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DOI: 10.1542/peds.2005-22152006;117;1712Pediatrics

Peter A. Dargaville and Beverley CopnellTherapies, and Outcome

The Epidemiology of Meconium Aspiration Syndrome: Incidence, Risk Factors,

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.ISSN:60007. Copyright 2006 by the American Academy of Pediatrics. All rights reserved. Print

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ARTICLE

The Epidemiology of Meconium AspirationSyndrome: Incidence, Risk Factors, Therapies,and Outcome

PeterA. Dargaville,MBBS FRACP,MDa,b, Beverley Copnell, RN, RSCN, BAppSc, PhDb,c, for theAustralianandNew Zealand Neonatal Network

aDepartment of Pediatrics, Royal Hobart Hospital, Hobart, Australia; bNeonatal Research Group, Murdoch Childrens Research Institute, Melbourne, Australia;cDepartment

of Neonatology, Royal Childrens Hospital, Melbourne, Australia

The authors have indicated they have no financial relationships relevant to this article to disclose.

ABSTRACT

OBJECTIVE. We sought to examine, in a large cohort of infants within a definable

population of live births, the incidence, risk factors, treatments, complications, and

outcomes of meconium aspiration syndrome (MAS).

DESIGN. Data were gathered on all of the infants in Australia and New Zealand who

were intubated and mechanically ventilated with a primary diagnosis of MAS(MAS

INT) between 1995 and 2002, inclusive. Information on all of the live births

during the same time period was obtained from perinatal data registries.

RESULTS. MASINT

occurred in 1061 of 2 490 862 live births (0.43 of 1000), with a

decrease in incidence from 1995 to 2002. A higher risk of MASINT

was noted at

advanced gestation, with 34% of cases born beyond 40 weeks, compared with

16% of infants without MAS. Fetal distress requiring obstetric intervention was

noted in 51% of cases, and 42% were delivered by cesarean section. There was a

striking association between low 5-minute Apgar score and MASINT

. In addition,

risk of MASINT was higher where maternal ethnicity was Pacific Islander or

indigenous Australian and was also increased after planned home birth. Uptake of

exogenous surfactant, high-frequency ventilation, and inhaled nitric oxide in-

creased considerably during the study period, with 50% of infants receiving 1

of these therapies by 2002. Risk of air leak was 9.6% overall, with an apparent

reduction to 5.3% in 20012002. The duration of intubation remained constant

throughout the study period (median: 3 days), whereas duration of oxygen

therapy and length of hospital stay increased. Death related to MAS occurred in 24

infants (2.5% of the MASINT

cohort; 0.96 per 100 000 live births).

CONCLUSIONS. The incidence of MASINT

in the developed world is low and seems to be

decreasing. Risk of MASINT

is significantly greater in the presence of fetal distress

and low Apgar score, as well as Pacific Islander and indigenous Australian ethnic-

ity. The increased use of innovative respiratory supports has not altered the

duration of mechanical ventilation.

www.pediatrics.org/cgi/doi/10.1542/

peds.2005-2215

doi:10.1542/peds.2005-2215

KeyWordsmeconium aspiration syndrome, risk

factors, gestational age, Apgar score, high-

frequency ventilation, nitric oxide,

pulmonary surfactants, pneumothorax

Abbreviations

MASmeconium aspiration syndrome

HFVhigh-frequency ventilation

iNOinhaled nitric oxide

MSAFmeconium-stained amniotic fluid

ANZNNAustralian And New Zealand

Neonatal Network

nCPAPnasal or nasopharyngeal

continuous positive airway pressure

MASINTmeconium aspiration syndrome

requiring intubation

Accepted for publication Nov 7, 2005Address correspondence to Peter Dargaville,

MBBS FRACP, MD, Department of Paediatrics,

Royal Hobart Hospital, Liverpool Street, Hobart

TAS 7000, Australia. E-mail: peter.dargaville@

dhhs.tas.gov.au

PEDIATRICS (ISSNNumbers:Print, 0031-4005;

Online, 1098-4275). Copyright 2006by the

AmericanAcademy of Pediatrics

1712 DARGAVILLE et al

http://pediatrics.aappublications.org/http://pediatrics.aappublications.org/http://pediatrics.aappublications.org/http://pediatrics.aappublications.org/


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MECONIUM ASPIRATION SYNDROME (MAS) is a dis-ease of the term and near-term infant that isassociated with considerable respiratory morbidity. The

disease is characterized by early onset of respiratory

distress in a meconium-stained infant, with poor lung

compliance and hypoxemia clinically and patchy opaci-

fication and hyperinflation radiographically.1,2 At least

one third of infants with MAS require intubation andmechanical ventilation,3,4 and newer neonatal therapies,

such as high-frequency ventilation (HFV), inhaled nitric

oxide (iNO), and surfactant administration are often

brought into play.5,6

In the past few decades, there seems to have been a

reduction in the incidence of MAS in many centers, at

least in the developed world.4,7,8 This observation has

largely been based on declining numbers in individual

centers, with only 1 population-based study examining

longitudinal trends in MAS incidence.7 The apparent

reduction in the risk of MAS has been attributed to

better obstetric practices, in particular, avoidance ofpostmaturity and expeditious delivery where fetal dis-

tress has been noted.8

In previous epidemiologic studies, some important

risk factors for the development of MAS have been

identified, either within the general birth population or

among infants born through meconium-stained amni-

otic fluid (MSAF). The presence of fetal compromise,

indicated by abnormalities of fetal heart rate tracings

and/or poor Apgar scores, is known to increase the risk

of MSAF7,9,10 and of MAS in the meconium-stained in-

fant.8,9,1115 Cesarean delivery is also associated with a

heightened incidence of MAS.

16

There is an apparentrelationship between maternal ethnicity and risk of

MSAF7,10,17,18 and the suggestion in several reports of an

increased risk of MAS in black Americans and Afri-

cans7,17,19 and Pacific Islanders.18,20 Advanced gestation

has also been recognized as a risk factor, both for

MSAF10,17,2123 and for MAS.8,11,12,20,2325

Therapy for infants with MAS, in particular, those

requiring intubation, is evolving rapidly. There is, how-

ever, a paucity of longitudinal data examining the pro-

portional uptake of newer therapies in ventilated infants

with MAS. Similarly, whereas it is clear that severe MAS

is associated with a relatively high risk of pneumothorax

and a relatively long duration of respiratory support and

oxygen therapy,1,2 the specific factors that predict severe

disease and long ventilator course are incompletely char-

acterized. The mortality has been quoted as lying be-

tween 5% and 37%,1 with the marked disparity in pub-

lished figures being attributable to the difficulties in

identifying the cause of death (respiratory versus non-

respiratory) and the skewed populations in which the

mortality risk is calculated.

A complete understanding of the epidemiology of

MAS has been hampered by the lack of population-

based studies and by difficulties in assembling large co-

horts of infants with confirmed disease. We have sought

to remedy this situation using the database of the Aus-

tralian and New Zealand Neonatal Network, supple-

mented by data from perinatal data registries. Our aims

with this study were to examine current indicators and

longitudinal trends for (1) the incidence of MAS, (2) the

risk factors for MAS among all live births, (3) the treat-

ments applied to ventilated infants with the disease, and(4) the complications and outcomes. In view of the

difficulty in reliably recognizing cases of mild to moder-

ate MAS, this investigation focused on infants with rel-

atively severe disease in whom intubation and mechan-

ical ventilation were required.

METHODS

Data on infants with MAS were obtained from the da-

tabase of the Australian and New Zealand Neonatal Net-

work (ANZNN). This is a voluntary collaboration be-

tween all 28 level III NICUs that was established in 1994

to monitor the care of high-risk newborns. A minimumdata set has been developed, with any infant satisfying

any of the following criteria being included in the data-

base: (1) need for assisted ventilation either through an

endotracheal tube or via nasal/nasopharyngeal continu-

ous positive airway pressure (nCPAP), (2) need for ma-

jor surgery, (3) gestation 32 weeks, and (4) birth

weight 1500 g. Data are supplied to ANZNN in de-

identified form by the individual units and are checked

for errors. For each infant, a primary respiratory diag-

nosis is entered.

For this study, the ANZNN database for the years

19952002 was searched for infants

35 weeks gesta-tion with a primary respiratory diagnosis of MAS. The

ANZNN defines MAS in a meconium-stained infant as

respiratory distress within 12 hours of age, displaying

symptoms such as hypoxia, tachypnea, gasping respira-

tions, and signs of underlying asphyxia, with a chest

radiograph showing overexpansion of the lungs with

widespread coarse infiltrates.26 It is important to note

that the diagnosis of MAS is ascribed by the clinicians

responsible for supplying data to the ANZNN database.

This analysis focused on cases of MAS requiring intuba-

tion and mechanical ventilation (MASINT

). Infants with

MAS treated with nCPAP only were excluded; such

infants, although meconium-stained, may have other

diagnoses as the predominant cause of respiratory dis-

tress, for example, transient tachypnea of the new-

born.27,28 All of the available antenatal and intrapartum

data and information pertaining to severity of the dis-

ease and medical management, were extracted from the

identified records. The presence of intrauterine growth

retardation was noted, defined as birth weight less than

the 10th percentile derived from Australian normative

data.29 For infants who died, the cause of death was

classified as being respiratory or nonrespiratory (ie, di-

rectly related or not related to the aspiration of meco-

PEDIATRICS Volume 117, Number 5, May 2006 1713



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nium) based on the International Classification of Dis-

eases code numbers and additional diagnostic

information entered in the ANZNN database.

Information regarding the total birth population in

Australia and New Zealand was also obtained for the

years 19952002. Data were gathered on the total num-

bers of live births and the incidence of potential risk

factors for MAS that could be matched to the ANZNNMAS

INTcohort. These factors included maternal ethnic-

ity, gender, place of birth, mode of delivery, gestational

age, and condition at birth as indicated by 5-minute

Apgar score. Australian data were obtained from the

annual reports of the Australian Institute of Health and

Welfare.30 Where variables were reported in terms of the

number of confinements, the same percentage was used

to project the number of live births. Variables treated in

this manner were indigenous births, home births, deliv-

ery by cesarean section, and instrumental deliveries.

Where data were stated to be missing or incomplete

from some states or territories (eg, the classification ofcesarean section as emergency or elective), the na-

tional average and previous trends were used to calcu-

late the totals.

For New Zealand, the total number of live births for

each year and data on maternal ethnicity and infant

gender were obtained from electronic documents made

available by Statistics New Zealand.31 Data on type of

delivery between 1999 and 2002 and numbers of instru-

mental vaginal deliveries between 1995 and 1998 were

obtained from the Ministry of Health reports on mater-

nity (eg, refs 32 and 33). Numbers of emergency and

elective cesarean section deliveries were not separatelyreported in the years 1995-1998, and estimates have

been made from subsequent trends. No reliable data on

home births in New Zealand were available. Summary

statistics on gestational age and 5-minute Apgar score

were reported differently from Australian data and could

not be included in the overall data set. For both coun-

tries, numbers of infants born in tertiary hospitals were

obtained from the annual reports of the ANZNN.26

Summary statistics were generated for all variables in

the MAS data set. The duration of intubation and nCPAP

were summed to give duration of respiratory support.

No assumptions were made about the distribution of

continuous variables. For binary and continuous vari-

ables, simple comparisons were made with 2 and

Mann-Whitney tests, respectively; longitudinal trends in

these variables were examined using the 2 test for trend

and linear regression, respectively. For all tests, aP .05

was considered statistically significant. Within the

MASINT

cohort, predictors of duration of respiratory sup-

port were sought using multiple linear regression anal-

ysis, with addition of all of the relevant variables to the

model in a stepwise manner. Binary variables were en-

tered as 1 or 0. Multivariate analysis could not be applied

to the entire birth population because of lack of access to

specific data from each individual without MASINT

.

RESULTS

Between 1995 and 2002, 1061 infants were admitted to

a level III NICU in Australia or New Zealand with

MASINT

, with the number ranging between 109 and 150

annually. An additional 107 infants with MAS treatedwith nCPAP only were excluded along with 2 infants

with a primary diagnosis of MAS in whom no respiratory

support was required. Median gestation for infants with

MASINT

was 40 weeks (interquartile range: 39 41

weeks), median birth weight was 3400 g (interquartile

range: 3000 3700 g), and 52.4% were male. Overall,

42% of infants with MASINT

were born in a tertiary

hospital, with the proportion being higher in New Zea-

land than Australia (64% vs 31%; P .001).

During the study period, there were 2 490 862 live

births in the 2 countries, giving an overall rate of MASINT

of 0.43 per 1000 live births. In Australia, there were 894infants with MAS

INTin 2 038 666 live births and in New

Zealand, 167 cases in 452 196 live births, yielding rates

of MASINT

of 0.44 and 0.37 per 1000 live births, respec-

tively. Combined longitudinal data from both countries

revealed an overall decrease in the incidence of MASINT

to a low of 0.35 per 1000 in 2002 (P .0087). Analysis

by country shows a steady decrease in incidence in Aus-

tralia between 1995 and 2002, with considerable fluctu-

ation but no clear trend in incidence in New Zealand.

Figure 1 shows the rate of MASINTper 1000 live births

at each week of gestation (Australian data only). Be-

tween 36 and 40 weeks, the rate varied between 0.24and 0.46 per 1000, with the lowest rate occurring at 38

weeks, and rose thereafter to a high of 1.42 per 1000 at

FIGURE 1

Incidence of MASINT

according to gestational age. Plot of incidence of MASINT

at each

week of gestation; Australian data only. See text for comparisons between gestational

age groups.




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42 weeks and beyond. Thirty-four percent of the MASINT

cohort were at 40 weeks gestation and 6.5% at 41

weeks compared with 16% and 2.0% of the total birth

population (P .001 in both cases). Figure 2 shows the

trends in incidence of MASINT

by gestational age group-

ing during the study period. A decrease in incidence was

noted over time at gestations 40 weeks but not at

gestational ages between 36 and 40 weeks.Antecedents of MAS

INT, with analysis by year and by

country, are shown in Table 1. More than half of the

infants were noted to have fetal distress prompting ob-

stetric intervention; 70% of these went on to deliver by

cesarean section or assisted vaginal delivery. Cesarean

section was the mode of delivery for 42% of the MASINT

infants overall. Fully 9.7% of the entire MASINT

cohort

were delivered by cesarean section without labor, pre-

ceded by the recognition of fetal distress in 77% of cases

and of intrauterine growth restriction in an additional

6%. The proportion of assisted vaginal deliveries de-

creased during the study period. The number of MASINTinfants with 5-minute Apgar score 7 and the number

requiring intubation in the delivery room also decreased.

Median Apgar scores at 5 minutes were lower among

infants born in New Zealand (6 vs 7; P .0012), and

intubation in the delivery room for resuscitation was

more commonly required (59% vs 43%; P .001).

The impact of selected antecedents on the risk of

MASINT, using combined data from all years, is shown in

Fig 3. There was a striking association between low

5-minute Apgar score and risk of MASINT, with an odds

ratio of 52. Among the demographic variables, infants

born to Pacific Islander mothers in New Zealand andAboriginal/Torres Strait Islander mothers in Australia

were 3 times more likely to develop MASINT, whereas

infants born to Maori mothers had no increased risk.

Gender of the infant was not a significant factor. All

forms of assisted delivery increased the risk of MASINT

to

some extent, with infants undergoing emergency cesar-

ean section being at the highest risk, almost sixfold

higher than other modes of delivery. Planned home

birth was associated with a 2.7-fold increase in risk of

MASINT.Figure 4 shows longitudinal trends in odds ratios for

selected risk factors during the study period. There was

considerable fluctuation in the odds ratio for most risk

factors, with no clear trend over time. The risk for infants

born to Aboriginal/Torres Strait Islander mothers did,

however, increase markedly from 1998, such that in

2002 the risk of MASINT

was 7 times that of the non-

indigenous population in Australia. Both emergency ce-

sarean section and birth in a tertiary center showed a

downward trend over the study period but continued to

be associated with an increased risk of MASINT

. The odds

ratio for an assisted vaginal delivery decreased rapidlyand was 1 after 1997.

With the knowledge of the antecedents of MASINT

in

the birth population overall, we sought to identify

changes in the demography of live births that might

explain the decrease in incidence of MASINT

in the latter

years of the study period. Compared with 1995, in 2002,

there were fewer deliveries beyond 41 weeks gestation

(1.6% vs 2.8%; P .001) and fewer infants with a

5-minute Apgar score 7 (1.4% vs 1.7%; P .001).

These factors combined account for 62% of the reduc-

tion in MAS incidence noted in this time period.

Table 2 shows the therapies received by infants withMASINT

. More than half of infants overall received either

surfactant, HFV or iNO, with upward trends in the use of

all of these therapies during the study period. Infants

receiving 1 of surfactant, HFV, or iNO were intubated

for a median of 5 days and required respiratory support

for a median of 6 days, compared with 2 and 3 days,

respectively, for infants who received none of these

therapies. Only 1.1% of the MASINT

cohort required

treatment with extracorporeal membrane oxygenation;

all infants treated with this therapy survived.

Table 3 shows the complications and outcomes for the

ANZNN MASINT

cohort. Although no clear trend was

discernible for the whole study period, the incidence of

air leak seemed to decrease in 20012002, being signif-

icantly lower for these 2 years compared with all of the

other years (5.3% vs 10.8%; P .013). Infants who

developed air leak required respiratory support for a

median of 5 days compared with 3.2 for those without

this complication. In the MASINT

cohort overall, the

duration of intubation and of respiratory support re-

mained relatively constant during the study period;

however, the duration of oxygen therapy and the length

of hospital stay increased. The overall mortality was

6.6% (70 of 1061), with the majority of these deaths

FIGURE 2

Incidence of MASINT

according to year in different gestational age groups: plot of inci-

dence of MASINT

per 1000 live births for gestations 36 to 40 weeks and for gestations

beyond 40 weeks; Australian data only. a Decrease in incidence between 1995 and 2002

for infants beyond 40 weeks gestation (P .010), with no discernible trend for 36 to 40

weeks.,41 weeks;, 36 to 40 weeks.




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being because of perinatal asphyxia (n 33) or congen-

ital anomalies (n 6). Death directly attributable to

aspiration of meconium occurred in 24 infants, equiva-

lent to 2.5% of the total MASINT

cohort and 0.96 per

100 000 live births. Mortality rates seemed to remain

constant during the study period. Of the 24 infants

whose death was directly related to MAS, 7 (29%) were

in relatively good condition at birth, not requiring im-

mediate intubation, and with a 5-minute Apgar 7. Air

leak occurred in 42% of MAS-related deaths compared

with 13% of infants dying from other causes (P .037)

and 8.6% of survivors (P .001). Infants dying of MAS

were more likely to have received surfactant, HFV, or

iNO (P .037), but 5 infants received none of these

therapies.

Forty-nine infants received home oxygen, with re-

quirement for this therapy increasing during the study

period. These infants had a longer duration of respira-

tory support, with a median of 7 days, compared with

3.8 days for infants who did not require home oxygen (P

.001). They were also more likely to receive surfac-

FIGURE 3

Risk factors forMASINT

withinthe total birth population: plot of oddsratios () and 95%

confidence interval (4and 3) for selected risk factors for MASINT

. Odds ratio (95%

confidenceinterval)alsoindicatedastext. a Australiandata only;b NewZealanddataonly.

TSI indicates Torres Strait Islander; All C S, all cesarean-section deliveries.

FIGURE 4

Longitudinal trends in odds ratio for selected risk factors. Plot of odds ratio by year for

ethnicity (A), place and mode of delivery (B), and 5-minute Apgar score (C) are shown.

Odds ratios for Aboriginal/Torres Strait Islander (TSI) are specific for Australia, and those

forPacific Islander arespecific forNew Zealand. EmergCS indicates cesarean section in

labor; Assist vag,assistedvaginaldelivery (definedin Table1); otherabbreviationsas per

Fig 3. a Increase in odds ratio forMASINT

among Aboriginal/TSIduring thestudyperiod (P

.0091). b Decrease over time in odds ratio for birth in a tertiary center and assisted

vaginal delivery (P .038 and 0.011, respectively). A, , Aboriginal/TSI; , Pacific Is-

lander;, Maori. B,, All CS;, Emerg CS;E, Assist vag;, tertiary birth. C,, 5-min

Apgar7.

TABLE 1 Antecedents ofMASAmongthe ANZNNMASINT

Cohort

Variable All Years 19951997 19982000 20012002 Longitudinal Trend (P)a

Fetal distress noted, % of total 51.1 45.3 55.5 54.0 1 (.019)All CS, % of total 41.8 40.4 39.9 47.1 Nil

CS in labor, % of total 32.0 30.6 31.9 34.8 Nil

Assisted vaginal delivery, % of total 11.1 16.1 7.8 7.9 2 (.001)Apgar scores

At 1 min, median, IQR 4 (26) 3 (26) 4 (26) 5 (2.56) 1 (.0017)At 5 min, median, IQR 7 (58) 6 (58) 7 (58) 7 (58) 1 (.0029)7 at 5 min, % of total 46.7 50.7 47.2 39.2 2 (.017)

Intubated in delivery room, % of total 46.1 51.2 45.5 38.2 2 (.0063)

Fetal distress noted indicates any distress of the fetus leading to intervention by the obstetric team; assisted vaginal delivery, delivery with the aid of forceps or Ventouse extraction; intubated

in delivery room, intubation required for the purposes of resuscitation, not for airway clearance; CS, cesarean section; IQR, interquartile range;1, increased over time;2, decreased over time.a Longitudinal trend analysis is in all cases based on comparison of data for each year from 19952002.




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tant, HFV, or iNO (P .026), although 16 infants re-

ceived none of these therapies.

In multiple linear regression analysis, duration of re-

spiratory support in MASINT

survivors was found to be

predicted by the following binary variables: cesarean

section in labor (coefficient: 1.33;P .003), fetal distress

(coefficient: 1.05; P

0.012), indigenous Australian orPacific Islander ethnicity (coefficient: 1.38; P 0.019),

and male gender (coefficient: 0.82; P 0.040). Gesta-

tional age, intrauterine growth restriction, and 5-minute

Apgar score did not independently predict duration of

respiratory support when added to the model.

DISCUSSION

In this study we investigated the epidemiology of MAS

in a large cohort of ventilated infants, with reference to

available data for the entire birth population during the

same period. We found that during the period 1995

2002, there was a reduction in the incidence of MASINT

to 0.40 cases per 1000 live births, a strong association

of MASINT

with low 5-minute Apgar score, a clear in-

crease in risk in Pacific Islander and indigenous Austra-

lian pregnancies, and a similar association with ad-

vanced gestation to that noted previously. A heightened

risk of MASINT

was also noted after planned home birth.

Our data show a median duration of respiratory support

of 4 days, with 31%, 19%, and 30% of cases receiving

exogenous surfactant, HFV, and iNO, respectively. Mor-

tality directly attributable to MAS was 2.5% in the

MASINT

cohort.

A strength of this study lies in the large numbers of

infants with MASINT in the ANZNN cohort (1061 in-

fants), in whom a relatively large individual data set has

been assembled. In addition, ANZNN data entry allows

only 1 primary respiratory diagnosis, with MAS being a

clearly defined and distinct entity. This allows exclusion

of meconium-stained infants with minimal evidence of

parenchymal disease in whom the main diagnosis isPPHN. We have also had the advantage of obtaining data

from large perinatal data registries in both countries,

meaning that the findings in the ANZNN cohort can be

placed in the context of the total population of 2 490 862

live births in which the cases of MASINT

occurred.

The low incidence of MASINTand its apparent reduc-

tion during the study period confirm that modern ob-

stetric practices can, for the most part, interrupt the

chain of events that results in significant aspiration of

meconium. The reduction in incidence cannot be as-

cribed to more zealous delivery room management, in

particular, tracheal suctioning. Indeed, in the latter part

of the study period, routine intubation of the trachea

after MSAF was largely abandoned in Australia and New

Zealand, contemporaneous with the publication of a

randomized, controlled trial finding no benefit from this

intervention in the vigorous infant.15 The decrease in

incidence parallels the findings of Yoder et al,8 who, in

selected birth cohorts from the same time period, found

a reduction in risk of MAS, attributed to avoidance of

postmaturity and more aggressive management of sus-

pected fetal distress. The reduced incidence of MASINT

over time in the present study would seem to relate to

similar factors, with advanced gestation and the propor-

TABLE 2 TherapiesReceivedby theANZNNMASINT

Cohort

Variable All Years 19951997a 19982000 20012002 Longitudinal Trend (P)

Surfactant, any type 30.8 20.1 35.7 42.9 1 (.001)HFV 19.1 14.9 16.0 29.5 1 (.001)INO 29.5 21.6 31.4 35.7 1 (.001)ECMO 1.1 1.1 0.7 1.8 Nil

Surfactant or HFV 42.4 29.2 41.3 53.3 1 (.001)Surfactant or HFV or iNO 50.6 39.2 50.8 58.8 1 (.001)NCPAP usedb 24.2 17.2 24.6 36.6 1 (.001)

Data shown are % of total in each case.1 indicates increased over time;2, decreased over time.a Data on HFV and iNO were not collected in 1995; all year percentages for these therapies, therefore, slightly underestimate the actual figures.b Either before or after the period of intubation and mechanical ventilation.

TABLE 3 Respiratory OutcomesandComplications in theANZNN MASINT

Cohort

Variable All Years 19951997 19982000 20012002 Longitudinal Trend (P)

Air leak, % of total 9.6 11.0 10.5 5.3 Nil

Duration of intubation, median (IQR), d 3 (26) 3 (26) 3 (26) 3 (1.56) Nil

Duration respiratory support, median (IQR), d 4 (27) 4 (27) 4 (27) 3.1 (27) Nil

Duration oxygen therapy, median (IQR), d 6 (315) 6 (313) 6 (315) 7 (317) 1 (.036)Length of hospital stay, median (IQR), d 13 (824) 10 (719) 14 (824) 17 (1029) 1 (.001)

Death, % of total 6.6 5.8 7.9 5.7 NilMAS-related death, % of total 2.5 2.3 2.5 3.2 Nil

Home oxygen, % of total 4.7 2.8 5.7 6.6 1 (.0093)

IQR indicates interquartile range;1, increased over time;2, decreased over time; duration respiratory support, the duration of intubation plus duration of nCPAP.




8/12

tion of infants having a 5-minute Apgar score 7 being

seen to decrease from 19952002.

Our data analysis allowed the computation of odds

ratios for a number of potential risk factors for MASINT

in

the total birth population. In Australian live births, we

noted a very strong association with a 5-minute Apgar

score 7, with an overall odds ratio of 52. This is, to our

knowledge, the first population-based study to quantifythe risk of MAS in relation to condition of the infant at

birth. The implication is that 1.3% of all live-born

infants with a 5-minute Apgar score 7 will subse-

quently be ventilated with MAS compared with 0.025%

of those with a 5-minute Apgar score 7. Other cohort

studies have documented the importance of condition at

birth in determining the risk of MAS developing in the

context of MSAF. For this latter association, Wiswell et

al,15 using stepwise linear regression, reported an odds

ratio of 21; others have found the risk to be approxi-

mately fourfold.8,12 There remains some dispute about

how this effect is mediated; the presence of fetal distressrequiring obstetric intervention in 50% of the ANZNN

MASINT

cohort suggests exaggerated fetal respiration and

in utero aspiration of meconium as a possible mecha-

nism.

The ethnology of MAS has been explored in this

study, with the finding of a 3 times greater risk of

MASINT

in Pacific Islanders and indigenous Australians

and, in the latter group, an apparent upsurge in risk in

2001 and 2002. These findings complement those of

other investigators in identifying ethnic groups of

heightened risk of MSAF and MAS. Black Americans

and Africans have been found to have a risk of MSAF 1.5to 2.6 times that of other ethnic groups,7,10,17,19 the ex-

planation for which may lie in earlier attainment of fetal

maturity and is not related to longer gestation.19 Pacific

Islanders in New Zealand have a 1.8-fold increase in risk

of MSAF.18 There are no published data regarding risk of

MSAF or MAS in indigenous Australians. Our popula-

tion-based estimate of the risk of MAS in Pacific Island-

ers (odds ratio: 2.7) is similar to that noted previously

within a single hospital (odds ratio: 3.6)20 and cannot be

entirely explained by the increase in the risk for MSAF

noted in this group. At least within the MASINT

cohort,

we could not identify any other possible explanatory

factors, with fetal distress, Apgar score, and gestation

being equivalent among Pacific Islanders, indigenous

Australians, and others (data not shown). The mecha-

nism by which ethnicity imparts additional risk of MAS

requires additional study. We found, as have others,18 no

increase in the risk of MAS among the New Zealand

Maori population.

The risk of MASINT

among live-born infants was in-

creased beyond 40 weeks gestation, with a 3.4-fold

increase in risk at 41 weeks. Only 1 other population-

based study has examined the relationship between ges-

tation and risk of MAS, reporting an odds ratio of 2.9 for

the risk of MAS beyond 41 weeks.24 The propensity to

develop MAS at advanced gestation would seem to be

related both to a higher risk of MSAF10,17,2123 and an

increased likelihood that MAS will occur in the presence

of MSAF,8,11,23 independent of other risk factors, such as

fetal distress and low Apgar scores.8

We found that place of birth was a predictor of

MASINT, with a higher risk for infants born in tertiarycenters (odds ratio: 1.65) and for planned home births

(odds ratio: 2.74). This latter finding is in contrast to the

reported outcome for planned home birth in Canada,

where no apparent increase in the risk of either MSAF or

MAS was noted.34 We also found cesarean delivery to be

associated with MASINT

, as has been documented previ-

ously in a smaller birth cohort.16 The need for cesarean

delivery is also known to be associated with a higher risk

of subsequent MAS in the setting of MSAF.11,12,15 Fetal

growth restriction has been linked previously to MAS,24

and we found a doubling of risk for MASINT

in growth-

restricted infants. Most infants with MASINTwere, how-ever, well-grown, with average birth weight being be-

tween the 25th and 50th percentile for gender and

gestation.29

A weakness of our investigation is that within the

total birth population it was not possible to ascertain the

incidence of MSAF, a requisite intermediary in the

pathogenesis of MAS. This limits, to some degree, our

capacity to distinguish whether the risk factors we de-

fined within the population exert their effect by increas-

ing the rate of MSAF, the risk of MAS in the presence of

MSAF, or both. Similarly, for this study we did not have

access to data from each individual in the total birthpopulation and, thus, can perform only univariate data

analysis. In the absence of multivariate regression anal-

ysis, it is not possible to define clearly whether the

heightened risks of MASINTrelated to ethnicity and ges-

tation are subsumed in a final common pathway of fetal

distress or low Apgar score. These questions clearly need

additional investigation in population-based epidemio-

logic studies.

Despite limited data to support the use of HFV and

exogenous surfactant in MAS, both of these treatments

were applied with increasing frequency over the study

period. Anecdotally, HFV in the form of oscillatory or jet

ventilation has been found to be effective in supporting

infants with MAS35,36 and may be a contributing factor to

the low requirement for extracorporeal membrane oxy-

genation in the ANZNN MASINT

cohort. In a national

survey of neonatal units in continental France, Nolent et

al37 found high-frequency oscillatory ventilation to be

used for MAS in 27 of 29 units; a similar situation exists

in Australia and New Zealand (P.A.D., unpublished

data).

Of the trials of bolus surfactant therapy published

during the study period,38,39 only that of Findlay et al38

show clear benefits beyond an improvement in oxygen-




9/12

ation. It is, therefore, somewhat surprising that exoge-

nous surfactant therapy has found such a prominent

place in the treatment of MASINT

. In the latter years of

the study period, exogenous surfactant was adminis-

tered to 40% of all infants with MASINT

. No data are

available in this study concerning surfactant dose and

retreatment.

Among the ANZNN MASINT cohort, 51% of infantsreceived 1 HFV, iNO, and exogenous surfactant, with a

documented increase in this proportion from 1996 to

2002. The uptake of these newer therapies over the

study period seems to have had no effect on the duration

of intubation, and the duration of oxygen therapy and

length of hospital stay have increased in the MASINT

cohort overall. These findings emphasize the supportive

rather than curative nature of these therapies in infants

with MASINT

.

The mortality risk for ventilated infants with MAS in

Australia and New Zealand remains significant. Overall

mortality was 6.6%, with deaths directly attributable tothe respiratory illness occurring in 2.5% of the entire

MASINT

cohort and 0.96 per 100 000 live births. This

latter figure compares favorably with other population-

based estimates of MAS-related mortality. Sriram et al7

found a mortality of 2.0 per 100 000 live-born infants in

the United States in 19982000; Nolent et al37 report

1.03 deaths per 100 000 births in France in 20002001,

but incomplete ascertainment of MASINT

cases in this

study may limit the reliability of this estimate. These

population-based estimates of mortality from MAS are

generally markedly lower than those derived from hos-

pital birth cohorts. The largest of these, studying cases ofMAS in 7 hospitals in the United States during the years

19731987 (total birth population: 176 790), found a

mortality rate of 28 per 100 000 live births. 4 Another

study found a mortality rate of 22 per 100 000 among

85 562 live births in 1 hospital in Saudi Arabia during

the period 1989 1994.40 The apparent high mortality in

hospital-based studies is a reflection of the high-risk

birth populations from which the estimates are made

and can be presumed to also be related to the time period

in which the studies were done, before the advent of a

number of newer therapies that seem to have improved

outcome in MAS. Other more recent studies of smaller

hospital-based cohorts have shown lower mortality, in-

cluding, in several instances, no MAS-related deaths.8,41

Pneumothorax remains an important complication of

MAS, occurring in 9.6% of the MASINT cohort overall,

with an apparent reduction to 5% in 20012002.

Other recent studies have reported an incidence of

pneumothorax in intubated infants of 8%,38 14%,42 and

20%,43 although this last study selected infants with

more severe disease. Despite the advances in respiratory

support for MAS, pneumothorax remains an important

indicator of disease severity, being present in 42% of

infants who ultimately died of MAS in the ANZNN co-

hort.

Durations of intubation and respiratory support did

not alter throughout the study period, although more

infants received nCPAP either before or after mechanical

ventilation. Disconcertingly, the duration of oxygen

therapy and length of hospital stay increased during the

study period, reaching a median of 8 and 17 days, re-spectively, in 2002. These figures emphasize the consid-

erable burden that MAS continues to place on afflicted

infants, their families, and the health care system.

CONCLUSIONS

We found in this study that the incidence of MAS re-

quiring intubation in 2 countries in the developed world

is low and seems to be decreasing. The risk of MASINT

is

significantly greater in the presence of fetal distress and

low Apgar score, as well as Pacific Islander and indige-

nous Australian ethnicity. MAS is now frequently

treated with newer therapeutic modalities, such as HFV,iNO, and exogenous surfactant, but the duration of ven-

tilation and oxygen therapy have not been improved as

a result. Mortality for MASINT

is low, but there remains

a significant risk of pneumothorax.

ACKNOWLEDGMENTS

We thank Deborah Donoghue and Samanthi Abeywar-

dana, past and current Australian and New Zealand Neo-

natal Network Project Officers, and the Directors and

participating units of the Australian and New Zealand

Neonatal Network: Australia: Professor John Whitehall

(Womens and Childrens Health Institute, the Towns-ville Hospital); Professor David Tudehope (Mater Moth-

ers Hospital, Brisbane); Dr David Cartwright (Neonatol-

ogy, Royal Womens Hospital, Brisbane); Dr Chris Wake

(NICU, John Hunter Hospital, Newcastle); Associate Pro-

fessor Nick Evans (the John Spence Nurseries, Royal

Prince Alfred Women and Infants, Sydney); Dr Robert

Guaran (Newborn Care, Liverpool Health Service, Liv-

erpool); Dr Robert Halliday (Neonatology, Childrens

Hospital at Westmead, Sydney); Dr Kei Lui (Newborn

Care, Royal Hospital for Women, Sydney); Dr Barry

Duffy, PICU, Sydney Childrens Hospital, Sydney); Dr

Lyn Downe (NICU, Nepean Hospital); Professor William

Tarnow-Mordi (Neonatal Medicine, Westmead Hospital,

Sydney); Associate Professor Graham Reynolds (Pediat-

rics and Child Health, Canberra Hospital, Canberra); Dr

Andrew Watkins (Neonatology [Medical], Mercy Hospi-

tal for Women, Melbourne); Dr Andrew Ramsden

(NICU, Monash Medical Centre, Melbourne); Dr Peter

McDougall (Neonatal Services, Royal Childrens Hospi-

tal, Melbourne); Dr Neil Roy (Neonatal Services, Royal

Womens Hospital, Melbourne); Dr Chris Bailey (Pedi-

atrics, Launceston General Hospital, Launceston); Asso-

ciate Professor Peter Marshall (Centre for Perinatal Med-

icine, Flinders Medical Centre, Adelaide); Dr Ross




10/12

Haslam (Newborn Services, Womens and Childrens

Hospital, Adelaide); Professor Karen Simmer (Medical

Director, Neonatology Clinical Care Unit, King Edward

Memorial Hospital, Perth); and Dr Charles Kilburn (Spe-

cial Care Nursery, Royal Darwin Hospital); New Zealand:

Dr Lindsay Mildenhall (Newborn Services, Middlemore

Hospital, Auckland); Dr Carl Kuschel (Newborn Ser-

vices, National Womens Hospital, Auckland); Dr DavidBourchier (Newborn Care, Waikato Hospital, Hamilton);

Dr Vaughan Richardson (Neonatal Unit, Wellington

Womens Hospital, Wellington); Dr Nicola Austin (New-

born Intensive Care, Christchurch Womens Hospital,

Christchurch); Dr Roland Broadbent (NICU, Dunedin

Hospital); Dr Graeme Lear (Neonatal Unit, Gisborne

Hospital); Dr Jenny Corban (Pediatrics, Hawkes Bay

Hospital); Dr Ken Dawson (Newborn Unit, Wairau Hos-

pital, Nelson Marlborough District Health Board); Dr Jeff

Brown (Child Health, Mid Central Health); Dr Stephen

Bradley (Pediatrics, Rotorua Hospital, Rotorua); Dr Paul

Tomlinson (Neonatal Unit, Southland Hospital, South-land); Dr John Doran (Child and Adolescent Commu-

nity Centre, Taranaki Base Hospital); Dr Hugh Lees (Spe-

cial Care Unit, Tauranga Hospital); Dr Philip Morrison

(Pediatrics, Timaru Hospital); Dr Chris Moyes (Child

Health, Whakatane Hospital); and Dr Peter Jankowitz

(Special Care Infant Unit, Whangarei Area Hospital).

REFERENCES

1. Cleary GM, Wiswell TE. Meconium-stained amniotic fluid and

the meconium aspiration syndrome: an update. Pediatr Clin

North Am. 1998;45:511529

2. Wiswell TE, Bent RC. Meconium staining and the meconium

aspiration syndrome: unresolved issues. Pediatr Clin North Am.

1993;40:955981

3. Coltart TM, Byrne DL, Bates SA. Meconium aspiration

syndrome: a 6-year retrospective study. Br J Obstet Gynaecol.

1989;96:411414

4. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration

syndrome: have we made a difference? Pediatrics. 1990;85:

715721

5. Bhutani VK, Chima R, Sivieri EM. Innovative neonatal venti-

lation and meconium aspiration syndrome. Indian J Pediatr.

2003;70:421427

6. Wiswell TE. Advances in the treatment of the meconium aspi-

ration syndrome. Acta Paediatr. 2001;90(suppl):2830

7. Sriram S, Wall SN, Khoshnood B, Singh JK, Hsieh HL, Lee KS.

Racial disparity in meconium-stained amniotic fluid and meco-nium aspiration syndrome in the United States, 19892000.

Obstet Gynecol. 2003;102:12621268

8. Yoder BA, Kirsch EA, Barth WH, Gordon MC. Changing ob-

stetric practices associated with decreasing incidence of meco-

nium aspiration syndrome. Obstet Gynecol. 2002;99:731739

9. Peng TC, Gutcher GR, Van Dorsten JP. A selective aggressive

approach to the neonate exposed to meconium-stained amni-

otic fluid. Am J Obstet Gynecol. 1996;175:296301

10. Alexander GR, Hulsey TC, Robillard PY, De Caunes F, Pa-

piernik E. Determinants of meconium-stained amniotic fluid in

term pregnancies. J Perinatol. 1994;14:259263

11. Karatekin G, Kesim MD, Nuhoglu A. Risk factors for meco-

nium aspiration syndrome. Int J Gynaecol Obstet. 1999;65:

295297

12. Meydanli MM, Dilbaz B, Caliskan E, Dilbaz S, Haberal A. Risk

factors for meconium aspiration syndrome in infants born

through thick meconium. Int J Gynaecol Obstet. 2001;72:915

13. Paz Y, Solt I, Zimmer EZ. Variables associated with meconium

aspiration syndrome in labors with thick meconium. Eur J

Obstet Gynecol Reprod Biol. 2001;94:2730

14. Rossi EM, Philipson EH, Williams TG, Kalhan SC. Meconium

aspiration syndrome: intrapartum and neonatal attributes.

Am J Obstet Gynecol.1989;161:1106111015. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room man-

agement of the apparently vigorous meconium-stained

neonate: results of the multicenter, international collaborative

trial. Pediatrics. 2000;105:17

16. Hernandez C, Little BB, Dax JS, Gilstrap LC, Rosenfeld CR.

Prediction of the severity of meconium aspiration syndrome.

Am J Obstet Gynecol. 1993;169:6170

17. Sedaghatian MR, Othman L, Hossain MM, Vidyasagar D. Risk

of meconium-stained amniotic fluid in different ethnic groups.

J Perinatol. 2000;20:257261

18. Urbaniak KJ, McCowan LM, Townend KM. Risk factors for

meconium-aspiration syndrome. Aust NZ J Obstet Gynaecol.

1996;36:401406

19. Patel RR, Steer P, Doyle P, Little MP, Elliott P. Does gestation

vary by ethnic group? A London-based study of over 122,000

pregnancies with spontaneous onset of labour. Int J Epidemiol.

2004;33:107113

20. Benny PS, Malani S, Hoby MA, Hutton JD. Meconium

aspiration: role of obstetric factors and suction.Aust NZ J Obstet

Gynaecol.1987;27:36 39

21. Eden RD, Seifert LS, Winegar A, Spellacy WN. Perinatal char-

acteristics of uncomplicated postdate pregnancies. Obstet Gy-

necol. 1987;69:296299

22. Ostrea EMJ, Naqvi M. The influence of gestational age on the

ability of the fetus to pass meconium in utero: clinical impli-

cations.Acta Obstet Gynecol Scand. 1982;61:275277

23. Usher RH, Boyd ME, McLean FH, Kramer MS. Assessment of

fetal risk in postdate pregnancies. Am J Obstet Gynecol. 1988;

158:25926424. Clausson B, Cnattingius S, Axelsson O. Outcomes of post-term

births: the role of fetal growth restriction and malformations.

Obstet Gynecol. 1999;94:758762

25. Sunoo CS, Kosasa TS, Nakayama RT, Hale RW. The incidence of

meconium-aspiration in Hawaii. Hawaii Med J. 1993;52:290293

26. Donoghue D; for the Australian and New Zealand Neonatal

Network.The Report of the Australian and New Zealand Neonatal

Network, 2002. Sydney, Australia: Australian and New Zealand

Neonatal Network; 2004

27. Liu WF, Harrington T. Delivery room risk factors for meconium

aspiration syndrome. Am J Perinatol. 2002;19:367378

28. Agrawal V, David RJ, Harris VJ. Classification of acute respira-

tory disorders of all newborns in a tertiary care center. J Natl

Med Assoc. 2003;95:585595

29. Roberts CL, Lancaster PA. Australian national birthweight per-

centiles by gestational age. Med J Aust. 1999;170:114118

30. Laws PJ, Sullivan PA.Australias Mothers and Babies, 2002. Sydney,

Australia: AIHW National Perinatal Statistics Unit; 2004

31. Statistics New Zealand. Births and deaths. 2005. Available at:

www.stats.govt.nz/datasets/population/births.htm. Accessed:

March 24, 2006

32. New Zealand Ministry of Health. Obstetric Procedures, 1988/

891997/98. Wellington, New Zealand: New Zealand Ministry

of Health;1999

33. New Zealand Ministry of Health. Report on Maternity: Maternal

and Newborn Information, 2002. Wellington, New Zealand: New

Zealand Ministry of Health; 2004

34. Janssen PA, Lee SK, Ryan EM, et al. Outcomes of planned




11/12

home births versus planned hospital births after regulation of

midwifery in British Columbia. CMAJ. 2002;166:315323

35. Davis JM, Richter SE, Kendig JW, Notter RH. High-frequency

jet ventilation and surfactant treatment of newborns with se-

vere respiratory failure. Pediatr Pulmonol. 1992;13:108112

36. Paranka MS, Clark RH, Yoder BA, Null DM. Predictors of

failure of high-frequency oscillatory ventilation in term infants

with severe respiratory failure. Pediatrics. 1995;95:400 404

37. Nolent P, Hallalel F, Chevalier JY, Flamant C, Renolleau S.

Meconium aspiration syndrome requiring mechanical

ventilation: incidence and respiratory management in France

(20002001) [in French]. Arch Pediatr. 2004;11:417422

38. Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement

therapy for meconium aspiration syndrome. Pediatrics. 1996;

97:4852

39. Lotze A, Mitchell BR, Bulas DI, et al. Multicenter study of

surfactant (beractant) use in the treatment of term infants with

severe respiratory failure. Survanta in Term Infants Study

Group.J Pediatr. 1998;132:40 47

40. Al Takroni AM, Parvathi CK, Mendis KB, Hassan S, Reddy I,

Kudair HA. Selective tracheal suctioning to prevent meconium

aspiration syndrome. Int J Gynaecol Obstet. 1998;63:259263

41. Blackwell SC, Carreno CA, Hassan SS, et al. Meconium stain-

ing and meconium aspiration syndrome: is there seasonal vari-

ation?Fetal Diagn Ther. 2001;16:208210

42. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM,

Vivas NI. Oropharyngeal and nasopharyngeal suctioning of

meconium-stained neonates before delivery of their shoulders:

multicentre, randomised controlled trial. Lancet. 2004;364:

597602

43. Chinese Collaborative Study Group for Neonatal Respiratory

Diseases. Treatment of severe meconium aspiration syndrome

with porcine surfactant: a multicentre, randomized, controlled

trial. Acta Paediatr. 2005;94:896902

HELMETUSEANDRISK OF HEAD INJURIES INALPINE SKIERSANDSNOWBOARDERS

Context: Although using a helmet is assumed to reduce the risk of head

injuries in alpine sports, this effect is questioned. In contrast to bicycling or

inline skating, there is no policy of mandatory helmet use for recreational

alpine skiers and snowboarders.

Objective: To determine the effect of wearing a helmet on the risk of head

injury among skiers and snowboarders while correcting for other potential

risk factors.

Design, Setting, and Participants: Case-control study at 8 major Nor-

wegian alpine resorts during the 2002 winter season, involving 3277 injuredskiers and snowboarders reported by the ski patrol and 2992 non-injured

controls who were interviewed on Wednesdays and Saturdays. The controls

comprised every 10th person entering the bottom main ski lift at each resort

during peak hours. The number of participants interviewed corresponded

with each resorts anticipated injury count based on earlier years. . . .

Results: Head injuries accounted for 578 injuries (17.6%). Using a helmet

was associated with a 60% reduction in the risk for head injury (odds ratio

[OR], 0.40; 95% confidence interval [CI], 0.30 0.55; adjusted for other risk

factors) when comparing skiers with head injuries with uninjured controls.

The effect was slightly reduced (OR, 0.45; 95% CI, 0.340.59) when skiers

with other injuries were used as controls. For the 147 potentially severe head

injuries, those who were referred to an emergency physician or for hospitaltreatment, the adjusted OR was 0.43 (95% CI, 0.250.77). The risk of head

injury was higher among snowboarders than for alpine skiers (adjusted OR,

1.53; 95% CI, 1.221.91).

Conclusion: Wearing a helmet is associated with reduced risk of head

injury among snowboarders and alpine skiers.

Sulheim S,Holme I, Ekeland A,BahrR. JAMA. February 22,2006

Noted by JFL, MD




12/12

DOI: 10.1542/peds.2005-2215

2006;117;1712PediatricsPeter A. Dargaville and Beverley Copnell

Therapies, and OutcomeThe Epidemiology of Meconium Aspiration Syndrome: Incidence, Risk Factors,

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