Discussion
In this prospective study of 272494 participants from UK Biobank, we
found that compared with those who had only one child, childless women
had the higher all-cause premature mortality and the lower years of life
expectancy, whereas those with two, three, or four children had the
lower all-cause premature mortality and the higher years of life
expectancy. And these associations were independent of biological
factors, lifestyle, socioeconomic level, and pre-existing diseases.
Similarly, this study found that the relationship between parity and
all-cause premature mortality was also observed in sensitivity analyses,
demonstrating the robustness of the results. Moreover, comparied with
women who had one child, the estimated values of FI, ΔKDM-biological age
and HD adjusted for multiple covariates in women with two or three
children were lower, and the correspondings in females with five or more
chilldren were higher.
Our study found that the childless women had the higher all-cause
mortality, and women who had two, three, or four children had the lower
all-cause mortality, compared to women with one child, which are similar
with the results reported in a Sweden
population[13]. Differently, the relationship
between five or more live births and all-cause premature mortality was
significant in the Sweden population. Although the correspondings
relationship in our study was not significant, there is also a clear
upward trend in the RCS curve, which may be attributed to the more
covariates we have corrected. The finding in subgroup analyses suggested
that association between the number of live births and hazard of
all-cause premature mortality appeared to be different among different
races, which may be attributed to the genetic reasons of race being a
potential factor affecting this relationship. In addition, obesity,
current-smoking, and excessive alcohol consumption mask the relationship
between parity and all-cause premature mortality, possibly due to the
fact that obesity[33,34],
smoking[35], and alcohol
consumption[36] themselves can cause a series of
physiological changes, damage health, and even lead to premature death.
For example, the obese persons are more likely to experience metabolic
changes during pregnancy than their normal weight
counterparts[37,38]. And in obese individuals,
lipids, oxidized LDL particles, and free fatty acids activate the
inflammatory process and trigger the atherosclerosis and
CVD[39-40]; and obesity leads to changes in the
structure and function of the heart[41], leading
to heart failure[42], atrial
fibrillation[43,44] and sudden cardiac
death[45]. Similarly,the chronic diseases also had
an impact on the relationship between parity and all-cause premature
mortality.
In addition, our study provides novel evidence to show the relationship
between parity and mortality. Our results on the cause-specific
premature mortality indicate that the hazard of all-cause premature
mortality associated with more number of live births could be partly
attributed to CVD-specific and cancer-specific premature mortality. Such
observations are consistent with previous evidence linking parity with
various conditions including cardiovascular
disease[46] and cancer[47].
For the subtypes of CVD-specific
premature mortality, we found that higher number of live births was
significantly associated with lower hazard of CHD-specific and
stroke-specific premature mortality, compared with women with one child.
These observations were supported by the results from the parity and
stroke study, and the parity and coronary heart diseases study, in which
parity may confer a moderate long-term protective effect on the risk of
subarachnoid hemorrhage (SAH)[48,49] and
CHD[50]. Future investigations are warranted to
explore the association of the number of live births with various
cardiovascular disease subtypes. In addition, evidence from experimental
and epidemiological studies has shown that parity was related to breast
cancer[51-53], ovarian
cancer[53,54], cervical
cancer[55]. We found that nulliparous women had
the highest hazard of all-cause premature mortality, which be partly
attributed to the continuous stimulation of ovarian hormones to the body
of nulliparous women may increases the cancer-specific premature
mortality, especially breast cancer and ovarian
cancer[5,6], and further increases the all-cause
premature mortality of nulliparous women.
For the first time, we reported that childless women was associated with
the lower life expectancy at the age of 40 years by 1.41 (95% CI:
0.78–2.01) years for women, and women with two, or three or four
children had an average 1.10 (95% CI: 0.63–1.74), 1.00 (95% CI:
0.54–1.74), 1.00 (95% CI: 0.05–1.84) higher years of life expectancy,
respectively, compared with participants who had one child. Meanwhile,
we found that accelerated biological aging and functional decline were
potential influencing factors, as the estimated values of FI,
ΔKDM-biological age and HD adjusted for multiple covariates have
significant changes. Our research is similar with the changes in HD
caused by parity in previous articles, giving rise to the U-shape for
the overall relationship between parity and biological
aging[56]. Moreover, we also found that women who
gave two or three births were the least likely to age, while women with
five or more children are the most likely to age, which can be
attributed the fact that reproduction can consume a large part of
resources, reducing the efforts invested in the maintenance and
repairment of somatic tissues, and then leading to aging and death in
women[57-60]. In addition, studies have shown that
the social and psychological pressure caused by women’s by high parity
may be another potential factor accelerating biological aging and
functional decline[61].
The present findings may have several public health implications. First,
the evidence is complementary to those on the association between the
number of live births and all-cause mortality and fills the gap in the
relationship between parity and all-cause premature mortality, life
expectancy, and aging. Second, the evidence may inform the
recommendations on behavioral changes regarding reproduce. The parity is
easily assessed in clinical and public settings, and may be useful for
future reproduce interventions.
Although our study have some advantages including the large sample size,
the extensive covariate correction, and the consistent results in
several sensitivity and subgroup analyses, several potential limitations
should be carefully considered in this study. Firstly, we could not
exclude the possibility that high number of live births is a marker for
a lower socioeconomic level. However, subgroup analyses indicated that
the positive association between the number of live births and hazard of
mortality was consistent across the subgroups of socioeconomic level.
Secondly, in this study we obtained maternal live births by questioning
“How many children have you given birth to? (Please include live births
only) ” Because this question did not include the number of
stillbirths, spontaneous miscarriages or termination that women may have
had previously, we could not obtain specific date associated with these
situations. As described earlier, if the number of births affects
long-term health conditions, the number of stillbirths, spontaneous
miscarriages or termination will also be an important source of
information. We need a further study including these basic facts in
order to investigate the effects of number of stillbirths, spontaneous
miscarriages or termination on long-term health. Thirdly, although we
controlled for many socioeconomic factors and lifestyle factors, we
lacked explicit information on marital status, on age at first birth ,
and on attitudes and values that may be associated with both fertility
and health. These unmet covariates may affect the relationship between
parity and all-cause premature death. Fourthly, an important limitation
of this study is that the UK Biobank is not representative of the
general population due to the voluntary
participation[24]. Further studies are needed to
conirm our findings, especially in populations that are more
representative of the UK population.
In conclusion, our study indicates that the relationships between the
number of live births and hazard of all-cause premature mortality, life
expectancy, and aging. obesity, current-smoking, and excessive alcohol
consumption may affect the association between the parity and all-cause
premature mortality. Further clinical trials are warranted to validate
these findings.