Prolonged second stage of labor and risk of subsequent spontaneous preterm birth

Journal Pre-proof Prolonged second stage of labor and risk of subsequent spontaneous preterm birth Nasim C. Sobhani, MD, Arianna G. Cassidy, MD, Marya G. Zlatnik, MD MMS, Melissa G. Rosenstein, MD MAS PII:

S2589-9333(20)30013-6

DOI:

https://doi.org/10.1016/j.ajogmf.2020.100093

Reference:

AJOGMF 100093

To appear in:

American Journal of Obstetrics & Gynecology MFM

Received Date: 25 November 2019 Revised Date:

10 February 2020

Accepted Date: 11 February 2020

Please cite this article as: Sobhani NC, Cassidy AG, Zlatnik MG, Rosenstein MG, Prolonged second stage of labor and risk of subsequent spontaneous preterm birth, American Journal of Obstetrics & Gynecology MFM (2020), doi: https://doi.org/10.1016/j.ajogmf.2020.100093. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Elsevier Inc. All rights reserved.

1 Title: Prolonged second stage of labor and risk of subsequent spontaneous preterm birth

Authors: Nasim C SOBHANI MD, Arianna G CASSIDY MD, Marya G ZLATNIK MD MMS, Melissa G ROSENSTEIN MD MAS

Affiliations: All authors are affiliated with the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco.

Conflicts of interest: The authors report no conflict of interest.

Source of funding: No external funding source.

Presentation: This study was presented in poster format at the Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists in Nashville, Tennessee from May 3 to May 6, 2019.

Corresponding author: Nasim Sobhani, MD, 550 16th Street, 7th Floor, Box 0132, San Francisco, California 94158 | Telephone: 415-502-3231 | Fax: 415-353-2226 | Email address: [email protected]

Main text word count: 3029

Abstract word count: 507

2 Condensation: A prolonged second stage ≥ 4 hours in the first pregnancy does not increase the risk of spontaneous preterm birth in the subsequent pregnancy.

Short title: Prolonged second stage and spontaneous preterm birth

AJOG at a glance A. Why was this study conducted? To determine whether length of second stage in the first pregnancy is associated with spontaneous preterm birth (sPTB) in the next pregnancy. B. What are the key findings? The risk of sPTB was not increased among women with a second stage ≥ 4 hours. Although the risk of sPTB appeared to be increased after a second stage ≥ 7 hours on univariate analysis, this finding was no longer statistically significant after adjusting for mode of delivery. There was a non-significant increase in the risk of sPTB among those who delivered via cesarean section following second stage ≥ 7 hours compared to those who delivered vaginally following second stage ≥ 7 hours. C. What does this study add to what is already known? These findings contribute to a growing body of evidence demonstrating that prolonged second stage alone does not contribute to sPTB risk. However, there appears to be an increase in sPTB among those with a very prolonged second stage and a cesarean delivery, suggesting an important interaction between mode of delivery, length of second stage, and risk of sPTB.

Keywords: cesarean delivery, labor duration, preterm delivery, second stage of labor

3 1

Abstract

2

Background: Preterm birth is the leading cause of neonatal morbidity and mortality in the

3

United States. While many risk factors for spontaneous preterm birth have been elucidated, some

4

women with a prior term delivery experience spontaneous preterm birth in the absence of any

5

identifiable risk factors. Cervical trauma during a prolonged second stage of labor has been

6

postulated as a potential contributor to subsequent spontaneous preterm birth.

7

Objective: This study was designed to examine the relationship between the length of the second

8

stage of labor in the first pregnancy and the risk of spontaneous preterm birth in the subsequent

9

pregnancy.

10

Study design: This was a retrospective cohort study of all women with two consecutive

11

singleton deliveries at a single institution between July 2012 and June 2018, with the first

12

delivery occurring at or beyond 37 weeks. Multiparous women and those who did not reach the

13

second stage of labor in the first pregnancy were excluded. Prolonged second stage was defined

14

as ≥ 4 hours, based on the 75th percentile for this cohort and on recommendations from the

15

National Institute of Child Health and Human Development. Very prolonged second stage was

16

defined as ≥ 7 hours, based on the 95th percentile for this cohort. The primary outcome was

17

spontaneous preterm birth before 37 weeks in the subsequent pregnancy. The Kruskal-Wallis test

18

compared median values for non-parametric continuous variables, Fisher’s exact tests compared

19

proportions for categorical variables, and logistic regression generated odds ratios.

20

Results: A total of 1,032 women met criteria for study inclusion, with an overall subsequent

21

spontaneous preterm birth rate of 3.1%. Prolonged second stage ≥ 4 hours was identified in

22

24.4% (252/1032) of the cohort, with 70.6% (178/252) of this group delivering vaginally. There

23

was no statistically significant difference in rate of spontaneous preterm birth in those with and

4 24

without prolonged second stage (4.4% (11/252) with vs 2.7% (21/780) without, P = 0.21, OR

25

1.6, 95% CI 0.8-3.5). Very prolonged second stage ≥ 7 hours was identified in 4.3% (44/1032) of

26

the cohort, with 45.4% (20/44) of this group delivering vaginally. There was a significantly

27

higher rate of spontaneous preterm birth in those with very prolonged second stage compared to

28

those without (9.1% (4/44) with vs 2.8% (28/988) without, P = 0.04, OR 3.4, 95% CI 1.1-10.2),

29

although this finding did not persist after controlling for mode of first delivery (adjusted OR

30

1.55, 95% CI 0.65-3.73). Spontaneous preterm birth after very prolonged second stage was

31

identified in only four patients, all of whom had a cesarean delivery with the first pregnancy.

32

Conclusion: A second stage ≥ 4 hours in the first pregnancy was not associated with an

33

increased risk of subsequent spontaneous preterm birth and was associated with a high rate

34

(>70%) of vaginal birth. A second stage ≥ 7 hours did not appear to be associated with an

35

increased risk of preterm birth, when adjusting for mode of first delivery. There was a non-

36

significant increase in the risk of preterm birth in those who delivered via cesarean section after a

37

second stage ≥ 7 hours.

5 38 39

Introduction Preterm birth (PTB) remains the leading cause of neonatal morbidity and mortality in the

40

United States and contributes to significant medical, psychosocial, and economic burden for

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affected patients and families.1,2 Many risk factors for spontaneous PTB (sPTB) have been

42

identified, including a prior history of sPTB, cervical shortening in the second trimester, tobacco

43

use, multifetal gestation, and intrauterine infection.3,4 The identification of these risks factors has

44

improved our ability to appropriately risk-stratify, manage, and treat women at risk of this

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serious obstetrical complication.5 Nevertheless, many cases of sPTB occur in women with no

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identifiable risk factors. It is possible that these women have risk factors that have not yet been

47

elucidated by clinical experience or biomedical research.

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Previously published studies have suggested an association between a prolonged second

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stage of labor and an increased risk of subsequent sPTB, thought to be mediated by occult

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cervical damage sustained during the prolonged second stage, which compromises cervical

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integrity for future pregnancies.6,7 Many prior studies have defined a prolonged second stage as

52

greater than or equal to three hours, with less than 10% of the studied cohort falling into this

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category.8,9 At our institution, it is not uncommon for women to have second stages of labor that

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last well beyond three hours, with a high rate of vaginal birth even after a prolonged second

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stage. This study was designed to examine the association between a prolonged second stage of

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labor and rates of subsequent sPTB in a population with a relatively high rate of prolonged

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second stage.

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Materials and Methods

59 60

This was a retrospective cohort study of all nulliparous women with two consecutive singleton deliveries at the University of California, San Francisco (UCSF) between July 2012

6 61

and June 2018, with the first delivery occurring at or beyond 37 0/7 weeks gestational age and

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the second delivery occurring at or beyond 20 0/7 weeks gestational age. We excluded those who

63

did not reach the second stage of labor in the first delivery (i.e. those who underwent an

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intrapartum cesarean delivery prior to reaching complete cervical dilation).

65

At UCSF, both physicians and certified nurse midwives work in a single,

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multidisciplinary team that is responsible for caring for all laboring patients. For all deliveries at

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our institution, details regarding maternal demographics, labor characteristics, and pregnancy

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outcomes are collected at the time of delivery by the managing clinicians and stored within the

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UCSF Perinatal Database. Daily chart review is performed by trained abstractors to ensure

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complete and accurate information, while monthly review of the database is performed by a

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physician for quality assurance. We utilized the UCSF Perinatal Database to obtain information

72

regarding maternal demographics (age, race, body mass index (with obesity defined as pre-

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pregnancy body mass index ≥ 30 kg/m2), and tobacco use), details of antepartum and intrapartum

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course (interpregnancy interval, placement of exam-indicated cervical cerclage, gestational age

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at delivery, and mode of delivery (cesarean delivery versus vaginal delivery, which included

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unassisted vaginal delivery and operative vaginal delivery)) and neonatal characteristics

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(birthweight). To ensure accurate validity of the primary predictor, length of the second stage of

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labor was obtained by chart review performed by two obstetricians (NCS and AGC), who

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calculated length of second stage based on the difference between the time of complete cervical

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dilation and the time of delivery, two timepoints that are consistently documented in the

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electronic medical record by the labor nurses. All cases were reviewed to ensure correct

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documentation and accurate length calculation.

7 83

Prolonged second stage (PSS) was defined as 4 hours or more, based on

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recommendations from the National Institute of Child Health and Human Development10 and on

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the 75th percentile for this cohort, and very prolonged second stage (VPSS) was defined as 7

86

hours or more, based on the 95th percentile for this cohort (Figure 1). The primary outcome was

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sPTB before 37 0/7 weeks in the subsequent pregnancy. Secondary outcomes for the subsequent

88

pregnancy included gestational age (GA) at delivery, neonatal birth weight, admission to

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neonatal intensive care unit (NICU), and placement of exam-indicated cervical cerclage, as this

90

is a marker for possible impending preterm birth.

91

We planned for two separate analyses. The first would dichotomize the length of the

92

second stage into PSS or not PSS and compare outcomes between those two groups. The second

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would dichotomize the length of second stage into VPSS or not VPSS and compare outcomes

94

between those two groups. The Kruskal-Wallis test compared median values for non-parametric

95

continuous variables, Fisher’s exact tests compared proportions for categorical variables, and

96

univariate and multivariate logistic regression generated unadjusted and adjusted odds ratios

97

(OR), respectively. Adjusted OR were obtained by adjusting for race, tobacco use, mode of

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delivery of first pregnancy, maternal age at second pregnancy, and short interpregnancy interval,

99

defined as < 12 months. Statistical significance was set at a P value of < 0.05. Statistical analyses

100

were performed using STATA v13.0 (StataCorp, College Station, TX, USA). This study was

101

approved by the UCSF Committee on Human Research (study number 18-25483, approval date

102

June 26, 2018).

103

Results

104 105

A total of 2,000 women had two consecutive deliveries at UCSF in the predefined time period. After excluding those based on criteria listed above (Figure 1), the remaining 1,032

8 106

women were included for study analysis. In this cohort, the median length of second stage of the

107

first pregnancy was 2.3 hours, ranging from 0.3 hours to 12 hours (Figure 2). The 75th, 90th, and

108

95th percentiles for length of second stage corresponded to 4 hours, 6 hours, and 7 hours,

109

respectively. In this cohort, the rate of operative vaginal delivery (OVD) in the first pregnancy

110

was 3.1%, and the rate of epidural use in the first pregnancy was 73%.

111

PSS was identified in 24.4% (n = 252) of this population. As expected, those with PSS

112

were significantly more likely to undergo a cesarean delivery in the first pregnancy (29.5% with

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PSS vs 2.6% without PSS, P < 0.001), although vaginal birth rates remained high at > 70% in

114

both groups. There was a higher median maternal age at the first pregnancy among those with

115

PSS (33 years (18-45) vs 32 years (16-48) without PSS, P < 0.001), a finding that was

116

statistically but not clinically significant. There were otherwise no differences in maternal

117

demographics or details of the first pregnancy between the two groups (Table 1). There was no

118

statistically significant difference in rate of subsequent sPTB between those with PSS and those

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without PSS in univariate analysis (4.4% with PSS vs 2.7% without PSS, P = 0.209, unadjusted

120

OR 1.65, 95% CI 0.78-3.47; Figure 3) and in multivariate analysis adjusting for race, tobacco

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use, mode of delivery of first pregnancy, maternal age at second pregnancy, and short

122

interpregnancy interval (adjusted OR 1.04, 95% CI 0.41-2.60). There were similarly no

123

statistically significant differences in secondary outcomes of median GA at delivery, median

124

birthweight, admission to NICU, or placement of cervical cerclage (Table 2).

125

VPSS was identified in 4.3% (n = 44) of this population. As expected, those with VPSS

126

were significantly more likely to undergo a cesarean delivery in the first pregnancy (54.6% with

127

VPSS vs 7.1% without VPSS, P < 0.001), although vaginal birth rates still approached 50% in

128

the VPSS group. There were otherwise no differences in maternal demographics or details of the

9 129

first pregnancy between the two groups (Table 3). There was a significantly higher rate of sPTB

130

in those with VPSS compared to those without VPSS (9.1% with VPSS (n = 4 of 44) vs 2.8%

131

without VPSS (n = 28 of 988), P = 0.04, unadjusted OR 3.43, 95% CI 1.15-10.24) (Figure 3,

132

Table 4). However, this difference did not persist after adjusting for race, tobacco use, mode of

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delivery of first pregnancy, maternal age at second pregnancy, and short interpregnancy interval

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(adjusted OR 1.76, 95% CI 0.49-6.29). There was minor difference in GA at delivery between

135

the two groups (39.7 weeks with VPSS vs 39.1 weeks without VPSS, P = 0.022), a finding that

136

was statistically but not clinically significant. The four cases of sPTB after VPSS delivered at

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23.4, 33.6, 34.6, and 35.0 weeks, for a median GA at delivery of 34.1 weeks. There was a

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significantly higher rate of NICU admission in the VPSS group (18.6% vs 7.2%, P = 0.013).

139

Notably, all women who experienced sPTB after VPSS (n = 4) were delivered via cesarean in the

140

first pregnancy (Figure 4). In examining mode of delivery as possible effect modifier, the

141

association between increased sPTB and VPSS was isolated to those who underwent a cesarean

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delivery, with a difference that approached but did not reach statistical significance, due to the

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small sample size (16.7% sPTB with cesarean delivery after VPSS vs 0% sPTB with vaginal

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delivery after VPSS, P = 0.08) (Figure 4). There were no other differences in secondary

145

outcomes between those with VPSS and those without VPSS.

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Discussion

147

Principal findings. In this cohort of over 1,000 women with two consecutive singleton

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deliveries at a single institution, length of second stage in the first pregnancy was not associated

149

with an increased risk of subsequent sPTB when dichotomizing the length of the second stage

150

into prolonged and not prolonged using the nationally accepted cutoff of 4 hours. Although the

151

risk of sPTB appeared to be increased after a second stage ≥ 7 hours on univariate analysis, this

10 152

finding was no longer statistically significant after adjusting for mode of delivery. There

153

appeared to be an increased risk of sPTB if second stage ≥ 7 hours was followed by a cesarean

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rather than a vaginal delivery; however, this finding did not reach statistical significance,

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possibly due to the small sample size within this sub-population (only four patients with second

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stage ≥ 7 hours, cesarean delivery, and sPTB).

157

Comparison with existing literature. These findings contribute to a growing body of

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literature evaluating associations among prolonged second stage in the first pregnancy, mode of

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delivery, and risk of sPTB in the next pregnancy. In our review, we identified three large

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retrospective studies that examined the association between prolonged second stage and risk of

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subsequent sPTB. Levine and Srinivas studied over 750 women with two consecutive deliveries

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over a five-year period at a single institution and found that a prolonged second stage of ≥ 3

163

hours alone was not associated with an increased risk of sPTB.8 When stratifying by mode of

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delivery, however, they demonstrated a two-fold increase in the risk of sPTB among those with a

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cesarean delivery after a prolonged second stage compared to those with a vaginal delivery after

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a prolonged second stage, although this did not reach statistical significance. Sciaky-Tamir,

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Shrim, and Brown completed a similar study of over 1,800 primiparous women over a seven-

168

year period at a single institution and also found that a prolonged second stage ≥ 3 hours was not

169

associated with an increased risk of subsequent sPTB.11 Although they found a significantly

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higher rate of cesarean delivery among those with a prolonged second stage, the authors did not

171

explore mode of delivery as a potential mediator of subsequent sPTB after prolonged second

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stage. Quiñones and colleagues completed an even larger study of over 6,700 primiparous

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women over a ten-year period at a single institution and found a significant increase in the risk of

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subsequent sPTB after a prolonged second stage ≥ 3 hours (hazard ratio 1.81, 95% CI 1.15-

11 175

28.4).9 When stratifying by mode of delivery, however, this finding was only maintained for

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those who underwent a cesarean delivery (hazard ratio 3.38, 95% CI 1.09-10.49 for cesarean

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group; hazard ratio 1.52, 95% CI 0.63-3.74 for vaginal group). Other studies have evaluated the

178

association between mode of delivery in the first pregnancy and risk of subsequent sPTB. Levine

179

and colleagues found a non-significant increase in the risk of sPTB in those with a prior second

180

stage cesarean delivery compared to those with a vaginal delivery, as well as a statistically

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significant increase in the risk of sPTB in those with a prior second stage cesarean delivery

182

compared to those with a prior first stage cesarean delivery.12 This study, however, did not

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evaluate the impact of the second stage duration on the effect of delivery mode on risk of sPTB.

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A similar study demonstrated a statistically significant increase in the risk of sPTB < 37 weeks

185

and sPTB < 32 weeks in those with a prior second stage cesarean compared to those with a prior

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vaginal delivery.13 Univariate analysis also suggested an association between prolonged second

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stage > 3 hours and increased risk of sPTB < 32 weeks; this finding, however, was no longer

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statistically significant when mode of delivery was included in the multivariate analysis. Taken

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together, these five large studies raise questions regarding whether any potential increased risk of

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sPTB is mediated by mode of delivery alone, duration of second stage alone, or a combination of

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the two factors.

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Research implications. This study is now the fourth large study to specifically examine

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the association between a prolonged second stage in the first pregnancy, mode of delivery in the

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first pregnancy, and the risk of sPTB in the next pregnancy. The next direction in this line of

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research is to pool individual patient data from these large studies to further elucidate the true

196

magnitude of sPTB risk after a prolonged second stage of labor and the impact of cesarean

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delivery on this risk. A study of this nature would help to determine the role of mode of delivery

12 198

on sPTB risk after a prolonged second stage and to understand whether the risk is truly limited to

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those with a cesarean delivery.

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Clinical implications. Identifying a robust association between length of the second stage

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of labor, mode of delivery, and risk of subsequent sPTB would help to better stratify patients at

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high risk of sPTB. However, much more research is required before clinical recommendations

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can be made, and unfortunately the data do not currently support any meaningful strategy to

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prevent preterm birth in a subsequent pregnancy. To support future research on labor

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characteristics and outcomes, clinicians should make a concerted effort to improve

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documentation of time in labor. We suggest a standardized delivery note template that would

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include not only the length of time in the second stage, but also the length of time in the active

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phase of the first stage and the length of time in the third stage. This record-keeping would

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improve our ability to study outcomes associated with labor characteristics and may potentially

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contribute to counseling and decision-making in the future.

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A finding that may be more immediately applicable to clinical care is the high rate of

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vaginal delivery among the PSS group; at 70.5%, this rate is higher that rates that have been

213

reported in similar studies. This finding should encourage providers to consider individualized

214

management of a prolonged second stage, rather than adhering to stringent cut-offs for

215

intervention (i.e. cesarean delivery for all patients after four hours in the second stage).

216

Strengths and limitations. Although this study includes a sizable number of women for

217

the overall cohort, the sample size for those with VPSS is small, and only four women with

218

VPSS had the primary outcome of subsequent sPTB. This study focuses on a single institution,

219

which may limit generalizability to other populations; patients in this study had longer second

220

stages than have been reported elsewhere with higher vaginal birth rates than have been reported

13 221

elsewhere. Another limitation of this study is the absence of information regarding proportion of

222

time in the second stage spent laboring down compared to actively pushing. Because this

223

information is not routinely documented in the electronic medical record, it was unavailable for

224

reliable abstracting and thus was not included in the study’s analysis. This study included only

225

deliveries that occurred at or beyond 20 weeks of gestation, which may contribute to an

226

underestimate in rate of sPTB, since pregnancies that ended between 16 to 20 weeks due to

227

cervical insufficiency were not included. Importantly, this study focused only on the risk of

228

subsequent sPTB after prolonged second stage and did not examine other adverse outcomes

229

associated with increasingly long second stage. Numerous studies have already demonstrated the

230

risks associated with increasing length of the second stage, including higher order perineal

231

lacerations, infection, and hemorrhage with or without blood transfusion or hysterectomy, risks

232

that may be related not only to the length of second stage but also to the mode of delivery (i.e.

233

operative vaginal delivery and cesarean delivery).14,15,16

234

The main strength of this study lies in the cohort’s unique labor demographics and

235

cesarean delivery rates, particularly when compared to those reported at other institutions.

236

Specifically, this cohort had a higher rate of prolonged second stage compared to other studies

237

(e.g. 6.3% ≥ 3 hours in Levine and Srinivas vs 24.4% ≥ 4 hours in this study) and a lower rate of

238

cesarean delivery following a prolonged second stage (e.g. 47.2% in Quiñones et al after a

239

second stage ≥ 3 hours vs only 29.5% in this study after a second stage ≥ 4 hours). The higher

240

rate of prolonged second stage and the lower rate of cesarean delivery at our institution is the

241

result of a commitment to individualizing patient care, promoting vaginal delivery, and reducing

242

cesarean delivery rates. Rather than adhering to stringent cutoffs, our providers evaluate overall

243

labor progress, fetal heart rate monitoring, and maternal status when considering when to

14 244

perform a cesarean delivery in the second stage. As a result, this population provides a more

245

nuanced understanding of the association between length of second stage, mode of delivery, and

246

subsequent sPTB.

247

Conclusions. A prolonged second stage ≥ 4 hours was not associated with an increased

248

risk of sPTB in the next pregnancy, regardless of mode of delivery. Although a very prolonged

249

second stage ≥ 7 hours was associated with an increased risk of subsequent sPTB on univariate

250

analysis, this finding was no longer statistically significant when adjusting for mode of delivery.

251

Notably, vaginal birth rates in this cohort of women with prolonged and very prolonged second

252

stages remained high (70.6% and 45.4%, respectively). We recommend further research into the

253

association between length of second stage, mode of delivery, and sPTB risk.

15 254

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low-risk nulliparas [SMFM abstract 28]. Am J Obstet Gynecol 2019;220(1):S23.

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https://doi.org/10.1016/j.ajog.2018.11.031

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Tables

302

Table 1. Maternal demographics and details of first delivery by duration of second stage of

303

labor, with prolonged second stage defined as ≥ 4 hours. Demographics and details of first delivery

2nd stage < 4 hrs

2nd stage ≥ 4 hrs P value

Maternal age at first pregnancy (years)

(n = 780)

(n = 252)

32 (16-48)

33 (18-45)

Race/ethnicity Caucasian

< 0.001 0.203

433 (55.5)

138 (54.5)

African American

25 (3.2)

2 (0.8)

Hispanic

49 (6.3)

13 (5.2)

Asian

190 (43.4)

68 (27.0)

Other

83 (10.6)

31 (12.3)

Tobacco use

14 (1.8)

5 (2.0)

0.792

Obese (body mass index ≥ 30 kg/m2)

45 (5.8)

12 (4.9)

0.635

Cervical laceration at first pregnancy

11 (1.4)

3 (1.2)

1.000

Cesarean delivery at first pregnancy

20 (2.6)

74 (29.5)

< 0.001

167 (21.4)

54 (21.4)

1.000

Short interpregnancy interval < 12 months 304 305

Data presented as n (%) for categorical variables and median (minimum-maximum) for non-

306

parametric continuous variables.

19 307

Table 2. Outcomes in subsequent pregnancy based on by duration of second stage in the first

308

pregnancy. 2nd stage < 4 hrs

2nd stage ≥ 4 hrs

(n = 780)

(n = 252)

21 (2.7)

11 (4.4)

0.209

39.6 (23.4-42.6)

39.7 (26.9-42.1)

0.143

54 (7.0)

25 (10.0)

0.133

Neonatal birth weight (grams)

3427 (410-4930)

3502 (390-4760)

0.225

Placement of cervical cerclage

5 (0.6)

1 (0.4)

1.000

Outcomes in subsequent pregnancy

P value

Spontaneous preterm birth < 37 weeks Gestational age at delivery (weeks) Admission to neonatal intensive care unit

309 310

Data presented as n (%) for categorical variables and median (minimum-maximum) for non-

311

parametric continuous variables.

20 312

Table 3. Maternal demographics and details of first delivery by duration of second stage of

313

labor, with very prolonged second stage (VPSS) defined as ≥ 7 hours. Demographics and details of first delivery

2nd stage < 7 hrs

2nd stage ≥ 7 hrs

(n = 988)

(n = 44)

32 (16-48)

33 (22-42)

P value

Maternal age at first pregnancy (years) Race/ethnicity Caucasian

0.091 0.948

545 (55.2)

26 (59.1)

African American

27 (2.7)

0 (0)

Hispanic

60 (6.1)

2 (4.6)

Asian

246 (24.9)

12 (27.3)

Other

110 (11.1)

4 (9.1)

Tobacco use

17 (1.7)

2 (4.6)

0.194

Obese (body mass index ≥ 30 kg/m2)

55 (5.6)

2 (4.7)

0.788

Cervical laceration at first pregnancy

12 (1.2)

2 (4.6)

0.117

Cesarean delivery at first pregnancy

70 (7.1)

24 (54.6)

< 0.001

215 (21.8)

6 (13.6)

0.260

Short interpregnancy interval < 12 months 314 315

Data presented as n (%) for categorical variables and median (minimum-maximum) for non-

316

parametric continuous variables.

21 317

Table 4. Outcomes in subsequent pregnancy based on by duration of second stage in the first

318

pregnancy, with very prolonged second stage (VPSS) defined as ≥ 7 hours. 2nd stage < 7 hrs

2nd stage ≥ 7 hrs

(n = 988)

(n = 44)

28 (2.8)

4 (9.1)

0.043

39.1 (23.4-42.6)

39.7 (26.9-42.1)

0.022

71 (7.2)

8 (18.6)

0.013

Neonatal birth weight (grams)

3445 (410-4930)

3518 (390-4290)

0.068

Placement of cervical cerclage

5 (0.5)

1 (2.3)

0.231

Outcomes in subsequent pregnancy

P value

Spontaneous preterm birth Gestational age at delivery (weeks) Admission to neonatal intensive care unit

319 320

Data presented as n (%) for categorical variables and median (minimum-maximum) for non-

321

parametric continuous variables.

322

22 323

Figure legends

324

Figure 1. Flow diagram of patient inclusion and exclusion.

325 326

Figure 2. Distribution of length of second stage.

327

Description: Vertical lines represent the 4-hour mark, corresponding to the 75th percentile and

328

the cutoff for prolonged second stage (PSS), and the 7-hour mark, corresponding to the 95th

329

percentile and the cutoff for very prolonged second stage (VPSS).

330 331

Figure 3. Preterm birth after prolonged second stage and after very prolonged second stage.

332

Description: Rate of subsequent spontaneous preterm birth (sPTB) with prolonged second stage

333

(PSS) ≥ 4 hours or very prolonged second stage (VPSS) ≥ 7 hours in the first pregnancy.

334 335

Figure 4. Effect of mode of delivery on preterm birth rates after prolonged second stage and

336

after very prolonged second stage.

337

Description: Rate of subsequent spontaneous preterm birth (sPTB) by prolonged second stage

338

(PSS) ≥ 4 hours and by very prolonged second stage (VPSS) ≥ 7 hours in the first pregnancy,

339

both stratified by mode of delivery in the first pregnancy.