1 Department of Preventive Medicine, College of Medicine, Ewha Medical Research Center, Ewha Womans University, 2 Department of Obstetrics and Gynecology, College of Medicine, Ewha Womans University, 3 Department of Occupational and Environmental Medicine, College of Medicine, Inha University and 4 Department of Epidemiology and Biostatistics and Institute of Health and Environmental Sciences, School of Public Health, Seoul National University, Korea
5 To whom correspondence should be addressed at: Department of Preventive Medicine, College of Medicine, Ewha Womans University, 9111, Mok-6-Dong, Yangcheon-Gu, Seoul, Korea (158710). e-mail: eunheeha{at}ewha.ac.kr
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Abstract |
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Key words: air pollution/carbon monoxide/low birth weight/PM10/nitrogen dioxide/sulphur dioxide
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Introduction |
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In recent years, air pollution is considered to be an important cause or risk factor for reproductive health. There have been growing concerns about the adverse effects of air pollution on birth outcomes such as LBW, intrauterine growth retardation (IUGR), preterm births and birth defects (Bobak and Leon, 1992; Dejmek et al., 1999
; Bobak, 2000
; Ritz et al., 2002
). A lot of evidence for the effect of air pollution on LBW has been published, although there are many other risk factors such as infant sex and race, paternal weight and height, gestational weight gain, parity, caloric intake, maternal morbidity during pregnancy, cigarette smoking and alcohol consumption (Kramer, 1987
). Studies conducted in China, the Czech Republic, and the United States reported a relationship between air pollution and LBW (Wang et al., 1997
; Bobak, 2000
; Maisonet et al., 2001
). The results of these studies, however, are not consistent, particularly regarding the effect period of each air pollutant.
Some studies reported that exposure during the first trimester was associated with an increased risk for LBW. In an animal study, the period shortly after conception was the most susceptible to the induction of developmental changes by air pollutants (Generoso et al., 1987; Rutledge, 1997
). Human studies also suggested that initial changes leading to IUGR might be triggered in early pregnancy, around the time of implantation (Khong et al., 1986
; Duvekot et al., 1995
). A number of epidemiological studies indicated that the risk for LBW or IUGR is also increased in the first trimester of pregnancy. Dejmek et al. (1999
) found the risk of IUGR associated with exposure to particles <10 µm in aerodynamic diameter (PM10) during the first month of pregnancy. Bobak (2000
) also reported that air pollutants [sulphur dioxide (SO2) and total suspended particulate] had greater effects on LBW in the first trimester than other trimesters.
On the contrary, other studies have suggested that exposure to air pollution during the last trimester has greater effects on LBW. Gruenwald (1978) showed that the peak period for weight growth is around 33 weeks gestation. In terms of air pollution, third trimester exposure to total suspended particles (TSP) and SO2 was associated with increased risk of LBW in Beijing (Wang et al., 1997
). In addition, carbon monoxide (CO) exposure during the third trimester was associated with LBW in Southern California (Ritz and Yu, 1999
) and the North-Eastern United States (Maisonet et al., 2001
).
These inconsistencies raise the issue of whether the peak effect period of air pollution on LBW differs across different populations and pollutants. Furthermore, previous studies investigated the relationship between air pollution and LBW using a broad range of exposure times. Thus, little is known about which specific exposure time of specific pollutants contributes to LBW. Therefore, we evaluated the specific timing of peak effects of air pollutants on LBW throughout the gestational period.
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Materials and methods |
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We obtained air pollution data from the Department of the Environment regarding concentrations of PM10 (by -ray absorption), SO2 (by ultraviolet fluorescence), CO (by non-dispersive infrared photometry) and nitrogen dioxide (NO2) by chemiluminescence between January 1, 1995 and December 31, 1998 in Seoul (Ministry of Environment and National Institute of Environmental Research, 1999). Exposure measurements during the study period were taken from 20 monitoring stations covering nearly all areas of the city. The major source of air pollution in the study area is automobile exhaust emissions. We averaged the hourly measurements arithmetically across all monitoring stations and calculated a 24 h average. These data were used to estimate the exposure during each trimester and each month of pregnancy on the basis of the gestational age and birth date of each newborn.
We used a generalized additive model (GAM), which allowed regressions to include non-parametric smooth functions in order to control the potential non-linear dependence of each birth on date and season (Hastie and Tibshirani, 1996). First, we included a smoothing function for date and/or season in the model using LOESS, a moving regression smoother to control for seasonal and long-term trends (Cleveland and Devlin, 1988
). The model fitted well when the date only was entered into the model. The selection criterion for goodness of fit was evaluated using Akaikes information criterion (AIC) (Akaike, 1973
). We similarly chose the number of degrees of freedom for gestational age that lowered the AIC. Second, we controlled the co-variates, which are known as risk factors for LBW. We applied the model both with and without parental occupation, and obtained the better-fitted model for this analysis without parental occupation. Finally, the optimal model included indicator variables for infant sex, birth order, maternal age, parental education level, time trend and gestational age.
We calculated average concentrations for each pollutant through the whole period, in each trimester (1st, 2nd and 3rd) and in each month of pregnancy. The gestational period was divided into three trimesters of 3 calendar months (Cunningham et al., 2001
). The air pollution data were analysed as both continuous and categorical variables. We categorized pollutant levels into quartiles. To assess an exposure response relationship, we applied the models in which dummy variables were used to indicate categories based on quartiles of the pollutant concentrations. Exposure in the bottom quartile for each pollutant was used as the reference category. We present the risk magnitudes as odds ratios (OR) of LBW associated with the interquartile change of each pollutant. In order to clarify the specific effect period of air pollution exposure on LBW, we created two separate subgroups based on exposure levels during pregnancy and analysed the two separately. To assess the effect of exposure during the latter 5 months of pregnancy, we formed subgroup 1, which included only mothers who were at low exposure levels (<25th of each air pollutant level) during the first 5 months of pregnancy. To assess the effect of exposure during the first 5 months of pregnancy, we restricted subgroup 2 to those who were at low exposure levels during the latter 5 months of pregnancy.
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Results |
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Discussion |
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The biological mechanisms whereby air pollution might influence birth weight remain to be explained. One hypothesized pathway is that placental inflammation may play an important role in the physiological pathway between air pollution exposure and LBW. It is possible that air pollution during pregnancy leads to placental inflammation, which impairs placental function (Dexter et al., 2000). Salafia et al. (1995
) reported that chronic inflammation brought about growth restriction, independently of placental vasculopathy. In the present study, PM10, SO2 and NO2 exposures from first through second trimesters appeared to have the largest effect on LBW. In terms of the biological mechanism on LBW, it is reasonable to consider PM10, SO2, and NO2 together rather than separately because they represent fine particles that are believed to be a risk pollutant (Ha et al., 2001
). In addition, these pollutants were correlated strongly with each other and exerted an effect on LBW within similar periods. Particle exposure in vitro and in exposed animals causes oxidative stress (Carter et al., 1997; Kadiiska et al., 1997
) and can increase the permeability of lung epithelium (Li et al., 1994), allowing particles access to the endothelial cells and the blood (Donaldson et al., 2001). PM10 and gaseous pollutants such as SO2 and NO2 lead to pulmonary inflammation with a systemic release of cytokines (Walters et al., 2001
; Nemmar et al., 2002
) and increase blood viscosity (Peters et al., 1997
; Prescott et al., 2000
). Increased blood viscosity is associated with decreased oxygen diffusion (Zondervan et al., 1988
) and may interfere with the supply of oxygen and nutrients to the fetus. In addition, some toxicants from air pollutants could cross the placenta with direct effects on fetal development (Dejmek et al., 1999
).
Alternatively, placental insufficiency may be an important pathway. Placental insufficiency reduces the oxygen and nourishment supplies to the fetus (Behrman, 1992) and leads to growth retardation (Cunningham et al., 2001a
,b
). Exposure to air pollution in early pregnancy could cause insufficient trophoblast formation, and lead to insufficient placental vascularization (Roberts et al., 1991
; Duvekot et al., 1995
). Chronic reductions of uteroplacental circulation due to the effects of air pollution could result in fetal hypoxia and IUGR (Wilson, 1971
; Werler et al., 1985
).
A number of potential mechanisms for CO have been suggested. The fetus in the uterus may be particularly susceptible to hypoxia from CO exposure even if the maternal blood level of CO is non-toxic (Gabrielli et al., 1995). Therefore, exposure to low levels of ambient CO during pregnancy could result in tissue hypoxia by increasing maternal and fetal carboxyhaemoglobin concentrations and decreasing fetal O2 tensions or O2 carrying capacity (Longo, 1976
). Furthermore, maternal CO inhalation can affect the fetus more severely than the mother in terms of oxygenation of tissues (Longo, 1977
).
This study has several limitations. We did not consider several potential risk factors for LBW, including parental weight and height, history of adverse pregnancy outcomes, maternal nutrition, gestational weight gain, cigarette smoking, alcohol consumption and occupational exposures (Paige and Davis, 1986; Kramer, 1987
; Teitelman et al., 1990
; Dejmek et al., 2002
). However, because these factors are not expected to be correlated with daily air pollution levels (Schwartz and Morris, 1995
), the estimated effects of air pollution are unlikely to be confounded by these factors. On the other hand, when two pollutants were evaluated together, the effects of CO on LBW in the first trimester remained significant. In the second trimester, PM10, SO2 and NO2 were associated with LBW after controlling for CO. However, it is difficult to interpret this result because of co-linearity among pollutants (Pitard and Viel, 1997
). In addition, we used data from an ambient air monitoring station in exposure assessment and this may have resulted in exposure misclassification. However, recent studies have suggested that outdoor monitors can be used as surrogates for personal exposure (Janssen et al., 1998
, 1999). Even if there is a measurement error, it would not much bias the estimates and used to underestimate the effect of air pollution (Schwartz and Levin, 1999
; Zeger et al., 2000
).
On the other hand, our study had several strengths. We examined various specific exposure periods for air pollutants during pregnancy. Although Dejmek and Ritz analysed air pollution on the basis of average monthly exposure for IUGR and birth defects respectively (Dejmek et al., 1999; Ritz et al., 2002
), ours is the first study, to our knowledge, to identify an association between LBW and monthly exposure during pregnancy. We suggest that exposure to CO, PM10, SO2 and NO2 during early to mid pregnancy contribute to risks for LBW. Elucidating the biological mechanism for the effect of specific air pollutants on LBW will certainly be a task for future study.
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Acknowledgement |
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References |
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Berhman, R.E. (1992) Nelson Textbook of Pediatrics. 14th edn. WB Saunders, Philadelphia, USA.
Bobak, M. and Leon, D.A. (1992) Air pollution and infant mortality in the Czech Republic, 198688. Lancet, 340, 10101014.[CrossRef][ISI][Medline]
Bobak, M. (2000) Outdoor air pollution, low birth weight, and prematurity. Environ. Health. Perspect., 108, 173176.[ISI][Medline]
Carter, J.D., Ghio, A.J., Samet, J.M. and Devlin, R.B. (1997) Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol. Appl. Pharmacol., 146, 180188.[CrossRef][ISI][Medline]
CDC (2002) Youth and Family: Low Birth Weight Babies. Available http://hnb.ffh.vic.gov.au/commcare/yafs_yf.nsf/ [accessed 3 March 2002].
Cleveland, W.S. and Delvin, S.J. (1988) Robust locally-weighted regression and smoothing scatterplots. J. Am. Stat. Assoc., 74, 829836.
Cunningham, F.G., Gant, N.F., Levend, K.J., Gilstrap, L.C 3rd., Hauth, J.C. and Wenstrom, K.D. (2001a) Williams Obstetrics 21st edn. McGraw-Hill Companies, New York, USA. p 130.
Cunningham, F.G., Gant, N.F., Levend, K.J., Gilstrap, L.C 3rd., Hauth, J.C. and Wenstrom, K.D. (2001b) Williams Obstetrics 21st edn. McGraw-Hill Companies, New York, USA. pp 745746.
Dejmek, J., Selevan, S.G., Ivan Benes, I., Solansky, I. and rám, R.J. (1999) Fetal growth and maternal exposure to particulate matter during pregnancy. Environ. Health. Perspect., 107, 475480.[ISI][Medline]
Dejmek, J., Solansky, I., Podrazilova, K. and Sram, R.J. (2002) The exposure of non-smoking and smoking mothers to environmental tobacco smoke during different gestational phases and fetal growth. Environ. Health. Perspect., 110, 601606.
Dexter, S.C., Pinar, H., Malee, M.P., Hogan, J., Carpenter, M.W. and Vohr, B.R. (2000) Outcome of very low birth weight infants with histopathologic chorioamnionitis. Obstet. Gynecol., 96, 172177.
Donaldson, K., Stone, V., Seaton, A. and MacNee, W. (2001) Ambient particle inhalation and the cardiovascular system: potential mechanisms. Environ. Health Perspect., 109, 523527.
Duvekot, J.J., Cheriex, E.C. and Pieters, F.A.A. (1995) Severely impaired growth is preceded by maternal hemodynamic maladaptation in very early pregnancy. Acta. Obstet. Gynecol. Scand., 74, 693697.[ISI][Medline]
Ministry of Environment and National Institute of Environmental Research (1999) Annual Report of Ambient Air Quality in Korea, 1998. Ministry of Environment, Gwacheon, South Korea.
Gabrielli, A., Layon, A.J. and Gallarher, T.J. (1995) Carbon monoxide intoxication during pregnancy: A case presentation and pathophysiologic discussion, with emphasis on molecular mechanisms. J. Clin. Anesth., 7, 8287.[CrossRef][ISI][Medline]
Generoso, W.M., Rutledge, J.C., Cain, K.T., Hughes, L.A. and Braden, P.W. (1987) Exposure of female mice to ethylene oxide within hours after mating leads to fetal malformation and death. Mutat. Res., 176, 269274.[ISI][Medline]
Gouveia, N. and Fletcher, T. (2000) Respiratory diseases in children and outdoor air pollution in Sao Paulo, Brazil: a time series analysis. Occup. Environ. Med., 57, 477483.
Gruenwald, P. (1978) Intrauterine growth. In Stave, V. (ed) Perinatal physiology. Plenum Press, New York, NY, USA. pp 118.
Ha, E.H., Hong, Y.C., Lee, B.E., Woo, B.H., Schwartz, J. and Christiani, D.C. (2001) Is air pollution a risk factor for low birth weight in Seoul? Epidemiology, 12, 643648.[CrossRef][ISI][Medline]
Hack, M., Flannery, D.J., Schluchter, M., Cartar, L., Borawski, E. and Klein, N. (2002) Outcomes in young adulthood for very-low-birth-weight infants. N. Engl. J. Med., 346, 149157.
Hastie, T.J. and Tibshirani, R.J. (1996) Generalized additive models. Chapman & Hall, London, UK.
Janssen, N.A., Hoek, G., Brunekreef, B., Harssema, H., Mensink, I. and Zuidhof, A. (1998) Personal sampling of particles in adults: relation among personal, indoor, and outdoor air concentrations. Am. J. Epidemiol., 147, 537547.[Abstract]
Janssen, N.A., Hoek, G., Harssema, H. and Brunekreef, B. (1999) Personal exposure to fine particles in children correlates closely with ambient fine particles. Arch. Environ. Health, 54, 95100.[ISI][Medline]
Kadiiska, M.B., Mason, R.P., Dreher, K.L., Costa, D.L. and Ghio, A.J. (1997) In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem. Res. Toxicol., 10, 11041108.[CrossRef][ISI][Medline]
Khong, T.Y., De Wolf, F., Robertson, W.B. and Brosens, I. (1986) Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br. J. Obstet. Gynaecol., 93, 10491059.[ISI][Medline]
Kramer, M.S. (1987) Determinants of low birth weight: methodological assessment and meta-analysis. Bulletin of the World Health Organization, 65, 663737.[ISI][Medline]
Li, X.Y., Donaldson, K., Rahman, I. and MacNee, W. (1994) An investigation of the role of glutathione in increased epithelial permeability induced by cigarette smoke in vivo and in vitro. Am. J. Respir. Crit. Care Med., 149, 15181525.[Abstract]
Lin, C.A., Martins, M.A., Farhat, S.C., Pope, C.A., 3rd, Conceicao, G.M., Anastacio, V.M., Hatanaka, M., Andrade, W.C., Hamaue, W.R., Bohm, G.M. et al. 1999. Air pollution and respiratory illness of children in Sao Paulo, Brazil. Paediatr. Perinat. Epidemiol., 13, 475488.
Longo, L.D. (1976) Carbon monoxide: effects on oxygenation of the fetus in utero. Science, 194, 523525.
Longo, L.D. (1977) The biological effects of carbon monoxide on the pregnant women, fetus, and newborn infant. Am. J. Obstet. Gynecol., 129, 69103.[ISI][Medline]
Loomis, D., Castillejos, M., Gold, D.R., McDonnell, W. and Borja-Aburto, V.H. (1999) Air pollution and infant mortality in Mexico City. Epidemiology, 10, 118123.[CrossRef][ISI][Medline]
Maisonet, M., Bush, T.J., Correa, A. and Jaakkola, J.J.K. (2001) Relation between ambient air pollution and low birth weight in the Northeastern United States. Environmen. Health. Perspect., 109 (Suppl), S351-S356.
Nemmar, A., Hoet, P.H.M., Vanquickenborne, B., Dinsdale, D., Thomeer, M., Hoylaerts, M.F., Vanbilloen, H., Mortelmans, L., Nemery, B. et al. (2002) Passage of inhaled particles into the blood circulation in humans. Circulation, 105, 411414.
Paige, D. and Davis, L.R. (1986) Fetal growth, maternal nutrition, and dietary supplementation. Clin. Nutr., 5, 191199.
Peters, A., Doring, A., Wichmann, H.E. and Koenig, W. (1997) Increased plasma viscosity during an air pollution episode: a link to mortality? Lancet, 349, 15821587.[CrossRef][ISI][Medline]
Pitard, A. and Viel, J.F. (1997) Some methods to address co-linearity among pollutants in epidemiological time series. Stat. Med., 16, 527544.[CrossRef][ISI][Medline]
Prescott, G.J., Lee, R.J., Cohen, G.R., Elton, R.A., Lee, A.J., Fowkes, F.G. and Agius R.M. (2000) Investigation of factors which might indicate susceptibility to particulate air pollution. Occup. Environ. Med., 57, 5357.
Ritz, B. and Yu, F. (1999) The effect of ambient carbon monoxide on low birth weight among children born in Southern California between 1989 and 1993. Environ. Health. Perspect., 107, 1725.[ISI][Medline]
Ritz, B., Yu, F., Fruin, S., Chapa, G., Shaw, G.M. and Harris, J.A. (2002) Ambient air pollution and risk of birth defects in Southern California. Am. J. Epidemiol., 155, 1725.
Roberts, J.M., Taylor, R.N. and Goldfein, A. (1991) Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. Am. J. Hypertens., 4, 700708.[ISI][Medline]
Rutledge, J.C. (1997) Developmental toxicity induced during early stages of mammalian embryogenesis. Mutat. Res., 396, 113127.[ISI][Medline]
Salafia, C.M., Ernst, L.M., Pezzullo, J.C., Wolf, E.J. and Rosenkrantz, T.S. (1995) The very low birth weight infant: maternal complications leading to preterm birth, placental lesions, and intrauterine growth. Am. J. Perinatol., 12, 106110.
Schwartz, J, Morris, R. (1995) Air pollution and hospital admission for cardiovascular disease in Detroit, Michigan. Am. J. Epidemiol., 142, 2335.[Abstract]
Schwartz, J. and Levin, R. (1999) Drinking water turbidity and health. Epidemiology, 10, 8690.[ISI][Medline]
Teitelman, A.M., Welch, L.S., Hellenbrand, K.G. and Btacken, M.B. (1990) Effect of maternal work activity on preterm birth and low birth weight. Am. J. Epidemiol., 131, 104113.[Abstract]
Ventura, S.J., Martin, J.A., Curtin, S.C. and Mathews, T.J. (1998) Report of final natality statistics, 1996. Monthly vital statistics report. vol 46, no. 11 (Suppl). National Center for Health Statistics, Hyattsville, Maryland, USA.
Walters, D.M., Breysse, P.N. and Wills-Karp, M. (2001) Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice. Am. J. Respir. Crit. Care. Med., 164, 14381443.
Wang, X., Ding, H., Ryan, L. and Xu, X. (1997) Association between air pollution and low birth weight: a community-based study. Environ. Health. Perspect., 105, 514520.[ISI][Medline]
Werler, M.M., Pober, B.R. and Holmes, L.B. (1985) Smoking and pregnancy. Teratology, 32, 473481.[ISI][Medline]
Williams, L., Spence, A. and Tideman, S.C. (1977) Implications of the observed effects of air pollution on birth weight. Soc. Biol., 24, 19.[ISI][Medline]
Wilson, E.W. (1971) The effect of smoking in pregnancy on the placental co-efficient. N.Z. Med. J., 74, 384385.
Woodruff, T.J., Grillo, J. and Schoendorf, K.C. (1997) The relationship between selected causes of postneonatal infant mortality and particulate air pollution in the United States. Environ. Health. Persp., 105, 608612.[ISI][Medline]
Zeger, S.L., Thomas, D., Dominici, F., Samet, J.M., Schwartz, J., Dochery, D. and Cohen, A. (2000) Exposure measurement error in time-series studies of air pollution: concepts and consequences. Environ. Health. Perspect., 108, 419426.[ISI][Medline]
Zondervan, H.A. Oosting, J., Smorenberg-Schoorl, M.E. and Treffers, P.E. (1988) Maternal whole blood viscosity in pregnancy hypertension. Gynecol. Obstet. Invest., 25, 8388.[CrossRef][ISI][Medline]
Submitted on August 8, 2002; accepted on November 11, 2002.