Clin Perinatol 33 (2006) 29 – 42

Intrapartum and Postdelivery Management of Infants Born to Mothers with Meconium-Stained Amniotic Fluid: Evidence-Based Recommendations Sithembiso Velaphi, MB ChBa, Dharmapuri Vidyasagar, MDb,T a

Department of Paediatrics, University of the Witwatersrand, 4 Wagenaar Road, Edenglen Edenvale, 1609, Johannesburg, South Africa b Department of Pediatrics, Division of Neonatology, University of Illinois at Chicago Medical Center, 840 South Wood Street, M/C 856, Chicago, IL 60612, USA

Meconium staining of the amniotic fluid (MSAF) occurs in 7% to 20% of live births [1–11]. It is associated with fetal acidosis, abnormalities in fetal heart rate, and low Apgar scores, suggesting hypoxia as the stimulant of passage of meconium in utero [12,13]. In animal studies, fetal hypoxia and acidosis induced through umbilical occlusion resulted in intrauterine gasping respirations sufficient to cause aspiration of meconium into the tracheobronchial tree [14–16]. When aspirated by the fetus before or during birth, meconium can obstruct the airways, leading to severe hypoxia, inflammation, and infection, and cause respiratory difficulties resulting in meconium aspiration syndrome (MAS) (Fig. 1) [17]. MAS occurs in 2% to 9% of infants born through MSAF [2,3,7,10,11,18,19] and has a mortality rate of 40% [2,17]. Meconium has been found below vocal cords in 20% to 45% of infants born through MSAF [1,3,5,8,18,20]. If the infant has not yet aspirated, removing the meconium from the airways (oropharynx or nasopharynx and trachea) before the first breath at or immediately after delivery should reduce the incidence of MAS. A study by Gregory et al [21] showed that suctioning of an infant born through MSAF reduced respiratory distress in the

T Corresponding author. E-mail address: [email protected] (D. Vidyasagar). 0095-5108/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.clp.2005.11.014 perinatology.theclinics.com

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INTRAUTERINE HYPOXIA (ACUTE OR CHRONIC)

MECONIUM STAINED AMNIOTIC FLUID

MECONIUM ASPIRATION

UPPER AIRWAY OBSTRUCTION (LARGE PLUGS)

DIFFUSE PARTICLE SPREAD

LOWER AIRWAY OBSTRUCTION ACUTE HYPOXIA MECHANICAL OBSTRUCTION

INCOMPLETE

CHEMICAL INFLAMMATION

INFECTION

COMPLETE

BALL VALVE OBSTRUCTION

PNEUMOMEDIASTINUM PNEUMOTHORAX HIGH PCO2

ATELECTASIS R to L SHUNT DROP in PaO2

HYPOXIA HYPERCAPNIA ACIDOSIS - Metabolic - Respiratory

Fig. 1. Pathophysiology of development of MAS. (From Vidyasagar D, Harris V, Pildes RS. Assisted ventilation in infants with meconium aspiration syndrome. Pediatrics 1975;56:208–13; with permission. n 1975 by the American Academy of Pediatrics.)

infant. This finding subsequently was supported by Ting and Brady [22], who reported that immediate tracheal suction lowered the morbidity and mortality rates among infants born through MSAF. Carson et al [23] reported that a combined approach of intrapartum oropharyngeal suctioning and endotracheal suctioning in MASF after birth was effective in reducing MAS. Subsequently, many studies reported positively on implementation of this combined approach [24–26], although others reported no change in incidence of MAS [1–3,5,18]. Several interventions to prevent aspiration of meconium in the presence of MSAF have been introduced over the past 3 decades (Fig. 2) [27], including (1) amnioinfusion to dilute the consistency of meconium, (2) suctioning the infant before the first breath, and (3) intubation and tracheal suctioning of the infant immediately after delivery. Because the presence of thick meconium in

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infants born to mothers with msaf Fetal Hypoxia Perinatal Interventions Meconium Passage Amnioinfusion Delivery

Suctioning: Combined and Pediatric Approach

Respiratory Distress

Yes

No

O2, IV Fluids Respiratory Failure CMV, Sedation, Surfactant

No Response HFV, iNO Therapy

Response Observation Response

No Response

Recovery

ECMO

No Response

Response

Death

Fig. 2. Intrapartum and delivery room management for prevention of MAS and subsequent management strategies of MAS. CMV, controlled mechanical ventilation; ECMO, extracorporeal membrane oxygenation; HFV, hig-frequency ventilation; iNO; inhaled nitric oxide; IV, intravenous.

the amniotic fluid has been associated with a poor outcome in infants, amnioinfusion has been suggested as a method to decrease fetal aspiration of the meconium. It is hypothesized that amnioinfusion dilutes the meconium, decreasing the potential of developing obstruction of airways and development of MAS. A meta-analysis of 13 studies reported that prophylactic intrapartum amnioinfusion for moderate or thick MSAF significantly reduced the incidence of MAS [31]. Because MAS does not occur in all infants born through MSAF, an attempt has been made to define risk factors associated with development of MAS. Some risk factors have included consistency of the MSAF (ie, moderate or thick MSAF significantly increases the risk for the need of oxygen support and MAS) [13], nonreassuring fetal heart rate tracing, meconium below the cords, and low Apgar scores [7,8,18,28–30]. An anticipated low 1-minute Apgar score and the presence of meconium in the trachea yielded a sensitivity of 88% and specificity of 79% for MAS in one study [8]. In another study, infants with fetal distress, Apgar score less than 7 at 1 and 5 minutes, and thick meconium had an 80%

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probability of developing respiratory symptoms [30]. The presence of perinatal fetal compromise increases the relative risk for pulmonary dysfunction 2.8 to 4.8 fold in infants born through MSAF [7]. Perhaps as a consequence of these observations, intubation and tracheal suctioning subsequently has been reserved for infants with respiratory depression because they are at high risk of developing MAS. The current recommendations of the American Academy of Pediatrics and American Heart Association through the Neonatal Resuscitation Program, and Pediatric Working Group of the International Liaison Committee on Resuscitation include (1) suctioning the mouth, pharynx, and nose as soon as the head is delivered before delivering the shoulders (intrapartum suctioning) regardless of whether the meconium is thin or thick, and (2) if the infant is not vigorous, has absent or depressed respirations, has decreased muscle tone, or has a heart rate less than 100 beats/min, intubating and suctioning the trachea (postpartum suctioning) before performing other resuscitation steps [32,33]. It also is recommended that in the presence of thick MSAF, amnioinfusion may be performed to dilute the meconium in an effort to prevent MAS. This article reviews and critically evaluates the available literature to determine whether the current recommendations on management of an infant born through MSAF should be maintained based on the current available evidence.

Evidence review An evidence review was performed to answer the following questions: 1. In the presence of thick MSAF, does amnioinfusion decrease the incidence of MAS? 2. Is there a benefit to routine intrapartum oronasopharyngeal suctioning after delivery of the head in the presence of MSAF? 3. What is the risk-to-benefit ratio to selective intubation and tracheal suctioning of an infant born to a mother with MSAF? An electronic search of Medline (Ovid), Embase, and the Cochrane Database of Systematic Reviews was performed to identify potentially relevant studies related to the above-listed questions. The key words used were meconium, suction, amnioinfusion, meconium-stained amniotic fluid, and meconium aspiration syndrome. The search yielded the following number of citations: meconium, 4301; meconium aspiration, 990; meconium-stained amniotic fluid, 412; amnioinfusion, 280; meconium and amnioinfusion, 80; meconium and suction, 136. Of the 80 reports on meconium and amnioinfusion, 35 publications included randomized clinical trials, meta-analyses, historical cases, or case series. These reports were classified according to the level of evidence. Of the 136 articles on meconium and suction, review articles, letters, commentaries, and articles that reported on suctioning of meconium outside the delivery room were excluded,

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and this left 26 articles for review. Selected articles were grouped according to the research design, level of evidence, and whether they supported or opposed the use of intrapartum or postnatal suctioning and amnioinfusion.

Amnioinfusion There is considerable discussion regarding the efficacy of amnioinfusion as an intervention to reduce the occurrence of MAS and its complications. Literature review Of the 80 studies that reported on amnioinfusion, 35 met the criteria for analysis. Twenty-three reports were in favor and 12 were either against or neutral on the role of amnioinfusion to reduce MAS. Wenstrom and Parsons [34] and Sadovsky et al [20] published the earliest studies reporting on the effect of amnioinfusion on the incidence of MAS. Both reports had small numbers of cases, assigned by random allocation. Both studies showed that amnioinfusion during labor complicated by meconium was a safe and effective procedure and was associated with a significant decrease in the incidence of meconium below the cords and MAS. The meta-analysis by Hofmeyr [35] reported in Cochrane Systematic Reviews concluded that amnioinfusion was effective in reducing the incidence of MAS, particularly when performed in settings where facilities for perinatal surveillance are limited. Not all studies of amnioinfusion were directly intended to study the effect on diluting thick meconium. Some studies assessed the effect of amnioinfusion in the presence of oligohydramnios. Under such circumstances, it is difficult to determine whether an improvement in outcome is due to dilution of thick meconium or due to an increase in amniotic fluid volume, reducing cord compression and fetal hypoxia [36–41]. Other studies have described a negative effect of amnioinfusion [42–44]. Among these, the study by Spong et al [42] showed no significant differences in perinatal outcome between the groups (ie, meconium below the cords was observed in 7% of the amnioinfusion group versus 4% of controls). The authors speculated that it was possible that infants in the amnioinfusion group were at an increased risk for meconium aspiration. They suggested that the benefit of amnioinfusion was due to alleviation of cord compression rather than related to dilution of meconium. More recently, Fraser et al [45] published a multinational, multicenter randomized control study of amnioinfusion in women with thick MSAF. This is a significant study for several important reasons: (1) It was a multinational randomized clinical trial, (2) a large number of patients were enrolled based on power analysis to answer definitively the question of benefits of amnioinfusion in reducing the MAS, and (3) the study addressed the potential beneficial role of amnioinfusion in the presence or absence of fetal heart rate deceleration concerns raised by Spong et al [42]. The fetal heart rate tracings and chest radiographs of

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infants were read centrally by independent blinded investigators. The study included 1998 women in labor from 56 centers at 36 or more weeks of gestational age with thick MSAF, stratified according to the presence or absence of abnormal fetal heart rate defined as variable decelerations and randomized into an amnioinfusion group or a standard treatment group. No difference in the incidence of primary outcome of MAS or in the number of perinatal deaths was noted (Table 1). MAS or perinatal death or both occurred in 4.5% of infants in the amnioinfusion group compared with 3.5% in the standard treatment group (relative risk [RR] 1.26; 95% confidence interval [CI] 0.82–1.95). There was no significant difference between the two groups in the rates of cesarean section (31.5% versus 29%) (RR 1.10; 95% CI 0.96–1.25). Some authors have expressed serious concerns regarding the complications of amnioinfusion, such as uterine rupture and amniotic fluid embolism [42–44]. In Fraser’s study [45], there were no differences in maternal morbidity or mortality rates between the groups. Based on these findings, the authors concluded that amnioinfusion in the presence of thick MSAF did not reduce the risk of perinatal deaths or moderate or severe MAS, and amnioinfusion should not be recommended for the prevention of MAS. How does one explain the lack of benefit from amnioinfusion in this study compared with the meta-analysis reported by Hofmeyer [35]? Possible explanations include fetal aspiration of meconium passage before amnioinfusion, the presence of long-term stress and fetal hypoxia, close observation using fetal surveillance that may have resulted in low incidence of MAS in the control group [46], heterogeneity, and the numbers of enrolled patients were small among the studies that were included in the meta-analysis. Table 1 Distribution of primary outcomes and other indicators of perinatal status according to study group Amnioinfusion (n = 986) Primary outcomes Perinatal death or meconium aspiration 44 (4.5%) syndrome Perinatal death 5 (0.5%) Moderate or severe meconium aspiration syndrome According to clinical criteria 43 (4.4%) On chest radiography 19 (1.9%) Neonatal resuscitation Oropharyngeal suctionings 921 (93.6%) Laryngoscopy 236 (24.0%) Suctioning of meconium below the cords 54 (5.5%) Any resuscitation 303 (30.7%) Secondary outcome: perinatal death, serious morbidity, or both Assisted ventilation or intubation for N 5 min 31 (3.1%) 5-min Apgar score b 7 26 (2.7%) Arterial pH b 7.05 22 (4.3%)

Control (n = 989)

Relative risk (95% CI)

35 (3.5%)

1.26 (0.82–1.95)

5 (0.5%)

1.00 (0.29–3.45)

31 (3.1%) 13 (1.3%)

1.39 (0.88–2.19) 1.47 (0.73–2.95)

941 254 70 322

(95.3%) (25.8%) (7.1%) (32.6%)

29 (2.9%) 29 (3.0%) 23 (4.9%)

0.98 0.93 0.77 0.94

(0.96–1.00) (0.80–1.08) (0.55–1.09) (0.83–1.07)

1.07 (0.65–1.77) 0.90 (0.53–1.51) 0.88 (0.50–1.56)

Adapted from Fraser WD, Hofmeyr J, Lede R, et al. Amnioinfusion for the prevention of the meconium aspiration syndrome. N Engl J Med 2005;353:909–17; with permission.

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Evidence-based recommendation for amnioinfusion According to the evidence strengthened by the Fraser study [45], amnioinfusion has no effect on the incidence of MAS and perinatal deaths (level of evidence 1). Routine amnioinfusion in the presence of MSAF to prevent MAS is not recommended. Gaps in knowledge It is unclear if routine amnioinfusion in women with MSAF would reduce the incidence of MAS in settings where there are no or limited fetal surveillance capabilities.

Intrapartum suctioning Literature review The presence of meconium below the cords is associated with an increased risk of developing MAS [5,8,19]. Suctioning meconium before the first breath (intrapartum) should decrease the risk of MAS. Carson et al [23] reported an incidence of MAS of 1.9% among 947 patients with a mortality rate of 28% during a period when only postdelivery intubation and suction was performed compared with an incidence of 0.4% among 273 patients (P = .07), and no deaths when intubation and suctioning was combined with intrapartum suctioning. A study by Wiswell et al [19] supported the use of intrapartum suctioning to reduce MAS when it reported on a subset analysis of a randomized controlled clinical trial. The incidence of MAS was 8.5% in infants who did not have intrapartum suction (n = 94) compared with 2.7% in infants who had intrapartum suction (n = 54; P = .013). By contrast, two prospective, nonrandomized clinical trials by Falciglia et al [3,5] compared early suctioning (suctioning by the obstetrician before delivery of the thorax) and late suctioning (suctioning by the obstetrician after delivery of the thorax) and showed no difference. In the first study, no differences in rate of meconium below the cords (36% versus 37%) or the incidence of MAS (20% in each group) between early and late suctioning were noted [3]. The second study reported a higher rate of meconium below the cords (53%) among the early suctioning group compared with the late suctioning group, which had a rate of 36% (P b.001), but there was no difference in the incidence of MAS between the two groups (P N.05) [5]. The reason for the differences in occurrence of meconium below the cords in the second study is unclear. Rossi et al [18] reported similar rates (37%) of finding meconium below the cords despite early oronasopharyngeal suction. This finding led to the suggestion that meconium aspiration occurs in utero in many infants, limiting the beneficial effect of intrapartum suctioning on the incidence of MAS. Autopsies of human

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stillbirths have shown the presence of meconium and amniotic fluid within the alveoli suggesting in utero aspiration [47]. This suggestion also was supported by the autopsy findings of meconium in the alveoli of an infant who died shortly after birth and never developed spontaneous respirations [48]. Animal studies have shown that fetal hypoxia and acidosis induce intrauterine respiratory efforts that can be substantial enough to open the laryngeal sphincter and result in aspiration of meconium in the presence of MSAF [14,15,49]. Infants born through MSAF have increased incidence of respiratory distress secondary to causes other than MAS [7,12]. Intrapartum suctioning of meconium may not always reduce respiratory distress. A large multicenter, randomized controlled clinical trial enrolled 2514 patients with MSAF with the desired goal to assess the effectiveness of intrapartum suctioning for the prevention of MAS [11]. This study also examined the effect of intrapartum suctioning in high-risk subgroups—infants with thick MSAF, infants with abnormal fetal heart rate patterns, infants with delivery by cesarean section, and infants needing resuscitation in the delivery room. This study showed that intrapartum suctioning does not reduce the need for endotracheal intubation, incidence of MAS, need for mechanical ventilation, and mortality even in the high-risk groups (Table 2). This report provides the most conclusive evidence so far showing the failure of intrapartum suctioning to prevent MAS in the presence of MSAF. Evidence-based recommendation Although some studies suggested that intrapartum suctioning might be effective for decreasing the risk of aspiration syndrome, subsequent evidence Table 2 Incidence of meconium aspiration syndrome, need for mechanical ventilation, and mortality among all patients and high-risk subgroups according to treatment group

All patients (N = 2514) Meconium aspiration syndrome Need for mechanical ventilation Mortality Thick consistency MSAF (n = 319, 13%) Meconium aspiration syndrome Need for mechanical ventilation Mortality Abnormal fetal heart rate during labor (n = 275, 11%) Meconium aspiration syndrome Need for mechanical ventilation Mortality

Suction (n = 1263)

No suction (n = 1251)

Relative risk (95% CI)

52 (4%) 24 (2%) 9 (1%) n = 151 22 (15%) 10 (7%) 5 (3%) n = 145

47 (4%) 18 (1%) 4 (0.3%) n = 168 23 (14%) 8 (5%) 3 (2%) n = 130

0.9 (0.6–1.3) 0.8 (0.4–1.4) 0.4 (0.1–1.5)

19 (13%) 11 (8%) 5 (3%)

17 (13%) 9 (7%) 2 (2%)

0.9 (0.5–1.6) 0.7 (0.3–1.8) 0.5 (0.1–2.2)

1.0 (0.5–1.8) 0.9 (0.4–2.1) 0.4 (0.0–2.3)

Adapted from Vain NE, Szyld EG, Prudent LM, et al. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364:597–602; with permission.

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from a large multicenter randomized trial (level of evidence 1) does not show such an effect. There is evidence to support discontinuation of the recommendation of routinely performing intrapartum oropharyngeal and nasopharyngeal suctioning for infants born to mothers with meconium staining of amniotic fluid (class 1 recommendation).

Gaps in knowledge In the setting where postdelivery intubation and endotracheal suctioning in a depressed infant is not performed, does intrapartum suctioning make a difference in the development of MAS?

Postdelivery intubation and endotracheal suctioning Literature review Endotracheal suctioning of a newborn born through MSAF immediately after delivery has been shown to lower morbidity and mortality [21,22,50]. Infants born through MSAF and treated by immediate tracheal suction had 100% survival [50]. Ting and Brady [22] reported that 57% of infants with no tracheal suctioning developed respiratory distress, and 25% died compared with 28% who developed respiratory distress and 1% who died among the infants who had tracheal suctioning. These findings also were supported by Wiswell and Henley [6], who reported an increased need for mechanical ventilation among infants whose trachea was not suctioned. In another study, 50% of infants with meconium in the trachea had abnormal radiologic findings, and 35% were sick compared with 20% with abnormal radiologic findings and no deaths among infants with any meconium in the trachea [21]. This study also indicated that the presence of meconium in the trachea does not translate into clinically apparent MAS because two thirds of infants who had meconium in the trachea were asymptomatic. Factors that increase the risk of MAS include fetal bradycardia, large amount of meconium in the airway, and low Apgar scores (ie, b 7 at 1 or 5 minutes) [6–8,12,28–30]. Intubation is not without side effects and has been associated with hypoxia, bradycardia, and laryngeal stridor [4,19,51–53]. It is appropriate to limit intubation for suctioning of meconium to infants who would benefit the most with minimal risks. Selective intubation of apneic infants who might be at increased risk for MAS was not associated with an increase in mortality and MAS [54]. No published randomized clinical trials have examined this specific question, however. Numerous studies have reported on outcomes of vigorous infants not intubated or suctioned at birth and born through thick or thin MSAF [4,7–10,19,55–57].

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In infants with thin MSAF and no fetal distress or neonatal depression, there were no differences in respiratory symptoms with or without intubation and intratracheal suctioning [9]. Suctioning of active and vigorous neonates born through thin MSAF does not alter the incidence of MAS [10]; 0.26% of infants born through MSAF with normal Apgar scores developed MAS compared with 46% of infants who had difficulty in establishing respiration or a heart rate less than or equal to 100 beats/min or both [56]. Vigorous infants born through thick or thin MSAF do not have an increased incidence of MAS or mortality if they are not intubated and suctioned at birth [8]. A large prospective randomized clinical trial that enrolled 2094 infants concluded that intubation and intratracheal suctioning of apparently vigorous meconium-stained infants does not result in a decreased incidence of MAS compared with no intubation and intratracheal suctioning [19]. A meta-analysis of three randomized studies [9,19,55] and one quasirandomized [4] study did not show a difference in incidence of MAS between intubated and nonintubated vigorous infants (Fig. 3) [57]. In addition, there is one study that showed that the incidence of MAS is not different between asphyxiated and nonasphyxiated infants [24]. Devices used for suctioning The devices that are used for postdelivery suctioning of meconium are a size 10 to 14 suction catheter and meconium aspirator attached to an endotracheal tube. The meconium aspirator has been shown to recover greater volume of meconium than the suction catheter at the same suctioning pressure, especially at suctioning pressures less than 100 mm Hg [53]. The mean percentage of meconium recovered through the meconium aspirator compared with suction catheter was 85% versus 73% at 80 mm Hg and 89% versus 81% at 150 mm Hg. The current recommendation to use the meconium aspirator for endotracheal suctioning of meconium if an infant requires intubation remains valid.

Fig. 3. Meta-analysis of three randomized studies [9,19,55] and 1 quasirandomized [4] study.

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Evidence-based recommendation Traditional teaching (level of evidence 5) recommended that meconiumstained infants have endotracheal intubation immediately after birth, and that suction be applied to the endotracheal tube as it is withdrawn. An analysis of randomized controlled trials (level of evidence 1) [57] showed that this practice offers no benefit if the infant is vigorous. A vigorous infant is defined as one who has strong respiratory efforts, good muscle tone, and a heart rate greater than 100 beats/min. Endotracheal intubation and suctioning for infants who are not vigorous should be performed immediately after birth (class indeterminate). Gaps in knowledge Although there are reports that depressed infants are at risk of developing MAS [7,12,28,30], data are insufficient to determine whether intubation and tracheal suctioning of depressed infants immediately after birth reduces the incidence of MAS. There is a need for randomized clinical trials specifically addressing the effect of intubation and tracheal suctioning of depressed infants born through MSAF on the subsequent occurrence of MAS.

Summary The evidenced-based recommendations regarding the management of infants born through MSAF are summarized in Table 3. These recommendations are based on large prospective randomized clinical trials. Several unanswered ques-

Table 3 Summary of current evidence-based recommendations regarding the management of infants born to mothers with meconium-stained amniotic fluid to prevent meconium aspiration syndrome Effects and Treatment protocol recommendations Amnioinfusion

Intrapartum oropharyngeal suctioning Postdelivery endotracheal suctioning of vigorous infants

LOET Reference

No benefit; is not 1 indicated in setting where fetal surveillance is available 1 No benefit; is not routinely recommended, even in high-risk infants No benefit intubation 1 and suctioning of vigorous infants is not recommended

Unanswered questions

Fraser et al [45]

Does it make a difference in settings where there is no or limited fetal surveillance? Vain et al [11] Does it make a difference if there is no endotracheal suctioning in a depressed infant? Wiswell et al [19] Does it reduce incidence Halliday and of MAS among depressed Sweet [57] infants?

T LOE 1-level of evidence 1 supported by at least one randomized clinical trial.

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tions remain, including the benefits of amnioinfusion in settings where there are no facilities for close surveillance and the effects of endotracheal suctioning in depressed infants born through MSAF on the incidence of MAS.

References [1] Dooley SL, Pesavento DJ, Depp R, et al. Meconium below the vocal cords at delivery: correlation with intrapartum events. Am J Obstet Gynecol 1985;153:767 – 70. [2] Davis RO, Philips III JB, Harris Jr BA, et al. Fatal meconium aspiration syndrome occurring despite airway management considered appropriate. Am J Obstet Gynecol 1985;151: 731 – 6. [3] Falciglia HS. Failure to prevent meconium aspiration syndrome. Obstet Gynecol 1988;71: 349 – 53. [4] Linder N, Aranda JV, Tsur M, et al. Need for endotracheal intubation and suction in meconiumstained neonates. J Pediatr 1988;112:613 – 5. [5] Falciglia HS, Henderschott C, Potter P, Helmchen R. Does DeLee suction at the perineum prevent meconium aspiration syndrome? Am J Obstet Gynecol 1992;167:1243 – 9. [6] Wiswell T, Henley MA. Intratracheal suctioning, systemic infection, and the meconium aspiration syndrome. Pediatrics 1992;89:203 – 6. [7] Yoder BA. Meconium-stained amniotic fluid and respiratory complications: impact of selective tracheal suction. Obstet Gynecol 1994;83:77 – 84. [8] Peng TCC, Gutcher GR, Van Dorsten JP. A selective aggressive approach to the neonate exposed to meconium-stained amniotic fluid. Am J Obstet Gynecol 1996;175:296 – 303. [9] Liu WF, Harrington T. The need for delivery room intubation of thin meconium in the lowrisk newborn: a clinical trial. Am J Perinatol 1998;15:675 – 82. [10] Chaturvedi P, Yadav B, Bharambe MS. Delivery room management of neonates born through meconium stained amniotic fluid. Indian Pediatr 2000;37:1251 – 5. [11] Vain NE, Szyld EG, Prudent LM, et al. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364:597 – 602. [12] Mahomed K, Nyoni R, Masona D. Meconium staining of the liquor in a low-risk population. Paediatr Perinat Epidemiol 1994;8:292 – 300. [13] Ziadeh SM, Sunna E. Obstetric and perinatal outcome of pregnancies with term labour and meconium-stained amniotic fluid. Arch Gynecol Obstet 2000;264:84 – 7. [14] Dawes GS, Fox HE, Leduc BM, et al. Respiratory movements and rapid eye movement sleep in the fetal lamb. J Physiol 1972;220:119 – 43. [15] Block MF, Kallenberger DA, Ken ID, et al. In utero meconium aspiration by the baboon fetus. Obstet Gynecol 1981;57:37 – 40. [16] Adams FH, Desiles DT, Towers B. Control of flow of the fetal lung fluid at the laryngeal outlet. Respir Physiol 1967;2:302 – 5. [17] Vidyasagar D, Harris V, Pildes RS. Assisted ventilation in infants with meconium aspiration syndrome. Pediatrics 1975;56:208 – 13. [18] Rossi EM, Philipson EH, Williams TG, et al. Meconium aspiration syndrome: intrapartum and neonatal attributes. Am J Obstet Gynecol 1989;161:1106 – 10. [19] Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics 2000;105:1 – 7 [20] Sadovsky Y, Amon E, Bade ME, et al. Prophylactic amnioinfusion during labor complicated by meconium: a preliminary report. Am J Obstet Gynecol 1989;161:613 – 7. [21] Gregory GA, Gooding CA, Phibbs RH, et al. Meconium aspiration in infants—a prospective study. J Pediatr 1974;85:848 – 52.

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