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Is Prenatal Caffeine Exposure Related to Neurodevelopment?

Is Prenatal Caffeine Exposure Related to Neurodevelopment?. Author 1 Author 2 PH251A: Practicum in Epidemiologic Methods 12/5/2007. Description of Question. Does prenatal coffee exposure increase the risk of poor neurodevelopment at ages 9 to 11?.

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Is Prenatal Caffeine Exposure Related to Neurodevelopment?

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  1. Is Prenatal Caffeine Exposure Related to Neurodevelopment? Author 1 Author 2 PH251A: Practicum in Epidemiologic Methods 12/5/2007

  2. Description of Question • Does prenatal coffee exposure increase the risk of poor neurodevelopment at ages 9 to 11?

  3. Reasons to Study Caffeine and Neurodevelopment • 71% of the caffeine in the US is consumed in the form of coffee (Faray, 2005) • Average American consumes 1.2 cups of coffee per day (FAS/USDA, 2002) • Widely ingested by pregnant women (Sobotka, 1989) • Can cross the placenta and reach the fetus; is metabolized more slowly during pregnancy • Associated with spontaneous abortion and low-birth weight in humans • Little information is available on the long-term effects of prenatal coffee exposure

  4. Summary of Background Literature Two studies directly address this question: • Jacobson et al (1984): Caffeine exposure predicted negative behavioral effects (p<0.05) • Barr et al (1989): Long term effects of caffeine on IQ at 4 and 7 years are null -- but they should conclude that they fail to find an effect

  5. Public Health Significance • Long-term effect or prenatal coffee exposure is still unknown • Because of the popularity of coffee, negative long-term effects would mandate wide-scale interventions to decrease prenatal consumption

  6. Primary Variables • Exposure Variable: Number of cups of prenatal coffee per day: • None or <1 a week • 1 to 2 cups/ day • 3 to 4 cups/ day • >4 cups/ day • Outcome Variable: • Peabody Picture Vocabulary Test: - Test for Verbal Intelligence - Scores range from 27 to 147 • Raven Colored Progressive Matrices - Test for perceptual reasoning - Scores range from 0 to 77

  7. Maternal Characteristics: - Age - BMI - Prenatal Smoking - Prenatal Alcohol - Prenatal Work - Marital Status - Peabody Score Paternal Age Total Family Income Child Characteristics - Age - Sex - Race - Birth weight - Gestational Length - Glasses Use Key Covariates

  8. Methods • Univariate and multivariate analyses were conducted to address the relationship between prenatal coffee exposure and Peabody and Raven Scores at ages 9 – 11. • Adjusted for confounders in the analyses. • Used restricted vs. full F-tests to help with model selection. • Looked at statistically significant interactions in the final model.

  9. Figure 1 (Subject Exclusion Flow Chart) Prospective Study Group – Total Number of Pregnancies N= 20,754 -4,826 Interview Before Delivery N= 15,928 -1,330 Live Births N= 14,899 - 301 Singleton Births N= 14,598 -451 No Severe Birth Anomalies N=14,147 -10,410 At Nine to Eleven Year Old Exam Total Children Examined N=3,737

  10. Results- Outline • Summary Statistics • Univariate Analysis • Crude RR • Multivariate Analysis • Included statistically significant (found in univariate analysis)and biologically relevant covariates. • Model selection: Checked different models, compared them using F-tests • Checked for normality assumptions • Checked for the effect of outliers in the final model

  11. Select Variables -Univariate Analysis

  12. Outcome by Exposure – Crude RRs

  13. Final Model – Key Results • Effect of prenatal coffee intake on child’s Peabody scores: statistically significant negative effect after controlling for the effect of other relevant covariates • Intake of 3-4 cups of coffee compared to no coffee is associated with 1.57 point reduction in Peabody scores: Effect is small but highly statistically significant.

  14. Final Model – Key Results • Similar Results if Raven Scores are used as an independent variable: Provide more confidence about the overall finding

  15. Final Model

  16. Comparison with previous studies • Barr et al (1991) fail to find an effect of prenatal caffeine exposure on child’s IQ at ages 4 and 7 -- However, this study does not control for the effect of mother’s IQ or its equivalent • In our analysis we find that mother’s IQ (measured as mother’s Peabody score) is a confounder. Mother’s Peabody score is positively correlated with both Child’s Peabody score and prenatal coffee intake. • If we do not control for this confounder, we fail to see an effect of prenatal coffee on child’s Peabody and Raven Scores.

  17. Other Findings • We explored the possibilities of interactions (effect modifications) of different independent variables such as: alcohol intake and coffee intake, alcohol intake and smoking, smoking and alcohol intake, race and coffee intake, mother’s Peabody scores and coffee intake, SES and coffee intake • We do not find statistically significant effect of interactions

  18. Other Findings • Other variables that were significant and that were positively associated with child’s peabody scores: • mother’s age, father’s occupation, mother’s peabody scores, high prenatal alcohol intake, child did not wear glasses, mother’s occupation, mother’s education, Child’s race (other), age of child at exam • Other studies that use the CHDS dataset do not use alcohol variable as covariate?? • Excluding alcohol variable do not affect the result of caffeine intake • Other variables that were significant and that were negatively associated with child’s peabody scores: • Female child, black race, 2-4 cups of coffee per day

  19. Conclusions • Prenatal coffee intake has a small negative effect on child’s neurodevelopment as assessed by Peabody (2% reduction) and Raven scores (4.3% reduction) • Effects precisely estimated • Caution in drinking 3-4 cups of coffee/ day during pregnancy is warranted

  20. Limitations and Future Research • Coffee is the only source of caffeine included • Milligrams of caffeine in each cup of coffee was unspecified in the CHDS dataset • No possible explanation for the counterintuitive effect of alcohol on child’s Peabody and Raven scores

  21. Bibliography • Barr HM and Streissguth AP. Caffeine Use During Pregnancy and Child Outcome: A 7-Year Prospective Study. Neurotoxicology and Teratology. 13:441-448; 1989. • FAS/USDA, Horticulture and Tropical Products Division. US Coffee Consumption. 2002. Accessed on 9/17/07. Available at: http://www.fas.usda.gov/htp/tropical/2002/06-02/coffusco.pdf. • Jacobson SW, Fein GG, Jacobson JL, Schwartz PM, Dowler JK. Neonatal Correlates of Prenatal Exposure to Smoking, Caffeine, and Alcohol. Infant Behavior and Development. 7:253-265; 1984. • Streissguth AP, Barr HM, Martin DC. Maternal Alcohol Use and Neonatal Habituation Assessed with the Brazelton Scale. Child Development. 54(5): 1109-1118; 1983. • Streissguth AP, Barr HM, Sampson PD. Moderate Prenatal Alcohol Exposure: Effects on Child IQ and Learning Problems and Age 7.5 Years. Alcoholism: Clinical and Experimental Research. 14(5): 662-669; 1990.

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