title: Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero.
abstract: OBJECTIVE
  To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation.
  
  
  METHODS
  A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation.
  
  
  RESULTS
  In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive value (PPV) was 56%. Combination of the HC and FCD criteria raised the PPV to 78%, decreasing the number of false positives from 11 to four, without missing any of the 14 micB cases.
  
  
  CONCLUSIONS
  Fetal vertical cranial biometric assessment in the mid-sagittal plane is feasible and correlates well with gestational age. In our series, a vertical cranial deformation was a frequent cause of a false Fmic diagnosis made on the basis of HC alone. Combination of the new vertical cranial biometric measurement with HC measurement can exclude these cases and thus improve diagnostic accuracy for Fmic. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: 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.
authors.forename: Z
authors.initials: Z
authors.lastname: Leibovitz
authors.affiliation: Maccabi Healthcare Services, North District, Israel.
authors.forename: C
authors.initials: C
authors.lastname: Shiran
authors.affiliation: Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Haratz
authors.affiliation: Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Tamarkin
authors.affiliation: Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Gindes
authors.affiliation: Department of Pathology, Wolfson Medical Center, Holon, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Schreiber
authors.affiliation: Tel Aviv Sourasky Medical Center, Lis Maternity Hospital, Division of Ob-Gyn Ultrasound, Tel Aviv, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Malinger
authors.affiliation: Department of Radiology, Tel Aviv Medical Center, Tel Aviv, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Ben-Sira
authors.affiliation: Genetics Institute, Wolfson Medical Center, Holon, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Lev
authors.affiliation: Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Shapiro
authors.affiliation: Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Bakry
authors.affiliation: Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Weizman
authors.affiliation: Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Zreik
authors.affiliation: Department of Pathology, Meir Medical Center, Kfar Saba, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Kidron
authors.affiliation: Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Egenburg
authors.affiliation: Department of Pathology, Bnai Zion Medical Center, Haifa, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Arad
authors.affiliation: Pediatric Neurology, Wolfson Medical Center, Holon, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Lerman-Sagie
mesh_terms: D001699:Biometry / Q000379:methods*; D003951:Diagnostic Errors / Q000517:prevention & control*; D005260:Female; D005865:Gestational Age; D006257:Head / Q000196:embryology*; D006801:Humans; D008831:Microcephaly / Q000175:diagnosis*; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods
keywords: craniosynostosis; fetal microcephaly; molding; prenatal reference chart; ultrasound; vertical cranial biometry