Part 11. The Fetus and Neonatal Infants

Part 11. The Fetus And The Neonatal Infant

Chap 78.  Overview of mortality and morbidity

; neonatal mortality

    - 1st 24hr of life ; 가장 높다.

  - 1세이하 death의 *65%

; perinatal mortality

    - deaths of fetuses and infants from the 20th wk of GA through the 28th day after birth

; infant mortality rate

    - socioeconomic, cultural, geographic variables, prenatal care, nutrition, social support, risk identification, and obstetric care

; LBW는 lethal congenital anomaly와 더불어 neonatal mortality의 중요한 factor

    - 미국에서는 LBW rate가 1981에서 1991년사이 6.6%에서 7.1% 로 증가

; premature birth의 원인

    - amniotic fluid infection with GU tract bacteria, PROM, uterine abnormality, placental bleeding, multifetal gestation, drug misuse, maternal chronic illness, fetal distress, and maternal pyelonephritis

; postneonatl mortality

    - deaths btw 28days and 1yr of life

; sudden infant death, infection, and trauma

    - delayed neonatal mortality가  postneonatal mortality의 중요한 인자

★Table 78-1 major causes of perinatal mortality

Chapter 79. The newborn infant

; Many of the newborn`s problems

    - poor adaptation due to asphyxia, premature birth, life-threatening congenital anomaies, or adverse effects of delivery

79.1 History In Neonatal Pediatrics

1) identify disabling diseases that are amendable by prompt preventive action or treatment importance

2) anticipate conditions that may be of later importance

3) uncover possible causative factors that may explain pathologic conditions regardless of their immediate or future significance

# Inclusion

    ; demographic and social data , past medical illnesses in child and family, prior maternal reproductive problems, events occurring ih the present pregnancy, description of the labor, delivery

79.2 Physical examinations of the newborn infant

; initial examination 은 가급적 빨리 시행한다.

General appearnace

; both active and passive muscle tone and any unusal posture should be recorded.

; coarse, tremulous movement with ankle or jaw myoclonus ; not pathologic

; ※Generalized Edema

    - prematurity, hypoproteinemia secondary to severe erythroblastosis fetalis, nonimmune hydrops, congenital nephrosis, Hurler syndrome, or unknown cause

Skin

; Vasomotor instability and ciculatory sluggishness로 인해 purple color를 띌 수 있다. 찰때는 acrocyanosis나타날 수 있다.

; *harlequin color change

    - 머리에서 pubis까지를 연결한 선을 중심으로 반은 red 반은pale color를 띠는 것

; anemia

    - erythroblastosis fetalis, subcapsular hematoma of the liver or spleen, subdural hemorrhae, or fetal-maternal or twin-twin transfusion

; mongolian spot

    - slate blue, well-demarcated areas of pigmentation이 buttock, back 또는 다른 부위

; skin of the premature infant

    - gelatinous and bleeds and bruises easily lanugo hair

; skin of the postterm infant

    - peeling, parchment-like skin

# *Erythema Toxicum

    - *생후 1-3일에 나타나는 vesiculopustular papule로 1주까지도 지속되며 주로 얼굴에 나타나나 다른 부위에도 생길 수 있다. eosinophil을 함유하고 있다.

; pustular melanosis

    - 주로 흑인에 많으며 생후 바로 나타나는 vesiculopustular eruption으로 neutrophil을 갖고 있고 chin, neck, back, extremity와 palm or sole 에 나타날 수 있고 2-3일까지 지속될 수 있는 benign lesion

; excessive skin fragility and extensability

    - Elers-Danlos syndrome, Marfan syndrome, congenital contractural arachnodactyly

Skull

; suture line, the size and tension of the anterior and posterior fontanelle을 만져봐야 한다.

# ♥Large Fontanelle과 연관된 질환

           Table 79-1

; craniotabes

    - parietal bone에서 sagittal suture근처의 vertex에서 있을 수 있으나 병적인 것은 아님.

; soft areas in the occipital region

    - osteogenesis imperfecta, cleidocranial dysostosis, lacunar skull, cretinism and Down syndrome

; megalencephaly

    - hydrocephaly, storage disease, achondroplasia, cerebral gigantism, neurocutaneous syndrome, or inborn error of metabolism or familial

Face

; epicanthal folds, widely spaced eyes, microphthalmia, long philtrum, and low-set ear

    - congenital syndrome

; asymmetry

    - 7th n. palsy

    - *Symmetric Facial Palsy

           / ※Mobius syndrome

           / absence or hypoplasia of the 7th n. nucleus

Eyes

※97 labyrinthine and neck reflex

    - spontaneous eye opening maneuver

    - held up and tipped gently forward and backward

; *conjunctival and retinal hemorrhage자체는 not significant

; ※슬 Leukocoria

    - cataract, tumor, chorioretinitis, ROP, or a persistanthyperplastic primary vitreous and warrants an ophthalmologic consultation

Ears

; deformity of the pinae가 가끔 보임

; preauricular skin tag

Nose

; nare should be symmetric.

Mouth

; neonatal teeth

    - normal

    - *Ellis-van Creveld, Hallermann-Streiff, and other syndrome

    - extraction 필요없음

; soft and hard palate - high arched palated, bifid uvula

; *Ebstein pearls

    - hard palate의  raphe양옆에  epithelial cell의  temporary accumulation

; active salivation 은 없다.

; relatively large tongue, short frenulum

; cheek - sucking pads

; throat

    - palatal arch때문에 보기 힘들지만 posterior palatal or uvular cleft를 놓치지 않으려면 잘 관찰하여야 함.

Neck

; Congenital torticollis

    - 머리는 병변쪽으로 face는 병변 반대쪽으로 기울어짐.

Chest

; Asymmetry, erythema, induration, and tenderness

    - breast abscess

; *Shield-shaped chest - Turner syndrome

Lung

; usual rate : 30-40/min

  - premature에서는 more rapid and fluctuates more widely

  - 60/min이상일때는 cardiac or pulmonary disease

; Cheyne-Stokes rhythm

    - premature에서 나타날 수 있다.

; weak groaning, whinning cry, or grunting

    - cardiopulmonarydisease

Heart

; normal - 90~180/min

; premature에서는 sudden onset sinus bradycardia나타날 수 있다.

; pulse - COA진단을 위해 U/E, L/E를 다 palpation하여야 한다.

Blood pressure

; auscultatory method

; Doppler method

; palpatory method

; flush method

Abdomen

; liver 가 만져질 수 있다. ( 2cm까지)

; gas는 생후 24시간에 rectum 에서 보여야 한다.

; ※89 Cystic Abdominal Mass

    - hydronephrosis, multicystic-dysplastic kidney, adrenal hemorrhage, hydrometrocolpos, intestinal duplication, choledochal, ovarian, omental or pancreatic cyst

; solid mass

    - neuroblastoma, congenital mesoblastic nephroma, hepatoblastoma, and teratoma

; solid flank mass due to renal vein thrombosis

    -hematuria, hypertension, and thrombocytopenia

    - asso. with

           / *polycythemia, dehydration, diabetic mothers, asphyxia, sepsis, and coagulopathies such as antithrombin III or protein C deficiency

; Abdominal distension

    - shortly after birth

           : obstruction or perforation of GI tract, meconium ileus

  - Later distension

           : lower bowel obstruction, sepsis, or peritonitis

; Scaphoid abdomen - diaphragmatic hernia

; Abdominal wall defect

    - omphalocele ( through the umbilicus )

  - gastroschisis ( lateral to midline )

; ♥Omphalocele동반된 기형

    - Beckwith-wiedemann syndrome, conjoined twin, 18-trisomy, meningomyelocele, imperforate anus

Genitalia

; genitalia와 breast는 maternal hormone영향으로 일시적으로 커지거나 discharge가 있을 수 있으나 observation

; imperforate hymen- hydrometrocolpos

; transitory hydrocele

; severe hypospadia, epispadia

    - suspect abnormal sex chromosome

    - e.g.) adrenogenital syndrome

; *생후 24시간 이내에 voiding하여야 함

Anus

; term infant의 99%, preterm infant의 95%가 48시간 이내에 meconium passage 함

; imperforate anus

Extremities

; polydactyly, syndactyly, abnormal dremoglyphic pattern

; hip evaluation; to R/O congenital dislocation

Neurologic examination

; Sx & Sg of fetal neuromuscular disease

    - breech presentation, failure to breath at birth, pulmonary hypoplasia, dislocated hips, undescended testes, thin rib, clubfoot

Ordinary Care Of The Newborn Infant

# ※Basic Requirements

  1) establish respiration

  2) adequate nutrition

  3) maintain normal temperature

  4) avoiding contact with infection

79.3 Routine Delivery Room Care

# Apgar score

    ; low score가 반드시 *fetal hypoxia를 의미하는 것은 아님

  ; *neonatal mortality나 cerebral palsy를 예견하는 지표도 아님

    ; 1 min Apgar score

           - need for immediate resuscitation

    ; 5-,10-,15-,20-min Apgar score

           - probability of successfully resuscitating the infant

★Table 79-2

Maintenance Of Body Heat

; estimated heat loss가 ※89객 adult의 4배

; usual delivery room temp.일 때 skin temp. 0.3℃/min, core temp. 0.1℃/min 감소

; heat loss

  - by convection, conduction, radiation, evaporation

; cold exposed term infant

    - metabolic acidosis, hypoxemia, hypoglycemia, increased renal excretion of water and solute

; ※89 Heat Production

    - increasing the metabolic rate and oxygen consumption

    - releasing norepinephrine --> fat oxidation을 통한 thermogenesis

    - increased muscular activity

; 갓 태어난 아기는 바로 닦이고 담요로 감싼다.

Antiseptic Skin And Cord Care

; umbilical cord

    - triple dye or bactericidal agents

; *chlorhexidine washing or a single hexachlorphene bath

    - *repeated hexachlorphene의 total body exposure는 neurotoxic 이므로 contraindication

Other measures

The eyes

    ; 1% silver nitrate drops

           - *best proven therapy

    ; alternative 0.5% erythromycin and 1.0% tetracycline sterile ophthalmic ointment, povidone-iodine(*2.5% solution)

IM of 1 mg of water-soluble vitamin K1(phytonadione)

; ※91 large amount 시 hyperbilirubinemia, kernicterus

Neonatal Screening

    ; hypothyroidism, sicke cell anemia, phenylketonuria, homocystinuria, galactosemia, adrenogenital syndrome, cystic fibrosis, possible HIV infection, maple syrup urine disease, other organic or amino acidopathies

79.4 Nursery Care

; Infant`s temp

    - 처음엔 rectal 그후 axilla로 잰다.

    - 첫 2-3일간은 4시간 간격, 그이후 8시간 간격

  - axillary temp. 36.4-37.0`C

79.5 Parent-Infant Bonding

Nursery And Breast-Feeding

1) immediate postpartum mother-infant contact with suckling

2) rooming-in

3) demand feeding

4) inclusion of fathers in prenatal breast-feeding education

5) support from experienced women

Drug And Breast-Feeding

Table 79-4

# ★Medical Contraindication

    ; HIV infection, primary CMV, hepatitis B virus(until receives HBIG & vaccine)

Chapter 80. High-Risk Pregnancies

★Table 80-1

㉿Table 80-2 maternal disease affecting the fetus or neonate

★Table 80-3

Genetic Factors

; chromosomal abnormalities, congenital abnormalities, inborn errors of metabolism, mental retardation, or any familial disease in blood relatives

Maternal Factors

# age

# maternal illness; multiple pregnancy, infection, certain drugs

# polyhydramnios & oligohydramnios

㉿★Table 80-4 conditions associated with disorders of amniotic fluid volume

# amniotic fluid index

    ; vertical diameter of amniotic fluid pockets

    ; >24cm - polyhydramnios

  ; <5cm - oligohydramnios

# 2nd trimester maternal AFP

    ; elevation

           - multifetal gestation, open neural tube defect, threatened abortion, hydrops with ascites, cystic hygroma, gastroschisis, omphalocele, congenital nephrosis, polycystic renal disease, epidermolysis bullosum, amniotic bands, ectopia cordis, placental hemangioma, retroplacental hemorrhage, Kell or Rh sensitization, matermal disease such as liver cancer, yalk sac tumor, viral hepatitis, and lupus anticoagulants

    ; ★low

           - incorrect GA estimate, *trisomy 18 or 21, IUGR

# Uterus large for the estimated stage of gestation

    ; multiple fetuses, hyhydramnios, excessively large infant

Chapter 81. The fetus

81.1 Fetal Growth And Maturity

; biparietal diameter, head-to-abdomen circumference ratio, femoral length and total uterine volume measurement

㉿Table 81-1 Fetal Diagnosis And Assessment

    ※87주 Amniocentesis

    ♥Cordocentesis

81.2 Fetal Distress

# Indications For BPP

    ; intrauterine growth retardation, postdate gestation, maternal DM, Rh sensitized pregnancy, previous history of stillbirth, maternal hypertension

# ★Continuous Fetal Heart Rate Monitoring

1) ※91 tachycardia ( >160/min)

    ; early fetal hypoxia, maternal fever, maternal hyperthyroidism, maternal β-sympathomimetic or atropine therapy, fetal anemia, fetal arrhythmia

2) fetal bradycardia

    ; fetal hypoxia, placental transfer of local anesthetic agents and β-adrenergic blocking agent, heart block with or without CHD

3) early deceleration

    ; head compression

4) variable deceleration

    ; cord compression

5) late deceleration

    ; *fetal hypoxemia

Fig. 81-4

# Fetal Scalp Blood Sampling

 *pH<7.25 ; fetal distress

 *pH<7.0 ; indication for early delivery

81.3 Maternal Disease And The Fetus

# Infectious disease

   miscarriage, stillbirth, or premature labor

# Noninfectious diseases

1) maternal DM

    ; organomegaly, hyperplasia of the β cells of the fetal pancreas, metabolic derangement, intrauterine death

2) PIH, chronic hypertension, renal disease

    ; SGA, prematurity, intrauterine death

3) uncontrlled maternal hyperthyroidism or hypothyroidism

    ; infertility, abrtion, premature labor, fetal death

4) untreated maternal PKU

    ; miscarriage, congenital malformation, injury to the brain of the nonPKU fetus

81.4 Maternal Medication And The Fetus

★Table 81-3, 81-4

81.5  Identification Fo Fetal Disease

# Indication

   1) abortion is being considered

   2) direct fetal treatment is possible

   3) intrauterine fetal demise를 피하기위한 결정이 필요할 때

   4) high-risk pregnancy or high-risk fetus의 history가 있을 때

# Real time ultrasonography

# Amniocentesis

    ; Indication

           - erythroblastosis fetalis, genetic indication, chromosomal abnormalities, neural tube defect, inborn metabolic errors, adrenogenital syndrome, thyroid dysfunction, lung maturation

    ; ※90 Index Of Pul. Maturation

           - saturated phosphatidylcholine

           - osmophilic bodies or phosphatidylglycerol

           - L/S ratio : *위의 두가지가 more specific

# ※87 Early Lung Maturation

    ; premature separation of the placenta, premature rupture of the fetal membrane, narcotic addiction, maternal hypertensive and renal vascular disease   

81.6 Treatment and Prevention of Fetal Disease

81.7 Teratogens

# Mechanisms Of Teratogenesis

  1) cell death without reparative regeneration

  2) mitotic delay

  3) delayed differentiation

  4) physical or vascular constraining

    5) reduced histogenesis secondary to cell depletion, necrosis, calcification, or scarring

  6) inflammation

 

1. Category A ; no risk based on evidence from controlled human trials

2. Category B ; either no risk from animal studies but no adequate studies in humans or some risk in animal studies that are not confirmed by human studies

3. Category C ; either definite risk from animal studies but no adequate human studies or no available data for animals or humans

4. Category D ; some risk but with a benefit that may exceed that risk for the treated life-threatening condition

5. *Category X ; contraindicated in pregnancy based on animal and human evidence and whose risk exceeds the benefits.

81.8 Radiation

; *maternal exposure의 limit : 임신 40주 동안 500mrad

; *therapeutic abortion : 10000mrad이상 노출되었을 때

Chapter 82  The High-Risk Infant

# retroplacental hematoma

# placental edema

    ; fetofetal transfusion syndrome, hydrops fetalis, congenital nephrosis, or hepatic disease

# Amnion nodosum, oligohydramnios

    ; pulmonary hypoplasia, renal agenesis

# short cord, noncoiled cord

    ; chromosomal abnormality, omphalocele

# meconium stain

    ; asphyxia, pneumonia

# single umbilical artery

    ; congenital abnormality

# *GA 30주미만과 1000g 미만에서 가장 neonatl mortality가 높다.

# 4000g이상, 42주이상에서도 마찬가지로 risk가 증가한다.

★Table 82-1

82.1 Multiple pregnancies

Incidence

; highest among blacks & east indians

    - lowest among the asians

; ovarian stimulants에 의한 infertility 치료로 인해 그 incidence가 증가하는 추세

Etiology

; monovular twin은 genetic factor와 무관

; polyovular twin

    - *more frequent beyond 2nd preg., older women, family history(+)

; conjoined twin

    - 대부분 여아, 수술의 가능성에 따라 예후가 달라진다.

; prenatal diagnosis of twins

    - large utrine size, 2 fetal heart tone, elevated maternal serum α-FP or HCG, confirmed by USG

Monozygotic Versus Dizygotic Twins

1) comparison of physical characteristics, detailed blood typing, DNA fingerprinting or tissue typing 

Placenta Examination

Problems Of The Twin Gestation

1) polyhydramnios, hyperemesis gravidarum, pre-eclampsia, prolonged rupture of membrane, vasa previa, velamentous insertion of the umbilical cord, abnormal presentation, and premature labor    

2) *IUGR, twin-twin transfusion, congenital anomalies

    ; monozygotic twin에 특히 문제가 된다.

3) ★Congenital Anomalies

    ; uterine compression deformity from crowding

           - hip dislocation

    ; vascular communication with embolization

           - ileal atresia, porencephaly, cutis aplasia

    ; vascular communication without embolization

           - acardiac twin

    ; unknown factors that cause twinning

           - conjoined twins, anencephaly, meningomyelocele

Placental Vascular Anatomoses

※97 Fetal Transfusion Syndrome

    ; monochorionic twin에서 발생

    ; Hb 5g/dl, Bwt. 20% 이상 차이남.

    ; maternal hydromnios 가 있으면 의심

    ; ※92짝짓기 Table 82-2

    ; *intrauterine death of one fetus --> DIC of another fetus

    ; Tx

           - *maternal digoxin, selective twin termination, Nd:YAG laser ablation of the anatomosis

Postnatal Identification

# Criteria for monovular twin

 1) same sex

 2) 겉모습이 유사

 3) hair colr, texture, natural curl등이 유사

 4) eye color, shade가 유사

 5) skin texture와 color가 유사

 6) hands, feet는 similar size

 7) anthropometric value ; close agreement

Prognosis

# *neonatal mortality는 차이가 없으나 perinatal mortality는 4배

# ※2nd baby는 anoxia의 위험이 더 많다.

    ; placenta separation after birth of first twin

    ; abnormal presentation

    ; decreased uterine tone

    ; close of cervix after birth of first twin

82.2 Prematurity And Intrauterine Growth Retardation

Definitions

# Prematurity ; WHO정의상 37주 이전에 출생

# LBW ; 2500gm less

# ELBW - less than 1000 g

Incidence

1) In USA, 30% fo LBW infant; IUGR

2) In developing country, 70% of LBW are IUGR.

VLBW infant

1) 50% of neonatal death, 50% of handicapped infant

2) survival ; 20% of 500-600g, 85-90% of those between 1250-1500g

Factor Related To Premature Birth And Low Birthweight

Table 82-3,4

# IUGR

    ; 제태기간에서 출생 체중이 10 percentile 미만인 경우

    ; Ponderal index

           - *체중(gm)/키³(cm³)x100

           - *normal 2.32~2.85

    ; Symmtric

           - earlier onset, chromosomal, genetic malformation, teratogenic, severe maternal hypertensive etiologies

    ; Asymmetric

           - later onset, poor maternal nutrition or late onset or exacerbation of maternal vascular disease

   ♥표 12-3

Assessment Of Gestational Age At Birth

; *neurologic maturity는 gestational age와 상관관계

; ※94주 한글판 볼 것

    - p244~p249

Nursery Care

1) need for incubator care and heart rate and respiration monitoring

2) need for increased oxygen

3) need for special attention to the details of feeding

Incubator Care

1) neutral thermal environment

    ; heat production minimal, infant`s core temp. within the normal range*(36.5-37℃)

2) humidity; *40-60%

3) administrating oxygen

Feeding

# NPO

    ; respiratory distress, hypoxia, circulatory insufficiency, excessive secretion, gagging, sepsis, CNS depression, immaturity, or signs of serious illness

# Gastrostomy feeding

    ; *increase in mortality을 보이므로 특별한 surgical condition을 제외하고는 금기

Initiation Of Feeding

# ♥Advantages

    ; reduce risk of hypoglycemia, dehydration, hyperbilirubinemia

# 1000gm이하도 가능

    ; 1ml of 5% dextrose, 1/2 strength로 시작

    ; 하루동안 2시간 간격으로 1/4 씩 strength 증가시켜 full-strength로 만든후 다음날 부터 1ml씩 양을증가

    ; *20ml/kg/24hr이상은 늘리면 안된다.

    ; *150ml/kg/24hr까지 일단 도달하면, 양은 늘리지 않고 칼로리를 늘린다.

# ※High protein intake인경우 : > 4.5g/kg/24hr

    ; abnormal plasma aminograms

    ; elevations in blood urea nitrogen, ammonia, sodium conc.

    ; metabolic acidosis

    ; untoward effects on neurologic development

# ♥LBW가 Physiologic anemia가 더 심한 이유

    ; smaller fetal iron stores

    ; greater expansion of blood volume due to rapid growth than term infant

    ; fetal or neonatal blood loss

# ★Required Vitamin

    ; vitamin C, D and other fat-soluble vitamin (Vit. E, Vit. K)

    ; folic acids

# Irion supplement

    ; *VLBW infant라도 체중이 두배가 될 때까지는 보충할 필요가 없다.

    ; *Vitamin E deficiency risk가 있는 경우에는 보충해서는 안된다.

           - hemolysis을 조장하고, vitamin E 흡수 장애

    ; *체중이 두배가 되면, Vitamin E을 중단하고, supplement (2mg/kg/24hr)

Fluid Requirements

TPN

# synthetic amino acid conc. ; 2.5-3 g/dl, hypertonic glucose; 10-25g/dl

# initial glucose

    ; 10-15g/kg/24hrs -> 25-30 g/kg/24hrs로 증량

# intralipid

    ; 0.5 g/Kg/d로 시작 -> 3 g/Kg/d까지 증량

  ; 0.5 g/Kg/d만으로 essential fatty acid deficiency를 예방할 수 있다.

# LBW의 경우 TPN으로 *100 Kcal/Kg/24hrs를 유지하면 15 g/Kg/d의 gain가능

# ※91주 1st 1wk peripheral TPN regimen

    ; 2.5 g/kg/d of amino acid

    ; 10 g/dl of glucose

    ; 2-3 g/Kg/d of intralipid

# ★Limited Glucose Conc. Via pph Line

    ; *12.5 g/dl

# IV supplimentation of tolerated oral feeding

    ; preterm에서 gavage feeding과 병행하는 것이 보통, 이때 iv fluid는 glucose, lipid, amino acid를 다 supply할 것

# ※89 Complication

    1) related catheter

           ; sepsis

           ; thrombosis

           ; extravasation of fluid

           ; accidental dislodgment of catheter

           ; phlebitis, cutaneous sloughs, superficial infection

    2) metabolic complication

           ; *hyperglycemia

                   --> *osmotic diuresis, dehydration

           ; azotemia

           ; increased risk of nephrocalcinosis

           ; hypoglycemia

           ; hyperlipidemia & possible hypoxemia from IV lipid infusions

           ; tissue accumulation of aluminum

           ; hyperammonemia

           ; cholestatic jaundice

           ; hyperchloremic acidosis

           ; essential FA deficiency

Prevention Of Infection

; wash rigorouly hand to elbow before and after handling the infant

; *▲important factor in successful care of premature infant

    - skill, experience, number of nursing staff

Immaturity Of Drug Metabolism

1) 대부분의 약이 kidney excretion 하므로 interval을 늘려야 한다.

2) liver 대사되는 약물은 smaller dose로.

Prognosis

♥Table 82-8

# *LBW infant가 term infant와 physical growth가 같아지는 시기

    ; 2nd yr

# Overall Incidence Of Neurologic And Developmental Handicap In VLBW

    ; *10-20%

           - cerbral palsy (3-6%)

           - moderate to severehearing and visual defect(1-4%),

           - learning difficulty(20%)

Predicting Neonatal Mortality

# Survival

    ; *22wk(0%), 23wk(15%), 24wk(56%), 25wk(79%)

# Birthweight-Speicific Neonatal Disease

    ; *Grade IV IVH, severe GBS pneumonia, pulmonary hypoplasia 

# Index for neonatal mortality

 CRIB ( Clinical Risk Index for Babies)

 SNAP( Score for Neonatal Acute Physiology)

Discharge From Hospital

# ♥Criteria

    ; all nutrition by nipple, either bottle or breast

    ; steady increment growth; 10-30 g/day

    ; open crib에서 안정적 체온유지

    ; no recent apnea or bradycardia

    ; parenteral drug should be discontinued

    ; 1800-2100gm

# oxygen therapy

    ; eye exam. for ROP

# All LBW ; hearing test

# umbilical catheter ; BP check for renal vascular hypertension detect

# Hb check; anemia detect

82.3 Post-Term Infants

; after 42wk of gestation

※87 Clinical Manifestations

; absence of lanugo, decreased or absent vernix caseosa, long nails, abundant scalp hair, white parchment-like or desquamating skin, increased alertness

Prognosis

; *delivery 3wk이상 delay되었을 때 3배이상 mortality가 높다.

Treatment

; careful obstetric monitoring

; 2-4wk이상되고 노산, fetal distress나타날 때는 labor induction이나 C-sec

 82.4 Large for gestational age

# *Predisposing factor

    ; maternal DM, obesity

# ※객 Higher Incidence of

    ; birth injury

           - cervical & brachial plexus injuries, phrenic nerve damage, fractured clavicles, cephalhematomas, subdural hematomas, ecchymoses of head & face

    ; congenital anomaly

           - congenital heart disease

    ; intellectual & developmental retardation

CHAP 83. Clinical Manifestations of Diseases in The Newborn Period

Central Cyanosis

★Table 83-1 Differential Diagnosis of neonatal cyanosis

; respiratory insufficiency

    - rapid, retraction of the thoracic cage

; CNS depression

    - irregular, weak often slow respiration

; CHD or methemoglobinemia

    - persisting cyanosis for several days without respiratory difficulty

Pallor

; acute hemorrhage, anemia, hypoxia, hypoglycemia, sepsis, *shock, *adrenal failure

Convulsion

; hypoxic-ischemic encephalopathy(from the asphyxia), ICH, cerebral anomaly, subdural effusion, meningitis, hypocalcemia, hypoglycemia, infarction, pyridoxine deficiency, hyponatremia, hypernatremia, inborn error of metabolism, drug withdrawal, familial seizure

; seizure in delivery room

    - unintentional injection of matenal local anesthetic into fetus

    - large amounts of hypotonic fluids to mother

           --> hyponatremia

※ Jitteriness

    ; normal newborns, DM mothers, birth asphyxia, drug withdrawal, polycythemic neonates

    ※87 96 DDx from convulsion

           - resembling tremor

           - stopped by holding the infant’s extremities

           - depend on sesory stimuli

           - not asso. with abnormal eye movements

 

	Jitteriness	Seizures
Abnormal gaze or eye movement	-	+
Response to sensory stimuli	+	-
Predominant movement	Tremor	Tonic clonic
Stopped by passive flexion	+	-
Abnormal EEG	-	+ or -

 

; seizures in premature

    - often subtle

    - asso. with abnormal eye or facial movements

    - tonic

    - *only apnea as 1st manifestation

; seizures in term

    - focal or multifocal

    - clonic or myoclonic

    - more subtle

Motor automatism

; *oral-buccal-lingual movement, rotatory limb activity(rowing, pedaling, swimming), tonic posturing or myoclonus

; following severe motor asphyxia 

; no accompanied EEG discharge

; poor response to anticonvulsant

; poor prognostic factor

Lethargy

; infection, asphyxia, hypoglycemia, hypercabnia, sedation from maternal analgesia or anesthesia, cerebral defect

★; after 2nd day --> infection

Irritability

; intraabdominal condition, meningeal irritation, drug withdrawal, infection, congenital glaucoma

※82객Hyperactivity

; hypoxia, pneumothorax, emphysema, hypoglycemia, hypocalcemia, CNS damage, drug withdrawal, *thyrotoxicosis, discomfort from the cold temp.

Failure to feed well

; most sick newborn

Fever

; *high environmental temp., overheated nurseries or incubators

    - *▲common

; dehydration fever, serious infection

Fall in body temperature

; infection, other serious disturbances

Apnea

Jaundice during the 1st 24hrs

; erythroblastosis fetalis, septicemia, cytomegalic inclusion disease, congenital rubellar syndrome, toxoplasmosis 

Jaundice after the 1st 24hrs

; septicemia, hemolytic anemia, galactosemia, hepatitis, congenital atresia, inspissated bile syndrome following erythroblstosis fetalis, syphillis, herpes simplex

Vomiting

; 1st day of life

    - UGI obstruction, IICP

; septicemia, overfeeding, inexperienced feeding technique, pyloric stenosis, milk allergy, duodenal ulcer, stress ulcer, adrenal insufficiency

Diarrhea

; overfeeding, AGE, malabsorption, infection

; mesenteric thrombosis, necrotizing enterocolitis, strangulated hernia, intussusception, torsion of ovary or testis

Abdominal distension

; intraabdominal mass, intestinal obstruction, enteritis, NEC, ileus accompanying sepsis, respiratory distress, hypokalemia

Failure to move an extremity

Chapter 84. Birth Injury

; not include amniocentesis, intrauterine trasfusion, scalp blood sampling, resuscitation procedures

※82주 Predisposing factors

    - macrosomia

    - prematurity

    - cephalopelvic disproportion

    - dystocia

    - prolonged labor

    - breech presentation

84.1 Cranial Injuries

Caput succedaneum

; diffuse, ecchymotic, edematous swelling of soft tissues of the scalp

; across midline and suture line

; *disappear within 1st few days

; no specific treatment

    - phototherapy for hyperbilirubinemia due to extensive ecchymoses

; asso. with molding

Erythema, abrasion, ecchymoses and subcutaneous fat necrosis

Subconjunctival and retinal hemorrhage

Petechiae

Cephalhematoma

; *subperiosteal hemorrhage

; *always limited 1 craial bone

; *no discoloration of the overlying scalp

; *no visible swelling until several hours after birth

; underlying skull fracture - linear not depressed

; *resorbed within 2wk-3mo but remain bony protubercephalohematoma as diploic space widening, cystlike defects for years

; calcify by the end of 2nd wk

; sensation of central depression --> not indication of underlying fracture or bony defect

; no treatment - contraindication for I & D

※ Cranial meningocele

    ; pulsation

    ; increased pressure on crying

    ; X-ray evidence of bony defect

Fracture of the skull

; linear fracture

    - *▲common

    - no treatment

84.2  Intracranial(Intraventricular) Hemorrhage

Etiology And Epidemiology

; trauma or asphyxia

    - rarely in primary hemorrhagic disturbance or congenital vascular anomaly

    - maybe in DIC, isoimmune thrombocytopenia, neonatal vitamin K deficiency

; massive subdural hemorrhage

    - more often in full-term than in preterm infant

; *intraventricular hemorrhage

    - *premature infants spontaneously

Pathogenesis of intraventricular hemorrhage

㉿ Gelatinous Subependymal Germinal Matrix

    ; embryonal neurons & fetal glial cells

    ; immature highly vascular area

    ; poor vascular support

    --> *predispose the premature infant

# ★Predisposing Factor

    ; prematurity, RDS, hypoxic ischemic encephalopathy, reperfusion of damaged vessel, increased or decreased cerebral blood flow, reduced vascular integrity, increased venous pressure, pneumothorax, hypervolemia, hypertension

# periventricular leukomalacia

    ; hypoxic-ischemic-hypotensive injury로 발생

    ; with or without severe IVH

    ; necrosis of the periventricular white matter and damage to the corticospinal fibers in the internal capsule.

Clinical manifestations

; *60-70% of 500-750 g, 10-20% of 1000-1500 g

; *rarely present at birth but 80-90% within 3rd days

    - delayed hemorrhage after 1wk in 10-15%

; *new onset IVH는 1개월이후에는 몸무게에 관계없이 드물다.

; *diminished or absent moro reflex, poor muscle tone, lethargy, apnea, somnolence

    - *▲common Sx

; *precipitous deterioration on 2nd or 3rd day in premature infants

    - apnea, pallor, or cyanosis, failure to suck well, abnormal eye signs, a high pitched shrill cry, muscular twitchings, convulsion, decreased muscle tone, paralyses, metabolic acidosis, shock, and a decreased hematocrit or its failure to increase after transfusion  

; tense bulging fontanelle

; PVL

    - usually asymptomatic till later infancy

    - *usually onset later as early echo dense phase (3-10 days), followed by echo-lucent(Cystic) phase(14-20 days)

Diagnosis

# Real Time USG

    ; *1000 g이하 infant

           - *1st 3-5 days and following wk

# ♥IVH Grades

    ; Grade I

         - bleeding confined to the germinal matrix-subependymal region or to less than 10% filling the ventricle

    ; Grade II

        - IVH with 10-50% filling the ventricle

    ; Grade III

        - more than 50% involvement with dilated ventricles

  ; Grade IV

        - Grade III with corticoperiventricular intraparenchymal lesion

# IVH의 75%는 grade I-II

# immaturity, severity of RDS 와 연관

    - severe RDS에서 risk가 더 높다.

# CSF tapping

    ; signs of increased intracranial pressure or SAH의심될 때, bacterial meningitis의심될 때

# 소수의 RBC나 xanthochromia는 intracranial hemorrhage가 아님

Prognosis

; *most not develop posthemorrhagic hydrocephalus

    - 10-15% of LBW have hydrocephalus

; Posthemorrhagic hydrocephalus

    - *regress or arrested in 65% of affected infants

; ♥Poor Prognosis

  1) GA less than 30wk

  2) prolonged mechanical ventilation (>28 days)

  3) intrapernchymal hemorrhage

  4) extensive PVL

    5) progressive hydrocephalus required VP shunt

; *intraparenchymal echo-densities greater than 1cm

    - *high mortality, high incidence of motor and cognitive deficit

Prevention

; management of CPD & operative delivery

; maternal Tx with steroids, IV immnunoglobulin

; fetal transfusion

; *neonatal administration of low-dose indomethacin & vitamin E

; *vitamin K

    - *Pb or phenytoin치료를 받는 산모는 출산전 반드시 맞아야 한다.

Treatment

; seizure - anticonvulsant

; anemia-shock

    - PRC transfusion or FFP

; acidosis

    - 1-2 mEq/Kg NaHCO3

; neurosurgical placement of the external ventriculostomy catheter in early stage of uncontrolled symptomatic hydrocephalus

84.3  Spine and Spinal Cord

; *4th cervical vertebra

    - cephalic presentation

; *lower cervical-upper thoracic vertebra

    - breech presentation

84.4  Peripheral Nerve Injuries

Brachial Palsy

Erb-Duchenne paralysis

; ※5th and 6th cevical nerves

; adduction and internal rotation of the arm with pronation of the forearm

; moro reflex absent on affected side

; sensory impairment on outer aspect of the arm

; forearm power & hand grasp preserved

Klumpke paralysis; rarer form

; ※85 7th and 8th cervical nerves and 1st thoracic nerve

; paralyzed hand

; *ipsilateral ptosis and miosis (Horner syndrome)

Differential Diagnosis

; cerbral injury, fracture, dislocation, epiphyseal separation of the humerus

Prognosis

; involvement of deltoid

    - *▲serious problem

; upper arm paralysis가 better prognosis

Treatment

; partial immobilization and appropriate positioning

; ♥in upper arm paralysis

    - abduction 90˚

    - full supination of forearm

    - slight extension at wrist with palm turned toward face

; ♥in lower arm paralysis

    - padding in the fist

; immobilization

    - *intermittent while infant asleep, between feedings

    - brace or splint during the 1st 1-2wk

; in entire arm paralysis

    - same treatment

    - *gentle massage and motion by 7-10days

; *if no improvement for 3-6mo

    - *neuroplasty, neurolysis, end-to-end anastomosis, nerve grafting

Phrenic Nerve Paralysis

; *3th, 4th, 5th cervical nerve

; Diagnosis

    - U/S or fluoroscopic exam

    - elevation of the diaphragm on paralyzed side

; recovery spontaneously by 1-3 mo    

Facial Nerve Paralysis

; *compression of facial nerve in utero

    - from labor or forceps

; nuclear agenesis of facial nerve

; affected side

    - forehead smooth, eye closure impossible, nasolabial fold absent, the corner of the mouth droops

84.5 Viscera

# Liver

    ; brain 다음으로 자주 injury받는 organ

    ; contributing factors

           - large infant, intrauterine asphyxia, coagulation disorder, extreme prematurity, hepatomegaly

    ; Laceration - surgical repair

# Rupture of spleen

# Adrenal Hemorrhage

  ; ★Causes

           - breech delivery in LGA or infant of DM mother

           - trauma, anoxia, severe stress, infection

    ; *90% unilateral, 75% Rt. side

84.6 Fracture

Clavicle

1) affected side arm movement 없음

2) absent moro reflex on affected side

3) spasm of the SCM with obliteration of the supraclavicular depression

4) prognosis ; excellent

Extremities

1) affected side; 못 움직이며 moro reflex없음

2) prognosis ; good

3) preterm infant; osteopenia

4) dislocation and epiphyseal separation

# nose ; dislocation of the cartilaginous portion of the septum

84.7 Hypoxia-ischemia

# Hypoxia

    ; arterial O₂ less than normal

# Ischemia

    ; cell or organ으로 정상기능을 할 만큼의 충분한 혈액공급이 안됨

※Etiology

Fetal Hypoxia

1) inadequate oxygenation of maternal blood

    ; hypoventilation during anesthesia, cyanotic heart disease, respiratory failure, CO poisoning

2) low maternal BP

3) inadequate relaxation of uterus

4) premature separation of placenta

5) compression or knotting of the cord

6) placental insufficiency

7) uterine vessel vasoconstriction by cocaine

After Birth

1) anemia

2) shock

3) deficit in arterial oxygen saturation resulting from failure to thrieve

    ; due to cerebral defect, narcosis, or injury

4) failure of oxygenation of an adequate amount of blood

    ; due to cyanotic CHD or deficient pulmonary function

Pathophysiology And Pathology

# *Bradycardia, Hypotension, Decreased Cardiac Output, Severe Metabolic & Respiratory Acidosis

    ; onset within minutes

    --> increased shunting through ductus venosus, ductus arteriosus, foramen ovale

           - initial circultory response

# Pathology of hypoxia-ischemia

    ; early congestion, fluid leak from increased capillary permeability, endothelial cell swelling

           --> coagulation necrosis, cell death

    ; congestion & petechiae in pericardium, pleura, thymus, heart, adrenals, meninges

# Prolonged Intrauterine Hypoxia

    ; result in PVL & pulmonary arteriole smooth muscle hyperplasia

# chronic fetal asphyxia & acute hypoxic ischemic injury

    --> ♥Gestational Age-Specific Neuropathology

    ; Term

           - *neuronal necrosis of the cortex(later cortical atrophy) & parasagittal ischemic injury

           - focal or multifocal cortical infarts

                   --> focal seizures or hemiplegia

    ; Preterm

           - *PVL(later spastic diplegia), status marmoratus of basal ganglia, IVH

# *excitory amino acids가 asphyxial brain injury에 중요한 역할을 한다.

Clinical Manifestations

# Sg Of Fetal Hypoxia

    ; IUGR with increased vascular resistance

    ; FHR monitoring

           - bradycardia

           - loss of beat-to-beat variability

           - variable or late deceleration

    ; fetal scalp blood

           - less than 7.20

# At Delivery

    ; meconium stained amniotic fluid

    ; depressed & fail to breathe

    ; hypotonia or change from hypotonia to extreme hypertonia

    ; pallor, cyanosis, slow heart rate, unresponsiveness to stimulation

    --> cerebral edema during next 24hr

    --> brain stem depression, seizure attack

★Table 84-1

Prognosis

# ♥Outcome Depends On

    1) metabolic and cardiopulmonary complication의 치료여부

    2) gestational age

    3) severity of the hypoxic-ischemic encephalopathy

# ♥Death Or Severe Cognitive & Motor Deficits Predictors

    ; low 20min Apgar score

    ; absence of spontaneous respiration at 20min of age

    ; persistence of abnormal neurologic signs at 2wk of age

# ※93주 Brain Death

    ; unresponsive to pain, auditory, or visual stimulation

    ; apnea with Pco₂ rising from 40 to over 60mmHg

    ; absent brain stem reflex(pupil, oculocephalic, oculovestibular, corneal, gag, sucking)

    --> above 3 findings occur in absence of hypothermia, hypotension, elevated levels of depressant drugs

           & inconsistently absence of cerebral blood flow on radionuclide scan & electrical acitivity on EEG

           & above 3 findings persistence for 2 days in term & 3 days in preterm

Chapter 85. Delivery Room Emergencies

# *▲common & important emergency in delivery room

    ; failure to initiate and maintain respirations

Respiratory Distress And Failure

; airway obstruction and of depression of CNS

# *Choanal Atresia, Bilateral

    ; *respiratory movements with mouth closed

           --> but fail to move air in and out of lung

# hypoplasia of the mandible

# diaphragmatic hernia

Failure To Initiate Or Sustain Respiration

1) pulmonary hypoplasia associated with potter syndrome

2) severe organized intrauterine pneumonia

3) narcosis

   treatment; initial physical stimulation and securing patent airway

※86,87 Resuscitation

# Goal

    ; prevent morbidity and mortality

    ; re-establish adequate spontaneous respiration and C.O

# successful respiration

    ; good chest rise, symmetric breath sound, improved pink color, HR greater than 100/min, spontaneous repiration, improved tone

# medication

    ; ※94 Indication

           - HR < 80/min following 30 sec of combined ventilation & chest compression

                   or during asystole

    ; epinephrine

           - *0.1-0.3 ml/Kg of 1:10,000 solution, IV or intratracheal

           - repeated every 5 min

           - if no response

                   / 5 to 10 times

  ; 10-20ml/Kg of volume expander

           - N/S, blood, 5% albumin, Ringer`s lactate

    ; sodium bicarbonate

           - 1-2mEq/kg, 0.5mEq/ml of 4.2% solution

           - 1mEq/kg/min

           - effective ventilation후에 준다.

    ; Dopamine(5-20 μg/Kg/min)

           - poor peripheral perfusion, weal pulses, hypotension, tachycardia, poor U.O

Shock

1) cyanosis, pallor, flaccidity, cold mottled skin, tachycardia or bradycardia, hepatsplenomegaly, convulsion

2) treatment; Rh^- O blood, plasma or electrolyte solution

Chapter 86. Dysmorphology

# Two Structural Defects

    ; single primary defect & multiple malformation syndrome

# ♥Seven Most Common Single Primary Defect In Development

   1. CDH

   2. Talipes equinovarus

   3. cleft lip with or without cleft palate

   4. cleft palate alone

   5. cardiac septal defect

   6. pyloric stenosis

   7. neural tube defect

# *next baby의 risk ; 2-5%

# multiple malformation syndrome

  ; due to chromosomal abnormality, single gene defect inherited in menelian pattern

표12-8, 12-9(p266-267)

Single Primary Defects In Development

Malformation

; *primary structural defect arising from localized error in morphogenesis

; e.g.) *cleft lip, congenital septal defect, pyloric stenosis

; multifactorial recurrence risk factors

    - 2-5%

; excellent prognosis after surgical correction

Deformation

; *alteration in shape or structure of a part that has differentiated normally

; mostly involve musculoskeletal system & caused by intrauterine molding

; intrinsically derived positional deformation

    --> *myotonic muscular dystrophy, Wernig-Hoffmann disease

; extrinsically derived deformation of prenatal onset

    --> fetal crowding

; other extrinsic factor

    - breech presentation, shape of amniotic cavity

; e.g.) *talipes equinovarus, congenital hip dislocation

    - *위 두가지를 제외하고는 대부분이 비 유전적 요인

    - *재발율이 매우 낮고, 예후는 매우 양호하여 자연적으로 교정되는 수가 많다.

Disruption

; *structural defect resulting from destruction of previously normally formed part

# ♥Two Basic Mechanism

    1) entanglement followed by tearing apart or amputation of normally developed structure

           - digit, arm, leg

    2) interruption of blood supply to a developing part

           - infarction, necrosis, resorption of structures

# Example

    ; *nonduodenal intestinal atresia, gastroschisis, porencephaly

# *genetic factor 는 주역할을 담당하지 않는다.

Sequence

; *single primary defect in early morphogenesis가 cascading process로 multiple abnormalities을 생성하는 하거나 tertiary errors in morphogenesis을 일으키는 것

# ♥Robin Malformation Sequence

    ; single prenatal onset defect in development, mandibular hypoplasia

           --> glossoptosis, blocking closure of the post. palatal shelves causing U-shaped cleft palate

# breech deformation sequence

    ; compression of developing fetal parts

           --> bathrocephaly, torticollis, facial asymmetry, dislocated hip, valgus anomalies of both feet

# amniotic band disruption sequence

    ; constriction caused by entanglement in multiple fibrous strands of amnion extending from plcental insertion of umbilical cord to surface of amnion-denuded chorion or floating withiin chorionic sac

           --> craniofacial and limb defects

Multiple Malformation Syndrome

    1) chromosomal and genetic abnormalities by teratogens

    2) intrauterine infection

           ; SGA, developmentally delayed, microcephaly or hydrocephalus, microphalmia, chorioretinitis, cataract, glaucoma, hepatosplenomegaly, thrombocytopenia

    3) Williams syndrome

           ; *deletion of one elastin allele located within 7q11.23

    4) Rubinstein-Taybi syndrome

           ; *microdeletion in 16p13.3

    5) Prader-Willi syndrome

           ; *deletion involving 15q11-12, paternal

    6) Brachmann-de Lange syndrome

           ; *single gene transmitted as an AD

    7) VATER association

           ; *vertebral defect, anal atresia, tracheoesophageal fistula with atresia, radial upper limb hypoplasia, renal defect

# evaluation 하는 목적

  (1) making specific overall diagnosis

  (2) accurate prognostication about the child`s future development

  (3) appropriate recurrence risk counseling for the parents

  (4) appropriate plan to help the child reach his or her potential

Chapter 87. Respiratory Tract Disorders

87.1 Transition to Pulmonary Respiration

The First Breath   

# Need pressure

    ; *10-50cm of H₂O for 0.5 to 1.0 sec-interval

    ; *약 50ml가 폐로 들어가 20-30ml는 FRC가 된다.

# Removal of the liquid of the lung

    ; *most - pulmonary circulation

    , others - pulmonary lymphatics, expelled by the infant, swallowed, or aspirated from the oropharynx

    ; impaired removal

           - C-sec, endothelial cell damage, neonatal sedation

# ※Stimuli of first breath

    ; fall in PO₂ and pH

    ; rise in PCO₂

  ; redistribution of CO after umbilical clamping

  ; decrease in BT

  ; variety of tactile stimuli

# ♥LBW infant 의 특징

    ; very compliant chest wall --> disadvantage in first breath

    ; least FRC --> atelectasis

    ; greater and persistent abnormalities in ventilation-perfusion ratio

# low PaO2(50-60mmHg), elevated PaCO2

    ; reflecting atelectasis, intrapulmonry shunting, hypoventilation

Breathing Pattern In Newborns

# periodic breathing

  ; more common in the premature infant

    ; shifting from regular rhythmicity to cyclic brief episodes of intermittent apnea

    ; *apneic pauses of 5-10sec followed by burst of rapid respiration at a rate of 50-60/min for 10-15sec

    ; no change in color or heart rate

    ; usually till premature infant are about 36wks

    ; *no prognostic significance

87.2 Apnea

Causes

※91 Table 87-1 Potential causes of neonatal apnea and bradycardia

# Mechanism

  1) depression of the CNS control of respiration

           ; hypoglycemia, meningitis, drugs, hemorrhage

  2) disturbances of oxygen delivery by perfusion

           ; shock, sepsis, anemia

  3) ventilation defects

           ; pneumonia, HMD, persistence of fetal circulation, muscle weakness

# Idiopathic apnea of prematurity

    ; absence of identifiable predisposing diseases

    ; type

           - obstructive type

                   / upper airway obstruction

                   / pharyngeal instability, neck flexion, nasal occlusion

                   / absent air flow but persistent chest wall movement

           - central type

                   / decrease of gestational age dependent reduced CNS stimulus

                   / immaturity of brain stem

                   / attenuated response to carbon dioxide & paradoxical response to hypoxia

           - mixed type

                   / *▲common

                   / obstructive apnea following central apnea

# short apnea

    ; 주로 central

    ; 15sec이상이면 more mixed

# *sleep state dependent

    ; *REM sleep에서 많다.

Clinical Manifestations

; cessation of breathing for longer than 15-20sec or any duration if accompanied by cyanosis and bradycardia

; *idiopathic apnea는 생후 1일에는 드물기때문에 다른 원인을 먼저 생각해야 한다.

; 2nd-7th day onset

; ※91 생후 2주후에 sudden onset apnea는 critical event이므로 즉시 evaluation해야 한다.

; longer apnea(>20sec)일수록 bradycardia동반

    - 95%

Treatment

; *gentle cutaneous stimulation

    - adequate therapy for mild and intermittent episodes

; bag and mask ventilation

    - recurrent prolonged apnea

; oxygen

; Drug therapy

    - *precipitating identifiable cause가 없는 경우에 사용

    - enhance central mechanism or improving iaphragmatic strength

    - *methylxanthine

           / loading 5mg/Kg, 1-2 mg/Kg every 8-12 hr using oral or IV

    - caffein

           / loading 10mg/kg, 2.5mg/kg/24hr

; transfusion of packed red blood cells

; nasal CPAP(3-5cmH₂O)

Prognosis

; *associated problem이 예후를 결정

    - IVH, bronchopulmonary dysplasia, retinopathy of prematurity

; *apnea of prematurity는 36wk postconceptional age에 호전된다.

; *not predict furture episodes of SIDS

87.3 Hyaline Membrane Disease

Incidence

; *inversely proportional to gestational age & birth weight

; *60-80% of less than 28wk

  - *15-30% of 32-36wk

  - *5% beyond 37wk

# ※81,87 Predisposing Factors

    ; maternal DM, delivery before 37wk gestaion, multifetal pregnancy, C/S delivery, precipitous delivery, asphyxia, cold stress, Hx of prior affected infants

Etiology And Pathophysiology

♣Fig. 87-1 Composition Of Surfactant

; *high surface tension and absence of surfactant

    --> correlate with failure of FRC & tendency of atelectasis

; mature level of surfactant

    - *usually present after 35wk

㉿Fig. 87-3

# ※92 Suppressive Factors Of Surfactant Synthesis

    ; asphyxia, hypoxemia, pulmonary ischemia, hypovolemia, hypotension, cold stress

; *최종 mechanism : atelectasis

    - alveolar atelectasis, hyaline membrane formation, interstitial edema

           --> less complaint lung

           --> greater pressure

           --> limiting intrathoracic pressure

           --> volume of thorax & lungs approach residual volume

           --> atelectasis

; highly complaint chest wall of preterm infant

    - less resistance against collapse

    - atelectasis를 조장

Patholgy

# gross; purplish red and liver like consistency

# microscopic finding

    ; extensive atelectasis, engorgement of intraalveolar capillaries and lymphatics

    ; alveolar ducts, alveoli, respiratory bronchioles lined with acidophilic, homogeneous or granular membrane

# *출생후 6-8hr이내에 사망한 경우에는 특징적인 hyaline membrane이 드물다.

Clinical Manifestations

; *usually appear within minutes of birth

; Characteristically

    - tachypnea, prominent(often audible) grunting, intercostal & subcostal retractions, nasal flaring, duskness

; increasing cyanosis

; breath sound

    - normal or diminished with a harsh tubular quality

    - fine rales on deep inspiration

; natural course

    - progressive worsening of cyanosis & dyspnea

; *apnea & irregular respiration

    - *tired infant일때 발생하는 ominous signs

    - immediate intervention

; mild cases인 경우에는 symptoms & signs 이 3일이내에 peak

; ★Death

    - *rare on 1st day of illness

    - *usually 2-7 days

    - *ass. with alveolar air leaks(interstitial emphysema, pneumothorax), pulmonary or intraventricular hemorrhage

Diagnosis

# ※87 X-ray

    ; not pathognomonic

    ; *fine reticular granularity and air bronchogram

         - more prominent early in the Lt. lower lobe due to cardiac shadow

    ; occasionally normal initial roentgenogram

           --> develop typical pattern at 6-12hr

    ; poor correlation between X-ray finding and clinical course

※89 Differential Diagnosis

    ; group B streptococcal sepsis

           - gram-positive cocci in the gastric or tracheal aspirates & buffy coat smear

           - positive test of urine for streptococcal antigen

    ; cyanotic heart disease

    ; PFC

    ; aspiration syndrome

    ; spontaneous pneumothorax, diaphragmatic eventration, congenital anomalies (cystic adenomatoid malformation, pulmonary lymphangiectasia, diaphragmatic hernia, lobar emphysema)

    ; transient tachypnea

    ; congenital alveolar proteinosis

Prevention

# Prevention Of Prematurity

    ; *▲important

# *administration of dexamethasone or betamethasone to women 48-72hr before delivery of fetuse at 32wk or less

    ; IVH, PDA, pneumothorax, NEC 의 빈도도 감소

# administration of 1 dose of surfactant

    ; 생후 24시간 이내

Treatment

; most cases of HMD

    - *self-limiting

# goals

    ; minimize abnormal physiologic variations & superimposed iatrogenic problems

# general principles

    ; gentle handling, minimal disturbance consistent with management

    ; 36.5~37℃ core temperature

    ; IV calorie & fluid infusion

           - 1st 24hrs

                   / 10% DW 65-75 ml/kg/24hr

           - subsequent

                   / 120-150 ml/Kg/24hr with electrolyte

# warm humidified oxygen

    ; ★PaO₂ 을 55-70 mmHg로 유지

           --> ※87 70% O₂ conc. 에서도 50mmHg이상 유지안 되면

           --> *CPAP 6-10 cm H₂O by nasal prongs

# ※86,92 Indications For Mechanical Ventilation

    ; arterial blood pH <7.20

    ; arterial blood PCO₂ of 60 mmHg or more

    ; arterial blood PO₂ of 50 mmHg or less at O₂ 70-100%

    ; presistent apnea

# ㉿96 Acceptable Range Assisted Ventilation

    ; PaO₂ of 55-70mmHg

    ; PCO₂ of 35-55mmHg

    ; pH of 7.25-7.45

    ; PEEP 4-6cmH2O

# rate ranges of ventilators

    ; conventional ventilator - 10~60 breaths/min

    ; HFJV - 150~600/min

    ; oscillators - 300~1800/min

# ♥Advantage of HFJV & oscillators

    ; more CO2 elimination

    ; lower mean airway pressure

    ; occasionally improve oxygenation of patients not responding conventional ventilator

# ♣Complication of HFJV

    ; necrotizing tracheal damage, esp. in hypotension or poor humidification

    ; gas trapping

# ♣Complication of oscillator

    ; *increased risk of air leaks, IVH, PVL

    ; gas trapping

# ★Surfactant Therapy

    ; *via E-tube, every 12hrs for a total of 4 doses

    ; BPD의 incidence를 낮추지는 않는다.

    ; ※94주 Immediate Effests

           - improved aloveolar-arterial oxygen gradients

           - reduced ventilator mean airway pressure

           - imcreased pulmonary compliance

           - improved appearance of X-ray finding

    ; ♥종류

           - Exosurf

                   / synthetic

                   / contain dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol

                   / latter two protein for improving spread

           - ALEC (artificial lung expanding compound)

                   / 7:3 mixture of dipalmitoyl-phosphatidylcholine and phosphatidylglycerol

           - survanta

                   / from minced bovine lung with lipid extraction

                   / enriched phosphatidylcholine, palmitic acid, TG

                   / no SP-A

           - Curosurf, infasurf

                   / natural

    ; ♥Complications

         - *transient hypoxia and hypotension, pulmonary hemorrhage, blockage of E-tube

# ※89 Alkali Therapy Complication

    ; skin sloughs due to infiltration

    ; increased serum osmolarity

    ; hypernatremia

    ; hypoglycemia

    ; hypokalemia

    ; liver injury

# Umbilical artery catherization

    ; *above bifurcation of the aorta(L3-L5)

    ; *above the celiac axis(T6-T10)

    ; ※87,93,94 Indication Of Removal

           - stable PaO2 & less than 40% of FiO2

# AB medication ; routine

Complications Of HMD And Intensive Care

※82,84,90 Complication Of Tracheal Intubation

    ; asphyxia, cardiac arrest during intubation or suctioning, subglottic stenosis

           - *▲serious complication

    ; bleeding d/t trauma, post. pharyngeal pseudodiverticula, difficult extubation, ulceration of nares, permanent narrowing of the nostril, scarring from the irritation or infection, erosion of the palate, avulsion of the vocal cord, laryngeal ulcer, persistent hoarseness, papilloma of a vocal cord, stridor or edema of the larynx

※86,93 Complication Of Umbilical Arterial Catheterization

 1) vascular embolization

 2) thrombosis

           / heparin infusion 1-10unit/ml

 3) spasm

 4) preforation

 5) ischemic or chemical necrosis of abdominal viscera

 6) infection

 7) accidental hemorrhage

 8) impaired circulation to a leg with gangrene

 9) renovascular hypertension

# ※85증례 Transient blanching of the leg

    ; due to reflex arterial spasm

    ; removal of catheter immediately

    ; Treatment

           - topical nitroglycerin over femoral artery

           - warming the opposite leg

           - local infusion of tolazoline(Priscoline) 1-2mg intraarterial over 5min

Complication Of Umbilical Vein Catheterization

; same as above

; portal hypertension & portal thrombosis

BPD

# Contributing factors

    ; oxygen therapy - *▲important

    ; alveolar shear stress, volutrauma, hypocapnic saponification, absorption atelectasis, and subsequent inflammation

# Clinical course

    ; HMD로 치료하던 환아가 3-4일째 호전보이지 않고, 더 악화됨

    ; X-ray changing

           - from complete opacification with air bronchogram & interstitial emphysema

                   to *small, round, lucent area resembling sponge

    ; histologic finding(10-20days)

           - less evidence of HM formation

           - progressive alveolar coalescence with atelectasis

           - interstitial edema

           - coarse focal thickening of basement membrane

           - mucosal metaplasia & hyperplasia

    ; surviving infant

           - *most recover at 6-12mo

           - some prolonged hospitalization & respiratory symptom

    ; cause of death

           - *Rt sided heart failure, viral necrotizing bronchiolitis

           - pathology

                   / cardiac enlargement

                   / emphysematous alveoli with hypertrophy of peribronchial smooth muscle of tributary bronchioles

                   / perimucosal fibrosis

                   / widespread metaplasia of bronchiolar mucosa

                   / thickening of BM

# ※94 Risk factor

  ; *prolonged periods of mechanical ventilation and oxygen therapy

           - *▲important

    ; *pulmonary interstitial emphysema, lower GA, male sex, low PCO₂ at 48hr, *PDA, high PIP, increased airway resistance in the 1st wk of life, family Hx of asthma

# ★Acceptable Blood Gas

    ; PCO2 of 50-70mmHg(if pH>7.30)

    ; PO2 of 55-60mmHg

    ; O2 saturation 90-95%

Treatment

    ; bronchodilators(aerozoliaed β-adrenergic), theophylline, diuretics

    ; fluid restriction

    ; treatment of infection

    ; high caloric density formula

    ; CPAP for tracheomalacia

    ; ★Dexamethasone

           - 0.5mg/kg/24hr IV two dose after 2-6wk of chronic lung disease

           - continued for 3 days

           - reduced to 0.3mg/kg/24hr for additional 3 days

           - reduced by 10% every 3 days until 0.1mg/kg/24hr

           - final dose every other day for 1wk

           - complications

                 / hypertension, poor growth, GI bleeding, hyperglycemia, infection, possible cardiomyopathy

    ; ★Complication

           - growth failure, transient psychomotor retardation, parental stress, *nephrolithiasis, osteopenia, subglottic stenosis

Prognosis

# ♥Poor Prognostic Signs

 ; prolonged ventilation, IVH, pulmonary hypertension, cor pulmonale, oxygen dependency beyond 1yr of life, extrapulmonary extravasation,              

Extrapulmonary Extravasation

PDA

# ※87 Predisposing factors   

    ; hypoxia, acidosis, increased pulmonary pressure secondary to vasoconstriction, severe hypotension, immaturity, local release of PG

# *초기에는 bidirectional or Rt to Lt shunting

    --> *HMD 호전되면서 Lt to Rt shunting

# ※81,82 Manifestations Of PDA

    1) persistent apnea for unexplained reasons in an infant recovering from HMD

    2) active heaving precordium, bounding peripheral pulse

    3) CO₂ retention

    4) increasing oxygen dependency

    5) cardiomegaly and increased pulmonary vascular marking

    6) hepatomegaly

# ※94 Treatment Of PDA

    ; 대부분은 general supportive measures, diuretics, fluid restriction에 잘 반응

    ; IV indomethacin

           - 0.2 mg/Kg at 12- to 24hr intervals for 3 doses

              or  0.1 mg/Kg/24hr for 6days

         - ★Containdications

                   / thrombocytopenia, bleeding disorders, oliguria, NEC, elevated Cr(>1.8mg/dl)

Anemia

;sampling

; oxygen dependent patient는 *Hct 40%유지

Prognosis

; surfactant

    - RDS mortality 40%감소 ( not morbidity )

87.4  Transient Tachycardia Of The Newborn (Respiratory Distress Syndrome Type II)

Clinical Manifestation

    ; term or normal preterm

    ; early onset

    ; tachypnea

    ; sometimes retraction or expiratory grunting

    ; occasionally cyanosis

           - relieved by minimal oxygen

    ; 3일 이내에 신속히 좋아짐

Pathogenesis

    ; ★slow absorption of fetal lung fluid

           --> decreased pulmonary compliance & tidal volume, increased dead space

Diagnosis

    ; ★Chest X-Ray

           - *prominent pulmonary vascular markings, fluid lines in ther fissures, overaeration, flat diaphragm, occasionally pleural fluid

    ; *uncommon hypoxemia, hypercapnia, acidosis

    ; DDx with RDS

         - sudden recovery, absence of reticular or air-bronchogram

87.5 Aspiration Of Foreign Material

; during prolonged labors and difficult delivery

; T-E fistula, esophageal and duodenal obstruction, GE reflux, improper feeding practices, depressant medicines

87.6 Meconium Aspiration

# meconium stain - 5-15% of births

    -> *5% develops mecoium aspiration

  -> *30% requires mechanical ventilation

    -> 5-10% expires

Clinical Manifestations

; *small airway obstruction

    --> respiratory distress within the 1st hr with tachypnea, retraction, grunting, cyanosis

; *pneumothorax, pneumomediastinum

; overdistension of chest

; usually improve within 72hr

; ※X-ray

    - patchy infiltrates, coarse streaking of both lung fields, increased A-P diameter, flattening of diaphragm

Prevention

; fetal distress monitoring

; *aminoinfusion & DeLee suctioning of oropharynx after head delivered

Treatment

; absence of fetal distress with thin meconium stained

    - no treatment

; depressed infant and thick meconium stained

    - *intubation & suction

; standard RDS management

; surfactant therapy, inhaled nitric oxide, ECMO

    - refractory conventional or HFJV therapy경우에 고려

Prognosis

; asphyxia후의 CNS injury와 동반된 다른 problem에 의해 결정

87.7 Primary Pulmonary Hypertension-PFC

; term and postterm

# ★Predisposing Factors

    ; birth asphyxia, meconium aspiration pneumonia, GBS sepsis, HMD, hypoglycemia, *polycythemia, pulmonary hypoplasia due to diaphragmatic hernia, amniotic fluid leak, *oligohydramnios, pleural effusion

# *idiopathic 일수도 있다.

Pathophysiology

; excessively high pulmonary vascular resistance

    --> pulmonary hypertension

    --> Rt to Lt shunting

; ★Mechanism

    1) maladaptive from an acute injury

    2) increased pulmonary artery medial muscle thickness & extension of smooth muscle layers into nonmuscular more peripheral pulmonary arterioles in response to chronic fetal hypoxia

    3) pulmonary hypoplasia

    4) obstructive owing to polycythemia or total anomalous pulmonary venous return

    5) alveolar capillary dysplasia

           - lethal familial disorder

           - thickened alveolar septum, reduced small pulmonary arteries & capillaries

Clinical Manifestations

; *ill within first 12hr

; severe cyanosis with tachypnea

    - polycythemia, idiopathic cause, hypoglycemia, asphyxia로 인한 경우

; cyanosis, grunting, flaring, retractions, tachycardia, shock

    - meconium aspiration, group B streptococcal pneumonia, diaphragmatic hernia, pulmonary hypoplasia로 인한 경우

; *multiorgan involvement

    - myocardial ischemia, papillary muscle dysfunction with MR, TR, cardiac stun

Diagnosis

; *cyanosis가 있는 all term infant는 반드시 의심

; *hypoxia

    - universal

    - *unreponsive to 100% oxygen

    - transient response to hyperoxic hyperventilation administered after endotracheal intubation or application of a bag & mask

; PaO₂ gradient >20mmHg

    - preductal(Rt. radial artery) & postductal(umbilical artery)

; *idiopathic 인 경우에는 chest X-ray 가 정상이다.

; DDx

    - cyanotic heart disease, associated etiologic entities that predispose to PFC

Treatment

# Initial management

    ; oxygen administration

    ; correction of acidosis, hypotension, and hypercabia

# Mechanical Ventilation Without Pancuronium Paralysis

    ; *PaO₂ of 50-70mmHg & PaCO₂ of 50-55mmHg

    ; tolazoline 1mg/kg

           - nonselective α-adrenergic antagonist

# Hyperventilation

    ; *PaCO₂ of 20-25mmHg & increasing pH of 7.50-7.60

    ; use pancuronium

    ; *conventional ventilation에 효과 없는 경우

    ; ★Complication

           - hyperinflation with reduced CO2 elimination

           - reduced cardiac output

           - barotrauma

           - pneumothorax

           - decreased cerebral blood flow

           - increased fluid requirements

           - edema resulting from pancuronium paralysis

    ; alkalination with sodium bicarbonate

           - pul. arterial vasodilatation

# Exogenous surfactant therapy

# Inhaled NO ; 10-20ppm(usually 50)

# Alveolar-Arterial Oxygen Gradient

    ; *[760-47] - PaCO2 - PaO2

    ; *predictor of mortality(80%이상)

# Oxygenation Index

    ; *(mean airway pressure x FiO2 x 100) / postductal PaO2

    ; *predictor of mortality(80%이상)

# ECMO

    ; ♥Indication

           - PFC

           - AaDO2 gradients greater than *620 for 8-12hr

           - *OI more than 40

           - severely ill infants with HMD, meconium aspiration pneumonia, group B streptococcal sepsis

           - hypoxic diaphragmatic hernia

                   / *ventilation index(rate X mean airway pressure) exceeds 1000 & PaCO2 exceeds 40mmHg

    ; veno-arterial bypass

           - Rt. internal jugular vein & carotid artery이용

    ; Circuit

           - *80% of estimated cardiac output(150-200ml/kg/min)을 돌린다.

           - rate of ECMO flow는 venous oxygen saturation을 >65%으로 유지하도록 한다.

           - *ventilator support는 room air로 weaning at low rate & pressure

    ; ♥Contraindication

           - risk of IVH

                   / <2kg, <35wk

           - irreversible lung disease

           - sign of systemic bleeding

           - severe asphyxia

           - lethal malformations

    ; *7-10days로 ventilation해야한다.

    ; ♥Complication

           - thromboembolism, air embolization, bleeding, stroke, seizures, atelectasis, cholestatic jaundice, thrombocytopenia, neutropenia, hemolysis, infectious complications, edema formation, *systemic hypertension

Prognosis

# associated hypoxic-ischemic encephalopathy와 pulmonary vascular resistance의 감소에 달려있다.

# *ECMO후 outcome이 좋다

    ; *85-90% survival, 70-75% normal 1yr life

87.8  Extrapulmonary Extravasation Of Air (Pneumothorax, Pneumomediattinum, And Pulmonary Interstitial Emphysema)

;Asymptomatic pneumothorax - 1~2% of all newborn infants

; more common in females and in term and postterm

# ※87주 Predisposing Factors

    - meconium aspirtion

    - HMD

    - vigorous resuscitation

    - assisted ventilation, esp. high inspirtory pressure

    - urinary tract anomalies

Etiology And Pathophysiology

# overinflation resulting in alveolar rupture

  ; *▲common cause

    ; spotaneous(=idiopathic) or secondary

# secondary pneumothorax

    ; underlying pulmonary disease such as lobar emphysema or rupture of congenital or pneumonic cyst

    ; trauma

    ; “ball-valve” type of bronchial or bronchiolar obstruction from aspiration

# Air leak 시기

    1) *within 24hr

           ; *asso. with pulmonary hypoplasia

           ; *others ass. with

                   - decreased amniotic fluid volume

                           / Potter syndrome

                                   : renal agenesis, renal dysplasia, chronic amniotic fluid leak

                   - decreased fetal breathing movement

                           / oligohydramnios, neuromuscular disease

                   - pulmonary space-occupying lesion

                           / diaphragmatic hernia, pleural effusion, chylothorax

                   - thoracic abnormalities

                           / asphyxating thoracic dystrophies

    2) 24-36hr

           ; meconium aspiration, pneumonia, HMD when lung compliance is reduced

    3) *after 36hr

           ; *recovery phase of HMD if inspiratory pressure & PEEP are not reduced

Interstitial Emphysema

; air from a ruptured alveolus escapes into interstitial spaces of the lung

Tension Pneumothorax

; elevate intrapleural pressure above atmospheric pressure

; compression of the vena cava and torsion of the great vessel

    -->  impaired venous return

Clinical Manifestation

# asymptomatic ; hyper-resonance and diminished breath sounds

# symptomatic

    ; tachypnea, dyspnea, and cyanosis

    ; *irritability, restlessness or apnea

           - *earliest sign

    ; chest

           - asymmetric, increased A-P diameter, bulging of the intercostal spaces

    ; shock

Pneumomediastinum

; *25% of pneumothorax patients

; *usually asymptomatic

, midthoracic bulging, neck vein distension, BP decreasing

; *subcutaneous emphysema

    - *pathognomonic

Pulmonary Interstitial Emphysema

; precedes the development of a pneumothorax or independently develop

; in severe cases

    - precedes development of BPD

Diagnosis

# pneumothorax

    ; collapsed lung의 edge가 뚜렷이 사진상 보임

# pneumomediastinum

    ; heart 주위와 heart, sternum사이에 hyperlucency가 보임

# transillumination of the chest

# *associated renal anomaly 을 검사해야 한다.

    ; USG

# ♥Pulmonary Hypoplasia을 의심할 수 있는 경우

    ; uterine compression(extremity contractures)

    ; small thorax on chest roentgenogram

    ; severe hypoxia with hypercarbia

    ; sign of primary disease(hypotonia, diaphragmatic hernia, Potter syndrome)

Pneumopericardium

; sudden shock with tachycardia, muffled heart sound, and poor pulses

Pneumoperiteneum

Treatment

; asymptomatic or mildly symptomatic

    - only observation

; *breathing 100% oxygen

    - accelerates the resorption of free pleural air into blood

; selective bronchial intubation

; use of pavulon

87.9 Interstitial Pulmonary Fibrosis

# Wilson and Milkity syndrome

    ; <1500 g, <32wks, *without history of RDS, incidious onset of dyspnea, tachypnea, retraction and cyanosis during the 1st 1mo

# symptoms and signs

   cough, wheezing, and rales

   Rt. sided heart failure

# diagnosis

; X-ray

    - bilateral coarsereticular streaky infiltration

  - overexpansion with small area of emphysema

# DDx

; pneumonia d/t CMV, pneumocystis carinii, Ureaplasma urealyticum, or chlamydia pneumonia

; cystic fibrosis

# treatment

; supportive care; oxygen, bronchodilator, diuretics, acid-base correction, correction of anemia, assisted ventilation

; a trial of EM

87.10  Pulmonary Hemorrhage

# Incidence

; 15% of neonates in the 1st 2wks(at autopsy)

; 1-4/1,000 live birth

; 3/4 of patients - less than 2,500 g

Clinical Manifestation

; respiratory distress

; *at birth or delayed several days

; variable chest X-ray finding

Etiology

; not identified

# ※82 Asso. disorders

    ; acute pulmonary infection, severe asphyxia, HMD, surfactant therapy, assisted ventilation, CHD, erythroblastosis fetalis, *hemorrhagic ds. of newborn, kernicterus, inborn error of ammonia metabolism, cold injury

    ; DIC

    ; Lt. heart failure

           - hemorrhagic pulmonary edema

Prognosis

; poor

    - death in 1st 48hr of life

    - 2/3

Chapter 88. Digestive System Disorders

Vomiting

; *대부분은 simply regurgitation from overfeeding or from failure to permit infant to eructate swallowed air이 원인이다.

# Bile-stained emesis

    ; *intestinal obstruction beyond duodenum

    ; also be idiopathic

# Vomiting In Esophageal Atresia

    ; occurs with first feeding

    ; suspected if unusual drooling from the mouth

    ; infant chokes on oral feeding이 되기전에 진단되어야 한다.

# Vomiting due to obstruction of small intestine

    ; begins on the 1st day

    ; frequent, persistent, usually nonprojectile, copious

    ; bile-stained

    ; abdominal distension, visible deep peristaltic waves

    ; reduced or absent bowel movement

    ; *Normal Gas Pattern

         - in the jejunum by 15-60 min

    - in the ileus by 2-3hr

       - in the colon by 3hr after birth

# persistent vomiting ; diaphragmatic hernia

# begins in the 2nd-3rd wks of life ; pyloric stenosis

# celiac disease, milk allergy, adrenal hyperplasia, galactosemia, hyperammonemia, IICP, septicemia, menigitis, UTI

Thrush(Oral Candidosis)

; healthy infant

    - transmission from maternal vaginal moniliasis

    - transmission from hospital nursery

; debilitated infants

    - more common

    - receiving antibiotic or immunosuppressive therapy

    - AIDS

Diarrhea

Constipation

※97 No Meconium Pass Within 36hr After Birth

    ; intestinal obstruction

    ; congenital aganglionic megacolon

    ; milk bolus obstruction

    ; meconium ileus

    ; meconium plug

# *Present During The 1st Mo Of Life

; CMC, cretinism, anal stenosis

Meconium Plugs

; *associated with small lt. colon syndrome in the infants of a diabetic mother, cystic fibrosis, rectal aganglionosis, maternal drug abuse, MgSO4 therapy for pre-eclampsia

; ※87주 Treatment

    - evacuated by irrigating with isotonic sodium chloride solution

    - enemas with iodinated contrast medium gastrograffin

; *제거후에도 세심한 관찰이 요한다.

    - *possible presence of congenital aganglionic megacolon

88.1 Meconium Ileus In Cystic Fibrosis

1. symptoms and signs

 1) abdominal distension

 2) persistent vomiting

2. diagnosis

 1) presumptive ; Hx of cystic fibrosis in a sibling

 2) palpation of doughy or cord like massof intestine

 3) X-ray finding

3. treatment; gastrograffin enema

Meconium Peritonitis

   abdominal distension, vomiting, and absence of stool

88.2  Neonatal Necrotizing Enterocolitis

; incidence - 1-5% of admissions of NICU

; rarely in term infants

Pathology And Pathogenesis

; pneumatosis intestinalis

; *distal ileum and proximal colon

    - *▲common

# ★Risk Factors

    ; polycythemia, hypertonic milk or medicine, too rapid feeding protocol

; *pemature에서는 stress 없이 일어날 수 있다.

; *infectious agents 가 중요한 역할

    - *Cl. perfringens, E. coli, Sta. epidermidis, rotavirus

Clinical Manifestation

; *onset in first 2wks

 - as late as 2mo in VLBW infants

; *abdominal distension with gastric retension

    - *first sign

; bloody stool

    - 25% of patients에서 관찰되고, insidous onset을 보이기도 함.

Diagnosis

# ※92,93 X-Ray Findings

    ; pneumatosis intestinalis

           - diagnostic finding

           - *50-75%에서만 관찰된다.

    ; portal vein gas

           - *sign of severe disease

    ; pneumoperitonium

           - perforation의미

# Differential Diagnosis

    ; obstruction, volvulus, indomethacin에 의해 perforation발생시는 NEC와는 달리 *less ill-apearance을 보인다.

Treatment

; cessation of feeding, nasogastric decompression

; fluid therapy

; systemic antibiotics

    - antipseudomonas(e.g. ticarcillin) and aminoglycoside

; ventilation

; ※Surgery

    - evidences of perforation

    - failure to respond to medical management

  - single fixed bowel loop

  - erythema of the abdominal wall or a mass

Prognosis

; medical management failure with pneumatosis intestinalis

    - *20%

  - 이중 25%는 die

# Complications

    ; short bowel syndrome due to massive resection

# Prevention

    ; jucidious feeding protocols

88.3 Jaundice And Hyperbilirubinemia In The Newborn

# Indirect bilirubin

    ; unconjugated, nonpolar, lipid-soluble pigment

    ; formed from hemoglobin

    ; by heme oxygenase, biliverdin reductase, nonenzymatic reducing agents in RES system

    ; neurotoxin

# Direct bilirubin

    ; polar, water-soluble ester glucuronide of bilirubin

    ; converted in liver cell microsome

    ; by uridine diphosphoglucuronic acid(UDPGA) glucuronyl transferase

Etiology

# ♣Unconjugated Hyperbilirubinemia

    1) increase the load of bilirubin

           ; hemolytic anemia, shortened red cell life due to immaturity or to transfuesd cells, increased enterohepatic circulation

    2) damage or reduce the activity of the transferase enzyme

           ; hypoxia, infection, possibly hypothermia, *thyroid deficiency

    3) compete for or block the transferase enzyme

           ; drugs & other substances requiring glucuronic acid conjugation for excretion

    4) leads to an absence of or decreased amounts of the enzyme or to reduction of bilirubin uptake bt the liver cell

           ; genetic defect, *prematurity

# ※90 Increasing Factors

    ; hypoproteinemia

    ; sulfisoxazole & moxalactam

           - displacement of bilirubin from its binding sites on albumin by competitive binding

    ; acidosis

    ; *increased FFA conc. due to hypoglycemia

    ; starvation

    ; hypothermia

# ※91 Factors that increse permeability of BBB or nerve cell memb to bilirubin or susceptibility of brain cells to its toxicity

    ; asphyxia

    ; prematurity

    ; hyperosmolality

    ; infection

Clinical Manifestation

; begins on face

    - face-5mg/dl, midabdomen-15mg/dl, soles-20mg/dl

; indirect bilirubin - bright yellow or orange

    direct bilirubin - greenish or muddy yellow

※★Differential Diagnosis

# 1st 24hrs

    ; erythroblastosis fetalis, cytomegalic inclusion disease, concealed hemorrhage, sepsis, rubella, congenital toxoplasmosis

# 2nd Or 3rd Day

  ; physiologic, *Crigler-Najjar Syndrome

# After The 3rd Day And Within The 1st Wk

  ; septicemia, infection(syphilis, toxoplasmosis, cytomegalic inclusion disease)

    ; polycythemia도 early jaundice 유발

# ★After The 1st Wk Of Life

    ; breast milk jaundice, septicemia, *congenital atresia of bile duct, hepatitis, rubella, herpetic hepatitis, galactosemia, hypothyroidism, congenital hemolytic anemia, crisis of other hemolytic anemia, hemolytic anemia due to drugs

# ※90주 Persistent Jaundice During 1st Mo

    ; inspissated Bile Syndrome, hyperalimentation-associated cholestasis, hepatitis, cytomegalic inclusion disease, syphilis, toxoplasmosis, familial nonhemolytic icterus, congenital atresia of bile duct, galactosemia, hypothyroidiam, pyloric stenosis

# Direct Bilirubinemia

    ; hepatitis, cholestasis, inborn error of metabolism, cystic fibrosis, sepsis

Physiologic Jaundice (Icterus Neonatorum)

; visible 2nd-3rd day

    - rising rate <5 mg/dl/24hr

    - peaking between the 2nd and 4th day at 5-6 mg/dl

    - decreasing to <2 mg/dl btw 5th and 7th day

# ★Pathogenesis

    ; increased bilirubin production following breakdown of fetal red blood cells

    ; transient limitation in the conjugation of bilirubin by the liver

; 6-7% of full-term - greater than 12.9mg/dl

; 3% of full-term - greater than 15mg/dl

# Risk Factors For Indirect Hyperbilirubinemia

   ; maternal diabetes, race(Chinese, Japanese, Korean, and Native American), prematurity, drugs(vitamin K₃, novobiocin), altitude, polycythemia, male sex, 21-trisomy, cutaneous bruising, cephalhematoma, oxytocin induction, breast feeding, weight loss, delayed stooling, sibling who had physiologic jaundice

# ★Persistent Indirect Hyperbilirubinemia Beyond 2wk

    ; hemolysis, hereditory glucuronyl transferase deficiency, breast milk jaundice, hypothyroidism, intestinal obstruction

# ♥Cause of Hyperbilirubinemia in Pyloric Stenosis

    ; caloric deprivation

    ; deficiency of hepatic UDP-glucuronyl transferase

    ; ileus-induced increased enterohepatic circulation of bilirubin

# ㉿Need For Search (Not Physiologic Jaundice)

    1) appears in the 1st 24hrs of life

    2) serum bilirubin is greater than 12 mg/dl in full-term or 10-14 mg/dl/24hr in preterm infant

    3) serum bilirubin is rising at a rate greater than 5 mg/dl/24hr

    4) jaundice persists after the 2nd wk of life

    5) direct-reacting bilirubin is greater than 1mg/dl at any time

Pathologic Hyperbilirubinemia

; risk factor

    - Asian race, prematurity, breast-feeding, or weight loss

; ※90 low bilirubin level에서도 kernicterus가 발생하는 경우

    - preterm infants

    - asphyxia

    - IVH

    - *hemolysis

    - drug

Jaundice Associated With Breast-Feeding

# max. concentration

    ; *10-30 mg/dl during the 2nd-3rd wk

# breast feeding 지속시, *3-10wk까지 low level로 지속될 수 있다.

# cessation of BMF

    ; 1-2일내에 떨어지고, feeding을 다시 해도 올라가지 않는다.

# ♥원인

    1) increase enterohepatic circulation

           ; increased caloric intake, delayed passage of meconium, increased level of beta glucuronidase, decreased urobilin formation

    2) inhibit glucuronyl transferase

           ; increased concentration of pregnanediol in milk

                   - 5-β-pregnane-3α, 20-β-diol

           ; *increased concentration of nonesterified fatty acid in milk - more important

# ♥DDx from early onset accentuated unconjugated hyperbilirubinemia

    ; higher bilirubin levels in 1st wk

    ; due to decreased milk intake with dehydration or reduced caloric intake

    ; Tx

           - frequent breast feeding(>10/24hr), rooming-in with night feedings

           - discouraging 5% dextrose or water supplementation

Transient Familial Neonatal Hyperbilirubinemia

; glucuronyltransferase inhibiting factor

Neonatal Hepatitis

Congenital Atresia Of The Bile Ducts

; jaundice persisting for more than 2wk or associated with acholic stools and dark urine

Inspissated Bile Syndrome

88.4 Kernicterus

; unconjugated biliubin이 brain cell에 침착되어 생기는 neurologic syndrome이다.

; *erythroblastosis fetalis가 있는 infant는 serum bilirubin level과 kernicterus가 직접적인 연관성이 있으나 healthy term infant에서는 그 연관성이 불분명하다.

; exceeding bilirubin binding capacity of albumin & other plasma protein and increasing plasma free bilirubin levels

    - enter brain by diffusion

; healthy term infant without hemolysis

    - *serum level이 25mg/dl이상이 되어야 kernicterus가 나타난다.

; *the less mature the infant, the greater the susceptibility to kernicterus

    - VLBW infant는 8-12mg/dl의 정도에서도 kernicterus가 나타난다.

Clinical Manifestation

; term infant - 2-5days after birth

    premature - 7th day

; initial sign

    - lethargy, poor feeding, loss of the Moro reflex

; *gravely ill, diminished tendon reflex, resp. distress

; opistotonus with bulging fontanel, twitching of face or limb, shril high-pitched cry

; convulsion, spasm

; rigidity is rare

; severe neurologic sign으로 진행한 환아의 대부분 사망

    - survivors few symptom for 2-3mo

           / 1년후 ; opisthotonus, muscular rigidity, irregular movement and convulsion

           / 2년후 ; opisthotonus, seizure는 감소하나, *irregular, involuntary movement, muscular rigidity, hypotonia는 계속증가한다.

           / 3년후

                   : complete nuerologic synd 이 분명해진다.       

                   : bilateral choreoathetosis with involuntary muscle spasm, extrapyramidal sign, seizure, mental deficiency, dysarthric speech, high frequency hearing loss, squint(사시), defective upward movement of the eye

                   : pyramidal sign, hypotonia, ataxia은 소수에서 나타난다.

; in midly affected infants

  - mild to moderate neuromuscular incoordination, partial deafness, minimal brain dysfunction

Pathology

; the surface of the brain is usually pale yellow

; stained yellow by unconjugated bilirubin

    - particularly in *corpus subthalamicum, hippocampus & adjacent olfactory area, striate body, thalamus, globus pallidus, putamen, inferior clivus, cerebellar nuclei, cranial nerve nuclei

; non pigmented areas may also be damaged

    - loss of neuron, reactive gliosis, atropy of involved fiber system

; injury hypothesis

    - *bilirubin interferes with oxygen utilization by cerebral tissue

Incidence & Prognosis

; untreated hemolytic ds. with more than 20mg/dl bilirubin level

    - 1/3 kernicterus

# Poor Prognosis

    ; overt neurologic sign

           - *75% 이상 die

        - 80% of affected survivor

                   / bilateral choreoasthetosis with involuntary muscle spasm

                   / mental retardation, deafness, spastic quadriplegia

Treatment Of Hyperbilirubinemia

# goal of therapy

; to prevent the concentration of indirect reacting bilirubin in the blood from reaching levels at which neurotoxicity may occur

# underlying cause 치료

; neurologic damage의 위험성을 증가시키는 physiologic factor의 치료 (eg. correction of acidosis)

# *6-12hr을 phototherapy를 해야 효과를 알 수 있다

Exchange Transfusion

㉿Table 88-2, 88-3

; 이 기준은 여러 가지 factor에의해 변경될 수 있다.

; *clinical sign이 나타나면 serum bilirubin level에 상관없이 exchange transfusion의 indication이 된다.

; healthy fullterm infant(physiologic or breast milk jaundice)

    - 25mg/dl이상에서도 잘 견딜 수 있다.

; sick premature infant - 낮은 level에서도 kernicterus가 발생할 수 있다.

Phototherapy

; bilirubin absorbs light maximally in the blue range(420-470nm)

# ♥Mechanisms

    ; by photoisomerization

           - *4z, 15Z-bilirubin → 4z, 15E-bilirubin

           - excreted in bile without conjugation

    ; by irreversible reaction

         - *native bilirubin → isomer lumbirubin

           - excreted by kidney in unconjugated form

; prophylactic phototherapy in VLBW infants may prevent hyperbilirubinemia and reduce the incidence of exchange transfusion

# ★Maximum intensive phototherapy

    ; special blue fluorescent tubes

    ; within 15-20cm

    ; fiberoptic phototherapy blanket in infant’s back

# ※객 Serum Bilirubin Level과 Hematocrit의 Monitor

    ; * every 4-8hr in infant with hemolytic ds.

    ; * older infant에서는 12-24hr interval

    ; *phototherapy  중단 후에도 적어도 24hr동안 moniter 해야한다.

           - since unexpected risese of bilirubin

# hemolytic disease가 있는 환아는 anemia 를 간과해서는 안된다.

    - 필요하면 transfusion

# ※82 Complication of phototherapy

    ; loose stool, erythematous macular rash, overheating & dehydration, chilling from exposure of the infant, bronze baby synd.

# Contraindication

    ; porphyria

# ★Bronze Baby Synd.

    ; dark, grayish brown discoloration of the skin undergoing phototherapy

  ; mixed type of hyperbilirubinemia with elevation of direct bilirubin

    ; last for many months

Phenobarbital

; physiologic jaundice에 한정된 사용

; enhance the conjugation and excretion of bilirubin

# not routinely recommanded for treating jaundice in the neonatal infant

    ; ※96객 이유

           - 투여하고 며칠이 지나야 bilirubin metabolism에 영향을 준다

    - phototherapy 보다 효과가 적다

    - untoward side effect가 있다

           - not add to the response to phototherapy

Tin(sn)-protoporphyrin

; reduction of bilirubin level

Chapter 89. Blood Disorder

89.1 Anemia in the Newborn Infant

# fetal Hb increases with advancing gestational age

# at term, cord blood Hb ; 16.8g/dl (14-20g/dl)

  - VLBW infant ; 1-2g/dl below those at term

# physiologic decrease

    ; 8-12wk in term infants(Hb 11g/dl)

  ; 6wk in premature(Hb 7-10 g/dl)

# Anemia at birth

    ; pallor, CHF or shock

  ; caused by hemolytic ds. of the newborn, tearing or cutting of the umbilical cord during delivery, abnormal cord insertion, commucating placental vessel, placenta previa or abruptio, nuchal cord, incision into the placenta, internal hemorrhage, thalassemia, congenital parvovirus infection or hypoplastic anemia, twin-twin transfusion in monozygotic twin with arteriovenous, placental connection

# Transplacental hemorrhage

    ; bleeding from the fetal into the maternal circulation

  ; *Kleihauer-Betke test

           - maternal blood에서 fetal Hb과 RBC를 증명한다

Fig 89-2

#Acute blood loss

    ; result in severe distress at birth, initially with a normal Hb level, no hepatosplenomegaly, early onset of shock

# Chronic blood loss

  ; *marked pallor, less distress, low Hb level with microcytic index

    ; if severe, CHF

# ※82,83,87주 Anemia Appearing In The First Few Days After Birth

    ; hemolytic ds. of the newborn, hemorrhagic ds, bleeding from an improperly tied or clamped umbilical cord, large cephalhematoma, intracranial hemorrhage, subcapsular bleeding from rupture of the liver, spleen, adrenals or kidney

# *Delayed anemia from hemolytic ds. of the newborn

    ; vitamin K in large dose in premature

        - Heinz body in the erythrocyte

    ; congenital hemolytic anemia

           - spherocytosis

         - G-6-PD and pyruvate kinase deficiency

    ; bleeding from hemangioma of the upper GI tract or from  ulcer (in a Meckel diverticulum or duplication)

    ; repeated blood sampling of infant

    ; *deficiency of minerals such as copper in TPN infant

# Anemia of prematurity

    ; 1-3mo, below 7-10g/dl

    ; apnea, poor weight gain, pallor, decreased activity, tachypnea, tachycardia, feeding problem

    ; ※기전

           - repeated phlebotomy for blood test

       - shortened red blood cell survival

       - rapid growth

    - physiologic effects of the transition from fetal to neonatal life

           - smaller iron store

           - decreased erythropoietin

# Treatment of neonatal anemia by blood transfusion

    ; severity of symptoms, the Hb level, presence of co-mobid ds(BPD, HMD) 에따라 결정

    ; asymptomatic full-term infant(10g/dl) may be observed.

    ; theophyllin치료에도 불구하고 apnea, bradycardia가 나타나는 Hb 10g/dl이하인 premature infant는 RBC transfusion이 도움이 된다

    ; *HMD, severe BPD는 Hb 12-14g/dl 유지

    ; PRC transfusion

           - 10-15ml/kg, rate 2-3ml/kg/hr

           - 2ml/kg 주면 Hb 0.5-1g/dl 오른다

    ; Hemorrhage가 있을 때

           - whole blood 또는 fluid therapy후 PRC사용

    ; Recombinant Human Erythropoietin(Rhuepo)

           - chronic anemia ass. with prematurity & BPD

        - anemia of prematurity ass. with low endogenous levels of serum erythropoietin, HuEpo-responsive erythrocyte progenitor cells

           - oral iron, vit E 같이 공급

         - dose

                   / 100-200U/kg/dose, 5day/wk

               / 400U/kg/dose, 3day/wk

               / 150-200U/kg/dose q 3day

89.2 Hemolytic Ds. Of The Newborn (Erythroblastosis Fetalis)

; passage of maternal Ab → increased rate of red cell destruction

; important cause of anemia and jaundice

; *원인(순서)

    - D antigen of the Rh group, incompatibility of ABO factors

    - C or E antigen

    - K(kell), Duffy, Lutheran antigen

    - C^w, C^x, D^u, M, S, P, MNS, Xg, Diego, Kidd

; *Anti-Lewis antibodies do not cause disese

Hemolytic ds. of the newborn due to Rh incompatibility

; 90% are due to D Ag

    - others C or E

Pathogenesis

; unsensitized Rh negative recipient mother에 Rh positve containing D Ag이 감작

    - by infused through error, inherited from Rh positve father during pregnancy, spontaneous or induced abortion

    --> Ab formation

           / *19S (IgG) Ab가 처음에 증가

           / *나중에 7S(IgG) Ab로 대치됨

                   - 이것이 cross the placenta & cause hemolytic manifestation

; ㉿Why Hemolytic Ds Rarely Occurs During A First Pregnancy in Rh incompitibility ?

    - Rh(+) fetal blood transfusion이 대부분 delivery 시기에 일어나 감작이 되거나 Ab transmit을 할 수가 없다.

    - 55% of Rh positive fathers are heterozygous(D/d)

    - Rh negative offspring

    - 50% of fetal to maternal transfusions

    - variable Ab formation of Rh(-) mother

; ㉿Why Hemolytic Ds Rarely Occurs During A First Pregnancy in ABO incompitibility ?

    - rapid removal by anti-A or anti-B in moter circulation

    - this IgM not cross placenta

; only about *5% ever have babies with hemolytic ds

; prevention

    - anti-D gamma globulin(RhoGAM), immediately following the delivery

Clinical Manifestation

; mild hemolysis to severe anemia

; massive enlargement of the liver and spleen due to compensatory hyperplasia of erythropoietic tissue

; Hydrops fetalis

    - paller, sign of cardiac compensation(cardiomegaly, respiratory distress), massive anasarca, circulatory collapse

    - severity는 level of anemia, degree of reduction in serum albumin와 연관되어 있다.

★Table 89-1

; petechia, purpura, thrombocytopenia

; DIC

; *jaundice는 일반적으로 태어날 때는 없고 생후 첫날 분명해진다

    - 출생때 나타나지 않는 이유는 *placental clearance때문이다. 그러나 심한 경우는 bilirubin pigmentation이 amniotic fluid, cord, vernix에 나타나고, yellow vernix caseosa가 된다.

; ※hypoglycemia due to hyperinsulinism, hypertrophy of the pancreatic islet cell

Laboratory Data

; direct Coombs test - positive

; anemia - hydrops fetalis(3-4g/dl)

; blood smear - polychromasia, nucleated RBC증가

; reticulocyte 증가

; thrombocytopenia in severe case

; the cord bilirubin ; 3-5mg/dl

; After intrauterine transfusion

    - normal Hgb conc.

    - negative direct coomb’s test

    - predominantly type O Rh(-) adult red cells

    - relatively normal smear

    - *marked elevation of both indirect & direct reatcing bilirubin

Diagnosis

; definite diagnosis - blood group incomptibility and corresponding antibody

Antenatal Dx

    ; assay of maternal titer of IgG Ab to D

           - *12-16wk, 28-32wk, 36wk

    ; ♥Suggestive Significant Hemolytic Ds

        - presence of measurable Ab titer at the beginning of pregnancy

               - rapid rise in titer

               - titer of 1:64 or greater

  ; ★Monitoring Of Severity Of Fetal Disease

           - if Ab titer 1:16 or greater during subsequent pregnancy

           - if previously affected infant or a stillbirth

           - ※97 Fetal hydrops monitoring methods

                   1) amniocentesis

                   2) percutaneous umbilical blood sampling(PUBS)

                   3) ultrasonography

# Real time ultrasound

    ; hydrops (skin or scalp edema, pleural or pericardial effusion, ascites)

    ; ★Early ultrasonographic signs of hydrops

           - organomegaly (liver, spleen, heart), double bowel wall sign (bowel edema), placental thickening

           - *pleural effusion이 ascites보다 먼저 오면 다른 원인을 생각해 보아야한다

    ; Extramedullay hematopoiesis

    → hepatic congestion → compress the intrahepatic vessels

    → venous stasis with portal hypertension

    → hepatocellular dysfunction, decreased albumin synthesis

    ; hydrops가 오는 빈도

           - fetal Hb <5 g/dl - invariables

    - < 7 g/dl - frequent

    - 7-9 g/dl - variable

# ♥Amniocentesis

    ; bilirubin is cleared by the placenta, significant proportion enters the amniotic fluid

    ; early as *18-20wks

  ; ★Indication

           - Ab titer > 1:16

           - father Rh(+)

           - ultrasonography상 hemolysis, hydrops, distress소견

    ; Spectrophotometric scanning

           - positive OD deviation at 450nm at normal

           - zone of OD 450이 zone III이면 highest risk

           - *반드시 life-threatening anemia나 intrauterine transfusion을 의미하지는 않는다.

# ♥PUBS Indication

    ; OD 450 in zone III

    ; hydrops

    ; other signs suggesting fetal anemia

Postnatal Diagnosis

; ABO blood group, Rh type, Hb, Hct, direct coombs

Treatment

# the main goal of therapy

    ; to prevent intrauterine or extrauterine death from severe anemia and hypoxia

  ; to avoid neurotoxicity from hyperbilirubinemia

Treatment Of Unborn Infant

    ; umbilical vein transfusion Ix

           - hydrops or fetal anemia *(Hct < 30%)

    - post transfusion Hct ; 45-55%, repeated every 3-5wk

    ; ♥Indication For Delivery

           - pulmonary maturity, fetal distress, complication of PUBS, 35-37wk of gestation

Treatment Of The Live Born Infant

; fresh, low titer, group O, Rh negative blood, cross-matched against the maternal serum

; correction of acidosis, small transfusion of compatible packed red blood cells

; volume expansion for hypotension

Exchange Transfusion

# ㉿Indication Of Early Exchange Transfusion

  ; cord Hb<10g/dl or bilirubin>5mg/dl

    ; previous kernicterus or severe erythroblastosis in sibiling

  ; reticulocyte count >15%

  ; prematurity

# dangerously high levels of serum bilirubin

    ; 6mg/dl in the first 6hr

    ; 10mg/dl in the second 6hr

    ; rates of rise > 0.5 - 1.0 mg/dl/hr

    --> but *unreliable marker

# Monitoring

    ; Hb, Hct, serum bilirubin은 처음에 4-6hr간격으로 monitoring

·blood type O, Rh negative donor with a low titer of anti-A and anti-B and

    should be compatible with the mother's serum by indirect coombs test

  ·transfusion전에 infant stomach을 비워야한다(aspiration 방지)

    body temperature 유지

    vital sign monitor

  ·45-60분 동안 20ml씩 aspiration & infusion

    ; *2 blood volume of the infant(2×85ml/kg)

  ·citrated blood → later metabolic alkalosis

    ; ※93주 Acute Complication (5-10% Infant)

       - transient bradycardia with or without calcium infusion, cyanosis, transient vasospasm, thrombosis, apnea with bradycardia requiring resuscitation, infectious risk(CMV, HIV, hepatitis), NEC

    ; exchange후에 bilirubin 4-8시간마다 check(d/t 몇시간내에 40-50% rebound한다)

※93주 Late Complication

    ; late anemia due to hemolytic or hyporegenerative

           - Tx - supplemental iron, erythropoietin, blood transfusion

    ; mild graft versus host reaction

           - diarrhea, rash, hepatitis, eosinophilia

    ; inspissated bile syndrome

           - hemolytic ds.가 있는 infant에서 direct, indirect bilirubin이 지속적으로 증가해 있는 상태

           - jaundice는 몇 주에서 몇 달내에 저절로 사라진다

    ; portal vein thrombosis

※96객 Prevention Of Rh Sensitization

    ; human anti-D globulin 300ug im within 72hr of delivery or abortion

           - 10ml의 antigenic fetal cell을 제거할 수 있다

         - 29-32주 and again at birth (40주)

                   / 더효과적이다

                   / large fetal-to-maternal transfer에 사용

Hemolytic disease of the newborn due to A & B incompatibility

; mother - type O, infant - type A or B

; ABO incompatibility는 20-25%에서 발생하지만 hemolysis ds는 10%에서만 발생 한다

; *usually the infant are of type A₁

; *prior immunization이 없더라도 발생할 수 있다.

    - due to *univalent imcomplete(albumin active) Ab

           / *7S (IgG) fraction으로 cross placenta

    - cf) natural Ab인 19S (IgM) fraction은 no cross placenta

Clinical Manifestation

; *most mild, only jaundice

    - 일반적으로 태어날 당시에 영향을 받지 않는다

; hydrops fetalis is extremly rare

; jaundice는 생후 24시간 이내에 나타난다

Diagnosis

; direct Coombs test - weakly positive

; spherocyte

 - Hb ; normal or 10-12g/dl

 - reti ; 10-15%

 - polychromasia, nucleated RBC

Treatment

; phototherapy

; ★exchange transfusion with blood of the same group as that of the mother

    - Rh type should match the infants

Other form of Hemolytic ds

 - <5%

 - direct Coombs test ; positive

 - anti-Kell Ab (hemolytic ds or anemia)

   (erythroid suppression → anemia)

 - congenital infection ; cytomegalic inclusion ds, toxoplasmosis, rubella, syphilis

                       hemolytic anemia, jaundice, hepatosplenomegaly,

                       thrombocytopenia

                       direct Coombs test - negative

 - homozygous  -thalassemia ; severe hemolytic anemia resembling hydrops fetalis

                              direct Coombs test - negative

 - hereditary spherocytosis ; anemia, jaundice

89.3 Plethora in the Newborn (polycythemia)

; Hct ≥ 65%

# ※82,87 Increased incidence

    ; high altitude

    ; *postmature

    ; SGA

  ; during first day of life (peak 2-3hr)

  ; in the recipient infant of a twin-twin transfusion

  ; after delayed clamping of the umbilical cord

  ; infants of diabetic mother

    ; 13-, 18-, 21-trisomy

  ; *adrenogenital synd

  ; *neonatal Graves ds.

  ; *hypothyroidism

  ; *Beckwith-wiedemann syndrome

Clinical Manifestation

 - anorexia, lethargy, seizure, cyanosis(PFC), tachypnea, respiratory distress,

    feeding disturbance, NEC, hyperbilirubinemia, renal failure, hypoglycemia,

    thrombocytopenia

Treatment

; phlebotomy & replacement with saline or albumin

; ※91 Partial Exchange Transfusion

  - *Hct to 50%

                                         observed - desired Hct

    volume of exchange(ml) = blood volume × --------------------------

                                             observed Hct

 

Long Term Prognosis

 - speech deficit, abnormal fine motor control, reduced IQ

89.4 Hemorrhage in the Newborn infant

Hemorrhagic Ds Of The Newborn

; ※96 moderate decrease of Factor II, VII, IX, X in all newborn by 48-72hr after birth

    - gradual return by 7-10days

    - ※96 이유

           / *lack of free vitamin K in the mother, absence of bacterial intestinal flora

        / breast milk is a poor source of vitamin K

# Classification

    ; *early onset(birth-24hr)

           - mother treated with Pb, phenytoin

                   / interfere with vitamin K function

    ; late onset (>1wk)

           - vitamin K malabsorption : neonatal hepatitis, biliary atresia

# Clinical Manifestation

    ; *GI, nasal, subgaleal, intracranial, circumcision시에 bleeding

  ; prolonged PT, PTT, CT

# vitamin K facilitate post-transcriptional carboxylation of factor II, VII, IX, X

    ; *이러한 factor가 carboxylation이 않될경우 PIVKA(protein induced in vitamin K absence)를 형성한다

# Prevention

    ; *1mg of natural oil-soluble vitamin K im(phylloquinone) at birth

 

Other Form Of Bleeding

; hematoma, melena, postcircumcision, umbilical cord

  ·factor VIII, IX deficiency의 5-35%만이 newborn period때 나타난다

# ※90 APT test

    ; *fetal Hb - alkali-resistant

  ; adult Hb - changed to alkaline hepatin

Chapter 90. Genitourinary System

Chapter 91. The Umbilicus

Umbilical Cord

 - cord의 구성 ; two umbilical artery, one vein

                 rudimentary allantois, remnant of omphalomesenteric duct

                 gelatinous substance (Wharton jelly)

 - umbilical cord의 sheath는 amnion에서 비롯  다

 - abnormally short cord ; fetal hypotonia

 - long cord ; true knots or wrapping around fetal part

 - straight unwristed cord ; fetal distress, anomaly, intrauterine fetal demise

 - blood vessel ; functionally closed patent anatomically for 10-20 days

 - artery → lateral umbilical ligament,

   vein → ligamentum teres, ductus venosus, ligamentum venosum

# ★delayed separation of the cord (1개월 이상)

    ; neutrophil chemotactic defect

    ; overwhelming bacterial infection

# a single umbilical artery

    ; 5-10/1000 births, 35-70/1000 twin births

  ; 1/3 - congenital anomaly

    ; 18-trisomy

Patent Of The Omphalomesenteric (Vitelline Duct)

   ; intestinal fistula, prolapse of bowel, polyp(cyst), Meckel diverticulum

Persistent Urachus(Urachal Cyst)

; failure of closure of the allantoic duct

Congenital Omphalocele

 - the sac is covered with peritoneum without overlying skin

 - herniation of intestine ; 1/5000

 - herniation of liver and intestine ; 1/10000

 - immediate surgical repair ; before infection, before the tissues have been

                              damaged by drying or by rupture of the sac

 - Beckwith synd ; omphalocele, macrosomia, hypoglycemia

Tumor

 ; angioma, enteroteraroma, dermoid cyst, myxosarcoma, cyst of urachal or

            omphalomesenteric duct remnant

Hemorrhage

 - due to trauma, inadequate ligation of the cord, failure of normal thrombus

    formation hemorrhagic ds. of newborn, septicemia, local infection

Granuloma

; persistence of exuberant granulation tissue at the base of the umbilicus

# Pathogenesis

    ; presence of saprophytic organisms

    --> delays separation of the cord & increase possibility of invasion by pathogenic organisms

    --> mild infection

    --> moist granulating area at base

# Clinical Manifestation

    ; soft, vascular, granular, dull red or pink, *seropurulent secretion

# Treatment

    ; cauterization with silver nitrate

        -repeated at intervals of several days until the base is dry

# DDx

    ; umbilical polyp

           - persistence of all or part of omphalomesenteric duct or of urachus

           - firm and resistent, bright red, mucoid secretion

           - Treatment

                   / surgical excision

Infection

 - hematogenous spread or extension to the liver or peritoneum의 위험성이 있다

 - septicemia 나 hepatitis가 있을지라도 나타나는 현상은 minimal(periumbilical

    erythema)일 수 있다.

 - Tx ; antibacterial therapy,

         if abscess, I&D

Umbilical hernia

 - due to an imperfect closure or weakness of the umbilical ring

 - common especially in low birth weight, female, black infant

 - covered by skin

 - consist of omentum or portions of small intestine

Treatment

    ; mostly apear before 6mo and then disappear spontaneouly by 1yr

대부분은 생후 1세때 저절로 사라진다

           - *large hernia(5-6cm)인 경우 5-6세때 저절로 사라진다

  ·strapping is ineffective, surgery is not advised

    ; ※♥84 Surgical Indication

           - persist to age of 3-4yr

           - symptoms as strangulation

    - larger after age of 1-2yr

    ; *2cm 이상의 defect가 있을 경우 저절로 닫힐 가능성이 적다.

Chapter 92. Methbolic Disturbances

Hyperthermia In The Newborn

   (transitory fever of the newborn, dehydration fever)

 - 38-39℃, 2nd - 3rd day of life

 - breast-fed infant, high environmental temperature

 - the rise in temperature may be associated with an increase in serum protein,

    sodium and hematocrit

 - more severe form of neonatal hyperthermia

  ·diminished sweating capacity

  ·41-44℃

  ·the skin is hot & dry, flushed & apathetic, stupor, grayish pallor, coma,

     convulsion, hypernatremia, convulsion

Neonatal cold injury

Clinical Manifestation

    ; *apathy, refusal of food, oliguria, coldness to touch

  ; BT ; 29.5 - 35

  ; immobility, edema, redness of the extremity

  ; bradycardia & apnea

  ; rhinitis

         - common

           - as are serious metabolic disturbance

                   / *hypogycemia, acidosis

  ; hemorrhagic manifestation(massive pulmonary hemorrhage)

Treatment

    ; warming, correcting hypotension, metabolic imbalance

  ; *mortality rate 25%

  ; *생존자의 10% brain damage

Edema

 - generalized edema ; hydrops fetalis, offspring of diabetic mother

 - in premature ; decreased ability to excrete water or sodium

 - HMD infant에서 CHF없이 edema 관찰될 수 있다

 - face & scalp edema ; umbilical cord에 의해 neck이 눌렸을때

 - hand or feet edema ; intrauterine pressure

 - heart failure

 - high-protein formula ; excessive solute load에 의해서 edema발생

 - anemia, vit E deficiency일 때도

 - idiopathic hypoproteinemia ; 몇 주에서 몇 달 지속되는데 원인은 불분명하고 benign

                               하다

# persistent edema of one or more extremities

    ; congenital lymphedema(Milroy ds.) in female, Turner synd

# general edema with hypoproteinemia

    ; congenital nephrosis, Hurler synd.

      after feeding hypoallergenic formulas to infant with cystic fibrosis of the

       pancreas

Hypocalcemia(=Tetany)

 - osteopenia of prematurity

 - very small premature infants with chronic illness

 - rickets-like synd. (pathologic fracture, demineralized bone)

 - cholestasis, vit D or calcium malabsorption

   urine Ca loss, poor calcium, phosphorus vit D intake

Hypomagnesemia

; unknown etiology but usually in association with hypocalcemia

; ★Asso. Condition

    - insufficient stores of skeletal Mg secondary to deficient placental transfer

    - decreased intestinal absorption

  - neonatal hypoparathyroidism

  - hyperphosphatemia

  - renal loss

  - defect in Mg & Ca homeostasis

  - iatrogenic

           / *exchange transfusion, TPN

  - *DM mother

Clinical Manifestation

; indistinguishable from hypocalcemia & tetany

; < 1.5mg/dl

    - *but clinical sign은 1.2mg/dl이하일 경우에 대부분 발생한다.

Treatment

; *MgSO₄ IM

  - *newborn 0.25ml/kg of 50% solution daily

    - hypomagnesemia가 교정될 때 hypocalcemia도 교정된다.

; oral maintenence therapy

; 1-2주후 d/c

Hypermagnesemia

Etiology

    ; eclampsia mother에서 MgSO₄로 치료받았을 경우에 발생한다.

Clinical Manifestation

  ; CNS depression, totally paralyzed

  ; hypoventilation, hypotension, lethargy, flaccidity, hyporeflexia

  ; normal의 upper limit ; 2.8mg/dl

  ; serious symptom ; >5mg/dl

  ; failure to pass meconium(Meconium plug synd)

Treatment

    ; exchange transfusion

    ; calcium salt & diruresis

Substance Abuse And Withdrawals

 - opiates cross placenta

 - heroin, methadone, alcohol, Pb, pentazocine, codeine, propoxyphene, diazepam ;

    withdrawal symptom

Heroin Addiction

; 50%에서 low birth weight infant

    - 1/2은 SGA

; the rate of still births is increased, but *not the incidence of congenital anomalies

Clinical Manifestation

; 50-75% 48시간이내에 나타남

; *tremor & hyperirritability

    - *▲prominent symptoms

    - *Tremor : hypoglycemia에 의한 경우에 구별이 힘들다. 그러나 more coarse, flapping, bilateral 로 구분이 가능하다.

; other symptoms

    - tachypnea, diarrhea, vomiting, high pitched cry, fist sucking, poor feeding, fever

    - less commonly sneezing, yawning, myoclonic jerks, convulsions, abnormal sleep cycles, nasal stuffiness, flushing alternating rapidly with pallor, lacrimation

; ※객 HMD, hyperbilirubinemia의 incidence는 감소함

  - HMD감소하는 이유

           / hyperventilation --> production of surfactant

  - hyperbilirubinemia 감소하는 이유

           / induction of glucuronyl transferase

Methadone Addiction

  ·severe withdrawal symptom

  ·20-90%

  ·no increased incidence of congenital anomaly

  ·clinical manifestation ; higher incidence of seizure(10-20%)

                          late onset (2-6wk of age) of symptom & sign

Alcohol Withdrawal

  ·uncommon

  ·hypogycemia, acidosis, seizure

Phenobarbital Withdrawal

  ·symptom ; 7일후에 시작

  ·acute stage ; irritability, constant crying, sleeplessness, hiccups, mouthing

                  movement

  ·subacute stage(2-4개월간) ; voracious appetite, frequent regurgitation &

                               gagging, episodic  irritability, hyperacusis,

                               sweating, disturbed sleep

Cocaine Addiction

  ·premature labor, abruptio placenta, fetal asphyxia

  ·IUGR, microcephaly, ICH, possible anomaly of the GI & renal tract

  ·SIDS

  ·rigidity, impaired state regulation, developmental delay, learning disability

Treatment

; indication

    - seizure, diarrhea, irritability, poor weight gain

  - Treatment of heroin & methadone with drawals has been successful using

     various combination of narcotics, sedative, hypnotics

; *Pb 8-10mg/kg/24hr in 4 divided dose

- chlorpromazine, 2.2mg/kg/24hr, 3-4 dose

  - Patients with severe autonomic symptom may require gradually diminishing

     doses of methadone or paregoric for 2-10wk

  - narcotic & Pb withdrawal requires swaddling frequent feedings, and protection

     from noxious external stimuli

Fetal Alcohol Syndrome

; moderate & high alcohol intake during pregnancy

    --> damage to embryonic and fetal fetal development

    --> specific malformation

# ※90주 Characteristics

    ; prenatal onset and persistence of growth deficiency for length, weight, head circumference

    ; facial abnormality

           - short palpebral fissure, epicanthal folds, maxillary hypoplasia, micrognathia, thin upper lip

    ; cardiac defects, primary septal defect

    ; minor joint and limb abnormality

           - some restriction of movement and altered palmar crease patterns

  ; delayed development and mental deficiency

           - from borderline to severe

# common cause of mental retardation

# alcohol may impair placental transfer of essential aminoacid & zinc

Late Metabolic Acidosis

; 5-10% of preterm low birthweight infant

; *acidosis during the 2nd or 3rd wk of life

; *no history of asphyxia, respiratory distress or other problem

Etiology

    ; cow's milk formulas of high protein and casein content shortly after birth

  ; abnormally high rate of endogenous acid formation

Treatment

    ; NaHCO3

    ; formula of lower protein content with a whey ; casein ratio of 60:40

Chaper 93. The Endocrine System

Pituitary Dwarfism

; not apparent at birth

; panhypopituitary male infant

    - neonatal hypogycemia, micropenis

Thyroid Deficiency

; apparent at birth

; constipation, prolonged jaundice, lethargy, poor peripheral circulation(mottled skin)

Temporary Hyperthyroidism

; occur at birth

; mother with hyperthyroidism receiving thyroid medication

Transient Hypoparathyroidism

; tetany of the newborn

Adrenal Gland

; acute adrenal hemorrhage & failure (breech or other traumatic delivery)

; adrenocortical hyperplasia (vomiting, diarrhea, dehydration, hyperkalemia, hyponatremia, shock, clitoral enlargement)

Congenitally Hypoplastic Adrenal Gland

; adrenal insufficiency during the first few weeks of life

Transient Diabetes Mellitus

; rare, seen only in the newborn

; dehydration, loss of weight, acidosis in SGA

93.1 Infant Of Diabetic Mother

# ※92 morphologic characteristics(large size , macrosomia) & high mobidity risk

# mother

    ; *polyhydramnios, pre-eclampsia, pyelonephritis, preterm labor, chronic hypertension

# fetal mortality rate

    ; *greater than 32wks

# *산모에게 vascular ds가 합병되었을 때는 low birth weight infant가 태어난다

# mortality rate ; 5배

Pathophysiology

# fetal hyperglycemia, fetal hyperinsulinemia

  → hepatic glucose uptake & glycogen synthesis ↑

  → lipogenesis, protein synthesis ↑

# hypertropy and hyperplasia of the pancreatic islet

# increased weights of the placenta and infant organs except brain

  ; myocardial hypertropy, increased amount of cytoplasm in liver cell, extramedullary hematopoiesis

# hyperinsulinism → fetal acidosis → still birth

# ♥Cause Of Hypoglycemia

    1) 태어나면서 placenta가 분리되면 glucose infusion이 갑자기 중단된다. 그러나 태아에게는 hyperinsulinism이 아직 존재하고 있는 상태이므로 hypoglycemia가 발생한다

    2) diminished epinephrine & glucagon → hypoglycemia

# congenital anomaly ; hyperglycemia-induced teratogenesis

Clinical Manifestation

; large & plump

 - result of increased body fat, enlarged viscera with puffy, plethoric face

; *생후 3일 동안은 jumpy, tremulous, hyperexcitable

    - hypotonia, lethargy, poor sucking이 올 수도 있다

; early hypoglycemia, later hypocalcemia

; hypoglycemia

    - *diabetic mother의 75%

  - *gestational diabetes의 25%

    - 이들중 small percentage만 symptomatic

    - *1-3hr에 blood glucose level이 최저, 4-6hr후부터 spontaneous recovery

; ♥Tachypnea During The First 5 Days Of Life

    - due to hypoglycemia, hypothermia, polycythemia, cardiac failure, transient tachynea, cerebral edema from birth trauma or asphyxia

; *RDS ↑

    - *due to antagonistic effect of cortisol, insulin against synthesis of surfactant

; cardiomegaly(30%), heart failure(5-10%), asymmetric septal hypertropy

; neurologic development & ossification center

    -immature

; increased incidence of hyperbilirubinemia, polycythemia, renal vein thrombosis

; ※Congenital Anomaly - 3배

  - cardiac malformation

           / VSD, ASD, COA, transposition of great vessel

  - lumbosacral agenesis

  - neural tube defect

    - hydronephrosis, renal agenesis

    - duodenal, anorectal atresis

    - holoprosencephaly

    - small left colon syndrome

    - *cardiac malformation과 lumbosacral agenesis가 가장 흔함

Prognosis

; the subsequent incidence of DM in infant is increased

Treatment

# asymptomatic infant

    ; blood sugar를 생후 1시간 이내에 check하여 6-8hr 동안 매시간마다 check한다

# if clinically well & normoglycemic

    ; 5% glucose의 oral feeding → breast milk or formula

    ; 생후 2-3시간에 시작, 3시간 interval로 계속함

# *bolus injection of hypertonic glucose should be avoided

    ; because they may cause further hyperinsulinemia → rebound hypoglycemia

93.2 Hypoglycemia

; early feeding

    - incidence를 감소시킨다

# ※89 Increased Incidence

    - prematurity, hypothermia, hypoxia, maternal diabetes, maternal glucose infusion in labor, IUGR

# ★Glucose Level In Healthy Term Infant

    - decline after birth untill 1-3hr

    - rarely less than *35 mg/dl between 1-3hr

    - rarely less than *40mg/dl between 3-24hr

    - rarely less than *45mg/dl after 24hr

# ㉿89,96 Four Pathophysiologic Group At High Risk Of Developing Hypoglycemia

    *1) Hyperinsulinism Group

           ; mother DM, gestational DM, severe erythroblastosis fetalis, insulinoma, β cell nesiodioblastosis, functional β cell hyperplasia, mutation in sulfonylurea receptor gene, *Beckwith syndrome, panhypopituitarism

    *2) Intrauterine Malnutrition Group

           ; resulting in reduced hepatic glycogen store & total body fat(IUGR, preterm)

           ; smaller of discordant twin, polycythemic infant, toxemic mother placenta abnromality

           ; other factors

                   - impaired gluconeogenesis, diminished free fatty acid oxidtion, low cortisol production rates, increased insulin level & decreased output of epinephrine in response to hypoglycemia

    *3) Very Immature or Severely Ill Infant Group

           ; increased metabolic need

           ; low birth weight infant with RDS, perinatal aspyxia, *polycythemia, hypothermia, systemic infection, heart failure with cyanotic congenital heart disease

    *4) Genetic or Primary Metabolic Defect Group

           ; galactosemia, glycogen storage ds., fructose intolerence, propionic acidemia, methylmalonic acidemia, tyrosinemia, maple syrup urine ds, long or medium-chain acyl-CoA dehydrogenase deficiency

Clinical Manifestation

; symptomatic hypoglycemia - SGA에서 highest incidence

★Fig. 93-2

; symptom의 대부분은 다른 condition과 함께 나타난다

  - infection, CNS anomaly, hemorrhage, edema, hypocalcemia, hypomagnesemia, asphyxia, drug withdrawal, apnea of prematurity, CHD, polycythemia

; ※87 Order Of Frequency

    - jitteriness or tremor, apathy, episodes of cyanosis, convulsion, intermittent apneic spell or tachypnea, weak or high pitched cry, limpness or lethargy, difficulty in feeding, eye rolling

; episodes of sweating, sudden pallor, hypothermia, cardiac arrest

※91 Treatment

; convulsion이 없는 경우

    - 10% glucose 200mg/kg(2ml/kg)

; convulsion이 있는 경우

    - 4ml/kg of 10% glucose

# Following therapy after initial therapy

    ; *glucose infusion - 8mg/kg/min

# ※87 20% glucose을 줘도 반응하지 않거나 유지되지 않는 경우

    ; *hydrocortisone 2.5mg/kg/6hr

    ; *prednisone 1mg/kg/24hr

# ★Steroid을 써도 반응하지 않는 경우

    ; diazoxide or long-acting somatostatine

# Monitoring

    ; initial therapy 후 serum glucose를 2시간마다 check하여 40mg/dl이상이 되게 한다

    ; 이후로는 4-6시간마다

    ; *high risk infant의 경우

           - 출생 1시간이내에 serum glucose

           - *처음 6-8시간까지는 2시간 간격

           - 24시간까지는 4-6시간 간격

# nesioblastosis & islet cell adenoma

    ; surgery

    ; glucagon + somatostatin

# intravenous infusion of glucose at 4mg/kg/min should be provided if oral feeding are poorly tolerated or if asymptomatic transient neonatal hypoglycemia develops.

Prognosis

; recur in 10-15%

Hypoglycemia With Macroglossia(Beckwith Synd)

; intractable neonatal hypoglycemia, macroglossia, large size, visceromegaly(liver, kidney), mild microcephaly, omphalocele, facial nevus flammeus, charicteristic earlobe crease

; increased risk of tumor( Wilm's tumor, hepatoblastoma, gonadoblastoma) and renal medullary dysplasia

; polycythemic, hyperinsulinemia

; partial duplication of chromosome IIp (insulin like growth factor II gene)

; prognosis is poor