Pesticides: Pregnancy outcome and fertility

1
Pesticides Pregnancy outcome and fertility

• Markku Sallmén
• Finnish Institute of Occupational Health

2
Pesticides

• The most extensively used group of toxic
  chemicals
• ca. 600 different active ingradients
• about 50,000 various formulations
• simultaneous exposure to different chemicals
  typical
• pesticide formulations may contain solvents

3
Pesticides

• Comparison between studies difficult
• Different pesticides are used for different
  purposes and in different areas
• Exposure levels vary considerably the highest
  exposures occur in developing countries in poorly
  controlled circumstances
• What is the affected gender?

4
DBCP

• The nematocide DBCP (dibromochloro-propane) is
  the most impressive occupational testicular toxin
  in men
• Toxic to spermatogonia, thus causing azoospermia
  and oligospermia
• only some affected workers had recovered from
  azoospermia to normal sperm count 7-11 years
  after exposure

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Pesticides shown adverse effects on
spermatogenesis

• DBCP
• 2,4-D (2,4-dichlorophenoxy acetic acid)
• ethylene dibromide
• chlordecone
• carbaryl

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Agent Orange

• A mixture of 2,4-D and 2,4,5-T (2,4,5-trichlorophe
  noxy acetic acid
• Association between paternal exposure and
  anencephaly and orofacial clefts
• Lowered sperm quality 10-20 years after military
  service among American Vietnam veterans

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Pesticides and male fecundability

• Study Association
• de Cock et al 1994
• Larsen et al 1998 -
• Thonneau et al 1999 -
• Curtis et al 1999 -
• Petrelli et al 2001
• Sallmén et al 2003 ()
• reduced fecundability, () suggestive
  association

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Pesticides and couples undergoing IVF treatment
(Tielemans et al)

• Reduced fertilization capacity
• Improved implantation rate
• Summary effect ?

9
Male pesticide exposure and spontaneous abortion

• Savitz et al 1994 reviewed 14 studies
• elevated RR in gt1 study YES
• RR gt 1.5 YES
• Evidence from high
• quality studies NO

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Male pesticide exposure and spontaneous abortion

• Study Association (OR)
• Arbuckle et al 1999
• farm couples, phenoxy herbicides
• lt20 weeks of gestation 1.1 0.6-1.9
• lt12 weeks of gestation 2.5 1.0-6.4
• husband not using protective 5.0 0.7-36.2
• equipment
• Petrelli et al 2000 3.8 1.2-12.0
• Crisostomo et al 2002 6.17 1.37-27.86

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Male pesticide exposure and spontaneous abortion

• Arbuckle et al 2001
• Ontario farm population
• timing of exposure
• preconceptional early (12 weeks) abortions
• postconceptional late (12-19 weeks) abortions

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Male pesticide exposure and congenital
malformations

• García 1998, a review on occupational exposure
  and congenital malformations
• 17 studies
• 4 studies showed an association
• Conclusion Inadequate evidence for either
  establishing a relationship between pesticides
  exposure in humans and birth defects or for
  rejecting it.

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Male pesticide exposure and congenital
malformations

• Pesticide applicators in the Red River Valley of
  Minnesota (Garry et al, 1996, 2002)
• 1996 a register-based study
• - excess in birth defects
• - seasonal pattern
• 2002 a cross-sectional interview study
• - rate of birth defects 7.6 (spring) vs. 3.7
  other season
• - herbicides risk of birth defects
• - fungisides determination of sex of the
  children

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Pesticides and female fertility

• Study Association
• Fuortes et al 1997
• Curtis et al 1999 -
• Abell et al 2000
• Greenlee et al 2003
• reduced fertility

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DDT/DDE and female fertilitya two-generation
study (Cohn et al 2003)

• Maternal serum Fecundability of
• concentration the daughter
• increasing DDT reduced fec.
• increasing DDE increased fec.

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Female pesticide exposure and pregnancy outcome

• Nurminen 1995, a review
• Definition of exposure
• ecological 5 studies
• place of residence 5 studies
• agricultural occupation 10 studies
• exposure at work 9 studies
• Conclusion the epidemiologic evidence is
  inconclusive as regards the risk of adverse
  pregnancy outcome

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Female pesticide exposure and spontaneous abortion

• Study Association
• Bell et al 2001 pesticides showed no strong
  association with fetal death

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Female pesticide exposure and congenital
malformations

• Study Association (OR)
• Medina-Carillo et al 2002 6.33 2.95-13.7
• occupational exposure
• Bell et al 2001 risk of malformation
• increased within the
• same square mile than the application

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Parental pesticide exposure and congenital
malformations

• Kristensen et al 1997 a study among Norwegian
  farmers
• Exposure to pesticides associated with
• spina bifida
• hydrocephaly
• limb reduction
• cryptorchidism
• hypospadias

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Female DDT/DDE exposure and preterm birth and
birth weight

• Study Association (OR)
• Longnecker et al 2001 concentration of DDE
• maternal serum DDE related to preterm
  birth in a dose- response manner
• Torres-Arreola et al 2003 a weak association
• maternal serum DDE with preterm birth
• Gladen at al 2003 no association with
• maternal milk DDE birth weight

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Parental pesticide exposure and childhood cancer

• There seems to be an association between father's
  work in agriculture and increased risk of brain
  tumors in their children
• Kristensen et al (1996) use of pesticides was
  associated with cancer at early age
• birth-month examination suggested
  paternal-mediated mechanism of pesticides

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Pesticides conclusion

• Several adverse outcomes in numerous studies
• some studies negative
• the evidence suggest, that exposure is associated
  with reproductive hazards
• gt exposure should be restricted
• Problem few harmful agents identified!