2010 BGD Tutorial - Applied Embryology and Teratology: Difference between revisions

Revision as of 12:49, 25 January 2010

Introduction

This Medicine Phase 2 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.

Due to time limitations, only a brief coverage can be given of any one topic. You should return here and later work through the linked online resources for a more detailed description and understanding of these issues.

The same content is covered in the previous online 2008 Tutorial - Applied Embryology and Teratology (Royal Hospital for Women)

Objectives

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 and infections.

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

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

Applied Embryology

This data Australia's mothers and babies 2007 summarised below is provided to help you as a clinician or researcher understand the current trends in reproductive medicine within Australia.

The information is based upon data from the publication Laws P & Sullivan EA 2009. Australia’s mothers and babies 2007. Perinatal statistics series no. 23. Cat. no. PER 48. Sydney: AIHW National Perinatal Statistics Unit and is provided for educational purposes only. The original full publication is available online from AIHW Perinatal statistics series no. 23.

Mothers

Australian Births by Year

289,496 women gave birth resulting in a total of 294,205 births
- increase of 4.3% from 2006, and 14.4% increase since 2004
2,177 were fetal deaths
29.9 years was the maternal mean age in 2007
- compared with 28.9 years in 1998
41.6% of mothers had their first baby and 33.5% had their second baby
10,883 women were Aboriginal or Torres Strait Islander (3.8% of all women who gave birth)
- 39.5% of all mothers in the Northern Territory
- 25.2 years was the average age of women who gave birth

Assisted reproduction technology

3.1% women received ART treatment
- ranging from 1.4% in the Australian Capital Territory to 3.7% in Tasmania
34.1 years was the average age of women who received ART
62.7% of mothers who received ART treatment were having their first baby and 37.3% had given birth previously

Smoking during pregnancy

16.6% of women smoked during pregnancy (similar proportion over the previous five years)

Preterm birth

7.4% of all mothers (less than 37 completed weeks of gestation)
- 38.8 weeks is the average duration of pregnancy

Multiple pregnancy

4,634 multiple pregnancies (1.6% of all mothers) increasing due to the increased use of ART
- 4,558 twin pregnancies, 76 triplet pregnancies and no quadruplet pregnancies

Presentation at birth

94.6% cephalic (any part vertex, face, or brow of the fetal head)
4.0% breech (buttocks or feet)

Method of birth

57.9% vaginal births
- 11.2% had an instrumental vaginal delivery (forceps or vacuum extraction)
30.9% caesarean section births
- 21.1% in 1998, 30.8% in 2006, rate recently stable
- 83.3% of these were repeat caesarean sections

Pre-existing and pregnancy-related medical conditions

epilepsy, diabetes mellitus and hypertension, antepartum haemorrhage, gestational diabetes, cord prolapse and retained placenta, pregnancy-induced hypertension, fetal distress in labour and post-partum haemorrhage rates

Postnatal length of stay

2.0 days non-instrumental vaginal birth
3.0 days vacuum extraction delivery
4.0 days caesarean section or forceps delivery

Babies

292,027 live births and 2,177 fetal deaths
- stillbirth rate of 7.4 per 1,000 births
most births occurred in March, August and October
105.6 sex ratio (number of male per 100 female liveborn babies)

Gestational age

90.9% term (37–41 weeks gestation)
8.1% were preterm and 33.2 weeks was the mean gestational age for all preterm births
- Preterm births were classified groups of 20–27 weeks, 28–31 weeks and 32–36 weeks

Birthweight

92.1% of liveborn babies had a birthweight in the range 2,500–4,499 grams
- average birthweight was 3,374 grams
17,976 (6.2%) low birthweight (weighing less than 2,500 grams)
2,956 (1.0%) very low birthweight (weighing less than 1,500 grams)
1,288 (0.4%) extremely low birthweight (weighing less than 1,000 grams)

Apgar scores - 1.4% of liveborn babies had a low Apgar score (between 0 and 6) at 5 minutes

Special care nurseries or neonatal intensive care units - 14.5% of liveborn babies were admitted to an SCN or NICU

Perinatal mortality

2,177 fetal deaths (7.4 per 1,000 births)
- fetal deaths are if the birthweight is at least 400 grams or the gestational age is 20 weeks or more
846 neonatal deaths (2.9 per 1,000 live births)
- neonatal deaths are those occurring in live births up to 28 completed days after birth

3,024 perinatal deaths
- perinatal death includes birthweight of at least 400 grams or, where birthweight is unknown, a gestational age of at least 20 weeks
23.5% congenital abnormalities (anomalies)
13.8% maternal conditions
12.6% unexplained antepartum death

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

(Data from the Victorian Perinatal Data Collection Unit in Victoria between 2003-2004)

Hypospadias (More? Genital Abnormalities - Hypospadia)
Obstructive Defects of the Renal Pelvis (More? Urogenital Abnormalities)
Ventricular Septal Defect (More? Cardiovascular Abnormalities - Ventricular Septal Defect)
Congenital Dislocated Hip (More? Musculoskelal Abnormalities - Congenital Dislocation of the Hip (CDH))
Trisomy 21 or Down syndrome - (More? Abnormal Development - Trisomy 21)
Hydrocephalus (More? Neural Abnormalities - Hydrocephalus)
Cleft Palate (More? Head Abnormalities)
Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued (More? Abnormal Development - Trisomy 18)
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)
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 3 major types are Genetic (inherited), Environmental (maternal) derived and Unknown (not determined or known) abnormalities. Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until pregnancy 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.

Australian Drug Categories

Legal drugs are classified, usually by each country's appropriate regulatory body, on the safety of drugs during pregnancy. In Australia, the Therapeutic Goods Authority has classes (A, B1, B2, B3, C, D and X) to define their safety. In the USA, drugs are classified by the Food and Drug Administration (FDA) into classes (A, B, C, D, and X) to define their safety.

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.

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

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 Systems Prenatal Diagnosis Fetal Origins Hypothesis | Intrauterine Growth Retardation Twinning Genetic Abnormalities | Down Syndrome | Edwards Syndrome Maternal Factors Neural Tube Defects Fetal Alcohol Syndrome Smoking Chemical Drugs Radiation Heavy Metal Iodine Deficiency Viral 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

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

Cite this page: Hill, M.A. (2024, May 4) Embryology 2010 BGD Tutorial - Applied Embryology and Teratology. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2010_BGD_Tutorial_-_Applied_Embryology_and_Teratology

What Links Here?

@@ Line 78: / Line 78: @@
 ====Gestational age====
 * '''90.9%''' term (37–41 weeks gestation)
-*  8.1% were preterm
+*  8.1% were preterm and '''33.2 weeks''' was the mean gestational age for all preterm births
-* '''33.2 weeks''' was the mean gestational age for all preterm births
 ** Preterm births were classified groups of 20–27 weeks, 28–31 weeks and 32–36 weeks