Exposures to Environmental Agents and Preterm Delivery

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Exposures to Environmental Agents and Preterm
Delivery

• Matthew P. Longnecker, MD, ScD
• NIEHS Epidemiology Branch
• (National Institute of Environmental Health
  Sciences)

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Overview of presentation

• Scope of review
• Method of review
• Potential Risk Factors (order nonspecific?
  specific)
• Occupational
• Air pollutants
• DDE, the metabolite of DDT
• Potential risk factors (with less supporting
  data)
• Things that appear not to be risk factors
• Discussion

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Scope Environmental Agents and Preterm Delivery

• Focused on risk factors for preterm delivery
• Risk factors for other reproductive outcomes
  can be different than for preterm birth
  and are not covered in this review
• Environmental agents considered are
• Non-biologic foreign substances (or radiation)
  to which exposure was unintentional

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Method of Identifying Reports

• Searched MEDLINE database using PubMed
• Key word preterm or Labor, PrematureMESH
  and ltexposuregt, where exposure was
• environmental, air pollution, DDE, arsenic,
  cadmium, lead, occupation, disinfection
  byproducts, video, etc.
• Reviewed reference lists
  to identify everything
  relevant
• Re-expressed results as needed
  to increase comparability of
  results across studies

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Potential Risk Factors1Occupational Exposures

• Many associated with preterm birth in 1 study
• Criteria for presentation here
• If
  RR gt 1.5 or
  statistically significant
  and
• reported in 2 or more studies

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Occupations/occupational exposures that met
criteria

• Maternal occupations
• Metal, electrical, janitorial, food service,
  textiles
• Maternal occupational exposures
• Solvents
• Paternal occupations
• Food service, textiles
• Paternal occupational exposures
• Pesticides (e.g., atrazine in one study)

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Maternal food service work and preterm
birth (an example)
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Potential Risk Factors1Occupational Exposures,
cont.

• Example demonstrates features of occupational
  data
• Associations neither strong nor consistent
• Exposure data vague or imprecise
• e.g., job categories vary across studies
• Associations with paternal occupation stronger
  and more numerous than those for maternal
  occupation in several studies
• Among possible explanations is a male-mediated
  effect

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Potential Risk Factors2Air Pollutants and
Preterm Birth

• Two types
• Tobacco smoke pollution (passive smoking)
• Traditional air pollutants (e.g., particulates,
  SO2)

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Potential Risk Factors2a Tobacco Smoke Pollution
N.B. Ahluwalia and Windham RRs gt among older
mothers
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Potential Risk Factors2bTraditional Air
Pollutants

• 3 studies with ecologic-time series designs
• Limited of air monitoring stations (n2-67)
• Little person-level data
• ? Preterm delivery associated with ? SO2
  (Xu, 1995 Bobak, 2000)
• Consistent ? with suspended particulates

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Relative Risk of Preterm Birthper 50 ?g/m3
Suspended Particulates
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Potential Risk Factors2bTraditional Air
Pollutants, cont.

• Subtle associations with preterm birth detected
  within the range of exposure seen in the U.S.
• U.S. data on SO2 lacking
• Collecting better data will be a challenge
• Individual-level measurements expensive
• Limited data indicate air pollution also related
  to infant mortality (see Brunekreef, 1999)

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Potential Risk Factors3DDE, the metabolite of
DDT

• DDT used for malaria control in 25 countries
• DDE, the metabolite of DDT, is ubiquitous
• U.S. serum levels 5 of those in malaria areas
• Exposures in the U.S. used to be much higher
• Recent study of U.S. women from the 1960s, done
  using stored sera,
  showed ? risk of preterm birth with DDE

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Odds ratios for preterm birth
Trend p lt 0.0001
Longnecker et al. Lancet 2001358110-4.
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Potential Risk Factors3DDE, the metabolite of
DDT, cont.

• Other published data consistent but were from
  studies in populations with lower exposure
• If effect real, relevant only to countries using
  DDT
• If effect real, what else might we have
  overlooked?
• knowledge of DDE mechanism would guide

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Potential Risk FactorsWith Less Supporting Data

• PCBs (polychlorinated biphenyls)
• Various other chemical exposures
• Occupational, e.g., ethylene oxide, polyvinyl
  alcohol
• Groundwater nitrate
• Metals
• Arsenic
• Cadmium
• Lead (both maternal and paternal)

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Maternal lead and preterm birthbest large
studies--data summary
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Things that appear not to be risk factors

• chlorinated water disinfection byproducts
• use of video display terminals

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Discussion--1

• None of the factors presented are established
  as related to risk of preterm delivery
• Instead is a list of suspected agents

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Discussion2Risk factors for preterm birth?

• Specific occupations/occupational exposures
• metal, electric, janitor, food, textiles,
  solvents, pesticides
• Air pollution
• Environmental tobacco smoke
• Particulates
• DDT use
• relevant for 25 countries

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Discussion--3

• What might have been missed by this review?
• Agents implicated for other reproductive
  outcomes, but not studied with respect to preterm
• mycotoxins, dusts, mercury, ethylene glycol
  ethers
• Agents implicated by animal studies
• Agents with subtle effects

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Discussion--4

• Implications for research priorities
• One approach study suspected agents
  with the highest
  prevalence of exposure
• Air pollution
• Food service work
• Paternal pesticide exposure
• Knowledge of toxic mechanism in humans
  could guide selection of agents to study