Dr Veenu Gupta MD MRCPsych Consultant, Child Psychiatrist Stockton on Tees, UK

Transcription

1 Dr Veenu Gupta MD MRCPsych Consultant, Child Psychiatrist Stockton on Tees, UK

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3 Extremely Preterm-EP Very Preterm-VP Preterm-P Late Preterm-LP

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5 There is greater improvement of survival at extremely low gestational ages Growing evidence suggests that preterm represent a spectrum of health and neurodevelopmental adversity Understanding of the life-course consequences of immaturity at birth Studying the outcomes of these infants remains critical for evaluating and enhancing clinical care, and planning long-term support

6 Impaired neurodevelopmental outcome is a significant long-term complication associated with preterm birth. The risk of neurodevelopmental impairment and behaviour and psychological problems increases with decreasing gestational age. There is an inverse relationship between birthweight and behaviour, indicating that the lower the birthweight the greater the behavioural problems Epidemiologic studies have, for many years, identified preterm birth as a significant risk factor for psychiatric disorders J Trop Pediatr (2013) 59 (4):

7 Neurodevelopmental Disorders

8 Neurodevelopmental Disorders Group of conditions with onset in the developmental period. Disorders typically manifest early in development. characterized by developmental deficits that produce impairments of personal, social, academic function Intellectual Disorders Communication Disorders Autism Spectrum Disorder Attention Deficit/Hyperactivity Disorder Specific Learning Disorder

9 Preterm and Psychiatric Disorders

10 Psychiatric Disorders in Extremely Preterm Children: Longitudinal Finding at Age 11 Years in the EPICure Study Three times more likely to have a psychiatric disorder than classmates (23% vs. 9%; odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7, 6.2). Risk was significantly increased for: attentiondeficit/hyperactivity disorder (ADHD; 11.5% vs. 2.9%; OR = 4.3; CI = 1.5 to 13.0 Emotional disorders (9.0% vs. 2.1%; OR = 4.6; CI = 1.3 to 15.9), with increased risk for anxiety disorders (OR = 3.5; CI = 1.0 to 12.4) Autism spectrum disorders (8.0% vs. 0%; p =.000). Johnson S et al. Child & Adol Psych 2010;49(5):

11 Prevalence of psychiatric disorders at 11 y of age in a whole population-based cohort of 219 EPT (<26 wk) children (blue columns) and 152 term-born classmates (red columns) in the UK EPICure Study. Johnson S et al. Child & Adol Psych 2010;49(5):

12 Diagnostic studies reported increased prevalence of psychiatric disorders- LBW/VLBW children -22 to 27% Overall, these studies reported remarkably similar prevalence estimates and ORs indicating a 3 to 4 fold increased risk for psychiatric disorders in childhood. EPICure Study-23% met criteria for DSM-IV-TR defined psychiatric disorders, Pediatric Research (2011) 69, 11R 18R;

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14 Problems Behaviour

15 Under controlled (Externalizing) Problems for others Attention-Deficit/ Hyperactivity Disorder Conduct Disorder More Prevalent in Boys Over controlled (Internalizing) Problems for self Childhood Depression Anxiety Disorders More Prevalent in Girls

16 Externalizing Behaviours- Aggressive Impulsive Coercive Non-compliant Internalizing behaviours- Withdrawn lonely Depressed Anxious

17 Clinical Cohort studies investigating preterm<37wks/lbw <25OO Most studies used behavioural screening questionnaires Conclusion significant excess of behaviour problems in most preterm/lbw cohorts Prevalence- LBW- 19 to 40% VPT/VLBW -13 to 46% EPT/ELBW: 19 to 32% There was less consensus for children born moderate to late preterm (32 36 wk of gestation) Pediatric Research (2011) 69, 11R 18R

18 Impaired neurodevelopmental outcome is a significant long term complication associated with preterm birth Meta-analysis 16 case-control studies of behavioural outcomes of school aged children who were born preterm, showed a 2.6 fold risk. Negative behavioural sequelae of preterm birth Externalizing behaviours - 9 of 13 studies Internalizing behaviours -9 of 12 studies Confirmed an inverse relationship between birthweight and behaviour, indicating that the lower the birthweight the greater the behavioural problems Pediatric Research (2011) 69, 11R 18R

19 Swedish national prospective follow-up study examined 11-year-old children who were born before 26 completed week All had been evaluated at a corrected age of 36 months. questionnaires used Child, parent and teacher Conclusion- These children are at increased risk of mental heath problems

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21 Intellectual Disability is a disorder with onset during the develop-mental period that includes deficit in intellectual adaptive functioning Deficits in intellectual functions such as: reasoning, problem solving, planning, abstract thinking, judgment, academic learning

22 Verbal Comprehension Perceptual Reasoning Working Memory Processing Speed

23 Neurodevelopmental outcomes following late and moderate prematurity: a population-based cohort study 1130 LMPT ( weeks) and 1255 term-born children were recruited at birth from September 2009 through December 2010 in East Midlands (UK) At 2 years corrected age, cognitive development was assessed using the Parent Report of Children's Abilities-Revised (PARCA-R) Conclusion- Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). Two-year-old children born late and moderately preterm are at double the risk for neurodevelopmental disability compared with term-born peers. Archives of Disease in Childhood - Fetal and Neonatal Edition 2015;100: F301-F308

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25 Mean difference (95% CI) in Parent Report of Children s Abilities-Revised (PARCA-R) z scores between late and moderately preterm (32 36 weeks gestation) and term-born (37 42 weeks gestation) infants. z Scores were calculated using the mean (SD) of the term reference group. Solid lines represent crude differences and dashed lines represent differences adjusted for sex, socio-economic status and small for gestational age (SGA) status. PRC, parent report composite.

26 Meta-analyses have identified - IQ is significantly associated with gestational age at birth Gestational age <28 weeks - 14-point weighted mean difference Greater deficits observed in children born <26 weeks gestation. Preterm vs term-born children -weighted mean differences of IQ points (0.7 SD to 0.8 SD ) Very preterm (VP; <32 weeks)/very low birthweight (VLBW; <1500 g) cohorts have reported small to medium effect sizes (0.25 SD to 0.57 SD) for deficits in inhibition, working memory, planning, cognitive flexibility and verbal fluency Deficits in executive functions have also been observed on parent and teacher reports in EP/ELBW children and appear to persist over time. Cognitive impairments far surpass rates of neurosensory disabilities in EP populations. Archives of Disease in Childhood 2017;102:

27 EPICure Study of births <26 weeks gestation illustrate the deficits observed in educational outcomes at 6 years of age 50% of EP children below average attainment compared with 5% of termborn classmates (OR 17.9, 95% CI 8.3 to 38.9),54 with a similar deficit observed at 11 years of age (50% vs 5%; OR18.2, 95% CI 8.0 to 41.4)51 Conclusion-Attainment in all school subjects was also significantly poorer than term-born EP children appear to have greatest difficulties in mathematics. Archives of Disease in Childhood 2017;102:97-102

28 Archives of Disease in Childhood 2017;102:97-102

29 The Bavarian Longitudinal Study is a prospective geographically defined cohort study (Linda D. Breeman, Julia Jaekel Followed 260 VP/VLBW and 229 term-born individuals from birth to adulthood. Data on cognitive function were assessed with developmental and IQ tests at 5 and 20 months and at 4, 6, 8, and 26 years of age. Very preterm (VP; gestational age,32 weeks) and very low birth weight (VLBW; abstract,1500 g) births are related to impaired cognitive function across the life span.

30 More than a quarter of VP/VLBW n = 69, 26.5%) and 3.9% (n = 9) of term-born adults were diagnosed with severe cognitive impairment, based on mean and variance of term born adult IQ scores.

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32 Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in Western countries Affects an estimated 3% to 5% of school-age children. Boys are about three times more likely than girls to be diagnosed with it. Kids with adhd act without thinking, are hyperactive, and have trouble focusing. They may understand what's expected of them but have trouble following through because they can't sit still, pay attention, or attend to details.

33 Method- Register study in a Swedish national cohort of children born between 1987 and 2000, followed up for ADHD medication in 2006 at the age of 6 to 19 years. Logistic regression was used to test Results- There was a stepwise increase in odds ratios for ADHD medication with increasing degree of immaturity at birth; 23 to 28 weeks -2.1 ( ) 29 to 32 weeks -1.6 ( ) 33 to 34 weeks -1.4 ( ) 35 to 36 weeks - 1.3( ) 37 to 38 weeks -1.1( ) Preterm and early term birth increases the risk of ADHD by degree of immaturity. This main effect is not explained by genetic, perinatal, or socioeconomic confounding. PEDIATRICS 2011; 127(5):

34 Model 1 -adjusted for year of birth, gender, and county of residence. Model 2 is adjusted for year of birth, gender, county of residence, birth order, maternal age, maternal education, single parenthood, public welfare, maternal smoking, and maternal/paternal psychiatric/addictive disorders. Model 3 is adjusted for year of birth, gender, county of residence, birth order, maternal age, maternal education, single parenthood, public welfare, maternal smoking, and maternal/paternal psychiatric/addictive disorders, low Apgar score and small for gestational age. CI indicates confidence interval. PEDIATRICS 2011; 127(5):

35 ADHD is the most prevalent and frequently studied psychiatric disorder in preterm/lbw populations Studies using DSM-based questionnaires reported a significant excess of ADHD VLBW/ELBW -ranging 16 to 19% VPT/VLBW -ranging 9 to 11% EPT/ELBW ranging 17 to 20% (indicating a GA-related gradient ) The pooled relative risk (RR) for ADHD in VPT/VLBW survivors in six studies was 2.64 (95% CI, ) Prevalence- Conclusion- The existing reports indicate a 2- to 3-fold increased risk for ADHD in VPT/VLBW children 4-fold increased in those born EPT/ELBW Pediatric Research (2011) 69;11R 18R

36 Pediatric Research (2011) 69;11R 18R

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38 Persistent deficits in social communication and social interaction across multiple contexts Deficits in social-emotional reciprocity (e.g., less interest in sharing enjoyments) Deficits in non-verbal communicative behaviors used for social interactions (e.g., abnormalities in eye contact, body postures, facial expressions) Deficits in developing, maintaining and understanding relationships (e.g., poor in understanding of others feelings, not interested in playing such as a peek-a-boo) Hyper or hypo reactivity to sensory input or unusual interests in sensory aspects of the environment (e.g., hyperactivity or lacks of aware)

39 large cohort study of 10-year-old children born at weeks' gestation This prospective multicentre (14 institutions in 5 states) study included children born at weeks' gestation in 2002 through 2004 Evaluated for autism spectrum disorder and intellectual disability at age 10 years. 857 (96%) were assessed for Autism spectrum disorder Study confirms that low gestational age is associated with increased risk for autism spectrum disorder irrespective of intellectual ability Whereas severe foetal growth restriction is strongly associated with autism spectrum disorder without intellectual disability Am J Obstet Gynecol Mar;216(3):304.e1-304

40 Prevalence of psychiatric disorders at 11 y of age in a whole population-based cohort of 219 EPT (<26 wk) children (blue columns) and 152 term-born classmates (red columns) in the UK EPICure Study. Johnson S et al. Child & Adol Psych 2010;49(5):

41 A retrospective cohort of infants born at 24 weeks between at 11 Kaiser Permanente Northern California hospitals (n = ). Cox proportional hazards regression models were used to evaluate the association between gestational age and ASD as well as potential risk factors in the neonatal intensive care unit and ASD. Results The prevalence of ASD in infants <37 weeks was 1.78% compared with 1.22% in infants born 37 weeks (P <.001) weeks(adjusted HR) 2.7 (95% CI ) weeks (adjusted HR) 1.4 (95% CI ) weeks (adjusted HR) 1.3 (95% CI ) Conclusions ASD was 3 times more prevalent in infants <27 weeks compared with term infants. Each week of shorter gestation was associated with an increased risk of ASD. High frequency ventilation and intracranial haemorrhage were associated with ASD among infants <34 weeks Jpeds;3476(13)

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43 The Neurodevelopmental disorders are significantly higher in preterm babies Professionals should utilise to counsel parents about critical care decisions around birth. Planning of appropriate services for early identification and long term care.

44 Thank You