Whether
you have been exposed to a chest x-ray, an infection, a chemical, or a drug
during pregnancy you may find some comfort in the knowing that the
majority of such exposures do not result in birth defects or other risks
to the fetus. Nonetheless, you should be aware that most drugs cross the
placenta, and that there is little information about the first-trimester
effects for many drugs in human pregnancy.
Therefore make sure
to ask your doctor before starting a medication during pregnancy.
Also make sure to ask your doctor before you stop taking a medication
such as levothyroxine (Synthroid®, Levoxyl®)
or insulin, since untreated illnesses can have a harmful effect on your pregnancy.
Medications
and Potential Teratogens in Pregnancy
An agent that causes a birth
defect to occur at a higher rate than expected is called a teratogen. The
agent may be a chemical, a drug, an infection, radiation, or a maternal
condition such as diabetes. It is often difficult to determine
whether a bad outcome was related to a specific external agent since there may
be many factors responsible including a mother's
underlying illness.
Most teratogens produce their effect during
the sensitive 5th to the 10th week (embryonic period) of development when the major organs are forming .
For example, thalidomide causes limb defects when taken during the the 21st to
the 36th day after conception, and tetracyclines do not produce
their effects until after the first trimester when the skeletal
system begins to form bone. However, some drugs such as ethanol may produce harmful
effects on functional development throughout pregnancy.
Table 1. Gestational Age When Organ Systems are Most Sensitive to Birth Defects.
Developmental stage
Embryonic Stage
Fetal Stage
Gestational
Age (Months)
1
2
3
Gestational
Age (Weeks)
1
2
3
4
5
6
7
8
9
10
11
12
13
Postconception Age
(weeks)
0
0
1
2
3
4
5
6
7
8
9
10
11
Developing Organ(s)
CNS*
Heart
Ear
Eyes
Limbs
Lip
Palate
Teeth
External
genitals
Weight ounces
1.3
1.6
2
2.6
grams
35
45
58
73
Length
inches
0.16
0.39
0.63
0.91
1.22
1.61
2.13
2.64
centimeters
0.4
1
1.6
2.3
3.1
4.1
5.4
6.7
The red bars in the table show the gestational age
when different organ systems are most sensitive to major birth defects in
that organ system. The gray bars show the gestational age when different
organ systems are sensitive to functional defects and minor malformations.
Some agents show a
strong dose-response effect with less severe birth defects occurring at
lower doses. For other agents such as radiation there appears to be a minimum threshold
level (5 rads) below which exposure to the agent is not believed to cause birth
defects.
Developmental
Stage Calculator Find out how far along you were in
pregnancy when
you were exposed to an agent.
The Food and Drug
Administration (FDA) created the following rating system
in 1979 to categorize the potential risk
to the fetus for a given drug.
Category A: Controlled
human studies have demonstrated no fetal risk
Category B: Animal
studies indicate no fetal risk, but no human studies OR adverse effects
in animals , but not in well- controlled human studies
Category C: No adequate
human or animal studies, OR adverse fetal effects in animal studies, but
no available human data.
Category D: Evidence
of fetal risk, but benefits outweigh risks.
Category X: Evidence
of fetal risk. Risks outweigh any benefits.
Unfortunately this system oversimplifies the issues relevant
to prescribing a medication to a pregnant patient. For example,
the
FDA system does not adequately address
the risk of disease versus no treatment, nor is it easy to apply to combination
prescription drugs with many active ingredients and the potential for drug
interactions.In
addition
when
using the FDA pregnancy risk categories there is a tendency to assume that a
category B drug is safer for human use than a category C drug when there may be no
human studies available to support the assumption.
Despite its shortcomings the FDA rating system (and others like it) will most
likely continue to be used as a rapid "first screen"
on the
the potential risk to the fetus for a
given drug.
Table 2 below is a list of some medications that appear to
have demonstrated no significant fetal
risk in human studies [1-16]
Table 2. Some Medications
Considered Safe for Use During Pregnancy
Condition
Medication
Asthma
Budesonide inhaled or nasal spray (Pulmicort®,
Rhinocort ®)
Bladder infection (UTI)
Nitrofurantoin (Macrobid®)
- Avoid in patients with possible G6PD deficiency
1. Schatz M, Zeiger RS, Harden K, Hoffman CC,
Chilingar L, Petitti D. The safety of asthma and allergy medications during
pregnancy. J Allergy Clin Immunol. 1997 100:301-6. 1997.
PubMed
2.
Briggs GG, Freeman RK, Yaffee FJ. Drugs in Pregnancy and Lactation:
Reference Guide to Fetal and Neonatal Risk. 7th ed. Baltimore: Williams &
Wilkins; 2005.
3. Martinez-Frias ML, Rodriguez-Pinilla E.
Epidemiologic analysis of prenatal exposure to cough medicines containing
dextromethorphan: no evidence of human teratogenicity. Teratology, 63:38-41.
2001
PubMed
4. Einarson A, Lyszkiewicz D, Koren G. The
safety of dextromethorphan in pregnancy : results of a controlled study. Chest.
119:466-9. 2001
PubMed
5. Shaw GM, Todoroff K, Velie EM, Lammer EJ:
Maternal illness, including fever, and medication use as risk factors for neural
tube defects. Teratology 57:1-7, 1998.
PubMed
6. Aselton P, Jick H, Milunsky A, Hunter JR,
Stergachis A. First-trimester drug use and congenital disorders. Obstet Gynecol.
65:451-5. 1985.
PubMed
11.
Czeizel AE,Use of cephalosporins during pregnancy and in the presence of
congenital abnormalities: a population-based, case-control study.Am J Obstet Gynecol. 2001 May;184(6):1289-96.
PMID: 11349204
12.
Czeizel AE, et al. A population-based case-control teratologic study of oral
erythromycin treatment during pregnancy.Reprod Toxicol. 1999 Nov-Dec;13(6):531-6.
PMID: 10613401
13.
Nørgård B,Population-based case control study of the safety of sulfasalazine
use during pregnancy.
Aliment Pharmacol Ther. 2001 Apr;15(4):483-6.
PMID: 11284776
14.
Czeizel AE and Vargha P.,A case-control study of congenital abnormality and
dimenhydrinate usage during pregnancy.
Arch Gynecol Obstet. 2005 Feb;271(2):113-8. Epub 2004 Oct 23.
PMID: 15517327
15.
Rockenbauer M,et al. Recall bias in a case-control surveillance system on
the use of medicine during pregnancy.
Epidemiology. 2001 Jul;12(4):461-6.
PMID: 11416783
16.
Czeizel AE,et al.No teratogenic effect after clotrimazole therapy during
pregnancy.
Epidemiology. 1999 Jul;10(4):437-40.
PMID: 10401880
Created: 12/18/2002 Mark A Curran, M.D. Update: 11/2/2004
Update: 8/24/2006
Update: 12/4/2007
Whether
you have been exposed to a chest x-ray, an infection, a chemical, or a drug
during pregnancy you may find some comfort in the knowing that the
majority of such exposures do not result in birth defects or other risks
to the fetus. Nonetheless, you should be aware that most drugs cross the
placenta, and that there is little information about the first-trimester
effects for many drugs in human pregnancy.
Therefore make sure
to ask your doctor before starting a medication during pregnancy.
Also make sure to ask your doctor before you stop taking a medication
such as levothyroxine (Synthroid®, Levoxyl®)
or insulin, since untreated illnesses can have a harmful effect on your pregnancy. 
