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OBSTETRICS
Impact of chorionicity on risk and timing of intrauterine
fetal demise in twin pregnancies
Jessica A. McPherson, MD; Anthony O. Odibo, MD, MSCE; Anthony L. Shanks, MD;
Kimberly A. Roehl, MPH; George A. Macones, MD, MSCE; Alison G. Cahill, MD, MSCI
OBJECTIVE: We sought to estimate the association between chorionic- pregnancies had an increased risk of a single demise (adjusted odds
ity and intrauterine fetal demise (IUFD) of one or both fetuses in twin ratio, 1.69; 95% confidence interval, 1.04 2.75) and a double demise
pregnancies. (adjusted odds ratio, 2.11; 95% confidence interval, 1.02 4.37). Of all
double demises, 70% occurred 24 weeks.
STUDY DESIGN: In a retrospective cohort of twins undergoing ana-
tomic survey, risk of IUFD in monochorionic and dichorionic twins was
CONCLUSION: Monochorionic twins carry an increased risk of fetal
compared. The primary outcome was IUFD of one or both fetuses; sec-
death compared to dichorionic twins. Double demise occurs primarily
ondary outcomes included nonanomalous fetal deaths.
24 weeks, regardless of chorionicity.
RESULTS: Of 2161 twin pregnancies meeting inclusion criteria, 86 had
at least 1 IUFD and 32 experienced a double fetal loss. Monochorionic Key words: intrauterine fetal demise, multiple gestation
Cite this article as: McPherson JA, Odibo AO, Shanks AL, et al. Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies. Am J
Obstet Gynecol 2012;207:190.e1-6.
twin pregnancy sonographic examina- estimated and compared by chorionic- 496 (23%) were monochorionic and
tions.9,10 Final chorionicity designation ity. Stratified analyses were performed to 1665 (77%) were dichorionic pregnan-
was made by the earliest available ultra- identify potentially confounding factors. cies (Figure).
sound and confirmed by pathology spec- Logistic regression analyses were used to The 2 groups were similar in terms of
imens in 71% of the pregnancies. Gesta- refine the risk estimate by chorionicity gravidity, nulliparity, rates of pre-
tional age was assigned based on the first for any IUFD in the pregnancy by adjust- eclampsia, pregestational diabetes, ges-
day of a womans last menstrual period. ing for confounding factors that were tational diabetes, history of preterm de-
If this dating was not consistent with dat- identified by unadjusted and stratified livery including spontaneous preterm
ing based on the earliest ultrasound (7 analyses, as well as those factors histori- delivery, IUGR, and having any major
days in the first trimester or 10 days in cally reported to be associated with congenital anomaly diagnosed during
the second trimester), the gestational age IUFD. Backward stepwise selection was the pregnancy (Table 1). Women carry-
was reassigned.11 In twin pairs that were used to reduce the number of variables in ing monochorionic twins on average
discordant in size at the time of a dating the model by assessing the magnitude of were younger, delivered at an earlier ges-
ultrasound, the biometry of the larger change in the effect size of remaining co- tational age, were more likely to be
twin was used to date the pregnancy as to variates. Differences in the explanatory smokers, and were more likely to report
err on the side of safety by maximizing model were tested using the likelihood alcohol exposure during the pregnancy.
sensitivity for abnormal growth. At the ratio test or Wald test.13 Statistically Women carrying dichorionic twins were
discretion of the providers but in accor- significant variables were included in more likely to have a body mass index
dance with typical practice at our insti- the final models. To estimate the risk of 30 kg/m2, be of African American race,
tution, ultrasounds were performed ev- stillbirth of either twin by chorionicity, have chronic hypertension, and have a
ery 2 weeks for monochorionic twins to conditional logistic regression adjust- history of an IUFD. Women excluded
assess for evidence of twin-to-twin trans- ing for twin clusters was used to ac- for lack of follow-up were generally sta-
fusion syndrome (TTTS),12 and every count for nonindependence of twin
tistically similar, although less advanced
3-4 weeks for all twins to assess growth. pairs and adjust for prior fetal death. A
maternal age, and they were more likely
Antenatal testing with twice-weekly subanalysis excluding pregnancies af-
to be African American, be obese, and
nonstress tests or biophysical profiles fected by known major congenital
use tobacco.
was initiated at 32 weeks unless there was anomalies and known chromosomal
Monochorionic pregnancies were at
a clinical indication for earlier testing. abnormalities was performed.
increased risk of at least 1 fetal demise
Dichorionic diamniotic pregnancies Next, the prospective risk of any
(adjusted odds ratio [OR], 1.69; 95% CI,
were compared to monochorionic diam- IUFD by chorionicity was calculated
1.04 2.75) as well as an increased risk of
niotic pregnancies. Monoamniotic preg- for each week of continuing gestation
a double fetal demise (adjusted OR, 2.11;
nancies, pregnancies affected by TTTS, using the number of ongoing pregnan-
singleton gestations, and higher-order cies as the denominator. In a subanaly- 95% CI, 1.02 4.37) when compared to
multiple gestations were excluded from sis of women who experienced IUFD of dichorionic pregnancies (Table 2). Risk
the study. The primary outcome was both twins, gestational age at loss of the of IUFD of either twin within a mono-
IUFD of one or both fetuses defined as second twin was described by chorio- chorionic compared to a dichorionic
fetal death 20 weeks and confirmed by nicity. Presence of intrauterine growth pregnancy was also significantly in-
ultrasound examination at our institu- restriction (IUGR), defined as birth- creased and remained increased after ad-
tion.9 If a fetal death occurred 20 weight 10th percentile by the Alexan- justing for fetal demise in a prior preg-
weeks, the pregnancy was not included der growth standard,14 was described nancy (adjusted OR, 1.74; 95% CI, 1.10
in the analysis. Risk of IUFD of either within pregnancies experiencing single 2.78). When excluding pregnancies
twin was estimated, as well as the risk of or double fetal loss. Finally, women who complicated by any major congenital
IUFD of either twin by week of continu- experienced a double fetal demise were anomaly, monochorionic pregnancies
ing gestation. In the subanalysis of compared to those who lost 1 twin to remained at increased risk of a single
women who experienced an IUFD of at identify possible factors, besides chorio- IUFD; the increased risk of a double fetal
least 1 fetus, the effect of chorionicity on nicity, associated with risk of a second demise did not reach statistical signifi-
timing of IUFD of the second twin was twin loss. Statistical analyses were per- cance. The prospective risk of IUFD
described. formed using STATA 10.0, special edi- within the pregnancy for ongoing preg-
Baseline characteristics of women by tion (StataCorp, College Station, TX). nancies by week of gestation starting at
chorionicity were compared. The Stu- 20 weeks is presented in Table 3. A
dent t test or Mann-Whitney U test was greater risk for any IUFD was observed
used for continuous variables and the 2 R ESULTS in women with monochorionic com-
or Fisher exact test was used for categor- Of 2445 twin intrauterine pregnancies, pared to dichorionic twins throughout
ical variables as appropriate. The relative 2333 met inclusion criteria. Of those, gestation, particularly in the second tri-
risk of IUFD within the pregnancy and 2161 (92.6%) had complete outcome mester. The risk for any IUFD decreased
the 95% confidence interval (CI) were data and were included in the analysis; as pregnancy progressed.
C OMMENT
Exclusion (n = 112): In our cohort, we found the risk of IUFD
- Monoamnioc twins
to be significantly increased in mono-
- TTTS
- Higher order mulples chorionic pregnancies. Second twin loss
after IUFD of the first twin occurred pre-
dominantly 24 weeks gestation, re-
gardless of chorionicity.
2333 twins meeng inclusion There is a paucity of published data on
criteria (95.4%)
the rare, but clinically important occur-
rence of stillbirth in twin pregnancies. In
a retrospective cohort study by Lee et al3
looking at 1000 twin pregnancies, they
Lost to follow-up (n = 172)
found a nearly 4-fold increase in IUFD in
monochorionic twin pregnancies when
compared to dichorionic pregnancies.
This is greater than the risk that we
found; however, in the initial analysis by
2161 twins with complete
follow-up (92.6%) Lee et al,3 pregnancies affected by TTTS,
growth discordance, IUGR, and major
anomalies were not excluded. When
those pregnancies were excluded, there
was no evidence for increased risk of fetal
496 monochorionic 1665 dichorionic
diamnioc twins (22.9%) diamnioc twins (77.1%) death in monochorionic pregnancies.
The authors did acknowledge that sam-
ple size was a possible limitation and
thus the lack of statistically significant
findings may represent a type II error.
30 cases of single 12 cases of double
fetal demise fetal demise
56 cases of single 20 cases of double The authors did not evaluate those preg-
fetal demise fetal demise
(6.0% of MC twins) (2.4% of MC twins) (3.4% of DC twins) (1.2% of DC twins) nancies suffering a second demise sepa-
rately and, therefore, did not comment
DC, dichorionic diamniotic; MC, monochorionic diamniotic; TTTS, twin-to-twin transfusion syndrome. on temporal risk of suffering a second
McPherson. Fetal death in twin pregnancies. Am J Obstet Gynecol 2012. loss after an initial demise.
Ong et al7 completed a systematic re-
view to evaluate morbidity and mortality
Within the 86 pregnancies that expe- 23, 70%). Only 10 patients with a double of a surviving twin after a single demise.
rienced at least 1 fetal death, 32 subse- demise experienced death of the second The review included 19 studies and a to-
quently had a second demise; 12 were twin after viability; 5 were monochori- tal of 904 twin pregnancies with at least a
monochorionic and 20 were dichori- onic and 5 were dichorionic. single demise. Nineteen of the 904 preg-
onic. Table 4 presents the timing of diag- There was no difference by chorionicity nancies progressed to complete preg-
nosis of the second demise by chorionic- in rate of growth restriction among the 118 nancy loss (2.1%), which was similar to
ity. Seven of 12 monochorionic and 15 of fetal deaths (86 pregnancies with at least a our study. They cited a 6-fold increased
20 dichorionic pregnancies had the sec- single demise and 32 with a double de- risk for complete pregnancy loss in
ond demise diagnosed 24 weeks mise). Growth restriction was present in 13 monochorionic pregnancies, which was
(58.3% vs 75.0%, Fisher exact P .81). of 76 (17.1%) fetuses in dichorionic and 10 higher than our findings. However, cho-
Double demises were diagnosed at the of 42 (23.8%) fetuses in monochorionic rionicity data were missing on 18%
same examination in 23 cases: 8 of the pregnancies (Fisher exact P .62) expe- of the pregnancies and gestational age of
monochorionic and 15 of the dichori- riencing an intrauterine death. Finally, the initial demise was missing in 36% of
onic pregnancies. The majority were si- when additional risk factors for IUFD of the pregnancies. A subset of the studies
multaneously diagnosed 24 weeks (17/ the second twin besides chorionicity included was lacking information on
TABLE 1
Characteristics of women with monochorionic compared to dichorionic
twins, and those excluded for lack of follow-up
Monochorionic Dichorionic No outcome
Characteristics n 496 n 1665 P valuea n 172
Age, y 29.8 6.2 31.4 5.9 .01 29.1 6.0
................................................................................................................................................................................................................................................................................................................................................................................
Age 35 y 23.2 29.3 .01 6.3
................................................................................................................................................................................................................................................................................................................................................................................
Gravidity 2.6 1.5 2.6 1.6 .78 3.1 2.2
................................................................................................................................................................................................................................................................................................................................................................................
Nulliparity 27.0 27.3 .91 27.8
................................................................................................................................................................................................................................................................................................................................................................................
Gestational age at delivery, wk 33.9 4.8 34.8 4.2 .01 N/A
................................................................................................................................................................................................................................................................................................................................................................................
BMI, kg/m 2
25.1 6.4 26.0 7.0 .01 27.04 7.5
................................................................................................................................................................................................................................................................................................................................................................................
BMI 30 kg/m 2
16.6 22.0 .01 22.8
................................................................................................................................................................................................................................................................................................................................................................................
African American 17.1 21.7 .03 46.2
................................................................................................................................................................................................................................................................................................................................................................................
Tobacco use 13.1 9.1 .01 14.6
................................................................................................................................................................................................................................................................................................................................................................................
Alcohol use 16.2 11.7 .01 10.3
................................................................................................................................................................................................................................................................................................................................................................................
Chronic hypertension 1.4 3.3 .03 2.1
................................................................................................................................................................................................................................................................................................................................................................................
Preeclampsia 17.9 20.9 .13 10.8
................................................................................................................................................................................................................................................................................................................................................................................
Pregestational diabetes 0.6 1.2 .26 1.9
................................................................................................................................................................................................................................................................................................................................................................................
Gestational diabetes 6.5 6.2 .82 8.1
................................................................................................................................................................................................................................................................................................................................................................................
History of IUFD 1.8 3.0 .15 1.9
................................................................................................................................................................................................................................................................................................................................................................................
History of preterm delivery 5.2 6.7 .25 7.1
................................................................................................................................................................................................................................................................................................................................................................................
Birthweight 10th percentile b
25.1 21.0 .32 N/A
................................................................................................................................................................................................................................................................................................................................................................................
c
Any anomaly 1.6 2.3 .33 2.5
................................................................................................................................................................................................................................................................................................................................................................................
Data are mean SD or percent unless otherwise specified.
BMI, body mass index; IUFD, intrauterine fetal demise; N/A, not applicable.
a
Comparing monochorionic and dichorionic groups only; b Based on Alexander birth standard; c Includes any major congenital anomaly identified in either twin.
McPherson. Fetal death in twin pregnancies. Am J Obstet Gynecol 2012.
TTTS, anomalies, and maternal illness. despite a robust literature search sum- Johnson and Zhang6 examined the
In a more recent review by Hillman et marizing 16 articles, this estimate was risk of IUFD in twin pregnancies and
al,8 summary statistics were provided based on only 17 pregnancies compli- survival of the remaining twin after a sin-
and were similar to those of Ong et al,7 cated by double fetal demise. Both the gle demise. A single fetal demise occurred
citing a 5-fold increased risk of complete small sample size and significant hetero- in 2.6% of twin pregnancies included in
pregnancy loss in monochorionic com- geneity make interpretation of these risk their study. They found that same sex
pared to dichorionic twins. However, estimates challenging. twins were 2 times more likely than oppo-
TABLE 2
Risk of intrauterine fetal demise in monochorionic compared to dichorionic twin pregnancies
Monochorionic Dichorionic Unadjusted RR Adjusted OR
Outcome n 496 n 1665 (95% CI) (95% CI) P value
Any IUFD (n 86) 6.0% (n 30) 3.4% (n 56) 1.76 (1.152.72) 1.69a (1.042.75) .03
................................................................................................................................................................................................................................................................................................................................................................................
IUFD of both (n 32) 2.4% (n 12) 1.2% (n 20) 1.65 (1.052.60) b
2.11 (1.024.37) .04
................................................................................................................................................................................................................................................................................................................................................................................
Any nonanomalous IUFD 5.7% (n 28) 3.0% (n 49) 1.61 (1.192.19) a
1.87 (1.123.10) .02
(n 77)
................................................................................................................................................................................................................................................................................................................................................................................
Nonanomalous IUFD of both 2.3% (n 11) 1.2% (n 19) 1.60 (0.992.58) b
2.02 (0.954.30) .07
(n 30)
................................................................................................................................................................................................................................................................................................................................................................................
CI, confidence interval; IUFD, intrauterine fetal demise; OR, odds ratio; RR, relative risk.
a
Adjusted for gestational age at delivery, history of IUFD; b Adjusted for history of IUFD.
McPherson. Fetal death in twin pregnancies. Am J Obstet Gynecol 2012.
also provide some guidance in the rare 4. American College of Obstetricians and Gyne- 10. AIUM. Practice guideline for the perfor-
circumstance of a single IUFD in an on- cologists. Multiple gestation: complicated twin, mance of obstetric ultrasound examinations,
triplet, and high-order multifetal pregnancy; 2007. Available at: http://www.aium.org/
going twin pregnancy, particularly given ACOG practice bulletin no. 56. Obstet Gynecol publications/guidelines/obstetric.pdf. Acces-
that death of the second twin occurs 2004;104:869-83. sed Sept. 1, 2011.
rarely after viability is reached, regardless 5. DAlton M, Simpson LL. Syndromes in twins. 11. American College of Obstetricians and Gy-
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