Elsevier

Brain and Development

Volume 35, Issue 1, January 2013, Pages 10-16
Brain and Development

Original article
Gray matter volumetric MRI differences late-preterm and term infants

https://doi.org/10.1016/j.braindev.2011.12.011Get rights and content

Abstract

Gray matter develops rapidly during the third trimester of pregnancy, which is a critical period for lipid deposition. We measured brain volume in term and late-preterm infants to determine if it is related to disabilities in late-preterm infants. In addition, we measured serum lipid concentrations to investigate the relationship between brain volume and lipid nutrition. Magnetic resonance imaging scans were obtained in 16 late-preterm and 13 term infants. We measured cerebrum, gray matter, and white matter volumes. We performed serum cholesterol, triglyceride (TG), and lipoprotein analyses in cord blood by high-performance liquid chromatography using gel permeation columns to assess lipid nutritional levels. The gray matter volume and percent cerebrum volume of gray matter were significantly smaller in late-preterm infants (p < 0.001). Head circumference and cerebrum and white matter volume did not differ between the two groups. Gray matter volume correlated positively with gestational age (r = 0.647, p < 0.001), head circumference (r = 0.688, p < 0.001), and high-density lipoprotein (HDL)-TG levels (r = 0.496, p = 0.006). Late-preterm infants had a normal head circumference and a lower gray matter volume than term infants. Gestational age and head circumference were significantly associated with gray matter volume. Only HDL-TG levels were significantly associated with gray matter volume. HDL-TG might contribute to the transport of fatty acids and gray matter development during the postnatal period. Thus, delayed gray matter development may partly contribute to neurodevelopmental disabilities in late-preterm infants.

Introduction

Recent advances in perinatal and neonatal medicine have improved the survival of preterm infants. However, a large number of children who are born preterm have adverse outcomes such as neurodevelopmental disabilities. Of infants with gestational ages less than 32 weeks and/or birth weights less than 1,500 g, a low percentage (10%) had severe disabilities when they reached school age, while 90% had serious difficulties in everyday life because of mild developmental abnormalities [1]. Infants with very low birth weights had a lower mean intelligence quotient, higher cognitive problems, and an increased incidence of attention deficit hyperactivity disorder than normal birth-weight infants [2], [3]. Lindström et al. [4] reported that 13.2% of children born between 24 and 28 weeks gestation and 5.6% of those born between 29 and 32 weeks gestation received economic assistance from society because of handicaps or persistent illnesses. Moreover, they reported that those born between 33 and 38 weeks gestation also carried significantly increased risks for disabilities and were responsible for 74% of the disabilities associated with preterm birth. Preterm birth is known to increase the risk of neurodevelopmental disabilities compared with full-term birth. The disabilities of late-preterm infants (34 0/7–35 6/7 gestational weeks at birth) have been highlighted recently. Late-preterm infants often have a higher incidence of complications, such as hypothermia, respiratory distress syndrome, transient tachypnea of the newborn, apnea, hypoglycemia, hyperbilirubinemia, feeding difficulties, sepsis, intraventricular hemorrhage, periventricular leukomalacia, and higher mortality than term infants [5], [6], [7], [8]. Later in life, these babies may have some neuropsychological problems such as learning difficulties and poor scholastic and behavioral problems [9], [10], [11]. The risk for neurodevelopmental disabilities are not only restricted to the very-preterm infant but also occurs in the late-preterm infant. However, the course of the disabilities in late-preterm infants is still unknown.

At 20 gestational weeks, the brain volume is 10% of that at term, and during the remaining 20 gestational weeks, the rest of the brain volume is completely acquired to reach term volume [12]. At late preterm, which is at 34 gestational weeks, the overall brain weight is 65% of term weight [7].

Fifty percent of the dry weight of the brain is composed of lipids, and half of the lipid content is made up of fatty acids [13]. Thus, lipids are an important part of fetal brain development. The third trimester of pregnancy is a critical period for lipid deposition in the human fetus [14]. The fetal brain develops remarkably during the third trimester of pregnancy, which is the time that late-preterm infants are born. A lipid nutritional deficiency may lead to brain development retardation in late preterm infants.

Several studies have shown that head circumference was an indicator of brain development. However, advanced neurological evaluations, such as those involving quantitative magnetic resonance imaging (MRI), are required. Recently, volumetric MRI has been used to characterize regional brain volume in neonates. Hüppi et al. [15] reported that the total brain volume of fetuses increased from 150 mL at 29 weeks of postmenstrual age to 400 mL at full term, and gray matter showed a linear increase of 1.4%, or 15 mL in absolute volume per week. Peterson et al. [16] reported that head circumference, postmenstrual age, and body weight at the time of scanning correlated with cortical gray matter and white matter volumes. Inder et al. [17] reported that, in comparison to term infants, preterm infants at term demonstrated reductions in cerebral cortical gray matter.

In the present study, we used volumetric MRI to quantify regional brain volume in 16 late-preterm infants and 13 term infants. The aim of this study was to determine the differences in brain volume between late-preterm and term infants. We hypothesized that a lower brain volume may cause neurodevelopmental disabilities in late-preterm infants. Furthermore, we measured serum lipid concentrations to investigate the relationship between brain volume and lipid nutritional levels. These results suggest that lipid nutrition has a great influence on brain development.

Section snippets

Subjects

From January 2008 to March 2009, 29 infants (20 men, 9 women) who were consecutively born by vaginal delivery or cesarean delivery in the maternity ward of Nihon University were included in the study. Sixteen were late-preterm infants, and 13 were term infants. Sixteen were appropriate-for-gestational-age, and 13 were small-for-gestational-age. None of the infants had intracranial diseases such as hydrocephalus, intraventricular hemorrhage, periventricular leukomalacia, or obstruction of

Anthropometry

The body weight and the head circumference were measured at birth and at the time of the MRI analyses. The body weight of each infant was determined to the nearest gram with an electronic scale. The head circumference was measured to the nearest 0.1 cm.

MRI analyses

Term infants were scanned within 2 weeks of their birth, and late-preterm infants were scanned at the time that they were near term- or at term-equivalent age. All infants were scanned while sedated using triclofos sodium. All infants were

Results

There was no difference in the number of male subjects between the late-preterm (n = 12, 88%) and term infant groups (n = 8, 62%) (p = 0.559). There was no difference in the number of small-for-gestational-age infants between the late-preterm (n = 8, 50%) and term infant groups (5, 39%) (p = 0.619).

The characteristics of the study subjects are shown in Table 1. Body weight and head circumference at birth were significantly smaller in late-preterm infants; however, the differences disappeared at the time of

Discussion

In this study, we showed that late-preterm infants had lower gray matter volume than term infants, despite the fact that head circumference at the time of the MRI scan did not differ. We also found that gestational age and age at full enteral feeding were significant determinants of gray matter volume. Furthermore, HDL-TG might have an important role into transport of fatty acids and the nutrition for brain development during both the fetal and postnatal period.

Head circumference has been shown

Conflict of interest

The authors declare no conflict of interest.

Acknowledgments

The authors thank the infants and their parents for participating in this study.

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