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NGDWeek3 Fetal NeonatalTransition

1. Explainthe physiologicaltransitionsthat occurat birth and explainhowalterationsin theseprocessescan causedisease. Transitionsincludemoving fromplacentaldependenceto independentfunctionfor gas exchange,nutritionalneeds,metabolicfunctionsandimmunologicalprotection. NEWBORN WITH RESPIRATORY DISTRESS **SYMPTOMS OF NEONATAL RESPIRATORY DISTRESS Dusky in room air Tachypnic Nasal flaring/intercostal indrawing/grunting DIFFERENTIAL DIAGNOSIS FOR NEONATAL RESPIRATORY DISTRESS TTB HD/RDS Meconium Aspiration syndrome Non-pulmonary causes o Anemia, Medication, Pneumothorax o Congenital heart disease or malformation o Upper airway obstruction o Persistent pulmonary HTN Treatment Self resolves in 1-3 days (extra little time for reabsorption of fluid) Respiratory failure is unlikely usually mildmoderate respiratory distrress

Cause/ Effects Transie nt Tachypn ea of Newbor n wet lung

Failure of fluid to leave lungs fully at birth Normally increased catecholamines in labor increased Na reabsorption + Vaginal delivery can also squeeze fluid out of lungs Failure of this failure to clear lungs of fluid

Prevalence and population More likely in term or near term infants More likely in infants delivered by C-section Most common cause of neonatal respiratory distress

Diagnosis CXR: hyperinflation of lung, (hyperaeration) flat domes of diaphragm, vascular markings in lungs, prominent interlobular fissures Tachypnea Intercostal retractions, grunting, nasal flaringindicate difficulty breathing (increased force and effort in breathing) and low gas exchange Hypoxia without hypercapnia

Respirat ory Distress

Decreased surfactant in immature lungs

Premie babies, immediate onset

Cyanotic, dusky color CXR: ground glass, loss of cardiac silhouette, loss of diaphragmatic silhouette, small lung volume

Surfactant with supportive care

Syndro me (Hyaline Membra ne Disease )

Increased surface tension in alveolus increased effort required to inflate air spaces

Will dissipate when babe begins making surfactant

May see atelectasis (collapsed lung) Histology: hyaline membranes and collapsed airspaces Tachypnea Intercostal retractions, grunting, nasal flaringindicate difficulty breathing (increased force and effort in breathing) and low gas exchange Hypoxia with hypercapnia Cyanotic, dusky color

Varying needs of respiratory support and O2

Meconiu m Aspirati on

Aspiration of meconium caused by stress during delivery Obstruction of small airways and alveoli Presents as Pneumonitis, disrupts surfactant, mechanical disruption of airway Idiopathic, or 2 to mechanical ventilation (ie too much air or too much force of ventilation, leading to gas escaping into pleural space)

Most likely in cases of fetal distress, difficult labor Usually stained amniotic fluid too Usually full term infants >34 weeks Primarily occurs in babies with lung diseaselike RDS, aspiration syndromes, ventilation, CPAP Forces air out into pleural space via lung lesion/laceration

Cyanotic, dusky color CXR: atelectasis, consolidation, hyperinflation of lungs, air trapping, spontaneous pneumothorax Audible grunting, severe retractions (subcostal, intercostal, sternal)

Pneumo thorax (air in the pleural space)

ACUTE increase in respiratory distress and O2 requirements Transillumination of chest cavity CXR: hyperaeration of lungs

If severe need 1 way valve chest tube (moderate to large pneumothorax requires drainage) Surgery


Developmental defect

CXR- hypolastic lungs and obvious

gmatic Hernia

(bowel loops, liver, spleen) in chest cavity


2. Review thermoregulation, with special emphasis on the neonate (continuation from PRIN) Fetus has a 0.5OC higher temperature than that mother with heat transfer via placenta and suppression of thermogenesis After birth, it is exposed to cooler environment with all kinds of heat transfer remove heat from the baby Conduction, Convetcion, Evaporation, Radiation Babies have brown fat which are mitochondria rich to hydrolyze fat resulting in heat production

3. Explain the basis for unique congenital, transplacental and neonatal infections and the responses to and sequelae of these infections Innate immunity Complement (C) o NO placental transfer all made by infant o At birth, 2/3 adult levels of C does not gain full function until 2 wks o Increased risk of infection with extracellular bugs in first 2 weeks (neonatal premature and term infant) o eg. E coli sepsis (frequently from mother GI tract) Neutrophils o Neonate has lower BM storage pool, and lower expression of migration receptors o Lower phagocytic activity; tendency to deplete neutrophils neutropenia o Increased risk of infection with extracellular bugs in first 2 months (premature and term infant)

Adaptive immunity B cells o Complete lack of anti-polysaccharide Ab o Lower levels of IgG, A (and M, if premature infant) than adult o Only IgG transported across placenta (passive fetal Abs), but most of them transferred in the last trimester, so only term neonates have similar levels to mother o Slower and decreased response, especially to encapsulated bacteria (Group B Strep!) T cells o Total numbers and TCR diversity in term neonates essentially the same as mother; however, they are nave in phenotype and function higher activation threshold slower to respond o Increased susceptibility to rapidly spreading intracellular infection (eg. CMV)

Barrier Skin (chemical and physical barrier and immune organ) Stratum corneum only develops >32 to 34th gestational week o Rapidly develops within 2 weeks of birth Premature infants: initially decreased physical barrier Increased susceptibility to infections with skin flora for premature

infants and briefly around birth (eg. Coagulase negative staphylococci) Exposure Pregnant = sexually active STDs (Treponema pallidum, HSV, HBV, HIV etc) Placental/fetal tropism : Listeria, Malaria Increased susceptibility to infections with STI bugs Note: congenital syphilis can be prevented with one simple test and one simple shot of penicillin, if indicated . If untreated, intrauterine death, perinatal mortality, or overt symptoms result.

Exposure Vaginal Colonization during pregnancy Lactobacilli consistently high GBS typically rises in the last 3-4 weeks of pregnancy (~36wks GA) o Tests for GBS therefore done at 36 weeks gestation, not earlier

Exposure postnatal colonization = increased exposure to all kinds of bugs Highest risk of infection is at birth! 4. Explain how the unique characteristics of newborn infants affect pharmacokinetics, drug efficacy and drug toxicology Particularly in the first year of life, dramatic developmental changes in the physiological and biochemical processes that govern drug pharmacokinetics take place. These changes have significant consequences for the way that infants respond to and deal with drugs. The major differences relate to body composition and the ADME processes of Pharmacokinetics (Absorption, distribution, metabolism, excretion). Absorption Oral delivery: increased gastric pH Transdermal delivery: stratum corneum is thinner Distribution Babies are born wet o Increased proportion of total body water compared with adults o Increases the volume of distribution of hydrophilic drugs Neonates have fewer plasma proteins o reduced overall protein content since it takes time for the proteins to be fully synthesized o lower binding capacities of those proteins that are present o Increases the free fraction of drugs that are normally extensively protein bound With less protein binding thereis a higher overall fraction of free (active) drug compared to the adult (protein bound) situation, again raising the risk of adverse effects. the blood-brain barrier is also not fully developed at birth, and this results in an increased susceptibility to CNS drugs and related side effects. Metabolism

Both the Phase I and II enzyme systems are incompletely developed in the neonate, and it takes at least 6 months to reach near adult levels o Especially the case with P450 enzymes o impairment in the capacity for drug elimination

Excretion Renal function is incompletely developed, and in fact for the first year of life GFR and renal tubular secretion only function at ~20% that of an adult. This markedly impairs the capacity for drug elimination in the urine and results in increased drug half lives and decreased clearance This is even more critical in babies who are born prematurely, where these differences are more dramatic yet. 5. Describe infant development (birth to 2 years) in cognitive, communication, fine and gross motor, adaptive/activities of daily living and social/emotional terms Cognitive The best measure of cognitive development in infancy and childhood is communication 0 4 Mo: Out of sight, out of mind 4 8 Mo: Infant will look for fallen object or reach for partially hidden object o Infant has learned that if an object is out of sight, it may still exist and have fallen on the ground. 8 12 Mo: Infant will search for a completely hidden object 12 18 Mo: Infant will search for an object after seeing it being moved 18 24 Mo: Infant will look puzzled and continue to search for missing object o The early understanding that objects continue to exist no matter where they were last seen

Communication Components of communication include receptive and expressive language o Literacy development included here Early language development requires interaction with RESPONSIVE sources, not TV. Expressive Language Pre-linguistic phase: o 1 4 Mo: Cooing o 4 8 Mo: Babbling and non-specific da-da/ma-ma o 8 12 Mo: Specific da-da/ma-ma, then first true word at approx. 1 year Linguistic Phase o 12 18 Mo: Single words (Minimum 10 different words by 18 months) o 18 24 Mo: 2 word sentences by 2 years of age (Minimum) Receptive Language o 1 4 Mo: Orientates to voice o 4 8 Mo: Responds to own name and tones of voice o 8 12 Mo: Understands No o 12 18 Mo: Follows 1 step commands; points to body parts when asked o 18 24 Mo: Follows 2 to 3 step commands; points to pictures when asked

Literacy Development Early literacy development is a predictor of academic success and other outcome measures o By 6 months: Infant will look at a book o 12 18 Mo: Infant will point to pictures; brings book to parent to read o 18 36 Mo: Infant will carry books with him/her; wants same story over and over Motor Motor skill attainment DOES NOT predict cognitive development; however, early motor delay may be the first indicator of a range of developmental problems such as cerebral palsy Fine Motor (visual and fine motor tasks) o Less than 1 Mo: Visual fixation o 3 Mo: Can bring hands to midline o 6 Mo: Puts toys in mouth o 8 Mo: Pincer grasp o 9 Mo: Grasp and figures out how to ring a bell Gross Motor o Gross motor development is dependent on several factors Balance of extensor and flexor tone Evolution of protective and equilibrium responses Decline of obligatory primitive reflexes Moro reflex persists until 4 mo. Asymmetric tonic neck reflex persists until 6 mo. Postural reflexes o Neonates tone is predominately flexor o Lower extremity hyperreflexia is common in infants under 4 months o Extensor plantar response is seen under 12 months o Gross motor milestones 4 Mo: Rolls prone to supine 5 Mo: Rolls supping to prone 6 Mo: Sits unsupported 8 Mo: Crawls 9-10 Mo: Cruises 12 Mo: Walks 15 Mo: Runs 18 Mo: Stairs with alternating feet

Adaptive/activities of daily living Involves the integration of all developmental domains into daily life o E.g. dressing, feeding, self-care, getting along in daily life Should develop at the same rate as intellectual development Social/Emotional Attachment - Specific bi-directional bond that develops between children and caregivers. o Caregiver must be emotionally available, perceptive, and able to meet the childs needs

Infant helps in the process by being aware, alert and reactive to caregiver Process starts in utero and continues to develop overtime o Secure attachment leads to better coping with stress, better performance at school and lays the foundation for relationships over the life of the child It allows you to go out on a limb and take risks more sense of security Social/Emotional Milestones o By 3 Mo: reciprocal interactions between infant and caregiver; empathy is recognized o 3-5 Mo: Infant demonstrates a clear preference for their primary caretakers o 9 Mo: Stranger anxiety develops o 18 Mo: Empathy is demonstrated o

Developmental Milestones Summary Table Age Birth1month 1-4 months 4-8 months
Visually follows an object being dropped Finds an object after watching it being hidden (1 towel) Infant searches of object after seeing it moved (2 towels) Knows object exists even when they are gone (misses object when absent) Looks at a book, likes storytime



Gross Motor
Roll to supine Roll supine to prone and can sit unsupporte d Crawl Cruise Walk

Fine Motor
Brings hands to midline Toys in mouth Pincer grasp Grasps Figures out how to ring a bell

Receptive language
Turns to voice Searches for speaker with eyes Responds to own name and tones of voice Understands no

Expressive language
Range of cries Babbling, cooing Babbling, dada

Social/emotio nal
Preference for primary caregivers


Thumb sucking Bangs toys and puts them in mouth

8-12 months

12-18 months

Points to pictures in a book. Brings book to parents Carries books. Wants the same story over and over


1 step commands, points to body parts 2-3 step commands, points to pictures when asked

Jargon speech, mama, dada, specific words (single) 10 words by 18 months

Stranger anxiety

Peek a boo


Symbolic play

18-24 months


2 word sentences (2 words by 2)

Imaginative play

Case Objectives 1. Describe the cardiorespiratory adaptations at birth (the transition from fetal to neonatal life) Source: Kliegman Birth: o Rapid decrease in pulmonary vascular resistance due to Mechanical expansion of lungs: increase in arterial Po2 ***continually remodelling over first few weeks further decrease pulmonary resistance- e.g. thinning of vascular smooth muscle, recruitment of new vessels. o increase in systemic vascular resistance due to removal of low resistance placental circulation Result: o Output from right ventricle follows the path of least resistance pulmonary circulation Shunt through ductus arteriosus reverses, becomes left to right, because pulmonary vascular resistance now lower than systemic vascular resistance Ductus arteriosus will eventually close due to high arterial PO2 (functional closure usually by 10-15hr), becomes the ligamentum arteriosum. o Increased volume of pulmonary blood flow returning to left atrium from the lungs increases left atrial volume and pressure, closes foramen ovale (usually functionally closed by 3 mo, may remain probe patent for several years) o Removal of placenta results in closure of ductus venosus. o Left ventricle coupled to high resistance systemic circulation, wall thickness and mas will nstart to increase. 2. Discuss how infection alters this adaptation Source: Kliegman As mentioned in the objective above, the cardiopulmonary transition relies on the decrease in pulmonary vascular resistance. This decrease is due to vasodilation of pulmonary vessels secondary to filling of lungs with gas, rise in PaO2, reduction in PaCO2, increased pH, and release of vasoactive substances. Infection will alter these changes. For example pulmonary edema secondary to pulmonary infection will interfere with filling of lung with gas, and will decrease PaO2 and increase PaCO2. The result is vasoconstricted pulmonary vessels pulmonary resistance does not decrease persistent pulmonary hypertension of the newborn. In our PBL case, GBS infection can cause this.