Maternal smoking during pregnancy was associated with an increased risk of major malformations in newborns. A study of over 2000 pregnancies found the risk of major malformations was 3.3 times higher for babies exposed to maternal smoking compared to non-exposed babies. Paternal smoking was also high among the smoking mothers, occurring in over 60% of smoking mothers compared to 38% of non-smoking mothers. Exposure to alcohol and lower education levels were also associated with increased risk of maternal smoking during pregnancy.

1. Smoking in Pregnancy
2016.7.12
전임의 부혜연

2. Smoking in Pregnancy
• 여성의 흡연율
• 2011년 6.8%, 2012년 7.9%, 2013년 6.2%, 2014년
5.7% (국민건강영양조사)
• In the US : about 16 % of pregnant women smoke
• In Korea : 8-10%

3. • Cigarette smoke contains over 4,000 chemicals and
toxins including
Nicotine
Tar
Arsenic
Lead
Carbon monoxide
At least 40 known cancer-causing agents
Smoking in Pregnancy

4. Carbon Monoxide
• Carbon monoxide(CO) + Hemoglobin (Hb)
Carboxyhemoglobin(COHb)
• Fetal concentrations are generally higher
d/t higher affinity
Decrease the amount of oxygen carried
to cells
Impair cytochrome enzymes
->Affects intracellular process

7. Nicotine
• Lipid-soluble
• Large distribution volume(2-3L/kg)
• Permeates cell membranes
• Absorbed by lung, skin, GI tract, nasal mucosa
• Actively secreted by renal tubules
• Elimination half life 1-3Hrs
• Major metabolite level(eg. Cotinine)->Most accurate
estimation

8. Adverse Effects in Pregnancy
• Increased miscarriage
risk
• Reduced fetal growth
• Congenital
malformation: Some,
Small
• Abnormal placentation
• Sudden infant death
syndrome
• Neurobehavioral
development
Reprotox

9. Fetal Growth and Prematurity
• Intrauterine growth restriction: most consistent
effect
200gm lighter
Dose-response relationship
Stopped during the first half of gestation
-> virtually normal birth weight
• Possible mechanisms)
Premature placental maturation
Chronic reduction in placental blood flow
Increase in Cadmium burden
Fetal hypoxia(d/t CO)

10. Long-term Effects
• Long-term growth and developmental studies
• Smoking in pregnancy might affect
Physical growth, mental development, and
behavioral problem
• Mean 8-point decrement in IQ test in heavy
smokers

11. Malformations
• Some reports suggested..
• Club foot ?
• Craniosynostosis : Premature closure of sagittal
suture(OR 1.48)
• Facial clefts(1/500->1/183)

13. Malformations
• Hydrocephaly, microcephaly
• Omphalocele, gastroschisis
• Limb reduction defects
• Congenital heart defect
• Paternal Smoking
• Increase in facial clefts
• Congenital heart defect

14. Other Pregnancy Outcomes
• Ectopic pregnancy
• Spontaneous abortion
• Fetal death
• Sudden infant death syndrome (SIDS)
• Placenta previa, placenta abruption and bleeding
early or late in pregnancy.

15. • Childhood cancer (leukemia)
• Paternal smoking around conception -> childhood
cancer prior to age 5 (leukemias, lymphomas, and
brain tumors)
• Pulmonary function
• ADHD?
• Later schizophrenia
• Higher food allergen sensitization (OR : 2.2)
• Obesity, hyprtension

16. Lactation
• Breastfeeding within 1 hour->nicotine concentration in milk
• Impeded iodine transport into milk in smoking mother

17. • To access maternal and fetal exposure
• Umbilical carboxyhemoglobin (COHb)
Elimination t½ of CO is around 5 hours.
Only if the mother had continued smoking
When elimination t½ is long enough
• Level of Cotinine
Meconium(first day of life)
Hair(3-4 months)
Biological Markers

19. • Cheil General Hospital
• Between January 2000 and December 2014
Maternal smoking
Pregnancy outcome
Paternal smoking

20. Control (n=1487)Smoking (n=540)
Smoking (n=268) Control (n=807)
AA 21
Transfer 638
F/u loss 21
AA 8
Transfer 257
F/u loss 7
Smoking (n=238) Control (n=739)
SA 68SA 30

21. Cases(n=268) Controls(n=807)
n (%) n (%) OR 95% CI P value
Age(mean±SD) 31.9±4.1 31.9±3.8 -0.5-0.6 0.82
Gravidity(mean±SD) 2.5±1.5 2.2±1.3 -0.5 to -0.1 <0.01
Parity(mean±SD) 0.4±0.6 0.6±0.6 0.2-0.4 <0.01
Body Mass Index
(mean±SD)
21.2±3.8 22.1±24.7 -0.9-2.7 0.31
Exposure to X-rays 48 17.9 153 18.9 0.9 0.7-1.3 0.71
Total dose(mSv) 2.9±6.8 2.3±6.7 -2.8-1.6 0.58
Gestational age at
Exposure
3.5±3.3 3.7±2.5 -0.9-1.2 0.75
Exposure to Alcohol 182 67.9 292 36.1 3.7 2.8-5.0 <0.01
Total dose(oz) 2.4±4.5 1.6±1.3 -1.6 to -1.3 0.01
Gestational age at
Exposure
4.4±2.7 4.3±3.0 -0.6-0.4 0.74
Paternal smoking 166 61.9 307 38.0 2.7 2.0-3.5 <0.01
Cigarettes/day 11.1±15.9 5.7±9.0 -7.0 to -3.9 <0.01

22. Cases(n=268) Controls(n=807)
n (%) n (%) OR 95% CI P value
Comorbidities
Hypertension 1 0.4 2 0.2 1.5 0.1-16.7 0.74
Thyroid disease 2 0.7 8 1 0.8 0.2-3.6 0.72
Type II Diabetes 0 0 3 0.4 0.7-0.8 0.32
Education level
Post-secondary
education
92 34.3 362 44.8 0.6 0.5-0.9 <0.01
High school 46 17.2 71 8.8 2.2 1.4-3.2 <0.01
Not answered 130 48.5 375 46.4 1.1 0.8-1.4 0.55
Occupation
Professional, technical
and related occupations
29 10.8 108 13.4 0.8 0.5-1.2 0.28
Excutive, administrative,
managerial and sales
occupations
123 45.9 353 43.7 1.1 0.8-1.4 0.53
Constructive workers 102 38.1 326 40.3 0.9 0.7-1.2 0.51
Unemployed 8 3 16 2 1.5 0.6-3.6 0.33
No answer 6 2.2 5 0.6 3.7 1.1-12.2 0.02

23. Case(n=268)
Mean
Cigarette/Day
(mean±SD)
8.0±6.3 1.0-40.0
Gestational age
at exposure
(weeks)
(mean±SD)
5.3±3.9 0-31.0
Table 2. Characteristics of Smoking group.

24. Table 3. Fetal and neonatal outcomes.
Cases(n=238) Controls(n=739)
n (%) n (%) OR 95% CI P value
Gestational age at birth
(weeks)(mean±SD)
39.1±2.2 39.2±1.4 -0.1-0.3 0.37
Birth weight(g)
(mean±SD)
3274.8±503.5 3309.7±428.0 -30-100 0.30
Birth length(cm)
(mean±SD)
49.2±5.0 49.4±3.7 -0.5-0.9 0.51
Head circumference(cm)
(mean±SD)
34.2±3.5 34.5±2.5 -0.2-0.7 0.31
Apgar score, 1 min
(mean±SD)
8.2±1.1 8.3±0.9 0-0.3 0.05
Apgar score, 5min
(mean±SD)
9.0±1.0 9.1±1.0 -0.1-0.2 0.21
Stillbirth 2/236 0.8 1/738 0.1 6.3 0.6-69.3 0.09
Major malformations 6 18.2 6 6.3 3.3 1.0-11.1 0.04
NICU admission 15 6.3 33 4.5 1.4 0.8-2.7 0.26
Length of stay at
NICU (days) (mean±SD)
0.7±2.6 0.6±2.7 -0.5-0.3 0.58

25. Major Malformations
Control(n=6) Case(n=6)
VSD 2
Microtia 2
Cleft palate 1
Necrotizing enterocolitis 1
Inguinal hernia 2
Both Hydrocele 1
Cryptorchidism 1
Polydactly 1
Hirchsprung Dz 1
Table 5. Details of major malformations.

26. Table 4. Fetal and neonatal outcomes by Paternal smoking.
Smoking(n=424) Controls(n=553)
n (%) n (%) OR 95% CI P value
Gestational age at birth
(weeks)(mean±SD)
39.2±1.6 39.2±1.7 -0.2-0.2 0.91
Birth weight(g)
(mean±SD)
3301.0±426.2 3301.4±463.5 -55.8-56.5 0.99
Birth length(cm)
(mean±SD)
49.2±3.2 49.4±2.5 -0.3-0.7 0.40
Head circumference(cm)
(mean±SD)
34.4±3.5 34.4±2.5 -0.3-0.4 0.78
Apgar score, 1 min
(mean±SD)
8.2±0.9 8.3±0.9 0-0.3 0.03
Apgar score, 5min
(mean±SD)
9.0±1.0 9.1±0.9 0-0.2 0.10
Stillbirth 1/423 0.2 2/551 0.4 0.6 0.1-7.2 0.73
Major malformations 8 12.3 4 6.3 2.1 0.6-7.3 0.25
NICU admission 19 4.5 29 5.3 0.9 0.5-1.6 0.61
Length of stay at
NICU (days) (mean±SD)
0.6±2.6 0.6±2.8 -0.3-0.3 0.95

27. Maternal
smoking
Alcohol
Exposure
Education
Major
malformation
Paternal
smoking