Early Childhood Temperamental Trajectories following Very Preterm Birth and Their Association with Parenting Style.

Childhood temperament is an early characteristic shaping later life adjustment. However, little is currently known about the stability of early temperament and its susceptibility to the environment in children born very preterm (VPT; <33 weeks' gestation). Here, we investigated infant-to-childhood temperamental trajectories, and their interaction with parental practices, in VPT children. Maternal reports of infant temperament were collected in 190 infants (mean age: 11.27 months; range 9−18 months) enrolled in the longitudinal Evaluation of Preterm Imaging (ePrime; Eudra: CT 2009-011602-42) study, using the ePrime questionnaire on infant temperament. At 4−7 years of age, further assessments of child temperament (Children's Behavior Questionnaire­Very Short Form) and parenting style (Arnold's Parenting Scale) were conducted. Results showed that more difficult temperament in infancy was associated with increased Negative Affectivity in childhood, regardless of parenting practices. This lends support to the stability of early temperamental traits reflecting negative emotionality. In contrast, a lax parenting style moderated the relationship between easy infant temperament and Negative Affectivity at 4−7 years, such that an easier infant temperament was increasingly associated with higher childhood Negative Affectivity scores as parental laxness increased. These results highlight a potential vulnerability of VPT infants considered by their mothers to be easy to handle, as they may be more susceptible to the effects of suboptimal parenting in childhood.

Neurodevelopmental Outcomes following Intrauterine Growth Restriction and Very Preterm Birth.

OBJECTIVES: To evaluate whether intrauterine growth restriction (IUGR) adds further neurodevelopmental risk to that posed by very preterm birth alone in terms of alterations in brain growth and poorer toddlerhood outcomes. STUDY DESIGN: Participants were 314 infants of very preterm birth enrolled in the Evaluation of Preterm Imaging Study (e-Prime) who were subsequently followed up in toddlerhood. IUGR was identified postnatally from discharge records (n = 49) and defined according to prenatal evaluation of growth restriction confirmed by birth weight <10th percentile for gestational age and/or alterations in fetal Doppler. Appropriate for gestational age (AGA; n = 265) was defined as birth weight >10th percentile for gestational age at delivery. Infants underwent magnetic resonance imaging at term-equivalent age (median = 42 weeks); T2-weighted images were obtained for voxelwise gray matter volumes. Follow-up assessments were conducted at corrected median age of 22 months using the Bayley Scales of Infant and Toddler Development III and the Modified-Checklist for Autism in Toddlers. RESULTS: Infants of very preterm birth with IUGR displayed a relative volumetric decrease in gray matter in limbic regions and a relative increase in frontoinsular, temporal-parietal, and frontal areas compared with peers of very preterm birth who were AGA. At follow-up, toddlers born very preterm with IUGR had significantly lower cognitive (effect size = 0.42) and motor (effect size = 0.41) scores and were more likely to have a positive Modified-Checklist for Autism in Toddlers screening for autism (OR = 2.12) compared with peers of very preterm birth who were AGA. CONCLUSIONS: IUGR might confer a neurodevelopmental risk that is greater than that posed by very preterm alone, in terms of both alterations in brain growth and poorer toddlerhood outcomes.

The effect of maternal position on venous return for pregnant women during MRI.

Magnetic resonance imaging (MRI) in pregnancy is commonly undertaken in the left lateral tilt (LLT) position to prevent inferior vena cava (IVC) compression and supine hypotensive events, although this may be suboptimal for image quality. The supine position may also have an adverse effect on fetal well-being. The spinal venous plexus may provide an alternative pathway for venous return in the presence of IVC compression. This study assesses morphology and blood flow of the IVC and spinal venous plexus for pregnant women in LLT and supine positions to ascertain the effect of maternal position on venous return during MRI. Eighty-two pregnant women underwent phase contrast MRI (PC-MRI) of the IVC and spinal venous plexus in the supine position; 25 were also imaged in the LLT position. Differences in life monitoring, IVC, spinal venous plexus and total venous return between the two positions were assessed. A linear regression assessed the relationship between flow in the IVC and the spinal venous plexus in the supine position. Increasing gestational age and the right-sided position of the uterus on IVC and spinal venous plexus venous return were also evaluated. Hypotension symptoms were similar in supine (10%) and LLT (8%) positioning. Supine positioning decreased IVC height (p < 0.004) and flow (p = 0.045) but flow in the spinal venous plexus increased (p < 0.001) compared with the LLT position. Total venous return showed no difference (p = 0.989) between the two positions. Additional measurements of flow in the aorta also showed no significant difference between the two groups (p = 0.866). Reduced IVC flow in the supine position was associated with increasing gestational age (p = 0.004) and degree of right-sided uterine position (p = 0.004). Women in the left lateral decubitus position who then rotated supine had greater flow in the IVC (p = 0.008) and spinal venous plexus (p = 0.029) than those who started supine. For the majority of women, the spinal venous plexus acts as a complementary venous return system for pregnant women in the supine position, maintaining vascular homeostasis. Further study is needed to assess the effects on the health of the fetus.

Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize these confounds and examine primary vulnerability mechanisms, we need to investigate very early brain development. Here, we tested the hypothesis that brain functional connectivity is altered in neonates who are vulnerable to this condition due to a family history of ASD. We acquired high temporal resolution multiband resting state functional magnetic resonance imaging (fMRI) in newborn infants with and without a first-degree relative with ASD. Differences in local functional connectivity were quantified using regional homogeneity (ReHo) analysis and long-range connectivity was assessed using distance correlation analysis. Neonates who have a first-degree relative with ASD had significantly higher ReHo within multiple resting state networks in comparison to age matched controls; there were no differences in long range connectivity. Atypical local functional activity may constitute a biomarker of vulnerability, that might precede disruptions in long range connectivity reported in older individuals diagnosed with ASD.

Possible relationship between common genetic variation and white matter development in a pilot study of preterm infants.

BACKGROUND: The consequences of preterm birth are a major public health concern with high rates of ensuing multisystem morbidity, and uncertain biological mechanisms. Common genetic variation may mediate vulnerability to the insult of prematurity and provide opportunities to predict and modify risk. OBJECTIVE: To gain novel biological and therapeutic insights from the integrated analysis of magnetic resonance imaging and genetic data, informed by prior knowledge. METHODS: We apply our previously validated pathway-based statistical method and a novel network-based method to discover sources of common genetic variation associated with imaging features indicative of structural brain damage. RESULTS: Lipid pathways were highly ranked by Pathways Sparse Reduced Rank Regression in a model examining the effect of prematurity, and PPAR (peroxisome proliferator-activated receptor) signaling was the highest ranked pathway once degree of prematurity was accounted for. Within the PPAR pathway, five genes were found by Graph Guided Group Lasso to be highly associated with the phenotype: aquaporin 7 (AQP7), malic enzyme 1, NADP(+)-dependent, cytosolic (ME1), perilipin 1 (PLIN1), solute carrier family 27 (fatty acid transporter), member 1 (SLC27A1), and acetyl-CoA acyltransferase 1 (ACAA1). Expression of four of these (ACAA1, AQP7, ME1, and SLC27A1) is controlled by a common transcription factor, early growth response 4 (EGR-4). CONCLUSIONS: This suggests an important role for lipid pathways in influencing development of white matter in preterm infants, and in particular a significant role for interindividual genetic variation in PPAR signaling.

Cardiovascular magnetic resonance of cardiac function and myocardial mass in preterm infants: a preliminary study of the impact of patent ductus arteriosus.

BACKGROUND: Many pathologies seen in the preterm population are associated with abnormal blood supply, yet robust evaluation of preterm cardiac function is scarce and consequently normative ranges in this population are limited. The aim of this study was to quantify and validate left ventricular dimension and function in preterm infants using cardiovascular magnetic resonance (CMR). An initial investigation of the impact of the common congenital defect patent ductus arteriosus (PDA) was then carried out. METHODS: Steady State Free Procession short axis stacks were acquired. Normative ranges of left ventricular end diastolic volume (EDV), stroke volume (SV), left ventricular output (LVO), ejection fraction (EF), left ventricular (LV) mass, wall thickness and fractional thickening were determined in "healthy" (control) neonates. Left ventricular parameters were then investigated in PDA infants. Unpaired student t-tests compared the 2 groups. Multiple linear regression analysis assessed impact of shunt volume in PDA infants, p-value ≤ 0.05 being significant. RESULTS: 29 control infants median (range) corrected gestational age at scan 34+6(31+1-39+3) weeks were scanned. EDV, SV, LVO, LV mass normalized by weight and EF were shown to decrease with increasing corrected gestational age (cGA) in controls. In 16 PDA infants (cGA 30+3(27+3-36+1) weeks) left ventricular dimension and output were significantly increased, yet there was no significant difference in ejection fraction and fractional thickening between the two groups. A significant association between shunt volume and increased left ventricular mass correcting for postnatal age and corrected gestational age existed. CONCLUSION: CMR assessment of left ventricular function has been validated in neonates, providing more robust normative ranges of left ventricular dimension and function in this population. Initial investigation of PDA infants would suggest that function is relatively maintained.