Z Leibovitz1,2, E Daniel-Spiegel3, G Malinger4,5, K Haratz2, M Tamarkin2, L Gindes2, L Schreiber6, L Ben-Sira7, D Lev8, I Shapiro1, H Bakry1, B Weizman1, A Zreik1, S Egenburg9, A Arad9, R Tepper10, D Kidron11, T Lerman-Sagie2. 1. Ultrasound Unit, Department of Obstetrics and Gynecology, Bnai Zion Medical Center, Haifa, Israel. 2. Unit of Fetal Neurology and Prenatal Diagnosis, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel. 3. Department of Obstetrics and Gynecology, Haemek Medical Center, Afula, Israel. 4. Lis Maternity Hospital, Division of OB-GYN Ultrasound, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 6. Department of Pathology, Wolfson Medical Center, Holon, Israel. 7. Department of Radiology, Tel Aviv Medical Center, Tel Aviv, Israel. 8. Genetics Institute, Wolfson Medical Center, Holon, Israel. 9. Department of Pathology, Bnai Zion Medical Center, Haifa, Israel. 10. Ultrasound Unit, Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel. 11. Department of Pathology, Meir Medical Center, Kfar Saba, Israel.
Abstract
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.
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.
Authors: Victor Chung Pam; Christopher Sabo Yilgwan; David Danjuma Shwe; IbrahimIshaya Abok; Nathan Shehu; Simji Samuel Gomerep; Isa Samson Ejiji; Amaka Ocheke; Francis Magaji Ajang; Josiah Tul Mutihir; Nentawe Gurumdimma; Daniel Egah; Stephen Oguche Journal: J Trop Pediatr Date: 2019-12-01 Impact factor: 1.165
Authors: S Fried; M Gafner; D Jeddah; N Gosher; D Hoffman; R Ber; A Mayer; E Katorza Journal: AJNR Am J Neuroradiol Date: 2021-08-12 Impact factor: 4.966
Authors: Annelies Wilder-Smith; Yinghui Wei; Thalia Velho Barreto de Araújo; Maria VanKerkhove; Celina Maria Turchi Martelli; Marília Dalva Turchi; Mauro Teixeira; Adriana Tami; João Souza; Patricia Sousa; Antoni Soriano-Arandes; Carmen Soria-Segarra; Nuria Sanchez Clemente; Kerstin Daniela Rosenberger; Ludovic Reveiz; Arnaldo Prata-Barbosa; Léo Pomar; Luiza Emylce Pelá Rosado; Freddy Perez; Saulo D Passos; Mauricio Nogueira; Trevor P Noel; Antônio Moura da Silva; Maria Elisabeth Moreira; Ivonne Morales; Maria Consuelo Miranda Montoya; Demócrito de Barros Miranda-Filho; Lauren Maxwell; Calum N L Macpherson; Nicola Low; Zhiyi Lan; Angelle Desiree LaBeaud; Marion Koopmans; Caron Kim; Esaú João; Thomas Jaenisch; Cristina Barroso Hofer; Paul Gustafson; Patrick Gérardin; Jucelia S Ganz; Ana Carolina Fialho Dias; Vanessa Elias; Geraldo Duarte; Thomas Paul Alfons Debray; María Luisa Cafferata; Pierre Buekens; Nathalie Broutet; Elizabeth B Brickley; Patrícia Brasil; Fátima Brant; Sarah Bethencourt; Andrea Benedetti; Vivian Lida Avelino-Silva; Ricardo Arraes de Alencar Ximenes; Antonio Alves da Cunha; Jackeline Alger Journal: BMJ Open Date: 2019-06-18 Impact factor: 2.692