Development challenges in early development – and HIV Linda Richter

1. Development challenges in early development – and HIV Linda Richter Human Sciences Research Council, South Africa Non-Abstract Session Children Growing up with HIV AIDS 2012, Washington DC 25 July 2012

2. Outline • Early development • New science of early child development – longitudinal perspectives • Experience-expectant, experience-dependent systems – programming • HIV and ART effects on early development • Conclusions

3. Early development • Children’s development occurs progressively, in sequence • One thing follows the other and is dependent on what goes before • There is no going back • Incomplete, ill-formed stages can lead to deficits • Especially in the absence of self-righting influences and experience • Many poor children have few, if any, second chances • Early development is a period of unique susceptibility to environmental influences

4. The first 1000 days 270 (pregnancy) + 365 (year 1) + 365 (year 2) = 1000 days • Period of unique susceptibility to deficits andcompensation • Driven by genetic potential, modified by environment • Epigenetics – genetic potential modified in utero ad early infancy by prevailing = anticipated environment • Subsequently less amenable to modification

5. Developmental progression First 1000 days Maternal health

6. Long-term consequences Of exposures and experiences in early development on long-term: • Health • Human capital • Psychosocial adjustment Data from low and middle income countries

7. Long-term studies in LMICs COHORTS – Consortium of Health-Oriented Research in Transitioning Societies

8. Health • Poor nutrition and growth, during foetal development and infancy • - Constrain adult height, offspring size (inter-generational) • - Increase risks for chronic disease – obesity, diabetes, cardiovascular disease • - Increase risks for mental illness • Early exposure to adverse experiences (neglect, domestic violence, parental mental ill-health or substance use) • - Increase risk of chronic disease, mental ill-health and social maladjustment

9. Human capital Stunting before age 3 years (<2SD) is associated with: • Less education - Lower cognitive test scores - Fewer grades passed - Less learning - average ± minus1 grade of schooling • Earnings • 8-20% less income • Food supplementation <3yrs, 40 yr follow-up (Guatemala) • Up to 46% difference in income • Fewer hours worked

10. Psychosocial adjustment • Poor in utero growth  mental illness (famine studies) • Adverse childhood experiences (ACE)  • - Tobacco, alcohol and drug use, suicide risk, depression • Toxic stress – stress responsivity - revving engine, hair trigger reaction • Influences ‘internal working models, expectations of relationships • Emotional and behavioural control

11. HIV (& ARVs) - early development • Pregnancy and delivery • Birth weight and growth • Feeding • Social and economic security • Psychosocial care • Maternal wellbeing and mental health

12. HIV - pregnancy complications • Been aware of possibility since at least1990 • Increased spontaneous abortion, perinatal mortality, prematurity, SGA, low birth weight, neonatal mortality (Brocklehurst & French 1998) • Earlier studies • ? poor pregnancy weight gain • Seemingly not associated with anti-viral drugs (Schulte et al, 2007) • Rather, advanced HIV disease, malaria, intestinal parasites

13. HIV, ART and mortality Brady et al (2011) • PACTG, USA, multicentre • 3 553 children, 1993-2006 • 298 deaths • Deaths decreased from 7.2 to 0.8 per 100 person- years by 2000, then stable • Co-variates – illness stage, time HAART initiation • Mortality ± 30 times higher than general USA pediatric population (similar in UK) • Mortality due to infections, multi-organ failure (end stage AIDS)

14. HIV, ART and growth Nielsen-Saines et al 2012 – Brazil, India, Thailand, Malawi, SA, Zimbabwe (n=236) - Infants followed up for 18 mo – survival very good • 77% gestation age >37 wks, 86% birth weight ≥2.5 kg • 8% congenital abnormalities; 30% neonatal medical conditions • Growth inversely correlated with maternal viral load – up to 18mo • 38% infants serious adverse events eg anaemia - associated with less/shorter maternal ARV exposure • ?Finding related to careful surveillance? Filtreau (2009) – poorer physical growth and development amongst HIV exposed, but uninfected children

15. HIV, ART and nutrition Infant and young child feeding • Low rates of exclusive breastfeeding • Early weaning, partly as a result of confusing policy (Kuhn & Coovadia, 2012) • Inadequate weaning diet, feedingfrequency low, non-active and non-responsive feeding • HIV, ART and effects of poor nutrition confounded, including by low levels of active, responsive feeding due to caregiving stresses

16. HIV, ART and development Abukaker et al (2008) – HIV: 7 studies in SSA, results comparable to West • Delayed motor development most apparent, detected earliest • Mental development delays by 18mo • Language by 24mo – language, mental harder to measure? • Less secure attachment, less positive affect Sherr et al (2009) – HIV: systematic review 42 studies • Quality variable • 81% of studies found cognitive deficits Williams et al (2010) – ART: PACTG, USA, multi-centre • 92% exposed to ART in utero, 8% not • Bayley Developmental Scales at 1 year • No differences in neurodevelopment (environmental effects?)

17. Home environment • Biological and environmental factors jointly influence developmental outcomes • In the USA, behavioural and emotional problems of CLWH attributed to social risks and not to HIV infection per se (Mellins et al 2004) • The social context of many families affected by HIV involves poverty, dislocation, isolation, stress, bereavement • Maternal wellbeing, including depression, and effects on caregiving

18. Lancet “Child Development” series 2007 and 2011 review the impacts of poverty and poor home environments on young children’s development over the long term

19. Caregiving • Infants and young children - experience-expectant and experience-dependent caregiving • Emotionally available and responsive • Alertto and delighted by the child’s unfolding developmental timetable • Attentive to signs of distress, discomfort, illness • Self-efficacy and capacity to respond • Requires: • Good health, lack of stress, emotional wellbeing • Support from partner and intimate others • Security and safety

20. HIV and caregiving • Conditions for optimal caregiving may not be present • Ill-health, preoccupation and anxiety – evidence on parenting in context of chronic illness • Lack of support and security, isolation • Depression • Life time prevalence among women 10-24% • Higher amongst women of lower SES, during pregnancy and when children are young • Amongst pregnant WLH as high as 53% (Levine et al, 2008); Chibanda et al, 2010) • Associated with poor child outcomes, treatment non- adherence generally (DiMatteo et al, 2000)

21. Conclusions • Available evidence suggests that long-term care and support critical to the survival, growth, health and wellbeing of CLWH and negative children exposed to HIV and ART • Less evidence than we should have on this important issue – much more research needed • - Eg first trimester exposure to ARV during embryogenesis • - Critical to follow-up • HIV+ children in LMICs • HIV- but HIV and ARV–exposed children in LMICs • Like with breastfeeding, advocate for knowledge and practice to make children’s development safer, healthier and happier • .