Ultrasound Obstet Gynecol 2021; 57: 126–133

Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.23515

Outcome of monochorionic twin pregnancy complicated by

Type-III selective intrauterine growth restriction
S. SHINAR1 , W. XING2 , V. PRUTHI1 , C. JIANPING2 , F. SLAGHEKKE3 , S. GROENE3 ,
E. LOPRIORE4 , L. LEWI5 , I. COUCK5 , Y. YINON6 , L. BATSRY6 , L. RAIO7 ,
S. AMYLIDI-MOHR7 , D. BAUD8 , F. KNEUSS8 , P. DEKONINCK9 , J. MOSCOU9 , J. BARRETT10 ,
N. MELAMED10 , G. RYAN1 , L. SUN2 and T. VAN MIEGHEM1
1
Ontario Fetal Centre, Division of Maternal Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University
of Toronto, Toronto, ON, Canada; 2 Fetal Medicine Unit &Prenatal Diagnosis Center, Shanghai 1st Maternity and Infant Hospital of
Tongji University, Shanghai, China; 3 Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands; 4 Department
of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands; 5 Department of Obstetrics and Gynecology, University Hospitals
Leuven, Leuven, Belgium; 6 Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv University,
Tel Aviv, Israel; 7 Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland; 8 Department of
Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland; 9 Department of Obstetrics and Gynaecology, Erasmus MC
University Medical Center, Rotterdam, The Netherlands; 10 Division of Maternal-Fetal Medicine, Department of Obstetrics and
Gynecology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada

K E Y W O R D S: fetal growth restriction; FGR; intrauterine growth restriction; MCDA; monochorionic; outcome; selective
IUGR; twins; Type III

CONTRIBUTION Methods We reviewed retrospectively all monochori-

What are the novel findings of this work?
In this multicenter study of 328 twin pregnancies with
Type-III selective intrauterine growth restriction (sIUGR),
fetal death complicated 11% of them. At viability, mor-
tality rates were very low (< 2% at 28 weeks). Delivery at
32 weeks was associated with a high rate of adverse neona-
tal outcome, which substantially decreased at 34 weeks
(11%), with a very low risk of fetal death (0.7%).
What are the clinical implications of this work?
With close fetal surveillance, the risk of unexpected fetal
death in Type-III sIUGR may be lower than reported
previously. Further multicenter studies are needed to
assess which factors truly predict fetal death, in order
to allow for optimal pregnancy management.
ABSTRACT
Objective Type-III selective intrauterine growth restric-
tion (sIUGR) is associated with a high and unpredictable
risk of fetal death and fetal brain injury. The objective
of this study was to describe the prospective risk of fetal
death and the risk of adverse neonatal outcome in a cohort
of twin pregnancies complicated by Type-III sIUGR and
treated according to up-to-date guidelines.
onic diamniotic twin pregnancies complicated by
Type-III sIUGR managed at nine fetal centers over
a 12-year period. Higher-order multiple gestations
and pregnancies with major fetal anomalies or other
monochorionicity-related complications at initial pre-
sentation were excluded. Data on fetal and neonatal
outcomes were collected and management strategies
reviewed. Composite adverse neonatal outcome was
defined as neonatal death, invasive ventilation beyond
the resuscitation period, culture-proven sepsis, necrotizing
enterocolitis requiring treatment, intraventricular hemo-
rrhage Grade > I, retinopathy of prematurity Stage > II or
cystic periventricular leukomalacia. The prospective risk
of intrauterine death (IUD) and the risk of neonatal com-
plications according to gestational age were evaluated.
Results We collected data on 328 pregnancies (656
fetuses). After exclusion of pregnancies that underwent
selective reduction (n = 18 (5.5%)), there were 51/620
(8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnan-
cies. Single IUD occurred in 19/328 (5.8%) pregnancies
and double IUD in 16/328 (4.9%). The prospective risk
of non-iatrogenic IUD per fetus declined from 8.1%
(95% CI, 5.95–10.26%) at 16 weeks, to less than 2%
(95% CI, 0.59–2.79%) after 28.4 weeks and to less
than 1% (95% CI, –0.30 to 1.89%) beyond 32.6 weeks.
In otherwise uncomplicated pregnancies with Type-III

Correspondence to: Dr S. Shinar, Ontario Fetal Center, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, 700 University
Avenue, M5G 1Z5 Toronto, ON, Canada (e-mail: shiri.shinar@sinaihealth.ca)
Accepted: 5 October 2020

© 2020 International Society of Ultrasound in Obstetrics and Gynecology ORIGINAL PAPER


Outcome of Type-III sIUGR
sIUGR, delivery was generally planned at 32 weeks, at
which time the risk of composite adverse neonatal out-
come was 29.0% (31/107 neonates). In twin pregnancies
that continued to 34 weeks, there was a very low risk of
IUD (0.7%) and a low risk of composite adverse neonatal
outcome (11%).
Conclusions In this cohort of twin pregnancies compli-
cated by Type-III sIUGR and treated at several tertiary
fetal centers, the risk of fetal death was lower than that
reported previously. Further efforts should be directed at
identifying predictors of fetal death and optimal antenatal
surveillance strategies to select a cohort of pregnancies
that can continue safely beyond 33 weeks’ gestation.
© 2020 International Society of Ultrasound in Obstetrics
and Gynecology
INTRODUCTION
Selective intrauterine growth restriction (sIUGR)
complicates 10–15% of monochorionic twin preg-
nancies1,2 and is commonly defined as an intertwin
estimated-fetal-weight (EFW) discordance of > 25%,
with one twin having an EFW below the 10th percentile.
This pathology increases the risk of intrauterine death
(IUD), (iatrogenic) preterm birth, Cesarean delivery
and adverse neonatal outcome, particularly in the
smaller fetus3 . A specific subtype of sIUGR, Type-III
sIUGR, makes up about a fifth of all sIUGR cases in
monochorionic twins and is characterized by unequal
placental sharing and large intertwin artery-to-artery
anastomoses4,5 , allowing for important and acute
hemodynamic shifts from one fetus to the other. On
ultrasound, this is recognized as intermittently absent
or reversed end-diastolic Doppler flow patterns in the
umbilical artery of the smaller fetus6 .
The clinical management of these pregnancies is
challenging, as many studies have documented a high
risk of unexpected fetal death (up to 15–20%) and, even
in cases of double survival, a high risk of brain injury
in the larger twin1,7,8 . Owing to the relative rarity of
Type-III sIUGR, however, large cohorts or trials assessing
the management and outcome of this condition are
lacking. As a consequence, there is significant uncertainty
regarding the best clinical management strategy, and wide
variability in clinical practice has been described3,9–13 .
Generally, expectant monitoring with iatrogenic preterm
delivery is recommended, with varying monitoring
intervals and gestational ages at delivery. For more severe
cases, intervention by either fetoscopic laser ablation of
anastomoses or selective reduction of the compromised
twin can be considered when fetal death is thought to be
impending10,13–16 .
As a first step towards providing further guidance on
the best clinical management, the purpose of this study
was to describe contemporary pregnancy characteristics
and fetal and neonatal outcomes of monochorionic twin
pregnancies complicated by Type-III sIUGR managed in
tertiary referral centers. The primary outcome was the
© 2020 International Society of Ultrasound in Obstetrics and Gynecology
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127
prospective risk of fetal death according to gestational
age, and a secondary outcome was the rate of adverse
neonatal outcome stratified by gestational age at delivery.
METHODS
This was a retrospective cohort study of all consecutive
monochorionic diamniotic twin pregnancies complicated
by Type-III sIUGR, managed longitudinally between 1st
January 2008 and 1st July 2019 in nine fetal medicine
centers. All cases, irrespective of gestational age at refer-
ral or diagnosis of Type-III sIUGR, were included in the
analysis. Type-III sIUGR was defined as EFW of one
twin < 10th percentile and intertwin EFW difference of
25% or more, in combination with intermittent absent or
reversed end-diastolic flow in the umbilical artery of the
smaller fetus on at least one occasion6,7,17 . The intertwin
EFW difference was calculated as ((EFW of larger fetus
– EFW of smaller fetus) / EFW of larger fetus) × 100.
Higher-order multiple gestations, pregnancies compli-
cated by major fetal structural or genetic anomalies and
pregnancies with missing neonatal data were excluded
from the analysis. Additionally, pregnancies compli-
cated by twin–twin transfusion syndrome (TTTS), twin
anemia–polycythemia sequence (TAPS) or twin reversed
arterial perfusion sequence at first presentation were
excluded.
The research ethics board at each participating
center approved the study protocol. All participating
centers have extensive experience in the management of
monochorionic twins and their associated complications,
and all have a level-3 neonatal intensive care unit (NICU)
associated with their perinatal unit.
Surveillance of Type-III sIUGR varied between centers.
The frequency of ultrasound examinations varied between
once a week to biweekly until 28 weeks’ gestation in
all centers, and usually twice a week thereafter. In
all centers but one, routine admission for inpatient
surveillance was recommended. The timing of admission
varied between 26 and 32 weeks’ gestation. In all
centers, glucocorticoids for fetal lung maturation were
administered prophylactically at 26–30 weeks. The timing
of delivery of otherwise uncomplicated Type-III sIUGR
pregnancies ranged between 32 + 0 and 35 + 6 weeks.
Fetal indications for urgent delivery were similar among
centers and included abnormal cardiotocogram, persistent
reversed end-diastolic velocity in the umbilical artery,
persistently abnormal ductus venosus flow (absent or
reversed a-wave) and a growth plateau accompanied
by oligohydramnios of the smaller twin. Four centers
attempted trial of labor under specific conditions, and the
remaining units routinely delivered all Type-III sIUGR
pregnancies by Cesarean section. Selective reduction
was offered in most centers when imminent death of
the smaller fetus was suspected based on persistently
reversed end-diastolic velocity in the umbilical artery with
abnormal ductus venosus flow before 24 weeks or when
the EFW of one fetus was < 500 g, often in combination
with oligohydramnios and an empty bladder. Selective
Ultrasound Obstet Gynecol 2021; 57: 126–133.
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128 Shinar et al.

reduction was done by cord occlusion or radiofrequency using McNemar’s χ-square test for categorical variables,
ablation. Preventative laser ablation of anastomoses was and between pregnancies undergoing selective reduction
typically not performed in any of the centers unless and those complicated by single IUD, using Fisher’s exact
the pregnancy was complicated by the co-occurrence of test for categorical variables; continuous variables were
TTTS. Individual institutional management guidelines are compared using Student’s t-test for normally distributed
provided in Table S1. data or non-parametric tests for non-Gaussian data;
For this study, we retrieved the following antenatal P < 0.05 was considered statistically significant. Data
variables: gestational age at first presentation with analysis was performed using Prism for Windows version
Type-III sIUGR, EFW discordance at initial presentation, 5.00 (GraphPad Software, La Jolla, CA, USA) and JMP7
presence of oligohydramnios in the smaller twin (defined (SAS Institute, Cary, NC, USA) statistical software.
as deepest vertical amniotic fluid pocket < 2 cm) or
polyhydramnios in the larger twin (defined as deepest
RESULTS
vertical amniotic fluid pocket > 8 cm prior to 20 weeks’
gestation, and > 10 cm after 20 weeks’ gestation18 ) at A total of 328 MCDA pregnancies (656 fetuses) met the
initial diagnosis, evolution to TTTS or TAPS, diagnosis inclusion criteria. The number of pregnancies included
of single or double IUD, selective reduction, fetoscopic from each center varied from five to 120. Maternal
laser ablation, preterm prelabor rupture of membranes, pregnancy characteristics are presented in Table 1. It is
spontaneous preterm birth before 37 weeks, diagnosis interesting to note that 32 (9.8%) pregnancies were the
of gestational hypertension or pre-eclampsia, steroid result of assisted reproduction.
administration, admission to hospital (for complications The mean gestational age at diagnosis of Type-III
or routine management), gestational age at delivery, sIUGR was 22.0 ± 4.6 weeks, with 231 (70.4%) preg-
indication for delivery and mode of delivery. nancies demonstrating intermittent absent or reversed
At discharge from the NICU, the following charac- end-diastolic flow in the umbilical artery at first presenta-
teristics were recorded for all liveborn neonates: birth tion. In the remainder (n = 97 (29.6%)), the umbilical flow
weight, 1- and 5-min Apgar scores, sex, need for and changes developed later in gestation. While 18 (5.5%)
duration of ventilation, mode of ventilation (invasive ven- pregnancies progressed to TTTS, with seven of these
tilation or continuous positive airway pressure (CPAP)), (38.9%) requiring laser treatment, none progressed to
respiratory distress syndrome (RDS), culture-proven sep- TAPS. Eighteen (5.5%) pregnancies underwent selective
sis, necrotizing enterocolitis (NEC) requiring intervention, reduction to a singleton pregnancy, because of perceived
retinopathy of prematurity (ROP) Stage > II, intraventric-
ular hemorrhage (IVH) Grade > I or cystic periventricular Table 1 Maternal characteristics and pregnancy complications in
leukomalacia (PVL) on a clinically indicated head ultra- 328 twin pregnancies with Type-III selective intrauterine growth
sound examination, and death before discharge from the restriction (sIUGR)
NICU. Composite adverse neonatal outcome was defined
as any one or more of the following: invasive ventilation Variable Value
beyond the resuscitation period, culture-proven sepsis, Age (years) 30.2 ± 4.9
NEC requiring treatment, ROP Stage > II, IVH Grade Gravidity 1 (1–3)
> I, cystic PVL or death prior to discharge. Parity 0 (0–1)
Maternal comorbidity* 38 (11.6)
Assisted reproduction† 32 (9.8)
Statistical analysis GA at diagnosis of Type-III sIUGR (weeks) 22.0 ± 4.6
Progression to TTTS 18 (5.5)
Descriptive statistics are presented as mean (SD) for GA at TTTS (weeks) 24.3 ± 5.7
normally distributed continuous variables and median Laser ablation for TTTS 7/18 (38.9)
(interquartile range) for non-Gaussian data. Categorical Progression to TAPS 0 (0)
Laser ablation for sIUGR 1 (0.3)
variables are presented as n (%). The prospective risk
Selective reduction of IUGR twin 18 (5.5)
of IUD was calculated as the number of cases occurring GA at selective reduction (weeks) 22.3 ± 3.1
after a certain gestational age divided by the number of Single IUD 19 (5.8)
live fetuses still in utero at that gestational age (fetus GA at single IUD (weeks) 27.8 ± 4.6
at-risk approach). Subanalysis was performed excluding Double IUD 16 (4.9)
pregnancies that underwent selective fetal reduction. GA at double IUD (weeks) 21.3 ± 3.8
Overall IUD 35 (10.7)
Sonographic characteristics at diagnosis were compared
PPROM 30 (9.1)
between pregnancies with double-twin survival, those Spontaneous PTD without PPROM 35 (10.7)
with IUD and those that underwent selective reduction, Pre-eclampsia 16 (4.9)
using Pearson’s χ-square test for categorical variables
and one-way ANOVA for continuous variables. If the Data are given as mean ± SD, median (interquartile range), n (%)
or n/N (%). *Defined as any chronic medical condition. †Ovula-
ANOVA result was significant, Tukey’s post-hoc tests tion induction and in-vitro fertilization. GA, gestational age; IUD,
were performed. intrauterine death; PPROM, preterm prelabor rupture of mem-
Neonatal outcomes were calculated for the entire cohort branes; PTD, preterm delivery; TAPS, twin anemia–polycythemia
and were compared between the larger and smaller twins, sequence; TTTS, twin–twin transfusion syndrome.

© 2020 International Society of Ultrasound in Obstetrics and Gynecology Ultrasound Obstet Gynecol 2021; 57: 126–133.
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Outcome of Type-III sIUGR 129

impending fetal death in all cases. One (0.3%) pregnancy 10.4% (95% CI, 8.07–12.75%) at 16 weeks, reaching
underwent laser ablation for sIUGR and was subsequently a nadir of 0% at 35 weeks, with 37 pregnancies still unde-
complicated by the death of the smaller fetus. After exclu- livered at that time, of which 23 still had two live fetuses
sion of pregnancies that underwent selective reduction, (Figure 1b). Of note, the 95% CIs for the prospective
there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 risk of IUD, both in all pregnancies and when excluding
(11.3%) (10.7% of the entire cohort of 328) pregnancies. selective reductions, start diverging at 33 weeks, reflecting
Single IUD occurred in 19/328 (5.8%) pregnancies, while the lower number of pregnancies continuing beyond that
16/328 (4.9%) were complicated by double IUD. One gestational age.
fetus was terminated due to cystic PVL and was consid- Pregnancies complicated by IUD (n = 35) were diag-
ered a single IUD. It is of note that double IUDs occurred nosed with Type-III sIUGR at a significantly lower
on average 6 weeks earlier in pregnancy than did sin- gestational age than were pregnancies in which both
gle IUDs (21.3 ± 3.8 vs 27.8 ± 4.6 weeks; P < 0.001). The fetuses survived to delivery (n = 275) (19.5 ± 3.3 weeks vs
prospective risk of non-iatrogenic IUD (excluding preg- 22.3 ± 4.7 weeks; P = 0.001) (Table 2). They were also
nancies that underwent selective reduction) declined from more likely to present with oligohydramnios of the
8.1% (95% CI, 5.95–10.26%) at 16 weeks to less than smaller twin at the time of diagnosis (8/35 (22.9%)
2% (95% CI, 0.59–2.79%) after 28.4 weeks and to less vs 24/275 (8.7%); P = 0.009). Oligohydramnios at pre-
than 1% (95% CI, –0.30 to 1.89%) beyond 32.6 weeks. sentation was also diagnosed more frequently among
From 35 weeks’ gestation onwards, there were no cases pregnancies that underwent selective reduction compared
of IUD, with 26 pregnancies still undelivered, of which with those with double survival (4/18 (22.2%) vs 24/275
23 still had two live fetuses (Figure 1a). When including (8.7%); P = 0.009). Although more severe weight dis-
selective reductions, the prospective risk of IUD was cordance at diagnosis was found in pregnancies that
underwent selective reduction (42.1 ± 11%) than in preg-
nancies with double survival (29.6 ± 8.9%) (P < 0.001),
(a) this was not the case for pregnancies complicated by IUD
(31.2 ± 9.2%) (P = 0.35).
Prospective risk of fetal death (%)

15
Overall, 251 (76.5%) women were admitted to hospital
for inpatient surveillance (Table 3). Of these, 192 (76.5%)
10
were admitted for routine monitoring, at a mean gesta-
tional age of 28.9 ± 3.5 weeks. The remainder (n = 59
5
(23.5%)) were admitted for maternal or fetal complica-
tions, including pre-eclampsia, worsening fetal hemody-
0
16 20 24 28 32 36 40 namics, TTTS or oligohydramnios. Mean gestational age
Gestational age (weeks) at delivery was 31.8 ± 3.6 weeks. The main indications
–5
for delivery were fetal distress (defined as non-reassuring
fetal heart rate monitoring or abnormal flow in the
(b)
ductus venosus), occurring in 106/308 (34.4%) preg-
Prospective risk of fetal death (%)

15 nancies, followed by elective delivery for Type-III sIUGR,

occurring in 100/308 (32.5%) pregnancies. Spontaneous
10 preterm delivery complicated 46/308 (14.9%) pregnancies
and pre-eclampsia complicated 16/308 (5.2%). Cesarean
5 section was the mode of delivery in 252/306 (82.4%)
cases, occurring in 92.6% of all pregnancies with double
0 survival.
16 20 24 28 32 36 40
The incidence of composite adverse neonatal outcome
Gestational age (weeks)
–5 is presented in Figure 2. The most common timing
for delivery was 32 + 0 to 32 + 6 weeks’ gestation
Figure 1 Prospective risk of intrauterine death in twin pregnancies (55 pregnancies). Delivery at this gestational age was
complicated by Type-III selective intrauterine growth restriction, associated with a risk of composite adverse neonatal
excluding (a) and including (b) those that underwent selective
outcome of 29.0% (31/107 neonates). This risk decreased
reduction, according to gestational age. Regression line and
95% CI are shown. to 10.5% (8/76 delivered neonates) at 34 weeks and to

Table 2 Factors associated with fetal mortality at diagnosis of Type-III selective intrauterine growth restriction in 328 twin pregnancies

Variable Double survival (n = 275) IUD (n = 35) Selective reduction (n = 18) P

EFW discordance (%) 29.6 ± 8.9 31.2 ± 9.2 42.1 ± 11.0 < 0.001*
Gestational age (weeks) 22.3 ± 4.7 19.5 ± 3.3 20.7 ± 3.4 0.001†
Oligohydramnios 24 (8.7) 8 (22.9) 4 (22.2) 0.009*†

Data are given as mean ± SD or n (%). Compared with double survival group, significant difference in: *selective-reduction group;
†intrauterine-death (IUD) group. EFW, estimated fetal weight.

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130 Shinar et al.

0% at 36 weeks and beyond (with 33 neonates delivered assessed (5-min Apgar score < 7, neonatal death,
from 36 weeks onward, of which 10 were twin pairs). culture-proven sepsis, ROP Stage > II, NEC and cystic
Neonatal outcomes stratified by twin size (smaller vs PVL) were significantly more common in the smaller twin
larger twin) are presented in Table 4. Mean birth-weight (P < 0.01 for all), except for invasive and non-invasive
discordance was 31.2 ± 11.3%. All adverse outcomes ventilation and IVH Grade > I, which were more common
in the larger twin (P < 0.01 for all), and RDS, which
was comparable (P = 0.73). Composite adverse neonatal
Table 3 Management of 328 twin pregnancies complicated by
outcome (excluding 5-min Apgar score < 7, non-invasive
Type-III selective intrauterine growth restriction (sIUGR)
ventilation and RDS) occurred more frequently in the
Variable Value smaller than in the larger twin (33.8% vs 29.2%;
P < 0.01).
Inpatient surveillance 251 (76.5) Compared with pregnancies complicated by sponta-
Admitted for fetal surveillance 192/251 (76.5)
GA at admission (weeks) 28.9 ± 3.5
neous single IUD, the surviving neonate’s birth weight
Admitted for complication 59/251 (23.5) was significantly greater in cases undergoing selective
Steroids for lung maturation 297 (90.5) reduction (2402 ± 843 g vs 1868 ± 641 g; P = 0.03), as
GA at steroids (weeks) 28.4 ± 2.0 was gestational age at delivery (35.7 ± 4.0 weeks vs
GA at delivery (weeks) 31.8 ± 3.6 32.1 ± 3.7 weeks; P = 0.008) (Table 5). In the presence
Indication for delivery
of single IUD, the risk of neurological sequelae (cys-
Spontaneous labor 46/308 (14.9)
Planned for sIUGR 100/308 (32.5)
tic PVL or IVH Grade > I) in the survivor (in all
Maternal indication* 20/308 (6.5) cases the larger twin) was 20.0% (3/15), whereas in
Fetal distress† 106/308 (34.4) cases of selective reduction, there was only a single
Other fetal‡ 36/308 (11.7) case of IVH Grade > I and there were no cases of
Mode of delivery cystic PVL.
Planned Cesarean section 247/306 (80.7)
Vaginal delivery 54/306 (17.6)
Cesarean section
All pregnancies 252/306 (82.4) DISCUSSION
Pregnancies with double survival 252/272 (92.6)
In this study of 328 monochorionic twin pregnancies
Data are given as n (%), n/N (%) or mean ± SD. *Maternal complicated by Type-III sIUGR, we found that IUD
indication for delivery included pre-eclampsia (n = 16), gestational complicated 11% of all cases. The prospective risk
hypertension (n = 2) and severe cholestasis of pregnancy (n = 2). of non-iatrogenic IUD was 8% in early pregnancy,
†Fetal distress included abnormal cardiotocography or absent or
reversed a-wave in ductus venosus. ‡Other fetal delivery
but decreased to less than 2% at 28.4 weeks with the
indications included fetal death or abnormal biophysical profile. institution of close fetal surveillance, and decreased
GA, gestational age. further to less than 1% beyond 32.6 weeks. In otherwise

100%
120 100

90
83% 83%
Composite adverse neonatal outcome (%)

100
78% 80
74%
71%
70
Number of neonates

80
60

60 45%
50

36%
40
40 29%
30

16% 20
20
11% 11%
10
0% 0% 0% 0% 0%
0 0
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Gestational age at delivery (weeks)

Figure 2 Frequency ( ) and percentage ( ) of composite adverse neonatal outcomes and frequency of healthy neonates ( ) in twin
pregnancies complicated by Type-III selective intrauterine growth restriction, according to gestational age at delivery.

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Outcome of Type-III sIUGR 131

uncomplicated Type-III sIUGR pregnancies, delivery
was generally planned at 32 weeks, nearly always by
Cesarean section, at which time the risk of composite
adverse neonatal outcome was still high (29%). For twin
pregnancies that continued to 34 weeks, there was a lower
risk of composite adverse neonatal outcome (11%) and a
very low risk of fetal death (0.7%).
It is generally agreed that the management of Type-III
sIUGR is particularly challenging, since fetal death is
perceived as unpredictable and the risk of neurological
injury to the larger twin is considered substantial, even in
the absence of cotwin demise1 . In 2004, Gratacós et al.1
reported a fetal death rate for the small twin of 14.2%
and an incidence of parenchymal brain lesion in the
larger cotwin of up to 20%. Studies on the management
and outcome of Type-III sIUGR are, however, scarce
and mostly involve small numbers1,15,19–21 . A recent
meta-analysis of six studies (170 twins) demonstrated
a pooled rate of fetal death of 13% for expectantly
managed pregnancies8 . We consider there to be three
possible reasons for the lower rate of fetal death observed
in our series. First, our cohort most probably included
some milder forms of Type-III sIUGR. This is evidenced
by the relatively low rate of selective reduction as well
as the lower neonatal-weight discordance than reported
previously. However, this is more likely to represent
the true ‘natural history’ of the condition. Second, we
excluded pregnancies with anomalous fetuses and those
that had TTTS at initial presentation, both of which
are known predictors of adverse outcome4 . Third, all
participating centers practiced close fetal surveillance after
viability, and pregnancies were delivered early. It is also
possible that in some cases the Doppler pattern changed
to Type-I sIUGR after the initial diagnosis, explaining
their favorable outcome11 .

Table 4 Outcomes of 587 neonates from twin pregnancies complicated by Type-III selective intrauterine growth restriction, overall and in
smaller and larger twins

Variable All (n = 587) Smaller twin (n = 275) Larger twin (n = 312) P

Birth weight (g) 1536.2 ± 580.1 1206.2 ± 433.9 1796.6 ± 587.5 < 0.001
5-min Apgar score 9 (8–9) 9 (5–9) 9 (8–9) 0.32
5-min Apgar score < 7 33 (5.6) 17 (6.2) 16 (5.1) < 0.01
Neonatal death 18 (3.1) 14 (5.1) 4 (1.3) < 0.01
Invasive ventilation 144 (24.5) 65 (23.6) 79 (25.3) < 0.01
Non-invasive ventilation (CPAP) 325 (55.4) 147 (53.5) 178 (57.1) < 0.01
Respiratory distress syndrome 282 (48.0) 125 (45.5) 157 (50.3) 0.73
Culture-proven sepsis 44 (7.5) 28 (10.2) 16 (5.1) < 0.01
NEC requiring treatment 25 (4.3) 14 (5.1) 11 (3.5) < 0.01
IVH Grade > I 12/532 (2.3) 3/246 (1.2) 9/286 (3.1) < 0.001
Cystic PVL 7/532 (1.3) 4/246 (1.6) 3/286 (1.0) < 0.01
ROP Stage > II 15 (2.6) 11 (4.0) 4 (1.3) < 0.01
Composite adverse neonatal outcome* 184 (31.3) 93 (33.8) 91 (29.2) < 0.01

Data are given as mean ± SD, median (interquartile range), n (%) or n/N (%). *Composite adverse neonatal outcome was defined as any one
of the following: neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis (NEC)
requiring treatment, intraventricular hemorrhage (IVH) Grade > I, retinopathy of prematurity (ROP) Stage > II or cystic periventricular
leukomalacia (PVL). CPAP, continuous positive airway pressure.

Table 5 Neonatal outcome of 27 survivors after single intrauterine death or selective reduction in twin pregnancies complicated by Type-III
selective intrauterine growth restriction

Variable Single IUD (n = 19) Selective reduction (n = 18) P

Gestational age at delivery (weeks) 32.1 ± 3.7 35.7 ± 4.0 0.008

Birth weight (g) 1868.4 ± 641.2 2401.9 ± 843.1 0.03
5-min Apgar score < 7 6 (31.6) 3 (16.7) 0.4
Neonatal death 1 (5.3) 0 (0) —
Invasive ventilation 5 (26.3) 3 (16.7) 0.47
Non-invasive ventilation (CPAP) 10 (52.6) 6 (33.3) 0.23
Respiratory distress syndrome 5 (26.3) 4 (22.2) 1
Culture-proven sepsis 1 (5.3) 1 (5.6) 1
NEC requiring treatment 0 (0) 0 (0) —
IVH Grade > I 1/15 (6.7) 1 (5.6) 1
ROP Stage > II 1 (5.3) 0 (0) —
Cystic PVL 2/15 (13.3)* 0 (0) —
Composite adverse neonatal outcome† 6 (31.6) 2 (11.1) 0.23

Data are given as mean ± SD, n (%) or n/N (%). *One cotwin was terminated owing to resultant periventricular leukomalacia (PVL).
†Composite adverse neonatal outcome was defined as any one of the following: neonatal death, invasive ventilation beyond the resuscitation
period, culture-proven sepsis, necrotizing enterocolitis (NEC) requiring treatment, intraventricular hemorrhage (IVH) Grade > I, retinopathy
of prematurity (ROP) Stage > II or PVL. CPAP, continuous positive airway pressure.

© 2020 International Society of Ultrasound in Obstetrics and Gynecology Ultrasound Obstet Gynecol 2021; 57: 126–133.

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The fact that the rate of late fetal death was low in
our cohort suggests that not all mortality in these twins
is truly unpredictable, which is similar to what is seen in
monoamniotic twins22 . Indeed, most fetal deaths occurred
prior to viability (Figure 1). Once viability had been
reached and delivery had become an option, the mortality
rate in our series became very low. Moreover, fetuses
that died typically presented with sIUGR earlier and
were more commonly complicated by oligohydramnios
at diagnosis (Table 2). However, the severity of growth
discordance, though associated with selective reduction,
was not associated with spontaneous IUD. Future studies
should be directed at better identifying which findings
truly predict impending death and at developing adequate
surveillance strategies to select those pregnancies that
would benefit from selective reduction or preterm delivery,
as well as those that can be continued safely beyond
32–33 weeks’ gestation.
With regard to neonatal outcome, we showed a
clear gestational-age dependent decrease in morbidity,
with low rates of neuromorbidity. However, given that
this was a retrospective study and most participating
centers routinely performed postnatal brain ultrasound
examinations only for neonates delivered before 32 weeks
or for those with neurological findings, the numbers
presented here may be an underestimation of the true
incidence of IVH or cystic PVL. Indeed, a recent
meta-analysis of Type-III sIUGR reported an incidence
of severe IVH (Grade III or IV) and PVL of 3.5%
and 11.6%, respectively8 . Further large, prospective,
multicenter studies will be needed to clarify the impact of
Type-III sIUGR on neonatal brain findings and long-term
neurodevelopment23 .
Strengths and limitations
The strengths of our study stem mainly from the
collaboration between a large number of international
expert centers across North America, Europe and Asia.
This allowed us to collect data on almost twice as
many Type-III sIUGR pregnancies than have been
reported collectively in the literature so far, thereby
increasing the validity of our findings. Moreover, such
multicenter collaboration allowed us to obtain sufficient
data covering a relatively short time-span, thereby
making the findings reflective of contemporary practice in
developed countries and avoiding bias due to changes
in management protocols. Nevertheless, our study is
limited by its retrospective design. This prevented us
from commenting reliably on factors that were not
routinely recorded, such as neuromorbidity. Additionally,
data on how umbilical artery Doppler parameters were
obtained were not collected uniformly. Moreover, we
comment only on findings at initial presentation. Further
studies will be needed to assess how longitudinal
changes in fetal growth, amniotic fluid volume and
Doppler results may affect or predict outcome. Since
the majority of pregnancies were delivered by 34 weeks’
gestation, we cannot comment reliably on the risks to
© 2020 International Society of Ultrasound in Obstetrics and Gynecology
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Shinar et al.
the fetuses of continuing the pregnancy beyond this
gestational age.
Conclusions
Our findings show that, with close fetal surveillance, the
risk of unexpected fetal death in Type-III sIUGR may
be lower than reported previously and that many deaths
are preventable with timely delivery. Further multicenter
studies are needed to assess which factors truly predict
fetal death, in order to allow for optimal selection of
pregnancies for selective reduction, preterm delivery or
expectant management beyond 32 weeks’ gestation.
ACKNOWLEDGMENTS
We would like to thank the referring physicians for
sending their patients to our centers for shared care and
follow-up. Special thanks to Nir Gazit for his contribution
to data analysis.
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SUPPORTING INFORMATION ON THE INTERNET
The following supporting information may be found in the online version of this article:
Table S1 Institutional practice guidelines for management of twin pregnancies complicated by Type-III sIUGR
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