This topic includes Introduction, common side effects from maternal medications on infants, guidelines for medication during lactation, effects of various medications on lactation and neonates
2. Maternal drug intake during nursing may have adverse effect
not only on lactation but also on the baby through the ingested
breast milk.
Any drug ingested by a nursing mother may be present in her
breast milk, but its concentration are usually low compared to
blood levels in the mother.
Usually such low levels are not of any clinical significance to
the infant.
However, milk concentration of some drugs may exceed those
in the maternal plasma so that therapeutic doses in the mother
may cause toxicity to the infant.
3. Common side effects from maternal medication on breastfed
infants are....
Diarrhoea (antibiotics)
irritability (antihistaminics)
Drowsiness (sedatives, antidepressants, antiepileptics)
Benefits of breastfeeding are well known.
The risk of drug exposure to the neonate must be weighed
against these benefits.
If the drug amount is 1 to 2 % of the mother, usually no
adverse effects are noted.
4. Factors involved in drug transfer into milk
Chemical properties of the drug
Molecular wright
Degree of protein biding
Ionic dilocation
Lipid solubility
Tissue pH
Drug concentration in maternal blood
Duration of exposure time
5. Guidelines for medication during lactation
Benefits of medication must outweigh the risks
Select drugs that are most widely tested and with short half
life
Monitor the infant during the course of therapy
Non- ionized, low molecular weight, lipid soluble
compounds are usually excreted through breast milk.
8. Teratology and prescribing in pregnancy:
Teratogen causes permanent alteration in the structure and/or
function of an organ, acting during the embryonic or fetal life.
The teratogens may be chemical agents (drugs) or physical
agents (radiation, heat).
The dose (amount) and duration of teratogen exposure may
cause variable response from no effect level to lethal level.
Final results of an abnormal development are: death,
malformation, growth restriction and functional disorder.
9. The term ‘placental barrier’ is a contradiction.
Virtually drugs cross the barrier with the exception of few with
large organic ions such as heparin and insulin.
Approximately 25% of human development defects are genetic
in origin, 2–3% are due to drug exposure and about 65% are
either unknown or from combination of genetic and
environmental factors.
10. Mechanism of Teratology
The actual mechanism is unknown. Teratogens may affect
through the following ways:
1. Folic acid deficiency
2. Epoxides or arena oxides
3. Environments and genes
4. Maternal disease and drugs
5. Homeobox genes
11. 1. Folic acid deficiency:-
It leads to deficient methionine production and RNA, DNA
synthesis.
Folic acid is essential for normal meiosis and mitosis.
Periconceptional folate deficiency leads to neural tube defects,
cleft lips and palate
12. 2. Epoxides or arena oxides:-
These 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.
13. 3. Environment and Genes:-
Abnormalities that are multifactorial depend on the ultimate
interaction between the environment and fetal gene mutation.
Genotype of the embryo and their susceptibility to teratogens
(valproic acid) are the important determinants.
Embryonic period (2nd–8th weeks) is most vulnerable.
Homozygous gene mutations are associated with more
anomalies.
14. 4. Maternal disease and drugs:-
Maternal disease and drugs (epilepsy and anticonvulsants)
have an increased risk of fetal anomalies.
Paternal exposure to drugs or mutagens (polycyclic
hydrocarbons) can cause gene mutation and chromosomal
abnormality in sperm.
15. 5. Homeobox genes:-
Homeobox genes are groups of regulatory genes that control
the expression of other genes involved in the normal
development of growth and diff erentiation.
Teratogens like retinoic acid can dysregulate these genes to
cause abnormal gene expression.
16. Timing of Teratogen exposure and the hazards:
Before D 31:
Teratogen produces an all or none effect.
The conceptus either does not survive or survives without
anomalies.
In early conception only few cells are there.
So any damage at that phase is irreparable and is lethal.
17. D 31-D 71:
D 31-D 71 is the critical period for organ formation.
Effects of teratogen depend on the following factors:
(i) Amount of the drug reaching the fetus,
(ii) Gestational age at the time of exposure,
(iii) Duration of exposure.
18. After D 71:
After D 71 development of other organs continues.
Diethylstilbestrol (DES) related uterine anomalies occur with
exposure around 20 weeks.
Brain continues to develop throughout pregnancy and
neonatal period.
Fetal alcohol syndrome occurs in late pregnancy.
20. Placental transfer of drugs:
Most drugs cross the placental barrier by simple diffusion. The
factors responsible for transfer are:
a. Molecular weight (molecular weight > 1,000 Da do not
cross the placenta)
b. Protein binding
c. Concentration of free drug
d. Lipid solubility
e. Degree of ionization tissue pH
f. Uteroplacental blood flow
g. Placental surface area.
The rate of drug transfer across the placenta is increased in
late pregnancy.
21. This is due to:
a. Increased unbound drug available for transfer
b. Increased uteroplacental blood flow
c. Increased placental surface area
d. Decreased thickness of the placental membranes
23. Keeping these in mind, the following guidelines are
formulated:
If the benefit outweighs the potential risks, only then can the
particular drug be used with prior counseling
Only, well tested and reputed drugs are to be prescribed and
that too using the minimum therapeutic dosage for the shortest
possible duration.
24. ALCOHOl:
Heavy drinkers (≥ 3 oz) have major risk to the fetus (6%).
Fetal Alcohol Syndrome (FAS) is defined as the presence of at
least one characteristic from each of the following three
categories:
1. Growth restriction before and/or after birth.
2. Facial anomalies: Small palpebral fi ssures, indistinct or
absent philtrum, epicanthic folds, fl attened 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).
25. PATERNALLY MEDICATED DRUGS AFFECTING HUMAN
PREGNANCY:
Adverse effects on human progeny has been observed in the
form of abortion, congenital malformations, low birth weight and
increased perinatal loss when the father has been exposed to
lead, anesthetic agents, smoking or caffeine ingestion.
These agents probably alter the morphology of the spermatozoa
or cause some change in the composition of the semen.