Neonatology
复旦大学儿科医院 曹 云
1,General Considerations
2,Respiratory Disorders
3,Jaundice and Hemolytic Disease
4,Neurological Disorders and
Infection
Neonatal Period 新生儿期
Neonate,Newborn 新生儿
Neonatology 新生儿学
Perinatal Period 围产期
Perinatal Infant 围产儿
Perinatology 围产医学
Perinatal Medicine
Classification
1,By gestational age (GA ) 胎龄
full-term infant,mature baby
37 weeks? GA ?42 weeks
pre-term infant,premature (immature) baby
GA < 37 weeks
extremely immature infant
22 weeks? GA ?28 weeks
post-term infant 过期产儿
GA ? 42 weeks
2,By birth weight (BW)
Normal birth weight 2500-3999 g
Low birth weight (LBW) < 2500 g
? Very low birth weight (VLBW) <1500 g
极低出生体重儿
? Extremely low birth weight (ELBW) < 1000 g
超低出生体重儿
Giant infant ? 4000 g 巨大儿
3.By gestational age and birth weight
Small for gestational age (SGA) 小于胎龄儿
BW < the 10th percentiles
Appropriate for gestational age (AGA) 适于胎龄儿
the 10th percentiles <BW< the 90th percentiles
Large for gestational age (LGA) 大于胎龄儿
BW > the 90th percentiles
Intrauterine Growth Curve
500
750
24 26 28 30 32 34 36 38 40 42 44 46 48 （ 周）
1000
1250
1500
1750
2000
2250
2750
3000
3500
3750
2500
4000
4250
4500
4750
5000
3250
小于胎龄
第 10 百分位
适于胎龄
平均体重
大于胎龄
第 90 百分位
3.By gestational age and birth weight
Small for gestational age (SGA) 小于胎龄儿
BW < the 10th percentiles
Appropriate for gestational age (AGA) 适于胎龄儿
the 10th percentiles <BW< the 90th percentiles
Large for gestational age (LGA) 大于胎龄儿
BW > the 90th percentiles
4,By postnatal age
? Early newborn infant,in the first one
of age
? Late newborn infant,between 2 and 4
weeks of age
5,High risk newborn 高危新生儿
Normal Newborn Infant
1,Physical appearance
2.Respiratory
? Onset of respiration
? Pulmonary Surfactant
? Respiratory Rate (RR)
40-50/min
? Abdominal respiration
3.Cardiovascular System
? Cessation of fetal
circulation
? Decrease of pulmonary
pressure
? Close of foramen ovale
and ductus arteriosus
? Variation of heart rate
Fetal circulation to
neonatal circulation
4,Gastrointestinal system
? Immature gastrointestinal function
Gastroesophageal Reflux (GER)
胃食道返流
? Pass meconium 胎粪
5,Renal
? Void within 48 hours of life
? Immature function
6,Hematological system
? Blood volume 85ml/kg
? High red blood cell with high fetal
hemoglobin (70-80%)
? Low activity of Clotting factors
? Physiologic anemia
7,Neurological system
? Neonatal reflexes:
Sucking reflex,Rooting reflex,
Moro reflex,Palmar grasp
? Anterior fontanelle (前囟 )
8,Immunology
? Immature
? Transplacental IgG
? IgM
? IgA,high level in breast milk
9,Temperature control
? Heat production
by brown fat
? Heat loss
large body surface area
little subcutaneous fat
special position
Neutral temperature
Environmental temperature
newborn,33－ 35oC
adult,25－ 26oC
11,Special physical conditions
Physical jaundice
Blood-tinged discharge from the vagina
Abnormally enlarge breast
10,Fluid,electrolyte and nutrition
Physical weight loss
Care of Normal Newborn Infant
? Level I
? Level II
? Level III
Special Care Nursery (SCN)
Neonatal Intensive Care Unit (NICU)
Care of Normal Newborn Infant (Contd.)
? Environment,temperature 22－ 26oC
? humidity 40－ 50 ％
? Infection control,sterilization and wash
? Keep warm,incubation and radiant
? Skin care,bath
? Care of umbilicus
Neonatal Intensive Care Unit (NICU)
Special Care Nursery
SCN
Hand washing
Care of Normal Newborn (Contd.)
6,Feeding,breast milk and formula
7,Vaccination,BCG,Hepatitis B
8,Neonatal screening：
PKU,hypothyroidism,galactosemia,
hearing
Preterm infant
1,Physical appearance
Skin,lanugo,plantar surface,
breast size
2,Respiratory system
? Immature
? Irregular breath
? Apnea of prematurity
? Respiratory distress syndrome
(RDS)
3,Gastrointestinal system
? Vomiting and aspiration
? Gastroesphageal reflux (GER)
胃食道返流
? Feeding intolerance
? NEC
? Jaundice
4,Neurological system
? Relate to the gestational age
? Weak reflex and low muscle tone
? Intraventricular hemorrhage (IVH) and
periventricular leukomalacia (PVL)
5,Temperature control
? Immature center
? Less heat production
? Large heat loss
6,Cardiovascular system
? PDA
7,Others
? Metabolic disorders
? Vitamin deficiency
? Anemia of prematurity
Problems of preterm infant
? Temperature
? Hypoglycemia
? Cardiovascular
disorders
? Respiratory disorders
? Fluid and electrolyte
? Renal disorders
? Hemelogical disorders
? Infection
? Gastrointestinal
disorders
? Jaundice
? Neurological disorders
? ROP
? Feeding problems
? Hearing and visual
problems
? Temperature
? Respiration
? Feeding
? Jaundice
? Infection
……
Care of Preterm Infant
1,Environment,cleaning,sterile,hand-washing
2,Feeding,Breast milk or preterm formula，
careful feeding,nasogastric feeding
3,Temperature control,incubator
4,Monitoring,respiration,acid-base balance、
blood sugar,infection,bilirubin,blood pressure、
renal function
5,Developmental supportive care of preterm
Postnatal infant
SGA
Giant
Infant
? Premature birth
? Birth asphyxia
? Neurological disorders
? Twin-twin transfusion
? Congenital annomalie
Twins
Neonatal Transport
Follow-up of high-risk infants
Respiratory Disorders
? Neonatal Respiratory Distress Syndrome
(NRDS)
新生儿呼吸窘迫综合症
Hyaline Membrane Disease (HMD)
肺透明膜病
?Neonatal Pneumonias
新生儿肺炎
? Meconium Aspiration Syndrome (MAS)
胎粪吸入综合症
? Asphyxia 窒息
? Transient Tachypnea of Newborn (TTN)
Wet Lung 湿肺
? Apnea 呼吸暂停
? Chronic Lung Disease (CLD)
慢性肺部疾病
Bronchopulmonary Dysplasia (BPD)
支气管肺发育不良
Case
???,GA 29W,prolonged rupture
of membranes (胎膜早破 )
Fetal heart monitoring is normal
Management,terminate pregnancy？
or continue pregnancy？
? Hyaline Membrane Disease
HMD
肺透明膜病
? Neonatal Respiratory Distress
Syndrome (NRDS)
新生儿呼吸窘迫综合症
Pulmonary Surfactant （ PS）
肺表面活性物质
? Synthesized by alveolar type II epithelial cells
? Function
1,To stabilize the lung during deflation
by reducing the surface tension
2,To prevent high surface tension
pulmonary
3,To provide a defense against infection
? Increases with advancing gestational age
1,Etiologies
Deficiency of surfactant
? Preterm
? Infants of diabetic mothers (IDM)
? Perinatal asphyxia
? Elective cesarean section (剖宫产 )
? Severe Rh hemolytic disease
? Genetic factors
2.Pathophysiology
lack of surfactant
atelectasis
Dysfunction of V/Q mismatch
Type II cells Hyaline membrane
PaCO2?,PaO2?
Poor perfusion endothelial injury mixed acidosis
pulmonary vasoconstriction
Pulmonary hypertension
3,Pathology
Hyaline Membrane Atelectasis
肺不张
4,Clinical Presentation
Preterm
Onset within 6 hours of age
Progressively severe
? Tachypnea 呼吸增快
? Retraction 吸气凹陷
? Grunting 呻吟
? Cyanosis 青紫
? Apnea 呼吸暂停
? Patent ductus arteriosus PDA
动脉导管开放
? Respiratory failure
? 新生儿持续肺动脉高压
Persistent Pulmonary Hypertension
of Newborn (PPHN)
5,Chest radiographs
Opacity
Diffuse reticular-granular infiltrates
Bronchograms (支气管充气征 )
Atelectasis
“white-out” (白肺 )
Grade I,II,III and IV
NRDS
Opacity
Diffuse reticular-granular infiltrates
,white out” Grade IV
6,Diagnosis and Differential Diagnosis
? Clinical features
? Chest radiographs,X-ray
? Differentiate with infectious pneumonia,
wet lung and aspiration pneumonia
7,Management
(1) Surfactant replacement
Timing,Prophylactic or rescue
Dosage,100－ 200 mg / kg/dose
Interval,Q10－ 12 h ? 2 or 3 times
Administration:
endotracheal tube (ETT)
Surfactant
administration
by ETT
(2)Continuous Positive Airway Pressure
CPAP
持续气道正压通气
(3)Mechanical ventilation
Mode：
IMV＋ PEEP
Setting：
FiO2,PIP,PEEP,I:T,RR
PS treatment
(4) Management of PPHN,inhaled nitric oxide
(5) Closure of PDA
(6) Supportive therapy
Temperature,acidosis,circulation，
fluids and nutrition,possible infection
8,Prevention
(1) Antenatal corticosteroids：
Dexamethasone or betamethasone
(2) After birth,surfactant
GA<30weeks,BW<1500g
Neonatal Pneumonia
Classification：
1,Aspiration pneumonia,Amniotic-fluid,
meconium or milk
2,Infectious pneumonia,prenatal,intrapartum
or post-natal infection
Meconium Aspiration Syndrome
MAS
胎粪吸入综合症
1,Causes
? Full-term and post-term infant
? Intrauterine asphyxia (窒息 )
? Birth Asphyxia
2,Pathogenesis
(1) Airway obstruction,air-trapping and
Air leak (pneumothorax 气胸 ),atelectasis
(2) Inflammatory and chemical pneumonia
(3) Inactivation of PS
3,Pathogenesis (Contd.)
(4) Acute respiratory distress syndrome
(ARDS)
(5) Persistent pulmonary hypertension
of Newborn (PPHN)
4,Clinical Presentation
? Signs of post-term
? Respiratory distress,tachypnea (呼吸增快 ),
nasal flaring (鼻煽 ),intercostal retractions (肋
间隙凹陷 )
? Cyanosis
? Increase in the anterior-posterior diameter of
the chest
? Air leak
? PPHN
? Respiratory failure
5,Chest radiographs
? Hyperinflation of the lung field
? Coarse,irregular patchy infiltrates
? Pneumothorax or pneumomediastinum
气胸或纵隔积气
MAS
Irregular patchy
infiltrates
MAS
Pneumothorax
Pneumomediastinum
6,Management
1,Clear airway,most important
2,Oxygen therapy
3,Mechanical ventilation：
conventional of high frequency ventilation
4,Surfactant
5,Management of PPHN,inhaled nitric oxide (NO)
6,Others,Pneumothorax,hypotention,acidosis
Apnea
呼吸暂停
Absence of breathing for > 20 seconds
cyanosis
Bradycardia 心率减慢
heart rate <100 beats/min
慢性肺部疾病
Chronic Lung Disease (CLD)
支气管肺发育不良
Bronchopulmonary Dysplasia (BPD)
湿肺
Wet Lung
Transient Tachypnea of Newborn (TTN)
Neonatal
Hyperbilirubinemia
新生儿高胆红素血症
Bilirubin (胆红素 )
Jaundice (黄疸 )
Hyperbilirubinaemia (高胆红素血症 )
Unconjugated (indirect) bilirubin (未结合胆红素 )
Conjugated (direct) bilirubin (结合胆红素 )
Free bilirubin (游离胆红素 )
Glucuronyl transferase
葡萄糖醛酸转移酶
?-glucuronidase
?-葡萄糖醛酸苷酶
Enterohepatic Circulation
肠肝循环
Neonatal bilirubin metabolism
? Increased bilirubin load on liver cell
1,Increased RBC volume
2,Decreased RBC survival
3,Increased early-labeled bilirubin
4,Increased enterohepatic circulation of
bilirubin
Neonatal bilirubin metabolism
(Contd.)
? Defective hepatic uptake of bilirubin
from plasma
1,Decreased ligandin (Y and Z protein)
2,Binding of ligandin by other anions
Neonatal bilirubin metabolism
(Contd.)
? Defective bilirubin conjugation
1,Decreased uridine diphosphate
glucuronyl transferase (UDPG-T) activity
2,Increased uridine diphosphoglucose
dehydrogenenase (?-glucuronidase) activity
? Decreased excretion of bilirubin
Neonatal bilirubin metabolism
(Contd.)
? Increased bilirubin production
? Decreased clearance of bilirubin
Summary
Physical Jaundice
? Onset of jaundice,2-3 days of age
? The time of peak level,4-6 days of age
? The resolving time
Full term,2 weeks of age
Preterm,3-4 weeks of age
? Level of total serum bilirubin,<12mg/dL
? Level of conjugated bilirubin,<1.5mg/dL
Nonphysiological Jaundice
? Onset of jaundice before 24 hours of age
? Any elevation of serum bilirubin that
requires phototherapy
? A rise of serum bilirubin levels of over
5mg/dL/day
? Signs of underlying illness
? Persist jaundice
Causes and Clinical Features
? Unconjugated hyperbilirubinemia
1,Fetomaternal blood group
incompatibility
2,Infection
3,Breast jaundice
4,Delayed meconium passage
5,Others,asphyxia,hemorrhage,
polycythemia (红细胞增多症 )
Causes and Clinical Features
? Conjugated Hyperbilirubinemia
1,Hepatitis
2,Obstructive disorders
3,Metabolic and endocrine condition
4,Cholestasis (胆汁淤积 )
Breastfeeding and Jaundice
母乳性黄疸
? Breast-milk jaundice
1,Late onset by day 5-7 of life
2,Rise to peak level by 2 weeks of age
3,Bilirubin fall rapidly if stop breastfeeding
4,Rule out pathological condition
5,Mechanism is unknown
Breastfeeding and Jaundice
? Breastfeeding jaundice
1,Early onset
2,High bilirubin levels after 3 days of life
3,Related to a decreased intake of milk
Bilirubin Encephalopathy
胆红素脑病
? Kernicterus (核黄疸 )
? Cellular toxicity of bilirubin
? Blood-Brain Barrier permeability
Hemolytic disease of the newborn
新生儿溶血病
Rh incompatibility
ABO incompatibility
Onset in fetal and neonatal period
Rhesus Hemolytic Disease
Rh 溶血病
Rh blood group
Rh-positive,D antigen,DD or Dd
Rh negative,dd
一,Pathogenesis
Mother RhD (－ ),Fetus RhD(＋ )
fetal RBC maternal
circulation
IgM
Second pregnancy placenta IgG
Primary
Sensitized fetal RBC Sensitized RBC bind to the Fc receptor
Hemolysis
First pregnancy
Mother,Rh D (－ ) neonate,Rh D (＋ )
Rh E (－ ) Rh E (＋ )
Rh C (－ ) Rh C (＋ )
May occur in neonate whose mother is
Rh-positive
二,Clinical Manifestations
1,Fetal hydrops (胎儿水肿 )
2,Jaundice,early onset,rise rapidly
and severe
3,Anemia
4,Hepatosplenomegaly (肝脾肿大 )
5,Bilirubin encephalopathy
三,Diagnosis
1,Clinical features
2,Laboratory findings
(1) Blood group of mother and infant
(2) Coombs’ test (抗人球蛋白试验 )
Direct Coombs’ test,identify sensitized RBC
ABO Hemolytic Disease
Mother,type O
Fetus,type A or B,O型 胎儿,
A或 B型
最多见的新生儿溶血病
一,Pathogenesis
A,B
substances
Enter
maternal
circulation
AntiA,AntiB
antibody IgG
Pregancy
placentafetausSensitize red
blood cells
Hemolysis
二,Clinical feature
Jaundice,anemia and Hepatosplenomegaly
三,Diagnosis
1,Blood group
2,Coombs’ Test
Direct Coombs’ test
Elution test
Management
1,Phototherapy (光疗 )
(1) Indication,full-term> 15 mg /dl
(2) Light,blue lamps,wavelength 450～
460nm
(3) Mechanism,photochemical reaction
Structural isomerization
(4) Technique,single or double phototherapy
Phototherapy
2,Decreasing free bilirubin
Albumin,plasma
3,Inhibiting bilirubin production
competitive inhibitors of heme oxygenase
(血红素加氧酶 )
4.Increasing bilirubin conjugation
Phenobarbital
5.Inhibiting hemolysis
High-dose intravenous immune globulin (IVIG)
静脉丙种球蛋白
6.Exchange transfusion (交换输血 )
(1) Indication
In Rh hemolytic disease,total
bilirubin>20mg/dl
(2) Mechanisms
Remove antibodies,antibody-coated RBCs
(sensitized red blood cells) and bilirubin，
correct anemia
(3) Blood
Rh hemolytic disease:Rh cross-matched against the
mother,ABO cross-matched against the infant
ABO hemolytic disease,type O cells with AB plasma
(4) Volume
Double the volume of the infant’s blood (two-volume
exchange),160ml/kg
(5) Complications
Hypocalcemia,hypoglycemia,Acid-base balance,
hyperkalemia,embolization,bleeding,infections
Neonatal
Neurological Disease
Children’s Hospital of
Fudan University
CAO YUN
Neonatal Hypoxic-Ischemic
Encephalopathy
新生儿缺氧缺血性脑病
Neonatal Intracerebral
Hemorrhage
新生儿颅内出血
Sequela(后遗症 ),cerebral palsy(脑瘫 )、
mental retardation,visual deficit
Hypoxic-Ischemic Encephalopathy,HIE
Hypoxic-Ischemic Brain Damage,HIBD
Hypoxia
Perinatal asphyxia,apnea,respiratory failure,
right to left shunt
Ischemia
Heart failure,Shock
Causes
Onset of HIE
Timing of Insults Percentage
Antepartum 20
Intrapartum 35
Antepartum ? antepartum 35
Postnatal 10
1,Cerebral hemodynamic alteration：
Initial changes,redistribution of
circulation (diving reflex) ? cerebral
blood flow↑
Continue insult,loss of vascular
autoregulation,systemic hypotension,
cerebral blood flow↓, cerebral ischemia
Pathogenesis
Pathogenesis (Cont’s)
2.Effects of Hypoxic-Ischemic Insults
on Energy Metabolism
(1) Brain glucose ?
(2) Lactate production ?
(3) ATP ?
(4) Energy failure
(5) Neuronal death
Pathogenesis (Cont’s)
3,Role of Free Radicals (自由基 )
(1) Perioxidation (过氧化 ) of membrane
phospholipids
(2) Damage to DNA
(3) Activation of proapoptotic (促凋亡 ) genes
Pathogenesis (Cont’s)
4,Calcium Reflux
(1) Activate phospholipases (磷脂酶 )
(2) Activate proteases (蛋白酶 )
(3) Activate nucleases (核酸酶 )
(4) ? neurotransmitter release
(5) Activate nitric oxide synthetases
(一氧化氮合成酶 )
Pathogenesis (Cont’s)
5,Neurotoxicity of Excitatory Amino
Acids (兴奋性氨基酸 )
(1) Na+ entry with H2O cell swelling
and lysis
(2) Ca+ entry Ca+-mediated events to
cell death
Pathogenesis (Cont’s)
6,Delayed Cell Death (迟发性神经元死亡 )
(1) Cell death,Necrosis (坏死 ) and Apoptosis
(凋亡 )
(2) Necrosis occurs in minutes
(3) Apoptosis,delayed cell death occurs over
hours or days or months
Neuropathology
1,Selective neuronal necrosis
选择性神经细胞坏死
2,Parasagittal cerebral injury
矢状旁区损伤
3,Periventricular leukomalacia
脑室周围白质软化
4,Periventricular-intraventricular hemorrhage
脑室周围 -脑室内出血
5,Focal ischemic brain necrosis
局灶缺血性脑坏死
Clinical Aspects
1,Level of consciousness
Hyperalertness (兴奋 ),irritability (激惹 ),
lethargy(嗜睡 ),stupor or coma
2,Brain stem disfunction
Respiratory disturbance,abnormal pupillary
response to light
3,Seizure (Jitteriness 抖动 )
4,Muscle tone
Hypertonia,weakness,hypotonia
5,Primitive reflex
Hyperactive,depress,absence
Severity of HIE in Full-term Neonate
Mild Moderate severe
Level of Hyperalertness Lethargy Coma
consciousness
Seizure -,Jitteriness Variable +
Primitive reflexes Exaggerated Suppressed Absent
Brain stem _ _ +
dysfunction
Muscle tone Hypertonia Weakness Floppy
Normal
Diagnosis
? History of hypoxia or ischemia
? Clinical features
? Neuroimaging
? Electrodiagnostic techniques
? Neuronal biochemistry
Neuroimaging
? Cranial Ultrasound
(头颅超声 )
1,Diffuse increased
echogenicity of
parenchyma
2,Effacement of cortical
sulci
3,Increased
periventricular echoes
Neuroimaging
? Computed Tomography (CT)
1 Focal or generalized low tissue attenuation
(低密度 )
2 Focal or generalized cerebral atrophy
3 Multicystic encephalomelacia (多囊脑软化 )
4 Limited value for early assessment in
preterm neonate
Neuroimaging
? Magnetic Resonance Imaging (MRI)
1 Demonstrate specific patterns of injury
2 Early diagnosis
3 Assessment neurodevelopment after injury
3 Limited application in acute HIE
Electrodiagnostic techniques
? Electroencephalogram (EEG)
Voltage suppression (低电压 ),burst
suppression (爆发抑制 ),isoelectric EEG
(电静息 ),slow wave,focal lateralized
epileptiform discharge (痫样放电 )
Neuronal biochemistry
? Markers in blood or cerebrospinal fluid
Neuron-specific enolase (NSE)
神经元烯醇化酶
Creatine kinase brain-specific
S-100 protein (S-100 蛋白 )
Management
1,Monitoring of vital signs
NICU,CNS,respiration,cardiovascular,
renal,GI,fluid ……
Management
2,Maintenance of Adequate
Ventilation and Perfusion
? Respiratory support,blood gas
? Avoidance of systemic hypotension or
hypertension
? Avoidance of hyperviscosity
Management
3,Maintenance of Adequate Glucose Levels
Normal level,3.9-6,6 mmol/L
4,Control of Seizure
Phenobarbital (苯巴比妥 )
5,Control of Brain swelling
Prevention of fluid overload
Mannitol (甘露醇 )
Management
6,Other Therapeutic Approaches
? Mild hypothemia
? Neuronal growth factor
7,Follow-up and Rehibitation
Intracranial Hemorrhage
1,Prematurity and hypoxia
Primarily in premature neonate
2,Birth trauma
Primarily in term neonate
3,Others Rapid volume expansion (扩容 )，
alteration in cerebral blood flow,
mechanical ventilation,coagulation defect
Causes
Type of Hemorrhage
1,Periventricular-intraventricular
Hemorrhage (PIVH)
脑室周围 -脑室内出血
Germinal Matrix Hemorrhage (GMH)
室管膜下生发层基质出血
Clinical Features
? Common in premeture
? Mild,asymptomatic state
? Moderate to severe,neurological
deterioration (apnea,brainstem
dysfunction,floppy,coma,hypotension,
bradycardia)
? May develop hydrocephylus (脑积水 )
Grading of Severity of IVH
Grade I,Germinal matrix hemorrhage
Grade II,Intraventricular hemorrhage
Grade III,Intraventricular hemorrhage with
dilated ventricle
Separate notation,
periventricular posthemorrhage infarction
脑室周围出血后梗塞
2,Subdural Hemorrhage (SDH)
硬膜下出血
Full term > premature
Uncommon
Clinically serious
Type of Hemorrhage (Cont’d)
Type of Hemorrhage (Cont’d)
3,Subarachnoid Hemorrhage (SAH)
蛛网膜下腔出血
Usually self-limited
Venous origin
Trauma or hypoxia
Rarely develop hydrocephalus
4,Intracerebellar Hemorrhage 小脑出血
1,Clinical features
2,Neuroimaging
Ultrasound Scan
CT,MRI
3,Lumbar puncture (LP)
Many RBCs,elevated protein,xanthochromia
(变黄色 )
Diagnosis
Management
1,Correction of major hemodynamic
disturbance and coagulation defect
2,Control seizure
3,Control intracranial pressure
4,Supportive care
5,Surgical intervention
6,Post-hemorrhagic hydrocephalus,V-P
shunt
复旦大学儿科医院 曹 云
1,General Considerations
2,Respiratory Disorders
3,Jaundice and Hemolytic Disease
4,Neurological Disorders and
Infection
Neonatal Period 新生儿期
Neonate,Newborn 新生儿
Neonatology 新生儿学
Perinatal Period 围产期
Perinatal Infant 围产儿
Perinatology 围产医学
Perinatal Medicine
Classification
1,By gestational age (GA ) 胎龄
full-term infant,mature baby
37 weeks? GA ?42 weeks
pre-term infant,premature (immature) baby
GA < 37 weeks
extremely immature infant
22 weeks? GA ?28 weeks
post-term infant 过期产儿
GA ? 42 weeks
2,By birth weight (BW)
Normal birth weight 2500-3999 g
Low birth weight (LBW) < 2500 g
? Very low birth weight (VLBW) <1500 g
极低出生体重儿
? Extremely low birth weight (ELBW) < 1000 g
超低出生体重儿
Giant infant ? 4000 g 巨大儿
3.By gestational age and birth weight
Small for gestational age (SGA) 小于胎龄儿
BW < the 10th percentiles
Appropriate for gestational age (AGA) 适于胎龄儿
the 10th percentiles <BW< the 90th percentiles
Large for gestational age (LGA) 大于胎龄儿
BW > the 90th percentiles
Intrauterine Growth Curve
500
750
24 26 28 30 32 34 36 38 40 42 44 46 48 （ 周）
1000
1250
1500
1750
2000
2250
2750
3000
3500
3750
2500
4000
4250
4500
4750
5000
3250
小于胎龄
第 10 百分位
适于胎龄
平均体重
大于胎龄
第 90 百分位
3.By gestational age and birth weight
Small for gestational age (SGA) 小于胎龄儿
BW < the 10th percentiles
Appropriate for gestational age (AGA) 适于胎龄儿
the 10th percentiles <BW< the 90th percentiles
Large for gestational age (LGA) 大于胎龄儿
BW > the 90th percentiles
4,By postnatal age
? Early newborn infant,in the first one
of age
? Late newborn infant,between 2 and 4
weeks of age
5,High risk newborn 高危新生儿
Normal Newborn Infant
1,Physical appearance
2.Respiratory
? Onset of respiration
? Pulmonary Surfactant
? Respiratory Rate (RR)
40-50/min
? Abdominal respiration
3.Cardiovascular System
? Cessation of fetal
circulation
? Decrease of pulmonary
pressure
? Close of foramen ovale
and ductus arteriosus
? Variation of heart rate
Fetal circulation to
neonatal circulation
4,Gastrointestinal system
? Immature gastrointestinal function
Gastroesophageal Reflux (GER)
胃食道返流
? Pass meconium 胎粪
5,Renal
? Void within 48 hours of life
? Immature function
6,Hematological system
? Blood volume 85ml/kg
? High red blood cell with high fetal
hemoglobin (70-80%)
? Low activity of Clotting factors
? Physiologic anemia
7,Neurological system
? Neonatal reflexes:
Sucking reflex,Rooting reflex,
Moro reflex,Palmar grasp
? Anterior fontanelle (前囟 )
8,Immunology
? Immature
? Transplacental IgG
? IgM
? IgA,high level in breast milk
9,Temperature control
? Heat production
by brown fat
? Heat loss
large body surface area
little subcutaneous fat
special position
Neutral temperature
Environmental temperature
newborn,33－ 35oC
adult,25－ 26oC
11,Special physical conditions
Physical jaundice
Blood-tinged discharge from the vagina
Abnormally enlarge breast
10,Fluid,electrolyte and nutrition
Physical weight loss
Care of Normal Newborn Infant
? Level I
? Level II
? Level III
Special Care Nursery (SCN)
Neonatal Intensive Care Unit (NICU)
Care of Normal Newborn Infant (Contd.)
? Environment,temperature 22－ 26oC
? humidity 40－ 50 ％
? Infection control,sterilization and wash
? Keep warm,incubation and radiant
? Skin care,bath
? Care of umbilicus
Neonatal Intensive Care Unit (NICU)
Special Care Nursery
SCN
Hand washing
Care of Normal Newborn (Contd.)
6,Feeding,breast milk and formula
7,Vaccination,BCG,Hepatitis B
8,Neonatal screening：
PKU,hypothyroidism,galactosemia,
hearing
Preterm infant
1,Physical appearance
Skin,lanugo,plantar surface,
breast size
2,Respiratory system
? Immature
? Irregular breath
? Apnea of prematurity
? Respiratory distress syndrome
(RDS)
3,Gastrointestinal system
? Vomiting and aspiration
? Gastroesphageal reflux (GER)
胃食道返流
? Feeding intolerance
? NEC
? Jaundice
4,Neurological system
? Relate to the gestational age
? Weak reflex and low muscle tone
? Intraventricular hemorrhage (IVH) and
periventricular leukomalacia (PVL)
5,Temperature control
? Immature center
? Less heat production
? Large heat loss
6,Cardiovascular system
? PDA
7,Others
? Metabolic disorders
? Vitamin deficiency
? Anemia of prematurity
Problems of preterm infant
? Temperature
? Hypoglycemia
? Cardiovascular
disorders
? Respiratory disorders
? Fluid and electrolyte
? Renal disorders
? Hemelogical disorders
? Infection
? Gastrointestinal
disorders
? Jaundice
? Neurological disorders
? ROP
? Feeding problems
? Hearing and visual
problems
? Temperature
? Respiration
? Feeding
? Jaundice
? Infection
……
Care of Preterm Infant
1,Environment,cleaning,sterile,hand-washing
2,Feeding,Breast milk or preterm formula，
careful feeding,nasogastric feeding
3,Temperature control,incubator
4,Monitoring,respiration,acid-base balance、
blood sugar,infection,bilirubin,blood pressure、
renal function
5,Developmental supportive care of preterm
Postnatal infant
SGA
Giant
Infant
? Premature birth
? Birth asphyxia
? Neurological disorders
? Twin-twin transfusion
? Congenital annomalie
Twins
Neonatal Transport
Follow-up of high-risk infants
Respiratory Disorders
? Neonatal Respiratory Distress Syndrome
(NRDS)
新生儿呼吸窘迫综合症
Hyaline Membrane Disease (HMD)
肺透明膜病
?Neonatal Pneumonias
新生儿肺炎
? Meconium Aspiration Syndrome (MAS)
胎粪吸入综合症
? Asphyxia 窒息
? Transient Tachypnea of Newborn (TTN)
Wet Lung 湿肺
? Apnea 呼吸暂停
? Chronic Lung Disease (CLD)
慢性肺部疾病
Bronchopulmonary Dysplasia (BPD)
支气管肺发育不良
Case
???,GA 29W,prolonged rupture
of membranes (胎膜早破 )
Fetal heart monitoring is normal
Management,terminate pregnancy？
or continue pregnancy？
? Hyaline Membrane Disease
HMD
肺透明膜病
? Neonatal Respiratory Distress
Syndrome (NRDS)
新生儿呼吸窘迫综合症
Pulmonary Surfactant （ PS）
肺表面活性物质
? Synthesized by alveolar type II epithelial cells
? Function
1,To stabilize the lung during deflation
by reducing the surface tension
2,To prevent high surface tension
pulmonary
3,To provide a defense against infection
? Increases with advancing gestational age
1,Etiologies
Deficiency of surfactant
? Preterm
? Infants of diabetic mothers (IDM)
? Perinatal asphyxia
? Elective cesarean section (剖宫产 )
? Severe Rh hemolytic disease
? Genetic factors
2.Pathophysiology
lack of surfactant
atelectasis
Dysfunction of V/Q mismatch
Type II cells Hyaline membrane
PaCO2?,PaO2?
Poor perfusion endothelial injury mixed acidosis
pulmonary vasoconstriction
Pulmonary hypertension
3,Pathology
Hyaline Membrane Atelectasis
肺不张
4,Clinical Presentation
Preterm
Onset within 6 hours of age
Progressively severe
? Tachypnea 呼吸增快
? Retraction 吸气凹陷
? Grunting 呻吟
? Cyanosis 青紫
? Apnea 呼吸暂停
? Patent ductus arteriosus PDA
动脉导管开放
? Respiratory failure
? 新生儿持续肺动脉高压
Persistent Pulmonary Hypertension
of Newborn (PPHN)
5,Chest radiographs
Opacity
Diffuse reticular-granular infiltrates
Bronchograms (支气管充气征 )
Atelectasis
“white-out” (白肺 )
Grade I,II,III and IV
NRDS
Opacity
Diffuse reticular-granular infiltrates
,white out” Grade IV
6,Diagnosis and Differential Diagnosis
? Clinical features
? Chest radiographs,X-ray
? Differentiate with infectious pneumonia,
wet lung and aspiration pneumonia
7,Management
(1) Surfactant replacement
Timing,Prophylactic or rescue
Dosage,100－ 200 mg / kg/dose
Interval,Q10－ 12 h ? 2 or 3 times
Administration:
endotracheal tube (ETT)
Surfactant
administration
by ETT
(2)Continuous Positive Airway Pressure
CPAP
持续气道正压通气
(3)Mechanical ventilation
Mode：
IMV＋ PEEP
Setting：
FiO2,PIP,PEEP,I:T,RR
PS treatment
(4) Management of PPHN,inhaled nitric oxide
(5) Closure of PDA
(6) Supportive therapy
Temperature,acidosis,circulation，
fluids and nutrition,possible infection
8,Prevention
(1) Antenatal corticosteroids：
Dexamethasone or betamethasone
(2) After birth,surfactant
GA<30weeks,BW<1500g
Neonatal Pneumonia
Classification：
1,Aspiration pneumonia,Amniotic-fluid,
meconium or milk
2,Infectious pneumonia,prenatal,intrapartum
or post-natal infection
Meconium Aspiration Syndrome
MAS
胎粪吸入综合症
1,Causes
? Full-term and post-term infant
? Intrauterine asphyxia (窒息 )
? Birth Asphyxia
2,Pathogenesis
(1) Airway obstruction,air-trapping and
Air leak (pneumothorax 气胸 ),atelectasis
(2) Inflammatory and chemical pneumonia
(3) Inactivation of PS
3,Pathogenesis (Contd.)
(4) Acute respiratory distress syndrome
(ARDS)
(5) Persistent pulmonary hypertension
of Newborn (PPHN)
4,Clinical Presentation
? Signs of post-term
? Respiratory distress,tachypnea (呼吸增快 ),
nasal flaring (鼻煽 ),intercostal retractions (肋
间隙凹陷 )
? Cyanosis
? Increase in the anterior-posterior diameter of
the chest
? Air leak
? PPHN
? Respiratory failure
5,Chest radiographs
? Hyperinflation of the lung field
? Coarse,irregular patchy infiltrates
? Pneumothorax or pneumomediastinum
气胸或纵隔积气
MAS
Irregular patchy
infiltrates
MAS
Pneumothorax
Pneumomediastinum
6,Management
1,Clear airway,most important
2,Oxygen therapy
3,Mechanical ventilation：
conventional of high frequency ventilation
4,Surfactant
5,Management of PPHN,inhaled nitric oxide (NO)
6,Others,Pneumothorax,hypotention,acidosis
Apnea
呼吸暂停
Absence of breathing for > 20 seconds
cyanosis
Bradycardia 心率减慢
heart rate <100 beats/min
慢性肺部疾病
Chronic Lung Disease (CLD)
支气管肺发育不良
Bronchopulmonary Dysplasia (BPD)
湿肺
Wet Lung
Transient Tachypnea of Newborn (TTN)
Neonatal
Hyperbilirubinemia
新生儿高胆红素血症
Bilirubin (胆红素 )
Jaundice (黄疸 )
Hyperbilirubinaemia (高胆红素血症 )
Unconjugated (indirect) bilirubin (未结合胆红素 )
Conjugated (direct) bilirubin (结合胆红素 )
Free bilirubin (游离胆红素 )
Glucuronyl transferase
葡萄糖醛酸转移酶
?-glucuronidase
?-葡萄糖醛酸苷酶
Enterohepatic Circulation
肠肝循环
Neonatal bilirubin metabolism
? Increased bilirubin load on liver cell
1,Increased RBC volume
2,Decreased RBC survival
3,Increased early-labeled bilirubin
4,Increased enterohepatic circulation of
bilirubin
Neonatal bilirubin metabolism
(Contd.)
? Defective hepatic uptake of bilirubin
from plasma
1,Decreased ligandin (Y and Z protein)
2,Binding of ligandin by other anions
Neonatal bilirubin metabolism
(Contd.)
? Defective bilirubin conjugation
1,Decreased uridine diphosphate
glucuronyl transferase (UDPG-T) activity
2,Increased uridine diphosphoglucose
dehydrogenenase (?-glucuronidase) activity
? Decreased excretion of bilirubin
Neonatal bilirubin metabolism
(Contd.)
? Increased bilirubin production
? Decreased clearance of bilirubin
Summary
Physical Jaundice
? Onset of jaundice,2-3 days of age
? The time of peak level,4-6 days of age
? The resolving time
Full term,2 weeks of age
Preterm,3-4 weeks of age
? Level of total serum bilirubin,<12mg/dL
? Level of conjugated bilirubin,<1.5mg/dL
Nonphysiological Jaundice
? Onset of jaundice before 24 hours of age
? Any elevation of serum bilirubin that
requires phototherapy
? A rise of serum bilirubin levels of over
5mg/dL/day
? Signs of underlying illness
? Persist jaundice
Causes and Clinical Features
? Unconjugated hyperbilirubinemia
1,Fetomaternal blood group
incompatibility
2,Infection
3,Breast jaundice
4,Delayed meconium passage
5,Others,asphyxia,hemorrhage,
polycythemia (红细胞增多症 )
Causes and Clinical Features
? Conjugated Hyperbilirubinemia
1,Hepatitis
2,Obstructive disorders
3,Metabolic and endocrine condition
4,Cholestasis (胆汁淤积 )
Breastfeeding and Jaundice
母乳性黄疸
? Breast-milk jaundice
1,Late onset by day 5-7 of life
2,Rise to peak level by 2 weeks of age
3,Bilirubin fall rapidly if stop breastfeeding
4,Rule out pathological condition
5,Mechanism is unknown
Breastfeeding and Jaundice
? Breastfeeding jaundice
1,Early onset
2,High bilirubin levels after 3 days of life
3,Related to a decreased intake of milk
Bilirubin Encephalopathy
胆红素脑病
? Kernicterus (核黄疸 )
? Cellular toxicity of bilirubin
? Blood-Brain Barrier permeability
Hemolytic disease of the newborn
新生儿溶血病
Rh incompatibility
ABO incompatibility
Onset in fetal and neonatal period
Rhesus Hemolytic Disease
Rh 溶血病
Rh blood group
Rh-positive,D antigen,DD or Dd
Rh negative,dd
一,Pathogenesis
Mother RhD (－ ),Fetus RhD(＋ )
fetal RBC maternal
circulation
IgM
Second pregnancy placenta IgG
Primary
Sensitized fetal RBC Sensitized RBC bind to the Fc receptor
Hemolysis
First pregnancy
Mother,Rh D (－ ) neonate,Rh D (＋ )
Rh E (－ ) Rh E (＋ )
Rh C (－ ) Rh C (＋ )
May occur in neonate whose mother is
Rh-positive
二,Clinical Manifestations
1,Fetal hydrops (胎儿水肿 )
2,Jaundice,early onset,rise rapidly
and severe
3,Anemia
4,Hepatosplenomegaly (肝脾肿大 )
5,Bilirubin encephalopathy
三,Diagnosis
1,Clinical features
2,Laboratory findings
(1) Blood group of mother and infant
(2) Coombs’ test (抗人球蛋白试验 )
Direct Coombs’ test,identify sensitized RBC
ABO Hemolytic Disease
Mother,type O
Fetus,type A or B,O型 胎儿,
A或 B型
最多见的新生儿溶血病
一,Pathogenesis
A,B
substances
Enter
maternal
circulation
AntiA,AntiB
antibody IgG
Pregancy
placentafetausSensitize red
blood cells
Hemolysis
二,Clinical feature
Jaundice,anemia and Hepatosplenomegaly
三,Diagnosis
1,Blood group
2,Coombs’ Test
Direct Coombs’ test
Elution test
Management
1,Phototherapy (光疗 )
(1) Indication,full-term> 15 mg /dl
(2) Light,blue lamps,wavelength 450～
460nm
(3) Mechanism,photochemical reaction
Structural isomerization
(4) Technique,single or double phototherapy
Phototherapy
2,Decreasing free bilirubin
Albumin,plasma
3,Inhibiting bilirubin production
competitive inhibitors of heme oxygenase
(血红素加氧酶 )
4.Increasing bilirubin conjugation
Phenobarbital
5.Inhibiting hemolysis
High-dose intravenous immune globulin (IVIG)
静脉丙种球蛋白
6.Exchange transfusion (交换输血 )
(1) Indication
In Rh hemolytic disease,total
bilirubin>20mg/dl
(2) Mechanisms
Remove antibodies,antibody-coated RBCs
(sensitized red blood cells) and bilirubin，
correct anemia
(3) Blood
Rh hemolytic disease:Rh cross-matched against the
mother,ABO cross-matched against the infant
ABO hemolytic disease,type O cells with AB plasma
(4) Volume
Double the volume of the infant’s blood (two-volume
exchange),160ml/kg
(5) Complications
Hypocalcemia,hypoglycemia,Acid-base balance,
hyperkalemia,embolization,bleeding,infections
Neonatal
Neurological Disease
Children’s Hospital of
Fudan University
CAO YUN
Neonatal Hypoxic-Ischemic
Encephalopathy
新生儿缺氧缺血性脑病
Neonatal Intracerebral
Hemorrhage
新生儿颅内出血
Sequela(后遗症 ),cerebral palsy(脑瘫 )、
mental retardation,visual deficit
Hypoxic-Ischemic Encephalopathy,HIE
Hypoxic-Ischemic Brain Damage,HIBD
Hypoxia
Perinatal asphyxia,apnea,respiratory failure,
right to left shunt
Ischemia
Heart failure,Shock
Causes
Onset of HIE
Timing of Insults Percentage
Antepartum 20
Intrapartum 35
Antepartum ? antepartum 35
Postnatal 10
1,Cerebral hemodynamic alteration：
Initial changes,redistribution of
circulation (diving reflex) ? cerebral
blood flow↑
Continue insult,loss of vascular
autoregulation,systemic hypotension,
cerebral blood flow↓, cerebral ischemia
Pathogenesis
Pathogenesis (Cont’s)
2.Effects of Hypoxic-Ischemic Insults
on Energy Metabolism
(1) Brain glucose ?
(2) Lactate production ?
(3) ATP ?
(4) Energy failure
(5) Neuronal death
Pathogenesis (Cont’s)
3,Role of Free Radicals (自由基 )
(1) Perioxidation (过氧化 ) of membrane
phospholipids
(2) Damage to DNA
(3) Activation of proapoptotic (促凋亡 ) genes
Pathogenesis (Cont’s)
4,Calcium Reflux
(1) Activate phospholipases (磷脂酶 )
(2) Activate proteases (蛋白酶 )
(3) Activate nucleases (核酸酶 )
(4) ? neurotransmitter release
(5) Activate nitric oxide synthetases
(一氧化氮合成酶 )
Pathogenesis (Cont’s)
5,Neurotoxicity of Excitatory Amino
Acids (兴奋性氨基酸 )
(1) Na+ entry with H2O cell swelling
and lysis
(2) Ca+ entry Ca+-mediated events to
cell death
Pathogenesis (Cont’s)
6,Delayed Cell Death (迟发性神经元死亡 )
(1) Cell death,Necrosis (坏死 ) and Apoptosis
(凋亡 )
(2) Necrosis occurs in minutes
(3) Apoptosis,delayed cell death occurs over
hours or days or months
Neuropathology
1,Selective neuronal necrosis
选择性神经细胞坏死
2,Parasagittal cerebral injury
矢状旁区损伤
3,Periventricular leukomalacia
脑室周围白质软化
4,Periventricular-intraventricular hemorrhage
脑室周围 -脑室内出血
5,Focal ischemic brain necrosis
局灶缺血性脑坏死
Clinical Aspects
1,Level of consciousness
Hyperalertness (兴奋 ),irritability (激惹 ),
lethargy(嗜睡 ),stupor or coma
2,Brain stem disfunction
Respiratory disturbance,abnormal pupillary
response to light
3,Seizure (Jitteriness 抖动 )
4,Muscle tone
Hypertonia,weakness,hypotonia
5,Primitive reflex
Hyperactive,depress,absence
Severity of HIE in Full-term Neonate
Mild Moderate severe
Level of Hyperalertness Lethargy Coma
consciousness
Seizure -,Jitteriness Variable +
Primitive reflexes Exaggerated Suppressed Absent
Brain stem _ _ +
dysfunction
Muscle tone Hypertonia Weakness Floppy
Normal
Diagnosis
? History of hypoxia or ischemia
? Clinical features
? Neuroimaging
? Electrodiagnostic techniques
? Neuronal biochemistry
Neuroimaging
? Cranial Ultrasound
(头颅超声 )
1,Diffuse increased
echogenicity of
parenchyma
2,Effacement of cortical
sulci
3,Increased
periventricular echoes
Neuroimaging
? Computed Tomography (CT)
1 Focal or generalized low tissue attenuation
(低密度 )
2 Focal or generalized cerebral atrophy
3 Multicystic encephalomelacia (多囊脑软化 )
4 Limited value for early assessment in
preterm neonate
Neuroimaging
? Magnetic Resonance Imaging (MRI)
1 Demonstrate specific patterns of injury
2 Early diagnosis
3 Assessment neurodevelopment after injury
3 Limited application in acute HIE
Electrodiagnostic techniques
? Electroencephalogram (EEG)
Voltage suppression (低电压 ),burst
suppression (爆发抑制 ),isoelectric EEG
(电静息 ),slow wave,focal lateralized
epileptiform discharge (痫样放电 )
Neuronal biochemistry
? Markers in blood or cerebrospinal fluid
Neuron-specific enolase (NSE)
神经元烯醇化酶
Creatine kinase brain-specific
S-100 protein (S-100 蛋白 )
Management
1,Monitoring of vital signs
NICU,CNS,respiration,cardiovascular,
renal,GI,fluid ……
Management
2,Maintenance of Adequate
Ventilation and Perfusion
? Respiratory support,blood gas
? Avoidance of systemic hypotension or
hypertension
? Avoidance of hyperviscosity
Management
3,Maintenance of Adequate Glucose Levels
Normal level,3.9-6,6 mmol/L
4,Control of Seizure
Phenobarbital (苯巴比妥 )
5,Control of Brain swelling
Prevention of fluid overload
Mannitol (甘露醇 )
Management
6,Other Therapeutic Approaches
? Mild hypothemia
? Neuronal growth factor
7,Follow-up and Rehibitation
Intracranial Hemorrhage
1,Prematurity and hypoxia
Primarily in premature neonate
2,Birth trauma
Primarily in term neonate
3,Others Rapid volume expansion (扩容 )，
alteration in cerebral blood flow,
mechanical ventilation,coagulation defect
Causes
Type of Hemorrhage
1,Periventricular-intraventricular
Hemorrhage (PIVH)
脑室周围 -脑室内出血
Germinal Matrix Hemorrhage (GMH)
室管膜下生发层基质出血
Clinical Features
? Common in premeture
? Mild,asymptomatic state
? Moderate to severe,neurological
deterioration (apnea,brainstem
dysfunction,floppy,coma,hypotension,
bradycardia)
? May develop hydrocephylus (脑积水 )
Grading of Severity of IVH
Grade I,Germinal matrix hemorrhage
Grade II,Intraventricular hemorrhage
Grade III,Intraventricular hemorrhage with
dilated ventricle
Separate notation,
periventricular posthemorrhage infarction
脑室周围出血后梗塞
2,Subdural Hemorrhage (SDH)
硬膜下出血
Full term > premature
Uncommon
Clinically serious
Type of Hemorrhage (Cont’d)
Type of Hemorrhage (Cont’d)
3,Subarachnoid Hemorrhage (SAH)
蛛网膜下腔出血
Usually self-limited
Venous origin
Trauma or hypoxia
Rarely develop hydrocephalus
4,Intracerebellar Hemorrhage 小脑出血
1,Clinical features
2,Neuroimaging
Ultrasound Scan
CT,MRI
3,Lumbar puncture (LP)
Many RBCs,elevated protein,xanthochromia
(变黄色 )
Diagnosis
Management
1,Correction of major hemodynamic
disturbance and coagulation defect
2,Control seizure
3,Control intracranial pressure
4,Supportive care
5,Surgical intervention
6,Post-hemorrhagic hydrocephalus,V-P
shunt
