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Maternal analgesic use and cardiovascular malformations
AEP Vol. 15, No. 8 September 2004: 630–665
P80 MATERNAL ANALGESIC USE AND CARDIOVASCULAR MALFORMATIONS CA Rowland, A Correa, JD Cragan, CJ Alverson, Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, GA PURPOSE: Certain drugs used during pregnancy have been associated with an increased risk of congenital malformations in offspring. Whether maternal use of analgesics increases the risk of cardiovascular malformations (CVM) is unclear. METHODS: We used data from the Baltimore-Washington Infant Study, a population-based case-control investigation of environmental factors and CVM, to examine CVM and maternal analgesic use during the periconceptional period (3 months before and 3 months after conception). During the period 1981–1989, 2,842 infants with CVM (case infants) and 3,516 nonmalformed infants (control infants) were ascertained with information on maternal drug use elicited from home interviews. We compared case and control infants on frequency of maternal use of analgesics during the periconceptional period using odds ratios (ORs) and 95% confidence intervals (CIs) for ORs. Fisher’s Exact CIs for ORs were estimated when one or more cell counts fell below 5. RESULTS: Periconconceptional use of any analgesic among control mothers was 20.0%, with the more commonly used analgesics being medications containing aspirin (10.2%), nonsteroidal antiinflammatory drugs (NSAIDs) (5.9%), and opioids (5.4%). Analyses type of analgesic and CVM diagnosis identified associations of: ibuprofen with transposition of the great arteries (TGA) (OR Z 2.1, CI Z 1.3, 3.4); atrioventricular septal defects (OR Z 1.8, CI Z 1.1, 2.8); and membranous ventricular septal defects (OR Z 1.5, CI Z 1.1, 2.1). Medications containing codeine were also associated with TGA (OR Z 1.9, CI Z 1.1, 3.2). CONCLUSION: Maternal use of ibuprofen or codeine containing analgesics during the periconceptional period might be associated with an increased risk of certain cardiovascular malformations in infants. Further investigation into these findings is needed to examine potential confounding by indication.
P81 CONTRACEPTIVE ADHERENCE AND FREQUENCY OF SEX AMONG ORAL CONTRACEPTIVE USERS: FINDINGS FROM THE CONTRACEPTIVE HISTORY, INITIATION, AND CHOICE STUDY LR Brunner-Huber, CJ Hogue, AD Stein, C Drews, M Zieman, J King, S Schayes, Department of Health Behavior and Administration, University of North Carolina-Charlotte, Charlotte, NC PURPOSE: Among oral contraceptive (OC) users, adherence to the dosage regimen and frequency of sex are major determinants of unintended pregnancy. Though integral to studies of fertility and contraceptive effectiveness, information on these determinants is limited. The purpose of the Contraceptive History, Initiation, and Choice (CHIC) Study is to determine factors related to adherence and frequency of sex. METHODS: Women between the ages of 18–45 who were using birth control were approached while waiting for appointments at
ABSTRACTS (ACE)
659
a family medicine clinic in Atlanta. Those who agreed signed an informed consent form and filled out a short baseline survey. Current OC users were invited to participate in a longitudinal study. Of 158 identified OC users, 98 returned 413 weekly diaries containing daily information on adherence and frequency of sex. Logistic regression for correlated responses was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women using OCs to regulate their menstrual cycles had increased odds of adherence (OR Z 2.74, 95% CI: 1.07, 7.02). Black women had decreased odds of having sex (OR Z 0.47, 95% CI: 0.23, 0.96), as did women experiencing menstrual bleeding (OR Z 0.56, 95% CI: 0.41, 0.78). With regards to adherence, there was no association between missing >1 pill during a week and sex (OR Z 0.94, 95% CI: 0.53, 1.64). However, women who deviated from their self-reported pill taking time by >2 hours had increased odds of having sex (OR Z 1.60, 95% CI: 1.13, 2.29). CONCLUSION: A diverse group of well-educated, sexually active OC users frequently forgot to take pills or did not take them at a consistent time, thereby increasing their risk of unintended pregnancy. Subgroup analyses of this exploratory study suggest associations that should be further investigated with respect to their impact on fertility, contraceptive effectiveness, and sexually transmitted infections.
P82 ASSOCIATION OF CAFFEINE METABOLITES IN UMBILICAL CORD BLOOD WITH IUGR AND PRETERM DELIVERY: A PROSPECTIVE COHORT STUDY OF 1609 PREGNANCIES LM Grosso, EW Triche, K Belanger, NL Benowitz, TR Holford, MB Bracken, Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Yale University, New Haven, CT PURPOSE: To examine the association between IUGR and preterm delivery (PTD) and fetal caffeine exposure when estimated by serum caffeine and paraxanthine in umbilical cord. METHODS: Prospective cohort study conducted in Connecticut and Massachusetts specifically testing the relation of caffeine and its metabolites, measured in cord blood (ng/ml) to IUGR (N Z 1606) and PTD (N Z 1609). Important covariates were controlled for in logistic regression models. Ridge regression for generalized linear models was used to control for collinearity among metabolites. All metabolite analyses were done blind to consumption data and reproductive outcomes. RESULTS: We observed a 24% increase in risk for IUGR per paraxanthine quartile change (Ridge adjusted OR 1.24; 95% CI 1.10, 1.39), while caffeine was protective for IUGR: Ridge adjusted OR 0.87 (95% CI 0.78, 0.97) per quartile change. When the ratio of paraxanthine:caffeine was modeled, there was a 6-fold increase in risk for IUGR for every one-unit increase in the ratio (MLE adjusted OR 6.03; 95% CI 2.14, 17.03). There was an 18% increase in risk for preterm delivery per paraxanthine quartile change (Ridge adjusted OR 1.18; 95% CI 1.05, 1.33). Caffeine was not associated with PTD nor was the paraxanthine:caffeine ratio. Maternal self-reported caffeine consumption during the third trimester was not associated with either outcome. CONCLUSIONS: Paraxanthine, rather than caffeine, may increase risk for IUGR and PTD. These findings may explain the equivocal literature evaluating reported consumption only. More
P80 MATERNAL ANALGESIC USE AND CARDIOVASCULAR MALFORMATIONS CA Rowland, A Correa, JD Cragan, CJ Alverson, Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, GA PURPOSE: Certain drugs used during pregnancy have been associated with an increased risk of congenital malformations in offspring. Whether maternal use of analgesics increases the risk of cardiovascular malformations (CVM) is unclear. METHODS: We used data from the Baltimore-Washington Infant Study, a population-based case-control investigation of environmental factors and CVM, to examine CVM and maternal analgesic use during the periconceptional period (3 months before and 3 months after conception). During the period 1981–1989, 2,842 infants with CVM (case infants) and 3,516 nonmalformed infants (control infants) were ascertained with information on maternal drug use elicited from home interviews. We compared case and control infants on frequency of maternal use of analgesics during the periconceptional period using odds ratios (ORs) and 95% confidence intervals (CIs) for ORs. Fisher’s Exact CIs for ORs were estimated when one or more cell counts fell below 5. RESULTS: Periconconceptional use of any analgesic among control mothers was 20.0%, with the more commonly used analgesics being medications containing aspirin (10.2%), nonsteroidal antiinflammatory drugs (NSAIDs) (5.9%), and opioids (5.4%). Analyses type of analgesic and CVM diagnosis identified associations of: ibuprofen with transposition of the great arteries (TGA) (OR Z 2.1, CI Z 1.3, 3.4); atrioventricular septal defects (OR Z 1.8, CI Z 1.1, 2.8); and membranous ventricular septal defects (OR Z 1.5, CI Z 1.1, 2.1). Medications containing codeine were also associated with TGA (OR Z 1.9, CI Z 1.1, 3.2). CONCLUSION: Maternal use of ibuprofen or codeine containing analgesics during the periconceptional period might be associated with an increased risk of certain cardiovascular malformations in infants. Further investigation into these findings is needed to examine potential confounding by indication.
P81 CONTRACEPTIVE ADHERENCE AND FREQUENCY OF SEX AMONG ORAL CONTRACEPTIVE USERS: FINDINGS FROM THE CONTRACEPTIVE HISTORY, INITIATION, AND CHOICE STUDY LR Brunner-Huber, CJ Hogue, AD Stein, C Drews, M Zieman, J King, S Schayes, Department of Health Behavior and Administration, University of North Carolina-Charlotte, Charlotte, NC PURPOSE: Among oral contraceptive (OC) users, adherence to the dosage regimen and frequency of sex are major determinants of unintended pregnancy. Though integral to studies of fertility and contraceptive effectiveness, information on these determinants is limited. The purpose of the Contraceptive History, Initiation, and Choice (CHIC) Study is to determine factors related to adherence and frequency of sex. METHODS: Women between the ages of 18–45 who were using birth control were approached while waiting for appointments at
ABSTRACTS (ACE)
659
a family medicine clinic in Atlanta. Those who agreed signed an informed consent form and filled out a short baseline survey. Current OC users were invited to participate in a longitudinal study. Of 158 identified OC users, 98 returned 413 weekly diaries containing daily information on adherence and frequency of sex. Logistic regression for correlated responses was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women using OCs to regulate their menstrual cycles had increased odds of adherence (OR Z 2.74, 95% CI: 1.07, 7.02). Black women had decreased odds of having sex (OR Z 0.47, 95% CI: 0.23, 0.96), as did women experiencing menstrual bleeding (OR Z 0.56, 95% CI: 0.41, 0.78). With regards to adherence, there was no association between missing >1 pill during a week and sex (OR Z 0.94, 95% CI: 0.53, 1.64). However, women who deviated from their self-reported pill taking time by >2 hours had increased odds of having sex (OR Z 1.60, 95% CI: 1.13, 2.29). CONCLUSION: A diverse group of well-educated, sexually active OC users frequently forgot to take pills or did not take them at a consistent time, thereby increasing their risk of unintended pregnancy. Subgroup analyses of this exploratory study suggest associations that should be further investigated with respect to their impact on fertility, contraceptive effectiveness, and sexually transmitted infections.
P82 ASSOCIATION OF CAFFEINE METABOLITES IN UMBILICAL CORD BLOOD WITH IUGR AND PRETERM DELIVERY: A PROSPECTIVE COHORT STUDY OF 1609 PREGNANCIES LM Grosso, EW Triche, K Belanger, NL Benowitz, TR Holford, MB Bracken, Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Yale University, New Haven, CT PURPOSE: To examine the association between IUGR and preterm delivery (PTD) and fetal caffeine exposure when estimated by serum caffeine and paraxanthine in umbilical cord. METHODS: Prospective cohort study conducted in Connecticut and Massachusetts specifically testing the relation of caffeine and its metabolites, measured in cord blood (ng/ml) to IUGR (N Z 1606) and PTD (N Z 1609). Important covariates were controlled for in logistic regression models. Ridge regression for generalized linear models was used to control for collinearity among metabolites. All metabolite analyses were done blind to consumption data and reproductive outcomes. RESULTS: We observed a 24% increase in risk for IUGR per paraxanthine quartile change (Ridge adjusted OR 1.24; 95% CI 1.10, 1.39), while caffeine was protective for IUGR: Ridge adjusted OR 0.87 (95% CI 0.78, 0.97) per quartile change. When the ratio of paraxanthine:caffeine was modeled, there was a 6-fold increase in risk for IUGR for every one-unit increase in the ratio (MLE adjusted OR 6.03; 95% CI 2.14, 17.03). There was an 18% increase in risk for preterm delivery per paraxanthine quartile change (Ridge adjusted OR 1.18; 95% CI 1.05, 1.33). Caffeine was not associated with PTD nor was the paraxanthine:caffeine ratio. Maternal self-reported caffeine consumption during the third trimester was not associated with either outcome. CONCLUSIONS: Paraxanthine, rather than caffeine, may increase risk for IUGR and PTD. These findings may explain the equivocal literature evaluating reported consumption only. More