In this study of the Chinese population with ACR less than the current microalbuminuria threshold, we found that higher parity degree was significantly associated with increasing risk of prevalent low-grade albuminuria. The association remained after adjusting for conventional risk factors and intermediates. To our current knowledge, no previous studies have provided evidence that parity degree is independently associated with low-grade albuminuria.
Using creatinine-based equations in detecting subtle changes in renal filtration function has inherent insensitivity and limitations in the early stages of kidney damage. In the present study, a positive association between eGFR and albuminuria was found. It is possible that kidney damage of the subjects in the cohort was in the early stage, as the average eGFR levels were still in the normal range. We assumed that prodromal renal hyper-filtration and increased glomerular pressure in the early stage of chronic kidney disease could be the cause of increased urinary albumin in the present study. Actually, in all models of logistic regression analysis, parity degree was independently associated with a greater prevalence of low-grade albuminuria even after adjustment for eGFR. Generally, 30 mg/g of ACR is considered the cut-off point of increased urinary excretion of albumin and used to predict chronic kidney disease. Recent studies have declared that the average ACR level is actually much lower in the early stage of kidney disease [22, 23]. Low-grade albuminuria, even within the previously defined normal range, is associated with development and progression of cardiovascular disease, which has received great attention in recent years [24, 25].
The present study extended the results of previous studies by confirming the association between parity degree and increased risk of prevalent low-grade albuminuria [3, 6, 12, 26]. Pregnancy produces significant alterations in women’s bodies, which may lead to constant but not temporary influence on women’s health [6, 27]. In fact, a higher number of offspring is also associated with lower socioeconomic status and child-rearing-related lifestyle risk factors. The accumulative effect that women experience in their later life could promote weight gain, insulin resistance, and dyslipidemia, which are often cited as adverse risk factors for cardiovascular diseases [3, 28]. The test for interaction between age and parity was significant, supporting an age difference for the association. Moreover, when comparing women with one childbirth to nulliparous women or to those with two childbirths, no significant difference regarding the relationship between parity of low-grade albuminuria was detected. Such results were consistent with some of the previous studies; therefore, our findings suggest that parity degree may have an accumulation effect with albuminuria risk in this population, which may be diluted by low risk in women with relatively fewer births [28].
The study highlights the importance of paying clinical attention to early albuminuria in women with multi-parity. The present findings emphasize that increasing is associated with subtle fluctuations in albumin excretion, which may reflect in pathophysiologic changes in the microvascular system. Moreover, as micro- and macroalbuminuria are much more serious manifestation of renal injury, it is likely that there are more metabolic risk factors associated with micro- and macroalbuminuria, some of which might veil the effect of parity degree. However, the underlying factors remain unclear and need further exploration. Reported data of abnormal albuminuria as low-grade or micro- and macroalbuminuria together could attenuate the main findings of this study, so we excluded individuals with increased urinary albumin excretion from the cohort.
Some biological and socioeconomic mechanisms that reflect pregnancy-related physiological changes may account for the possible link between number of offspring and low-grade albuminuria. The increase in parity degree with increased exposure to arterial hypertension and anti-insulin hormones may represent a combination of short-term effects of parity on susceptible subjects who have gestational hypertension and diabetes, and long-term effects on the macro- and micro-vascular system who have arteriosclerotic cardiovascular disease and increased urinary albumin excretion [28,29,30]. Another possible interpretation is that a higher number of offspring is usually related to lifestyle and socioeconomic status change, which may have potential influence on the risk of later albuminuria [31, 32]. Actually, both the harmful and protective aspects of these factors may take part in albuminuria development; thus, based on our findings, we suggest that unhealthy lifestyle characteristics, such as cigarette smoking, excessive drinking, and poor dietary habit, be eliminated, especially in families with high parity degree.
There are several limitations to be considered. Firstly, the cross-sectional design was a limitation of this study, and no causal inference can be drawn. The prospective association of parity degree with incident low-grade albuminuria in other cohorts is needed to verify our findings. Moreover, we will aim to conduct longitudinal research to examine the association between parity and outcomes of cardiovascular diseases, after adjustment for albuminuria. Secondly, self-reported information on pregnancies was not accurate enough, as recall bias may have affected association of parity degree with low-grade albuminuria in the present study. More detailed and accurate information about the disorders during the pregnancies or abnormal obstetrical outcomes (e.g. preterm labor, pregnancy hypertension, fetal growth restriction) should be collected to strengthen the findings of the study. Thirdly, as mentioned in our previous publication, urinary albumin excretion was evaluated on a spot morning urine sample, which may not have accurately reflected the true level of albuminuria [33]. Actually, 24-h urine collection or three samples from three consecutive days would have provided more stable results for albumin excretion [34]. However, spot specimens for urinary ACR correlate well with those of 24-h collection and multiple urine samples, so urinary ACR assessment by spot samples could be a reliable alternative in epidemiological specimen collection [35, 36]. Fourthly, although we adjusted for a spectrum of covariates associated with ACR in the multivariate regression analyses, other potential mediators, such as social status, personal income levels, and family lifestyle factors, could potentially have been residually confounding and should have been adjusted in the present study. Despite the above limitations, the current study included a large community-based cohort of individuals and was the first to examine the association between parity degree and risk of prevalent low-grade albuminuria, both of which add to the strength of our findings.
