NEONATAL PHYSIOLOGY

Presenter : Dr Rahul Goel

Moderator: Dr Basant Kumar
• Definitions
• Neonatal mortality
• Respiratory Physiology
• Cardiopulmonary
• Haematology
• Thermoregulation
• Hyperbilirubinemia
• Carbohydrate, Fat and Protein metabolism
 Definitions
• Neonatal period: birth to 4 weeks

Early neonatal period- up to 7 days

Late neonatal period- > 7 days till 28 days

• Post neonatal period (infancy) : 29 days up to 365 days.

• Perinatal period: 22nd weeks of gestation till 7 days.

• Live birth: product of conception, after separation from

mother shows s/o life.
 Classifications
By gestational age: irrespective of BW

1. Term neonate- 37 to 42 weeks

2. Preterm – before 37 weeks
3. Post term- > 42 weeks

By birth weight: irrespective of GA

4. LBW neonates- <2500 gm

5. VLBW neonates- <1500gm
6. ELBW neonates- < 1000gm
 Neonatal Mortality
Neonatal mortality rate in India is 24.9 per 1000 live births.
Prematurity, sepsis, and asphyxia are the common causes of neonatal deaths

Ministry of Health and Family Welfare, Government of India. National Family Health Survey (NFHS-5)
2019-21. Available at: https://main.mohfw.gov.in/sites/default/files/NFHS-5_Phase-II_0.pdf.
 Neonatal Mortality

Coran’s Paediatric Surgery 8th ed

AIRWAY PHYSIOLOGY
 Expansion of the Lungs at Birth
• At birth, the walls of the alveoli are collapsed due to
surface tension of the viscid fluid that fills them.

• >25 mm Hg of negative inspiratory pressure is

required to open the alveoli for the first time.

• First inspirations of the normal neonate is capable of

creating as much as 60 mm Hg negative pressure.
 Compliance curves

autoPEEPing

Patterns in Preterm and Term Infants Immediately After Birth, Arjan B te Pas, Connie Wong, C Omar F
Kamlin, Jennifer A Dawson, Colin J Morley & Peter G Davis, Nature Volume 65, pages 352–356 (2009)
Normal Values
Volume Adult Neonate

IRV 60 80
Tidal volume 6 6
ERV 10 35
Residual volume 16 23
Cardiopulmonary Physiology
Primary Changes in Pulmonary and Systemic
Vascular Resistances at Birth
• first, loss of the tremendous blood flow through the
placenta >> doubles the systemic vascular resistance
at birth.
• Second, the pulmonary vascular resistance greatly
decreases as a result of expansion of the lungs.

Both reduces the resistance to blood flow through the lungs as

much as fivefold, which reduces the pulmonary arterial pressure,
right ventricular pressure, and right atrial pressure .
 Cardiopulmonary Physiology
Successful transition from fetal to postnatal circulation
requires

1. Increased pulmonary blood flow, removal of the placenta

2. Closure of the intracardiac shunts (foramen ovale)
3. Extracardiac shunts (ductus venosus and ductus arteriosus)
closure.

These changes produce an adult circulation in series with

right ventricular output equalling that of the left.
 Closure of the Ductus Arteriosus
• The low right atrial pressure and the high left atrial
pressure at birth.

• Functionally closing the foramen ovale within the first

few breaths of life.

• The foramen ovale is completely closed in 50% of

children by 5 years.

• It remains probe patent in 30% of adults.

 Closure of the Ductus Arteriosus
• Fetal vessel that allows the oxygenated blood from the placenta to bypass the
lungs in utero.

• Functional closure of the ductus arteriosus occurs by 60 hours in 93% of term

infants.

• 48 weeks: permanent structural closure occurs via endothelial destruction and

sub-intimal proliferation.

• Hypoxia, acidemia or structural anomaly can increase pulmonary vascular

resistance and potentially re-open the ductus arteriosus or foramen ovale.

• This allows a right-to-left shunt, which worsens hypoxia.

• This effect is seen in persistent pulmonary hypertension of the newborn.

 PDA
• In one of several thousand infants, the ductus fails to
close, resulting in a patent ductus arteriosus

• The patency of the ductus is promoted by

prostaglandin E2.

• In fact, administration of the drug indomethacin,

which blocks synthesis of prostaglandins, often leads
to closure.
 Closure of the Ductus Venosus
• Connection between PV and IVC that closes
functionally in few hours after birth and true
obliteration is completed in 15‐20 days and
ligamentum venosum is formed.

• The portal venous pressure rises from near 0 to 6 to

10 mm Hg, which is enough to force portal venous
blood flow through the liver sinuses.
 Closure of the Ductus Venosus
PDV is a rare disease and results in diversion of portal
blood into the systemic circulation and is a type of
congenital portosystemic shunt.

Liver dysfunction and encephalopathy.

Sidhu PS, Lui F. Embryology, Ductus Venosus. 2023 Jul 24. In: StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 31613539.
 Neonatal Cardiac Output
• At term, the neonatal cardiac output is
approximately 200 ml/kg/ minute.

• > 2 times that of adults.

• Circulating thyroid and catecholamine

hormones increase myocardial
maturity in late gestation.

• At birth, large surge of catecholamines.

• The neonatal myocardium is more

dependent on heart rate to increase
cardiac output.

CO= SV x HR
Haematology
 Haematology
• Neonatal blood contains both adult (α2β2) and fetal
haemoglobin (α2γ2).

• HbF (70% in term, >95% in preterm): greater affinity for

oxygen
1. Maintain the molecular structure and function in a more acidic
environment.
2. Facilitates oxygen transfer across the placenta from maternal HbA.

• Post delivery, the high oxygen affinity of HbF becomes

detrimental as oxygen is not readily given up at the tissue
level.
 HbF Oxygen Dissociation Curve
• Increased pH and lower carbon
dioxide concentration further
limiting oxygen delivery to the
peripheries.

• At term, HbF makes up 70-80%

of total haemoglobin; this is
increased to 90% of total
haemoglobin in the preterm
baby.

• 2,3-diphosphoglycerate levels
increases-shifting the curve to
the right.

• HbF is replaced with HbA at

approximately 6 months of age.
 Physiological Anaemia of Infancy

Jopling J, Henry E, Wiedmeier SE, et al. Reference ranges for hematocrit and blood hemoglobin concentration
during the neonatal period: data from a multihospital health care system. Pediatrics 2009; 123:e333
 Physiological Anaemia of Infancy
• 8-10 weeks of age.
• Haematopoiesis - liver in utero but is restricted to
bone marrow from 6 weeks post delivery-limiting
potential sites for haemoglobin synthesis.
• HbF is lost faster than HbA is synthesized.
• Low levels of erythropoietin due to improved tissue
oxygenation after birth.
• Decreased lifespan of HbF-laden red blood cells.
• Relative increase in the blood volume.
 Clotting
• Clotting factors do not cross the placenta.
• However, factors V, VIII and XIII are at adult
concentrations before birth.
• The vitamin K-dependent clotting factors (II, VII, IX, X,
protein C and S): initially low
1. lack of Vitamin K stores
2. Immature hepatocyte function
3. h/o Maternal drugs
4. Sepsis/ asphyxia
5. Deficient in breast milk
• Prolongation in prothrombin time.
 Clotting

Due to the immature liver in the newborn,

vitamin K clotting factors are deficient (II, VII, IX
& X) for the first few months of life.

Vitamin K is administered in the delivery room

to prevent hemorrhagic disease of the newborn.
 Clinical Implication

Davenport, Patricia and Sola-Visner, Martha,” Hemostatic Challenges in Neonates”, Frontiers in Pediatrics,
9,2021,10.3389/fped.2021.627715, ISSN 2296-2360
Thermoregulation
 Thermoregulation
• Normal body temperature: 36.5 to 37.5 ˚C

• Hypothermia: < 36.5 ˚C

1. Cold stress- 36.0 to 36.4 ˚C
2. Moderate- 32 to 35.9 ˚C
3. Severe- < 32 ˚C

• Hyperthermia: > 37.5 ˚C

 Source of Heat Loss
• Radiation- 38%
• Convection- 32%
• Conduction- 3%
• Evaporation- 22%
• Raising the temperature of feedings- 3%
• Others- 2%

Nursan Dede Çınar, Tuncay Muge Filiz,Neonatal thermoregulation,Journal of Neonatal Nursing,

Volume 12, Issue 2,2006,Pages 69-74,
 Susceptibility to Cold

• Substantial body surface area exposure

• Volatile and intravenous anaesthetics: Inhibit Non‑shivering

Thermogenesis

• General Anaesthesia : Inhibit central thermoregulation by

hypothalamus

• Core temperature : Drops by 1-2°C in 1st hour of anaesthesia

 Thermo-Neutral Environment
Minimizes neonatal energy requirements in maintaining
a normal core temperature of 36.5-37.5˚C rectal (axilla
is 0.5-1.0 ˚C lower).

Components
1. Radiation heaters
2. increased ambient theatre temperature
3. warming blanket, plastic covers and head covering reduce radiation and
evaporative losses.
4. Warmed intravenous fluids
5. humidified warm airway gases
 Source of Heat Production
• Increased physical activity: crying, increased body
movements.

• Cutaneous vasoconstriction

• Brown fat: 6% of term bodyweight

 Brown Adipose Tissue

Non-shivering thermo-genesis
Sympathetically innervated fat collection
Axilla, groin, nape of neck, interscapular area and peri renal area.
Nor-epinephrine uncoupled beta-oxidation.
 Response To Cold Stress

Smith's Anesthesia for Infants and Children (Eighth Edition), 2011, Pages 157-178, Thermoregulation:
Physiology and Perioperative Disturbances, Luginbuehl, Bruno Bissonnette, Peter J. Davis
Coupled vs Uncoupled Oxidation
Infant Radiant Warmer
Heated Mattress
Hotline IV Fluid Warmer
Humidified Warm Airway
JAUNDICE
 Physiology
• Conjugation pathway for bilirubin - inactive at birth but is fully
established at 2 weeks.

• Unconjugated bilirubin levels rise during the first 48 hours

1. Rapid breakdown of HbF
2. Poor conjugating abilities of the immature liver.
3. Presence of haemolysis
4. Sepsis
5. dehydration or excessive bruising

• Uncontrolled, pathological levels of circulating bilirubin can cross the

blood brain barrier causing kernicterus and subsequent developmental
delay.
• Bilirubin levels gradually fall over the first 2weeks
 Physiology
• 60% term infant become visibly jaundiced in first week:
benign.

• 5-10% have clinically significant jaundice: require

intervention.

• Physiological or pathological.

• Breastfeeding jaundice (1/3rd ): inadequate feeding.

• Breast milk jaundice (2-4%): unconjugated

hyperbilirubinemia.
Pathological jaundice
 Phototherapy
• Convert insoluble bilirubin into soluble isomer and
excreted in urine and stools.
• Bilirubin has to present on skin: no role of
prophylactic phototherapy.
• Mechanism:
1. Configurational isomerization - Z to E isomer.
2. Structural isomerization- irreversible, lumirubin.
3. Photo-oxidation- minor reaction
• Types of light: CFL, LED, Halogen, Fibroptic.
Phototherapy
 Key points
• Make sure ambient temperature: 25-28˚C
• Remove all clothes, except diaper
• Eye patch is must
• Safe distance: 30 -45 cm
• Optimum breastfeeding/ IVF
• Monitor baby temperature every 2 hrs
• Monitor TSB 12 hours apart.
• Stop phototherapy: 2 TSB values fall below age
specific cut off.
Carbohydrate, Fat and Protein
Metabolism
 Glucose
• The brain can use only glucose or ketone bodies; it is
not able to oxidize lipids directly: euglycemia
>>favourable neurologic outcomes.
• Glucose turnover: neonates (3 to 5) >adults (2 to 3
mg kg/min)- relatively increased brain/body mass
ratio.
• 0–6 months 60 g/day of carbohydrate
• 7–12 months 95 g/day of carbohydrate
• Glucose production in term neonates
1. Glycogenolysis ( 40%)
2. Gluconeogenesis from glycerol (20%), alanine and other amino acids
(10%), and lactate (30%).
 Glucagon/Insulin Axis in the
Perinatal Period
• Islet cell function is relatively unresponsive for the first 2
weeks of neonatal life
• Response to hyperglycemia

-Increases in insulin secretion and decreases in glucagon secretion are

relatively slow

• Slow response to hypoglycemia

-it may be some time before insulin secretion is decreased and glucagon
secretion is increased to stimulate gluconeogenesis
 Neonatal Hypoglycemia
• Plasma glucose < 45mg/Dl (blood <40)
• At risk neonates:

1. SGA- weight for gestation < 3rd centile

2. Premature: GA < 35 weeks
3. BW< 2000gm
4. Infant of diabetic mother
5. Large for date baby- weight for gestation> 97th centile
6. Hypothermia
7. Sepsis
8. Birth asphyxia
Causes
Clinical Features
Energy Requirement
 Calorie Value

10% dextrose solution - 0.34 kcal/ml

10% lipid solution - 1.1 kcal/ml
10% aminoacid- 0.4 kcal/ml
 Protein
• Preterm lose 1.5 g/kg/d
• Term lose 0.7 g/kg/d
Aim: To achieve nitrogen retention at in utero rates without
causing metabolic disturbances

• AA intake of 1-2 g/kg/d at caloric intake of 30-60 Kcal/kg/d :

neutral protein balance
 Protein
• Early (DOL 1) - AA supplementation in preterm in
adequate doses is beneficial and safe

• Improves : Nitrogen retention

Postnatal growth
Head growth
 Requirements

Age Group Protein

Preterm 1.5-3.5 g AA/kg

Term 1.5-3 g AA/kg

 Neonatal AA Solution
• Should contain essential AAs &
conditionally essential (cysteine, tyrosine
& taurine)
• Current AA are crystalline AA which
contain both essential and non essential
AAs
• Adult AA solution is different
• 6%,10%
 Lipids

• High energy density, energy efficiency, isotonic with plasma

• Osmolality : 268m Osm/L irrespective of lipid concentration,
so safe to administer from peripheral line
• enable the delivery of fat-soluble vitamins
• Provides 30% of total calories and 25-40% of non protein
energy
• Even a short delay of 3 to 7 days leads to biochemical EFA
deficiency
 Lipids

• EFA deficiency can be prevented with introduction of 0.5 to 1.0 g/kg

per day of lipid infusion
• Early lipid administration from day 1
• Start 2g/kg/day and can increase not more than 4g/kg/day
• Lipids are vulnerable to Photo-oxidation in light , leading to toxic Lipid
Peroxide formation.
• So, should be photo-protected with sterile opaque sheet/foil.
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