Environmental Impact on Congenital Anomalies CONCLUSIONS

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Environmental Impact on Congenital
AnomaliesCONCLUSIONS

• Luc Hens
• Human Ecology Department
• Vrije Universiteit Brussel
• E-mail human.ecology_at_vub.ac.be

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Issues

1. Problem formulation
2. Methodological approaches
3. Mechanisms
4. Communications

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Congenital Anomalies
Cardiac defects Limb anomalies Chromosomal syndromes Urinary system Central nervous system and neural tube Oral clefts 25 17 12 15 10 6
commonly studied in relation to environmental
exposure
After Dolk and Vrijheid, 2003
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Chemicals associated with congenital anomalies in
humans

• Pharmaceuticals (DES, Thalidomide, Wafarin)
• Hair dyes
• Pesticides
• Non-pesticide ED (bisphenol A, phtalates, TCDD,
  vinyl chloride)
• Heavy metals (Pb, Hg, Cd, As, Cr and Ni)
• Organic solvents (styrene)

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Exposure conditions associated with congenital
anomalies

1. Drinking water (heavy metals, nitrates,
   chlorinated substances)
2. Residence near (hazardous) waste deposit sites
3. Pesticides in agricultural areas
4. Air pollution
5. Food contamination (dioxins, PCBs)
6. Industrial point sources (smelters, incinerators)
7. Disasters (Hiroshima, Minamata)
8. (Working conditions hair dressers)

Examples in Kos 2005 workshop
After Dolk and Vrijheid, 2003
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Problem situation

1. Embryonic and fetal life are sensitive periods to
   environmental exposures
2. Increasing number of chemicals and exposure
   conditions are associated with congenital
   anomalies
3. Increasing prevalence of selected congenital
   anomalies (hypospadias, cryptorchidism,
   gastroschisis) in industrialized countries
4. Convergence between pollutants in environmental
   health outcomes
5. Links between congenital anomalies, fertility and
   pregnancy loss (mechanisms?, risk factors?)

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Epidemiological evidence

1. Limited
2. RR is significant for environmental exposure
3. Limitations3.1 statistical power, sensitivity,
   dilution3.2 consistency of diagnosis (e.g.
   hypospadias)3.3 missing what is real
   finding what is not real

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Risk figures
Living near deposite sites
1.1 Non-chromosomal anomalies 1.33
1.2 Chromosomal anomalies 1.2
Vrijheid and Dolk, 2005
Pesticide purchase and tractor pesticide spraying equipment
2.1 Cryptorchidism and vegetable farming 1.7
1.2 Chromosomal anomalies 2.3
Kristensen et al., 1997
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Risk figures
DDE in mother blood, third trimester of pregnancy
3.1 Cryptorchidism 1.3
3.2 Hypospadia 1.2
Longnecker et al., 2002
Total effective xenoestrogen burden (TEXB)
4.1 Cryptorchidism 2.8

Olea et al., 2005
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Developmental toxicological evidence

1. Standard tests exist (two generation essay)
2. Interesting developments (e.g. stem cells)
3. No single test

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Clinical evidence

1. Historical examples of the alert physician1.1
   Thalidomide1.2 Anticonvulsants1.3 PCBs
2. Systematic survelance of public health
   (Eurocat)2.1 Limited information2.2 Important
   methodological challenges2.3 More coordination
   necessary

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Wildlife evidence

1. Selected cases1.1 EDs cause abortion in sea
   lions1.2 DDT/DDE cause cryptorchidism in rodents
2. Congenital defects in relation to pollution are
   found in2.1 fish intersex2.2 amphibians
   intersex, gonidal dysgenesis, hermaphroditism2.3
   Mammals impaired reproduction, hermaphroditism,
   abnormal testes, impaired spermatogenesis
3. Fast accumulating evidence

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Examples of mechanisms

1. Thalidomide I and F growth factor mediated
   mechanism
2. Steroidogenesis in testes
3. Testicular dysgenesis syndrome (TDS)

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Changing concepts

1. Not only dose matters (practical threshold)
2. Exposure window sensitivity period timing is
   crucial
3. Individual susceptibility
4. Long latency
5. Consider mixture (of chemicals, of chemicals with
   body molecules)

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Information

1. Parents prior to conception
2. Prenatal service providers and counsellors (e.g.
   OTIS)
3. Decision makers3.1 principles3.2 messages

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Core messages for couples

1. Be aware of pollutants in your lifestyle
   (cosmetics, medical drugs, food, pesticide use in
   gardening)
2. Care about your internal environment (long term)
3. Health practices iodine intake, folic acid,
   antioxidants and breastfeeding

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Core messages for counselors

1. Evaluate environmental aspects (not only
   genetics)
2. Defining and communicate risk
3. Bring down avoidable medication during
   pregnancy3.1 prescription behavior3.2
   alternatives

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Principles for decision making

1. How much evidence is enough?1.1 Bradford Hill
   criteria1.2 Related models (e.g. IPCC criteria)
2. Preventable conditions
3. Precautionary principles

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Core messages for policy making

1. Even if the proportion of congenital anomalies
   attributable to environmental pollution might not
   be high, any excess cases represent a failure of
   our environmental health protection system
2. Precautionary new generation of standards
3. Growing evidence mainly from wildlife to bring
   EDCs under prior authorization under REACH

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At last

1. Submit manuscripts not later than August 20th
   2005
2. THANK YOU