Autism in Toddlers Born Very Preterm

Pritchard, M. A.; Dassel, Therese De; Beller, Elaine; Bogossian, Fiona; Johnston, Linda; Paynter, Jessica; Russo, Santo; Scott, James G.

doi:10.1542/peds.2015-1949

Cited by 43 publications

(25 citation statements)

References 35 publications

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“…Preterm neonates are reported to be at high risk for autism spectrum disorder (Fevang et al, 2016, Limperopoulos et al, 2008, Pritchard et al, 2016), with brain alterations in socio-emotional networks during neonatal period. (Padilla et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Prenatal stress alters amygdala functional connectivity in preterm neonates

Mayes

Kwon

Lacadie

et al. 2016

NeuroImage: Clinical

111

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Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders.We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used.When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth.Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

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Section: Discussionmentioning

confidence: 99%

Prenatal stress alters amygdala functional connectivity in preterm neonates

Mayes

Kwon

Lacadie

et al. 2016

NeuroImage: Clinical

111

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“…However, although these rates are higher than the 9% generally reported in unselected samples,30 33 the true proportion with ASD is likely to be lower as infants may screen positive due to the range of neurodevelopmental impairments commonly observed after EP birth rather than autistic features per se 31 32 34. Where the M-CHAT follow-up interview is used to improve specificity, as prescribed by the authors, a positive screen rate of 13% has been reported in EP infants and a 1.8% prevalence of diagnoses at 2–4 years 35. The M-CHAT is therefore likely to identify children at risk for a range of developmental disorders and should be used with caution when screening for ASD until its predictive validity for later diagnoses is ascertained.…”

Section: Outcomes In Childhood and Adolescencementioning

confidence: 99%

Early and long-term outcome of infants born extremely preterm

2016

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There is no question that birth at extremely low gestational ages presents a significant threat to an infant's survival, health and development. Growing evidence suggests that gestational age may be conceptualised as a continuum in which births before 28 weeks of gestation (extremely preterm: EP) represent the severe end of a spectrum of health and developmental adversity. Although comprising just 1%-2% of all births, EP deliveries pose the greatest challenge to neonatal medicine and to health, education and social services for the provision of ongoing support for survivors with additional needs. Studying the outcomes of these infants remains critical for evaluating and enhancing clinical care, planning long-term support and for advancing our understanding of the life-course consequences of immaturity at birth. Here we review literature relating to early and long-term neurodevelopmental, cognitive, behavioural and educational outcomes following EP birth focusing on key themes and considering implications for intervention. SURVIVAL AND NEONATAL OUTCOMESNeonatal survival is in continuous evolution, particularly at extremely low gestational ages. Survival at the lowest gestational ages (23-24 weeks) varies in population-based reports, primarily as different countries and hospitals assume contrasting stances as to the provision of active care (figure 1). Data from the USA most vividly demonstrate this variation; 1 survival is highest in situations where more active obstetric and neonatal management is practised.2 Interpreting survival without knowing the proportion of live births for whom active stabilisation was given is impossible and reports need to be explicit with regard to this. Using population data, neonatal survival in England after birth at 22-25 weeks gestation increased by 13% from 39% (95% CI 35% to 43%) in 1995 to 52% (95% CI 49% to 55%) in 2006, 3 and routine data suggest that has continued since. Survival is highly dependent on the place of birth, being better in larger neonatal services which more frequently undertake active care. 4 In contrast, the prevalence of major neonatal morbidities-bronchopulmonary dysplasia, periventricular brain injury, retinopathy of prematurity and sepsis/necrotising enterocolitis-is essentially unchanged, despite continually evolving and less invasive strategies.

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“…Although the prevalence of ASD is 1 to 2% in the general population, 6,7 the prevalence in preterm children is several magnitudes higher (1.8 to 8% 8–11 ). Sensory, motor, and cognitive impairments, 11–13 as well as emotional/behavioral dysregulation, 14 which can affect the validity of the M-CHAT, occur more often in very preterm toddlers than term children.…”

mentioning

confidence: 99%

“…Sensory, motor, and cognitive impairments, 11–13 as well as emotional/behavioral dysregulation, 14 which can affect the validity of the M-CHAT, occur more often in very preterm toddlers than term children. Therefore, misclassification rates might be higher among preterm children with such deficits.…”

mentioning

confidence: 99%

Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm

Kim

Joseph

Frazier

et al. 2016

The Journal of Pediatrics

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Objective To examine the predictive validity of the Modified Checklist for Autism in Toddlers (M-CHAT) administered at 24 months of age for autism spectrum disorder (ASD) diagnosed at 10 years in a U.S. cohort of 827 Extremely Low Gestational Age Newborns (ELGAN) followed from birth. Study design We examined the sensitivity, specificity, positive predictive value and negative predictive value of the M-CHAT in predicting an ASD diagnosis at age 10 based on gold-standard diagnostic instruments. We then assessed how these predictive parameters were affected by sensorimotor and cognitive impairments, and socioeconomic status (SES), as well as emotional/behavioral dysregulation at age 2. Results Using standard criteria, the M-CHAT had a sensitivity of 52%, a specificity of 84%, a positive predictive value (PPV) of 20%, and the negative predictive value (NPV) of 96%. False positive and false negative rates were high among children who had hearing and vision impairments. High false positive rates were also associated with lower SES, motor and cognitive impairments, and emotional/behavioral dysregulation at age 2. Conclusions Among extremely preterm children with ASD, almost one-half were not correctly screened by the M-CHAT at age 2. Sensorimotor and cognitive impairments, SES, and emotional/behavioral dysregulation contributed significantly to M-CHAT misclassifications. Clinicians are advised to consider these factors when screening very preterm toddlers for ASD.

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Autism in Toddlers Born Very Preterm

Cited by 43 publications

References 35 publications

Prenatal stress alters amygdala functional connectivity in preterm neonates

Prenatal stress alters amygdala functional connectivity in preterm neonates

Early and long-term outcome of infants born extremely preterm

Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm

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