Measuring head circumference

Definition of microcephaly

The most common definition of microcephaly is “HC that is > 2 standard deviations (SD) below the mean compared to age- and gender-matched population-based samples,”⁴ a definition supported by child neurologists,⁵ developmental pediatricians,⁶ pediatric endocrinologists, and geneticists.⁶ The term severe microcephaly is used for HC more than 3 SD below the mean.⁶ Although HC measures skull size, it typically also reflects overall brain volume^7,8 and has been described as a “widely used proxy of neural growth and brain size.”⁹ Brain size outside of normal values is an important risk factor for cognitive and motor delay.^6,10 Microcephaly at birth has been termed primary microcephaly and that acquired after birth is secondary microcephaly.⁶

Measurement and plotting of HC

Measuring occipital-frontal HC is quick and easy, involving a nonelastic tape measure and 1 to 2 minutes of a clinician’s time to measure (at least twice) and plot the measurement on the appropriate growth chart.⁶ According to MedlinePlus of the US National Library of Medicine, HC is a measure of the largest area of a child’s head or the distance around the back of the head with the tape measure held above the eyebrows and ears.¹¹ In a recent reliability study of 57 adults from the lay public and 25 mothers of typically developing children, all were provided with a measuring tape and written instructions, including a diagram, on how to measure either their own HC or that of their children.⁹ High rates of interrater reliability were reported for the lay assessors’ measurements relative to HC measurements taken by 2 trained researchers; the 95% CIs for the intraclass correlation coefficients were not statistically different between the lay groups and the researchers,⁹ thus supporting the simplicity and accuracy of HC measurements. Even in infants with positional plagiocephaly or brachycephaly, standardized HC measurements have been shown to be highly reproducible.¹²

The HC measurement should then be plotted on an age- and sex-appropriate growth chart (Box 1)^8,13–15 to determine its percentile. If HC is more than 2 SD below the mean (third centile) and similar to height and weight, it is defined as proportional microcephaly; if length and weight are well above the third centile but HC is at or below, then the term disproportionate microcephaly is used.⁶

In a population-based, longitudinal study involving 633 full-term children (level II evidence), Gale and colleagues examined the influence of head growth from birth to ages 1, 4, and 8 years on IQ at 4 and 8 years.¹⁶ Although only HC at birth (prenatal growth) and head growth at 1 year were related to later IQ in the study by Gale and colleagues,¹⁶ authors of a more recent retrospective study (level II evidence) of 680 children with microcephaly recommended that HC should be measured at birth and repeatedly throughout infancy and early childhood.⁶ This recommendation is supported by the American Academy of Pediatrics.¹⁷

In addition to measuring and plotting the child’s HC, the initial evaluation should include the child’s medical and developmental history, HC measurements for the parents, and a complete physical examination.¹⁸ One conundrum in plotting HC is which growth chart to use (Box 1).^8,13–15 The World Health Organization (WHO) charts¹⁴ were recommended for use in Canada by the Dietitians of Canada, the Canadian Paediatric Society, the College of Family Physicians of Canada, and Community Health Nurses of Canada.¹⁵ However, the WHO charts have been criticized for under-referring children at 1 year of age because the new second centile is approximately 2 cm smaller than before.¹⁹ As Baxter commented on this discrepancy: At that age a head circumference that was on the 2nd centile on the old charts would now be between the 25th and 50th centile on the new charts, or a child following the new 2nd centile would be demonstrating a marked acquired, or postnatal, microcephaly on the old charts.¹⁹

The authors of the most recent and largest study of children with microcephaly,⁶ conducted in Germany, recommended the growth charts from the US Centers for Disease Control and Prevention¹³ rather than the WHO charts because the mean occipital-frontal circumference for children in industrialized countries is larger than the standard values provided by WHO. For Canadian infants born preterm (23–37 weeks’ gestation), HC reference curves were recently published⁸ by the Canadian Neonatal Network (Box 1).^8,13–15

Causes of microcephaly

Causes of microcephaly include genetic syndromes, environmental teratogens, or structural brain anomalies. Both primary and secondary microcephaly can result from chromosomal abnormalities (eg, trisomy 13, 18, or 21), specific gene defects, intrauterine infections or teratogens, craniosynostosis, or diseases in the mother⁶; secondary microcephaly can also arise from perinatal or postnatal brain damage.⁶ According to an evidence-based review on evaluation of children with microcephaly, hundreds of different syndromes include microcephaly among their characteristics.¹⁸

In a retrospective review of 51 children with secondary (acquired) microcephaly ages 0.7 to 11.3 years (level II evidence), Baxter and colleagues classified the various causes into 5 categories: idiopathic, familial, syndromic, symptomatic, or mixed (at least 2 of the foregoing causes).²⁰

In their retrospective study of 680 children with microcephaly (level II evidence), von der Hagen et al reported that only 403 of the children (59.3%) received a presumed diagnosis of cause, as shown in the following categories: genetic or presumably genetic (28.5%), perinatal brain injury (26.8%), postnatal brain injury (1.9%), and craniosynostosis (2.1%); cause was unclear for the remaining 277 (40.7%).⁶ Among children for whom primary or secondary microcephaly could be differentiated (n = 287), 38% of cases were deemed primary and 62% were deemed secondary.⁶

Disabilities and outcomes

Children with microcephaly often present with concurrent disabilities. Because head size tends to represent brain volume, the most common associated disability is intellectual delay. In their retrospective study (level II evidence), von der Hagen et al reported that 65% of the children had been diagnosed with intellectual disability or neurodevelopmental delay.⁶ In a sample of 1393 children with developmental disabilities identified through chart review at an Israeli child developmental centre (level II evidence), Watemberg and colleagues found that 15.4% of the sample had microcephaly and, of those, 53.7% had intellectual delays ranging from borderline intelligence to severe mental retardation.¹⁰

Of 51 children with secondary (acquired) microcephaly identified in a retrospective chart review (level II evidence), Baxter and colleagues reported developmental quotient (DQ) or IQ scores for 34 children at a mean age of 4.5 years.²⁰ The median DQ or IQ was 63 for this subsample, with the idiopathic group having the highest median score (83) and the syndromic group having the lowest (45).²⁰ Although these results confirm that microcephaly predicts developmental delay overall, the authors found no significant correlation between DQ or IQ and concurrent HC z scores.²⁰

In a retrospective chart review of 312 high-risk survivors who had been cared for in a level 3 neonatal intensive care unit in Montreal (level II evidence), 38 (12.2%) were found to have microcephaly at 2 years of age and were also identified as developmentally delayed.⁷ However, the degree of microcephaly did not correlate significantly with the degree of developmental delay.⁷

In a retrospective review of 57 children with secondary microcephaly followed for an average of 4.2 years at 2 Boston medical centres (level II evidence), Rosman et al sought to determine whether growth parameters could predict developmental outcome.²¹ More than 40% of the sample (n = 24) had idiopathic microcephaly. Head circumference, body weight, and height were each significant predictors of DQ (P < .001). Developmental quotient was also significantly correlated (P < .05) with final growth measurements, but the relationship between HC and DQ was the weakest of the 3 (r = 0.13), possibly owing to the fact that 13 of the children (23% of the sample) had DQs that were within normal limits despite being microcephalic.²¹

Finnish researchers conducted a prospective, longitudinal study of 1056 healthy children born at term (level II evidence).²² Measures of weight, length, and HC were collected at 5, 20, and 56 months of age and compared with scores on cognitive tests at 56 months. For each SD below the mean in HC at birth, the children showed cognitive scores that were 1.31 points lower, thus supporting a relationship between putative congenital brain size and later development even in those without frank microcephaly.²²

In summary, there is a clear predictive relationship between HC at birth and developmental outcomes on standardized tests, but the absolute correlation between the 2 is relatively weak and sometimes non-significant (a finding which could relate to the small sample sizes in most of the studies).

Another common clinical finding in children with microcephaly is epilepsy. Of the 215 children with microcephaly in the Israeli study, 28.3% also had epilepsy; other associated diagnoses included cerebral palsy (21.4%), language delay (33%), and strabismus (22.3%).¹⁰ In the most recent and largest study of children with microcephaly in Germany, 43% presented with epilepsy. Other comorbidities included ophthalmologic disorders (30%), cardiac anomalies (14%), and renal, urinary tract, and skeletal anomalies (13% to 14% each), leading the study authors to emphasize the need for an interdisciplinary approach to microcephaly.⁶

Interventions for children with microcephaly

Although there are no specific interventions to enhance brain growth, secondary microcephaly can be prevented in some conditions, eg, through dietary interventions in infants with phenylketonuria at birth²³ or through surgical release of sutures for craniosynostosis in infants before 1 year of age.²⁴ For infants born with microcephaly due to inadequate maternal nutrition, enhanced postnatal nutrition has been postulated to account for increased HC.²⁵ Infants with microcephaly who show developmental delays might benefit from early intervention programs or developmental physical and occupational therapy. Such programs, as well as interdisciplinary management by various medical specialists, have been recommended for children with conditions that often include microcephaly (eg, congenital cytomegalovirus infection,²⁶ autism spectrum disorder,²⁷ de Lange syndrome²⁸). Although not specific to infants and young children with microcephaly, a systematic review (level I evidence) of the effects of early intervention showed that specific developmental motor training programs positively influenced infant motor development.²⁹ In a pretest-posttest study of early language intervention for 455 children from birth to 3 years of age with suspected speech or language delay (level II evidence), the 6-month intervention resulted in statistically significant (P < .001) improvements in language quotient; about 20% of these children had microcephaly.³⁰