hypertension is considered as the first leading risk factor for the global burden of disease .
epidemiological observations have led to the hypothesis that the risk of developing some chronic noncommunicable diseases ( ncds ) in adulthood is influenced not only by genetic and adult lifestyle factors but also by environmental factors acting in early life .
concept , several factors determine the blood pressure ( bp ) level in childhood , which is associated with the adult bp levelrough the  tracking  phenomenon .
therefore , prevention of ncds , namely , cardiovascular diseases in adulthood should begin from childhood .
in addition , hypertension in childhood may induce target organ damages such as left ventricular hypertrophy , thickening of the carotid vessel wall , retinal vascular changes , subtle cognitive changes , and even premature development of atherosclerosis .
the prevalence of hypertension is increasing in the pediatric population in line with the childhood obesity epidemic and lifestyle widespread changes .
alarming data exist on the considerable prevalence of overweight children and its metabolic consequences not only in the industrialized countries but also in developing countries .
the strong relationship of even the early stages of hypertension with obesity and environmental factors such as air pollution , noise pollution , and passive smoking suggest that its prevalence will be escalating in the near future .
there is a growing body of evidence , which shows that impaired maternal nutrition may negatively influence vascular health in later life .
more specifically , the dietary calcium ( ca ) intake of pregnant women may be associated with the bp of their infants , and ca intake is inversely correlated to systolic bp in young children .
some recent experimental and observational studies in humans and animals have reported an association between maternal ca intake during pregnancy and bp in the offspring , but others did not confirm it . we conducted a systematic review of studies reporting the association of maternal ca intake either by food or supplements with bp in the offspring .
we searched pubmed and scopus as the main international electronic data sources . the medical subject headings ( mesh ) including entry terms of pubmed and emtree of scopus were used for most comprehensive and efficient searches .
we searched the databases using the following strategy : for scopus [ title - abs - key ( maternal or mother ) and title - abs - key ( calcium ) and title - abs - key ( blood pressure ) ] , and for pubmed [  others  ( mesh ) ) or maternal ) and  blood pressure(mesh ) and  dietary supplements(mesh ) ) or calcium ] .
duplicates were removed ; the relevant papers were selected in three phases . in the first and second phases ,
titles and abstracts of the papers were screened and irrelevant papers were excluded . in the last phase ,
the full text of recruited papers was explored intensely to select only relevant papers . for any additional pertinent studies ,
the reference list of all reviews and relevant papers was screened as well . in the next step ,
identification of main findings of the studies was conducted on a case - by - case basis and included consideration of any statistical analyses that might have been conducted and consistency of the general pattern across exposure groups .
the required information that was extracted from all eligible papers were as follows : 
 general characteristics of the study ( first author 's name , publication year , study year , study design)participantssupplement , age of the offspring , loss to follow - up , andoutcomes . 
 
general characteristics of the study ( first author 's name , publication year , study year , study design ) age of the offspring , loss to follow - up , and
we searched pubmed and scopus as the main international electronic data sources . the medical subject headings ( mesh ) including entry terms of pubmed and emtree of scopus were used for most comprehensive and efficient searches .
we searched the databases using the following strategy : for scopus [ title - abs - key ( maternal or mother ) and title - abs - key ( calcium ) and title - abs - key ( blood pressure ) ] , and for pubmed [  others  ( mesh ) ) or maternal ) and  blood pressure(mesh ) and  dietary supplements(mesh ) ) or calcium ] .
duplicates were removed ; the relevant papers were selected in three phases . in the first and second phases ,
titles and abstracts of the papers were screened and irrelevant papers were excluded . in the last phase ,
the full text of recruited papers was explored intensely to select only relevant papers . for any additional pertinent studies ,
the reference list of all reviews and relevant papers was screened as well . in the next step ,
identification of main findings of the studies was conducted on a case - by - case basis and included consideration of any statistical analyses that might have been conducted and consistency of the general pattern across exposure groups .
the required information that was extracted from all eligible papers were as follows : 
 general characteristics of the study ( first author 's name , publication year , study year , study design)participantssupplement , age of the offspring , loss to follow - up , andoutcomes . 
 
general characteristics of the study ( first author 's name , publication year , study year , study design ) age of the offspring , loss to follow - up , and
based on our search strategy , we found 636 records . after removing duplicates , during the three refine steps on the papers titles , abstracts , and full texts and considering the inclusion criteria ,
flowchart of study selection summary of maternal calcium supplementation and offspring blood pressure this systematic review of the literature identified four randomized trials and three observational studies .
three studies included infants less than 1 year of age and seven included children between 1 year and 9 years of age .
a number of maternal ca supplementation trials have been conducted on pregnant women in recent years , primarily to investigate the potential for reducing the risk of preeclampsia .
all of the four trials have published follow - up data on the offspring , focusing on bp as an outcome .
the study of belizan et al . is a good quality randomized trial , which randomized 1,194 women during early pregnancy to either 2 g ( four tablet of calcium carbonate of 500 mg ) of oral ca supplementation or placebo .
the follow - up only included the 614 participants from the private hospital ( approximately 50% of the original sample ) .
the proportion of children with high systolic bp was lower in the ca group ( 11.4 % ) than in the placebo group ( 19.3% ) [ relative risk ( rr ) 0.59 ; confidence interval ( ci ) 0.39 - 0.90 ] .
the proportion of children with high diastolic bp was also lower in the ca group [ 10.2% vs 12.7% ( 0.80 ; 0 ; 49 - 1.30 ) ] .
a large reduction in the incidence of hypertension in children at 7 years of age was found in this study . there was a modest , statistically insignificant effect on systolic bp but a clinically and statistically significant effect on the incidence of high systolic bp at 7 years of age .
this study also reported that the effect was stronger among overweight children ; other studies did not observe this though the sample sizes were too small to exclude such a difference . for children under 12 months ,
randomized 4,589 women during early pregnancy to receive either 2 g of oral ca supplementation or placebo .
patients from only one out of five medical centers were included in the follow - up ( 559 out of 4,589 subjects ) .
loss of follow - up was 53% at 3 months and 90% at 2 years .
the authors acknowledged this to be a problem , adding that a large proportion of the cohort had not reached 2 years of age by the end of the study .
the trial provided evidence that maternal ca supplementation was associated with lower systolic bp in the offspring at 2 years .
systolic bp was 2.2 mmhg lower in the ca - supplemented infants than in the placebo group ( p > 0.05 ) . at 2 years of age , systolic bp was 4.8 mm hg lower in the ca supplemented group ( p < 0.05 ) , whereas diastolic bp was lower by 3 mmhg .
designed their study to explore the association between infant bp and maternal dietary intake of ca , potassium , and magnesium .
the authors measured the offspring bp in hospital when the babies were 2 - 4 days old and at home at 1 month , 6 months , and 12 months .
there were no significant associations between the mothers pregnancy intake of these cations and the newborns bp .
however , at 1 month of age maternal prenatal ca intake had a significant inverse association with systolic bp . at 6 months of age ,
maternal prenatal intakes of all three cations were significantly and inversely associated with diastolic bp . at 12 months of age ,
gillman et al . used the data from a cohort study of pregnant women conducted in the united states .
this study was designed to assess the effects of the mother 's diet on the mother 's and the offspring 's health .
it assessed maternal ca intake during the first and second trimesters using a validated semi - quantitative food frequency questionnaire ( ffq ) , and measured offspring bp at birth and at 6 months .
the authors reported figures for ca from food sources and from prenatal supplements , and then performed two independent analyses accordingly .
after further adjustment for demographic , anthropometric , dietary , social , and economic variables , the decrease in 6-month systolic bp was 3.0 mmhg ( 95% ci , 4.9 to 1.1 ) for each 500 mg increment of maternal supplemental ca intake during pregnancy .
morley et al . used the data from a population - based survey in tasmania designed to investigate sudden infant death syndrome .
mothers of all live - born twins during the study period were approached after birth for data collection including nutritional supplement consumption during pregnancy .
data on ca consumption from other sources ( i.e. , foods ) were not available .
children were assessed at a mean age of 9 years and their bp was measured .
conducted a study with 389 children from a rural area of gambia whose mothers received ca supplement ( 1,500 mg ca / day from 20 weeks of gestation until delivery ) or placebo in west africa .
the study was part of a european union consortium investigation of the early life nutritional determinants of disease ( framework 6 :  early nutrition programming project  ) .
at the time of this follow - up study , the surviving offspring were aged between 5 years and 10 years ( mean age : 7.4 years , standard deviation ( sd ) 6 1.2 ] .
this study found no evidence that maternal calcium supplementation ( 1,500 mg ca / day ) of rural gambian women during the second half of pregnancy was associated with the offspring 's bp at 5 - 10 years of age .
hiller et al . followed up 414 participants with live - born infants who lived in south australia .
mothers and their children attended the women 's and children 's hospital for anthropomorphic examination .
there was no indication that ca supplementation during pregnancy had an impact on either systolic or diastolic bp at follow - up among women with preeclampsia , pregnancy - induced hypertension ( pih ) , or severe pih .
however , some evidence showed that their children tended to have lower bp at follow - up .
this interaction between maternal ca supplementation and the child 's bp at follow - up was the strongest for women with more severe pih and preeclampsia .
the evidence indicated by this body of research suggests a connection between dietary ca intake during pregnancy and the offspring 's bp .
a good quality trial found a large reduction in the incidence of hypertension in children at 7 years of age . for infants under 1 year of age ,
it is well - known that the determinant of bp varies with age , and it has been shown that the impact of factors affecting the fetal environment are seen particularly after adolescence . this problem is magnified because of the difficulties in measuring bp accurately in early ages .
it is unclear whether this is a true biological differential effect or a statistical artefact resulting from the greater variability within individuals of diastolic pressure compared with systolic pressure . among the seven studies reported , we found four randomized trials .
the validity of the evidence from observational studies for assessing the effect of interventions is controversial .
apart from the methodological problems of the original articles , other limitations of this analysis should be pointed out .
the sources and dose of dietary ca vary widely among the observational studies , and so do the methods used to assess the amount consumed .
it is well - known that the determinant of bp varies with age , and it has been shown that the impact of factors affecting the fetal environment are seen particularly after adolescence . this problem is magnified because of the difficulties in measuring bp accurately at an early age .
six out of the seven studies included in the current review were conducted in developed countries , and on populations in which the maternal ca intake was adequate or even higher than the recommended levels during pregnancy .
given the evidence that the effect of ca might be apparent only when there is a deficit , the external validity of these results might be compromised . in hawkesworth 's study from a region of habitually very low dietary calcium intake , there was no association between maternal calcium supplementation and offspring bp . as a whole ,
the main limitation in all the observational studies was loss to follow - up . for two of these studies ,
higher maternal calcium intake during pregnancy was associated with lower offspring systolic bp in all studies but the effect was statistically significant in only three of them .
the argentinean follow - up reported an interaction between the intervention and childhood bmi ; for individuals with a bmi above the mean ( 15.7 ) , maternal calcium supplementation was associated with lower systolic bp .
these studies did not observe an increase in effect estimates as the body mass index increased .
gillman 's study suggested that the bp - lowering effect of ca might be limited to the three quartiles of the offspring 's body mass index .
most of the protective effect of ca supplementation during pregnancy is concentrated in children with high body mass index ; if this finding is confirmed , it might have important preventive implications because this subgroup is at higher risk of elevated bp and adult hypertension .
high maternal ca intake with lower maternal bp could reduce fetal exposure to maternal hormones or substances related to elevated bp .
the observed effect could reflect a long - term programming of elevated bp in utero by ca supplementation in the mother .
this is consistent with the results obtained from observational studies that an early fetal exposure to calcium reduces bp during childhood .
in general , our findings confirm the association of maternal ca intake during pregnancy and offspring bp .
however , more research is needed to confirm these findings , given the small sample sizes and the methodological problems in many of the studies conducted so far . more studies on populations with low ca intake are also needed . if confirmed , these findings could have important public health implications .
ca supplementation during pregnancy is simple and inexpensive and may be a way to reduce the risk of elevated bp and its sequels in the next generation .
the study was funded as a thesis of isfahan university of medical sciences , isfahan , iran .
the study was funded as a thesis of isfahan university of medical sciences , isfahan , iran .
all authors contributed in the conception of the work , conducting the study , revising the draft , approval of the final version of the manuscript , and agreed for all aspects of the work .
 background : evidence proposes that maternal calcium ( ca ) supplement during pregnancy may be inversely associated with the off spring 's blood pressure ( bp ) level . 
 it is suggested that increased maternal ca intake during pregnancy may result in lower bp in the off spring . 
 the reduction in the incidence of hypertension in mothers is documented but the effects on the off spring are uncertain.materials and methods : we conducted a systematic review of the literature to summarize the evidence supporting an association between maternal dietary ca intake during pregnancy and the bp in the off spring . in this systematic review , 
 relevant papers were selected in three phases . 
 after quality assessment , a reviewer extracted the data while the other one checked the extracted data . 
 we summarized the information regarding the association of maternal ca intake either by food or supplements with bp in the off spring.results:four randomized trials and three observational studies were included in this review . 
 the results were more consistent among the studies including older children ( 1 - 9 years ) where a higher maternal ca intake was associated with a reduction in the off spring 's systolic bp . 
 one large randomized trial found a clinically and statistically significant reduction in the incidence of elevated bp in 7-year - old children [ relative risk ( rr ) = 0.59 , 95% confidence interval ( ci ) 0.39 - 0.90].conclusion : overall , our findings confirm the beneficial effects of maternal ca intake during pregnancy for the off spring 's bp level . 