Neonatology Lecture Notes

Neonatology Lecture Notes

Lecturer Information

  • Lecturer: Dr. Joseph Bird

  • Email: joseph.bird@anglia.ac.uk

  • Module Code: SCI 009

Learning Outcomes

  • At the conclusion of this lecture, students will be able to:

    • Describe the complications of pregnancy and fetal development.

    • Interpret the pathologies of neonatology using knowledge of the underpinning biological mechanisms.

Lecture Outline

  • In previous lectures, pathologies resulting in infertility and available reproductive technologies were studied.

  • This lecture extends the study of development to pathologies of the embryo and neonate, including:

    • Ectopic pregnancy

    • Hydatidiform mole

    • Teratogenicity

    • Common neonatal complications, such as jaundice, respiratory distress syndrome, and necrotizing enterocolitis.

Complications of Pregnancy and Fetal Development

  • Causes of pregnancy complications:

    • Fetal (First Trimester):

    • Chromosome abnormalities (e.g., triploidy, trisomies).

    • Maternal:

    • Endocrine issues.

    • Physical factors (e.g., uterine abnormalities, fibroids).

    • Immunological conditions.

    • Maternal diabetes.

    • Materno-Fetal (Third Trimester):

    • Infections (e.g., rubella, CMV, herpes virus, syphilis, toxoplasmosis, Listeria sp., parvovirus).

    • Spontaneous fetal loss.

Ectopic Pregnancy

  • Definition:

    • Implantation occurs outside of the endometrial cavity (e.g., fallopian tube, ovary, pelvic peritoneum).

  • Predisposing Factors:

    • Inflammatory diseases (e.g., pelvic inflammatory disease affecting fallopian tubes).

    • Fallopian tube adhesions.

  • Pathophysiology:

    • The conceptus invades surrounding tissue, causing intraperitoneal hemorrhage; blood loss may be considerable.

Treatments for Ectopic Pregnancy

  • Monitoring of Progress:

    • Identified by declining serum hCG levels.

    • Early pregnancies may self-resolve.

    • Small risk of fallopian tube rupture.

  • Medication:

    • Methotrexate:

    • Abortion induction (abortifacient); subsequent pregnancies during treatment must be avoided.

    • Risk of liver toxicity when combined with alcohol.

    • Small risk of fallopian tube rupture.

  • Surgery:

    • Excision (salpingectomy, laparoscopic surgery) of the conceptus.

    • Frequency includes removal of the affected fallopian tube, reducing fertility.

    • Limited fertility impact.

    • Anti-D RhD treatment for RhD negative mothers is necessary for future pregnancies.

Diagnosis of Ectopic Pregnancy

  • Differential Diagnosis:

    • Pregnancy of Unknown Location (PUL):

    • Hemodynamically Stable:

      • Pain or no pain.

      • Measure serum hCG levels.

    • Probable Ectopic:

      • Repeated transvaginal ultrasonography after 7 days if hCG expected to exceed 1000 IU/L.

    • Laparoscopy: Consider for appropriate cases based on hCG levels and stability.

Gestational Trophoblastic Disease (GTD)

  • Definition:

    • Trophoblast forms the wall of the blastocyst during fetal development and can develop into tumor cells.

    • Occurs in approximately 0.2% of pregnancies.

  • Types of GTD:

    • Hydatidiform mole (benign).

    • Invasive mole (malignant).

    • Choriocarcinoma (malignant).

    • Placental site trophoblastic tumor (malignant).

    • Epithelioid trophoblastic tumor (malignant).

Hydatidiform Moles

  • Complete Moles:

    • Contains no maternal DNA and fetal tissue (ovum with no functional DNA).

    • Caused by duplication of a single spermatozoan or fertilization of an empty ovum by two spermatozoa.

  • Partial Moles:

    • Contain fetal cells; usually triploid in origin.

    • Poorly viable fetus with malformed structures.

  • Diagnosis: Elevated serum hCG levels.

  • Treatment: Methotrexate and dactinomycin; more advanced cases may require chemotherapy, which can advance menopause.

Teratogenicity

  • Definition:

    • Disruption to normal embryo or fetal development by environmental agents (e.g., drugs, chemicals, radiation).

  • Effects:

    • Spectrum of abnormalities from gross structural defects to non-birth manifestations such as growth retardation and delayed mental development.

    • Approximately 3% of neonates are affected.

Six Principles of Teratology

  1. Susceptibility to teratogenesis depends on the genotypes of both the conceptus and environmental factors.

  2. Susceptibility varies with developmental stage; critical periods for exposure exist.

  3. Teratogenic agents have specific actions on developing cells and tissues.

  4. The access of influences depends on their nature and maternal exposure level.

  5. There are four manifestations of deviant development: Death, Malformation, Growth Retardation, Functional Defect.

  6. The likelihood of visible defects increases with dosage from NOAEL to LD100.

Teratogens

  • Types of Teratogens:

    • Chemical agents: Alcohol (foetal alcohol syndrome), thalidomide (malformations), and certain medications (e.g., imatinib).

    • Nutritional deficiencies: Folate deficiency (spina bifida).

    • Infections: Rubella, Zika virus.

    • Physical restraints: Causes conditions such as Potter syndrome due to oligohydramnios.

    • Genetic factors: Polymorphisms related to susceptibility.

Teratomas

  • Definition:

    • Tumors containing differentiated tissues/organs (e.g., hair, bones).

    • Generally benign but can be malignant.

  • Clinical Implications:

    • Mass effect can obstruct organ functions and compete for nutrients.

    • Diagnosis via ultrasound in neonates, young children, and adults.

Neonatology Overview

  • Classification:

    • Sub-specialty of pediatrics focusing on the medical care of newborn infants and premature children.

  • Perinatal Period Definition:

    • The period immediately before and after birth; typically from 20-28 weeks of gestation to 1-4 weeks post-birth.

Pre-eclampsia

  • Onset: At approximately 20 weeks of gestation; occurs in up to 8% of pregnancies.

  • Severity Spectrum:

    • Mild pre-eclampsia (~6%) may be symptomless but needs monitoring.

  • Risk Factors: Family history, obesity, age, multiple pregnancies, prolonged intervals between pregnancies.

Fetal Viability

  • Definition:

    • The point when the fetal viability, or potential to survive outside the womb, occurs, typically between 23-24 weeks gestation.

    • The respiratory system is the last organ to mature functionally.

Clinical Complications of Prematurity

  • Common Issues:

    • Cerebral palsy in up to 25% of extremely low birth weight (ELBW) infants.

    • Neurosensory deficits (1-10% of ELBW infants).

    • Intellectual disabilities (IQ < 80 in ~15% of ELBW infants).

    • Other complications: Severe growth disturbances, epilepsy, chronic lung disease.

Neonate Survival Developments

  • Historical Milestones:

    • 1898: First premature infant incubator station in Chicago.

    • 1952: The Apgar score developed for newborn evaluation.

    • 1965: First American NICU established.

    • Introduction of mechanical ventilation and surfactant therapy has improved neonatal survival rates.

Trends in Neonatal Mortality

  • Survival Rates Relative to Gestational Age:

    • 50% at 24 weeks, 70% at 25 weeks, 90% at 27-28 weeks.

    • Mortality drops at 33 weeks, nearing rates similar to full-term births.

Infant and Neonatal Complications

  • Preterm Birth Complications:

    • Thermoregulation issues, apnoea of prematurity, and transient irritability.

    • Increased risks of hyperbilirubinaemia, fluid and electrolyte imbalance, and more.

Common Neonatal Complications

  • Conditions contributing to neonatal morbidity:

    • Hyaline membrane disease (HMD)

    • Necrotizing enterocolitis (NEC)

    • Intraventricular hemorrhage (IVH)

    • Patent ductus arteriosus (PDA).

  • 1 in 50 babies can be born with malformations.

Neonatal Jaundice

  • Risks and Complications:

  • 80% of extremely preterm infants require treatment due to jaundice, associated with:

    • Increased breakdown of fetal red cells

    • Immature bile excretory function

    • Coexisting infections.

Respiratory Distress Syndrome (RDS)

  • Hyaline Membrane Disease (HMD):

    • Develops in the first 24 hours post-birth.

    • Alveoli exhibit collapsed lung texture, with necrotic tissues causing dysfunction.

  • Surfactant Characteristics:

    • Composed of lecithin and sphingomyelin; critical in reducing alveolar surface tension.

  • Management:

    • Increased incidence seen in cases of acute caesarean before labor onset.

Neonatal Hepatitis

  • Definition:

    • Liver inflammation due to infections during pregnancy or neonatal period.

    • Symptoms include jaundice, malabsorption, poor weight gain.

    • Complications can lead to cirrhosis and mental retardation.

Necrotizing Enterocolitis (NEC)

  • More prevalent in premature infants, associated with feeding practices.

  • Onset: Typically occurs in the second to third week of life.

Monitoring and Prenatal Testing

Invasive Prenatal Testing Options

  • Amniocentesis:

    • Genetic analysis of amniotic fluid, risks approximately 0.1%.

  • Chorionic Villus Sampling:

    • Placental biopsy, performed at 10-12 weeks, risks approximately 0.2%.

  • Percutaneous Umbilical Cord Blood Sampling:

    • Blood sampling for genetic analysis and biochemical tests, risks 1-2%.

Non-Invasive Prenatal Testing

  • Options:

    • Maternal blood tests for various markers:

    • Alpha-fetoprotein, Oestriol, hCG, Inhibin A.

  • Usage:

    • Indicators for chromosomal abnormalities, neural tube defects, and other fetal anomalies.

Genetic Testing

  • Single Gene Disorders:

    • Examples include Cystic Fibrosis (CFTR gene), Achondroplasia (FGFR3).

  • Chromosomal Changes:

    • Aneuploidies like Down syndrome and structural changes like Cri du chat syndrome.

Newborn Testing

  • Heel Prick Tests:

    • Mass spectrometry for metabolic disorders and detection of congenital gliopathies like phenylketonuria.

Summary

  • Just being born is a significant achievement with numerous complications and challenges requiring attention.