2012, Volume 28, Number 2, Page(s) 154-161
Evaluation of Fetal Autopsy Findings in the Hatay Region: 274 Cases
Sibel HAKVERDİ1, İsmail GÜZELMANSUR2, Arif GÜNGÖREN3, Serhat TOPRAK1, Mehmet YALDIZ1, Ali Ulvi HAKVERDİ2
1Department of Pathology, Mustafa Kemal University, Faculty of Medicine, Antakya/HATAY, TURKEY
2Department of Radiology, Antakya Mozayik Obstetric and Pediatric Hospital, Antakya/HATAY, TURKEY
3Department of Obstetrics and Gynecology, Mustafa Kemal University, Faculty of Medicine, Antakya/HATAY, TURKEY
Keywords: Autopsy, Fetal diseases, Prenatal diagnosis, Hatay
The aim of this study was to present the incidence of fetal
anomalies in our region of Hatay, Turkey in order to determine the
efficiency of prenatal diagnosis through fetal autopsy, and to compare
our statistical data with other national and international studies.
Material and Method: This study was conducted on 274 fetuses
from terminated pregnancies due to abnormal prenatal findings
and intrauterine deaths from 2005 to September 2010. Fetuses were
evaluated through postmortem examination, external measurements,
X-rays, Magnetic Resonance Images, Multislice Computerized
Tomography and photographs. The autopsy was completed by the
histological examination of each organ.
Results: Autopsy was conducted on 274 fetuses. A fetal anomaly was
detected in 160 (58.39%) cases. The central nervous system contained
the most frequent structural defects (79 cases, 49.38%), followed by
malformations in the musculoskeletal system in 36 cases (22.5%).
The most frequent multiple system anomalies were central nervous
system defect and bilateral adrenal agenesis, musculoskeletal system
malformations and urinary system defects. Fetal autopsy provided
additional findings in 43 cases (26.88%).
Conclusion: Fetal autopsy is a very important procedure and an
integral part of the general prenatal management. New findings
through this method may suggest invaluable data for parents about
potential risks in future pregnancies.
Congenital anomalies have become an important cause
of perinatal mortality and morbidity in both developing
and developed countries. It has been shown through some
studies that these can be reduced substantially by means of
improved prenatal, obstetric and postnatal care1
The prenatal diagnosis based on ultrasound scan findings
may not be adequate for the parents to make the decision
of pregnancy termination. Therefore, clinicians, geneticists,
pediatric surgeons, radiologists and pathologists are
required to be consulted for certain diagnosis of anomalies
as well as the application of right methods so as to overcome
A further issue to be dealt with thoroughly is the
implications of anomalies in fetuses for future pregnancies.
Women will normally want to know whether their future
pregnancies will end in similar anomalies in their fetuses,
and so the exact data obtained from autopsy examination
can be offered to them. A specialist pediatric pathologist
might provide important information about the possible
risk of recurrence2,3.
The autopsy is quite significant in giving complementary
information4. We therefore always recommend at our
center that an autopsy should be performed on almost all
fetuses ranging from pregnancies terminated due to fetal
anomalies to intrauterine fetal death.
The aim of this study was to present the distribution of fetal
anomalies in our region of Hatay province, to determine
the efficiency of postnatal diagnosis through fetal autopsy,
to compare our statistical data with other studies, and to
evaluate the need to employ advanced screening methods
for higher precision in diagnosis.
All terminated pregnancies from 12 to 40 weeks due to
abnormal prenatal findings, and intrauterine fetal deaths
(IUFD) from 2005 to September 2010 at Mustafa Kemal
University, Medical Faculty, Gynecological and Obstetric
Clinic-Hatay (a total of 274 fetuses) were evaluated
prospectively. Among these fetuses, 115 with abnormal
prenatal findings were referred to the high risk pregnancy
clinic from prenatal outpatient clinics of our hospital
for further investigation and 159 of them were directly
received as intrauterine dead fetuses. After obstetric and
ultrasonographic evaluation of these cases’ family histories,
detailed patient history and examinations of other affected
family members were carried out.
The families were informed about the technique of
fetal physical examination by the obstetrician and were
asked whether they wanted this evaluation or not. After
termination of pregnancy, all of the fetuses were referred
to our department for autopsy with the written consent
of the patients as regards the analysis procedures.
Autopsy was conducted on all the fetuses in our clinic:
anthropometrical measurements including height, weight,
head circumference, hand, middle finger, foot length, chest,
and arm span were taken and all fetuses were photographed.
All cases were X-rayed in order to detect some specific localised
skeletal defects. Karyotype analysis was done in all
45 cases with an undiagnosed multiple malformation. Amniocentesis
(35 cases) and fetal cord blood samples (10 cases) after termination were also used for chromosomal evaluation.
Furthermore, multislice computerized tomography
(MSCT), a more advanced method of screening, was used
in 12 cases with skeletal dysplasia. We also used MSCT in
a congenital cervical neuroblastoma case to view the degree
of invasion of the tumour into the bone and cerebral tissues.
In 2 sacrococcygeal teratoma cases, we obtained magnetic
resonance images (MRI) to see the depth of invasion of the
tumor into soft tissues.
All the fetuses were carefully examined, their photographs
and radiographs were taken and the results were recorded
on the computer. The autopsy was completed by the
histological examination of each organ, including the
umbilical cord in all of the cases, and the placenta in 20
fetuses by the Department of Pathology. On the other hand,
patients rejected autopsy because of moral and religious
reasons for 41 fetuses and we examined the fetus, took
photographs and radiographs and recorded the findings.
The annual average birth rate in Hatay Province is 29.583
and these two hospitals handle an average of 9.000 of
these cases (32.40%)5
. Two hundred and seventy-four
consecutive fetuses were examined during the five-year
study period from January 2005 to September 2010. Among
these fetuses, 115 were from women whose pregnancy
had been terminated medically for prenatally detected
fetal abnormalities and 159 were dead in utero. Of these,
autopsy was performed in 233 (85%) cases. A fetal anomaly
was detected in 160 (58.39%) cases. Among the fetuses with
no fetal anomaly, 49 were detected to have autolysis, 12
hydrops fetalis, and 2 adrenal gland and liver calcification.
Among the dead fetuses, 47 cases were found to have
no pathology (Table I
). Forty-one families rejected the
autopsy. In twenty cases there were central nervous system
anomalies such as anencephaly, spina bifida etc. Ten cases
showed musculoskeletal system malformation. No gross
pathological finding was identified in the rest.
As regards the causes of fetal anomalies, we focused on some
other aspects related to couples, such as the consanguinity,
regional factors and family history, which might yield clues
about genetic transmission probabilities. In 44 (27.5 %)
cases, the couples were married to their cousins, which
Among the cases with anomalies, 60 (37.5%) were female,
90 (56.25%) were male, and the sex of 10 cases (6.25%)
could not be detected. In 1 case, the fetus was diagnosed
to have Piepkorn syndrome (short ribs, short neck, wideset
eyes, narrow and short ribcage), and one year later the second fetus from the second pregnancy of the same
mother had the same pathology. In the other case, we found
gastroschisis, encephalocele, and micrognathia. Two years
later, the fetus from the second pregnancy of the mother
was found to have gastroschisis and musculoskeletal
anomaly. In both cases, the women were informed about
the possible risks in their future pregnancies and the second
pregnancies with anomalies would therefore be ended in
the earlier stages of pregnancy.
Neural tube defect and other defects in the central
nervous system were the most frequent structural defects,
accounting for 79 (49.38%) of the cases. These were, in
turn, followed by malformations in the musculoskeletal
system in 36 (22.5%), and in genital organs and the urinary
system in 19 (11.86%) cases. The final detailed diagnoses
based on autopsy and cytogenetics are listed in Table II and
summarized with photographs in Figures 1A-D, 2A-D.
Click Here to Zoom
|Figure 1: A) Fetal Anencephaly, B) Radial Ray Malformation, C) Piepkorn Syndrome, D) Thanatophoric Dwarfism.
Routine karyotype analysis was not offered in cases of neural
tube defects. Chromosomal abnormalities accounted for 11
(24.44%) of the 45 cases. This includes trisomy 21, trisomy 18, trisomy 13 and 2q deletion syndrome. Down’s syndrome
was the most common finding in this group8.
In cases multiple system anomalies, the most frequent
one was central nervous system defect and bilateral
adrenal agenesis, followed by musculoskeletal system
malformations and urinary system defects (renal dysplasia,
In 12 cases, an umbilical cord and placenta pathology
were present: 3 cases of chorangiosis and 9 cases of single
umbilical artery (7.5 %).
A congenital tumor was detected in 7 ( 4.38%) cases, 5 of
which were sacrococcygeal teratoma, 1 congenital facial
hemangioma and 1 congenital cervical neuroblastoma.
In the fetuses examined after prenatal diagnosis of
malformations, the ultrasound findings in 156 cases but four
were confirmed by fetal autopsy. In the ultrasonographic
examination, three of these four cases were found to
have intrauterine growth retardation, oligohydramnios/
anhydramnios and abnormality (cystic change) in the kidney; however, the result of the autopsy showed no
pathology in the kidney. One of them was diagnosed to
have widespread calcification in the liver, and two of them
only to have intrauterine growth retardation. The last case
with cardiac anomaly was diagnosed on ultrasonographic
examination, but there was no cardiac abnormality at
autopsy. None of these four cases were terminated at the
beginning, but died without reason. The reason of death
could not be explained. The placenta was not examined.
Fetal autopsy provided additional findings in 43 cases
(26.88%), in 19 of which a revision of the diagnosis led to
a significant change in the risk of recurrence in subsequent
pregnancies (Table III).
The number of published studies on congenital anomalies
in the Turkish population is limited. We found four studies
from PubMed about neonatal congenital anomalies1,6-8
. There are also some studies on specific anomaly groups
such as neural tube defect9-11
Informing and offering pregnancy termination in Turkey is
not as difficult as it is in other Muslim countries. Laws give
permission for pregnancy termination due to congenital
anomalies, and families mostly approve the termination.
However, in spite of legal freedom and personal tendency,
41 families rejected autopsy because of the social pressure
on them and the psychological, cultural and religious
notions they have1,3,12.
The annual birth rate in Turkey is 1.241.6175. We have
not found any studies about the annual fetal anomaly rate.
In our region, the annual average birth rate is 29.583 and
we have found the annual fetal anomaly rate to be 0.10%
The autopsy rate in our study among the fetuses referred to
us was 85% (233/274), while it was 79.9% in the Dickinson13, 84 % to 67% in the Boyd and all cases (100 %) in the
Central nervous system (CNS) disorders were the most
frequent group of disorders in pregnancy losses, perinatal and postnatal mortalities and congenital anomalies, with
a reported frequency of 20–45% (45.5%, Pinar14, 1998;
29.4%, Ceylaner10, 2007; 26.4%, Nielsen15, 2006;
34.8%, Amini4, 2006; and 21.75%, EURO CAT16,
2003). In our study, 79 of the 160 cases had CNS, with a
rate of 48.75%. The results we obtained were higher than
those found in the studies of other investigators1,2,7,14.
This difference might suggest that regional differences and
consanguinity, a common practice in most of Turkey and
particularly in our region, should be taken into account.
As in the other studies, fetal loss investigations included
radiographs, chromosomal analysis, fetal autopsy and
histopathology of the placenta17,18. Skeletal radiograph
is an obligatory part of fetal autopsy protocol, particularly
if skeletal dysplasia is suspected as in the case of short
limbs. Although skeletal dysplasia might be reconsidered
by ultrasound, only postmortem radiography can yield
an accurate diagnosis19,20. This is significant as the
risk of recurrence ranges from negligible to 25%. In the
series of Tunçbilek E et al., the most frequent congenital
malformations were those in the musculoskeletal
system8. However, in our series, malformations of the
musculoskeletal system were the second most frequent at a
rate of 36/160 (22.5%) cases as suspected by ultrasonography
and confirmed by postmortem radiography.
As reported in some studies, chromosomal abnormalities
are the most common findings in fetal abnormalities13,14. In our study, we only analyzed chromosomal
anomalies in 45 cases due to various reasons. In our series,
we also found the rate of chromosomal abnormalities to be
high, accounting for 11 (24.44%) of the 45 cases. Down’s syndrome (8 cases) was the most common finding in this
Some series have focused on whether some anomalies
identified in fetal fetuses were accompanied by other
anomalies, and whether the rate of correlation between
the different anomalies was significant. Nielsen LAet
al. found well-known associations of CNS with specific
morphological anomalies and specific organ weights, and
also suggested an association between adrenal hypoplasia
and cephalocele15. We found a significant correlation
between central nervous system malformations (78 cases)
and adrenal agenesis (4 cases) with a rate of 5.13%. Our
findings are similar to those identified by Nielsen LA et al.,
which shows that the correlation between central system
malformations and adrenal agenesis is a significant factor
to be further investigated in other studies15. However,
Ceylaner G et al. found that the additional malformation was
that occurring in the muscoloskeletal system1. We have
also found that the second most frequent correlation was
between congenital malformations of the musculoskeletal
system (36 cases) and renal pathology (renal agenesis, renal
dysplasia) in 5 cases with a rate of 13.9 %.
Generally, prenatal ultrasound is expected to detect
major fetal structural anomalies, and although detection
rates may vary, the majority of severe fetal anomalies are
recognized prenatally21-23. Nonetheless, additional
findings which may influence the risk of recurrence can
be obtained with fetal autopsy. For example, if a fetus
found to have a neural tube defect (recurrence risk 3-5%)
by ultrasonography yielded additional findings like
polydactyly and renal malformation on fetal autopsy, the revised diagnosis would be Meckel syndrome, which has
autosomal recessive inheritance with a recurrence risk of
25% in subsequent pregnancies. In this study, four cases of
Meckel Gruber Syndrome, 4 cases of infantile (autosomal
recessive) polycystic renal disease (recurrence risk of 25%),
5 cases of cystic renal dysplasia and 6 cases of bilateral renal
agenesis (recurrence risk of 3%) had not been previously
identified with ultrasonographic examination, but only
diagnosed through the histopathological examination of
The additional finding rate as a result of fetal autopsy was
27% (35/132) in Boyd’s study3. In Dickinson’s study13,
the risk alteration for subsequent pregnancies appeared to
have changed by 49.4% in 45 cases, and Sankar VH and
Phadke SR2 obtained significant additional information
about 38% of the cases and the recurrence risk change
was 18% in his analysis of 138 fetuses in a 5-year period.
Fetal autopsy provided additional findings in 43 cases in
our study. The recurrence risk increased in 11 of the 43
(25.58%) cases. This result was in accordance with the
results of previous similar studies.
Consanguinity in a population is a very important factor
regarding the appearance of congenital defects and
recessively transmitted hereditary diseases. Several studies
from different regions in Turkey have shown consanguinity
rates to range from 11.7 to 35.2%24. We only interviewed
the parents of fetuses with anomalies about consanguinity,
and we found a rate of 27.5 % (44/160 cases). However,
there has been no study on the rate of consanguinity in
our region so far. We were therefore unable to compare our
results. Studies are needed on this subject.
We employed MSCT in order to detect the depth of tumor
invasion into bones and cerebral tissues in 1 congenital
cervical neuroblastoma case (Figure 2). We also used the
same method in skeletal dysplasia cases. We used MRI to
see the depth of invasion of the tumour into soft tissues in
sacrococcygeal teratoma cases. We believe that advanced
imaging tools can yield better results with higher precision,
and should be employed more frequently.
Click Here to Zoom
|Figure 2: A) Congenital Cervical Neuroblastoma, B) Anencephaly and Gastroschisis, C) Anencephaly-Iniencephaly-Thoracal Rashisisis,
D) Sacrococcygeal Teratoma.
In summary, the quality of devices is continually increasing
and yielding more accurate results with an ultrasound
scan. However, the role of fetal autopsy remains very
important in order to clearly identify some other defects
in terminated fetuses. Parents can also be better informed
about the possible risks in future pregnancies with the help
of the findings received through fetal autopsy so that they
can take necessary precautions. A larger number of cases is
required for a more accurate evaluation.
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