Cytogenetic Studies in Perinatal Death
Authors: Smith A. , Bannatyne P. , Russell P. , Ellwood D. , den Dulk G. 
Published: February 2008

EDITORIAL COMMENT: We have accepted this paper for publication to make obstetricians more aware of the role of cytogenetics in the investigation of perinatal deaths. All 15 of the infants with abnormal karyotypes had morphological congenital anomalies, but the authors do not make it clear how many of these malformations were diagnosed antenatally (ultrasound) or after the child was born, but before autopsy was performed. This information in a large consecutive series of stillbirth and neonatal deaths would be useful, to give the clinician an idea of abnormal karyotype yields in growth retarded, malformed, and apparently normal, well nourished stillborn infants. The value of finding an abnormal karyotype is that it assists genetic counselling — what is the risk of recurrence and does the abnormality warrant genetic amniocentesis or chorion biopsy in a future pregnancy?

Ideally tissue culture should be performed in all perinatal deaths and malformed infants but tissue culture facilities do not permit this luxury — the test is labour intensive and one scientist can handle only about 200 specimens in one year's work, so the editor learned from one reviewer.

Amniocentesis/cordocentesis is not without risk expecially if the infant is growth retarded; moreover when there is an intrauterine death the mother and the clinician are likely to be more interested in prompt, safe delivery, rather than in amniocentesis for karyotyping the fetus. Furthermore we know of no data showing that cells from amniotic fluid grow well in culture when obtained after intrauterine death has occurred.

Our reviewer (a pathologist) supports the use of amniocentesis when fetal growth retardation is recognized, with or without malformations (and of course when there is no maternal factor to account for the growth retardation), whatever the period of gestation; in these cases the incidence of chromosome abnormalities will be high. However, he does not support attempts at tissue culture in normally formed, normally nourished macerated stillbirths, because the yield of chromosomal abnormalities is likely to be low.

The authors emphasize that the placenta is usually more viable than other fetal tissues for culture and karyotyping. Readers should also remember that the placenta should be examined by the pathologist (the obstetrician examines all placentas) in all cases of abnormal pregnancy; when parents will not consent to autopsy they will usually agree to examination of the placenta.

Summary: Following tissue culture cytogenetic studies were performed on tissue obtained from 136 fetuses who died in the perinatal period (98 stillbirths and 38 neonatal deaths). The gestational age of the stillbirths was evenly distributed between 20 and 40 weeks (1 was 42 weeks) while 74% of the neonatal deaths were term babies. Analyzable metaphases were obtained in 45 stillbirth specimens (46%) and 32 neonatal specimens (84%). Abnormal karyotypes were identified in 7 of the stillbirths (15.5%) and 8 of the neonatal deaths (25%) and all these were from babies with congenital anomalies identified at autopsy.

Time delays were crucial to the success of culture from stillbirths, but specimens obtained from neonatal deaths could be grown successfully up to 3 days after death. Generally the placenta was more viable than other tissues, including skin, cartilage and muscle. Whereas growth was obtained in 69% of fresh unexplained stillbirths, no tissue from the macerated stillbirths grew. This is a group which may have a high abnormality rate.

We recommend that if fetal assessment during pregnancy suggests a compromised fetus and there are no maternal factors to account for this, an amniocentesis be performed.