Fetal calcifications are associated with chromosomal abnormalities.
OBJECTIVE
The biological importance of calcifications occasionally noted in fetal tissues (mainly liver) at autopsy or ultrasound is largely unexplored. Previous reports hint at an association to infection, circulatory compromise, malformations or chromosomal abnormalities. To identify factors associated with calcifications, we have performed a case-control study on the largest cohort of fetuses with calcifications described thus far.


METHODS
One-hundred and fifty-one fetuses with calcifications and 302 matched controls were selected from the archives of the Department of Pathology, Karolinska University Hospital. Chromosome analysis by karyotyping or quantitative fluorescence-polymerase chain reaction was performed. Autopsy and placenta reports were scrutinized for presence of malformations and signs of infection.


RESULTS
Calcifications were mainly located in the liver, but also in heart, bowel, and other tissues. Fetuses with calcifications showed a significantly higher proportion of chromosomal abnormalities than controls; 50% vs. 20% (p<0.001). The most frequent aberrations among cases included trisomy 21 (33%), trisomy 18 (22%), and monosomy X (18%). A similar distribution was seen among controls. When comparing cases and controls with chromosomal abnormalities, the cases had a significantly higher prevalence of malformations (95% vs. 77%, p=0.004). Analyzed the other way around, cases with malformations had a significantly higher proportion of chromosomal abnormalities compared with controls, (66% vs. 31%, p<0.001).


CONCLUSIONS
The presence of fetal calcifications is associated with high risk of chromosomal abnormality in combination with malformations. Identification of a calcification together with a malformation at autopsy more than doubles the probability of detecting a chromosomal abnormality, compared with identification of a malformation only. We propose that identification of a fetal tissue calcification at autopsy, and potentially also at ultrasound examination, should infer special attention towards co-existence of malformations, as this would be a strong indicator for a chromosomal abnormality.
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, CMM L8:02, Karolinska University Hospital, S-171 76, Stockholm, Sweden.
Ellika
E
Sahlin
Center for Perinatal Pathology and Department of Pathology, Karolinska University Hospital, Huddinge and Karolinska Institutet, S-141 86, Stockholm, Sweden.
Meeli
M
Sirotkina
Center for Perinatal Pathology and Department of Pathology, Karolinska University Hospital, Huddinge and Karolinska Institutet, S-141 86, Stockholm, Sweden.
Andreas
A
Marnerides
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, CMM L8:02, Karolinska University Hospital, S-171 76, Stockholm, Sweden.
Erik
E
Iwarsson
Center for Perinatal Pathology and Department of Pathology, Karolinska University Hospital, Huddinge and Karolinska Institutet, S-141 86, Stockholm, Sweden.
Nikos
N
Papadogiannakis
D002114:Calcinosis / Q000150:complications* / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000150:complications* / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004314:Down Syndrome / Q000150:complications / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005865:Gestational Age; D006801:Humans; D059785:Karyotype; D011247:Pregnancy; D012189:Retrospective Studies; D014314:Trisomy / Q000235:genetics; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics