The Impact of Labor Stage Duration on Adverse Maternal and Neonatal Outcomes in Multiparous Women: A Retrospective Cohort Study

Background The duration of first and second stages of labor was increased in the consensus that College Studies showed increased adverse maternal and neonatal outcomes in nulliparous women with prolonged second stage of labor. It is not very clear that the impact of labor stage duration on multiparous women. Methods A retrospective cohort study was performed. Cephalic, term, singleton multiparous women were included, who planned for vaginal delivery. Adverse maternal outcomes were defined as referral cesarean delivery, instrumental delivery, postpartum hemorrhage, perineal laceration (3rd and 4th degree), hospitalization stay ≥ 90%th, and adverse neonatal outcomes as NICU, shoulder dystocia, Apgar score ≤ 7(5 min), neonatal resuscitation, assisted ventilation required immediately after delivery. We defined the total stage included the first and second stage of labor. Results There were 7109 parturients included, The duration of first stage was 6.2(3.6–10.0) hours in multiparous women, the second stage was 0.3(0.2–0.7) hours, the total stage was 6.9(4.1–10.7) hours. In the first stage, the rate of overall adverse outcomes was 21%, 23.4%, 28.8%, 35.5%, 38.4% in < 6 h, 6-11.9 h, 12-17.9 h, 18-23.9 h, ≥ 24 h, increased significantly (X 2 = 57.64, P0.001). Compared with < 6 h, ARR(95%CI) were 1.10(0.92,1.31), 1.33(1.04,1.70), 1.80(1.21,2.68), 2.57(1.60,4.15);In the second stage, the rate of overall adverse outcomes increased from 20.0%, 30.7%, 38.5%, to 61.2%, 69.6% in < 1 h, 1-1.9 h, 2-2.9 h, 3-3.9 h, ≥ 4 h ( X 2 = 6 h as a reference; Adjusted Gestational age, Maternal age, Maternal Height, Gestational weight gain, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Ethnicity, Epidural, anesthesia, Induction, Oxytocin. Multivariable logistic regression model was used to assess risks of cutoff value of labor stage for adverse delivery outcomes. Adjusted Gestational age, Maternal age, Maternal Height, Gestational weight gain, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Ethnicity, Epidural, anesthesia, Induction, Oxytocin. Multivariable logistic regression model was used to assess risks of cutoff value of labor stage for adverse delivery outcomes. Adjusted Gestational age, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Ethnicity, Epidural, anesthesia, Oxytocin. Assisted ventilation Multivariable logistic regression model was used to assess risks of cutoff value of labor stage for adverse delivery outcomes. Adjusted Gestational age, Maternal age, Maternal Height, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Epidural, anesthesia, Induction, Oxytocin.


Background
In 2014, "Safe prevention of the primary cesarean delivery" which was recommended by American College of Obstetricians and Gynecologists(ACOG) as "obstetric care consensus", to reduce cesarean delivery rates [1]. There were recommendations that a prolonged latent phase should not be indication for cesarean delivery, and no specific absolute maximum length of time spent in first and second stage of labor beyond which all women should undergo operative delivery. The consensus pointed out that prolonging the labor stage may reduce the rate of primary cesarean delivery. After the consensus, the relationship of second labor stage and the adverse delivery outcomes has been widely studied. The published clinical researches since 2016 supported the original contention that the prolongation of the second stage beyond historical precepts was unsafe [2,3]; The implementation of the guidelines could not reduce the rate of cesarean delivery, on the contrary increased the adverse outcomes of mothers and neonatus [4]; Some supporters reported that the new policy of labor management successfully decreased primary cesarean deliveries, but increased the other immediate maternal and neonatal complications [5].
Most of studies focus on the second stage of labor and nulliparous women. We also need to know how long is safe for multiparous women in first stage and total stage. WHO proposal [6], the active phase started ≥ 5 cm and duration up to 10 hours for multiparous women, with no mention the first stge. In this study, the total stage was covered first and second stages before delivery, because first stage and second stage cannot be absolutely distinguished sometimes. The duration of first labor stage in multiparous women was shorter than in nulliparous [7]. In nulliparous women, the prolonged first or second stage of labor was related to adverse outcomes [5,[8][9][10], and there was a correlation between the first and second stages of labor [11]. It is not very clear that the duration of the first stage, the second stage and the total stage of labor on delivery outcomes in multiparous women. We assumed that prolonged labor stage may lead to increased adverse outcomes, aimed to evaluate the effect of the duration of labor stage on delivery outcomes in multiparous women, to understand the process of labor and make better choices.

Methods
This is a retrospective cohort study, the data was collected from electronic medical records in Harvard University Partners Healthcare Systems (PARTNERS) between January 1, 2016 and December 31, 2018, including seven hospitals as Brigham and Women's Hospital, Massachusetts General Hospital, Newton-Wellesley Hospital, North Shore Medical Center, Martha's Vineyard Hospital, Cooly Dickinson Hospital and Nantucket Cottage Hospital. The information of demographics and obstetrics characteristics were collected: gestational age, maternal age, maternal height, weight gain, BMI, gravidity, parity, baby weight, baby height, ethnicity, epidural anesthesia, induction, oxytocin, etc, and adverse maternal outcomes: referral cesarean delivery, instrumental delivery, postpartum hemorrhage, perineal laceration (3rd and 4th degree), hospitalization stay ≥ 90%th (length of stay ≥ 90%th), and adverse neonatal outcomes: NICU, shoulder dystocia, Apgar score ≤ 7(5 min), neonatal resuscitation, assisted ventilation required immediately after delivery.
The inclusion criteria was multiparous women (parity ≥ 1), with singleton gestation, 37-41 + 6 gestational weeks, cephalic presentation (excluding face and brow), vaginal delivery, unexpected cesarean delivery during the first or second stage of labor. The exclusion criteria was scheduled cesarean delivery, previous cesarean delivery history, stillbirth, pregnancy induced hypertension, gestational diabetes, and missing data of the duration of first or second labor stage, or other data. A flow chart was showed in Fig. 1. The duration of first labor stage was divided into five subgroups as < 6 h, 6-11.9 h, 12-17.9 h, 18-23.9 h, ≥ 24 h. The duration of second labor stage was divided into five subgroups as < 1 h, 1-1.9 h, 2-2.9 h, 3-3.9 h, ≥ 4 h. We defined the total stage of labor including first labor stage and second labor stage, it was divided into three subgroups as < 12 h, 12-23.9 h, ≥ 24 h.
Data description was presented as mean ± standard deviation (Mean ± SD) or median (interquartile ranges, IQR) for continuous variables and percentages for categorical variables. Chi-square test was used for categorical variables as group comparison. Mantel Haenszel test was used for Linear trend X 2 analyses. The duration of labor stage were defined as independent variables. The adverse outcomes were defined as dependent variables. Multivariable logistic regression model was used to assess the relationship between the duration of labor stage and adverse delivery outcomes. Adjusted Risk Ratio (ARR) and 95% Confidence Interval (CI) were used to expressed the association in multivariable logistic models with the shortest duration of the labor stage(< 6 h of the first stage; < 1 h of the second stage; < 12 h of the total stage) as control (RR = 1.00), after adjusting the factors such as gestational age, maternal age, height, weight gain, BMI, gravidity, parity, baby weight, epidural anesthesia, induction, oxytocin. All statistical tests of hypotheses will be two sided and criterion for statistical significance is α = 0.05. Statistical analyses were done with SPSS version 21.0 software (IBM).

Results
There were 43577 deliveries in Harvard University Partners Healthcare Systems (PARTNERS) between January 1, 2016 and December 31, 2018, including 29,943 vaginal deliveries and 13,634 cesarean deliveries, the rate of cesarean delivery was 31.3%. There were 7109 multiparous women, who planned for vaginal delivery and encounter the labor process, 76.3% with epidural anesthesia, 27.8% with oxytocin ( Table 1). The duration of first stage was 6.2(3.6-10.0) hours in multiparous women, the second stage was 0.3(0.2-0.7) hours, the total stage was 6.9(4.1-10.7) hours. The rate of overall adverse outcomes was 23.6%, the rate of maternal adverse outcomes were 9.4%, the rate of neonatal adverse outcomes were 17.1%, others adverse outcomes were showed in Table 2.   18.5%, increased significantly (X2 = 7.75, P = 0.005). There were significant differences in incidence of referral cesarean delivery, instrumental delivery, length of stay ≥ 90%th, shoulder dystocia, Apgar ≤ 7(5 min), neonatal resuscitation, assisted ventilation in different duration of the first stage (Table 3, Fig. 2). In order to analysis the effect of duration on adverse outcomes, with < 6 h as the reference, multivariable logistic regression showed ARR(95%CI) of overall adverse outcomes were 1. 10 Fig. 7).

Discussion
In decades, Friedman's Chart has been used to assist in the management of labor process [12], but that was questioned recently. Zhang and others [13] proposed a new delivery curve, that was areference of the consensus in 2014. After promulgation of the consensus in 2014, there has been a constant debate on it. Cohen and Friedman [14], claimed that the new curve incorrectly explained the Friedman curve. Studies [4,5] also suggested that prolonging the labor stage will not reduce the rate of cesarean section delivery, but will increase the adverse outcomes of delivery. Most of these suggestions were preferred to give a specific cutoff value, to divide normal and abnormal labor stage, for artificial intervention recommendation, or for clinical implementation. Even so, there was no recommendation for the duration of first stage and total stage in the consensus, there was not paying attention to the multiparous women. We wanted to show the details about labor stages of multiparous women, and their adverse delivery outcomes in this study. There was 5.3% of multiparous women that first stage ≥ 18 hours, 3.7% of second stage ≥ 3 hours, and 2.6% of total stage ≥ 24 hours, that had been forbidden by the consensus or Friedman's Chart. Only 1.4% were referral cesarean delivery, 2.9% were instrumental vaginal delivery in the study, when the gross rate of cesarean delivery was 31.29%. We found that the effects of the duration of labor stages on the adverse outcomes were very complex.
A prolonged latent phase (> 14 h in multiparous women) should not be indication for cesarean delivery [1], but with the prolongation of the duration of first stage, the overall rate of maternal and neonatal complications increased from 21.0-38.4%. Both maternal and neonatal complications showed an increasing trend. Compared with less than 6 hours of first stage, the risk of long time stay in hospital, low Apgar score and admission to NICU was increased in 6-11.9 hours, the risk of assisted ventilation, referral cesarean delivery and instrumental delivery was increased in 12-17.9 hours, the risk of long stay in hospital and referral cesarean delivery was increasing after 18 hours continuously, even if adjusted confounder factors such as birth weight. The prolonged hospitalization time may be related to operative labor, urinary retention and infection caused by prolonged labor stage.
Zhang and his colleagues pointed out that "our failure to reduce the rate of cesarean section may be due to our failure to fully understand the delivery process, especially the first stage of labor" [15].
Defining an abnormal first stage of labor based on maternal and neonatal outcomes [8,16], our results confirm that the prolongation of first stage of labor increased the adverse maternal and neonatal outcomes in multiparous women. We should take a dynamic view on cutoff value of first stage, and pay attention to complications even at the beginning of labor. We should pay attention to the risk of referral cesarean delivery, prolonged hospital stay, neonatal assisted ventilation and transfer to NICU ,instrument assisted delivery more than 12 hours. The risk of referral cesarean delivery, prolonged hospital stay were increased 3.15 times and 4.27 times ≥ 18 hours than 18 hours in first stage. Therefore, we should comprehensively evaluate the possibility of vaginal delivery and the adverse outcomes, especially when the duration of first stage ≥ 18 hours. We should minimize the first stage, so as to reduce the adverse outcomes, to reduce operation delivery.
The second stage is the most important stage of labor. Doctors want to find a balance point between less operation delivery and less adverse outcomes. Before diagnosing arrest of labor in second stage, if maternal and fetal conditions permit, allowed at least 2 h of pushing in multiparous women, longer durations may be appropriate on individualized basis as long as progress is being documented, even instrumental delivery, nonetheless with a reduced risk of cesarean delivery; independent of the duration of second stage of labor was safe for the neonate [17]. The effect of the duration of the second stage of labor on the outcomes of labor has been studied widely and deeply, but the results were not consistent. Zipori, Y found the new policy of labor management successfully decreased primary cesarean deliveries, with a small rise in instrumental deliveries, and also increased the other immediate maternal and neonatal complications [5]. Laughon SK thought that prolonged second stage was associated with increased chorioamnionitis, perineal lacerations, neonatal sepsis, asphyxia and perinatal mortality, proposed that the benefits of prolonging the second stage of labor to improve vaginal delivery should be weighed against the adverse outcomes of mothers and infants [18]. A randomized controlled study in 2016 showed that prolonging the second stage of labor can improve vaginal delivery and reduce the rate of cesarean section, but the difference between the adverse outcomes of mothers and infants was not statistically significant [19]. Thuillier C et al reported the new consensus recommendations was associated with a reduction of the rate of primary cesarean delivery performed for arrest of labor with no apparent increase in immediate adverse neonatal outcomes in nulliparous women and with epidural anesthesia [20].
In our study, there were 76.3% women delivered with epidural analgesia, 27.8% with oxytocin. With the extension of the second stage, the rate of adverse delivery outcomes increased rapidly from 20% in ≤ 1 hour, 30.7% in 1-1.9 h, 38.5% in 2-2.9 h, to 61.2% in 3-3.9 h, 69.6% in ≥ 4 hours. Except for shoulder dystocia, almost all adverse outcomes showed an increasing trend. The duration of second stage was also an independent risk factor to these adverse outcomes compared with ≤ 1 hour. The longer the duration, the greater the risk. The risk of the maternal outcomes were increasing every more hour of second stage rapidly and independently, in referral cesarean delivery, instrumental delivery, postpartum hemorrhage, lacerations, length of stay ≥ 90%th. It should be noticed that the duration of second stage of labor was also an independent risk factor for increasing adverse neonatal outcomes, low Apgar score at 5 minutes, neonatal resuscitation, assisted ventilation and admission to NICU, but that was not very significant in the first stage of labor.
The duration of second stage is very important for labor, even though it does not account for much longer of total stage. We should pay more attention to the management of the second stage of labor, taking some harmless measures to make it shorter by upright position or immediate pushing [21,22].
It is important to assess fetal position in second stage of labor, occiput posterior position and transverse position in labor is associated with more painful and prolonged labor, free position and manual rotation of fetal occiput in setting of fetal malposition in second stage of labor were reasonable interventions to consider before instrumental assist delivery or cesarean delivery as soon as possible [1,23,24]. For prolonged labor stage, we should evaluate fetal heart monitoring and fetal head descending, to make them safe.
Few studies have made recommendations on the duration of total stage of labor. There were relationship between the durations of the first and the second stages of labor, the duration of the second stage significantly increased concomitantly with increasing duration of the first stage [11], so the duration of total stage of labor was meaningful for outcomes. In this study, with the increase of the total stage of labor, the rate of adverse outcomes increased by 21.5%, 30.8%, 42.4%, in 12 h, 12-17.9 h, ≥ 18 h of total stage. It was an independent risk factor for referral cesarean delivery, instrumental delivery, and length of stay ≥ 90%th after 12 hours of total labor stage. The risk of postpartum hemorrhage increased 1.84 times over 24 hours, compared with less than 12 hours. It was reasonable to set the cutoff value at 12 hours of total stage, to reduce operation delivery and long hospital stay. For the parturients with a long duration of first stage, we should be alert to prolonging second stage. In total labor stage, the first labor stage was accounts for the main part, and the latent phase was a important part of first stage, therefore, we should pay attention to the management of the duration of labor stage at the beginning of it. If the latent phase was more than 10 hours in multiparous women, we should try to find out problems, deal with it, and promote the progress of labor, rather than waiting.
The major strength of the present study lies in a multiple center cohort study after the new management of labor for 3 years. We confirmed that with prolonging of the first, the second and the total stage of labor, the adverse maternal and neonatal outcomes were increased, the longer the duration of stage, the higher risk of adverse outcomes. The limitation of the study was the data collected retrospectively. Only multiparous women were included, whether the rate of cesarean delivery decreased was not involved. We did not perform a stratified analysis on epidural analgesia, induction and oxytocin. We cannot provide an optimal recommended duration of labor stage, because the adverse outcomes was increased with labor stage progress synchronously. The first stage was not divided into latent phase and active phase, to discriminate which phase was increased. In addition, the determination when to enter the labor process was not consistent exactly, the time of admission was often been act as the beginning of the first labor stage, resulting in the recorded labor stage shorter than the real stage. The time cannot be defined very clearly from the first stage to the second sage, because the examination of fully dilated cervix is not promptly, that is not easy to solve.

Conclusion
The prolonged labor stage may lead to increased adverse outcomes, no matter in the first stage, the second stage or the total stage of labor, and it was a independent risk factors for adverse maternal and neonatal outcomes. There was no cutoff value of the duration of labor stage, the risk was increasing synchronously with labor stage. In particular, the second stage should be shorten within one hour. We suggest monitoring the status of mothers and neonates at the beginning of labor, and take active measures to make labor stage shorter, to reduce the incidence of adverse delivery outcomes.

Availability of data and materials
The datasets used in the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate
This study was approved by PARTNERS, the ethical approval number was 2018P002646.

Consent for publication
It is not applicable.

Figure 1
The flow chart.

Figure 2
Adverse outcomes in the first stage of labor in multiparous women.

Figure 3
Forest plots for multivariable logistic regression model of the first labor stage. To assess the relationship between the duration of labor stage and adverse delivery outcomes, the left was compared with 1h, the right was compared with cutoff value. Adjusted Gestational age, Maternal age, Maternal Height, Gestational weight gain, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Ethnicity, Epidural, anesthesia, Induction, Oxytocin.

Figure 4
Adverse outcomes in the second stage of labor in multiparous women.

Figure 5
Forest plots for multivariable logistic regression model of the second labor stage. To assess the relationship between the duration of labor stage and adverse delivery outcomes, the left was compared with 1h, the right was compared with cutoff value. Adjusted Gestational age, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Ethnicity, Epidural, anesthesia, Oxytocin.

Figure 6
Adverse outcomes in the total stage of labor in multiparous women.

Figure 7
Forest plots for multivariable logistic regression model of the total labor stage. To assess the relationship between the duration of labor stage and adverse delivery outcomes, the left was compared with 12h, the right was compared with cutoff value. Adjusted Gestational age, Maternal age, Maternal Height, Maternal BMI, Gravidity, Parity, Baby weight, baby height, Epidural, anesthesia, Induction, Oxytocin .