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Hiroko Takita, Junichi Hasegawa*, Masamitsu Nakamura, Tatsuya Arakaki, Tomohiro Oba,
Ryu Matsuoka and Akihiko Sekizawa
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98 Takita et al., Recent causes of IUFD
calculated by dividing the total number of coils by the length of the 2001–2007 and 35 cases (0.48%) in 2008–2014. The back-
cord in centimeters after delivery. Hyper-coiled cord was defined in ground of all deliveries and IUFDs are shown in Tables 1
cases of umbilical coiling index > = 0.3 coils/cm.
and 2. The background of all deliveries in our institution
did not differ between the two periods, except for rates of
pregnancy after assisted reproduction technology (ART)
Statistical analyses
and cesarean section rate. These rates increased recently.
However, the background of IUFD did not differ between
All statistical analyses were performed using the Statistical Pack-
age for the Social Sciences (SPSS) (Windows version 20.0 J; Chicago, the two periods.
IL, USA). Categorical variables are reported as frequencies and were The prevalence rates of the causes of IUFD in 2001–
compared using Fisher’s exact test. 2007 and 2008–2014 are shown in Figure 1. In 2001–2007,
the leading cause of IUFD was fetal factors (43.2%), the
prevalence was only 8.6% in 2008–2014 (P < 0.01). Mean-
Ethics statement while, the prevalence of umbilical cord abnormalities
relatively increased from 30.0% in 2001–2007 to 54.5% in
This study was approved by the Ethics Committee of our hospital 2008–2014 (P = 0.06).
(No. 1182). The identities of the patients were treated with confiden-
Details of the fetal abnormalities are demonstrated
tiality and protected. No personal data were collected in the present
in Table 3. In 2001–2007, 56% of IUFDs due to fetal mor-
study. The investigation was conducted according to the principles
expressed in the Declaration of Helsinki. phological abnormalities, and more than half of the cases
with fetal factors were due to chromosomal abnormalities.
(Trisomy 18 and 21 with fetal morphological abnormalities
were frequently observed.) However, in 2008–2014, only
Results three cases of IUFD were due to fetal factors which were
Trisomy 21 with a body stalk anomaly, absence of ductus
The number of deliveries in our center was 6878 in venosus, and selective IUGR.
2001–2007 and 7326 in 2008–2014, respectively. IUFD The prevalence of cord factors between the two
after 20 weeks’ gestation occurred in 38 cases (0.53%) in periods is demonstrated in Figure 2. HCC and umbilical
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Takita et al., Recent causes of IUFD 99
Discussion
In the present analysis of IUFDs, the increase in the preva-
lence of cord factors was higher in the period 2008–2014
than in the period 2001–2007. Conversely, the prevalence
of fetal factors decreased. With the improvements in fetal
Figure 1: The prevalence rates of the causes of IUFD in 2001–2007 ultrasonographic evaluation, various fetal abnormalities
and 2008–2014.
have been detected during pregnancy and appropriate
management and interventions have been provided.
Table 3: Details of fetal factors.
The earlier prenatal diagnosis also has an influence
in this direction. In our institution, morphological fetal
Fetal abnormalities assessment during the second trimester had started to
perform since 2000. Then, more detail assessment was
2001–2007 (16) Trisomy 18 6
added with the passing of the years. On the other hand,
Trisomy 21 (2 cases: atrial ventrial defect) 3
Holopoloencephaly 1
the first trimester morphological assessment had started
Multiple anomalies (single umbilical 3 in our institution since 2008. When we explained abnor-
cord, body stalk anomaly) mal fetal findings to patients in the first trimester, some
Cardiac anomaly (Ebstein) 1 patients desired to undergo amniocentesis or chorionic
Splenohepatomegaly 1 villous sampling. In our institution between 2011 and
Ventriculomegaly 1 2013, it is demonstrated that about half of the cases found
2008–2014 (3) Trisomy 21 (body stalk anomaly) 1 morphological abnormalities during the first trimester
Absence of ductus venosus 1 ultrasound screening resulted in artificial abortion after
Monochorionic diamniotic twin (severe 1
results of prenatal diagnosis with genetic counseling [5].
fetal growth restriction)
A similar situation was observed in the USA, where the
gestational ages at prenatal diagnosis and the abortion
rate for Down syndrome declining significantly since 2005
have been reported [6]. These changes are likely attribut-
able to the improvements in early screening that lead to
higher rates of chorionic villus sampling [6].
Basically, increased prenatal diagnosis during early
gestation and selection of artificial abortion made the
prevalence of umbilical cord abnormalities associated
with IUFD increase relatively. However, the other reason
might be associated with the increasing incidence of ART
pregnancy because ART pregnancy has been reported to
adversely affect placental and umbilical cord develop-
ment [7, 8]. ART pregnancies are associated with higher
risks of placenta previa (RR 3.71), placental abruption
(RR 1.83), polyhydramnios (RR 1.74), and oligohydram-
nios (RR 2.14) [8]. The incidence of VCI was also reported
Figure 2: The prevalence of cord factors in 2001–2007 and to increase along with increases in fertility problems and
2008–2014. maternal obesity [9]. VCI occurs in 1.5% of term singleton
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100 Takita et al., Recent causes of IUFD
placentas; however, its incidence increased to 3.65% in after 20 weeks’ gestation decreased, whereas that of IUFD
ART pregnancies [10]. associated with umbilical cord and placental factors
Advanced maternal age was reported as risk factors of tended to increase. The remaining causes of IUFD that
HCC, which is significantly associated with adverse perina- mostly occurred in the earlier gestation or during the
tal outcome and cesarean delivery [11]. HCC and umbilical antepartum period involved umbilical cord abnormali-
constriction at the umbilical ring are often observed in still- ties. The prediction of such conditions and further reduc-
born fetuses and were addressed in several studies [12, 13]. tion in the incidence of IUFD might be difficult even if
In the present study, among umbilical cord abnormalities, precise ultrasonography is performed in all pregnant
HCC and its constriction were the most frequent causes of women.
IUFD in both study periods. The umbilical ring at the fetal
abdominal wall is considered the weakest point in the Author’s statement
umbilical cord. It is thought that an extremely coiled cord Conflict of interest: Authors state no conflict of interest.
or its extension is associated with sudden fetal death [14]. Material and methods: Informed consent: Informed
Good peripartum outcomes of cord factors are con- consent has been obtained from all individuals included
sidered to be dependent on prenatal diagnosis and appro- in this study.
priate management during delivery [12, 15]. For example, Ethical approval: The research related to human subject
vasa previa should be diagnosed prenatally and cesarean use has complied with all the relevant national regula-
delivery should be performed at 35 weeks of gestation or tions, and institutional policies, and is in accordance
earlier before membrane rupture, labor, or significant with the tenets of the Helsinki Declaration, and has been
bleeding occurs [16]. Thus, we also performed antepartum approved by the authors’ institutional review board or
systematic ultrasonographic screening to detect umbili- equivalent committee.
cal cord and placental abnormalities [15]. Almost all cases Contribution to authorship: Takita H., Hasegawa J. and
with VCI and vasa previa could be antenatally diagnosed Nakamura M. designed the research. All the authors col-
in our hospital [17]. In fact, no cases of IUFD caused by VCI lected the data. Takita H., Hasegawa J. and Arakaki T.
occurred in the recent study period. analyzed and interpreted the data. Takita H., Hasegawa
Meanwhile, many IUFDs due to HCC are supposed to J. and Sekizawa A. drafted the manuscript. Takita H. and
be unavoidable because IUFD associated with HCC sud- Hasegawa J. performed the statistical analyses.
denly occurred without foreshadow. High venous veloc- Funding: None.
ity and increased venous pulsation at the umbilical ring
were reported as predictive findings of fetal compromise.
However, as IUFD due to HCC often occurred not only in
early pregnancy but also before the onset of labor or mem- References
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