Lange termijn prognose na zeer premature geboorte de pops 19 studie
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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. Uitspraak van een “ex-prematuur”.

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

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Lange termijn prognose na zeer premature geboorte de pops 19 studie

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


Uitspraak van een ex prematuur

Uitspraak van een “ex-prematuur”

  • “Het is geen ziekte om te vroeg geboren te zijn, maar het is niet zomaar iets.”


Incidence of very preterm birth

Incidence of very preterm birth

CBS-gegevens


Very preterm birth and in hospital mortality

Very preterm birth and in-hospital mortality

CBS-gegevens


Changed characteristics over time of very preterm populations

Changed characteristics over time of very preterm populations


Lange termijn prognose na zeer premature geboorte de pops 19 studie

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


Cohort retrieval

Cohort retrieval

Hille, et al. (Pediatrics 2005)


Very preterm birth and development of handicaps

Very preterm birth and development of handicaps

Walther, et al. (Early Hum Dev 2000)


Very preterm birth and functional outcomes at 19 y

Very preterm birth and functional outcomes at 19 y

Hille, et al. (Pediatrics 2007)


Very preterm birth and functional outcomes at 19 y1

Very preterm birth and functional outcomes at 19 y

Hille, et al. (Pediatrics 2007)


Lange termijn prognose na zeer premature geboorte de pops 19 studie

Hille, et al. (Pediatrics 2007)


Very preterm birth and iq at 19 y

Very preterm birth and IQ at 19 y

Weisglas-Kuperus, et al. (Arch Dis Child Fetal Neonatal Ed 2008)


Causes of intrauterine and neonatal growth retardation

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


Growth velocity

Growth velocity

Wit, et al. (Pediatrics 2006)


Very preterm birth and height development

Very preterm birth and height development

Finken, et al. (Pediatrics 2006)


Very preterm birth and perinatal morbidity

Very preterm birth and perinatal morbidity

Finken, et al. (Pediatrics 2006)


Very preterm birth catch up growth and adult height

Very preterm birth, catch-up growth and adult height

Finken, et al. (Pediatrics 2006)


Preterm birth and insulin resistance at 7 y

Preterm birth and insulin resistance at 7 y

Hofman, et al. (NEJM 2004)


Preterm birth and insulin resistance in adulthood

Preterm birth and insulin resistance in adulthood

Hovi, et al. (NEJM 2007)


Very preterm birth and body composition at 19 y

Very preterm birth and body composition at 19 y

Euser, et al. (Am J Clin Nutr 2005); Finken, et al. (Diabetologia 2006)


Very preterm birth and blood pressure at 19 y

Very preterm birth and blood pressure at 19 y

Keijzer-Veen, et al. (Pediatrics 2005)


Birth size childhood growth and later coronary artery disease

Birth size, childhood growth and later coronary artery disease

Eriksson, et al. (BMJ 2001)


Birth size postnatal catch up growth and insulin level at 1 y

Birth size, postnatal catch-up growth and insulin level at 1 y

Soto, et al. (JCEM 2003)


Very preterm birth and metabolic profile at 19 y

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)


Very preterm birth and insulin resistance at 19 y

Very preterm birth and insulin resistance at 19 y

Finken, et al. (Diabetologia 2006)


Catch up growth and later disease causal factor or epiphenomenon

Nutrition

Catch-up growth

Disease

Catch-up growth and later disease: causal factor or epiphenomenon?


Nutritional intervention in preterm infants

Nutritional intervention in preterm infants


Nutritional intervention in preterm infants1

Nutritional intervention in preterm infants

Singhal, et al. (Lancet 2003); Singhal, et al. (Lancet 2004)


Nutritional intervention in preterm infants2

Nutritional intervention in preterm infants

Lucas, et al. (BMJ 1998)


Nutritional intervention in preterm infants3

Nutritional intervention in preterm infants

Singhal, et al. (Lancet 2001); Singhal, et al. (Lancet 2003); Singhal, et al. (Lancet 2004)


Lange termijn prognose na zeer premature geboorte de pops 19 studie

Maternal behaviour

Epigenetic modifications

Altered GR expression


Preterm birth and adrenocortical function at 20 y

Preterm birth and adrenocortical function at 20 y

Szathmari, et al. (Horm Res 2001)


Gr r23k polymorphism very preterm birth and height development

GR R23K polymorphism, very preterm birth and height development

Finken, et al. (JCEM 2007)


Gr r23k polymorphism very preterm birth and metabolic profile at 19 y

GR R23K polymorphism, very preterm birth and metabolic profile at 19 y

Finken, et al. (JCEM 2007)


Long term effects in animals of antenatal glucocorticoid treatment

Long-term effects in animals of antenatal glucocorticoid treatment

  • Raised blood pressure

  • Hyperglycemia

  • Renal morphology and function:

    • Smaller kidneys with less glomeruli

    • Lower GFR


Short term benefits of antenatal glucocorticoid treatment

Short-term benefits of antenatal glucocorticoid treatment

Roberts & Dalziel (Cochrane Datab Syst Rev 2006)


Short term benefits of antenatal glucocorticoid treatment1

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)


Long term effects of antenatal glucocorticoid treatment

Long-term effects of antenatal glucocorticoid treatment


Gr n363s polymorphism very preterm birth and waist circumference at 19 y

GR N363S polymorphism, very preterm birth and waist circumference at 19 y

Finken, et al. (in preparation)


Conclusions 1

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


Conclusions 2

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


Recommendations

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


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