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Page 1: ars.els-cdn.com  · Web viewRosenberg. 1985. crs. sperm concentration. selection, performance. 3. 8. 37.5. probably low. moderate. imprecision (underpowered), risk of bias. low.

Supplemental Table 1. Rating Level of EvidenceFirst Author

Year Article Type

Reproductive Endpoints Type of Bias Present (Biases marked no)

Number of Bias Questions Answered No

Total Number of Bias Questions

Percentage of Bias

Bias Ranking

Initial Confidence

Downgrade Factors

Upgrade Factors

Confidence of Evidence

Direction (effect/ no effect)

Level of Evidence

Bull 1999 crs fecundity ratio performance, attrition, detection

3 8 37.5 probably low

moderate imprecision (underpowered)

low no effect inadequate

spontaneous abortions low no effect inadequateDesrosiers 2012 coh glaucoma/anterior chamber

defectsdetection 2 8 25.0 definitely

lowmoderate imprecision (low

sample size)low effect low

colonic atresia/stenosis low effect lowlimb deficiency, intercalary low effect lowASD (atrial septal defect) secundum or NOS

low effect low

Johnson 1987 coh confounding bias, detection bias

2 7 28.6 probably low

Moderate imprecision (underpowered)

very low no effect N/A

Khalifa 1997 cas sperm concentration other, confounding, performance, detection

4 6 66.7 probably high

very low imprecision (case study), risk of bias

very low effect N/A

sperm motility very low effect N/Asperm morphology very low effect N/Atesticular tissue disruption very low effect N/A

Mandani et al

2013 hct sperm motility – phenol - hydroquinone

selection, performance

2 9 22.2 definitely low

high large magnitude of effect, dose response

high effect high

sperm motility – catechol high effect highsperm viability – phenol - hydroquinone

high effect high

sperm motility – catechol high effect highsperm nuclear DNA Integrity high effect high

Rosenberg 1985 crs sperm concentration selection, performance

3 8 37.5 probably low

moderate imprecision (underpowered), risk of bias

low no effect inadequate

sperm concentration with hours worked

low no effect inadequate

sperm morphology probably low

moderate risk of bias moderate no effect inadequate

sperm morphology with hours worked

moderate no effect inadequate

Wang 2001 crs sperm concentration detection 2 8 25.0 definitely low

moderate risk of bias moderate effect moderate

sperm count moderate effect moderatesperm motility moderate effect moderateseminal volume moderate no effect Inadequatesperm viability moderate no effect Inadequateyears of exposure and various semen parameters

moderate no effect Inadequate

sperm concentration vs. years smoked and years of exposure were combined

moderate effect low

R.T. Gun 2004 coh prostate cancer selection, detection 3 8 37.5 probably low

low residual confounding

moderate effect moderate

testicular cancer selection, detection 3 8 37.5 probably low low no effect inadequate

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lowcervical cancer selection, detection 3 8 37.5 probably

lowlow imprecision very low no effect N/A

breast cancer selection, detection 3 8 37.5 probably low

low low no effect inadequate

R.T. Gun 2006 coh prostate cancer selection, detection 3 8 37.5 probably low

low residual confounding

moderate effect moderate

testicular cancer selection, detection 3 8 37.5 probably low

low low no effect inadequate

Benjamin A. Rybicki

2006 cas prostate cancer risk associated with lifetime occupational respiratory PAH exposure from petroleum

detection 1 8 12.5 definitely low

low low no effect inadequate

prostate cancer risk associated with lifetime occupational cutaneous PAH exposure from petroleum

detection 1 8 12.5 definitely low

low low no effect inadequate

John Kaldor

1984 coh prostate cancer other, detection, confounding, selective reporting

4 8 50.0 probably low

low dose response

moderate effect moderate

testicular cancer other, detection, confounding, selective reporting

4 8 50.0 probably low

low low no effect inadequate

breast cancer other, detection, confounding, selective reporting

4 8 50.0 probably low

low low no effect inadequate

cervical cancer other, detection, confounding, selective reporting

4 8 50.0 probably low

low low no effect inadequate

uterine cancer other, detection, confounding, selective reporting

4 8 50.0 probably low

low low no effect inadequate

Martin T. Schechter

1989 coh prostate cancer detection, confounding

3 8 37.5 probably low

low imprecision very low N/A N/A

breast cancer other, detection, confounding

4 8 50.0 probably low

low imprecision very low N/A N/A

gynecologic cancer other, detection, confounding

4 8 50.0 probably low

low imprecision very low N/A N/A

D. Christie 1991 coh prostate cancer selection, detection 4 8 50.0 probably low

low low no effect inadequate

testicular cancer selection, detection 4 8 50.0 probably low

low imprecision very low N/A N/A

R. J. Lewis 2003 coh prostate cancer selection, confounding, detection, selective reporting

4 8 50.0 probably low

low imprecision very low N/A N/A

testicular cancer selection, confounding, detection, selective reporting

4 8 50.0 probably low

low imprecision very low N/A N/A

breast cancer selection, confounding, detection, selective

4 8 50.0 probably low

low imprecision very low N/A N/A

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reportingcervical cancer selection,

confounding, detection, selective reporting

4 8 50.0 probably low

low imprecision very low N/A N/A

uterine cancer selection, confounding, detection, selective reporting

4 8 50.0 probably low

low imprecision very low N/A N/A

ovarian, fallopian tube, and broad ligament cancers

selection, confounding, detection, selective reporting

4 8 50.0 probably low

low imprecision very low N/A N/A

Bengt Järvholm

1997 coh prostate cancer selection, confounding, performance, detection

5 8 62.5 probably high

low risk of bias Very low N/A N/A

Chun-Yuh Yang

2002a

coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Shaina L. Stacy

2015 coh preterm birth attrition bias, detection bias

2 8 25.0 definitely low

moderate moderate no effect inadequate

Joan A. Casey

2016 coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias dose response

high effect high

Meng-Chiao Lin

2001a

coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

Shang-Shyue Tsai

2003 coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

Chun-Yuh Yang

2002b

coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

Chun-Yuh Yang

2004 coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

Lisa M. McKenzie

2014 coh preterm birth confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias high effect (protective)

high

Gösta Axelsson

1988 crs miscarriage confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Miguel San Sebastián

2002 crs miscarriage attrition bias, detection bias, other bias

3 8 37.5 probably low

moderate risk of bias large magnitude of effect

high effect high

Xiping Xu 1998 crs miscarriage confounding bias, detection bias, other bias

3 8 37.5 probably low

moderate risk of bias large magnitude of effect

high effect high

Gösta Axelsson

1989 crs miscarriage selection bias, confounding bias, attrition bias

3 8 37.5 probably low

low risk of bias, imprecision (low sample size)

very low not rated N/A

Miguel San Sebastián

2002 crs Stillbirth confounding bias, attrition bias, detection bias, other bias

4 8 50.0 probably low

moderate risk of bias, imprecision (low sample size)

low no effect inadequate

Lenice 2002 cac Stillbirth confounding bias, 2 8 25.0 probably moderate risk of bias, low no effect inadequate

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Minussi Oliveira

detection bias low imprecision (low sample size)

Chun-Yuh Yang

2002a

coh low birth weight (term) confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Lenice Minussi Oliveira

2002 cac low birth weight confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Joan A. Casey

2016 coh birth weight (term) confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Gösta Axelsson

1988 crs birth weight confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

Meng-Chao Lin

2001b

coh low birth weight (term) confounding bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

Lisa M. McKenzie

2014 coh low birth weight (term) confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect (protective)

moderate

Gösta Axelsson

1988 crs+coh

low birth weight confounding bias, detection bias

2 8 25.0 definitely low

moderate moderate effect (protective)

moderate

Shaina L. Stacy

2015 coh birth weight attrition bias, detection bias

2 8 25.0 definitely low

moderate moderate effect moderate

small for gestational age attrition bias, detection bias

2 8 25.0 definitely low

moderate moderate effect moderate

Gösta Axelsson

1989 crs+coh

birth weight selection bias, confounding bias, attrition bias

3 8 37.5 probably low

low risk of bias , imprecision (low sample size)

very low not rated N/A

Lenice Minussi Oliveira

2002 cac birth defects (not specified) confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias , imprecision (low sample size)

low no effect inadequate

Lisa M. McKenzie

2014 coh birth defects (oral clefts) confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate no effect inadequate

birth defects (congenital heart defect)

confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

birth defects (neural tube defects)

confounding bias, attrition bias, detection bias

3 8 37.5 probably low

moderate risk of bias moderate effect moderate

C. Chevrier 2006 cac birth defects (oral clefts) attrition bias 1 8 12.5 definitely low

moderate imprecision (low sample size)

large magnitude of effect

moderate effect moderate

Gösta Axelsson

1988 crs+coh

birth defects (not specified) selection bias, confounding bias, detection bias, other bias

4 8 50.0 probably low

low risk of bias , imprecision (low sample size)

very low not rated N/A

Chun-Yuh Yang

2000b

coh sex ratio selection bias, confounding bias, detection bias

2 8 25.0 definitely low

moderate moderate no effect inadequate

Chun-Yuh Yang

2000a

coh sex ratio selection bias, confounding bias, detection bias

2 8 25.0 definitely low

moderate moderate effect moderate

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Supplemental Table 2. Detailed Endpoint Summaries

Reference Group Study Group

Endpoint Exposure Type

Publication Year

First Author

Study Location

n Description n Description Health Effect (Effect/No Effect)

Comparison Results Level of Confidence

Level of Evidence

Birth Outcomes Associated with Maternal Exposure

preterm birth residential exposure

2002a Yang Taiwan 19,673 Women who had singleton deliveries living in 16 municipalities where the number of workers in the petroleum and petrochemical industry comprised less than 2% of the municipality's total population

20,077 Women who had first-parity singleton deliveries living in 16 petrochemical industrial municipality where the number of workers in the petroleum and petrochemical industry comprised equal or greater than 2% of the municipality's total population

no effect Study group vs. Reference group

OR=1.03 (95% CI=0.94-1.13)

moderate inadequate

preterm birth residential exposure

2015 Stacy USA 3,604 (first quartile)

Women living in the area with an inverse distance weighted count of unconventional wells >0, but <0.87

3,905 (second quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥0.87, but <2.60

no effect Second quartile vs. First quartile

OR=0.82 (95% CI=0.68-0.98) (actual number mentioned in text)

moderate inadequate

3,791 (third quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥2.60, but <6.00

Third quartile vs. First quartile

OR≈1.1 (95% CI crossing 1) (data presented in figure, no actual number)

4,151 (fourth quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥6.00

Fourth quartile vs. First quartile

OR≈1.0 (95% CI crossing 1) (data presented in figure, no actual number)

preterm birth residential exposure

2016 Casey USA 2,590 (first quartile)

Women living in the area within the first quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

2,648 (second quartile)

Women living in the area within the second quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

effect Second quartile vs. First quartile

OR=1.3 (95% CI=1.0-1.8)

high high

2,642 (third quartile)

Women living in the area within the third quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

Third quartile vs. First quartile

OR=1.6 (95% CI=1.1-2.4)

2,616 (fourth quartile)

Women living in the area within the fourth quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies

Fourth quartile vs. First quartile

OR=1.9 (95% CI=1.2-2.9)

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during 2009 and 2013preterm birth residential

exposure2001a Lin Taiwan 49,673 A 10% random sample of all

women in Taiwan who had first-parity singleton between 1993 and 1996 and who did not live in the study region.

2,027 Women who had first-parity singleton deliveries and who lived in two petrochemical municipalities.

effect Study group vs Reference group

OR=1.41 (95% CI=1.08-1.82)

moderate moderate

preterm birth residential exposure

2003 Tsai Taiwan 49,670 A 10% random sample of all women in Taiwan who had first-parity singleton between 1994 and 1997 and who did not live in the study region.

14,545 Women who had first-parity singleton deliveries and who lived within a circle of 2km radius around the multiple sources of industrial complexes including petrochemical industries

effect Study group vs Reference group

OR=1.11 (95% CI=1.02-1.21)

moderate moderate

preterm birth residential exposure

2002b Yang Taiwan 51,789 A 10% random sample of all women in Taiwan who had first-parity singleton between 1993 and 1996 and who did not live in the study region.

5,338 Women who had first-parity singleton deliveries and who lived in area with petrochemical complexes.

effect Study group vs Reference group

OR=1.18 (95% CI=1.04-1.34)

moderate moderate

preterm birth residential exposure

2004 Yang Taiwan 50,388 A 10% random sample of all women in Taiwan who had first-parity singleton between 1994 and 1997 and who did not live in the study region.

7,095 Women who had first-parity singleton deliveries and who lived near three oil refinery plants.

effect Study group vs Reference group

OR=1.14 (95% CI=1.01-1.28)

moderate moderate

preterm birth residential exposure

2014 McKenzie USA 65,506 Women who delivered live babies during 1996 and 2009 and who lived an area with no natural gas wells within 10 miles

18,884 (low exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells (first tertile calculated by an inverse distance weighted approach)

effect (protective)

Low exposure vs Reference group

OR=0.96 (95% CI=0.89-1.0)

high high

18,854 (medium exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the second tertile calculated by an inverse distance weighted approach

Medium exposure vs Reference group

OR=0.93 (95% CI=0.87-1.0)

19,384 (high exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells (third tertile calculated by an inverse distance weighted approach)

High exposure vs Reference group

OR=0.91 (95% CI=0.85-0.98)

miscarriage residential exposure

1988 Axelsson Sweden 705 Women who lived in an area without petrochemical industries and who have had pregnancies between

607 Women who lived near petrochemical industries and who have had pregnancies between

no effect Study group vs Reference group

OR=1.15 (95% CI=0.75-1.76)

moderate inadequate

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1963 and 1981 1963 and 1981miscarriage residential

exposure2002 Sebastián Ecuador 586 Women living in 14

communities at least 30 km upstream from any oil field

791 Women living 9 communities within 5 km of an oil field, following a downstream direction

effect Study group vs Reference group

OR=2.47 (95% CI=1.61-3.79)

high high

miscarriage occupational exposure

1998 Xu China 1,621 (based on self-reported exposure); 1,233 based on employment history recorded exposure)

Women who worked in petrochemical plants, but did not occupationally expose to petrochemicals during the first trimester of pregnancy. Current and past exposure was assessed by self-report via questionnaire developed by professional industrial hygienist or employment record.

1,232(based on self-reported exposure); 1,620 (based on employment history recorded exposure)

Women working in petrochemical plants and occupationally exposed to petrochemicals during the first trimester of pregnancy. Current and past exposure was assessed by self-report via questionnaire developed by professional industrial hygienist or employment record.

effect Study group vs Reference group

OR=2.9 (95%CI=2.0-4.0) based on self-reported exposure; OR=2.7 (95% CI=1.8-3.9) based on employment history recorded exposure

high high

miscarriage occupational exposure

1989 Axelsson Sweden 47 Women who were not involved in laboratory work at the petrochemical plant

55 Women involved in laboratory work at a petrochemical plant during 1973 and 1987

effect Study group vs Reference group

observed/expected=3, p<0.05

very low N/A

stillbirth residential exposure

2002 Sebastián Ecuador 586 Women living in 14 communities at least 30 km upstream from any oil field

791 Women living in 9 communities within 5 km of an oil field, following a downstream direction

no effect Study group vs Reference group

OR=0.85 (95% CI=0.35-2.05)

low inadequate

stillbirth residential exposure

2002 Oliveira Brazil 230 The first newborns from the same hospital weighing ≥2,500g without malformations and of case-matching sex.

230 Stillborn (>500g) selected from 17,113 birth records in Brazil from 1983 to 1998.

no effect Geographic distance: Region close to petrochemical plant vs Reference region

OR=0.78 (95% CI=0.22-2.72) p=0.659

low inadequate

230 The first newborns from the same hospital weighing ≥2,500g without malformations and of case-matching sex.

230 Stillborn (>500g) selected from 17,113 birth records in Brazil from 1983 to 1998.

Wind direction: Region with preferential wind direction vs Reference region

OR=0.98 (95% CI=0.38-2.54) p=0.959

low birth weight (term)

residential exposure

2002a Yang Taiwan 19,673 Women who had singleton deliveries living in 16 municipalities where the number of workers in the petroleum and petrochemical industry comprised less than 2% of the municipality's total population

20,077 Women who had first-parity singleton deliveries living in 16 petrochemical industrial municipality where the number of workers in the petroleum and petrochemical industry comprised equal or greater than 2% of the municipality's total population

no effect Study group vs Reference group

OR=1.07 (95% CI=0.95-1.22)

moderate inadequate

low birth weight

residential exposure

2002 Oliveira Brazil 986 The first newborns from the same hospital weighing ≥2,500g without malformations and of case-matching sex.

987 Newborns with low birth weight selected from 17,113 birth records in Brazil from 1983 to 1998.

no effect Geographic distance: Region close to petrochemical plant vs Reference region

OR=1.50 (95% CI=0.90–2.50) p=0.117

moderate inadequate

986 The first newborns from the 987 Newborns with low birth Wind direction: OR=1.42 (95%

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same hospital weighing ≥2,500g without malformations and of case-matching sex.

weight selected from 17,113 birth records in Brazil from 1983 to 1998.

Region with preferential wind direction vs Reference region C

CI=0.87–2.31) p=0.158

birth weight (term)

residential exposure

2016 Casey USA 2341 (first quartile)

Women living in the area within the first quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

2384 (second quartile)

Women living in the area within the second quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

no effect Second quartile vs. First quartile

Difference in mean: -16 g (95% CI= -44 to 11)

moderate inadequate

2336 (third quartile)

Women living in the area within the third quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

Third quartile vs. First quartile

Difference in mean: 1 g (95% CI=-34 to 36)

2332 (fourth quartile)

Women living in the area within the fourth quartile of natural gas development activity calculated by an inverse-distance squared model and delivered babies during 2009 and 2013

Fourth quartile vs. First quartile

Difference in mean: -20 g (95% CI=-56 to 16)

birth weight residential exposure

1988 Axelsson Sweden 221 (first baby)

Women who lived in an area without petrochemical industries and who have had pregnancies between 1963 and 1981

185 Women who lived near petrochemical industries and who have had pregnancies between 1963 and 1981

no effect first baby (Study group vs Reference group)

Mean±SD: 3464 ± 507 vs 3405 ± 581; difference in mean: 59 g, p>0.05

moderate inadequate

198 (second baby)

Women who lived in an area without petrochemical industries and who have had pregnancies between 1963 and 1981

186 Women who lived near petrochemical industries and who have had pregnancies between 1963 and 1981

Second baby (Study group vs Reference group)

Mean±SD: 3621 ± 529 vs 3557 ± 509; difference in mean: 64 g, p>0.05

112 (third baby)

Women who lived in an area without petrochemical industries and who have had pregnancies between 1963 and 1981

99 Women who lived near petrochemical industries and who have had pregnancies between 1963 and 1981

Third baby (Study group vs Reference group)

Mean±SD: 3667 ± 546 vs 3607 ± 553; difference in mean: 60 g, p>0.05

low birth weight (term)

residential exposure

2001b Lin Taiwan 868 Women who had first-parity singleton deliveries and who lived in a control area without petrochemical air pollution between 1993 and 1996

1,677 Women who had first-parity singleton deliveries and who lived in a petrochemical area between 1993 and 1996

effect Study group vs Reference group

OR=1.77 (95% CI=1.0-3.1)

moderate moderate

low birth weight (term)

residential exposure

2014 McKenzie USA 60,653 Women who delivered live babies during 1996 and 2009 and who lived an area with no natural gas wells within 10 miles

17,525 (low exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells (first tertile calculated by an inverse distance weighted

effect (protective)

Low exposure vs Reference group

OR=1.0 (95% CI=0.9-1.1)

moderate moderate

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approach)17,565 (medium exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells (second tertile calculated by an inverse distance weighted approach)

Medium exposure vs Reference group

OR=0.86 (95% CI=0.77-0.95)

18,104 (high exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells (third tertile calculated by an inverse distance weighted approach)

High exposure vs Reference group

OR=0.9 (95% CI=0.8-1.0)

low birth weight

residential exposure

1988 Axelsson Sweden 1,527 Women who lived in an area without petrochemical industries and who have had pregnancies between 1963 and 1981

1,255 Women who lived near petrochemical industries and who have had pregnancies between 1963 and 1981

effect (protective)

Study group vs Reference group

exposed area: observed/expected=0.66 (95% CI=0.44, 0.94)

moderate moderate

birth weight residential exposure

2015 Stacy USA 3,604 (first quartile)

Women living in the area with an inverse distance weighted count of unconventional wells >0, but <0.87

3,905 (second quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥0.87, but <2.60

effect Second quartile vs. First quartile

3370.4±540.5 vs 3343.9±543.9 (difference in mean: 26.5 g) p>0.05

moderate moderate

3,791 (third quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥2.60, but <6.00

Third quartile vs. First quartile

3345.4±553.5 vs 3343.9±543.9 (difference in mean: 1.5 g) p>0.05

4,151 (fourth quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥6.00

Fourth quartile vs. First quartile

3323.1±558.2 vs 3343.9±543.9 (difference in mean: -20.8 g ) p=0.02

birth weight (small for gestational age)

3,604 (first quartile)

Women living in the area with an inverse distance weighted count of unconventional wells >0, but <0.87

3,905 (second quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥0.87, but <2.60

effect Second quartile vs. First quartile

OR≈1.1 (95% CI crossing 1) (data presented in figure, no actual number)

moderate moderate

3,791 (third quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥2.60, but <6.00

Third quartile vs. First quartile

OR≈1.2 (95% CI crossing 1) (data presented in figure, no actual number)

4,151 (fourth quartile)

Women living in the area with an inverse distance weighted count of unconventional wells ≥6.00

Fourth quartile vs. First quartile

OR=1.34 (95% CI=1.10-1.63) (actual number mentioned in text)

birth weight occupational exposure

1989 Axelsson Sweden 1,238 (general population)

All singleton infants born in the same city during 1973-1981

40 Women involved in laboratory work at a petrochemical plant during 1973 and 1987

effect (protective)

Study group vs Reference group

no statistical conclusion

very low N/A

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birth defects (not specified)

residential exposure

2002 Oliveira Brazil 158 The first newborns from the same hospital weighing ≥2,500g without birth defects and of case-matching sex.

159 Newborns with birth defects selected from 17,113 birth records in Brazil from 1983 to 1998.

no effect Geographic distance: Region close to petrochemical plant vs Reference region

OR=0.30 (95% CI=0.70–1.27) p=0.103

low inadequate

birth defects (not specified)

158 The first newborns from the same hospital weighing ≥2,500g without birth defects and of case-matching sex.

159 Newborns with birth defects selected from 17,113 birth records in Brazil from 1983 to 1998.

Wind direction: Region with preferential wind direction vs Reference region

OR =1.08 (95% CI=0.30–3.88) p=0.907

birth defects (oral clefts)

residential exposure

2014 McKenzie USA 66,626 Women who delivered live babies during 1996 and 2009 and who lived an area with no natural gas wells within 10 miles

19,214 (low exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the first tertile calculated by an inverse distance weighted approach

no effect Low exposure vs Reference group

OR=0.65 (95% CI=0.43-0.98)

moderate inadequate

19,209 (medium exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the second tertile calculated by an inverse distance weighted approach

Medium exposure vs Reference group

OR=0.89 (95% CI=0.61-1.3)

19,793 (high exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the third tertile calculated by an inverse distance weighted approach

High exposure vs Reference group

OR=0.82 (95% CI=0.55-1.2)

birth defects (congenital heart defect)

66,626 Women who delivered live babies during 1996 and 2009 and who lived an area with no natural gas wells within 10 miles

19,214 (low exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the first tertile calculated by an inverse distance weighted approach

effect Low exposure vs Reference group

OR=1.1 (95% CI=0.93-1.3)

moderate moderate

19,209 (medium exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the second tertile calculated by an inverse distance weighted approach

Medium exposure vs Reference group

OR=1.2 (95% CI=1.0-1.3)

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19,793 (high exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into third tertile calculated by an inverse distance weighted approach

High exposure vs Reference group

OR=1.3 (95% CI=1.2-1.5)

birth defects (neural tube defects)

66,626 Women who delivered live babies during 1996 and 2009 and who lived an area with no natural gas wells within 10 miles

19,214 (low exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the first tertile calculated by an inverse distance weighted approach

effect Low exposure vs Reference group

OR=0.65 (95% CI=0.25-1.7)

moderate moderate

19,209 (medium exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the second tertile calculated by an inverse distance weighted approach

Medium exposure vs Reference group

OR=0.80 (95% CI=0.34-1.9)

19,793 (high exposure)

Women who delivered live babies during 1996 and 2009 and who lived in an area within 10-mile radius of natural gas wells falling into the third tertile calculated by an inverse distance weighted approach

High exposure vs Reference group

OR=2.0 (95% CI=1.0-3.9)

birth defects (oral clefts)

occupational exposure

2006 Chevrier France 10 Children hospitalized for treatment of some other disorders without any birth defects, cancer or genetic disease and matched with cases by sex, age, maternal geographic origin, and residence

17 Child diagnosed with cleft lip and/or cleft palate requiring surgery during 1998 and 2001 at seven hospitals.

effect Study group vs Reference group

OR=3.64 (95% CI=1.5-8.8)

moderate moderate

birth defects (not specified)

residential exposure

1988 Axelsson Sweden 1,527 Women who lived in an area without petrochemical industries and who have had pregnancies between 1963 and 1981

1,255 Women who lived near petrochemical industries and who have had pregnancies between 1963 and 1981

effect Study group vs Reference group

observed/expected=0.68 based on registry of birth defects. observed/expected=0.79 based on Medical Birth Registry.

very low N/A

sex ratio residential exposure

2000a Yang Taiwan no data Did not have a reference group.

92,601 All babies born by mothers living near a petroleum refinery plant during 1971 and 1996

no effect Study group vs Reference group

Not significant (Z-scores for individual year of a total of 26 years were listed in table)

low inadequate

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sex ratio residential exposure

2000b Yang Taiwan no data Did not have a reference group.

208,501 All babies born by mothers living in petrochemical industrial municipalities during 1987 and 1996

effect Study group vs Reference group

M/F=109.3 (Z=2.96, p=0.003)

low moderate

Semen quality, Fertility and Birth Outcomes Associated with Adult Male Exposures

Sperm and Fertilitysperm concentration

occupational 1985 Rosenberg unknown 74 other petroleum refinery workers

42 petroleum refinery's waste water facility workers

no effect reference group vs study group

unexposed=80.8mill/ML; exposed=66.9mill/mL: p=0.16

low inadequate

sperm concentration

occupational 1997 Khalifa Saudi Arabia

1 Petroleum field worker 0 none effect during exposure vs. after employment

During employment = 0.025 mill/ml-3.2 mill/ml; after employment=12 mill/ml-20.6 mill/ml

very low N/A

sperm concentration

occupational 2001 Wang China 49 Non-exposed/non-smoker 23 Exposed/Non-smoker effect Non-smokers: Exposed vs. unexposed

control=60.07 mill/mL, exposed=52.52 mill/ml

moderate moderate

81 Non-exposed/smoker 45 Exposed/smoker Smokers: Exposed vs. unexposed

control=55.32 mill/ml, exposed=41.49 mill/ml

49 Non-exposed/non-smoker 45 Exposed/smoker Exposed/smoker vs. unexposed/non-smoker

control=60.07 mill/mL, exposed=41.49 mill/ml (p<0.01)

81 Non-exposed/smoker 23 Exposed/Non-smoker Exposed/non-smoker vs. unexposed/smoker

control=55.32 mill/ml, exposed=52.52 mill/ml

sperm count occupational 2001 Wang China 49 Non-exposed/non-smoker 23 Exposed/Non-smoker effect Non-smokers: Exposed vs. unexposed

Control=152 mill/ejac, Exposed=127.02 mill/ejac

moderate moderate

81 Non-exposed/smoker 45 Exposed/smoker Smokers: Exposed vs. unexposed

control=141.86 mill/ejac, exposed=108.48 mill/ejac (p<0.05)

49 Non-exposed/non-smoker 45 Exposed/smoker Exposed/smoker vs. unexposed/non-smoker

control=152 mill/ejac, exposed=108.48 mill/ejac (p<0.05)

sperm motility

occupational 1997 Khalifa Saudi Arabia

1 Petroleum field worker 0 none effect during exposure vs. after employment

During employment: Rapid=0-15, Sluggish=0-15%; after employment: Rapid=30-40,

very low N/A

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sluggish=5-15%sperm motility

experimental 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite phenol-hydroquinone

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect control vs. 0.05 ppm

Control=76%, 0.05ppm=30.2% (p<0.001)

high high

control vs. 0.1 ppm

Control=76%, 0.1ppm=27% (p<0.001)

control vs. 0.2 ppm

Control=76%, 0.2ppm=12% (p<0.001)

control vs. 0.3 ppm

Control=76%, 0.3ppm=2.2% (p<0.001)

sperm motility

experimental 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite catechol

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect control vs. 0.05 ppm

Control=76%, 0.05ppm=52% (p<0.01)

high high

control vs. 0.1 ppm

Control=76%, 0.1ppm=44% (p<0.01)

control vs. 0.2 ppm

Control=76%, 0.2ppm=30% (p<0.01)

control vs. 0.3 ppm

Control=76%, 0.3ppm=24% (p<0.01)

sperm motility

occupational 2001 Wang China 49 Non-exposed/non-smoker 23 Exposed/Non-smoker effect Non-smokers: Exposed vs. unexposed

Control=2.41, scale, exposed=2.02 (p<0.05)

moderate moderate

81 Non-exposed/smoker 45 Exposed/smoker Smokers: Exposed vs. unexposed

Control=2.45, scale, Exposed=2.01 (p<0.01)

49 Non-exposed/non-smoker 45 Exposed/smoker Exposed/smoker vs. unexposed/non-smoker

Control=2.41, scale, exposed=2.01 (p<0.01)

81 Non-exposed/smoker 23 Exposed/Non-smoker Exposed/non-smoker vs. unexposed/smoker

Control=2.45, scale, exposed =2.02 (p<0.01)

sperm viability

occupational 2001 Wang China 49 Non-exposed/non-smoker 23 Exposed/Non-smoker no effect Non-smokers: Exposed vs. unexposed

Control=61.44%, Exposed=63.41% (p>0.05)

moderate inadequate

81 Non-exposed/smoker 45 Exposed/smoker Smokers: Exposed vs. unexposed

control=60.28%, exposed=60.78% (p>0.05)

49 Non-exposed/non-smoker 45 Exposed/smoker Exposed/smoker vs. unexposed/non-smoker

Control=61.44%, exposed=60.78% (p>0.05)

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81 Non-exposed/smoker 23 Exposed/Non-smoker Exposed/non-smoker vs. unexposed/smoker

control=60.28%, exposed=63.4% (p>0.05)

sperm viability

occupational 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite phenol-hydroquinone

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect control vs. 0.05 ppm

Control=59%, 0.05ppm=49%

high high

control vs. 0.1 ppm

Control=59%, 0.1ppm=41%

control vs. 0.2 ppm

Control=59%, 0.2ppm=32%(p<0.01)

control vs. 0.3 ppm

Control=59%, 0.3ppm=13%(p<0.001)

sperm viability

occupational 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite catechol

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect control vs. 0.05 ppm

Control=60%, 0.05ppm=52%(p<0.01)

high high

control vs. 0.1 ppm

Control=60%, 0.1ppm=44%(p<0.01)

control vs. 0.2 ppm

Control=60%, 0.2ppm=30%(p<0.001)

control vs. 0.3 ppm

Control=60%, 0.3ppm=24%(p<0.001)

DNA Damage - Intact DNA

occupational 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite phenol-hydroquinone

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect reference group vs study group

Control=86.5%, phenol-hydroquinone=47.9%(p<0.001)

high high

DNA Damage - Denatured SS DNA

reference group vs study group

Control=14.5%, phenol-hydroquinone=63.3%(p<0.001)

DNA Damage - Effective DNA

reference group vs study group

Control=73.5%, phenol-hydroquinone=40.5%(p<0.001)

DNA Damage - Intact DNA

occupational 2013 Mandani 12 Healthy human semen samples (sperm count 75-110 mill/mL) exposed to Benzene metabolite catechol

10 Healthy human semen samples (sperm count 75-110 mill/mL)

effect reference group vs study group

Control=86.5%, catechol=55.3%(p<0.001)

high high

DNA Damage - Denatured SS DNA

reference group vs study group

Control=14.5%, catechol=44.7%(p<0.001)

DNA Damage - Effective DNA

reference group vs study group

Control=73.5%, catechol=47%(p<0.001)

sperm concentration

occupational 1985 Rosenberg unknown 74 other petroleum refinery workers

39 petroleum refinery's waste water facility workers

no effect reference group vs study group

unexposed=49.1%; exposed=44.5%

low inadequate

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(p=.94)sperm motility

occupational 1997 Khalifa Saudi Arabia

1 Petroleum field worker 0 none effect during exposure vs. after employment

During employment = 10-90%; after employment=10-35%

very low N/A

fertility occupational 1999 Bull unknown 51 offshore operators (Non-exposed)

30 offshore mechanics (exposed)

no effect Offshore operators vs. offshore mechanics

Fecundity Ratio=0.8 (95% CI=0.49-1.32)

low inadequate

51 offshore operators (Non-exposed)

95 offshore drilling personnel (exposed)

Offshore operators vs. offshore drilling

Fecundity Ratio=0.89 (95% CI=0.61-1.29)

Birth Outcomes Arising from Paternal Exposurefetal Loss occupational 1999 Bull unknown 86 pregnancies - offshore

operators (Non-exposed)59 pregnancies - offshore

mechanics (exposed)no effect Offshore

operators vs. offshore mechanics

OR= 1.1 (95% CI=0.4-3.1)

low inadequate

86 pregnancies - offshore operators (Non-exposed)

172 pregnancies - offshore drilling personnel (exposed)

Offshore operators vs. offshore drilling

OR = 1.4 (95% CI=0.6-3.2)

birth defects occupational 2012 Desrosiers USA 4066 fathers of children without major birth defects (20 worked in petroleum and gas)

9998 fathers of children with birth defects (71 worked in petroleum and gas)

effect reference group vs study group

OR=2 (95% CI=0.8-5.1)

low low

birth defects occupational 2012 Desrosiers USA 4066 fathers of children without major birth defects (20 worked in petroleum and gas)

9998 fathers of children with birth defects (71 worked in petroleum and gas)

effect reference group vs study group

OR=2.8 (95% CI=0.9-9.1)

low low

birth defects occupational 2012 Desrosiers USA 4066 fathers of children without major birth defects (20 worked in petroleum and gas)

9998 fathers of children with birth defects (71 worked in petroleum and gas)

effect reference group vs study group

OR=2.6 (95% CI=1.1-6.5)

low low

birth defects occupational 2012 Desrosiers USA 4066 fathers of children without major birth defects (20 worked in petroleum and gas)

9998 fathers of children with birth defects (71 worked in petroleum and gas)

effect reference group vs study group

OR=1.6 (95% CI=1.0-2.4)

low low

childhood cancer

occupational 1987 Johnson USA 30 Unaffected children of Chemical, petroleum and rubber industries workers

20 Affected children of Chemical, petroleum and rubber industries workers

no effect reference group vs study group

OR=1.3 (95% CI= 0.8-2.4)

very low N/A

6 Unaffected children of Petroleum refining industry workers

8 Affected children of Petroleum refining industry workers

OR=2.7 (95% CI= 0.9-7.8)

6 Unaffected children of Petroleum refinery workers

6 Affected children of Petroleum refinery workers

OR=2.0 (95% CI=0.6-6.2)

Reproductive Cancer

prostate cancer

occupational 2006 Rybicki USA 244 men without cancer with occupational respiratory exposure to petroleum

637 men with prostate cancer with respiratory exposure to petroleum

no effect reference group vs study group

OR 1.12 (95% CI 0.73-1.73); p=0.61

low inadequate

prostate occupational 2006 Rybicki USA 244 men without cancer with 637 men with prostate no effect reference group OR 0.74 (95% CI low inadequate

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cancer cutaneous exposure to petroleum

cancer with cutaneous exposure to petroleum

vs study group 0.48-1.13); p=0.16

prostate cancer incidence

occupational 1991 Christie Australia not reported

incidence rates of general population

15,000 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.0 (95% CI 0.4-1.9)

low inadequate

prostate cancer incidence

occupational 2004 Gun Australia not reported

incidence rates of general population

15,956 Australian Institute of Petroleum employees

effect reference group vs study group

SIR of 1.19 (95% CI 1.00 to 1.40)

moderate moderate

prostate cancer incidence

occupational 2006 Gun Australia not reported

incidence rates of general population

16,547 Australian Institute of Petroleum employees

effect reference group vs study group

SIR of 1.18 (95% CI 1.04 to 1.34)

moderate moderate

prostate cancer incidence

residential 1984 Kaldor USA 411,180 low exposure area (Area 2) 300,494 (Area 3); 486,691 (Area 4)

Area 3: "medium" exposure level group Area 4: "high" exposure level group

effect reference group vs two study groups

trend (p=0.002) for increasing prostate cancer incidence rates with areas of increasing exposure

moderate moderate

prostate cancer incidence

residential 1989 Schechter Canada not reported

expected cancer rates of three rural areas in Southern Alberta selected that were socio-demographically similar to cohort area

1,126 rural residents of Southern Alberta, Canada living near natural gas refineries

no effect reference group vs study group

SIR 1.76 (95% CI 0.84-4.38)

very low N/A

prostate cancer incidence

occupational 1997 Järvholm Sweden not reported

incidence rates of general population

4,128 Swedish petroleum industry workers

no effect reference group vs study group

SIR 1.1 (90% CI 0.78-1.5)

very low N/A

prostate cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

17,230 Canadian petroleum industry workers

no effect reference group vs study group

SIR of 0.67 (95% CI 0.41-1.03)

very low N/A

testicular cancer incidence

occupational 2004 Gun Australia not reported

incidence rates of general population

15,956 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.24 (95% CI 0.68 to 2.08)

low inadequate

testicular cancer incidence

occupational 2006 Gun Australia not reported

incidence rates of general population

16,547 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.33 (95% CI 0.80 to 2.08)

low inadequate

testicular cancer incidence

residential 1984 Kaldor USA 411,180 low exposure area (Area 2) 300,494 (Area 3); 486,691 (Area 4)

Area 3: "medium" exposure level group Area 4: "high" exposure level group

no effect reference group vs two study groups

no trend (p>0.1) low inadequate

testicular cancer incidence

occupational 1991 Christie Australia not reported

incidence rates of general population

15,000 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.0 (95% CI 0.2-2.8)

very low N/A

testicular cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

17,230 Canadian petroleum industry workers

no effect reference group vs study group

SIR of 0.82 (95% CI 0.45-1.37)

very low N/A

cervical cancer incidence

residential 1984 Kaldor USA 421,995 low exposure area (Area 2) 303,397 (Area 3); 506,191 (Area 4)

Area 3: "medium" exposure level group Area 4: "high" exposure level group

no effect reference group vs two study groups

no trend (p>0.1) low inadequate

uterine cancer incidence

residential 1984 Kaldor USA 421,995 low exposure area (Area 2) 303,397 (Area 3); 506,191 (Area 4)

Area 3: "medium" exposure level group Area 4: "high" exposure level group

no effect reference group vs two study groups

no trend (p>0.1) low inadequate

cervical cancer incidence

occupational 2004 Gun Australia not reported

incidence rates of general population

867 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.61 (95% CI 0.33 to 4.71)

very low N/A

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cervical cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

8,062 Canadian petroleum industry workers

effect reference group vs study group

SIR of 0.42 (95% CI 0.17-0.86)

very low N/A

uterine cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

8,062 Canadian petroleum industry workers

effect reference group vs study group

SIR of 0.31 (95% CI 0.06-0.89)

very low N/A

ovarian, fallopian tube, and broad ligament cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

8,062 Canadian petroleum industry workers

no effect reference group vs study group

SIR of 1.40 (95% CI 0.78-2.30)

very low N/A

gynecologic cancer incidence

residential 1989 Schechter Canada not reported

expected cancer rates of three rural areas in Southern Alberta selected that were socio-demographically similar to cohort area

1,038 rural residents of Southern Alberta, Canada living near natural gas refineries

no effect reference group vs study group

1 case out of 1038 residents (no statistical analysis)

very low N/A

breast cancer incidence

residential 1984 Kaldor USA 421,995 low exposure area (Area 2) 303,397 (Area 3); 506,191 (Area 4)

Area 3: "medium" exposure level group Area 4: "high" exposure level group

no effect reference group vs two study groups

no trend (p>0.1) low inadequate

breast cancer incidence

occupational 2004 Gun Australia not reported

incidence rates of general population

867 Australian Institute of Petroleum employees

no effect reference group vs study group

SIR of 1.02 (95% CI 0.53 to 1.79)

low inadequate

breast cancer incidence

occupational 2003 Lewis Canada not reported

incidence rates of general population

8,062 Canadian petroleum industry workers

no effect reference group vs study group

SIR of 1.02 (95% CI 0.80-1.28)

very low N/A

breast cancer incidence

residential 1989 Schechter Canada not reported

expected cancer rates of three rural areas in Southern Alberta selected that were socio-demographically similar to cohort area

1,038 rural residents of Southern Alberta, Canada living near natural gas refineries

no effect reference group vs study group

9 cases out of 1038 residents (no statistical analysis)

very low N/A