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Severe microcephaly with associated brain atrophy at 24 weeks. The brain parenchyma is atrophic and echoegenic (arrow) with ventriculomegaly (v) and enlarged subarachnoid space (s).
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A considerable number of central nervous system pathologies remain undiagnosed during the first two trimesters of pregnancy. This group of disorders includes anomalies of brain proliferation, migration and cortical organization. Due to the fact that a detailed ultrasound examination of the fetal brain is usually not performed during the third trime...
Citations
... Jeanty's reference range is the most used despite being based on a small group of fetuses and despite the development of new reference ranges that in addition to being based on large populations, also utilize more advanced measurement modalities (Leibovitz et al., 2016b). The-3SD cut-off in the study by Chervenak et al., was found to be highly sensitive but not specific for the diagnosis of microcephaly, while using-4SD cut-off yielded higher specificity with no false positive cases (Chervenak et al., 1984(Chervenak et al., , 1987Malinger et al., 2003). ...
... Cases with SGP or micro-lissencephaly have poor prognosis. These patterns usually develop late in pregnancy or sometimes after birth (Malinger et al., 2003). ...
... A new workup algorithm is suggested, based on the advances in both fields of ultrasound and genetic testing (Figure 2). The first workup algorithm was suggested by Malinger et al. (2003). Genetic testing was not included in this algorithm as little was known at that time. ...
Microcephaly is a sign, not a diagnosis. Its incidence varies widely due to the differences in the definition and the population being studied. It is strongly related to neurodevelopmental disorders. Differences in definitions and measurement techniques between fetuses and newborns pose a great challenge for the diagnosis and prognostication of fetal microcephaly. A false positive diagnosis can result (in countries where it is legal) in erroneous termination of pregnancy, where a false negative diagnosis might lead to the birth of a microcephalic newborn. Microcephaly in growth restricted fetuses deserves special attention and separate evaluation as it is an important prognostic factor, and not necessarily part of the general growth retardation. Several genetic syndromes incorporating microcephaly and intrauterine growth retardation (IUGR) are discussed. Deceleration of the head circumference (HC) growth rate even when the HC is still within normal limits might be the only clue for developing microcephaly and should be considered during fetal head growth follow up. Combining additional parameters such as a positive family history, associated anomalies, and new measurement parameters can improve prediction in about 50% of cases, and thus should be part of the prenatal workup. Advances in imaging modalities and in prenatal genetic investigation along with the emergence of new growth charts can also improve diagnostic accuracy. In this article, we review the different definitions and etiologies of fetal microcephaly, discuss difficulties in diagnosis, investigate the reasons for the low yield of prenatal diagnosis, and provide improvement suggestions. Finally, we suggest an updated algorithm that will aid in the diagnosis and management of fetal microcephaly.
... The measurement of biparietal diameter (BPD) and head circumference (HC) should be in the normal range (± 2SD), according to the chosen growth charts. Technical issues -A detailed neurosonographic examination should be performed for fetuses with HC greater than 2 standard deviations below or above the mean [9,10], when the skull shape is abnormal or when US beam penetrance is reduced. ...
These guidelines follow the mission of the World Association of Perinatal Medicine, in collaboration with the Perinatal Medicine Foundation, which brings together groups and individuals worldwide, with the aim to improve prenatal detection of Central Nervous System anomalies and the appropriate referral of pregnancies with suspected fetal anomalies. In addition, this document provides further guidance for healthcare practitioners with the goal of standardizing the description of ultrasonographic abnormal findings.
... The cause of CA is multifactorial in 25% of fetuses affected, environmental pollution and exposure to ionizing radiation are also implicated while the cause is still unknown in 60%4 of cases [3][4][5]. The introduction of ultrasound for prenatal detection of CA over 5 decades ago, has seen remarkable advancement in technology and now remains an invaluable screening and diagnostic tool for congenital disorders [6,7]. Some medical and physical conditions present before or develop during pregnancy which predispose the fetus or mother to complications. ...
Introduction:
Congenital anomalies (CA) are structural or functional disorders present at birth. Routine prenatal ultrasound screening has become an indispensable tool for early detection of CA in developed countries which will facilitate appropriate preemptive actions for safe guarding the health of both mother and the unborn fetus. The prevalence of CA in the general population has been researched widely but very few studies exist on the prevalence of CA among high risk pregnancies. Aims and objective: the aim of this study was to determine the prevalence and pattern of congenital anomalies among high risk pregnant women in Ibadan, South West, Nigeria.
Methods:
this multicenter cross sectional study was conducted in three different hospitals in Ibadan, South West, Nigeria between August 2018 and July 2019. High risk pregnant women that met the inclusion criteria were recruited for the study. Participants underwent detailed fetal anomaly scans at gestational ages between 18-26 weeks during the study period using a Voluson P6 ultrasound machine (GE Healthcare Korea). Written informed consents were obtained from the participants. All the fetuses with ultrasound diagnosed congenital anomalies were followed up till either termination of pregnancy or delivery. Ethical approval was obtained for the study. The data were analyzed using SPSS.
Results:
a total of 418 high risk pregnant women underwent detailed fetal anomaly scan and CAs were detected in 13(3.1%) of them. Spontaneous abortion was the most common maternal risk factor reported although the association between it and congenital anomaly was not significant. The highest number of anomalies were detected in the genitourinary system while the least was in the central nervous system.
Conclusion:
the prevalence of high risk pregnant women is high in our environment but the incidence of CA among them is similar to that reported in the general population. Thus, prenatal ultrasonographic screening for congenital anomalies is necessary for all pregnant women irrespective of their risk status.
... 31 Microcephaly is a neurological syndrome that can be associated with other malformations and is closely related to the development of the central nervous system (CNS). 32 Its definition and clinical relevance vary among authors. 33 instance, cutoff points of head circumference measures 2 or 3 standard deviation (SD) (from the mean expected values for age and sex) have been adopted. ...
Ana Cristina Simões e Silva,1,2 Janaina Matos Moreira,1,2 Roberta Maia Castro Romanelli,2 Antonio Lucio Teixeira1,3 1Interdisciplinary Laboratory of Medical Investigation, 2Department of Pediatrics, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil; 3Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA Abstract: Before 2007, Zika virus (ZIKV) was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain–Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations. Keywords: Zika virus, microcephaly, Guillain–Barré syndrome, neurodevelopmental disorders
... The accurate diagnosis of Fmic is important in order to differentiate fetuses that will be born with an abnormally small HC and with associated developmental abnormalities from those who will be normocephalic and develop normally 12 . ...
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.
... In a recent update on a classification of malformations of cortical development by Barkovich The correct prediction of MICB based on prenatal biometry is suboptimal 19 . In our series, the established reference 8 resulted in over-diagnosis of FMIC in 43% of cases, leading to erroneous termination of 6 pregnancies with apparently normal fetuses. ...
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.
... Fetal ultrasound studies included biometry and a structured search for anomalies with particular emphasis on those characteristic of CMV infection: presence of ventriculomegaly, periventricular hyperechogenicity with or without cysts, brain calcifications, intraventricular adhesions, malformations of cortical development, callosal or cerebellar insults, brain atrophy, or hemorrhage (Malinger et al., 2003b). Multiplanar fetal neurosonography was performed using a unified protocol as previously described (Malinger et al., 2003a(Malinger et al., , 2006. The patients were initially evaluated by US examination following seroconversion and at 3-to 4-week intervals until 35-38 weeks of pregnancy. ...
We evaluated the neuropsychological outcome of children with proven congenital cytomegalovirus (CMV) infection and normal consecutive fetal neurosonographic examinations.
We retrospectively reviewed laboratory and imaging findings of children with congenital CMV infection. The study group consisted of children with a positive polymerase chain reaction (PCR) in amniotic fluid and virus isolation in urine in the first week of life, and normal fetal ultrasonographic (US) examination findings, including a normal multiplanar neurosonographic evaluation. Patients with abnormal magnetic resonance (MR) findings were not excluded. The study and control groups were evaluated for cognitive, language, and motor development at one follow-up examination conducted at 11-81 months of age.
Children with congenital CMV infection and normal fetal brain findings in the US examination did not differ from the control group in terms of cognitive, language, motor, emotional-behavioral, and executive functioning. There were no differences between congenitally infected children who had a normal fetal brain MR examination and children whose fetal brain MR examination raised suspicion of a possible brain insult.
Normal neurosonographic examinations during pregnancy appear to predict a normal early neuropsychological outcome in fetuses with congenital CMV infection. Outcome did not correlate with suspected abnormal white matter on fetal MR imaging.
... According to the OMIM (Online Mendelian Inheritance in Man) Database, there are 216 syndromes associated with macrocephaly (http://www.ncbi.nlm.nih.gov/omim). Most of them are not amenable to prenatal diagnosis 4 and, although case reports have been published 5 -30 , macrocephaly has never been assessed as a presenting sign in the fetus. ...
To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly.
We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated.
Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached.
When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign.
... Between 2001 and 2005, we followed 45 pregnant women, at the Fetal Neurology Clinic of the Wolfson Medical Center, for suspected fetal microcephaly. All patients underwent a complete ultrasound examination, followed by multiplanar fetal neurosonography performed using a unified protocol as described previously 14,15 . Eligible children of these pregnancies formed the study group. ...
To assess the neurodevelopmental outcome of children with prenatally diagnosed isolated microcephaly defined as head circumference more than 2 SD below the gestational mean.
Children aged 2-6 years who had been diagnosed in utero as having head circumference measurements more than 2 SD below the gestational mean were compared with normocephalic children, utilizing a standard neuropsychological battery. Comparisons were also made within the study group.
HCs were between -2 and -4.8 SD, only one fetus having a HC below -3 SD. Children with a prenatal head circumference between 2 SD and 3 SD below the gestational mean did not differ significantly from the control group regarding cognitive, language and motor functioning. However, they exhibited more behavioral-emotional problems. There were no significant differences between children who had suffered from intrauterine growth restriction and those who had not, or between those with familial and those with non-familial microcephaly. Nevertheless, linear regression analysis showed that head circumference in utero helps predict cognitive functioning later in life.
Prenatally diagnosed head circumference between 2 SD and 3 SD below the gestational mean is not a risk factor for later abnormal neuropsychological development.
... The most common form of macrocephaly is benign familial macrocephaly 2 -4 , which is transmitted as an autosomal dominant trait 5 . A Swedish study found isolated macrocephaly in 0.5% of the population 8 . ...
... During these 9 years, 109 patients underwent a targeted ultrasound examination in the third trimester because of suspected macrocephaly. Multiplanar fetal neurosonography was performed using a protocol described previously 5,24 and macrocephaly was diagnosed when the head circumference was greater than 2 SD for gestational age, based on the charts published by Kurmanavicius et al. 25 . ...
To evaluate the neurodevelopmental outcome of children with prenatally diagnosed head circumference greater than 2 SD above the mean for gestational age and no associated anomalies detected by ultrasound.
This was a retrospective study of 17 fetuses, diagnosed in the third trimester by ultrasound as having isolated macrocephaly, defined as head circumference greater than 2 SD above the mean for gestational age. We evaluated their performance on a standardized neuropsychological battery at age 2-7 years, and compared them with 17 normocephalic children.
The range of fetal head circumference in the study group was 2.0-2.9 SD. There were no significant differences between the groups in cognitive, language and motor domains. The study group scored significantly worse than the control group on three parameters, reflecting executive functioning, behavior and social-emotional development. Children with familial macrocephaly showed significantly better executive functioning compared with children with non-familial macrocephaly. Multiple linear regression analysis found paternal head circumference to be the only significant variable in positively predicting the cognitive functioning of the child.
The finding in utero of a head circumference 2-3 SD above the mean for gestational age with no associated anomalies does not appear to be a significant risk factor for abnormal long-term neuropsychological development. Our study provides information important for parental counseling prenatally.
