TERATOGENIC PREGNANCY

Mochamad Maroef Fakultas Kedokteran Universitas Muhamadiyah Malang

A teratogen is an agent that can produce a permanent alteration of structure or function in an organism exposed during embyronic or fetal life.

There is no such thing as a teratogenic agent.

Many agents can produce a teratogenic effect under some circumstances.

Factors That Influence Teratogenicity

Nature Dose Route
Frequency

of the agent

of exposure Duration of exposure

Factors That Influence Teratogenicity

Gestational

timing Concurrent exposures Concurrent illness Genetic susceptibility

Mother Fetus

Principal Mechanisms of Teratogenesis

Cell

growth or proliferation Cell death Cell migration Cell and tissue interactions Disruptions

Mutagenesis
Principal

mechanisms

Gene mutation Chromosomal abnormalies

Before

or after conception Males and females both affected

Birth Defects Caused By Teratogenic Exposures Are Preventable.

Prevention of Birth Defects Caused by Teratogenic Exposures is an Important Public Health Problem.

Public Health Concerns

Prevention

of known teratogenic exposures

Alcohol Infectious diseases Isotretinoin, thalidomide

Public Health Concerns

Occupational

exposures Environmental exposures Drugs of abuse Medications

Medications
Over-the-counter

medicines Herbals and dietary supplements Prescription drugs

Medications
Frequently

used by pregnant women Biologically active Taken systemically Taken in high doses Information about teratogenicity very limited

Lack of Knowledge Is a Problem

Exposures that really do pose a risk remain unrecognized Pregnant women may not receive treatments that benefit their own health or that of the fetus

Lack of Knowledge Is a Problem

Labeling

tends to provoke anxiety, often unnecessarily Women may be advised or choose to terminate pregnancy to avoid risk

Public Health Priorities

teratogenic risks of important exposures Prevention of exposures that are known to be teratogenic Recognition of pregnancies at high risk
Characterizing

7 wks pc

Effects on Development
Preconception

(the stage is set):

Intergenerational Effects
Genetic Cultural Non-genetic Familial Intergenerational Effects

Stress Diet Drugs, environmental chemicals

Effects on Development
Conception

to pre-birth

Prenatal Effects
Conception, zygote (0 to 2 weeks), embryo (2 weeks to 2 months), fetus (2 months to birth)
50% of zygotes are miscarried (mother is unaware) The zygote, embryo, and fetus are susceptible to a variety of teratogens (ionizing radiation, alcohol, drugs, hormones, chemicals, and perhaps the subtle effects of non-ionizing radiation).

Non Ionizing Radiation

These are electromagnetic waves (microwave, radio, ELF emitted from powerlines). They are non ionizing because they do not knock out electrons from atoms. At high intensities they can heat up things (e.g., microwave ovens). At low intensities they can CAUSE BIOLOGICAL EFFECTS not by heating tissue, but instead by modifying gene expression and interfering with cellular communication. These effects Have been demonstrated to occur within intensity and frequency windows (Electromagnetic Biology and Medicine, 25: 217225, 2006).

How safe are cell phones?

Prenatal and Postnatal Exposure to Cell Phone Use and Behavioral Problems in Children Divan, Kheifets, Obel, & Olsen 2008

Neurons and glial cells (astrocytes) were exposed to non-ionizing Cell-phone radiation (GSM 800 1900 MHz) for 2 hours.

Zhao, Zou, & Knapp (2007) Neuroscience Letters, V 412, 34-38

Birth Defects
Incidence

High

Risk Pregnancies

Teratogens
Epigenetic

Period

Other Concerns
Poverty

Child

Abuse (ex. Kenneth) Substance Abuse Fetal Alcohol Syndrome*

Fetal Alcohol Syndrome

Leading cause of birth defects in the U.S. Oldest known cause of developmental disabilities Bible (Judges 13:3-4) Behold now, thou art barren and barest not; but thou shalt conceive and bear son. Now therefore beware, I pray thee, and drink not wine nor strong drink Estimated Alcohol use among women ages 18-44
50% / 11% Binge (4 or more drinks on any occasion)

Why, if most people understand the alcohol is harmful to a embryo or fetus, is FAS so prevalent?

Pre-embryonic period (Weeks 1 + 2)

Pre-embryonic period (Weeks 1 + 2)

Embryonic Period
Week:

- CNS 5 - Heart 8 - Internal Organs

Embryo

to Fetus

Fetal Period
2nd

- 6th Month

24

weeks vs. 28 weeks - 9th Month

6th

Birth

Health Habits During Pregnancy

Drugs,

Alcohol, Tobacco Nutrition

Mother directly influences the nutritional status of her baby Eating for two
Exercise

Moderate physical activity is recommended

Exercise and Pregnancy

Clapp (Western Reserve University) 1998 Sustained exercise

3x / week / 20 minutes / session

Findings:
No effect on conception No effect on increase in spontaneous abortion No increased incidence of anomalies 80% gave birth on or before their due dates compared to 50 percent of control group (no prem) 70% who delivered vaginally completed 3rd stage labor in less than 4 hours compared to 30% control 1/3 fewer cesareans Conclusion Exercise is good, but check with Doctor first (consider lifestyle, exercise history, and overall health)

Prenatal Diagnostic Procedures

Ultrasound Amniocentesis Chorionic Villus Sampling (CVS) Alpha-fetoprotein Glucose Tolerance Test

What can go wrong

Heredity Malnutrition Drugs Maternal Infections / Diseases Trauma

Chromosomal Anomalies
Usually

lead to intellectual disability *Most common Trisomy 21 Down Syndrome

THE

END