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\begin{document}

\title{Comprehensive post-mortem evaluation in Intrauterine deaths /still
births in improving uptake of autopsy and future pregnancy outcomes}



\author[1]{Seema Thakur}%
\author[2]{Khushboo Kadam}%
\author[2]{Preeti Paliwal}%
\author[1]{Shubhnita Singh}%
\author[3]{Chanchal Singh}%
\author[4]{Rachna Gupta}%
\author[5]{Savita Dagar}%
\author[2]{Sudhir Jain}%
\author[6]{Akshatha  Sharma }%
\author[2]{Renu Saxena}%
\author[2]{Kamal Saxena }%
\author[2]{Sudha Kohli}%
\author[2]{Vandana Thareja}%
\author[2]{Rajni Saxena }%
\author[2]{Renu Caprihan}%
\author[2]{Vimal Grover}%
\author[2]{Manorma Bhutani}%
\author[2]{Anita  Gupta }%
\author[2]{Neena Kumar}%
\author[2]{Vandana Gupta }%
\author[2]{Mamta Mittal }%
\author[2]{Sunita  Verma}%
\author[2]{Arpana  Jain}%
\author[2]{Jyoti Chakerverty }%
\author[2]{Mukta  Kapila}%
\author[2]{Swati  Mittal }%
\author[2]{Sunita Kapoor}%
\author[2]{Deepa Khurana}%
\affil[1]{Fortis Hospital Shalimar Bagh}%
\affil[2]{Affiliation not available}%
\affil[3]{Birthright, by Rainbow Hospitals, New Delhi}%
\affil[4]{Sunehri Devi Hospital}%
\affil[5]{Birthright, by Rainbow Children's Hospitals, New Delhi}%
\affil[6]{Indraprastha Apollo Hospital}%


\vspace{-1em}



  
  \date{May 28, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: Post-mortem examination of a baby following spontaneous or
missed miscarriage in the second trimester or intrauterine death to
provide a complete or partial explanation of the pregnancy loss. Method:
A total of 100 cases of intrauterine deaths were consecutively collected
from January 2010-May 2019 for etiological diagnosis according to the
standard protocol and involved external examination, dysmorphological
examination, internal examination and full body antero-posterior and
lateral radiographs. Histopathology of placenta was done. Cases were
also subjected to genetic testing such as FISH/microarray. A clinical
correlation was done by a Obstetrician-geneticist to reach an
etiological diagnosis. Results: Two third of cases were referred after
intrauterine death post 30 weeks of gestation. 24/100 cases were with
fetal anomalies.Genetic causes present in 12\% cases. 65.5\% cases were
associated with the pathology of the placenta. 30\% cases were with cord
lesions. The results were inconclusive in 14\% of the cases.
Conclusions: In this study we looked for establishing etiological
diagnosis and tried to see contribution of each test in finding the
cause. This will help the obstetrician in counselling parents for the
utility of post-mortem excamination and thus better able to guide for
future recurrence risk and management.%
\end{abstract}%



\sloppy


\textbf{Comprehensive post-mortem evaluation in Intrauterine deaths
/still births}

\textbf{in improving uptake of autopsy and future pregnancy outcomes}

Dr Seema Thakur\textsuperscript{1}, Dr. Khushboo
Kadam\textsuperscript{2}, Dr.Preeti Paliwal\textsuperscript{3},
Dr.Shubhnita Singh\textsuperscript{4}, Dr Chanchal
Singh\textsuperscript{5}, Dr. Rachna Gupta\textsuperscript{6}, Dr.
Savita Dagar\textsuperscript{7}, Dr. Sudhir Jain\textsuperscript{8}, Dr.
Akshatha Sharma\textsuperscript{9}, Dr Renu Saxena\textsuperscript{10},
Dr. K.K Saxena\textsuperscript{11}, Dr.Sudha Kohli\textsuperscript{12},
Dr Vandana Thareja\textsuperscript{13}, Dr Rajni
Saxena\textsuperscript{14}, Dr.Renu Caprihan\textsuperscript{15}, Dr.
Vimal Grover\textsuperscript{16}, Dr. M Bhutani\textsuperscript{17}, Dr.
Anita Gupta\textsuperscript{18}, Dr. Neena Singh
Kumar\textsuperscript{19}, Dr. Vandana Gupta\textsuperscript{20}, Dr.
Mamta Mittal\textsuperscript{21}, Dr. Arpana
Jain\textsuperscript{22},Dr. Sunita Verma\textsuperscript{23}, Dr Jyoti
Chakroborty\textsuperscript{24}, Dr. Mukta Kapila\textsuperscript{25},
Dr. Swati Mittal\textsuperscript{26}, Dr Sunita
Kapoor\textsuperscript{27}, Dr. Deepa Khurana\textsuperscript{28}

1,2,4- Dept. Of Genetic and Fetal Diagnosis, Fortis hospital Delhi-NCR

3,10,12- Institute of Medical Genetics and Genomics, Sir Ganga Ram
Hospital, New Delhi

5-Senior Consultant, Dept. of Fetal Medicine, Rainbow Children Hospital,
Delhi

6- Senior Consultant, Dept. of Fetal Medicine Sunhari Devi Hospital,
Sonepat

7. Senior Consultant, Dept. of Fetal Medicine, Venkateshwar Hospital,
Delhi

8- Emeritus Professor, Deptt of Pathology

9- Senior Consultant, Dept. of Fetal Medicine, Apollo Hospital, Delhi

11. Senior Consultant, Dept. of Radiodiagnosis, Sir Ganga Ram Hospital,
Delhi

13- Consultant Radiologist, Vandana Diagnostic, Malviya Nagar, New Delhi

14, 15- Senior Consultant, Dept. of Radiodiagnosis, Fortis Lafemme,
Delhi

16-19- Senior Consultant, Dept. of Obs \& Gynae, Fortis Lafemme, Delhi

20-23- Senior Consultant, Dept. of Obs \& Gynaecology, Fortis Hospital,
Shalimar Bagh, New Delhi

24- Senior Consultant, Dept. of Pathology, Fortis Hospital, Shalimar
Bagh, New Delhi

25,26- Senior Consultant, Dept. of Obs \& Gynaecology, Fortis Memorial
Research Institute, Gurgaon

27,28- Senior Consultant, Dept. of Pathology, City X- ray, Tilak Nagar,
New Delhi

\textbf{Running title:} Post- mortem evaluation in still births/IUD

\textbf{Corresponding Author:}

Dr. Seema Thakur

Fortis Hopital, AA Block, Shalimar Bagh, New Delhi

Fortis lafemme, GK 11, New Delhi

Email: seematranjan@gmail.com

\textbf{Tweetable abstract:}

Post-mortem examination of a baby following spontaneous or missed
miscarriage in the second trimester or intrauterine death may provide a
complete or partial explanation of the pregnancy loss. Autopsy is the
single most useful investigation and provides information that adds to
the clinical diagnosis in nearly half of cases and is also a valuable
audit of clinical care.

We have analysed 100 cases for etiological diagnosis in still birth/
intrauterine deaths and suggest that post mortem comprehensive
evaluation has a diagnostic yield of 86\% and reducing the unexplained
causes to 14\%

\textbf{ABSTRACT}

\textbf{Objective:} Post-mortem examination of a baby following
spontaneous or missed miscarriage in the second trimester or
intrauterine death to provide a complete or partial explanation of the
pregnancy loss.

\textbf{Method:} A total of 100 cases of intrauterine deaths were
consecutively collected from January 2010-May 2019 for etiological
diagnosis according to the standard protocol and involved external
examination, dysmorphological examination, internal examination and full
body antero-posterior and lateral radiographs. Histopathology of
placenta was done. Cases were also subjected to genetic testing such as
FISH/microarray. A clinical correlation was done by a
Obstetrician-geneticist to reach an etiological diagnosis.

\textbf{Results:} Two third of cases were referred after intrauterine
death post 30 weeks of gestation. 24/100 cases were with fetal
anomalies. Genetic causes present in 12\% cases. 65.5\% cases were
associated with the pathology of the placenta. 30\% cases were with cord
lesions. The results were inconclusive in 14\% of the cases.

\textbf{Conclusions} : In this study we looked for establishing
etiological diagnosis and tried to see contribution of each test in
finding the cause. This will help the obstetrician in counselling
parents for the utility of post-mortem excamination and thus better able
to guide for future recurrence risk and management.

\textbf{Key words}

Intrauterine death, still birth, Fetal Autopsy, chromosomal microarray,
placental histopath, short cord, genetic counselling

\textbf{Introduction}

Fetal death is defined as the delivery of a fetus showing no signs of
life as indicated by the absence of breathing, heart beats, pulsation of
the umbilical cord, or definite movements of voluntary
muscles.\textsuperscript{1}It is divided in early (\textless{}22 weeks
of gestation), intermediate (between 22 and 27 weeks of gestation) and
late (\textgreater{} 28 weeks of gestation) depending on gestational
age. Of these, early are designated as abortions whereas intermediate
and late are known as stillbirths.\textsuperscript{1}

Intrauterine fetal death (IUFD) at any time during pregnancy is
devastating for the expecting couple as well as their families and it is
at such times that issues like the cause of the death of the fetus and
the fear of recurrence of such mishap in future pregnancies crop up.
These are major concerns for the couples as well as care givers; hence
the determination of cause and mechanism of death is important to
facilitate counseling of parents, management of subsequent pregnancies
and future interventions if possible. However majority of times these
questions remains unanswered due to several underlying factor and hence
counseling parents is often unsatisfactory.

Despite these limitations of ascertaining the precise cause it is
important to identify etiological factors that might themselves
contribute in IUD or can be indicative of other factors that can play a
significant role in IUD. The causes include maternal, fetal, placental
lesions, cord accidents and genetic causes that should be investigated
as per ACOG guidelines as a part of postmortem investigation of
intrauterine death.\textsuperscript{2}In the present study we have
analysed 100 cases of IUFD. Our primary objective was to calculate the
importance of various investigations in systematic postmortem
examination protocol. This will help the obstetrician in counselling
parents for the utility of post-mortem excamination and thus better able
to guide for future recurrence risk. Such protocol based evaluations are
much needed in our country as India is listed as a country with highest
number of still birth.

\textbf{Material \& Methods:}

We included 100 fetus in this series which were referred for fetal
post-mortem for intrauterine deaths during January 2010- May 2019.we
included all cases more than 12 weeks of gestation. These were referred
from various hospitals and clinics across Delhi-NCR to us. All the cases
included in the study had no anomaly detected on the ultrasound. Our
centre is involved in fetal autopsy and is a referral centre for such
work. Parental consent was taken in all cases after counselling about
the utility of fetal autopsy. Fetal post-mortem involved external
examination, dysmorphological examination by the clinical geneticist,
internal examinations, full body antero- posterior and lateral
radiographs. Histopathology studies were advised for fetal organs and
placenta in all cases and genetic testing was done in all cases that
included karyotyping and in case of culture failure reflex FISH/QF PCR
studies were done for chromosomes 13, 16,18,21, 22 and sex chromosomes
before 2016. After 2016, microarray (mainly 315 k) was the preferred
test. Additionally DNA storage was done for all cases for further
genetic evaluations if needed. A final interpretation and correlation
was done by an obstetrician- clinical geneticist to correlate all fetal
investigations to identify underlying etiology.

We have complied with the ethical conduct of research involving human
subjects as per Helsinki declaration. Consent for autopsy and all
investigations were taken from all cases in the study. Consent for
including in research was also obtained in every case.

Results:

From January 2010 to May 2019 a total of 100 intrauterine fetal deaths
were included in the study.

Median age of mothers was 30.63 years (22--39 years) and median
gestational age at determination of IUD was 24 weeks and 4 days (12
weeks and 0 days-- 40 weeks and 0 days) (Table 1). Number of male
fetuses was 54; whereas female fetuses were 43 and remaining three had
ambiguous genitalia. 98 cases involved singleton pregnancy and only 2
involved twin pregnancies. Growth restriction was present in 48\% cases.
Two cases had overgrowth.

Distribution of etiological diagnosis is depicted in Table 2.

Autopsy showed external anomaly in 16 out of 100 cases whereas internal
anomaly was noted in 8 cases (Table 2). External anomaly involved mainly
ear malformations and digit amputations and these were not picked up on
ultrasound. (Fig 1) Of the 8 cases with internal anomaly three had
malformations of gastrointestinal tract including volvulus (Table 3).
Infantogram suggested skeletal dysplasia in one case with short limbs.

Short cord (\textless{}10\textsuperscript{th} centile for gestation) was
present in 22 cases. (Table-3). One case has long cord. Nuchal cord was
present in 2 cases (Table 3, Fig 2). 4 cases had associated single
umbilical artery. Hypocoiling was observed in cases with short cord
whereas hypercoiling was also noted (Fig-3 a,b,c). Placental
histopathology was done in 83\% of cases. (Table 2) Placental lesions
were present in 65.5\% of cases (Table-4). Placental infarction was seen
in 14 cases (Table 3,Fig-3d \& e). Placental haemorrhage was found in 14
cases (Table 3, Fig-4). In 12 cases placental examination showed
chorioamnionitis (Table-3)

Genetic analysis was performed in 93\% cases with intrauterine death
(Table 2). Before 2016, fluorescence in-situ hybridization (FISH) for 5
common aneuploidies was performed for 40 out of 57 cases (FISH was done
after culture failure). After 2016, Single Nucleotide Polymorphism (SNP)
chromosomal microarray was offered in 36 cases. 12\% cases were of
genetic disorders and this included 8 cases of common aneuploidy of
chromosome 21, 18, 16 and sex chromosome aneuploidy, one case of
abnormal microarray three syndromic cases- two of Treacher Collin
syndrome and one case of suspected Beckwith Weidmann syndrome (Table 3,
Figure 4). We found 2 cases of trisomy 21 and 2 cases of 47, XYY. We
obtained one case each of trisomy 18, trisomy 16, monosomy 21 and
triploidy. Microarray showed 19p deletion in one case (Table 3)

The eliological detection rate for IUD/stillbirth are represented in
Table-4

Figure 5 shows venn diagram of all investigations done and the
association of multiple etiological factors in this study.

\textbf{Discussion:}

Our study highlights the importance of comprehensive analysis for all
stillbirth/IUD cases. This study has important implications for clinical
practice and research. In our study we identified that cord (30\%) and
placental abnormalities (65.5\%) are associated with major causes of
still birth (Table 2). We further segregated these placental changes
into subcategories and of which infarction and haemorrhage were major
contributors (Table 3;fig 3 d,e, 4). We found genetic causes in 12\%
cases and the cause of death was unexplained in 14\% cases.

Kortwig and colleagues present data on the analysis of 1025 cases of
still births.\textsuperscript{3}In this study placental examination was
found helpful in 95.7\% of cases, autopsy was helpful in 72.6\% cases,
followed by cytogenetic analysis in 20\% cases. Secondary analysis of
512 cases of still birth was done by Page etal in still birth
collaborative research 2006-2008\textsuperscript{.4} Usefulness of
placenta histopathology was 64.6\%, fetal autopsy 42.4\% and genetic
analysis 11.9\%. We noted placental lesions in 65.5\% cases. Man et al
conducted a study on 1064 intrauterine deaths and noted that in around
30-60\% \% of cases, the cause of death was unexplained even after
careful clinical review, fetal external examination/imaging and
placental examination.\textsuperscript{5}

Our data however showed a higher percentage of associated pathology
which can be explained by systematic analysis of cases in a dedicated
unit. Pekkola et al did a standardized postmortem examination and a
re-evaluation of the results and report unexplained cases in only 10.2\%
cases.\textsuperscript{6}

Autopsy that included thorough evaluation of fetus revealed fetal growth
restriction in 48 cases. With the advancement of technology and follow
up ultrasonography, majority of fetal malformations can be identified in
utero, however external malformations are very difficult to identify and
can be easily seen on external examination of fetus. These not only help
in the characterisation of the fetal abnormalities but can further help
in delineating the course of further investigations or syndromic
diagnosis.

In the present study genetic testing was undertaken for ninety three
percent cases and majority of cases were subjected to karyotype and in
case of culture failure FISH test was undertaken.

Microarray was introduced at a later stage as first tier test for
product of conception. We could identify a genetic cause in 12\% percent
of cases. This percentage can be higher if microarray is done for all
cases of still births. (Table 2) Previous studies have shown that
chromosomal abnormalities are present in 6--13\% of stillbirths and this
percentage is higher in pregnancies with fetal
malformations.\textsuperscript{7}The difference in the percentages can
be partly due to the cell culture failure and partly because of limited
resolution of karyotyping. Unfortunately, cost is a barrier for many
patients and it may not be feasible to perform in all cases.

In our study we were able to identify two cases of Treacher Collins
syndrome and one case of Beckwith Weidman syndrome based on the
phenotype. This stresses on the fact that extensive analysis should be
undertaken before samples are sent for genetic analysis and deciding the
most cost effective test. Gross dysmorphism is indicative of underlying
chromosomal abnormalities or genetic syndrome. Our study with these
examples is thus suggestive of a need for comprehensive analysis that
can be informative and can be cost effective.

It has been noted that most of the abnormalities are not seen in
isolation and thus a combined risk assessment is much needed. In our
study we identified an overlapping in cause in 20 \% with maximum number
of overlaps seen in fetal growth restriction and placental
abnormalities. Altered fetal growth and placental abnormalities are the
strongest and most prevalent known risk factors for stillbirth. However,
most pregnancies with placental abnormalities or fetal growth
aberrations do not result in stillbirth.

Counseling for utility of fetal autopsy and genetic testing is important
to improve the uptake of autopsy. Due to lack of knowledge in this area,
health care personnels are unable to convince the parents about benefits
of autopsy and this leads to decreased uptake. Kortwig et al suggest
that basic fetal workup of still birth should include three tests:
autopsy, placenta histopathology and cytogenetic investigations.
{[}3{]}. They suggest this approach to be most cost effective. ACOG
practice guidelines also suggest that most important investigation in
such evaluations are autopsy, placenta histopathology and
karyotyping.{[}2{]} However, perinatal autopsy is underutilised in most
of the centers. There are multiple factors with regard to this but
parental refusal to autopsy seems most important reason. This refusal is
mainly due to the inability of the treating obstetrician to communicate
regarding the utility of fetal autopsy. The present articles thus adds
the following points that clinicians/ counsellors can highlight
regarding the detection rates while counselling to increase the uptake
of fetal autopsy and genomic investigations (Table 4)

1. Clinical evaluation by an experienced clinical geneticist can provide
an answer to 16\%.

2. Internal post mortem adds to further 8\%

3. Genetic tests are abnormal in 12\% cases.

4. Placental histopathology is helpful in 65.5\% cases

5. Cord abnormalities are noted in 30\% cases

6. Complete evaluation can identify cause 86\% of such cases

\textbf{Conclusions:} Counselling for utility of fetal autopsy and
genetic testing is important to improve the uptake of autopsy. The
present manuscript thus adds the following points that counsellors can
highlight regarding the detection rates while counselling such as:
clinical evaluation by an experienced clinical geneticist, internal
post-mortem; and placental histopathology and genetic analysis to detect
possible abnormalities. This will help in the informed decision making
by the parents and the cost effective analysis for etiological diagnosis
of these cases and thus improving the standards of care in prevention
and further guide research in this complex and sensitive issue. An
understanding of these interrelationships may contribute to a better
understanding of stillbirth mechanisms and thus a prenatal
identification of placental findings and fetal growth abnormalities can
improve stillbirth prediction and thus prevention.

\textbf{Acknowledgements}

Anisha Raju, THB , Gurugram for technical help in formatting article,
fig and tables

\textbf{Conflicts of Interests: NoneFunding- NoneEthics statement-}

Ethical clearance: This was a retrospective study so ethical clearance
was not taken

We have complied with the World Medical Association Declaration of
Helsinki regarding ethical conduct of research involving human subjects

\textbf{Contribution to Authorship}ST(1)- Main person doing the entire
study KK(2)- Assistant to ST SS(4)- Assistant to ST PP(3)-
Cytogenetecist, Helped in manuscript writing and data collection
RS(10),SK (12)- Molecular Geneticist doing genetic testing CS(5)- Fetal
medicine consultant involved in care of the patients and data collection
RG(6)- Fetal medicine consultant involved in care of the patients and
data collection SD(7)- Fetal medicine consultant involved in care of the
patients and data collection SJ(8)-Pathologist AS(9)- )- Fetal medicine
consultant involved in care of the patients and data collection VT(13)-
Radiologist for infantograms KKS(11)- Radiologist for infantograms
RS(14),RC(15)-Radilogist involved in patient care MB (16),VG(17),
AG(18),NS(19)- Obstetrician involved in care of the patients and data
collection VG(20), MM (21)AJ (22),SV(23)- Obstetrician involved in care
of the patients and data collection JC(24)- Pathologist involved in
patient care MK(25),SM(26) --Obstetrician involved in care of the
patients and data collection SK(27),DK (28)- Pathologist involved in
patient care

\textbf{References}

\begin{enumerate}
\tightlist
\item
  National Center for Health Statistics. State definitions and reporting
  requirements for live births, fetal deaths, and induced terminations
  of pregnancy. 1997 revision. Hyattsville (MD): NCHS; 1997. Available
  at: http://www. cdc.gov/nchs/data/misc/itop97.pdf. Retrieved November
  19, 2008. (Level II-3)
\item
  Ruth C. Fretts, Clinical management guidelines for
  obstetrician--gynaecologists. ACOG practice bulletin. Number 102.
  2009. 113, 748-761.
\item
  Korteweg FJ, Erwich JJHM, Timmer A, et al. Evaluation of 1025 fetal
  deaths: proposed diagnostic workup. Am J Obstet Gynecol 2012;206:
  53.e1-12.
\item
  Page JM, Lindquist L C, Thorsten V,Parker C B, Reddy U M, Dudley D J
  Diagnostic Tests for Evaluation of Stillbirth Results From the
  Stillbirth Collaborative Research Network , Obstet Gynecol
  2017;129:699--706
\item
  Man J, Hutchinson J C, Heazell A E, M. Ashworth M, Levine S and N. J.
  Sebire N J. Stillbirth and intrauterine fetal death: factors affecting
  determination of cause of death at autopsy .Ultrasound Obstet Gynecol
  2016; 48: 574--578
\item
  Pekkola M, Tikkanen M , Loukovaara M, Lohi J, Paavonen J and
  Stefanovic. Postmortem examination protocol and systematic
  re-evaluation reduce the proportion of unexplained stillbirths. J
  Perinat Med 2020;48(8)771-777
\item
  Reddy UM,~Page GP,~Saade GR. Karyotype versus microarray testing for
  genetic abnormalities after stillbirth. N Engl J Med.~2012 Dec
  6;367(23):2185-93.
\end{enumerate}

\textbf{Legends to Figures}

Fig-1: IUD at 35 weeks in Suspected Treacher Collin syndrome evere
Retrognathia, absent mandible, hypoplastic maxilla, High arched palate,
low set ears bilateral, Left ear- absent upper part of ear, absent
external auditory meatus on left side, Right ear: Accessory ear tag,
narrow external auditory meatus

Fig-2: IUD at 34 weeks, Nuchal cord, Hypocoiling

Fig-3: (clockwise)Placental and cord lesions associated with IUD

3a-Hypocoiling, Abnormal decrease in the number of coils of umbilical
cord.

3b-Marginal cord insertion, Umbilical cord is attached close to disc
margin.

3c-Hypercoiling, Increased coils \textgreater{} 2 coils per 5 cm, can
cause significant fetal retardation and death

3d-Perivillous fibrin deposition, Thickened placenta with pale grey
areas of fibrin deposition

3e-Infarction, A pale grey area of late infarct

Fig-4: RetroplacentalHaemorrhage, Dark red hemorrhagic clotson maternal
surface.

Fig-5: Venn diagram showing the overall distribution of cases and the
overlapping spectrum of different underlying abnormalities



\textbf{Table-1 Case Summary}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Categories} & \textbf{Number (N)}\tabularnewline
\midrule
\endhead
\textbf{Age of Mother (Years)} & \textbf{Age of Mother
(Years)}\tabularnewline
20-24 & 8\tabularnewline
25-29 & 43\tabularnewline
30-34 & 39\tabularnewline
35-40 & 9\tabularnewline
\textbf{Gestation age at IUD/Still birth (Weeks)} & \textbf{Gestation
age at IUD/Still birth (Weeks)}\tabularnewline
13-20 & 37\tabularnewline
21-27 & 36\tabularnewline
28-36 & 21\tabularnewline
36-40 & 6\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table-2 Distribution of cases in various categories and cause
for IUD}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Categories}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Categories}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Number}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Number}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Genetic\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Genetic\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12/93\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12/93\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Malformations\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
External\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
16/100 8\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
16/100 8\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Internal\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Placental\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Placental\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Placental\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
57/87\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cord\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cord\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cord\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
30/100\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Unknown\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14/100\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table-3- Details of Etiological Diagnosis to determine
Intrauterine Death/Stillbirth}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Categories} & \textbf{Number}\tabularnewline
\midrule
\endhead
\textbf{Fetal autopsy findings (n=100)} & \textbf{Fetal autopsy findings
(n=100)}\tabularnewline
Dysmorphology & Not conclusive\tabularnewline
External malformations & 16\tabularnewline
Internal malformation & 8\tabularnewline
FGR (Fetal Growth restriction) & 48\tabularnewline
Overgrowth & 2\tabularnewline
\textbf{Genetic diagnosis associated with IUD (n=12)} & \textbf{Genetic
diagnosis associated with IUD (n=12)}\tabularnewline
Trisomy 21 & 2\tabularnewline
Trisomy 16 & 1\tabularnewline
XYY & 2\tabularnewline
Treacher Collins syndrome & 2\tabularnewline
Beckwith Weidman & 1\tabularnewline
19 p deletion & 1\tabularnewline
Trisomy 18 & 1\tabularnewline
Triploidy & 1\tabularnewline
Monosomy 21 & 1\tabularnewline
\textbf{Placental lesions associated with IUD (n=83)} &
\textbf{Placental lesions associated with IUD (n=83)}\tabularnewline
Infarction & 14\tabularnewline
Chorioamnionitis & 12\tabularnewline
Placental Haemorrhage & 14\tabularnewline
Chorioangiosis & 1\tabularnewline
Marginal/ Velamentous insertion & 2\tabularnewline
Deciduitis & 1\tabularnewline
Fibrin deposition & 13\tabularnewline
Normal & 22\tabularnewline
Not available & 17\tabularnewline
\textbf{Fetal anomaly associated with IUD (n=8)} & \textbf{Fetal anomaly
associated with IUD (n=8)}\tabularnewline
Cardiac anomaly & 1\tabularnewline
Volvulus & 2\tabularnewline
Urorectal malformation & 1\tabularnewline
Hydrops fetalis & 2\tabularnewline
Hypoplastic lungs & 1\tabularnewline
Skeletal dysplasia & 1\tabularnewline
\textbf{Cord Lesion associated with IUD (n=30)} & \textbf{Cord Lesion
associated with IUD (n=30)}\tabularnewline
Short cord & 22\tabularnewline
Long cord & 1\tabularnewline
Single umbilical artery & 4\tabularnewline
4 umbillical artery & 1\tabularnewline
Nuchal cord & 2\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table-4 Detection Rate of various tests for IUD}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
\textbf{Test} & \textbf{Detection rate (\%)}\tabularnewline
\midrule
\endhead
Autopsy external examination & 16\tabularnewline
Autopsy internal examination & 8\tabularnewline
Genetic testing & 12\tabularnewline
Placenta & 65.5\tabularnewline
Cord & 30\tabularnewline
\bottomrule
\end{longtable}

Figure 1 Figure 2\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Fig 3\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure
4

Fig 5\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

