UNSW Embryology

Abnormal Development - Herbal Drugs

© Dr Mark Hill (2009)

Acknowledgements

Introduction

This page introduces the possible effects of maternal use of herbal 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. The following are some 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.

The National Center Complementary and Alternative Medicine (USA) provides excellent summary information sheets on many of the commonly used herbal treatments, though many of these information sheets do not include information about herbal drug use during pregnancy. (More? NCCAM)

Page Links: Introduction | Some Recent Findings | St. John's Wort | Ginkgo Biloba | Infant Drug Clearance Rate | Australian NHMRC Recommendations | Maternal Derived Abnormalities | WWW Links | References | Glossary

Some Recent Findings

St. John's Wort

St. John's Wort (Hypericum perforatum) has been used to treat mental disorders, nerve pain, depression, anxiety, and/or sleep disorders. HSTAT "The safety of using hypericum during pregnancy or lactation has not been proven so it should be avoided." Research shows that St. John's wort can also interact with other pharmaceutical drugs affecting the way the body processes or breaks down (metabolises) many other drugs.

Side Effects and Cautions

St. John's wort may cause increased sensitivity to sunlight.

Other side effects can include anxiety, dry mouth, dizziness, gastrointestinal symptoms, fatigue, headache, or sexual dysfunction.

Research shows that St. John's wort interacts with some drugs. The herb affects the way the body processes or breaks down many drugs; in some cases, it may speed or slow a drug's breakdown. Drugs that can be affected include:

Indinavir and possibly other drugs used to control HIV infection

Irinotecan and possibly other drugs used to treat cancer

Cyclosporine, which prevents the body from rejecting transplanted organs

Digoxin, which strengthens heart muscle contractions

Warfarin and related anticoagulants

Birth control pills

Antidepressants

When combined with certain antidepressants, St. John's wort may increase side effects such as nausea, anxiety, headache, and confusion.

St. John's wort is not a proven therapy for depression. If depression is not adequately treated, it can become severe. Anyone who may have depression should see a health care provider. There are effective proven therapies available.

It is important to inform your health care providers about any herb or dietary supplement you are using, including St. John's wort. This helps to ensure safe and coordinated care.

(Data from NCCAM (USA) St. John's Wort)

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."

National Center Complementary and Alternative Medicine (USA) St. John's Wort | St. John's Wort information sheet

Ginkgo Biloba

National Center Complementary and Alternative Medicine (USA) Ginkgo Biloba Ginkgo Biloba information sheet Kava (Piper methysticum),

Kava

Kava (Piper methysticum),

National Center Complementary and Alternative Medicine (USA) Ginkgo Biloba Ginkgo Biloba information sheet

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)

Australian NHMRC Recommendations

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

• Birthweight less than 1500g or gestational age less than 32 weeks
• Small-for-gestational-age neonates
• Perinatal asphyxia
• Apgar score less than 3 at 5 minutes
• clinical evidence of neurological dysfunction
• delay in onset of spontaneous respiration for more than 5 minutes and requiring mechanical ventilation
• Clinical evidence of central nervous system abnormalities ie., seizures, hypotonia
• Hyperbilirubinaemia of greater than 350umol/l in full term neonates
• Genetic, dysmorphic or metabolic disorders or a family history of serious genetic disorder
• Perinatal or serious neonatal infection including children of mothers who are HIV positive
• Psychosocial problems eg., infants of drug-addicted or alcoholic mothers.

References

Reviews

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.

NCBI Bookshelf

Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), (2003)

Improving Treatment for Drug-Exposed Infants

St. John's Wort

WWW Links

Food and Drug Administration (USA)

Evaluating the Risks of Drug Exposure in Human Pregnancies

National Center Complementary and Alternative Medicine (USA) NCCAM | Herbal Supplements: Consider Safety, Too

American Pregnancy Association

Natural Herbs and Vitamins During Pregnancy

Other Maternal Factors Prenatal

Alcohol "Fetal Alcohol Syndrome" | Smoking | Chemical | Drug Use |Legal Drugs | Folic Acid | Nutrition |

Iodine Deficiency | Infection | Rubella | Sexually Transmitted Diseases | Syphilis

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

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

Other Embryos ----------------- All Species Chicken Fly Frog Guinea Pig Mouse Rabbit Rat Worm Zebrafish	Development Notes ----------------- All Notes Part 1 All Notes Part 2 News Menstrual Cycle Prenatal Diagnosis Embryo Stages Week 1 Week 2 Week 3 Week 4 Placenta Fetal Development Birth Postnatal Dev Abnormal Dev Serial Images Mechanisms Molecular Dev Genes/DNA Statistics Histology History Class Notes	System Notes ----------------- All Systems Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Sensory Ear Eye Endocrine Urogenital Genital Musculoskeletal Integumentary Class Notes	Carnegie Stages ----------------- Embryo Stages Embryo stages Scanning EM Stage 1 Stage 3 Stage 7 Stage 8 Stage 9 Stage 10 Stage 11 Stage 12 Stage 13 Stage 14 Stage 15 Stage 16 Stage 17 Stage 18 Stage 19 Stage 20 Stage 21 Stage 22 Stage 23
Movies ----------------- Embryo Growth Ultrasound Week 1 Week 2 Week 3 Week 4 Stage 13/14 Stage 22 Neural Head and Neck Heart Vasculature Gastrointestinal Urogenital Other Embryos Larsen Internet

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.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

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.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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