Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?
OBJECTIVE
To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction.


METHODS
Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history.


RESULTS
Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively.


CONCLUSIONS
The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.|Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
Z
Z
Leibovitz
Department of Obstetrics and Gynecology, Haemek Medical Center, Afula, Israel.
E
E
Daniel-Spiegel
Lis Maternity Hospital, Division of OB-GYN Ultrasound, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
G
G
Malinger
Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
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K
Haratz
Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
M
M
Tamarkin
Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
L
L
Gindes
Department of Pathology, Wolfson Medical Center, Holon, Israel.
L
L
Schreiber
Department of Radiology, Tel Aviv Medical Center, Tel Aviv, Israel.
L
L
Ben-Sira
Genetics Institute, Wolfson Medical Center, Holon, Israel.
D
D
Lev
Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
I
I
Shapiro
Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
H
H
Bakry
Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
B
B
Weizman
Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
A
A
Zreik
Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
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S
Egenburg
Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
A
A
Arad
Ultrasound Unit, Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel.
R
R
Tepper
Department of Pathology, Meir Medical Center, Kfar Saba, Israel.
D
D
Kidron
Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
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T
Lerman-Sagie
D002508:Cephalometry / Q000379:methods*; D005260:Female; D005865:Gestational Age; D006801:Humans; D000069342:Medical Overuse / Q000706:statistics & numerical data; D008831:Microcephaly / Q000175:diagnosis*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D016216:Ultrasonography, Prenatal / Q000379:methods*
fetal microcephaly; head circumference; prenatal diagnosis