confidential: for review only · complete list of authors: smith, rachel; imperial college london,...

Confidential: For Review O

nly

Impacts of London's road traffic air and noise pollution on

birth weight: a retrospective population-based cohort study

Journal: BMJ

Manuscript ID BMJ.2017.039236

Article Type: Research

BMJ Journal: BMJ

Date Submitted by the Author: 03-May-2017

Complete List of Authors: Smith, Rachel; Imperial College London, Epidemiology & Biostatistics Fecht, Daniela; UK Small Area Health Statistics Unit, MRC-PHE Centre for Environment and Health, Imperial College London, Department of Epidemiology & Biostatistics Gulliver, John; MRC-PHE Centre for Environment and Health, Imperial

College London, Dept Epidemiology and Biostatistics, School of Public Health Beevers, Sean; MRC-HPA Centre for Environment and Health, King’s College, Environmental Research Group Dajnak, David; MRC-PHE Centre for Environment and Health, Environmental Research Group, King's College London Blangiardo, Marta; Small Area Health Statistics Unit, MRC-HPA Centre for Environment and Health, Imperial College London, Dept Epidemiology and Biostatistics, School of Public Health Ghosh, Rebecca; Small Area Health Statistics Unit, MRC-HPA Centre for Environment and Health, Imperial College London, Dept Epidemiology and Biostatistics, School of Public Health

Hansell, Anna; Imperial College London, Epidemiology and Public Health Kelly, Frank; King's College London Anderson, H Ross; MRC-PHE Centre for Environment and Health, Environmental Research Group, King's College London; Population Health Research Institute, St George’s, University of London Toledano, Mireille; Imperial College London, Epidemiology and Biostatistics

Keywords: birth weight, small for gestational age, air pollution, noise pollution, road traffic, particulate matter

https://mc.manuscriptcentral.com/bmj

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TITLE: Impacts of London's road traffic air and noise pollution on birth weight: a

retrospective population-based cohort study

AUTHORS: Rachel B Smith, research associate1, Daniela Fecht, research fellow

2, John

Gulliver, senior lecturer1, Sean D Beevers, senior lecturer

3, David Dajnak, deputy manager

3,

Marta Blangiardo, senior lecturer1, Rebecca E. Ghosh, research associate

2, Anna L Hansell,

reader & assistant director2, Frank J Kelly, professor

3, H Ross Anderson, emeritus

professor3,4

and Mireille B Toledano, reader1§

AFFILIATIONS:

1MRC-PHE Centre for Environment and Health, Department of Epidemiology and

Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk

Place, London, W2 1PG, UK; 2UK Small Area Health Statistics Unit, MRC-PHE Centre for

Environment and Health, Department of Epidemiology and Biostatistics, School of Public

Health, Imperial College London, W2 1PG, UK; 3

MRC-PHE Centre for Environment and

Health, Environmental Research Group, School of Biomedical Sciences, King's College

London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK; 4

Population Health Research Institute, St George’s, University of London, Cranmer Terrace,

London, SW17 0RE, UK.

§Corresponding author

ADDRESS CORRESPONDENCE TO: Dr Mireille B Toledano, MRC-PHE Centre for

Environment and Health, Department of Epidemiology and Biostatistics, School of Public

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Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, W2 1PG, UK,

Tel: +44 (0)2075943298, E-mail: [email protected]

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Abstract

Objective: To investigate the relationship between exposure to both air and noise pollution

from road traffic and birth weight outcomes.

Design: Retrospective population-based cohort study

Setting: Greater London and surrounding counties up to the M25 motorway (2,317 km2),

UK, 2006-2010

Participants: 572,910 live singleton births occurring within the M25 motorway between

2006-2010

Main outcome measures: Term birth weight, term low birth weight (LBW), small-for-

gestational age (SGA) at term

Results: Average air pollutant exposures across pregnancy were 41µg/m3 nitrogen dioxide

(NO2), 73µg/m3 nitrogen oxides (NOX), 14 µg/m

3 particulate matter with aerodynamic

diameter <2.5 µm (PM2.5), 23 µg/m3 particulate matter with aerodynamic diameter <10 µm

(PM10) and 32 µg/m3 ozone (O3), and average day (LAeq,16hr) and night-time (Lnight) noise

levels were 58 dB and 53 dB respectively. Interquartile range increases in NO2, NOX, PM2.5,

PM10 and source-specific PM2.5 from traffic exhaust (PM2.5 traffic-exhaust) and traffic non-exhaust

(brake/tyre wear and re-suspension) (PM2.5 traffic-non-exhaust) were significantly associated with

mean term birth weight reductions of 7 to 13g, 2-6% increased odds of term LBW (except

PM10), and for PM2.5 traffic-exhaust and PM2.5 2-3% increased odds of term SGA. Only PM2.5

traffic-exhaust was consistently associated with reduced birth weight after adjustment for each of

the other air pollutants. Air pollutant associations were robust to adjustment for road traffic

noise. Significant trends of decreasing birth weight across increasing road traffic noise

categories were observed, but were attenuated to null when adjusted for primary traffic air

pollutants.

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Conclusions: Our findings suggest that air pollution from road traffic in London, which is

dominated by diesel exhaust emissions, is adversely affecting fetal growth. Primary PM2.5

from vehicle exhausts appears to be driving these associations in this study. An apparent

relationship with noise appears to reflect confounding by traffic air pollutant co-exposures.

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Introduction

Air pollution is a major public health issue. It has been associated with reduced fetal

growth,(1) via which it may have extensive and permanent influences on the life course.(2)

A key contributor to urban ambient pollution is road traffic, and critically, vehicle emissions

are released close to people. Urban particulate matter includes a large contribution from

outside the urban area, and locally-emitted particles. Exposure is complex, close to roads an

individual would be exposed to more primary exhaust and non-exhaust (brake/tyre wear and

re-suspension) particles, but further away to more nitrate and secondary organic aerosol as a

proportion of their total particulate dose.

However, traffic also produces noise, which has been associated with e.g. hypertension and

cardiovascular disease.(3) Research on noise and birth outcomes is more limited, but a

possible effect on low birth weight has been suggested.(4)

Evidence about the relative roles of air and noise pollution on birth weight is limited and

inconsistent.(5-7) To address health impacts of traffic effectively these need to be better

understood. In this study, the largest to date, we investigate long-term exposure to both

traffic-related air and noise pollution during pregnancy in relation to birth weight.

Methods

Births data

The study boundary was the M25, an orbital motorway encompassing most of Greater

London (2,317 km2). 671,509 singleton births occurring within the M25 during 2006-2010

were extracted from the UK National Births/Stillbirth registers held at the UK Small Area

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Health Statistics Unit (SAHSU) and supplied by the Office for National Statistics. These

registers provide routinely collected data on all births in the country, including date of birth,

birth weight, sex and mother’s age. We appended gestational age and baby’s ethnicity from

the NHS Numbers for Babies (NN4B) dataset, with 99.2% linkage.

Birth addresses were geocoded using Quick Address Software.(8) Births in middle layer

super output areas (MSOAs) overlapping the M25 were excluded (N=7,493) because area-

level covariates would reflect populations inside and outside the study area. We obtained

2011 census output area (COA)-level data as follows: Carstairs deprivation index (9) from

UK Census 2011 standardised across COAs in study area; and 2014 tobacco

expenditure/week (population ≥16 years) from CACI Ltd, as a smoking proxy.

Air pollution exposures

Average monthly concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOX), ozone

(O3), particulate matter with diameter <2.5µm (PM2.5) and <10µm (PM10), and PM2.5 from

traffic exhaust (PM2.5 traffic-exhaust) and traffic non-exhaust (PM2.5 traffic-non-exhaust = brake/tyre

wear and re-suspension) were estimated at 20m x 20m grid resolution across the study area,

using dispersion modelling (KCLurban).(10) NO2, NOX, PM2.5 traffic-exhaust and PM2.5 traffic-non-

exhaust are primary traffic pollutants (i.e. locally-emitted). PM2.5 and PM10 are dominated by

regional and long-range particles and secondary particles formed through atmospheric

chemical reactions but also include particles from primary traffic sources, whilst O3 is a

regional, secondary pollutant - these are more homogeneously distributed than primary traffic

pollutants. The KCLurban model uses Atmospheric Dispersion Modelling System v4 and

road source model v2.3; data on emissions from the London Atmospheric Emissions

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Inventory (LAEI);(11) empirically derived NO-NO2-O3 and PM relationships; and hourly

meteorological information.(10) Further details of the KCLurban model are available at the

study project website.(12) Using a Geographic Information System, each birth address was

linked to the pollutant model grid according to its geocoded XY coordinates and assigned

monthly air pollutant concentrations for a specific 20m x 20m grid cell. For each birth

record, we calculated the time-weighted average concentrations for NOX, NO2, PM2.5 traffic-

exhaust, PM2.5 traffic-non-exhaust, PM2.5, PM10 and O3 across pregnancy and each trimester

(Trimester 1 defined as days 1-93, Trimester 2 as days 94-186 and Trimester 3 as day 187 to

day preceding delivery). The time-weighting was based on the proportion of the pregnancy

or trimester in each calendar month.(13, 14) To define trimesters, gestation length (available

as ‘completed’ weeks of pregnancy) was converted to days, and 4 days (rounded up from the

mid-point 3.5 days) was added to adjust for potential underestimation where true gestation

length was not an exact number of completed weeks.

Noise exposures

A-weighted road traffic noise levels were modelled to 0.1 dB(A) resolution for all geocoded

birth addresses using the TRAffic Noise EXposure (TRANEX) model(15): LAeq,16hr (average

sound level 0700-2300 hours); Lnight (2300-0700); Lday (0700-1900); Leve (1900-2300); Lden

(logarithmic composite of Lday, Leve, and Lnight with 5 dB(A) added to the Leve and 10 dB(A)

added to Lnight). We modelled noise for one mid-point year (2007) and applied these values

to other years for the same address locations because temporal variability in noise over the

study period was negligible.(15) Noise could not be estimated for 4.5% of births due to

receptor placement issues,(15) however these births were randomly distributed. We flagged

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addresses exposed to Lday>50dB(A) from railways or aircraft (Heathrow Airport and City

Airport). Railway and City Airport noise data were from Environmental Noise Directive

strategic noise mapping (2006 annual average), and Heathrow Airport noise from annual

average contours (2001) from the Civil Aviation Authority.

Outcomes/Exclusions

Term low birth weight (LBW) was defined as birth weight<2500g and gestation≥37 weeks,

and SGA as birth-weight-for-gestational-age <10th centile by sex/ethnicity.

We initially excluded births with gestational age <24 or >44 weeks (n=1083), missing or

implausible (<200g or >9000g) birth weight (n=5,747), and missing gestational age

(n=6,617). Birth weight outliers were then identified and excluded according to Tukey’s rule

(16) (i.e. values >2*IQR below the first quartile and above the third quartile for each

gestational week) both overall and separately according to sex and ethnicity (White, Asian,

Black, Other) for the calculation of sex-ethnicity-specific birth weight-for-gestational-age

centiles. Stillbirths were retained at this stage, because excluding stillbirths overestimates

centiles for gestation <28 weeks by up to 30%.(17) 0.58% of the observations overall were

identified as outliers. We calculated smoothed sex-ethnicity-specific birth weight-for-

gestational-age centile curves according to the LMS method (18) using LMSChartMaker

Light V.2.54 software (19) which has been used in previous research.(20-23) The software

has a maximum data input of 100,000 records, so a subsample of 100,000 was randomly

selected if the number of records for a given sex/ethnicity subgroup exceeded this.

Representativeness of these 100,000 samples for their particular subgroup with respect to

exposures/potential confounders was checked and confirmed. We defined SGA as birth-

weight-for-gestational-age <10th centile by sex/ethnicity (to account for constitutional

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differences in birth weight by sex and ethnic group, and thus better identify pathologically

small infants). We did not calculate centiles/SGA for the ethnic group ‘Other’, as it does not

represent a meaningful homogeneous ethnic group for analysis. We excluded birth weight

outliers (n=3,712), stillbirths (n=3,597), births missing noise exposure (n=30,622) and

missing ethnicity (n=39,728), leaving 572,910 live births eligible for birth weight analyses,

and 499,862 for SGA analyses.

Statistical Methods

Air pollutant exposures were analysed as continuous measures, rescaled to interquartile range

(IQR) increments and pollutant-specific increments [NO2 (10 µg/m3), NOX (20 µg/m

3), PM2.5

traffic-exhaust (1 µg/m3), PM2.5 traffic-non-exhaust (1 µg/m

3), PM2.5 (5 µg/m

3), PM10 (10 µg/m

3), O3 (10

µg/m3)]. As all noise metrics were highly correlated (ρ≥0.997), we limited analysis to one

day-time (LAeq,16hr) and one night-time (Lnight) metric. Noise metrics were right skewed, so

were categorised (LAeq,16hr <55dB (reference), 55-<60dB, 60-<65dB, ≥65dB; and Lnight <50dB

(reference), 50-<55dB, 55-<60dB, 60-<65dB, ≥65dB).

We analysed continuous birth weight using linear regression, and LBW/SGA using logistic

regression. We analysed birth weight and SGA overall and limited to term births. All

models were adjusted for maternal age (<25, 25-29, 30-34, ≥35); birth registration type

(within marriage, joint-same address, joint-different address, sole registered); Carstairs

deprivation quintile; tobacco expenditure; season and year of birth; and a random intercept

for MSOA. Birth weight and LBW were also adjusted for sex, gestational age (linear and

quadratic terms), and baby’s ethnicity (White, Asian, Black, Other). We ran two-air-

pollutant models for birth weight, assessing collinearity using the variance inflation factor

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(VIF). In joint air pollutant-noise models we further adjusted air pollutants for noise, and

vice versa.

We ran sensitivity analyses on joint air pollutant-noise models evaluating possible effect

modification by ethnicity (exposure x ethnicity interaction term); stratifying by term/preterm;

and excluding those exposed to aircraft/railway noise >50dB. All analyses were conducted in

Stata version 13.

Patient involvement: As this was a registry-based study there was no patient involvement.

Results

5.68% and 9.47% of births were classified as LBW and SGA respectively (Table 1). Over

the study period 2006-2010, mean birth weight increased, pregnancy average exposures to

NO2, NOX, PM2.5 traffic-exhaust , PM2.5, and PM10 decreased but increased for PM2.5 traffic-non-exhaust

and O3 , and the proportion of births with high noise exposures increased (Table 1), the latter

reflecting change in spatial distribution of birth addresses over time, as noise modelling was

not time-varying. Air pollutant exposures were positively correlated (0.46-1.00), except with

O3 (-0.46 to -0.77); day and night-time noise were very highly correlated (~1.00), and noise

was positively correlated with air pollutants (0.15-0.50) except O3 (~-0.15) (Supplementary

Table 1). Deprivation, tobacco expenditure, ethnicity, birth registration type, maternal age,

season and year were significantly associated with outcomes and exposures (Supplementary

Tables 2 and 3).

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Air pollution

In single-pollutant adjusted models, IQR increases in exposure to NO2, NOX, PM2.5 traffic-

exhaust, PM2.5 traffic-non-exhaust, PM2.5 and PM10 during pregnancy were significantly associated

with term birth weight reductions of 7 to 13g (Figure 1/Supplementary Table 4) and increased

odds of term LBW (except PM10)( Supplementary Table 5). Only PM2.5 traffic-exhaust and PM2.5

were significantly associated with increased odds of term SGA (Supplementary Table 6).

Protective associations were observed for O3. In two-air-pollutant models, only PM2.5 traffic-

exhaust was consistently associated with a significant reduction in term birth weight when

adjusted for each of the other pollutants (Figure 1). The model with PM2.5 traffic-exhaust and

PM2.5 traffic-non-exhaust is not presented, due to multicollinearity. After adjustment for PM2.5 traffic-

exhaust, no other pollutant demonstrated a significant reduction in birth weight: NO2, NOX and

O3 were attenuated to null, whilst PM2.5 and PM10 became positively associated with birth

weight.

Noise

In adjusted models, high day- and night-time noise exposures were associated with

significant reductions in term birth weight, with a significant linear trend. Lnight≥65dB (vs.

reference <50dB) was associated with a -13g (95% CI: -18, -8) mean difference in term birth

weight (Supplementary Table 4). There were no significant associations between noise and

term LBW or SGA in adjusted models (Supplementary Tables 5 and 6).

Air pollution and noise

Air pollutant associations with term birth weight, LBW and SGA were robust to adjustment

for noise (Figures 2 and 3/Table 2), with only small changes to coefficients/ORs. In these

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fully adjusted models, a per IQR increase (0.35 µg/m3) in PM2.5 traffic-exhaust was associated

with the largest birth weight reduction of -13g (95% CI: -15, -10), and 4% and 2% increased

odds of term LBW and SGA respectively. PM2.5 traffic-exhaust was the only air pollutant to be

significantly associated with term SGA after adjustment for noise.

Associations between night-time noise and term birth weight were attenuated to null when

adjusted, in turn, for primary traffic-related air pollutants (NO2, NOX, PM2.5 traffic-exhaust, PM2.5

traffic-non-exhaust), however a significant association remained for high night-time noise, albeit

with some attenuation, after adjustment for PM2.5, PM10, and O3 in turn (Figure 2). Similarly,

high day-time noise was not associated with reduced birth weight after adjustment for air

pollutants, except O3 (Figure 3).

Findings were very similar for birth weight and SGA when not limited to term births (not

shown).

Primary traffic air pollutant exposures in all trimesters were inversely associated with term

birth weight (p<0.001), and 3rd

trimester effect sizes were largest (Supplementary Table 7),

but there was little difference in magnitude between trimesters for other outcomes (not

shown). First and 3rd

trimester PM2.5, and 1st trimester PM10 were also significantly inversely

associated with term birth weight.

Compared to unadjusted analyses, effect sizes were generally reduced in single/joint pollutant

adjusted models (Table 2, Supplementary Tables 4-6). Given the strong relationship between

exposures and COA-level deprivation, we ran birth weight models without adjustment for

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Carstairs to check for overadjustment, however there were only small changes in birth weight

coefficients (<1g) and the pattern of results was unchanged (not shown). The inclusion of a

random intercept for MSOA (to models adjusted for all other covariates described) resulted in

considerable attenuation of associations between air pollutants and term birth weight (-18 to -

28% for primary traffic air pollutants, and -35 to -49% for pollutants including regional/urban

background contributions), but relatively small changes to associations for noise, term LBW

or SGA.

All sensitivity analyses were conducted on joint air pollutant-noise models. Noise analyses

were largely unchanged after excluding those exposed to aircraft/rail noise >50dB (not

shown). We noted significant interactions between ethnicity and both primary traffic air

pollutant and noise exposures in term birth weight analyses (not shown). Ethnicity-noise

interactions were still present after excluding those exposed to high aircraft/rail noise (Lday)

>50dB (which like ethnicity is spatially patterned across London). In ethnicity-stratified

models, inverse relationships between term birth weight and traffic-related air pollutants held

across all ethnic strata, but associations were generally strongest in White, then Black, then

Asian strata. In models adjusted for primary traffic-related air pollution (PM2.5 traffic-exhaust),

noise was not associated with reduced term birth weight in any ethnic strata (not shown).

Discussion

To our knowledge, this is the largest UK study on air pollution and birth weight, and the first

UK study and largest study worldwide of birth weight and noise exposure. We observed that

long-term exposure during pregnancy to NO2, NOX, PM2.5 overall and specifically from

traffic exhaust and non-exhaust sources, and PM10, were all associated with a detrimental

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impact on growth in utero, across London. However, our findings from two-pollutant models

suggest that it is PM2.5 traffic-exhaust, i.e. near-road exposure to fine particulate matter emitted

from vehicle exhausts (and emitted at much higher levels from diesel vs. petrol vehicles), that

is driving the air pollutant associations with reduced birth weight in this study setting, and

that apparent adverse effects of PM2.5 are mediated by PM2.5 traffic exhaust. Whilst road traffic

noise was inversely related to birth weight, this relationship was not robust to adjustment for

primary traffic air pollutants, including PM2.5 traffic-exhaust, and appeared to reflect confounding

by primary traffic air pollutant co-exposures.

This study, which is by far the largest on air pollution and noise to date, benefits from

address-level exposure assessment. For noise particularly, this represents an advance on

previous studies which have estimated noise exposure with lower spatial precision, e.g.

postcodes,(6) 50m/250m buffers around maternal address,(5) or based on road proximity,(24)

and consequently reduces potential exposure misclassification. We avoided selection bias by

using all birth registration data. Individual-level smoking/deprivation data were unavailable,

but we adjusted for these factors at COA-level and for birth registration type, which relates to

individual-level qualifications/housing tenure,(25) and thus socio-economic status. However,

we cannot exclude the possibility of residual confounding by maternal/passive smoking. We

could not account for residential mobility during pregnancy (~16% in UK(26)), nor

exposures away from maternal residence (e.g. workplace, transport), indoor air pollution, or

exposure modification due to behaviours (e.g. opening windows) or building characteristics

(e.g. bedroom façade). These could contribute to exposure misclassification. Third trimester

exposures may be least prone to exposure measurement bias from residential mobility, as

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exposures were assigned to birth address, which may partly explain stronger associations for

third trimester primary traffic air pollutant exposures.

Our single-air-pollutant model findings are consistent with recent meta-analyses which report

reduced mean birth weight and increased risk of LBW associated with NO2,(1) PM2.5,(27)

and PM10.(1, 28) Meta-analysis results for O3 are less clear: -10.0g (95% CI: -32.4, 12.4)

reduction in birth weight and OR for LBW of 1.01 (95% CI: 0.82, 1.25) per 20ppb increase in

pregnancy exposure to O3.(1) To our knowledge, only three Californian studies, have

examined source-specific PM2.5 and birth weight. Converted to the same IQR (0.35 µg/m3)

scale as our PM2.5 traffic-exhaust analyses, these studies each report 2% increased odds of term

LBW for PM2.5 from diesel and 3-4% increased odds for PM2.5 from gasoline,(29-31)

consistent in magnitude with our OR for term LBW of 1.04 per IQR increase. Reduced birth

weight/LBW has been associated with certain chemical constituents of PM2.5: potassium,

zinc, nickel, titanium, vanadium, organic carbon, nitrate, and elemental carbon.(27)

Elemental carbon is a major fraction of diesel exhaust particulate matter,(32) so our findings

for PM2.5 traffic-exhaust could also reflect adverse effects of elemental carbon. To our

knowledge, no previous study has reported two-pollutant models including source-specific

PM2.5. Our finding that adverse effects of PM2.5 upon birth weight, which have been widely

reported, may be mediated by PM2.5 traffic-exhaust is an important and novel contribution to

scientific knowledge.

The most recent systematic review of noise exposure and birth weight found “evidence

supportive of associations between LBW and noise exposure” but that this was

inconsistent,(4) based on 10 occupational studies, 4 aircraft noise studies, and 2 traffic noise

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studies. Three previous studies have examined long-term air pollution and noise exposures

jointly.(5-7) Our findings are consistent with a small cohort study (n=6438) in Barcelona,

which found elevated risks of term LBW and SGA associated with noise (non-significant)

and air pollution exposures (strongest for PM2.5, PM2.5-10, and PM10 and significant for 3rd

trimester for term LBW) in single-exposure adjusted models, but in a joint-exposure model

term LBW risk was associated with 3rd

trimester PM2.5 (per 3.6µg/m3 OR 1.31 [95% CI: 1.07,

1.61]), but not noise (per 6.7dB(A) OR 0.89 [95% CI: 0.71, 1.12]).(5) Term birth weight was

not associated with NO2, NOX, or road traffic noise, in either fully-adjusted single-exposure

models or joint-exposure models in the Danish National Birth Cohort (n=75,166).(7) Our

findings contrast with a registry based study in Vancouver (n=68,238), which found

associations between all transportation (road traffic/railway/aircraft) noise (Lden) and reduced

birth weight/LBW which remained after adjustment for PM2.5, PM10 and primary road traffic

air pollution (NO2, NO), however associations for air pollution exposure were attenuated to

null by adjustment for transportation noise.(6) Road traffic noise demonstrated similar

associations with birth weight (in single-exposure models, but road traffic noise adjusted for

air pollution was not analysed).(6) We, however, found that adjustment for PM2.5 or PM10

did not fully control for confounding of noise by air pollution while adjustment for primary

traffic air pollutants did. This should be noted by other researchers investigating potential

health effects of road traffic noise. Compared to London, the noise distribution in Vancouver

was wider (Lden mean 60.2/range 6.2–89.0 dB(A)), mean air pollution exposures were lower

and with less contrast in Vancouver (PM2.5 mean 4.1/range 0-11.3; NO2 mean 33.7/range: 0–

64.5) and Denmark (NO2 median 11.0 µg/m3, 5

th-95

th percentiles: 7.1–26.3 µg/m

3), and air

pollutant-noise correlations were lower in Vancouver (correlations with road traffic noise:

0.05 for NO2, 0.09 for PM2.5; and all transportation noise: 0.18 for NO2, 0.16 for PM2.5), but

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higher in Denmark (0.47 for NO2).(6, 7) These differences, which could reflect differences in

pollutant sources, may contribute to the contrasting findings from Denmark/Vancouver

compared to our study.

Biological mechanisms via which air pollution or noise may impair fetal growth are not

established. Hypothesised mechanisms for air pollution are oxidative stress; endocrine

disruption; changes to maternal-placental blood flow and oxygen/nutrition transfer;(33)

placental mitochondrial damage;(34) and placental growth/function,(35) whilst those for

noise are stress-triggered endocrine/immune response disruption, plasma catecholamine

increase/placental blood flow decrease,(4) hypertension,(36) and sleep disturbance.(37)

Convincing evidence that maternal passive smoking during pregnancy is causally related to

reduced birth weight,(38) strongly supports the biological plausibility of an association

between ambient air pollution and reduced birth weight, by analogy.

In conclusion, this study suggests that air pollution from road traffic, and specifically locally-

emitted PM2.5 from vehicle exhausts, is having a detrimental impact upon babies’ health in

Greater London, before they are born. There is limited evidence, and no consensus, as to the

effect of traffic-related noise on birth weight. Our results, from by far the largest study to

date, found no independent effect of traffic-related noise on birth weight, and suggest any

apparent relationship reflects traffic air pollutant co-exposures. Our findings should be

broadly generalisable to other UK and European cities/urban areas with comparable exposure

levels and profiles. At city scale, environmental health policies aimed at reducing locally-

emitted particulate matter, e.g. by tackling diesel vehicle emissions, could reduce the burden

of LBW, SGA, and subsequent morbidity. With the annual number of births projected to

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continue increasing in London,(39) the absolute health burden will increase at the population

level, unless air quality in London improves.

What is already known on this subject:

● Road traffic pollution comprises not only air pollutants such as NO2 and particulate

matter, but also noise.

● There is a large body of research demonstrating associations between maternal exposure

to ambient air pollution during pregnancy and reduced birth weight, low birth

weight/small for gestational age.

● The relationship between road traffic noise and birth weight is unclear, and research

examining traffic-related air pollutant and noise co-exposures together is very limited, so

the extent to which observed air pollution associations might be attributable to road traffic

noise is poorly understood.

What this study adds:

● We demonstrate evidence for reduced birth weight specifically in relation to the air

pollution profile of London, which has 19% of all births in England and Wales (40) per

year.

● Our findings suggest that it is exposure to fine particulate matter from road traffic exhaust

emissions specifically that is driving the air pollutant associations with reduced birth

weight in London, but that there is no independent effect of traffic-related noise on birth

weight.

● This study provides local evidence for UK clinicians caring for and advising pregnant

women and for UK policymakers, which suggests reducing exposure to traffic-related air

pollution, and particularly diesel exhaust emissions, could reduce the burden of low birth

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weight, small for gestational age, and subsequent morbidity, and ultimately give babies in

urban environments a healthier start in life.

Acknowledgements: We thank Margaret Douglass and Peter Hambly of the SAHSU

database team for technical support and the TRAFFIC study group for their constructive

comments. CACI tobacco expenditure data is © Copyright 1996-2014 CACI Limited. We

attest that we have obtained appropriate permissions and paid any required fees for use of

copyright protected materials.

Funding: This work was funded by the UK Natural Environment Research Council, Medical

Research Council, Economic and Social Research Council, Department of Environment,

Food and Rural Affairs, and Department of Health (NE/I00789X/1, NE/I008039/1) through

the cross-research council Environmental Exposures & Health Initiative. The work of the UK

Small Area Health Statistics Unit (SAHSU) is funded by Public Health England as part of the

MRC-PHE Centre for Environment and Health, funded also by the UK Medical Research

Council (MR/L01341X/1). The funders had no role in the study design; in the collection,

analysis and interpretation of data; in the writing of the report; and in the decision to submit

the article for publication.

Contributors: MBT, JG, HRA, SDB, FJK contributed to study conception and design; DF,

JG, SDB, DD, HRA and FJK to exposure assessment; and RG, DF and ALH to acquisition of

health and confounder data. RBS contributed to study design, wrote the statistical analysis

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plan, conducted the data analyses, and drafted the initial report. MBT contributed to the

statistical analysis plan, the data analyses and initial drafting of the report. MB contributed to

the study design and statistical analysis plan. All authors contributed to interpreting the

analyses and critically revising the article, approved the final draft, and agree to be

accountable for all aspects of the work. MBT is the guarantor of this paper. All authors had

full access to all of the data in the study and can take responsibility for the integrity of the

data and the accuracy of the data analysis.

Competing Interests: All authors have completed the ICMJE uniform disclosure form at

www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the

submitted work other than those detailed above; no financial relationships with any

organisations that might have an interest in the submitted work in the previous three years; no

other relationships or activities that could appear to have influenced the submitted work.

Copyright: The Corresponding Author has the right to grant on behalf of all authors and does

grant on behalf of all authors, a worldwide licence to the Publishers and its licensees in

perpetuity, in all forms, formats and media (whether known now or created in the future), to

i) publish, reproduce, distribute, display and store the Contribution, ii) translate the

Contribution into other languages, create adaptations, reprints, include within collections and

create summaries, extracts and/or, abstracts of the Contribution, iii) create any other

derivative work(s) based on the Contribution, iv) to exploit all subsidiary rights in the

Contribution, v) the inclusion of electronic links from the Contribution to third party material

where-ever it may be located; and, vi) licence any third party to do any or all of the above.

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Ethical approval: The study uses SAHSU data, supplied from the Office for National

Statistics; data use and link between UK National Births and Stillbirth register data and NHS

Numbers for Babies (NN4B) was covered by approval from the National Research Ethics

Service - 12/LO/0566 and 12/LO/0567- and by the Health Research Authority Confidentiality

Advisory Group (HRA-CAG) for Section 251 support (HRA – 14/CAG/1039).

Transparency: The lead author (the manuscript's guarantor) affirms that the manuscript is an

honest, accurate, and transparent account of the study being reported; that no important

aspects of the study have been omitted; and that any discrepancies from the study as planned

(and, if relevant, registered) have been explained.

Data sharing: Health data are available from the data providers on application with

appropriate ethics and governance permissions, but we do not hold data provider, ethics, or

governance permissions to share the dataset with third parties.

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Figures

Figure 1: Adjusted mean difference in term birth weight (g), associated with IQR

increases in air pollutants, in single- and two- air pollutant models

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All models in Figure 1 are adjusted for sex, maternal age, birth registration type, tobacco

expenditure (COA-level), Carstairs quintile (COA-level), individual-level ethnicity,

gestational age as linear and quadratic terms, season of birth, year, and random intercept for

MSOA in addition to including the air pollutants shown above. NO2 and NOX were not

entered into the same model together as they were too highly correlated. PM2.5 and PM10 were

not entered into the same model together as PM2.5 is a substantial subset of PM10 (>50% by

mass).

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Figure 2: Adjusted mean difference in term birth weight (g), associated with night-time

noise (Lnight) and air pollutants, in single-exposure and joint-exposure models

Lnight is night-time noise. All models in Figure 2 are adjusted for sex, maternal age, birth

registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level),

individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year,

and random intercept for MSOA, in addition to including the air pollutant and/or noise

metrics shown above.

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Figure 3: Adjusted mean difference in term birth weight (g), associated with day-time

noise (LAeq,16hr) and air pollutants, in single-exposure and joint-exposure models

LAeq,16hr is day-time noise. All models in Figure 3 are adjusted for sex, maternal age, birth

registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level),

individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year,

and random intercept for MSOA in addition to including the air pollutant and/or noise metrics

shown above.

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Confidential: For Review Only26

Table 1: Characteristics of the study population (n=572,910), and distribution of pregnancy outcomes and exposures.

Variable N Mean

birth

weight (g)

LBW

(%)

term

LBW

(%)

SGA*

(%)

Mean pregnancy average concentration (µg/m3) % exposed ≥65dB

NO2 NOX PM2.5

traffic-

exhaust

PM2.5

traffic-non-

exhaust

PM2.5 PM10 O3 LAeq,16hr Lnight

Total population 572,910 3330 5.68 2.55 9.47 40.6 72.5 0.6 0.7 14.4 23.1 31.9 14.2 6.3

Infant sex

Male 293,322 3386 5.25 2.05 9.49 40.6 72.5 0.61 0.73 14.4 23.1 31.9 14.2 6.2

Female 279,588 3271 6.13 3.08 9.46 40.6 72.4 0.61 0.73 14.4 23.1 31.9 14.2 6.3

Maternal age

<25 107,450 3252 6.80 3.31 12.56 40.8 73.0 0.62 0.73 14.5 23.2 31.7 15.8 7.1

25-29 148,347 3311 5.73 2.77 9.62 40.5 72.3 0.61 0.73 14.4 23.1 31.9 15.3 6.9

30-34 178,961 3364 5.01 2.18 8.52 40.4 72.1 0.61 0.72 14.4 23.0 32.0 13.6 6.0

>=35 138,152 3367 5.62 2.23 8.20 40.6 72.7 0.61 0.72 14.4 23.1 31.8 12.3 5.3

Ethnicity

White 301,426 3415 4.25 1.71 9.50 39.8 70.5 0.59 0.70 14.3 22.9 32.3 12.9 5.5

Asian 99,773 3135 8.78 5.11 9.58 40.9 73.1 0.62 0.74 14.4 23.1 31.7 15.0 6.4

Black 98,687 3275 7.06 2.76 9.29 42.0 76.2 0.66 0.78 14.6 23.5 31.0 15.3 7.2

Other 73,024 3318 5.45 2.32 41.4 74.6 0.64 0.76 14.5 23.3 31.5 16.6 7.8

Birth registration

Within marriage† 366,767 3342 5.20 2.48 8.48 40.6 72.6 0.61 0.73 14.4 23.1 31.8 13.8 6.0

Sole registration 39,090 3240 8.15 3.43 12.67 41.4 74.5 0.64 0.75 14.6 23.3 31.4 15.7 7.4

Joint/same addr. 111,924 3358 5.45 2.20 10.17 40.0 70.9 0.60 0.71 14.4 23.0 32.3 14.8 6.7

Joint/different addr. 55,129 3258 7.58 3.21 12.59 40.8 73.1 0.63 0.74 14.4 23.1 31.7 14.5 6.5

Season of birth

Winter 138,297 3317 5.93 2.66 9.66 39.7 70.3 0.61 0.72 13.9 22.6 30.9 14.4 6.4

Spring 141,415 3328 5.71 2.59 9.65 43.4 79.9 0.68 0.79 14.8 23.8 27.3 13.9 6.0

Summer 146,600 3337 5.59 2.50 9.34 41.9 76.0 0.63 0.75 15.0 23.8 33.0 14.1 6.3

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Variable N Mean

birth

weight (g)

LBW

(%)

term

LBW

(%)

SGA*

(%)

Mean pregnancy average concentration (µg/m3) % exposed ≥65dB

NO2 NOX PM2.5

traffic-

exhaust

PM2.5

traffic-non-

exhaust

PM2.5 PM10 O3 LAeq,16hr Lnight

Autumn 146,598 3337 5.50 2.48 9.27 37.3 63.7 0.54 0.65 13.9 22.2 36.2 14.3 6.4

Year of birth

2006 108,190 3317 6.08 2.79 10.23 42.3 77.6 0.72 0.71 16.1 25.1 30.4 13.7 6.0

2007 113,092 3324 5.82 2.57 9.55 40.6 71.7 0.63 0.69 14.8 24.1 34.2 13.9 6.1

2008 113,213 3330 5.74 2.58 9.35 42.1 77.7 0.63 0.76 14.5 23.5 30.6 14.1 6.2

2009 116,454 3336 5.51 2.50 9.24 41.0 73.0 0.60 0.77 14.0 22.6 27.4 14.2 6.3

2010 121,961 3340 5.29 2.36 9.08 37.2 63.2 0.51 0.69 12.9 20.5 36.5 14.8 6.6

Carstairs quintile

1 - least deprived 89,401 3418 3.82 1.55 7.72 37.3 64.1 0.51 0.61 14.1 22.5 33.7 9.2 2.6

2 97,039 3380 4.56 2.03 8.81 39.3 69.3 0.57 0.69 14.3 22.8 32.6 13.6 5.6

3 106,936 3337 5.53 2.43 9.37 40.4 71.9 0.60 0.72 14.4 23.0 32.0 15.2 6.7

4 126,815 3303 6.28 2.89 10.07 41.1 73.8 0.63 0.74 14.5 23.2 31.6 15.9 7.2

5 - most deprived 152,719 3263 7.08 3.30 10.56 43.0 78.6 0.70 0.81 14.7 23.6 30.5 15.2 7.9

London

Inner 183,575 3332 5.62 2.52 9.87 45.1 84.3 0.78 0.88 14.8 24.0 29.4 17.1 9.5

Outer 389,335 3329 5.71 2.57 9.29 38.4 66.9 0.54 0.65 14.2 22.7 33.1 12.8 4.8

Abbreviations: LBW, low birth weight (<2500g); SGA, small-for-gestational-age. *SGA, % out of a total 499537 for whom sex-ethnicity-

specific SGA calculated. †includes civil partnerships.

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Table 2: Joint air-pollutant-noise models: Mean difference (95% CI) in birth weight (g) and OR (95%CI) for LBW and SGA associated

with air and noise pollution amongst term births

Joint air pollutant-noise model* Joint air pollutant-noise model* Joint air pollutant-noise model*

Term birth weight (g) Term LBW Term SGA

Exposure N MD (95%CI) p-value OR (95% CI) p-value N OR (95% CI) p-value

NO2 (per IQR) 540,365 -10.52 (-12.71, -8.33) <0.001 1.03 (1.00, 1.06) 0.043 471489 1.01 (0.99, 1.03) 0.176

NOX (per IQR) 540,365 -10.18 (-12.35, -8.00) <0.001 1.03 (1.00, 1.06) 0.029 471489 1.01 (1.00, 1.03) 0.161

PM2.5 traffic-exhaust (per IQR) 540,365 -12.68 (-15.04, -10.32) <0.001 1.04 (1.01, 1.08) 0.009 471489 1.02 (1.00, 1.04) 0.025

PM2.5 traffic-non-exhaust (per IQR) 540,365 -7.46 (-9.32, -5.61) <0.001 1.02 (1.00, 1.05) 0.087 471489 1.01 (0.99, 1.02) 0.388

PM2.5 (per IQR) 540,365 -11.24 (-14.88, -7.60) <0.001 1.06 (1.01, 1.12) 0.022 471489 1.03 (1.00, 1.06) 0.054

PM10 (per IQR) 540,365 -5.54 (-8.31, -2.76) <0.001 1.03 (0.99, 1.07) 0.176 471489 1.00 (0.98, 1.03) 0.761

O3 (per IQR) 540,365 4.48 (2.45, 6.50) <0.001 0.96 (0.94, 0.99) 0.013 471489 0.99 (0.98, 1.01) 0.413

LAeq,16hr

<55dB 157491 Reference Reference 138696 Reference 55-<60 dB 265603 3.95 (1.18, 6.71) 0.005 0.97 (0.93, 1.01) 0.181 232346 0.99 (0.96, 1.01) 0.242

60-<65 dB 40755 -0.45 (-5.19, 4.29) 0.852 1.01 (0.94, 1.08) 0.851 35334 1.01 (0.97, 1.05) 0.766

>=65dB 76516 4.35 (0.21, 8.49) 0.039 0.97 (0.91, 1.04) 0.389 65113 0.99 (0.95, 1.02) 0.423

p for trend 540365 0.113 0.535 471489 0.581

Lnight

<50dB 162260 Reference Reference 142880 Reference 50-<55 dB 257045 2.15 (-0.62, 4.92) 0.128 0.98 (0.94, 1.02) 0.392 224864 0.99 (0.97, 1.02) 0.638

55-<60 dB 40256 -0.54 (-5.29, 4.21) 0.824 0.99 (0.92, 1.07) 0.868 34960 1.02 (0.98, 1.06) 0.376

60-<65 dB 46994 1.71 (-2.86, 6.29) 0.462 1.00 (0.93, 1.07) 0.933 40344 0.99 (0.95, 1.03) 0.675

>=65dB 33810 0.97 (-4.77, 6.71) 0.739 0.97 (0.89, 1.06) 0.527 28441 1.01 (0.96, 1.06) 0.736

p for trend 540365 0.726 0.715 471489 0.803

*Models are adjusted as follow:

Term birth weight: Adjusted model covariates: sex, maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile

(COA-level), individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year (linear term) and random intercept for

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MSOA.

Term LBW: Adjusted model covariates: sex, maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-

level), individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year (linear term) and random intercept for

MSOA.

Term SGA: Adjusted model covariates: maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level),

season of birth, year (linear term) and random intercept for MSOA.

*All air pollution estimates are adjusted for daytime noise (LAeq,16hr), and noise estimates are adjusted for traffic-related air pollution exposure

(PM2.5 traffic-exhaust).

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Supplementary Table 1: Air pollution and road traffic noise exposures in the study population (N=572,910) and their correlations

Air pollutants (pregnancy average) (µg/m

3) Noise (annual average 2007)

(dB)

NO2 NOX PM2.5 traffic-

exhaust

PM2.5 traffic-

non-exhaust

PM2.5 PM10 O3 LAeq,16hr Lnight Lday Leve Lden

Summary statistics Mean 40.6 72.5 0.61 0.73 14.4 23.1 31.9 58.1 53.2 58.4 56.8 59.8

SD 6.7 18.0 0.24 0.25 1.4 2.3 6.2 5.2 5.4 5.2 4.9 5.2

Min 20.6 26.6 0.16 0.20 10.3 13.6 4.9 54.7 49.6 55.0 53.7 56.3

IQR 8.6 23.7 0.35 0.29 2.2 3.0 8.4 3.5 3.9 3.6 3.1 3.7

Max 191.6 543.7 7.10 6.59 26.6 48.8 55.8 86.0 80.0 86.4 84.4 86.7

Spearman’s

correlation

NO2 1.00

NOX 1.00 1.00

PM2.5 traffic-exhaust 0.95 0.95 1.00

PM2.5 traffic-non-

exhaust 0.90 0.89 0.93 1.00

PM2.5 0.68 0.69 0.68 0.46 1.00

PM10 0.77 0.78 0.78 0.58 0.95 1.00

O3 -0.76 -0.77 -0.68 -0.66 -0.46 -0.53 1.00

LAeq, 16hr 0.31 0.29 0.38 0.47 0.15 0.23 -0.14 1.00

Lnight 0.33 0.32 0.41 0.50 0.16 0.24 -0.15 1.00 1.00

Lday 0.30 0.29 0.38 0.47 0.15 0.23 -0.14 1.00 1.00 1.00

Leve 0.31 0.30 0.38 0.48 0.15 0.23 -0.14 1.00 1.00 1.00 1.00

Lden 0.32 0.31 0.40 0.50 0.15 0.24 -0.15 1.00 1.00 1.00 1.00 1.00

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Supplementary Table 2: Mean difference (95% CI) in birth weight (g) and OR (95%CI) for LBW and

SGA associated with potential confounding factors (univariate linear/logistic regression) amongst all live

singleton births

Birth weight (g) LBW SGA (sex/ethnicity-specific)

Variable N MD (95%CI) p-value N cases OR (95% CI) p-value N cases OR (95% CI) p-value

Gestational Age (weeks) 572,910 171.14 (170.54, 171.74) <0.001 32,532 0.39 (0.39, 0.39) <0.001

Tobacco expenditure (£) (COA) 572,910 -17.59 (-18.32, -16.87) <0.001 32,532 1.07 (1.07, 1.08) <0.001 47360 1.05 (1.04, 1.05) <0.001

Sex

Male 293,322 Reference 15,389 Reference

Female 279,588 -114.96 (-117.79, -112.13) <0.001 17,143 1.18 (1.15, 1.21) <0.001

Maternal age

<25 107,450 Reference 7305 Reference 11575 Reference

25-29 148,347 58.75 (54.45, 63.05) <0.001 8495 0.83 (0.81, 0.86) <0.001 12528 0.74 (0.72, 0.76) <0.001

30-34 178,961 111.46 (107.32, 115.61) <0.001 8969 0.72 (0.70, 0.75) <0.001 13404 0.65 (0.63, 0.67) <0.001

>=35 138,152 114.58 (110.21, 118.95) <0.001 7763 0.82 (0.79, 0.84) <0.001 9853 0.62 (0.60, 0.64) <0.001

p for trend 572,910 <0.001 <0.001 <0.001

Ethnicity

White 301,426 Reference 12,825 Reference

Asian 99,773 -280.32 (-284.18, -276.46) <0.001 8760 2.17 (2.11, 2.23) <0.001

Black 98,687 -140.59 (-144.47, -136.71) <0.001 6970 1.71 (1.66, 1.76) <0.001

Other 73,024 -97.67 (-102.03, -93.31) <0.001 3977 1.30 (1.25, 1.34) <0.001

Birth in marriage

Within marriage† 366,767 Reference 19,073 Reference 27319 Reference

Sole registration 39,090 -102.07 (-107.79, -96.35) <0.001 3185 1.62 (1.56, 1.68) <0.001 4224 1.57 (1.51, 1.62) <0.001

Joint/same addr. 111,924 16.04 (12.37, 19.71) <0.001 6095 1.05 (1.02, 1.08) 0.001 9982 1.22 (1.19, 1.25) <0.001

Joint/different addr. 55,129 -84.11 (-89.02, -79.21) <0.001 4179 1.50 (1.44, 1.55) <0.001 5835 1.55 (1.51, 1.60) <0.001

Year

2006 108,190 Reference 6583 Reference 9666 Reference

2007 113,092 7.06 (2.48, 11.64) 0.003 6578 0.95 (0.92, 0.99) 0.008 9406 0.93 (0.90, 0.96) <0.001

2008 113,213 13.58 (9.01, 18.16) <0.001 6503 0.94 (0.91, 0.97) 0.001 9208 0.90 (0.88, 0.93) <0.001

2009 116,454 19.20 (14.65, 23.75) <0.001 6415 0.90 (0.87, 0.93) <0.001 9401 0.89 (0.87, 0.92) <0.001

2010 121,961 22.88 (18.38, 27.38) <0.001 6453 0.86 (0.83, 0.89) <0.001 9679 0.88 (0.85, 0.90) <0.001

p for trend 572,910 <0.001 <0.001 <0.001

Season

Winter 138,297 Reference 8195 Reference 11646 Reference

Spring 141,415 11.09 (7.02, 15.17) <0.001 8074 0.96 (0.93, 0.99) 0.015 11932 1.00 (0.97, 1.03) 0.938 Summer 146,600 20.51 (16.48, 24.55) <0.001 8193 0.94 (0.91, 0.97) <0.001 11912 0.96 (0.94, 0.99) 0.008

Autumn 146,598 20.49 (16.45, 24.52) <0.001 8070 0.92 (0.90, 0.95) <0.001 11870 0.96 (0.93, 0.98) 0.001

Carstairs quintile (COA)

1 - least deprived 89,401 Reference 3418 Reference 6244 Reference

2 97,039 -38.31 (-43.28, -33.35) <0.001 4423 1.20 (1.15, 1.26) <0.001 7537 1.16 (1.12, 1.20) <0.001

3 106,936 -80.98 (-85.84, -76.12) <0.001 5913 1.47 (1.41, 1.54) <0.001 8649 1.24 (1.19, 1.28) <0.001

4 126,815 -115.96 (-120.64, -111.28) <0.001 7959 1.68 (1.62, 1.76) <0.001 10916 1.34 (1.30, 1.38) <0.001

5 - most deprived 152,719 -155.46 (-159.97, -150.94) <0.001 10,819 1.92 (1.84, 2.00) <0.001 14014 1.41 (1.37, 1.46) <0.001

p for trend 572,910 <0.001 <0.001 <0.001

Inner/Outer London

Inner 183,575 Reference 10,308 Reference 15670 Reference Outer 389,335 -3.69 (-6.74, -0.64) 0.018 22,224 1.02 (0.99, 1.04) 0.156 31690 0.94 (0.92, 0.95) <0.001

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Supplementary Table 3: Mean difference (95% CI) in exposure metric associated with potential confounding factors (univariate linear

regression) amongst all live singleton births NO2 (pregnancy average, µg/m3) NOX (pregnancy average, µg/m3) PM2.5 traffic-exhaust (pregnancy average,

µg/m3)

PM2.5 traffic-non-exhaust (pregnancy

average, µg/m3)

Variable N MD (95%CI) p-value MD (95%CI) p-value MD (95%CI) p-value MD (95%CI) p-value

Gestational Age (completed weeks) 572,910 0.02 (0.01, 0.03) <0.001 0.06 (0.03, 0.08) <0.001 0.00 (0.00, 0.00) 0.004 0.00 (-0.00, 0.00) 0.184

Tobacco expenditure (£) (COA) 572,910 0.79 (0.78, 0.79) <0.001 2.03 (2.01, 2.05) <0.001 0.03 (0.03, 0.03) <0.001 0.03 (0.03, 0.03) <0.001

Sex

Male 293,322 Reference Reference Reference Reference

Female 279,588 -0.02 (-0.05, 0.02) 0.300 -0.05 (-0.14, 0.05) 0.322 -0.00 (-0.00, 0.00) 0.265 -0.00 (-0.00, 0.00) 0.483

Maternal age

<25 107,450 Reference Reference Reference Reference

25-29 148,347 -0.27 (-0.32, -0.22) <0.001 -0.71 (-0.85, -0.57) <0.001 -0.01 (-0.01, -0.01) <0.001 -0.01 (-0.01, -0.01) <0.001

30-34 178,961 -0.35 (-0.40, -0.29) <0.001 -0.87 (-1.01, -0.73) <0.001 -0.01 (-0.02, -0.01) <0.001 -0.01 (-0.02, -0.01) <0.001

>=35 138,152 -0.14 (-0.19, -0.08) <0.001 -0.30 (-0.45, -0.16) <0.001 -0.01 (-0.01, -0.01) <0.001 -0.01 (-0.01, -0.01) <0.001

p for trend 572,910 <0.001 <0.001 <0.001 <0.001

Ethnicity

White 301,426 Reference Reference Reference Reference

Asian 99,773 1.07 (1.02, 1.12) <0.001 2.61 (2.48, 2.74) <0.001 0.03 (0.03, 0.03) <0.001 0.04 (0.04, 0.04) <0.001

Black 98,687 2.25 (2.21, 2.30) <0.001 5.74 (5.61, 5.87) <0.001 0.07 (0.07, 0.08) <0.001 0.08 (0.08, 0.08) <0.001

Other 73,024 1.59 (1.54, 1.65) <0.001 4.06 (3.92, 4.21) <0.001 0.05 (0.05, 0.06) <0.001 0.06 (0.06, 0.06) <0.001

Birth in marriage

Within marriage† 366,767 Reference Reference Reference Reference

Sole registration 39,090 0.74 (0.67, 0.81) <0.001 1.90 (1.71, 2.09) <0.001 0.03 (0.03, 0.03) <0.001 0.03 (0.03, 0.03) <0.001

Joint/same address 111,924 -0.66 (-0.70, -0.61) <0.001 -1.70 (-1.82, -1.58) <0.001 -0.02 (-0.02, -0.02) <0.001 -0.02 (-0.02, -0.02) <0.001

Joint/different address 55,129 0.21 (0.15, 0.27) <0.001 0.52 (0.35, 0.68) <0.001 0.01 (0.01, 0.01) <0.001 0.01 (0.01, 0.01) <0.001

Year

2006 108,190 Reference Reference Reference Reference

2007 113,092 -1.74 (-1.79, -1.69) <0.001 -5.82 (-5.97, -5.68) <0.001 -0.09 (-0.09, -0.09) <0.001 -0.02 (-0.03, -0.02) <0.001

2008 113,213 -0.24 (-0.29, -0.19) <0.001 0.14 (-0.01, 0.28) 0.059 -0.08 (-0.08, -0.08) <0.001 0.05 (0.04, 0.05) <0.001

2009 116,454 -1.27 (-1.32, -1.21) <0.001 -4.54 (-4.68, -4.40) <0.001 -0.12 (-0.12, -0.12) <0.001 0.06 (0.06, 0.06) <0.001

2010 121,961 -5.05 (-5.11, -5.00) <0.001 -14.41 (-14.55, -14.27) <0.001 -0.21 (-0.21, -0.21) <0.001 -0.03 (-0.03, -0.02) <0.001

p for trend 572,910 <0.001 <0.001 <0.001 <0.001

Season

Winter 138,297 Reference Reference Reference Reference

Spring 141,415 3.74 (3.69, 3.78) <0.001 9.61 (9.48, 9.74) <0.001 0.07 (0.06, 0.07) <0.001 0.07 (0.07, 0.07) <0.001

Summer 146,600 2.22 (2.17, 2.27) <0.001 5.75 (5.62, 5.87) <0.001 0.02 (0.01, 0.02) <0.001 0.03 (0.03, 0.03) <0.001

Autumn 146,598 -2.41 (-2.45, -2.36) <0.001 -6.57 (-6.70, -6.45) <0.001 -0.08 (-0.08, -0.08) <0.001 -0.06 (-0.06, -0.06) <0.001


1 - least deprived 89,401 Reference Reference Reference Reference

2 97,039 2.04 (1.99, 2.10) <0.001 5.16 (5.01, 5.32) <0.001 0.07 (0.07, 0.07) <0.001 0.08 (0.07, 0.08) <0.001

3 106,936 3.10 (3.04, 3.16) <0.001 7.82 (7.67, 7.98) <0.001 0.10 (0.10, 0.10) <0.001 0.11 (0.11, 0.11) <0.001

4 126,815 3.84 (3.79, 3.90) <0.001 9.67 (9.52, 9.82) <0.001 0.12 (0.12, 0.12) <0.001 0.14 (0.13, 0.14) <0.001

5 - most deprived 152,719 5.69 (5.64, 5.74) <0.001 14.49 (14.34, 14.63) <0.001 0.19 (0.19, 0.19) <0.001 0.20 (0.20, 0.20) <0.001

p for trend 572,910 <0.001 <0.001 <0.001 <0.001

Inner/Outer London

Inner 183,575 Reference Reference Reference Reference

Outer 389,335 -6.71 (-6.75, -6.68) <0.001 -17.44 (-17.53, -17.35) <0.001 -0.25 (-0.25, -0.24) <0.001 -0.23 (-0.23, -0.22) <0.001

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Supplementary Table 3 cont/d.

PM2.5 (pregnancy average, µg/m3) PM10 (pregnancy average, µg/m3) O3 (pregnancy average, µg/m3) LAeq,16hr (dB) Lnight (dB)

Variable MD (95%CI) p-value MD (95%CI) p-value MD (95%CI) p-value MD (95%CI) p-value MD (95%CI) p-value

Gestational Age (weeks) 0.01 (0.01, 0.01) <0.001 0.02 (0.01, 0.02) <0.001 -0.02 (-0.03, -0.02) <0.001 0.00 (-0.00, 0.01) 0.266 0.00 (-0.00, 0.01) 0.399

Tobacco expenditure (£) (COA) 0.08 (0.08, 0.08) <0.001 0.17 (0.16, 0.17) <0.001 -0.42 (-0.42, -0.41) <0.001 0.15 (0.14, 0.15) <0.001 0.18 (0.17, 0.19) <0.001

Sex

Male Reference Reference Reference Reference Reference

Female -0.01 (-0.01, 0.00) 0.173 -0.00 (-0.02, 0.01) 0.455 -0.00 (-0.03, 0.03) 0.981 0.01 (-0.02, 0.03) 0.666 0.01 (-0.02, 0.03) 0.674

Maternal age

<25 Reference Reference Reference Reference Reference

25-29 -0.08 (-0.09, -0.07) <0.001 -0.13 (-0.15, -0.11) <0.001 0.20 (0.15, 0.25) <0.001 -0.07 (-0.11, -0.03) 0.001 -0.09 (-0.13, -0.04) <0.001

30-34 -0.10 (-0.11, -0.09) <0.001 -0.19 (-0.21, -0.18) <0.001 0.27 (0.22, 0.32) <0.001 -0.37 (-0.41, -0.33) <0.001 -0.39 (-0.43, -0.35) <0.001

>=35 -0.09 (-0.10, -0.08) <0.001 -0.17 (-0.18, -0.15) <0.001 0.10 (0.05, 0.15) <0.001 -0.58 (-0.62, -0.54) <0.001 -0.61 (-0.65, -0.56) <0.001

p for trend <0.001 <0.001 <0.001 <0.001 <0.001

Ethnicity

White Reference Reference Reference Reference Reference

Asian 0.10 (0.09, 0.11) <0.001 0.20 (0.19, 0.22) <0.001 -0.66 (-0.71, -0.62) <0.001 0.35 (0.31, 0.38) <0.001 0.37 (0.33, 0.40) <0.001

Black 0.26 (0.25, 0.27) <0.001 0.52 (0.51, 0.54) <0.001 -1.34 (-1.38, -1.29) <0.001 0.45 (0.41, 0.49) <0.001 0.53 (0.49, 0.57) <0.001

Other 0.16 (0.15, 0.18) <0.001 0.34 (0.32, 0.35) <0.001 -0.82 (-0.87, -0.77) <0.001 0.62 (0.58, 0.66) <0.001 0.67 (0.62, 0.71) <0.001

Birth in marriage

Within marriage† Reference Reference Reference Reference Reference

Sole registration 0.13 (0.11, 0.14) <0.001 0.25 (0.22, 0.27) <0.001 -0.43 (-0.50, -0.37) <0.001 0.38 (0.33, 0.44) <0.001 0.42 (0.37, 0.48) <0.001

Joint/same address -0.07 (-0.08, -0.06) <0.001 -0.12 (-0.14, -0.11) <0.001 0.42 (0.38, 0.46) <0.001 0.19 (0.15, 0.22) <0.001 0.19 (0.15, 0.22) <0.001

Joint/different address 0.01 (-0.01, 0.02) 0.364 0.04 (0.02, 0.06) 0.001 -0.10 (-0.16, -0.05) <0.001 0.13 (0.09, 0.18) <0.001 0.16 (0.11, 0.21) <0.001

Year

2006 Reference Reference Reference Reference Reference

2007 -1.28 (-1.28, -1.27) <0.001 -0.97 (-0.99, -0.96) <0.001 3.75 (3.71, 3.79) <0.001 0.04 (-0.01, 0.08) 0.091 0.04 (-0.01, 0.08) 0.097

2008 -1.56 (-1.57, -1.56) <0.001 -1.56 (-1.57, -1.55) <0.001 0.18 (0.14, 0.22) <0.001 0.07 (0.03, 0.11) 0.001 0.07 (0.03, 0.12) 0.002

2009 -2.11 (-2.12, -2.10) <0.001 -2.45 (-2.46, -2.43) <0.001 -2.99 (-3.03, -2.95) <0.001 0.10 (0.06, 0.14) <0.001 0.10 (0.06, 0.15) <0.001

2010 -3.19 (-3.20, -3.18) <0.001 -4.59 (-4.60, -4.57) <0.001 6.07 (6.03, 6.12) <0.001 0.19 (0.14, 0.23) <0.001 0.19 (0.15, 0.24) <0.001

p for trend <0.001 <0.001 <0.001 <0.001 <0.001

Season

Winter Reference Reference Reference Reference Reference

Spring 0.91 (0.91, 0.92) <0.001 1.24 (1.22, 1.26) <0.001 -3.57 (-3.61, -3.53) <0.001 -0.07 (-0.11, -0.03) <0.001 -0.07 (-0.11, -0.03) <0.001

Summer 1.10 (1.09, 1.11) <0.001 1.19 (1.17, 1.21) <0.001 2.07 (2.03, 2.11) <0.001 -0.03 (-0.06, 0.01) 0.161 -0.03 (-0.07, 0.01) 0.135

Autumn -0.04 (-0.05, -0.03) <0.001 -0.35 (-0.36, -0.33) <0.001 5.26 (5.23, 5.30) <0.001 -0.01 (-0.05, 0.02) 0.493 -0.01 (-0.05, 0.02) 0.459


1 - least deprived Reference Reference Reference Reference Reference

2 0.16 (0.15, 0.18) <0.001 0.37 (0.35, 0.39) <0.001 -1.10 (-1.15, -1.04) <0.001 0.83 (0.78, 0.88) <0.001 0.89 (0.85, 0.94) <0.001

3 0.25 (0.24, 0.27) <0.001 0.56 (0.54, 0.58) <0.001 -1.74 (-1.80, -1.69) <0.001 1.07 (1.03, 1.12) <0.001 1.17 (1.12, 1.21) <0.001

4 0.34 (0.33, 0.35) <0.001 0.75 (0.73, 0.77) <0.001 -2.17 (-2.22, -2.12) <0.001 1.17 (1.13, 1.22) <0.001 1.30 (1.25, 1.34) <0.001

5 - most deprived 0.56 (0.55, 0.57) <0.001 1.18 (1.16, 1.20) <0.001 -3.18 (-3.23, -3.13) <0.001 1.20 (1.16, 1.24) <0.001 1.41 (1.37, 1.45) <0.001

p for trend <0.001 <0.001 <0.001 <0.001 <0.001

Inner/Outer London

Inner Reference Reference Reference Reference Reference

Outer -0.63 (-0.64, -0.62) <0.001 -1.29 (-1.30, -1.28) <0.001 3.68 (3.64, 3.71) <0.001 -0.80 (-0.83, -0.77) <0.001 -1.05 (-1.08, -1.02) <0.001

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Supplementary Table 4: Mean difference in term birth weight (g) associated with air and noise pollution (with 95% confidence

intervals)

Unadjusted single-exposure model Adjusted single-exposure model

Term birth weight (g) Term birth weight (g)

Exposure N MD (95%CI) p-value MD (95%CI) p-value

NO2 (per IQR) 540,365 -20.67 (-22.30, -19.04) <0.001 -10.97 (-12.98, -8.96) <0.001

NOX (per IQR) 540,365 -20.15 (-21.81, -18.49) <0.001 -10.74 (-12.76, -8.73) <0.001

PM2.5 traffic-exhaust (per IQR) 540,365 -23.09 (-24.89, -21.29) <0.001 -12.43 (-14.51, -10.35) <0.001

PM2.5 traffic-non-exhaust (per IQR) 540,365 -17.24 (-18.68, -15.80) <0.001 -7.41 (-8.96, -5.86) <0.001

PM2.5 (per IQR) 540,365 -14.61 (-16.58, -12.65) <0.001 -12.94 (-16.41, -9.47) <0.001

PM10 (per IQR) 540,365 -14.38 (-16.08, -12.69) <0.001 -7.27 (-9.84, -4.70) <0.001

O3 (per IQR) 540,365 14.53 (12.81, 16.25) <0.001 5.12 (3.11, 7.12) <0.001

LAeq,16hr

<55dB 157,491 Reference Reference

55-<60 dB 265,603 -3.80 (-6.74, -0.87) 0.011 2.02 (-0.73, 4.78) 0.150

60-<65 dB 40,755 -14.63 (-19.76, -9.49) <0.001 -4.70 (-9.39, -0.02) 0.049

>=65dB 76,516 -19.88 (-23.95, -15.81) <0.001 -5.23 (-9.00, -1.45) 0.007

p for trend 540,365 <0.001 0.001

Lnight

<50dB 162,260 Reference Reference

50-<55 dB 257,045 -6.63 (-9.56, -3.70) <0.001 0.08 (-2.67, 2.83) 0.956

55-<60 dB 40,256 -14.62 (-19.76, -9.47) <0.001 -4.64 (-9.33, 0.06) 0.053

60-<65 dB 46,994 -17.33 (-22.17, -12.49) <0.001 -4.34 (-8.76, 0.09) 0.055

>=65dB 33,810 -31.65 (-37.17, -26.13) <0.001 -12.66 (-17.77, -7.55) <0.001

p for trend 540,365 <0.001 <0.001

Adjusted model covariates: sex, maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level),

individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year (linear term) and random intercept for MSOA.

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Supplementary Table 5: Odds of term LBW (<2500g and ≥37 weeks gestation) associated with air and noise pollution (OR, 95%

confidence intervals)


Term LBW Term LBW

Exposure N N cases OR (95% CI) p-value OR (95% CI) p-value

NO2 (per IQR) 540,365 13,804 1.10 (1.07, 1.12) <0.001 1.03 (1.00, 1.06) 0.025

NOX (per IQR) 540,365 13,804 1.09 (1.07, 1.12) <0.001 1.03 (1.01, 1.06) 0.017

PM2.5 traffic-exhaust (per IQR) 540,365 13,804 1.10 (1.08, 1.13) <0.001 1.04 (1.01, 1.07) 0.006

PM2.5 traffic-non-exhaust (per IQR) 540,365 13,804 1.07 (1.05, 1.09) <0.001 1.02 (1.00, 1.04) 0.050

PM2.5 (per IQR) 540,365 13,804 1.10 (1.08, 1.13) <0.001 1.06 (1.01, 1.12) 0.013

PM10 (per IQR) 540,365 13,804 1.09 (1.07, 1.12) <0.001 1.03 (0.99, 1.07) 0.105

O3 (per IQR) 540,365 13,804 0.92 (0.90, 0.95) <0.001 0.96 (0.93, 0.99) 0.009

LAeq,16hr

<55dB 157,491 3,956 Reference Reference

55-<60 dB 265,603 6,719 1.01 (0.97, 1.05) 0.721 0.98 (0.94, 1.02) 0.334

60-<65 dB 40,755 1,093 1.07 (1.00, 1.14) 0.052 1.02 (0.95, 1.10) 0.517

>=65dB 76,516 2,036 1.06 (1.00, 1.12) 0.032 1.01 (0.95, 1.07) 0.775

p for trend 540,365 0.012 0.572

Lnight

<50dB 162,260 4,032 Reference Reference

50-<55 dB 257,045 6,546 1.03 (0.99, 1.07) 0.214 0.99 (0.95, 1.03) 0.664

55-<60 dB 40,256 1,054 1.06 (0.99, 1.13) 0.126 1.01 (0.94, 1.09) 0.771

60-<65 dB 46,994 1,253 1.07 (1.01, 1.15) 0.027 1.02 (0.95, 1.09) 0.554

>=65dB 33,810 919 1.10 (1.02, 1.18) 0.013 1.03 (0.95, 1.11) 0.510

p for trend 540,365 0.002 0.349

Adjusted model covariates: sex, maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level),

individual-level ethnicity, gestational age as linear and quadratic terms, season of birth, year (linear term) and random intercept for MSOA.

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Supplementary Table 6: Odds of term small-for-gestational-age (SGA) associated with air and noise pollution (odds ratios with 95%

confidence intervals)


Term sex-ethnic-specific SGA Term sex-ethnic-specific SGA

Exposure N N cases OR (95% CI) p-value OR (95% CI) p-value

NO2 (per IQR) 471489 44966 1.05 (1.04, 1.07) <0.001 1.01 (1.00, 1.03) 0.076

NOX (per IQR) 471489 44966 1.05 (1.04, 1.07) <0.001 1.01 (1.00, 1.03) 0.071

PM2.5 traffic-exhaust (per IQR) 471489 44966 1.07 (1.06, 1.08) <0.001 1.02 (1.01, 1.04) 0.009

PM2.5 traffic-non-exhaust (per IQR) 471489 44966 1.03 (1.02, 1.05) <0.001 1.01 (1.00, 1.02) 0.144

PM2.5 (per IQR) 471489 44966 1.08 (1.07, 1.10) <0.001 1.03 (1.00, 1.06) 0.024

PM10 (per IQR) 471489 44966 1.07 (1.05, 1.08) <0.001 1.01 (0.99, 1.03) 0.428

O3 (per IQR) 471489 44966 0.96 (0.94, 0.97) <0.001 0.99 (0.97, 1.01) 0.308

LAeq,16hr

<55dB 138696 13113 Reference Reference 55-<60 dB 232346 22008 1.00 (0.98, 1.03) 0.859 0.99 (0.97, 1.01) 0.417

60-<65 dB 35334 3458 1.04 (1.00, 1.08) 0.058 1.02 (0.98, 1.06) 0.463

>=65dB 65113 6387 1.04 (1.01, 1.07) 0.011 1.00 (0.97, 1.04) 0.771

p for trend 471489 0.004 0.567

Lnight

<50dB 142880 13406 Reference Reference 50-<55 dB 224864 21351 1.01 (0.99, 1.04) 0.256 1.00 (0.98, 1.02) 0.902

55-<60 dB 34960 3433 1.05 (1.01, 1.09) 0.012 1.03 (0.99, 1.07) 0.205

60-<65 dB 40344 3899 1.03 (1.00, 1.07) 0.088 1.00 (0.96, 1.04) 0.902

>=65dB 28441 2877 1.09 (1.04, 1.13) <0.001 1.03 (0.99, 1.08) 0.140

p for trend 471489 <0.001 0.156

Adjusted model covariates: maternal age, birth registration type, tobacco expenditure (COA-level), Carstairs quintile (COA-level), season of

birth, year (linear term) and random intercept for MSOA.

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nly

37

Supplementary Table 7: Adjusted trimester-specific air pollutant associations with term

birth weight (models adjusted for road traffic noise co-exposure)

(To allow comparison between trimesters for a given pollutant we present analyses per

specific µg/m3 increments, as the IQR varied between pregnancy and trimester-specific

averages).

Exposure

Exposure window

Term birth weight (g)

MD (95%CI) p-value

NO2 (per 10 µg/m3) Pregnancy -12.17 (-14.71, -9.64) <0.001

Trimester 1 -5.54 (-7.38, -3.69) <0.001

Trimester 2 -5.49 (-7.29, -3.68) <0.001

Trimester 3 -7.28 (-9.12, -5.44) <0.001

NOX (per 20 µg/m3) Pregnancy -8.58 (-10.41, -6.75) <0.001

Trimester 1 -3.76 (-5.07, -2.44) <0.001

Trimester 2 -3.98 (-5.29, -2.68) <0.001

Trimester 3 -5.14 (-6.48, -3.80) <0.001

PM2.5 traffic-exhaust (per 1 µg/m3) Pregnancy -36.44 (-43.22, -29.67) <0.001

Trimester 1 -22.04 (-27.52, -16.55) <0.001

Trimester 2 -23.93 (-29.40, -18.45) <0.001

Trimester 3 -26.65 (-32.40, -20.90) <0.001

PM2.5 traffic-non-exhaust (per 1 µg/m3) Pregnancy -25.74 (-32.14, -19.34) <0.001

Trimester 1 -14.48 (-19.68, -9.28) <0.001

Trimester 2 -17.10 (-22.31, -11.89) <0.001

Trimester 3 -18.94 (-24.21, -13.67) <0.001

PM2.5 (per 5 µg/m3) Pregnancy -25.95 (-34.35, -17.55) <0.001

Trimester 1 -6.11 (-9.51, -2.71) <0.001

Trimester 2 -2.24 (-5.51, 1.04) 0.180

Trimester 3 -4.01 (-7.45, -0.58) 0.022

PM10 (per 10 µg/m3) Pregnancy -18.23 (-27.36, -9.10) <0.001

Trimester 1 -11.82 (-16.85, -6.80) <0.001

Trimester 2 -1.86 (-6.33, 2.60) 0.414

Trimester 3 -1.55 (-6.01, 2.91) 0.496

O3 (per 10 µg/m3) Pregnancy 5.36 (2.94, 7.79) <0.001

Trimester 1 1.27 (-0.35, 2.89) 0.124

Trimester 2 2.24 (0.66, 3.82) 0.005

Trimester 3 3.31 (1.69, 4.94) <0.001

Birth weight models adjusted for: sex, maternal age, birth registration type, tobacco

expenditure (COA-level), Carstairs quintile (COA-level), individual-level ethnicity,

gestational age as linear and quadratic terms, season of birth, year (linear term), random

intercept for MSOA and daytime noise (LAeq,16hr). N for term birth weight = 540,365.

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confidential: for review only · complete list of authors: smith, rachel; imperial college london,...

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