the human cytomegalovirus ( cmv ) or human herpesvirus 5 is one of the major causes of congenital infections .
its clinical manifestations range from asymptomatic forms ( 90% of cases ) to severe fetal damage and , in rare cases , death due to abortion . furthermore
, 10%15% of the children who are asymptomatic at birth may develop late sequelae , especially hearing defects , after a period of months or even years .
latency following a primary infection ( first contact with the virus ) may be punctuated by periodic reactivations that give rise to recurrent infections , and in utero   transmission may occur during either primary or recurrent infections .
actually recurrent infections may be due to reinfection with a new strain or to reactivation , but it is likely that most recurrent infections are due to reinfection .
the risk of congenital infection is much higher during primary infection [ 25 ] , when the rate of transmission from mother to fetus is 30%40% [ 1 , 6 ] , as against 0.15%2.2% during reactivations or reinfections [ 1 , 69 ] when , furthermore , most of the newborns are asymptomatic .
symptomatic cases are due more to reinfection than reactivation [ 2 , 10 ] .      
it has been reported that the risk of fetal damage is greater if the primary infection occurs during the first trimester of pregnancy [ 1113 ] .
the prevalence of congenital infection ranges from 0.2% to 2.5% in different populations [ 1420 ] , in which the risk factors include particular races or ethnic groups , a low socioeconomic status , premature birth , and admission to an intensive care unit [ 6 , 17 ] .
furthermore , the prevalence of congenital infection varies with the prevalence of the infection in the population .     
the seroprevalence of cmv among women of childbearing age ranges from 35% to 95% in different countries   [ 12 , 2124 ] and , as well as increasing with age , may also depend on sexual activity and occupation , particularly occupations involving close contacts with children in a community setting . in the case of parents ,
contact with the urine or saliva of their children is a major source of infection [ 2527 ] .      
the incidence of primary infection among pregnant women ranges from 0.5% and 4% [ 28 , 29 ] ; the rate of seroconversion during pregnancy ranges from 0.4% to 2% [ 12 , 13 , 30 , 31 ] and depends on the seroprevalence of the infection in the population , being 3.7% among women belonging to populations with a low seroprevalence ( 55% ) and 1.0%1.6% among those belonging to populations with a high seroprevalence ( 85% ) .
the risk of acquiring infection during pregnancy is 0.71.38  100 pregnancies [ 23 , 29 ] among seronegative women , and 0.20.8  100 pregnancies among women as a whole .    
as far as prevention is concerned , in addition to health education campaigns , the serological screening of pregnant women has been proposed . however , there is no consensus in the scientific community concerning the implementation of screening , and it is not recommended by any public health system because of its cost / benefit ratio , although many doctors in israel , belgium , and france do test their pregnant patients .
furthermore , although the current public health legislation in italy ( law decree 245 of 10 september 1998 ) does not include free cmv antibody screening during pregnancy , it is prescribed by many general practitioners .     
the aim of this study was to assess the incidence and risk of acquiring cmv infection in pregnant women in an urban area in northern italy in the period 20052007 .
during the three years 20052007 , the microbiology unit of hospital of legnano , received samples for the detection of cmv antibodies from 2817 pregnant women ( mean age 32 years , range 1546 ; 2522 ( 89.5% ) were italian and 295 ( 10.5% ) of foreign origin ) .      
forty - eight women ( 1.7% ) were 20 or less than 20 years of age , 928 ( 32.9% ) women were aged between 21 and 30 , 1750 ( 62.1% ) aged between 31 and 40 , and 91 ( 3.2% ) between 41 and 50 .
2318 women ( 82.3% ) underwent their first screening in the first trimester ( group a ) , 316 ( 11.2% ) in the second trimester ( group b ) , and 183 ( 6.5% ) in the third ( group c ) .
the requests were made by the general practitioners as part of the routine screening required during pregnancy .      
all of the samples were analyzed for the presence of anti - cmv igg and igm antibodies by means of an enzyme - linked immunosorbent assay ( elisa ) ( eti - cytok - g - plus , eti - cytok - m reverse plus , diasorin , saluggia , italy ) .
the cutoff value used to determine igg was 0.4 iu / ml , whereas the samples were considered igm - positive when their absorbence was equal to , or greater than the control cutoff value .     
the igm - positive samples were confirmed using an enzyme - linked fluorescent assay ( elfa ) ( vidas cmv igm , biomrieux , lyon , france ) and were considered positive when their index was   0.90 , borderline when their index was between 0.70 and 0.90 , and negative when their index was   > 0.70 . as igm anti
- cmv antibodies may test positive for more than 12 months and may be produced during reactivation or reinfection , the samples that were igm - positive at elisa were also tested for igg avidity ( liaison cmv igg avidity , diasorin saluggia , italy ) , which was considered low if the index was   < 0.2 , moderate if it was between 0.2 and 0.3 , and high if it was   0.3 .
low igg avidity levels strongly suggest an infection contracted less than three months before , whereas a high avidity tends to exclude this .the elisa igm - positive samples were also tested   for the presence of rheumatoid factor ( arthri - slidex , biomrieux , lyon , france ) . in the case of positivity for igm ,
the patients ' general practitioners were contacted and advised to evaluate the case and refer patients to a reference center .    
at the first screening , the elisas showed that 1925 women ( 68.3% ; 95% ci : 66.6%70.0% ) were positive for anti - cmv igg ( positive or negative for igm ) and 26 ( 0.9% ; 95% ci : 0.55%1.25% ) were positive for igm antibodies ( 25 in the first trimester , and one in the second trimester for whom no previous data were available as she did not undergo screening during the first trimester ) .
table 1 shows the results of igm and igg elisa by trimester of first screening ( groups a 
elfa of the 26 elisa igm - positive samples showed that 17 ( 65.4% ) were positive or borderline , and nine were negative ( 34.6% ) , including the sample that was igm - positive at elisa screening in the second trimester .
none of the differences in the prevalence of igg and igm between contiguous age classes was statistically significant .
of the 892 women who were anti - cmv antibody negative at first screening , 687 ( 77.0% ) were in the first trimester of pregnancy ( group a ) , 131 ( 14.7% ) in the second trimester ( group b ) , and 74 ( 8.3% ) in the third ( group c ) .     
three hundred and seventy - four of the women of group a ( 54.4% ) were also screened in the second trimester , and 258 ( 37.6% ) were also screened in the third ( table 2 ) .
of these , two became positive for igm ( confirmed by elfa ) and igg , one in the second trimester ( 0.3% ) , and one in the third ( 0.4% ) , for a mean seroconversion rate of 0.32% .      
of the 131 women of group b , 64 ( 48.9% ) were also screened in the third trimester ; there were no cases of seroconversion ( table 2 ) .       of the 1899 women who were anti -
cmv igg antibody positive ( and negative for igm ) at first screening , 1606 ( 84.6% ) were in the first trimester of pregnancy ( group a ) , 184 ( 9.7% ) in the second trimester ( group b ) , and 109 ( 5.7% ) in the third ( group c ) .
one hundred and fifteen of the women of group a ( 7.2% ) were also screened in the second trimester , and 66 ( 4.1% ) were also screened in the third .
of the 184 women of group b , 20 ( 10.9% ) were also screened in the third trimester ( table 2 ) .
nineteen of the 28 igm - positive samples at elisa ( 67.9% ) were confirmed as being igm - positive by means of elfa , and 13 ( 46.4% ) showed low or moderate igg avidity .
the 19 elfa - confirmed cases ( 17 first screened in the first trimester , and the two seroconversions ) included six ( 31.6% ) with a high degree of igg avidity , five ( 26.3% ) with moderate avidity , and eight ( 42.1% ) with a low degree of avidity ( table 3 ) .  

table 4 shows the results of the confirmatory igm elfa and igg avidity tests by trimester of pregnancy .
in particular , of the five cases showing moderate avidity , one was recorded in our files as having been seronegative for both igg and igm four and a half months before ( i.e. , about two months before conception ) , and another was the case of seroconversion in the third trimester after being seronegative in the first and second . in the remaining three cases ,
the only data available were those of the initial positive sample , but the general practitioner of one of these women , who was contacted after the detection of igm positivity , reported symptoms compatible with ongoing cmv infection .
no symptoms were reported by the general practitioners in any of the other two cases nor additional information was available .
all of the 13 cases with low or moderate igg avidity were therefore considered as having primary infection : 11 ( 84.6% ) occurring in the first trimester , one ( 7.7% ) in the second , and one ( 7.7% ) in the third ( both seroconversions ) .      
unfortunately there were no data regarding the transmission of infection to the fetus because the igm - positive women were all referred for further investigations to reference centers throughout the area .
the cumulative incidence of cmv infection ( new cases observed during pregnancy ) calculated on the basis of the 13 cases with low or moderate igg avidity was 1.4% ( 95% ci : 0.971.83 ) , and the risk of infection during pregnancy , calculated on the basis of all of the women ( seronegative and seropositive ) , was 0.5  100 pregnancies ( 95% ci : 0.240.76 ) . the differences in incidence and risk by age was not statistically significant . to take into account the loss to follow - up within the groups and different admission to the study of women during different trimester ,
there were also calculated the density incidence as cases / pregnant woman - trimester and the correlated risk for all women ( seronegative and seropositive ) :   they were , respectively , 0.8% ( 95% ci : 0.471.13 ) and 0.4% ( 95% ci : 0.170.63 ) .
the overall prevalence of anti - cmv igg antibodies in our pregnant women was 68.3% ( 95% ci : 66.670.0 ) , without any significant differences between age classes .     
as first pregnancies in italy generally occur later than they did in the past , the majority of women have already recovered from primary infection by the time they reach childbearing age and almost certainly by the time of their first pregnancy . moreover , in this study 95% of the women had an age between 21 and 40 years while age classes of 20 or less than 20 and over 40 years were under - represented ; so this could be a further cause of the lack of difference in seroprevalence .     
on the basis of the results of the igg avidity test , the cumulative incidence of cmv infection was 1.4% ( 95% ci : 0.971.83% ) , the density incidence was 0.8% ( 95% ci : 0.471.13 ) , and the risk of infection was 0.5% ( 95% ci : 0.240.76% ) without any significant differences by age .      
seroconversion or clinical data indicating acute infection were available for three of the five cases with moderate avidity in this study , thus moderate avidity was considered as a potential marker of acute infection .
moderate and low igg avidity were considered together , and both were included in the calculation of incidence .
however , the incidence may be an underestimate because only about half of the seronegative women underwent further screening in the second trimester and about one - third in the third , and so some cases of seroconversion may have been missed .      
for the same reason , the proportion of primary infections ( 84.6% ) occurring in the first trimester may be overestimated ; however , assuming the same rate of seroconversion among the seronegative women who did not undergo further screening , the majority of primary infections occurred in the first trimester .       the fact that 84.6% of the primary infections occurred in the first trimester may have been due to different behaviors before the pregnancy was recognized , whereas greater care during pregnancy may lead to less exposure .
the fact that there were no differences related to the age of the women indicates the same type of behavior at different ages .
it is therefore important to start screening in the first trimester of pregnancy , when there is a greater risk of infection and in order to have initial findings to compare with subsequent follow - up . in the absence of baseline data ,
the presence of igg without igm in women undergoing their first screening in the third trimester raises doubts as it may be the result of a previous infection occurring at any time in life before the pregnancy ; however , although this is statistically the most probable situation , the possibility of an infection occurring in the first trimester with the subsequent loss of igm can not be excluded .      
finally some limitations of the study must be taken into account as no outcome data for newborns , substantial loss to follow - up , and limited testing of igg positive women for reinfections or reactivations .
however , for the latter two cases , as there are no official recommendations , the follow - up was performed at the discretion of the general practitioner with compliance of pregnant woman who , above all , must pay for cmv antibody screening .       in conclusion , although screening is not recommended by any public health system ( including italy 's ) because of its cost / benefit ratio , it is actually adopted by many general practitioners in our area . such screening provides an opportunity to identify seronegative women who can be counselled about using appropriate hygienic measures to prevent infection , especially in relation to their behavior with children , who are a major source of infection .
furthermore , the screening identified primary infections in pregnant women who could be referred to reference centers to check for prenatal infection .
amniocentesis , funicolocentesis , ultrasonography , and magnetic resonance imaging can all be used to detect infection and allow the planning of appropriate interventions ( e.g. , antiviral therapy , termination of pregnancy ) .        although some authors consider that screening is not justified on the grounds of its economic cost , the imperfect nature of congenital infection prognostic criteria , the risk of spontaneous abortions induced by invasive tests such as amniocentesis , and the few data concerning effective treatments during pregnancy , it is unthinkable to deny pregnant women appropriate information concerning the health of their unborn child as this raises a number of ethical and legal questions .
the incidence and risk of cmv infection in pregnancy found in our area , therefore , support the use of serological screening , certainly in the first trimester when the risk of infection is higher and , in the case of seronegative women , possibly also one screening in the second trimester and one in the third .
 the fetal consequences of cmv infection make it one of the most serious infections contracted during pregnancy , but the scientific community is divided over the proposed implementation of preventive screening for anti - cmv antibodies . 
 the aim of this study was to assess the incidence and risk of infection during pregnancy in 2817 women who underwent anti - cmv igg and igm antibody screening during the period 20052007 . 
 the prevalence of anti - cmv igg antibodies was 68.3% ( 95% ci : 66.670.0 ) ; the seroconversion rate in the 892 seronegative women was 0.32% ; the results of igg avidity testing revealed an cumulative incidence of 1.4% ( 95% ci : 0.971.83 ) , density incidence of 0.8% ( as cases / pregnant woman - trimester ) ( 95% ci : 0.471.13 ) , and a risk of infection of 0.5% ( 95% ci : 0.240.76 ) . the screening identified 13 cases of primary infection ( 84.6% of which occurred in the first trimester of pregnancy ) . 
 the possibility to identify these cases and consequently to plan appropriate interventions , supports the use of screening during pregnancy , especially in the first trimester when the risk of infection is greater . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion