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Health Effects of Exposure to
Environmental Tobacco Smoke

Table 3.1

Studies of Birthweight and ETS Exposure

Defined by paternal Smoking Status

Authors (year)
Country

Study Design

Difference in Mean Birthweight by Exposure1

MacMahon et al. (1966)
US (Massachusetts)
Retrospective mail questionnaire
(12,192 white singletons)
(5,935 maternal nonsmokers)
-22g (-57, 13) females
-20g (-55, 15) males

-28g for pipe/cigar (n.s.)
no consistent effect by amount
Comstock & Lundin (1967)
US (Maryland)
Special census linked to vital records (448 births) -42g (no statistics provided)
Underwood et al. (1967)
Worldwide
Naval records of labor and delivery; cross-sectional (48,505 singletons with
24,674 maternal nonsmokers)
-7 to -3g, by amount smoked
Borlee et al. (1978)
Belgium
Retrospective interview (175 normal live births, 202 malformed) -228g (-429.0, -26.7) crude
(p = 0.06 for paternal smoking impact analysis that controlled for maternal smokers) 2
Magnus et al. (1984)
Norway
Retrospective interview of
twins (parents of offspring studied)
(3130 families; 5,188 births)
regression for categories of
about 10 cigs/day:
crude: -48g (-65, -31)
adjusted for maternal

smoking2: -5g (-23, 13)

Rubin et al. (1986)
Denmark
Interview at delivery
(500 term live births >2000g)
adjusted for maternal smoking:

-6.1g/cig (-12, -0.2) 2

-120g/pack

MacArthur & Knox (1987)
England
Unknown
(180 mothers who quit smoking in pregnancy)
-14g crude
not significant in an analysis for the effect of paternal smoking

 

1 All effect measures assessed in non-smoking mothers unless otherwise specified
(e.g., "smoking adjusted"). All 95% confidence intervals calculated by reviewers from available data.

n.s. = not statistically significant (p>0.05).

2 Control for at least some confounders (see text discussion of studies).

3 Based on living with a household smoker, not only the spouse.

Table 3.1 (continued)

Studies of Birthweight and ETS Exposure

Defined by paternal Smoking Status

Authors (year)
Country

Study Design

Difference in Mean Birthweight by Exposure1

Schwartz-Bickenbach et al. (1987)
Germany
Interview at delivery
(54 pairs-smoke and not, followed while breast-feeding)
-205g (-440, 30.1), crude
Campbell et al. (1988)
England
Interview 1 month post- delivery
(518 white singles)
-113g (-216, - 8)2

(from regression after adjusting for maternal smoking)

Brooke et al. (1989) 3
England (London)
Prospective interview
(1513 white births with
1,018 nonsmokers)
-18g or 0.5% reduction2

(p = 0.56)

Chen et al. (1989) 3

China (Shangai)

Retrospective mail
questionnaire (1,058 births)
-11g (-81.9, 64.1)
paternal smoking >10/day

-15g (-94.5, 64.5)
any other smokers >10/day

adj made no difference2
no dose effect

Saito (1991)
Japan
Interview at infant care visit
(3,000 couples)
smoke any: -33.4g (-66.3, -0.5) For 40 cigs/day:

-111g (-191.0, -31.7), crude

Mathai et al. (1990)2
England (Liverpool)
Prospective interview
(285 white singles)
-66g (-213.0, 81.1), crude
Mathai et al. (1992)
India (Vellore)
Interview
(994 singletons)
-63g (-114g, -12)2
Zhang & Ratcliffe (1993)
China (Shangai)
Interview post-delivery
(1,785 singleton term births)
-30g (-66,7)2
-62g for 15-19 cigs/day
but + 32 for > 20/day
Martinez et al. (1994)
US (Arizona)
Interview at delivery
(1219 births, 907 nonsmokers)
-34g (-63, -5)2 per 10 cigarettes

 

1 All effect measures assessed in non-smoking mothers unless otherwise specified
(e.g., "smoking adjusted"). All 95% confidence intervals calculated by reviewers from available data.

n.s. = not statistically significant (p>0.05).

2 Control for at least some confounders (see text discussion of studies).

3 Based on living with a household smoker, not only the spouse.

 

 

Table 3.2

Studies of Fetal Growth and ETS Exposure at home
Defined by paternal Smoking Status

 

Study

Odds Ratios (95% CI)4

Authors (year)
Location

Study Design

Low Birth Weight (LBW)

IUGR/SGA

Preterm

Underwood et al. (1967)1
Worldwide
Naval records of labor and delivery
(24,674 nonsmoking mothers)
0.9 (0.8, 1.0) any
1.05 (0.82, 1.3) >30 cigs
- - 0.9 (0.8, 1.0) any
1.05 (0.8, 1.3)
>30 cigs
Yerulshalmy (1971)1
US (N. California)
Prospective study of Kaiser members
(9,793)
0.9 (n.s.) mother nonsmoker
1.4 (p<0.05) mother smoker
- - - -
Mau & Netter (1974)1
Germany
Prospective interview
(5,183; 3,696 nonsmokers)
1.4 (1.0, 1.9)
>10 cigs/day
1.2 (0.9, 1.7)
>10 cigs/day
1.2 (0.9, 1.6)
>10 cigs/day
Nakamura et al. (1988)
Japan (Osaka)
Prospective interview
(2,371 nonsmokers)
1.4 (0.9, 2.2)3
-----------------------------------
In non-working women:
1.7 (1.0, 2.9)3
1.2 (0.8, 2.0)

------------------

1.4 (0.8, 2.4)

1.2 (0.8, 1.8)

----------------------

1.1 (0.7, 1.8)

Chen et al. (1989)1,2
China (Shanghai)
Retrospective, self-administered
(1,163)
1.5 (0.75, 3.2)
- - - -
Saito (1991)1
Japan (Osaka)
Retrospective interview
(3,000 couples)
- - 1.3 (1.1, 1.5) 1.0 (0.8, 1.3)
Mathai et al. (1992)1,2
India
Interview, but timing unclear
(994)
1.0 (0.4, 2.3)

(LBW defined as <2000g)

- - 1.6 (0.8, 2.9)
Zhang & Ratcliffe (1993)
China (Shanghai)
Interview post-delivery
(1,785 term births of nonsmokers)
- - 1.1 (0.83, 1.5) - -

1 Odds ratios and/or confidence intervals estimated from published data, not published by original authors.

2 Based on any household smoker, instead of only paternal smoker.

3 Controlled for confounders.

  • 4 n.s. indicates lack of statistical significance at p = 0.05.

    IUGR - Intrauterine Growth Retardation; SGA - small for age gestational; LBW at term.

  • Table 3.3
    Studies of Fetal Growth and ETS Exposure

    of maternal Non-Smokers From Multiple ETS Sources

    Study

    Results2

    Authors (year)
    Country(study size 1)

    ETS Level
    (% Exposed)

    Difference in Mean Weight

    IUGR/LBW
    OR (95% CI)

    Martin & Bracken (1986)
    US (Connecticut) (n=2,473)
    Prospective interview
    > 2 hr/day at home or work (34%) -24 g adjusted (-60,13)

    -85 g (p< 0.002) crude

    2.2 (1.1-4.5) LBW
    Ogawa et al. (1991)
    Japan (n=5,336)
    Interview around delivery
    > 2 hr/day at home, work or elsewhere (35%)
    -10.8 g (n.s.)

    -24 g (-47, -2) crude

    1.0 (0.7-1.5) LBW
    Lazzaroni et al. (1990)
    Italy (n=648; examined
    births >2000g, > 37 wks gestation)

    Interview postpartum

    > 1 hr/day at home or work (25%) -38 g (-106.9, 30.7)
    -17 g/hr (-35, 1.3)
    - -
    Ahlborg & Bodin (1991)
    Sweden (n=2,461 employed)

    Interviewed during month 2 or 3 of pregnancy
    Home exposure only (16%)
    ----------------------------
    Most time at work in rooms with smokers (11%)
    -34 g (-82, 15)
    (very small numbers)
    -------------------------------
    20 g (-37, 77)
    0.7 (0.21-2.3) LBW
    (based on 3 infants)

    ------------------------

    1.1 (0.33-3.6) LBW
    1.4 (0.33-5.9) LBW
    if worked full-time

    Fortier et al. (1994)

    Canada (Quebec)

    (n = 4,644 non smokers)

    Interview within few months post partum

    Home only
    (13%)

    ----------------------------

    Work only
    (28%)

    ----------------------------

    Home and Work
    (8%)

    -------------------------------

    -------------------------------

    0.98 (0.67- 1.44) IUGR

    ------------------------

    1.18 (0.90-1.56) IUGR

    ------------------------

    0.94(0.60-1.49) IUGR

     

  • 1 The study size (n) presented is for term births to nonsmokers, not the total study size.

    2 Effect measure adjusted for a number of confounders, unless otherwise indicated as "crude". Abbreviations: LBW - low birth weight; IUGR - intrauterine growth retardation.

    3 The analysis adjusted for LBW in previous births. This may result in substantial under estimation of effect.

  • Table 3.3 (continued)

     

    Studies of Fetal Growth and ETS Exposure

    of maternal Non-Smokers From Multiple ETS Sources

     

    Study

    Results

    Authors (year)
    Country (study size1
    ETS Ascertainment

    ETS Level
    (% Exposed)

    Difference in Mean Weight

    IUGR/LBW3
    OR (95% CI)

    Mainous & Hueston (1994)
    US (nationwide) (n=3,253)

    Retrospective survey
    Categorized as:
    never (23%)
    occasional (46%)
    often (17%)
    always (13%)
    -84g (-150, -18) for highest exposure, crude
    No decrement at lower
    levels
    1.6 (0.92, 2.7) LBW

    with high exposure

    (p < 0.01 dose response trend)

    Chen & Petitti (1995)

    US (California) (n=111 cases,
    124 controls, whites)

    Retrospective interview
    Assessed in 4 locations
    and as average hrs/week

    Any exposure (54%)
    30 hours/wk (7%)
    - - 30 hrs/week:
    0.5 (0.14, 1.7) IUGR

    work only:
    1.0 (0.39, 2.6) IUGR

    home only:
    0.5 (0.13, 1.8) IUGR

    Roquer et al. (1995)
    Spain (n=129)

    Interview at delivery
    "Significant"
    defined as exposed to
    20 cigarettes/day
    -192 (-365, -19), crude
    1. (0.57, 6.1)
    2. IUGR
    3. crude
    Rebagliato et al. (1995)
    Spain (n=710)

    Interview in 3rd trimester
    Assessed hours per week from 4 sources
    Any exposure (88%)
    42 hours/week (22%)
    Any: -85g, crude
    any 42 hours/wk: -41g
    (-144, 61)2
    spouse 42hrs/wk: 31g
    (-103, 165)
    - -
  • 1 The study size (n) presented is for term births to nonsmokers, not the total study size.

    2 Effect measure adjusted for a number of confounders, unless otherwise indicated as "crude". Abbreviations: LBW = low birth weight; IUGR = intrauterine growth retardation.

  • 3 The analysis adjusted for LBW in previous births. This may result in substantial under estimation of effect.

    Table 3.4
    Studies of Fetal Growth and ETS Exposure
    Determined by Biomarkers

     

    Study

    Results

    Authors (year)
    Location

    Design
    (size)

    Biomarker
    Levels1

    Weight Difference

    Low Birth Weight

    Hauth et al.
    (1984)
    US (Texas)
    Maternal serum at labor
    Cord blood at delivery
    (163; 134 nonsmokers)
    Mean in ETS = 26 + 2.5 umol/L SCN vs. 23 + 1.5 in nonsmokers cord blood (n.s.) Correlation of wt and SCN = -0.74 in smokers (p<0.001) vs.
    r = 0.02 in ETS exposed,
    r = 0.15 in nonsmokers
    --
    Haddow et al. (1988)
    U.S. Maine
    Serum drawn early in 2nd trimester
    (1231 nonsmokers)
    1-10 ng/ml cotinine vs. <0.5 in nonsmokers -104 g (adj.)
    (-173,-35)

    -28 g/ng/ml
    cotinine
    (CI = -55, -2,)
    "rate 29%"
    (e.g., OR :

    1.29)
    no statistics or numbers provided

    Mathai et al.
    (1990)
    England
    Urine at 16 weeks
    (285;
    184 nonsmokers)
    Mean in ETS = .85 + 2.8 vs.
    .29 + 1.4 g cotinine/mg creatinine in nonsmokers
    -25 g/g cotinine/mg creatinine (p0.001)
    (includes smokers)
    --
    Eskenazi et al.
    (1995)
    U.S. (California)

    Serum in 2nd
    trimester, stored for 25 years
    (3,578;
    2,292 nonsmokers)
    2 - 10 ng/ml cotinine versus
    <2 ng/ml

    continuous cotinine level
    -45g (adj.)
    (-126, 36)
    inclding smokers: 1g per ng/ml cotinine (adj.)
    (-1.14, -0.79)
    1.35 (0.60, 3.0)
    crude
    Rebagliato et al.
    (1995)
    Spain
    Saliva in 3rd trimester
    (n=710 nonsmokers)
    0.5 = unexposed
    Quintiles of cotinine
    (Mean in ETS exposed = 1.2 ng/ml)
    Any: -35g, crude
    Highest quintile
    (>1.7ng/ml):
    -87g, (adj.)
    (-174, -1)
    - -

     

    1 Abbreviations: SCN = thiocyanate, CI = confidence interval, OR = odds ratio,
    r = correlation coefficient.

    Table 3.5
    ETS Exposure in Relation to Spontaneous Abortion and Perinatal Death
    1

     

    Authors (yr)
    Location

    Design
    (study size)

    Exposure Definition

    Results

    Comments

    Comstock & Lundin (1967)2
    Maryland
    Sample from special census, vital records
    (n = 234 still births,
    158 neonatal)
    Paternal smoking (non-smoking mother) RR = 1.45 (0.9-2.4) for NM. No effect on SB. (noted increased NM in small group where mom started smoking after pregnancy). Adjusted for infant sex and patient education only. Exposure not specific to pregnancy. Completeness of FD records?
    Mau & Netter (1974)2
    Germany
    Interview in early pregnancy (n = 5,183) Paternal smoking by amount
    (>10 cigs/day)
    RR of perinatal death = 1.5 (C.I.= 1.1-2.3)
    RR for SB = 1.2 (n.s.)
    RR for SAB = 1.1 (n.s.)
    Considered confounders, but RR not adjusted. Methods sketchy.
    No dose response.
    Lindbohm et al. (1991)
    Finland
    Case-control study of SABs in lead-monitored men and wives (n=213 SABs, 300 controls) Paternal smoking status OR for SAB =
    1.3 (0.9-1.9)
    Not adjusted. Includes maternal smokers. Generalizability?
    Ahlborg & Bodin (1991)
    Sweden
    Prospective questionnaire (n = 4,687 pregnancies) "Live with smoker."

    Most time at work with smokers

    (non-smoking mother)
    RR for SAB + SB and ETS at home = 1.0
    at work = 1.5 (0.98-2.4)
    RR = 2.2 (1.2-3.8) for
    early SAB & work ETS.
    Adjusted. Work exposure more intense.
    Windham et al. (1992)
    California
    Case-control (n = 626 SABs, 1,300 births) > 1 hr/day (yes/no) in first 20 weeks.
    Paternal smoking (non-smoking mother)
    OR for SAB = 1.6
    (1.2-2.1)
    late SAB (> 12 wks)
    OR = 1.9 (1.4-2.7)
    Adjusted. No effect of paternal smoking when adjusted.

    1 Includes stillbirth or fetal death and neonatal mortality.

    2 Odds ratios and confidence intervals calculated from data, not by original authors.

    Abbreviations: SAB = spontaneous abortion, SB = stillbirth, NM = neonatal mortality, FD = fetal death, RR = rate ratio, OR = odds ratio.

    Table 3.6
    ETS Exposure and Congenital Malformations

     

    Authors (yr)
    Location

    Design
    (study size)

    Exposure Definition1

    Results

    Comments

    Mau & Netter (1974)2
    Germany
    Interview in early pregnancy
    (n = 5,183)
    Paternal smoking by amount
    (>10/day)
    RR for severe BD = 2.6 (1.5-4.7)
    RR for facial clefts = 7.0 (p<.05)
    Cardiac defects = 1.9 (n.s.)
    NTDs = 1.7 (n.s.)
    Looked at some confounders, but not adjusted. Little information on methods.
    Holmberg & Nurminen (1980)
    Finland
    Case-control, registry based (n = 120 CNS anomalies & 120 cntrls) Paternal smoking at conception OR = 1.3 (0.74-2.5) Not adjusted.
    Includes maternal smokers.
    Hearey et al. (1984)
    California
    NTD cluster, case-cntrl
    (n = fathers of 8 cases & 17 controls)
    Retrospective interview
    Father smoke peri-conceptional (father interviewed) OR = 16.0 (p<0.05) unmatched Not adjusted.
    (Includes maternal smokers.)
    n.s. in matched analysis.
    Small numbers.
    Seidman et al. (1990)2
    Israel
    Interview post-partum
    (n = 17,152 infants)
    Paternal smoking (amount) RR = 1.45 (0.73 - 2.8)
    for >30 cigs/day2 and major BDs. RR = 1.1 (0.85, 1.5) for minor BDs.
    Multivariate adjustment (results not shown). Little dose-response. Effect of maternal smoking seen in older women only.
    Savitz et al. (1991)
    California
    Prospective in HMO members (Child Health & Development Study)
    (n = 14,685 births)
    Paternal smoking at prenatal interview OR = 2.4 (n.s.) for hydrocephalus
    OR = 2.0 for VSD and urethral stenosis (n.s)
    OR = 1.7 for CLP (n.s.)
    OR = 0.6 for NTDs (n.s.)
    Multivariate adjustment includes smoking mothers.
    Multiple comparisons. Little dose response.
    Zhang et al. (1992)2
    China
    Case-control interview in hospital
    (n = 1012 cases, 1012 controls)
    Paternal smoking RR = 1.2 (1.0 - 1.5) for all BD. Numerous types elevated, but n.s.
    RR = 1.6 for CP
    RR <1.5 for hydrocephalus
    RR <1.0 for VSD
    RR = 2.0 (1.1, 3.7)2 for NTDs
    Not adjusted but low-risk subgroup. Greater association with multiple vs. single defects. No dose-response. Multiple comparisons.

    1 Among non-smoking women unless otherwise specified. Exposure ascertained from mother unless otherwise specified.
    2 Confidence interval calculated by reviewer.

    Abbreviations: BD = birth defects, NTD = neural tube defects, CNS = central nervous system, VSD = ventricular septal defect,
    CLP = cleft lip and/or cleft palate, CP = cleft palate, n.s. = not significant or p > 0.05.

    Table 3.7
    ANIMAL STUDIES OF TOBACCO SMOKE EXPOSURE
    AND FETAL GROWTH

     

    Mainstream or Unidentified Type of Smoke


    Authors (year)


    Species


    Exposure Period

    Fetal Weight
    at Term

    Essenberg et al. (1940) rats mating through lactation "2/3rds under weight" (no statistics)
    Younoszai et al. (1969) rats day 3 - 22 gestation -16%
    Wagner et al. (1972) mice day 11 - +16 days gestation -16% (not significant)
    Haworth & Ford (1972) rats day 3-20 gestation -19%
    Reckzeh et al. (1975) rats day 1-18 gestation -6% (not significant)
    Reznik & Marquard (1980) rats day 0-21 gestation -31%
    Peterson et al. (1981) mice day 6-17 gestation -4% (not significant)
    Bertolini et al. (1982) rats day 1-20 gestation -9% (not significant)
    Tachi & Aoyama (1983) rats day 0-21 gestation -30%
    Bassi et al. (1984) rats day 5-20 gestation -21%
    Amankwah et al. (1985) mice day 0 - birth -4%
    Rogers & Kuehl (1988) baboons "throughout pregnancy" -17% (no statistics)

    Sidestream Smoke

    Authors (year)

    Species

    Exposure Period

    Fetal Weight

    at Term

    Leichter (1989) rats day 1-20 gestation -9%
    Witschi et al. (1994) rats day 3-10 gestation 0% (not significant)
    Rajini et al. (1994) rats day 3, 6-10 and 13-17 gestation -7%
    Mohtashamipur et al. (1987) (abstract) rats "1st, 2nd and 3rd week of pregnancy" "significant losses"

    no statistics

     

    REFERENCES FOR CHAPTER 3 –
    DEVELOPMENTAL TOXICITY I: PERINATAL MANIFESTATIONS

     

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