Objectives: Research on developmental outcomes of preterm birth has traditionally focused on adverse effects. This study investigated the prevalence and correlates of resilience in 146 extremely preterm/extremely low birth weight (EPT/ELBW) children (gestational age <28 weeks and/or birth weight <1000 g) attending kindergarten and 111 term-born normal birth weight (NBW) controls. Methods: Adaptive competence (i.e., “resilience” in the EPT/ELBW group) was defined by scores within grade expectations on achievement tests and the absence of clinically elevated parent ratings of child behavior problems. The “adaptive” children who met these criteria were compared to the “maladaptive” children who did not on child and family characteristics. Additional analyses were conducted to assess the conjoint effects of group (ELBW vs. NBW) and family factors on adaptive competence. Results: A substantial minority of the EPT/ELBW group (45%) were competent compared to a majority of NBW controls (73%), odds ratio (95% confidence interval)=0.26 (0.15, 0.45), p<.001. Adaptive competence was associated with higher cognitive skills, more favorable ratings of behavior and learning not used to define adaptive competence, and more advantaged family environments in both groups, as well as with a lower rate of earlier neurodevelopmental impairment in the EPT/ELBW group. Higher socioeconomic status and more favorable proximal home environments were associated with competence independent of group, and group differences in competence persisted across the next two school years. Conclusions: The findings document resilience in kindergarten children with extreme prematurity and highlight the role of environmental factors as potential influences on outcome. (JINS, 2019, 25, 362–374)

Objectives: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. Methods: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. Results: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. Conclusions: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372–381)

Objectives: Children and adolescents who were born very preterm (≤32 weeks’ gestation) are vulnerable to experiencing cognitive problems, including in executive function. However, it remains to be established whether cognitive deficits are evident in adulthood and whether these exert a significant effect on an individual’s real-lifeachievement. Methods: Using a cross-sectional design, we tested a range of neurocognitive abilities, with a focus on executive function, in a sample of 122 very preterm individuals and 89 term-born controls born between 1979 and 1984. Associations between executive function and a range of achievement measures, indicative of a successful transition to adulthood, were examined. Results: Very preterm adults performed worse compared to controls on measures of intellectual ability and executive function with moderate to large effect sizes. They also demonstrated significantly lower achievement levels in terms of years spent in education, employment status, and on a measure of functioning in work and social domains. Results of regression analysis indicated a stronger positive association between executive function and real-life achievement in the very preterm group compared to controls. Conclusions: Very preterm born adults demonstrate executive function impairments compared to full-term controls, and these are associated with lower achievement in several real-life domains. (JINS, 2017, 23, 381–389)

Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks’ gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years’ corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] −1.95, 95% confidence interval [−5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610–621)

Objective: To assess the association of mode of conception and sex concordance with neonatal outcomes in very preterm twins. Study design: Twin pairs born at gestational age ≤32 weeks and admitted to a Level 3 neonatal intensive care unit (NICU) in 2010–2011 were retrospectively identified from the Canadian Neonatal Network™ database. A composite outcome representing neonatal mortality or any severe morbidity (intraventricular hemorrhage grades ≥3 or periventricular leukomalacia, retinopathy of prematurity stages ≥3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥2) was compared between twins conceived using assisted reproduction technologies (ARTs) or spontaneously (SP), and tested for association with sex concordance in individual-level and pair-wise multivariable logistic regression analyses. Results: Study subjects included 1,508 twins from 216 ART (53 [25%] male–male, 104 [48%] male–female, and 59 [27%] female–female) and 538 SP (192 [36%] male–male, 123 [23%] male–female, and 223 [41%] female–female) pairs. No statistically significant association was detected between mode of conception and the composite outcome of mortality/morbidities. The composite outcome was significantly higher in same-sex than in opposite-sex twins (OR = 1.68; 95% CI = [1.09, 2.59]). This relationship was most pronounced in ART pairs (OR = 2.25; 95% CI = [1.02, 4.98]), with increased rates in one or both twins from male–male versus opposite-sex ART pairs (OR = 3.0; 95% CI = [1.07, 8.36]). Conclusion: Same-sex pairing was associated with higher mortality/morbidities in very preterm twins admitted to the NICU, and can be used in clinical practice to identify twins at higher risk of adverse neonatal outcomes.

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001–2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, odds ratio (95% confidence interval) = 7.32 (3.32, 16.16), p < .001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention. (JINS, 2011, 17, 1067–1079)

Uterine infections during pregnancy predispose to pre-term birth and postnatal morbidity, but it is unknown how prenatal bacterial exposure affects maturation of the immature gut. We hypothesised that a prenatal exposure to gram-negative lipopolysaccharide (LPS) has immunomodulatory effects that improve resistance towards necrotising enterocolitis (NEC) in pre-term neonates. At approximately 85 % gestation, pig fetuses were injected intramuscularly with saline or LPS (0·014 mg/kg), or intra-amniotically with LPS (0·4 mg/kg). Pigs were delivered by caesarean section 3–5 d later and fed colostrum (C) or formula (F) for 48 h. Gut indices did not differ between pigs injected intramuscularly with saline or LPS, and these groups were therefore pooled into two control groups according to diet (control-F, n 32 and control-C, n 11). Control-F pigs showed reduced villus heights, mucosal structure, gut integrity, digestive enzymes, elevated NEC incidence (38 v. 0 %, P < 0·05) and several differentially expressed immune-related genes, relative to control-C pigs. Compared with the control-F and control-C groups, values in formula-fed pigs given intra-amniotic LPS formula (n 17) were intermediate for villus height, enzyme activities, intestinal permeability and NEC incidence (18 %, P = 0·2 relative to control-F), and numbers of differentially expressed immune genes. In conclusion, prenatal exposure of the fetal gut to Gram-negative bacteria may modulate the immediate postnatal response to an enteral diet and colonising bacteria.

Executive function and attention difficulties are reported in very preterm (VPT) children at school entry, but it is unclear if these remain at later ages and/or if these difficulties are mediated by more basic functions, such as processing speed. Processing speed has been shown to underlie academic and behavioral problems in VPT children in middle childhood (Mulder, Pitchford, & Marlow, 2010, 2011), so may also underpin executive function and attention difficulties. We investigated this by comparing VPT (gestational age <31 weeks; N = 56) to term children (N = 22) aged 9–10 years on a comprehensive battery of executive function and attention tasks from the Test of Everyday Attention for Children (Manly, Robertson, Anderson, & Nimmo-Smith, 1999) and NEPSY (Korkman, Kirk, & Kemp, 1998). Selective and sustained attention, inhibition, working memory, shifting, verbal fluency, planning, and processing speed were examined. Group differences favoring term children were shown on most executive function tasks (i.e., inhibition, working memory, verbal fluency, and shifting), all of which were mediated by slow processing speed in the VPT group, except response inhibition. Seemingly, processing speed is an important determinant underpinning many neuropsychological deficits seen in VPT children in middle childhood. (JINS, 2011, 17, 445–454)

Individuals born very preterm (VPT) are at increased risk of perinatal brain injury and long-term cognitive and behavioral problems. Executive functioning, in particular, has been shown to be impaired in VPT children and adolescents. This study prospectively assessed executive function in young adults who were born VPT (<33 weeks of gestation) [n = 61; mean age, 22.25 (±1.07) years; range, 20.62–24.78 years] and controls [n = 64; mean age, 23.20 (±1.48) years; range, 19.97–25.46 years]. Tests used comprised the Wechsler Abbreviated Scale of Intelligence (WASI), the Hayling Sentence Completion Test (HSCT), the Controlled Oral Word Association Test (COWAT), the Animal and Object test, the Trail-Making Test (TMT), and the Test of Attentional Performance (TAP). VPT participants showed specific executive function impairments in tasks involving response inhibition and mental flexibility, even when adjusting for IQ, gender, and age. No significant associations were observed between executive function test scores and perinatal variables or neonatal ultrasound classification. The results suggest that, although free from major physical disability, VPT young adults perform worse than controls on tasks involving selective aspects of executive processing, such as mental flexibility and response inhibition. (JINS, 2007, 13, 571–581.)