American Journal of Epidemiology Advance Access originally published online on January 25, 2007
American Journal of Epidemiology 2007 165(9):1023-1030; doi:10.1093/aje/kwk092
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ORIGINAL CONTRIBUTIONS |
Fertility Rates in Women with Asthma, Eczema, and Hay Fever: A General Population-based Cohort Study
1 Division of Epidemiology and Public Health, School of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom
2 Division of Respiratory Medicine, School of Medical and Surgical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom
3 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom
Correspondence to L. J. Tata, Division of Epidemiology and Public Health, School of Community Health Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG5 1PG, United Kingdom (e-mail: laila.tata{at}nottingham.ac.uk).
Received for publication July 10, 2006. Accepted for publication October 10, 2006.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The protective association between having older siblings and the risk of subsequent allergic disease may be due to decreased fertility among women with allergic disease. In this study, the authors compared fertility rates among women with asthma, eczema, or hay fever with those in the general female population. Computerized primary-care data from the United Kingdom were used to conduct a cohort analysis of 491,516 women. General fertility rates and age-specific fertility rates for 1994–2004 were estimated. Using Poisson regression, the authors compared fertility rates among women with asthma, eczema, or hay fever with rates in women without these diagnoses. Fertility rates were 53.0 and 52.3 livebirths per 1,000 person-years in women with and without asthma, respectively. The fertility rate ratio for women with asthma compared with women without asthma was 1.02 (95% confidence interval (CI): 1.00, 1.04) after adjustment for age, smoking, body mass index, and socioeconomic status. Equivalent fertility rate ratios for eczema and hay fever were 1.15 (95% CI: 1.13, 1.17) and 1.08 (95% CI: 1.06, 1.10), respectively. The authors found no evidence that the fertility rates of women with asthma, eczema, or hay fever are lower than those of women in the general population.
asthma; birth rate; cohort studies; eczema; fertility; hypersensitivity; rhinitis; rhinitis, allergic, seasonal
Abbreviations: CI, confidence interval; FRR, fertility rate ratio; IQR, interquartile range; THIN, The Health Improvement Network
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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There is strong evidence for a reduced risk of allergic disease in children of higher birth order (i.e., children with more older siblings), and this phenomenon has yet to be explained by environmental factors (1–6). Given the heritability of allergic disease, one possible explanation is that women with allergic disease have smaller families, either by choice or because of reduced biologic fertility. Some studies of women with atopy and hay fever have indicated that they do tend to have fewer children (7–9). While this has not been found specifically for women with asthma (8, 9), selected data indicate that these women may have more pregnancies ending in adverse perinatal outcomes (10).
Clinical and laboratory evidence provides some support for the possibility of reduced biologic fertility in women with allergic disease. Women with asthma or allergy have been found to more often have later menarche (11), irregular menstruation (12), and endometriosis (13). Conversely, the physiology of atopic status towards T-helper 2 cell cytokine production compared with T-helper 1 cell cytokine production may actually promote conception and maintenance of pregnancy (14–16). However, to our knowledge, no study has yet investigated fertility rates in terms of the number of livebirths among women with allergic disease. Therefore, we conducted a study to estimate population-based fertility rates in women with asthma, eczema, and hay fever as compared with women from the general population without allergic disease. We used data from The Health Improvement Network (THIN) (17), a source of longitudinal data from general practice records in the United Kingdom.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Data set and study population
THIN (17) is a computerized primary-care database of anonymized patient records, with a high standard of in-practice recording of all major medical diagnoses, medical events, and prescriptions. At the time of data collection for this study, the database contained information from 255 general practices across England and Wales, comprising longitudinal patient records for 3.9 million people. Over half of THIN practices previously contributed data to the General Practice Research Database, which has been used extensively in research, and independent studies have found high validity of medical diagnoses in the database, including data on births and respiratory diseases (18–20).
Upon joining THIN, all contributing general practices must use the latest version of Vision software (21), a practice management software program from In Practice Systems Ltd. (London, United Kingdom), for their prospective recording. Although retrospective data were available for each patient, we limited this study to obstetric data entered into Vision, in order to obtain an accurate measure of incident births across our study period. We identified all women who had data entered after the in-practice implementation of Vision software, which resulted in a study period of January 1, 1994–November 30, 2004. Only women contributing data at 15–44 years of age, which we defined as the potentially fertile period, were included in our cohort. Diagnoses of allergic disease (asthma, eczema, and hay fever) recorded at any time in the general practice record were extracted for all women in the cohort.
Extraction of data on livebirths and covariates
For each woman, we identified all livebirths occurring during the potentially fertile period (ages 15–44 years) by linking obstetric delivery codes in her THIN general practice records to the births of registered children in her household at the same time. For each woman, we additionally extracted data on smoking, body mass index (weight (kg)/height (m)2), and socioeconomic status (quintile of the Townsend deprivation index). The Townsend deprivation index is a measure of area-level socioeconomic deprivation which has been well-validated in health-services research to explain the variation observed in a range of health outcomes (22, 23). For this study, Townsend deprivation index, based on patients' home postcodes, was available for women in only 176 (69 percent of) THIN general practices, since the process of integrating this variable into the database for research purposes was in development. In THIN, the Townsend deprivation index is categorized in quintiles from the national census, which ensures that it is representative of deprivation relative to the whole of the United Kingdom population.
Statistical analysis
Using Poisson regression in Stata 8.0 software (Stata Corporation, College Station, Texas), we estimated the fertility rate as the number of livebirths per 1,000 person-years women contributed to the potentially fertile period, which is analogous to the general fertility rate (number of livebirths per 1,000 female population aged 15–44 years) calculated yearly as a standard demographic measure of fertility in populations (24). Our method of calculation differed slightly from the standard general fertility rate, because we used person-years as our denominator; women in our study were observed for part of one or more calendar years, as opposed to the midyear population number of women used in national statistics. To account for variation by age, we calculated fertility rates in each 5-year age group using a Lexis expansion (25), which allows women to contribute person-time to successive 5-year age groups as they get older through the study. Each woman in the study may have contributed person-time and birth events to one or more 5-year age groups, and we calculated separate rates and rate ratios using the person-time contributed to and births occurring in each specific age group. Therefore, our age-specific fertility rates were directly comparable with the standard presentation of general fertility rates in national data.
We then carried out three separate analyses to estimate fertility rates in women with diagnoses of asthma, eczema, or hay fever and compared each of these rates with fertility rates in women without the respective diagnosis. We calculated overall and age-specific fertility rate ratios (FRRs) comparing each cohort of women (diagnosis of asthma, eczema, or hay fever) with the respective comparison cohort. Since some women had overlapping allergic disease diagnoses, we repeated our analyses using cohorts of exposed women with two allergic disease diagnoses (asthma and eczema, asthma and hay fever, and eczema and hay fever) and cohorts of women with all three allergic disease diagnoses. To address this as an issue of specificity of diagnosis, we also repeated the analyses after excluding women with more than one diagnosed allergic disease.
In multivariate analyses, we explored the potentially confounding effects of smoking, body mass index, and socioeconomic status. Since women in this analysis may have had more than one child during the potentially fertile period, we allowed for clustering by woman using the robust standard error option. Missing values for covariates were fitted as a separate category, and all models were refitted using women with complete data. To best approximate total family size, we restricted the analyses to women who had complete records starting from the beginning of the potentially fertile period (age 15 years) and recalculated the FRR for each allergic disease cohort in relation to its comparison cohort.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Study population
Using THIN data, we extracted a cohort of 491,516 women who were between 15 and 44 years of age during the study period, from January 1994 to November 2004. Of these women, 61,528 (13 percent) had a diagnosis of asthma, 68,764 (14 percent) had a diagnosis of eczema, and 56,914 (12 percent) had a diagnosis of hay fever. Some women (6 percent) had two of these diagnoses, and a small proportion (1 percent) had all three diagnoses (figure 1).
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The distributions of women with asthma, eczema, or hay fever across categories of smoking status, body mass index, and quintile of the Townsend deprivation index, in comparison with the general population cohort, are shown in table 1. Distributions of covariates for the whole cohort were identical to those in the three comparison cohorts of women with no asthma (n = 429,735), no eczema (n = 422,673), and no hay fever (n = 433,341), so only the results for comparison with the whole cohort are presented here. Women with a diagnosis of allergic disease were more likely to have smoking status or body mass index recorded than women in the whole cohort. The proportion of current smokers was higher among women with asthma and eczema compared with women in the whole cohort, but not among those with hay fever. Women with asthma were more likely to be overweight or obese than women in the whole cohort. The distributions of Townsend index quintiles (available for approximately 55 percent of the population) were skewed towards the least deprived quintile and were similar for all cohorts.
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Study follow-up time for women with asthma, eczema, and hay fever (3.3 years (interquartile range (IQR), 2.1–5.1), 3.8 years (IQR, 2.3–5.8), and 3.7 years (IQR, 2.3–5.6), respectively) was marginally longer than that for women in the whole population (3.1 years; IQR, 1.8–4.9).
Fertility rates
Women in our study population had 91,147 livebirths over a total of 1,740,000 fertile person-years of follow-up, resulting in an overall fertility rate of 52.4 livebirths per 1,000 person-years (95 percent confidence interval (CI): 52.0, 52.7).
Women with asthma had 12,344 livebirths over a total of 233,000 fertile person-years, whereas women without asthma had 78,803 livebirths over a total of 1,507,000 fertile person-years. This equated with fertility rates of 53.0 and 52.3 livebirths per 1,000 person-years in women with and without asthma, respectively (table 2), resulting in a crude FRR of 1.01 (95 percent CI: 1.00, 1.04). After adjustment for age, smoking status, body mass index, and Townsend index, the overall FRR (FRR = 1.02, 95 percent CI: 1.00, 1.04) was almost identical to the crude FRR. Although women with asthma tended to have slightly higher fertility rates when younger and lower fertility rates when older, compared with women without asthma, adjusted age-specific FRRs were similar to the adjusted FRR for all ages (table 2), indicating that there was no substantial age variation in relative fertility between the two groups. However, women aged 20–29.9 years with asthma had a small, statistically significant increase in fertility rates of approximately 6 percent compared with women without asthma.
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For women with eczema, the overall fertility rate was higher than that in women without eczema (59.4 and 51.0 livebirths per 1,000 person-years in women with and without eczema, respectively), resulting in a 17 percent higher fertility rate (crude FRR = 1.17, 95 percent CI: 1.15, 1.19) which remained higher after adjustment for age, smoking status, body mass index, and Townsend index (FRR = 1.15, 95 percent CI: 1.13, 1.17) (table 3). Fertility rates in each age group were also higher in women with eczema than in women without eczema, and the relative increases in fertility rate were similar across all age groups but the lowest (15–22 percent).
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Women with hay fever also had a higher overall fertility rate than women without hay fever (57.7 and 51.5 livebirths per 1,000 person-years in women with and without hay fever, respectively), resulting in a 12 percent higher fertility rate (crude FRR = 1.12, 95 percent CI: 1.10, 1.14) that was reduced to a rate only 8 percent higher after adjustment for age, smoking status, body mass index, and Townsend index (FRR = 1.08, 95 percent CI: 1.06, 1.10) (table 4). The pattern of age-specific fertility rates in women with hay fever was similar to that in women with eczema, showing a similar relative increase in each age group (8–12 percent) compared with women without hay fever, with the exception of the youngest women.
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When we repeated our analysis using a cohort of women with all three allergic disease diagnoses (n = 6,200), we found a 7 percent increase in fertility rate (FRR = 1.07, 95 percent CI: 1.01, 1.12) compared with women with no allergic disease diagnoses (n = 345,262). This small increase in fertility rate compared with women with no diagnoses was also similar for women with any two allergic disease diagnoses (for women with both asthma and eczema, FRR = 1.12 (95 percent CI: 1.09, 1.16); for women with both asthma and hay fever, FRR = 1.05 (95 percent CI: 1.02, 1.09); and for women with both eczema and hay fever, FRR = 1.12 (95 percent CI: 1.09, 1.16)). In our specificity analyses, when we excluded women with more than one allergic disease diagnosis, which represented 7 percent of the whole population, our adjusted FRRs were similar to those in our main analyses for women with asthma only (FRR = 0.98, 95 percent CI: 0.96, 1.01), eczema only (FRR = 1.17, 95 percent CI: 1.14, 1.19), and hay fever only (FRR = 1.09, 95 percent CI: 1.07, 1.12).
The FRR analyses for each allergic disease were repeated using only women with no missing data for the covariates; the resulting estimates were similar to those from analyses of the full data set. We also restricted models to the 100,528 women with data available from the beginning of the fertile period (age 15 years) onwards. The adjusted FRR for women with asthma observed from the age of 15 years onwards was similar to that in the overall analysis for women with asthma (FRR = 1.03, 95 percent CI: 0.99, 1.07). However, for women with eczema and hay fever, the rates among women observed from the age of 15 years onwards were modestly lower than the rates for all women (FRR = 1.09 (95 percent CI: 1.04, 1.13) and FRR = 1.02 (95 percent CI: 0.98, 1.06), respectively).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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We found no evidence that the fertility rates of women with asthma, eczema, or hay fever are lower than those of women in the general population. Indeed, there is some evidence that fertility rates among women with eczema and hay fever may have been slightly higher than those expected in the general population during our study period. This was generally true across all but the youngest age groups. In this study, we did not directly measure individual fertility or clinical infertility in women, and therefore the results do not provide etiologic information on the biologic fecundity or fertility of women with and without allergic disease. However, our findings of similar fertility rates in women with and without allergic disease do indicate that reduced fertility in women with allergic disease does not explain the increase in allergy among children of low birth order that has been observed on a population level. Our study shows that women with allergic disease do not have fewer children than women without allergic disease in the United Kingdom population.
Strengths and limitations
Deriving our fertility rates from a large general-population-based cohort representative of the United Kingdom female population and our stratification of these fertility rates by age enabled us to obtain the first precise estimates of fertility among women with allergic disease that are comparable to national estimates of the general fertility rate. Our overall fertility rate of 54.2 livebirths per 1,000 person-years was similar to the average national general fertility rate of 57.8 over the same calendar period as our study (1995–2005), and although our women had more babies when they were over the age of 30 years, our age-specific rates were also similar to those from national statistics (26). This suggests that our methods for extracting birth data and linking children to their mothers captured nearly all births and is thus a valid method of determining incidence rates of livebirth in this population. Although THIN is a relatively new general practice database, validation studies carried out using the General Practice Research Database, from which over half of THIN general practices originate, have indicated that recording of births and major diagnoses, including respiratory conditions, is accurate and complete (18–20). We do not think there was any reason for significant differential recording of births between women with and without allergic disease. However, because of the nature of general practice registration, we only captured a relatively short follow-up period in each woman's entire reproductive life, and we did not have data on total family size or attained parity. We addressed this with a restricted analysis, using women who had data from the start of their fertile period (age 15 years) onwards; this analysis showed FRRs similar to those of the overall analysis, indicating that the measure of fertility rates on a population level for women throughout the entire fertile period is a good proxy for family size.
A potential limitation of our study is that comprehensive data on ethnicity were not available in THIN because ethnicity is not routinely recorded for patients in general practices in the United Kingdom. However, it is unlikely that confounding by ethnicity would have had an important effect on our findings, since studies of the association between ethnicity and the prevalence of allergic disease diagnosis in the United Kingdom have shown inconsistent results (27–29), indicating that there is little evidence for a strong direct association between ethnicity and allergic disease diagnosis in the United Kingdom. We also recognize that missing data for smoking, body mass index, and socioeconomic status is a disadvantage of using general practice records; however, this is comparable with the proportion of missing data from nonresponse in epidemiologic cross-sectional surveys and follow-up studies. In our study, these variables did not have important confounding effects, as their distributions were similar between women with and without allergic disease. Furthermore, our generous study power enabled us to restrict the analysis to women with full data, which showed effect sizes almost identical to those of the overall analysis.
Interpretation in the context of other studies
Although, to our knowledge, this was the first study to calculate fertility rates in women with allergic disease, an inverse relation between atopy and number of offspring has been previously demonstrated through raised maternal serum immunoglobulin E levels (30), skin-prick test sensitivity (8, 31), and reported allergic disease (7, 9, 14). Previous investigators have not found associations between the number of previous pregnancies or livebirths and wheezing or asthma (8, 9, 31). Most research has only assessed the cross-sectional relation between the number of previously born children or pregnancies and women's current atopic or allergic disease status (7–9, 14, 30). The largest cross-sectional study, a Danish telephone survey of over 30,000 pregnant women, showed a lower self-reported prevalence of hay fever among women who had previously been pregnant or had had a livebirth; however, the prevalences of hay fever were very similar between women with one, two, or more than two previous livebirths (14). Similar results were found in a general population study of women in Italy, where Forastiere et al. (9) reported an inverse trend between number of livebirths and maternal hay fever; however, individual odds ratios for hay fever among women with two, three, or four or more children, as compared with only one child, were not statistically significant, and no associations were found between hay fever and number of previous pregnancies.
Prospective studies have shown mixed results (31, 32). Sunyer et al. (32) found that although women with atopy initially had fewer children, there was no difference in the number of children after 8 years of follow-up. This indicates that these women may tend to delay having their first child, which is partially in keeping with our finding of only young women with allergic disease having a slightly lower relative fertility compared with young women without allergic disease. Harris et al. (31) did observe a loss of maternal atopy or hay fever (but not asthma) with each intervening pregnancy over a 7-year period; however, that study was carried out only in women who had initially had livebirths, and although the effect was still present after adjustment for maternal age, it did not reach statistical significance at the 5 percent level. Nevertheless, this proposed successive loss of allergy through each pregnancy (31, 33, 34), rather than a decrease in number of livebirths among women with allergic disease, is in keeping with the birth order effect.
Reasons for our finding of a possibly increased fertility rate in women with eczema or hay fever but not in women with asthma are unclear. While it is possible that this is a true effect, it may also be due to differential ascertainment of diagnoses via antenatal care. Women visiting their general practitioner for antenatal care probably have a greater chance of being diagnosed with a medical condition, particularly milder cases of eczema or hay fever, than women not receiving antenatal care who visit the general practitioner less often. There is probably not such a significant increase in ascertainment of asthma diagnoses through antenatal care as compared with regular physician visits, since symptoms of asthma are generally more severe and require prescription medication. An alternative explanation may be a physiologic promotion of conception in these women related to a balance towards T-helper 2 cells in allergic disease (15, 16). However, a potentially beneficial effect of the T-helper 2 cell phenotype on fertility does not aid in explaining why we did not find the same increased fertility rates in women with asthma, although it may be possible that a proportion of women with asthma diagnoses do not have allergy-related disease. Allergy testing for people diagnosed with asthma is not routinely carried out in general practice, so we were not able to separate women with and without atopy in our analysis.
Conclusions
Our results provide reassuring evidence that the fertility rates of women with asthma, eczema, or hay fever are not lower than those of women in the general population. Our estimates of similar or possibly increased fertility in the cohorts with allergic disease do not support the proposal that a protective effect of higher birth order on allergic disease development is mediated through women with allergic disease having fewer children. This is an important finding for women with allergic disease and their clinicians.
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ACKNOWLEDGMENTS |
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This research was funded by a grant from Asthma UK.
Conflict of interest: none declared.
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
|---|
- Strachan DP. (1989) Hay fever, hygiene, and household size. BMJ 299:1259–60.
[Free Full Text] - Strachan DP. (2000) Family size, infection and atopy: the first decade of the "hygiene hypothesis.". Thorax 55:suppl 1, S2–10.[CrossRef][Medline]
- Karmaus W and Botezan C. (2002) Does a higher number of siblings protect against the development of allergy and asthma? A review. J Epidemiol Community Health 56:209–17.
[Abstract/Free Full Text] - McKeever TM, Lewis SA, Smith C, et al. (2002) Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol 109:43–50.[CrossRef][Web of Science][Medline]
- Gibbs S, Surridge H, Adamson R, et al. (2004) Atopic dermatitis and the hygiene hypothesis: a case-control study. Int J Epidemiol 33:199–207.
[Abstract/Free Full Text] - Cullinan P, Harris JM, Newman Taylor AJ, et al. (2003) Can early infection explain the sibling effect in adult atopy? Eur Respir J 22:956–61.
[Abstract/Free Full Text] - Karmaus W and Eneli I. (2003) Maternal atopy and the number of offspring: is there an association? Pediatr Allergy Immunol 14:470–4.[CrossRef][Web of Science][Medline]
- Sunyer J, Anto JM, Harris J, et al. (2001) Maternal atopy and parity. Clin Exp Allergy 31:1352–5.[CrossRef][Web of Science][Medline]
- Forastiere F, Sunyer J, Farchi S, et al. (2005) Number of offspring and maternal allergy. Allergy 60:510–14.[CrossRef][Web of Science][Medline]
- Namazy JA and Schatz M. (2005) Treatment of asthma during pregnancy and perinatal outcomes. Curr Opin Allergy Clin Immunol 5:229–33.[Web of Science][Medline]
- Doull IJ. (2004) The effect of asthma and its treatment on growth. Arch Dis Child 89:60–3.
[Abstract/Free Full Text] - Svanes C, Real FG, Gislason T, et al. (2005) Association of asthma and hay fever with irregular menstruation. Thorax 60:445–50.
[Abstract/Free Full Text] - Sinaii N, Cleary SD, Ballweg ML, et al. (2002) High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 17:2715–24.
[Abstract/Free Full Text] - Westergaard T, Begtrup K, Rostgaard K, et al. (2003) Reproductive history and allergic rhinitis among 31145 Danish women. Clin Exp Allergy 33:301–5.[CrossRef][Web of Science][Medline]
- Makhseed M, Raghupathy R, Azizieh F, et al. (2001) Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Hum Reprod 16:2219–26.
[Abstract/Free Full Text] - Piccinni MP, Scaletti C, Maggi E, et al. (2000) Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J Neuroimmunol 109:30–3.[CrossRef][Web of Science][Medline]
- Bourke A, Dattani H, Robinson M. (2004) Feasibility study and methodology to create a quality-evaluated database of primary care data. Inform Prim Care 12:171–7.[Medline]
- Howard LM, Kumar C, Leese M, et al. (2002) The general fertility rate in women with psychotic disorders. Am J Psychiatry 159:991–7.
[Abstract/Free Full Text] - Hansell A, Hollowell J, Nichols T, et al. (1999) Use of the General Practice Research Database (GPRD) for respiratory epidemiology: a comparison with the 4th Morbidity Survey in General Practice (MSGP4). Thorax 54:413–19.
[Abstract/Free Full Text] - Soriano JB, Maier WC, Visick G, et al. (2001) Validation of general practitioner-diagnosed COPD in the UK General Practice Research Database. Eur J Epidemiol 17:1075–80.[CrossRef][Web of Science][Medline]
- In Practice Systems Ltd. (2007) Vision 3(In Practice Systems Ltd, London, United Kingdom) (http://www.inps3.co.uk).
- Morris R and Carstairs V. (1991) Which deprivation? A comparison of selected deprivation indexes. J Public Health Med 13:318–26.
[Abstract/Free Full Text] - Shohaimi S, Welch A, Bingham S, et al. (2004) Area deprivation predicts lung function independently of education and social class. Eur Respir J 24:157–61.
[Abstract/Free Full Text] - United Kingdom Office for National Statistics. (2003) Population trends—summer 2003. (Population trends no. 112). London(Office for National Statistics, United Kingdom).
- Breslow NE. (1987) Day NE, eds. Statistical methods in cancer research. Vol 2. The design and analysis of cohort studies. (IARC Scientific Publication no. 82). Lyon(International Agency for Research on Cancer, France).
- United Kingdom Office for National Statistics. Age-specific fertility rates and numbers by age of mother, 1995 –2005. (2006) (Table). In: Birth statistics—review of the Registrar General on births and patterns of family building in England and Wales, 2005. (Series FM1, no. 34)(HMSO, London, United Kingdom) (http://www.statistics.gov.uk/downloads/theme_population/FM1_34/FM1_no34_2005.pdf).
- Netuveli G, Hurwitz B, Levy M, et al. (2005) Ethnic variations in UK asthma frequency, morbidity, and health-service use: a systematic review and meta-analysis. Lancet 365:312–17.[Web of Science][Medline]
- Netuveli G, Hurwitz B, Sheikh A. (2005) Ethnic variations in incidence of asthma episodes in England & Wales: national study of 502,482 patients in primary care. Respir Res 6:120.[CrossRef][Medline]
- Neame RL, Berth-Jones J, Kurinczuk JJ, et al. (1995) Prevalence of atopic dermatitis in Leicester: a study of methodology and examination of possible ethnic variation. Br J Dermatol 132:772–7.[Web of Science][Medline]
- Karmaus W, Arshad SH, Sadeghnejad A, et al. (2004) Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clin Exp Allergy 34:853–9.[CrossRef][Web of Science][Medline]
- Harris JM, White C, Moffat S, et al. (2004) New pregnancies and loss of allergy. Clin Exp Allergy 34:369–72.[CrossRef][Web of Science][Medline]
- Sunyer J, Anto JM, Plana E, et al. (2005) Maternal atopy and changes in parity. Clin Exp Allergy 35:1028–32.[CrossRef][Web of Science][Medline]
- Rangaraj S and Doull I. (2003) Hormones not hygiene? Birth order and atopy. Clin Exp Allergy 33:277–8.[CrossRef][Web of Science][Medline]
- Doull IJ. (2001) Does pregnancy prevent atopy? Clin Exp Allergy 31:1335–7.[CrossRef][Web of Science][Medline]
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