The Peer Education in Pregnancy Study is a randomized controlled trial examining the effect of community educators working with pregnant women at risk for having children with asthma (defined as the unborn child having a first-degree relative with asthma, hay fever, or eczema) on modification of factors in the home known to exacerbate the disease. The intervention did not include discussion of acetaminophen use. The primary end points of the study are wheezing and allergic symptoms in the first year of life, as well as wheezing, allergic symptoms, and diagnosed asthma in children 3 to 5 years of age. All women in the study received general health education. Half of the women, in addition, received a series of home visits from a community health educator to identify and decrease asthma triggers. Of a total of 5,443 women identified as being pregnant, 354 (6.5%) could not be located and 380 (7.0%) were not interested in participating. Of the remainder, 86% were not eligible (did not have a history of asthma or allergies, were more than 4 months pregnant, had a miscarriage, or did not live in the targeted area). A total of 483 women were initially enrolled. Of those, 100 dropped out before the second visit, at which time 383 were randomized into the trial. To date, all infants have reached 1 year of age: 11 families withdrew before year 1 (2.9% of women randomized). We have followed up 351 mother-child pairs (91.6%) to 1 year. Six women were excluded from analyses because of missing data on critical variables, leaving 345 (90.1%) available for this report. Demographic information of women initially enrolled, randomized, and followed up for 1 year are given in . The mean age of the mothers whose children were followed up to 1 year of age was 26 years, with 65% of Mexican background. For 38% of the women, this was the first pregnancy. Demographic variables were similar among the groups.
Peer Education in Pregnancy Study Demographic Variables
Acetaminophen use was determined from 4 different questionnaires: (1) at enrollment (first trimester): “Since you became pregnant, which of the following nonprescription medications have you taken . . . acetaminophen (Tylenol)?”; (2) at the second visit (4-5 months of gestation); (3) at the third visit (7-8 months of gestation): “Since our last visit, which of the following nonprescription medication have you taken . . . acetaminophen (Tylenol)?”; and (4) at the first postpartum visit (visit 4): “Between our last visit and delivery which of the following nonprescription medications did you take . . . acetaminophen (Tylenol)?” A total of 70% of women had used acetaminophen at least once in pregnancy: 40.1% in early pregnancy (first trimester); 38.1% in middle pregnancy, 49.0% in late pregnancy (after 4-5 months of gestation as determined from a positive response on either visit 3 or 4), and 59.9% in either middle or late pregnancy (after the first trimester).
Development of respiratory end points was determined by any positive response to the following questions at visit 4 (child 4 to 6 weeks old), at visit 5 (child 6 months old), at visit 6 (child 12 months old), or during telephone calls at 3 and 9 months: “During this time period has he/she had any wheezing (whistling in the chest)?”; “Did the wheezing ever disturb the baby's sleeping at night?”; “Have there been any times when he/she coughed frequently throughout the day or night, during this time period?”; “Did the coughing ever disturb the baby's sleeping at night?”; “Was your baby treated in the emergency room for breathing problems (coughing, congestion, runny nose, wheezing) during this time period?”; “Was your baby admitted to the hospital, other than the ER [emergency room], with breathing problems (coughing, congestion, runny nose, wheezing) during this time period?”; and “Has a doctor ever told you that your baby has asthma?”
Respiratory symptoms were common in the first year of life, with 33.0% reporting some wheezing, 21.5% reporting wheezing that disturbed sleep, 65.4% reporting coughing that disturbed sleep, 33.9% going to the emergency department for a respiratory problem, 10.1% being hospitalized for a respiratory problem, and 4.6% being diagnosed as having asthma.
Smoking in pregnancy was determined from the following questions: “Have you ever smoked?”; “Have you smoked any cigarettes in the last 7 days?”; If no, “How long ago did you stop smoking?” Exposure to passive smoke was determined from the following questions: “In an average week about how many hours are you exposed to other peoples' cigarette smoke at home, including by family members and visitors” and “In an average week, about how many hours are you exposed to other peoples' cigarette smoke outside the home?” (any positive answer was considered yes). Active smoking in pregnancy was rare (10.1% early in pregnancy and 5.2% later). Among Mexican women, it was particularly rare, with 18.2% born in the United States and 4.4% born in Mexico smoking early in pregnancy. Exposure to passive smoke, however, was common, with 31.9% being exposed in the home, 52.8% being exposed elsewhere, and 62.3% exposed to some passive smoke either at home or elsewhere.
Breastfeeding was determined on the first visit after delivery (when the infant was 4 to 6 weeks old): “Have you ever breastfed your baby since giving birth?” and “Are you still breastfeeding your baby?” Most women breastfed their infants (87.8%), with 68.7% breastfeeding for 4 or more weeks. Early use of formula was also common, with 70.1% starting at birth and another 14.8% beginning in the first month of life. Thus, most women fed their infants with a combination of breast milk and formula.
Other potential confounders included family history of asthma evaluated at baseline by questionnaire history of a first-degree relative of the unborn child having a history of asthma, antibiotic use in pregnancy evaluated by questionnaire at 7 to 8 weeks of gestation and at 4 to 6 weeks of age (between the last visit and delivery), birth weight of the child evaluated by questionnaire when the child was 4 to 6 weeks of age, and antioxidant intake evaluated at 7 to 8 months of gestation using the 1992 Block National Cancer Institute Health Habits and History Questionnaire in English and the Hispanic Food Frequency Questionnaire.30,31
For analyses of potential confounders, in this article antioxidants were assumed to include vitamin A, vitamin C, vitamin E, lycopene, lutein, beta-carotene, alpha-carotene, and cryptoxanthin. Except for the vitamins, no specific antioxidant intakes are recommended, especially for pregnancy.32
Therefore, to evaluate for possible confounding by antioxidants, for each woman each of these vitamins or antioxidants was determined to be above or below the median intake, then summed to give an antioxidant score for each participant. Women were assumed to have high antioxidant intake if intakes were above the median for 5 or more of the 8 antioxidants; they were assumed to have low antioxidant intake if they had intakes above the median for 4 or fewer of the 8 antioxidants. Dietary data were available for only 312 of the 345 women included in this analysis. Final analyses, therefore, were performed with and without adjustment for level of antioxidant intake.
Statistical analyses were performed using SAS statistical software, version 9.1 (SAS Institute Inc, Cary, North Carolina). The χ2 statistic tested the significance of differences between potential confounding variables and both acetaminophen use and respiratory end points. Logistic regression models were used to estimate the effect of acetaminophen use during pregnancy on the child's respiratory symptoms in the first year of life. Odds ratios (ORs) and 95% confidence intervals (CIs) are presented. Multivariate models controlled for maternal age, child's sex, home environment intervention group, maternal Mexican ethnicity, child breastfed for 4 or more weeks, active smoking in middle to late pregnancy, exposure to passive smoke during pregnancy, low birth weight (<2,500 g), antibiotic use in late pregnancy, age at which formula introduced (categorized by birth, <4 weeks, 4-12 weeks, and >12 weeks), and family history of asthma. Additional analysis also controlled for infections during pregnancy and low intake of antioxidants during pregnancy. The study was approved by the University of Illinois at Chicago Human Subjects Institutional Review Board.