Drugs and Pregnancy

Drugs in Pregnancy and LactationDr.Mohamed Abdel Bagi Abdel GaniM.B.B.S UofKRegistrar and Lecturer Obs&Gyn DepartmentSchool of Medicine-Ahfad University For Women.

Important Points

The essence of prescribing in pregnancy is to weigh between the benefit to the mother of giving or continuing a pre-med in pregnancy and the risk to her baby. (applied also in lactation)

As women delay becoming pregnant until later life, more and more will become pregnant whilst taking medication for common conditions such as essential hypertension.

Also some women with conditions that were once thought incompatible with pregnancy are now becoming pregnant due to improved medication (e.g.women with CF transplant recipients).

Teratogenesis: defined as dysgenesis of fetal organs in terms of either structure or function

Timing Of ExposurePre-embryonic phase: from conception till day 17. (implantation and blastocyst formation). And here usually the complication is miscarriage.

Embryonic phase: from day 17- day 55. (organogenesis). Exposure leads to congenital malformations. the earlier the timing of the insult, the greater the damage.

Fetal phase: from 8wks after conception to term. The effects of drugs on fetal growth and function of organs.

Placental transfer of drugsMost drugs cross the placental barrier by simple diffusion. The factors responsible for transfer are:(i) Molecular weight (molecular weight > 1000 Da do not cross the placenta) (ii) Concentration of free drug.(iii) Lipid solubility. (iv) Uteroplacental blood flow. (v) Placental surface area.

The rate of drug transfer across the placenta is increased in late pregnancy.This is due to:(i) increased unbound drug available for transfer.(ii) increased uteroplacental blood flow.(iii) increased placental surface area.(iv) decreased thickness of the placental membranes.

Mechanism of Teratogenecity

The actual mechanism is unknown.But teratogens may act by the following mechanisms:

Folic acid deficiency e.g methotrexate. (affection of D.N.A and R.N.A).

Epoxides or arena oxides are the oxidative inter metabolites of many drugs like hydantoin and carbamazepine. These intermediary metabolites have carcinogenic and teratogenic effects unless they are detoxified by fetal epoxide hydrolase.

Environment and Genes An interaction between the environment and genes (not well understood).

Maternal disease and drugs like epilepsy and anticonvulsants have a high risk of fetal anamolies.Paternal exposure to drugs or mutagens (polycyclic hydrocarbons) can cause gene mutation and chromosomalabnormality in sperm.Homeobox genes are groups of regulatory genes that control the expression of other genes involved in the normal development of growth and differentiation. Teratogens like retinoic acid can dysregulate these genes to cause abnormalgene expression.

General principles for using The benefits from continuing medication in pregnancy and when breast-feeding often outweigh the potential risks.

Prepregnancy assessment should be offered to all women of childbearing age on regular medication with the option to change to alternative medication where possible.

Try to avoid 1st trimester use if possible.

Use drugs already used in pregnancy rather than new ones.

Use the minimum dose to achieve the desired effect.

The latest information on specific medications should be sought to enable the clinician to adequately assess the risks involved and allow the woman to make an informed choice.

ALCOHOL

Have major risk to the fetus. Which is:Fetal Alcohol Syndrome (FAS):defined as the presence of at least one characteristics from each of the following 3 categories :1. Growth restriction before and/or after birth.2. Fetal anomalies: Small palpebral fissures, indistinct or absent philtium, epicanthic folds, flattened nasal bridge, short length of nose, thin upper lip, low set and unparallel ears and retarded midfacial development.3. CNS dysfunction: Microcephaly, mental retardation, abnormal neurobehavioral development (attention deficit with hyperactivity).

Smoking

Has a high risk to the mother and her baby.Risks include:-Miscarriage.placental abruption.placenta praevia.premature rupture of membranes.preterm delivery.low birthweight.cleft lip and cleft palate.perinatal mortality.sudden infant death syndrome.impaired cognitive development.