The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women Eran Weiner, Nataly Fainstein, Adam Pomeranz, Letizia Schreiber, Jacob Bar & Michal Kovo To cite this article: Eran Weiner, Nataly Fainstein, Adam Pomeranz, Letizia Schreiber, Jacob Bar & Michal Kovo (2015): Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.3109/14767058.2015.1119117 To link to this article: http://dx.doi.org/10.3109/14767058.2015.1119117
Accepted author version posted online: 13 Nov 2015. Published online: 07 Dec 2015. Submit your article to this journal
Article views: 28
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [University of Sydney Library]
Date: 16 March 2016, At: 02:23
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–5 ! 2015 Taylor & Francis. DOI: 10.3109/14767058.2015.1119117
ORIGINAL ARTICLE
Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women Eran Weiner1, Nataly Fainstein1, Adam Pomeranz1, Letizia Schreiber2, Jacob Bar1, and Michal Kovo1
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
1
Department of Obstetrics & Gynecology and 2Department of Pathology, The Edith Wolfson Medical Center, Holon, Israel Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract
Keywords
Objective: The objective of this study is to correlate between pregnancy outcome and placental pathology in emergent cesarean deliveries (ECD) for non-reassuring-fetal-heart-rate (NRFHR) performed in women in their active phase of labor versus those performed in non-laboring women. Methods: A retrospective cohort study. Data were reviewed for all pregnancies necessitating ECD for NRFHR between January 2009 and December 2013. Maternal outcome, neonatal outcome, and placental pathology parameters were compared between ECDs performed during active phase of labor and those performed before the active phase of labor (non-labor group). Results: During the study period, a total of 661 ECDs were performed due to NRFHR. Compared with the active labor group (n ¼ 335), the non-labor group (n ¼ 326) had more pre-eclampsia (p ¼ 0.033), small for gestational age (SGA) (p ¼ 0.016), and preterm labor (p50.001). Worse composite neonatal outcome was observed in the non-labor group compared with the active labor group, p50.001. By a stepwise logistic regression model, non-labor was independently associated with adverse neonatal outcome (1.88 OR CI; 1.19–2.96, p ¼ 0.007). Placental inflammatory lesions were more common in the active labor group (p¼ 0.043), and abnormal cord insertions were more common in the non-labor group (p ¼ 0.002) as well as placental weight510th% (p ¼ 0.019). Conclusion: Higher rate of pregnancy complications, abnormal cord insertion, smaller placentas, and worse neonatal outcome are associated with ECD for NRFHR when performed before the phase of active labor.
Active labor, emergent cesarean deliveries, neonatal outcome, non-reassuring fetal heart rate, placental pathology
Introduction Continuous fetal heart rate monitoring (FHRM) during labor has been used over the last five decades for antenatal assessment and detection of fetuses at risk of hypoxemia and acidemia [1]. Immediate delivery or even emergent cesarean deliveries (ECD) are performed when there is a suspicion of ‘‘fetal distress’’ based on the diagnosis of non-reassuring fetal heart rate (NRFHR monitoring [2]. The mechanisms leading to NRFHR tracings are complex and broad, involving pregnancy complications, maternal and fetal diseases, clinical events, and sentinel events [3] that compromise oxygen supply to the fetus. The exact mechanism is not always clear, although often intra-operative findings or placental histopathology findings may clarify possible etiologies [4–6]. Several studies Address for correspondence: Eran Weiner, Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon 58100, Israel. Tel: +972 3 5028329. Fax: +972 3 5028503. E-mail: [email protected]
History Received 28 October 2015 Revised 6 November 2015 Accepted 9 November 2015 Published online 3 December 2015
investigated the association between maternal and neonatal complications and the timing of a cesarean delivery (CD). Studies have shown that maternal and neonatal complications were more common in ECDs compared with elective cases [7]. Others have shown an increased morbidity both after a prolonged second stage [8–10] and in comparison with the first stage of labor [11,12]. Yet, studies investigating the effect of the stage of labor on maternal and neonatal outcomes in ECDs due to NRFHR are scarce. We hypothesized that ECDs performed not in the active phase of labor will be associated with increased adverse neonatal outcome and more placental lesions, as compared with those performed during the active phase of labor, suggesting an existing chronic placental dysfunction and prolonged in-utero insult affecting the fetus. Thus, we aimed to correlate between pregnancy outcome and placental pathology in ECD for NRFHR performed in women in the active phase of labor versus those performed in women not in labor.
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
2
E. Weiner et al.
J Matern Fetal Neonatal Med, Early Online: 1–5
Methods
Placental examination
We performed a retrospective review of the medical records of all women who underwent ECD for NRFHR, at the labor ward at Edith Wolfson Medical Center, Holon, Israel, from January 2009 to December 2013. Cases eligible for the study were identified from our computerized data system. The study group included women who delivered a singleton, between 24 and 42 weeks, by ECD for NRFHR as the only indication, and their placentas were sent to histopathological evaluation. Excluded from the study were women with additional indications for ECD, as abnormal progress in labor, initial maternal refusal for CD, women with evidence of fetal or neonatal malformations, or cases with missing data. For the purposes of the study, the study population was divided into two groups: women who had ECD before the active phase of labor (non-labor group), or after they reached the active phase of labor, defined as cervical dilatation of 4 cm, accompanied by cervical effacement of 80%, and regular uterine contractions, at least three contractions in 10 min (active labor group). Approval was obtained from the Local Ethics Committee.
As part of our departmental protocol, in every case of ECD for NRFHR, placentas are sent to histopathological evaluation. Placental pathology examinations were performed using our standard protocol, by a single pathologist (author L. S.). Placental lesions were classified by maternal or fetal origin, according to the criteria adopted by the Society for Pediatric Pathology [16] and as we previously reported [4]. Briefly, placental weight was determined 24 h after delivery, and the percentile was determined according to placental weight charts [17]. Each placenta was fixed in formalin, and at least five samples were embedded in paraffin blocks for microscopic assessment. Lesions of maternal vascular supply included placental hemorrhages (marginal and retro-placental), vascular changes associated with maternal malperfusion (acute atherosis and mural hypertrophy), and villous changes associated with maternal malperfusion (increased syncytial knots, villous agglutination, increased intervillous fibrin deposition, distal villous hypoplasia, and villous infarcts). Lesions of fetal vascular supply were defined as findings consistent with fetal thrombo-occlusive disease: vascular lesions (thrombosis of the chorionic plate and stem villous vessels) and villous changes (hypovascular, fibrotic, and avascular villi). Findings consistent with chorioamnionitis were defined by the presence of an inflammatory neutrophil infiltrate at two or more sites on the chorionic plate and extra-placental membrane. Maternal inflammatory response (MIR), was divided into three stages: stage 1 – characterized by the presence of a few scattered neutrophils in the subchorionic space; stage 2 – characterized by many neutrophils (11–30 per HPF) in the lower half of the chorionic plate; and stage 3 – characterized by dense infiltrates of neutrophils (430 per HPF) throughout the chorionic plate. Fetal inflammatory response (FIR) was also divided into three stages: stage 1 – early, umbilical phlebitis; stage 2 – intermediate, umbilical arteritis; and stage 3 – concentric umbilical perivasculitis (necrotizing funisitis). Placental histologic examination also included the detection of meconium stained membranes associated with columnar change in amniotic epithelium or the appearance of pigmented macro-phages. The umbilical cord was examined for the detection of hypercoiling and abnormal cord insertion. Umbilical coiling index was calculated by dividing the total number of coils by the length of the cord in centimeters. Hypercoiling was diagnosed in cases of umbilical coiling index 40.3 coils/cm [18]. Abnormal cord insertion was defined as either velamentous or marginal insertion. Gross anomalies in the umbilical cord (entanglements, true knots, and short cord) were recorded by the surgeons during the operation.
Data collection The following data collected from the womens’ medical and surgical files included demographic and labor characteristics: age, gravidity and parity, body mass index (BMI), gestational diabetes mellitus (GDM), pre-gestational DM (PGDM), thrombophilia (defined as any thrombophilia, inherited or acquired, that necessitated thromboprophylaxis according to the practice bulletins of the American College of Obstetricians and Gynecologists) [13,14], pre-eclampsia, trials of labor after a previous cesarean delivery (TOLAC), gestational age at delivery, oligohydramnios (amniotic fluid index 55 cm), the presence of intra-partum fever 438 C, and meconium. Gestational age was confirmed by first-trimester ultrasonography. Immediately after birth, all neonates were examined by pediatricians. Birthweight percentile for gestational age was assigned using the updated Israeli growth charts [15]. Small for gestational age (SGA) was defined as actual birthweight 510th% for gestational age. The following information was collected from the neonatal records: Apgar scores, cord blood pH, sepsis (positive blood or cerebrospinal fluid culture), need for blood transfusion, need for phototherapy, respiratory distress syndrome, need for mechanical ventilation or support, necrotizing enterocolitis, intraventricular hemorrhage (all grades), hypoxic ischemic encephalopathy, seizures, and death. Intra-operative and post-partum maternal complications including bleeding necessitating intraoperative blood transfusions during the operation, surgical extensions of the uterine incisions 43 cm, injuries to adjacent organs, endometritis, defined as fever with abnormal uterine tenderness in the absence of other findings, suggesting another source of infection, the need for blood transfusion in the post-partum period, relaparotomy, wound infection/hematoma, pelvic abscess, thromboembolism, and anesthesia-related complications, such as postdural puncture headache necessitating blood patch.
Statistical analysis Data were analyzed with SPSS software, version 15.0 (SPSS Inc., Chicago, IL). Continuous variables were calculated as mean ± SD or median and range, as appropriate. Categorical variables were calculated as rate (%). Continuous parameters were analyzed by Student’s t-test and categorical variables by the Chi-square test or by Fisher exact test, as appropriate. p value of 50.05 was considered statistically significant.
ECD for NRFHRM and labor
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
DOI: 10.3109/14767058.2015.1119117
Intra-operative maternal composite outcome was defined as one or more of the following complications: surgical extensions of the uterine incision 43 cm, intra-operative bleeding necessitating blood transfusion, or injury to an adjacent organ. Post-partum maternal composite outcome was defined as one or more of the following complications: endometritis, pelvic abscess, blood transfusion, wound infection/hematoma, relaparotomy, postdural puncture headache, or thromboembolism. Composite adverse neonatal outcome was defined as one or more of the following complications: neonatal sepsis, blood transfusion, phototherapy, respiratory morbidity (the presence of respiratory distress syndrome, or transient tachypnea of the newborn, or mechanical ventilation or need for respiratory support) cerebral morbidity (the presence of intra-ventricular hemorrhage, or seizures or hypoxicischemic encephalopathy) necrotizing enterocolitis, or death. To identify independent risk factors for adverse neonatal outcome, a multivariate stepwise forward logistic regression analysis was performed. Composite adverse neonatal outcome served as a dependent variable and phase of labor (active versus pre-active labor), gestational age, maternal age, nulliparity, maternal BMI, maternal DM, SGA, oligohydramnios, preterm labor, thrombophilia, placental maternal and fetal vascular supply lesions and inflammatory lesions, served as independent variables.
Table 1. Maternal and delivery characteristics of the study groups.
Maternal age (years) Gestational age (weeks) Cervical dilatation at ECD Nulliparity BMI (kg/m2) Gestational DM (GDM) Pre-gestational DM (PGDM) Pre-eclampsia Oligohydramnios SGA 510th percentile Preterm labor 534 weeks Intra partum fever 438 C Thrombophilia Meconium
Non-labor group, n¼326
Active labor group, n¼ 335
p value
29.2 ± 5.2 38.5 ± 3.1 2.5 (0–3.5) 187 (57.4) 24.5 ± 5.5 19 (5.8) 9 (2.8) 35 (10.7) 32 (9.8) 80 (24.5) 28 (8.6) 6 (1.8) 9 (2.8) 111 (34.1)
29.1 ± 5.2 39.6 ± 1.9 6.1 (4–10) 197 (58.8) 24.4 ± 5.1 16 (4.8) 2 (0.6) 20 (6) 18 (5.4) 56 (16.7) 4 (1.2) 20 (6) 2 (0.6) 103 (30.7)
0.96 50.001 50.001 0.753 0.909 0.604 0.034 0.033 0.038 0.016 50.001 0.008 0.034 0.405
All data are shown as number (%), mean ± standard deviation or median (range), as appropriate. DM, diabetes mellitus; BMI, body mass index; TOLAC, trial of labor after cesarean section; patient in active labor is defined as patients with cervical dilatation of 4 cm associated with regular contractions; SGA, small for gestational age, ECD, emergent cesarean delivery. All significant results (p50.05) were bolded for clearification.
Table 2. Neonatal outcome in the study groups. Non-labor Active labor group, group, n¼ 335 p value n¼326
Results During the study time period, 5005 cesarean deliveries (CDs) were performed out of 22 217 deliveries (22.5%), of them, 661 ECDs (13.2%) were performed due to NRFHR, as the only indication. Out of 661 cases eligible for the study, 326 (49.3%) were performed before the active phase of labor (non-labor group) with a median cervical dilation of 2.5 cm (range 0–3.5 cm), and 335 (50.7%) were performed during the active phase of labor (active labor group) with a mean cervical dilation of 6.1 cm (range 4–10 cm). Table 1 presents the background and delivery characteristics of the two groups. There were no between-group differences in maternal age, nulliparity, BMI, and meconium-stained amniotic fluid. The non-labor group had lower gestational age at delivery, 38.5 ± 3.1 versus 39.6 ± 1.9 weeks, p50.001, and higher rate of preterm labor 534 weeks, 8.6% versus 1.2%, p50.001, respectively, as compared with the active labor group. Higher rate of pregnancy complications was observed in the non-labor group as compared with the active labor group: pre-eclampsia (p ¼ 0.033), PGDM (p ¼ 0.03), oligohydramnios (p ¼ 0.038), SGA (p¼ 0.016), and thrombophilia (p ¼ 0.034). The active labor group had a higher rate of intrapartum fever 438 C as compared with the non-labor group, 1.8% versus 0.6%, p ¼ 0.008, respectively. Neonatal outcome parameters are summarized in Table 2. Neonates in the non-labor group had longer duration of hospitalization, 8.9 ± 12.5 d versus 5.8 ± 6.2 d, p50.001, higher rates of admission to NICU, 39.3% versus 28.9%, p ¼ 0.005, and higher rates of 5-min Apgar score 7, 6.1% versus 1.8%, p ¼ 0.004, respectively, as compared with neonates in the active labor group. Additionally, neonates in the non-labor group had higher rates of respiratory morbidity (0.001), cerebral morbidity (p ¼ 0.010), neonatal sepsis (p ¼ 0.022), and blood transfusions (p50.001) as compared
3
Neonatal hospitalization (days) NICU admission Umbilical cord pH 7.1 5-minute Apgar score 7 Respiratory morbidity* Cerebral morbidity** Neonatal sepsis Necrotizing enterocolitis Blood transfusions Phototherapy Neonatal death Composite adverse neonatal outcome
8.7 128 26 20 57 9 15 1 16 36 4 77
(2–58) 5.3 (2–40) (39.3) 97 (28.9) (7.9) 25 (7.5) (6.1) 6 (1.8) (17.5) 24 (7.1) (2.7) 1 (0.3) (4.6) 5 (1.5) (0.3) 0 (4.9) 2 (0.6) (11) 23 (6.9) (1.2) 3 (0.9) (23.6) 38 (11.3)
50.001 0.005 0.884 0.004 50.001 0.01 0.022 0.493 50.001 0.075 0.721 50.001
All data are shown as number (%), mean ± standard deviation, or median (range), as appropriate. NICU, neonatal intensive care unit. Respiratory morbidity includes the presence of respiratory distress syndrome, or transient tachypnea of the newborn, or mechanical ventilation or need for respiratory support. Cerebral morbidity includes the presence of intra-ventricular hemorrhage (all grades), or seizures or hypoxicischemic encephalopathy. All significant results (p50.05) were bolded for clearification.
with neonates in the active labor group. Composite adverse neonatal outcome was higher in the non-labor group than in the active labor (23.6% versus 11.3% p50.001), respectively. By using a stepwise logistic regression model, non-active labor was independently associated with adverse neonatal outcome (1.88 OR, 95% CI: 1.19–2.96, p ¼ 0.007), and delivery434 weeks was found to be independently associated with better neonatal outcome (0.036 OR, 95% CI: 0.014– 0.098, p50.001). Placental histopathology findings and umbilical cord abnormalities in the study groups are summarized in Table 3. Mean placental weight was lower in the non-labor group as compared with the active labor group, 457 ± 114 g versus 484 ± 102 g, respectively, p ¼ 0.002. The rate of placental
4
E. Weiner et al.
J Matern Fetal Neonatal Med, Early Online: 1–5
Table 3. Placental lesions in the study groups. Non-labor group, n¼326
Table 4. Intra-operative and post-partum maternal complications. Active labor group, n¼ 335 p value
Placental weight (g) 457.6 ± 114.7 484.5 ± 102.9 Placental weight510% percentile 37 (11.3) 21 (6.3) Hypercoiled cord 51 (15.6) 40 (11.9) Abnormal cord insertion 67 (20.5) 39 (11.6) Maternal vascular supply lesions Placental hemorrhage Vascular lesions related to maternal malperfusion Villous changes related to maternal malperfusion
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
Fetal vascular supply lesions Vascular lesions consistent with FTOD Villous lesions consistent with FTOD Inflammatory lesions MIR stages 1–3 FIR stages 1–3
0.002 0.019 0.176 0.002
17 (5.2) 20 (6.1)
12 (3.6) 20 (6)
0.345 1
106 (32.5)
107 (31.9)
0.933
22 (6.7)
21 (6.3)
0.875
32 (9.8)
37 (11)
0.613
65 (19.9) 36 (11)
90 (26.9) 39 (11.6)
0.043 0.902
Continuous variables are presented as mean ± SD and categorical variables as n (%). FTOD, fetal thrombo-occlusive disease; MIR, maternal inflammatory response; FIR, fetal inflammatory response. All significant results (p50.05) were bolded for clearification.
weight 510th percentile was higher in the non-labor group compared with the active labor group, 11.3% versus 6.3%, p ¼ 0.019. Abnormal cord insertions were also more common in the non-labor group as compared with the active labor group, 20.6% versus 11.5%, p ¼ 0.002. Compared with the non-labor group the active group had a higher rate of placental lesions consistent with MIR, 26.9% versus 19.9%, respectively, p ¼ 0.043. Other maternal or fetal vascular supply lesions did not differ between the groups. Macroscopic umbilical cord gross abnormalities did not differ between the two groups. Umbilical cord entanglements were found in 37.7% of the cases in the non-labor group versus 32.8% in the active labor group (p ¼ 0.193). True knots were found in 2.4% of the cases in the non-labor group versus 3.6% in the active labor group (p ¼ 0.497). Short cord550 cm was found in 3.2% of the cases in the non-labor group versus 3.9% in the active labor group (p ¼ 0.672). Maternal intra-operative and postpartum complications are summarized in Table 4. Composite adverse intra-operative and post-partum outcomes were higher in the pre-active labor group compared with the non-labor group, p50.001 and p ¼ 0.024, respectively.
Discussion In the present study, we found that ECDs due to NRFHRM performed before the active phase of labor, as compared with those performed during the active phase of labor, were associated with a significantly higher rate of pregnancy complications and worse neonatal outcome, independent of gestational age at delivery (1.88 OR, 95% CI: 1.19–2.96, p ¼ 0.007). The existence of maternal diseases and pregnancy complications is probably associated with hypoxic insults that are slow in onset and persist over time, allowing the fetus to
Non-labor Active labor group, group, n¼ 335 p value n¼326 Mean maternal hospitalization (days) 4.8 ± 1.8
4.6 ± 1.3
Intraoperative complications Surgical extensions 43 cm Intraoperative blood transfusions Injuries to adjacent organ Composite intraoperative complications
22 3 1 25
48 5 2 55
Postoperative complications Endometritis Pelvic abscess Blood transfusions Wound infection/hematoma Relaparotomy* Thromboembolism PDPH Composite postoperative complications
6 (1.8) 0 5 (1.5) 6 (1.8) 2 (0.6) 1 (0.3) 6 (1.8) 26 (8.0)
(6.7) (0.9) (0.3) (7.7)
0.101
(14.3) (1.5) (0.6) (16.4)
0.001 0.725 1 50.001
15 (4.5) 1 (0.3) 5 (1.5) 16 (4.8) 2 (0.6) 0 7 (2.1) 45 (13.4)
0.074 1 1 0.049 1 0.493 1 0.024
All significant results (p50.05) were bolded for clearification.
make some adaptations during pregnancy. Yet, these compensated fetuses have reduced physiological reserve, and will develop abnormal fetal heart rate patterns necessitating ECD, even during the pre-labor uterine contractions, before progression of labor into its active phase. Similarly, another study found a higher rate of pre-labor ECDs in women with type 1 DM but with suboptimal glycemic control [19]. Furthermore, active labor has a well-known beneficial role on early and late neonatal outcome [20–24], attributed to both mechanical and hormonal factors, yet lacking in cases ECDs are performed in non-laboring women. The association between NRFHR tracings and placental pathology has been investigated [5,25], thus it was interesting to find differences between the studied groups even though both groups included cases with NRFHR monitoring. We found higher rates of pathological umbilical cord insertion and a higher rate of placental weights 510th percentile in ECDs performed before the active phase of labor. It is well established that pathological cord insertion is associated with labor complications and neonatal morbidity [26,27]. Moreover, Redline et al. [3] studied umbilical cord abnormalities and placental lesions in 125 neurological impaired neonates, demonstrating that cord abnormalities, including abnormal cord insertions, are more common in placentas with fetal thrombotic vasculopathy, a known placental lesion associated with cerebral palsy. Although in the current study we found no differences between groups in the rate of placental fetal vascular supply lesions, abnormal cord insertion could still be associated with abnormal blood supply to the fetus and slowly evolving fetal hypoxia. Furthermore, it is well known that placental inflammatory lesions are associated with abnormal fetal heart rate [5,6]. We observed a higher rate of placental maternal inflammatory lesions in the active phase of labor group, a finding also known to be associated with prolonged labor and ruptured membranes [28]. In the current study, we found that ECDs performed in the active phase of labor were associated with a higher rate
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
DOI: 10.3109/14767058.2015.1119117
of maternal morbidity, intra-operatively, mostly extensions of the uterine incision, and post-operatively, endometritis and wound infections. These findings are in concordance with previous studies demonstrating higher maternal morbidities due to intra-operative trauma, especially in second-stage CDs [12,29,30]. The present study is unique in several aspects; first, to our knowledge, this is the first report of differences between ECDs performed in non-labor versus active phase of labor, with a thorough description of maternal and neonatal outcome, and with placental histology evaluation. Second, we used validated placental pathological criteria adopted by the Society for Pediatric Pathology [16] with methodical differentiation among lesions of maternal and fetal origin vascular supply abnormalities, inflammatory lesions, as well as cord abnormalities. Third, this is a large cohort that included cases with NRFHR tracings as the only indication for ECD. Our study is not without limitations: first, we are aware of the problematic term of ‘‘NRFHR’’ which is subject to considerable variations of interpretation among maternal– fetal medicine specialists [2,31] making standardization problematic. Yet, we found that category 2 FHR tracings [32] were observed in similar rates in the non-labor group as in the active phase of labor group (92.6% versus 90.1%, respectively). Second, the definition of active phase of labor is also not clear-cut and the transition between non-active and active phase of labor is variable. In conclusion, ECDs performed before the active phase of labor are associated with higher rates of pregnancy complications, abnormal cord insertion, lower placental weight, and worse neonatal outcome as compared with those performed during the active phase of labor.
Declaration of interest The authors report that they have no conflicts of interest.
References 1. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev 2013;5: CD006066. 2. Chauhan SP, Klauser CK, Woodring TC, et al. Intrapartum nonreassuring fetal heart rate tracing and prediction of adverse outcomes: interobserver variability. Am J Obstet Gynecol 2008; 199:623 e621–5. 3. Redline RW. Clinical and pathological umbilical cord abnormalities in fetal thrombotic vasculopathy. Hum Pathol 2004;35:1494–8. 4. Weiner E, Bar J, Fainstein N, et al. Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate. Eur J Obstet Gynecol Reprod Biol 2015;185:103–7. 5. Robinson BK, Su E, Grobman W, et al. The association of histologic placental inflammation with category II fetal heart tracings. Pediatr Dev Pathol 2012;15:298–302. 6. Salafia CM, Mangam HE, Weigl CA, et al. Abnormal fetal heart rate patterns and placental inflammation. Am J Obstet Gynecol 1989;160:140–7. 7. Lilford RJ, van Coeverdende Groot HA, Moore PJ, Bingham P. The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. Br J Obstet Gynaecol 1990;97:883–92. 8. Koyama S, Tomimatsu T, Kanagawa T, et al. Cervical insufficiency following cesarean delivery after prolonged second stage of labor: experiences of two cases. J Obstet Gynaecol Res 2010;36:411–13.
ECD for NRFHRM and labor
5
9. Vyas NA, Vink JS, Ghidini A, et al. Risk factors for cervical insufficiency after term delivery. Am J Obstet Gynecol 2006;195: 787–91. 10. Sung JF, Daniels KI, Brodzinsky L, et al. Cesarean delivery outcomes after a prolonged second stage of labor. Am J Obstet Gynecol 2007;197:306 e301–5. 11. Lurie S, Raz N, Boaz M, et al. Comparison of maternal outcomes from primary cesarean section during the second compared with first stage of labor by indication for the operation. Eur J Obstet Gynecol Reprod Biol 2014;182:43–7. 12. Seal SL, Kamilya G, Mukherji J, et al. Outcome in second-versus first-stage cesarean delivery in a teaching institution in eastern India. Am J Perinatol 2010;27:507–12. 13. American College of Gynecologists Women’s Health Care P: ACOG Practice Bulletin No. 138: inherited thrombophilias in pregnancy. Obstet Gynecol 2013;122:706–17. 14. American College of Gynecologists Committee on Practice B-O: ACOG Practice Bulletin No. 118: antiphospholipid syndrome. Obstet Gynecol 2011;117:192–9. 15. Dollberg S, Haklai Z, Mimouni FB, et al. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311–14. 16. Redline RW, Heller D, Keating S, Kingdom J. Placental diagnostic criteria and clinical correlation – a workshop report. Placenta 2005; 26:S114–17. 17. Pinar H, Sung CJ, Oyer CE, Singer DB. Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med 1996; 16:901–7. 18. Strong Jr TH, Jarles DL, Vega JS, Feldman DB. The umbilical coiling index. Am J Obstet Gynecol 1994;170:29–32. 19. Miailhe G, Le Ray C, Timsit J, Lepercq J. Factors associated with urgent cesarean delivery in women with type 1 diabetes mellitus. Obstet Gynecol 2013;121:983–9. 20. Huang L, Chen Q, Zhao Y, et al. Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. J Asthma 2015;52:16–25. 21. Farchi S, Di Lallo D, Franco F, et al. Neonatal respiratory morbidity and mode of delivery in a population-based study of lowrisk pregnancies. Acta Obstet Gynecol Scand 2009;88:729–32. 22. Zanardo V, Simbi AK, Franzoi M, et al. Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery. Acta Paediatr 2004;93:643–7. 23. Ly NP, Rifas-Shiman SL, Litonjua AA, et al. Cord blood cytokines and acute lower respiratory illnesses in the first year of life. Pediatrics 2007;119:e171–8. 24. Thomopoulos TP, Skalkidou A, Dessypris N, et al. Prelabor cesarean delivery and early-onset acute childhood leukemia risk. Eur J Cancer Prev 2015. 25. Kovo M, Schreiber L, Ben-Haroush A, et al. Association of nonreassuring fetal heart rate and fetal acidosis with placental histopathology. Placenta 2011;32:450–3. 26. Tantbirojn P, Saleemuddin A, Sirois K, et al. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta 2009;30:1083–8. 27. Hasegawa J, Matsuoka R, Ichizuka K, et al. Velamentous cord insertion: significance of prenatal detection to predict perinatal complications. Taiwan J Obstet Gynecol 2006;45:21–5. 28. Bar J, Schreiber L, Golan A, Kovo M. Placental factor in spontaneous term labor in uncomplicated pregnancy. J Matern Fetal Neonatal Med 2012;25:2704–7. 29. Allen VM, O’Connell CM, Baskett TF. Maternal and perinatal morbidity of caesarean delivery at full cervical dilatation compared with caesarean delivery in the first stage of labour. BJOG 2005;112: 986–90. 30. Alexander JM, Leveno KJ, Rouse DJ, et al. Comparison of maternal and infant outcomes from primary cesarean delivery during the second compared with first stage of labor. Obstet Gynecol 2007; 109:917–21. 31. Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008;199: 587–95. 32. American College of Gynecologists: ACOG Practice Bulletin No. 106: intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol 2009;114:192–202.
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women Eran Weiner, Nataly Fainstein, Adam Pomeranz, Letizia Schreiber, Jacob Bar & Michal Kovo To cite this article: Eran Weiner, Nataly Fainstein, Adam Pomeranz, Letizia Schreiber, Jacob Bar & Michal Kovo (2015): Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.3109/14767058.2015.1119117 To link to this article: http://dx.doi.org/10.3109/14767058.2015.1119117
Accepted author version posted online: 13 Nov 2015. Published online: 07 Dec 2015. Submit your article to this journal
Article views: 28
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [University of Sydney Library]
Date: 16 March 2016, At: 02:23
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–5 ! 2015 Taylor & Francis. DOI: 10.3109/14767058.2015.1119117
ORIGINAL ARTICLE
Pregnancy outcome and placental pathology in emergent cesarean deliveries for non-reassuring fetal heart rate in laboring versus non-laboring women Eran Weiner1, Nataly Fainstein1, Adam Pomeranz1, Letizia Schreiber2, Jacob Bar1, and Michal Kovo1
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
1
Department of Obstetrics & Gynecology and 2Department of Pathology, The Edith Wolfson Medical Center, Holon, Israel Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract
Keywords
Objective: The objective of this study is to correlate between pregnancy outcome and placental pathology in emergent cesarean deliveries (ECD) for non-reassuring-fetal-heart-rate (NRFHR) performed in women in their active phase of labor versus those performed in non-laboring women. Methods: A retrospective cohort study. Data were reviewed for all pregnancies necessitating ECD for NRFHR between January 2009 and December 2013. Maternal outcome, neonatal outcome, and placental pathology parameters were compared between ECDs performed during active phase of labor and those performed before the active phase of labor (non-labor group). Results: During the study period, a total of 661 ECDs were performed due to NRFHR. Compared with the active labor group (n ¼ 335), the non-labor group (n ¼ 326) had more pre-eclampsia (p ¼ 0.033), small for gestational age (SGA) (p ¼ 0.016), and preterm labor (p50.001). Worse composite neonatal outcome was observed in the non-labor group compared with the active labor group, p50.001. By a stepwise logistic regression model, non-labor was independently associated with adverse neonatal outcome (1.88 OR CI; 1.19–2.96, p ¼ 0.007). Placental inflammatory lesions were more common in the active labor group (p¼ 0.043), and abnormal cord insertions were more common in the non-labor group (p ¼ 0.002) as well as placental weight510th% (p ¼ 0.019). Conclusion: Higher rate of pregnancy complications, abnormal cord insertion, smaller placentas, and worse neonatal outcome are associated with ECD for NRFHR when performed before the phase of active labor.
Active labor, emergent cesarean deliveries, neonatal outcome, non-reassuring fetal heart rate, placental pathology
Introduction Continuous fetal heart rate monitoring (FHRM) during labor has been used over the last five decades for antenatal assessment and detection of fetuses at risk of hypoxemia and acidemia [1]. Immediate delivery or even emergent cesarean deliveries (ECD) are performed when there is a suspicion of ‘‘fetal distress’’ based on the diagnosis of non-reassuring fetal heart rate (NRFHR monitoring [2]. The mechanisms leading to NRFHR tracings are complex and broad, involving pregnancy complications, maternal and fetal diseases, clinical events, and sentinel events [3] that compromise oxygen supply to the fetus. The exact mechanism is not always clear, although often intra-operative findings or placental histopathology findings may clarify possible etiologies [4–6]. Several studies Address for correspondence: Eran Weiner, Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon 58100, Israel. Tel: +972 3 5028329. Fax: +972 3 5028503. E-mail: [email protected]
History Received 28 October 2015 Revised 6 November 2015 Accepted 9 November 2015 Published online 3 December 2015
investigated the association between maternal and neonatal complications and the timing of a cesarean delivery (CD). Studies have shown that maternal and neonatal complications were more common in ECDs compared with elective cases [7]. Others have shown an increased morbidity both after a prolonged second stage [8–10] and in comparison with the first stage of labor [11,12]. Yet, studies investigating the effect of the stage of labor on maternal and neonatal outcomes in ECDs due to NRFHR are scarce. We hypothesized that ECDs performed not in the active phase of labor will be associated with increased adverse neonatal outcome and more placental lesions, as compared with those performed during the active phase of labor, suggesting an existing chronic placental dysfunction and prolonged in-utero insult affecting the fetus. Thus, we aimed to correlate between pregnancy outcome and placental pathology in ECD for NRFHR performed in women in the active phase of labor versus those performed in women not in labor.
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
2
E. Weiner et al.
J Matern Fetal Neonatal Med, Early Online: 1–5
Methods
Placental examination
We performed a retrospective review of the medical records of all women who underwent ECD for NRFHR, at the labor ward at Edith Wolfson Medical Center, Holon, Israel, from January 2009 to December 2013. Cases eligible for the study were identified from our computerized data system. The study group included women who delivered a singleton, between 24 and 42 weeks, by ECD for NRFHR as the only indication, and their placentas were sent to histopathological evaluation. Excluded from the study were women with additional indications for ECD, as abnormal progress in labor, initial maternal refusal for CD, women with evidence of fetal or neonatal malformations, or cases with missing data. For the purposes of the study, the study population was divided into two groups: women who had ECD before the active phase of labor (non-labor group), or after they reached the active phase of labor, defined as cervical dilatation of 4 cm, accompanied by cervical effacement of 80%, and regular uterine contractions, at least three contractions in 10 min (active labor group). Approval was obtained from the Local Ethics Committee.
As part of our departmental protocol, in every case of ECD for NRFHR, placentas are sent to histopathological evaluation. Placental pathology examinations were performed using our standard protocol, by a single pathologist (author L. S.). Placental lesions were classified by maternal or fetal origin, according to the criteria adopted by the Society for Pediatric Pathology [16] and as we previously reported [4]. Briefly, placental weight was determined 24 h after delivery, and the percentile was determined according to placental weight charts [17]. Each placenta was fixed in formalin, and at least five samples were embedded in paraffin blocks for microscopic assessment. Lesions of maternal vascular supply included placental hemorrhages (marginal and retro-placental), vascular changes associated with maternal malperfusion (acute atherosis and mural hypertrophy), and villous changes associated with maternal malperfusion (increased syncytial knots, villous agglutination, increased intervillous fibrin deposition, distal villous hypoplasia, and villous infarcts). Lesions of fetal vascular supply were defined as findings consistent with fetal thrombo-occlusive disease: vascular lesions (thrombosis of the chorionic plate and stem villous vessels) and villous changes (hypovascular, fibrotic, and avascular villi). Findings consistent with chorioamnionitis were defined by the presence of an inflammatory neutrophil infiltrate at two or more sites on the chorionic plate and extra-placental membrane. Maternal inflammatory response (MIR), was divided into three stages: stage 1 – characterized by the presence of a few scattered neutrophils in the subchorionic space; stage 2 – characterized by many neutrophils (11–30 per HPF) in the lower half of the chorionic plate; and stage 3 – characterized by dense infiltrates of neutrophils (430 per HPF) throughout the chorionic plate. Fetal inflammatory response (FIR) was also divided into three stages: stage 1 – early, umbilical phlebitis; stage 2 – intermediate, umbilical arteritis; and stage 3 – concentric umbilical perivasculitis (necrotizing funisitis). Placental histologic examination also included the detection of meconium stained membranes associated with columnar change in amniotic epithelium or the appearance of pigmented macro-phages. The umbilical cord was examined for the detection of hypercoiling and abnormal cord insertion. Umbilical coiling index was calculated by dividing the total number of coils by the length of the cord in centimeters. Hypercoiling was diagnosed in cases of umbilical coiling index 40.3 coils/cm [18]. Abnormal cord insertion was defined as either velamentous or marginal insertion. Gross anomalies in the umbilical cord (entanglements, true knots, and short cord) were recorded by the surgeons during the operation.
Data collection The following data collected from the womens’ medical and surgical files included demographic and labor characteristics: age, gravidity and parity, body mass index (BMI), gestational diabetes mellitus (GDM), pre-gestational DM (PGDM), thrombophilia (defined as any thrombophilia, inherited or acquired, that necessitated thromboprophylaxis according to the practice bulletins of the American College of Obstetricians and Gynecologists) [13,14], pre-eclampsia, trials of labor after a previous cesarean delivery (TOLAC), gestational age at delivery, oligohydramnios (amniotic fluid index 55 cm), the presence of intra-partum fever 438 C, and meconium. Gestational age was confirmed by first-trimester ultrasonography. Immediately after birth, all neonates were examined by pediatricians. Birthweight percentile for gestational age was assigned using the updated Israeli growth charts [15]. Small for gestational age (SGA) was defined as actual birthweight 510th% for gestational age. The following information was collected from the neonatal records: Apgar scores, cord blood pH, sepsis (positive blood or cerebrospinal fluid culture), need for blood transfusion, need for phototherapy, respiratory distress syndrome, need for mechanical ventilation or support, necrotizing enterocolitis, intraventricular hemorrhage (all grades), hypoxic ischemic encephalopathy, seizures, and death. Intra-operative and post-partum maternal complications including bleeding necessitating intraoperative blood transfusions during the operation, surgical extensions of the uterine incisions 43 cm, injuries to adjacent organs, endometritis, defined as fever with abnormal uterine tenderness in the absence of other findings, suggesting another source of infection, the need for blood transfusion in the post-partum period, relaparotomy, wound infection/hematoma, pelvic abscess, thromboembolism, and anesthesia-related complications, such as postdural puncture headache necessitating blood patch.
Statistical analysis Data were analyzed with SPSS software, version 15.0 (SPSS Inc., Chicago, IL). Continuous variables were calculated as mean ± SD or median and range, as appropriate. Categorical variables were calculated as rate (%). Continuous parameters were analyzed by Student’s t-test and categorical variables by the Chi-square test or by Fisher exact test, as appropriate. p value of 50.05 was considered statistically significant.
ECD for NRFHRM and labor
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
DOI: 10.3109/14767058.2015.1119117
Intra-operative maternal composite outcome was defined as one or more of the following complications: surgical extensions of the uterine incision 43 cm, intra-operative bleeding necessitating blood transfusion, or injury to an adjacent organ. Post-partum maternal composite outcome was defined as one or more of the following complications: endometritis, pelvic abscess, blood transfusion, wound infection/hematoma, relaparotomy, postdural puncture headache, or thromboembolism. Composite adverse neonatal outcome was defined as one or more of the following complications: neonatal sepsis, blood transfusion, phototherapy, respiratory morbidity (the presence of respiratory distress syndrome, or transient tachypnea of the newborn, or mechanical ventilation or need for respiratory support) cerebral morbidity (the presence of intra-ventricular hemorrhage, or seizures or hypoxicischemic encephalopathy) necrotizing enterocolitis, or death. To identify independent risk factors for adverse neonatal outcome, a multivariate stepwise forward logistic regression analysis was performed. Composite adverse neonatal outcome served as a dependent variable and phase of labor (active versus pre-active labor), gestational age, maternal age, nulliparity, maternal BMI, maternal DM, SGA, oligohydramnios, preterm labor, thrombophilia, placental maternal and fetal vascular supply lesions and inflammatory lesions, served as independent variables.
Table 1. Maternal and delivery characteristics of the study groups.
Maternal age (years) Gestational age (weeks) Cervical dilatation at ECD Nulliparity BMI (kg/m2) Gestational DM (GDM) Pre-gestational DM (PGDM) Pre-eclampsia Oligohydramnios SGA 510th percentile Preterm labor 534 weeks Intra partum fever 438 C Thrombophilia Meconium
Non-labor group, n¼326
Active labor group, n¼ 335
p value
29.2 ± 5.2 38.5 ± 3.1 2.5 (0–3.5) 187 (57.4) 24.5 ± 5.5 19 (5.8) 9 (2.8) 35 (10.7) 32 (9.8) 80 (24.5) 28 (8.6) 6 (1.8) 9 (2.8) 111 (34.1)
29.1 ± 5.2 39.6 ± 1.9 6.1 (4–10) 197 (58.8) 24.4 ± 5.1 16 (4.8) 2 (0.6) 20 (6) 18 (5.4) 56 (16.7) 4 (1.2) 20 (6) 2 (0.6) 103 (30.7)
0.96 50.001 50.001 0.753 0.909 0.604 0.034 0.033 0.038 0.016 50.001 0.008 0.034 0.405
All data are shown as number (%), mean ± standard deviation or median (range), as appropriate. DM, diabetes mellitus; BMI, body mass index; TOLAC, trial of labor after cesarean section; patient in active labor is defined as patients with cervical dilatation of 4 cm associated with regular contractions; SGA, small for gestational age, ECD, emergent cesarean delivery. All significant results (p50.05) were bolded for clearification.
Table 2. Neonatal outcome in the study groups. Non-labor Active labor group, group, n¼ 335 p value n¼326
Results During the study time period, 5005 cesarean deliveries (CDs) were performed out of 22 217 deliveries (22.5%), of them, 661 ECDs (13.2%) were performed due to NRFHR, as the only indication. Out of 661 cases eligible for the study, 326 (49.3%) were performed before the active phase of labor (non-labor group) with a median cervical dilation of 2.5 cm (range 0–3.5 cm), and 335 (50.7%) were performed during the active phase of labor (active labor group) with a mean cervical dilation of 6.1 cm (range 4–10 cm). Table 1 presents the background and delivery characteristics of the two groups. There were no between-group differences in maternal age, nulliparity, BMI, and meconium-stained amniotic fluid. The non-labor group had lower gestational age at delivery, 38.5 ± 3.1 versus 39.6 ± 1.9 weeks, p50.001, and higher rate of preterm labor 534 weeks, 8.6% versus 1.2%, p50.001, respectively, as compared with the active labor group. Higher rate of pregnancy complications was observed in the non-labor group as compared with the active labor group: pre-eclampsia (p ¼ 0.033), PGDM (p ¼ 0.03), oligohydramnios (p ¼ 0.038), SGA (p¼ 0.016), and thrombophilia (p ¼ 0.034). The active labor group had a higher rate of intrapartum fever 438 C as compared with the non-labor group, 1.8% versus 0.6%, p ¼ 0.008, respectively. Neonatal outcome parameters are summarized in Table 2. Neonates in the non-labor group had longer duration of hospitalization, 8.9 ± 12.5 d versus 5.8 ± 6.2 d, p50.001, higher rates of admission to NICU, 39.3% versus 28.9%, p ¼ 0.005, and higher rates of 5-min Apgar score 7, 6.1% versus 1.8%, p ¼ 0.004, respectively, as compared with neonates in the active labor group. Additionally, neonates in the non-labor group had higher rates of respiratory morbidity (0.001), cerebral morbidity (p ¼ 0.010), neonatal sepsis (p ¼ 0.022), and blood transfusions (p50.001) as compared
3
Neonatal hospitalization (days) NICU admission Umbilical cord pH 7.1 5-minute Apgar score 7 Respiratory morbidity* Cerebral morbidity** Neonatal sepsis Necrotizing enterocolitis Blood transfusions Phototherapy Neonatal death Composite adverse neonatal outcome
8.7 128 26 20 57 9 15 1 16 36 4 77
(2–58) 5.3 (2–40) (39.3) 97 (28.9) (7.9) 25 (7.5) (6.1) 6 (1.8) (17.5) 24 (7.1) (2.7) 1 (0.3) (4.6) 5 (1.5) (0.3) 0 (4.9) 2 (0.6) (11) 23 (6.9) (1.2) 3 (0.9) (23.6) 38 (11.3)
50.001 0.005 0.884 0.004 50.001 0.01 0.022 0.493 50.001 0.075 0.721 50.001
All data are shown as number (%), mean ± standard deviation, or median (range), as appropriate. NICU, neonatal intensive care unit. Respiratory morbidity includes the presence of respiratory distress syndrome, or transient tachypnea of the newborn, or mechanical ventilation or need for respiratory support. Cerebral morbidity includes the presence of intra-ventricular hemorrhage (all grades), or seizures or hypoxicischemic encephalopathy. All significant results (p50.05) were bolded for clearification.
with neonates in the active labor group. Composite adverse neonatal outcome was higher in the non-labor group than in the active labor (23.6% versus 11.3% p50.001), respectively. By using a stepwise logistic regression model, non-active labor was independently associated with adverse neonatal outcome (1.88 OR, 95% CI: 1.19–2.96, p ¼ 0.007), and delivery434 weeks was found to be independently associated with better neonatal outcome (0.036 OR, 95% CI: 0.014– 0.098, p50.001). Placental histopathology findings and umbilical cord abnormalities in the study groups are summarized in Table 3. Mean placental weight was lower in the non-labor group as compared with the active labor group, 457 ± 114 g versus 484 ± 102 g, respectively, p ¼ 0.002. The rate of placental
4
E. Weiner et al.
J Matern Fetal Neonatal Med, Early Online: 1–5
Table 3. Placental lesions in the study groups. Non-labor group, n¼326
Table 4. Intra-operative and post-partum maternal complications. Active labor group, n¼ 335 p value
Placental weight (g) 457.6 ± 114.7 484.5 ± 102.9 Placental weight510% percentile 37 (11.3) 21 (6.3) Hypercoiled cord 51 (15.6) 40 (11.9) Abnormal cord insertion 67 (20.5) 39 (11.6) Maternal vascular supply lesions Placental hemorrhage Vascular lesions related to maternal malperfusion Villous changes related to maternal malperfusion
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
Fetal vascular supply lesions Vascular lesions consistent with FTOD Villous lesions consistent with FTOD Inflammatory lesions MIR stages 1–3 FIR stages 1–3
0.002 0.019 0.176 0.002
17 (5.2) 20 (6.1)
12 (3.6) 20 (6)
0.345 1
106 (32.5)
107 (31.9)
0.933
22 (6.7)
21 (6.3)
0.875
32 (9.8)
37 (11)
0.613
65 (19.9) 36 (11)
90 (26.9) 39 (11.6)
0.043 0.902
Continuous variables are presented as mean ± SD and categorical variables as n (%). FTOD, fetal thrombo-occlusive disease; MIR, maternal inflammatory response; FIR, fetal inflammatory response. All significant results (p50.05) were bolded for clearification.
weight 510th percentile was higher in the non-labor group compared with the active labor group, 11.3% versus 6.3%, p ¼ 0.019. Abnormal cord insertions were also more common in the non-labor group as compared with the active labor group, 20.6% versus 11.5%, p ¼ 0.002. Compared with the non-labor group the active group had a higher rate of placental lesions consistent with MIR, 26.9% versus 19.9%, respectively, p ¼ 0.043. Other maternal or fetal vascular supply lesions did not differ between the groups. Macroscopic umbilical cord gross abnormalities did not differ between the two groups. Umbilical cord entanglements were found in 37.7% of the cases in the non-labor group versus 32.8% in the active labor group (p ¼ 0.193). True knots were found in 2.4% of the cases in the non-labor group versus 3.6% in the active labor group (p ¼ 0.497). Short cord550 cm was found in 3.2% of the cases in the non-labor group versus 3.9% in the active labor group (p ¼ 0.672). Maternal intra-operative and postpartum complications are summarized in Table 4. Composite adverse intra-operative and post-partum outcomes were higher in the pre-active labor group compared with the non-labor group, p50.001 and p ¼ 0.024, respectively.
Discussion In the present study, we found that ECDs due to NRFHRM performed before the active phase of labor, as compared with those performed during the active phase of labor, were associated with a significantly higher rate of pregnancy complications and worse neonatal outcome, independent of gestational age at delivery (1.88 OR, 95% CI: 1.19–2.96, p ¼ 0.007). The existence of maternal diseases and pregnancy complications is probably associated with hypoxic insults that are slow in onset and persist over time, allowing the fetus to
Non-labor Active labor group, group, n¼ 335 p value n¼326 Mean maternal hospitalization (days) 4.8 ± 1.8
4.6 ± 1.3
Intraoperative complications Surgical extensions 43 cm Intraoperative blood transfusions Injuries to adjacent organ Composite intraoperative complications
22 3 1 25
48 5 2 55
Postoperative complications Endometritis Pelvic abscess Blood transfusions Wound infection/hematoma Relaparotomy* Thromboembolism PDPH Composite postoperative complications
6 (1.8) 0 5 (1.5) 6 (1.8) 2 (0.6) 1 (0.3) 6 (1.8) 26 (8.0)
(6.7) (0.9) (0.3) (7.7)
0.101
(14.3) (1.5) (0.6) (16.4)
0.001 0.725 1 50.001
15 (4.5) 1 (0.3) 5 (1.5) 16 (4.8) 2 (0.6) 0 7 (2.1) 45 (13.4)
0.074 1 1 0.049 1 0.493 1 0.024
All significant results (p50.05) were bolded for clearification.
make some adaptations during pregnancy. Yet, these compensated fetuses have reduced physiological reserve, and will develop abnormal fetal heart rate patterns necessitating ECD, even during the pre-labor uterine contractions, before progression of labor into its active phase. Similarly, another study found a higher rate of pre-labor ECDs in women with type 1 DM but with suboptimal glycemic control [19]. Furthermore, active labor has a well-known beneficial role on early and late neonatal outcome [20–24], attributed to both mechanical and hormonal factors, yet lacking in cases ECDs are performed in non-laboring women. The association between NRFHR tracings and placental pathology has been investigated [5,25], thus it was interesting to find differences between the studied groups even though both groups included cases with NRFHR monitoring. We found higher rates of pathological umbilical cord insertion and a higher rate of placental weights 510th percentile in ECDs performed before the active phase of labor. It is well established that pathological cord insertion is associated with labor complications and neonatal morbidity [26,27]. Moreover, Redline et al. [3] studied umbilical cord abnormalities and placental lesions in 125 neurological impaired neonates, demonstrating that cord abnormalities, including abnormal cord insertions, are more common in placentas with fetal thrombotic vasculopathy, a known placental lesion associated with cerebral palsy. Although in the current study we found no differences between groups in the rate of placental fetal vascular supply lesions, abnormal cord insertion could still be associated with abnormal blood supply to the fetus and slowly evolving fetal hypoxia. Furthermore, it is well known that placental inflammatory lesions are associated with abnormal fetal heart rate [5,6]. We observed a higher rate of placental maternal inflammatory lesions in the active phase of labor group, a finding also known to be associated with prolonged labor and ruptured membranes [28]. In the current study, we found that ECDs performed in the active phase of labor were associated with a higher rate
Downloaded by [University of Sydney Library] at 02:23 16 March 2016
DOI: 10.3109/14767058.2015.1119117
of maternal morbidity, intra-operatively, mostly extensions of the uterine incision, and post-operatively, endometritis and wound infections. These findings are in concordance with previous studies demonstrating higher maternal morbidities due to intra-operative trauma, especially in second-stage CDs [12,29,30]. The present study is unique in several aspects; first, to our knowledge, this is the first report of differences between ECDs performed in non-labor versus active phase of labor, with a thorough description of maternal and neonatal outcome, and with placental histology evaluation. Second, we used validated placental pathological criteria adopted by the Society for Pediatric Pathology [16] with methodical differentiation among lesions of maternal and fetal origin vascular supply abnormalities, inflammatory lesions, as well as cord abnormalities. Third, this is a large cohort that included cases with NRFHR tracings as the only indication for ECD. Our study is not without limitations: first, we are aware of the problematic term of ‘‘NRFHR’’ which is subject to considerable variations of interpretation among maternal– fetal medicine specialists [2,31] making standardization problematic. Yet, we found that category 2 FHR tracings [32] were observed in similar rates in the non-labor group as in the active phase of labor group (92.6% versus 90.1%, respectively). Second, the definition of active phase of labor is also not clear-cut and the transition between non-active and active phase of labor is variable. In conclusion, ECDs performed before the active phase of labor are associated with higher rates of pregnancy complications, abnormal cord insertion, lower placental weight, and worse neonatal outcome as compared with those performed during the active phase of labor.
Declaration of interest The authors report that they have no conflicts of interest.
References 1. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev 2013;5: CD006066. 2. Chauhan SP, Klauser CK, Woodring TC, et al. Intrapartum nonreassuring fetal heart rate tracing and prediction of adverse outcomes: interobserver variability. Am J Obstet Gynecol 2008; 199:623 e621–5. 3. Redline RW. Clinical and pathological umbilical cord abnormalities in fetal thrombotic vasculopathy. Hum Pathol 2004;35:1494–8. 4. Weiner E, Bar J, Fainstein N, et al. Intraoperative findings, placental assessment and neonatal outcome in emergent cesarean deliveries for non-reassuring fetal heart rate. Eur J Obstet Gynecol Reprod Biol 2015;185:103–7. 5. Robinson BK, Su E, Grobman W, et al. The association of histologic placental inflammation with category II fetal heart tracings. Pediatr Dev Pathol 2012;15:298–302. 6. Salafia CM, Mangam HE, Weigl CA, et al. Abnormal fetal heart rate patterns and placental inflammation. Am J Obstet Gynecol 1989;160:140–7. 7. Lilford RJ, van Coeverdende Groot HA, Moore PJ, Bingham P. The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. Br J Obstet Gynaecol 1990;97:883–92. 8. Koyama S, Tomimatsu T, Kanagawa T, et al. Cervical insufficiency following cesarean delivery after prolonged second stage of labor: experiences of two cases. J Obstet Gynaecol Res 2010;36:411–13.
ECD for NRFHRM and labor
5
9. Vyas NA, Vink JS, Ghidini A, et al. Risk factors for cervical insufficiency after term delivery. Am J Obstet Gynecol 2006;195: 787–91. 10. Sung JF, Daniels KI, Brodzinsky L, et al. Cesarean delivery outcomes after a prolonged second stage of labor. Am J Obstet Gynecol 2007;197:306 e301–5. 11. Lurie S, Raz N, Boaz M, et al. Comparison of maternal outcomes from primary cesarean section during the second compared with first stage of labor by indication for the operation. Eur J Obstet Gynecol Reprod Biol 2014;182:43–7. 12. Seal SL, Kamilya G, Mukherji J, et al. Outcome in second-versus first-stage cesarean delivery in a teaching institution in eastern India. Am J Perinatol 2010;27:507–12. 13. American College of Gynecologists Women’s Health Care P: ACOG Practice Bulletin No. 138: inherited thrombophilias in pregnancy. Obstet Gynecol 2013;122:706–17. 14. American College of Gynecologists Committee on Practice B-O: ACOG Practice Bulletin No. 118: antiphospholipid syndrome. Obstet Gynecol 2011;117:192–9. 15. Dollberg S, Haklai Z, Mimouni FB, et al. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311–14. 16. Redline RW, Heller D, Keating S, Kingdom J. Placental diagnostic criteria and clinical correlation – a workshop report. Placenta 2005; 26:S114–17. 17. Pinar H, Sung CJ, Oyer CE, Singer DB. Reference values for singleton and twin placental weights. Pediatr Pathol Lab Med 1996; 16:901–7. 18. Strong Jr TH, Jarles DL, Vega JS, Feldman DB. The umbilical coiling index. Am J Obstet Gynecol 1994;170:29–32. 19. Miailhe G, Le Ray C, Timsit J, Lepercq J. Factors associated with urgent cesarean delivery in women with type 1 diabetes mellitus. Obstet Gynecol 2013;121:983–9. 20. Huang L, Chen Q, Zhao Y, et al. Is elective cesarean section associated with a higher risk of asthma? A meta-analysis. J Asthma 2015;52:16–25. 21. Farchi S, Di Lallo D, Franco F, et al. Neonatal respiratory morbidity and mode of delivery in a population-based study of lowrisk pregnancies. Acta Obstet Gynecol Scand 2009;88:729–32. 22. Zanardo V, Simbi AK, Franzoi M, et al. Neonatal respiratory morbidity risk and mode of delivery at term: influence of timing of elective caesarean delivery. Acta Paediatr 2004;93:643–7. 23. Ly NP, Rifas-Shiman SL, Litonjua AA, et al. Cord blood cytokines and acute lower respiratory illnesses in the first year of life. Pediatrics 2007;119:e171–8. 24. Thomopoulos TP, Skalkidou A, Dessypris N, et al. Prelabor cesarean delivery and early-onset acute childhood leukemia risk. Eur J Cancer Prev 2015. 25. Kovo M, Schreiber L, Ben-Haroush A, et al. Association of nonreassuring fetal heart rate and fetal acidosis with placental histopathology. Placenta 2011;32:450–3. 26. Tantbirojn P, Saleemuddin A, Sirois K, et al. Gross abnormalities of the umbilical cord: related placental histology and clinical significance. Placenta 2009;30:1083–8. 27. Hasegawa J, Matsuoka R, Ichizuka K, et al. Velamentous cord insertion: significance of prenatal detection to predict perinatal complications. Taiwan J Obstet Gynecol 2006;45:21–5. 28. Bar J, Schreiber L, Golan A, Kovo M. Placental factor in spontaneous term labor in uncomplicated pregnancy. J Matern Fetal Neonatal Med 2012;25:2704–7. 29. Allen VM, O’Connell CM, Baskett TF. Maternal and perinatal morbidity of caesarean delivery at full cervical dilatation compared with caesarean delivery in the first stage of labour. BJOG 2005;112: 986–90. 30. Alexander JM, Leveno KJ, Rouse DJ, et al. Comparison of maternal and infant outcomes from primary cesarean delivery during the second compared with first stage of labor. Obstet Gynecol 2007; 109:917–21. 31. Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol 2008;199: 587–95. 32. American College of Gynecologists: ACOG Practice Bulletin No. 106: intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol 2009;114:192–202.
