Disease of the fetus and new born

Hyaline memb disease - 출생후 blood-gas exchange 를 위해 infant’s lung 은 fluid 가

제거되고 air 가 차게되며 blood volume 이 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)

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 insufficiency 의 다른 원인; sepsis, pneumonia, meconium aspiration, pneumothorax, diaphr

agmatic hernia, persistant fetal circulation, heart failure

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 cell 의 ischemic necrosis

Hyaline memb disease

Treatment- admission to NICU- arterial PCO2 40mmHg 이하인경우 : oxygen therapy 가 필요 Oxygen tension : 50 ~ 70 mmHg 가 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

Hyaline memb disease

Surfactant Tx- utilized for prophylaxis of preterm infant at risk for respiratory dis

tress- respiratory distress 확진될 경우에도 사용

Complication- persistent hyperoxia : injury the alveoli & capillary bronchopulmonary dysplasia pulmonary hypertension retinopathy of prematurity

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 distress 의 risk 는 적음 < 2 : neonatal respiratory distress 의 risk 는 증가 (more predictive than gestational age or birth weight) -> some pregnancy complication(DM) : mature L/S ratio 때 도 respiratory distress 가 나타날 수 있음

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%

Prevention

- other test

• foam stability (shake test)

: mixed with ethanol

stable foam at the air-liquid interface -> lung maturation

Problem : ① amniotic fulid reagents, glassware 의

contamination 이 검사결과에 영향을 줌

② false negative 가 많다

• lumadex – FSI test

• fluorescent polarization

• amniotic fluid absorbance at 650-nm

• lamellar body count

• DPPC test

Retinopathy of prematurity

Pathology - retina vascularization : fourth month Optic nerve 주위에서 시작 -> 이 시기 retinal vessel 은 excessive oxygen 에 의해 쉽게 dama

ge 를 받음 retina 의 temporal portion 이 가장 손상받기 쉬움 - oxygen therapy : vascular damage site 에서 neovascularization -> new ressel penetrate the retina -> hemorrhage Adhesion Detach the retina - oprevention : 40% 이하의 oxygen 을 포함하는 공기흡입 Large dose of VIT E

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

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

Meconium aspiration

Prevention ; head delivery 후 chest 분만전에 oropharyngeal suctioning tracheal suctioning

Amnioinfusion - relieve of variable deceleration in labor - cord compression 으로 인한 cariable deceleration 감소 -> prevent mecoium aspiration - may benefit only meconium is thick - not benefit : meconium aspiration has occurred before onset of

labor

Mecomium aspiration

Management- shoulder 가 delivery 되기전에 infant’s mouth, nares 를 suctio

n- hypopharynx 에 있는 meconium 을 보면서 suctioning- intubation 후 low aierway 의 meconium suctioning- stomach is emtied ( avoid further meconium aspiration )

Intraventricular hemorrhage

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

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 leukom

alacia

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 con

gestion 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

Periventricular-intraventricular hemorrhage

Incidence and severity- depend on gestational age- half of all neonates born before 34 weeks have evidence of hem

orrhage- 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% survial3.2 % handicapgrade 3,4 : 50% survial rate

Periventricular-intraventricular hemorrhage

Contributing factor- immaturity- respiratory distress syn, mechanical ventilation- cord arterial Ph : 7.2 감소-> grade 3, 4 hemorrhage 의 위험도 증가

Prevention and treatment- administration of corticosteoid before delivery- phenobarbital or Vit E- avoiding significant hypoxia

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

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 discorder 와 연관 ) 2. Diplegia (preterm low birth weight infant 에서 혼합 ) 3. Hemiplegia 4. Choreoathetoid type 5. Mixed varieties 35% : hemiplegic 20% : quadriplegic 15% : extrapyramidal type 25% 에서 IQ 50 미만의 MR 이 동반

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

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 5 배증가 incidence of cerebral palsy 는 3 배증가 - low score at 1 and 5 minute : indicator for need resuscitation

Cerebral palsy

Umbilical cord blood gas - asphixia 의 definition 에서 중요한 것은 metabolic acidosis

이다 . - significant acidemia : Ph < 7.0 - umbilical artery PH : used to assess predictability of neonatal d

eath

Nucleated re blood cell - response to hypoxia 으로 나타나는 immature cell - degree of hypoxia - hematological makers maternal and new born infection, placen

tal infection

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 infant 의 40% : grade 3,4 hemorrhage : no hemorrhage or grade 1, 2 hemorrhage 가 있는 infant

보다 cerebral palsy 위험이 16 배 높다 Infection, inflammation Neonatal hypotension Prolonged rupture of memb Chorioamnionitis Neonatal acidosis Ritodrine therapy

Periventricular leukomalacia

Preterm fetus and periventricular leukomalacia

-before 32 weeks, blood supply to the brain ; ventriculopedal system Ventriculofugal system -> 이 두 blood supply 가 만나는 곳은 lat ventricle

근처로 vascular anastomosis 가 없어서 ischemia의 위험성이 있다 .

Periventricular leukomalacia

Perinatal infection- key element between preterm birth, intracranial hemorrhage periventricu

lar 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 infant 에서 intravascular hemorrhage &

periventricular 의 severity incidence 가 높다

Periventricular leukomalacia

Prenention - corticosteoid- aggressive Tx of prophylaxis against infection-magnesium sulfate; intracranial vascular tone 을 stabilize 시킴 Cerebral bleed flow 를 minimize 하게 변동시킴 Reperfusion injury 를 reduce 시킴 Calcium – mediated intracellular damage 를 block Cytokine 과 bacterial endotoxin 의 synthesis 를 reduce

Periventricular leukomalacia

Neuroradiological imaging- CT, MR : cerebral palsy 의 timing neuropathology 를 define 하는 데 사용됨- cranial ultrasound : antenatal injury 의 diagnosing

에 critical periventricular leukomalacia 의 진단에도 쓰임- MRI : cerebral palsy 의 development 와 관련된 intra

cranial lesion 의 study 에 사용

Neonatal encephalopathy

Term infant 의 earliest days 에서 neurological function 의 disturbance 를 나타내는 sysndtrome 으로 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

Neonatal encephalopathy

Mental retardation- 3 per 1000 children- etiologic factor Some etiological factor for severe mental retardation Prenatal 73 chromosimal 36 mutant genes 7 Multiple congenital anomalies 20 Acquired infections, diabetes, growth restriction 10 Prenatal 10 Asphyxia or hypoxia 5 Unidentified causes 5 Postnatal 11 Unknown 6

Neonatal encephalopathy

Seizure disorder- accompany cerebral palsy- isolated seizure disorder epilepsy : not caused by perinatal hypo

xia- major predictor ; fetal malformation (cerebral and noncerebral ) family history

Anemia

35 주 이후 cord hemoglobin concentration 이 14 g/ dl 이하이면 abnormal

Delayed cord clamping : hemoglobin value 를 20% 상승시킬 수 있다 . Placenta is cut or torn, fetal vessel is perforated or laceration, cord c

lamping 전 placenta 보다 태아가 높게 위치될 경우 -> hemoglobin may fall

Feta-to-maternal hemorrhage - acid elution technique : maternal circulation 에 있는 fetal red cell 을

발견할 수 있다 . - fetal intravascular compartment 에서 blood cell 의 small vol 이 ma

ternal intervillous space 로 들어갈 수 있다 . - large hemorrhage : uncommon Isoimmuniztion

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 hemorrhage 의 양측정 -> D negative 인 woman 에게 줄 D-immune globulin 의 dose 를 결정하는 데

중요 Fetal red cell = MBV * maternal Hct * % fetal cell KB New born Hct

Isoimmunization

Specific red cell antigen 이 없는 사람이 antigen 에 노출되었을 때 antibody 가 생성되게 된다 .

이 antibody 는 blood transfusion 받는 사람이나 pregnancy 중 태아에게 해로운 영향을 줄 수 있다 .

Fetus 의 erythrocyte 가 maternal circulation 에 도달하면 immune response 가 일어나게 되고 드물게 isoimmunization 이 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

Anemia

D negative woman : D positive infant ABO – compatible infant -> isoimmunization of

16% ABO – incompatible infant -> isoimmuniation of 2%

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 compatibility 를

보이지만 5% 만이 clinical 하게 영향을 받음 ABO incompatibility : mild disease ( neonatal jaundice, anemia ) Not erythroblastosis fetalis ABO incompatibility 가 CDE incompatibility 와 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 disease 가 일어남

ABO blood group system

Criteria for diagnosis1. Mother : group o, with anti – A & anti-B antibody Ferus : group A, B or AB2. First 24hr 이내 jaundice 의 onset3. 다양한 정도의 anemia, reticulocytosis, erythroblastosis 가

있을 때4. Hemolysis 의 다른 cause 가 제외되었을 때

Tx Tx

- similar to D-isoimmunization- simple or exchange transfusion : group o blood is used

CDE (RHESUS) blood group system

이 red cell antigen 은 임상적으로 중요함 왜냐하면 , D 또는 Rhesus antigen 이 없는 사람은

한번노출로써 immunized 되기 때문이다 . CDE gene 은 다른 blood group gene 과 independent 하게

유전되고 , chromosome 1 의 short arm 에 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 antigen 은 D antigen 보다 immunogenicity 가

낮으나 erythroblastosis fetalis 를 일으킬 수 있다 .

Other blood group incompatibility

Rarer red cell antigen 에 의해 발생되는 antenatal hemolytic disease 는 indirect coombs test 로 screening 할 수 있다 .

544 antibodies 중 72% 가 CDE group , anti-D 가 가장 흔하다 .

Kell antigen

Uncommon Kell-positive blood 의 transfusion 의 결과로 senstinization

됨 Maternal-fetal incompatibility 의 결과로 senstinization 이

일어날수 있음 ->rapid & severe fetal anemia

Other antigen

Kidd (Jka), Duffy(Fya), c, E, C ->erythroblastosis 를 일으킬수 있음 대부분 이 antigen 의 isoimmunization 은 blood transfusion

후에 일어난다 . Anti-C isoimmunization : previous preg 의 결과로써 흔하다 ->moderate to severe hemolysis 를 일으킴