Lessons from the Study of NonEnvironmental Factors

1
Lessons from the Study of Non-Environmental
Factors

• Epidemiologic Clues to the Study of the
  Environment and Preterm Birth

2
Overview of Presentation

• Influences on preterm birth often different from
  those affecting birthweight
• Diversity of predictors suggests multiple
  etiologic pathways
• Optimal subdividision of outcome unclear
• Difficult to isolate causal agents from behaviors
  socioeconomic conditions
• Promise for biological markers

3
Established Strong Predictors of Preterm Birth

• Multiple gestation
• Prior preterm birth
• African-American ethnicity

4
Probable Influences on Preterm Birth

• Reproductive tract infection
• Tobacco use
• Low prepregnancy weight
• Low socioeconomic status
• Other prior adverse pregnancy outcomes

5
Possible Influences on Preterm Birth

• Iron, folate,Vitamin C
• Cocaine, other illicit drugs
• Physical activity
• Psychological stress

6
Determinants of Preterm Birth Versus Reduced
Birthweight

• Modest overlap among preterm, LBW, SGA
• More marked birthweight differentials associated
  with race, SES, tobacco use
• Birthweight is more accurate than gestational
  age, more widely available
• Consider both preterm birth, growth restriction

7
Diverse Predictors Suggest Multiple Etiologic
Pathways

• Identified predictors suggest multiple small
  contributors, perhaps including environment
• Risks related to ethnicity, social class,
  tobacco, possible role of stress suggest diverse
  contributors

8
Etiologic Heterogeneity of Preterm Birth

• Risk factors may vary because of multiple causal
  pathways
• None are predominant
• Heterogeneity in causal pathways dilutes
  magnitude of association includes relevant with
  irrelevant subsets of preterm birth

9
Division Based on Clinical Presentation

• Clinical presentation idiopathic preterm labor,
  preterm premature rupture of membranes, medical
  indication
• Challenges questionable accuracy, may not be
  linked to etiology
• Generally accepted to isolate medically indicated
  from spontaneous less common to isolate preterm
  labor from preterm PROM

10
Evidence for Distinct and Shared Etiology

• Mixed evidence that risk factors for preterm
  labor and preterm PROM differ larger RRs for
  PROM for tobacco, African-American ethnicity
• Some evidence that major medical indications for
  intervention are shared hypertension, growth
  restriction predict spontaneous preterm birth,

11
Division Based on Degree of Prematurity

• Consequences differ markedly by gestational age
  do etiologic factors differ as well?
• Some indication of greater role for race,
  infection in early preterm births
• Implicit acceptance that determinants are common
  across lt37 wk spectrum
• Continuous measure of gestational age not
  recommended

12
Division Based on Pathophysiologic Mechanisms

• Most logical and potentially valuable, least
  extensively explored
• Klebanoff Infection/inflammation vs. vascular
  compromise
• Much overlap with pathways for pregnancy-induced
  hypertension, other complications

13
Difficult to Isolate Causes from Behavior,
Socioeconomic Conditions

• Exposures associated with unfavorable
  circumstances cocaine, physically demanding work
• Exposures associated with favorable circumstances
  leisure-time physical activity, prenatal
  vitamins
• Challenge to isolation of environmental agents

14
Potential for Use of Biological Markers

• Time course of pregnancy permits true prospective
  studies
• Applied in studies of nutrition, tobacco,
  cocaine, infection
• Prenatal care offers unusual specimen collection
  opportunities
• Potential value of placenta not fully developed

15
Lessons for the Study of Environmental Factors

• Recognize challenges in studying this endpoint
  accuracy, heterogeneity
• Consider established/suspected risk factors as
  models, potential confounders

16
Lessons for the Study of Environmental Factors

• Look for interface of environment with suspected
  pathophysiologic mechanisms
• Make full use of biological markers where
  applicable
• Integrate expertise in environmental sciences and
  reproductive health