RHEUMATOLOGY
Rheumatology 2014;53:860866 doi:10.1093/rheumatology/ket456 Advance Access publication 6 January 2014
Original article Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou Biobank Cohort Study Peymane Adab1, Chao Qiang Jiang2, Elizabeth Rankin3, Yee Wah Tsang1, Tai Hing Lam4, Johanna Barlow1, G. Neil Thomas1, Wei Sen Zhang2 and Kar Keung Cheng1 Abstract
Methods. We used baseline data from 7349 women 550 years of age in the Guangzhou Biobank Cohort. Questionnaires were used to obtain socio-demographic, lifestyle and obstetric history data, including parity, OC use and breastfeeding practices. The main outcome was RA. Women were asked about history of RA and were examined to assess joint swelling. RF levels were measured. The presence of RA was defined in two ways: (i) as reporting physiciandiagnosed RA or pain and swelling in at least three joints (including the wrist), and (ii) also having at least one of the following: positive RF, morning stiffness or objective swelling of the small joints of the hands.
CLINICAL SCIENCE
Results. Compared with those who had never breastfed, breastfeeding was associated with half the risk of RA. The risk was lower with increasing duration of breastfeeding [adjusted odds ratio (OR) 0.54 (95% CI 0.29, 1.01) for breastfeeding at least 36 months; P for trend = 0.04]. OC use had no relationship with RA. Conclusion. Breastfeeding (especially longer duration) but not OC use is associated with a lower risk of RA. This has potentially important implications for future RA disease burden, given the declining rates of breastfeeding and the one-child policy in China. Further research is needed to explain the biological mechanism. Key words: breastfeeding, rheumatoid arthritis, risk factors, epidemiology, oral contraceptives, Chinese.
Introduction RA is a chronic inflammatory multisystem disease characterized by joint destruction. Although the clinical course can vary widely, it is recognized as a major cause of 1 Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK, 2Department of Occupational Health, Guangzhou Number 12 People’s Hospital, Guangzhou, China, 3Department of Rheumatology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK and 4School of Public Health, University of Hong Kong, Hong Kong, SAR China.
Submitted 1 March 2013; revised version accepted 25 November 2013. Correspondence to: Elizabeth Rankin, Department of Rheumatology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, UK. E-mail: [email protected]
morbidity and disability. While the aetiology of RA remains elusive, epidemiological studies have suggested that hormonal factors are important [1]. RA is more common in women than in men, especially before the menopause [2]. During pregnancy, disease activity tends to diminish, but often flares up again in the post-partum period [3, 4]. Some, but not all, studies suggest that the use of oral contraceptives (OCs) can be protective against developing RA [5]. The relationship between breastfeeding one’s children and the risk of developing RA in the future has also been examined and data are conflicting. While large population-based cohort studies have found that breastfeeding is associated with a lower risk of [6] and mortality from RA [7], other casecontrol studies have suggested that breastfeeding increases risk, including the risk of
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Objective. Hormonal and reproductive factors are implicated in the aetiology of RA, but results of previous studies have been mixed. The aim of this cross-sectional study was to assess the relationships between RA, use of oral contraceptives (OCs) and history of breastfeeding in a population of older women from South China.
Guangzhou Biobank Cohort Study
severe disease [8, 9]. The post-partum flare of RA has also been linked to breastfeeding [10] and is thought to be mediated through increased concentration of prolactin [8]. Furthermore, it is unclear from previous studies whether it is breastfeeding or childbirth and pregnancy, per se, that influence the risk of RA. Apart from being inconclusive, these previous studies are based on populations in developed countries in the West, where patterns of breastfeeding and OC use differ from those in many developing countries. Data from the UK suggest that in 2010, 12% of mothers exclusively breastfed their babies for at least 4 months [11], compared with >50% of women in Asia [12]. We used baseline data from the Guangzhou Biobank Cohort Study (GBCS) to examine the relationships between parity, breastfeeding and OC use in relation to RA in a relatively understudied population.
Methods
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Results Baseline data were available for 7349 women with a mean age of 63.5 years (range 5093). Overall, 7323 had all data for assessment of RA status, of whom 9.1% fulfilled definition 1 and 3.4% fulfilled definition 2 for RA in this study (Table 1). The general characteristics of the study population are described in Table 2. The majority of women had at least
861
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Details of the GBCS have been published elsewhere [13]. In brief, 30 000 men and women 550 years of age were selected from a community social and welfare association and invited to take part over three recruitment phases. In each recruitment phase the measurements and questionnaires were slightly modified, although some core measures were maintained throughout. Participants were eligible if they were ambulatory and not receiving treatment for life-threatening diseases, such as cancer. They attended a central recruitment centre where trained nurses and technicians carried out a comprehensive structured interview and examination. Participants were also asked to complete a structured questionnaire during their visit that included questions on socioeconomic status, family and personal disease histories and lifestyle habits. No additional data were collected for this particular study; all data reported are based on the original GBCS. The GBCS was approved by the Guangzhou Medical Ethics Committee of the Chinese Medical Association, Guangzhou, China. The ethical approval includes broad consent to perform clinical research related to the aims of the cohort study. As the study reported here falls within these research aims, no additional ethical approval was required to perform this analysis of the anonymized baseline data collected for the cohort study. Relevant to this study, subjects were asked in detail about their smoking and disease history. Specifically, they were asked to indicate whether a doctor had ever told them that they had any of 18 particular conditions. This included a question about arthritis. If they indicated yes, they were asked further details about the type of arthritis and the date of diagnosis. They were also asked directly about whether they had any recurrent or continuous pain, swelling or stiffness in any joints, and if so, which joints were affected. The presence and duration of morning stiffness were also recorded. All participants had their joints examined by a trained nurse and any tenderness or swelling and the affected joints were noted. Participants recruited in the first phase, but not subsequent phases, also had blood samples analysed for RF by nephelometry and a value >20 IU/ml was considered positive. In women,
information on their reproductive history was obtained, including parity, breastfeeding history and whether and for how long they had ever used OCs. Specifically, women were asked about whether they had ever been pregnant and the number of live births, and for each child they were asked to recall whether they had breastfed and, if so, for how many months. They were also asked to recall whether they had ever used OCs and, if so, the age at which they started and the number of years that they used the pill. For this analysis, data on 10 413 subjects who were enrolled in the first phase of the study (between 2003 and 2004) were used because all of the relevant measures (including blood samples for RF) were only undertaken in these initial subjects and further confined to women (n = 7349) (Fig. 1). We defined RA in two ways. First, all women who reported physician-diagnosed RA or those who reported pain in at least three joints commonly affected by RA, including the wrist, were included (definition 1). Second, we used a stricter definition (definition 2) where those fulfilling definition 1 were only included if they also had at least one of the ACR criteria for RA that were collected in the study. These included morning stiffness, positive RF, swelling or tenderness of the wrist or MCP joints on examination or reporting of pain and swelling in three or more relevant joints including the wrist. Women who reported never having been pregnant were considered to be nulliparous and the number of live births among the rest was recorded as a measure of parity. Among those who had live births, the number of children who were breastfed and the duration of breastfeeding for each were obtained. The total duration of breastfeeding was categorized into four groups (none, 3 years). Women were also categorized according to OC use (never, 15 or >5 years). The relationships between each breastfeeding, parity (number of live births) and OC use with RA (using both definitions) were examined, first by univariate and then by multivariate methods, adjusting for potential confounding factors including age, level of education, BMI and smoking. When examining the relationship between breastfeeding and RA, only parous women were included; two multivariate models were run, first as above and then adjusting for the number of live births. Sensitivity analyses were done with three alternative definitions of RA: (i) reported physician-diagnosed RA, (ii) those with three or more ACR criteria or (iii) those with reported physician-diagnosed RA and three or more relevant joints affected, examining the relationships between each of these and the duration of breastfeeding.
Peymane Adab et al.
FIG. 1 Flow diagram of participants selected for this analysis Phase of recruitment
Phase 1 (n= 10413)
Females (n=7349)
Parity: No children (n=201) ≥1 child (n=7108) Data missing (n=40)
Phase 2 (n=10018)
Phase 3 (n=10088)
Excluded: No blood sample for analysis of RF
Excluded: Males (n=3064)
OCP use: Never (n=6482) Yes (n=834) Data missing (n=33)
TABLE 1 Number of women who had various characteristics associated with RA No. (%) with that criterion RA diagnostic criterion Total population Reported physician-diagnosed RA, mean (range), years ACR criteria available in study: RF positive Morning stiffness Pain or swelling in 53 joints including hand or wrist Swelling/tenderness of wrist or MCP on examination Any one of the above ACR criteria Any two of the above ACR criteria Any three of the above ACR criteria All four of the above ACR criteria Physician-diagnosed RA Definition 1 (physician-diagnosed RA or pain/swelling in 53 joints, including wrist) Definition 2 (definition 1 and at least one ACR criteria)
one live birth, and of these, >95% had breastfed their child for at least 1 month. Only 11% had ever used the contraceptive pill, and mostly for short duration. The mean age at first pregnancy was 24 years (range 1445), while the mean age for diagnosis of RA (for those who reported a doctor diagnosis) was 47.5 years (range 878). Women with RA (whichever definition) were significantly more likely to be overweight (Table 2), less likely to have ever breastfed their children and had breastfed for a shorter duration overall (although the latter was not statistically significant). They were also slightly more likely to have a lower level of education and to have ever smoked. The mean number of live births per woman was 2.9 and did not differ between those with and without RA. Similarly, the number of children who were breastfed
862
47.5 (878) 990 610 37 153 1447 135 16 2 650 669
(13.5) (8.3) (0.5) (2.1) (19.8) (1.8) (0.2) (120 000 women aged 530 with no RA at baseline were followed up for 26 years and a doseresponse relationship between breastfeeding duration and clinically confirmed RA incidence was found [relative risk (RR) 0.5 (95% CI 0.3, 0.8) for 524 months total duration of breastfeeding]. A matched casecontrol study from Sweden [20] with 136 incident cases of RA also found a doseresponse relationship between breastfeeding duration and RA [OR 0.46 (95% CI 0.24, 0.91) for breastfeeding duration 513 months compared with none]. However, in both those studies breastfeeding prevalence was much lower than in this study (67% of parous women had ever breastfed in both studies, compared with >90% in this study population). The total duration of breastfeeding was shorter, and both were conducted in populations in the West, where the prevalence of RA is higher. Furthermore, both studies concluded that their findings need to be replicated in other populations because previous reports were conflicting. Although the beneficial effects of breastfeeding for the mother and child are widely known, the findings from this study have further important implications for policy and research. Women who took part in the study reported
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OR (95% CI) for RA (definition 2)
Model 2b
Peymane Adab et al.
Guangzhou Biobank Cohort Study
Rheumatology key messages Increasing duration of breastfeeding is associated with reduced risk of RA among Chinese women. . There is no relationship between oral contraceptive use and risk of RA among Chinese women. .
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Acknowledgements We thank the Guangzhou Health and Happiness Association for the Respectable Elders for convoking the participants. Biobank Cohort Study investigators include X. Q. Lao, W.S.Z., M. Cao, T. Zhu, B. Liu, C.Q.J. (coprincipal investigator) (the Guangzhou Number 12 People’s Hospital); C. M. Schooling, S. M. McGhee, R. F. Fielding, G. M. Leung, T.H.L. (co-principal investigator) (University of Hong Kong); P.A., G.N.T., K.K.C. (coprincipal investigator) (University of Birmingham). All authors contributed to the study design, took part in the interpretation of findings and contributed to the final manuscript. E.R. conceived the idea for this paper and with P.A. coordinated completion of the manuscript. Y.W.T. and J.B. developed the definition algorithms for defining RA and undertook the initial analyses, supervised by P.A. and E.R. Y.W.T. wrote the first draft of the manuscript. P.A. reviewed and refined the analyses, updated the literature review and wrote the final draft. C.Q.J., K.K.C. and T.H.L. originally designed the idea of the GBCS and have been responsible for obtaining funding. C.Q.J. oversaw data collection and facilities for participant recruitment and contributed to the final manuscript. K.K.C. contributed to the detailed design of the study and provided critical comments on the manuscript. T.H.L., W.S.Z. and G.N.T. have all contributed to amendments of the manuscript and suggestions for data analysis. All authors checked and commented on the final draft and approved it. The GBCS was funded by the University of Hong Kong Foundation for Educational Development and Research, Hong Kong; Guangzhou Public Health Bureau and Guangzhou Science and Technology Bureau, Guangzhou, China; and the University of Birmingham, Birmingham, UK. Disclosure statement: The authors have declared no conflicts of interest.
References 1 Oliver JE, Silman AJ. Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol 2006;35:16974. 2 Symmons D, Harrison B. Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. I. Risk factors for the development of inflammatory polyarthritis and rheumatoid arthritis. Rheumatology 2000;39:83543. 3 Hazes JM. Pregnancy and its effect on the risk of developing rheumatoid arthritis. Ann Rheum Dis 1991;50: 712. 4 Silman A, Kay A, Brennan P. Timing of pregnancy in relation to the onset of rheumatoid arthritis. Arthritis Rheum 1992;35:1525. 5 Hazes JM, van Zeben D. Oral contraception and its possible protection against rheumatoid arthritis. Ann Rheum Dis 1991;50:724. 6 Karlson EW, Mandl LA, Hankinson SE et al. Do breastfeeding and other reproductive factors influence future risk
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here were born in the 1940s and 1950s, before the one-child policy in China was introduced in the late 1970s, and at a time when breastfeeding was more prevalent. The consequent decline in breastfeeding rates supports the need for prospective studies to examine whether this translates to an increase in incident RA in the future. More importantly, replication of the association between breastfeeding and lower risk of RA in a different population reinforces the need for further research to understand the hormonal mechanisms involved in the onset of RA. The anti-inflammatory effects of pregnancyrelated hormones and the short-term beneficial effects in RA are well known [21]. However, the longer-term effects of pregnancy and the benefits of lactation are less clear. One potential proposed mechanism is through progesterone, which is anti-inflammatory and the levels of which rise during pregnancy and continue to be high during breastfeeding, through receptors developed on lymphocytes [22]. This may result in long-term protective effects. Another proposed mechanism is related to cortisol, which also has anti-inflammatory effects and has been shown to be significantly higher among post-menopausal women who have breastfed, with higher levels with increasing duration of breastfeeding [23]. A third, more novel potential mechanism is through the effects of prolonged breastfeeding leading to a reduction of the burden of persistent organic pollutants (POPs) in mothers [24]. High levels of POPs have been shown to influence the immune system and increase the risk of RA in women [25]. In relation to OC use, our findings are again similar to those reported in the US [6] and Swedish studies [20], but contrast with the findings of observational studies showing that the use of OCs is associated with a lower risk of RA [26]. A more recent prospective study looking at selfreported OC use [27] and a systematic review of older observational studies [28] suggest that OCs have a benefit before disease onset and in early disease and may moderate disease severity. It is important to note that relatively few women in this study had ever used OCs (slightly >10%), which differs from populations in the West. In this study population, smoking rates were also very low (7.8% had ever smoked), which is in keeping with smoking rates among women in China [29]. Although smoking rates were slightly higher among those with RA (9.1%), there was no statistically significant relationship between smoking and RA, which is in contrast to many other studies [3032], but is likely explained by the low overall smoking prevalence. The different patterns of exposure in this population make this a unique opportunity for exploring risk factors identified in other settings.
Peymane Adab et al.
of rheumatoid arthritis? Results from the Nurses’ Health Study. Arthritis Rheum 2004;50:345867. 7 Brun JG, Nilssen S, Kvale G. Breast feeding, other reproductive factors and rheumatoid arthritis. A prospective study. Br J Rheumatol 1995;34:5426. 8 Brennan P, Ollier B, Worthington J et al. Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin? Lancet 1996;348:1069. 9 Jorgensen C, Picot MC, Bologna C et al. Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis. Ann Rheum Dis 1996;55:948. 10 Barrett JH, Brennan P, Fiddler M et al. Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis. Arthritis Rheum 2000;43:10105. 11 McAndrew F, Thompson J, Fellows L et al. Infant Feeding Survey. 2010. Health and Social Care Information Centre. 2012. http://www.hscic.gov.uk/catalogue/PUB08694 (11 October 2013, date last accessed).
21 Straub RH, Buttgereit F, Cutolo M. Benefit of pregnancy in inflammatory arthritis. Ann Rheum Dis 2005;64: 8013. 22 Szekeres-Bartho J, Barakonyi A, Par G et al. Progesterone as an immunomodulatory molecule. Int Immunopharmacol 2001;1:103748. 23 Lankarani-Fard A, Kritz-Silverstein D, Barrett-Connor E et al. Cumulative duration of breast-feeding influences cortisol levels in postmenopausal women. J Womens Health Gend Based Med 2004;10:6817. 24 Thomsen C, Haug LS, Stigum H et al. Changes in concentrations of perfluorinated compounds, polybrominated diphenyl ethers, and polychlorinated biphenyls in Norwegian breast-milk during twelve months of lactation. Environ Sci Technol 2010;44:95506.
13 Jiang C, Thomas GN, Lam TH et al. Cohort profile: the Guangzhou Biobank Cohort Study, a Guangzhou-Hong Kong-Birmingham collaboration. Int J Epidemiol 2006;35: 84452.
26 Doran MF, Crowson CS, O’Fallon WM et al. The effect of oral contraceptives and estrogen replacement therapy on the risk of rheumatoid arthritis: a population based study. J Rheumatol 2004;31:20713.
14 Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31:31524.
27 Camacho EM, Lunt M, Farragher TM et al. The relationship between oral contraceptive use and functional outcome in women with recent-onset inflammatory polyarthritis: results from the Norfolk Arthritis Register. Arthritis Rheum 2011;63:218391.
15 Walitt BT, Constantinescu F, Katz JD et al. Validation of self-report of rheumatoid arthritis and systemic lupus erythematosus: the Women’s Health Initiative. J Rheumatol 2008;35:8118. 16 Xiang YJ, Dai SM. Prevalence of rheumatic diseases and disability in China. Rheumatol Int 2009;29:48190. 17 Li R, Sun J, Ren L-M et al. Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing. Rheumatology 2012;51:7219. 18 Symmons D, Turner G, Webb R et al. The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology 2002;41:793800.
28 Spector TD, Hochberg MC. The protective effect of the oral contraceptive pill on rheumatoid arthritis: an overview of the analytic epidemiological studies using meta-analysis. J Clin Epidemiol 1990;43:122130. 29 Li Q, Hsia J, Yang G. Prevalence of smoking in China in 2010. N Engl J Med 2011;364:246970. 30 Kallberg H, Ding B, Padyukov L et al. Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis 2011;70:50811.
19 Hazes JM, Dijkmans BA, Vandenbroucke JP et al. Pregnancy and the risk of developing rheumatoid arthritis. Arthritis Rheum 1990;33:17705.
31 Karlson EW, Lee IM, Cook NR et al. A retrospective cohort study of cigarette smoking and rheumatoid arthritis in female health professionals. Arthritis Rheum 1999;42: 9107.
20 Pikwer M, Bergstrom U, Nilsson JA et al. Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of rheumatoid arthritis. Ann Rheum Dis 2009; 68:52630.
32 Di Giuseppe D, Orsini N, Alfredsson L et al. Cigarette smoking and smoking cessation in relation to risk of rheumatoid arthritis in women. Arthritis Res Ther 2013; 15:R56.
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12 Hoddinott P, Tappin D, Wright C. Breast feeding. BMJ 2008;336:8817.
25 Lee DH, Steffes M, Jacobs DR. Positive associations of serum concentration of polychlorinated biphenyls or organochlorine pesticides with self-reported arthritis, especially rheumatoid type, in women. Environ Health Perspect 2007;115:8838.
Rheumatology 2014;53:860866 doi:10.1093/rheumatology/ket456 Advance Access publication 6 January 2014
Original article Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou Biobank Cohort Study Peymane Adab1, Chao Qiang Jiang2, Elizabeth Rankin3, Yee Wah Tsang1, Tai Hing Lam4, Johanna Barlow1, G. Neil Thomas1, Wei Sen Zhang2 and Kar Keung Cheng1 Abstract
Methods. We used baseline data from 7349 women 550 years of age in the Guangzhou Biobank Cohort. Questionnaires were used to obtain socio-demographic, lifestyle and obstetric history data, including parity, OC use and breastfeeding practices. The main outcome was RA. Women were asked about history of RA and were examined to assess joint swelling. RF levels were measured. The presence of RA was defined in two ways: (i) as reporting physiciandiagnosed RA or pain and swelling in at least three joints (including the wrist), and (ii) also having at least one of the following: positive RF, morning stiffness or objective swelling of the small joints of the hands.
CLINICAL SCIENCE
Results. Compared with those who had never breastfed, breastfeeding was associated with half the risk of RA. The risk was lower with increasing duration of breastfeeding [adjusted odds ratio (OR) 0.54 (95% CI 0.29, 1.01) for breastfeeding at least 36 months; P for trend = 0.04]. OC use had no relationship with RA. Conclusion. Breastfeeding (especially longer duration) but not OC use is associated with a lower risk of RA. This has potentially important implications for future RA disease burden, given the declining rates of breastfeeding and the one-child policy in China. Further research is needed to explain the biological mechanism. Key words: breastfeeding, rheumatoid arthritis, risk factors, epidemiology, oral contraceptives, Chinese.
Introduction RA is a chronic inflammatory multisystem disease characterized by joint destruction. Although the clinical course can vary widely, it is recognized as a major cause of 1 Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, Birmingham, UK, 2Department of Occupational Health, Guangzhou Number 12 People’s Hospital, Guangzhou, China, 3Department of Rheumatology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK and 4School of Public Health, University of Hong Kong, Hong Kong, SAR China.
Submitted 1 March 2013; revised version accepted 25 November 2013. Correspondence to: Elizabeth Rankin, Department of Rheumatology, University Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, UK. E-mail: [email protected]
morbidity and disability. While the aetiology of RA remains elusive, epidemiological studies have suggested that hormonal factors are important [1]. RA is more common in women than in men, especially before the menopause [2]. During pregnancy, disease activity tends to diminish, but often flares up again in the post-partum period [3, 4]. Some, but not all, studies suggest that the use of oral contraceptives (OCs) can be protective against developing RA [5]. The relationship between breastfeeding one’s children and the risk of developing RA in the future has also been examined and data are conflicting. While large population-based cohort studies have found that breastfeeding is associated with a lower risk of [6] and mortality from RA [7], other casecontrol studies have suggested that breastfeeding increases risk, including the risk of
! The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://rheumatology.oxfordjournals.org/ by guest on June 9, 2015
Objective. Hormonal and reproductive factors are implicated in the aetiology of RA, but results of previous studies have been mixed. The aim of this cross-sectional study was to assess the relationships between RA, use of oral contraceptives (OCs) and history of breastfeeding in a population of older women from South China.
Guangzhou Biobank Cohort Study
severe disease [8, 9]. The post-partum flare of RA has also been linked to breastfeeding [10] and is thought to be mediated through increased concentration of prolactin [8]. Furthermore, it is unclear from previous studies whether it is breastfeeding or childbirth and pregnancy, per se, that influence the risk of RA. Apart from being inconclusive, these previous studies are based on populations in developed countries in the West, where patterns of breastfeeding and OC use differ from those in many developing countries. Data from the UK suggest that in 2010, 12% of mothers exclusively breastfed their babies for at least 4 months [11], compared with >50% of women in Asia [12]. We used baseline data from the Guangzhou Biobank Cohort Study (GBCS) to examine the relationships between parity, breastfeeding and OC use in relation to RA in a relatively understudied population.
Methods
www.rheumatology.oxfordjournals.org
Results Baseline data were available for 7349 women with a mean age of 63.5 years (range 5093). Overall, 7323 had all data for assessment of RA status, of whom 9.1% fulfilled definition 1 and 3.4% fulfilled definition 2 for RA in this study (Table 1). The general characteristics of the study population are described in Table 2. The majority of women had at least
861
Downloaded from http://rheumatology.oxfordjournals.org/ by guest on June 9, 2015
Details of the GBCS have been published elsewhere [13]. In brief, 30 000 men and women 550 years of age were selected from a community social and welfare association and invited to take part over three recruitment phases. In each recruitment phase the measurements and questionnaires were slightly modified, although some core measures were maintained throughout. Participants were eligible if they were ambulatory and not receiving treatment for life-threatening diseases, such as cancer. They attended a central recruitment centre where trained nurses and technicians carried out a comprehensive structured interview and examination. Participants were also asked to complete a structured questionnaire during their visit that included questions on socioeconomic status, family and personal disease histories and lifestyle habits. No additional data were collected for this particular study; all data reported are based on the original GBCS. The GBCS was approved by the Guangzhou Medical Ethics Committee of the Chinese Medical Association, Guangzhou, China. The ethical approval includes broad consent to perform clinical research related to the aims of the cohort study. As the study reported here falls within these research aims, no additional ethical approval was required to perform this analysis of the anonymized baseline data collected for the cohort study. Relevant to this study, subjects were asked in detail about their smoking and disease history. Specifically, they were asked to indicate whether a doctor had ever told them that they had any of 18 particular conditions. This included a question about arthritis. If they indicated yes, they were asked further details about the type of arthritis and the date of diagnosis. They were also asked directly about whether they had any recurrent or continuous pain, swelling or stiffness in any joints, and if so, which joints were affected. The presence and duration of morning stiffness were also recorded. All participants had their joints examined by a trained nurse and any tenderness or swelling and the affected joints were noted. Participants recruited in the first phase, but not subsequent phases, also had blood samples analysed for RF by nephelometry and a value >20 IU/ml was considered positive. In women,
information on their reproductive history was obtained, including parity, breastfeeding history and whether and for how long they had ever used OCs. Specifically, women were asked about whether they had ever been pregnant and the number of live births, and for each child they were asked to recall whether they had breastfed and, if so, for how many months. They were also asked to recall whether they had ever used OCs and, if so, the age at which they started and the number of years that they used the pill. For this analysis, data on 10 413 subjects who were enrolled in the first phase of the study (between 2003 and 2004) were used because all of the relevant measures (including blood samples for RF) were only undertaken in these initial subjects and further confined to women (n = 7349) (Fig. 1). We defined RA in two ways. First, all women who reported physician-diagnosed RA or those who reported pain in at least three joints commonly affected by RA, including the wrist, were included (definition 1). Second, we used a stricter definition (definition 2) where those fulfilling definition 1 were only included if they also had at least one of the ACR criteria for RA that were collected in the study. These included morning stiffness, positive RF, swelling or tenderness of the wrist or MCP joints on examination or reporting of pain and swelling in three or more relevant joints including the wrist. Women who reported never having been pregnant were considered to be nulliparous and the number of live births among the rest was recorded as a measure of parity. Among those who had live births, the number of children who were breastfed and the duration of breastfeeding for each were obtained. The total duration of breastfeeding was categorized into four groups (none, 3 years). Women were also categorized according to OC use (never, 15 or >5 years). The relationships between each breastfeeding, parity (number of live births) and OC use with RA (using both definitions) were examined, first by univariate and then by multivariate methods, adjusting for potential confounding factors including age, level of education, BMI and smoking. When examining the relationship between breastfeeding and RA, only parous women were included; two multivariate models were run, first as above and then adjusting for the number of live births. Sensitivity analyses were done with three alternative definitions of RA: (i) reported physician-diagnosed RA, (ii) those with three or more ACR criteria or (iii) those with reported physician-diagnosed RA and three or more relevant joints affected, examining the relationships between each of these and the duration of breastfeeding.
Peymane Adab et al.
FIG. 1 Flow diagram of participants selected for this analysis Phase of recruitment
Phase 1 (n= 10413)
Females (n=7349)
Parity: No children (n=201) ≥1 child (n=7108) Data missing (n=40)
Phase 2 (n=10018)
Phase 3 (n=10088)
Excluded: No blood sample for analysis of RF
Excluded: Males (n=3064)
OCP use: Never (n=6482) Yes (n=834) Data missing (n=33)
TABLE 1 Number of women who had various characteristics associated with RA No. (%) with that criterion RA diagnostic criterion Total population Reported physician-diagnosed RA, mean (range), years ACR criteria available in study: RF positive Morning stiffness Pain or swelling in 53 joints including hand or wrist Swelling/tenderness of wrist or MCP on examination Any one of the above ACR criteria Any two of the above ACR criteria Any three of the above ACR criteria All four of the above ACR criteria Physician-diagnosed RA Definition 1 (physician-diagnosed RA or pain/swelling in 53 joints, including wrist) Definition 2 (definition 1 and at least one ACR criteria)
one live birth, and of these, >95% had breastfed their child for at least 1 month. Only 11% had ever used the contraceptive pill, and mostly for short duration. The mean age at first pregnancy was 24 years (range 1445), while the mean age for diagnosis of RA (for those who reported a doctor diagnosis) was 47.5 years (range 878). Women with RA (whichever definition) were significantly more likely to be overweight (Table 2), less likely to have ever breastfed their children and had breastfed for a shorter duration overall (although the latter was not statistically significant). They were also slightly more likely to have a lower level of education and to have ever smoked. The mean number of live births per woman was 2.9 and did not differ between those with and without RA. Similarly, the number of children who were breastfed
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47.5 (878) 990 610 37 153 1447 135 16 2 650 669
(13.5) (8.3) (0.5) (2.1) (19.8) (1.8) (0.2) (120 000 women aged 530 with no RA at baseline were followed up for 26 years and a doseresponse relationship between breastfeeding duration and clinically confirmed RA incidence was found [relative risk (RR) 0.5 (95% CI 0.3, 0.8) for 524 months total duration of breastfeeding]. A matched casecontrol study from Sweden [20] with 136 incident cases of RA also found a doseresponse relationship between breastfeeding duration and RA [OR 0.46 (95% CI 0.24, 0.91) for breastfeeding duration 513 months compared with none]. However, in both those studies breastfeeding prevalence was much lower than in this study (67% of parous women had ever breastfed in both studies, compared with >90% in this study population). The total duration of breastfeeding was shorter, and both were conducted in populations in the West, where the prevalence of RA is higher. Furthermore, both studies concluded that their findings need to be replicated in other populations because previous reports were conflicting. Although the beneficial effects of breastfeeding for the mother and child are widely known, the findings from this study have further important implications for policy and research. Women who took part in the study reported
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OR (95% CI) for RA (definition 2)
Model 2b
Peymane Adab et al.
Guangzhou Biobank Cohort Study
Rheumatology key messages Increasing duration of breastfeeding is associated with reduced risk of RA among Chinese women. . There is no relationship between oral contraceptive use and risk of RA among Chinese women. .
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Acknowledgements We thank the Guangzhou Health and Happiness Association for the Respectable Elders for convoking the participants. Biobank Cohort Study investigators include X. Q. Lao, W.S.Z., M. Cao, T. Zhu, B. Liu, C.Q.J. (coprincipal investigator) (the Guangzhou Number 12 People’s Hospital); C. M. Schooling, S. M. McGhee, R. F. Fielding, G. M. Leung, T.H.L. (co-principal investigator) (University of Hong Kong); P.A., G.N.T., K.K.C. (coprincipal investigator) (University of Birmingham). All authors contributed to the study design, took part in the interpretation of findings and contributed to the final manuscript. E.R. conceived the idea for this paper and with P.A. coordinated completion of the manuscript. Y.W.T. and J.B. developed the definition algorithms for defining RA and undertook the initial analyses, supervised by P.A. and E.R. Y.W.T. wrote the first draft of the manuscript. P.A. reviewed and refined the analyses, updated the literature review and wrote the final draft. C.Q.J., K.K.C. and T.H.L. originally designed the idea of the GBCS and have been responsible for obtaining funding. C.Q.J. oversaw data collection and facilities for participant recruitment and contributed to the final manuscript. K.K.C. contributed to the detailed design of the study and provided critical comments on the manuscript. T.H.L., W.S.Z. and G.N.T. have all contributed to amendments of the manuscript and suggestions for data analysis. All authors checked and commented on the final draft and approved it. The GBCS was funded by the University of Hong Kong Foundation for Educational Development and Research, Hong Kong; Guangzhou Public Health Bureau and Guangzhou Science and Technology Bureau, Guangzhou, China; and the University of Birmingham, Birmingham, UK. Disclosure statement: The authors have declared no conflicts of interest.
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