Metals and welding: Pregnancy outcome and fertility Markku Sallmén Finnish Institute of Occupational Health

Simultaneous exposure to several metals n Studies around Rönnskär copper smelter ð excess of spontaneous abortion, and stillbirths in pregnancies of wives of men exposed to lead, copper, zinc, gold, silver, cadmium, mercury, arsenic, and sulfur dioxide ð carry-home exposure to the wives remains a possible alternative explanation

Population-based studies n Rachootin and Olsen 1983 ð case couples examined or treated for a problem of infertility at Odense University Hospital ð questionnaire information on job and exposure ð female exposure to lead, mercury, and cadmium were associated with infertility

Environmental exposure to lead n Study in Kosovo in the vicinity of a lead smelter ð current (1986) blood lead levels 0.77 µmol/l (range ) among women in exposed town; 0.25 ( ) in reference town ð no excess of spontaneous abortion was observed in exposed women as compared with women in reference town

Female Lead Exposure and Spontaneous Abortion B-Pb µmol/l OR95% CI r Taskinen Measured within a year of pregnancy: > r Borja-Aburto et al >

Maternal lead exposure and fecundability n Sallmén et al 1995 Þ study among women biologically monitored for exposure to lead blood leadFDR95% CI <0.5 µmol/l µmol/l µmol/l Eight most heavily exposed subjects: µmol/l

Maternal lead exposure and cognitive development; prospective studies StudyMean Blood LeadEffect Boston7.37 µg/dl+ Cincinnati >14.1+ Cleveland > 6.5- Port Pirie14.4->21.2->17.6+ Sydney9.1->8.1->12.5- Yugoslavia >24.3(+/-)

Fecundability ratios by number of amalgams prepared per week and number of poor mercury hygienic factors; Rowland et al 1994 No of amalgamsNo of poor hygienic factors per week ( )( )( ) ( )( )( ) > ( )( )( )

Female mercury exposure and pregnancy outcome n Human data scanty and inconsistent n suggestive findings on menstrual disorders, spontaneous abortion, stillbirth and congenital malformations n also negative findings n teratogenic and fetotoxic in animal tests n => exposure should be restricted

Female and Cadmium n Lower birth weight, pregnancy complications, poor mental development suggested n Classified as a carcinogen n => reasonable to restrict the exposure of pregnant women

Lead and semen quality Apostoli et al 1997: n Exposure to lead at blood lead 1.9 µmol/L (40 µg/dL) is hazardous for male reproductive function n reduced sperm count, volume, and density n changed sperm motility and morphology n a modest effect on endocrine profile is possible Viskum et al 1999: n The effect is, at least partially, reversible

Male lead exposure and clinically defined infertility Sitarek et al 1998 (in Polish with English abstract), infertility as the number of couples waiting 12 months or more for their pregnancy GroupN (all)% infertile Controls < 1 µmol/L µmol/L > 1.9 µmol/L exp. level unknown

Studies on Birth Rates and Male Exposure to Lead StudyPbB level Effect n Selevan et al µmol/l+ n Coste et al µmol/l- n Gennart et al µmol/l+ n Lin et al – duration of exp. >5 years,2.4 µmol/l+ n Bonde and Kolstad µmol/l- + reduced fertility, - no effect

Relative Risk (RR) of Infertility and Male Exposure to Lead; Sallmén et al 2000 Estimated PbB RR 95% C.I. µmol/L >

Fecundability Density Ratio (FDR) of Pregnancies by Father’s Exposure to Lead; Sallmén et al 2000 Estimated PbB µmol/l N FDR 95% C.I > > 1.5 (combined)

Male Lead Exposure and Spontaneous Abortion Study PbB µmol/l OR 95% CI Selevan > Al-Hakkak p<.01 Lindbohm > Alexander >

Male Lead Exposure and Congenital Malformations or Perinatal Death StudyPbB µmol/l OR 95% CI M: Sallmén 1992> P: Kristensen 1993exposed P/M: Alexander > M=malformation study P=perinatal death study

Male Mercury Exposure and Spontaneous Abortion n Alcser et al 1989 (lifetime sum of individual quarter-year mercury levels) HGU-LEQUOR95% CI µg/L µg/L n Cordier et al 1991 U-HG µg/LOR95% CI >

Welding and semen quality: Danish study among 430 first-time pregnancy planners n Hjollund et al 1998  no clear differences attributable to welding in proportions of morphologically normal sperm, sperm motility, or sex hormones  finding may not apply to high-level exposure to welding fume or heat  no differences in urine concentration of chromium, manganese, or nickel between welders and non-welding metal workers

Welding and time to pregnancy: Danish study among 430 first-time pregnancy planners n Hjollund et al 1998  no overall effect of male welding on fertility  a decreased fecundability among smoking welders associated with both current and previous exposure; not a priori hypothesis  clear improvement of the work environment in Denmark during last decades