This is the first population-based study conducted in the MENA region (a region with a high burden of CVD) which examines the impact of the number of parity/live birth(s) on incident CVD events among both sexes during more than 15 years of follow-up.
Among women, the number of live births has a J-shaped association with incident CVD, with the lowest risk for those with 2 births. After adjustment for a wide series of important risk factors including age, T2DM, hypertension, hypercholesterolemia, smoking and positive history of premature CVD -all of which remained significant risk factors in our analysis - each unit increase in parity was associated with a 5% higher risk of CVD events among women. Moreover, women with ≥ 4 parities had a more than 80% higher risk for incident CVD (marginally significant). Focusing on men, in comparison with participants who had 1 live birth, those with 2, 3 and ≥ 4 live births had about 100% higher risk for incident CVD in the presence of important traditional risk factors.
The findings of the current study about the association of parity number with incident CVD among women are consistent with a meta-analysis study on this issue by Li et al. in which they found a non-linear J-shaped dose-response relationship between the number of parity and CVD among women. They also reported that each unit increase in the number of live birth led to a 4% increased risk of incident CVD; however, the authers showed significant high heterogeneity between studies (I2 = 89.6%). In another meta-analysis, Lv et al. also found a similar J-shaped association between parity number and CVD mortality with the lowest risk for women with 4 live births. They also found that each live birth was associated with a 1% non-significant increased risk for CVD mortality (I2 = 86.4%). It should be noted that the significant heterogeneity in these two meta-analyses[8, 20] could be related to different study populations, sample sizes and other epidemiologic aspects of studies. Marginally significant increased CVD risk for women with ≥ 4 parities in our results agrees with the findings of other studies[21, 22]. Furthermore, our findings are in line with some previous cohort studies on CVD morbidity and mortality risk assessment which show a J- or U-shaped association with the lowest risk for women with 2 live births or parities[7, 23]. However, in some others, there is no relation among women across the number of parity/live birth(s)[10, 12, 24] or their significance of association was lost after adjustment for other factors[11, 25, 26].
Although most of the previous studies on the current issue, focused only on women, the limited data on men was controversial as well. Similar to the current report, Peters et al. reported that in comparison with Chinese men who had 1 child, men with ≥ 2 children and men with ≥ 3 children had a higher risk of incident CHD and stroke, respectively. Among Chinese men, they also showed that each additional child significantly increased the risk of CHD and stroke by 3% and 2%, respectively, although we did not find a linear relationship between the number of live births and incident CVD among Tehranian men. On the other hand, Eisenberg et al. found a negative association between the number of offspring with CVD mortality and each additional child decreased the risk of CVD mortality by 2% among American men. Furthermore, some previous studies could not detect any significant association between the number of live births and CVD mortality and morbidity among men[27, 28]; however, some others reported a J- or U-shaped association among men which was similar to their female population study[23, 29].
A possible explanation for the association between parity and incident CVD in women is the biologic pathway. During pregnancy, some physiologic changes can have adverse effects for incident CVD which remained even after delivery, including weight gain, dyslipidemia, increased plasma glucose and insulin resistance as well as endothelial dysfunction and inflammatory and hemostatic processes[6–8]. In the light of multiple pregnancies, exposure time to these changes increased[8, 30]. This accumulative effect of repeating parity on traditional risk factors might be an important neglected residual confounding factor in the current study and similar researches in this field.
Beside the impact of the biologic pathway, psycho-socio-economic factors were reported to have a potentially important role in the pathway between number of children and CVD development in both parents[13, 14]. In a previous study on a Swedish population, Barclay et al. compared the effect of the number of live births on CVD mortality between adoptive and biologic parents. They showed that CVD mortality is higher in biological parents than adoptive parents which means that the biologic pathway had inevitable effects for this issue. On the other hand, finding a U-shaped pattern in this study among adoptive male parents suggested that the biological pathway couldn't be the only explanation for their findings and the socioeconomic and lifestyle pathway should be considered as another explanation. Moreover, some previous studies[14, 16, 23] have found a similar pattern for men and women in their population study which confirmed the strong role of socioeconomic and lifestyle pathway. It should be considered that during our study recruitment period, the policy of the Iranian government was based on reducing population growth; so there was minimal economic support for Iranian parents. Furthermore, according to the data of the statistical center of Iran in 2017, household income per capita reduced with increased family size  which means parents with more children might be under greater economic pressure. These economic problems could have adverse effects on socioeconomic status which can lead to CVD development through psychosocial factors (anxiety and depression development), using unhealthier diet, smoking initiation, limiting leisure-time physical activity, poor access to health care and little knowledge about diseases[33–35]. Since the head of the Iranian family is traditionally the father , the stronger effect the of number of children among men is expectable through the socioeconomic and life style pathway; the issue needs serious and deep investigations in future studies.
The strengths of the current study consist of addressing the effect of the number of parity/live birth(s) on CVD development among both sexes in the MENA region (a region with high burden of CVD) for the first time, with standardized measurements for assessment of traditional risk factors rather than relying on self-reported data and adjudicated CVD events. The current study was limited in several ways. First, potential risk factors were considered at the time of baseline phases and possible changes in risk factors as well as the number of parity/live birth(s), were not considered during the follow-up period. Second, the number of participants who hadn't had children was too low to permit us to compare the impact of nulliparity with ever parity. Third, we did not have access to valid data on participant job status, income and diet which can clarify the socioeconomic and lifestyle pathway. Although we considered education status as a socioeconomic determinant, there was no strong relationship between education levels and economic status among Iranian population . Fourth, our population study included only residents of a metropolitan city and cannot be generalized to rural populations.