neonatology

week 2 specialist topics in biomed

ectopic pregnancy

• implantation outside of endometrial cavity (uterus) e.g in fallopian tube, ovary, pelvic peritoneum

• predisposed by inflammatory diseases

• conceptus invades surrounding tissue causing intraperitoneal haemorrhage- blood loss may be considerable

spontaneous foetal loss

causes:

• foetal: first trimester, chromosomal abnormalities

• maternal: endocrine, physical, immunological, maternal diabetes

• maternofoetal: third trimester, infection (rubella, CMV, herpes, syphillis)

treatments of ectopic pregnancy

• monitoring of progress

  • identified by declining serum hCG levels

  • for early stage pregnancies which are small and may self resolve

  • small risk of fallopian tube rupture

• methotrexate

  • induces abortion- subsequent pregnancies during treatment need to be avoided

  • liver toxicity when combined with alcohol

  • small risk of fallopian tube rupture

• surgery

  • excision

  • limited impact on fertility

  • anti-D rhesus needed for RhD negative mothers

gestational trophoblastic disease (GTD)

• trophoblast that forms the wall of the blastocyst during foetal development

• implantation of the fertilised egg into the uterine wall

  5 types:

  • hydatidiform mole

  • invasive mole (malignant)

  • choriocarcinoma (malignant)

  • placental site trophoblastic tumour (malignant)

  • epithelioid trophoblastic tumour (malignant)

hydatiform mole

• complete hydatidiform moles

  • contains no maternal DNA and foetal tissue

  • due to single spermatozoan duplication and fertilisation in an empty ovum or 2 separate spermatozoa fertilise an empty ovum

• partial hydatidiform moles

  • contain foetal cells

  • triploid in origin, one set of maternal haploid genes and 2 sets of paternal haploid genes due to dispermic fertilisation of a normal ovum

  • foetus generally malformed and is not viable

• diagnosis includes elevated serum hCG

• treatment by methrotrexate, dactinomycin

• more advanced cases may require radiotherapy

• use of chemotherapy may advance menopause by several years

why dispermic hydatiform moles don’t develop

lack of maternal X chromosome to initiate morula and separation of chorion (placental tissue) and amnion (foetal tissue)

hydatidiform mole

• beta- hCG levels, 100000 mIU/mL

• serum inhibin A and activin A levels

• blood cell count with platelets (anaemia and coagulability)

• blood urea nitrogen, serum creatinine levels, blood type Rh factor

• possible hyperthyroidism

teratogenicity

• disruption to normal development of an embryo or foetus by environmental agents

• spectrum of abnormalities: range from gross structural abnormalities to non-birth manifestations (growth retardation, delayed mental development, alterations in pubertal development)
  gross abnormalities may halt pregnancy or produce congenital malformations

hydatiform mole table of complete mole vs. partial mole

six principles of teratology

1. susceptibility to teratogenesis depends on genotype of conceptus and manner in which this interacts with adverse environmental factors

2. susceptibility to teratogenesis varies with developmental stage at the time of exposure to an adverse influence (critical periods of susceptibility to agents and organ systems affected by these agents)

3. teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events

4. access of adverse influences to developing tissues depends on nature of influence, several factors affec ability of a teratogen

5. four manifestations of deviant development

6. manifestations of deviant development increase in frequency and degree as dosage increases from the NOAEL (no observable adverse effect level) to a dose producing 100% lethality

teratology

the study of abnormalities in an organism’s physiological development , including congenital abnormalities and their causes

teratogens

• mutations

• chromosomal aberrations

• disturbances in cell division

• changes in nucleic acid composition and protein synthesis

• reduction in the amount of essential constituents for biosynthesis

• reduction of energy supply for embryonic and foetal development

• disturbances of enzyme systems

• disturbances in the regulation of water/electrolyte balance

• changes in membrane characteristics

teratogens 2

• toxic substances (e.g alcohol: foetal alcohol syndrome), thalomide (phocomelia), tyrosine kinase inhibitors

• malnutritions

• micro-organisms/infections (rubella)

• physical restraint of foetus (Potter syndrome)

• genetic disorders

teratoma

• tumours containing normal differentiated tissues/organs (eyes, hair, bone)

• generally benign

• mass effect on developing foetus:

  • obstruction on movement of fluid through organs

  • competing with foetus for nutrients

• may be diagnosed in utero, neonates and young children and in children and adults

• graded 0-4 (only 4 is malignant)

• elevated serum α- fetoprotein is biomarker for grade 4 teratomas

perinatal period

• period immediately before and after birth

• 20th-28th week of gestation and ends 1-4 weeks after birth

• adaptations to extra-uterine life from aquatic environment

• physiological systems not developed yet (immune system)

pre-eclampsia

• onset of hypertension at 20 weeks

• 8% of pregnancies

• continuum of severity- mild pre eclampsia may be relatively symptomless but needs monitoring

• due to placental malfunction

• risk factors: family history, obesity, age, multiple babies

viability

• point at which the foetus becomes viable- potentially able to live outside mother’s womb albeit artificial aid

• age of viability appears to be between 23 and 24 weeks of gestation corresponding to foetal lung development

• respiratory system is last organ system to achieve functional maturity

clinical complications of prematurity

• cerebral palsy: 25% of extremely premature infants (extremely low birth weight)

• neurosensory deficits

• mental retardation

• severe growth disturbance

• epilepsy

• chronic lung disease

• surviving infants with severe handicap according to gestational age and birth weight

survivability

• correlates with gestational age

• 50% of babies born at 24 weeks

• 70% of babies born at 25 weeks

• 90% of babies born at 27-28 weeks

• neonatal mortality rate improves with each extra gestational week achieved at delivery

• mortality rate at 33 weeks is very low: comparable to low mortality rate of babies born at term

preterm birth

associated with many changes:

• thermoregulation

• hypoglycaemia

• hyperbilirubinaemia

• fluids and electrolytes

• apnoea of permaturity

• anaemia of prematurity

fluids and electrolytes

• preterm infants have proportionally more fluid in EC compartment than in IC, making them more susceptible to free water loss

• disturbances of fluid balance contributes to IV haemorrhage and patent ductus arteriosus

• frequent problems are hyperkelemia, hyponatremia and contributes to kidney failure

• immature renal function: decreased ability to excrete excessive water loads

• poorly keratinised skin

common neonatal complications

• neonatal malignant neoplasms

• genetic disorders

• trauma

• intrauterine complications

• intraventricular haemorrhage

anaemia of prematurity

• occurs between 2nd and 3rd month of life in term infants

• occurs earlier and is more severe than in term babies

• immature erythropoiesis

• decreased survival of RBCs in premature infant

• deficiences of folate, vit B12, iron

sudden unexplained infant death (SUID)

• pulmonary oedema is commona nd non specific in SUID cases

neonatal pulmonary oedema

• increased pressure in microcirculation of lungs

• cause of respiratory distress in newborns

• may be due to:

  • severe perinatal asphyxia

  • heart failure

  • hyaline membrane disease

  • persistent patency of ductus arteriosus

  • pneomonitis from group B

  • chronic lung disease

neonatal diarrhoea

• 6.72 per 1000 hospitalised newborn

• infection: virus, bacteria, parasite

• food allergy or sensitivity to medicines

• drinking too much

• poisoning

neonatal jaundice

• free bilirubin crosses blood brain barrier in neonates

• injury to developing bran, hearing impairment, cerebral palsy etc

hyperbilirubinaemia

• 80% of preterm infants develop significant jaundice requiring treatment

• increased breakdown of foetal red cels

• immaturity of biliary excretory function of liver

• reduced bowel motility with increased enterohepatic circulation

• coexisting sepsis

• risk of kernicterus

respiratory distress syndrome (RDS)

• hyaline membrane disease

• appearance develops between 12-24 hours of life

• lungs are airless, congested, liver-like consistency

• basophilic debris of necrotic epithelium present in early phase

• thick eosinophilic hyaline membranes (consists of necrotic bronchiolar epithelium and fibrin) lining the respiratory bronchioles and alveolar ducts in developed phase

• collapse of a lung

• reparative changes occur in survivors by 48 hours by phagocytosis of membranes, regeneration of epithelium and mild fibrosis

RDS 2

• surfactant synthesised by type II pneumocytes

• consists of lecithin, sphingomyelin and surfactant associated proteins

• reduces surface tension at air air-liquid barrier in alveoli

• produced in considerable amounts after 35 weeks of gestation but modulation by variety of stimulation is possible

• increased incidence of RDS than expected for gestational age: acute caesarean section before onset of labour, asphyxia, infants of diabetic mothers

• decreased incidence of RDS than expected for gestational age: pre eclampsia, recurrent vaginal bleeding

• significantly higher risk of RDS in second as compared to first of twin pairs

neonatal hepatitis

• onset between 1-2 months after birth

• liver inflammation due to viral infection during pregnancy or shortly after birth

• enlarged liver and spleen, jaundice, mal-adsorption of vitamins, poor weight gain

• may progress to liver cirrhosis and mental retardation

• hepatitis A, B, C also implicated

• liver cirrhosis will require transplant

• diagnosis includes biopsy and blood tests

necrotising enterocolitis (NEC)

• NEC more prevalent in premature infants but can also be observed in near-term or term infants

• in preterm infants the incidence is inversely related to gestational age

• NEC in term infants:

  • initiating event: ischaemic insult to gut frequently following birth asphyxia

• NEC in premature infants:

  • associated with enteral feeding, not with birth asphyxia

  • higher incidence in patent ductus arteriosus

  • average age of onset in preterm babies is the 2nd/3rd week of life

rubella (German measles)

• togavirus, enveloped, single stranded RNA genome

• infection causes physical deformity, cardiac, cerbral ophthalmic, and aditory defects

• maternal infection in first 12 weeks of pregnancy

• teratogenic mechanism currently unclear but may include necrosis, apoptosis, mitochondrial abnormalities, cytoskeleton disruption

• immunisation and screening of teenage girls before pregnancy

• lack of compliance with vaccination programmes

post-partum thyroiditis

• missing or poorly developed gland

• faulty pituitary gland

• inappropriate thyroid hormone production

causes:

• pharmaceutical medication during pregnancy

• insufficient maternal dietary iodine

• inappropriate thyroid function due maternal antibody activity

diagnosis:

• heel-prick blood test to screen for hypothyroidism shortly after birth

treatment:

• levothyroxine, cheap and simple

prenatal testing

• invasive:

  • amniocentesis

  • chorionic villus sampling