Introduction

The frequency of developmental defects ranges from 2% to 3% of all fetuses, 30% of which are related to genetic disorders. Congenital anomalies are the most severe disorders of the central nervous system that account for 40% of deaths of all children in the first year of life and survivors they cause a variety of neurological disorders, mental retardation, or drug-resistant epilepsy. ¹ In India, low birth weight, prematurity, sepsis, and infections are still the leading causes. ²

Sonography is non-invasive, widely available, safe, and has high sensitivity in identifying CNS malformations, autopsy findings are essential to arrive at a definitive diagnosis. The spectrum of CNS malformations includes anencephaly, exencephaly, cranial meningocele, meningomyelocele, spina bifida, Arnold Chiari malformation, syringomyelia, prosencephalies, agenesis of corpus callosum, agenesis of the cerebellum, Dandy-Walker syndrome, congenital hydrocephalus etc. ³ The most common CNS malformation are neural tube defects (NTDs). The perinatal autopsy also helps in identifying any associated anomalies. ^{4, 5}

Methodology

This study was done in a tertiary care hospital, where 644 perinatal autopsies with the gestational age of 22 weeks to perinatal day 7 were conducted after obtaining informed consent from the parents. The study was done over a period of 5 years between August 2015 to July 2020. Autopsies were performed following standard protocols. All relevant clinical data were collected. Ethical committee clearance was obtained for the study.

Result

Of the total 644 perinatal autopsies, 62 (9.6%) cases showed involvement of CNS. The most common mode of death in perinatal autopsies with CNS malformations was intrauterine death accounting for 46 (74.3%) cases followed by termination. The birth weight of the fetuses ranged from 50g to 2750g. Out of the 62 cases, 32 cases were female showing slight female preponderance.

The Spectrum also included a single case of Hypoplastic cerebellum, Hypoplastic vermis, Cerebellar agenesis, Choroid plexus cyst, Meningoncephalocele, Microcephaly, Sacrococcygeal teratoma, Dolicocephaly, Unilateral dilatation of occipital horns of lateral ventricle and Absent vermis accounting to1.6%. SeeTable 1.

In the present study, 6 (9.7%) cases of CNS malformations were associated with known syndromes namely Edward syndrome, Potter’s syndrome, and Klippel-Feil syndrome (Table 2)

Along with CNS in 21 (33.9%) cases we observed associated malformations of other systems with 7 cases involving the musculoskeletal system, 3 cases involving the genitourinary system, and 5 (8.1%) cases showing multisystem involvement.

Discussion

The major cause of fetal and neonatal deaths as well as disability cases worldwide are congenital malformations. The pattern and prevalence of congenital malformations vary over time and geographical location. These differences can be attributed to the complex interaction of known and unknown genetic and environmental factors like socio-cultural, racial, and ethnic factors. ⁶

A significant number of congenital malformations cannot be determined by antenatal investigations such as Ultrasonography (USG), and maternal serum enzyme hormone assays, for which autopsies are a must. ^{6, 7}

In the present study, the incidence of congenital anomalies is 19.4% which correlated with Naik et al. ⁷ showing an incidence of 19.6%. The incidence of CNS anomalies in the present study is 9.6% which is closely correlated with the study conducted by Naik et al. ⁷ showing an incidence of 8.7%. The most common CNS malformation seen in the present study was Anencephaly (Figure 1); 14 cases (22.6%) which is comparable to other studies.

Other neural tube defects like spina bifida (10 cases), meningocele (10 cases), and meningomyelocele (1 case) were the common CNS malformations seen in the present study which is in accordance with the previous studies (Table 3 ).

The incidence of iniencephaly was observed to be 1.1% in a study conducted by Pinar et al. ⁸ Iniencephaly is a rare neural tube defect characterized by extreme retroflexion of the head with the absence of the neck due to spinal deformities. The incidence of iniencephaly is reported to be 1 in 65,000 births in India and is more common in female fetuses.Figure 2 ⁹ In our study, we encountered one case of iniencephaly accounting for 1.6%. It was associated with a diaphragmatic hernia, poly spleen, bilateral club foot, and single umbilical artery.

Dandy–Walker malformation (DWM)Figure 4 is a rare intracranial congenital abnormality that affects the cerebellum and some of its components; particularly the cerebellar vermis, and fourth ventricle, and is characterized by an enlarged posterior fossa. ¹⁰ DWM occurs as an autosomal dominant inherited disorder and occurs in one in 25000 – 35000 pregnancies. ¹⁰

DWM is often associated with other CNS and/or extra-CNS abnormalities, with a high frequency of total or partial callosal defect, focal polymicrogyria, heterotopias, and malformed or ectopic inferior olives. In the present study, 3 cases of Dandy-Walker malformation were seen accounting for 4.8%. One case was associated with spina bifida and one case was with a single umbilical artery. Sirenomelia (Mermaid syndrome) is a rare and fatal congenital defect characterized by varying degrees of lower limb fusion, thoracolumbar spinal anomalies, sacrococcygeal agenesis, genitourinary, and anorectal atresia. ¹¹ This condition is found in approximately one out of every 100,000 live births. More than half the cases of sirenomelia result in stillbirth, and this condition is 100 times more likely to occur in identical twins than in single births or fraternal twins. It results from a failure of normal vascular supply from the lower aorta in utero. In this study, we studied 1 case of sirenomelia with Potter’s syndrome showing hypoplastic lower limb, sacral agenesis, hypoplastic lower limb, absent external genitalia, dilated anus and rectum, and single umbilical artery.Figure 5

Another rare case seen in this study was acardiac acephalus in a monochorionic monoamniotic twin gestation. The anomalies seen were sacral spina bifida and subcutaneous edema.

Acardiac twin is an extremely rare and bizarre complication of monochorionic twin pregnancy occurring at an incidence of 1 in 34,600 deliveries or 1 % monozygotic twins. ¹² Acardiac twins are a result of TRAP i.e., Twin reversed arterial perfusion where one twin is structurally normal called the donor twin and a recipient twin receives all its blood supply from the donor twin through its vascular connections on the surface of the placenta. ^{13, 14}

schizencephaly is a rare congenital abnormality of the brain affecting 1.48/100,000 live/stillbirths. ¹⁵ In schizencephaly the clefts of the brain extend through the hemispheres from the ventricles to the pial surface. One case of schizencephaly was seen in the present study.

Conclusion

The present study emphasizes the importance of perinatal autopsy for understanding the cause of death and also confirmation of the antenatal diagnosis. In the present study, we observed that the incidence of neural tube defects was higher compared to other anomalies. With the improvements in socioeconomic conditions, maternal nutrition, maternal health, and health education the incidence of neural tube defects can be reduced. Rare CNS malformations seen in the present study were iniencephaly, schizencephaly, and acardiac acephalous.

Understanding CNS malformations can give valuable information that can be further helpful in the genetic counseling of the parents. Thus, the fetal autopsy is essential to confirm the antenatal diagnosis and also to arrive at a definitive diagnosis.