1. Maternal Smoking and Infant Birth Weight Lucinda England, MD, MSPH National Institute of Child Health and Human Development (NICHD)

2. Lucinda England, MD, MSPH • Post-doctoral Fellow in the Division of Epidemiology, Statistics, and Prevention Research, NICHD • Interests: smoking and fetal growth, smoking and preeclampsia • This research was conducted while the author was an Epidemic Intelligence Officer at the Centers for Disease Control and Prevention

3. Learning Objectives • Understand the relationship between tobacco exposure during pregnancy and fetal growth • Understand the limitations of methods currently available for measuring tobacco exposure

4. Learning Objectives (Continued) • Appreciate the importance of understanding the nature of the relationship between exposure and outcome

5. Smoking during pregnancy increases likelihood of • Low birth weight • Intrauterine growth restriction • Preterm delivery • SIDS • Maternal complications

6. Quitting during pregnancy improves birth weight, but... • Only one-in-four pregnant smokers quits successfully • One-in-three pregnant smokers cuts back • It is unknown if cutting back is beneficial

7. How do we measure tobacco exposure? 1. Self report: Inexpensive, but has several limitations a) Some may not report use honestly b) Recall bias c) People tend to round to the nearest pack or half-pack

8. How do we measure tobacco exposure? 2. Biomarkers: Objective way to validate and quantify exposure a) Thiocyanate b) Carbon monoxide c) Cotinine

9. Biomarkers: cotinine • Primary metabolite of nicotine • Popular biomarker because it: -Has long half life (20 hours) -Can be detected in serum, urine, or saliva -Is stable in stored specimens

10. Unresolved research issues: 1. Can cotinine concentration be used to predict how much a woman smokes? 2. Does a pregnant woman who cuts back improve her infant’s birth weight?

11. To address these issues, we need to know the following: 1. What is the nature of the relationship between cotinine and cigarettes per day? 2. What is the nature of the relationship between tobacco exposure and birth weight?

12. Methods

13. Data source: A collaborative project between the CDC and three state health departments Study population: Self-reported smokers attending public prenatal clinics from 1987-1990 and giving birth to live, term, singleton infants

14. Outcome= birth weight Exposure = tobacco • Measured in two ways: • Self-reported cigarettes smoked per day • Urine cotinine concentration • Obtained at two points in time: • At entry into prenatal care • In the 3rd trimester

15. Analysis I:Relationship between cigarette smoking and urine cotinine • General linear models were used to quantify the amount of cotinine variability explained by self reported cigarettes smoked per day.

16. Analysis II: Tobacco exposure and birth weight • General linear models were used to generate mean adjusted birth weight. • Birth weight was plotted against cigarettes per day and against urine cotinine concentration.

17. Results

18. Study population • 5,572 women screened • 4,005 women eligible • 3,395 women had at least one set of corresponding measures of exposure • 2,481 women still smoking in 3rd trimester

19. Cigarettes per day and urine cotinine (See Figure 1) • Median urine cotinine concentration increased as cigarettes per day increased. • Urine cotinine concentration reached a plateau at > 15 cigarettes per day.

20. Cigarettes per day and urine cotinine (See Figure 1) • Urine cotinine concentration varied considerably at all levels of cigarette smoking. • The amount of variation in urine cotinine concentration explained by cigarettes per day (r2) was only 14 percent.

21. Figure 1. Box and whiskers plot of urine cotinine by cigarettes per day Click for larger picture

22. Tobacco exposure and birth weight • Mean adjusted birth weight decreased as cigarettes per day increased (See Figure 2). • The relationship was not linear: the sharpest decline in birth weight seen at low levels of smoking. • A similar pattern seen with cotinine concentration (see Figure 3).

23. Figure 2. Mean adjusted infant birth weight by 3rd trimester smoking Click for larger picture

24. Figure 3. Mean adjusted infant birth weight by 3rd trimester cotinine Click for larger picture

25. Discussion

26. Answers to research questions: 1. What is the relationship between urine cotinine and cigarettes smoked per day? Answer: Urine cotinine concentration does not correlate closely with cigarettes per day.

27. Answers to research questions: 2. What is the relationship between tobacco exposure and birth weight? Answer: Birth weight declines sharply at low levels of exposure, then levels off.

28. Study Limitations • We don’t know time elapsed between last cigarette smoked and urine collection. • We don’t have information on types of cigarette smoked or how cigarettes were smoked.

29. Conclusions • Our ability to quantify tobacco exposure is limited; both self-reported cigarette use and urine cotinine have serious limitations. • More research is needed to uncover the mechanisms through which tobacco causes fetal growth restriction.

30. Conclusions • Studies of the effects of smoking reduction on health outcomes are needed before recommending reduction as an alternative to quitting.

31. Suggested readings England et al. Measures of maternal tobacco exposure and infant birth weight at term. Am J Epidemiol, 2001;153:954-60. England et al. Effects of smoking reduction during pregnancy on the birth weight of term infants. Am J Epidemiol, (in press). Ellard GA et al. Smoking during pregnancy: the dose dependence of birthweight deficits. Br J Obstet Gynaecol, 1996; 103:806-13. Klebanoff MA et al. Serum cotinine concentration and self- reported smoking during pregnancy. Am J Epidemiol, 1998; 148:259-62. Haddow JE et al. Cigarette consumption and serum cotinine in relation to birth weight. Br J Obstet Gynaecol, 1987;94:678-81.