Talk:2010 BGD Tutorial - Applied Embryology and Teratology

From Embryology

UNSW Embryology

Beginnings, Growth and Development- Phase 2

Introduction

This Phase 2 Medical tutorial introduces the topics of Applied Embryology and Teratology. This one and a half hour presentation uses your existing knowledge of normal human development in an applied clinical manner in relation to our existing knowledge of teratogens. In addition, you should begin considering the variables that will not change and those that will in future medical practice.

Subsequently, only a brief coverage can be given of any one topic. You should come back and look later at the online resources for more detailed descriptions.


Applied Embryology: timeline of development, birth statistics, abnormalities statistics, unintended pregnancies, trophoblastic disease, embryonic development, placenta, fetal development, folic acid, multiple pregnancies.

Teratology: definitions, critical periods, medications, chromosomal abnormalities, environmental factors, infection

Textbook Reading: Human Embryology, WJ. Larsen; The Developing Human: Clinically Oriented Embryology. Moore & Persaud

Tutorial Handout: Tutorial – Applied Embryology and Teratogenicity (8 pages, PDF document)

Applied Embryology

The data below are highlights from the AIHW National Perinatal Statistics Unit annual publication: "Australia's mothers and babies 2005"

Australia's mothers and babies 2005

267,793 women gave birth to 272,419 babies in Australia.

15,214 more births (5.9%) than reported in 2004.

Mothers

  • 9,867 were of Aboriginal or Torres Strait Islander origin, making up 3.7% of all mothers.

17.4% reported smoking at all during pregnancy. (More? Smoking)

58.5% had a spontaneous vaginal birth (0.4% vaginal breech birth, 3.5% forceps and 7.2% vacuum extractions). (More? Birth Overview)

30.3% gave birth by caesarean section (19.5% in 1996) (More? Caesarean Delivery)

83.2% had previously had a caesarean section

1.7% had a multiple pregnancy (More? Twinning)

3.0 days median length of stay in hospital (caesarean section 5.0 days)

Babies

8.1% were preterm (less than 37 weeks gestation) (More? Premature Birth | Low Birth Weight)

6.4% of liveborn babies were of low birthweight (less than 2,500 grams) (More? Low Birth Weight | Fetal Origins Hypothesis)

105.5 male / 100 female live births

15.5% of liveborn babies admitted to a special care nursery or neonatal intensive care unit.

6,044 were admitted to level III neonatal intensive care units in Australia and met ANZNN’s high risk criteria, of which 78.0% were preterm.

7.3 /1,000 births fetal death rate (More? Stillbirth and Perinatal Death)

3.2 /1,000 neonatal death rate / live births

10.5 /1,000 perinatal death rate / births

Socioeconomic status of women who gave birth

Women who gave birth in 2005 and were in the least disadvantaged quintile were older and less likely to be Indigenous or smoke during pregnancy, compared with women in the other quintiles.

Proportion of women who had induced or no labour, and the proportion who had an instrumental delivery or caesarean section, increased with socioeconomic advantage.

Proportion of babies with less favourable outcomes, such as preterm birth and low birthweight, decreased with socioeconomic advantage.

(Reference: AIHW National Perinatal Statistics Unit Australia's mothers and babies 2005)

Applied Embryology Links: Normal Development- Statistics | Normal Development- Australian Statistics | World Infant Health Statistics | Abnormal Development - Australian Congenital Malformations Classifications

Unintended Pregnancy

1995 USA National Survey of Family Growth (NSFG)

  • 49% of pregnancies in the USA (excluding miscarriages)
  • 31% of pregnancies resulting in a live birth are unintended

Unintended pregnancy is either

  • mistimed (woman wanted to be pregnant later)
  • unwanted (did not want to ever be pregnant)

(Reference: Pregnancy Risk Assessment Monitoring System USA)

Assisted Reproduction Technology

Assisted Reproduction Technology (ART) may include more techniques than, but is sometimes also used to identify, In vitro Fertilization (IVF) (More? In Vitro Fertilization).

  • 51,017 treatment cycles reported to ANZARD in Australia and New Zealand in 2005.
    • 91.1% were from Australian fertility centres
    • 8.9% from New Zealand‚Äôs centres
    • an increase of 13.7% of ART treatment cycles from 2004.
  • 35.5 years average age of women (35.2 years in 2002).
  • Women aged older than 40 years has increased from 14.3% in 2002 to 15.3% in 2005.

Single Embryo Transfers (SET)

  • Significant increase in the number of SET embryos transfer cycles
    • 2002 28.4%
    • 2005 48.3%
  • increase of SET cycles resulted more singleton deliveries (singleton deliveries 2005 was 85.9%)
  • single-embryo transfer babies had better outcomes compared to babies born to women who had a double-embryo transfer (DET).
    • 2005 3,681 SET babies and 5,589 DET babies.
  • Singletons babies
    • 96.1% SET
    • 61.6% DET
  • Preterm babies
    • 11.7% SET
    • 30.6% DET
  • Low birthweight liveborn babies
    • 8.0% SET
    • 25.0% DET

Perinatal mortality rate is a measure of perinatal outcomes.

  • 2005, for all babies born following ART treatment
    • perinatal mortality rate was 14.7 deaths per 1,000 births
    • 23.8% decrease from 19.3 deaths per 1,000 births in 2004
  • Perinatal mortality rate was the lowest among singletons born following SET (7.3 deaths per 1,000 births) in 2005.

(Reference: AIHW National Perinatal Statistics Unit Assisted Reproduction Technology in Australia and New Zealand 2005)

Australian Birth Anomalies System

"The national collation and reporting of birth anomalies data has been suspended in recent years due to concerns about data quality and comparability."

  • Variability among states and territories in scope of birth anomalies data collections
    • sources of birth anomalies notifications
    • definitions and classifications used
    • method of data collection
    • available resources
  • Variability among the states and territories in the timing and method of the provision of birth anomalies data to the AIHW National Perinatal Statistics Unit (NPSU) for national collation and reporting.
  • New Australian Birth Anomalies System should be data for birth anomalies detected up to 1 year of age
    • including data on terminations of pregnancies with birth anomalies
    • regardless of gestational age (i.e. including less than 20 weeks gestation)
  • System will initially be based on data from the states able to detect birth anomalies at least up to 1 year of age
    • NSW, VIC, WA and SA
    • further extending the period of detection in the future

(Reference: modified from AIHW Website)

Ten most frequently reported birth defects in Victoria between 2003-2004 (More? Australian Statistics - Victoria)

  1. Hypospadias (More? Genital Abnormalities - Hypospadia)
  2. Obstructive Defects of the Renal Pelvis (More? Urogenital Abnormalities)
  3. Ventricular Septal Defect (More? Cardiovascular Abnormalities - Ventricular Septal Defect)
  4. Congenital Dislocated Hip (More? Musculoskelal Abnormalities - Congenital Dislocation of the Hip (CDH))
  5. Trisomy 21 or Down syndrome - (More? Abnormal Development - Trisomy 21)
  6. Hydrocephalus (More? Neural Abnormalities - Hydrocephalus)
  7. Cleft Palate (More? Head Abnormalities)
  8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued (More? Abnormal Development - Trisomy 18)
  9. Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%). (More? Kidney Abnormalities - Renal Agenesis)
  10. Cleft Lip and Palate - occur with another defect in 33.7% of cases. (More? Head Abnormalities)

Links: Australian Birth Anomalies | Australian Anomalies Classification | Abnormal Development - Australian Statistics - Victoria |

Abnormal Development

There are many different ways that developmental abnormalities can occur the 2 major types are Genetic (inherited) and Environmental (maternal) derived abnormalities. Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until then had gone undetected.

Teratology Links: Abnormal | [images/hcriticaldev.gif Critical Periods of Development]

Teratology

Now consider how different environmental effects during the pregnancy may influence outcomes.

Teratogen (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? [images/hcriticaldev.gif Critical Periods of Development])

Absolute risk the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)

Relative risk the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.

Mutagen a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.

Fetotoxicant is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).

Synergism when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.

Toxicogenomics the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.

Teratology Links: Abnormal Development | Genetic Abnormalities | Maternal Factors | [images/hcriticaldev.gif Critical Periods of Development] | Abnormal Development - Maternal | Abnormal Development - Fetal Alcohol Syndrome | Abnormal Development - Viral Infection | Rubella Virus | Abnormal Development - Hyperthermia | Abnormal Development - Drugs | Genetic Abnormalities | Abnormal Development - Trisomy 21 (Down Syndrome)

Australian Fetal Risk Categories

Different countries have their own authorities that classify the relative risk of drugs to the fetus. The Australian drug classification is carried out by the Australian Government Therapeutic Goods Authority (TGA) in the United States it is the . Within the authority the Australian Drug Evaluation Committee (ADEC) applies the following classification to drugs as well as indicating some therapeutic goods that have not been generally included in this categorisation. There is also an electronic 1999 PDF document Prescribing Medicines in Pregnancy (4th Edition) that is still available, but currently under revision. (More? Abnormal Development - Drugs)

Pregnancy Category A Have been taken by a large number of pregnant women and women of childbearing age without an increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

Pregnancy Category B1 Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

Pregnancy Category B2 Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

Pregnancy Category B3 Have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Pregnancy Category C Have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible.

Pregnancy Category D Have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects.

Pregnancy Category X Have such a high risk of causing permanent damage to the fetus that they should NOT be used in pregnancy or when there is a possibility of pregnancy.

Links: Abnormal Development - Drugs | Australian Fetal Risk Categories | USA FDA Fetal Risk Categories | Therapeutic Goods Authority | Australian Drug Evaluation Committee (ADEC) | Prescribing Medicines in Pregnancy | Appendix A: Therapeutic goods exempted from pregnancy classification |

Applied Embryology Links

The following are links to relevant notes pages that cover the key embryology concepts in this tutorial. These pages and their links will provide further detailed information.

Development Week by Week

Fetal Development

Birth | APGAR | Neonatal

Week 2 Abnormalities - Trophoblastic Disease | Placenta

Neural Abnormalities | Abnormal Development - Folic Acid and Neural Tube Defects | Week 3 - Neuralation

Cardiovascular Abnormalities

Twinning

Week 1 Blastocyst | [BGDlab3_5.htm BGD - Early Cell Division] | Molecular Development

Teratology Links

The following are links to relevant notes pages that cover the key teratology concepts in this tutorial. Links from these pages will provide further detailed information.

Abnormal Development | Genetic Abnormalities | Maternal Factors

[images/hcriticaldev.gif Critical Periods of Development]

Abnormal Development- Australian Statistics | Normal Development- Australian Statistics

Abnormal Development - Drugs

Genetic Abnormalities | Abnormal Development - Trisomy 21 (Down Syndrome)

Abnormal Development - Maternal

Abnormal Development - Fetal Alcohol Syndrome

Abnormal Development - Viral Infection | Rubella Virus

Abnormal Development - Hyperthermia

Additional Abnormal Development Links

Australian Statistics | Normal Development- Birth - Stillbirth and Perinatal Death | Abnormalities by SystemsPrenatal DiagnosisFetal Origins Hypothesis | Intrauterine Growth RetardationTwinningGenetic Abnormalities | Down Syndrome | Edwards SyndromeMaternal FactorsNeural Tube DefectsFetal Alcohol SyndromeSmokingChemicalDrugsRadiationHeavy MetalIodine DeficiencyViral Infection | Rubella | Parvovirus | Databases | NINDS Factsheets

External Abnormal Development Links

AIHW National Perinatal Statistics Unit Congenital malformations, Australia 1997

Victorian Birth Defects Register (VBDR) | VBDR brochure Food and Drug Administration (USA) Evaluating the Risks of Drug Exposure in Human Pregnancies

Centers for Disease Control and Prevention (CDC, USA) Pregnancy Risk Assessment Monitoring System (PRAMS) collects state-specific, population-based data on maternal attitudes and experiences before, during, and shortly after pregnancy.

Motherisk (Canada) Drugs, chemicals, radiation and herbal products in pregnancyOffice of Children's Health Protection (USA) Critical Periods in Development OCHP Paper Series on Children's Health and the Environment (2003) (PDF document)International Society for the Study of Trophoblastic Diseases Trophoblastic Diseases