Introduction

Macrocephaly is the abnormal enlargement of the head that affects up to 5% of children.¹ It is usually diagnosed shortly after birth when head circumferences are measured and documented. Those born with a head circumference larger than the 97th centile for their sex and age (number of weeks) are diagnosed with macrocephaly, though it is not likely to be associated with the development of neurological disorders unless the head circumference measures above the 99.7th centile. Such neurological disorders include autism spectrum disorder, seizures, and, in untreated cases, increased mortality.² Macrocephaly can be and should be diagnosed during pregnancy to allow for early intervention, treatment of the underlying causes, and the prevention of the associated complications. Below, we discuss how imaging can be used to diagnose macrocephaly prenatally and its implications for the birth and developmental outcomes. 

Understanding macrocephaly

In simple terms, macrocephaly is simply the enlargement of the foetus’ head, of which there are multiple associated causes. These include:²

Hydrocephalus

Hydrocephalus is the obstruction of the flow of cerebrospinal fluid, causing it to build up in the brain, resulting in an enlarged head circumference. This needs to be monitored to prevent further complications and reduce the risk of mortality.

Neonatal brain tumours

Neonatal brain tumours can obstruct the cerebrospinal fluid, resulting in hydrocephalus and ultimately enlarging the foetus’ head.³ This highlights the importance of early diagnosis, as it allows for early intervention to prevent further complications and risk.

Genetic causes 

Some genetic diseases and syndromes can increase the head circumference, such as fragile X syndrome, which is accompanied by intellectual disability.²

High cell count in the brain

Anatomic macrocephaly is when the number of cells in the brain is higher than usual, causing the enlargement of the head. This can be inherited (familial) or benign.

Brain haemorrhage

A brain haemorrhage is bleeding in the brain, which causes the volume to increase and results in the enlargement of the head.

Imaging techniques in prenatal diagnosis of macrocephaly

Ultrasound scans (USS)

A USS uses high-frequency sound waves to produce an image, similar to sonar on a ship or submarine.⁴ It is frequently used to view the foetus during pregnancy as it is non-invasive, non-ionising, and relatively easy to use, allowing it to be safe for both the foetus and the mother. USS can be used to measure the head circumference of a foetus and therefore, be used as a diagnostic tool for macrocephaly, depending on the gestational age.⁵ However, this method of imaging does pose some limitations, particularly the accuracy of the head circumference measurements, which are dependent on the sonographer and the resolution of the images. If macrocephaly is suspected, USS is not sufficient to visualise the internal structures of the brain and investigate the potential underlying causes. As a result, other imaging techniques must be used in conjunction with the USS, such as magnetic resonance imaging (MRI).

Magnetic resonance imaging (MRI)

In brief, MRI is another non-ionising imaging tool used to diagnose macrocephaly.⁶ Essentially, it is a large magnet that spins around the body to align hydrogen ions that are abundantly present in the body. When these align, radio waves from the MRI machine are pulsed through these hydrogen ions, causing them to misalign. During periods in which the radio waves are switched off, the hydrogen ions realign and release radio waves, which are detected and interpreted by the MRI’s computer to produce a high-resolution image. 

If prenatal macrocephaly is detected in a foetus, MRI can be used for a detailed assessment of the internal brain structures and increased accuracy of head circumference measurements.⁷ This allows the clinician to have better visualisation of the brain compared to USS, which can help rule out or determine underlying causes, such as hydrocephalus, where cerebrospinal fluid movement is obstructed in one of the brain structures. 

However, using MRI prenatally does pose some limitations.⁸ These include: 

• Lack of accessibility and waiting times 
• Movement of the foetus can distort the images and reduce accuracy for diagnosis 
• Higher cost compared to USS
• A scan takes a long time to take, and some patients can find it uncomfortable or claustrophobic 

Computed tomography (CT)

In rare cases where USS or MRI are insufficient or inappropriate, CT may be used to diagnose prenatal macrocephaly. In short, CT scans create three-dimensional scans of the body by taking multiple X-rays around the body.⁹ These X-rays create cross-sectional images of an area of the body, which are then compiled together by the computer. This detailed scan enables the clinician to examine the body's structures as a whole, making it a very useful diagnostic tool. 

Unfortunately, because CT relies on multiple X-rays to be taken, it exposes the mother and foetus to radiation.¹⁰ Cautions must be taken to limit such a risk, and CTs should only be used in cases where a serious underlying cause is suspected and other non-ionising imaging methods fail. 

Clinical implications of diagnosing macrocephaly prenatally

Impact on maternal and foetal health

 A significant enlargement of the foetus’ head can cause delivery difficulties and increase the risk of a necessary cesarean section; therefore, early monitoring is needed to prepare for such a delivery.¹¹

Family impact 

If macrocephaly is diagnosed prenatally, parents and family need to be counselled on the implications, prognosis, and further testing that may be required to identify the underlying cause. For example, if a genetic cause is suspected or further imaging of a structural cause is suspected, then genetic testing will be carried out.

Postnatal follow-up 

Early detection and intervention are required to prevent developmental delay and associated brain damage. Follow-ups may be necessary to monitor any changes and manage them.¹²

Summary

• Macrocephaly is the enlargement of a child’s head, with a circumference measuring above the 97th centile 
• Causes can be structural, genetic, or anatomic 
• First-line imaging includes USS, followed by MRI or CT scans for more detailed imaging to determine the underlying cause 
• Early detection is necessary to monitor the condition, find the underlying cause, and to treat it to prevent any complications 
• Complications include birthing difficulties and developmental delays