TABLE 3.
Endpoints assessed.
| Endpoint | Exposure type | Publication year | First author | Study location | Health effect (effect/no effect) | Results | Level of confidence | Level of evidence |
|---|---|---|---|---|---|---|---|---|
| Birth outcomes associated with maternal exposure | ||||||||
| Preterm birth | ||||||||
| Preterm birth | Residential | 2002a | Yang (30) | Taiwan | No effect | OR 1.03(95% CI, 0.94–1.13) | Moderate | Inadequate |
| Preterm birth | Residential | 2015 | Stacy (35) | USA | No effect | OR ≈ 1.0(95% CI, crossing 1) (data presented in figure, no actual number) for fourth quartile vs. first quartile exposure | Moderate | Inadequate |
| Preterm birth | Residential | 2016 | Casey (29) | USA | Effect | OR 1.9(95% CI, 1.2–2.9) for fourth quartile vs. first quartile exposure | High | High |
| Preterm birth | Residential | 2001a | Lin (25) | Taiwan | Effect | OR 1.41 (95% CI, 1.08–1.82) | Moderate | Moderate |
| Preterm birth | Residential | 2003 | Tsai (23) | Taiwan | Effect | OR 1.11 (95% CI, 1.02–1.21) | Moderate | Moderate |
| Preterm birth | Residential | 2002b | Yang (24) | Taiwan | Effect | OR 1.18 (95% CI, 1.04–1.34) | Moderate | Moderate |
| Preterm birth | Residential | 2004 | Yang (26) | Taiwan | Effect | OR 1.14(95% CI, 1.01–1.28) | Moderate | Moderate |
| Preterm birth | Residential | 2014 | McKenzie (32) | USA | Effect | OR 0.91 (95% CI, 0.85–0.98) | High | High |
| Miscarriage | ||||||||
| Miscarriage | Residential | 1988 | Axelsson (27) | Sweden | No effect | OR 1.15(95% CI, 0.75–1.76) | Moderate | Inadequate |
| Miscarriage | Residential | 2002 | Sebastian (34) | Ecuador | Effect | OR 2.47 (95% CI, 1.61–3.79) | High | High |
| Miscarriage | Occupational | 1998 | Xu (36) | China | Effect | OR 2.7 (95% CI, 1.8–3.9) | High | High |
| Miscarriage | Occupational | 1989 | Axelsson (28) | Sweden | Effect | Observed/expected = 3, P<.05 | Very low | NA |
| Stillbirth | ||||||||
| Stillbirth | Residential | 2002 | Sebastian (34) | Ecuador | No effect | OR 0.85 (95% CI, 0.35–2.05) | Low | Inadequate |
| Stillbirth | Residential | 2002 | Oliveira (33) | Brazil | No effect | OR 0.78 (95% CI, 0.22–2.72) P=.659 | Low | Inadequate |
| Birth weight | ||||||||
| Low birth weight (term) | Residential | 2002a | Yang (39) | Taiwan | No effect | OR 1.07(95% CI, 0.95–1.22) | Moderate | Inadequate |
| Low birth weight | Residential | 2002 | Oliveira (33) | Brazil | No effect | OR 1.42 (95% CI, 0.87–2.31) | Moderate | Inadequate |
| Birth weight (term) | Residential | 2016 | Casey (29) | USA | No effect | Difference in mean: −20 g (95% CI, −56–16) for fourth quartile vs. first quartile exposure | Moderate | Inadequate |
| Birth weight | Residential | 1988 | Axelsson (27) | Sweden | No effect | Mean ± SD: 3,464 ±507 vs. 3,405 ± 581; difference in mean: 59 g, P>.05 for first baby | Moderate | Inadequate |
| Low birth weight (term) | Residential | 2001b | Lin (31) | Taiwan | Effect | OR 1.77(95% CI, 1.0–3.1) | Moderate | Moderate |
| Low birth weight (term) | Residential | 2014 | McKenzie (32) | USA | Effect | OR 0.9 (95% CI, 0.8–1.0) for high exposure vs. reference | Moderate | Moderate |
| Low birth weight | Residential | 1988 | Axelsson (27) | Sweden | Effect | exposed area: observed/expected = 0.66 (95% CI, 0.44, 0.94) | Moderate | Moderate |
| Birth weight | Residential | 2015 | Stacy (35) | USA | Effect | 3,323.1 ± 558.2 vs. 3,343.9 ± 543.9 (difference in mean: −20.8g) P=.02 for fourth quartile vs. first quartile exposure | Moderate | Moderate |
| Birth weight (small for gestational age) | Residential | 2015 | Stacy (35) | USA | Effect | OR 1.34(95% CI, 1.10–1.63) for fourth quartile vs. first quartile exposure | Moderate | Moderate |
| Birth weight | Occupational | 1989 | Axelsson (28) | Sweden | Effect | No statistical conclusion | Very low | NA |
| Birth Defects | ||||||||
| Birth defects (not specified) | Residential | 2002 | Oliveira (33) | Brazil | No effect | OR 1.08 (95% CI, 0.30–3.88) | Low | Inadequate |
| Birth defects (oral clefts) | Residential | 2014 | McKenzie (32) | USA | No effect | OR 0.82 (95% CI, 0.55–1.2) for high exposure vs. reference | Moderate | Inadequate |
| Birth defects (congenital heart defect) | Residential | 2014 | McKenzie (32) | USA | Effect | OR 1.3 (95% CI, 1.2–1.5) for high exposure vs. reference | Moderate | Moderate |
| Birth defects (neural tube defects) | Residential | 2014 | McKenzie (32) | USA | Effect | OR 2.0 (95% CI, 1.0–3.9) for high exposure vs. reference | Moderate | Moderate |
| Birth defects (oral clefts) | 2006 | Chevrier(30) | France | Effect | OR 3.64 (95% CI, 1.5–8.8) | Moderate | NA | |
| Birth defects (not specified) | Residential | 1988 | Axelsson (27) | Sweden | Effect | Observed/expected = 0.68 based on registry of congenital malformation, observed/expected = 0.79 based on medical birth registry | Very low | NA |
| Sex ratio | ||||||||
| Sex ratio | Residential | 2000a | Yang (37) | Taiwan | No effect | Not significant (Z scores for individual year of a total of 26 y were listed in table) | Moderate | Inadequate |
| Sex ratio | Residential | 2000b | Yang (24) | Taiwan | Effect | Male/female = 109.3 (Z=2.96, P=.003) | Moderate | Moderate |
| Semen quality, fertility, and birth outcomes associated with adult paternal exposures | ||||||||
| Sperm and Fertility | ||||||||
| Sperm concentration | Occupational | 1985 | Rosenberg (40) | Unknown | No effect | Unexposed = 80.8 mill/mL; exposed = 66.9 mill/mL: P=.16 | Low | Inadequate |
| Sperm concentration | Occupational | 1997 | Khalifa (42) | Saudi Arabia | Effect | During employment = 0.02B mill/mL to 3.2 mill/mL; after employment = 12 mill/mL to 20.6 mill/mL | Very low | NA |
| Sperm concentration | Occupational | 2001 | Wang (41) | China | Effect | Control = 60.07 mill/mL, exposed = 52.52 mill/mL | Moderate | Moderate |
| Sperm count | Occupational | 2001 | Wang (41) | China | Effect | Control = 152 mill/ejac, exposed = 127.02 mill/ejac | Moderate | Moderate |
| Sperm motility | Occupational | 1997 | Khalifa (42) | Saudi Arabia | Effect | During employment: rapid = 0–15, sluggish = 0–15%; after employment: rapid = 30–40, sluggish = 5–15% | Very low | NA |
| Sperm motility | Occupational | 2001 | Wang (41) | China | Effect | Control = 2.41, scale, exposed = 2.02 (P<.05) | Moderate | Moderate |
| Sperm motility | Experimental | 2013 | Mandani (43) | Unknown | Effect | Control = 76%, 0.3 ppm = 2.2%(P<.001) | High | High |
| Sperm motility | Experimental | 2013 | Mandani (43) | Unknown | Effect | Control = 76%, 0.05 ppm = 52%(P<.01) | High | High |
| Sperm viability | Occupational | 2001 | Wang (41) | China | No effect | Control = 61.44%, Exposed = 63.41 % (P>.05) | Moderate | Inadequate |
| Sperm viability | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 59%, 0.05 ppm = 49% | High | High |
| Sperm viability | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 60%, 0.05 ppm = 52% (P<.01) | High | High |
| DNA damage, intact DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 86.5%, phenol-hydroquinone = 47.9% (P<.001) | High | High |
| DNA damage, denatured SS DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 14.5%, phenol-hydroquinone = 63.3% (P<.001) | High | High |
| DNA damage, effective DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 73.5%, phenol-hydroquinone = 40.5% (P<.001) | High | High |
| DNA damage, intact DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 86.5%, catechol = 55.3% (P<.001) | High | High |
| DNA damage, denatured SS DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 14.5%, catechol = 44.7% (P<.001) | High | High |
| DNA damage, effective DNA | Occupational | 2013 | Mandani (43) | Unknown | Effect | Control = 73.5%, catechol = 47% (P<.001) | High | High |
| Sperm morphology | Occupational | 1985 | Rosenberg (40) | Unknown | No effect | Unexposed = 49.1%; exposed = 44.5% (P=.94) | Low | Inadequate |
| Sperm morphology | Occupational | 1997 | Khalifa (42) | Saudi Arabia | Effect | During employment = 10–90%; after employment = 10–35% | Very low | NA |
| Fertility | Occupational | 1999 | Bull (44) | Unknown | No effect | FR 0.89 (95% CI, 0.61–1.29) | Low | Inadequate |
| Paternal birth outcomes | ||||||||
| Miscarriages | Occupational | 1999 | Bull (44) | Unknown | No effect | OR 1.1 (95% CI, 0.4–3.1) | Low | Inadequate |
| OR 1.4 (95% CI, 0.6–3.2) | ||||||||
| Birth defects | Occupational | 2012 | Desrosiers (45) | USA | Effect | OR 2 (95% CI, 0.8–5.1) | Low | Low |
| Birth defects | Occupational | 2012 | Desrosiers (45) | USA | Effect | OR 2.8 (95% CI, 0.9–9.1) | Low | Low |
| Birth defects | Occupational | 2012 | Desrosiers (45) | USA | Effect | OR 2.6 (95% CI, 1.1–6.5) | Low | Low |
| Birth defects | Occupational | 2012 | Desrosiers (45) | USA | Effect | OR 1.6(95% CI, 1.0–2.4) | Low | Low |
| Childhood cancer | Occupational | 1987 | Johnson (46) | USA | No effect | OR 2.7 (95% CI, 0.9–7.8) | Very low | NA |
| Reproductive cancer | ||||||||
| Prostate cancer | ||||||||
| Prostate cancer | Residential | 1984 | Kaldor (49) | USA | Effect | Trend (P=.002) for increasing prostate cancer incidence rates with areas of increasing exposure | Moderate | Moderate |
| Prostate cancer | Residential | 1989 | Schechter(52) | Canada | No effect | SIR 1.76 (95% CI, 0.84–4.38) | Very low | NA |
| Prostate cancer | Occupational | 2006 | Rybicki (48) | USA | No effect | OR 1.12 (95% CI, 0.73–1.73); P=.61 | Low | Inadequate |
| Prostate cancer | Occupational | 2006 | Rybicki (48) | USA | No effect | OR 0.74 (95% CI, 0.48–1.13); P=.16 | Low | Inadequate |
| Prostate cancer | Occupational | 1991 | Christie (47) | Australia | No effect | SIR 1.0 (95% CI, 0.4–1.9) | Low | Inadequate |
| Prostate cancer | Occupational | 2004 | Gun (22) | Australia | Effect | SIR 1.19(95% CI, 1.00–1.40) | Moderate | Moderate |
| Prostate cancer | Occupational | 2006 | Gun (21) | Australia | Effect | SIR 1.18 (95% CI, 1.04–1.34) | Moderate | Moderate |
| Prostate cancer | Occupational | 1997 | Jarvholm (50) | Sweden | No effect | SIR 1.1 (90% CI, 0.78–1.5) | Very low | NA |
| Prostate cancer | Occupational | 2003 | Lewis (51) | Canada | No effect | SIR 0.67 (95% CI, 0.41–1.03) | Very low | NA |
| Testicular cancer | ||||||||
| Testicular cancer | Residential | 1984 | Kaldor (49) | USA | No effect | No trend (P>.1) | Low | Inadequate |
| Testicular cancer | Occupational | 2004 | Gun (22) | Australia | No effect | SIR 1.24 (95% CI, 0.68–2.08) | Low | Inadequate |
| Testicular cancer | Occupational | 2006 | Gun (21) | Australia | No effect | SIR 1.33 (95% CI, 0.80–2.08) | Low | Inadequate |
| Testicular cancer | Occupational | 1991 | Christie (47) | Australia | No effect | SIR 1.0(95% CI, 0.2–2.8) | Very low | NA |
| Testicular cancer | Occupational | 2003 | Lewis (51) | Canada | No effect | SIR 0.82 (95% CI, 0.45–1.37) | Very low | NA |
| Reproductive tract cancer | ||||||||
| Cervical cancer | Residential | 1984 | Kaldor (49) | USA | No effect | No trend (P>.1) | Low | Inadequate |
| Uterine cancer | Residential | 1984 | Kaldor (49) | USA | No effect | No trend (P>.1) | Low | Inadequate |
| Gynecologic cancer | Residential | 1989 | Schechter (52) | Canada | No effect | 1 case out of 1,038 residents (no statistical analysis) | Very low | NA |
| Cervical cancer | Occupational | 2004 | Gun (22) | Australia | No effect | SIR 1.61 (95% CI, 0.33–4.71) | Very low | NA |
| Cervical cancer | Occupational | 2003 | Lewis (51) | Canada | Effect | SIR 0.42 (95% CI, 0.17–0.86) | Very low | NA |
| Uterine cancer | Occupational | 2003 | Lewis (51) | Canada | Effect | SIR 0.31 (95% CI, 0.06–0.89) | Very low | NA |
| Ovarian, fallopian tube, and broad ligament cancer | Occupational | 2003 | Lewis (51) | Canada | No effect | SIR 1.40 (95% CI, 0.78–2.30) | Very low | NA |
| Breast cancer | ||||||||
| Breast cancer | Residential | 1984 | Kaldor (49) | USA | No effect | No trend (P>.1) | Low | Inadequate |
| Breast cancer | Residential | 1989 | Schechter (52) | Canada | No effect | 9 cases out of 1,038 residents (no statistical analysis) | Very low | NA |
| Breast cancer | Occupational | 2004 | Gun (22) | Australia | No effect | SIR 1.02 (95% CI, 0.53–1.79) | Low | Inadequate |
| Breast cancer | Occupational | 2003 | Lewis (51) | Canada | No effect | SIR 1.02 (95% CI, 080–1.28) | Very low | NA |
Note: Results are limited to highest dose group or most relevant exposure group. Complete results in more descriptive detail can be found in Supplemental Table 2. China = People’s Republic of China; CI = confidence interval; FR = fecundity ratio; OR = odds ratio; ppm = parts per million; SD = standard deviation; SIR = standard incidence ratio; NA = not applicable.