guidelines however do not take account specific clinical conditions, and impart a “one-size fits all” approach to FHR tracings. Our results suggest that there are clinical conditions, such as IUGR, which impart differences in intrapartum FHR patterns. As we learn more about these differences, it is possible that intrapartum EFM patterns should be interpreted differently based on a priori risk of acidemia, but there remains much work that needs to be done to determine how this information should be used clinically.
References 1 Intrapartum fetal heart rate monitoring: nomenclature, interpre-
2
3 4
5
6
7
8
Note Dr. Cahill is a Robert Wood Johnson Foundation Physician Faculty Scholar, which supported this work. Data from this study was presented as a poster on February 16, 2013 at the SMFM Annual Meeting (Abstract 748).
Conflict of Interest The authors report no conflict of interest.
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tation, and general management principles. ACOG Practice Bulletin No. 106, American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114(1):192–202 Baschat AA, Galan HL, Gabbe SG. Intrauterine growth restriction. In Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics: Normal and Problem Pregnancies. 6th ed. Philadelphia, PA: Saunders Elsevier; 2012:706–741 Baschat AA. Fetal responses to placental insufficiency: an update. BJOG 2004;111(10):1031–1041 Arduini D, Rizzo G, Caforio L, Boccolini MR, Romanini C, Mancuso S. Behavioural state transitions in healthy and growth retarded fetuses. Early Hum Dev 1989;19(3):155–165 Gagnon R, Hunse C, Bocking AD. Fetal heart rate patterns in the small-for-gestational-age human fetus. Am J Obstet Gynecol 1989; 161(3):779–784 Henson G, Dawes GS, Redman CW. Characterization of the reduced heart rate variation in growth-retarded fetuses. Br J Obstet Gynaecol 1984;91(8):751–755 Macones GA, Hankins GD, Spong CY, Hauth J, Moore T. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: update on definitions, interpretation, and research guidelines. Obstet Gynecol 2008; 112(3):661–666 Cahill AG, Roehl KA, Odibo AO, Macones GA. Association and prediction of neonatal acidemia. Am J Obstet Gynecol 2012; 207(3):206.e1–206.e8 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87(2):163–168 Rizzo G, Capponi A, Pietropolli A, Bufalino LM, Arduini D, Romanini C. Fetal cardiac and extracardiac flows preceding intrauterine death. Ultrasound Obstet Gynecol 1994;4(2):139–142 Nijhuis IJ, ten Hof J, Mulder EJ, et al. Fetal heart rate in relation to its variation in normal and growth retarded fetuses. Eur J Obstet Gynecol Reprod Biol 2000;89(1):27–33
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Effect of Growth Restriction on Fetal Heart Rate Patterns in the Second Stage of Labor Kristina A. Epplin, MD1 Methodius G. Tuuli, MD, MPH1 Anthony O. Odibo, MD, MSCE2 Kimberly A. Roehl, MPH1 George A. Macones, MD, MSCE1 Alison G. Cahill, MD, MSCI1 1 Department of Obstetrics and Gynecology, Washington University in
St. Louis, St. Louis, Missouri 2 Department of Obstetrics and Gynecology, University of South Florida, Tampa, Florida
Address for correspondence Kristina A. Epplin, MD, Department of Obstetrics and Gynecology, Washington University in St. Louis, Campus Box 8064, 660 S. Euclid Avenue, St. Louis, MO 63110 (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
fetal monitoring fetal heart rate growth restriction IUGR
Objective We aimed to estimate the effect of intrauterine growth restriction (IUGR) on electronic fetal monitoring (EFM) patterns in the second stage of labor. Study Design We performed a 5-year retrospective cohort study of consecutive singleton, nonanomalous, term gestations. We compared IUGR infants, those with a birth weight less than the 10th percentile, with non-IUGR infants, those greater than or equal to the 10th percentile. Our primary outcome was the EFM patterns in the 30 minutes before delivery. A secondary analysis was performed excluding infants with composite morbidity. Logistic regression was used to adjust for body mass index, race, nulliparity, induction, and protracted labor. Results Out of the 5,388 infants, 652 (12.1%) were IUGR. IUGR fetuses had less accelerations (29.0 vs. 35.9%, p < 0.01), even among apparently normal infants (29.0 vs. 36.4%, p < 0.01). IUGR fetuses had a higher risk of decelerations, and in all, IUGR accounted for 6% of late decelerations (attributable risk 0.06, 95% confidence interval 0.02–0.10). There was no significant association between IUGR and bradycardia or minimal variability. Conclusion Growth restriction at term confers an increased risk of late decelerations, even in the absence of neonatal morbidity. EFM patterns may require different interpretations based on a priori risk and clinical factors.
Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality, and is associated with a higher incidence of intrapartum acidemia.1,2 During normal fetal development, fetal behavior and variation of the fetal heart rate become increasingly sophisticated with increasing gestation. In growth-restricted fetuses with chronic hypoxemia and placental dysfunction, there is a delay in all aspects of central nervous system (CNS) maturation.3,4 Small previous studies on electronic fetal monitoring (EFM) in growthrestricted fetuses have suggested that there is an increase in the baseline fetal heart rate (FHR) due to a delay in CNS
maturation.5 These studies have also suggested that there is diminished FHR variation in response to growth restriction and chronic hypoxemia.6 However, there is limited data on intrapartum FHR patterns, a time during which obstetricians rely on EFM to guide management decisions. Intrapartum EFM is used by obstetric providers with common nomenclature endorsed by the American College of Obstetricians and Gynecologists, the Society of Maternal-Fetal Medicine, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) since a 2008 consensus conference.7 However, despite differences in a priori
received August 17, 2014 accepted after revision December 2, 2014 published online January 21, 2015
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1543954. ISSN 0735-1631.
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Am J Perinatol 2015;32:873–878.
Effect of IUGR on EFM Patterns in the Second Stage of Labor risk of acidemia with specific clinical conditions, nurses and providers still use the same system for nomenclature and interpretation. At present, data are lacking to identify differences in intrapartum EFM patterns that are specifically attributable to a variation in clinical characteristics. We aimed to estimate differences in intrapartum EFM patterns between term IUGR infants and non-IUGR infants in the second stage of labor, and their relationship to adverse neonatal outcomes.
Materials and Methods We conducted a 5-year retrospective cohort study, from 2004 through 2008, of consecutive term deliveries at a single, large, tertiary care medical center in the Midwest. The aim of the parent study was to estimate the correlation between FHR patterns in the second stage of labor and acidemia at birth.8 Women included in the cohort had term ( 37 weeks), cephalic, nonanomalous, singleton gestations who reached the second stage of labor. All included participants had at least 10 minutes of EFM in the 30 minutes before birth, and had available umbilical cord gases. There is an institutional policy of universal EFM use and obtaining umbilical cord gases. Those excluded were women who did not labor and women who delivered by cesarean delivery before complete dilation. The study was conducted with the approval of the institutional review board. Detailed maternal sociodemographic information, obstetric and medical history, intrapartum course, complications data, and neonatal characteristics were collected from the medical record by trained research personnel. The active phase of labor was determined from the medical record and was considered as the time for which a patient had a documented cervical examination of 6 to 10 cm. IUGR was defined as birth weight less than the 10th percentile for gestational age at delivery defined by the Alexander birth weight reference curves.9 These infants were compared with all infants greater than or equal to the 10th percentile. Pregnancies were dated by last menstrual period (LMP) if known and concordant with ultrasound (7 days of firsttrimester ultrasound or 14 days of second-trimester ultrasound). If the LMP was unknown or discordant the earliest available ultrasound was used. The FHR tracing in the 30 minutes before delivery was interpreted prospectively by two formally trained and credentialed obstetric research nurses blinded to all clinical and outcome data using NICHD criteria. The 30 minutes of EFM data before delivery were divided into three 10-minute periods and analyzed individually. The average baseline for each of these 10-minute periods was calculated and rounded to the nearest 5 beats per minute (bpm). Baseline heart rate characteristics were determined such as ever bradycardia < 110 bpm, ever < 120 bpm, or ever tachycardia > 160 bpm, if that was the predominant pattern in at least one of three 10-minute periods. Variability was classified as ever absent or minimal, or ever marked if that was the predominant pattern in one of the three 10-minute periods. The descriptor “mostly” was used if a pattern was predominant in two of the three periods. American Journal of Perinatology
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“Always” was used if a pattern was predominant in all three 10-minute periods, such as always absent or minimal, or always moderate. For example, if a fetal heart tracing had moderate variability predominating in two periods it was deemed “mostly moderate.” If the moderate variability was predominant in all three it was deemed as “always moderate.” If only one 10-minute period was available, the predominant pattern was categorized as “ever.” If only two 10-minute periods were available, the predominant pattern was categorized as “mostly.” Accelerations and decelerations were described as present if they occurred in any of the three periods. The absolute number of each were calculated, and decelerations were further classified as early, variable, late, or prolonged according to NICHD guidelines.7 EFM patterns before delivery were compared between IUGR and non-IUGR infants. A sensitivity analysis was performed, comparing IUGR to non-IUGR infants among only those apparently normal infants, excluding those with composite morbidity: arterial cord pH < 7.20, 5 minute Apgar < 7, or neonatal intensive care unit admission. Baseline characteristics were compared between groups using a chisquare and Fisher exact tests for categorical variables, and Student t-test or Mann-Whitney U test for continuous variables. Normality was determined by the Shapiro–Wilk test. Attributable risks (AR), adjusted odds ratios (aOR), and 95% confidence intervals (CIs) were calculated to estimate the association of growth restriction and specific EFM patterns. Stepwise backward multivariable logistic regression was used to adjust estimates of risk for potentially confounding factors. Differences between hierarchical explanatory models were assessed using the Wald test. The final models adjusted for obesity (body mass index 30 kg/m2), maternal race, prior vaginal delivery, smoking, prolonged first stage of labor, and labor induction. Model fit for the final models was assessed with the Hosmer–Lemeshow goodness-of-fit test. All statistical analyses were completed using STATA software package, version 12, special edition (StataCorp LP., College Station, TX).
Results The initial study population included 8,622 deliveries. All multiple gestations, anomalous infants, infants who delivered preterm, infants who delivered via first stage cesarean deliveries, and incarcerated mothers were excluded from this study. Only infants who had sufficient EFM and available umbilical cord gases were included (►Fig. 1). Of 5,388 pregnancies included in this study, 652 (12.1%) were IUGR. Maternal demographics and clinical characteristics are presented in ►Table 1. Labor type and use of regional anesthesia did not differ significantly among groups. Mothers of IUGR infants were more likely to be younger, nulliparous, of black race, use tobacco and alcohol, have a lower body mass index, and be of a lower gravidity. They were more likely to have an operative delivery, and were less likely to deliver via cesarean. They were less likely to have had a prior vaginal delivery, and were more likely to have had a prior cesarean. Growthrestricted infants were more likely to be born at a statistically younger gestational age as compared with non-IUGR infants.
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Fig. 1 Study population including all available cases, and all excluded cases.
IUGR infants had a shorter total time of active labor, and had a shorter second stage of labor. Baseline heart rate characteristics between IUGR and non-IUGR fetuses were compared in ►Table 2. There was no statistical difference between the two groups in regards to ever bradycardia or ever baseline < 120 bpm. Growthrestricted fetuses were less likely to have tachycardia (aOR 0.67, 95% CI 0.50–0.90). IUGR accounted for 4% of the lower rate of tachycardia (AR 0.4, 95% CI 0.07 to 0.02). There was no difference between IUGR and non-IUGR fetuses in regards to absent or minimal, moderate, or marked variability. Growth-restricted fetuses had less accelerations than their non-IUGR counterparts (aOR 0.63, 95% CI 0.63–0.93), accounting for 7% of reduction in accelerations (AR 0.07, 95% CI 0.11 to 0.03). IUGR fetuses had a higher rate of late decelerations (aOR 1.29, 95% CI 1.07 1.55), with a 6% increased frequency accounted for by growth restriction (AR 0.06, 95% CI 0.02 0.08). However, there was no difference between the total number of decelerations, and no difference between early, variable, or prolonged decelerations. Differences in intrapartum EFM patterns attributable to IUGR persisted when we excluded women with adverse neonatal outcomes (►Table 3). Growth-restricted fetuses without adverse neonatal outcomes were less likely to have tachycardia in the 30 minutes before delivery (aOR 0.74, 95% CI 0.55–0.99), with a 3% reduction attributable to IUGR (AR 0.03, 95% CI 0.06 to 0.01). There continued to be no difference between the groups in regards to ever bradycardia, ever < 120 bpm, or variability patterns.
When women with adverse neonatal outcomes were excluded, the FHR differences in the rates of accelerations and decelerations attributed to IUGR remained (►Table 3). IUGR fetuses were less likely to have accelerations (aOR 0.75, 95% CI 0.62–0.91), with a 7% reduction attributed to IUGR (0.0.7, 95% CI 0.11 to 0.04). Among the apparently normal infants, growth restriction still conferred a 6% increased risk of late decelerations (AR 0.6, 95% CI 1.06 1.55) without a statistical difference in the other NICHD categories of decelerations.
Conclusion We found that there are differences in the FHR patterns of IUGR fetuses compared with non-IUGR fetuses, and that these differences persist in the absence of neonatal morbidity in term infants. We found a modest increase in the rate of late decelerations attributable to IUGR. There was also a small reduction in fetal tachycardia and a decrease in the rate of accelerations. There were no differences in variability patterns. The fetus develops multiple systemic responses to growth restriction. The fetal cardiovascular responses to placental insufficiency can be categorized into early and late responses.2 Early adaptive responses result in preferential nutrient shunting to essential organs, and late responses occur once these redistributive responses fail.3 Late adaptive responses result in elevations in placental blood flow resistance and progressive placental insufficiency. These American Journal of Perinatology
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Table 1 Maternal demographics and clinical characteristics
Maternal age (y)
IUGR (n ¼ 652)
No IUGR (n ¼ 4736)
p-Value
23.6 6.0
24.5 5.9
< 0.01
BMI
29.5 6.6
31.9 6.9
< 0.01
Gravidity (median, IQ range)
2 (1–3)
2 (1–4)
< 0.01
Prior vaginal delivery
319 (48.9%)
2,873 (60.7%)
< 0.01
Nulliparous
307 (47.1%)
1,686 (35.6%)
< 0.01
Prior cesarean delivery
55 (8.4%)
292 (6.2%)
0.03
Gestational age (wk)
38.8 1.1
39.0 1.2
< 0.01
Black race
544 (83.4%)
3,380 (71.4%)
< 0.01
Induction
226 (34.6%)
1,427 (30.1%)
0.06
Augmentation
193 (29.6%)
1,527 (32.2%)
Labor
233 (35.7%)
1,782 (37.6%)
Length of active labor (min) (median, IQ range)
Spontaneous
205 (102–365)
245 (130–425)
< 0.01
Length of second stage (min) (median, IQ range)
20 (9–40)
25 (12–57)
< 0.01
Regional anesthesia
548 (84.1%)
3,969 (83.8%)
0.87
Vaginal, spontaneous
554 (85.0%)
4,064 (85.8%)
0.03
Vaginal, operative
94 (14.4%)
588 (12.4%)
Cesarean
Mode of delivery
4 (0.6%)
84 (1.8%)
Tobacco use
168 (25.8%)
812 (17.1%)
< 0.01
Alcohol use
17 (2.6%)
67 (1.4%)
0.03
Diabetes mellitus
26 (4.0%)
53 (1.1%)
0.12
Gestational diabetes
42 (6.5%)
128 (2.7%)
0.08
Abbreviations: BMI, body mass index; IQ, interquartile range; IUGR, intrauterine growth restriction.
responses can potentially lead to myocardial dysfunction and fetal demise.10 In normal fetal development, advancing gestation coincides with an increase in vagal tone which results in a decrease in baseline heart rate, and an increase in shortand long-term variability, FHR variation, and the amplitude of accelerations.2,3 When placental insufficiency disrupts normal development, the fetus adapts via many systemic responses which impact fetal behavioral responses and FHR characteristics. The 2008 NICHD report discussed the need for further EFM research given its highly prevalent use in obstetric practice.7 There are limited data regarding specific maternal or fetal conditions and their potential impact on FHR tracings. Currently, there are small observational studies and case reports regarding growth restriction and FHR patterns.5,6,11 One study suggested that IUGR infants have a higher proportion of “lower amplitude” accelerations, and a lower amount of total accelerations altogether.5 Another small study examining 27 growth-restricted fetuses, found that there was a higher baseline FHR in IUGR fetuses.6 Multiple studies have found that there is a lower rate of FHR variation in IUGR fetuses as compared with non-IUGR controls.6,11 These were small observational studies that were limited by their sample American Journal of Perinatology
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size, and they did not examine fetuses in the absence of neonatal morbidity which we believe assists in best approximating the attributable risk of IUGR for specific FHR patterns. Our findings supported prior data that growth-restricted fetuses had a reduced rate of accelerations, and a decreased risk of fetal tachycardia. Our study did not find a difference in FHR variation among IUGR fetuses and controls. Our study offers several advantages over previous studies. We analyzed a large cohort of women, which allowed us to adjust for potentially confounding factors. Our data also included markers of neonatal morbidity. This allowed us to exclude those infants in a secondary analysis to determine that the differences we found were due to IUGR and not due to confounders associated with IUGR. Another strength of our study is that all FHR tracings were interpreted prospectively by two formally trained research nurses who were blinded to clinical data using the 2008 NICHD guidelines and previously demonstrated to have a high rate of reproducibility. This confers generalizability to our study given that human interpretation is how EFM is used in clinical practice. Our study is not without limitations to consider. We excluded all preterm and anomalous gestations from our cohort, which could potentially limit the ability to generalize
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Table 2 Unadjusted and adjusted risk estimates of fetal heart rate characteristics overall IUGR (n ¼ 652)
No IUGR (n ¼ 4736)
Attributable risk (95% CI)
Adjusted ORa (95% CI)
Baseline Ever bradycardia < 110 bpm
12 (1.8%)
71 (1.5%)
0.00 (0.01 to 0.01)
1.10 (0.58–1.07)
Ever baseline < 120 bpm
77 (11.8%)
436 (9.2%)
0.03 (0.00 to 0.05)
1.19 (0.91–1.56)
Ever tachycardia > 160 bpm
60 (9.2%)
642 (13.6%)
0.04 (0.07 to 0.02)
0.67 (0.50–0.90)
Ever absent or minimal
289 (44.3%)
2,047 (43.2%)
0.01 (0.03 to 0.05)
1.04 (0.87–1.24)
Mostly absent or minimal
182 (27.9%)
1,186 (25.1%)
0.03 (0.01 to 0.07)
1.17 (0.96–1.42)
Always absent or minimal
91 (14.0%)
585 (12.4%)
0.02 (0.01 to 0.04)
1.14 (0.89–1.48)
Mostly moderate
445 (68.3%)
3,356 (70.9%)
0.03 (0.06 to 0.01)
0.88 (0.73–1.06)
Always moderate
313 (48.0%)
2,303 (48.6%)
0.01 (0.05 to 0.03)
0.99 (0.83–1.17)
Ever marked
28 (4.3%)
238 (5.0%)
0.01 (0.02 to 0.01)
0.77 (0.51–1.16)
Accelerations present
189 (29.0%)
1,699 (35.9%)
0.07 (0.11 to 0.03)
0.77 (0.63–0.93)
Number of accelerations (median, IQ range)
0 (0–1)
0 (0–1)
p < 0.01
–
Decelerations present
630 (96.6%)
4,526 (95.6%)
0.01 (0.00 to 0.03)
1.25 (0.76 2.03)
Number of decelerations (median, IQ range)
7 (4–9)
6 (3–9)
p ¼ 0.02
–
Early decelerations
18 (2.8%)
126 (2.7%)
0.00 (0.01 to 0.01)
1.08 (0.65–1.81)
Accelerations
Decelerations
Variable decelerations
590 (90.5%)
4,199 (88.7%)
0.02 (0.01 to 0.04)
1.23 (0.91–1.66)
Late decelerations
447 (68.6%)
2,971 (62.8%)
0.06 (0.02–0.10)
1.29 (1.07–1.55)
Prolonged decelerations
332 (50.9%)
2,280 (48.2%)
0.03 (0.01 to 0.07)
1.10 (0.92–1.31)
Abbreviations: bpm, beats per minute; CI, confidence interval; IUGR, intrauterine growth restriction; IQ, interquartile; OR, odds ratio. a Adjusted for obesity, race, prior vaginal delivery, smoking, prolonged first stage of labor, and induction.
Table 3 Unadjusted and adjusted risk estimates of fetal heart rate characteristics, excluding women with composite of adverse neonatal outcomes IUGR (n ¼ 641)
No IUGR (n ¼ 4570)
Attributable risk (95% CI)
Adjusted ORa (95% CI)
Ever bradycardia < 110 bpm
12 (1.9%)
70 (1.5%)
0.00 (0.01 to 0.01)
1.09 (0.58–2.05)
Ever baseline < 120 bpm
75 (11.7%)
427 (9.3%)
0.02 (0.00 to 0.05)
1.15 (0.88–1.52)
Ever tachycardia > 160 bpm
58 (9.1%)
568 (12.4%)
0.03 (0.06 to 0.01)
0.74 (0.55–0.99)
Ever absent or minimal
284 (44.3%)
1,974 (43.2%)
0.01 (0.03 to 0.05)
1.04 (0.87–1.24)
Mostly absent or minimal
181 (28.2%)
1,146 (25.1%)
0.03 (0.01 to 0.07)
1.18 (0.97–1.44)
Baseline
Variability
Always absent or minimal
91 (14.2%)
558 (12.2%)
0.02 (0.01 to 0.05)
1.18 (0.91 1.53)
Mostly moderate
435 (67.9%)
3,247 (71.1%)
0.03 (0.07 to 0.01)
0.86 (0.71–1.03)
Always moderate
308 (48.1%)
2,235 (48.9%)
0.01 (0.05 to 0.03)
0.97 (0.82–1.16)
Ever marked
28 (4.4%)
225 (4.9%)
0.01 (0.02 to 0.01)
0.81 (0.53–1.22) (Continued)
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Table 3 (Continued) Attributable risk (95% CI)
Adjusted ORa (95% CI)
1,661 (36.4%)
0.07 (0.11 to 0.04)
0.75 (0.62–0.91)
0 (0–1)
p < 0.01
–
619 (96.6%)
4,364 (95.5%)
0.01 (0.00 to 0.03)
1.26 (0.77–2.05)
Number of decelerations (median, IQ range)
7 (4–9)
6 (3–9)
p ¼ 0.01
–
Early decelerations
17 (2.7%)
122 (2.7%)
0.00 (0.01 to 0.01)
1.02 (0.60–1.72)
Variable decelerations
579 (90.3%)
4,048 (88.6%)
0.02 (0.01 to 0.04)
1.21 (0.90–1.64)
Late decelerations
438 (68.3%)
2,860 (62.6%)
0.06 (0.02–0.10)
1.28 (1.06–1.55)
Prolonged decelerations
323 (50.4%)
2,188 (47.9%)
0.03 (0.02 to 0.07)
1.08 (0.91–1.29)
IUGR (n ¼ 641)
No IUGR (n ¼ 4570)
Accelerations present
186 (29.0%)
Number of accelerations (median, IQ range)
0 (0–1)
Decelerations present
Accelerations
Decelerations
Abbreviations: bpm, beats per minute; CI, confidence interval; IUGR, intrauterine growth restriction; IQ, interquartile; OR, odds ratio. a Adjusted for obesity, race, prior vaginal delivery, smoking, prolonged first stage of labor, induction.
our data for all IUGR fetuses. However, by excluding these infants, we eliminated the possible confounding factors that could have been introduced into our cohort. Another potential limitation is that we evaluated EFM patterns in the 30 minutes before delivery. This could have caused us to miss differences in FHR patterns between IUGR and non-IUGR fetuses earlier in labor. However, we chose to evaluate this time period given that the 30 minutes before delivery are most proximate to the outcomes measured and represent a critical time for clinical decision-making. Since the 2008 National Consensus Conference, practitioners have had universal guidelines for the interpretation of FHR patterns. These guidelines however do not take account specific clinical conditions, and impart a “one-size fits all” approach to FHR tracings. Our results suggest that there are clinical conditions, such as IUGR, which impart differences in intrapartum FHR patterns. As we learn more about these differences, it is possible that intrapartum EFM patterns should be interpreted differently based on a priori risk of acidemia, but there remains much work that needs to be done to determine how this information should be used clinically.
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Note Dr. Cahill is a Robert Wood Johnson Foundation Physician Faculty Scholar, which supported this work. Data from this study was presented as a poster on February 16, 2013 at the SMFM Annual Meeting (Abstract 748).
Conflict of Interest The authors report no conflict of interest.
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