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. 2021 Oct 20;16(10):e0258303. doi: 10.1371/journal.pone.0258303

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study

Clémentine Pierre 1,2,*, Audrey Leroy 1, Adeline Pierache 3, Laurent Storme 1,2, Véronique Debarge 1,2, Sandrine Depret 1, Thameur Rakza 1,2, Charles Garabedian 1,2, Damien Subtil 1,2
Editor: Frank T Spradley4
PMCID: PMC8528279  PMID: 34669715

Abstract

Background

The effect on neonatal mortality of mode of delivery of a fetus in breech presentation at an extremely preterm gestational age remains controversial.

Objective

To compare mortality associated with planned vaginal delivery (PVD) of fetuses in breech presentation with that of fetuses in breech presentation with a planned cesarean delivery (PCD).

Material and methods

Retrospective study reviewing records over a 19-year period in a level 3 university referral center of singleton infants born between 25+0 and 27+6 weeks of gestation, alive on arrival in the delivery room, and weighing at least 500 grams at birth. Infants in the first group were in breech presentation with PVD and the second in breech presentation with PCD. The principal endpoint was neonatal death.

Results

During the study period, we observed 113 breech presentations with PVD, and 80 breech presentations with PCD. Although not significant after adjustment, neonatal mortality in the breech PVD group was more than twice that of the breech PCD group (19.5 vs 7.8%, P = 0.031, ORa = 2.6, 95% CI 0.8–9.3, NNT = 8). This higher neonatal mortality in the breech PVD group was exclusively associated with a higher risk of death in the delivery room (12.4 vs 0.0% P = 0.001, OR not calculable, NNT = 8). In these extremely preterm breech presentations with PVD, neonatal mortality in the delivery room was associated with entrapment of the aftercoming head, cord prolapse, and a short duration of labor.

Conclusion

For deliveries between 25+0 and 27+6 weeks’ gestation, vaginal delivery in breech presentation is associated with a higher risk of death in the delivery room.

Introduction

Preterm birth is the leading cause of perinatal mortality and morbidity [1, 2].

The conditions of birth of preterm infants can play a determinant role in their immediate and long-term prognosis. This prognosis is best if the birth is preceded by antenatal corticosteroid therapy and takes place in a center appropriate to the extent of prematurity (moderately preterm at 32–36 weeks of gestation (weeks), very at 28–32 weeks, and extremely before 28 weeks) [3–5]. Although mode of delivery does not necessarily appear to be a prognostic factor in preterm deliveries [6]. the situation when the fetus is simultaneously in breech presentation and very preterm is somewhat uncertain [7].

Before 32 weeks of gestation, vaginal delivery may involve risks [8], although they are not unanimously reported [9]; they appear most frequent for extremely preterm delivery [7, 8]. Most authors report that a trial of vaginal delivery for fetuses in breech presentation before 28 weeks is accompanied by an increase in neonatal mortality [7, 10–15], although a few have not reported it in extremely preterm infants [16, 17]. The cause of this possible excess of neonatal mortality is mostly not specified. Few countries recommend a routine cesarean delivery in this situation [18]; others make no recommendations at all about mode of delivery [19, 20].

In view of these gaps and uncertainty in the literature, we conducted a study to measure the potential neonatal excess risk of mortality associated with vaginal delivery of fetuses in breech presentation born extremely preterm. In order to better understand the possible excess mortality in case of trial of labor, total neonatal mortality was separated as i) death during delivery plus ii) death in the neonatal intensive care unit (NICU).

Material and methods

This retrospective study examined files of patients in our university hospital level 3 maternity ward from the start of 1997 to the end of 2015. Women were eligible for one of these study groups if they had a singleton pregnancy in breech or cephalic presentation and gave birth between 25+0 and 27+6 weeks of gestation during the study period by vaginal or cesarean delivery to a liveborn infant with a birth weight of at least 500 g. Other presentations, medically indicated terminations of pregnancy, fetal deaths, fetuses with congenital malformation, and pregnancies involving imminent threats to the mother or fetus justifying an emergency cesarean (e.g., eclampsia or abruptio placentae) were not eligible.

To measure the potential excess neonatal mortality for fetuses in breech presentation born extremely preterm after planned vaginal delivery (breech PVD), we compared them with fetuses in breech presentation born after planned cesarean delivery (breech PCD).

The women’s characteristics were collected from their obstetric files: maternal age, smoking, parity, previous cesarean delivery, spontaneous or induced preterm delivery, premature rupture of the membranes (yes/no), corticosteroid therapy (yes/no), duration of labor (from arrival in delivery room to delivery), gestational age at delivery. Mode of delivery was defined by what had been planned before or at the very start of labor, regardless of outcome. Accordingly, a woman arriving in labor for whom vaginal delivery was judged possible was included in the PVD group, even if a cesarean delivery was finally performed during labor. Data collected about delivery included cord prolapse during labor, entrapment of the aftercoming head/difficulties during delivery and use of forceps. We also extracted data about the neonatal outcome: birth weight, 5-minute Apgar score, both the umbilical artery pH, base deficit and lactates at birth. We also noted the presence (yes/no) in the newborn of intraventricular hemorrhage of grade 3 or 4 on transfontanellar ultrasound, or grade 3 or 4 leukomalacia, whether or not associated with cerebral hyperechogenicity for more than 10 days, and the onset of intracranial hemorrhages. The principal endpoint was total neonatal mortality defined as i) death during delivery plus ii) death in the neonatal intensive care unit (NICU). The use of retrospective data for this study was reported to the French Data Protection Authority (2020–460). Under French regulations, this study is exempt from IRB review because it is an observational study using anonymised data from medical records.

Women are informed that their records can be used for the evaluation of medical practices and are provided the option to opt out of these studies. They have signed an non-objection form for the use of data from their medical file.

Categorical variables are expressed as numbers (percentage). Quantitative variables are expressed as means (± standard deviation, SD) in the case of normal distribution or medians [interquartile range, IQR] otherwise. Normality of distributions was assessed using histograms and the Shapiro-Wilk test. Comparisons of mothers’ characteristics according to planned mode of delivery (PVD vs PCV) were performed with Chi-square tests for categorical variables (or Fisher’ exact tests when expected cell frequency was <5), Student t or Mann-Whitney U tests (regarding the normality of distributions) for quantitative variables and Cochran Armitage trend tests for ordinal variables. Comparisons in outcomes (newborn conditions) between the two planned mode of delivery (PVD vs PCD) were done using logistic regression models for binary outcomes and linear regression model for umbilical artery pH. Comparisons in neonatal mortality outcome were further adjusted for pre-specified confounding factors (weight, gestational age and gender at delivery). Odds ratios (ORs) for binary outcomes and difference in means for umbilical artery pH were derived from regression models as effect sizes with theirs 95% confidence intervals (CIs).

In infants born in breech planned vaginal delivery (PVD), factors associated with death in the delivery room were assessed using univariable logistic regression models; no multivariable regression model was done regarding the small number of events. Odds ratios (ORs) and theirs 95% confidence intervals (CIs) were calculated as effect sizes. Finally, comparisons in the risk of head entrapment and neonatal deaths in delivery room for breech PVD according to gestational age (25 vs 26 vs 27 SA) were done using Cochran Armitage trend tests. Statistical testing was conducted at the two-tailed α-level of 0.05. Data were analyzed using the SAS software version 9.4 (SAS Institute, Cary, NC).

Results

During the 19-year study period, our hospital had 90,320 deliveries, including 1,144 (1.3%) singleton deliveries between 25+0 and 27+6 weeks of gestation (Fig 1). After the exclusion of 72 women whose fetuses weighed less than 500 grams at birth, 42 presentations that were neither cephalic nor breech, 273 medically indicated terminations of pregnancy, 100 fetal deaths, 18 congenital malformations, 14 emergency cesareans due to imminent threats to the mother or fetus, and 6 missing files, there remained 619 deliveries of live singletons between 25+0 and 27+6 weeks of gestation with a birth weight of at least 500 grams eligible for our study. Among these 619 women, 173 women had a cephalic PVD and 253 a cephalic PCD. Finally, 113 had a fetus in breech PVD—including 4 who finally had cesarean deliveries during labor (3.5%)—and 80 women had a breech PCD, all delivered according to plan. Among the planned cesareans, 88.2% performed incisions into the uterine body.

Fig 1. Flow chart.

Fig 1

* including 4 cesareans during labor; ** none born by vaginal delivery.

The characteristics of the women in the breech PVD and PCD group were very different (Table 1). In the PCD group, women were somewhat older and they had more often previous history of c-section. In this group, most of the deliveries were induced, gestational age was higher by several days, and the mean birth weight was more than 100 grams lower.

Table 1. Mothers’ characteristics and pregnancy outcomes according to planned type of delivery (PVD: Planned vaginal delivery, PCD: Planned cesarean delivery).

1. PVD 2. PCD P
n = 113 n = 80
Maternal age (years) 27.3 ± 6.0 29.9 ± 5.5 0.002
Smoker 30/108 (27.8) 13/78 (16.7) 0.076
BMI1 (kg/m2) 23.5 ± 5.3 25.1 ± 7.8 0.16
Nulliparous 62/113 (54.9) 42/79 (53.2) 0.82
Previous cesarean section 6/113 (5.3) 18/79 (22.8) <0.001
Spontaneous preterm delivery 113/113 (100) 26/80 (32.5) <0.001
Preterm premature rupture of the membranes 59/113 (52.2) 22/80 (27.5) <0.001
Antenatal corticosteroid therapy 102/113 (90.3) 77/80 (96.3) 0.11
Anesthesia/analgesia < 0.001
    None 61/111 (55.0) 0/79 (0)
    Locoregional 50/111 (45.0) 41/79 (51.9)
    General 0/111 (0) 38/79 (48.1)
Duration of labor (min)2 47.5 [10–110] - -
    <60 minutes 57/110 (51.8) - -
Gestational age at delivery (weeks) 26.3 [25.6–26.9] 27.1 [26.6–27.4] < 0.001
    25–25+6 39/113 (34.5) 7/80 (8.7) < 0.001
    26–26+6 46/113 (40.7) 25/80 (31.3)
    27–27+6 28/113 (24.8) 48/80 (60.0)
Birth weight (grams) 870 ± 130 760 ± 180) <0.001
    500–699 9/113 (8.0) 35/80 (43.7) < 0.001
    700–899 53/113 (46.9) 28/80 (35.0)
    ≥900 51/113 (45.1) 17/80 (21.3)
Birthweight < 3rd percentile 6 (5.3) 42 (52.5) <0.001
Sex ratio (male) 75/113 (66.4) 33/80 (41.3) <0.001

Values are expressed as mean ± standard deviation, median [interquartile range] or no./total no. (percentage).

1: 49 missing values (13 in PCD group), 2: 3 missing values in PVD group.

The neonatal conditions according to planned mode of delivery are described in Table 2. In the PVD group, more than a quarter of the infants presented at birth with either entrapment of the aftercoming head or difficult instrumental deliveries, significantly higher than in the PCD group (27.4 vs 6.3%, p<0.001, OR 5.7, 95% CI 2.1–15.3)) Forceps were clearly used more frequently in the breech PVD group than in the PCD group (12.4 vs 0.0%, p = 0.001). There was no difference between PVD and PCD groups according low 5-min Apgar scores. Among the children whose pH could be measured (n = 164, 85.0%), there was no significant difference between the groups in the number with severe neonatal acidosis (umbilical artery pH < 7.0), or with metabolic acidosis (base deficit > -12 mM/L), or with significantly elevated lactates. However, unadjusted analysis showed that total neonatal mortality in the breech PVD group was more than twice that in the breech PCD group (19.5 vs 7.8%, p = 0.031, OR 2.9, 95% CI [1.1–7.4], NNT = 8). This higher rate of neonatal mortality in the PVD group was associated exclusively with a higher risk of death in the delivery room (12.4 vs 0.0% p = 0.001, OR not calculable, NNT = 8). Finally, the newborns who left the delivery room alive for the NICU did not differ between the groups for neonatal mortality (7.1 vs 7.8%, p = 0.85, OR 0.9, 95% CI [0.3–2.7]) and neonatal severe morbidity: frequency of maternal-fetal infections, grade 3 or 4 intraventricular hemorrhages, periventricular leukomalacia of grade ≥ 3, hyperechogenicity > 10 days, or intracranial hemorrhages were identical in both groups.

Table 2. Newborn conditions according to planned mode of delivery.

1. PVD 2. PCD P Unadjusted Adjusted
n = 113 n = 80 OR [95% CI] ORa [95% CI] *
Entrapment of the aftercoming head/difficulties during delivery 31/113 (27.4) 5/80 (6.3) <0.001 5.7 [2.1–15.3]
Use of forceps 13/105 (12.4) 0/80 (0.0) 0.001 NA
5-min Apgar < 7 17/95 (17.9) 15/79 (19.0) 0.85 0.9 [0.4–2.0]
Umbilical artery pH1 7.30 ± 0.12 7.25 ± 0.10 0.012 0.04 [0.01–0.08]
    < 7.0 2/96 (2.1) 1/68 (1.5) 1.00 NA
Base deficit > -12 mM/L 5/89 (5.6) 2/65 (3.1) 0.46 1.9 [0.4–10.0]
Lactates>10 mM/L on arrival at NICU 7/88 (8.0) 5/50 (10.0) 0.68 0.8 [0.2–2.6]
Umbilical artery < 7.0, base deficit > -12 mM/L or lactates>10 mM/L on arrival at NICU 13 (11.5) 8 (10.0) 0.74 1.2 [0.4–3.5]
Global neonatal mortality 22/113 (19.5) 6/77 (7.8) 0.031 2.9 [1.1–7.4] 2.6 [0.8–9.3]
    • In the delivery room 14/113 (12.4) 0/77 (0.0) 0.001 NA NA
    • In the NICU 8/113 (7.1) 6/77 (7.8) 0.85 0.9 [0.3–2.7] 0.7 [0.2–2.9]
Maternal-fetal infection 14/99 (14.1) 10/77 (13.0) 0.82 1.1 [0.5–2.6]
Intraventricular hemorrhage grade 3–4 8/99 (8.1) 9/76 (11.8) 0.41 0.7 [0.2–1.8]
Leukomalacia ≥ 3 or hyperechogenicity > 10 days 17/99 (17.2) 11/72 (15.3) 0.74 1.2 [0.5–2.6]
Intracranial hemorrhage 8/98 (8.2) 2/31 (6.5) 0.76 1.3 [0.3–6.4]

Values are expressed as mean ± standard deviation or no./total no. (percentage). ORa: Adjusted for weight, gestational age and gender at delivery.

*: Difference mean were calculated as effect size for continuous variables. NA: not applicable.

1: 29 missing values (12 in PCD group).

The risk of death in the delivery room for breech PVDs remained stable around 12% over our 19-year study period: 18, 11, 20 and 10% during 5 years consecutive periods (chi2 for trend, Cochran-Armitage test, p = 0.62). Table 3 presents the factors associated with death in the delivery room among the 113 newborns in the breech PVD group. These deaths were significantly associated with a short duration of labor (<60mn) (78.6 vs 46.5%, p = 0.035, OR 4.2, 95% CI 1.1–16.1), cord prolapse (21.4 vs 1.0%, p = 0.006, OR 26.7, 95% CI 2.6–279.5) and entrapment of the aftercoming head (64.3 vs 22.2%, p = 0.002, OR 6.3, 95% CI 1.9–20.7). Cord prolapse, however, affected only 4 fetuses (3 of whom died in the delivery room), while more than a quarter of breech PVD fetuses had intracervical head entrapment (n = 31, 27.4%), and a third of them died in the delivery room (n = 9, 29.0%). Twelve of these cases of entrapment of the aftercoming head required the performance of a cervicotomy (10.6%), half of which were themselves accompanied by death in the delivery room (42.9 vs 6.1%, p<0.001, OR 11.6, 95% CI 3.0–44.5). On the other hand, deaths in delivery room were not significantly associated with nulliparity, premature rupture of the membranes, chorioamnionitis, type of breech, or a lower gestational age. Finally, among all deaths in delivery room for breech fetuses, head entrapments concern 9/14 and cord prolapse 3/14, risks known to be associated with breech presentation in vaginal delivery.

Table 3. Factors associated with death in the delivery room of infants born in breech planned vaginal delivery (breech PVD).

Died in the delivery room Alive at discharge from delivery room P OR [95% CI]
n = 14 n = 99
Duration of labor < 60 min 11/14 (78.6) 46/99 (46.5) 0.035 4.2 [1.1–16.1]
Cord prolapse 3/14 (21.4) 1/99 (1.0) 0.006 26.7 [2.6–279.5]
Entrapment of the aftercoming head 9/14 (64.3) 22/99 (22.2) 0.002 6.3 [1.9–20.7]
    including cervicotomy 6/14 (42.9) 6/99 (6.1) <0.001 11.6 [3.0–44.5]
Nulliparous women 8/14 (57.1) 54/99 (54.5) 0.86 1.1 [0.4–3.4]
Preterm premature rupture of membranes 10/14 (71.4) 49/99 (49.5) 0.13 2.6 [0.7–8.7]
Chorioamnionitis 8/11(72.7) 51/68 (75.0) 0.87 0.9 [0.2–3.7]
Complete breech 8/14 (57.1) 51/99 (51.5) 0.69 1.3 [0.4–3.9]
Gestational age 25 weeks (vs 26 or 27) 8/14 (57.1) 31/99 (31.3) 0.065 2.9 [0.9–9.1]

Values are expressed as no./total no. (percentage). NA: not applicable

Table 4 reports the risk of head entrapment and death in delivery room according to gestational age in the cases of PVD. The risk of head entrapment barely changed with gestational age (mean: 27%). Death in delivery room fell as gestational age increased, and nearly all the neonatal deaths occurred in children born at 25 or 26 weeks (92.9%). Finally, the risk of death associated with head entrapment was significantly highest at the lowest gestational ages (50.0% at 25 weeks, 22.2% at 26 weeks, and 10.0% at 27 weeks).

Table 4. Risk of head entrapment and neonatal deaths in delivery room.

Head entrapment Death in delivery room Head entrapment with death in delivery room
n = 31/113 (27.4) n = 14/113 (12.4) n = 9/31 (29.0)
25 SA (n = 39) 12/39 (30.8) 8/39 (20.5) 6/12 (50.0)
26 SA (n = 46) 9/46 (19.6) 5/46 (10.9) 2/9 (22.2)
27 SA (n = 28) 10/28 (35.7) 1/28 (3.6) 1/10 (10.0)
p 0.78 0.035 0.037

Values are expressed as no./total no. (percentage).

Discussion

Our study showed that among planned vaginal deliveries between 25 and 27 weeks, breech presentation was associated with neonatal mortality more than twice for that for breech presentations with PCD. It showed that the increased neonatal mortality for breech PVD infants we observed was associated with the excess of mortality in the delivery room.

This reduction in neonatal mortality with planned c-section before 28 weeks is accordingly consistent with the published data up to now. The reduction of crude neonatal mortality from 19.5% to 7.5% that we observed has been found in several series of extremely preterm fetuses, with gestational age limits a little different from those we chose. These reductions range from 25 to 13% in a large multicenter study between 24 and 28 weeks in the United States [7], 32 to 10% in a Swedish registry study of births between 25 and 28 weeks [10], from 44 to 24% in a retrospective single-center Canadian study of fetuses aged 23 to 25 weeks [12] from 55 to 20% in a study of infants born in Australia and New Zealand between 23 and 27 weeks [14], from 65 to 43% in infants born between 24 and 26 weeks in a single-center Australian study [11], and by half among infants born between 22 and 27 weeks in the Swedish EXPRESS cohort [15]. Two large retrospective multicenter studies in France also found reductions in neonatal mortality for fetuses with a somewhat higher gestational age, although these did not reach statistical significance—from 11 to 7% and from 16 to 12% (26–29 weeks) [16, 17]. In a meta-analysis published in 2018, Grabovac et al. assembled data from 15 studies combining 12,335 infants in breech presentation with PVD between 23 and 27 weeks and observed a significant diminution of the risk of neonatal mortality for cesarean deliveries [13].

One of the criticisms that can be made of studies that compared breech presentations with PVD with breech by PCD [11, 13–15] is that PVD are the culmination of spontaneous labor, while those by PCD include a high proportion of induced deliveries, which is a very different obstetric context. Furthermore, the reason why 26 of the 139 fetuses (18.7%) whose labor was spontaneous had a PCD and not a PVD in our study was not always known. Our results, however, are consistent with other studies. Two studies argue in favor of a specific risk of PVD in case of breech presentation, that is not found in case of cephalic presentation. In a multivariate analysis of more than 1000 fetuses born in the USA between 24 and 27 weeks, Reddy et al. observed that the risk of mortality tripled among the breech PVDs compared with the breech PCDs, although they observed no significant increase in neonatal mortality between cephalic presentations with PVD and with PCD [7]. Similarly in the Australian series by Thomas et al., the doubled rate of neonatal mortality observed in preterm breech presentations between 24 and 26 weeks was not found among the infants with cephalic presentations [11]. These data are therefore consistent and tend to indicate that the excess mortality of extremely preterm infants in breech presentations is indeed associated with the presentation.

Until now, none of the studies examining neonatal mortality in extremely preterm infants in breech presentation have differentiated deaths in the delivery room from deaths in the NICU [9, 11–17]. In our study, the mortality of the newborns transferred to the NICU after birth was identical in both groups, thus corresponding to the mortality associated with this extreme preterm delivery. This shows that the increased neonatal mortality for breech PVD infants we observed was associated exclusively with the excess of mortality in the delivery room. In these vaginal births with death in delivery room, head entrapments concern 9/14 and cord prolapse 3/14: that is, 12 out of 14 were associated with risks known to be related to breech presentation in vaginal delivery. Thus, mortality in the delivery room appears to be associated mainly with an excess number of complications that are strongly related to breech presentations [21]. Although these risks have been mentioned by others [14, 16, 17], our study is original in highlighting the cause of this excess mortality in the delivery room.

Our study has several limitations. First, the groups compared retrospectively are far from identical in terms of gestational age and birth weight (aged a few days extra, but very often severely stunted in the PCD group). This is common to all retrospective studies of this type [14, 15, 19]. Secondly, our retrospective study covers a 19-year period in a single center, with changes in practices and neonatal results during this period. Nonetheless, the absence of variation in the risk of death in the delivery room of fetuses in breech presentation during the study period argues in favor of a risk specific to breech presentation. Moreover, to limit as much as possible the bias associated with changes in the practices for active management, we limited our analysis to fetuses born at and after 25 weeks of gestation and weighing more than 500 grams. In our center, these children have systematically received active management, as evidenced by the rate of antenatal corticosteroid therapy of at least 90% in each group.

Although no guidelines currently recommend a specific mode of delivery for extremely preterm infants in breech presentation, our study finally militates in favor of their systematic cesarean delivery. When labor occurs spontaneously, the decision about a cesarean must be made rapidly since the duration of labor is very short. A cesarean at this very early gestational age exposes the woman to a high risk of well-known complications [22, 23] especially to a scar in the uterine body in most cases (88% of the cesareans in our study) and to an excess risk of maternal mortality [24–26]. Maternal morbidity is also substantial [6, 26–28] with complications in the short term (postpartum hemorrhages and severe anemia, thromboembolic and infectious events) and the long term—for subsequent pregnancies (uterine rupture, preterm delivery, abnormalities of placentation). The balance between benefits and risks—high for both the fetus and the mother—must be evaluated and considered. For the fetal risks, our study shows that a cesarean may avoid a neonatal death every 8 interventions. This evidence is important for professionals but also for parents, who must always be informed as clearly as possible about each conceivable option. It is important to recall that in extremely preterm births, a systematic cesarean is part of active management of fetuses at the limit of viability, to increase their survival and decrease the risk of long-term sequelae [5, 15, 19, 29, 30]. Finally, our study shows a cesarean could be systematically proposed for breech presentations before 28 weeks of gestation.

Data Availability

All relevant data are within the paper.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Frank T Spradley

29 Dec 2020

PONE-D-20-34255

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study

PLOS ONE

Dear Dr. pierre,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Two experts in the field handled your manuscript, and we are grateful for their time and contributions. Although interest was found in your study, numerous concerns arose that require your attention. Please address ALL of the reviewers' comments in your revised manuscript.

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We look forward to receiving your revised manuscript.

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Frank T. Spradley

Academic Editor

PLOS ONE

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

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Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thanks you for giving me the opportunity to review this mansucript

How should preterm breech fetus be planned to deliver ? This is an intersting topic. Given that it is not a frequent situation, all experiences are welcome to counsel women.

In fact, this mansucript is incomplete and flawed by many methodologic bias that need to be adressed before publication.

Moreover, the text is not well structured because there are an amount of data and the results should be separated.

Therefore, the manuscript IS VERY SPRAWLING (breech versus cephalic, factors associated with mortality in vaginal delivery, explanation of risk of entrapment ....)

Results of this manuscript could be interesting if the authors performed several changes so that readers could undertsand and compared the results to their own data.

See below the main comments

1. The aim of the study is to compare Planned vaginal delivery and planned caesarean delivery for preterm breech delivery. Therefore, the aim IS NOT to study if preterm breech delivery has an increased risk of perinatal death.

One may suppose that breech fetus are at an increased risk of perinatality. The increased risk observed in these fetuses coule be linked to antenatal or underlying disorders that may be associated with the breech presentation and so not solely due to the mode of delivery. In that way, it is intersting to compare cephalic versus breech presentation.

However it is not your topic.

When you councel a women, you are not going to councel her by saying : as compared to cephalic presention, breech presentation is at increased risk, so let's perform a CS.

You are going to explain , by comparing the MODE of delivery for preterm breech delivery, the safer is ... or is not..

Moreover, by excluding congenital malformation, birthweight < 500g, medical termination of pregnancy and fetal detah, if the ratio cephalic/breech is not equally distributed as compared to the selected population, selection bias is highly probable. As I could read : 69,1% of preterm cephalic had CS versus 31,25 % of preterm breech . This important difference can not be a random ratio. It reflects selection bias that may favor cephalic presentation

Therefore, in my opinion group 2 is not necessary. Only data on the overall neonatal mortality rate of preterm cephalic fetus is necessary to give to have an overview of the practice in your center

2. Period study : authors should explained why they ended the inclusion to the years 2015

3. Main problem of external validity that need to be adressed

- the group 1 :CS rate during labor 3,5%

This is a french study. I could compare this results with 2 recent french studies : Kayem et al (26-30 WP) (20%) and lorthe (24-34 WP)et al (18,4%)

How can the authors explain this important difference ?

External validity is questionable .. ?

4. As written in the text, the authors argued for a high experience in breech delivery. Therefore in the method, authors should give the selection criteria for a trial of labor

5. Period study. Between 1997-2015, several pediatrics improvments have been performed . Authors performed a chi-square test by comparing neonatal mortality betwwen 1997-2005 and 2005-2015. I am not convinced by this method that is very biased and unprecised.Therefore to be sure that there is no time varying effect, authors should at least give :

- A run line series plot for the 2 groups

- And if you can Check for trends and then you can perform a correlation test (not useful for some statisticien), or computing the variance of the 2 groups if they are independent (not reasonable assumption, because it is the same hospital ?) or Vector Auto-regression model if the 2 groupes are dependant

6. The authors found an increased risk of neonatal morbidity in planned vaginal delivery. What we want to know is : why ? Is it solely the mode of delivery or the obstetrical underliyng condition or selection bias ?

Missing important data : reason for CS DELIVERY ? Reason for preterm delivery ?

According to recent french data , (delorm et al. 2016), cause of preterm delivery could be a prognotic factors (such as low birthweight...) .

As I can read in the table 1, in the group 3 (PCD), 32,5% had spontaneous preterm delivery. What was the reason to perform CS ?

Therfore the main problem is the allocation to PVD or PCD ? This is not well described in the manuscript

Due to its retrospective nature the authors should be very precise to describe the reason for the mode of delivery

7- As written in the results, group 1 and 3 are very different. Therefore, all these confounding variables need to be addressed in a regression analysis

8- Discrepencies in the data : Latter deliveries but lower Birthweight in PCD ... This may reflect either selection bias or codding bias or different policies for planned dleivery that need to be explained.

9- Duration of labor : less than 60min in 50%. Authors should explained how they defined the beginning of the labor.

10- missing data, that need to be adressed in group 1 and 3 : type of breech (franck, non franck, footling), clinical chorioamnionitis, use of tocolysis, the use of magnesium sulphate, economic status, admission after labor onset (in utero transfer), sex ratio, use of antibiotics, detailed of breech vaginal delivery management

11- Regression analysis should be detailed. In the table 2 (with some form typo), I could read adjusted OR. However I could not see either in the method nor in the result section the explanation of this adjustment.

Factors of death have been studied only in the PVD group?

Usually to perform adjused analysis, you should select factor according :

*confounding factors

*no colliders

* avoiding unnecessary covariate

* avoiding multicolinearity

And then you run a regression

12. Table 3-4 : This table adresses the factors associated with mortality in PVD. This is very intersting and could be a rational for another manuscript.

In conclusion, due to the amount of data, I suggested to the authors :

- To study mode of delivery on breech fetus : PVD vs PCD. To perform a classical analysis of the causal framework between mode of delivery and mortality

- Or to to study only group 1 and to perform an analysis (by regression, or a detailed descriptive analysis) to understand the neonatal mortality after PVD

Reviewer #2: Pierre and colleagues compare neonatal outcomes along three groups of singleton preterm deliveries: planned breech vaginal delivery, planned cephalic vaginal delivery, planned breech cesarean delivery.

The authors did a nice job in the discussion explaining how their research adds to the literature (consideration of spontaneous vs induced preterm delivery; distinction between death in delivery room vs NICU). The introduction would be strengthened by similarly setting up a distinction between what is known from prior literature and what this study adds.

My biggest concern is the difference in findings between the bivariate analysis and adjusted analysis, how these findings are explained, and the conclusions drawn from them. The bivariate analysis demonstrates that neonatal mortality in the breech PVD group was twice that of the cephalic PVD group (OR = 2.5) and almost triple that of the breech PCD group (OR = 2.9). However, as reported, there are significant differences in gestational age, birthweight, and rates of induction between the breech vaginal and breech c-section groups. After adjusting for GA and birthweight, there is no longer a significant difference in morbidity between the breech vaginal and breech c-section groups. Gestational age is the known key factor in outcomes for premature deliveries, so this is not unexpected. In the abstract, the highlighted results should be the adjusted ORs. The conclusions drawn should be that differences in neonatal mortality between breech vaginal and breech c-section groups were no longer significant after controlling for gestational age and birthweight (although differences between cephalic PVD and breech PVD groups persist). It is also unclear if the adjusted OR are adjusted for variables other than GA and birthweight? This should be described clearly. Other clinically relevant variables like induction, parity, receipt of steroids, presence of chorio, should be evaluated in bivariate analysis and considered for inclusion in the adjusted logistic regression.

The discussion should comment on why the authors think the GA is higher in the PCD groups but the birthweight is lower.

If data on sex of the neonates is available, that could be added to the adjusted model as a control. Male fetuses are known to have worse outcomes, and sex is often included in outcome prediction (https://www.nichd.nih.gov/research/supported/EPBO/use).

Regarding decisions to deliver vaginally vs by c-section, it would be helpful to explain in the methods how PVD vs PCD is determined from record review. Was there any hospital protocol to make this decision, or did the attending obstetrician use their personal clinical judgement? A context about the number of different providers making these decisions would also be helpful. Since this is an observational retrospective study, this study is limited by non-measured factors (potential confounds) that made healthcare providers decide to deliver some of these breech fetuses vaginally and others by c-section. This should be added to the discussion.

The term “global” neonatal mortality is confusing. I recommend changing it to “total” and defining it clearly as death during delivery + death in NICU. Was NICU followup stopped at 28 days (definition of neonatal mortality) or continued though discharge?

Table 3: What is “Gestational age 25 weeks” compared to? Is this 25/0-25/6 compared to >26 weeks? The title is confusing.

Table 4: The title is confusing. Categories with <5 items should be compared using Fisher’s Exact, not Chi Squared. In “25 SA”, “26 SA”, etc, what does “SA” mean?

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PLoS One. 2021 Oct 20;16(10):e0258303. doi: 10.1371/journal.pone.0258303.r002

Author response to Decision Letter 0


26 May 2021

We thank the reviewers for their comments and questions which we answered in the attached "response to reviewer" file attached at the manuscript

Attachment

Submitted filename: Responses to the reviewers.docx

Decision Letter 1

Frank T Spradley

15 Jun 2021

PONE-D-20-34255R1

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study

PLOS ONE

Dear Dr. pierre,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 30 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Frank T. Spradley

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Some comments

Thanks you for giving me to review the revised manuscript. I am convinced that the manuscript could deserve publication. However to improve the clarity, the understanding and in fact external validity some comments need to be addressed

Some data needs to be published especially the excess of neonatal death due to head entrapment for example. In my opinion the authors should just simplified some analysis, the table 2 and the process of selection of women.

1. As the primary outcomes is the combined neonatal death in delivery room and in NICU, there is a little discrepencies between the sentences in the introduction and in the material and method

In order to better understand the possible excess mortality in case of trial of labor, we wanted to differentiate the mortality occurring in the delivery room from that occurring in the neonatal intensive care unit.

The principal endpoint was total neonatal defined as i) death during delivery plus ii) death in the neonatal intensive care unit (NICU).

2. I read the manuscript for a second time and I try to be a "new reader". I may not understand fully the objectives of the authors.

Firstly , The authors want to provide data to counsel women when : (i) preterm delivery is occuring (ii) fetus is in breech.

Therefore, the group of planned CS should not be a mixture of induce/spontaneous labor and real planned CS. Women with induction of labor should be in the planned vaginal birth

In fact, women with spontaneous preterm labor in breech or with premature preterm rupture of membrane or with medically indication birth should be offered 2 options: PVD or PCD = PVD (spontaneous or induction) vs PCD

So the authors should clearly explained the 26 women with spontaneous labor in the PCD group. I may imagine that it is women with spontaneous preterm labor and the obstetrician may have chosen to perform CS. However, should these women include in PCD group? May be yes in latent phase of labor, no in active phase of labor

Secondly the difficulty is that the group of PVD might be a group with worse prognosis. Therefore, the reader need to understand why the obstetrician chose PVD or PCD

3. Reason for neonatal morbidity should be given as no difference was observed between APGAR, chorioamniotis, IVH, hemorrhage, leukomalacia ?? What is the effect of antenatal corticosteroids?

4. Statistical analysis:

I am not convinced by the adjusted OR because some factors might be effect modifier

One simple possibility to understand the factors associated with neonatal mortality is to perform stratified analysis and mantel haenzel test to distinguish confounding factors and effect modifier: especially for gestational age, use of antenatal corticosteroids, gender, birthweight (500 – 600 – 700 – 800 or < 3°percentile vs no), by providing crude and adjusted M-H OR. In fact multiple logistic regression is somewhat not useful with small sample size and collinearity (birthweight and gestational age ++).

5. Can the authors explained the increased death in delivery room with cord prolapse ? Cord prolapse during expulsive stage or during active phase labor. As only 3.4% of women in PCD had CS , can the authors explaine the management according to cord prolapse?

6. The significance of this excess of mortality disappeared after adjusting for gestational age, birthweight and gender at delivery

This sentence should be deleted as statistical significance is trivial when analyzing neonatal death. In 2016, the American Statistical Association released a statement in The American Statistician warning against the misuse of statistical significance and P values

Not all values inside are equally compatible with the data, given the assumptions. The point estimate is the most compatible, and values near it are more compatible than those near the limits

In your manuscript, whatever the OR, there is a clear association between mode of delivery and neonatal death. The only question is why ?

In fact the authors should clearly explained the management during labor, and the other comment previously written (reason for PCD, effect modifier or confounding, discrepancies between no diiference for pH and other morbidity while neonatal death in delivery room only occurred after PVD)

7. Our study was carried out in a university maternity which performs around 5,000 deliveries per year. The selection criteria for a trial of labor has been the subject of a protocol and regular publications. Adjaoud S, J Gynecol Obstet Biol Reprod 2017 ; 46 :445-8.

I disagree with the authors. In this article, the protocol is for term breech trial and not for preterm delivery…..

I cited : « Women were included if they had given birth during the study period to a singleton child at term, in either breech or vertex presentation. Multiple pregnancies, medically indicated terminations of pregnancy, and in utero deaths were excluded from the study »

8; Table 2 :

typo 10 and 12% instead of 0,10 et 0,12.

I am not convinced with the p value for mean pH

Item asphyxia should be given i.e : ph < 7 or base excess or lactate

Reviewer #2: Overall, the authors did a very nice job with revisions and the paper is stronger and more statistically accurate.

Continued minor issues:

In the abstract, the conclusion states that “For deliveries between 25+0 and 27+6 weeks' gestation, vaginal delivery in breech presentation is associated with a significantly higher risk of death in the delivery room.” Again, I would be careful with using this language of “significance” when differences in mortality were significant in the adjusted analysis.

I understand the rationale of not adjusting for many variables given the small sample size, but I do think that parity (history of vaginal delivery) is a clinically very important variable when it comes to head entrapment risk and successful vaginal delivery. If you choose not to adjust for parity, I recommend specifically mentioning that as a limitation in the discussion.

In the third paragraph of the results, I recommend specifying that the initial results you describe are “bivariate analysis” or “unadjusted analysis.”

Adding a column to table 2 with adjusted OR (with a footnote explaining what is was adjusted for) may help readers better understand the difference in OR/significance for mortality in bivariate analysis vs adjusted analysis.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2021 Oct 20;16(10):e0258303. doi: 10.1371/journal.pone.0258303.r004

Author response to Decision Letter 1


24 Aug 2021

In the revisions requested by the reviewers, we have responded in the file "responses to reviewers" join to the revised version of the manuscript

Attachment

Submitted filename: Responses to reviewers.docx

Decision Letter 2

Frank T Spradley

24 Sep 2021

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study

PONE-D-20-34255R2

Dear Dr. pierre,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Frank T. Spradley

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors provided answers to the comments

The article can be published

In that form the article is short and more concise

Reviewer #2: Overall, the authors did a very nice job with revisions. I have no further concerns or suggestions for improvement. The paper has interesting and clinically relevant findings.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Acceptance letter

Frank T Spradley

11 Oct 2021

PONE-D-20-34255R2

Is vaginal delivery of a fetus in breech presentation at an extremely preterm gestational age associated with an increased risk of neonatal death? A comparative study

Dear Dr. pierre:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Frank T. Spradley

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Responses to the reviewers.docx

    Attachment

    Submitted filename: Responses to reviewers.docx

    Data Availability Statement

    All relevant data are within the paper.


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