Aims Epidemiological evidence showed that prevalence rates of cataract were higher in women than in men. Female reproductive factors were hypothesised to be linked with this sex difference. In this study, we explored possible effects of parity and reproductive factors on the risk of cataract.
Methods Women (14 337 total; aged 45–86 years) were recruited from the Dongfeng-Tongji cohort study. All subjects completed baseline questionnaires and medical examinations and provided baseline blood samples. Cataract was diagnosed by the ophthalmologist in the ocular examination. Logistic regression models were used to evaluate the association between parity and the risk of cataract.
Results The prevalence rate of cataract in the study population was 6.8% (972/14 337). After adjustment for potential confounders, women who had undergone two, three, and four or more live births had 1.52 times (95% CI 1.13 to 2.04), 1.67 times (95% CI 1.27 to 2.29) and 1.72 times (95% CI 1.22 to 2.42), respectively, higher risk of cataract compared with women who had undergone one live birth. The risk increased by an estimated 11.3% for each additional live birth. Women who had undergone hormone replacement therapy (OR 1.61; 95% CI 1.05 to 2.47), had diabetes mellitus (OR 1.33; 95% CI 1.11 to 1.58) and/or had the habit of drinking alcohol (OR 1.51; 95% CI 1.08 to 2.10) had a higher risk of cataract. Neither menopause status nor history of contraceptive use was associated with cataract.
Conclusions The findings suggested that parity was an independent risk factor for the development of cataract in Chinese women.
- Public health
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Cataract is the leading cause of blindness worldwide, accounting for 51% of total blindness.1 The prevalence of cataract is increasing because of longer life expectancy, aging, changes in lifestyle and the increasing prevalence of obesity.2 In the USA, the prevalence rate of cataract is as high as 17.2% among people older than 40 years, and the number of people with cataract is estimated to be 30.1 million by 2020.3 Additionally, cataract is responsible for considerable suffering and is a substantial economic burden to society. Therefore, it is of significance to identify risk factors of cataract for the prevention and treatment of blindness.
Evidence from epidemiological data showed that women have a higher risk of cataract compared with men.4 Mechanisms for this sex-specific difference are unclear, and it has been argued that female reproductive factors may play a role in the development of cataract. Pregnancy involves dramatic alterations in physiology, metabolism and lifestyle. All these changes including the state of insulin resistance,5 weight gain or obesity, and postpartum weight retention may have long-term and not only temporary adverse effects on the prospective health of women.6 Some studies have reported that pregnancy was associated with diabetes mellitus and hypertension.7 ,8 These alterations related to reproductive history may have a role in cataract formation. Some studies suggested that female reproductive factors including menopause status, history of contraceptive use and hormone replacement therapy were associated with cataract.9 The relationship between parity and the development of cataract in later life has been a topic of research for many years, but the findings are inconsistent.
Therefore, the aim of this study was to investigate for the first time the relationship between parity and the risk of cataract formation among perimenopausal and postmenopausal Chinese women.
Materials and methods
The Dongfeng-Tongji cohort study was launched in 2008 among retirees of Dongfeng Motor Corporation (DMC) in Shiyan City, Hubei province. DMC was founded in 1969 and is one of the three largest auto manufactures in China. Details on Dongfeng-Tongji cohort design, fundamental and methods were previously reported.10 Between 2008 and 2010, 87.0% (n=27 009 out of 31 000) retired employees who agreed to participate in the study were recruited and then completed the baseline questionnaires, medical examination, and provided baseline blood samples.
Of 27 009 eligible participants, there were 14 957 women. We excluded women with no live birth from our study (n=205) (reasons for this exclusion and an additional analysis are discussed in the online supplementary file). Participants with missing information on parity or on diagnosis of cataract were also excluded (n=415). In total, we excluded 620 subjects from this study (accounting for 4.1% of the study population). The final sample size for the present study was 14 337 women (aged 45–86 years).
Signed informed consent was obtained from all participants and the study was approved by the Medical Ethics Committee of the School of Public Health, Tongji Medical College.
Assessment of cataract
All participants took the ocular examination using a slit lamp, and the Lens Opacity Classification System (LOCS II) was used for lens grading.11 We defined a definite cataract as LOCS II grade 2 or worse for at least one of the three main types of cataract, including nuclear, cortical and posterior subcapsular cataract. Individuals with a history of cataract surgery were also defined as having cataract in our study.11
Parity was defined as the total number of live births. Parity was categorised into four groups: one live birth, two live births, three live births, and four or more live births.
Assessment of covariates
Demographic information on age, marital status (eg, married, widowed, divorced, unmarried) and education level (eg, primary or below, junior high school, high school, college or above) was collected via questionnaires. Lifestyle information on physical activity, cigarette smoking status and alcohol drinking status was also collected via questionnaires. Regular physical activity was defined as exercising for more than 20 min per day and more than three times per week over the last 6 months. Information regarding the number of live births, abortions, menopause status, history of contraceptive use, and history of hormone replacement therapy was obtained via a reproductive questionnaire. Items in the medical examination included height, weight, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose, and levels of triglyceride, total cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C). Body mass index (BMI) was calculated via dividing weight in kilograms by the square of the height in metres. In the present study, participants with diabetes mellitus were defined as those who had high fasting plasma glucose (≥7.0 mmol/L); who self-reported a physician diagnosis of diabetes mellitus; or who were using antidiabetic treatment. Similarly, participants with hypertension included those self-reporting a physician diagnosis of hypertension; those using antihypertensive medication; and those with SBP greater than 140 mm Hg or DBP greater than 90 mm Hg.
Categorical variables were reported as proportion (%) and numerical data were reported as mean±SD. Differences were analysed with a t test for numerical variables and χ2 tests for categorical variables. The Cochran–Armitage test for trend was used to analyse the association between cataract and the number of live births. We used cataract as a dependent variable and a series of multivariable logistic regression models to calculate the ORs and 95% CIs across parity groups. ORs were adjusted simultaneously for several potential risk factors by multiple logistic regression analysis. Variables potentially related to cataract formation that were considered in the models were age (years), BMI (kg/m²), marital status, education level, physical activity status (yes or no), current smoking status (yes or no), current alcohol drinking status (yes or no), diabetes mellitus (yes or no), hypertension (yes or no), the number of abortions, menopause status (yes or no), history of contraceptive use (yes or no), history of hormone replacement therapy (yes or no), and levels of triglyceride (mmol/L), CHOL (mmol/L) and LDL-C (mmol/L). All statistical analyses were performed using SPSS software (V.17.0).
Table 1 shows the characteristics of the study subjects by the presence of cataract. Of the total 14 337 eligible study participants, 972 (6.8%) were diagnosed with cataract. Compared with participants who did not have cataract, those with cataract were older (69.22 vs 59.75 years of age, p<0.001), were more likely to have higher BMI (24.67 vs 24.51, p=0.001), to have more live births (3.10 vs 2.08 live births, p<0.001), to smoke (4.0% vs 2.1%, p<0.001), to have diabetes mellitus (27.7% vs 17.0%, p<0.001) and hypertension (67.0% vs 51.1%, p<0.001), and were less likely to have a history of contraceptive use (19.1% vs 23.7%, p=0.001). On examination, the cataract group had higher triglyceride levels (1.63 vs 1.50 mmol/L, p=0.001) and higher CHOL levels (5.45 vs 5.34 mmol/L, p=0.001). There was no significant association between history of hormone replacement therapy and cataract.
The prevalence rate of cataract ranged from 1.7% in women who had experienced one live birth to 5.3% in women who had undergone two live births, 10.8% in women who had undergone three live births, and 18.7% in women who had undergone four or more live births. Without any adjustment, women who had undergone two live births (OR 3.23; 95% CI 2.52 to 4.14), three live births (OR 6.93; 95% CI 5.43 to 8.86), or four or more live births (OR 13.22; 95% CI 10.34 to 16.90) had a significantly higher risk for cataract compared with women who had undergone one live birth (p for trend, <0.001). Adjustment for age and BMI attenuated the apparent negative effects of parity, but higher parity (two live births: OR 1.44; 95% CI 1.11 to 1.88; three live births: OR 1.66; 95% CI 1.26 to 2.19; and four or more live births: OR 1.72; 95% CI 1.28 to 2.31) were still significantly associated with an increased risk of cataract (p for trend, <0.001). Further control for potential confounders demonstrated that ORs were 1.52 (95% CI 1.13 to 2.04), 1.67 (95% CI 1.27 to 2.29) and 1.72 (95% CI 1.22 to 2.42) for women who had experienced two, three, and four or more live births, respectively (p for trend, <0.001) (table 2).
The multivariable results for other potential risk factors are shown in table 3. A positive relationship between history of hormone replacement therapy and risk of cataract was observed in the present study (OR 1.61; 95% CI 1.05 to 2.47). Diabetes mellitus (OR 1.33; 95% CI 1.11 to 1.58) and alcohol drinking (OR 1.51; 95% CI 1.08 to 2.10) were marginally related to higher risk of cataract. There was no significant relationship between history of contraceptive use and the risk of cataract.
The findings of this study supported an important influence of female reproductive factors and other related risk factors on cataract formation in older women. Our study showed that higher parity was associated with an increased risk of cataract. After controlling for potential confounders, a positive graded association between parity and risk of cataract was observed, suggesting that higher parity was an independent risk factor for cataract in this population of Chinese women.
Previous epidemiological studies have examined the association between pregnancy and cataract, but few studies have explored the effect of parity on the later development of cataract, and the results have not been consistent. The positive linear relation between parity and risk of cataract observed in the present study was consistent with the results previously reported in a study of younger women. A case–control study of 357 women aged 35–45 years observed that women who had more than three children had a twofold higher risk of cataract, and the risk increased by 20% for each additional child.12 On the contrary, the Beaver Dam Eye Study suggested a possible protective effect of an increasing number of live births on the risk of cataract.13 In addition, several studies showed that parity was not found to have a significant association with the incidence of cataract after controlling for potential confounding factors.9 ,14 ,15 However, parity was not the primary interest in these studies and the findings were not discussed comprehensively.
The mechanism underlying the link between parity and cataract is unclear. There are dramatic changes in anatomy, physiology and lifestyle during pregnancy, which may contribute to mothers having an increased risk of cataract. Some investigators indicated that the adverse effect of parity on cataract development might be attributed to a reduction in lifetime exposure to circulating oestrogens.16 Some population-based studies have found that women with early menarche and/or late menopause have a decreased risk of cataract, indicating protective effects of oestrogen on the lenses of women. In the Beaver Dam Eye Study, for example, it was demonstrated that the risk of more severe nuclear sclerosis increased by about 26% for each 5-year increment in age at menarche; and for each 5 years of age older at the time of menopause, the risk of cortical cataract decreased by 11%.17 These epidemiological findings provided some evidence that oestrogen may play a protective role in reducing the risk of cataract. Therefore, we postulated that the increased risk of cataract for women with higher parity may be due to the change of oestrogen levels induced by completed pregnancy. However, because of the lack of plausible physiological or biological data in support of a causal association between parity and increased risk for cataract, in the future this hypothesis needs to be confirmed by laboratory measurements.
Pregnancy may result in obesity and postpartum weight retention, which are of great significance to a woman's health in later life.6 ,18 It is a traditional practice to give considerable attention to the safety and dietary nutrition of pregnant women in Chinese society. Pregnant women in China are generally not allowed to participate in almost any form of physical activity to avoid the occurrence of accidents. Furthermore, according to Chinese traditional customs, women may be bedridden for a month after delivery.19 Lack of exercise and a high-calorie diet were closely associated with a higher risk of weight gain or obesity, important risk factors for cataract in later life.20 A study of 16 460 Chinese women reported that the average pregnancy weight gain was 17.1±4.9 kg,21 which was much higher than the recommended criteria.22 Nevertheless, BMI failed to fully explain the positive association between parity and cataract observed in our study as the association was attenuated but remained statistically significant after additional adjustment for BMI. However, one limitation is that the BMIs used as a covariate in this study were measured after the development of cataract. The conclusion would be more convincing if BMI measured just after delivery had been used as a covariate.
Another possible factor for the positive relationship between parity and cataract is the state of insulin resistance in peripheral tissues induced by high levels of several diabetogenic hormones and cortisol during pregnancy.5 Previous studies have demonstrated that parity was a novel risk factor for diabetes mellitus,7 ,23 and patients with type 2 diabetes have a 97% higher risk of cataract compared with subjects without diabetes.24 A positive association between diabetes mellitus and the risk of cataract observed in our study also supported the speculation that parity might increase the risk of cataract through mediation by pathophysiological changes, such as insulin resistance.
This study had several strengths. First, the relatively larger sample size means the statistical significance was robust. Second, with standardised questionnaires and measurements, the data on demographics, lifestyle, history of diseases and reproductive factors were available and considered valid, which enhanced the reliability of the findings. Moreover, all subjects took the ocular examination and cataract was diagnosed by ophthalmologists with same instruments at several hospitals belonging to the DMC. Hence, ascertainment bias was unlikely in this study.
There were also some limitations that should be considered in the present study. First, the data were cross sectional; therefore, although we demonstrated that a higher risk of cataract was associated with an increasing number of live births, causal and temporal associations could not be inferred. However, cataract is often an age-related disease, generally occurring in older people. It was reported that about one-third of patients with advanced stages of cataract were found in people aged 60–69 years, and two-thirds of those were found in individuals aged 70 years or more, but were only rarely observed in subjects aged less than 60 years.2 The mean age for completing childbirth in China was 28.2 years.25 Therefore, this suggested that the majority of participants developed cataract after completion of childbearing, making reverse causation unlikely in this study. Second, this study did not differentiate the types of cataract. Parity may have different effects on the formation of various cataract types. Nevertheless, the main interest in our study was the effect of parity on the risk of cataract in general, not on a specific type of cataract defined by anatomical position.
In conclusion, parity may be a risk factor for cataract independent of potential confounders. The results should be interpreted cautiously and additional longitudinal studies, including weight gain measurements, and changes in physiology and lifestyle during pregnancy and the postpartum period should be conducted to clarify these issues.
We thank the Dongfeng-Tongji cohort participants and the staff at DMC in Dongfeng General Hospital for the data collection.
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
- Data supplement 1 - Online supplement
Contributors YT and YW conceived and designed the study; JW, GX, LS and SY performed the statistical analysis; HY and YW performed the experiments; YT drafted the article; YW, C.M and YL contributed to the critical revision of the article. All authors gave their comments on the article and approved the final version.
Funding This research was supported by the National Natural Science Foundation of China (81273083), the Fundamental Research Funds for the Central Universities (2014TS051), the 111 project, the Program for Changjiang Scholars, the Innovative Research Team in University, the China Medical Board 12-113.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Medical Ethics Committee of the School of Public Health, Tongji Medical College.
Provenance and peer review Not commissioned; externally peer reviewed.
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