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Impact of fetal hypoxia duringlabour in the mature infant –development and diseases laterin life.Nana Wiberg, KK, Lund.


Brain sizeAntioxidant defenseGlutamate receptorsMyelinWater contentIschemia causesEnergy deficiencyGlutamate toxicity (= excitotoxicity)Lactic acidosis (pass cell membranescells. Causes cerebral edema by attracting water).Free radicalsdamage neurons, glial and mesenchymal


+Impairedcerebrovascularautoregulation+SystemichypotensionDepolarizationEnergy depletionloss of functionGlutamate discharge in synaptic cleftOpening of glutamate receptorsCalcium influxActivationcatabolic enzymes + NO synthaseNO productionImpairment of oxidativephosphorylation = freeradicalsCellular injury


Moderate ischemiaAcuteBasal ganglia andthalamiAthetoid and dystonicCP, intact or mildlyimpaired cognitivedevelopmentProlongedWatershed regionsModerate, spasticquadriplegia,variable cognitivedeficits


Severe ischemiaAcuteCerebral cortex addedto basal ganglia andthalamiSevere, spasticquadriplegia, cortial visualimpairment, microcephaly,cognitive deficitsProlongedExtensive corticalpathologySpastic quadriplegia,severe visual and cognitiveimpairment, microcephaly


Intrapartum hypoxia account onlyfor 15% of affected children


“Birth asphyxia refers to theimpairment of the normalexchange of respiratory gasesduring the birth process and theensuing adverse effects on thefetus”.Relevant to define pathological acidosis as the threshold atwhich the incidence of adverse clinical events starts tocorrelate strongly


Neonatal asphyxia refers topH < 7.005 min AS < 5Multiorgan failureEarly onset of moderate or severeencephalopathy


To predict hypoxia prevent progressionfrom mild to moderate/severe hypoxiaFetal scalp blood samplingCTGSTANTo confirmUmbilical cord blood


Apgar score5-min AS 0-35-min AS 4-6Persistent low 10-min AS1-year mortality 59%CP 75 % normal 5-min ASAS and acid/base values?Moderate/Severe acidemia86-89 % have normal AS


The majority (75%) of neonates withencephalopathy pH > 7.00But still: NE is caused by brain hypoxiaAcidosis paradox : neonates withoutacidemia still hypoxic but are unable todevelop acidemia as response = mechanicaleffects on the brain circulation


Malin G et al. BMJ 201051 articles481 753 newbornsfollow-up 0-8 years (metaanalysisfor long-term, only for CP)Association ofpH/adverse outcomenotpH as a prognostic test


The OR for an association oflow pH and neonatal mortality was strong(OR 16.9, 95% CI 9.7-29.5)Threshold effectcut-off pH 7.00;association did not reach significance overallcut-off pH 7.10association reach significance


The OR for an association oflow pH and neonatal morbidity was strong(OR 10.6, 95% 0.8-135.8 )Threshold effect ofmost substantial association –cut-off pH 7.00


Low arterial cord pHNEOR 13.8 (6.6-28.9, 95% CI 5.2-36.4)CPOR 2.3 (1.3-4.2, 95% CI 1.1-5.0)


Ellis et al BMJ 2000, 320,1229-36


Robertson 1993 (n=143) †Mild NE Moderate NE Severe NE40% 1 gr ofdisabilitiesManeum 2001 (n= 28)†recover 25% frontal lopedisabilitiesMarlow 2005 (n=65)†Follow-up (18 month to 12 years) † or(15 to 19 years) ‡ of children with NE6% CP anddisabilityCognitivedisabilities42% CP anddisabilityCognitivedisabilitiesThornberg 1995 (n=17) † recover ½ recover, ½ CP SeveredisabilitiesLindström 2008 (n= 43) ‡ 13% CP, 51%learningdisabilities,19% no imparmentEllis 1999 (n=131) † 15-25%death/disability50-100%death/disability


Cognitive dysfunction,Learning disabilities, attention, planning,short-term memory, motor/sensimotorcontrol,time perception, social function,languageMarlow N. BMJ 2005


ConclusionsAssociation with pH and neonatal outcome and CPAssociation of moderate to severe NE to cognitivedysfunction and CPbut results are conflicting


NeededLarge prospective cohort studies with longtermfollow up of different neonatalwellbeing measurements; accounting forpotential confounding factors, and not onlyin high-risk population


Thank you for your attention.


Useful predictorsfetal CTGseverity of acidosischest compressionapneaage of seizure onsetencephalopathy categoryneonatal behavioral examinationelectroencephalogram/brain imaging

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