UNSW Banner

UNSW Embryology

Abnormal Development - Drugs

© Dr Mark Hill (2008)

Acknowledgements

Introduction

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 had prior to any reproductive decision.

Legal drugs are classified usually by each country's appropriate regulatory body. 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. Another important consideration is that drugs are "cleared" in newborn infants (and during late fetal development) at a much slower rate that that seen in adults. (More? Infant Drug Clearance Rate)

Congenital Malformations Australia statistics

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 | FDA 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

Some Recent Findings

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)

FDA Fetal Risk Categories

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)

Infant Drug Clearance Rate

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.

Approximate Infant Drug Clearance

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)

Teratology

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.

Epilepsy

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).

Benzodiazepines modulate the action of inhibitory neurotransmitter GABA at their receptor and may effect developing neural development/differentiation.

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.

Antidepressant Drugs

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.

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."

Bipolar Drugs

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.

Analgesics Drugs

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

Acne Drugs

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."

Isotretinoin (Accutane) Risk Management Approaches Table

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

Herbal Drugs

The following are herbal drugs 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.

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)

USA Top 200 Prescriptions

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

Conjugated Estrogens

Synthroid

Knoll

Levothyroxine

Trimox

Apothecon

Amoxicillin

Hydrocodone w/APAP

Watson

Hydrocodone w/APAP

Prozac

Lilly

Fluoxetine

Prilosec

Astra

Omeprazole

Zithromax

Pfizer

Azithromycin

Lipitor

Parke-Davis

Atorvastatin

Norvasc

Pfizer

Amlodipine

Claritin

Schering

Loratadine

Lanoxin

Glaxo Wellcome

Digoxin

Zoloft

Pfizer

Sertraline

Albuterol Aerosol

Warrick

Albuterol

Paxil

SK Beecham

Paroxetine

Amoxicillin

Teva Pharm

Amoxicillin

Prempro

Wyeth-Ayerst

Conj. Estrogens/Medroxyprogesterone

Zestril

Zeneca

Lisinopril

Vasotec

Merck

Enalapril

Augmentin

SK Beecham

Amoxicillin/Clavulanate

Cephalexin

Teva Pharm

Cephalexin

Zocor

Merck

Simvastatin

Glucophage

B-M Squibb

Metformin

Coumadin

Dupont

Warfarin

Acetaminophen/Codeine

Teva Pharm

Acetaminophen/Codeine

lbuprofen

Greenstone

Ibuprofen

Furosemide

Mylan

Furosemide

Cipro

Bayer Pharm

Ciprofloxacin

Trimethoprim/Sulfa

Teva Pharm

Trimeth/Sulfameth

Cardizem CD

Hoech Mar R

Diltiazem

Pravachol

B-M Squibb

Pravastatin

Biaxin

Abbott

Clarithromycin

Propoxyphene N/APAP

Mylan

Propoxyphene N/APAP

Levoxyl

Jones Pharma

Levothyroxine

Procardia XL

Pfizer

Nifedipine

Prednisone

Schein

Prednisone

Prevacid

Tap Pharm

Lansoprazole

Ultram

McNeil

Tramadol

Alprazolam

Greenstone

Alprazolam

Ambien

Searle

Zolpidem

Amoxil

SK Beecham

Amoxicillin

Accupril

Parke-Davis

Quinapril

K-Dur-20

Schering

Potassium Chloride

Glucotrol XL

Pfizer

Glipizide

Hydrocodone w/APAP

Mallinckrodt

Hydrocodone w/APAP

Triamterene/HCTZ

Geneva

Triamterene/HCTZ

Ortho Tri-Cyclen

Ortho Pharm

Norgestimate/Ethinyl Estradiol

Lotensin

Novartis

Benazepril

Prinivil

Merck

Lisinopril

Hytrin

Abbott

Terazosin

Veetids

Apothecon

Penicillin VK

Propoxyphene N/APAP

Teva Pharm

Propoxyphene N/APAP

Relafen

SK Beecham

Nabumetone

Zyrtec

Pfizer

Cetirizine

Cardura

Pfizer

Doxazosin

Claritin D 12HR

Schering

Loratidine/Pseudoephedrine

Allegra

Hoech Mar R

Fexofenadine

Pepcid

Merck

Famotidine

Triphasil

Wyeth-Ayerst

L-Norgestrel/Ethinyl Estradiol

Humulin N

Lilly

Human Insulin-NPH

Dilantin

Parke-Davis

Phenytoin

Ortho-Novum 7/7/7

Ortho Pharm

Norethindrone/Ethinyl Estradiol

Atenolol

Geneva

Atenolol

Toprol-XL

Astra

Metoprolol

Flonase

Glaxo Wellcome

Fluticasone

Lorazepam

Mylan

Lorazepam

Amitriptyline

Mylan

Amitriptyline

Cefzil

B-M Squibb

Cefprozil

Depakote

Abbott

Divalproex

Imdur

Schering

Isosorbide Mononitrate S.A.

Viagra

Pfizer

Sildenafil Citrate

Diflucan

Pfizer

Fluconazole

Propulsid

Janssen

Cisapride

Alprazolam

Geneva

Alprazolam

Triamterene/HCTZ

Mylan

Triamterene/HCTZ

Atenolol

Mylan

Atenolol

Fosamax

Merck

Alendronate

Adalat CC

Bayer Pharm

Nifedipine

Cozaar

Merck

Losartan

Atenolol

ESI Lederle

Atenolol

Lescol

Novartis

Fluvastatin

Hydrocodone w/APAP

Qualitest

Hydrocodone w/APAP

Albuterol Neb Soln

Warrick

Albuterol

Glyburide

Copley

Glyburide

Wellbutrin SR

Glaxo Well

Bupropion HCL

Vancenase AQ DS

Schering

Beclomethasone

Zithromax Susp

Pfizer

Azithromycin

Clonazepam

Teva Pharm

Clonazepam

Naproxen

Teva Pharm

Naproxen

Carisoprodol

Schein

Carisoprodol

Daypro

Searle

Oxaprozin

Monopril

B-M Squibb

Fosinopril

Ceftin

Glaxo Wellcome

Cefuroxime

Claritin D 24HR

Schering

Loratidine/Pseudoephedrine

Hydrochlorothiazide

Purepac

Hydrochlorothiazide

Acetaminophen/Codeine

Purepac

Acetaminophen/Codeine

Nitrostat

Parke-Davis

Nitroglycerin

Atrovent Inh

Boehr lngel

Ipratropium

Humulin 7O/30

Lilly

Human Insulin 70/30

Rezulin

Parke-Davis

Troglitazone

Lotrisone

Schering

Clotrimoxazole/Betamethasone

Serevent

Glaxo Wellcome

Salmeterol

Ziac

Wyeth-Ayerest

Bisoprolol/HCTZ

Hydrochlorothiazide

ESI Lederle

Hydrochlorothiazide

Cycrin

ESI Lederle

Medroxyprogesterone

lbuprofen

Par Pharm

Ibuprofen

Lo/Ovral 28

Wyeth-Ayerst

Norgestrel/Ethinyl Estradiol

Diazepam

Mylan

Diazepam

Xalatan

Pharmacia/Upjohn

Latanoprost

Imitrex

Glaxo Wellcome

Sumatriptan

Roxicet

Roxane

Oxycodone/APAP

Metoprolol Tartrate

Mylan

Metoprolol

Verapamil SR

Zenith

Verapamil

Furosemide Oral

Watson Lab

Furosemide

Medroxyprogesterone

Greenstone

Medroxyprogesterone

Desogen

Organon

Desogestrel/EthinylEstradiol

Ery-Tab

Abbott

Erythromycin

Mevacor

Merck

Lovastatin

Ortho-Cyclen

Ortho Pharm

Norgestimate/Ethinyl Estradiol

Azmacort

Rhn-Plnc Rr

Triamcinolone aerosol

Klor-Con

Upsher-Smith

Potassium Chloride

Cyclobenzaprine

Schein

Cyclobenzaprine

Neurontin

Parke-Davis

Gabapentin

Ranitidine

Novopharm

Ranitidine

Penicillin VK

Teva Pharm

Penicillin VK

Lorazepam

Purepac

Lorazepam

Axid

Lilly

Nizatidine

Risperdal

Janssen

Risperidone

Bactroban

SK Beecham

Mupirocin

Hydrochlorothiazide

Zenith

Hydrochlorothiazide

Cyclobenzaprine

Mylan

Cyclobenzaprine

Zantac

Glaxo Well

Ranitidine

Macrobid

Procter & Gamble

Nitrofurantoin

Serzone

Bristol-Myers Squibb

Nefazodone

Temazepam

Mylan

Temazepam

Clonidine

Mylan

Clonidine

Cephalexin

Apothecon

Cephalexin

Verapamil SR

Mylan

Verapamil

Guaifenesin/PPA

Duramed

Guaifenesin/Phenylpropanolamine

Flovent

Glaxo Wel

Fluticasone Propionate

Glyburide

Greenstone

Glyburide

Naproxen

Mylan

Naproxen

BuSpar

B-M Squibb

Buspirone

Furosemide

Zenith

Furosemide

Levaquin

Ortho Pharm

Levofloxacin

Tri-Levlen

Berlex

L-Norgestrel/Ethinyl Estradiol

Zestoretic

Zeneca

Lisinopril/HCTZ

Hyzaar

Merck

Losartan/HCTZ

Neomycin/Polymx/HC

Schein

Neomycin/Polymx/HC

Estradiol

Watson

Estradiol

Loestrin-FE 1.5/30

Parke-Davis

Norethindrone/Ethinyl Estradiol

Methylprednisolone

Duramed Ph

Methylprednisolone

Provera

Pharmacia/Upjohn

Medroxyprogesterone

Ortho-Cept

Ortho Pharm

Desogestrel/Ethinyl Estradiol

Ranitidine

Mylan

Ranitidine

Alprazolam

Purepac

Alprazolam

Tobradex

Alcon Lab

Tobramycin/Dexamethasone

Phenergan Supp

Wyeth-Ayerst

Promethazine

Estraderm

Novartis

Estradiol

Estrace

B-M Squibb

Estradiol

Allopurinol

Mylan

Allopurinol

Potassium Chloride

ETHEX

Potassium Chloride

Propranolol LA

ESI Lederle

Propranolol LA

Loestrin-Fe 1/20

Parke-Davis

Norethindrone/Ethinyl Estradiol

Humulin R

Lilly

Human Insulin Regular

Elocon

Schering

Mometasone

Tamoxifen

Barr

Tamoxifen

Gemfibrozil

Teva Pharm

Gemfibrozil

Lasix

Hoech Mar R

Furosemide

Ranitidine

Geneva

Ranitidine

Endocet

Endo

Oxycodone/APAP

Altace

Hoech Mar R

Ramipril

Effexor

Wyeth-Ayerst

Venlafaxine

Timoptic XE

Merck

Timolol

Diovan

Novartis

Valsartan

Rhinocort

Astra

Budesonide

Xanax

Pharmacia/Upjohn

Alprazolam

Deltasone

Pharmacia/Upjohn

Prednisone

Warfarin

Barr

Warfarin

Lotrel

Novartis

Amlodipine/Benazepril

Climara

Berlex

Estradiol

Plendil

Astra

Felodipine SR

Cimetidine

Mylan

Cimetidine

Glipizide

Mylan

Glipizide

Alesse 28

Wyeth-Ayerst

Levonorgestrel/Ethinyl Estradiol

Albuterol Aerosol

Zenith

Albuterol

Trazodone

Sidmak

Trazodone

Miacalcin Nasal

Novartis

Calcitonin Salmon

Necon 1/35

Watson Lab

Norethindrone/Ethinyl Estradiol

Amaryl

Hoech Mar R

Glimepiride

Propacet 100

Teva Pharm

Propoxyphene N/APAP

Metoprolol Tartrate

Geneva

Metoprolol

Lorabid

Lilly

Loracarbef

Accolate

Zeneca

Zafirlukast

Sumycin

Apothecon

Tetracycline HCL

Zyban

Glaxo Well

Bupropion HCL SR

Promethazine tabs

ESI Lederle

Promethazine

Dyazide

SK Beecham

Hydrochlorothiazide/Triamterine

Adderall

Shire Rchwd

Amphetamine Mixed Salts

Amitriptyline

Sidmark

Amitriptyline

Retin-A

Ortho Derm

Tretinoin

(Data: American Druggist - February 1999 PP 42-43)

Australian NHMRC Recommendations

The Australian NHMRC (1988) recommends neonates be assessed for follow-up care under the following conditions.

References

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.

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.

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.

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

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)

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States

Management of Chronic Hypertension During Pregnancy

Improving Treatment for Drug-Exposed Infants

St. John's Wort

Pregnant, Substance-Using Women

WWW Links

Food and Drug Administration (USA)

Evaluating the Risks of Drug Exposure in Human Pregnancies

Other Maternal Factors Prenatal

Alcohol "Fetal Alcohol Syndrome"

Smoking

Chemical

Drug Use

Legal Drugs

Folic Acid

Nutrition

Infection

Rubella

Sexually Transmitted Diseases

Syphilis

cytomegalovirus

Iodine Deficiency

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

Heart Disease

Heart Failure

Rheumatic Heart Disease

Birth Defects of Heart

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

Maternal derived abnormalities

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)

Non-Maternal Postnatal Factors

Sudden Infant Death Syndrome (SIDS)

Malnutrition

Infection

Trauma

Iodine Deficiency

chemical

see also Normal Childhood Development

Congenital abnormalities

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).

Finally

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.

Where to Next?

You should look at normal development. Development Notes

Alternatively, go on to look at Systematic Development of organs and tissues.

Glossary of Terms

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

Quick Links

Finally

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.

Other Embryos

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.

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G