Journal of Perinatology (2009) 29, 201–204
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ORIGINAL ARTICLE
Fetal macrocrania: diagnosis, delivery and outcomes
MR Laye1, BC Moore2, MA Kosek3, LK Bufkin4, JC Morrison4 and JA Bofill4
1
Regional Maternal-Fetal Medicine, Spartanburg Regional Medical Center, Spartanburg, SC, USA; 2Department of Obstetrics and
Gynecology, The University of Tennessee College of Medicine Chattanooga, Chattanooga, TN, USA; 3Division of Neonatology,
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA and 4Division of Maternal-Fetal Medicine,
Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA
Objective: To describe fetal macrocrania including prenatal diagnosis,
delivery considerations and clinical outcomes.
Study Design: A retrospective case series was developed by reviewing
26 885 ultrasounds performed between 1 March 2003 and 30 June 2007
for the prenatal diagnosis of macrocrania. Medical records of each
mother/infant pair were reviewed for demographic information,
ultrasound findings, obstetric management and outcomes.
Result: Twenty-three fetuses were diagnosed with macrocrania. Median
gestational age at diagnosis was 31.1 weeks (range 18.3–38.1) and at
delivery was 36.9 weeks (range 30.7–39.9). Fifteen patients (65%)
underwent amniocentesis for karyotype; none were aneuploid but one had
a duplication on chromosome 7. All the 23 infants were liveborn. Twenty-
one deliveries were by Cesarean (91%), with thirteen of these by classical
incision (62%). Of the infants, 5 (22%) died shortly after birth, 16 (70%)
were stabilized in the neonatal intensive care unit and were discharged
alive and 2 (8%) were transferred to another center and subsequently
died. Eighteen babies required ventriculoperitoneal shunting (78%).
Conclusion: Macrocrania is a diagnosis usually made in children but
can also be made prenatally. Fetal macrocrania is usually a result of
ventriculomegaly due to an obstructive process to cerebrospinal fluid flow.
Abdominal delivery is usually required, often necessitating a classical
uterine incision. Targeted ultrasonography, extensive counseling of
parents and delivery at a tertiary care center with availability of
neurosurgery is recommended.
Journal of Perinatology (2009) 29, 201–204; doi:10.1038/jp.2008.196;
published online 4 December 2008
Keywords: prenatal diagnosis; ultrasound; anomaly; ventriculomegaly
Introduction
Terms used to describe a large head are often used interchangeably.
However, this is incorrect because the different terms represent
Correspondence: Dr MR Laye, Regional Maternal-Fetal Medicine, 853 North Church Street,
Suite 610, Spartanburg, SC 29303, USA.
E-mail: m_ryan_laye@hotmail.com
Received 1 June 2008; revised 21 October 2008; accepted 24 October 2008; published online
4 December 2008
different entities. Making the distinction is important because use of
the correct term may yield information about the underlying process
causing the clinical finding, and may confer information about
prognosis and/or management. Macrocrania is defined as an
abnormal increase in the size of the skull, with the facial area being
disproportionately small in comparison. In contrast, macrocephaly
is excessive size of the whole head, whereas megalencephaly
represents overgrowth of the brain.1
Macrocrania is a term rarely encountered in obstetrics or
prenatal diagnosis but is a very common diagnosis in pediatrics
and in radiology, affecting up to 5% of pediatric patients.2
Unfortunately, diagnostic criteria are inconsistent. A review of the
literature on the topic shows criteria that are both objective and
subjective. Objective measures are inconsistent from study to study
and include children with a head circumference >95th–98th
percentile for age, disproportionate head size compared with body
length and weight, and rapidly enlarging head circumference on
serial measurements.3,4 The descriptors ‘disproportionate’ and
‘rapidly enlarging’ are not well defined. A large-appearing head by
observation is an example of a subjective measure.4
In the pediatric population, macrocrania is most commonly due
to abnormal fluid collections in the head.3 These most commonly
include abnormalities in the ventricular system of the central
nervous system (ventriculomegaly) or external hydrocephalus
(abnormal fluid collection in the subarachnoid space with normal
cerebral ventricles).2 When ventriculomegaly is noted, this is most
often due to obstruction in the flow of cerebrospinal fluid, such as
is seen with stenosis or atresia of the aqueduct of Sylvius.4 Other
differential diagnostic considerations when macrocrania is
encountered include space occupying lesions such as tumors,
hemorrhages, large arachnoid cysts and myelomeningoceles.2,5
It has long been advocated that children considered to have
macrocrania be evaluated with imaging studies to determine the
need for surgical versus nonsurgical management.2,6 Which
modality to use is the subject of some debate. The classic way to
evaluate children with macrocrania was to use ventriculography
and cerebral angiography. Due to the desire to avoid these invasive
tests in children, these were limited to only the most severe cases.
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The introduction of computed tomography (CT) permitted outpacing the other biometric parameters by greater than or
noninvasive evaluation of these cases, allowing those with lesser equal to 4 weeks size.
degrees of head enlargement to be included.3 Cranial ultrasound (2) Fetal head size greater than would likely be successfully
has since been shown to correlate well with CT, with no significant delivered vaginally as evidenced by a biparietal diameter of
abnormality missed using this modality. This, coupled with the greater than or equal to 11 cm (given that a completely dilated
desire to avoid ionizing radiation in children, led to cranial cervix is usually 10 cm).
ultrasonography being advocated as a first line method of imaging
the head in pediatrics.4 CT or magnetic resonance imaging is now
used in cases that are unclear, finer discrimination is needed, or Results
for imaging the external subarachnoid spaces.6 A total of 26 885 ultrasound studies were reviewed and 23 fetuses
Given the frequency of ultrasonography during pregnancy and diagnosed with macrocrania were identified. None were lost to
that evaluation of the head and intracranial contents is a part of each follow-up and all deliveries were at our institution. The
targeted sonogram, many of the same diagnoses made in children demographics of this cohort are summarized in Table 1. Fifteen
with macrocrania should be made in the fetus. The paucity of patients (65%) underwent genetic amniocentesis; none were
information in the obstetric literature regarding the prenatal diagnosis aneuploid but one had a duplication on chromosome 7. All the 23
of macrocrania, the associated obstetric management and outcomes is fetuses were liveborn. Continuous variables regarding infant birth
striking. Accordingly, we created this retrospective case series at our data are summarized in Table 2. Fifteen infants (65%) were male.
tertiary referral center so that we could better counsel patients and
referring physicians when a fetus with an abnormally large head is Table 1 Demographic variables of patients diagnosed with macrocrania
encountered on ultrasound. Our main interests included Demographic variable Median result (range)
demographics of patients whose fetuses were diagnosed with
macrocrania, obstetric management and delivery considerations in Maternal age 23 years (15–36)
Gravidity 2 (1–7)
these pregnancies and outcomes including duration of stay in the
Parity 1 (0–4)
neonatal intensive care unit (NICU), need for surgery shortly after
Gestational age at diagnosis 31.1 weeks (18.3–38.1)
delivery and ultimate survival. Gestational age at delivery 36.9 weeks (30.7–39.9)

Methods Table 2 Infant birth data of patients diagnosed with macrocrania

The Institutional Review Board of the University of Mississippi
Variable Median result (range)
Medical Center (UMC), the primary perinatal referral center for the
state of Mississippi, approved this retrospective review of deidentified Birth weight 3308 g (2230–4305)
data (IRB File no. 2007–0016). Sonographers, maternal–fetal APGAR at 5 min 9 (2–9)
medicine fellows and attending physicians performed all Head circumference 42.5 cm (35.5–59)
ultrasounds in the Antenatal Diagnostic Unit at UMC. Ultrasound
studies performed during a 52-month period from March 2003 to
June 2007 were reviewed and those cases in which the prenatal Table 3 Underlying causes of macrocrania by diagnosis
diagnosis of macrocrania was suspected were identified. This was Diagnosis Number of infants
followed by a review of both maternal and neonatal medical (% of all infants)
records. Demographic variables, fetal information including
diagnoses, obstetric management including amniocentesis and Stenosis/atresia of the aqueduct of Sylvius 10 (43.5)
results, timing and mode of delivery and neonatal data including Meningomyelocele 3 (13.0)
survival were recorded for each mother/infant pair. VATER anomalad 3 (13.0)
Communicating hydrocephalus 1 (4.3)
Diagnostic criteria were based on those used for children after
Hydranencephaly 1 (4.3)
birth. However, choosing a particular percentile above which we
Dandy–Walker defect 1 (4.3)
could make the diagnosis would have been arbitrary given the
Goldenhar syndrome 1 (4.3)
discrepancies by different authors in the pediatric literature as Pseudoporencephaly 1 (4.3)
described above. Therefore, we considered a fetus to have Intracranial hemorrhage 1 (4.3)
macrocrania if either or both of the following were met: Agenesis of corpus callosum and interhemispheric cyst 1 (4.3)
(1) A rapidly enlarging head as evidenced by the head
Total 23 (B100)
measurements (head circumference and biparietal diameter)

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Twenty-one deliveries were by Cesarean (91%), with thirteen of
these by classical uterine incision (62%). Of the infants, 5 (22%)
died shortly after birth, 16 (70%) were stabilized in the NICU with
subsequent discharge and 2 (8%) were transferred to another
center and subsequently died. Median length of stay in the NICU
was 21 days (range 3–101). Eighteen babies (78%) required
ventriculoperitoneal shunting; the median day of life for this
procedure was day 2 (range 1–20).
The underlying causes of the macrocrania encountered on
prenatal sonography are listed in Table 3. All diagnoses were
Table 4 Summary of ultrasound findings, diagnoses, outcomes, and NICU length of stay (LOS) for each patient. The diagnoses in parentheses were made after delivery
and were not documented antepartum
confirmed after delivery by appropriate imaging, consultation and
autopsy where appropriate. A patient-by-patient summary of
ultrasound findings, diagnoses (before and after delivery),
outcomes and length of NICU stay can be seen in Table 4.
Discussion
This case series documents our experience with fetal
macrocrania, and to our knowledge is the first to specifically
describe the diagnosis prenatally. Therefore, our data may be

Pt no. Ultrasound findings Diagnoses Outcome NICU LOS

(days)

1 Midline falx, no neural tissue above brainstem Hydranencephaly Died 4

2 Dilation of lateral and third ventricles Aqueductal stenosis Survived 21
3 Dilation of lateral and third ventricles Aqueductal stenosis Survived 7
4 Dilation of lateral and third ventricles Aqueductal stenosis (VATER anomalad: Transferred, Died 15
imperforate anus,
tracheal stenosis, single kidney, hemivertebrae)
5 Dilation of lateral and third ventricles, posterior fossa cyst, Dandy–Walker malformation, (ear tags, Survived 50
single umbilical artery perimembranous VSD)
6 Dilated lateral and third ventricles, polyhydramnios Aqueductal stenosis, (periauricular skin tags, Survived 20
truncus arteriosus)
7 Dilated lateral and third ventricles Aqueductal stenosis (Goldenhar syndrome: Survived 45
left anotia, right microtia, hypertelorism,
cleft palate)
8 Absence of CSP, intrahemishperic cyst, hypertelorism, absent clavicles Agenesis of the corpus callosum, Survived 4
intrahemispheric cyst, (pachygyria)
9 Unilateral absence of brain parenchyma extending to skull table Pseudoporencephaly Survived 22
10 Dilation of lateral and third ventricles Aqueductal stenosis Survived 13
11 Dilated lateral and third ventricles, cleft lip and palate, single umbilical artery, VATER anomalad (imperforate anus, Died 27
hemivertebrae, clenched right hand ambiguous genitalia)
12 Dilated lateral and third ventricles, thoracolumbar ONTD Meningomyelocele Survived 34
13 Dilated lateral and third ventricles Aqueductal stenosis Survived 44
14 Disorganized intracranial tissue, visible clot and fibrin stranding in skull Intracranial hemorrhage Died 4
15 Dilated lateral and third ventricles Aquedutal stenosis Survived 13
16 Dilated lateral and third ventricles, dilated loops of small bowel, ventricular Aqueductal stenosis, jejunal atresia, Died 23
septal defect, polyhydramios (interrupted aortic arch)
17 Dilated lateral and third ventricles, lumbosacral ONTD, talipes Meningomyelocele Survived 31
equinovarus deformity
18 Dilation of lateral and third ventricles, polyhydramnios Aqueductal stenosis Survived 50
19 Dilation of lateral and third ventricles, hypoplastic cerebellum Aqueductal stenosis Survived 21
20 Dilation of lateral and third ventricles, lumbosacral ONTD Meningomyelocele Survived 19
21 Dilated lateral and third ventricles, esophageal atresia, hemivertebrae, VATER anomalad, Died 101
bifid great toe, pulmonary hypoplasia, preaxial polydactyly, (tracheoesophageal fisulta)
malformed tibia and fibula on right, ventriculoseptal defect, short ribs
22 Dilated lateral and third ventricles Aqueductal stenosis Survived 22
23 Tetraventricular dilation, polyhydramnios, micrognathia, atriventricular Communicating hydrocephalus, Transferred, died 3
septal defect, hypoplastic left ventricle AV canal defect,
(coarctation of aorta, interrupted IVC)
Abbreviations: AV, atrioventricular; IVC, inferior vena cava; NICU, neonatal intensive care unit;ONTD, open neural tube defect; VSD, ventricular septal defect.

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204
useful in counseling patients and detailing physicians on what to
expect once the diagnosis is made. However, our data must be
viewed in light of what has been reported in infants after birth.
Our median gestational age at diagnosis (31.1 weeks) is
somewhat later than expected. However, in our study the most
frequent cause of macrocrania was stenosis/atresia of the aqueduct
of Sylvius. This leads to progressive ventriculomegaly and although
the diagnosis of ventriculomegaly can be made earlier in gestation,
the diagnosis of macrocrania is only possible after weeks or months
when the ventriculomegaly has become severe enough to cause
marked expansion of the fetal head.
The median gestational age at delivery (36.9 weeks) is more a
reflection of the management of these patients than the natural
history of infants with macrocrania. Management of prenatal
patients with suspected fetal macrocrania at the University of
Mississippi includes observation with monthly scans to follow the
size of the head and amniocentesis at 37 weeks followed by delivery
if lung maturity is documented. This strategy allows for patients
from our fairly rural state to deliver at a tertiary institution. Indeed,
70% of infants (16/23) in this series underwent amniocentesis for
fetal lung maturity, whereas the other 30% had preterm labor or an
indicated preterm delivery before undergoing the amniocentesis as
planned.
The underlying diagnoses leading to fetal macrocrania in this
series were similar to that recorded in pediatric populations. Donat
reported in 1981 that hydrocephalus from ventriculomegaly is the
leading cause of macrocrania in children,3 and the current case
series echoes this finding. Babcock et al. reported in 1988 that in
infants with macrocrania, 5 of 11 (45.5%) infants with
significantly abnormal findings on cranial sonography had
aqueductal stenosis.4 This is very similar to the 43.5% incidence of
aqueductal stenosis reported in this series.
We noted a majority of male fetuses diagnosed with
macrocrania. Our 65% male predominance is very close that
previously reported in children. Medina reported 59 of 88 (67%)
children diagnosed with macrocrania were male,2 whereas Donat
reported 53 of 72 (73.6%) children were male.3 This might be
explained by the high number of diagnoses of aqueductal stenosis,
which is known to have an X-linked form.
Ventriculoperitoneal shunting was required in this series in 78%
of infants. However, this is much higher than expected, based on
pediatric literature. Medina et al. reported in 2001 that only 18% of
children with macrocrania required surgical treatment.2 This
marked difference is likely due to worse ventriculomegaly in those
infants diagnosed prenatally. Further, some of the infants shunted
in this series did not survive and therefore may not have been
included in pediatric investigations.
There were no intrauterine fetal demises. However, our overall
survival rate with prenatally diagnosed macrocrania was only 70%.
This reflects the diagnoses made underlying the macrocrania and
will vary from case to case. For example, all three of the infants
Journal of Perinatology
with the VATER anomalad and the infant with hydranencephaly
died shortly after birth but all cases with isolated aqueductal
stenosis survived. Long-term outcomes for survivors will also
vary based upon the underlying diagnoses and are a potential
further course of investigation. The pediatric literature reflects that
infants do well if the macrocrania is due to external hydrocephalus
or mild ventriculomegaly.2,4,6,7 However, when moderate to
severe ventriculomegaly is noted, especially when associated with
cerebral atrophy, outcomes are poor. Bosnjak et al. reported
only 2 of 20 patients with cerebral atrophy were neurologically
normal at presentation and in most cases the initial abnormal
finding persisted at follow-up.6 Babcock et al. reported that
19% of term infants and 25% of preterm infants with
macrocrania were neurologically or developmentally abnormal
on follow-up that ranged from 1 month to 5 years.4 The diagnosis
of macrocrania has also been linked to epilepsy and autistic
disorders.8
In summary, the diagnosis of macrocrania is possible
prenatally. Fetal macrocrania is usually a result of
ventriculomegaly due to an obstructive process to cerebrospinal
fluid flow. Suspicion for macrocrania necessitates a targeted
sonographic evaluation by personnel experienced in prenatal
diagnosis to evaluate for the underlying pathology leading to the
macrocrania. This allows extensive counseling of parents,
arrangements for delivery at a tertiary care center with availability
of neurosurgery, and evaluation for mode of delivery. Abdominal
delivery is usually required, often necessitating a classical uterine
incision.
Acknowledgments
No financial support was obtained for this study.
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