The historic 1952 pollution episode in

London, when a rapid increase in smog led to

dramatic increases in daily mortality, including infant mortality (Her Majesty’s Public

Health Service 1954), stimulated early studies

into the effect of air pollution on population

health. There is now widespread evidence

that short-term increases in ambient air pollution increase mortality and morbidity in

adults and children, even at exposure levels

below the World Health Organization

(WHO) Air Quality Guidelines for Europe,

and U.S. Environmental Protection Agency

(EPA) standards (Brunekreef et al. 1995;

Committee on the Medical Effects of Air

Pollution 1998; Dockery and Pope 1994;

Holgate et al. 1999; Katsouyanni et al. 1997;

Künzli et al. 2000; Lebowitz 1996; Pope

et al. 1995; Samet et al. 2000; Schwartz

1994a; Sydbom et al. 2001; U.S. EPA 1987;

WHO 1987). The findings are particularly

consistent for particulate air pollution; most

of the current evidence is available for inhalable particulate air pollution [particulate matter (PM) with a 50% cutoff aerodynamic

diameter < 10 μm (PM10) and < 2.5 μm

(PM2.5)] (Dominici et al. 2003; Katsouyanni

et al. 1997). The effects were found to be

stronger in susceptible population groups,

such as the elderly, young children, and people with preexisting cardiovascular and respiratory conditions (Gouveia and Fletcher

2000; Pope 2000; Saldiva et al. 1995;

Schwartz 1994b). Long-term exposure to particulate air pollution has also been associated

with increases in total mortality and in cardiopulmonary mortality and respiratory morbidity (European Environment Agency 2003;

Pope 2000; Pope et al. 1995). The large overall impact of air pollution on human health

and a nonthreshold linear relationship with

some health outcomes (e.g., mortality and

hospital admission) have prompted the WHO

to put air pollution and its health effects on its

agenda. It also led the U.S. EPA to draft its

2003 criteria document, which forms the basis

for reevaluating the current U.S. ambient air

quality standards for PM (U.S. EPA 2003;

WHO 2002).

The health of infants and children is particularly vulnerable to environmental pollution and is the focus of the recently published

European Environment and Health Strategy

(European Comission 2003). Infant mortality

remains the major contributor to childhood

mortality worldwide, despite significant

declines over the last two decades. Infant mortality rates vary considerably across regions

and population groups, and the reasons for

this variation are not fully understood.

Environmental exposures, including ambient

air pollution, may account partly for excesses

in infant deaths. We undertook a systematic

review to summarize the epidemiologic evidence for an association between levels of particulate air pollution and infant outcomes.

This work was part of a broader systematic

review of the association between ambient air

pollution and fetal (Glinianaia et al. 2004)

and infant health outcomes.

Materials and Methods

Identification of publications and review

process. Our methods were based on the

guidelines published by the U.K. National

Health Service Centre for Reviews and

Dissemination (2001). We identified relevant

publications using database searches with a

comprehensive list of search terms and other

established search methods (for details, see

Glinianaia et al. 2004).

The inclusion criteria for articles were

a) nonaccidental exposure to directly measured PM; b) an infant (during the first year of

life) health outcome; c) publication between

1 January 1966 and 31 December 2003 in the

English language; and d) availability through

the British Library (London, UK) or the

Internet. Articles describing outcomes related

to occupational or accidental exposure were

excluded, as were articles that were available as

abstracts only. Only one relevant article on

infant morbidity was identified by our comprehensive literature search (Gehring et al.

2002); all others explored infant mortality as

an infant health outcome.

Those articles meeting the inclusion criteria were appraised by pairs of reviewers using

a piloted data extraction form based on previous reviews (Bell et al. 1998; Rankin et al.

1998). We extracted information on study

design, measurement methods for pollutants

and outcomes, statistical techniques, confounding factors, and results.

Exposure measurements. Most reviewed

studies used total suspended particulates (TSP)

(Bobak and Leon 1992, 1999b; Chay and

Greenstone 1999, 2003; Ha et al. 2003; Hunt

and Cross 1975; Joyce et al. 1989; Lave and

Seskin 1972; Penna and Duchiade 1991;

Shinkura et al. 1999), PM10 (Lipfert et al. 2000;

Environmental Health Perspectives • VOLUME 112 | NUMBER 14 | October 2004 1365

Address correspondence to S.V. Glinianaia, School of

Population and Health Sciences, Faculty of Medical

Sciences, University of Newcastle, Newcastle upon

Tyne, NE2 4HH, United Kingdom. Telephone:

0191-222-5891. Fax: 0191-222-8211. E-mail:

svetlana.glinianaia@ncl.ac.uk

The major part of the work on this review was

supported by funds from the School of Population

and Health Sciences (Epidemiology and Public

Health), University of Newcastle. Additional literature searching and reviewing of articles published in

2002–2003 and revision to the manuscript in

response to reviewers’ comments were supported by

Wellcome Trust grant 072465/Z/03/Z.

The authors declare they have no competing

financial interests.

Received 12 November 2003; accepted 3 June 2004.

Does Particulate Air Pollution Contribute to Infant Death? 

A Systematic Review

Svetlana V. Glinianaia, Judith Rankin, Ruth Bell, Tanja Pless-Mulloli, and Denise Howel

Public Health Research Group, School of Population and Health Sciences, Faculty of Medical Sciences, University of Newcastle,

Newcastle upon Tyne, United Kingdom

There is now substantial evidence that both short- and long-term increases in ambient air pollution

are associated with increased mortality and morbidity in adults and children. Children’s health is

particularly vulnerable to environmental pollution, and infant mortality is still a major contributor

to childhood mortality. In this systematic review we summarize and evaluate the current level of

epidemiologic evidence of an association between particulate air pollution and infant mortality. We

identified relevant publications using database searches with a comprehensive list of search terms

and other established search methods. We included articles in the review according to specified

inclusion criteria. Fifteen studies met our inclusion criteria. Evidence of an association between particulate air pollution and infant mortality in general was inconsistent, being reported from locations

with largely comparable pollution levels. There was some evidence that the strength of association

with particulate matter differed by subgroups of infant mortality. It was more consistent for postneonatal mortality due to respiratory causes and sudden infant death syndrome. Differential findings for various mortality subgroups within studies suggest a stronger association of particulate air

pollution with some causes of infant death. Research is needed to confirm and clarify these links,

using the most appropriate methodologies for exposure assessment and control of confounders.

Key words: infant mortality, particulate air pollution, postneonatal respiratory mortality, sudden

infant death syndrome, systematic review. Environ Health Perspect 112:1365–1370 (2004).

doi:10.1289/ehp.6857 available via http://dx.doi.org/ [Online 3 June 2004]

Children’s Health Review
Woodruff et al. 1997), or PM2.5 (Gehring et al.

2002; Loomis et al. 1999) as measures of exposure to PM. One study used visibility as a measure of particulate air pollution (Knöbel et al.

1995). Where possible, we recalculated effect

estimates (odds and risk ratios, mean changes) as

the expected change in outcome for an increase

in air pollution levels by 10 μg/m3 (TSP, PM10,

PM2.5). This facilitated comparison across studies using the same particle size measurements.

Infant mortality. The following definitions

were used as reported in the studies: Infant

mortality is the number of deaths within the

first year of life per 1,000 live births; neonatal

mortality (NM), the number of neonatal deaths

within 0–27 days of life per 1,000 live births;

postneonatal mortality (PNM), the number of

deaths between 28 days and 1 year of life per

1,000 live births (Bobak and Leon 1992,

1999b; Lipfert et al. 2000) or per 1,000 neonatal survivors (Woodruff et al. 1997). Infant

deaths are conventionally divided into neonatal

and postneonatal deaths. The underlying causes

of death differ in these time periods; in particular, preterm birth is the largest contributor to

neonatal death (Maternal and Child Health

Research Consortium 2001). Many reviewed

studies also categorized mortality by cause of

death (definitions are given in Table 1).

Study design. A study was described as ecologic if both outcome and exposure data were

measured at a geographic area–based level.

A study was described as time series when an

ecologic study was based in one geographically

defined population with data collected at different points in time. In semi-individual studies (cohort, case–control, and cross-sectional),

outcome data were collected at an individual

level and air pollution data were measured at

an area-based level.

Although considered, a meta-analysis was

not undertaken due to the heterogeneity

of methodologies used in the studies. The

results are summarized narratively with 95%

confidence intervals (CIs) for estimates where

possible. Given the different ways in which the

studies have reported results, we could consistently report only whether any association or

Children’s Health | Glinianaia et al.

1366 VOLUME 112 | NUMBER 14 | October 2004 • Environmental Health Perspectives

Table 1. Studies investigating the association between PM and infant mortality.

Reference, Study design, Estimate (95% CI)

country, data sample size, exposure by exposure and type Adjustment for

collection period period(s) considered of mortality confounding factors

Continued, next page

Studies exploring multiple outcomes

Bobak and Leon 1999b Matched case–control Per 10-μg/m3 increase in TSP: Socioeconomic factors,

Czech Republic 2,006 cases and Total infant: AOR = 1.03 (0.99–1.06) maternal age and parity,

1989–1991 7,952 controls Infant respiratory: AOR = 1.12 (1.01–1.28)a gestational age, BW,

with data on TSP Infant nonrespiratory: AOR = 1.01 (0.98–1.05) birth length

Total neonatal: AOR = 1.00 (0.96–1.06) Also adjusted for other

Neonatal respiratory: AOR = 0.93 (0.67–1.32)a pollutants examined (SO2

Neonatal nonrespiratory: AOR = 1.00 (0.96–1.06) and NOx), but the results

Mean over period Total postneonatal: AOR = 1.04 (0.99–1.10) are not given

between birth and death Postneonatal respiratory: AOR = 1.14 (1.02–1.32)a

Postneonatal nonrespiratory: AOR = 1.02 (0.96–1.08)

SIDS: AOR = 0.91 (0.75–1.12)

Lipfert et al. 2000 Cross-sectional Per 10-μg/m3 increase in PM10: Socioeconomic factors,

USA 1,443,768 births and Total infant: AOR = 1.12 (1.09–1.15) mother’s smoking, month of birth

1990 13,041 infant deaths; Infant respiratory: AOR = 1.18 (1.11–1.26)b Not adjusted for other

2,354 infant deaths AOR = 1.14 (0.96–1.35)a pollutants examined

due to respiratory causesb Total neonatal: AOR = 1.13 (1.09–1.18) (SO2, CO, SO4

2–)

341 infant deaths Neonatal respiratory: AOR = 1.17 (1.09–1.26)b

due to respiratory causesa

8,362 neonatal deaths; Total postneonatal: AOR = 1.10 (1.04–1.15)

4,679 postneonatal deaths Postneonatal respiratory: AOR = 1.21 (1.05–1.39)b

1,918 SIDS deaths SIDS: AOR = 1.15 (1.07–1.24)

Annual mean

Bobak and Leon 1992 Ecologic > 84.7 (top quintile) vs. < 53.6 μg/m3 TSP (bottom quintile): Socioeconomic factors

Czech Republic ∼ 222,370 live births Total neonatal: AOR = 1.18 (1.00–1.39), Also adjusted for other

1986–1988 2,699 infant deaths test for trend p = 0.071 pollutants examined (SO2, NOx),

Annual mean Total postneonatal: AOR = 1.53 (1.20–1.97), but the results are not given

test for trend p < 0.001

Postneonatal respiratory: AOR = 3.16 (1.52–6.55),a

test for trend p = 0.001

Woodruff et al. 1997 Cohort Per 10-μg/m3 increase in PM10: Socioeconomic factors,

USA All infants: 3,788,079 Total postneonatal: AOR = 1.04 (1.02–1.07) mother’s smoking, month of birth

1989–1991 Postneonatal respiratory mortality in normal-BW

First 2 months of life infants: AOR = 1.20 (1.06–1.36)a

Postneonatal respiratory in LBW infants:

AOR = 1.05 (0.91–1.22)a

Postneonatal nonrespiratory:

AOR = 1.00 (0.99–1.00)

SIDS: AOR = 1.12 (1.07–1.17)

Ha et al. 2003 Time series Per 10-μg/m3 increase in PM10: Seasonality, temperature,

South Korea 1,045 postneonatal deaths Total postneonatal: ARR = 1.03 (1.02–1.04) relative humidity, day of week

1995–1999 Daily mean on event day Postneonatal respiratory: ARR = 1.18 (1.14–1.21)

Chay and Greenstone 1999 Ecologic Total infant mortality: a 10-μg/m3 Maternal, infant, and

USA 101,730 infant deaths increase in TSP associated with 3.5 more socioeconomic factors,

1980–1982 of > 8.5 million births deaths per 10,000 live births (SE = 1.9) and weather data

70,649 neonatal deaths Total neonatal mortality: a 10-μg/m3 (measured at county level)

Changes in annual mean increase in TSP associated with 3.4 more

TSP induced by recession deaths per 10,000 live births (SE = 1.7)
difference was statistically significant at the

5% level.

Results

Study methods. Fifteen studies met our

inclusion criteria, and the findings of the

14 articles addressing mortality are summarized in Table 1. Key aspects of study quality

(i.e., study design, sample size, control for

confounders) are also reported. Table 1 gives

estimates unadjusted for other pollutants

because there was no consistency as to whether

associations with PM were reported after

adjustment for other pollutants.

The studies varied by design, geographic setting, PM source and composition, copollutant

exposures, exposure period investigated, and

outcome. Ten studies were ecologic or time

series (Bobak and Leon 1992; Chay and

Greenstsone 1999, 2003; Ha et al. 2003; Joyce

et al. 1989; Knöbel et al. 1995; Lave and

Seskin 1972; Loomis et al. 1999; Penna and

Duchiade 1991; Sinkura et al. 1999), two were

cross-sectional (Hunt and Cross 1975; Lipfert

et al. 2000), two were cohort studies (Gehring

et al. 2002; Woodruff et al. 1997), and one a

matched case–control study (Bobak and Leon

1999b). All used area-based estimates of air

pollution exposure, except for the German

study, which used a Geographic Information

Systems model to provide individual ambient

pollution estimates (Gehring et al. 2002).

Thirteen studies used direct measurements of

PM from routine monitoring of the ambient

air pollution level by monitoring stations in

the study areas (Bobak and Leon 1992,

1999b; Chay and Greenstone 1999, 2003;

Ha et al. 2003; Hunt and Cross 1975; Joyce

et al. 1989; Lave and Seskin 1972; Lipfert

et al. 2000; Loomis et al. 1999; Penna

and Duchiade 1991; Sinkura et al. 1999;

Woodruff et al. 1997), and one study used visibility as a measure of particulate air pollution,

which was reported to be highly correlated

with PM10 levels (Knöbel et al. 1995).

Five of the ecologic and time-series studies

used the annual mean concentrations of particles (Bobak and Leon 1992; Chay and

Children’s Health | Particulate air pollution and infant death

Environmental Health Perspectives • VOLUME 112 | NUMBER 14 | October 2004 1367

Table 1. Continued

Reference, Study design, Estimate (95% CI)

country, data sample size, exposure by exposure and type Adjustment for

collection period period(s) considered of mortality confounding factors

Chay and Greenstone 2003 Ecologic Total infant mortality: a 10-μg/m3 Maternal, infant, and

USA > 4 million births in increase in TSP associated with 13 more socioeconomic factors

1971–1972 489 U.S. counties deaths per 10,000 live births (SE = 5.6) (measured at county level)

Total neonatal mortality: a 10-μg/m3

Change in annual mean TSP increase in TSP associated with 6.6 more

induced by Clean Air Act deaths per 10,000 live births (SE = 4.4)

Penna and Duchiade 1991 Ecologic Total infant mortality: no significant Socioeconomic factors

Brazil Sample size not given association with TSP level

1980 Infant mortality due to pneumonia: a 10-μg/m3

Annual geometric mean increase in average PM level associated

and the year’s daily with 2.2 more deaths per 10,000 live births, p = 0.014

maximum No significant association with annual maximum TSP

Lave and Seskin 1972 Ecologic Total infant mortality: a 10-μg/m3 increase in Socioeconomic factors, weather

USA Minimum biweekly level minimum TSP level associated with 3.4 more deaths

1960 per 10,000 live births, p < 0.05

Annual mean Total neonatal mortality: a 10-μg/m3

Exact sample size not increase in TSP associated with 0.66

given (based on 117 SMSAs) more deaths per 10,000 live births, p > 0.05

Studies exploring one outcome only

Total infant mortality

Loomis et al. 1999 Time series Per 10-μg/m3 increase in PM2.5: lag 3–5 days; Mean temperature of the 3 days

Mexico ARR = 1.069 (1.025–1.113) before death. Also adjusted for

1993–1995 2,798 infant deaths other pollutants examined (O3,

0–6 days before death NO2), but the results are not given

Hunt and Cross 1975 Cross-sectional Higher risk of IM in one of four 3-month periods No adjustment for any

USA 66 infant deaths in (with reported air pollution episodes), p < 0.001 confounders

1970 3,739 live births Proportion of IM from respiratory causes was Primarily descriptive statistics

Exposure period not specified higher in same 3-month period (p = 0.02)

Total neonatal mortality

Joyce et al. 1989 Ecologic Per 10-μg/m3 increase in TSP: AOR = 1.04 (p > 0.05) Low BW

USA Sample size not given

1976–1978 4-year mean (1975–1978)

Shinkura et al. 1999 Time series Per 10-μg/m3 increase in TSP: RR = 1.01 (0.99–1.04) Season, calendar year, sex,

Japan 98 neonatal deaths but data not reported

1978–1988 in ∼ 29,790 live births

Mean of birth month

SIDS

Knöbel et al. 1995 Time series For visibility 1–3 km vs. 22–37 km: Weather, season, population size,

Taiwan 3,816,000 live births ARR on day of death = 3.8 (2.8–5.1), level of urbanization, daily

1981–1991 3,005 deaths (estimated ARR during 9 days before death = 5.1 (3.2–8.1) incidence of respiratory tract

based on the crude rate) infections

Day of death, 1–9 days

before death

Abbreviations: AOR, adjusted odds ratio; ARR, adjusted rate ratio; BW, birth weight; IM, infant mortality; LBW, low birth weight, < 2,500 g; RR, relative risk; SIDS, sudden infant death syndrome; SMSAs, standard metropolitan statistical areas. Values in parentheses after AOR or ARR are 95% CI. Where possible, study results were re-expressed as the estimated effect of

increasing air pollution levels by 10 μg/m3 (TSP, PM10, PM2.5). PNM due to respiratory causes identified by the International Classification of Diseases, 9th Revision (ICD-9; World Health

Organization 1977).

aICD-9 codes 460–519 (Bobak and Leon 1999b; Lipfert et al. 2000; Woodruff et al. 1997). bICD-9 codes 460–519 and 769, 770 (Lipfert et al. 2000). SIDS deaths were defined as those with an

ICD-9 cause code of 798.0 (Bobak and Leon 1999b; Woodruff et al. 1997); in one study the SIDS cases also included deaths from suffocation (Knöbel et al. 1995).
Greenstone 1999, 2003; Lave and Seskin

1972; Penna and Duchiade 1991), whereas the

others used means over other periods (Joyce

et al. 1989; Shinkura et al. 1999) or investigated different periods before death (Ha et al.

2003; Knöbel et al. 1995; Loomis et al. 1999).

In the case–control study, exposure was

assigned as the mean of all 24-hr particulate

air pollution measurements for the period

between birth and death of the index case

(Bobak and Leon 1999b), whereas in the U.S.

cohort study, the mean of the PM levels for the

first 2 months of life was used (Woodruff et al.

1997). In the two cross-sectional studies, the

exposure period was not specified in one

(Hunt and Cross 1975), whereas the other

used the annual mean of PM10 (Lipfert et al.

2000). In the German cohort study on respiratory morbidity, the estimated annual averages

of PM2.5 were used (Gehring et al. 2002).

Adjustments for some maternal and socioeconomic factors were made by a number of

studies (Table 1); a few also adjusted for maternal smoking (Gehring et al. 2002; Lipfert et al.

2000; Woodruff et al. 1997), other air pollutants (Bobak and Leon 1992, 1999b; Lipfert

et al. 2000; Loomis et al. 1999), and/or season/

weather (Chay and Greenstone 1999; Ha et al.

2003; Knöbel et al. 1995; Lave and Seskin

1972). One older cross-sectional study did not

adjust for any confounding factors (Hunt and

Cross 1975). Considering the comparative precision of the exposure measurements and the

adjustment for key confounding factors in mortality studies, the Czech case–control study

(Bobak and Leon 1999b) and the U.S. cohort

study (Woodruff et al. 1997) used the strongest

designs, and their results are highlighted in the

findings below.

Study findings. Mortality outcomes: infant

mortality. The eight studies exploring PM and

total infant mortality found little evidence of a

consistent association (Table 1). Five studies of

varying designs reported some positive associations (Chay and Greenstone 2003; Hunt and

Cross 1975; Lave and Seskin 1972; Lipfert

et al. 2000; Loomis et al. 1999), although the

strength of evidence and critical exposure

period differed. Three other studies (Bobak

and Leon 1999b; Chay and Greenstone 1999;

Penna and Duchiade 1991) reported nonsignificant associations. The case–control study

(Bobak and Leon 1999b) found little evidence

of any association with TSP levels [odds ratio

(OR) = 1.03; 95% CI, 0.99–1.06].

The three studies investigating infant mortality due to respiratory causes reported a

significant association with PM (Bobak and

Leon 1999b; Lipfert et al. 2000; Penna and

Duchiade 1991) but used different measures of

effects. The case–control study (Bobak and

Leon 1999b) reported a weak association with

TSP levels (OR = 1.12; 95% CI, 1.01–1.28).

These three studies also reported total infant

mortality, and the strength of association was

consistently lower than for respiratory mortality,

although no formal comparisons were made.

The single study reporting infant mortality due to nonrespiratory causes found no significant association between PM levels and

mortality due to this cause (Bobak and Leon

1999b) (OR = 1.01; 95% CI, 0.98–1.05), in

contrast to their more positive findings for

respiratory mortality.

Neonatal mortality. Total NM did not

show a consistent association with PM, with

one U.S. study reporting a positive association

(Lipfert et al. 2000), two studies with borderline findings (Bobak and Leon 1992; Chay and

Greenstone 1999), and five studies from different geographic settings reporting no evidence

of an association (Bobak and Leon 1999b;

Chay and Greenstone 2003; Joyce et al. 1989;

Lave and Seskin 1972; Shinkura et al. 1999).

The case–control study was the only one to

explore NM due to both respiratory and nonrespiratory causes. It reported little evidence of

an association between TSP levels and either

type of NM: respiratory, OR = 0.93 (95% CI,

0.67–1.32); nonrespiratory, OR = 1.00 (95%

CI, 0.96–1.06) (Bobak and Leon 1999b).

Another study examining respiratory NM

reported a significant association with PM10

similar in strength to the association reported

for total NM (Lipfert et al. 2000).

Postneonatal mortality. Four of five studies investigating a relationship between PM

and total PNM, including a cohort study

(OR = 1.04; 95% CI, 1.02–1.07) (Woodruff

et al. 1997), reported significant positive associations (Bobak and Leon 1992; Ha et al.

2003; Lipfert et al. 2000). The case–control

study did not find a significant association

(OR = 1.04; 95% CI, 0.99–1.10) (Bobak and

Leon 1999b); the difference between this and

the cohort study was in the precision of the

estimates. Two (Bobak and Leon 1999b;

Lipfert et al. 2000) of the five studies explored

PNM in addition to total infant and total NM

and reported similar strengths of association

for all these mortality types.

In all studies examining both total and respiratory PNM (Bobak and Leon 1992, 1999b;

Ha et al. 2003; Lipfert et al. 2000; Woodruff

et al. 1997), the association between PM level

and respiratory mortality was statistically significant and stronger than for total mortality,

although no formal comparisons were made.

This was true for infants of normal birth

weight in the cohort study, but the results

were inconclusive for the subgroup of infants

with low birth weight (Woodruff et al. 1997).

In the two studies where both postneonatal

respiratory and nonrespiratory mortalities

were investigated, there was little evidence of

an association between PM levels and nonrespiratory mortality (Bobak and Leon 1999b;

Woodruff et al. 1997).

Sudden infant death syndrome (SIDS) was

found to be associated with ambient PM concentrations in two U.S. studies (Lipfert et al.

2000; Woodruff et al. 1997). A Taiwanese

time-series study found a positive association

between SIDS and reduced visibility during

1–9 days before death (Knöbel et al. 1995),

but adjustment for confounders was limited.

Although the U.S. cohort study found a significant association with PM10 (OR = 1.12;

95% CI, 1.07–1.17), the Czech case–control

study did not find a significant association

with TSP (OR = 0.91; 95% CI, 0.75–1.12)

(Bobak and Leon 1999b).

Morbidity outcomes: respiratory morbidity. The only study investigating respiratory

morbidity in infants reported significant associations between exposure to PM2.5 and some

(cough without infection and dry cough at

night) but not other (wheeze, asthmoid or

other types of bronchitis, respiratory infections,

and sneezing, runny/stuffed nose) respiratory

symptoms (Gehring et al. 2002).

Discussion

Main findings. Our review suggests some evidence of an association between PM levels and

different subgroups of infant mortality. There

were differences in the magnitude and consistency of association by cause of death, with

PNM due to respiratory causes and SIDS

being more consistently associated with PM

levels. However, it is problematic to compare

cause-specific associations between studies

because of variations in definitions and diagnostic criteria of causes of death. Differential

findings for various mortality subgroups within

some studies suggest a stronger association of

particulate air pollution with some causes of

infant death. The only study investigating respiratory morbidity in infants reported significant associations between exposure to PM2.5

and some but not other respiratory symptoms

(Gehring et al. 2002).

Methodologic issues. We were unable to

take publication, language, and reporting

biases into account when identifying relevant

publications, which may have overestimated

the strength of any associations.

Summarizing the findings was complicated

by the considerable differences in methodologies used. Many articles reported the results

relating to a number of combinations of PM,

outcome, and exposure period, resulting in

multiple comparisons, which in turn increased

the likelihood of positive findings.

More than half of the reviewed studies

were ecologic or time series in design.

Controlling for confounding factors in such

studies is more difficult than in individualbased studies because of the extra potential

sources of bias due to the aggregation of subjects into groups (Morgenstern and Thomas

1993). Even in semi-individual studies, few

Children’s Health | Glinianaia et al.

1368 VOLUME 112 | NUMBER 14 | October 2004 • Environmental Health Perspectives
adjusted for key confounding factors at an

individual level, because some used area-based

level data and others did not adjust for confounders. Other important individual risk

factors, such as smoking and environmental

exposures from other air pollutants (e.g., sulfur

dioxide, nitrogen dioxide), were rarely controlled for. Adequate control for confounders is

essential to accurately estimate the magnitude

of any association between low-level particulate

air pollution exposure and infant health, and

inadequate control may partly account for

some inconsistency between studies.

Air pollution exposure was generally estimated by small numbers of monitors, which

may not estimate individual exposures accurately for all infants; this could result in misclassification of exposure. The potential for

bias is also affected by monitoring decisions

(e.g., annual or daily means). The absence of

information about indoor air pollution may

underestimate individual exposure. These factors are likely to be nondifferential and therefore reduce the precision of effect estimates.

Studies exploring the health effects of

PM may report inconsistent results because

the definitions and measurement techniques

are variable. The toxicity of equal-sized PM

depends on its chemical composition, which,

in turn, depends on the mixture of sources

generating them and their dispersion (Mage

2002). For example, the PM10:TSP ratio

ranges from 50 to 60% for U.S. sampling

sites (Dockery and Pope 1994), whereas in

the Czech Republic PM10 has been estimated

to constitute about 80% of TSP (Bobak and

Leon 1999a). The reviewed studies also varied

in relation to average levels and ranges of PM,

and copollutant exposures. Despite differences in air pollution sources and levels, the

findings of an association between PM levels

and postneonatal respiratory mortality are

fairly consistent across studies and regions.

Another possible explanation for inconsistency of findings is differences between settings in the distribution of timing and cause

of death within infant mortality. For instance,

the definitions of respiratory causes of death

and SIDS varied across studies (Bobak and

Leon 1992, 1999b; Knöbel et al. 1995;

Lipfert et al. 2000; Woodruff et al. 1997) and

were not always fully reported (Lipfert et al.

2000). Accurate diagnosis of deaths due to

SIDS depends on a postmortem investigation,

and this was not available for all cases coded

as SIDS in one study (Knöbel et al. 1995).

For this reason, within-study comparisons,

when different subgroups and causes of death

were examined in the same study, may be

more valid than between-study comparisons.

The magnitudes of association reported in

the reviewed studies are low and could be

accounted for by the factors considered above.

However, their magnitude is of the same order

as that found between PM and adult mortality, which is accepted as a true relationship

(Committee on the Medical Effects of Air

Pollution 1998; WHO 2002).

Potential mechanisms. Although the epidemiologic evidence linking increases in PM

with excess mortality and morbidity in adults

is now strong, the mechanisms for such a link

are not yet well understood. To date, toxicologic studies have not identified unequivocally

specific PM constituents or mechanisms to

account for the epidemiologic observations.

Infants and children are considered potentially

susceptible populations in risk assessments,

including risk from PM (U.S. EPA 1999),

because of their immature immune system,

potential impact on lung growth and development, and viral infections common in infants.

However, few human and animal studies have

compared immature and adult organisms with

regard to their susceptibility to inhaled particles (Mauderly 2000). For adults, three potential mechanisms have been put forward for the

PM effect: an inflammatory response that

alters blood coagulation, an allergic immune

response, and an alteration in cardiac autonomic function resulting in the reduction of

heart rate variability (Donaldson et al. 2001;

Granum and Lovik 2002; Liao et al. 2004;

Pope 2000). All three potential mechanisms

may be pertinent in infants, but the degree of

their influence may vary at various stages of

infant development. In particular, they may

be more applicable to postneonatal death,

because this is thought to be affected more by

the infant’s external environment than is NM

(Pharoah and Morris 1979). Neonatal deaths

are more affected by conditions originating in

the perinatal period, with immaturity-related

conditions being the main cause of death.

However, if there is a small adverse effect of

particulate air pollution on fetal growth and

duration of pregnancy, as discussed previously

(Glinianaia et al. 2004), it may also indirectly

contribute to neonatal deaths.

The mechanisms of SIDS, the most common cause of postneonatal death in developed

countries, are not well understood, although a

number of pathways have been proposed. One

of the currently most compelling hypotheses for

the occurrence of SIDS is an abnormality of

brain development and maturation, with a tendency to central apnea and disturbed cardiorespiratory control mechanisms (Goldwater

2003; Harper 2000; Kahn et al. 2003; Kinney

and Filiano 2001). Unsafe sleeping environment, exposure to environmental tobacco

smoke (ETS), and lower socioeconomic status

are critical risk factors for SIDS. It has been

suggested that the association between postnatal exposure to tobacco smoke and SIDS is

causal (Anderson and Cook 1997; McMartin

et al. 2002). The potential mechanisms of

action proposed for ETS (abnormal pulmonary

development, reduced pulmonary function,

abnormalities in cardiorespiratory control

system, promotion of respiratory infections)

(Chan-Yeung and Dimich-Ward 2003;

Goldwater 2003; Hofhuis et al. 2003; Strachan

and Cook 1997) might be similar to those for

particulate air pollution, because ETS is known

to contain a substantial proportion of PM.

Implications. Current epidemiologic evidence suggests a link between ambient PM

exposure and some subgroups of infant

mortality, even at relatively low PM levels

reported in the reviewed studies, which are

comparable with current levels experienced in

developed countries. More research is needed

to further clarify whether there is a real effect

of particulate air pollution on infant health

and to quantify this effect. Future studies

should explore overall and cause-specific

infant mortality, using robust study designs

with individual level information on key confounding variables. Exposure assessment

should include details of level, size, and composition of PM and co-pollution exposure.

The use of physiologic measurements (e.g.,

lung function in older children) and biomarkers of exposure or effect (e.g., methemoglobin

as a biomarker of carbon monoxide poisoning, cotinine as a marker of exposure to ETS,

placental DNA adduct levels as biomarkers of

effect of polycyclic aromatic hydrocarbons)

could promote understanding of causal effects

of air pollution on infant and children’s

health. If a causal association between exposure to PM and infant death exists, widespread exposure to particulate air pollution

may be an important determinant of infant

mortality at a population level.

REFERENCES

Anderson HR, Cook DG. 1997. Passive smoking and sudden infant

death syndrome: review of the epidemiological evidence.

Thorax 52:1003–1009.

Bell R, Luengo S, Petticrew M, Sheldon T. 1998. Screening for

ovarian cancer: a systematic review. Health Tech Assess

2:1–84.

Bobak M, Leon DA. 1992. Air pollution and infant mortality in the

Czech Republic, 1986–88. Lancet 340:1010–1014.

Bobak M, Leon DA. 1999a. Pregnancy outcomes and outdoor

air pollution: an ecological study in districts of the Czech

Republic 1986–8. Occup Environ Med 56:539–543.

Bobak M, Leon DA. 1999b. The effect of air pollution on infant

mortality appears specific for respiratory causes in the

postneonatal period. Epidemiology 10:666–670.

Brunekreef B, Dockery DW, Krzyzanowski M. 1995. Epidemiologic

studies on short-term effects of low levels of major ambient

air pollution components. Environ Health Perspect 103:3–13.

Chan-Yeung M, Dimich-Ward H. 2003. Respiratory health effects

of exposure to environmental tobacco smoke. Respirology

8:131–139.

Chay KY, Greenstone M. 1999. The Impact of Air Pollution on Infant

Mortality: Evidence from Geographic Variation in Pollution

Shocks Induced by a Recession. Working paper W 7442.

Cambridge, MA:National Bureau of Economic Research.

Chay KY, Greenstone M. 2003. Air Quality, Infant Mortality, and

the Clean Air Act of 1970. Working paper W 10053.

Cambridge, MA:National Bureau of Economic Research.

Committee on the Medical Effects of Air Pollution. 1998. The

Quantification of the Effects of Air Pollution on Health in the

United Kingdom. London:Her Majesty’s Stationery Office.

Children’s Health | Particulate air pollution and infant death

Environmental Health Perspectives • VOLUME 112 | NUMBER 14 | October 2004 1369
Dockery DW, Pope CA III. 1994. Acute respiratory effects of

particulate air pollution. Annu Rev Public Health 15:107–132.

Dominici F, McDermott A, Daniels M, Zeger SL, Samet JM. 2003.

Mortality among residents of 90 cities. In: Revised Analyses

of Time-Series Studies of Air Pollution and Health (Lamont J,

ed). Boston:Health Effects Institute, 9–24. Available: http://

www.healtheffects.org/Pubs/TimeSeries.pdf [accessed

29 April 2004].

Donaldson K, Stone V, Seaton A, MacNee W. 2001. Ambient

particle inhalation and the cardiovascular system: potential

mechanisms. Environ Health Perspect 109:523–527.

European Commission. 2003. A European Environment and Health

Strategy. Brussels:European Commission, 11 June. Available:

http://europa.eu.int/comm/press_room/presspacks/pdf/

com_en.pdf [accessed 22 October 2003].

European Environment Agency. 2003. Environment and human

health. In: Europe’s Environment: The Third Assessment.

Report No. 10. Copenhagen:European Environment

Agency. Available: http://reports.eea.eu.int/environmental_

assessment_report_2003_10/en/kiev_chapt_12.pdf

[accessed 22 October 2003].

Gehring U, Cyrys J, Sedlmeir G, Brunekreef B, Bellander T,

Fischer P, et al. 2002. Traffic-related air pollution and respiratory health during the first 2 years of life. Eur Respir J

19:690–698.

Glinianaia SV, Rankin J, Bell R, Pless-Mulloli T, Howel D. 2004.

Particulate air pollution and fetal health: a systematic review

of the epidemiologic evidence. Epidemiology 15:36–45.

Goldwater PN. 2003. Sudden infant death syndrome: a

critical review of approaches to research. Arch Dis Child

88:1095–1100.

Gouveia N, Fletcher T. 2000. Time series analysis of air pollution

and mortality: effects by cause, age and socioeconomic

status. J Epidemiol Commun Health 54:750–755.

Granum B, Lovik M. 2002. The effect of particles on allergic

immune responses. Toxicol Sci 65:7–17.

Ha EH, Lee JT, Kim H, Hong YC, Lee BE, Park HS, et al. 2003.

Infant susceptibility of mortality to air pollution in Seoul,

South Korea. Pediatrics 111:284–290.

Harper RM. 2000. Sudden infant death syndrome: a failure

of compensatory cerebellar mechanisms? Pediatr Res

48:140–142.

Her Majesty’s Public Health Service. 1954. Mortality and

Morbidity during the London Fog of December 1952. Reports

on Public Health and Medical Subjects. London:Her

Majesty’s Stationery Office.

Hofhuis W, de Jongste JC, Merkus PJ. 2003. Adverse health

effects of prenatal and postnatal tobacco smoke exposure

on children. Arch Dis Child 88:1086–1090.

Holgate ST, Samet JM, Koren HS, Maynard RL, eds. 1999. Air

Pollution and Health. London:Academic Press.

Hunt VR, Cross WL. 1975. Infant mortality and the environment of

a lesser metropolitan county: a study based on births in one

calendar year. Environ Res 9:135–151.

Joyce TJ, Grossman M, Goldman F. 1989. An assessment of

the benefits of air pollution control: the case of infant

health. J Urban Econ 25:32–51.

Kahn A, Groswasser J, Franco P, Scaillet S, Sawaguchi T,

Kelmanson I, et al. 2003. Sudden infant deaths: stress,

arousal and SIDS. Early Hum Dev 75:S147–S166.

Katsouyanni K, Touloumi G, Spix C, Schwartz J, Balducci F,

Medina S, et al. 1997. Short-term effects of ambient sulphur

dioxide and particulate matter on mortality in 12 European

cities: results from time series data from the APHEA project.

Br Med J 314:1658–1663.

Kinney HC, Filiano JJ. 2001. Brain research in sudden infant death

syndrome. In: Sudden Infant Death Syndrome: Problems,

Progress and Possibilities (Byard RW, Krouse HF, eds).

London:Arnold, 118–137.

Knöbel HH, Chen CJ, Liang KY. 1995. Sudden infant death

syndrome in relation to weather and optimetrically measured air pollution in Taiwan. Pediatrics 96:1106–1110.

Künzli N, Kaiser R, Medina S, Studnicka M, Chanel O, Filliger P,

et al. 2000. Public-health impact of outdoor and traffic-related

air pollution: a European assessment. Lancet 356:795–801.

Lave LB, Seskin EP. 1972. Air pollution, climate, and home

heating: their effects on U.S. mortality rates. Am J Public

Health 62:909–916.

Lebowitz MD. 1996. Epidemiological studies of the respiratory

effects of air pollution. Eur Respir J 9:1029–1054.

Liao D, Duan Y, Whitsel EA, Zheng ZJ, Heiss G, Chinchilli VM,

et al. 2004. Association of higher levels of ambient criteria

pollutants with impaired cardiac autonomic control: a

population-based study. Am J Epidemiol 159:768–777.

Lipfert FW, Zhang J, Wyzga RE. 2000. Infant mortality and air

pollution: a comprehensive analysis of US data for 1990.

J Air Waste Manage Assoc 50:1350–1366.

Loomis D, Castillejos M, Gold DR, McDonnell W, Borja-Aburto VH.

1999. Air pollution and infant mortality in Mexico City.

Epidemiology 10:118–123.

Mage DT. 2002. A particle is not a particle is not a PARTICLE.

J Expo Anal Environ Epidemiol 12:93–95.

Maternal and Child Health Research Consortium. 2001.

Confidential Enquiry into Stillbirths and Deaths in Infancy

(CESDI) 8th Annual Report: Focusing on Stillbirths, European

Comparisons of Perinatal Care, Paediatric Portmortem

Issues, Survival Rates of Premature Babies—Project 27/28.

London:Maternal and Child Health Research Consortium.

Mauderly JL. 2000. Animal models for the effect of age on

susceptibility to inhaled particulate matter. Inhal Toxicol

12:863–900.

McMartin KI, Platt MS, Hackman R, Klein J, Smialek JE,

Vigorito R, et al. 2002. Lung tissue concentrations of nicotine in sudden infant death syndrome (SIDS). J Pediatr

140:205–209.

Morgenstern H, Thomas D. 1993. Principles of study design in

environmental epidemiology. Environ Health Perspect

101:23–38.

National Health Service Centre for Reviews and Dissemination.

2001. Undertaking Systematic Reviews of Research on

Effectiveness: CRD’s Guidance for Those Carrying Out or

Commissioning Reviews. Report No. 4 (2nd ed). York,

UK:Centre for Reviews and Dissemination.

Penna ML, Duchiade MP. 1991. Air pollution and infant mortality

from pneumonia in the Rio de Janeiro metropolitan area.

Bull Pan Am Health Organ 25:47–54.

Pharoah PO, Morris JN. 1979. Postneonatal mortality. Epidemiol

Rev 1:170–183.

Pope CA III. 2000. Epidemiology of fine particulate air pollution

and human health: biologic mechanisms and who’s at risk?

Environ Health Perspect 108:713–723.

Pope CA III, Bates DV, Raizenne ME. 1995. Health effects of

particulate air pollution: time for reassessment? Environ

Health Perspect 103:472–480.

Rankin J, Carlin L, White M. 1998. A Review of the Literature on

Interventions to Reduce Mortality from Breast and Cervical

Cancer in Minority Ethnic Groups. London:Cancer Research

Campaign.

Saldiva PH, Pope CA III, Schwartz J, Dockery DW, Lichtenfels AJ,

Salge JM, et al. 1995. Air pollution and mortality in elderly

people: a time-series study in São Paulo, Brazil. Arch

Environ Health 50:159–163.

Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. 2000.

Fine particulate air pollution and mortality in 20 U.S. cities,

1987–1994. N Engl J Med 343:1742–1749.

Schwartz J. 1994a. Air pollution and daily mortality: a review

and meta analysis. Environ Res 64:36–52.

Schwartz J. 1994b. What are people dying of on high air pollution

days? Environ Res 64:26–35.

Shinkura R, Fujiyama C, Akiba S. 1999. Relationship between

ambient sulfur dioxide levels and neonatal mortality near

the Mt. Sakurajima volcano in Japan. J Epidemiol 9:344–349.

Strachan DP, Cook DG. 1997. Health effects of passive smoking.

1. Parental smoking and lower respiratory illness in infancy

and early childhood. Thorax 52:905–914.

Sydbom A, Blomberg A, Parnia S, Stenfors N, Sandstrom T,

Dahlen SE. 2001. Health effects of diesel exhaust emissions.

Eur Respir J 17:733–746.

U.S. EPA. 1987. Ambient Air Quality Standards for Particulate

Matter: Final Rules. Fed Reg 52:24634–24655.

U.S. EPA. 1999. Air Quality Criteria for Particulate Matter, vols.

1–3. EPA/600/P-99/002a. Washington, DC:U.S. Environmental

Protection Agency.

U.S. EPA. 2003. Air Quality Criteria for Particulate Matter.

Fourth External Review Draft, June 2003. Research

Triangle Park, NC:U.S. Environmental Protection Agency,

Office of Research and Development, National Center for

Environmental Assessment.

Woodruff TJ, Grillo J, Schoendorf KC. 1997. The relationship

between selected causes of postneonatal infant mortality

and particulate air pollution in the United States. Environ

Health Perspect 105:608–612.

WHO. 1977. International Statistical Classification of Diseases,

Injuries, and Causes Of Death, 9th Revision. Geneva:World

Health Organization.

WHO 1987. Air Quality Guidelines for Europe. WHO Regional

Publications, European Series No. 23. Copenhagen:World

Health Organization.

WHO. 2002. Reducing Risks, Promoting Healthy Life. The World

Health Report 2002. Geneva:World Health Organization.

Available: http://www.who.int/whr/2002/en/ [accessed

20 October 2003].

Children’s Health | Glinianaia et al.

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