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Disease of the fetus and new born

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1 Disease of the fetus and new born
Hyaline memb disease - 출생후 blood-gas exchange를 위해 infant’s lung은 fluid가 제거되고 air가 차게되며 blood volume이 증가하게 된다. - surfactant : synthesis by type 2 pneumocyte Stabilize the air expanded alveoli by lowering surface tension ->prevent lung collapse during expiration - surfactant 부족 ->repiratory distress characterized by the formation of hyaline membrane(distal bronchioles and alveoli)

2 Hyaline memb disease Clinical course
- tachypnea, chest wall retraction - whimper and grunt while expiration - poor peripheral circulation & systemic hypotension - x-ray : diffuse reticulogranular infiltrate air bronchogram - respiratory insufficiency의 다른 원인 ; sepsis, pneumonia, meconium aspiration, pneumothorax, diaphragmatic hernia, persistant fetal circulation, heart failure

3 Hyaline memb disease Pathology -without sulfactant
-> alveoli are not stable low pressure cause collapse on end expiration -> partial maintenance of the fetal circulation (pulmonary HTN) RT to LT shunt -> airway 의 lining cell의 ischemic necrosis

4 Hyaline memb disease Treatment - admission to NICU
- arterial PCO2 40mmHg 이하인경우 : oxygen therapy가 필요 Oxygen tension : 50 ~ 70 mmHg가 적당함 (excess oxygen -> epithelium & retina 의 damage - CPAP ( Continuous Positive Airway Pressure) -> prevent the collapse of unstable alveoli & reduce motality rate -> 단점 : venous retrun 감소 barotrauma bronchopulmonary dysplasia

5 Hyaline memb disease Surfactant Tx
- utilized for prophylaxis of preterm infant at risk for respiratory distress - respiratory distress 확진될 경우에도 사용 Complication - persistent hyperoxia : injury the alveoli & capillary bronchopulmonary dysplasia pulmonary hypertension retinopathy of prematurity

6 Hyaline memb disease Prevention
- elective preterm birth can be avoided - amniocentesis for fetal lung maturity -lecithin-to-sphingomyelin (L/S) ratio -> 34 weeks : concetration of lecithin begin to rise -> L/S ratio > 2 : neonatal respiratory distress의 risk는 적음 < 2 : neonatal respiratory distress의 risk는 증가 (more predictive than gestational age or birth weight) -> some pregnancy complication(DM) : mature L/S ratio 때 도 respiratory distress가 나타날 수 있음

7 Hyaline memb disease Prevention
- phosphatidylglycerol -> enhance the surface – active properties of lecithin & sphingomyelin -> its identification : more assurance not absolute guarantee ->TD X –FLM measure the surfactant – albumin ratio in amnionic fluid TDX 50 이상 : lung maturity in 100%

8 Prevention - other test • foam stability (shake test)
: mixed with ethanol stable foam at the air-liquid interface -> lung maturation Problem : ① amniotic fulid reagents, glassware의 contamination이 검사결과에 영향을 줌 ② false negative가 많다 • lumadex – FSI test • fluorescent polarization • amniotic fluid absorbance at 650-nm • lamellar body count • DPPC test

9 Retinopathy of prematurity
Pathology - retina vascularization : fourth month Optic nerve주위에서 시작 -> 이 시기 retinal vessel 은 excessive oxygen에 의해 쉽게 damage를 받음 retina의 temporal portion이 가장 손상받기 쉬움 - oxygen therapy : vascular damage site에서 neovascularization -> new ressel penetrate the retina -> hemorrhage Adhesion Detach the retina - oprevention : 40%이하의 oxygen을 포함하는 공기흡입 Large dose of VIT E

10 Respiratory distress in the term infant
Common cause : sepsis, intrauterine – acquired pneumonia, persistent pul hypertension, meconium aspiration syn, pulmonary hemorrhage treatment : similar to that for respiratory distress from surfactant deficiency in preterm labor - oscillatory ventilation - nitric oxide

11 Meconium aspiration Characteristics : chemical pneumonitis
mechanical obstrction of the airway Persistent pul hypertension ( severe case ) Risk factor : postterm preg Fetal growth restriction Diminished amniotic fluid vol Cord compression, uteroplacental insufficiency

12 Meconium aspiration Prevention Amnioinfusion
; head delivery 후 chest 분만전에 oropharyngeal suctioning tracheal suctioning Amnioinfusion - relieve of variable deceleration in labor - cord compression으로 인한 cariable deceleration감소 -> prevent mecoium aspiration - may benefit only meconium is thick - not benefit : meconium aspiration has occurred before onset of labor

13 Mecomium aspiration Management
- shoulder 가 delivery 되기전에 infant’s mouth, nares를 suction - hypopharynx에 있는 meconium을 보면서 suctioning - intubation후 low aierway의 meconium suctioning - stomach is emtied ( avoid further meconium aspiration )

14 Intraventricular hemorrhage
4 major categories - subdural hemorrhage (trauma) - subarachnoid hemorrhage ( trauma, hypoxia ) - intracerebella hemorrhage (trauma, hypoxia) - intraventricular hemorrhage ( trauma, hypoxia )

15 Periventricular–intraventricular hemorrhage
Common problem in preterm neonate Develop within 72 hours of birth ,as late as 24 days Almost half are clinically silent Large lesion – hydrocephalus, periventricular leukomalacia

16 Periventricular–intraventricular hemorrhage
Pathology - germinal matrix capillary network : 1. The subependymal germinal matrix provides poor support for the vessels coursing through it 2. Venous anatomy in this region cause venous stasis and congestion susceptible to vessel bursting with increased intravascular pressure 3. Vascular autoregulation is impaired before 32 seeks - extensive hemorrhage – not cause death neurodevelopmental handicap - periventricular leukomalacia : hemorrhage 보다는 ischemia 의 결과

17 Periventricular-intraventricular hemorrhage
Incidence and severity - depend on gestational age - half of all neonates born before 34 weeks have evidence of hemorrhage - severity : ultrasound CT - grade 1 : hemorrhage limited to the germinal matrix grade 2 : intraventricular hemorrhage grade 3 : hemorrhage with rentricular dilation - grade 1,2 : over 90% survial 3.2 % handicap grade 3,4 : 50% survial rate

18 Periventricular-intraventricular hemorrhage
Contributing factor - immaturity - respiratory distress syn, mechanical ventilation - cord arterial Ph : 7.2 감소 -> grade 3, 4 hemorrhage의 위험도 증가 Prevention and treatment - administration of corticosteoid before delivery - phenobarbital or Vit E - avoiding significant hypoxia

19 Periventricular-intraventricular hemorrhage
Outcome in extreme prematurity - limits of viability : 22 ~ 25weeks -> neurological, ophthalmological, pulmonary injury 가 문제가 됨 surfactant therapy : < 23wks – no survived 23wks-98% / 24wks- 74% / 25wks-31% -> died or neurologic abnormality

20 Cerebral palsy Nonprogressive motor disorder of early infant onset involving one or more limbs with resulting muscular spasticity or paralysis Epilepsy and MR may also be associated Major type : 1. Spastic quadriplegia (MR, seizure discorder와 연관) 2. Diplegia (preterm low birth weight infant에서 혼합) 3. Hemiplegia 4. Choreoathetoid type 5. Mixed varieties 35% : hemiplegic 20% : quadriplegic 15% : extrapyramidal type 25% 에서 IQ 50 미만의 MR이 동반

21 Cerebral palsy Incidence and epidemiological correlates
- 1~2 per 1000 livebirth - < 2500g : 15/1000 500~1500g : 13 ~ 90 /1000 -risk factor : 1. evidence of genetic abnormalities(maternal MR, microcephaly, congenital malformation) 2. birthweight less than 2000g 3, gestational age less than 32 weeks 4. Infection

22 Cerebral palsy Apgar score - use to predict neurological impairment
- 5 minute apgar score of 3 or less : increase motality and cerebral palsy - 1 minute apgar score of 3 or less : incidence of death 는 5배증가 incidence of cerebral palsy는 3배증가 - low score at 1 and 5 minute : indicator for need resuscitation

23 Cerebral palsy Umbilical cord blood gas
- asphixia 의 definition에서 중요한 것은 metabolic acidosis이다. - significant acidemia : Ph < 7.0 - umbilical artery PH : used to assess predictability of neonatal death Nucleated re blood cell - response to hypoxia 으로 나타나는 immature cell - degree of hypoxia - hematological makers maternal and new born infection, placental infection

24 Periventricular leukomalacia
Cystic area deep in the white matter after hemorrhage infarction and ischemia Tissue ischemia -> necrosis : irreversibly damage Cerebral palsy 가 있는 low-birth weight infant의 40% : grade 3,4 hemorrhage : no hemorrhage or grade 1, 2 hemorrhage 가 있는 infant 보다 cerebral palsy 위험이 16배 높다 Infection, inflammation Neonatal hypotension Prolonged rupture of memb Chorioamnionitis Neonatal acidosis Ritodrine therapy

25 Periventricular leukomalacia
Preterm fetus and periventricular leukomalacia -before 32 weeks, blood supply to the brain ; ventriculopedal system Ventriculofugal system -> 이 두 blood supply가 만나는 곳은 lat ventricle근처로 vascular anastomosis가 없어서 ischemia의 위험성이 있다.

26 Periventricular leukomalacia
Perinatal infection - key element between preterm birth, intracranial hemorrhage periventricular leukomalacia, cerebral palsy maternal of intrauterine infection -> cytokine production -> prostaglandin production ↓ ↓ ↓ direct toxic dffect preterm birth periventricular ↓ cerebral palsy ← leukomalacia ← immature and hemorrhage developmen - spotaneous labor or membrane rupture 가 있는 infant에서 intravascular hemorrhage & periventricular 의 severity incidence가 높다

27 Periventricular leukomalacia
Prenention - corticosteoid - aggressive Tx of prophylaxis against infection -magnesium sulfate ; intracranial vascular tone을 stabilize시킴 Cerebral bleed flow를 minimize하게 변동시킴 Reperfusion injury를 reduce시킴 Calcium – mediated intracellular damage를 block Cytokine과 bacterial endotoxin의 synthesis를 reduce

28 Periventricular leukomalacia
Neuroradiological imaging - CT, MR : cerebral palsy 의 timing neuropathology를 define하는 데 사용됨 cranial ultrasound : antenatal injury의 diagnosing에 critical periventricular leukomalacia의 진단에도 쓰임 - MRI : cerebral palsy 의 development와 관련된 intracranial lesion의 study에 사용

29 Neonatal encephalopathy
Term infant 의 earliest days에서 neurological function의 disturbance 를 나타내는 sysndtrome으로 정의됨 ; difficulty respiration, depressed tone & reflex, subnormal level of consciousness, frequent seizure Hypoxic – ischemic insult 의 결과로 일어난다고 생각되나 원인을 알 수 없는 경우도 많음 Mild – hyperalertness, irritability, jitterness, hypertonia, hypotonia Moderate – lethargy, severe hypertoia, seizure Severe – coma, multiple seizure, recurrent apnea

30 Neonatal encephalopathy
Mental retardation - 3 per 1000 children - etiologic factor Some etiological factor for severe mental retardation Prenatal chromosimal mutant genes Multiple congenital anomalies Acquired infections, diabetes, growth restriction 10 Prenatal Asphyxia or hypoxia Unidentified causes Postnatal Unknown

31 Neonatal encephalopathy
Seizure disorder - accompany cerebral palsy - isolated seizure disorder epilepsy : not caused by perinatal hypoxia - major predictor ; fetal malformation (cerebral and noncerebral ) family history

32 Anemia 35주 이후 cord hemoglobin concentration이 14 g/ dl 이하이면 abnormal
Delayed cord clamping : hemoglobin value를 20%상승시킬 수 있다. Placenta is cut or torn, fetal vessel is perforated or laceration, cord clamping 전 placenta 보다 태아가 높게 위치될 경우 -> hemoglobin may fall Feta-to-maternal hemorrhage - acid elution technique : maternal circulation에 있는 fetal red cell을 발견할 수 있다. - fetal intravascular compartment에서 blood cell 의 small vol 이 maternal intervillous space로 들어갈 수 있다. - large hemorrhage : uncommon Isoimmuniztion

33 Anemia Fetal-to-maternal hemorrhage
- heart pattern : severe anemia -> sinusoidal pattern chronic anemia -> no fetal heart rate abnormality - significant hemorrhage : neurological fetal impairment - acute hemorrhage -> fetal hypotension Diminished perfusion Ischemia Cerebral infarction - cause of large fetal – to – maternal hemorrhage : chorioangioma, placental abruption - fetal- maternal hemorrhage의 양측정 -> D negative 인 woman 에게 줄 D-immune globulin의 dose를 결정하는 데 중요 Fetal red cell = MBV * maternal Hct * % fetal cell KB New born Hct

34 Isoimmunization Specific red cell antigen이 없는 사람이 antigen에 노출되었을 때 antibody가 생성되게 된다. 이 antibody는 blood transfusion 받는 사람이나 pregnancy중 태아에게 해로운 영향을 줄 수 있다. Fetus의 erythrocyte가 maternal circulation에 도달하면 immune response가 일어나게 되고 드물게 isoimmunization이 일어나게 된다. 드문이유 : -> varying rate of occurrence of red cell antigen -> variable antigenicity -> insufficient transplacental passge of antigen or antibody -> variability of the maternal immune response to the antigen -> protection from isoimmunization by ABO incompatibility of fetus and mother

35 Anemia D negative woman : D positive infant
ABO – compatible infant -> isoimmunization of 16% ABO – incompatible infant -> isoimmuniation of 2%

36 ABO blood group system Incompatibility for blood group antigen A and B
-> Most common cause of hemolytic disease in the new born All infant 의 20%가 ABO maternal blood group in compatibility를 보이지만 5%만이 clinical 하게 영향을 받음 ABO incompatibility : mild disease ( neonatal jaundice, anemia ) Not erythroblastosis fetalis ABO incompatibility 가 CDE incompatibility와 다른점 - ABO disease is frequently seen in firstborn infant - although disease is common, milder than D-isoimmunization - ABO incompatibility can affect future pregnancies - caucasian, Africa-American infant 에서 ABO disease가 일어남

37 ABO blood group system Criteria for diagnosis Tx
1. Mother : group o, with anti – A & anti-B antibody Ferus : group A, B or AB 2. First 24hr 이내 jaundice의 onset 3. 다양한 정도의 anemia, reticulocytosis, erythroblastosis가 있을 때 4. Hemolysis의 다른 cause가 제외되었을 때 Tx - similar to D-isoimmunization - simple or exchange transfusion : group o blood is used

38 CDE (RHESUS) blood group system
이 red cell antigen은 임상적으로 중요함 왜냐하면, D또는 Rhesus antigen이 없는 사람은 한번노출로써 immunized되기 때문이다. CDE gene은 다른 blood group gene과 independent하게 유전되고, chromosome 1 의 short arm에 위치하고 있다. Native american, chinese, asiatic people 은 99% D positive Caucasian : 87% D-positive Basques : 34% D- negative Rhesus blood group system : five red cell protein or antigen ( c, C, D, e and E ) D antigen 이 없는 것이 D- negative C. c. E. e antigen은 D antigen 보다 immunogenicity가 낮으나 erythroblastosis fetalis를 일으킬 수 있다.

39 Other blood group incompatibility
Rarer red cell antigen 에 의해 발생되는 antenatal hemolytic disease는 indirect coombs test로 screening할 수 있다. 544 antibodies중 72%가 CDE group , anti-D가 가장 흔하다.

40 Kell antigen Uncommon Kell-positive blood 의 transfusion의 결과로 senstinization 됨 Maternal-fetal incompatibility의 결과로 senstinization이 일어날수 있음 ->rapid & severe fetal anemia

41 Other antigen Kidd (Jka), Duffy(Fya), c, E, C
->erythroblastosis를 일으킬수 있음 대부분 이 antigen의 isoimmunization 은 blood transfusion 후에 일어난다. Anti-C isoimmunization : previous preg 의 결과로써 흔하다 ->moderate to severe hemolysis를 일으킴

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