TERATOGENIC - PREGNANCY

Mochamad Ma’roef

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.

Nature of the agent

Factors That Influence Teratogenicity

Dose Route Frequency of exposure Duration of exposure

Gestational timing

Factors That Influence Teratogenicity

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.

Prevention of known teratogenic exposures

Public Health Concerns

– Alcohol – Infectious diseases– Isotretinoin, thalidomide

Occupational exposures

Public Health Concerns

Environmental exposures Drugs of abuse Medications

Over-the-counter medicines

Medications

Herbals and dietary supplements

Prescription drugs

Frequently used by pregnant women

Medications

Biologically active Taken systemically Taken in high doses Information about

teratogenicity very limited

Pregnant women may not receive treatments that benefit their own health or that of the fetus

Lack of Knowledge Is a Problem

Exposures that really do pose a risk remain unrecognized

Women may be advised or choose to terminate pregnancy to avoid risk

Lack of Knowledge Is a Problem

Labeling tends to provoke anxiety, often unnecessarily

Characterizing teratogenic risks of important exposures

Public Health Priorities

Prevention of exposures that are known to be teratogenic

Recognition of pregnancies at high risk

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 effectsHave been demonstrated to occur within intensity and frequency ‘windows’ (Electromagnetic Biology and Medicine, 25: 217–225, 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-ionizingCell-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: 4 - CNS 5 - Heart 8 - Internal Organs

Embryo to Fetus

Fetal Period

2nd - 6th Month

24 weeks vs. 28 weeks

6th - 9th Month

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