The document discusses several key topics related to drug use and fetal development: 1) Drugs taken during pregnancy can affect both the mother and fetus, so treatment requires balancing risks. The thalidomide catastrophe showed drugs can cause severe birth defects. 2) The placenta allows most drugs to cross into the fetus, with some exceptions like heparin and insulin. Scientific data on effects is limited due to ethics around testing on pregnant women and fetuses. 3) Certain drugs like warfarin, phenytoin, carbamazepine and sodium valproate are definitely teratogenic and increase risks of birth defects significantly if taken during pregnancy.

1. Catch-22
Damned if you do,
damned if you don’t

2. Drugs in pregnancy
Affect both mother & fetus,
so drug treatment is all about
balancing risks

3. Catastrophe
 Thalidomide causing phocomelia

4. Physiology of pregnancy
 Cardiovascular
 Cardiac output increases by 30-50% from 6th
-30th
week,
with increase in HR & stroke volume
 Blood
 Total blood volume increases, with plasma volume increasing
more than hematocrit, causing dilutional decrease in
hemoglobin
 Urinary
 GFR increases, causing decrease in BUN & creatinine &
increased frequency of urination
 Renin-angiotensin-aldosterone system activation causes
salt & water retention

5. continued
 Respiratory
 Respiratory rate increases to decrease CO2 & increase O2
 GIT
 GI motility decreases causing dyspepsia & constipation
 Alkaline phosphatase increases due to release from placenta
 Endocrine
 Enlarged pituitary releases more prolactin to ensure lactation
 Placenta produces
TSH like hormone that increases free T4,
CRH increases adrenal hormones promoting edema,
HPL & insulinase increase insulin resistance,
MSH increases pigmentation- melasma

6. Periods of fetal development
 Pre-implantation
 1st
week
 Damage causes abortion
 Organogenesis
 2nd
-8th
week
 Organs are formed
 Damage can cause structural malformation
 Growth or maturation
 3rd
-9th
month
 Damage may modify function of organs

8. Placental barrier
Most drugs cross placenta,
exception being heparin & insulin

9. Scientific data
Insufficient, largely due to concern
about teratogenecity

10. Definitely teratogenic drugs
 Warfarin- 25%
 Phenytoin- ~6%
 Carbamazepine- 6%
 Na valproate- 2%
 Lithium- 2%
 Retinoids- high

11. Fetal ultrasound
At ~10 & ~18 weeks
detects most of clinically
significant structural abnormalities

12. FDA categorization of drugs
 A- safest, based on human studies
 B- no risk in animal studies, not enough
human data
 C- inadequate studies in animals or
humans
 D- evidence shows harm to fetus, but
benefits may outweigh risks
 X- risks outweigh benefits, do not use

13. Safest drugs in pregnancy
Mineral & vitamin supplements
Others, use if necessary

14. Important drugs
 Antibiotics-
 B- penicillin, cephalo., metro., NFT, clinda., azithro.
 C- chloroquine, quinolones, fluconazole, albendazole
 D- doxycycline, aminoglycosides
 Cardiovascular-
 B- LMW heparin
 C- β-blockers, dihydropyridine CCB, methyldopa,
furosemide, digoxin, heparin
 D- ACEI, ARB, warfarin, thiazides, diltiazem
 Other-
 B- acetaminophen, insulin
 C- aspirin, clonidine, rofecoxib, glyburide, metformin
 D- NSAID, diazepam, carbamazepine, valproic acid
 Vaccines-

C- OPV, MMR, BCG, HBV/HAV & rabies vaccine

15. Smoking in pregnancy
 Increases risk of-
 Spontaneous abortion
 Abruptio placentae, placenta previa, PROM
 Preterm birth
 Low birth weight
 Sudden infant death syndrome
 Best to quit, may require nicotine
replacement

16. Alcohol in pregnancy
 Ethanol freely crosses the placenta
 Complications are dose related,
worse in first trimester
 Fetal alcohol syndrome-
 Growth retardation
 Facial abnormalities- shortened palpebral fissure,
low-set ears, midfacial hypoplasia, thin upper lip
 CNS dysfunction- microcephaly, MR, behavioural disturbances
 Best is no alcohol