PDA IN PRETERMS

DR MANISH SAXENA
FELLOW PED CARDIOLOGY
CARE HOSPITAL
• PDA occurs commonly in premature infants.
• Incidence ranges from 15-37 % in babies less
than 1750 gm
• The role of genetic variation i.e. single
nucleotide polymorphism in transcription
factor AP-2b, tumor necrosis factor receptor-
associated factor 1, and prostacyclin synthesis
may play a role in persistent patency of ductus
arteriosus in preterm neonates .
FETAL AND TRANSITIONAL DUCTUL
CIRCULATION
High PVR & low SVR thus
Rt left shunt through
large DUCTUS

Onset of respiration ,
decrease PVR and
increased SVR causes
duct to shunt LtRt
 DUCTUL PATENCY
Fetal ductul patency maintained by low arterial oxygen content

PGE2 – more in fetus than mother

- falls to maternal within hrs of birth

Glucocorticoids – they decrease sensitivity of DA to PGE2 thus facilitating

constriction

Nitric oxide appears to mediate dilation in new born with high O2 tension
but not in fetus
DUCTUL CONSTRICTION & CLOSURE

Increase O2 Decrease
tension circulating PGE2
PERMANENT DUCTUL CLOSURE
Closure starts at PA end

Completion of anatomic closure may take several months

Begins with constriction with resultant hypoxia in ductal wall.

Hypoxia results in VEGF production.

Proliferation and infolding of endothelial cells( intimal mounds)

Migration of undifferentiated smooth muscle cells

 Impact of Gestational age

TERM INFANTS

-Functional closur occurs in 50% by 24

hrs, 90% by 48hrs and virtually “all”
patients by 72 hrs
 Preterm infants

-delayed in preterms ( inversly prop to GA)

- in healthy preterms( > 30 wks) ductus functionally

closes by 4 day( J Pediatrics 1993,122: S59)

- Sick infants (<30 wks) 65% of ductus patent at 4 days

-Respiratory illness predisposes to PDA, closure less likely

in HMD, those not receiving antenatal steroids.
 causes

Oxygen has less constriction effect on ductus in preterms

Ductul hypoxia does not lead to ( or lesser degree) cell

death and VEGF production, intimal mound formation and
functional closure

For the above reason there are chances of reopening of

closed ductus in preterms.
 Physiological effects and clinical
implications

Shunt is left to right

Qp/ Qs can be upto 3

Physiological consequences depend on size, and

response of heart, lung and other organs to shunt
 Pulmonary effects

Increased hydrostatic
Pulmonary edema,
pressure and increased
Increased PBF hemorrhage, BPD,
lung filtration in pulm
ventilator dependence
microvasculature( lymph)
 Systemic and cerebral blood flow effects

Cerebral blood flow is altered ( diastolic flow

decreased/absent/ retrograde)

Lower cerebral oxygen saturation and mean BP with higher

fractional tissue oxygen extraction

All contribute towards IVH

Decreased abdominal aortic blood flow cvontribute toward

development of NEC
 Clinical features

Risk of hsPDA inversely proportional to GA and

birth wt.

Typically babies develop signs during first 2-3 days

of life( earlier in hose receiving Surfactant).

CHF may develop later in first week.

 Clinical findings
Murmur best heard in LIC and ULSB, it can be only systolic initially but
later continuous.

“Silent” PDA , no murmur ( day 1-3) deterioration of respiratory status,

circulatory instability and cardiomegaly

Prominent LV impulse

Bounding pulses

Widened pulse pressure (> 25 mm Hg/ > 0.5 of systolic BP)

Tachypnea, apnea, increased Pco2, increased mechanical ventilation

requirements
 COMPLICATIONS
Pulmonary edema

Bronchopulmonary dysplasia

NEC

Heart failure

IVH

Prolonged ventilator or oxygen support

Longer hospitalization
 DIAGNOSIS

BNP and N terminal pro

Chest x ray (less sensitive 2D ECHO with Doppler
Clinical features BNP ( varying sensitivity
and specific) color flow mapping
and specificity)
 Hs PDA
• PDA which leads to pulmonary overcirculation
and systemic undercirculation increasing their
subsequent complications
• PDA > 1.5 mm diameter
• PDA : LPA ratio small (< 0.5), moderate (≥0.5 -
<1), large( ≥1) during first 4 days of life.
• Flow patterns in PDA (pulmonary hypertension
pattern, closing, growing, pulsatile)
MANAGEMENT

Prevention of PDA
(Prophylactic
therapy)

PDA closure
 APPROACHES

Conservative
management with Pharmacological
Surgical ligation
supportive closure
therapies alone
 SUPPORTIVE THERAPY
Thermoneutral environment and adequate oxygenation to
minimisze demands on LV function

Use of PEEP in babies with respiratory compromise( PEEP decreases

LTRT)

Maintenance of hematocrit at 35-40%

Avoidance of loop diuretics( frusemide increases renal PGE2

synthesis)

Moderate fluid restriction b/w 110-130ml/kg/day in hsPDA

especially those with severe respiratory disease
 Pharmacological closure

Cox inhibitors are effective in closing PDA by inhibiting PGE2 synthesis

Agents used ibuprofen, indomethacin, Paracetamol

Started in patients with hsPDA prior to onset of signs of heart failure

In very preterm ( < 28 wks), those without antenatal steroid exposure, increased
severity of RD and intrauterine inflamation may fail to respond after initial course
and require 2nd course
IBUPROFEN

Preferred agent as lower risk of NEC and transient renal insufficiency

DOSE 10 mg/kg stat f/b 2 additional doses of 5mg/kg 24 hrs apart.

Oral and intravenous are equally effective

INDOMETHACIN

Dose 0.2 mg/kg 3doses at 12 hrs interval

Complication include increase bleeding risks, transient renal insufficiency and NEC.
 C/I to COX inhibitors
Proven or suspected untreated infection.

Active bleeding ( esp GI or intracranial hemorrhage)

Thrombocytopenia and/or coagulation defects

Suspected or proven NEC

Significant renal impairment

Duct dependent circulation

 PARACETAMOL

Limited data on its use is reported which

shows it may be useful in closing PDA.

Routine use is NOT recommended

Concerns regarding hepatotoxicity and

long term effect on neurodevelopment.
 Surgical ligation
It may be performed after one or two courses of COX inhibitors or if they are C/I.

Post operative decrease CO as preload decrease and afterload increase.Immediate

post-op care includes continuous cardiovascular monitering and inotropic support

Early results show hospital mortality of 10-20% due to continuing RD, ICH,
NEC& DIC

Postoperative morbidity includes BPD, IVH,NEC, ROP

Late morbidity includes BPD, BLINDNESS, CP

 Prophylactic therapy
TIPP trial showed significant reduction in incidence of PDA ( 21% vs 49%)

Overall BPD incidence was similar

Those babies who did not develop PDA had higher incidence of BPD, greater oxygen
supplementation, less wt loss ( water retention)

Prophylactic Ibuprofen also decreased incidence of PDA at D3 of life, but with side effects.

Based on above results prophylactic treatment to reduce incidence of PDA is not

recommended as potential adverse effects and no evidence of long term benefit for babies
not developing PDA
 Course of management

Initial conservative management

fluid restriction b/w 110-130ml/kg/day

Use of permissive hypercapnea, low PaO2 targets and use of PEEP in mechanically
ventilated to facilitate weaning from ventilator, thus minimising risk of BPD

Chlorthiazide for those with fluid retention and increased interstitial pulmonary fluid.

Maintenance of Hct above 35% and thermoneutral environment

A course of COX inhibitor for babies who are ventilator
dependent after few days and have significant PDA
confirmed by ECHO.

A second course of COX inhibitor if follow up echo shows

failure of closure

Surgical ligation for patients that remain on high ventilator

settings with large PDA and failed medical therapy.
 Interventional therapy

Not in common practice

Technically possible now to closePDA in babies < 1.5 kg

Flipper coils & ADO have been used

There are concerns regarding late femoral vein thrombosis and device embolisation.

Selected cases can be considered as an alternative to thoracotomy when medical

therapy has failed ( N Wilson et al Arch Dis Child Fetal neonatal Ed 2007; 92: 248-50)