Effects of Exposure to Tobacco Smoke on Maternal and Child Health

Gayle C. Windham

California – China Environmental Health Training Program

Shanghai, April 6-9, 2004

Background-- Smoking Rates in U.S.Background-- Smoking Rates in U.S.

60

50

40

30

20

10

0

Men

Women

Year

1965 1970 1975 1980 1985 1990 1995 2000

Per

cen

t

International Smoking Rates in WomenInternational Smoking Rates in Women

Country Early 1970’s Early 1990’s

Australia 29% 21%Canada 35% 29%England 42% 28%Japan 15-17% 13-15%Norway 37-38% 26-33%

China 2-4%

Background--Active Smoking and Background--Active Smoking and Reproductive HealthReproductive Health

• Smoking women have increased risks of conception delay and infertility.

• Male smokers have increased risks of sperm damage and reduced sperm quality.

• Female smokers appear to have altered menstrual function—painful periods, shorter cycles, and irregular cycles.

• Women smokers have a younger age at natural menopause. ~US SGR, BMA

Background--Active Smoking and Background--Active Smoking and Pregnancy OutcomePregnancy Outcome

• For over 40 years it has been known that babies born to mothers who smoke during pregnancy weigh less than babies of non-smokers.

• Birth weight decreases with amount smoked, with a mean difference of about 250 grams.

• Smoking during pregnancy is also associated with low birth weight or small for gestational age (RR 1.5-5).

• Most studies find an association of smoking and preterm delivery, but not as clear a dose-response pattern. ~US SGR, BMA

Background--Active Smoking and Background--Active Smoking and Pregnancy Outcome, cont.Pregnancy Outcome, cont.

• Smokers have increased risks of PROM, abruptio placentae, and placenta previa.

• Modest increase in risk for ectopic pregnancy and spontaneous abortion.

• The risk for perinatal death (stillbirth and neonatal) and for SIDS is increased in offspring.

• Smoking may increase risks of some birth defects, but not malformations overall.

~US SGR, BMA

Background--IssuesBackground--Issues Are the effects of smoking greater in certain sub-

groups, such as by ethnicity or maternal age? Timing of effects? Some evidence indicates

benefits from early smoking cessation. Which of the hundreds of compounds in smoke are

the culprits? Nicotine, Carbon monoxide, also lead, cadmium, toluene, carbon disulfide and PAH’s.

Can exposure to ETS, which contains most of the same compounds, lead to similar adverse reproductive outcomes?

Health Studies of ETS--IssuesHealth Studies of ETS--Issues

Cotinine levels in smokers average 100 times that of ETS-exposed non-smokers: What level of effect can be expected, and is it detectable?

ETS exposure may be nearly ubiquitous in some societies: How measure exposure?

Spouse smoking status Questionnaire about multiple sources Environmental measurement Biomarker measurement

What variables are potential confounders?

Spontaneous Abortion Case-Control Study, Spontaneous Abortion Case-Control Study, 1986-19871986-1987

CASES: SABs < 20 weeks, hospital path labs

626 (81%) interviewed retrospectively (16 months post-LMP on average)

CONTROLS: Livebirths, frequency matched by hospital and last menstrual period.

1300 (86%) interviewed (18.5 months)

SACCS: Ascertainment of ExposureSACCS: Ascertainment of Exposure

ETS: Regularly spent “1 hour or more per day in a room (at home or work) where someone (else) was smoking” during pregnancy (or first 20 weeks).

MATERNAL SMOKING: Average amount during first trimester.

PATERNAL SMOKING:Amount smoked during three months before

LMPpregnancy (or 20 weeks).

SACCS Results: SAB and ETSSACCS Results: SAB and ETS

Variable Exp. AOR 95% C.I.

ETS of 1+ hrs/day 38% 1.5 1.2-1.9

Paternal smoke (>20c) 6% 1.0 0.6-1.5

ETS w/ paternal smoker 2.0 1.1-3.6

Little effect of maternal smoking after adjustment!

Windham et al. AJE 1992;135:1394-1403

SACCS Results: Growth and ETSSACCS Results: Growth and ETSAmong Non-Smoking Women

Outcomes AOR 95% C.I.Low Birthweight (<2500gms) 1.0 0.52-2.1LBW at term 1.8 0.64-4.8Small for Gest Age (<10th %) 1.4 0.79-2.5Preterm Delivery (<37 weeks) 0.85 0.57-1.3

ETS effects similar to light maternal smoking (1-10 cigarettes/day).

Windham et al. Paediatric and Perinatal Epidem 1999;13:35-57

Pregnancy Outcome Study,1990-1991Pregnancy Outcome Study,1990-1991 Recruitment Recruitment

7,881 CALLED FOR PRENATAL APPT

16% Refused further contact

6% Ineligible or Excluded

6,179 (78%) ELIGIBLE AND WILLING

4.9% No longer pregnant on re-contact

2.2% Refused interview

6.9% Never contacted or Ineligible

5,342 (86.5%) COMPLETED INTERVIEWS

POS PREGNANCY OUTCOMESPOS PREGNANCY OUTCOMES

• LIVEBIRTH 4,613 86.4• STILLBIRTH 32 0.6• MISCARRIAGE 499 9.3• ABORTION 128 2.4• OTHER EXCLUSIONS 70 1.3

• TOTAL IN ANALYSIS 5,144 96.3

POS: Ascertainment of ETSPOS: Ascertainment of ETS

HOME: Hours/day since LMP near someone smoking at home

WORK: Hours/day around someone smokingat work

TOTAL: Home plus Work

PATERNAL SMOKING:

Current smoking status (first trimester)

Smoking status during three monthsbefore LMP#cigs/day

POS Results: SAB and ETSPOS Results: SAB and ETS

VARIABLE Exp. AOR 95% C.I.

Any Home ETS 11% 1.15 0.86-1.6

Any Work ETS 23% 0.88 0.66-1.2

Any ETS (0.5+ hrs) 28% 1.0 0.80-1.3

High Caffeine + ETS 1% 3.4 1.7-7.0

High Alcohol + ETS 0.2% 2.9 0.72-11.6

Windham et al. AJE 1999;149:243-247

POS Results : Growth and Heavy ETSPOS Results : Growth and Heavy ETS (7+ hours/day) (7+ hours/day)

Outcomes AOR 95% C.I.

Low Birthweight (<2500gms) 1.8 0.82-4.1

Small for Gest Age (<10th %) 0.62 0.25-1.5

Preterm Delivery (<37 weeks) 1.6 0.87-2.9

Very Preterm (<35 weeks) 2.4 1.0-5.3

ETS effects stronger in non-White races and for preterm delivery, in older women (> 30).

Windham et al. Epidemiology 2000;11:427-433

† Adjusted‡ All women (includes smokers), adjustedNote: “cigs/day” refers to amount of exposure from others’ smoking

Difference in Mean Birthweight (grams)

-205

-228

-66

-61

-113

-11

-63

-34

-30

-33

-20

Mathai et al. ’90

Schwartz-Bickenbach et al. ’87

Borlee et al. ’78

‡Rubin et al. ’86 (per 10 cigs/day)

‡Campbell et al. ’88

Chen et al. ’89 (>10 cigs/day)

†Mathai et al. ’92

†Martinez et al. ’94 (per 10 cigs/day)

Zhang and Ratcliff ’93

Saito ’91

MacMahon et al. ’66 (males)

‡Magnus et al. ’84 (per 10 cigs/day)

-500 -400 -300 -200 -100 0 100 200

-5

Studies of Mean Birth Weight in ETS-Exposed and Unexposed Pregnancies: Paternal Smoking Status

Studies of Mean Birth Weight in ETS-Exposed and Unexposed Pregnancies: Multiple Sources

-192

-87.3

-38

-24

-24

-34

-84

14

-45

-104

Roquer et al. ’95 (20 cigs/day)

†Lazzaroni et al. ’90

†Rebagliato et al. ’95 (cotinine >1.7 ng/ml)

†Haddow et al. ’88 (cotinine 1-10 ng/ml)

†Windham et al. ’99

†Eskenazi et al. ’95 (cotinine >2 ng/ml)

Mainous and Hueston ’94 (high exp)

†Ahlborg and Bodin ’91 (home exposure only)

†Martin and Bracken ’86 (2 hrs/day)

Ogawa et al. ’91 (2 hrs/day)

† Adjusted‡ All women (includes smokers), adjustedNote: “cigs/day” refers to amount of exposure from others’ smoking

Difference in Mean Birthweight (grams)

-500 -400 -300 -200 -100 0 100 200

Meta-Analysis: Differences in Mean Meta-Analysis: Differences in Mean Birth Weight by ETS ExposureBirth Weight by ETS ExposureStudies Pooled Weightincluded N difference (g) and (95% CI)

All 22 -25 (-34, -16)Non-smokers 19 -31 (-42, -20) Adj. Diffs. 11 -29 (-41, -16)Multiple sources of ETS exp. 10 -28 (-43, -13)Biomarker studies 3 -82 (-126, -37)Windham GC et al. Paed Perinat Epid 1999:13;35-57

Studies of LBW or SGA in ETS-Exposed and Unexposed Pregnancies: Household Smoker

0.1

†Adjusted‡OR and CI calculated from data, sometimes estimated. In a few studies, rate ratios were calculated (Zhang and Ratcliff, Ahlborg and Bodin).

Odds (or Rate) Ratios (log scale)

1.5

1.0

1.4

1.1

1.3

1.4

1.1

‡Mathai et al. ’92

‡Chen et al. ’89

†Nakamura et al. ’88

Zhang and Ratcliff ’93

‡Saito ’91

‡Mau and Netter ’74 (>10 cigs)

‡Underwood et al. ’67 (>30 cigs)

1 10

Studies of LBW or SGA in ETS-Exposed and Unexposed Pregnancies: Multiple Sources

0.1

†Adjusted‡OR and CI calculated from data, sometimes estimated. In a few studies, rate ratios were calculated (Zhang and Ratcliff, Ahlborg and Bodin).

Odds (or Rate) Ratios (log scale)

1 10

1.9

0.5

1.0

1.35

2.2

1.6

1.1

1.0

1.8

Roquer et al. ’95 (20 cigs/day)

†Chen and Pettiti ’95 (30 hrs/wk)

†Windham et al. ’99

†Ahlborg and Bodin ’91 (home exposure)

Eskenazi et al. ’95 (cotinine >2 ng/ml)

†Martin and Bracken ’86 (2 hrs/day)

†Mainous and Hueston ’94 (high exp)

†Fortier et al. ’94

†Ogawa et al. ’91 (2 hrs/day)

Meta-Analysis: Risk of Low Birth Meta-Analysis: Risk of Low Birth Weight or Small for Gestational AgeWeight or Small for Gestational Age

Studies Pooled included N OR (95%

CI)

Term LBW or SGA 11 1.2 (1.1, 1.3) Adj. estimates 6 1.1 (0.9, 1.3)

LBW only 8 1.0 (0.9, 1.1) Adj. estimates 3 1.4 (1.0, 1.9) Windham et al. Paed Perinat Epid 1999:13;35-57

Biomarker Studies of Low Birthweight/ SGA*Biomarker Studies of Low Birthweight/ SGA*

Authors Exposure Estimate of effect

SERUM:Haddow et al., ‘88 1-9.9 ng/ml ~1.29Eskenazi et al., ‘95 2-10 ng/ml 1.35 (0.60, 3.0)Kharrazi et al., i.p. Log increase 1.4 (0.91, 2.2), adj (term LBW) High (0.24+) 1.8 (0.65, 4.8), adj

HAIR:Nafstad* et al., ’98 > 0.75ug/g 3.2 (1.3, 8.0)Jaakola et al., ’01 > 4.0 ug/g 1.6 (0.55, 4.4) adj

Studies of Preterm Delivery and ETSStudies of Preterm Delivery and ETS

Exposure Measure N Range of Effects (ORs)

Household smokers 4 1.2-1.6 (1.9 older women)

Work & Home 5 1.2-1.8 any; 1.6-1.9 high(2.8 in older women)

Biomarkers 2 1.2-1.3/quartile(increase with >dose)

Do we need additional studies?Do we need additional studies?Several agencies (WHO, CALEPA, SGR) have concluded that ETS exposure adversely affects birth weight.

Purpose~

Examine susceptible sub-groups in further detail Examine other pregnancy outcomes Determine which aspects of ETS (dose,

duration, and timing of exposure) are most important

Summaries: CalEPA, 1997Summaries: CalEPA, 1997

Effects Causally Associated with ETS Exposure • Developmental:

Low birthweight or small for gestational age

Sudden infant death syndrome• Respiratory Effects in Children:

Acute lower respiratory tract infections

Asthma induction and exacerbation

Middle ear infections and chronic symptoms

Summaries: CalEPA, 1997, cont.Summaries: CalEPA, 1997, cont.

Effects with Suggestive Evidence

• Developmental:Spontaneous abortionAdverse impact on cognition and behavior

• Respiratory Effects :Exacerbation of cystic fibrosisDecreased pulmonary function

Summaries: WHO Consultation onSummaries: WHO Consultation on Child Health, 1999 Child Health, 1999

ETS Exposure is Causally Associated with:

• Increased risk of LRI’s in first years of life

• Increased severity and frequency of symptoms in children with asthma

• Increased risk of acute and chronic middle ear disease

• Chronic respiratory symptoms in school-age children

Summaries: British Medical Association Summaries: British Medical Association

Conclusive Evidence that ETS Exposure causes the same (above) conditions in children, with RRs of 1.4 (asthma) to 2.1 (SIDS), and Population Attributable Proportions of 11% (SIDS) to 23% (respiratory tract infections).

Summaries: WHO Consultation, cont.Summaries: WHO Consultation, cont.

Maternal Smoking is:

• A major cause of SIDS (mostly during pregnancy but some post-natal).

• A cause of small reductions in lung function (mostly during pregnancy).

• A cause of LBW during pregnancy; ETS exposure of non-smoking women is a cause of small reductions in birth weight.

Summaries: WHO Consultation, cont.Summaries: WHO Consultation, cont.

Parental Smoking is:• Associated with learning difficulties, behavioral

problems, and language impairment; ETS to non-smoking women and children may contribute.

• Suggested to increase the risk of some childhood cancers; may be pre- or post-natal exposure.

• Associated (as ETS) with physiological changes in children that may increase their risk of Cardiovascular disease as adults.

WHO ConclusionWHO Conclusion

“ETS is a real and substantial threat to child health, causing death and suffering throughout the world.”

“Swift action to highlight the need for strong public policies to protect children from exposure to tobacco smoke is essential.”