maternal moderate and severe anemia have been considered as conditions that affect adversely maternal and perinatal outcomes .
for such reason the identification of these cases is important since appropriate treatment may reduce the risk for adverse outcomes .
iron is the most common treatment currently used to control iron deficiency and anemia particularly in low - income countries , where anemia is more frequent .
physiologically , hemoglobin concentration drops during gestation , and for such reason the hemoglobin cutoff to define anemia was set at 11  g / dl of hb .
maternal hb levels are higher at high altitudes in all trimesters of pregnancy than at sea level .
however , the reduction of hemoglobin levels during pregnancy occurs in populations at low and at high altitudes .
this is due to plasma volume expansion as a mechanism to improve arterial uterine flow to the placentae .
thus , a normal hb value at first booking in the first trimester does not preclude the presence of anemia in a second measurement of hemoglobin as pregnancy advances .
a recent study showed a higher risk for anemia in pregnant women with low body mass index ( bmi ) .
, anemia , particularly moderate and severe anemia is associated with high risk for low birthweight [ 3 , 9 , 10 ] , it is important to monitor hemoglobin values during pregnancy .
the present study has been designed to determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes .
we will determine rates of anemia , normal hemoglobin values and erythrocytosis ( hb > 14.5  g / dl ) .
in addition , risk factors for moderate / severe anemia will be assessed in a multivariable analysis .
this is a secondary analysis of a large data base obtained from the perinatal information system in peru which includes 379,816 pregnant women and their babies obtained from 43 maternity units in peru .
data were obtained at the three geographical regions in peru : coast , highlands , and amazon .
the study was authorized by the institutional review board at the universidad peruana cayetano heredia .
as the study used secondary analysis of data , the study was exempt from formal review . from the total sample size
, a selection was made of all women diagnosed as nonanemic and without erythrocytosis at first booking ( hb ranging from 11 to 14.5  g / dl ) and having a second measurement of hemoglobin during the same pregnancy .
, 57,231 pregnant women were living at low altitude ( < 2000  m ) , 11,349 women at moderate altitude ( 20003000  m ) , and 20,714 women were living at high altitudes ( > 3000  m ) .
data on gestational age at first and second hemoglobin measurement were recorded . with a second hemoglobin value , rates of pregnant women with anemia ( hb < 11 g / dl ) , normal hemoglobin values ( 1114.5  g / dl ) , and erythrocytosis ( hb>14.5  g / dl ) were determined . as demonstrated previously , no correction of hemoglobin cutoff to define anemia at high altitude is needed ; hence , the present study used the definition of anemia as suggested who for populations at sea level [ 1 , 11 ] .
the degrees of anemia were classified as mild ( hb 9.010.9  g / dl ) , moderate ( hb 7.0 < 9  g / dl ) , and severe ( hb < 7  g / dl ) . body mass index was calculated from prepregnancy body weight and height .
low bmi was defined as < 19.9  kg / m and high bmi as > 25 
altitude was defined as low ( 01999  m ) , moderate ( 20002999  m ) , and high (  3000  m ) .
the following perinatal outcomes were assessed : stillbirths , preterm deliveries and small for gestational age .
stillbirths were diagnosed when fetal deaths occurred after 20 weeks of gestation or with a weight higher than 500  g. preterm births were defined as deliveries before 37 weeks of gestational age .
small for gestational age was defined if birthweight was below the 10th percentile of the williams reference chart .
the adverse maternal outcomes assessed were preeclampsia , premature rupture of membranes ( prom ) , and postpartum hemorrhage ( pph ) .
preeclampsia was defined as the presence of pregnancy - induced hypertension ( systolic pressure of 140  mm  hg and/or diastolic pressure of 90  mm  hg ) and proteinuria ( 300  mg/24  h ) after 20 weeks of gestation .
pph was defined as women after parturition with blood losses of 500  ml or more .
data are assessed according level of altitude ( low , moderate , and high ) and according to degree of anemia ( moderate / severe and mild ) , and erythrocytosis .
if data were normally distributed , then a one - way analysis of variance were used ( anova ) .
data expressed in proportions were assessed by the chi - square test . the confidence interval ( ci )
the prevalences of women with moderate / severe anemia ( hb < 9  g / dl ) , mild anemia ( hb 910.9  g / dl ) , normal hemoglobin ( hb 1114.5  g / dl ) , and erythrocytosis ( hb > 14.5  g / dl ) were calculated for the total sample , as well as for groups at different altitudes ( low , moderate , and high altitude ) .
estimates of crudes and adjusted odds ratio ( or ) with 95% ci were computed as measures of association between the variables .
a logistic regression analysis to determine the risk for moderate / severe anemia at second hemoglobin measured was assessed .
the estimates were adjusted for gestational age at second hemoglobin , hemoglobin value at first measurement , altitude , maternal age , body mass index , maternal education , marital status , prenatal care visits , parity , the presence of preeclampsia , cardiopathy , and diabetes .
concentration of hemoglobin at first booking in nonanemic women increased as altitude increased ( p < 0.05 ) , whereas birthweight decreased as altitude increased .
no differences were observed in gestational age at birth at the three altitude groups studied .
concentration of hemoglobin at second measurement also was increased as altitude increases , but values were lower than those at first measurement , particularly at low altitude , in which values were reduced to 94% , whereas at moderate altitude . they were reduced to 98.4% and at high altitude to 99.2% .
gestational age at first and second hemoglobin was higher as altitude of residence increased ( table 1 ) .
most of the studied sample remained with normal hemoglobin values at second hemoglobin measurement ( 75.1 ) .
however , 21.4% of women became anemic at the second hb measurement . in all , 2.8% resulted with moderate / severe anemia and 3.5% with erythrocytosis ( figure 1 ) .
women with anemia in the second hb measurement showed lower hb measurements in the first hb .
conversely , women with erythrocytosis at the second hb measurement showed higher hb levels in the first measurement ( table 2 ) . in all cases hb was higher as altitude increased .
the rate of stillbirths was higher with moderate / severe anemia and with erythrocytosis ( p < 0.05 ) , which remained higher after controlling for confounders ( table 3 ) .
the rate of preterm births was increased in women with severe anemia ( 9.01% ; or = 1.81 ) . after adjusting for confounders , moderate / severe anemia ( or = 1.73 ) and mild anemia ( or = 1.28 ) were risks for preterm deliveries ( table 4 ) .
the rate of sga was significantly higher in mothers with erythrocytosis , almost twice , than in women with normal hemoglobin .
lowest rate of sga was observed with a maternal hb level of 910.9  g / dl ( mild anemia ) ( table 5 ) .
the rate of preeclampsia was significantly higher in moderate / severe and mild anemia and in mothers with erythrocytosis , which remained after controlling for confounders ( table 6 ) .
the highest risk for pph was observed with moderate / severe anemia ( twenty times higher than in woman with normal hb levels ) ( table 8) .
an increased risk for moderate / severe anemia was associated with higher gestational age at second measurement of hemoglobin , bmi < 19.9  kg / m , living without partner , prenatal visits care < 5 , first parity , multiparity , and preeclampsia .
lower risk for moderate / severe anemia were observed with normal high hb level at first booking , living at moderate and high altitude , and with high bmi ( table 9 ) .
the present study has been designed to determine changes in hb levels after a first hb measurement in 89,294 pregnant women detected normality ( hb 1114.5  g / dl ) . according to the study results
an increase in the rate of anemia according to pregnancy progress has been previously published in other settlings .
moderate / severe anemia has been characterized as the conditions more associated with maternal and perinatal adverse outcomes .
our results demonstrated that 2.8% of women classified as nonanemic in the first hb measurement showed moderate / severe anemia in the second measurement .
our data showed that moderate / severe anemia were associated with stillbirths , preterm births , preeclampsia , and pph .
the strength of this study is that it was done thanks to a large sample of women recorded through a perinatal information system that included 379,816 pregnant women and their newborn babies from different maternity units throughout peru .
this database is an important tool for monitoring conditions and trends related to pregnancies and newborns , including service characteristics and women 's risk factors .
data revealed that a percentage of women became anemic during the progression of pregnancy despite having a first normal hb measurement .
this is an important finding since moderate and severe anemia are harmful for mothers and neonates .
risks for moderate / severe anemia are preventable , or can be managed through appropriate management , such as with prenatal care , parity , preeclampsia , and low bmi .
increasing the number of prenatal visits will result in better monitoring of hemoglobin values , and can control or reduce the effect of preeclampsia .
low bmi is a characteristic of low - income countries and is associated with increased risk of maternal anemia , low birthweight , and preterm births .
the present results are in accordance with other studies where low prevalence of anemia was observed in women with highest bmi , and high prevalence of moderate / severe anemia were associated with malnutrition [ 14 , 15 ] .
our data suggest that in situation in which a normal hemoglobin value was first observed in a woman with low body mass index , supplementation with iron should be recommended .
it is interesting to note that populations living at moderate and high altitudes had lower risk for moderate / severe anemia in a second measurement of hemoglobin during pregnancy .
this suggests that women living in these altitudes bearing normal hemoglobin values at first booking should not be treated with iron supplementation . in recent years
, it has been demonstrated that anemia defined as less than 11  g / dl of hb is lower at moderate and at high altitudes , since populations at these altitudes are characterized by increased hemoglobin values to compensate for the effect of altitudinal hypoxia [ 3 , 10 ] .
however , we assumed that most cases of anemia were related to iron deficiency , which was supported by the finding that low bmi was associated with moderate / severe anemia .
however , results of our analysis were similar to those obtained in a study in which bmi was obtained at first prenatal care .
it is possible that erythrocytosis found in the second measurement of hb after a normal value of hb at first booking could be due to the effect of iron supplementation , since in peru a ministry of health regulation orders pregnant women be supplemented with iron .
however , low adherence may explain the low prevalence of erythrocytosis in a second hb measurement during pregnancy .
the results of this study confirm that prevalence of anemia increases as pregnancy progresses and that a normal value at first booking should not be considered sufficient , as further hb values should be indicated and observed during the course of pregnancy .
 
 objective . to determine changes in hemoglobin concentration at second measurements after a normal hemoglobin concentration was detected at first booking during pregnancy at low and at high altitudes 
 . methods . 
 this is a secondary analysis of a large database obtained from the perinatal information system in peru which includes 379,816 pregnant women and their babies from 43 maternity units in peru 
 . results . 
 most women remained with normal hemoglobin values at second measurement ( 75.1% ) . 
 however , 21.4% of women became anemic at the second measurement . 
 in all , 2.8% resulted with moderate / severe anemia and 3.5% with erythrocytosis ( hb>14.5  g / dl ) . in all cases 
 hb was higher as altitude increased . 
 risk for moderate / severe anemia increased associated with higher gestational age at second measurement of hemoglobin , bmi < 19.9  kg / m2 , living without partner , < 5 antenatal care visits , first parity , multiparity , and preeclampsia . 
 lower risk for moderate / severe anemia was observed with normal high hb level at first booking living at moderate and high altitude , and high bmi . 
 conclusion . 
 prevalence of anemia increases as pregnancy progress , and that a normal value at first booking may not be considered sufficient as hb values should be observed throughout pregnancy . 
 bmi was a risk for anemia in a second measurement . 