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. Percent

International Smoking Rates in Women CountryEarly 1970’sEarly 1990’s Australia29%21% Canada35%29% England42%28% Japan15-17%13-15% Norway37-38%26-33% China2-4%

Background--Active Smoking and Reproductive 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 Pregnancy 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 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--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--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, 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 (86%) interviewed (18.5 months)

SACCS: 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 LMP  pregnancy (or 20 weeks).

SACCS Results: SAB and ETS Variable Exp. AOR 95% C.I. ETS of 1+ hrs/day 38% Paternal smoke (>20c) 6% ETS w/ paternal smoker Little effect of maternal smoking after adjustment! Windham et al. AJE 1992;135:

SACCS Results: Growth and ETS Among Non-Smoking Women Outcomes AOR 95% C.I. Low Birthweight (<2500gms) LBW at term Small for Gest Age (<10 th %) Preterm Delivery (<37 weeks) 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, 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 OUTCOMES LIVEBIRTH4, STILLBIRTH MISCARRIAGE ABORTION OTHER EXCLUSIONS TOTAL IN ANALYSIS5,

POS: Ascertainment of ETS HOME:Hours/day since LMP near someone smoking at home WORK:Hours/day around someone smoking at work TOTAL:Home plus Work PATERNAL SMOKING: Current smoking status (first trimester) Smoking status during three months before LMP  #cigs/day

POS Results: SAB and ETS VARIABLE Exp. AOR 95% C.I. Any Home ETS 11% Any Work ETS 23% Any ETS (0.5+ hrs) 28% High Caffeine + ETS 1% High Alcohol + ETS 0.2% Windham et al. AJE 1999;149:

POS Results : Growth and Heavy ETS (7+ hours/day) Outcomes AOR 95% C.I. Low Birthweight (<2500gms) Small for Gest Age (<10 th %) Preterm Delivery (<37 weeks) Very Preterm (<35 weeks) ETS effects stronger in non-White races and for preterm delivery, in older women (> 30). Windham et al. Epidemiology 2000;11:

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

Meta-Analysis: Differences in Mean Birth Weight by ETS Exposure StudiesPooled Weight includedNdifference (g) and (95% CI) All22 -25(-34, -16) Non-smokers19 -31(-42, -20) Adj. Diffs (-41, -16) Multiple sources of ETS exp (-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

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

Meta-Analysis: Risk of Low Birth Weight or Small for Gestational Age StudiesPooled includedN OR (95% CI) Term LBW or SGA11 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* Authors Exposure Estimate of effect SERUM: Haddow et al., ‘ ng/ml ~1.29 Eskenazi et al., ‘ 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 ETS Exposure MeasureNRange of Effects (ORs) Household smokers (1.9 older women) Work & Home any; high (2.8 in older women) Biomarkers /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, 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. Effects with Suggestive Evidence Developmental: Spontaneous abortion Adverse impact on cognition and behavior Respiratory Effects : Exacerbation of cystic fibrosis Decreased pulmonary function

Summaries: WHO Consultation on 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 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. 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. 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 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.”