This page introduces the possible effects of maternal use of legal drugs (therapeutic chemicals/agents) on development. In some cases these drugs are prescribed to treat pre-existing or pregnancy related maternal medical conditions. In all cases, a discussion with a medical practioner should be had prior to any reproductive decision. |
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The placenta and fetal tissues may deal with drugs differently from adult target tissues. In particular, drugs are "cleared", metabolised and excreted, at a different rate in both the fetus and in newborn infants. In general there is a much lower rate of clearance (More? Infant Drug Clearance Rate).
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 (More? Australian Fetal Risk Categories). 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 (More? FDA Fetal Risk Categories).
There are also a growing range of herbal drugs which may not have undergone this type of study and classification (More? Herbal Drugs)
The importance of careful evaluation of drugs can be historically demonstrated with the teratogenic effects of thalidomide, a drug given to treat "morning sickness" in the first trimester of pregnancy, which affected musculoskeletal development. (More? thalidomide) This current page also gives examples of some other current drugs which have been shown to impact on development.
Links: Introduction | Some Recent Findings | Australian Fetal Risk Categories | USA FDA Fetal Risk Categories | Canadian HPFB Fetal Risk Categories | Infant Drug Clearance Rate | Teratology | Epilepsy | Antidepressant Drugs | Bipolar Drugs | Acne Drugs | Herbal Drugs | USA Top 200 Prescriptions | Australian NHMRC Recommendations | Maternal Derived Abnormalities | WWW Links | References | Glossary
Effects of in utero antiepileptic drug exposure. Meador KJ. Epilepsy Curr. 2008 Nov-Dec;8(6):143-7.
"Recent studies demonstrate an increased teratogenic risk for valproate and a probable increased risk for phenobarbital. Carbamazepine and lamotrigine appear relatively safe; however, results are inconclusive concerning a specific risk for cleft lip/palate for both drugs as well as a dose-dependent effect for malformations associated with lamotrigine. Data regarding teratogenic risks for other antiepileptic drugs are inadequate. Additional studies are needed to delineate further the risks for all antiepileptic drugs and determine the underlying mechanisms."
Noorlander CW, Ververs FF, Nikkels PG, van Echteld CJ, Visser GH, Smidt MP. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE. 2008 Jul 23;3(7):e2782. (More? Heart Development)
"Women are at great risk for mood and anxiety disorders during their childbearing years and may become pregnant while taking antidepressant drugs. ....These results indicate that prenatal fluoxetine exposure affects fetal development, resulting in cardiomyopathy and a higher vulnerability to affective disorders in a dose-dependent manner."
Chen J, Han M, Manisastry SM, Trotta P, Serrano MC, Huhta JC, Linask KK. Molecular effects of lithium exposure during mouse and chick gastrulation and subsequent valve dysmorphogenesis. Birth Defects Res A Clin Mol Teratol. 2008 Apr 16. (More? Bipolar Drugs)
"The Wnt/beta-catenin signaling in prechordal plate cells is normally repressed by Wnt antagonists and Hex is up-regulated. The antagonism occurring at the receptor level is bypassed by Li exposure by its intracellular inactivation of GSK-3 directly to augment Wnt signaling."
A recent study on Danish data has shown that selective serotonin reuptake inhibitors (SSRIs) taken during early pregnancy may also increase the risk of having a child with a congenital malformation (More? Antidepressant Drugs - SSRI)
Australian drug classification is carried out by the Australian Government Therapeutic Goods Authority (TGA). Within the authoority the Australian Drug Evaluation Committee (ADEC) applies the following classification to drugs and there are some therapeutic goods that have not been generally included in this categorisation. There is also an electronic 1999 PDF document Prescribing Medicines in Pregnancy (4th Edition) that is still available, but currently under revision.
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.
Links: Therapeutic Goods Authority | Australian Drug Evaluation Committee (ADEC) | Prescribing Medicines in Pregnancy | Appendix A: Therapeutic goods exempted from pregnancy classification |
In the United States the government Food and Drug Administration (FDA) has established the following drug classification.
Category A Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester, there is no evidence of a risk in later trimesters, and the possibility of fetal harm appears remote.
Category B Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal reproduction studies have shown on adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of risk in later trimesters).
Category C Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
Category D There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (eg, if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Category X Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
(More? USA Top 200 Prescriptions)
In Canada the Health Products and Food Branch (HPFB) provides information on health-related risks and benefits of health products and food.
Infants have a much lower drug clearance rate compared to adults (see table below). Glomerular filtration rates (GFR) for newborn term infants are within days about one third of adult values.
Post-conceptual Age (weeks) |
Clearance of Drug (percentage of adults) |
24-28 |
5% |
28-34 |
10% |
34-40 |
33% |
40-44 |
50% |
44-68 |
66% |
> 68 |
100% |
(Data from Drug Safety in Lactation)
Some teratological terms used to describe 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? 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.
Nearly all of the original established antiepileptic drugs (AEDs) have potential teratogenic effects, either directly or from their metabolically derived products.
Valproic acid (dipropylacetic acid) is used in humans as an anticonvulsant or as a mood stabilizer and has potent teratogenic effects. Malformations include: Craniofacial abnormalities (small/broad nose, small/abnormal ears, long/flat philtrum, thin vermillion border, epicanthal folds hypertelorism, high/broad forehead, micro/retrognathia, bifrontal narrowing), Organ malformations (musculoskeletal system, skin and appendages, cardiac , genital, brain) , developmental deficits (growth retardation, hypotonia, mental retardation) (modified from Costa etal., 2004).
A recent Australian study of rates for major congenital malformations from the Australian Registry using drug monotherapy showed: Valproate = 16.8%, Carbamazepine = 3.8%, Lamotrigine = 0%, Phenytoin = 5.9%. Furthermore valproate also had dose effects 34.5% malformations >1,400 mg/day vs 5.5% at ≤1,400 mg/day (Vajda etal., 2006).
Benzodiazepines modulate the action of inhibitory neurotransmitter GABA at their receptor and may effect developing neural development/differentiation.
References:
Effects of in utero antiepileptic drug exposure. Meador KJ. Epilepsy Curr. 2008 Nov-Dec;8(6):143-7.
Foetal malformations and seizure control: 52 months data of the Australian Pregnancy Registry.Vajda FJ, Hitchcock A, Graham J, Solinas C, O'Brien TJ, Lander CM, Eadie MJ. Eur J Neurol. 2006 Jun;13(6):645-54.
Costa LG, Steardo L, Cuomo V. Structural effects and neurofunctional sequelae of developmental exposure to psychotherapeutic drugs: experimental and clinical aspects. Pharmacol Rev. 2004 Mar;56(1):103-47.
Palmieri C, Canger R. Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing? CNS Drugs. 2002;16(11):755-64.
Yerby MS. The use of anticonvulsants during pregnancy. Semin Perinatol. 2001 Jun;25(3):153-8.
Selective serotonin reuptake inhibitors (SSRIs) are drugs are used in the treatment of depression, mood and anxiety disorders. This class of drugs occurs under many commercial names and includes: tricyclics, atypical antidepressant, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and several novel antidepressants. Over the last few years several studies have reported the teratogenic effects of members of this class of drugs, including hormonal disruption (hypothalamic-pituitary-adrenal axes), heart defects (More? Heart Development) and a range of other congenital malformations.
References:
Noorlander CW, Ververs FF, Nikkels PG, van Echteld CJ, Visser GH, Smidt MP. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE. 2008 Jul 23;3(7):e2782.
Selective serotonin reuptake inhibitors (SSRIs) these drugs are used in the treatment of depression and a recent study on Danish data has shown that SSRIs taken during early pregnancy may also increase the risk of having a child with a congenital malformation. Some examples include: citalopram (brand name of Celexa), fluoxetine (brand name of Prozac), paroxetine (brand name of Paxil) and sertraline (brand name of Zoloft). (More? Australia healthinsite - SSRIs | BMJ - Editorial)
Wogelius P, Norgaard M, Gislum M, Pedersen L, Munk E, Mortensen PB, Lipworth L, Sorensen HT. Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Congenital Malformations. Epidemiology. 2006 Oct 4;
"The 150,780 women with no SSRI prescriptions gave birth to 5112 (3.4%) children with congenital malformations. The 1051 women with SSRI prescriptions any time during early pregnancy gave birth to 51 (4.9%) children with congenital malformations. The corresponding adjusted relative risk (aRRs) was 1.34 (95% confidence interval = 1.00-1.79). The 453 women with prescriptions during the second or third month of pregnancy gave birth to 31 (6.8%) children with congenital malformations."
Morrison JL, Riggs KW, Rurak DW. Fluoxetine during pregnancy: impact on fetal development. Reprod Fertil Dev. 2005;17(6):641-50. Review.
Lithium (Li, atomic number 3) is an alkali metal used in a salt form to treat people with bipolar disorder and associated episodes of mania (frenzied, abnormally excited mood) and therefore acts as an antimanic agents. Lithium has been associated with fetal cardiac teratogenicity possibly by affecting Wnt/beta-catenin signaling. Lithium as a metal can also be found in our environment (More? Abnormal Development - Metals).
References:
Chen J, Han M, Manisastry SM, Trotta P, Serrano MC, Huhta JC, Linask KK. Molecular effects of lithium exposure during mouse and chick gastrulation and subsequent valve dysmorphogenesis. Birth Defects Res A Clin Mol Teratol. 2008 Apr 16.
Manisastry SM, Han M, Linask KK. Early temporal-specific responses and differential sensitivity to lithium and Wnt-3A exposure during heart development. Dev Dyn. 2006 Aug;235(8):2160-74.
Acetaminophen
"Acetaminophen (APAP) is the most common drug overdose in pregnancy. Available data regarding APAP overdose in pregnancy is limited to case reports and a small prospective case series. APAP has been demonstrated to cross the placenta and in toxic doses may harm the fetal and maternal hepatocytes. Fetal hepatocytes metabolize APAP into both active and toxic metabolites. These toxic metabolites may cause fetal hepatic necrosis. N-acetylcysteine (NAC) has also been demonstrated to cross the placenta and may bind toxic metabolites in both the mother and the fetus."
(Text: Wilkes JM, Clark LE, Herrera JL. Acetaminophen overdose in pregnancy. South Med J. 2005 Nov;98(11):1118-22. Review.)
USA Prescription Listing Acetaminophen/Codeine
In 1982 a treatment for severe acne (cystic acne) which contains isotretinoin (commercial name: Accutane, by Roche) was identified as a teratogen. Isotretinoin is a retinoid or vitamin A derivative. As retinoids have a role in differentiation of many different tissues, maternal treatment with these drugs can impact severely on normal embryonic development.
Over time there have been a number of different risk management approaches used for this drug, the current one (March 2006) is the manufacturers of isotretinoin programme called iPLEDGE.
"iPLEDGE is a comprehensive distribution system that includes mandatory registration of patients, healthcare providers, pharmacies, and wholesalers. It allows real-time linkage of pregnancy-test results for verification prior to the dispensing of isotretinoin."
Overview of History of Isotretinoin (Accutane) Risk Management Approaches
(Table from: What Is the Best Approach to Reducing Birth Defects Associated with Isotretinoin? Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. PLoS Medicine Vol. 3, No. 11, e483 doi:10.1371/journal.pmed.0030483)
Honein MA, Lindstrom JA, Kweder SL. Can we ensure the safe use of known human teratogens?: The iPLEDGE test case. Drug Saf. 2007;30(1):5-15. Review.
Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. What is the best approach to reducing birth defects associated with isotretinoin? PLoS Med. 2006 Nov;3(11):e483. PLOS article link
Links: FDA USA - warning about online buying Accutane | iPLEDGE Program | Medline Plus - Acne | Medline Plus - isotretinoin | niams NIAMS USA - Acne | CBS 2003 News Link
The following herbal drugs have been used for a number of different maternal conditions: Ginkgo Biloba, Kava (Piper methysticum), St. John's wort (Hypericum perforatum), Tian Ma (Gastrodia elata), Valerian (Valeriana officinalis). In some cases very little is known about the potential teratogenic effects of these drugs (More? Herbal Drugs).
HSTAT St. John's Wort | Appendix II: Side Effects, Adverse Effects, Precautions, and Warnings "The safety of using hypericum during pregnancy or lactation has not been proven so it should be avoided." "St. John's wort induces the CYP 450 3A4 metabolic pathway which is also used by many prescription drugs used to prevent conditions (transplant rejection or pregnancy oral contraceptives), health care providers should alert patients about these potential drug interactions."
(More? Herbal Drugs)
In the USA, drugs are classified by the Federal Drug Authority (FDA) into classes (A, B, C, D, and X) to define the safety of drugs during pregnancy.
Below is a table of the 1998 USA Prescriptions (*ranking based On More Than 2.4 Billion US Prescriptions), note that many drugs are not approved for use in Australia and may appear under different commercial names.
This Drug List is also available alphabetically sorted locally and on the www.rxlist.com.
|
Brand Name |
Manufacturer |
Generic Name |
|
Premarin |
Wyeth-Ayerst |
|
|
Synthroid |
Knoll |
|
|
Trimox |
Apothecon |
|
|
Hydrocodone w/APAP |
Watson |
|
|
Prozac |
Lilly |
|
|
Prilosec |
Astra |
|
|
Zithromax |
Pfizer |
|
|
Lipitor |
Parke-Davis |
|
|
Norvasc |
Pfizer |
|
|
Claritin |
Schering |
|
|
Lanoxin |
Glaxo Wellcome |
|
|
Zoloft |
Pfizer |
|
|
Albuterol Aerosol |
Warrick |
|
|
Paxil |
SK Beecham |
|
|
Amoxicillin |
Teva Pharm |
|
|
Prempro |
Wyeth-Ayerst |
|
|
Zestril |
Zeneca |
|
|
Vasotec |
Merck |
|
|
Augmentin |
SK Beecham |
|
|
Cephalexin |
Teva Pharm |
|
|
Zocor |
Merck |
|
|
Glucophage |
B-M Squibb |
|
|
Coumadin |
Dupont |
|
|
Acetaminophen/Codeine |
Teva Pharm |
|
|
lbuprofen |
Greenstone |
|
|
Furosemide |
Mylan |
|
|
Cipro |
Bayer Pharm |
|
|
Trimethoprim/Sulfa |
Teva Pharm |
|
|
Cardizem CD |
Hoech Mar R |
|
|
Pravachol |
B-M Squibb |
|
|
Biaxin |
Abbott |
|
|
Propoxyphene N/APAP |
Mylan |
|
|
Levoxyl |
Jones Pharma |
|
|
Procardia XL |
Pfizer |
|
|
Prednisone |
Schein |
|
|
Prevacid |
Tap Pharm |
|
|
Ultram |
McNeil |
|
|
Alprazolam |
Greenstone |
|
|
Ambien |
Searle |
|
|
Amoxil |
SK Beecham |
|
|
Accupril |
Parke-Davis |
|
|
K-Dur-20 |
Schering |
|
|
Glucotrol XL |
Pfizer |
|
|
Hydrocodone w/APAP |
Mallinckrodt |
|
|
Triamterene/HCTZ |
Geneva |
|
|
Ortho Tri-Cyclen |
Ortho Pharm |
|
|
Lotensin |
Novartis |
|
|
Prinivil |
Merck |
|
|
Hytrin |
Abbott |
|
|
Veetids |
Apothecon |
|
|
Propoxyphene N/APAP |
Teva Pharm |
|
|
Relafen |
SK Beecham |
|
|
Zyrtec |
Pfizer |
|
|
Cardura |
Pfizer |
|
|
Claritin D 12HR |
Schering |
|
|
Allegra |
Hoech Mar R |
|
|
Pepcid |
Merck |
|
|
Triphasil |
Wyeth-Ayerst |
|
|
Humulin N |
Lilly |
|
|
Dilantin |
Parke-Davis |
|
|
Ortho-Novum 7/7/7 |
Ortho Pharm |
|
|
Atenolol |
Geneva |
|
|
Toprol-XL |
Astra |
|
|
Flonase |
Glaxo Wellcome |
|
|
Lorazepam |
Mylan |
|
|
Amitriptyline |
Mylan |
|
|
Cefzil |
B-M Squibb |
|
|
Depakote |
Abbott |
|
|
Imdur |
Schering |
|
|
Viagra |
Pfizer |
|
|
Diflucan |
Pfizer |
|
|
Propulsid |
Janssen |
|
|
Alprazolam |
Geneva |
|
|
Triamterene/HCTZ |
Mylan |
|
|
Atenolol |
Mylan |
|
|
Fosamax |
Merck |
|
|
Adalat CC |
Bayer Pharm |
|
|
Cozaar |
Merck |
|
|
Atenolol |
ESI Lederle |
|
|
Lescol |
Novartis |
|
|
Hydrocodone w/APAP |
Qualitest |
|
|
Albuterol Neb Soln |
Warrick |
|
|
Glyburide |
Copley |
|
|
Wellbutrin SR |
Glaxo Well |
|
|
Vancenase AQ DS |
Schering |
|
|
Zithromax Susp |
Pfizer |
|
|
Clonazepam |
Teva Pharm |
|
|
Naproxen |
Teva Pharm |
|
|
Carisoprodol |
Schein |
|
|
Daypro |
Searle |
|
|
Monopril |
B-M Squibb |
|
|
Ceftin |
Glaxo Wellcome |
|
|
Claritin D 24HR |
Schering |
|
|
Hydrochlorothiazide |
Purepac |
|
|
Acetaminophen/Codeine |
Purepac |
|
|
Nitrostat |
Parke-Davis |
|
|
Atrovent Inh |
Boehr lngel |
|
|
Humulin 7O/30 |
Lilly |
|
|
Rezulin |
Parke-Davis |
|
|
Lotrisone |
Schering |
|
|
Serevent |
Glaxo Wellcome |
|
|
Ziac |
Wyeth-Ayerest |
|
|
Hydrochlorothiazide |
ESI Lederle |
|
|
Cycrin |
ESI Lederle |
|
|
lbuprofen |
Par Pharm |
|
|
Lo/Ovral 28 |
Wyeth-Ayerst |
|
|
Diazepam |
Mylan |
|
|
Xalatan |
Pharmacia/Upjohn |
|
|
Imitrex |
Glaxo Wellcome |
|
|
Roxicet |
Roxane |
|
|
Metoprolol Tartrate |
Mylan |
|
|
Verapamil SR |
Zenith |
|
|
Furosemide Oral |
Watson Lab |
|
|
Medroxyprogesterone |
Greenstone |
|
|
Desogen |
Organon |
|
|
Ery-Tab |
Abbott |
|
|
Mevacor |
Merck |
|
|
Ortho-Cyclen |
Ortho Pharm |
|
|
Azmacort |
Rhn-Plnc Rr |
|
|
Klor-Con |
Upsher-Smith |
|
|
Cyclobenzaprine |
Schein |
|
|
Neurontin |
Parke-Davis |
|
|
Ranitidine |
Novopharm |
|
|
Penicillin VK |
Teva Pharm |
|
|
Lorazepam |
Purepac |
|
|
Axid |
Lilly |
|
|
Risperdal |
Janssen |
|
|
Bactroban |
SK Beecham |
|
|
Hydrochlorothiazide |
Zenith |
|
|
Cyclobenzaprine |
Mylan |
|
|
Zantac |
Glaxo Well |
|
|
Macrobid |
Procter & Gamble |
|
|
Serzone |
Bristol-Myers Squibb |
|
|
Temazepam |
Mylan |
|
|
Clonidine |
Mylan |
|
|
Cephalexin |
Apothecon |
|
|
Verapamil SR |
Mylan |
|
|
Guaifenesin/PPA |
Duramed |
|
|
Flovent |
Glaxo Wel |
|
|
Glyburide |
Greenstone |
|
|
Naproxen |
Mylan |
|
|
BuSpar |
B-M Squibb |
|
|
Furosemide |
Zenith |
|
|
Levaquin |
Ortho Pharm |
|
|
Tri-Levlen |
Berlex |
|
|
Zestoretic |
Zeneca |
|
|
Hyzaar |
Merck |
|
|
Neomycin/Polymx/HC |
Schein |
|
|
Estradiol |
Watson |
|
|
Loestrin-FE 1.5/30 |
Parke-Davis |
|
|
Methylprednisolone |
Duramed Ph |
|
|
Provera |
Pharmacia/Upjohn |
|
|
Ortho-Cept |
Ortho Pharm |
|
|
Ranitidine |
Mylan |
|
|
Alprazolam |
Purepac |
|
|
Tobradex |
Alcon Lab |
|
|
Phenergan Supp |
Wyeth-Ayerst |
|
|
Estraderm |
Novartis |
|
|
Estrace |
B-M Squibb |
|
|
Allopurinol |
Mylan |
|
|
Potassium Chloride |
ETHEX |
|
|
Propranolol LA |
ESI Lederle |
|
|
Loestrin-Fe 1/20 |
Parke-Davis |
|
|
Humulin R |
Lilly |
|
|
Elocon |
Schering |
|
|
Tamoxifen |
Barr |
|
|
Gemfibrozil |
Teva Pharm |
|
|
Lasix |
Hoech Mar R |
|
|
Ranitidine |
Geneva |
|
|
Endocet |
Endo |
|
|
Altace |
Hoech Mar R |
|
|
Effexor |
Wyeth-Ayerst |
|
|
Timoptic XE |
Merck |
|
|
Diovan |
Novartis |
|
|
Rhinocort |
Astra |
|
|
Xanax |
Pharmacia/Upjohn |
|
|
Deltasone |
Pharmacia/Upjohn |
|
|
Warfarin |
Barr |
|
|
Lotrel |
Novartis |
|
|
Climara |
Berlex |
|
|
Plendil |
Astra |
|
|
Cimetidine |
Mylan |
|
|
Glipizide |
Mylan |
|
|
Alesse 28 |
Wyeth-Ayerst |
|
|
Albuterol Aerosol |
Zenith |
|
|
Trazodone |
Sidmak |
|
|
Miacalcin Nasal |
Novartis |
|
|
Necon 1/35 |
Watson Lab |
|
|
Amaryl |
Hoech Mar R |
|
|
Propacet 100 |
Teva Pharm |
|
|
Metoprolol Tartrate |
Geneva |
|
|
Lorabid |
Lilly |
|
|
Accolate |
Zeneca |
|
|
Sumycin |
Apothecon |
|
|
Zyban |
Glaxo Well |
|
|
Promethazine tabs |
ESI Lederle |
|
|
Dyazide |
SK Beecham |
|
|
Adderall |
Shire Rchwd |
|
|
Amitriptyline |
Sidmark |
|
|
Retin-A |
Ortho Derm |
(Data: American Druggist - February 1999 PP 42-43)
The Australian NHMRC (1988) recommends neonates be assessed for follow-up care under the following conditions.
Reviews
Honein MA, Lindstrom JA, Kweder SL. Can we ensure the safe use of known human teratogens?: The iPLEDGE test case. Drug Saf. 2007;30(1):5-15. Review.
Abroms L, Maibach E, Lyon-Daniel K, Feldman SR. What is the best approach to reducing birth defects associated with isotretinoin? PLoS Med. 2006 Nov;3(11):e483. Review.
Morrison JL, Riggs KW, Rurak DW. Fluoxetine during pregnancy: impact on fetal development. Reprod Fertil Dev. 2005;17(6):641-50. Review.
Palmieri C, Canger R. Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing? CNS Drugs. 2002;16(11):755-64.
Yerby MS. The use of anticonvulsants during pregnancy. Semin Perinatol. 2001 Jun;25(3):153-8.
Morrell MJ. The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia. 1996;37 Suppl 6:S34-44.
Articles
Noorlander CW, Ververs FF, Nikkels PG, van Echteld CJ, Visser GH, Smidt MP. Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE. 2008 Jul 23;3(7):e2782.
Zupanc ML. Antiepileptic drugs and hormonal contraceptives in adolescent women with epilepsy. Neurology. 2006 Mar 28;66(6 Suppl 3):S37-45.
Kaindl AM, Asimiadou S, Manthey D, Hagen MV, Turski L, Ikonomidou C. Antiepileptic drugs and the developing brain. Cell Mol Life Sci. 2006 Feb;63(4):399-413.
NCBI Bookshelf
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), (2003)
Management of Chronic Hypertension During Pregnancy
Improving Treatment for Drug-Exposed Infants
Pregnant, Substance-Using Women
Food and Drug Administration (USA)
Evaluating the Risks of Drug Exposure in Human PregnanciesAlcohol "Fetal Alcohol Syndrome"
Infection
cytomegalovirus
Trauma
These links require online access to Merck Manuals on Women's Health Issues. http://www.merck.com/mrkshared/mmanual_home2/sec22/sec22.jsp
Risk Factors Present Before Pregnancy
Risk Factors That Develop During Pregnancy
Diseases that complicate Pregnancy
Problems Affecting the Fetus or Newborn
Mitral Valve Prolapse
High Blood Pressure
Anemias
Kidney Disease
Infectious Disease
Diabetes
Thyroid
Liver
Asthma
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Myasthenia Gravis
Idiopathic Thrombocytopenic Purpura
>Surgery During Pregnancy
Relate to lifestyle, environment and nutrition. Some examples of this form of abnormality are the impact of excess alcohol on neural development (Fetal alcohol syndrome), viral infection (rubella) at a critical stage of development, inadequate dietry folate intake (neural tube defects), effects of prescription drugs (Thalidomide- limb development) and even maternal endocrine function (thyroid development).
In addition to these obvious maternally-derived abnormalities, there is growing evidence that the interuterine environment has a strong influence on later postnatal health. This theory is based on the early statistical analysis of disease/longevity in babies with low birth weights in England by Barker, and has been called the "Barker Hypothesis". (More? Barker Hypothesis)
Sudden Infant Death Syndrome (SIDS)
Malnutrition
Infection
Trauma
see also Normal Childhood Development
These developmental abnormalities usually involve only small DNA mutations affecting individual or a few genes, two exceptions are the major chromosomal abnormalities usualy trisomy; trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) (also trisomy 9, 13, 15). Note that the occurance of chromosomal abnormalities also increases with increasing maternal age. There are many pamphlets providing information about prenatal diagnosis (see NSW State Health Publication Checking your baby's health before birth).
Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.
This current page is a link to Normal and Abnormal Development and Population Data.
You should look at normal development. Development Notes
Alternatively, go on to look at Systematic Development of organs and tissues.
| 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 |
For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.
The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.
Home Page
Embryo stages
Fetal Dev
Dev Notes 1
Dev Notes 2
System Notes
Acknowledgements
Abnormal Development
Australian Statistics
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
Herbal Drugs
Illegal Drugs
Heavy Metal
Iodine Deficiency
Viral Infection
Rubella
Parvovirus
Varicella
Databases
NINDS Factsheets
School of Med Sci
UNSW Medicine
University of NSW
UNSW Cell Biology
NCBI Books
Dev Biol (Gilbert)
How and why do things go wrong in development?
This page gives introduces the effects of therapeutic drugs and links to several external resources for further information. Both Herbal Drugs and Illegal Drugs are covered on other pages.
Abnormalities in human development can be due to many different maternal factors and we now know that there may exist a complex interaction of different environmental factors (synergism) that can influence development.
UNSW Embryology is for educational use only.
Please email Dr Mark Hill if you wish to make a comment about this current project.
