Lange-termijn prognose na zeer premature geboorte: de POPS-19 studie

1. Lange-termijn prognose na zeer premature geboorte: de POPS-19 studie Dr. Martijn J.J. Finken Afdelingen Kindergeneeskunde en Klinische Epidemiologie PAOG nascholing Jeugdgezondheidszorg Maastricht 2009

2. Uitspraak van een “ex-prematuur” • “Het is geen ziekte om te vroeg geboren te zijn, maar het is niet zomaar iets.”

3. Incidence of very preterm birth CBS-gegevens

4. Very preterm birth and in-hospital mortality CBS-gegevens

5. Changed characteristics over time of very preterm populations

6. POPS • Project On Preterm and Small-for-gestational-age infants cohort: • 94% of all liveborns in the Netherlands in 1983 with: • gestational age <32 weeks and/or • birth weight <1,500 g

7. Cohort retrieval Hille, et al. (Pediatrics 2005)

8. Very preterm birth and development of handicaps Walther, et al. (Early Hum Dev 2000)

9. Very preterm birth and functional outcomes at 19 y Hille, et al. (Pediatrics 2007)

10. Very preterm birth and functional outcomes at 19 y Hille, et al. (Pediatrics 2007)

11. Hille, et al. (Pediatrics 2007)

12. Very preterm birth and IQ at 19 y Weisglas-Kuperus, et al. (Arch Dis Child Fetal Neonatal Ed 2008)

13. Intrauterine growth: Maternal factors: Maternal height and parity Intoxications Medical conditions before or during pregnancy Placental factors: Anatomic and functional variants Fetal factors: Congenital infections Syndromes Hormones: IGF-I, IGF-II, insulin and cortisol Neonatal growth after preterm birth: Respiratory distress syndrome Bronchopulmonary dysplasia Infections Inadequate caloric intake Farmacologic effects: corticosteroids Causes of intrauterine and neonatal growth retardation

14. Growth velocity Wit, et al. (Pediatrics 2006)

15. Very preterm birth and height development Finken, et al. (Pediatrics 2006)

16. Very preterm birth and perinatal morbidity Finken, et al. (Pediatrics 2006)

17. Very preterm birth, catch-up growth and adult height Finken, et al. (Pediatrics 2006)

18. Preterm birth and insulin resistance at 7 y Hofman, et al. (NEJM 2004)

19. Preterm birth and insulin resistance in adulthood Hovi, et al. (NEJM 2007)

20. Very preterm birth and body composition at 19 y Euser, et al. (Am J Clin Nutr 2005); Finken, et al. (Diabetologia 2006)

21. Very preterm birth and blood pressure at 19 y Keijzer-Veen, et al. (Pediatrics 2005)

22. Birth size, childhood growth and later coronary artery disease Eriksson, et al. (BMJ 2001)

23. Birth size, postnatal catch-up growth and insulin level at 1 y Soto, et al. (JCEM 2003)

24. Very preterm birth and metabolic profile at 19 y Euser, et al. (Am J Clin Nutr 2005); Finken, et al. (Diabetologia 2006); Finken, et al. (Pediatr Res 2006)

25. Very preterm birth and insulin resistance at 19 y Finken, et al. (Diabetologia 2006)

26. Nutrition Catch-up growth Disease Catch-up growth and later disease: causal factor or epiphenomenon?

27. Nutritional intervention in preterm infants

28. Nutritional intervention in preterm infants Singhal, et al. (Lancet 2003); Singhal, et al. (Lancet 2004)

29. Nutritional intervention in preterm infants Lucas, et al. (BMJ 1998)

30. Nutritional intervention in preterm infants Singhal, et al. (Lancet 2001); Singhal, et al. (Lancet 2003); Singhal, et al. (Lancet 2004)

31. Maternal behaviour Epigenetic modifications Altered GR expression

32. Preterm birth and adrenocortical function at 20 y Szathmari, et al. (Horm Res 2001)

33. GR R23K polymorphism, very preterm birth and height development Finken, et al. (JCEM 2007)

34. GR R23K polymorphism, very preterm birth and metabolic profile at 19 y Finken, et al. (JCEM 2007)

35. Long-term effects in animals of antenatal glucocorticoid treatment • Raised blood pressure • Hyperglycemia • Renal morphology and function: • Smaller kidneys with less glomeruli • Lower GFR

36. Short-term benefits of antenatal glucocorticoid treatment Roberts & Dalziel (Cochrane Datab Syst Rev 2006)

37. Short-term benefits of antenatal glucocorticoid treatment • Higher glucose and insulin levels in cord blood • Less often inotropic support Verhaeghe, et al. (JCEM 2005); Moise, et al. (Pediatrics 1995)

38. Long-term effects of antenatal glucocorticoid treatment

39. GR N363S polymorphism, very preterm birth and waist circumference at 19 y Finken, et al. (in preparation)

40. Conclusions (1) • Preterm infants have a metabolic profile similar to that of children born SGA • Preterm infants with neonatal growth retardation display a growth pattern similar to that of children born SGA • At present, there is no trial data available suggesting a beneficial effect of rhGH therapy in short children born very preterm who had experienced neonatal growth retardation

41. Conclusions (2) • Activation of the HPA axis may contribute to adverse metabolic health after preterm birth • The GR R23K variant, associated with decreased sensitivity to glucocorticoids, protects against postnatal growth failure and insulin resistance after very preterm birth • The GR N363S variant, associated with increased sensitivity to glucocorticoids, predisposes to adverse body composition after perinatal glucocorticoid treatment in indivduals born very preterm

42. Recommendations • Children born very preterm and SGA or experiencing neonatal growth retardation should be flagged • Body composition should be monitored throughout childhood • Waist circumference is a more valuable tool than BMI for determination of body fatness