Intended for healthcare professionals

Practice Clinical updates

Fetal microcephaly

BMJ 2018; 361 doi: (Published 04 June 2018) Cite this as: BMJ 2018;361:k2232
  1. Aamod Nawathe, subspecialty trainee in fetal maternal medicine1,
  2. Jane Doherty, general practitioner2,
  3. Pranav Pandya, consultant and lead in fetal medicine1
  1. 1Fetal Maternal Medicine, University College London Medical School, London WC1E 6BT, UK
  2. 2Nexus Health Group, London SE1 6JP
  1. Correspondence to: P Pandya pranavpandya{at}

What you need to know

  • Fetal microcephaly can be isolated or be associated with other congenital anomalies

  • Causes include genetic, chromosomal, infections, exposure to toxins (such as alcohol), metabolic, intrauterine growth restriction, or a normal variant

  • The consequences of microcephaly can include neurodevelopmental delay, cerebral palsy, epilepsy, and problems with eyesight and hearing

  • There is no treatment that can reverse the effects of microcephaly in utero

  • Advise women diagnosed with primary toxoplasmosis or cytomegalovirus infection to wait for at least six months before conception

Fetal microcephaly, a small head circumference in utero or at birth is a rare but important clinical finding that may occur as part of a range of conditions or, rarely, as a normal variant. The prevalence of prenatal microcephaly in Europe is 1.53 per 10 000,1 2.3 per 10 000 in India,2 and about 6 per 10 000 in the US.3 Identifying microcephaly is important because the smaller the fetal head circumference the greater the risk of developmental and intellectual delay.4

Although there is no treatment available, early diagnosis allows for timely investigations, as well as allowing parents to receive appropriate counselling about long term prognosis. This update discusses the diagnosis and management of fetal microcephaly, and is aimed at obstetricians, midwives, and general practitioners.

Sources and selection criteria

We searched PubMed and the Cochrane Library using the MESH term “microcephaly” and subheadings such as Zika virus, preconception counselling, prenatal diagnosis, toxoplasmosis, and cytomegalovirus. Our search included randomised controlled trials, systematic and observational reviews and relevant case reports from 1965 to 2017. We excluded non-English articles without reliable translation or other internet sources of uncertain accuracy.

What is fetal microcephaly?

Microcephaly is a head circumference significantly smaller than the average for the gestational age (fig 1).6 Fetal microcephaly has been defined as head circumference smaller than 3 standard deviations below the mean.78

Fig 1
Fig 1

Range of microcephaly. (Adapted from Centers for Disease Control and Prevention5)

Making a prenatal diagnosis of microcephaly can be challenging for several reasons, including uncertain gestational age, lack of customised charts to account for factors such as ethnicity, and, of course, the absence of a routine third trimester scan.9 Prospective observational studies have shown that ultrasound measurements themselves are subject to intra-observer and inter-observer variations,1011 so the diagnosis may not be made until after birth.

What are the causes of fetal microcephaly?

Microcephaly may be identified as part of a range of heterogenous conditions including genetic or chromosomal disorders, infection, exposure to toxins such as alcohol, metabolic errors, intrauterine growth restriction, or, rarely, a normal variant (see box 1). Fetal microcephaly can be an isolated finding or may be associated with other anomalies. The underlying aetiology can be confirmed in just over half of cases, and this figure may increase with advances in genetic testing such as exome sequencing.13

Box 1

Causes of microcephaly (adapted from Pilu et al12)

Microcephaly with associated malformations

  • Chromosomal or genetic

    • Chromosomal—Trisomy 13, trisomy 18, trisomy 21

    • Single gene defects—Meckel-Gruber syndrome, Smith-Lemli-Opitz syndrome, Bloom syndrome, Nijmegen breakage syndrome, De Lange syndrome

  • Environmental

    • Intrauterine growth restriction

    • Prenatal infections—Toxoplasmosis, cytomegalovirus, Zika virus, HIV

    • Prenatal exposure to drugs—Fetal alcohol syndrome, fetal hydantoin syndrome

    • Inborn errors of metabolism—Maternal phenylketonuria syndrome

  • Unknown aetiology

Microcephaly without associated malformations

  • Genetic—Autosomal recessive primary microcephaly, Paine syndrome, Alpers disease

  • Environmental—Maternal malnutrition, hypoxia

  • Unknown aetiology


What are the consequences of fetal microcephaly?

Up to 55% of human brain comprises of cerebral cortex, and most neurones are generated by 21 weeks of gestation.14 Fetal microcephaly is therefore likely to be associated with a relatively smaller cerebral cortex with fewer neurones, thus making head circumference a proxy marker of neural growth.1415161718 The consequences of microcephaly, as shown by longitudinal observational studies, include neurodevelopmental delay or impairment in other areas of development such as gross motor, visual-motor, language, and epilepsy.1519 Therefore, infants with microcephaly are at risk of long term morbidity such as epilepsy and developmental delay.20 Furthermore observational studies have shown a correlation between the severity of microcephaly and severity of mental retardation.421

How is it diagnosed?

Figure 2 outlines how specialists might approach investigation and management of fetal microcephaly in a tertiary centre.

Fig 2
Fig 2

Suggested approach to further investigation and management of fetal microcephaly based on expert opinion22


During routine antenatal care note whether the woman has a history that might increase the risk of fetal microcephaly, such as drug use, alcohol consumption, known chromosomal or genetic syndrome, or travel to areas with high prevalence of Zika virus (such as Brazil) while pregnant or within eight weeks before conception. Most cases of fetal microcephaly are detected by routine ultrasound examination at 18-20 weeks or on a subsequent scan.23 In these circumstances refer women to a fetal medicine unit to take a detailed history and for further ultrasound assessment and appropriate investigations.

Further investigations

Ultrasound—A detailed ultrasound scan is the first line investigation to confirm the diagnosis and identify other fetal anomalies such as ventriculomegaly.24 Specific ultrasound markers of congenital infection include ventriculomegaly, echodense areas suggestive of calcifications, and growth restriction.

Blood tests—When a congenital anomaly is suspected, maternal blood is then taken to screen for infections such as toxoplasmosis or cytomegalovirus. If clinical infection with Zika virus is suspected then Zika serology testing is offered four weeks after return from an area where Zika fever is endemic. Screening for maternal infections such as toxoplasmosis or cytomegalovirus by testing for antibodies such as IgG, IgM and the IgG avidity (which measures the strength of binding of IgG to the virus antigen) can help in differentiating a recent from an old infection.2526

Amniocentesis—The woman is usually also offered an amniocentesis to make a diagnosis of a chromosomal abnormality (such as Down’s syndrome), a specific genetic syndrome (as recommended by a clinical geneticist), and for direct analysis of infectious pathogens if there is a suspicion on maternal serology (such as cytomegalovirus or Toxoplasma).252728 Further tests to investigate inborn errors of metabolism are needed if an underlying genetic abnormality is suspected as suggested by a retrospective study.13

If the microcephaly is “isolated” (no other anomalies seen with no evidence of infection) then offer serial ultrasound scans every four weeks to monitor changes in fetal biometry and intracranial structures. Fetal magnetic resonance imaging (MRI) on the brain is an adjunct to ultrasound and can provide further information about brain development.29

How is fetal microcephaly managed?

During pregnancy

If drug or alcohol misuse is suspected, involve the safeguarding team and offer support to reduce or stop alcohol or drug use.

Refer women with fetal microcephaly to a tertiary fetal medicine centre with a multidisciplinary team that includes a fetal medicine expert, virologist, neonatologist, neuroradiologist, and a geneticist to counsel depending on the suspected underlying aetiology.

Microcephaly, either isolated or with other anomalies, is associated with significantly increased risk of neurodisability, and, after appropriate counselling by the multidisciplinary team, termination of pregnancy may be discussed as an option with the parents. If the parents continue the pregnancy, offer appropriate guidance from the multidisciplinary team, which may include contacting a specific charity or support group (see “Information for patients” box).

Options for delivery

Discussing options for delivery with parents needs to be tailored to the underlying cause. Vaginal delivery is usually recommended unless there are obstetric contraindications such as placenta praevia.30

What is the prognosis and postnatal follow-up?

The prognosis for a fetus with microcephaly could range from normal development to a wide range of neurodisability depending on factors such as severity of the microcephaly, and the underlying cause (box 1).

A retrospective study found a lack of data on how to counsel parents when isolated microcephaly is detected incidentally in the third trimester with no other abnormalities.31 Although fetal MRI is offered in the presence of other malformations,2932 sometimes even a combination of MRI and an ultrasound scan is not helpful in counselling parents about the prognosis.33 In a large retrospective study evaluating 680 cases of postnatal microcephaly, 29% of cases had an underlying genetic cause.13 Although the outcomes for patients with non-isolated microcephaly varied widely, neurodevelopmental delay, intellectual disability, and refractory epilepsy were the most common reasons for referral to specialist paediatric services for further assessment.13 A few studies have tried to investigate the correlation between neurodevelopmental delay and isolated microcephaly but with conflicting results. One study showed the risk of neurodevelopmental delay to be 10.5% when head circumference is between two and three standard deviations below the mean,4 while others showed no significant difference.3435

Although fetal brain growth cannot be altered, some interventions carried out postnatally may help prevent the progression of microcephaly in certain conditions. For example, dietary interventions in infants diagnosed with phenylketonuria36 or enhancing postnatal nutrition if microcephaly is due to inadequate maternal nutrition37 can enhance head circumference, as shown in a retrospective study of 193 growth restricted children. A review of the literature has shown that infants with microcephaly due to congenital cytomegalovirus infection or syndromes such as de Lange syndrome may benefit from early interventional programmes and occupational therapy.3839

What is the risk of microcephaly in a subsequent pregnancy?

The risk in a subsequent pregnancy depends on the underlying cause, and counselling needs to be individualised accordingly. If the underlying cause is autosomal dominant then the risk of recurrence is 1:2 (50%) if one of the parents is affected and 1:4 (25%) if the pattern is autosomal recessive. The risk of microcephaly due to past infection is minimal.

Postnatal counselling

When counselling women postnatally, take into account the gestational age at onset of microcephaly, any antenatal insult such as intracranial haemorrhage, any syndromic features, and any family history of microcephaly.40 Depending on the circumstances, you may need to involve a clinical geneticist, virologist, or specialist in paediatric infectious diseases. Although there are no robust data, it is advisable to wait for six months before conceiving if primary congenital infection with Toxoplasma or cytomegalovirus is confirmed.2541

Information for patients

Education into practice

  • To what extent does this article increase your confidence in assessing risk factors for fetal microcephaly when seeing a pregnant woman at her booking visit?

  • How might you offer counselling to a woman who had a diagnosis of fetal microcephaly in a previous pregnancy? What might you do differently as a result of reading this article?

  • Do you follow up babies diagnosed with fetal microcephaly antenatally to confirm the prenatal diagnosis and monitor the neonatal outome?

How patients were involved in the creation of this article

Patient involvement was not possible as we were unable to find a patient who was willing to share their experiences due to the sensitive nature of the topic


  • Contributors: AN did the literature search and wrote the paper. PP verified and revised the paper. He is the guarantor. JD added inputs from a primary care level.

  • Competing interests: We have read and understood BMJ policy on declaration of interests and have no competing interests to declare.

  • Provenance and peer review: Commissioned; externally peer reviewed.