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 (<10th 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.