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Teratogen Information

for Health Care Providers

Definition of teratogen:
A teratogen is an exposure (substance, organism or process) in pregnancy that has a harmful effect on the fetus. Teratogens can be diseases, medications, drugs and environmental exposures. There are many things that can influence the teratogenicity of exposures and these include the timing of the exposure during pregnancy, the dose a fetus is exposed to, a threshold above which you will see a teratogen have an effect, among other things. There are still many things we do not know about the teratogenicity of many exposures.

  • General themes to keep in mind in prenatal exposures context:
    • 50% of pregnancies are unplanned
    • 1/33 babies is born with a birth defect in North America
    • The whole picture needs to be taken into account. Ex: a woman on an antipsychotic drug known to be teratogenic: As with any therapeutic decision, one must weigh the risk of possible adverse outcomes if treatment is stopped with the benefits of treating that mother with a specific medication.
    • Many of the exposures listed below are associated with a risk of a fetus developing a birth defect. This does not mean that a fetus exposed to the specific teratogen will develop a birth defect
    • A harm reduction approach can be the most effective approach
    • This information does not take the place of medical care and advice from a health care provider

Below is a list of several teratogens that may have an effect on a fetus with some accompanying information. This list is far from exhaustive.

Mercury

  • Mercury exposure during pregnancy can lead to neurotoxicity and affect a baby’s brain development (OTIS 2011)
  • The fetus is much more sensitive to mercury neurotoxicity than the adult
  • EPA/FDA joint Consumer Advisory, 2004 (USA):
     - Do not eat: Shark, swordfish, King Mackerel, Tilefish
     - Do eat: up to 12oz/wk (two average meals) of a variety of fish and shellfish that are lower in mercury.
     - Fish commonly low in mercury: shrimp, canned light tuna, salmon, Pollock, catfish
  • For specific guidelines on fish consumption see section on resources below

Diabetes

  • Even well controlled diabetic women appear to have a greater incidence of major malformations than non-diabetic women
  • The risk of malformations does not vary over a broad range of glycemic control but rises sharply with very poor control
  • Diabetic women have a threefold excess risk over the general population of having a child with a congenital malformation (Harper 2010)
  • We still don’t know the mechanism responsible for this increase in congenital malformations
  • It appears there is no increased risk for women who have preclinical or gestational diabetes (Harper 2010)

Alcohol

  • Alcohol affects fetal development and is an established teratogen. Many things will influence the effects that alcohol will have on any given child: the quantity of alcohol consumed, the time period over which the alcohol was consumed, the mother's genetic make-up and her ability to metabolise (digest) alcohol, the baby's genetic make-up and their ability to metabolise alcohol, the mother's nutritional status (if she is eating well or has any deficiencies), etc.
  • Fetus is vulnerable throughout gestation therefore any intervention at any stage of pregnancy to reduce alcohol consumption is beneficial
  • Estimated prevalence of FASD in Canada and US: 1% of all births (Healthy Child Manitoba 2012)
  • FASD is underdiagnosed 
     -Lack of recognition of signs
     -Reluctance to label women as users
     -Unfamiliarity with diagnostic criteria among health care providers
     -89% of full and partial FAS diagnosed after age 6 years
  • Heavy drinking during pregnancy correlates with:
     ->30 years of age
     -Ethnic group / genetic background
     -Lower SES group
     -No prenatal care
     -Increased parity, previously affected child
     -Maternal undernutrition
     -History of previous alcohol problems
  • Alcohol exposure during pregnancy increases the risk of major malformations including brain damage, cardiac defects, ocular defects among several others
  • The safest choice for a pregnant or breastfeeding woman is to drink no alcohol at all
    Things that can help:
  • Documentation of alcohol consumption is very variable: If you don’t ask then you won’t find out! (Confirmed exposure is one of the diagnostic criteria)
  • Research has shown that early identification leads to interventions, services and improved outcomes
  • Growing up in a stable, caring home provides an important protective effect for children with FASD
     -Parent education and training is important
     -Explicit instruction of the children works best rather than through observation and process of abstracting
     -Multiple interventions are critical
     -Access of such interventions implemented through framework of available community services is best

SSRIs (Selective Serotonin Reuptake Inhibitor) for treatment of depression

  • Data is inconsistent but reassuring when looking at associations with major malformations, although some specific SSRIs have been linked to specific birth defects, ex: paroxetine has been linked to cardiac defects
  • There appears to be a risk of persistent pulmonary hypertension of the newborn with late pregnancy exposures (PPHN)
  • Very little data exists on neurobehavioral impacts on school aged children whose mothers took antidepressants during pregnancy

Maternal infections

  • The following table is a very brief summary indicating whether the infection stated is known to have a teratogenic effect or not on the fetus. Not all fetuses in the first column will suffer a teratogenic effect even if mom has this infection while pregnant. For details find a reputable source for further information.

Can have a teratogenic effect

No known teratogenic effect

May have a teratogenic effect

Cytomegalovirus (CMV)

Parvovirus

Herpes

Rubella (German measles)

Echovirus

Varicella (Chicken pox)

Coxsackie virus

Toxoplasmosis

HIV

Syphilis

Lyme

Influenza

Rubella or German measles (Boston Children’s Hospital 2014, Yukon H&SS 2014)

  • A mother who is infected with rubella in her first trimester has a high risk of passing the infection on to her fetus.
  • After the fourth month of pregnancy the fetus is less likely to be harmed by the virus
  • A fetus that is infected in the first trimester has a high risk of being born with congenital rubella syndrome, the symptoms of which can include: heart defects, eye defects, intellectual disability, growth retardation, and deafness
  • Prevention is the best defense against congenital rubella syndrome
  • Women who are not immune to rubella and are planning a pregnancy should be vaccinated with the MMR vaccine at least 28 days before becoming pregnant. The vaccine contains a live virus; therefore women who are pregnant should not be vaccinated.

Obesity

  • Two thirds of US pregnant women are overweight or obese
  • Obese women have a twofold increase for neural tube defects over the general population
  • Lower but present increased risk for cardiac anomalies and cleft palate
  • Risk increases as BMI increases
  • Underlying causation is still unknown
     -Difficulty of ultrasound detection, folate deficiency and glucose control are all important contributors
  • Obesity as a continuous exposure during pregnancy is an important contributor to childhood – adolescent – adult obesity cycle

Thalidomide (reference below)

  • Was used to treat symptoms in early pregnancy in the 1950s and early 1960s
  • Was found to cause severe birth defects, the most recognisable of which were severe limb defects

Resources on teratogens:

  • Local resources
    • Yukon’s Alcohol and Drug Services
      www.hss.gov.yk.ca/pdf/ads-brochure.pdf
      6118 6th Avenue
      Whitehorse, Yukon
      Business hours:

      From Whitehorse (8:00 am – 4:30 pm)    667-5404
      From communities, no charge (8:00 am – 4:30 pm) 1-855-667-5777 local 5404
      For after-hours support:
      From Whitehorse (4:30 pm – 8:00 am) 667-8473
      From communities, no charge (4:30 pm – 8:00 am) 1-855-667-5777 local 8473
      Fax:    867-667-8471
       
    • CASY – Congenital Anomalies Surveillance Yukon
      www.hss.gov.yk.ca/casy.php
      Business hours:
      Contact: Shannon Ryan
      Tuesday - Friday from 9:00 am – 3:30 pm 
      From Whitehorse 667-8563
      From communities, no charge 1-800-661-0408, ext. 8563
      CASY@gov.yk.ca

Online resources on teratogens

o MotheRisk: www.motherisk.org/women/index.jsp

  • Free Canadian resource (affiliated with OTIS)
  • provides information about the risk or safety of prescription and over-the-counter drugs, herbal products, chemicals, x-rays, chronic disease and infections during pregnancy and while breastfeeding for mothers and health care providers
  • Motherisk helplines (available 9am-5pm EST Mon-Fri)
    1-877-327-4636 Alcohol and Substance (available 9am-5pm in all Canadian time zones Mon-Fri)
    1-800-436-8477 Morning Sickness
    1-888-246-5840 HIV and HIV Treatment
    1-877-439-2744 Motherisk Helpline
    416-813-6780 Motherisk Helpline

o OTIS now known as MotherToBaby: www.mothertobaby.org/

  • Free resource
  • Info on medication and herbal supplement safety, drugs of abuse, alcohol, chemicals, illnesses and more during pregnancy and breastfeeding

o TERIS (Teratogen Information System): depts.washington.edu/terisweb/index.html

  • $150 annual charge for access
  • Info on effects of 1343 agents during pregnancy available
  • Includes Shepard's Catalog of Teratogenic Agents

o Reprotox:  www.reprotox.org/Default.aspx

  • $199 for one year, $349 for two years
  • Info on the effects of medications, chemicals, infections, and physical agents on pregnancy, reproduction, and development

• Online resources for fish consumption:

References:

The information in this resource was mainly compiled from information gathered at the Human Teratogens: Environmental Factors which Cause Birth Defects Conference held in April 2013 in Boston, Massachusetts and sponsored by the Genetics Unit, MassGeneral Hospital for Children and the Department of Continuing Education, Harvard Medical School unless otherwise specified.

Boston Children’s Hospital (2014) KidsMD Health Topics: Congenital Rubella retrieved from: www.childrenshospital.org/health-topics/conditions/congenital-rubella

Harper, Peter S. (2010) Practical Genetic Counselling, (7th edition), London, Edward Arnold

Healthy Child Manitoba (2012) Position Paper: Developing a National Prevalence Plan for FASD in Canada.

Otis (2011) Mother to Baby: Methylmercury and Pregnancy retrieved from: www.mothertobaby.org/files/methylmercury.pdf

Thalidomide Victims Association of Canada (2014) Thalidomide: The Canadian Tragedy retrieved from: http://www.thalidomide.ca/the-canadian-tragedy/

Yukon H&SS (2013) Yukon Immunization Program Manual retrieved from:  www.hss.gov.yk.ca/yipm.php

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