Neonatal physiology and Physiological changes after birth

Respiratory system

Foetal system

• Lungs begin to develop in week 3 of gestation and continue to fully develop by week 16.  Type I and type II pneumocytes are differentiated by 20-22 weeks, and surfactant produced at around 24 weeks.
• Alveolar development continues after birth up to the age of 5 (increasing in number by five times to 300 million).
• During foetal life, the lungs are filled with fluid (amniotic like).  This fluid is compressed from the lung during vaginal delivery.

The first breath

• Factors from the external environment e.g. sound, temperature change, touch etc, stimulate the nervous system to initiate the first breath
  • Central chemoreceptors stimulated by hypoxia and hypercarbia drive further respiration
• Initial breaths require high inspiratory (70-100cmH20) and expiratory (18-115cmH20) pressures to expand the alveoli and to force out amniotic fluid from the airways, respectively
  • This is to overcome the high surface tension
  • Expiration is initially active (i.e. using accessory muscles)
  • The effort required to breathe reduces as fluid leaves the lungs and the alveoli expand.
• In the newborn, the chest wall is more compliant and the lung less compliant (relative to an adult chest)
  • this increases the closing capacity (the volume at which the alveoli collapse) to exceed the functional residual capacity (volume after passive expiration)
    • i.e. alveoli should collapse during breathing – which is not good
  • To overcome this, the newborn creates positive end expiratory pressure in the lungs due to:
    • high-resistance nasal airways
    • partial closure of the vocal cords and glottis
    • post-inspiratory stimulation of inspiratory muscles during expiration
• Newborns have an increased respiratory rate of around 30-60bpm
  • this is to compensate for a decreased inspiratory reserve volume (due to a flatter diaphragm and relatively horizontal ribs) by increasing the minute volume (volume inspired in 1 minute)
    • high resp rate also, in part, compensates for a high metabolic rate

Perfusion/ventilation differences

• The circulatory shunts present in foetal circulation remain present, temporarily, in the newborn.  As a result, the work of breathing in the first week or so of life is increased, but quickly reduces as shunt systems diminish.

Apnoea

• All newborns can have periods of apnoea as their central respiratory drive is immature (improves with age)
  • <5 secs normally
  • premature babies can have prolonged apnoeic episodes (>15 secs) with or without associated bradycardia.

ANAESTHESIA in the newborn can be very risky- physiological PEEP and intercostal muscle tone is lost, reducing the FRC.  Combined with an increased shunt fraction and high metabolic rate, this can cause rapid desaturation.

Cardiac system

Foetal circulation

• Oxygenated blood is preferentially delivered to the brain, myocardium and upper body
  • Facilitated by intra-cardiac (foramen ovale) and extra-cardiac (ductus arteriosus/venosus) shunts
    • Oxygenated blood from the placenta either returns via the liver (~50%) or via the ductus venosus (50% straight to heart via the IVC)
    • The latter is directed through the Eustachian valve and the foramen ovale to bypass pulmonary circulation and supply the head/upper torso.
    • The rest of the (deoxygenated) blood from the liver, SVC, and coronary sinus is preferentially directed to the descending aorta, bypassing the pulmonary system mainly via the ductus arteriosus.
  • Foetal circulation is therefore 2 systems running in parallel- the left ventricle provides 35% of the cardiac output, and the right providing 65%.

Changes at birth

• Umbilical vessels constrict in response to stretching and increased O2 content at delivery.  Clamping of these vessels remove the placenta from circulation and therefore increase systemic vascular resistance.
• Blood flow through the ductus venosus is reduced, causing passive closure over 3-7 days, reducing blood return to the IVC.
• Lung expansion causes a drop in pulmonary vascular resistance and an increase in the return to the left atrium.
  • Combined, the pressures to the right atrium (previously high) and left atrium (previously low) are swapped
  • This causes closure of the foramen ovale within the first few breaths
• The drop in pulmonary vessel resistance and rise in systemic resistance reverses the direction of blood flowing through the ductus arteriosus
  • The ductus arteriosus is thought to diminish as a result of the loss of placenta-derived prostaglandins

  • In babies with hypoxia, acidaemia, structural anomalies etc, the ductus arteriosus may remain patent, which can, in fact, worsen hypoxia (left-right shunting).

Cardiac output

• The high pulse rate (120-160bpm) seen in newborns is mainly to keep up with the high metabolic demand of thermogenesis, feeding, breathing etc.
• As a result, the newborn has a very high cardiac output (200ml/kg/min cf ~80ml/kg/min of adult)
• Following the Frank-Starling law, because of both the high heart rate and immature (stiffer) myocardium, cardiac output is influenced more by heart rate than stroke volume.

Blood

Haemoglobin

• Blood is produced by the liver in utero but is limited to the bone marrow several weeks after birth.
• HbF (α2γ2- higher O2 affinity cf HbA- α2β2) is good in foetal life when O2 needs to be transferred from maternal Hb to foetal Hb at the placenta.  However, at birth, foetal Hb becomes detrimental as oxygen delivery to the tissues is impaired.  This is made worse by increased pH and lower CO2 following delivery.
• HbF accounts for 80% of all Hb in a term baby (can be more in preterm infants)
• Oxygen delivery is facilitated by increased 2,3-diphosphoglycerate (2,3-DPG), which binds to deoxygenated Hb, shifting the oxygenation curve to the right.
• HbF is replaced with HbA by around 6 months
  • However, HbF is lost faster than HbA is produced, leading to a physiological anaemia of infancy at 8-10 weeks

Clotting

• Clotting factors do not cross the placenta.  However, factor V, VIII and XIII are at adult concentrations before birth
• Vit K-derived clotting factors (II, VII, IX, X, protein C and S) are low at birth due to a lack of vit K stores and immature hepatocyte function.
  • Milk is a poor source and endogenous synthesis by gut flora does not occur until several weeks old.
  • Newborns are, therefore, given vit K prophylaxis to protect against haemorrhagic disease.

Thermoregulation

• In utero, the environmental temperature is around body temperature.  At birth, the environmental temperature drops dramatically.  Neonates (particularly preterm) are at high risk of hypothermia
  • 2.5-3 times higher surface area to body mass ratio
  • limited store of subcutaneous fat
  • inability to shiver until 3 months
• Heat can be lost by
  • radiation (39%)- can be reduced by increasing room temperature
    • NB if room temp exceeds body temp, then heat gain will occur.  This can be harmful in preterm babies as sweating for thermoregulation only develops at 36 weeks
  • convection (34%)- can be reduced by warming air and minimising air flow
  • evaporation (24%)- can be reduced by increasing humidity and reducing air flow (in premature babies, a plastic bag/covering can be used)
  • conduction (3%)
• Heat can be generated by
  • limb movement
  • stimulation of brown fat

Hepatic function

• Enzyme pathways take around 3 months to activate
  • Including conjugation pathway for bilirubin (activates around 2 weeks)
    • Because of this- unconjugated bilirubin levels tend to rise within first 48 hours due to HbF breakdown and lack of hepatic function
    • This can be exacerbated by haemolysis, sepsis, dehydration etc
    • Neonatal jaundice is common, but bilirubin levels should stabilise within 2 weeks

Renal Function

• Whilst all nephrons are usually present at birth, immature blood flow limits the concentrating ability of newborns (about half the capacity of an adult), and there is a low GFR (20-40).
  • These increase to adult levels by the age of 2
  • Make the baby more susceptible to both dehydration and fluid overload.
• However, this enables the baby to counteract the effect of parathyroid hormone (phosphate loss) which increases after birth to help increase calcium levels needed for growth

Body Fluid

• At birth in a term child, around 75% of total body weight is water (compared to 50-65% of normal adult)
  • Preterm babies can have significantly higher total body water composition (around 80-85%)
• Around 40% of a newborn baby’s fluid is extracellular (compared to 30% in normal adults)
  • In preterm infants the distribution is around 65% ECF and 35% ICF
• For the first 12-24 hours of life, urine output is limited to 0.5ml/kg/hour due to poor renal perfusion.  Once the cardiovascular system has fully adapted, the kidneys begin to excrete excess sodium (and ECF)- natriuresis.
  • Causes a steady weight loss for the first 5 days of life (1-2% of body weight) and reduces the ECF to ‘normal’ 30%

Fluid requirements

• Fluid replacement should be considered in
  • premature infants in whom there is concern about fluid balance
  • babies with respiratory failure/distress
  • surgical babies
  • babies with excessive urinary losses (inc. renal failure, caffeine and diuretics)
  • consider carefully in phototherapy
• Insensible fluid losses in the newborn equal around 12ml/kg/day, though this can vary with the environment
  • 25-week old infant may be losing up to 15× this ammount
• Losses from the stool are also higher in newborns at aroun 5ml/kg/day
• Any fluid replacement in neonates must take into account the natriuresis that occurs within the first few days of life
  • Sodium should not be given in the first two days of life(to avoid hypernatraemia/fluid overload)
  • Potassium is also not required in the first 1-2 days of life, but can be prescribed thereafter depending on serum potassium levels
    • 4.5-5.5: 1mmol/kg/day; 3.5-4.5: 2mmol/kg/day; 2.5-3.5: 3+ mmol/kg/day; <2.5: 4+mmol/kg/day
    • Hyperkalaemia >7.5mmol/l should be treated with bicarbonate/calcium chloride
  • 10% dextrose is preferred and should be given
    • 60-80ml/kg/day for the first few days (more in low birth weight babies)
    • Increasing by 10-25ml/kg/day until 1 week- 150ml/kg/day in the first week in term infants (higher in pre-term)

Nutrition

• In utero, most nutrition comes from the placenta, although the gut is formed usually by 25 weeks (around 0.3g/kg/day of protein is provided from swallowed amniotic fluid)
  • In the last 6 weeks of gestation, fat deposition increases (by almost 2 fold) and glycoogen stores increase (to 9-times that of adult) to try and prepare for change at birth
    • Thus this can be a huge problem for preterm infants, given the high energy requirement for growth and thermal regulation
• At birth, high levels of catecholamines initiate glycogenolysis, lipolysis and gluconeogenesis.
  • glucose stores are low 2 hours post-delivery
  • glycogen stores depleted around 12 hours post-delivery
  • infants then begin to break down fat until enteral feeding
    • Neonates need nutrition to gain weight and prevent metabolic starvation which may cause developmental delay