Importance of Neuroimaging in Infants with Microcephaly
3Global Newborn Society (https://www.globalnewbornsociety.org/)
Corresponding Author: Sabrina Rangwani, Department of Radiology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, United States of America, Phone: +832 824 7237, e-mail: firstname.lastname@example.org
How to cite this article: Rangwani S, Orman G, Mhanna M. Importance of Neuroimaging in Infants with Microcephaly. Newborn 2023;2(2):148–157.
Source of support: Nil
Conflict of interest: Dr Akhil Maheshwari is associated as Editor-in-Chief of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of the Editor-in-Chief and his research group.
Dr Thierry AGM Huisman is associated as the Editorial Board member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this editorial board member and his research group.
Received on: 07 June 2023; Accepted on: 30 June 2023; Published on: 30 June 2023
Microcephaly is diagnosed in infants and children with a head circumference (HC) 2 standard deviations less than average, accounting for age and gender. There is not a standard method of diagnosis, as growth charts vary by country and methodology used. The most popular method of diagnosis is the use of a tape to measure a child’s head. There are various conundrums that affect diagnoses: volume of the brain, deformities in skull shape that affect size measurements, and the etiology of microcephaly. The size of the skull is not the most important factor in diagnosing microcephaly, but rather the volume of the brain. Finally, a distinction between primary and secondary microcephaly must be made; primary microcephaly develops prenatally, and secondary microcephaly develops postnatally. The effects of primary microcephaly are generally more severe, but through imaging, it can be detected before birth. This article analyzes various conditions in which neuroimaging can add considerable information to current methods of clinical evaluation. There is a clear need for a multifaceted approach.
Keywords: Aminoacylase-2, Apert, Brain volume, Brain volume loss, Canavan’s disease, Cavum septum pellucidum, child abuse, Crouzon, cytomegalovirus, Ex vacuo enlargement of ventricles, Head circumference, Meckel-Gruber syndrome, Melting brain, near-drowning, Neuroimaging, Skull deformities, Thalami, TORCH, Toxoplasma gondii, Trisomy 13, Trisomy 18, Trisomy 21, Twin-to-twin transfusion syndrome, Vein of Galen aneurysmal malformation, Zika virus, Zika.
Microcephaly is diagnosed in infants and children with a head circumference (HC) 2 standard deviations less than average, accounting for age and gender.
There are various conundrums that affect diagnoses: volume of the brain, deformities in skull shape that affect size measurements, and the etiology of microcephaly.
A distinction between primary and secondary microcephaly must be made; primary microcephaly develops prenatally, and secondary microcephaly develops postnatally.
This article analyzes various conditions in which neuroimaging can add considerable information to current methods of clinical evaluation. There is a need for a multifaceted approach.
Microcephaly in infants and children is defined as a head circumference (HC) 2 standard deviations (SD) below the mean compared with age and gender-matched healthy population.1–5 Severe microcephaly refers to a HC more than 3 SD below the mean, whereas proportional microcephaly is characterized by HC, height, and weight scalars that are simultaneously 2–3 SD below the mean.6–10 It is generally acknowledged that HC is correlated to overall brain volume; however, there are many confounding factors that may offer alternatives to this claim.6,11–14 The HC measures the size of the skull which may be normal, while the brain volume is too small for age.12,15,16 For example, global brain volume loss with co-existing ex vacuo ventriculomegaly may be accompanied by a normal skull size.9,17–20 An additional limiting factor using the HC as an indicator of microcephaly is that currently no global standards or guidelines exist on using HC growth charts.21–23 Depending on the included normal population, various growth charts exist.24–28 As such, determining microcephaly requires a careful selection of the correct growth charts.25,29,30
Microcephaly can be primary, related to a genetic or unknown cause, or secondary, which is obviously related to another illness.2,3,31–34 Furthermore, the evolution of the HC over time should also be considered.14,35 Neuroimaging plays a vital role in the diagnostic workup of suspected microcephaly.36–38 CT and MRI allow qualitative and quantitative evaluation of the brain.39–41 Combining the data of the HC and neuroimaging findings is essential for adequate diagnosis.42–43 Neuroimaging should assist to differentiate between microcephaly secondary to a brain malformation, disruption or destruction.43–45 The goal of this paper is to outline the basic aspects of diagnosing microcephaly as well as various anatomical imaging findings that may result in a normal HC measurement while the brain is overall too small in volume. Every (neuro-) radiologist should be familiar with these pitfalls.
Primary microcephaly is usually noticeable at birth, indicating an onset in utero. In contrast, secondary microcephaly is acquired postnatally.7,36 There are many etiologies for both causes of microcephaly, which are addressed in the Etiology section of this review.
Prenatally, HC is typically measured with ultrasound studies.46–52 Using the axial image of the brain at the level of thalami and cavum septum pellucidum, a circular or ovoid curser is placed around the skull to mimic postnatal HC measurement techniques.53–55 Bi-parietal diameter, as well as other biomarkers, such as the femur length and abdominal circumference, should also be measured to differentiate between an isolated microcephaly versus a proportional microcephaly due to intrauterine growth retardation.56–61
Postnatally, HC is first evaluated clinically through cross-sectional and longitudinal measurements.6,62 The measuring tape is wrapped around the widest possible circumference of the child’s head in an axial plane above the eyebrow and above the ears including the most prominent part of the back of the head.62 Typically, the measurement is done three times and the largest measurement is selected.63 Temporal evolution of HC is critical and serial HC measurements can be useful if there are concerns such as progressing neurologic deficits.35,64,65 Infants with microcephaly often present with developmental and intellectual disability, epilepsy, cerebral palsy, language delay, strabismus.66–68 However, microcephaly may be just one manifestation of a multisystem disorder; cardiac anomalies, renal, urinary tract, and skeletal anomalies may accompany microcephaly.6,69–74 Consequently, microcephaly requires a full diagnostic workup to exclude additional organ involvement, or multisystem syndromes.
Correct and relevant evaluation of microcephaly can be more challenging than initial impressions. Several misleading conundrums or pitfalls exist of which the (neuro-) radiologist should be aware. The very first conundrum is that there are variations between country-specific growth charts, possibly due to different cultural, socioeconomic or health standards impacting growth or the average height and weight of various age groups in a certain country.21,75–78 The large ranges of “normal” growth parameters (Figs 1 and 2) may result in an infant being diagnosed to have microcephaly in one, but not in a neighboring country.8
A second conundrum is that the size/volume of the brain is much more important than the size of the skull, but external measurements only measure the size/circumference of the skull.80,81 Imaging in important because even though the HC usually correlates well with the brain volume, there are situations in which slower brain growth leaves “extra space” within the skull.80 Acquired pediatric brain volume loss following accidents such as near-drowning may present with a normal HC with ex vacuo enlargement of the ventricles, subarachnoid spaces, and brain sulci.82 These infants may show widened diploic spaces of the skull on follow-up. Some may also show progressive enlargement of the paranasal sinuses including that of the mastoid air-cell complex, reactive to the brain volume loss.83 The severity of these manifestations might vary based on age, gender, and ethnicity (Fig. 3). Neuroimaging is essential to identify these pitfalls of a normal HC measurement despite global brain volume loss.84 Serial imaging and HC measurements beyond the time of an apparent acute injury will increase diagnostic accuracy.85 Correlation with the clinical history is equally important. An infant with a high-grade hydrocephalus secondary to aqueductal stenosis may initially present with an enlarged HC.86 After ventriculo-peritoneal shunting, the ventricles may decompress, typically resulting in a decreasing or normalizing HC.87 The measured HC may however underestimate possible brain volume loss. Long-standing hydrocephalus may impair normal brain development and/or result in irreversible brain injury.88 The HC may pseudonormalize, or in some cases, the HC remains unchanged/increased due to reactive skull thickening.89,90
An additional conundrum seen in many syndromes/systemic diseases is in deformities that alter the shape of the skull, resulting in skewed HC measurements and overdiagnosis of microcephaly.7 Various syndromic cranio-synostoses, such as Apert or Crouzon syndrome present with a significant skull deformity due to premature closure of skull sutures.91,92 In these infants, clinical assessment may need to be supported by appropriate neuroimaging.93,94
A final conundrum to be recognized is that the overall volume of the brain may not always correlate with neurocognitive and senso-motor functionality.95,96 For instance, in Canavan’s disease, a rare and fatal autosomal recessive degenerative CNS disorder caused by deficiency of aminoacylase-2, infants and young children typically present with an enlarged HC due to a significant increased overall brain volume.97 However, a few cases might present with microcephaly.96 Most patients present with intellectual disability, loss of previously acquired motor skills, feeding difficulties, hypotonia, spasticity, paralysis, blindness, and seizures.97
Etiology-related Conundrum: Microcephaly due to Malformation, Disruption/Deformation, or Destruction
Primary microcephaly can be seen in the setting of a prenatal brain malformation, brain disruption/deformation, or brain destruction. Familiarity with these three different etiologies is important for correct diagnosis, determining treatment options, predicting outcome, and counseling of the parents and families including recurrence risk for future pregnancies.
Primary, congenital brain malformation refers to an anomalous or abnormal brain development which may be an isolated occurrence such as agenesis of the corpus callosum or secondary to a chromosomal disorder as in Joubert syndrome. Such findings could also be one of the manifestations in a multisystem condition such as Aicardi syndrome. Brain disruption/deformation sequence refers to a process where exposure to toxin(s) as in intrauterine alcohol exposure or in inborn error(s) of metabolism, infections, such as ToRCH (toxoplasmosis, others, rubella, cytomegalovirus (CMV), and herpes simplex, and now including Zika virus infections), or an ischemic/hemorrhagic (thrombo-embolic) event, interferes with the normal brain development. The timing of the event is often more impactful than the intrinsic nature of the injury; the earlier the event occurs during gestation, the more severe might be the resultant brain disruption/deformation sequence at delivery (Fig. 4). In contrast to the “programmed” brain malformation, in the setting of a brain disruption/deformation sequence the brain had the potential to be normally developed. However, many developmental abnormalities may arise in altered neuronal migration, cortical organization, sulcation/gyration, and myelination. In these infants, brain malformations are usually evident at birth. Brain destruction refers to a process where initially normally developed brain is injured/destructed due to an acute event like a focal hemorrhage or ischemia. Congenital microcephaly may be seen in all the settings of brain malformation, brain disruption/deformation sequences, as well as in brain destruction. It is essential for physicians to be familiar with these different qualities and etiologies of microcephaly.
The (neuro-)radiologist should recognize and describe the additional findings that may be seen in children with microcephaly. Focal or diffuse migrational abnormalities, ventriculomegaly, cerebellar dysplasia/hypoplasia, abnormal or delayed myelination, white and gray matter calcifications and white matter gliosis may exist. The combination of findings assists narrowing down the differential diagnosis.
There are many causes of microcephaly. Primary (genetic) microcephaly is believed to result from early exhaustion of the neuronal precursors or accelerated apoptosis.1 Imaging of the brains of those with primary microcephaly typically show a simplified gyral pattern, shallow sulci, and/or delayed, or impaired myelination. The cortical ribbon is typically of normal thickness with a normal internal laminar organization, the corpus callosum may be thin, and the brain may be hypoplastic but is typically completely formed. Genetic syndromes, including chromosomal abnormalities, are a common etiology of microcephaly. This category includes trisomy 13, 18, and 21. There is often a more severe prognosis in those who develop microcephaly due to a chromosomal abnormality.36
Etiologies of Congenital Microcephaly
Congenital infectious microcephaly is often viral (cytomegalovirus, CMV), whereas postnatal microcephaly is more frequently due to a bacterial infection (Fig. 5). Cytomegalovirus infections occurring during early gestation result in white matter loss, ventriculomegaly, cortical anomalies, and microcephaly. Cytomegalovirus infections seen during later pregnancy cause microcephaly less frequently but may still cause many of the aforementioned anomalies. Microcephaly is infrequent in infants who acquire CMV infections during later pregnancy, but many infants may still develop ventriculomegaly. Cytomegalovirus has an affinity for the germinal matrix; intrauterine infections are associated with cortical abnormalities and periventricular calcification. Many patients also show acute and chronic vasculitis, which may cause brain injury due to ischemia.
Intrauterine infections or exposure to teratogens are frequently associated with adverse prognosis. Many maternal diseases have been identified as important causes of microcephaly. Neurotropic infectious agents, such as Zika and TORCH viruses, CMV, rubella, and Toxoplasma gondii, have all been linked with congenital microcephaly. In mothers with phenylketonuria who have high serum levels of phenylalanine, the amino acid may be transmitted to the fetus and at high levels, may act as a teratogen. In other cases, maternal infections may be vertically transmitted to the fetus and cause neural tissue destruction that progresses to calcification.98 Vertical transmission of the Zika virus can result in global white matter volume loss, a matching small-sized skull, and cortical or central gray matter calcifications. In these fetuses who are infected in utero, there may be evidence of overlapping/simultaneous disruptive and destructive processes. These neurotropic infections result in extensive damage in the fetal central nervous system (CNS), particularly if the infection occurs during the first or second trimester. There may also be disruption of subsequent brain development.
Microcephaly may also be seen in other conditions. For instance, infants who developed twin-to-twin transfusion syndrome (TTTS) in utero can show severe microcephaly (Fig. 6).99 In TTTS, identical twins who shared a placenta (monochorionic-diamniotic pregnancy) may develop injuries due to multiple placental arterio-arterial, arteriovenous, and veno-venous connections.100,101 These connections disrupt the normal balance of fetal perfusion and blood volumes. In symptomatic TTTS, a “donor” twin shunts/pumps blood to the other “recipient” twin.102 Due to the excessive blood volume, the recipient twin may develop progressive heart failure while the donor twin remains small for gestational age.103 Progressive brain injury may result in severe destructive microcephaly.104 In other infants, microcephaly may also result from progressive heart failure in fetuses with a Vein of Galen aneurysmal malformation (VGAM).105 The combination of fetal heart failure, systemic and cerebral venous congestion, steal phenomena, and hydrocephalus results in progressive white and gray matter injury which explains the microcephaly. This process is also known as “melting brain.”106 Placental insufficiency, either due to a too small placenta, chorioamnionitis, placental infarctions, or placenta dehiscence with subsequent fetal hypoperfusion or thromboembolic processes are also linked to fetal and neonatal microcephaly.107–110
Infants who develop perinatal hypoxic-ischemic injury usually do not have microcephaly in the perinatal period, but they may show progressive brain volume loss during follow-up.111,112 Similarly, infants who have had to suffer from diffuse brain injury related to child abuse (Fig. 7), near-drowning, trauma, or inborn errors of metabolism with accumulating neurotoxins may develop microcephaly due to arrested brain growth within the first few years.68,113–116
Finally, congenital meningoencephaloceles can also be associated with microcephaly.117 These are embryonic development abnormalities, characterized by a sac-like protrusion of the brain, meninges, and other intracranial structures through the skull. Nearly 75% of encephaloceles are occipital118 (Fig. 8). These malformations can be seen as isolated or be seen as a part of multisystem conditions, such as the Meckel-Gruber syndrome.119–121
Microcephaly refers to a HC measuring less than 2 SD below average and may be secondary to multiple etiologies, including malformation, disruption/deformation sequence, destruction, and idiopathic forms of microcephaly. Microcephaly may become apparent during a physical exam and the first step is to get a good/reliable HC measurement and then follow-up measurements for temporal evolution. HC has typically been recognized as an indirect marker of brain size. However, a normal HC does not exclude microcephaly. Neuroimaging is essential for correct diagnosis and may reveal anatomical findings that are causative of normal HC measurements. Measuring the HC is not sufficient and may underestimate the degree of microcephaly due to the various conundrums discussed in this paper. The size of the brain is much more important than the size of the skull. There are multiple factors that must be considered in the diagnosis of microcephaly, including but not limited to, primary vs secondary, congenital vs acquired, malformation vs disruption vs destruction. The differential diagnosis list is broad and there are multiple etiologies. Lastly, a multidisciplinary approach is the key to timely diagnosis and appropriate management.
2. von der Hagen M, Pivarcsi M, Liebe J, et al. Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature. Dev Med Child Neurol 2014;56(8):732–741. DOI: 10.1111/dmcn.12425.
3. Opitz JM, Holt MC. Microcephaly: General considerations and aids to nosology. J Craniofac Genet Dev Biol 1990;10(2):175–204. PMID: 2211965.
5. Asif M, Abdullah U, Nurnberg P, Tinschert S, Hussain MS. Congenital microcephaly: a debate on diagnostic challenges and etiological paradigm of the shift from isolated/non-syndromic to syndromic microcephaly. Cells 2023;12(4). DOI: 10.3390/cells12040642.
6. Harris SR. Measuring head circumference: update on infant microcephaly. Can Fam Physician 2015;61(8):680–684. PMID: 26505062.
7. DeSilva M, Munoz FM, Sell E, et al. Congenital microcephaly: case definition and guidelines for data collection, analysis, and presentation of safety data after maternal immunisation. Vaccine 2017;35(48 Pt A):6472–6482. DOI: 10.1016/j.vaccine.2017.01.044.
8. Shen S, Xiao W, Zhang L, et al. Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks. BMC Pregnancy Childbirth 17 2021;21(1):214. DOI: 10.1186/s12884-021-03705-9.
9. Apostolova LG, Babakchanian S, Hwang KS, et al. Ventricular enlargement and its clinical correlates in the imaging cohort from the ADCS MCI donepezil/vitamin E study. Alzheimer Dis Assoc Disord 2013;27(2):174–181. DOI: 10.1097/WAD.0b013e3182677b3d.
11. Kawasaki Y, Yoshida T, Matsui M, et al. Clinical factors that affect the relationship between head circumference and brain volume in very-low-birth-weight infants. J Neuroimaging 2019;29(1):104–110. DOI: 10.1111/jon.12558.
12. Treit S, Zhou D, Chudley AE, et al. Relationships between head circumference, brain volume and cognition in children with prenatal alcohol exposure. PLoS One 2016;11(2):e0150370. DOI: 10.1371/journal.pone.0150370.
13. Lee JJ, McGue M, Iacono WG, et al. The causal influence of brain size on human intelligence: evidence from within-family phenotypic associations and GWAS modeling. Intelligence 2019;75:48–58. DOI: 10.1016/j.intell.2019.01.011.
14. Martini M, Klausing A, Luchters G, et al. Head circumference – a useful single parameter for skull volume development in cranial growth analysis? Head Face Med 2018;14(1):3. DOI: 10.1186/s13005-017-0159-8.
15. Bartholomeusz HH, Courchesne E, Karns CM. Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults. Neuropediatrics 2002;33(5):239–241. DOI: 10.1055/s-2002-36735.
16. Cheong JL, Hunt RW, Anderson PJ, et al. Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome. Pediatrics 2008;121(6):e1534–1540. DOI: 10.1542/peds.2007–2671.
17. Oyedeji GA, Olamijulo SK, Osinaike AI, et al. Head circumference of rural Nigerian children--the effect of malnutrition on brain growth. Cent Afr J Med 1997;43(9):264–268. PMID: 9509647.
18. Catena A, Martinez-Zaldivar C, Diaz-Piedra C, et al. On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood. Br J Nutr 2019;122(s1):S40–S48. DOI: 10.1017/S0007114516004281.
19. Kim M, Park SW, Lee JY, et al. Differences in brain morphology between hydrocephalus ex vacuo and idiopathic normal pressure hydrocephalus. Psychiatry Investig 2021;18(7):628–635. DOI: 10.30773/pi.2020.0352.
20. Kitagaki H, Mori E, Ishii K, et al. CSF spaces in idiopathic normal pressure hydrocephalus: morphology and volumetry. AJNR Am J Neuroradiol 1998;19(7):1277–1284. PMID: 9726467.
22. Perez-Bermejo M, Alcala-Davalos L, Perez-Murillo J, et al. Are the growth standards of the World Health Organization valid for Spanish Children? The SONEV study. Front Pediatr 2021;9:700748. DOI: 10.3389/fped.2021.700748.
23. Souza AI, de Siqueira MT, Ferreira A, et al. Geography of microcephaly in the Zika Era: a study of newborn distribution and socio-environmental indicators in Recife, Brazil, 2015–2016. Public Health Rep 2018;133(4):461–471. DOI: 10.1177/0033354918777256.
25. Group WHOMGRS. Assessment of differences in linear growth among populations in the WHO multicentre growth reference study. Acta Paediatr Suppl 2006;450:56–65. DOI: 10.1111/j.1651-2227.2006.tb02376.x.
29. Boghossian NS, Horbar JD, Murray JC, et al. Anthropometric charts for infants with trisomies 21, 18, or 13 born between 22 weeks gestation and term: the VON charts. Am J Med Genet A 2012;158A(2):322–332. DOI: 10.1002/ajmg.a.34423.
30. Bertozzi A, Gazeta RE, Fajardo TCG, et al. Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study. J Pediatr (Rio J) 2021; 97(4):433–439.DOI: 10.1016/j.jped.2020.08.010.
31. Boonsawat P, Joset P, Steindl K, et al. Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly. Genet Med 2019;21(9):2043–2058. DOI: 10.1038/s41436-019-0464-7.
34. Tavasoli AR, Memar EHE, Ashrafi MR, et al. Primary and secondary microcephaly, global developmental delay, and seizure in two siblings caused by a novel missense variant in the ZNF335 gene. J Mol Neurosci 2022;72(4):719–729. DOI: 10.1007/s12031-021-01955-y.
35. Dupont C, Castellanos-Ryan N, Seguin JR, et al. The predictive value of head circumference growth during the first year of life on early child traits. Sci Rep 2018;8(1):9828. DOI: 10.1038/s41598-018-28165-8.
37. ML CL, Carvalho AL, Ventura PA, et al. Clinical, neuroimaging, and neurophysiological findings in children with microcephaly related to congenital Zika virus infection. Int J Environ Res Public Health 2019;16(3). DOI: 10.3390/ijerph16030309.
40. Oishi K, Faria AV, Yoshida S, et al. Quantitative evaluation of brain development using anatomical MRI and diffusion tensor imaging. Int J Dev Neurosci 2013;31(7):512–524. DOI: 10.1016/j.ijdevneu.2013.06.004.
42. Emerson RW, Adams C, Nishino T, et al. Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age. Sci Transl Med 2017;9(393): eaag2882. DOI: 10.1126/scitranslmed.aag2882.
43. Ashwal S, Michelson D, Plawner L, et al. Practice parameter: Evaluation of the child with microcephaly (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2009;73(11):887–897. DOI: 10.1212/WNL.0b013e3181b783f7.
45. Russell LJ, Weaver DD, Bull MJ, et al. In utero brain destruction resulting in collapse of the fetal skull, microcephaly, scalp rugae, and neurologic impairment: the fetal brain disruption sequence. Am J Med Genet 1984;17(2):509–521. DOI: 10.1002/ajmg.1320170213.
47. Yang C, Yang Z, Liao S, et al. A new approach to automatic measure fetal head circumference in ultrasound images using convolutional neural networks. Comput Biol Med 2022;147:105801. DOI: 10.1016/j.compbiomed.2022.105801.
48. Zeng W, Luo J, Cheng J, et al. Efficient fetal ultrasound image segmentation for automatic head circumference measurement using a lightweight deep convolutional neural network. Med Phys 2022;49(8):5081–5092. DOI: 10.1002/mp.15700.
49. Wang X, Wang W, Cai X. Automatic measurement of fetal head circumference using a novel GCN-assisted deep convolutional network. Comput Biol Med 2022;145:105515. DOI: 10.1016/j.compbiomed.2022.105515.
50. Zeng Y, Tsui PH, Wu W, et al. Ultrasound image segmentation for automatic head circumference biometry using deeply supervised attention-gated V-Net. J Digit Imaging 2021; 34(1):134–148.DOI: 10.1007/s10278-020-00410-5.
52. Li P, Zhao H, Liu P, Cao F. Automated measurement network for accurate segmentation and parameter modification in fetal head ultrasound images. Med Biol Eng Comput 2020; 58(11):2879–2892.DOI: 10.1007/s11517-020-02242-5.
53. Falco P, Gabrielli S, Visentin A, et al. Transabdominal sonography of the cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy. Ultrasound Obstet Gynecol 2000;16(6):549–553. DOI: 10.1046/j.1469-0705.2000.00244.x.
54. Serhatlioglu S, Kocakoc E, Kiris A, et al. Sonographic measurement of the fetal cerebellum, cisterna magna, and cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy. J Clin Ultrasound 2003;31(4):194–200. DOI: 10.1002/jcu.10163.
55. Tao G, Lu G, Zhan X, et al. Sonographic appearance of the cavum septum pellucidum et vergae in normal fetuses in the second and third trimesters of pregnancy. J Clin Ultrasound 2013; 41(9):525–531.DOI: 10.1002/jcu.22084.
56. Ashrafunnessa, Jehan AH, Chowdhury SB, et al. Construction of fetal charts for biparietal diameter, fetal abdominal circumference and femur length in Bangladeshi population. Bangladesh Med Res Counc Bull 2003;29(2):67–77. PMID: 14674622.
57. Dubiel M, Krajewski M, Pietryga M, et al. Fetal biometry between 20–42 weeks of gestation for Polish population. Ginekol Pol 2008;79(11):746–753. PMID: 19140496.
58. Leung TN, Pang MW, Daljit SS, et al. Fetal biometry in ethnic Chinese: biparietal diameter, head circumference, abdominal circumference and femur length. Ultrasound Obstet Gynecol. Mar 2008; 31(3):321–327.DOI: 10.1002/uog.5192.
59. Sherer DM, Sokolovski M, Dalloul M, et al. Nomograms of the axial fetal cerebellar hemisphere circumference and area throughout gestation. Ultrasound Obstet Gynecol 2007;29(1):32–37. DOI: 10.1002/uog.3879.
60. Johnsen SL, Wilsgaard T, Rasmussen S, et al. Longitudinal reference charts for growth of the fetal head, abdomen and femur. Eur J Obstet Gynecol Reprod Biol 2006;127(2):172–185. DOI: 10.1016/j.ejogrb.2005.10.004.
61. Zaliunas B, Jakaite V, Kurmanavicius J, et al. Reference values of fetal ultrasound biometry: results of a prospective cohort study in Lithuania. Arch Gynecol Obstet 2022;306(5):1503–1517. DOI: 10.1007/s00404-022-06437-z.
62. Terrin G, De Nardo MC, Boscarino G, et al. Early protein intake influences neonatal brain measurements in preterms: an observational study. Front Neurol 2020;11:885. DOI: 10.3389/fneur.2020.00885.
63. Casadei K, Kiel J. Anthropometric Measurement. StatPearls Publishing; 2022. In: StatPearls [internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2022 Sep 6. PMID: 30726000.
65. Bouthoorn SH, van Lenthe FJ, Hokken-Koelega AC, et al. Head circumference of infants born to mothers with different educational levels; the Generation R Study. PLoS One. 2012;7(6):e39798. DOI: 10.1371/journal.pone.0039798.
71. Picker-Minh S, Mignot C, Doummar D, et al. Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD. Orphanet J Rare Dis 2016;11(1):52. DOI: 10.1186/s13023-016-0433-z.
73. Magini P, Smits DJ, Vandervore L, et al. Loss of SMPD4 causes a developmental disorder characterized by microcephaly and congenital arthrogryposis. Am J Hum Genet 3 2019;105(4):689–705. DOI: 10.1016/j.ajhg.2019.08.006.
74. Chograni M, Alkuraya FS, Maazoul F, et al. RGS6: a novel gene associated with congenital cataract, mental retardation, and microcephaly in a Tunisian family. Invest Ophthalmol Vis Sci 18 2014;56(2):1261–1266. DOI: 10.1167/iovs.14-15198.
75. Bonthuis M, van Stralen KJ, Verrina E, et al. Use of national and international growth charts for studying height in European children: development of up-to-date European height-for-age charts. PLoS One. 2012;7(8):e42506. DOI: 10.1371/journal.pone.0042506.
76. Yang Z, Duan Y, Ma G, et al. Comparison of the China growth charts with the WHO growth standards in assessing malnutrition of children. BMJ Open 25 2015;5(2):e006107. DOI: 10.1136/bmjopen-2014-006107.
77. Elaabsi M, Loukid M, Lamtali S. Socio-economic and cultural determinants of mothers and fathers for low birth weight newborns in the region of Marrakech (Morocco): a case-control study. PLoS One 2022;17(6):e0269832. DOI: 10.1371/journal.pone.0269832.
78. Morisaki N, Kawachi I, Oken E, et al. Social and anthropometric factors explaining racial/ethnical differences in birth weight in the United States. Sci Rep 21 2017;7:46657. DOI: 10.1038/srep46657.
80. Lindley AA, Benson JE, Grimes C, 3rd edition, et al,Herman AA. The relationship in neonates between clinically measured head circumference and brain volume estimated from head CT-scans. Early Hum Dev 1999; 56(1):17–29.DOI: 10.1016/s0378-3782(99)00033-x.
81. Miyabayashi H, Nagano N, Kato R, et al. Reference values for cranial morphology based on three-dimensional scan analysis in 1-month-old healthy infants in Japan. Neurol Med Chir (Tokyo) 15 2022;62(5):246–253. DOI: 10.2176/jns-nmc.2021-0384.
84. Wang S, Fan P, Xiong D, et al. Assessment of neonatal brain volume and growth at different postmenstrual ages by conventional MRI. Medicine (Baltimore) 2018;97(31):e11633. DOI: 10.1097/MD.0000000000011633.
85. Parikh NA, Lasky RE, Kennedy KA, et al. Perinatal factors and regional brain volume abnormalities at term in a cohort of extremely low birth weight infants. PLoS One. 2013;8(5):e62804. DOI: 10.1371/journal.pone.0062804.
86. Xian Z, Fung SH, Nakawah MO. Obstructive hydrocephalus due to aqueductal stenosis from developmental venous anomaly draining bilateral medial thalami: a case report. Radiol Case Rep 2020;15(6):730–732. DOI: 10.1016/j.radcr.2020.02.014.
89. Nigri F, Gobbi GN, da Costa Ferreira Pinto PH, et al. Hydrocephalus caused by unilateral foramen of Monro obstruction: a review on terminology. Surg Neurol Int 2016;7(Suppl 12):S307–S313. DOI: 10.4103/2152-7806.182392.
90. Lucey BP, March GP Jr., Hutchins GM. Marked calvarial thickening and dural changes following chronic ventricular shunting for shaken baby syndrome. Arch Pathol Lab Med 2003;127(1):94–97. DOI: 10.5858/2003-127-94-MCTADC.
92. Kabbani H, Raghuveer TS. Craniosynostosis. Am Fam Physician 2004;69(12):2863–2870. PMID: 15222651.
96. Zhou Y, Muller HG, Zhu C, et al. Network evolution of regional brain volumes in young children reflects neurocognitive scores and mother’s education. Sci Rep 20 2023;13(1):2984. DOI: 10.1038/s41598-023-29797-1.
97. Bokhari MR, Samanta D, Bokhari SRA. Canavan Disease. StatPearls. 2022. In: StatPearls [internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2022 Sep 6. PMID: 28613566.
98. Frenkel LD, Gomez F, Sabahi F. The pathogenesis of microcephaly resulting from congenital infections: why is my baby’s head so small? Eur J Clin Microbiol Infect Dis 2018;37(2):209–226. DOI: 10.1007/s10096-017-3111-8.
99. Borse V, Shanks AL. Twin-To-Twin Transfusion Syndrome. StatPearls. 2022. [updated 2022 Oct 10]. In: StatPearls [internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from https://www.ncbi.nlm.nih.gov/books/NBK563133
100. Lewi L. Monochorionic diamniotic twin pregnancies pregnancy outcome, risk stratification and lessons learnt from placental examination. Verh K Acad Geneeskd Belg. 2010;72(1–2):5–15. PMID: 20726437.
103. Bhat R. Twin to twin transfusion syndrome. Kathmandu Univ Med J (KUMJ). 2010;8(29):87–90. PMID: 21209514.
104. Spruijt MS, Lopriore E, Tan R, et al. Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome: is there still room for improvement? J Clin Med 2019; 8(8):1226. DOI: 10.3390/jcm8081226.
105. Li TG, Zhang YY, Nie F, et al. Diagnosis of foetal vein of galen aneurysmal malformation by ultrasound combined with magnetic resonance imaging: a case series. BMC Med Imaging 2020;20(1):63. DOI: 10.1186/s12880-020-00463-6.
107. Mir IN, Johnson-Welch SF, Nelson DB, et al. Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia. Am J Obstet Gynecol 2015;213(6):849 e1–7. DOI: 10.1016/j.ajog.2015.09.072.
109. McElrath TF, Allred EN, Kuban K, et al. Factors associated with small head circumference at birth among infants born before the 28th week. Am J Obstet Gynecol 2010;203(2):138 e1–e8. DOI: 10.1016/j.ajog.2010.05.006.
110. Leibovitz Z, Shiran C, Haratz K, et al. Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero. Ultrasound Obstet Gynecol 2016;47(5):593–599. DOI: 10.1002/uog.15886.
111. Mercuri E, Ricci D, Cowan FM, et al. Head growth in infants with hypoxic-ischemic encephalopathy: correlation with neonatal magnetic resonance imaging. Pediatrics 2000;106(2 Pt 1):235–243. DOI: 10.1542/peds.106.2.235.
112. Cordes I, Roland EH, Lupton BA, et al. Early prediction of the development of microcephaly after hypoxic-ischemic encephalopathy in the full-term newborn. Pediatrics 1994;93(5):703–707. PMID: 8165065.
117. Naidich TP, Altman NR, Braffman BH, et al. Cephaloceles and related malformations. AJNR Am J Neuroradiol 1992;13(2):655–690. PMID: 1566723.
120. Fraser FC, Lytwyn A. Spectrum of anomalies in the Meckel syndrome, or: “Maybe there is a malformation syndrome with at least one constant anomaly”. Am J Med Genet 1981;9(1):67–73. DOI: 10.1002/ajmg.1320090112.
121. Markovic I, Bosnjakovic P, Milenkovic Z. Occipital encephalocele: cause, incidence, neuroimaging and surgical management. Curr Pediatr Rev. 2020;16(3):200–205. DOI: 10.2174/1573396315666191018161535.
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.