Developmental Correlates of Head Circumference at Birth and Two Years in a Cohort of Extremely Low Gestational Age Newborns

doi:10.1016/j.jpeds.2009.04.002

The Journal of Pediatrics

Volume 155, Issue 3, September 2009, Pages 344-349.e3

https://doi.org/10.1016/j.jpeds.2009.04.002 Get rights and content

Objectives

To evaluate the developmental correlates of microcephaly evident at birth and at 2 years in a cohort born at extremely low gestational age.

Methods

We assessed development and motor function at 2 years of 958 children born before the 28th week of gestation, comparing those who had microcephaly at birth or 2 years with children with normal head circumference while considering the contribution of neonatal cranial ultrasound lesions.

Results

A total of 11% of infants in our sample had microcephaly at 2 years. Microcephaly at 2 years, but not at birth, predicts severe motor and cognitive impairments at 2 years. A total of 71% of children with congenital microcephaly had a normal head circumference at 2 years and had neurodevelopmental outcomes comparable with those with normal head circumference at birth and 2 years. Among children with microcephaly at 2 years, more than half had a Mental Developmental Index <70, and nearly a third had cerebral palsy. The risks were increased if the child also had cerebral white matter damage on a cranial ultrasound scan obtained 2 years previously.

Conclusion

Among extremely low gestational age newborns, microcephaly at 2 years, but not at birth, is associated with motor and cognitive impairment at age 2.

Section snippets

Methods

The ELGAN study was designed to identify characteristics and exposures that increase the risk of structural and functional neurologic disorders in ELGANs. During the years 2002–2004, women delivering before 28 weeks gestation at 14 participating institutions in 11 cities in 5 states were asked to enroll in the study. The enrollment and consent processes were approved by the individual institutional review boards.

Mothers were approached for consent either on antenatal admission or shortly after

Results

The head circumferences at birth and at 24 months appear to be shifted modestly to the left of the normal distribution, with an overrepresentation of children whose head circumference is more than 2 SD below the expected mean, or Z-score < −2 (microcephaly). A total of 10% of infants in our sample had a birth head circumference Z-score < −2, and 10% had a head circumference Z-score at 2 years that was < −2. If the head circumference measure had a normal Gaussian distribution, 2.3% would have a

Discussion

This large-scale, prospective study of ELGANs used algorithms to define CP diagnoses and considered brain ultrasound lesions in evaluating the risk of CP and cognitive impairment at 2 years associated with head circumference at birth and at 2 years. We report 3 novel findings. First, 71% of infants born with congenital microcephaly no longer were considered to have microcephaly at age 2 years. Second, congenital microcephaly is not a risk factor for CP or cognitive impairment unless the

References (40)

R.W. Cooke et al.
Head circumference as an index of brain weight in the fetus and newborn
Early Hum Dev
(1977)
B. Latal-Hajnal et al.
Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome
J Pediatr
(2003)
C. Bardin et al.
Outcome at 5 years of age of SGA and AGA infants born less than 28 weeks of gestation
Semin Perinatol
(2004)
C. Wocadlo et al.
Developmental outcome at 12 months corrected age for infants born less than 30 weeks gestation: influence of reduced intrauterine and postnatal growth
Early Hum Dev
(1994)
P.L. Yudkin et al.
New birth weight and head circumference centiles for gestational ages 24 to 42 weeks
Early Hum Dev
(1987)
E. Kan et al.
The association of growth impairment with neurodevelopmental outcome at eight years of age in very preterm children
Early Hum Dev
(2008)
A. Leviton et al.
Methodologic issues in epidemiologic studies of congenital microcephaly
Early Hum Dev
(2002)
K.H. Marks et al.
Head growth in sick premature infants—a longitudinal study
J Pediatr
(1979)
J. Peterson et al.
Subnormal head circumference in very low birth weight children: neonatal correlates and school-age consequences
Early Hum Dev
(2006)
E.F. Maalouf et al.
Magnetic resonance imaging of the brain in a cohort of extremely preterm infants
J Pediatr
(1999)

V. Bhushan et al.

The reliability of neonatal head circumference measurement

J Clin Epidemiol

(1991)

M. Hack et al.

Differential effects of intrauterine and postnatal brain growth failure in infants of very low birth weight

Am J Dis Child

(1989)

C.R. Gale et al.

Critical periods of brain growth and cognitive function in children

Brain

(2004)

C.R. Gale et al.

The influence of head growth in fetal life, infancy, and childhood on intelligence at the ages of 4 and 8 years

Pediatrics

(2006)

J.L. Cheong et al.

Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome

Pediatrics

(2008)

T.E. Inder et al.

Abnormal cerebral structure is present at term in premature infants

Pediatrics

(2005)

C. Dorman

Microcephaly and intelligence

Dev Med Child Neurol

(1991)

K. Kuban et al.

Positive screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in extremely low gestational age newborns

J Pediatr

(2009)

K.C. Kuban et al.

An algorithm for identifying and classifying cerebral palsy in young children

J Pediatr

(2008)

K. Kuban et al.

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

J Child Neurol

(2005)

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Extreme prematurity: Risk and resiliency
2022, Current Problems in Pediatric and Adolescent Health Care
Individuals born extremely preterm (before 28 weeks of gestation) comprise only about 0.7% of births in the United States and an even lower proportion in other high resource countries. However, these individuals account for a disproportionate number of children with cerebral palsy, intellectual deficit, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy. This review describes two large multiple center cohorts comprised of individuals born extremely preterm: the EPICURE cohort, recruited 1995 in the United Kingdom and the Republic of Ireland, and the Extremely Low Gestational Age Newborn (ELGAN), recruited 2002–2004 in five states in the United States. The primary focus of these studies has been neurodevelopmental disorders, but also of interest are growth, respiratory illness, and parent- and self-reported global health and well-being. Both of these studies indicate that among individuals born extremely preterm the risks of most neurodevelopmental disorders are increased. Early life factors that contribute to this risk include perinatal brain damage, some of which can be identified using neonatal head ultrasound, bronchopulmonary dysplasia, and neonatal systemic inflammation. Prenatal factors, particularly the family's socioeconomic position, also appear to contribute to risk. For most adverse outcomes, the risk is higher in males. Young adults born extremely preterm who have neurodevelopmental impairment, as compared to those without such impairment, rate their quality of life lower. However, young adults born extremely preterm who do not have neurodevelopmental impairments rate their quality of life as being similar to that of young adults born at term. Finally, we summarize the current state of interventions designed to improve the life course of extremely premature infants, with particular focus on efforts to prevent premature birth and on postnatal efforts to prevent adverse neurodevelopmental outcomes
Head circumference in infants undergoing Foker process for long-gap esophageal atresia repair: Call for attention
2021, Journal of Pediatric Surgery
We extended our pilot study in infants following long-gap esophageal atresia (LGEA) repair to report head circumference, an easily obtainable indirect measure of brain size. Data are presented in the context of previously reported body weight and T2-weighted MRI measures of intracranial and brain volumes.
Clinical information and head circumference were obtained for term-born (n = 13) and premature (n = 13) infants following LGEA repair with Foker process, as well as healthy term-born controls (n = 20) <1-year corrected age who underwent non-sedated research MRI. General Linear Model univariate analysis with corrected age at scan as a covariate and Bonferroni adjusted p values assessed group differences.
We report no difference in head circumference between the three groups. Such findings paralleled trends in body weight and total intracranial volume but not in brain volume as previously reported for the same pilot cohort.
Results suggest uncompromised somatic and head growth after repair of LGEA. In contrast, a novel finding of discrepancy between head circumference (novel data) and brain size (previously published data) in the same cohort suggests that head circumference might not be the best indirect measure of brain size in selected group of patients.
Prediction of neurodevelopment in preterm infants: From the neonatal intensive care unit into adulthood
2021, Diagnosis, Management and Modeling of Neurodevelopmental Disorders: The Neuroscience of Development
Prematurity is a chronic condition with consequences extending from birth into adulthood. Risk factors for neurodevelopmental impairment in preterm babies include gender, gestational age, and birth weight. However, direct effects of prematurity can be modified by subsequent experiences and postnatal environmental factors determining long-term cognitive and academic outcomes. Most studies that focus on prediction of neurodevelopment at 2 years of age use neurological examination, general movements, serial and term-age neuroimaging (brain sonography and magnetic resonance), and other tools with variable accuracy of results. The majority of preterms survive with only mild to moderate disability, with lower intelligence quotients and impaired executive functions, working and visual memory, and social skills. Neurodevelopment at school age in preterms is likely to affect multiple domains and is associated with lower school grades, primarily in math, language, and physical education. Adolescent and adulthood implications of prematurity are not fully determined and include a higher risk of psychiatric and behavioral disorders, as well as metabolic conditions.
Establishing a conceptual framework of the impact of placental malaria on infant neurodevelopment
2019, International Journal of Infectious Diseases
A novel conceptual framework to describe the relationship between placental malaria and adverse infant neurodevelopmental outcomes is proposed. This conceptual framework includes three distinct stages: (1) maternal and environmental risk factors for the development of placental malaria; (2) placental pathology and inflammation associated with placental malaria infection; and (3) postnatal impacts of placental malaria. The direct, indirect, and bidirectional effects of these risk factors on infant neurodevelopment across the three stages were critically examined. These factors ultimately culminate in an infant phenotype that not only leads to adverse birth outcomes, but also to increased risks of neurological, cognitive, and behavioural deficits that may impact the quality of life in this high-risk population. Multiple risk factors were identified in this conceptual framework; nonetheless, based on current evidence, a key knowledge gap is the uncertainty regarding which are the most important and how exactly they interact.
Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years
2019, Journal of Pediatrics
Citation Excerpt :
First, although circulating inflammation-associated proteins in the first 2 weeks of life are associated with overall reduced brain volumes at 10 years of age, white matter volumes do not seem to be associated with inflammation-related proteins. This observation is surprising given that early life imaging studies generally show that structural brain alterations in extremely premature newborns are predominantly of white matter.11,27 One possible explanation for this inconsistency is that brain volume does not fully capture the inflammation-associated impact on brain structure.
To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition.
We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions.
Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r = −0.18; P = .021), and cerebellum and brainstem was highly correlated with grey matter (r = 0.55; P < .001) and white matter (r = 0.29; P < .001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P = .016), but the association with white matter was marginally significant (P = .051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ.
Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.
Combined predictors of neurodevelopment in very low birth weight preterm infants
2019, Early Human Development
To evaluate the combined prognostic value of neurological examination, head circumference and cranial ultrasound for neurodevelopmental delay (NDD) in very low birth weight (VLBW, <1500 g) preterm infants.
Prospective follow-up study. Preterm infants with VLWB were assessed for NDD using the Mullen Scales of Early Learning test at 24 months of corrected age. Abnormal neurological examination (≥2 deviant items of Hammersmith neurological examination), microcephaly and major ultrasound abnormalities, each performed at term age, were evaluated as predictors of NDD in a multivariable Poisson model.
35/132 infants (26.5%) had NDD. In the multivariable analysis, microcephaly (RR, 3.2; 95% CI, 1.6–6.7) and major ultrasound abnormalities (RR, 2.7; 95% CI, 1.3–5.7) were associated to NDD. The combination of the two tests showed the highest positive predictive value (100%; 95% CI, 51%–100%), while the combination of normal neurological examination, no major US findings and normal head size at term showed the highest negative predictive value (89%; 95% CI, 78%–95%). The maximum under receiver operating characteristic curve area was for microcephaly or major ultrasound abnormalities (AUC 0.74 (0.65–0.83)).
The combination of head circumference, cranial ultrasound and neurological examination at term age is useful to predict NDD in VLBW preterm infants.

View all citing articles on Scopus

: Financial support for this research was provided by the National Institute of Neurological Disorders and Stroke (cooperative agreement 1 U01 NS 40069-01A2). The authors declare no conflicts of interest.

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Original ArticleDevelopmental Correlates of Head Circumference at Birth and Two Years in a Cohort of Extremely Low Gestational Age Newborns

Objectives

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Early Hum Dev

J Pediatr

Semin Perinatol

Early Hum Dev

Early Hum Dev

Early Hum Dev

Early Hum Dev

J Pediatr

Early Hum Dev

J Pediatr

J Clin Epidemiol

Differential effects of intrauterine and postnatal brain growth failure in infants of very low birth weight

Am J Dis Child

Critical periods of brain growth and cognitive function in children

Brain

The influence of head growth in fetal life, infancy, and childhood on intelligence at the ages of 4 and 8 years

Pediatrics

Head growth in preterm infants: correlation with magnetic resonance imaging and neurodevelopmental outcome

Pediatrics

Abnormal cerebral structure is present at term in premature infants

Pediatrics

Microcephaly and intelligence

Dev Med Child Neurol

Positive screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in extremely low gestational age newborns

J Pediatr

An algorithm for identifying and classifying cerebral palsy in young children

J Pediatr

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

J Child Neurol

Original Article
Developmental Correlates of Head Circumference at Birth and Two Years in a Cohort of Extremely Low Gestational Age Newborns