REVIEW Obstetric Approaches to the Prevention of Meconium Aspiration Syndrome

Journal of Perinatology (2008) 28, S14–S18 r 2008 Nature Publishing Group All rights reserved. 0743-8346/08 $30 www.nature.com/jp REVIEW Obstetric approaches to the prevention of meconium aspiration syndrome

H Xu, S Wei and WD Fraser Department of Obstetrics and Gynecology, Hoˆpital Sainte-Justine, Universite´ de Montre´al, Montreal, QC, Canada

Definition of meconium aspiration syndrome Meconium aspiration syndrome (MAS) is associated with increased Rossi et al.20 has defined MAS as respiratory distress in the first 4 h risk for perinatal mortality and morbidities. To provide an overview of the after birth with oxygen requirement and chest roentgenogram advances in our knowledge concerning the obstetric approaches to the showing characteristic features of MAS. Recently, Cleary and prevention of MAS. The evidence of the effectiveness of intrapartum Wiswell have defined MAS as respiratory distress in an infant born surveillance, amnioinfusion, and delivery room management in the through MSAF, which cannot be otherwise explained. Mild MAS has prevention of MAS are reviewed in the present paper. Meconium aspiration been defined as requiring <40% oxygen for <48 h, moderate MAS syndrome remains one of the most common but challenging conditions as requiring >40% concentration of oxygen therapy for at least for obstetricians and pediatricians. The available evidence did not 48 h, and severe MAS if requiring assisted mechanical ventilation, demonstrate a beneficial effect of either of obstetric strategies in the that is, often associated with persistent pulmonary hypertension.1,20 prevention of MAS. They further pointed out that the severity of MAS does not Journal of Perinatology (2008) 28, S14–S18; doi:10.1038/jp.2008.145 necessarily correspond to the degree of chest radiographic abnormality. MAS is associated with a range of radiographic features including coarse, patchy infiltrates, consolidation, atelectasis, pleural effusions, air leaks, hyperinflation, a wet-lung picture and hypovascularity.1 In some cases, the chest film may be Introduction interpreted as normal.1 Meconium staining of the amniotic fluid (MSAF) occurs in <5% of preterm, 7 to 22% of term deliveries, increasing to between 23 and 52% of births at >42 weeks.1–7 The mechanisms influencing meconium passage are complex, involving hormonal and Pathophysiology and risk factors neuroregulatory functions, chronic hypoxia or reflecting The pathophysiology of MAS is complex and remains controversial. maturation of the fetal gastrointestinal system.8–11 MSAF is Many factors, such as airway obstruction, alveolar or parenchymal associated with an increased risk of neonatal morbidity and inflammation, impaired surfactant production and function and mortality. Meconium aspiration syndrome (MAS) is the most direct toxicity of meconium constituents could be involved in the 1,21,22 serious neonatal pathology associated with MSAF. It has been pathophysiology of the MAS. It has been suggested that the reported to occur in 1.7 to 35.8% of cases complicated with MSAF, extent of lung destruction is not closely correlated to the quantity of and 1 to 3% of liveborn infants.1,12–14 The case fatality rate of MAS meconium in lung tissue but rather to the degree of hypoxia and 23 22 has been reported to be high, ranging from 5 to 40%.1,13–17 acidosis present at delivery. Ghidini and Spong postulated that Approximately one-third of babies with MAS require intubation and the pathologic events leading to mild, moderate or severe cases of mechanical ventilation, and other new therapies such as high MAS may be different. Severe MAS may not be in fact causally frequency ventilation, inhaled nitric oxide and surfactant related to the aspiration of meconium but rather may be caused by administration, although the effectiveness of certain of these other pathologic processes occurring in utero, such as chronic 22 technologies remain controversial.2,17–19 Serious complications asphyxia, infection or persistent pulmonary hypertension. The resulting from MAS include pneumothorax, convulsion hypothesis is in fact supported by the lack of evidence that the and death. severity of MAS directly correlates with the amount of meconium aspirated, the consistency of meconium and the duration of Correspondence: Dr WD Fraser, Department of Obstetrics and Gynecology, Hoˆpital Sainte- exposure to meconium.1,15,20,22,23 It is still unclear whether Justine, Universite´ de Montreál, 3175 Chemin de la Coˆte Sainte-Catherine, Montreal, QC, Canada H3T 1C5. obstruction of airways because of aspiration of meconium has a E-mail: [email protected] pivotal role in the progress of MAS. MAS can occur before delivery, Obstetric management of MAS HXuet al S15 even in the absence of labor, being reported in infants delivered by AI significantly reduces the risk of FHR decelerations and cesarean elective cesarean section.24 section.45–52 Although the presence of meconium during labor is known to AI has been also proposed as a method to reduce MAS. Potential be associated with an increased risk of perinatal morbidity and mechanisms through which AI could act include mechanical mortality, most babies have favorable outcomes. Early recognition cushioning of the umbilical cord, which could correct or prevent of infants at the highest risk for the development of MAS could be recurrent umbilical compressions that lead to fetal acidemia, a essential for optimizing the clinical preventive strategies. A vast condition predisposing to MAS; and dilution of meconium that array of risk factors for the occurrence of MAS have been identified could reduce its mechanical and inflammatory effects in the either using unselected obstetrical populations or infants born pathogenesis of MAS. through MSAF. Those factors are heavy MSAF, nulliparity, postterm To date, more than 15 randomized or quasi-randomized trials delivery, fetal heart rate (FHR) abnormalities during labor, of AI for MSAF have been reported, with conflicting results.53,54 The presence of meconium below the vocal cords, cesarean delivery and methodological quality varied across studies. The largest trial (over the low Apgar scores.13,14,20,25–30 It has been reported that there is 1998 participants) was an international trial performed in 56 an apparent relationship between maternal ethnicity and risk of centers where EFM and neonatal intubation and suctioning for MSAF, and the risk of MAS having been observed to be increased in babies with respiratory difficulty were routinely available.55 Analysis black Americans, Africans and Pacific Islanders.30–32 was by intention to treat. The primary outcome was a composite indicator that included the occurrence of perinatal death and/or moderate or severe MAS. The results indicated that AI showed no Intrapartum fetal monitoring effect on the primary outcome (relative risk; RR 1.26, 95% The goal of continuous electronic fetal heart rate monitoring confidence interval; CI 0.82 to 1.95). Furthermore, the frequencies (EFM) is to detect fetal hypoxemia and therefore reduce the risk of of oropharyngeal suctioning, laryngoscopy or intubation in the adverse neonatal outcomes. However, the effectiveness of this delivery room were similar between groups, as were the proportion approach to care has been questioned. Randomized trials of EFM, of babies with meconium visualized below the vocal cords. There with or without fetal blood gas and acid–base assessment, which were no differences between groups in the occurrence of the were conducted in the unselected obstetrical population, have combined outcome of perinatal mortality and/or serious morbidity found no evidence that this approach to care reduces the risk of (RR 1.13, 95% CI 0.88 to 1.47). In addition, an analysis that fetal or neonatal mortality or morbidity.33–39 stratified for the presence or absence of variable FHR decelerations Intrapartum monitoring has been recommended to screen for before randomization found no effect on the primary outcome early signs of fetal hypoxia, a risk factor for MAS. Several authors either, although the study was underpowered to detect such effects have noted an increase in the frequency of FHR abnormalities in within strata. association with MSAF.15,20,40,41 It has been reported that, in the We recently conducted a systematic review, integrating the presence of MSAF, fetal tachycardia, variable and late decelerations results of the largest trial.54 Studies were included if they were and decreased long-term variability are risk factors for MAS. randomized controlled trials that evaluated the effect of Certain authors investigated the relationships among abnormal prophylactic AI during labor with MSAF; treatment was randomly cardiotocograms in labor, MSAF and adverse neonatal outcomes allocated (AI versus controls). All included studies were further such as low arterial cord blood pH, and low Apgar scores. The subjected to a score-based quality assessment for randomized authors did not find that the presence of abnormal FHR patterns studies that was adapted from the Jadad score. The main analysis increased the overall correlation between MSAF and adverse was based on the studies that were considered to be of high quality. outcome.7,42 In contrast, Umstad et al.43 investigated the predictive The meta-analysis included a total of 4030 women, 1999 allocated value of abnormal FHR patterns in early labor and found that the to AI and 2031 allocated to control. Of these, 3178 women were presence of meconium in the amniotic fluid improved the recruited in clinical settings with standard peripartum surveillance predictive properties of the test. and 852 women were randomized in centers with limited peripartum surveillance, defined as the nonavailability of EFM during labor. The methodological quality varied across studies. Amnioinfusion Heterogeneity was noted across studies with respect to the AI Amnioinfusion (AI), or transcervical infusion of saline into the protocols and the end points evaluated. In the setting of standard amniotic cavity, was used first to relieve persistent variable FHR peripartum surveillance, the results failed to demonstrate a decelerations during labor or to prevent the occurrence of reduction in the risk of MAS (RR 0.59, 95% CI 0.28 to 1.25), decelerations in presence of oligohydramnios.44 Results of Apgar-5 <7 (RR 0.90, 95% CI 0.58 to 1.41) or caesarean delivery randomized controlled trials, including a meta-analysis indicate (RR 0.89, 95% CI 0.73 to 1.10). However, in clinical settings with that, in the presence of oligohydramnios, prophylactic intrapartum limited peripartum surveillance, AI appeared to reduce the risk of

Journal of Perinatology Obstetric management of MAS HXuet al S16

MAS (RR 0.25, 95% CI 0.13 to 0.47). Several findings from this severity of MAS and the risk of respiratory distress.61–63 They meta-analysis are worthy of comment. Firstly, the observed suggested that combined approach of intrapartum oropharyngeal heterogeneity in the stratum of studies conducted in centers with suctioning and endotracheal suctioning was effective in the standard surveillance is largely attributable to our recent large reduction of MAS. trial. The source of this heterogeneity remains largely unexplained. Vain et al. conducted a multicenter international trial to assess The most significant finding of the meta-analysis is the apparent the effectiveness of oropharyngeal and nasopharyngeal suctioning discordance in the observed effect of AI on MAS between centers before delivery of the shoulders for the prevention of MAS. They with standard and limited peripartum surveillance. Continuous found that the incidence of MAS, need for mechanical ventilation, EFM is a key component in the prevention of asphyxia in patients and neonatal mortality was similar between groups (suction versus with MSAF. Therefore, the application of this technology may no suction). In addition, they found no evidence of a benefit of reduce the contribution of severe asphyxia to the risk of occurrence intrapartum suctioning on the occurrence of MAS, MAS requiring of MAS. It would appear that in settings where this technology is mechanical ventilation, or mortality.64 routinely used, AI confers no additional benefit over EFM in terms Regarding the postdelivery management such as routine of prevention of MAS. However, in settings where continuous EFM endotracheal suctioning and intubation, reports from observational is not routinely available, AI may be beneficial for the reduction of studies suggested that intratracheal suctioning could prevent the MAS. Further studies in such settings are warranted to confirm this occurrence of MAS for meconium-stained neonates and significantly hypothesis. decreased the mortality subsequent to that disorder.65–67 Intubation AI may not be without risk. The use of AI has been reported to is not without risk and has been associated with hypoxia, be associated with adverse events. Complications including uterine bradycardia and laryngeal stridor.67–70 Should endotracheal overdistension and hypertonia, uterine rupture in association with suctioning and intubation be applied universally in infants born previous uterine scar, FHR abnormality, umbilical cord prolapse through MSAF or selectively reserved for those who are depressed and chorioamnionitis have been reported.56–59 Four cases of after birth is another topic of controversy. Some investigators maternal deaths have been reported associated with the AI.58,59 suggested that a selective approach may be useful and Several authors have reported the occurrence of excessive uterine justified,6,8,71–73 whereas other suggested that universal intubation contractions or unusually rapid labor progress related to AI. In the and suctioning was the best strategy to prevent potential morbidity AI group of Fraser et al.’s55 trial, 10 women (1.1%) experienced and mortality related to meconium staining.67 bleeding, and in 63 (6.9%) women, hypertonicity, hydramnios or Linder et al.68 suggested that nondepressed meconium-stained uterine overdistension was diagnosed during the procedure whereas infants did not benefit from immediate intratracheal suctioning the incidence of other maternal complications were comparable and such intervention could be harmful. Liu and Harrington between AI and control groups. conducted a randomized trial to assess if intubation of the low-risk American College of Obstetricians and Gynecologists has newborn with thin meconium affects the incidence of respiratory recently published a Committee Opinion that concludes that symptoms. They were unable to demonstrate the beneficial effect of routine prophylactic AI for the dilution of MSAF should be carried intubation and intratracheal suctioning in the infant with thin out only in the setting of additional clinical trials. However, they meconium and an otherwise low-risk pregnancy.74 To address this state that AI remains a reasonable approach to the treatment of question, Wiswell et al.69 conducted a multicenter randomized repetitive variable decelerations, regardless of amniotic fluid trial, involving a total of 2094 neonates, to investigate meconium status.60 whether intubation and suctioning of apparently vigorous, meconium-stained neonates would reduce the risk of MAS. There were no significant differences between intubation and expectant Delivery room management management groups in the rates of MAS or other respiratory Routine oropharyngeal suctioning before delivery of the infants’ disorders. Moreover, intratracheal suctioning showed no benefit shoulders has long been involved in preventing MAS. The findings over expectant management even for infants born through the of observational studies remain conflicting.20,26,61–63 Falciglia thickest consistency MSAF. They further identified the independent et al.26 compared infants with meconium-stained fluid who risk factors for the development of MAS using stepwise logistic underwent ‘early’ oronasopharyngeal DeLee suctioning with a regression. The results indicated that the use of oropharyngeal similar group of infants whose airways were suctioned ‘late’ (after suctioning lead to a decreased risk of MAS (8.5% in infants who did chest delivery). They found no evidence of benefit of oropharyngeal not have intrapartum suction versus 2.7% in infants with suctioning in the prevention of MAS. Rossi et al.20 also reported the intrapartum suctioning). The authors concluded that endotracheal similar rates of meconium visualized in the vocal cords despite intubation and suctioning still be performed in infants born early oropharyngeal suctioning. In contrast, several authors through MSAF, if they are not vigorous, if they need positive reported that intrapartum pharyngeal suctioning reduced the pressure ventilation or they develop symptoms of respiratory

Journal of Perinatology Obstetric management of MAS HXuet al S17 distress. Furthermore, a recently published meta-analysis of four 13 Davis RO, Phillips III JB, Harris Jr BA, Wilson ER, Huddleston JF. Fatal meconium randomized trials demonstrated no significant benefit of routine aspiration syndrome occurring despite airway management considered appropriate. endotracheal intubation and suctioning at birth over routine Am J Obstet Gynecol 1985; 151: 731–736. resuscitation including oropharyngeal suction of vigorous, 14 Urbaniak KJ, McCowan LM, Townend KM. Risk factors for meconium aspiration 75 syndrome. Aust N Z J Obstet Gynaecol 1996; 36: 401–406. meconium-stained infants born at term. The authors 15 Hernandez C, Little BB, Dax JS, Gilstrap III LC, Rosenfeld CR. Prediction of the severity recommended that intubation and suctioning be restricted to of meconium aspiration syndrome. 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