three hundred twin placentas ( 77 separate dichorionic diamniotic [ didis ] , 147 fused dichorionic diamniotic [ didif ] , 66 monochorionic diamniotic [ modi ] , 8 monochorionic monoamniotic [ momo ] , and 2 unknown type ) and 1,270 singleton placentas were consecutively collected at samsung medical center , seoul , republic of korea , from 2009 to 2012 . the study was approved by the institutional review board of the hospital ( 2011 - 07 - 063 ) . preterm birth was defined as delivery before 37 weeks of gestation and was categorized as ( 1 ) spontaneous preterm births resulting from preterm labor and intact membranes , and preterm premature rupture of membranes ; and ( 2 ) indicated preterm births due to maternal and/or fetal conditions necessitating preterm births . iugr was defined as birth weight below the 10th percentile , and discordant growth in twins was defined as more than 15% difference in birth weight . tissue samples of the full - thickness placental disc ( n=2 ) and chorioamniotic membranes roll ( n=1 ) for each placenta , and also of the dividing membranes if present , were obtained for microscopic examination and were formalin - fixed for 24 hours . vue , cca , and cd were diagnosed according to the previously described criteria in the literature . briefly , vue was defined as lymphohistiocytic infiltration affecting varying proportions of the villous tree of the placenta without any signs or symptoms of infection in either the mother or the infant . it is sub - classified as basal type , which involves villi anchoring to the basal plate , and nonbasal ( distal and proximal ) type , which involves distal villi ( terminal and mature intermediate villi ) and/or stem villi . the diagnosis of cca was made when there was lymphocytic infiltration into the chorionic trophoblast layer and/or chorioamniotic connective tissue . cd was diagnosed when lymphocytic infiltration was diffuse and/or any plasma cells were detected in the decidua . the cases were examined by a single pathologist ( j .- s.k . ) who was blind to clinical information . the chi - square test and fisher exact test were performed to compare proportions , and the mann - whitney u test was performed to determine the differences in the median values between the study groups . the spss ver . 21 ( ibm co. , armonk , ny , usa ) was employed for all statistical analyses . there were significant differences in the gestational age at delivery , gravity , labor at delivery , preterm birth , and iugr between singleton and twin pregnancies ( p<.05 ) . maternal age , previous abortion , the ratio of spontaneous / indicated preterm birth , and hypertensive disorders were not significantly different . the frequencies of the three types of chronic placental inflammation ( vue , cca , and cd ) were not statistically different between twin and singleton placentas . twin placentas had a tendency of high frequency of vue ( 11.3% [ 34/300 ] vs 7.9% [ 100/1,270 ] , p=.054 ) and cd ( 13.0% [ 36/300 ] vs 9.7% [ 123/1,270 ] , p=.09 ) compared with singleton placentas , whereas they showed a tendency of low frequency of cca ( 9.3% [ 28/300 ] vs 13.3% [ 169/1,270 ] , p=.062 ) ( fig . the frequency of the non - basal type of vue was higher in twin placentas than in singleton placentas ( 6.0% [ 18/300 ] vs 3.2% [ 41/1,270 ] , p<.05 ) . there was no difference in the frequency of basal vue between twin and singleton placentas ( 5.3% [ 16/300 ] vs 4.6% [ 59/1,270 ] , p>.05 ) ( fig . there were no significant differences in the frequencies of vue ( 10.2% [ 23/225 ] vs 15.1% [ 11/73 ] ) , cca ( 9.3% [ 21/225]vs 9.6% [ 7/73 ] ) , or cd ( 13.8% [ 31/225 ] vs 11.0% [ 8/73 ] ) between dichorionic ( didis and didif ) and monochorionic ( modi and momo ) placentas ( p>.05 ) . cd was significantly more frequent in didis twin placentas compared with singleton placentas ( 16.9% [ 13/77 ] vs. 9.7% [ 123/1,270 ] , p<.05 ) , but the frequencies of vue and cca were not significantly different among the twin types . the frequency of vue increased with increasing gestational age at birth in both singleton and twin placentas ; however , there was no significant difference in the frequency of vue between singleton and twin placentas when the cases were matched by gestational age ( fig . 2a ) . when the study population was divided into preterm and term births , term twin placentas were affected by non - basal vue more frequently than term singleton placentas ( 12.9% [ 9/70 ] vs 3.6% [ 14/384 ] , p<.01 ) , but the difference was not detected in preterm placentas ( fig . the frequencies of basal vue were not significantly different between singleton and twin placentas either at preterm or at term ( fig . cca was found less frequently in twin placentas than singleton placentas of preterm birth ( 9.6% [ 22/230 ] vs 14.8% [ 131/886 ] , p<.05 ) ( fig . the decrease of cca in twin placentas compared with singleton placentas was significant at 3336 weeks of gestation ( late preterm birth ) ( 10.0% [ 12/120 ] vs 17.9% [ 90/503 ] , p<.05 ) . cca in singleton placentas was most commonly observed at late preterm stage ( 3336 weeks of gestation ) during gestation as previously reported ; however , cca in twin placentas was most frequent at 2932 weeks unexpectedly ( 14.0% [ 6/43 ] ) ( fig . 3b ) . cd was detected at similar frequencies between preterm and term placentas ( fig . the high frequency of cd in didis twin placentas compared with singleton placentas was more prominent at term ( 31.6% [ 6/19 ] vs 8.3% [ 32/384 ] , p<.01 ) ( fig . 4b ) . vue in singleton placentas was found more frequently in iugr cases than in non - iugr cases ( 12.9% [ 36/278 ] vs 6.5% [ 64/985 ] , p<.001 ) . of these cases , non - basal vue was more frequent in iugr cases than in non - iugr cases ( 7.6% [ 21/278 ] vs 2.0% [ 20/985 ] ) , p<.001 ) . non - basal vue in twin placentas was more frequent in iugr cases than in non - iugr cases ( 9.8% [ 12/122 ] vs 3.4% [ 6/175 ] , p<.05 ) , though vue showed no significant correlation with iugr in twin placentas ( 13.1% [ 16/122 ] vs 10.3% [ 18/175 ] ) ( fig . vue was more frequent in indicated preterm birth than in spontaneous birth of singleton placentas ( 10.2% [ 24/235 ] vs 6.3% [ 41/651 ] , p<.05 ) ( fig . non - basal vue was more frequent in indicated preterm birth than in spontaneous birth of both singleton and twin placentas ( singleton , 5.5% [ 13/235 ] vs 2.2% [ 14/651 ] ; twin , 9.1% [ 5/55 ] vs 2.3% [ 4/175 ] , p<.05 ) ( fig . when the frequencies of chronic placental inflammation were compared after preterm cases were divided into spontaneous and indicated preterm birth groups , none of the chronic inflammation conditions showed any statistically significant differences between singleton and twin placentas ( fig . cca showed a tendency toward higher frequency in twin pregnancies with babies of a different sex than with those of the same sex ( 13.8% [ 15/109 ] vs 6.9% [ 13/189 ] , p=.052 ) , whereas the frequencies of vue and cd were not significantly different between twin pregnancies of a different sex and those of the same sex . the frequencies of chronic inflammation in twin placentas had no significant correlation with primigravida , previous abortion , intrauterine fetal death , or discordant growth ( p>.05 ) . chronic placental inflammation was detected in either one or both twin placentas ( vue , 7.3% [ 22/300 ] vs 4.0% [ 12/300 ] ; cca , 5.4% [ 16/300 ] vs 4.0% [ 12/300 ] ; cd , 7.7% [ 23/300 ] vs 6.0% [ 18/300 ] ) . the presence of chronic inflammation in one or both twin placentas was not correlated with other clinical and placental characteristics , including baby sex , chorionicity , and discordant growth . there were 11 cases of iugr in only one fetus of twin pregnancies with vue , of which eight cases had vue in only one placenta and the other three cases had vue in both placentas , suggesting a tendency of correlation between iugr and vue that was not statistically significant . there were significant differences in the gestational age at delivery , gravity , labor at delivery , preterm birth , and iugr between singleton and twin pregnancies ( p<.05 ) . maternal age , previous abortion , the ratio of spontaneous / indicated preterm birth , and hypertensive disorders were not significantly different . the frequencies of the three types of chronic placental inflammation ( vue , cca , and cd ) were not statistically different between twin and singleton placentas . twin placentas had a tendency of high frequency of vue ( 11.3% [ 34/300 ] vs 7.9% [ 100/1,270 ] , p=.054 ) and cd ( 13.0% [ 36/300 ] vs 9.7% [ 123/1,270 ] , p=.09 ) compared with singleton placentas , whereas they showed a tendency of low frequency of cca ( 9.3% [ 28/300 ] vs 13.3% [ 169/1,270 ] , p=.062 ) ( fig . the frequency of the non - basal type of vue was higher in twin placentas than in singleton placentas ( 6.0% [ 18/300 ] vs 3.2% [ 41/1,270 ] , p<.05 ) . there was no difference in the frequency of basal vue between twin and singleton placentas ( 5.3% [ 16/300 ] vs 4.6% [ 59/1,270 ] , p>.05 ) ( fig . there were no significant differences in the frequencies of vue ( 10.2% [ 23/225 ] vs 15.1% [ 11/73 ] ) , cca ( 9.3% [ 21/225]vs 9.6% [ 7/73 ] ) , or cd ( 13.8% [ 31/225 ] vs 11.0% [ 8/73 ] ) between dichorionic ( didis and didif ) and monochorionic ( modi and momo ) placentas ( p>.05 ) . cd was significantly more frequent in didis twin placentas compared with singleton placentas ( 16.9% [ 13/77 ] vs. 9.7% [ 123/1,270 ] , p<.05 ) , but the frequencies of vue and cca were not significantly different among the twin types . the frequency of vue increased with increasing gestational age at birth in both singleton and twin placentas ; however , there was no significant difference in the frequency of vue between singleton and twin placentas when the cases were matched by gestational age ( fig . when the study population was divided into preterm and term births , term twin placentas were affected by non - basal vue more frequently than term singleton placentas ( 12.9% [ 9/70 ] vs 3.6% [ 14/384 ] , p<.01 ) , but the difference was not detected in preterm placentas ( fig . the frequencies of basal vue were not significantly different between singleton and twin placentas either at preterm or at term ( fig . 2c ) . cca was found less frequently in twin placentas than singleton placentas of preterm birth ( 9.6% [ 22/230 ] vs 14.8% [ 131/886 ] , p<.05 ) ( fig . the decrease of cca in twin placentas compared with singleton placentas was significant at 3336 weeks of gestation ( late preterm birth ) ( 10.0% [ 12/120 ] vs 17.9% [ 90/503 ] , p<.05 ) . cca in singleton placentas was most commonly observed at late preterm stage ( 3336 weeks of gestation ) during gestation as previously reported ; however , cca in twin placentas was most frequent at 2932 weeks unexpectedly ( 14.0% [ 6/43 ] ) ( fig . 3b ) . cd was detected at similar frequencies between preterm and term placentas ( fig . the high frequency of cd in didis twin placentas compared with singleton placentas was more prominent at term ( 31.6% [ 6/19 ] vs 8.3% [ 32/384 ] , p<.01 ) ( fig . vue in singleton placentas was found more frequently in iugr cases than in non - iugr cases ( 12.9% [ 36/278 ] vs 6.5% [ 64/985 ] , p<.001 ) . of these cases , non - basal vue was more frequent in iugr cases than in non - iugr cases ( 7.6% [ 21/278 ] vs 2.0% [ 20/985 ] ) , p<.001 ) . non - basal vue in twin placentas was more frequent in iugr cases than in non - iugr cases ( 9.8% [ 12/122 ] vs 3.4% [ 6/175 ] , p<.05 ) , though vue showed no significant correlation with iugr in twin placentas ( 13.1% [ 16/122 ] vs 10.3% [ 18/175 ] ) ( fig . vue was more frequent in indicated preterm birth than in spontaneous birth of singleton placentas ( 10.2% [ 24/235 ] vs 6.3% [ 41/651 ] , p<.05 ) ( fig . non - basal vue was more frequent in indicated preterm birth than in spontaneous birth of both singleton and twin placentas ( singleton , 5.5% [ 13/235 ] vs 2.2% [ 14/651 ] ; twin , 9.1% [ 5/55 ] vs 2.3% [ 4/175 ] , p<.05 ) ( fig . when the frequencies of chronic placental inflammation were compared after preterm cases were divided into spontaneous and indicated preterm birth groups , none of the chronic inflammation conditions showed any statistically significant differences between singleton and twin placentas ( fig . cca showed a tendency toward higher frequency in twin pregnancies with babies of a different sex than with those of the same sex ( 13.8% [ 15/109 ] vs 6.9% [ 13/189 ] , p=.052 ) , whereas the frequencies of vue and cd were not significantly different between twin pregnancies of a different sex and those of the same sex . the frequencies of chronic inflammation in twin placentas had no significant correlation with primigravida , previous abortion , intrauterine fetal death , or discordant growth ( p>.05 ) . chronic placental inflammation was detected in either one or both twin placentas ( vue , 7.3% [ 22/300 ] vs 4.0% [ 12/300 ] ; cca , 5.4% [ 16/300 ] vs 4.0% [ 12/300 ] ; cd , 7.7% [ 23/300 ] vs 6.0% [ 18/300 ] ) . the presence of chronic inflammation in one or both twin placentas was not correlated with other clinical and placental characteristics , including baby sex , chorionicity , and discordant growth . there were 11 cases of iugr in only one fetus of twin pregnancies with vue , of which eight cases had vue in only one placenta and the other three cases had vue in both placentas , suggesting a tendency of correlation between iugr and vue that was not statistically significant . in this study , the frequency of vue , non - basal type , was higher in twin placentas than in singleton placentas . non - basal vue had a correlation with iugr in twin placentas as in singleton placentas . unexpectedly , cca was found less frequently in twin placentas than in singleton placentas of preterm birth . the frequency peak of cca in twin placentas was present at 2932 weeks in contrast to that of singleton placentas at 3336 weeks . cca was more frequent in twin pregnancies of a different sex than in those of the same sex . chronic placental inflammation is present as chronic villitis , cca , and cd , depending on the affected compartment of the placenta . some of the chronic placental inflammation may be caused by infectious agents , such as viruses , bacteria , and parasites . however , evidence of infectious etiology is not identified in most cases of chronic placental inflammation . maternal anti - fetal rejection is suggested to play a role in the pathogenesis of these conditions . destruction of chorionic villi ( vue ) and chorionic trophoblast layer ( cca ) of fetal origin by infiltration of maternal cd8 + t cells , along with activation of fetal macrophages , is the histopathological hallmark of these lesions . the pathogenetic mechanism of a rejection process is also supported by the elevation of local and systemic t - cell chemokines and the presence of fetal hla - specific antibodies in the maternal serum . vue of non - basal type was more frequent in twin placentas than singleton placentas , and the difference was more prominent at term when vue was detected more often in singleton placentas . the increased fetal antigen burden in twin placentas could be related to its high frequency . in contrast , basal vue was detected at a similar frequency between singleton and twin placentas . basal vue may be influenced partly by a different immunologic mechanism compared with non - basal vue , which is supported by the presence of plasma cells in basal villitis as well as its association with cd . cd did not show a frequency difference between twin and singleton placentas in this study ; however , the frequency of cd was increased in didis twin placentas . didis twin placentas are the type with the highest chance of dizygosity , which has more fetal antigens than the other types of twin placentas . this result suggests that it is also an anti - fetal rejection phenomenon , at least in part , which is relevant to the increase of cd in egg donor pregnancies . the frequency of cca was increased in twin placentas of a different sex , which also indicated the increased fetal antigen burden . twin pregnancies with different fetal sex are definitely dizygotic , therefore these placentas could have higher allograft antigenicity compared with those with the same fetal sex . further studies are required to elucidate why there was no significant difference in vue and cd between twin placentas with different fetal sex and those with the same sex . as previously reported , cca was most frequent at 3336 weeks gestation in singleton placentas in this study , while the highest frequency of cca in twin placentas was detected at 2932 weeks of gestation , which is earlier than in singleton placentas . in general , maturation of twin placentas the period of vulnerability to cca may be shifted earlier due to accelerated maturation of twin placentas . these results suggest that cca is also a manifestation of host anti - graft rejection , but a maturationrelated factor may play a role in cca . the association of vue with iugr is well known by previous studies [ 28,30 - 32 ] . in this study , it was confirmed in singleton placentas , and the non - basal type of vue was associated with iugr in twin placentas . this result also explains the high frequency of vue in indicated preterm birth , which included most of the iugr cases . several previous reports showed that villitis was more severe in the placenta of the twin that weighed less , though the correlation was not confirmed statistically [ 23 - 25 ] . in this study , the degree of vue was not included for analysis . the absence of a significant association of iugr with the total vue in twin placentas might be influenced by various twin - specific factors resulting in iugr , such as limitation of the uterine space , insufficient uteroplacental function , twin - to - twin transfusion syndrome , and so on . first , the enrollment of the study population was not prospective or fully consecutive , because some placentas from normal term pregnancies were not included . the institution where the placentas were collected was a tertiary medical center that takes care of more complicated cases ; therefore , the cases likely do not represent the pregnancies of the general population . second , the twin placentas were subdivided according to chorionicity but not zygosity , which would more reliably represent an increased antigen burden . however , it was clearly demonstrated that non - basal vue was increased in twin placentas , and that cca was decreased in preterm twin placentas . it is suggested that vue and cca are the region - specific manifestations of maternal anti - fetal rejection in the placenta , but their pathophysiology are partly different .
background : chronic placental inflammation , such as villitis of unknown etiology ( vue ) and chronic chorioamnionitis ( cca ) , is considered a placental manifestation of maternal anti - fetal rejection . 
 the aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies.methods:three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in seoul , republic of korea from 2009 to 2012 . 
 hematoxylin and eosin sections of tissue samples ( full - thickness placental disc and chorioamniotic membranes ) were reviewed.results:non-basal vue was more frequent in twin placentas than in singleton placentas ( 6.0% vs 3.2% , p < .05 ) . in preterm birth , 
 cca was found less frequently in twin placentas than in singleton placentas ( 9.6% vs 14.8% , p < .05 ) , reaching its peak at an earlier gestational age in twin placentas ( 2932 weeks ) than in singleton placentas ( 3336 weeks ) . 
 cca was more frequent in twin pregnancies with babies of a different sex than with those with the same sex ( 13.8% vs 6.9% , p=.052 ) . 
 separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas ( 16.9% vs 9.7% , p<.05).conclusions : the higher frequency of non - basal vue in twin placentas and of cca in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti - fetal rejection related to increased fetal antigens in twin pregnancies . 
 the peak of cca at an earlier gestational age in twin placentas than in singleton placentas suggests that cca is influenced by placental maturation .