- A term newborn weighing 3.2 kg didn’t cry after birth and liquor was thick meconium stained (27.4.18).
- Immediately after birth endotracheal intubation and tracheal aspiration had been done in operation theater.
- Baby was placed in artificial ventilator in NICU
- But with 100% O2 support saturation couldn’t be elevated more than 70%
- CXR Oligaemic lungs
- So echocardiography was done in next morning
Finally he was diagnosed as Persistent fetal circulation and managed accordingly, but patient expired after 12 hours because circulation was not reversed.
- Cardiovascular system starts functioning from 3rd week of gestation and continues till death.
- Fetal circulation is low pressure, low O2 saturated parallel circulation.
- Only fetus can survive with this low saturated circulation.
Unique structure for fetal circulation
Four cardiovascular structures unique to the fetus are important for maintaining this parallel circulation:
- Ductus venosus,
- Foramen ovale, and
- Ductus arteriosus
Fetus can be compared with fish in water
But for the survival of new born, shifting of fetal circulation to neonatal circulation is must.
- Preferentially high O2 saturation is ensured in upper parts of body by using various shunts or foramens.
- As a result liver, brain, coronary arteries get highly saturated blood and lower part of the body that gets low saturated blood.
Conversion of fetal circulation to neonatal circulation
Clamping of Umbilical cord
Contraction of umbilical vein
Deoxygenated blood returns to heart
Pulmonary flow increases as PVR falls
Oxygenated blood returns to left atrium
Foramen ovale closes
Oxygenated Blood enters in Aorta
Closure of ductus arteriosus
Fibrosis of Umbilical arteries
Physiological Pulmonary Hypertension in fetus
- High PVR in fetus is maintained by-
i. Compression of pulmonary blood vessels by fluid filled alveoli
ii. Lack of rhythmic distension of lungs
iii. Narrowing of vascular lumen by cuboidal configuration of endothelial cell
i. Hypoxic pulmonary vasoconstriction due to low resting arteriolar & alveolar O2 tension
ii. AA metabolism ( leukotrians, thromboxane)
iii. Lack of vascular vasodilator ( NO, PGI2)
3 factors play role in postnatal pulmonary pressure fall
Right to left shunting in fetus
Changes in fetal circulation after birth
Following events occur after birth
A. Pulmonary vascular resistance falls and pulmonary blood flow increases
B. Systemic vascular resistance rises
C. Ductus arteriosus closes
D. Foramen ovale closes
E. Ductus venosus closes
A & B. Changes in Pulmonary & systemic vascular resistance
C. Closure of ductus venosus
- The functional closure of ductus venosus occurs during 1st minutes after birth.
- It occurs due to decrease in pressure in portal sinus , resulting in retraction and narrowing of its origin – giving a slit like appearance.
- Organic closure is completed between 15 to 20 days after birth.
D. Closure of Foramen ovale
- Following birth pressure of each atrial chamber changes.
- Pressure changes force septum primum to close over septum secondum.
- Usually fusion of the septum primum & septum secondum occurs over a period of 1-2 weeks in 70% cases.
E. Closure of ductus arteriosus
In 2 phase: (Usually within 10-15 hours)
1. Functional closure:
Occurs immediately after birth
Contraction and cellular migration of medial smooth muscle in the wall of ductus arteriosus
2. Permanent sealing and conversion to ligamentum arteriosus ( formation of connective tissue and replacement of muscle fiber by fibrosis.)
- Persistent fetal circulation (PFC)
- Persistent Pulmonary Hypertension (PPHN)
- Patent Ductus Arteriosus (PDA)
- Patent foramen ovale (PFO)
- Complex congenital heart disease and role of PDA/PFO and its
Persistence fetal circulation (PFC) & Persistent Pulmonary Hypertension (PPHN):
Definition of PFC
- Persistent fetal circulation is defined as persistence of right to left atrial or ductal shunting or both in the presence of elevated right ventricular pressure and otherwise normal heart.
- Described by Gersony et al in 1969.
- Incidence : 1/1500 live births , term
- Male are more affected
- Mortality 25-30% if not treated.
Definition of PPHN
- Persistent pulmonary hypertension of newborn is the persistence of the high pulmonary arterial pressure after birth which is a characteristic of the fetal circulation.
- PPHN is associated with substantial infant mortality and morbidity.
- Mortality 25-30% if not treated
Causes of PPHN/PFC
Causes of increased vascular resistance in PPHN/PFC are Idiopatic
- Low oxygen tension
- Relatively low basal production of vasodilator products (PGI2, Nitric Oxide )
- Increased production of vasoconstrictions (endothelin and Leukotriene’s) and altered smooth muscle activity.
Risk factors for PFC
- It is relatively rare condition which is seen in newborn with
- Respiratory distress syndrome (RDS),
- Meconioum aspiration syndrome (MAS),
- Congenital diaphragmatic hernia
- Perinatal asphyxia or ischemia.
Risk factors for PPHN
- Common risk factors for PPHN are
- Newborn with respiratory distress syndrome (RDS),
- Overwhelming sepsis,
- Meconium aspiration syndrome,
- Congenital Diaphragmatic hernia
- Intra-uterine hypoxemia/ ischemia and/or
- Neonatal hypoxemia/ischemia.
Clinical features of PFC/ PPHN
These babies usually present with
- Respiratory distress
- Oxygen dependency
- Low cardiac output state
- Differential cyanosis
- Chest X-ray: Oligamic lung field with charecteristic findings with or without cardiomegaly.
- ABG: Hypoxemia without any change of CO2 level and may or may not associated with metabolic acidosis.
- ECG: Right ventricular dominance
- Echocardiography – confirm the diagnosis.
- Echocardiography is the most sensitive and specific investigation which help to confirm the diagnosis of PPHN. Parameters used in our setting are
–Right ventricular dimension and thickness
–Left ventricular dimension and thickness
–Direction of shunt through holes in atrial, ventricular or ductus level
–Calculation of pulmonary artery systolic and diastolic pressure from tricuspid and pulmonary regurgitation jet.
Treatment of PFC/PPHN
- Treatment protocol formulated and used for PFC/PPHN in our center is cheap, affordable and effective which was proved from our low mortality rate.
- First line treatment:
a. High flow O2 therapy (Optiflow) for 72 hours (Vasodilatation), Tab. Cardopril(Pul vasodilator)
b. Inj. Frusemide(load reduction)
c. Inj. Digoxin (RV dysfunction)
2. Second line treatment:
a. Tab. Sildenafil/Busentan / MgSo4
b. Alkalinasation by hyperventilation.
c. High frequency / Rated ventilator support due to profound hypoxemia and acidosis
d. Some of the patients required ionotropic support with low dose Dopamine and/ Dobutamine.
3. Third line treatment: Prostacycline, Nitric Oxide (iNO) and ECMO if available.
Cause of death in PPHN
- Respiratory failure
- Profound hypoxemia
- Low cardiac output state
- RV failure/ arrhythmia/ cardiomyopathy.
PPHN/ PFC in Bangladesh
- NICU of Dhaka city was landed with a new crisis of newborn since the year 2000. Those were O2 dependency, cyanosis, respiratory distress in patients with healthy lungs and CNS.
- Echo was also normal initially by professional Echocardiographer.
- Then the cause was thoroughly evaluated by experienced pediatric cardiologist and PPHN/PFC were detected in these large number of cases.
- Then new protocol was formulated to handle on the basis of resources available in our set up.
- In last 5 years 7500 (Approx) patients were detected.
- Mortality is around 1% if properly treated .
Perinatal Asphyxia and PFC/PPHN
- The word Asphyxia means – Extreme condition caused by lack of oxygen in blood.
- The word hypoxia means deficiency in the amount of oxygen reaching to body tissue.
- Perinatal asphyxia is caused by
– Antenatal asphyxia
– Natal asphyxia
– Post natal asphyxia
Is Postnatal Asphyxia misnomer ?
- Causes of antenatal and natal asphyxia is almost known.
- But the causes of post natal hypoxia may be due to ineffective conversion of fetal circulation to neonatal circulation that is Persistent fetal circulation or persistent pulmonary hypertension.
- So is the word postnatal(perinatal ) Aspyxia misnomer ?
PATENT DUCTUS ARTERIOSUS (PDA)
- When ductus is remained patent after birth- it is called PDA.
- In fetus blood shunted from Rt to Lt but in newborn blood shunted from LT to Rt .
- Incidence: 5-10% of all CHD excluding premature infants.
- Male female ratio 1:2
Issue in PDA
- PDA in preterm baby
- Isolated PDA in term baby
- PDA with complex congenital heart disease
PDA in preterm baby
- About 50% of infant under 1500 gm have patency of the Ductus.
- Incidence is high in hyaline membrane disease.
- Heart failure is very common in pre terms with PDA
Physiology of patency in preterm baby
- In preterm baby:
–Increase concentration of circulating PGE2
–Smooth muscle of ductus is highly sensitive to PGE2
Treatment of PDA in preterm with haemodynamic impairment
- Restricton of fluid intake
- O2 inhalation
- Antifailure therapy
- Inj Indomethacine 12 hrly x 3 doses.
Ibuprofen daily x 3 doses.
Paracetamol 8 hrly x 48 hours
Isolated PDA in term baby
- PDA persisting beyond the 1st few wk of life in a term infant rarely closes spontaneously or with pharmacologic intervention.
- PDA in term baby rarely causes heart failure during newborn period.
Physiology of patency in term baby
- In term baby:
–Sensitivity of smooth muscle to PGE2 is lost
–Decrease PGE2 concentration due to pulmonary metabolism
Treatment of isolated PDA in Term Babies
- Without haemodynamic impairment
– no treatment require
2. With haemodynamic impairment
– Antifailure therapy.
PDA with complex congenital heart disease
- PDA is seen in 10% of patients with other congenital heart lesions.
- Some complex CHD is dependent to PDA for maintaining systemic circulation.
- Whereas some other CHD is dependent for maintaining pulmonary circultion.
Complex congenital heart disease dependent on PDA
- They are divided in three groups
- Severe restriction of pulmonary flow
a. Pulmonary atresia
b. Tricuspid atresia
c. Tetralogy of Fellot
2. Severe restriction of systemic flow
a. Aortic syenosis
b. Coarctation of aorta
c. Left heart hypoplastic syndrome
3. Cardiac anomalies
a. Transposition of great arteries
- In these complex congenital Heart lesions, babies can only survive if ductus remains patent.
- We can keep ductus patent by
a) Pharmacological intervention
b) Transcatheter intervention (PDA stenting) Surgery
Pharmacological intervention; short term solution
1.Inj Prostaglandin E₁ should be given to maintain patency of the ductus.
Dose: Inj Prostin .01- 0.1 microgram/kg/min
2.Followed by PDA stenting or BT shunt
Note: there are some serious side effects of PGE1, so this drug should not be started if it is not strictly indicated and unless next management option is planned.
Catheter intervention : PDA stenting Mid term solution
Surgery : BT Shunt (intermediate term solution)
- Blalock Taussig shunt is the communication between pulmonary artery and subclavian artery which is synonimous to PDA
Patent Foramen Ovale (PFO)
- A Foramen Ovale is a normal interatrial communication present in fetal life .
- However it may persists as PFO in 25% – 30% of adults.
PFO: Essential part of circulation : Complex CHD
- Usually it has no hemodynamic significance.
- But may play an important role if other structural heart defects are present.
Treatment of PFO
An isolated PFO doesn’t require surgical treatment, although it may be a risk for paradoxical systemic embolism
PFO needs Enlargement: Lifesaving BAS
- But PFO is required for survival of some other disease like TGA, TA, MA, HLHS, HRHS
- Balloon atrial septostomy (BAS) is a procedure to enlarge PFO or create ASD in diseases where intraatrial shunt is must for survival.
Protocol for performing Echocardiography in newborn
- 1st ECHO is done in any symptomatic newborn presented with
ii. Unexplained respiratory distress
iv. Heart failure
2. Repeat ECHO 72 hours after pharmacological intervention ( PFC/ PPHN/ PDA in preterm)
3. Post interventional to see outcome of balloon valvoplasty, Balloon coarctoplasty.
4. Screening Echocardiography (usually after newborn period)
–Mother getting hormone replacement therapy
– Associated with various syndrome
Functional Echocardiography by neonatologist/intensivist
- Functional Echocardiography is the bedside utilization of cardiac ultrasound to measure functional and haemodynamic changes longitudinally.
- These includes
»Functions of heart
»Changes of fetal circulation
- Modern NICU must be equipped with a portable echocardiography machine and neonatologist must be trained on longitudinal functional assessments.
We usually diagnose all perinatal hypoxic condition as Peri natal Asphyxia. Possibly many post natal hypoxia are due to ineffective conversion of fetal circulation to neonatal circulation. So in all case of post natal hypoxia we can think of PFC/ PPHN and it is not very far when it will be proved by research works.
We have enough evidence so far which lead to this observation.