Control Term Research Articles

Early relations between language development and the quality of mother–child interaction in very-low-birth-weight children

BackgroundIt is not clearly understood how the quality of early mother–child interaction influences language development in very-low-birth-weight children (VLBW). AimsWe aim to analyze associations between early language and the quality of mother–child interaction, and, the predictive value of the features of early mother–child interaction on language development at 24months of corrected age in VLBW children. Study designA longitudinal prospective follow-up study design was used. MethodsThe participants were 28 VLBW children and 34 full-term controls. Language development was measured using different methods at 6, 12 and at 24months of age. The quality of mother–child interaction was assessed using PC-ERA method at 6 and at 12months of age. ResultsAssociations between the features of early interaction and language development were different in the groups of VLBW and full-term children. There were no significant correlations between the features of mother–child interaction and language skills when measured at the same age in the VLBW group. Significant longitudinal correlations were detected in the VLBW group especially if the quality of early interactions was measured at six months and language skills at 2years of age. However, when the predictive value of the features of early interactions for later poor language performance was analyzed separately, the features of early interaction predicted language skills in the VLBW group only weakly. ConclusionsThe biological factors may influence on the language development more in the VLBW children than in the full-term children. The results also underline the role of maternal and dyadic factors in early interactions.

Social perception in children born at very low birthweight and its relationship with social/behavioral outcomes.

BackgroundResearch has shown that children born very prematurely are at substantially elevated risk for social and behavioral difficulties similar to those seen in full-term children with autism spectrum disorders (ASDs).MethodsTo gain insight into core deficits that may underlie these difficulties, in this study, we assessed the social perceptual skills of 8- to 11-year-old children born at very low birthweight (VLBW) (<1,500 g) and age-matched, full-term controls, using the Child and Adolescent Social Perception Measure. We also assessed social and behavioral outcomes with two parent-report measures used in ASD screening.ResultsChildren in the preterm group had normal range estimated verbal IQ. However, we found that they were impaired in their ability to use nonverbal cues from moving faces and bodies, and situational cues, to correctly identify the emotions of characters depicted in videotaped social interactions. Their performance on this task was related to the number of ‘autistic-like’ traits they displayed.ConclusionsThis research highlights links between social perceptual deficits and poor social and behavioral outcomes in children born very prematurely. The results also suggest that even those who have escaped major intellectual/language problems are at risk for social and behavioral problems that can be of clinical concern.

Assisting the development of infants born prematurely using a self-regulation framework and relationship-based intervention process

Purpose: An intervention for improving the self-regulatory abilities of preterm babies over the first year at home is described and evaluated. Motor control was addressed as a significant aspect of regulatory competence. Parent concerns were addressed using video replay to establish parents’ interpretation of infant behaviour. Methods: LBW infants (< 32weeks; < 1500 gms) were randomly assigned into one of 4 blocks (control-intervention- control-intervention) along with a full term control group. Independent outcomes were conducted at 12 months. Results: Preterm intervention (N = 24) scored significantly higher ( p < .001) on Mental and Psychomotor Bayley Scales than preterm control infants (N = 22) though not as high as the full-term control group (N = 23). In motor development the largest gains were made by the most premature infants. The preterm intervention and full-term groups scored significantly higher on the HOME than the preterm control group ( p < .007). Conclusions: This model has implications for cost-effective practice by using key times for home visiting or community nursing to assist parents at home.

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children. A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels. After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up. Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass.

Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia

Background: 2-methoxyestradiol (2-ME), a natural metabolite of 17β-estradiol, is synthesized by catechol-O-methyltransferase (COMT). The aim of this study was to explore the maternal 2-ME concentration and placental COMT expression in the different trimesters of normal pregnancy and preeclamptic pregnancies, as well as the effects of 2-ME on cell proliferation and migration of HTR-8/SVneo under normoxic (20% O₂) and hypoxic (2.5% O₂) conditions. Methods: 2-ME levels were examined by ELISA. COMT protein expression was analyzed by Western blot and immunohistochemistry. Cell proliferation and migration were measured by crystal violet assay and transwell system under either normoxia or hypoxia. Results: Maternal 2-ME concentration was elevated with the progression of pregnancy, in contrast, 2-ME was lower in women diagnosed with mild preeclampsia (mPE; 23%) and severe preeclampsia (sPE; 32%) as compared with normotensive full term pregnancies. Meanwhile, preterm controls had lower levels of 2-ME than full term controls. Soluble cytoplasmic COMT (S-COMT), but not membrane-bound COMT (MB-COMT) levels in placentas were increased by 2.5 fold in the full term vs. the first trimester placentas. Furthermore, 2-ME suppressed cell proliferation under 20% O₂ but not 2.5% O₂, while 2-ME promoted cell migration under 2.5% but not 20% O₂in vitro. Conclusion: Considering 2.5% O₂ is a state more closely mimicking in vivo condition, these data suggest a decrease in 2-ME levels may inhibit trophoblast cell migration, possibly leading to PE.

Preterm birth does not increase the risk of traumatic dental injuries or unintentional injuries

To evaluate the prevalence of traumatic dental injuries (TDIs) and unintentional injuries (UIs) in Swedish children from 0 to 12 years of age, comparing those who were born preterm with matched full-term controls. The associations between TDI and UI and medical health problems or socio-demographic characteristics were also studied. This cross-sectional, case-control study used dental record reviews and interviews to obtain TDI data on 187 matched pairs aged from 0 to 6 (Sample I) and a structured questionnaire to study TDI and UI among 82 matched pairs aged from 0 to 12 (Sample II). Reports of TDI in the primary teeth and permanent teeth from 0 to 12 years of age were significantly more common in the control than preterm born children (p = 0.032). No significant differences were seen in the 0-6 age group. When it came to UI, there were no statistical significant differences between the preterm and control groups and no correlations between TDI and UI and medical health problems or socio-demographic characteristics. The study indicates that preterm children are no more exposed to TDI or UI than matched full-term controls. In fact, the control group parents reported significantly higher prevalence of TDI in the primary and permanent teeth.

Ventral stream sensitivity in “healthy” preterm-born adolescents: Psychophysical and neuropsychological evaluation

BackgroundDeficits of motion processing have been reported in premature and very low birth-weight subjects during infancy, childhood and adolescence. Less is known about ventral stream functioning in preterms. AimThe aim of this study is to investigate ventral stream functioning in a sample of “healthy” adolescents born preterm with normal outcome and without brain damage. Study designWe enrolled thirty preterm-born adolescents (mean age: 14.2years, mean gestational age 28.9weeks, mean birth weight 1097g), and 34 age-matched term-born controls (mean age: 14.5years). All subjects were administered a psychophysical test known as “Form Coherence Task” and a comprehensive standardized battery of neuropsychological tests suitable for investigating ventral stream functioning including Street Completion Test, Poppelreuter–Ghent Test and the first part of the Visual Object and Space Perception (VOSP) battery. Dorsal stream visual functioning was investigated by the second part of the VOSP. ResultsPreterm (PT) subjects showed the same results in all “ventral” tasks with respect to full-term controls without any correlation to gestational age or birth weight. We found a significant negative correlation between Form Coherence Task and Letters Task (p=.014) and between Form Coherence and Silhouette Tasks (p=.017). No correlation was observed between Form Coherence Task and Street and Ghent Tests. A statistical difference was instead found between PTs and controls in two tasks of the VOSP battery that mostly involve the dorsal stream. ConclusionsPreterm birth per se (in absence of evident brain lesions) is not sufficient to compromise the development of ventral pathway.

Experimental Modelling of the Consequences of Brief Late Gestation Asphyxia on Newborn Lamb Behaviour and Brain Structure

Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient in utero asphyxia in late gestation fetal sheep, on the newborn lamb after birth. Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term), the cuff was inflated to induce umbilical cord occlusion (UCO), or sham (control). Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i) use all four legs, (ii) attain a standing position, (iii) find the udder, and (iv) successfully suckle - compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies.

Impact of ethnicity and extreme prematurity on infant pulmonary function

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth) and forced expired volume (FEV0.5) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23–27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30–36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37–42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z-scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: −1.02[−1.60; −0.44] z-scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5/FVC ratio. FEV0.5, FVC, and FEV0.5/FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5/FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects.

Placental glucose transporter 3 (GLUT3) is up-regulated in human pregnancies complicated by late-onset intrauterine growth restriction

IntroductionTransport of glucose from maternal blood across the placental trophoblastic tissue barrier is critical to sustain fetal growth. The mechanism by which GLUTs are regulated in trophoblasts in response to ischemic hypoxia encountered with intrauterine growth restriction (IUGR) has not been suitably investigated. ObjectiveTo investigate placental expression of GLUT1, GLUT3 and GLUT4 and possible mechanisms of GLUT regulation in idiopathic IUGR. MethodsWe analyzed clinical, biochemical and histological data from placentas collected from women affected by idiopathic full-term IUGR (n = 10) and gestational age-matched healthy controls (n = 10). ResultsWe found increased GLUT3 protein expression in the trophoblast (cytotrophoblast greater than syncytiotrophoblast) on the maternal aspect of the placenta in IUGR compared to normal placenta, but no differences in GLUT1 or GLUT4 were found. No differential methylation of the GLUT3 promoter between normal and IUGR placentas was observed. Increased GLUT3 expression was associated with an increased nuclear concentration of HIF-1α, suggesting hypoxia may play a role in the up-regulation of GLUT3. DiscussionFurther studies are needed to elucidate whether increased GLUT3 expression in IUGR is a marker for defective villous maturation or an adaptive response of the trophoblast in response to chronic hypoxia. ConclusionsPatients with IUGR have increased trophoblast expression of GLUT3, as found under the low-oxygen conditions of the first trimester.

Impaired lung function and health status in adult survivors of bronchopulmonary dysplasia

More infants with bronchopulmonary dysplasia (BPD) now survive to adulthood, but little is known regarding persisting respiratory impairment. We report respiratory symptoms, lung function and health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full-term controls. Respiratory symptoms (European Community Respiratory Health Survey) and HRQoL (EuroQol (EQ)-5D) were measured in 72 adult BPD survivors (mean ± sd study age 24.1 ± 4.0 years; mean ± sd gestational age 27.1 ± 2.1 weeks; and mean ± sd birth weight 955 ± 256 g) cared for in the regional neonatal intensive care unit, Royal Maternity Hospital, Belfast, UK (between 1978 and 1993). These were compared with 57 non-BPD controls (mean ± sd study age 25.3 ± 4.0 years; mean ± sd gestational age 31.0 ± 2.5 weeks; and mean ± sd birth weight 1238 ± 222 g) and 78 full-term controls (mean ± sd study age 25.7 ± 3.8 years; mean ± sd gestational age 39.7 ± 1.4 weeks; and mean ± sd birth weight 3514 ± 456 g) cared for at the same hospital. Spirometry was performed on 56 BPD, 40 non-BPD and 55 full-term participants. BPD subjects were twice as likely to report wheeze and three times more likely to use asthma medication than controls. BPD adults had significantly lower forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity than both the preterm non-BPD and full-term controls (all p<0.01). Mean EQ-5D was 6 points lower in BPD adults compared to full-term controls (p<0.05). BPD survivors have significant respiratory and quality of life impairment persisting into adulthood.

Normal pulmonary gas exchange efficiency and absence of exercise-induced arterial hypoxemia in adults with bronchopulmonary dysplasia

Cardiopulmonary function is reduced in adults born very preterm, but it is unknown if this results in reduced pulmonary gas exchange efficiency during exercise and, consequently, leads to reduced aerobic capacity in subjects with and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively large alveolar to arterial oxygen difference (AaDO2) and resulting exercise-induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in adults born very preterm with and without BPD. Measurements of pulmonary function, lung volumes and diffusion capacity for carbon monoxide (DLco) were made at rest. Measurements of maximal oxygen consumption, peak workload, temperature- and tonometry-corrected arterial blood gases, and direct measure of hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle ergometer exercise in ex-preterm subjects ≤32-wk gestational age, with BPD (n = 12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing room air. Both BPD and PRE had reduced pulmonary function and reduced DLco compared with CONT. The AaDO2 was not significantly different between groups, and there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 ≥ 40 Torr) in any subject group preexercise or at any workload. Arterial O2 content was not significantly different between the groups preexercise or during exercise. However, peak power output was decreased in BPD and PRE subjects compared with CONT. We conclude that EIAH in adult subjects born very preterm with and without BPD does not likely contribute to the reduction in aerobic exercise capacity observed in these subjects.

Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely

Children born very preterm (⩽32weeks gestation) exhibit greater internalizing (anxious/depressed) behaviors compared to term-born peers as early as 2years corrected age (CA); however, the role of early stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we examined the relationship between neonatal pain and internalizing behavior at 18months CA in children born very preterm and examined whether parent behavior and stress moderated this relationship. Participants were 145 children (96 very preterm, 49 full term) assessed at 18months CA. Neonatal data were obtained from medical and nursing chart review. Neonatal pain was defined as the number of skin-breaking procedures. Cognitive ability was measured with the Bayley Scales of Infant Development II. Parents completed the Parenting Stress Index III, Child Behavior Checklist 1.5–5, and participated in a videotaped play session with their child, which was coded using the Emotional Availability Scale IV. Very preterm children displayed greater Internalizing behaviors compared to full-term control children (P=.02). Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing behavior (all P<.05); higher parent education (P<.03), lower Parenting Stress (P=.001), and fewer children in the home (P<.01) were associated with lower Internalizing behavior in very preterm children, after adjusting for neonatal medical confounders, gender, and child cognitive ability (all P>.05). Parent Emotional Availability and stress were not associated with Internalizing behaviors in full-term control children. Positive parent interaction and lower stress appears to ameliorate negative effects of neonatal pain on stress-sensitive behaviors in this vulnerable population.

Long‐term biometric optic components of diode laser‐treated threshold retinopathy of prematurity at 9 years of age

To assess quantitatively the biometric optic components and its relationship with refractive status in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP). A prospective, cross-sectional study in which ultrasound biometric measurement of optic components and cycloplegic refraction were performed on 24 consecutive preterm children with diode laser-treated threshold ROP at the age of 9 years. The study results were compared with 1021 age-matched full-term control children from a national survey. The eyes with laser-treated ROP showed statistically significantly thicker lens (3.94 versus 3.39 mm), steeper vertical corneal curvature (7.47 versus 7.67 mm) and shallower anterior chamber depth (ACD) (2.91 versus 3.58 mm) than age-matched full-term controls, but no difference in axial length (23.32 versus 23.24 mm). The laser-treated eyes had a mean spherical equivalent (SE) of -4.49 D compared with mean SE of -0.44 D in controls. Of 46 eyes studied, 93% of eyes were myopic and 28.3% with high myopia (<-6.0 D) compared with the 32% prevalence of myopia in controls. In preterm children, younger gestational age tended to correlate with shallower ACD (r = 0.352) and thicker lens (r = -0.298); lower birth weight tended to correlate with shallower ACD (r = 0.372) and steeper cornea (r = 0.360). There were higher prevalence and greater magnitude of myopia in preterm children. The significantly thicker lens, steeper corneal curvature and shallower anterior chamber depth are the major factors contributing to the development of myopia in preterm school children with laser-treated threshold ROP.

Differential associations between infant affective and cortisol responses during the Still Face paradigm among infants born very low birth weight versus full-term

Psychological stress responses may have both emotional and cortisol reactivity correlates, but there are limited data addressing the association between generalized negative and positive emotional states and cortisol reactivity to a psychological stressor among infants born very low birth weight (VLBW; <1250g) compared to infants born full-term. Examining this relationship between behavioral (affect) and physiological (cortisol) responses may provide insight into the nature of regulation difficulties identified in infants born VLBW. The purpose of this study was to assess the association between infant affective and cortisol responses to the Still Face paradigm (SF) in a cohort of six- to eight-month old infants born VLBW compared with infants born full-term (N=53 total; N=29 and N=24, respectively). Infant affect was coded in 1-s intervals while mother–infant dyads participated in the SF paradigm, and percent positive affect and percent negative affect were calculated separately for each SF episode. We had hypothesized that because infants born VLBW are at increased risk for dysregulation, they would show, compared to full-term controls, greater dysregulation in the form of less synchrony (i.e., less correlated affective and cortisol responses) across the two SF stressors (episodes 2 and 4). This hypothesis was largely supported: the associations between affective and cortisol responses were different for the two groups across the two stressors for percent positive affect (both stressor episodes 2 and 4) and percent negative affect (episode 4 only). For the full-term group, follow up correlations revealed significant negative associations between percent positive affective and cortisol responses for both stressors. Mothers’ responsiveness did not explain the term group association differences between infant affective and cortisol responses across stressors. The (lack of) association of stress reactivity systems may index dysregulation or dysregulation correlates in preterm children. Understanding how this lack of coordination among stress systems relates to greater dysregulation, learning, and attentional difficulties may be important in recognizing early precursors to such problems in preterm children, and in this way, aid in early intervention efforts. Future research is warranted to determine how these findings relate to infants’ stress reactions in naturalistic settings, and the directionality and temporal relationship between cortisol and infant affective stress responses.

A Critical Role for TLR4 Induction of Autophagy in the Regulation of Enterocyte Migration and the Pathogenesis of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) develops in response to elevated TLR4 signaling in the newborn intestinal epithelium and is characterized by TLR4-mediated inhibition of enterocyte migration and reduced mucosal healing. The downstream processes by which TLR4 impairs mucosal healing remain incompletely understood. In other systems, TLR4 induces autophagy, an adaptive response to cellular stress. We now hypothesize that TLR4 induces autophagy in enterocytes and that TLR4-induced autophagy plays a critical role in NEC development. Using mice selectively lacking TLR4 in enterocytes (TLR4(ΔIEC)) and in TLR4-deficient cultured enterocytes, we now show that TLR4 activation induces autophagy in enterocytes. Immature mouse and human intestine showed increased expression of autophagy genes compared with full-term controls, and NEC development in both mouse and human was associated with increased enterocyte autophagy. Importantly, using mice in which we selectively deleted the autophagy gene ATG7 from the intestinal epithelium (ATG7(ΔIEC)), the induction of autophagy was determined to be required for and not merely a consequence of NEC, because ATG7(ΔIEC) mice were protected from NEC development. In defining the mechanisms involved, TLR4-induced autophagy led to impaired enterocyte migration both in vitro and in vivo, which in cultured enterocytes required the induction of RhoA-mediated stress fibers. These findings depart from current dogma in the field by identifying a unique effect of TLR4-induced autophagy within the intestinal epithelium in the pathogenesis of NEC and identify that the negative consequences of autophagy on enterocyte migration play an essential role in its development.

Leptin may enhance hepatic insulin sensitivity in children and women born small for gestational age

ObjectiveChildren born small for gestational age (SGA) are at risk for developing type 2 diabetes. Lipodystrophy leads to early type 2 diabetes and leptin reverses the metabolic consequences of the disease. Low IGF-binding protein 1 (IGFBP1) can predict the development of type 2 diabetes. The aim of this study was to determine leptin, insulin, and IGFBP1 in children and adult women born preterm or SGA to evaluate the role of leptin as a compensatory mechanism in insulin resistance development.MethodsSeventy-six children (8.5–10 years, 41 girls and 35 boys) and 45 women (23–30 years) were studied. The children comprised subjects born appropriate for gestational age (<30 gestational weeks) (n=22), born SGA at term (n=23), and full-term normal-weight controls (n=31). Among the women, the corresponding figures were, n=10, n=18, and n=17 respectively. Fasting levels of IGFBP1, leptin, insulin, and IGF1 were determined and total adiponectin only in women.ResultsIn girls and women, term SGA subjects had higher leptin levels in relation to BMI SDS (P=0.042 and P=0.03 respectively). More than half of IGFBP1 variability was explained by leptin and insulin in children. In term SGA women, IGFBP1 level was lower compared with controls (P=0.012) and the regression line of IGFBP1 on insulin was suppressed below −1 s.d. of a reference material.ConclusionLeptin levels were elevated in term SGA girls and women, in particular in adult women, but not found in preterm girls and women. IGFBP1 was lower in term SGA women. In children, leptin and insulin were strong suppressors of IGFBP1. We speculate that higher leptin levels could be a protective event to enhance hepatic insulin sensitivity.

Decreased Right Temporal Activation and Increased Interhemispheric Connectivity in Response to Speech in Preterm Infants at Term-Equivalent Age

Preterm infants are at increased risk of language-related problems later in life; however, few studies have examined the effects of preterm birth on cerebral responses to speech at very early developmental stages. This study examined cerebral activation and functional connectivity in response to infant-directed speech (IDS) and adult-directed speech (ADS) in full-term neonates and preterm infants at term-equivalent age using 94-channel near-infrared spectroscopy. The results showed that compared with ADS, IDS increased activity in larger brain areas such as the bilateral frontotemporal, temporal, and temporoparietal regions, both in full-term and preterm infants. Preterm infants exhibited decreased activity in response to speech stimuli in the right temporal region compared with full-term infants, although the significance was low. Moreover, preterm infants exhibited increased interhemispheric connectivity compared with full-term controls, especially in the temporal and temporoparietal regions. These differences suggest that preterm infants may follow different developmental trajectories from those born at term owing to differences in intrauterine and extrauterine development.

Follow‐up study of 2‐year‐olds born at very low gestational age in Estonia

To study very low gestational age (VLGA, <32weeks) infants at 2years of age and to identify the predictors of adverse outcomes. A population-based cohort of 155 surviving VLGA infants born in Estonia in 2007 was followed up and compared with a matched full-term (FT) control group. A logistic regression model was used to test associations between risk factors and adverse outcomes. No impairment was found in 60% of the VLGA infants. Neurodevelopmental impairment was noted in 12% of VLGA infants, with 8% of the infants affected by cerebral palsy without independent walking, 5% with cognitive delay, 10% with language delay and 1% with hearing impairment. The differences between preterm and FT infants in terms of the mean Cognitive, Language, and Motor Composite Scores assessed using the Bayley-III scales were in excess of 0.5SD. Somatic growth delay was a significant problem among preterm infants. The existence of severe neonatal cerebral lesions was the most significant predictor of adverse outcomes. In all domains studied, adverse conditions were more prevalent among VLGA infants than among the FT control group. Efforts to reduce neonatal morbidity in preterm infants should be a key priority for health care in Estonia.

Astigmatism and biometric optic components of diode laser-treated threshold retinopathy of prematurity at 9 years of age

To assess the prevalence of astigmatism and its relationship with biometric optic components in preterm school children with diode laser-treated threshold retinopathy of prematurity (ROP). A prospective, cross-sectional study in which cycloplegic keratometry, refraction, and ultrasound biometric measurement of optic components were performed on 24 consecutive preterm children with diode laser-treated threshold ROP at the age of 9 years. The study results were compared with data on 1021 age-matched full-term control children from a national survey. The laser-treated eyes had a mean astigmatism of 3.47 D, with a mean spherical equivalent of -4.49 D. Of the 46 eyes studied, 98% of eyes showed astigmatism ≥0.5 D and 50% had high astigmatism (>3.0 D). Most astigmatic eyes (97.7%) showed with-the-rule astigmatism, with the mean plus cylinder axis at 89.30(o). Further correlation analysis showed the astigmatism in refraction was highly correlated with the corneal astigmatism (r=0.921, P<0.001) and the vertical corneal curvature (r=0.405, P=0.005). There was significantly steeper vertical corneal curvature (P=0.003) and flatter horizontal corneal curvature (P=0.031) in eyes with laser-treated ROP when compared with age-matched full-term controls. The eyes with laser-treated ROP also show significantly thicker lens (3.93 mm) and shallower anterior chamber depth (ACD; 2.92 mm) than full-term controls (P<0.001). There is significantly higher prevalence and greater magnitude of astigmatism in eyes with laser-treated threshold ROP compared with full-term controls. The steeper vertical corneal curvature component contributes to the increased astigmatism in eyes with laser-treated ROP.