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The effect of meconium thickness level on neonatal outcome
Early Human Development 142 (2020) 104953
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The effect of meconium thickness level on neonatal outcome ⁎
T
Ohad Gluck , Michal Kovo, Daniel Tairy, Hadas Ganer Herman, Jacob Bar, Eran Weiner Department of Obstetrics & Gynecology, the Edith Wolfson Medical Center, Holon, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
A R T I C LE I N FO
A B S T R A C T
Keywords: Meconium stained amniotic fluid Meconium level Adverse neonatal outcome
Background: Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of meconium stained amniotic fluid (MSAF) and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes. Aims: To study if different thickness levels of MSAF correlate with adverse neonatal outcome. Study design: A retrospective cohort study. Subjects: The medical records and neonatal charts of all women with a singleton pregnancy, who underwent a trial of labor, at 37 + 0/7 weeks or beyond, between 10/2008 and 7/2018 were reviewed. Outcome measures: The cohort was divided according to the level of meconium reported during labor into four groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). Composite neonatal outcome included at least one of the following: umbilical artery pH ≤ 7.1, sepsis, need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome, need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic ischemic encephalopathy, periventricular leukomalacia, seizures, hypoglycemia, hypothermia, and death. Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. Multivariant logistic regression was performed in order to eliminate possible cofounders. Results: Overall, 24,445 deliveries were reviewed (C-20,185, LM-1074, IM-2736, HM-450). Composite adverse neonatal outcome was more common with increasing thickness of MSAF. On multivariable analysis, IM and HM were independently associated with composite adverse neonatal outcome. Conclusion: The degree of meconium thickness independently correlates with composite adverse neonatal outcome.
1. Introduction Meconium-stained amniotic fluid (MSAF) is the passage of meconium by a fetus in utero during the antenatal period or in labor [1–27]. MSAF during labor is reported in 7%–22% of deliveries [2]. Although the exact etiology of why meconium passage occurs is unclear, several risk factors for MSAF have been suggested, such as prolonged labor, post term pregnancy, low birth-weight, oligohydramnios, fetal growth restriction, hypertensive disorders, cholestasis of pregnancy, anemia, older maternal age, and drug abuse [3]. It has been previously associated with adverse fetal outcomes such as meconium aspiration syndrome and perinatal asphyxia [4–6]. MSAF has also been found to be
associated with maternal complications such as amniotic fluid embolism, peripartum febrile morbidity, and assisted vaginal delivery [3]. Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of MSAF and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes [7–9]. Starting October 2008, we implemented an institutional protocol that mandates obstetricians and midwives to report their subjective impression of the color of amniotic fluid (clear, meconium stained, bloody) during every delivery (both vaginal and cesarean) and to specifically report their subjective impression of MSAF thickness. Prior to October 2008, the color of amniotic fluid was described occasionally
Abbreviations: MSAF, Meconium-stained amniotic fluid; C group, clear group; LM group, light meconium group; IM group, intermediate meconium group; HM group, heavy meconium group; ACOG, American college of obstetricians and gynecologists; SGA, small for gestational age; MAS, meconium aspiration syndrome; HIE, hypoxic ischemic encephalopathy ⁎ Corresponding author at: Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon 58100, Israel. E-mail address: [email protected] (O. Gluck). https://doi.org/10.1016/j.earlhumdev.2020.104953 Received 10 July 2019; Received in revised form 5 January 2020; Accepted 6 January 2020 0378-3782/ © 2020 Elsevier B.V. All rights reserved.
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The following neonatal adverse outcomes were collected: umbilical artery pH ≤ 7.1, sepsis (positive blood or cerebrospinal fluid culture), need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome (MAS), need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage- all grades, hypoxic ischemic encephalopathy (HIE), periventricular leukomalacia, seizures, hypoglycemia (blood glucose < 40 mg/ dL), hypothermia, and death. The following data regarding pregnancy outcome were collected from the chart of each patient: induction of labor, placental abruption (diagnosed clinically or pathologically), mode of delivery (vaginal, assisted vaginal, or cesarean, as well as the indications for CD), intrapartum fever, chorioamnionitis, manual revision of the uterine cavity, manual removal of the placenta, postpartum hemorrhage (that necessitated medical and/or surgical treatment), and postpartum blood transfusion. Intrapartum fever was defined as elevated temperature (38.0 °C or greater) during labor with no other signs of chorioamnionitis. Clinical chorioamnionitis was diagnosed in the presence of maternal fever (temperature 38.0 °C or greater) with no evidence of an extra uterine cause, accompanied by at least two of the following: fetal tachycardia, maternal tachycardia, leukocytosis, uterine tenderness, or new onset of foul-smelling vaginal discharge.
(not routinely), according to the medical team's judgment. Therefore, ten years after the implementation of the protocol, we aimed to study the association between the various MSAF thickness levels and specific adverse neonatal outcomes. 2. Methods 2.1. Study population Data were retrieved from the computerized database. After a report was generated for any data points of interest, a manual review of each chart was done to ensure accurate reporting by a trained member of the research team. The medical records, delivery details, and neonatal data of all patients with singleton pregnancies who underwent a trial of labor at 37 + 0/7 gestational weeks or beyond, between October 2008 (the time at which documentation of amniotic fluid characteristics in all delivery reports became mandatory) and July 2018, from a single university hospital, were reviewed. We excluded all deliveries < 37 weeks, multiple pregnancies, terminations of pregnancy, intra uterine fetal deaths, pregnancies with a known major fetal malformation, cases with bloody amniotic fluid, elective cesarean deliveries and cases with missing data. The study was approved by our institutional ethical review board (decision number 0232-16-WOMC dated 28/11/2017), and has been carried out in accordance with The Code of Ethics of the World Medical Association. As this study is based on encrypted data analysis only, informed consent was not needed. The cohort was divided according to the level of meconium reported during labor, by the midwife or obstetrician (including residents), into 4 groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). In cases of transitioning of the impression of MSAFP thickness during labor (a total of 5 cases), MSAF was recorded according to highest level of meconium staining. Maternal demographics, neonatal outcomes, and pregnancy complications were compared between the groups.
2.3. Outcomes The primary outcome was defined as a composite of one or more early neonatal complications, as detailed above. Secondary outcomes included delivery maternal and complications, as described earlier. 2.4. Statistics Data analysis was performed with Epi info 7 (Centers for Disease Control and Prevention, Atlanta, GA). Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. A p value < 0.05 was considered statistically significant. Post-hoc tests were performed to separate the groups from each other. A multivariate logistic regression analysis model was used to identify the independent associations with composite adverse neonatal outcome, which served as the dependent variable. The following confounders serve as independent variables: labor induction, trial of labor after cesarean delivery, assisted vaginal delivery, in labor cesarean delivery, SGA, the different degrees of meconium, oligohydramnios and polyhydramnios.
2.2. Data collection The following characteristics were collected from the medical chart of each patient: maternal age, gravidity, parity, pre-pregnancy weight and height (according to which the body mass index was calculated), gestational diabetes mellitus, pre-gestational diabetes mellitus, chronic hypertension, preeclampsia, smoking, gestational age at delivery, prepregnancy diagnosis of thrombophilia (defined as any thrombophilia, inherited or acquired, that necessitated thrombo-prophylaxis) [10,11], drug abuse, oligohydramnios, polyhydramnios, epidural analgesia, and trials of labor after a previous cesarean delivery. Gestational age was calculated based on the woman's first ultrasound examination in the pregnancy and last menstrual period [12]. A woman was considered to have diabetes mellitus if she had a diagnosis of type 1/type 2 in the medical record or gestational diabetes mellitus based on the current American College of Obstetricians and Gynecologists criteria (ACOG) [13]. Chronic hypertension and preeclampsia were diagnosed according to the current ACOG criteria [14], as adapted by our institution for hypertensive disorders' diagnosis and management. Oligohydramnios was defined as an amniotic fluid index ≤5 cm and polyhydramnios as amniotic fluid index ≥24 cm [15]. A neonatologist was present in any delivery from MSAF, and performed an immediate initial examination of the newborn. Further actions, such as suction or NICU admission were performed according to clinical judgment. Birth weight percentiles for gestational age were assigned using the updated local growth charts [16]. Small for gestational age (SGA) was defined as actual birthweight≤10th percentile for gestational age.
3. Results A total of 30,215 deliveries occurred at our institution during the study period. After excluding cases which did not meet the inclusion criteria– 24,445 deliveries were analyzed: C group −20,185 (82.6%), LM group −1074 (4.4%), IM group −2736 (11.2%), and HM-450 (1.8%) group (Fig. 1). Maternal demographics of the groups are presented and compared in Table 1. The groups statistically differed in terms of: the rate of induction of labor, epidural analgesia, gestational age at delivery, delivery at ≥41 weeks, delivery at ≥42 weeks, as well as the rate of trials of labor after a previous cesarean delivery. Neonatal outcomes are presented in Table 2. The groups differed in terms of the primary outcome - composite adverse neonatal outcome, as well as birthweight, and the rate of SGA. Notably, the groups also differed in individual components of the composite adverse outcome: HIE, hypothermia, mechanical ventilation, MAS, and blood transfusion (all p values < 0.001). Pregnancy outcomes of the study groups are presented in Table 3. 2
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Fig. 1. Cohort analysis flowchart. Study population.
delivery) and various adverse pregnancy outcomes, including maternal and neonatal morbidities. Our main findings were: 1) MSAF (of any level) was reported in 17.4% of deliveries studied, which is similar to that described in literature [17–19]. 2) Intermediate meconium (IM) and heavy meconium (HM) were found to be risk factors for composite adverse neonatal outcome, as well as in-labor cesarean deliveries and SGA. 3) As MSAF was thicker, higher rates of SGA, HIE, mechanical ventilation support, MAS, and neonatal blood transfusion, as well as maternal blood transfusion and assisted vaginal delivery, were observed. The association between MSAF and neonatal outcome has been studied thoroughly, however the correlation between different
The groups differed in the rate of assisted vaginal deliveries, cesarean deliveries, as well as maternal blood transfusion (all p values < 0.001). A logistic regression model, presented in Table 4, was composed to account for the independent associations with composite neonatal outcome. Intermediate meconium and heavy meconium were independently associated with composite adverse neonatal outcome, as well as assisted vaginal delivery, in-labor cesarean deliveries, and SGA.
4. Discussion In the current study we aimed to investigate the correlation between different levels of meconium thickness (subjectively described during Table 1 Maternal demographics and pregnancy characteristics of the study groups. Parameter
Clear (n = 20,185)
Light (n = 1074)
Intermediate (n = 2736)
Heavy (n = 450)
P value
Maternal age (years) Maternal age > 35 years GA at delivery (weeks) GA ≥ 41.0 weeks GA ≥ 42.0 weeks Gravidity Parity Nulliparity Body mass index (kg/m2) Diabetes mellitus Gestational diabetes mellitus Chronic hypertension Preeclampsia Smoking Thrombophilia Drug abuse Oligohydramnios Polyhydramnios Induction of labor Epidural analgesia TOLAC
29.8 ± 5.3 3140 (15.5) 39.2 ± 1a,b,c 2867 (14.1) a,b,c 173 (0.9) a,b,c 2.7 ± 1.6 1.2 ± 1.2 6783 (33.4) 23.7 ± 3.7 138 (0.7) 1399 (6.9) 157 (0.8) 1322 (6.5) 2644 (13.0) 414 (2.0) 134 (0.7) 640 (3.2) 415 (2.0) 5941 (29.2) a 11,882 (54.5) a,b 1778 (8.8) a
29.6 ± 5.2 164 (15.2) 39.6 ± 1 a 246 (22.7) a 22 (2.1) a 2.7 ± 1.8 1.3 ± 1.3 326 (30.1) 23.8 ± 3.6 11 (1.0) 77 (7.1) 8 (0.7) 68 (6.3) 135 (12.5) 20 (1.9) 10 (0.9) 33 (3.1) 23 (2.1) 333 (30.8) 900 (83.3) a 84 (7.8)
29.5 ± 5.4 376 (13.7) 39.6 ± 1 b 654 (23.9) b 77 (2.8) b 2.7 ± 1.7 1.2 ± 1.3 925 (33.7) 23.6 ± 3.2 22 (0.8) 197 (7.2) 25 (0.9) 195 (7.1) 371 (13.5) 58 (2.1) 18 (0.7) 113 (4.1) 54 (2.0) 895 (32.6) a 2309 (84.0) b 175 (6.4)
29.7 ± 5.1 63 (13.9) 39.6 ± 1 c 105 (23.1) c 18 (4.0) c 2.6 ± 1.6 1.2 ± 1.3 159 (35.1) 24.0 ± 4.3 1 (0.2) 21 (4.6) 1 (0.2) 23 (5.1) 61 (13.5) 5 (1.1) 3 (0.7) 16 (3.5) 13 (2.9) 138 (30.5) 342 (75.5) b 25 (5.5) a
0.142 0.089 < 0.001 < 0.001 < 0.001 0.638 0.257 0.127 0.99 0.308 0.259 0.454 0.372 0.981 0.527 0.777 0.061 0.648 0.03 < 0.001 < 0.001
Continuous variables are presented as mean ± SD and categorical variables as n (%). GA- gestational age; TOLAC – trial of labor after a previous Cesarean. Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance. 3
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Table 2 Neonatal outcomes in the study groups. Outcome
Clear (n = 20,185)
Composite adverse neonatal outcome Birthweight (gr) Small for gestational age Need for immediate ventilation Umbilical artery Ph ≤ 7.1 Seizures Hypoxic-ischemic encephalopathy Intraventricular hemorrhage Periventricular leukomalacia Hypoglycemia Hypothermia Mechanical ventilation Meconium aspiration syndrome Respiratory distress syndrome Necrotizing enterocolitis Phototherapy Sepsis Blood transfusion Neonatal death
436 (2.2)a 3275 ± 479 1434 (7.1) a 55 (0.27) a 77 (0.4) 9 (0.04) 4 (0.02) a,b 3 (0.01) 0 (0) 130 (0.6) 3 (0.01) a 55 (0.3) a 15 (0.07) a 6 (0.03) 2 (0.01) 170 (0.8) 0 (0) 19 (0.1) a 0 (0)
Light (n = 1074)
a,b
Intermediate (n = 2736)
25 (2.3) 3385 ± 398 48 (4.4) a 19 (0.69) b 3 (0.3) 0 (0) 0 (0) c,d 0 (0) 0 (0) 5 (0.5) 0 (0) b 5 (0.5) b 5 (0.5) a 1 (0.1) 0 (0) 10 (0.9) 0 (0) 1 (0.1) b 0 (0)
a,c
82 (3.0) a 3341 ± 423 217 (7.9) a 5 (0.47) c 6 (0.2) 4 (0.2) 4 (0.2) a, c 1 (0.04) 0 (0) 23 (0.8) 0 (0) c 19 (0.7) c 30 (1.1) a 0 (0) 0 (0) 22 (0.8) 0 (0) 10 (0.4) a,b 0 (0)
b,d
Heavy (n = 450)
P value
24 (5.3) a 3270 ± 436 c,d 59 (13.0) a 12 (2.67) a,b,c 0 (0) 0 (0) 2 (0.4) b,d 0 (0) 0 (0) 3 (0.7) 2 (0.4) a,b,c 12 (2.7) a,b,c 9 (2.0) a 1 (0.2) 0 (0) 8 (1.8) 0 (0) 4 (0.9) a,b 0 (0)
< 0.001 < 0.001 < 0.001 < 0.001 0.306 0.134 < 0.001 0.810 1.0 0.554 < 0.001 < 0.001 < 0.001 0.069 0.935 0.196 1.0 < 0.001 1.0
Continuous variables are presented as mean ± SD and categorical variables as n (%). Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance.
thickness levels of meconium and neonatal outcome had been scarcely described. A few small studies found that thick meconium was associated with an increased risk for perinatal complications during labor (such as low Apgar scores and cesarean deliveries) and MAS, however, they did not asses additional neonatal or maternal outcomes [19–24]. The current study re-validates the results described above, and, due to the large cohort, further demonstrates this association with different neonatal morbidities, most of which are severe, and may be associated with long term disability (such as HIE, mechanical ventilation, hypothermia, and neonatal blood transfusion). Table 5 presents a summary of all previously published publications on this topic, emphasizing the very large sample size and detailed outcomes of the current study. Interestingly, although we observed a correlation between meconium thickness and the rate of in-labor cesarean deliveries, no between group differences was observed in rate of cesarean deliveries due to non-reassuring fetal heart rate monitor. As MSAF has been previously associated with prolonged labor [3], the higher rate of in labor cesarean deliveries with increasing MSAF thickness probably reflects a higher rate of dysfunctional labors and resultant CD. Higher rates of maternal blood transfusion among MSAF patients might be explained by the higher rates of assisted vaginal deliveries and cesarean deliveries, which are known risk factors for extensive blood loss and the need for
Table 4 The results of a multivariate regression analysis model for composite adverse neonatal outcome. Variable
aOR
95% CI
P value
Induction of labor TOLAC Assisted vaginal delivery In-labor Cesarean delivery Cesarean delivery due to NRFHRM Small for gestational age Light meconium Intermediate meconium Heavy meconium Oligohydramnios Polyhydramnios
0.99 0.84 1.70 1.82 1.03 1.96 1.61 1.51 2.42 0.98 1.20
0.82 0.58 1.32 1.31 0.53 1.53 0.77 1.18 1.56 0.61 0.70
0.937 0.348 < 0.001 < 0.001 0.923 < 0.001 0.474 0.001 < 0.001 0.96 0.494
-
1.19 1.20 2.18 2.51 1.98 2.50 1.75 1.93 3.75 1.60 2.07
Values reflect the results of multivariate logistic regression analysis. Model was adjusted for all the variables listed in the table. Values in bold are statistically significant. TOLAC – trial of labor after a previous Cesarean delivery, NRFHRM- non-reassuring fetal heart rate monitor.
Table 3 Delivery outcomes and complications in the study groups. Outcome
Clear (n = 20,185)
Light (n = 1074)
Assisted vaginal delivery In-labor Cesarean delivery Cesarean delivery due to NRFHRM Placental abruption Intrapartum fever Chorioamnionitis Manual revision of the uterine cavity Manual removal of the placenta Post-partum hemorrhage Maternal blood transfusion
3347 (16.5) a 934 (4.6) a,b,c 207 (1.0) 415 (2.0) 104 (0.5) 88 (0.4) 8074.0)) 457 (2.3) 1362 (6.7) 1248 (6.1) a,b,c
147 (13.6) 69 (6.4) a 8 (0.7) 23 (2.1) 4 (0.4) 9 (0.8) 48 (4.4) 30 (2.8) 85 (7.9) 80 (7.4) a
a,b
Continuous variables are presented as mean ± SD and categorical variables as n (%). NRFHRM- non-reassuring fetal heart rate monitor. Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance. 4
Intermediate (n = 2736)
Heavy (n = 450)
P value
470 (17.1) b 173 (6.3) b 24 (0.9) 65 (2.4) 21 (0.8) 11 (0.4) 101 (3.7) 64 (2.3) 204 (7.4) 210 (7.6) b
98 (21.6) a,b 32 (7.1) c 4 (0.9) 13 (2.9) 2 (0.4) 1 (0.2) 23 (5.1) 13 (2.9) 41 (9.1) 37 (8.2) c
< 0.001 < 0.001 0.730 0.460 0.313 0.222 0.440 0.575 0.065 0.003
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Table 5 Summary of available studies. Study
Sample size
Meconium levels
Increased maternal risks*
Increased neonatal risks*
Additional finding
Gluck et al., 2019 (Current study)
4260 MSAF 20,185 controls
Heavy > intermediate > light > clear
AVD, CD Blood transfusion
Incidence of MSAF rises with gestational age at delivery
Mohammad et al., 2018 [22]
149 MSAF
Thick > thin
CD
Shrestha et al., 2018 [21] Rodriquez et al., 2018 [23]
167 MSAF
Thick > thin
503 MSAF 3807 controls
Thick > green > yellow > clear
No correlation to meconium thickness Intrapartum fever AVD CD
Small for gestational age Hypoxic-ischemic encephalopathy Hypothermia Mechanical ventilation MAS Blood transfusion NRFHRM Low Apgar scores MAS Neonatal intensive care unit No correlation to meconium thickness
Incidence of MSAF rises with gestational age at delivery
Sheiner et al., 2002 [19]
106 MSAF 480 controls
Thick > thin > clear
AVD CD
Ziadeh et al., 2000 [20]
390 MSAF 400 controls
Mod-Thick > thin > clear
Chorioamnionitis Labor dystocia CD
Trimmer et al., 1991 [24]
106 MSAF
Thick > moderate > thin
Not studied
NRFHRM Need for neonatal advanced resuscitation Low Apgar scores Fetal‑neonatal mortality NRFHRM Low 1-min Apgar scores Neonatal intensive care unit indications NRFHRM Arterial cord acidosis Oxygen support Low 1&5-min Apgar scores MAS Neonatal intensive care unit No correlation to acidemia, Apgar scores, and meconium aspiration syndrome
Incidence of oligohydramnion higher with MSAF
*In association with increased meconium thickness. AVD- assisted vaginal delivery; CD- cesarean delivery; NRFHRM- non-reassuring fetal heart rate monitor; MAS- Meconium aspiration syndrome.
neonate could be considered and tailored more specifically according to MSAF thickness.
blood transfusion [25,26]. The presence of meconium may also be associated with a reduced uterine contractility following delivery and subsequent postpartum hemorrhage, although this did not attain statistical significance (p = 0.06). Our study is notable for several strengths: First, we were able to study a large cohort of ten years, following the implementation of a protocol which mandated documenting the thickness of MSAF, which minimized selection bias. Second, the large cohort enabled us to investigate the association between different thickness levels of meconium and detailed neonatal and maternal outcomes. It also allowed for the investigation of less common adverse outcomes and the detection of differences in their occurrence. Our study is not without limitations. First, we are aware that MSAF thickness described by the obstetrician or midwife during labor was based on subjective impression, and no clear standardization was applied. While a previous study suggested visual assessment cannot provide a valid basis for assigning different care policies to different degrees of meconium staining, it consisted of a small sample size, and has not been validated clinically [9]. Second, our study lacks long term follow-up, as we only studied short term outcomes. Third, due to the study's retrospective design, the effect of obstetric interventions during labor based on meconium thickness remains to be established in a prospective setting. Lastly, the use of a composite outcome may be viewed as a limitation of this study. However, we believe the use of a composite was necessary because the individual components of the composite are rare complications. We have described and validated the same composite neonatal outcomes in our previous publications with other pregnancy complications [27]. In conclusion, MSAF thickness is independently associated with adverse neonatal outcomes. This data emphasizes the importance of a detailed description of MSAF observed during labor. Actions in labor and delivery, from the presence of neonatologist at time of delivery, closer surveillance of the neonate, and up to specific therapies to the
Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of competing interest None. Acknowledgments Meir Azran, Computing and Information Systems, E. Wolfson Medical Center, Holon, Israel. Ela Smirin, archive, E. Wolfson Medical Center, Holon, Israel. References [1] National Collaborating Centre for Women'’s and Children'’s Health (UK), Intrapartum Care [Internet]. Intrapartum Care: Care of Healthy Women and Their Babies During Childbirth, National Institute for Health and Care Excellence (UK), 2014 [cited 2019 Apr 16]. Available from http://www.ncbi.nlm.nih.gov/pubmed/ 25950072. [2] V.L. Katz, W.A. Bowes, Meconium aspiration syndrome: reflections on a murky subject, Am. J. Obstet. Gynecol. 166 (1 Pt 1) (1992 Jan) 171–183 Internet. cited 2018 Dec 4. Available from http://www.ncbi.nlm.nih.gov/pubmed/1733193. [3] D Addisu, A Asres, G Gedefaw, S Asmer, Prevalence of meconium stained amniotic fluid and its associated factors among women who gave birth at term in Felege Hiwot comprehensive specialized referral hospital, North West Ethiopia: a facility based cross-sectional study, BMC Pregnancy Childbirth 18 (1) (2018 Dec 30) 429 Internet. cited 2018 Dec 3. Available from https://bmcpregnancychildbirth biomedcentral.com/articles/10.1186/s12884-018-2056-y. [4] M.C. Walsh, J.M. Fanaroff, M.C. Walsh, Meconium stained fluid: approach to the mother and the baby, Clin. Perinatol. 34 (2007) 653–665 Internet. cited 2018 Dec 6. Available from https://www-clinicalkey-com.wolfson-ez.medlcp.tau.ac.il/
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service/content/pdf/watermarked/1-s2.0-S0095510807000802.pdf?locale= en_US. R.Y. Bhat, A. Rao, Meconium-stained amniotic fluid and meconium aspiration syndrome: a prospective study, Ann. Trop. Paediatr. 28 (3) (2008) 199–203 Internet. Sep 18 [cited 2018 Dec 6. Available from http://www.ncbi.nlm.nih.gov/ pubmed/18727848. L. Hiersch, E. Krispin, A. Aviram, A. Wiznitzer, Y. Yogev, E. Ashwal, Effect of meconium-stained amniotic fluid on perinatal complications in low-risk pregnancies at term, Am. J. Perinatol. 33 (4) (2015 Oct 19) 378–384 Internet. cited 2018 Dec 3. Available from http://www.thieme-connect.de/DOI/DOI?10.1055/s-00351565989. Trimmer KJ, Gilstrap LC 3rd. “Meconiumcrit” and birth asphyxia. Am. J. Obstet. Gynecol.. 1991 Oct; 165(4 Pt 1):1010–3. B. Morad, S. Kaplan, D. Zangen, Y. Rabine, B. Kaplan, S. Zangen, D. Rabinerson, D. Peleg, P. Merlob, Management of meconium-stained neonates, J Obstet Gynaecol (Lahore) 18 (3) (1998 Jan 2) 223–226 Internet. cited 2018 Dec 6. Available from http://www.ncbi.nlm.nih.gov/pubmed/15512063. M.L. van Heijst, G. van Roosmalen, M.J. Keirse, Classifying meconium-stained liquor: is it feasible? Birth 22 (4) (1995) 191–195 Internet. Dec [cited 2018 Dec 6. Available from http://www.ncbi.nlm.nih.gov/pubmed/8573233. American College of Obstetricians and Gynecologists Women’’s Health Care Physicians, ACOG practice bulletin no. 138: inherited thrombophilias in pregnancy, Obstet. Gynecol. 122 (3) (2013 Sep) 706–717 Internet. cited 2018 Dec 4. Available from http://insights.ovid.com/crossref?an=00006250-201309000-00039. American College of Obstetricians and Gynecologists Committee on Practice Bulletins-Obstetrics, Practice bulletin no. 118: antiphospholipid syndrome, Obstet. Gynecol. 117 (1) (2011) 192–199 Internet. Jan [cited 2018 Dec 4. Available from http://www.ncbi.nlm.nih.gov/pubmed/21173671. American College of Obstetricians and Gynecologists, ACOG practice bulletin no. 101: ultrasonography in pregnancy, Obstet. Gynecol. 113 (2, Part 1) (2009 Feb) 451–461 Internet. cited 2018 Dec 4. Available from http://www.ncbi.nlm.nih.gov/ pubmed/19155920. American College of Obstetricians and Gynecologists, Clinical Management Guidelines for Obstetrician –Pregestational Diabetes Mellitus, 133(1) (2019), pp. 1–25. ACOG Committee on Obstetric Practice, ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists, Int. J. Gynaecol. Obstet. 77 (1) (2002 Apr) 67–75 Internet. cited 2016 Sep 9. Available from http://www.ncbi.nlm.nih. gov/pubmed/12094777. S. Kehl, A. Schelkle, A. Thomas, A. Puhl, K. Meqdad, B. Tuschy, et al., Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial, Ultrasound Obstet. Gynecol. 47 (6) (2016 Jun) 674–679 Internet. cited 2018 Dec 4. Available from http://www.ncbi.nlm.nih.gov/pubmed/26094600. S. Dollberg, Z. Haklai, F.B. Mimouni, I. Gorfein, E.-S. Gordon, Birth weight standards in the live-born population in Israel, Isr. Med. Assoc. J. 7 (5) (2005 May) 311–314 Internet. cited 2016 Oct 28. Available from http://www.ncbi.nlm.nih.
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Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
The effect of meconium thickness level on neonatal outcome ⁎
T
Ohad Gluck , Michal Kovo, Daniel Tairy, Hadas Ganer Herman, Jacob Bar, Eran Weiner Department of Obstetrics & Gynecology, the Edith Wolfson Medical Center, Holon, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
A R T I C LE I N FO
A B S T R A C T
Keywords: Meconium stained amniotic fluid Meconium level Adverse neonatal outcome
Background: Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of meconium stained amniotic fluid (MSAF) and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes. Aims: To study if different thickness levels of MSAF correlate with adverse neonatal outcome. Study design: A retrospective cohort study. Subjects: The medical records and neonatal charts of all women with a singleton pregnancy, who underwent a trial of labor, at 37 + 0/7 weeks or beyond, between 10/2008 and 7/2018 were reviewed. Outcome measures: The cohort was divided according to the level of meconium reported during labor into four groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). Composite neonatal outcome included at least one of the following: umbilical artery pH ≤ 7.1, sepsis, need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome, need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic ischemic encephalopathy, periventricular leukomalacia, seizures, hypoglycemia, hypothermia, and death. Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. Multivariant logistic regression was performed in order to eliminate possible cofounders. Results: Overall, 24,445 deliveries were reviewed (C-20,185, LM-1074, IM-2736, HM-450). Composite adverse neonatal outcome was more common with increasing thickness of MSAF. On multivariable analysis, IM and HM were independently associated with composite adverse neonatal outcome. Conclusion: The degree of meconium thickness independently correlates with composite adverse neonatal outcome.
1. Introduction Meconium-stained amniotic fluid (MSAF) is the passage of meconium by a fetus in utero during the antenatal period or in labor [1–27]. MSAF during labor is reported in 7%–22% of deliveries [2]. Although the exact etiology of why meconium passage occurs is unclear, several risk factors for MSAF have been suggested, such as prolonged labor, post term pregnancy, low birth-weight, oligohydramnios, fetal growth restriction, hypertensive disorders, cholestasis of pregnancy, anemia, older maternal age, and drug abuse [3]. It has been previously associated with adverse fetal outcomes such as meconium aspiration syndrome and perinatal asphyxia [4–6]. MSAF has also been found to be
associated with maternal complications such as amniotic fluid embolism, peripartum febrile morbidity, and assisted vaginal delivery [3]. Despite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of MSAF and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes [7–9]. Starting October 2008, we implemented an institutional protocol that mandates obstetricians and midwives to report their subjective impression of the color of amniotic fluid (clear, meconium stained, bloody) during every delivery (both vaginal and cesarean) and to specifically report their subjective impression of MSAF thickness. Prior to October 2008, the color of amniotic fluid was described occasionally
Abbreviations: MSAF, Meconium-stained amniotic fluid; C group, clear group; LM group, light meconium group; IM group, intermediate meconium group; HM group, heavy meconium group; ACOG, American college of obstetricians and gynecologists; SGA, small for gestational age; MAS, meconium aspiration syndrome; HIE, hypoxic ischemic encephalopathy ⁎ Corresponding author at: Department of Obstetrics & Gynecology, The Edith Wolfson Medical Center, P.O. Box 5, Holon 58100, Israel. E-mail address: [email protected] (O. Gluck). https://doi.org/10.1016/j.earlhumdev.2020.104953 Received 10 July 2019; Received in revised form 5 January 2020; Accepted 6 January 2020 0378-3782/ © 2020 Elsevier B.V. All rights reserved.
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The following neonatal adverse outcomes were collected: umbilical artery pH ≤ 7.1, sepsis (positive blood or cerebrospinal fluid culture), need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome (MAS), need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage- all grades, hypoxic ischemic encephalopathy (HIE), periventricular leukomalacia, seizures, hypoglycemia (blood glucose < 40 mg/ dL), hypothermia, and death. The following data regarding pregnancy outcome were collected from the chart of each patient: induction of labor, placental abruption (diagnosed clinically or pathologically), mode of delivery (vaginal, assisted vaginal, or cesarean, as well as the indications for CD), intrapartum fever, chorioamnionitis, manual revision of the uterine cavity, manual removal of the placenta, postpartum hemorrhage (that necessitated medical and/or surgical treatment), and postpartum blood transfusion. Intrapartum fever was defined as elevated temperature (38.0 °C or greater) during labor with no other signs of chorioamnionitis. Clinical chorioamnionitis was diagnosed in the presence of maternal fever (temperature 38.0 °C or greater) with no evidence of an extra uterine cause, accompanied by at least two of the following: fetal tachycardia, maternal tachycardia, leukocytosis, uterine tenderness, or new onset of foul-smelling vaginal discharge.
(not routinely), according to the medical team's judgment. Therefore, ten years after the implementation of the protocol, we aimed to study the association between the various MSAF thickness levels and specific adverse neonatal outcomes. 2. Methods 2.1. Study population Data were retrieved from the computerized database. After a report was generated for any data points of interest, a manual review of each chart was done to ensure accurate reporting by a trained member of the research team. The medical records, delivery details, and neonatal data of all patients with singleton pregnancies who underwent a trial of labor at 37 + 0/7 gestational weeks or beyond, between October 2008 (the time at which documentation of amniotic fluid characteristics in all delivery reports became mandatory) and July 2018, from a single university hospital, were reviewed. We excluded all deliveries < 37 weeks, multiple pregnancies, terminations of pregnancy, intra uterine fetal deaths, pregnancies with a known major fetal malformation, cases with bloody amniotic fluid, elective cesarean deliveries and cases with missing data. The study was approved by our institutional ethical review board (decision number 0232-16-WOMC dated 28/11/2017), and has been carried out in accordance with The Code of Ethics of the World Medical Association. As this study is based on encrypted data analysis only, informed consent was not needed. The cohort was divided according to the level of meconium reported during labor, by the midwife or obstetrician (including residents), into 4 groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). In cases of transitioning of the impression of MSAFP thickness during labor (a total of 5 cases), MSAF was recorded according to highest level of meconium staining. Maternal demographics, neonatal outcomes, and pregnancy complications were compared between the groups.
2.3. Outcomes The primary outcome was defined as a composite of one or more early neonatal complications, as detailed above. Secondary outcomes included delivery maternal and complications, as described earlier. 2.4. Statistics Data analysis was performed with Epi info 7 (Centers for Disease Control and Prevention, Atlanta, GA). Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. A p value < 0.05 was considered statistically significant. Post-hoc tests were performed to separate the groups from each other. A multivariate logistic regression analysis model was used to identify the independent associations with composite adverse neonatal outcome, which served as the dependent variable. The following confounders serve as independent variables: labor induction, trial of labor after cesarean delivery, assisted vaginal delivery, in labor cesarean delivery, SGA, the different degrees of meconium, oligohydramnios and polyhydramnios.
2.2. Data collection The following characteristics were collected from the medical chart of each patient: maternal age, gravidity, parity, pre-pregnancy weight and height (according to which the body mass index was calculated), gestational diabetes mellitus, pre-gestational diabetes mellitus, chronic hypertension, preeclampsia, smoking, gestational age at delivery, prepregnancy diagnosis of thrombophilia (defined as any thrombophilia, inherited or acquired, that necessitated thrombo-prophylaxis) [10,11], drug abuse, oligohydramnios, polyhydramnios, epidural analgesia, and trials of labor after a previous cesarean delivery. Gestational age was calculated based on the woman's first ultrasound examination in the pregnancy and last menstrual period [12]. A woman was considered to have diabetes mellitus if she had a diagnosis of type 1/type 2 in the medical record or gestational diabetes mellitus based on the current American College of Obstetricians and Gynecologists criteria (ACOG) [13]. Chronic hypertension and preeclampsia were diagnosed according to the current ACOG criteria [14], as adapted by our institution for hypertensive disorders' diagnosis and management. Oligohydramnios was defined as an amniotic fluid index ≤5 cm and polyhydramnios as amniotic fluid index ≥24 cm [15]. A neonatologist was present in any delivery from MSAF, and performed an immediate initial examination of the newborn. Further actions, such as suction or NICU admission were performed according to clinical judgment. Birth weight percentiles for gestational age were assigned using the updated local growth charts [16]. Small for gestational age (SGA) was defined as actual birthweight≤10th percentile for gestational age.
3. Results A total of 30,215 deliveries occurred at our institution during the study period. After excluding cases which did not meet the inclusion criteria– 24,445 deliveries were analyzed: C group −20,185 (82.6%), LM group −1074 (4.4%), IM group −2736 (11.2%), and HM-450 (1.8%) group (Fig. 1). Maternal demographics of the groups are presented and compared in Table 1. The groups statistically differed in terms of: the rate of induction of labor, epidural analgesia, gestational age at delivery, delivery at ≥41 weeks, delivery at ≥42 weeks, as well as the rate of trials of labor after a previous cesarean delivery. Neonatal outcomes are presented in Table 2. The groups differed in terms of the primary outcome - composite adverse neonatal outcome, as well as birthweight, and the rate of SGA. Notably, the groups also differed in individual components of the composite adverse outcome: HIE, hypothermia, mechanical ventilation, MAS, and blood transfusion (all p values < 0.001). Pregnancy outcomes of the study groups are presented in Table 3. 2
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Fig. 1. Cohort analysis flowchart. Study population.
delivery) and various adverse pregnancy outcomes, including maternal and neonatal morbidities. Our main findings were: 1) MSAF (of any level) was reported in 17.4% of deliveries studied, which is similar to that described in literature [17–19]. 2) Intermediate meconium (IM) and heavy meconium (HM) were found to be risk factors for composite adverse neonatal outcome, as well as in-labor cesarean deliveries and SGA. 3) As MSAF was thicker, higher rates of SGA, HIE, mechanical ventilation support, MAS, and neonatal blood transfusion, as well as maternal blood transfusion and assisted vaginal delivery, were observed. The association between MSAF and neonatal outcome has been studied thoroughly, however the correlation between different
The groups differed in the rate of assisted vaginal deliveries, cesarean deliveries, as well as maternal blood transfusion (all p values < 0.001). A logistic regression model, presented in Table 4, was composed to account for the independent associations with composite neonatal outcome. Intermediate meconium and heavy meconium were independently associated with composite adverse neonatal outcome, as well as assisted vaginal delivery, in-labor cesarean deliveries, and SGA.
4. Discussion In the current study we aimed to investigate the correlation between different levels of meconium thickness (subjectively described during Table 1 Maternal demographics and pregnancy characteristics of the study groups. Parameter
Clear (n = 20,185)
Light (n = 1074)
Intermediate (n = 2736)
Heavy (n = 450)
P value
Maternal age (years) Maternal age > 35 years GA at delivery (weeks) GA ≥ 41.0 weeks GA ≥ 42.0 weeks Gravidity Parity Nulliparity Body mass index (kg/m2) Diabetes mellitus Gestational diabetes mellitus Chronic hypertension Preeclampsia Smoking Thrombophilia Drug abuse Oligohydramnios Polyhydramnios Induction of labor Epidural analgesia TOLAC
29.8 ± 5.3 3140 (15.5) 39.2 ± 1a,b,c 2867 (14.1) a,b,c 173 (0.9) a,b,c 2.7 ± 1.6 1.2 ± 1.2 6783 (33.4) 23.7 ± 3.7 138 (0.7) 1399 (6.9) 157 (0.8) 1322 (6.5) 2644 (13.0) 414 (2.0) 134 (0.7) 640 (3.2) 415 (2.0) 5941 (29.2) a 11,882 (54.5) a,b 1778 (8.8) a
29.6 ± 5.2 164 (15.2) 39.6 ± 1 a 246 (22.7) a 22 (2.1) a 2.7 ± 1.8 1.3 ± 1.3 326 (30.1) 23.8 ± 3.6 11 (1.0) 77 (7.1) 8 (0.7) 68 (6.3) 135 (12.5) 20 (1.9) 10 (0.9) 33 (3.1) 23 (2.1) 333 (30.8) 900 (83.3) a 84 (7.8)
29.5 ± 5.4 376 (13.7) 39.6 ± 1 b 654 (23.9) b 77 (2.8) b 2.7 ± 1.7 1.2 ± 1.3 925 (33.7) 23.6 ± 3.2 22 (0.8) 197 (7.2) 25 (0.9) 195 (7.1) 371 (13.5) 58 (2.1) 18 (0.7) 113 (4.1) 54 (2.0) 895 (32.6) a 2309 (84.0) b 175 (6.4)
29.7 ± 5.1 63 (13.9) 39.6 ± 1 c 105 (23.1) c 18 (4.0) c 2.6 ± 1.6 1.2 ± 1.3 159 (35.1) 24.0 ± 4.3 1 (0.2) 21 (4.6) 1 (0.2) 23 (5.1) 61 (13.5) 5 (1.1) 3 (0.7) 16 (3.5) 13 (2.9) 138 (30.5) 342 (75.5) b 25 (5.5) a
0.142 0.089 < 0.001 < 0.001 < 0.001 0.638 0.257 0.127 0.99 0.308 0.259 0.454 0.372 0.981 0.527 0.777 0.061 0.648 0.03 < 0.001 < 0.001
Continuous variables are presented as mean ± SD and categorical variables as n (%). GA- gestational age; TOLAC – trial of labor after a previous Cesarean. Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance. 3
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Table 2 Neonatal outcomes in the study groups. Outcome
Clear (n = 20,185)
Composite adverse neonatal outcome Birthweight (gr) Small for gestational age Need for immediate ventilation Umbilical artery Ph ≤ 7.1 Seizures Hypoxic-ischemic encephalopathy Intraventricular hemorrhage Periventricular leukomalacia Hypoglycemia Hypothermia Mechanical ventilation Meconium aspiration syndrome Respiratory distress syndrome Necrotizing enterocolitis Phototherapy Sepsis Blood transfusion Neonatal death
436 (2.2)a 3275 ± 479 1434 (7.1) a 55 (0.27) a 77 (0.4) 9 (0.04) 4 (0.02) a,b 3 (0.01) 0 (0) 130 (0.6) 3 (0.01) a 55 (0.3) a 15 (0.07) a 6 (0.03) 2 (0.01) 170 (0.8) 0 (0) 19 (0.1) a 0 (0)
Light (n = 1074)
a,b
Intermediate (n = 2736)
25 (2.3) 3385 ± 398 48 (4.4) a 19 (0.69) b 3 (0.3) 0 (0) 0 (0) c,d 0 (0) 0 (0) 5 (0.5) 0 (0) b 5 (0.5) b 5 (0.5) a 1 (0.1) 0 (0) 10 (0.9) 0 (0) 1 (0.1) b 0 (0)
a,c
82 (3.0) a 3341 ± 423 217 (7.9) a 5 (0.47) c 6 (0.2) 4 (0.2) 4 (0.2) a, c 1 (0.04) 0 (0) 23 (0.8) 0 (0) c 19 (0.7) c 30 (1.1) a 0 (0) 0 (0) 22 (0.8) 0 (0) 10 (0.4) a,b 0 (0)
b,d
Heavy (n = 450)
P value
24 (5.3) a 3270 ± 436 c,d 59 (13.0) a 12 (2.67) a,b,c 0 (0) 0 (0) 2 (0.4) b,d 0 (0) 0 (0) 3 (0.7) 2 (0.4) a,b,c 12 (2.7) a,b,c 9 (2.0) a 1 (0.2) 0 (0) 8 (1.8) 0 (0) 4 (0.9) a,b 0 (0)
< 0.001 < 0.001 < 0.001 < 0.001 0.306 0.134 < 0.001 0.810 1.0 0.554 < 0.001 < 0.001 < 0.001 0.069 0.935 0.196 1.0 < 0.001 1.0
Continuous variables are presented as mean ± SD and categorical variables as n (%). Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance.
thickness levels of meconium and neonatal outcome had been scarcely described. A few small studies found that thick meconium was associated with an increased risk for perinatal complications during labor (such as low Apgar scores and cesarean deliveries) and MAS, however, they did not asses additional neonatal or maternal outcomes [19–24]. The current study re-validates the results described above, and, due to the large cohort, further demonstrates this association with different neonatal morbidities, most of which are severe, and may be associated with long term disability (such as HIE, mechanical ventilation, hypothermia, and neonatal blood transfusion). Table 5 presents a summary of all previously published publications on this topic, emphasizing the very large sample size and detailed outcomes of the current study. Interestingly, although we observed a correlation between meconium thickness and the rate of in-labor cesarean deliveries, no between group differences was observed in rate of cesarean deliveries due to non-reassuring fetal heart rate monitor. As MSAF has been previously associated with prolonged labor [3], the higher rate of in labor cesarean deliveries with increasing MSAF thickness probably reflects a higher rate of dysfunctional labors and resultant CD. Higher rates of maternal blood transfusion among MSAF patients might be explained by the higher rates of assisted vaginal deliveries and cesarean deliveries, which are known risk factors for extensive blood loss and the need for
Table 4 The results of a multivariate regression analysis model for composite adverse neonatal outcome. Variable
aOR
95% CI
P value
Induction of labor TOLAC Assisted vaginal delivery In-labor Cesarean delivery Cesarean delivery due to NRFHRM Small for gestational age Light meconium Intermediate meconium Heavy meconium Oligohydramnios Polyhydramnios
0.99 0.84 1.70 1.82 1.03 1.96 1.61 1.51 2.42 0.98 1.20
0.82 0.58 1.32 1.31 0.53 1.53 0.77 1.18 1.56 0.61 0.70
0.937 0.348 < 0.001 < 0.001 0.923 < 0.001 0.474 0.001 < 0.001 0.96 0.494
-
1.19 1.20 2.18 2.51 1.98 2.50 1.75 1.93 3.75 1.60 2.07
Values reflect the results of multivariate logistic regression analysis. Model was adjusted for all the variables listed in the table. Values in bold are statistically significant. TOLAC – trial of labor after a previous Cesarean delivery, NRFHRM- non-reassuring fetal heart rate monitor.
Table 3 Delivery outcomes and complications in the study groups. Outcome
Clear (n = 20,185)
Light (n = 1074)
Assisted vaginal delivery In-labor Cesarean delivery Cesarean delivery due to NRFHRM Placental abruption Intrapartum fever Chorioamnionitis Manual revision of the uterine cavity Manual removal of the placenta Post-partum hemorrhage Maternal blood transfusion
3347 (16.5) a 934 (4.6) a,b,c 207 (1.0) 415 (2.0) 104 (0.5) 88 (0.4) 8074.0)) 457 (2.3) 1362 (6.7) 1248 (6.1) a,b,c
147 (13.6) 69 (6.4) a 8 (0.7) 23 (2.1) 4 (0.4) 9 (0.8) 48 (4.4) 30 (2.8) 85 (7.9) 80 (7.4) a
a,b
Continuous variables are presented as mean ± SD and categorical variables as n (%). NRFHRM- non-reassuring fetal heart rate monitor. Values in bold are statistically significant. Letters in superscript indicate between variables statistically significance. 4
Intermediate (n = 2736)
Heavy (n = 450)
P value
470 (17.1) b 173 (6.3) b 24 (0.9) 65 (2.4) 21 (0.8) 11 (0.4) 101 (3.7) 64 (2.3) 204 (7.4) 210 (7.6) b
98 (21.6) a,b 32 (7.1) c 4 (0.9) 13 (2.9) 2 (0.4) 1 (0.2) 23 (5.1) 13 (2.9) 41 (9.1) 37 (8.2) c
< 0.001 < 0.001 0.730 0.460 0.313 0.222 0.440 0.575 0.065 0.003
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Table 5 Summary of available studies. Study
Sample size
Meconium levels
Increased maternal risks*
Increased neonatal risks*
Additional finding
Gluck et al., 2019 (Current study)
4260 MSAF 20,185 controls
Heavy > intermediate > light > clear
AVD, CD Blood transfusion
Incidence of MSAF rises with gestational age at delivery
Mohammad et al., 2018 [22]
149 MSAF
Thick > thin
CD
Shrestha et al., 2018 [21] Rodriquez et al., 2018 [23]
167 MSAF
Thick > thin
503 MSAF 3807 controls
Thick > green > yellow > clear
No correlation to meconium thickness Intrapartum fever AVD CD
Small for gestational age Hypoxic-ischemic encephalopathy Hypothermia Mechanical ventilation MAS Blood transfusion NRFHRM Low Apgar scores MAS Neonatal intensive care unit No correlation to meconium thickness
Incidence of MSAF rises with gestational age at delivery
Sheiner et al., 2002 [19]
106 MSAF 480 controls
Thick > thin > clear
AVD CD
Ziadeh et al., 2000 [20]
390 MSAF 400 controls
Mod-Thick > thin > clear
Chorioamnionitis Labor dystocia CD
Trimmer et al., 1991 [24]
106 MSAF
Thick > moderate > thin
Not studied
NRFHRM Need for neonatal advanced resuscitation Low Apgar scores Fetal‑neonatal mortality NRFHRM Low 1-min Apgar scores Neonatal intensive care unit indications NRFHRM Arterial cord acidosis Oxygen support Low 1&5-min Apgar scores MAS Neonatal intensive care unit No correlation to acidemia, Apgar scores, and meconium aspiration syndrome
Incidence of oligohydramnion higher with MSAF
*In association with increased meconium thickness. AVD- assisted vaginal delivery; CD- cesarean delivery; NRFHRM- non-reassuring fetal heart rate monitor; MAS- Meconium aspiration syndrome.
neonate could be considered and tailored more specifically according to MSAF thickness.
blood transfusion [25,26]. The presence of meconium may also be associated with a reduced uterine contractility following delivery and subsequent postpartum hemorrhage, although this did not attain statistical significance (p = 0.06). Our study is notable for several strengths: First, we were able to study a large cohort of ten years, following the implementation of a protocol which mandated documenting the thickness of MSAF, which minimized selection bias. Second, the large cohort enabled us to investigate the association between different thickness levels of meconium and detailed neonatal and maternal outcomes. It also allowed for the investigation of less common adverse outcomes and the detection of differences in their occurrence. Our study is not without limitations. First, we are aware that MSAF thickness described by the obstetrician or midwife during labor was based on subjective impression, and no clear standardization was applied. While a previous study suggested visual assessment cannot provide a valid basis for assigning different care policies to different degrees of meconium staining, it consisted of a small sample size, and has not been validated clinically [9]. Second, our study lacks long term follow-up, as we only studied short term outcomes. Third, due to the study's retrospective design, the effect of obstetric interventions during labor based on meconium thickness remains to be established in a prospective setting. Lastly, the use of a composite outcome may be viewed as a limitation of this study. However, we believe the use of a composite was necessary because the individual components of the composite are rare complications. We have described and validated the same composite neonatal outcomes in our previous publications with other pregnancy complications [27]. In conclusion, MSAF thickness is independently associated with adverse neonatal outcomes. This data emphasizes the importance of a detailed description of MSAF observed during labor. Actions in labor and delivery, from the presence of neonatologist at time of delivery, closer surveillance of the neonate, and up to specific therapies to the
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