Obstetrics & Gynecology:
Placental Cord Insertion and Birth Weight Discordancy in Twin Gestations
Hanley, Maryellen L. MD, MPH; Ananth, Cande V. PhD, MPH; Shen‐Schwarz, Susan MD; Smulian, John C. MD, MPH; Lai, Yu‐Ling RNC, MSN; Vintzileos, Anthony M. MD
Division of Maternal‐Fetal Medicine, and Section of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey‐Robert Wood Johnson Medical School, St. Peter's University Hospital, and Department of Pathology, St. Peter's University Hospital, New Brunswick, New Jersey.
Reprints are not available. Address correspondence to: Maryellen L. Hanley, MD, MPH, University of Medicine and Dentistry of New Jersey‐Robert Wood Johnson Medical School, St. Peter's University Hospital, 254 Easton Avenue, MOB‐4th Floor, New Brunswick, NJ 08903–0591; E‐mail: email@example.com.
Received June 20, 2001. Received in revised form October 15, 2001. Accepted October 25, 2001.
OBJECTIVE: To evaluate whether abnormal umbilical cord insertion (UCI) into the placenta is a risk factor for birth weight discordancy in twin gestations.
METHODS: Pathology records of all liveborn twins delivered between January 1993 and June 1996 were reviewed. The information collected included gestational age at delivery, birth weight, gross placental pathology, and placental UCI—velamentous, marginal, or disc. Discordancy in birth weight was defined as an intrapair difference of at least 20%. Analyses were stratified on placental chorionicity. Odds ratios and 95% confidence intervals for birth weight discordancy were calculated based on the presence of an abnormal (velamentous or marginal) placental UCI relative to normal (disc) UCI on both placentae, after adjusting for potential confounders.
RESULTS: There were 447 twin pairs identified. Dichorionic diamniotic placentation was present in 358 pairs (80.1%), monochorionic diamniotic in 84 (18.8%), and monochorionic monoamniotic in five (1.1%). There was a 13‐fold increase in the risk of birth weight discordancy in monochorionic diamniotic twins in the presence of a velamentous UCI (odds ratio 13.5, 95% confidence interval 1.4, 138.4), with a rate of birth weight discordancy of 46%. This relationship was not demonstrated in dichorionic diamniotic twins (odds ratio 1.0, 95% confidence interval 0.3, 3.5).
CONCLUSION: Birth weight discordancy in twins is a different entity depending on chorionicity. The substantial increase in birth weight discordancy in monochorionic diamniotic twins that accompanies velamentous UCI underscores the need for prenatal detection and increased surveillance in these twins.
As a group, twins contribute disproportionately to the overall perinatal mortality rate. The risk of perinatal death is three‐ to ten‐fold higher for twins compared with singletons.1–5 However, this complication is influenced by placentation with dichorionic diamniotic twins demonstrating lower mortality rates than monochorionic diamniotic.4–6 The excess mortality of twins is predominately related to low birth weight.3,7–9 Low birth weight may be a consequence of prematurity, fetal growth restriction, or a combination of these influences. Although various cutoffs have been proposed, discordant fetal growth is often associated with unfavorable perinatal outcomes.8,10–14 When there is birth weight discordance of greater than 20%, the likelihood that one of the twins will be small for gestational age (SGA) is 50%.12 Discordant growth has been associated with a 6.5‐fold increased risk for fetal death and a 2.5‐fold increased risk for perinatal mortality in twins.13 Therefore, identification of predictors of birth weight discordancy could be useful in the antepartum management of twin gestations.
The umbilical cord insertion (UCI) into the placenta is described as central, eccentric, marginal, or velamentous as it relates to the chorionic plate. Central and eccentric both insert into the disc of the placenta; marginal is usually defined as insertion within 2 cm of the disc edge, whereas velamentous inserts directly into the membranes. A velamentous insertion is reported to occur in approximately 1–2% of singleton pregnancies.15 However the prevalence of this finding is higher in multiple gestations ranging from 13% to 21% for twins.15,16 It is more frequently identified in monochorionic twin gestations and has been associated with the twin‐to‐twin transfusion syndrome.15–18 Our objective was to evaluate whether abnormal UCI of the placenta is a risk factor for birth weight discordancy in twin gestations.
MATERIALS AND METHODS
All liveborn twin gestations delivering at St. Peter's University Hospital in New Brunswick, New Jersey, from January 1993 to June 1996 were identified retrospectively. This was accomplished through a review of our pathology database. It is the practice at our institution that all twin placentae are examined by pathology. Once identified, data collection included the following: maternal age, gravidity, parity, gestational age at delivery, infant gender, birth weight, placental weight, chorionicity, gross placental pathology (cord twist, membrane insertion, number of cord vessels, cord spiraling), and placental UCI insertion site—disc (normal), marginal, or velamentous. Antepartum data regarding conception (spontaneous versus in vitro fertilization), as well as sonographic information, was not available for review. Birth weight discordancy was defined as an intrapair difference of 20% or more, based on the weight of the larger twin. Placental weight discordancy was defined similarly. There are limited data available regarding placental weight discordancy “standards.” We chose 20% based on extrapolation from our cutoff for birth weight discordancy because birth weight is grossly proportional with placental mass. Because the placentae of the monochorionic diamniotic twins were not separated and weighed individually, analysis of placental weight discordancy was restricted to dichorionic diamniotic twins.
Complete histopathologic evaluation was available on a subset of these placentae delivered between January 1994 and December 1995. The histologic lesions recorded included: advanced villous maturation, meconium changes, and chronic lesions of the placenta (villous fibrosis, villous infarction, decidual vasculopathy, and chronic villitis). Discordant histopathologic lesions were defined as histologic findings present in only one of the twin placentae. A single perinatal pathologist (SSS) reviewed all placentae.
The primary outcome evaluated was birth weight discordancy. Statistical analyses included contingency tables for categorical data, Student t test and Mann‐Whitney U test for continuous outcomes, and multivariable logistic regression models to control confounding variables. Odds ratio (OR) and 95% confidence intervals (CI) were calculated based on the presence of an abnormal placental UCI (velamentous or marginal) relative to normal UCI on both placentae. All analyses were stratified by placental chorionicity. The etiologic fraction for birth weight discordancy with respect to velamentous cord insertion was determined by the following formula: p(OR−1)/[1+p(OR−1)], where OR is the unadjusted odds ratio and p denotes the proportion of outcome.19 The etiologic fraction assists in determining the impact of abnormal UCI on birth weight discordancy. We used chorionicity‐specific twin birth weight nomograms to identify SGA infants.20 These were defined as birth weight less than the 10th percentile. In the subset of placentae with complete histopathologic evaluation, the rate of discordant lesions was determined based on twins with and without birth weight discordancy.
Of a total of 447 pairs, 358 (80.1%) were dichorionic diamniotic, 84 (18.8%) were monochorionic diamniotic, and five (1.1%) were monochorionic monoamniotic. The demographic characteristics of the study population are displayed in Table 1. There were no clinically relevant differences between the two groups. The rates of birth weight and placental weight discordancy in the population are presented in Table 2. The rates of each of the groups of twins were similar. There were 25 pairs that had missing birth weight data in one or both twins. Of these, 17 (4.7%) were in the dichorionic diamniotic group, seven (8.3%) were in the monochorionic diamniotic group, and one (20%) was from the monochorionic monoamniotic group. The percentage of missing birth weight data from the dichorionic diamniotic and monochorionic diamniotic twins was not statistically significant. The monochorionic monoamniotic twins were excluded from all further analyses because all of these twins had normal disc UCI.
The distribution of the different combinations of UCI sites of the twin pairs was significantly different between the monochorionic and diamniotic twins (P < .001). This is presented in Table 3. Only 23.8% of the monochorionic diamniotic twins had a normal disc insertion for both twins. The combination of a normal and velamentous UCI was nearly three times more common in the monochorionic diamniotic twins (P < .001). We then evaluated whether these twins with an abnormal UCI were more likely to be discordant at birth as compared with those of normal UCI of both discs (referent). The risk of birth weight discordancy in monochorionic diamniotic twins is 15 times greater when one of the twins has a velamentous UCI as compared with those of normal UCI of both discs (Table 4). In contrast, abnormal UCI did not confer any significant increased risk for birth weight discordancy in dichorionic diamniotic twins. Analysis was then restricted to monochorionic diamniotic twins to further evaluate this association between birth weight discordancy and velamentous cord insertion. After controlling for gestational age and cord twist, velamentous UCI was associated with an OR of 13.5 for birth weight discordancy, although with wide confidence intervals (Table 5). The etiologic fraction of a velamentous cord insertion in relation to birth weight discordancy in monochorionic diamniotic twins was 78%. This implies that 78% of the discordancy in this population of monochorionic diamniotic twins could be attributed to velamentous UCI. Conversely, we then asked the question, if birth weight discordancy is identified, what is the likelihood that an abnormal UCI is present? Fifteen pairs of monochorionic twins demonstrated birth weight discordancy. Within this group, only one pair had normal disc insertions for both twins. Therefore, 95.4% of discordant monochorionic twins had either one or two abnormal UCI. In 91% of the cases (ten of 11) with one abnormal UCI and one normal disc UCI, the abnormal UCI was associated with the smaller twin. The SGA rate was calculated for monochorionic diamniotic twins and is also presented in Table 5. The likelihood of one or both twins being SGA was two‐ to three‐fold greater when one or both of the UCI was abnormal.
Because UCI did not appear to be a risk factor for birth weight discordancy in dichorionic diamniotic twins, multivariable logistic regression was used as an exploratory model to identify if any other variables were associated with this outcome. Only maternal age and placental weight discordancy were significantly associated with birth weight discordancy (Table 6). Only 9% of the birth weight discordancy of the dichorionic diamniotic twins was explained by these two variables (maternal age and placental weight discordancy). This suggests that the majority of birth weight discordancy of dichorionic diamniotic twins was related to other factors beyond what we were able to evaluate.
Because birth weight discordancy was associated with placental weight discordancy, we further evaluated whether this was due to placental mass or histopathologic lesions of the placenta. We reviewed the placentae of the 252 twins for which there was complete histology. The chorionicity distribution, the demographic characteristics, as well as birth weight and placental weight discordancies, were comparable with the entire twin population. The four monochorionic monoamniotic pairs and the six twin pairs that were missing birth weight data were excluded, leaving 242 twins for analysis. The placentae were evaluated for discordant lesions (ie, lesions present in only one of the twin placentae). The only discordant histopathologic lesion associated with birth weight discordancy was advanced villous maturation (Table 7). This lesion was also associated with birth weight discordancy in the monochorionic diamniotic twins. When discordant villous maturation was associated with birth weight discordancy, the lesion was usually found in the placenta of the smaller twin: 75% (three of four) of the monochorionic diamniotic twins and 89% (eight of nine) of the dichorionic diamniotic twins.
Our findings confirm the work of others that abnormal UCI is a common finding in twins.15,16 Only 56.1% of our dichorionic diamniotic twins had normal cord insertions of both placentae. The finding was even more pronounced for the monochorionic diamniotic twins in whom only 23.8% demonstrated normal UCI. Machin reviewed 60 twin pairs of monochorionic diamniotic twins and found that only 28% had normal disc insertions for both twins.16 However, in that study, Machin combined the marginal and velamentous insertions together, which would obscure the relative effects of either abnormal insertion.16 Machin also reported that when one placenta was normal and the other abnormal (velamentous or marginal), 33% demonstrated a birth weight discordancy of 20% or more.16 This percentage is intermediate to our findings. Our results of 20% discordancy in those monochorionic diamniotic twins with marginal/disc insertions compared with the 46% rate of discordancy in the velamentous/disc insertions indicate that it is the velamentous insertion that contributes more profoundly to discordancy. In addition, unlike Machin,16 we controlled for other confounding placental findings and were able to provide a more unbiased assessment of risk associated with this combination of UCI.
Abnormal UCI in monochorionic diamniotic twins has been associated with the twin‐to‐twin transfusion syndrome (TTT).17,18 In a series by Fries et al, 38 pairs of monochorionic diamniotic twins were evaluated, and 11 (28.9%) developed the TTT syndrome.17 Of those affected pregnancies, 63.6% had a velamentous cord insertion. The incidence of TTT in the group with normal insertions was 18.5%. There were 12 pregnancies with a velamentous insertion and more than half (n = 7, 58.3%) developed TTT. Bruner et al evaluated a series of twins with the oligohydramnios‐polyhydramnios sequence and the TTT syndrome.18 Their numbers were small, eight monochorionic diamniotic twins, but all suspected donors had a velamentous or marginal cord insertion, and all the suspected recipients had normal cord insertions. Thus, abnormal UCI into the placenta appears to be an important risk factor for TTT syndrome.
Several studies have demonstrated that the placental cord insertion can be reliably identified during an ultrasound examination.21–25 The identification of UCI has become much easier since the introduction of color Doppler technology. Although gestational age range has varied in many of these studies, Nomiyama et al prospectively evaluated placental cord insertion at 18–20 weeks.23 In this study, cord insertion was visualized 99.8% of the time. This suggests that abnormal insertions can be detected early enough to be clinically useful. Because the rate of discordancy in monochorionic diamniotic twins is markedly influenced by UCI, an attempt to identify this prenatally should be undertaken. The identification of an abnormal UCI can alter counseling and the intensity of surveillance of the pregnancy. Conversely, the finding of a normal UCI should provide some reassurance in monochorionic diamniotic twins.
Documentation of UCI in dichorionic diamniotic twins may not be as helpful in identifying those at risk for developing discordant growth. It appears that there are distinct differences in the underlying causes for discordancy in the dichorionic diamniotic twins as compared with the monochorionic diamniotic twins. Maternal age, placental weight discordancy, and advanced villous maturation (the variables associated with discordancy in our population) provide limited if any antenatal information. Eberle et al evaluated the placental pathology in discordant twins.26 They did not find differences in placental weights; however, the number of dichorionic diamniotic twins in their study (n = 99) is less than half of what we evaluated, and our larger sample size may explain the varying results. These authors did find differences in the number of histologic lesions seen in the placenta of the smaller twin and, despite differing methodologies between the studies, the similar findings underscore the role of placental pathology in divergent growth in twins. The type of lesion we found to be statistically significant (advanced villous maturation) varied from Eberle et al.26 These authors found that villous fibrosis and hypovascularity were seen more frequently in the lighter twin's placenta. However, Naeye reported that advanced villous maturation is the most frequent abnormality identified in the placenta.27 Although not specifically in twins, he reported that this lesion is thought to be related to low uteroplacental blood flow and has been associated with stillbirth, hypoxia, and fetal growth restriction.27 This is consistent with our findings that the lesion was found predominantly in the placenta of the smaller twin who may indeed have been growth restricted. We were unable to identify variables that predominantly contribute to the discordancy found in dichorionic diamniotic twins. This may reflect both the heterogeneous nature of discordant growth in this group of twins, as well as the limited number of variables available for review.
In summary, the likelihood of an abnormal UCI in twins is high. Ultrasound identification of this finding has been reported as reliable and should be undertaken during the evaluation of twins especially in cases when monochorionic diamniotic twins are suspected. In this group, the risk of birth weight discordancy in those with a velamentous UCI is nearly 50%. Although this variable is not amenable to intervention, its presence or absence warrants appropriate patient counseling and surveillance of fetal growth.
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