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Review

Relationship Between Prolonged Second Stage of Labor and Short-Term Neonatal Morbidity: A Systematic Review and Meta-Analysis

by
Nuria Infante-Torres
1,
Milagros Molina-Alarcón
2,
Angel Arias-Arias
1,
Julián Rodríguez-Almagro
3,* and
Antonio Hernández-Martínez
3
1
Mancha Centro Hospital, Av. Constitución, 3, Alcázar de San Juan, 13600 Ciudad Real, Spain
2
Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Nursing, University of Castilla-La Mancha, Av. de España, s/n, 02001 Albacete, Spain
3
Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Nursing, University of Castilla-La Mancha, Camilo José Cela, 14, 13071 Ciudad Real, Spain
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(21), 7762; https://doi.org/10.3390/ijerph17217762
Submission received: 2 September 2020 / Revised: 14 October 2020 / Accepted: 21 October 2020 / Published: 23 October 2020
(This article belongs to the Special Issue Policies and Strategies in Sexual and Reproductive Health)

Abstract

:
To evaluate the association between prolonged second stage of labor and the risk of adverse neonatal outcomes with a systematic review and meta-analysis. PubMed, Scopus and EMBASE were searched using the search strategy “Labor Stage, Second” AND (length OR duration OR prolonged OR abnormal OR excessive). Observational studies that examine the relationship between prolonged second stage of labor and neonatal outcomes were selected. Prolonged second stage of labor was defined as 4 h or more in nulliparous women and 3 h or more in multiparous women. The main neonatal outcomes were 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death. Data collection and quality assessment were carried out independently by the three reviewers. Twelve studies were selected including 266,479 women. In nulliparous women, a second stage duration greater than 4 h increased the risk of 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit and neonatal sepsis and intubation. In multiparous women, a second stage of labor greater than 3 h was related to 5 min Apgar score <7, admission to the Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity. Prolonged second stage of labor increased the risk of 5 min Apgar score <7 and admission to the Neonatal Intensive Care Unit in nulliparous and multiparous women, without increasing the risk of neonatal death. This review demonstrates that prolonged second stage of labor increases the risk of neonatal complications in nulliparous and multiparous women.

1. Introduction

The second stage of labor is the period of time between full cervical dilatation and birth of the baby, during which the woman has an involuntary urge to bear down, as a result of expulsive uterine contractions [1].
The description of the onset of the second stage of labor in clinical practice is often not precisely known. If complete dilatation is found on vaginal examination, it remains uncertain how long this cervical status has been present [2].
Multiple observational studies [2,3,4] have observed an increase in maternal complications associated with a prolonged second stage of labor, such as operative vaginal delivery, third-/fourth-degree perineal lacerations, caesarean delivery, urinary retention, postpartum hemorrhage and chorioamnionitis, as well as an increase in neonatal complications like seizures, hypoxic-ischemic encephalopathy, sepsis and increased mortality. However, the criteria these studies used to define the second stage of labor are heterogenous.
Thus, diagnosis and management of prolonged second stage of labor and its complications are difficult and often pose a dilemma to the obstetrician regarding timing and type of intervention [5]. Additionally, evidence on the duration of the second stage of labor is of very low certainty [1] and it is unclear whether there is a point of time from which the risk of perinatal complications increases and at which health professionals should intervene to prevent adverse events [3,6].
Nevertheless, there are professionals involved in childbirth care that try to reduce the duration of the second stage by obstetric interventionism in order to avoid neonatal complications. Paradoxically, these interventions, such as immediate pushing (initiated as soon as complete dilation is identified) [7], instrumental birth [8] or fundal pressure [9], may themselves increase the risk of neonatal morbidity.
In the past, a prolonged second stage of labor had been defined as a period of time that lasted beyond 2 h with epidural analgesia or 1 h without epidural analgesia for multiparous women. For nulliparous women, a prolonged second stage is defined as a period of time that lasted beyond 3 h with epidural analgesia or 2 h without epidural analgesia [10]. Recently, though, the American College of Obstetricians and Gynecologists (ACOG) [11] and the National Institute for Health and Care Excellence (NICE) [12] have allowed longer durations in specific cases. In spite of this, the correct management of the second stage of labor should be individualized according to birth progress, fetal malposition or the use of epidural analgesia [11,12]. For example, the Eunice Kennedy Shriver National Institute of Child Health and Human Development document suggested allowing one additional hour for the use of epidural analgesia. Thus, at least 3 h in multiparous women and 4 h in nulliparous women would be considered to diagnose a prolonged second stage of labor [11].
Thus, our objective was to evaluate the evidence on the association between prolonged second stage of labor (defined as 4 h in nulliparous women and 3 h in multiparous women) and the risk of adverse neonatal outcomes.

2. Materials and Methods

This systematic review with a meta-analysis was done according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) [13,14].

2.1. Data Sources and Searches

The adopted search strategy was: “Labor Stage, Second” (Mesh) AND (length OR duration OR prolonged OR abnormal OR excessive). Studies were identified in three main databases: PubMed [15], Scopus [16] and EMBASE [17], from 1 January 1990 to 1 November 2019. As well as published studies, we included non-published studies which had been included in the conference proceedings of the main scientific associations and indexed in the databases consulted. All languages were included. The search results for each database are provided in detail in Table A1.
All members of the research team had prior training in the methodology of systematic reviews, literature reviews and critical reading. AAA and AHM are also experts in meta-analysis.
Studies were included according to four criteria: (I) duration of second stage of labor greater than 4 h in nulliparous women; (II) duration of second stage of labor greater than 3 h in multiparous women; (III) studies reporting neonatal outcomes in relation to duration of second stage of labor; (IV) studies that stratified results by parity. Reference lists from the selected studies were also examined to locate further studies not identified using the search strategy. Two authors (NIT and AAA) independently performed the literature search and excluded any articles that did not meet the established inclusion criteria. A third author (MMA) was consulted to resolve any disagreements or uncertainty regarding inclusion.

2.2. Main Outcomes

The primary outcomes were 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death. All neonatal outcomes examined by the available studies were included in this review. The definitions of some of the variables included in our study are shown in Table 1.

2.3. Data Extraction and Quality Assessment

Data collection and quality assessment were carried out independently by the three reviewers (NIT, AHM and JRA). We tried to contact the authors of several studies to provide us with data that did not appear in their manuscripts.
We used the Joanna Briggs Institute Critical Appraisal tools for use in JBI Systematic Reviews to assess the risk of bias in each included study [24]. Eleven domains were assessed to appraise the methodological quality of a study and to determine the extent to which a study had addressed the possibility of bias in its design, conduct and analysis.

2.4. Data Synthesis

For the categorical results, the odds ratio (OR) was used along with its 95% confidence intervals (95% CI). To calculate the OR, either the Mantel–Haenszel fixed-effects or Der Simonian–Laird random-effects models were used, depending on whether there was heterogeneity between the studies. Heterogeneity was assessed using the I2 and the statistical Cochran’s Q tests. I2 values of < 25%, 25–50 and >50% normally correspond to small, medium and large heterogeneity, respectively [14,25,26]. Publication bias was also evaluated using the Egger asymmetry test and funnel plots [14,27]. Statistical significance was defined at the ≤0.05 level.
All calculations were done with the StatsDirect statistical software, version 2.7.9. (Stats Direct Ltd., Cheshire, England) [14].

3. Results

3.1. Study Selection

A total of 1868 studies were selected from the literature search. After removing any duplicated articles, 267 were selected by title and abstract. After applying the inclusion/exclusion criteria, twelve articles were selected for the qualitative and quantitative analyses (meta-analysis) (Figure 1).

3.2. Study Characteristics

The description of the studies included in this systematic review are shown in Table 2. The sample included 268,624 women. The selected studies were conducted in Canada [4,18,28], United States [19,20,21,29,30], China [31], Sweden [22,32] and Spain [23]. The sample size of these studies ranged from 307 [31] to 121,490 [4]. All studies were restricted to singleton infants with cephalic presentation. Eight of these articles studied nulliparous women [18,20,21,22,28,30,31,32], two studied multiparous women [19,23] and two studied both (nulliparous and multiparous women) [4,29]

3.3. Study and Data Quality

The included studies had a low risk of bias, except for three studies that did not identify confounding factors [18,28,31] and four studies that did not include strategies to deal with confounding factors [18,28,30,31] (Table A2).
With regard to the selection of subjects, all studies except one [31] specified inclusion and exclusion criteria, selecting all women (nulliparas and/or multiparas) with singleton cephalic presentation that reached second stage of labor within a specific period of time.
Seven of the studies included in the meta-analysis [4,18,20,21,23,28,32] correctly defined prolonged second stage of labor (in this case, second stage of labor longer than 4 h in nulliparas and longer than 3 h in multiparas). Conversely, only three of them [18,21,28] established the maneuver used once prolonged second stage of labor was diagnosed (instrumental birth, continuing maternal pushing, caesarean, etc.).
As for data and information collection, five studies [4,22,23,30,32] included missing or incomplete data as exclusion criteria, so they were not included in the analysis.

3.4. Main Outcomes and Meta-Analysis

3.4.1. Nulliparous Women

5 min Apgar score <7

To determine the relation between prolonged second stage of labor in nulliparous women (Table A3) and risk of low 5 min Apgar score (<7), six studies were included (n = 116,624) [4,18,28,30,31,32]. A significant increase in low 5 min Apgar score was observed when the second stage of labor lasted more than 4 h with respect to when the second stage of labor was ≤ 4 h. (OR = 1.65; 95% CI: 1.20–2.27). For this analysis, a random-effects model was used since heterogeneity was observed (Cochran’s Q p-value = 0.0041; I2 = 71.0) (Figure 2a; Table 3).

Admission to Neonatal Intensive Care Unit

To assess the risk of admission to the Neonatal Intensive Care Unit, eight studies were employed (n = 156,650) [4,18,20,21,22,28,29,30].
The risk significantly increased when the second stage of labor lasted more than 4 h with respect to when the second stage of labor was ≤ 4 h (OR, 1.63; 95%CI 1.44–1.84). For this analysis, a random-effects model was used since medium heterogeneity was observed (Cochran’s Q p-value = 0.057; I2 = 48.8) (Figure 2B; Table 3).

Neonatal Sepsis

By combining three studies (n = 82,053) [4,20,21], we found that the risk of neonatal sepsis increased when the duration of the second stage of labor was longer than 4 h with respect to when the second stage of labor was ≤ 4 h (OR, 1.57; 95% CI 1.07–2.29). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran’s Q p-value = 0.7962; I2 = 0.0) (Table 3).

Neonatal Death

Two studies (n = 28,032) [18,21] were employed to determine the relationship between prolonged second stage of labor and risk of neonatal death, and no differences were found (OR, 7.21; 95% CI 0.37–139.71) (Table 3).

Other Neonatal Outcomes

No significant associations were reported between prolonged second stage in nulliparous women and 1 min Apgar score < 1, 5 min Apgar score ≤ 3, umbilical artery pH < 7, acidosis, meconium-stained amniotic fluid, meconium aspiration, birth depression, minor or major trauma, birth trauma, shoulder dystocia, brachial plexus injury, Erb’s palsy, resuscitation at birth, heart compressions, hypoxic ischemic encephalopathy, hypothermia treatment or composite neonatal morbidity. When the results of two studies were combined [20,22], only an increased risk of neonatal intubation in women with a second stage of labor > 4 h was observed (OR, 2.19; 95% CI 1.23–3.90) (Table 3).

3.4.2. Multiparous Women

5 min Apgar Score < 7

To determine the relation between prolonged second stage of labor in multiparous women (Table A4) and risk of low 5 min Apgar score (< 7), three studies were included (n = 72,857) [4,19,23]. A significant increase in low 5 min Apgar score was observed when the second stage of labor lasted more than 3 h with respect to when the second stage of labor was ≤ 3 h (OR, 3.67; 95% CI 2.49–5.43). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran’s Q p-value = 0.987; I2 = 0.0) (Figure 2C; Table 3).

Admission to the Neonatal Intensive Care Unit

To assess the risk of admission to the Neonatal Intensive Care Unit, three studies were employed (n = 76,692) [4,19,29]. The risk significantly increased when the second stage of labor lasted more than 3 h with respect to when the second stage of labor was ≤ 3 h (OR, 2.41; 95% CI 2.02–2.88). For this analysis, a fixed-effects model was used since no heterogeneity was observed (Cochran’s Q p-value = 0.417; I2 = 0.0) (Figure 2D; Table 3).

Neonatal Sepsis

None of the studies that analyzed multiparous women considered this variable when assessing neonatal morbidity in relation to the duration of the second stage of childbirth (Table 3).

Neonatal Death

None of the studies that analyzed multiparous women considered this variable when assessing neonatal morbidity in relation to the duration of the second stage of childbirth (Table 3).

Other Neonatal Outcomes

No significant associations were reported between prolonged second stage in multiparous women and umbilical artery pH < 7.0, umbilical artery pH < 7.10, umbilical artery base excess ≥12, meconium aspiration, shoulder dystocia, prolonged neonatal stay, advanced neonatal resuscitation, birth depression, minor or major trauma or any perinatal morbidity. After combining two studies [19,29], only an increase in the risk of meconium staining was observed (OR, 1.29; 95%CI, 1.01–1.66), and an increase in composite neonatal morbidity (OR,1.97; 95% CI, 1.39–2.80) was observed after another two studies were combined [19,23] (Table 3).

3.4.3. Publication Bias

We did not observe publication bias for the study in any of the variables studied (Table A3 and Table A4).
We can observe a summary of results obtained following meta-analysis of all variables studied in nulliparous and multiparous women in Table 3.

4. Discussion

4.1. Main Findings

Our meta-analysis results suggested that duration of second stage of labor of more than 4 h in nulliparous women increased the risk of low 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal intubation. In multiparous women, when the second stage of labor was longer than 3 h, the risk of 5 min Apgar score < 7, admission to Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity increased.
However, a prolonged second stage of labor did not increase the risk of any of the other variables studied, such as umbilical artery pH < 7, birth depression, neonatal death meconium aspiration or shoulder dystocia.

4.2. Comparison with Existing Literature

The literature has very limited data on neonatal outcomes of women with duration of second stage of labor of more than 4 h in nulliparas and of more than 3 h in multiparas. We were only able to locate 12 articles with these durations for this review.
An example of this is a recent systematic review by Gimovksy et al., which evaluated the maternal and fetal morbidities associated with prolonged second stage of labor in nulliparous women with epidurals, in which the authors defined prolonged second stage as greater than three hours [33]. Only two papers were included in this systematic review, and very discordant neonatal outcomes were analyzed, which did not allow the results to be combined in order to establish conclusions that would be useful for decision-making in clinical practice.
Another systematic review studied the influence of prolonged second stage of labor on the risk of adverse maternal and neonatal outcomes from 1980 until 2005 [34]. It did not report associations between prolonged second stage and adverse neonatal outcomes, but most of the studies analyzed in this review defined the prolongation of the second stage as more than 2 h, without differentiating according to parity. In addition, it did not conform to the new recommendations of allowing longer durations.
Only one randomized controlled trial [35] specifically addressed the effect of this change in obstetric practice on maternal and neonatal outcomes. In that trial, a policy of extending the second stage of labor for at least 1 h in nulliparous women with epidural anesthesia with respect to “usual labor” (3 h) decreased the incidence of caesarean birth by more than half compared with the common practice (19.5%, 8 of 41, vs. 43.2%, 16 of 37; RR, 0.45; 95% CI, 0.22–0.93). Maternal or neonatal morbidity were not statistically different between the groups. Unfortunately, the trial was underpowered to detect significant differences in the frequency of adverse maternal or neonatal outcomes between groups because the sample studied was very small (only 78 nulliparous women) (35).
However, Zipori et al. [36] recently published another study comparing maternal and neonatal outcomes over two distinct time periods. In period I, the duration of the second stage of labor was considered prolonged according to ACOG limits, and it was called a “classic labor curve” (10). The “new labor curve” of period II allowed nulliparous and multiparous women to continue the second stage of labor for an additional 1 h before diagnosing second-stage arrest. Primary caesarean deliveries decreased with the new policy of labor management, with a small rise in instrumental deliveries, but it also increased other immediate maternal and neonatal complications, such as higher rate of lower umbilical artery cord pH.

4.3. Strengths and Limitations

One of the strengths of this study is that it is the first systematic review to define prolonged second stage of labor according the most recent recommendations (11), that is, 4 h for nulliparous women and 3 h for multiparous women. Most of the studies had large sample sizes with sufficient numbers of participants in each group to lend power to the findings, and the majority of them used methods to control for potential confounding factors.
Among the limitations of our systematic review is that neonatal outcome measures were discordant in the included studies, meaning it was difficult to combine data to summarize important clinical findings, and that the definition of two variables (admission to NICU and composite neonatal morbidity) differed among included studies. None of the studies considered the pushing duration or pushing techniques employed (delayed pushing or immediate pushing). Finally, since they were observational studies, there is a risk of confounding bias even though many of the studies included techniques to control confounding.

5. Conclusions

In nulliparous women, a prolonged second stage of labor is not related with an increased risk of neonatal death. However, it is related with an increased risk of 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis or intubation. In multiparous women, a prolonged second stage of labor is related with an increased risk of 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, meconium staining and composite neonatal morbidity.
These potential risks associated with a prolonged second stage of labor in both nulliparous and multiparous women should serve as an incentive for professionals involved in childbirth care to increase supervision of mothers who exceed these durations.
More studies are needed, especially clinical studies, to guarantee the safety of newborns when the second stage of labor exceeds 4 h in nulliparous women and 3 h in multiparous women.

Author Contributions

Conceptualization, N.I.-T. and J.R.-A.; Methodology, M.M.-A. and A.A.-A.; Formal Analysis, A.H.-M. and J.R.-A.; Writing—Original Draft Preparation, N.I.-T. and M.M.-A.; Writing—Review & Editing, N.I.-T. and A.A.-A.; Supervision, J.R.-A. and A.H.-M.; Project Administration, A.H.-M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

Appendix A

Table A1. Search strategies.
Table A1. Search strategies.
Search Strategies
Search StrategyDatabaseHits
“Labor Stage, Second” (Mesh) AND (length OR duration OR prolonged OR abnormal OR excessive)PubMed501
Scopus590
Embase777
Search Strategy “PICO”
PopulationNulliparous and Multiparous women
InterventionSecond stage labor > 4 h in nulliparous
Second stage labor > 3 h in multiparous
ComparisonSecond stage labor ≤ 4 h in nulliparous
Second stage labor ≤ 3 h in multiparous
OutcomeNeonatal morbidity: 5 min Apgar score < 7, admission to the Neonatal Intensive Care Unit, neonatal sepsis and neonatal death.
Table A2. Checklist for Cohort Studies.
Table A2. Checklist for Cohort Studies.
.1995;
Menticoglou
2007;
Cheng
2009;
Allen
2009;
Rouse
2011;
Li
2012;
Bleich
2015;
Altman
2015;
Hunt
2017;
Sandström
2017; Ogunyemi2018;
Souter
2019;
Infante
1. Were the two groups similar and recruited from the same population?Unclear *No *No *Unclear *Unclear *Unclear *Unclear *Unclear *Unclear *Unclear *Unclear *Unclear *
2. Were the exposures measured similarly to assign people to both exposed and unexposed groups?YesYesYesYesYesYesYesYesYesYesYesYes
3. Was the exposure measured in a valid and reliable way?YesYesYesYesNoYesYesYesYesYesYesYes
4. Were confounding factors identified?NoYesYesYesNoYesYesNoYesYesYesYes
5. Were strategies to deal with confounding factors stated?NoYesYesYesNoYesYesNoYesYesNoYes
6. Were the groups/participants free of the outcome at the start of the study (or at the moment of exposure)?YesYesYesYesYesYesYesYesYesYesYesYes
7. Were the outcomes measured in a valid and reliable way?YesYesYesYesYesYesYesYesYesYesYesYes
8. Was the follow up time reported and sufficient to be long enough for outcomes to occur?YesYesYesYesYesYesYesYesYesYesYesYes
9. Was follow up complete, and if not, were the reasons to loss to follow up described and explored?YesYesYesYesYesYesYesYesYesYesYesYes
10. Were strategies to address incomplete follow up utilized?NANAYesNANANAYesNAYesNANAYes
11. Was appropriate statistical analysis used?UnclearYesYesYesUnclearYesYesUnclearYesYesUnclearYes
NA: not applicable, *: groups recruited from the same population.
Table A3. Neonatal morbidity outcomes in nulliparous women (≤4 h versus >4 h second-stage labor).
Table A3. Neonatal morbidity outcomes in nulliparous women (≤4 h versus >4 h second-stage labor).
1 min Apgar Score <75 min Apgar Score <75 min Apgar Score <45 min Apgar Score ≤3Umbilical Artery
pH <7
AcidosisBirth DepressionResuscitation at DeliveryIntubationHeart Compressions
Author≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h
1995; MenticoglouNRNR81/57337/308NRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2009; AllenNRNR589/51,02875/4908NRNRNRNRNRNRNRNR862/51,028138/4908NRNRNRNRNRNR
2009; RouseNRNRNRNR3/39830/143NRNR15/39831/143NRNRNRNRNRNR19/39831/143NRNR
2011; Li17/2958/123/2951/12NRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2012; BleichNRNRNRNRNRNR17/21,5642/42783/21,5644/427NRNRNRNR138/21,56413/427NRNRNRNR
2015; AltmanNRNR188/29,97639/282032/29,9768/2820NRNRNRNRNRNRNRNRNRNRNRNRNRNR
2015; HuntNRNR33/62944/886NRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2017; SandströmNRNRNRNRNRNRNRNRNRNR330/30,45331/2976NRNRNRNR58/38,73113/380836/38,73110/3808
2017; OgunyemiNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2018; SouterNRNR200/16,68284/3347NRNRNRNRNRNRNRNRNRNR851/16,682248/3347NRNRNRNR
Egger Bias
(p-value)
0.7861NC 0.8132 NCNC
I2 95% CI 71.0 (2.1–85.6)NC NC NCNC
Q Cochran
(p-value)
0.00410.7026 0.8132 <0.0010.681
OR 95% CI 1.65 (1,20–2.27) *2.27 (1.08–4.74) * 2.30 (0.94–5.69) 2.60 (0.81–8.63) *2.19 (1.23–3.90)
Meconium AspirationMeconium-Stained Amniotic FluidAdmission to NICUNeonatal SeizuresSepsisBirth TraumaMinor TraumaMajor TraumaShoulder Dystocia
Author≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h
1995; MenticoglouNRNRNRNR64/57332/3085/57330/308NRNRNRNRNRNRNRNRNRNR
2009; AllenNRNRNRNR3071/51,028505/4908NRNR195/51,02830/4908NRNR1311/51,028162/490878/51,02816/4908NRNR
2009; RouseNRNRNRNR167/398314/143NRNR6/39830/143NRNRNRNRNRNRNRNR
2011; LiNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2012; BleichNRNRNRNR172/21,5648/42741/21,56413/42739/21,5640/427NRNRNRNRNRNRNRNR
2015; AltmanNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNRNR
2015; HuntNRNRNRNR12/62924/886NRNRNRNRNRNRNRNRNRNRNRNR
2017; Sandström58/38,73110/3808NRNR2373/38,731360/380878/38,73117/3808NRNRNRNRNRNRNRNRNRNR
2017; OgunyemiNRNR309/421537/272372/420137/272NRNRNRNR33/38141/250NRNRNRNRNRNR
2018; SouterNRNRNRNR817/16,682221/3347NRNRNRNRNRNRNRNRNRNR367/16,68274/3347
Egger Bias
(p-value)
0.8326NCNC
I2 95% CI 48.8 (0.0–75,4)92.3 (78.6–95,8)0.0 (0–72.9)
Q Cochran
(p-value)
0.0573<0.0010.7962
OR 95% CI 1.63 (1.53–1.74)4.67 (0,78–27.78) *1.57 (1.07–2.29)
Brachial Plexus InjuryErb’s PalsyHypoxic Ischemic EncephalopathyHypothermia TreatmentComposite Neonatal MorbidityNeonatal Death
Author≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h≤4 h>4 h
1995; MenticoglouNRNRNRNRNRNRNRNRNRNR0/57330/308
2009; AllenNRNRNRNRNRNRNRNRNRNRNRNR
2009; Rouse10/39831/143NRNRNRNRNRNR98/39836/143NRNR
2011; LiNRNRNRNRNRNRNRNRNRNRNRNR
2012; BleichNRNR82/21,5642/427NRNRNRNRNRNR3/21,5640/427
2015; AltmanNRNRNRNRNRNRNRNRNRNRNRNR
2015; HuntNRNRNRNRNRNRNRNRNRNRNRNR
2017; SandströmNRNRNRNR75/38,73122/380816/38,7317/3808NRNRNRNR
2017; OgunyemiNRNRNRNRNRNRNRNRNRNRNRNR
2018; SouterNRNRNRNRNRNRNRNRNRNRNRNR
Egger Bias
(p-value)
NC
I2 95% CI NC
Q Cochran
(p-value)
NC
OR 95% CI 7.21 (0.37–139.71) *
NR: not reported; NR: not calculated; CI: confidence interval; * Random effects (DerSimonian–Laird); Bold: Significant results are highlighted.
Table A4. Neonatal Morbidity Outcomes in Multiparous Women (≤3 h versus >3 h second stage of labour).
Table A4. Neonatal Morbidity Outcomes in Multiparous Women (≤3 h versus >3 h second stage of labour).
5 min Apgar Score <7Umbilical Artery pH <7.0Umbilical Artery pH <7.10Umbilical Artery Base Excess>−12Birth DepressionAdvanced Neonatal
Resuscitation
Meconium Amniotic Fluid or Meconium StainingNICU AdmissionProlonged Neonatal Stay
Author≤3 h>3 h≤3 h>3 h≤3 h>3 h≤3 h>3 h>3 h≤3 h≤3 h>3 h≤3 h>3 h≤3 h>3 h≤3 h>3 h
2007; Cheng60/490111/25717/49011/257NRNR31/49013/257NRNRNRNR1061/490173/257145/490114/257445/490134/257
2009; Allen311/64,58617/968NRNRNRNRNRNR553/64,58627/968NRNRNRNR2409/64,58690/968NRNR
2017; OgunyemiNRNRNRNRNRNRNRNRNRNRNRNR290/575912/276410/570040/278NRNR
2019; Infante3/20810/64NRNR37/18583/54NRNRNRNR39/20813/64NRNRNRNRNRNR
Egger Bias
(p-value)
NC NCNC
I2 95% CI0% (0.0%–72.9%) NC0% (0.0%–72.9%)
Q Cochran
(p-value)
0.987 0.1210.417
OR 95% CI3.67 (2.49–5.43) 1.29 (1.01–1.66)2.41 (2.02–2.88)
Minor TraumaMajor TraumaShoulder DystociaComposite Neonatal MorbidityAny Perinatal Morbidity
Author>3 h>3 h≤3 h>3 h≤3 h>3 h≤3 h>3 h≤3 h>3 h
2007; ChengNRNRNRNR117/490110/257361/490133/257NRNR
2009; Allen586/64,58627/968104/64,5862/968NRNRNRNR3662/64,586128/968
2017; OgunyemiNRNRNRNRNRNRNRNRNRNR
2019; InfanteNRNRNRNRNRNR70/20816/64NRNR
Egger Bias
(p-value)
NC
I2 95% CI NC
Q Cochran
(p-value)
0.330
OR 95% CI 1.97 (1.39–2.80)
NR: not reported; NR: not calculated; CI: confidence interval; Random effects (DerSimonian–Laird); Bold: Significant results are highlighted.

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Figure 1. PRISMA flow diagram of the literature reviewing process.
Figure 1. PRISMA flow diagram of the literature reviewing process.
Ijerph 17 07762 g001
Figure 2. Forest plot for 5 min Apgar Score < 7 in nulliparous women (a), admission to NICU in nulliparous women (b), 5 min Apgar Score < 7 in multiparous women (c) and (d) admission to NICU in multiparous women.
Figure 2. Forest plot for 5 min Apgar Score < 7 in nulliparous women (a), admission to NICU in nulliparous women (b), 5 min Apgar Score < 7 in multiparous women (c) and (d) admission to NICU in multiparous women.
Ijerph 17 07762 g002
Table 1. Definition of variables.
Table 1. Definition of variables.
DefinitionsAuthors
1995;
Menticoglou [18]
2007; Cheng [19]2009; Allen [4]2009; Rouse [20]2012; Bleich [21]2017; Sandström [22]2019; Infante [23]
AcidosisNRNRNRNRNRA pH value <7.05 and base excess <−12 in the umbilical artery.NR
Birth depressionNRNRDelay in initiating and maintaining respirations after birth requiring resuscitation by mask or endotracheal tube for at least 3 min, a 5 min Apgar score of 3 or less, or neonatal seizures due to hypoxic-ischemic encephalopathy.NRNRNRNR
IntubationNRNRNRIntubation in delivery room.NRNRNR
Heart compressionsNRNRNRNRNRResuscitation in delivery room with heart compressions and/or intubation.NR
Advanced neonatal resuscitationNRNRNRNRNRNRType III: Oxygen therapy with positive intermittent pressure.
Type IV: Endotracheal intubation,
Type V: Cardiac massage and/or using drugs
Admission to Neonatal Intensive Care UnitNeed for admission to the Neonatal Intensive Care Unit for any reason at all or with a 5 min Apgar score < 7 or arterial cord pH < 7.20.NRNeonatal intensive care unit admission with duration of stay longer than 24 h.Admission to a neonatal intensive care unit for >48 h.NRNRNR
Prolonged neonatal stayNRNeonatal stay >2 d for vaginal delivery and >4 d for caesarean delivery.NRNRNRNRNR
Neonatal seizuresNRNRNRNRSeizures in the first 24 h of life.NRNR
SepsisNRNRPositive blood culture, septicemia or systematic infection.NRPositive blood culture.NRNR
Minor traumaNRNROne or more of the following neonatal traumas: linear skull fracture, other fractures (clavicle, ribs, numerus, or femur), facial palsy, or cephalohematoma.NRNRNRNR
Major traumaNRNROne or more of the following neonatal traumas: depressed skull fracture, intracranial hemorrhage, or brachial plexus palsy.NRNRNRNR
Composite neonatal morbidityNRComposite variable for 5 min Apgar <7, UA pH <7.0, UA base excess ≥12, shoulder dystocia, NICU stay, and birth trauma (which includes brachial plexus injury, facial nerve palsy, clavicular fracture, skull fracture, head laceration, and cephalohematoma defined and diagnosed by the attending pediatrician).Composite of any of the other neonatal outcomes.Any of the following occurrences: a 5 min Apgar score <4, an umbilical artery pH <7.0, seizures, intubation, stillbirth, neonatal death, or admission to a NICU.NRNRComposite of any of the other neonatal outcomes.
Neonatal deathDeath during the second stage of labor or in the first 28 d of lifeNRNRNRNRNRNR
NR: not reported.
Table 2. Characteristics of the studies analyzed.
Table 2. Characteristics of the studies analyzed.
YEAR OF PUBLICATION
AUTOR
COUNTRYSTUDY DESIGNPOPULATION
UNDER STUDY
DURATION OF SECOND STAGE OF LABOUR n (%)DELIVERY MODE N (%)USE OF EA
N (%)
INCLUSION/EXCLUSION CRITERIA
0–1 h1–2 h2–3 h3–4 h>4 hSpontaneous Vaginal DeliveryOperative Vaginal DeliveryCaesarean Section
NULLIPAROUS1995/
Menticoglou
[18]
CanadaCohort study60412622 (43.4)1805 (29.9)927 (15.3)379 (6.3)308 (5.1)4942 (81.8)932 (15.5)167 (2.7)NR
  • January 1988 to December 1992. Singleton babies in cephalic presentation.
  • BW ≥ 2500 g
  • Fetal death diagnosed before labor and caesarean section before labor or during the first stage of labor were excluded.
2009/
Rouse
[20]
United StatesSecondary analysis of a clinical trial41261901 (46.1)1251
(30.3)
614 (14.9)217 (5.2)143 (3.5)3054 (74.0)765 (18.5)307 (7.5)3916 (95.0)
  • Nulliparous women with a singleton vertex fetus who labored spontaneously or were induced at ≥ 36 WG and who reached the second stage of labor.
  • Exclusion criteria included maternal fever and serious medical conditions.
2011/
Li
[31]
ChinaCase-control study307206 (67.1)29 (9.4)60 (19.5)12 (4.0)NRNRNRNR
  • NR
2012/
Bleich
[21]
United StatesCohort study21,99113,736 (62.5)4933
(22.4)
1833
(8.3)
1062
(4.8)
427 (2.0)19,326 (87.9)1367 (6.2)1298 (5.9)13,676 (62.2)
  • Nulliparous women who reached the second stage of labor.
  • Singleton live-born infants at ≥ 37 WG and cephalic presentation.
  • Between January 2003 to December 2008.
  • Fetal malformations, placenta previa and multiple gestation were excluded.
2015/
Altman
[32]
SwedenCohort study32,79610,731 (32.7)9491
(29.0)
5856
(17.8)
3898
(11.9)
2820 (8.6)NR6728 (20.5)NR19,417 (59.2)
  • First live singleton infant in cephalic presentation at ≥ 37 WG.
  • From January 2008 to December 2012.
  • Caesarean and induced deliveries and deliveries with incomplete data were excluded.
2015/
Hunt
[28]
CanadaCohort study1515NCNCNC629 (41.5)886 (58.5)615 (40.6)662 (43.7)238 (15.7)NR
  • Nulliparous women who delivered non-anomalous, term (≥ 36 WG), cephalic, live singleton neonatal weight ≥ 2500 g and who had a prolonged second stage of labor.
  • Between January 1993 and April 2006.
2017/
Sandström
[22]
SwedenCohort study42,53913,558 (31.9)12,225 (28.7)7710 (18.1)5238 (12.3)3808 (9.0)NRNRNRNR
  • Between January 2008 to December 2013.
  • Nulliparous women with cephalic presentation at 37 WG or later.
  • Elective caesarean deliveries, emergency caesareans during first stage of labor and deliveries with incomplete data were excluded (without labor partograph or notation on complete dilation of the cervix).
2018/
Souter
[30]
United StatesCohort study in a poster session20,02916,682 (83.3)3347 (16.7)14,942 (74.6)3015 (15.0)2072 (10.4)20,029 (100)
  • Singleton deliveries at 37 + 0 to 42 + 6 WG between January 2012 and December 2016
MULTIPAROUS2007/
Cheng
[19]
United StatesCohort study51584112 (79.7)550 (10.7)239 (4.6)257 (5.0)4480 (86.8)414 (8.1)263 (5.1)2274 (44.1)
  • Between 1991 and 2001.
  • All term and post-term, cephalic, live singleton births to multiparous women who had spontaneous onset of labor.
  • Caesarean delivery before the completion of the first stage of labor, placenta previa, intrauterine fetal demise or known lethal congenital anomalies were excluded.
2019/
Infante
[23]
SpainCohort study21451589 (74.1)327 (15.2)165 (7.7)64 (3.0)2070 (96.5)75 (3.5)NR1675 (78.1)
  • Women who had given birth vaginally, with cephalic presentation and singleton babies between 2013 and 2016.
  • Births with < 35 WG and antepartum fetal death were excluded.
NULLIPAROUS AND MULTIPAROUS2009/
Allen
[4]
CanadaCohort study55,936 nulliparous38,790 (69.3)7832 (14.0)4406 (7.9)4908 (8.8)101,897 (83.8)15,865 (13.1)3734 (3.1)61,077 (50.3)
  • Between 1988 and 2006.
  • Liveborn singleton at or after 37 WG reaching full cervical dilatation.
  • Deliveries that occurred before onset of labor, a major congenital anomaly, at least one previous caesarean delivery, severe pregnancy-related medical disorders or missing outcome data were excluded
65,554 multiparous59,227 (90.3)4171 (6.3)1188 (1.8)968 (1.6)
2017/
Ogunyemi
[29]
United StatesPoster session10,487 *NCNCNCNCNCNRNRNRNR
  • Singleton at term.
NC: not calculated, NR: not reported, EA: epidural analgesia, BW: birthweight, WG: weeks gestation, *: no data on nulliparous/multiparous.
Table 3. Summary of results obtained following meta-analysis of all variables studied in nulliparous women. Summary of results obtained following meta-analysis of all variables studied in multiparous women.
Table 3. Summary of results obtained following meta-analysis of all variables studied in nulliparous women. Summary of results obtained following meta-analysis of all variables studied in multiparous women.
VariableNumber of StudiesNumber of SubjectsEgger Bias
(p-Value)
I2 95% CICochran’s Q
(p-Value)
OR 95% CI
1 min Apgar Score <71307NCNCNCNC
5 min Apgar score <76116,6240.786171.0 (2,1–85,6)0.00411.65 (1.20–2.27)
5 min Apgar score <4236,922NCNC0.70262.27 (1.08–4.74)
5 min Apgar Score <3121,991NCNCNCNC
Umbilical artery pH <7229,1170.8132NC0.81322.30 (0.94–5.69)
Umbilical artery pH <7.1000NRNRNRNR
Umbilical artery base excess >−1200NRNRNRNR
Acidosis133,429NCNCNCNC
Birth depression155,936NCNCNCNC
Resuscitation at delivery242,020NCNC<0.0012.60 (0.81–8.63)
Intubation246,665NCNC0.6812.19 (1.23–3.90)
Heart compressions142,539NCNCNCNC
ANR00NRNRNRNR
Meconium aspiration142,539NCNCNCNC
Meconium-stained amniotic fluid14487NCNCNCNC
Admission to Neonatal Intensive Care Unit8156,6500.832648.8 (0.0–75.4)0.05731.63 (1.44–1.84)
Prolonged neonatal stay00NRNRNRNR
Neonatal seizures370,571NC92.3 (78.6–95.8)<0.0014.67 (0.78–27.78)
Neonatal sepsis382,053NC0.0 (0–72.9)0.79621.57 (1.07–2.29)
Birth trauma14064NCNCNCNC
Minor trauma155,936NCNCNCNC
Major trauma155,936NCNCNCNC
Shoulder dystocia120,029NCNCNCNC
Brachial plexus injury14126NCNCNCNC
Erb’s palsy121,991NCNCNCNC
Hypoxic ischemic encephalopathy142,539NCNCNCNC
Hypothermia treatment142,539NCNCNCNC
Composite neonatal morbidity14126NRNRNRNR
Any perinatal morbidity00NRNRNRNR
Neonatal death228,032NCNCNC7.21 (0.37–139.71)
VariableNumber of StudiesNumber of SubjectsEgger Bias
(p-Value)
I2 95% CICochran’s Q
(p-Value)
OR 95% CI
1 min Apgar Score < 700NRNRNRNR
5 min Apgar score < 7372,857NC0.0 (0.0–72.9)0.9873.67 (2.48–5.43)
5 min Apgar score < 400NRNRNRNR
5 min Apgar Score ≤ 300NRNRNRNR
Umbilical artery pH < 715158NCNCNCNC
Umbilical artery pH < 7.1011912NCNCNCNC
Umbilical artery base excess > −1215158NCNCNCNC
Acidosis00NRNRNRNR
Birth depression165,554NCNCNCNC
Resuscitation at delivery00NRNRNRNR
Intubation00NRNRNRNR
Heart compressions00NRNRNRNR
ANR12145NCNCNCNC
Meconium aspiration00NRNRNRNR
Meconium-stained amniotic fluid211,193NCNC0.1211.29 (1.01–1.66)
Admission to Neonatal Intensive Care Unit376,692NC0.0 (0.0–72.9)0.4172.41 (2.02–2.88)
Prolonged neonatal stay15158NCNCNCNC
Neonatal seizures00NRNRNRNR
Neonatal sepsis00NRNRNRNR
Birth trauma00NRNRNRNR
Minor trauma165,554NCNCNCNC
Major trauma165,554NCNCNCNC
Shoulder dystocia15158NCNCNCNC
Brachial plexus injury00NRNRNRNR
Erb’s palsy00NRNRNRNR
Hypoxic ischemic encephalopathy00NRNRNRNR
Hypothermia treatment00NRNRNRNR
Composite neonatal morbidity27303NCNC0.3301.97 (1.39–2.80)
Any perinatal morbidity165,554NCNCNCNC
Neonatal death00NRNRNRNR
ANR: advanced neonatal resuscitation; NC: not calculated; NR: not reported.
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Infante-Torres, N.; Molina-Alarcón, M.; Arias-Arias, A.; Rodríguez-Almagro, J.; Hernández-Martínez, A. Relationship Between Prolonged Second Stage of Labor and Short-Term Neonatal Morbidity: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 7762. https://doi.org/10.3390/ijerph17217762

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Infante-Torres N, Molina-Alarcón M, Arias-Arias A, Rodríguez-Almagro J, Hernández-Martínez A. Relationship Between Prolonged Second Stage of Labor and Short-Term Neonatal Morbidity: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health. 2020; 17(21):7762. https://doi.org/10.3390/ijerph17217762

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Infante-Torres, Nuria, Milagros Molina-Alarcón, Angel Arias-Arias, Julián Rodríguez-Almagro, and Antonio Hernández-Martínez. 2020. "Relationship Between Prolonged Second Stage of Labor and Short-Term Neonatal Morbidity: A Systematic Review and Meta-Analysis" International Journal of Environmental Research and Public Health 17, no. 21: 7762. https://doi.org/10.3390/ijerph17217762

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