2.  Any agent chemical, viruses,environmental
agents , physical factors and drugs that acts
during embryonic or fetal development to
produce a permanent alteration of form or
function
 HADEGAN-agent that interferes with normal
maturation and function of an organ
 TROPHOGEN-agent that alters growth
 (affects process occuring after organogenesis
or even after birth)

3.  Careful delineation of clinical cases
 Rare environmental exposure associated with
rare defect,with atleast 3 reported cases-
easiest if defect is severe
 Proof that the agent acts on the embryo or
fetus directly or indirectly
 Proven eposure to agent at critical times in
prenatal development
 The association must be biologically plausible

4.  Consisitent
findings by 2 or more
epidimiological studies of high quality.
 Teratogenicity
in experimental
animals,especially primates.

5.  Almost all drugs
cross the placenta to
Some extent
 Weigh therapeutic benefits
of drug to mother against
its risk potential to developing fetus

6.  1. Animal species and Race  often animal study
data of either safety or teratogenicty don not
indicate the definite and conclusive proof of
being same in human being .
 2. Chemical- nature , dose , specificity , Dose
. Gestation period of exposure , duration of
exposure , their absorption and circulation as
free / protein bound form ,rate of detoxification
. Excretion / clearance from body, ability to
cross placenta , concentration in fetal tissue etc.
 Physiological changes in pregnancy also modify
drug effect and on fetus ---
(a) Absorption is altered due to delay in
gastric emptying by increased progesterons.
(b) increased GFR increases clearance thruogh
Kidneys.

7. (c). Increased liver enzyme activity by
increased levels of Estrogen and progeston
lead to fast clearance .
(d). How and how much drug / chemical is
able to cross placental barrier ---to reach to
fetus , water soluble substances pass
through easily by direct effusion depending
upon concentration gradient ,Low molecular
weight substances cross fast, while macro
sized and with high molecular weight
substances do not cross placenta , Free
molecules cross easily as compared to
Protein bond .Some chemicals need active
transfer mechanism like Phosphorilization.

8.  4. Period of Gestation and Exposure to teratogen

Teratogens can cause cell death , alter tissue
proliferation and growth pattern( hypoplasia ,
aplasia , asynchronous growth)., interferring
with cellular differentiation or other
morphogenic process.
Tertogenic effect is maximum during period of
organogenesis ( bb3-8 -10 weeks )after LMP( 35 –
70 days post LMP ).Mental physical / maturaton
of organ function and their coordination to each
other and growth of ear , eye , gonads occur in
later weeks of gestation .

9. DEPENDS ON :
1. Molecular weight
2. Concentration of free drugs
3. Lipid solubility
4. Utero placental blood flow
5. Placental surface area.
6. More transfer of drugs at term

10.  86%of women take medication during
pregnancy
 Despitethis , most drugs are not labeled for use
during pregnancy
 1/2 of pregnancies unplanned
 <50% of women know they are pregnant by
4th week and ~20% still don’t know by 8th
week

13. Category Animal Human Risk Administration
risk
A No No risk Yes
risk
B No No adequate Yes
risk studies
C Risk No adequate If benefits>
studies Risk
D Risk< Benefit If No
alternative
X Risk> Benefit Contraindicated

14. A review of 152531 pregnant women in 4yrs-
64% women were prescribed other drugs then
vitamins in 270 days, which were
 Category C – 37.8%
 Category D -4.8%
 Category X -4.6%
Hence a planned pregnancy should be the
answer

16.  Nature of agent
 Dose
 Route
 Frequency of exposure
 Duration of exposure
 Gestational timing
 Concurrent illness
 Genetic susceptibility(mother, fetus)

17.  BEFORE DAY 31 : All or none effect(cell death
or malformation)
 Day31 to 71 : Effects depend on amount of
drugs and duration of exposure.
 AFTERDAY 71 : DES related anomalies
around 20 weeks.
Fetal alcohol syndrome in late pregnancy.

19. DISRUPTION OF FOLIC ACID METABOLISM
 Leadsto deficient methionine production and
RNA, DNA synthesis.
 Preconceptional folate deficiency leads to
neural tube defects, cleft lip and palate

20.  EPOXIDE AND ARENA DRUGS
 Are
oxidative inter metabolites of drugs like
hydantoin and carbamazipine
 Havecarcinogenic and teratogenic potential
unless detoxified by fetal epoxidehydrolase

21.  ENVIRONMENT AND GENES : Genotype of the
embryo and their susceptibility to teratogens.
 MATERNAL disease AND DRUGS EXPOSURES :
Causes gene mutation and chromosomal
anomalies.
 HOMEOBOX GENES : Regulatory genes are
dysregulated by teratogens.

22. Paternal Exposures
 The process by which germ cells mature into
functional spermatogonia takes 64 days, drug
exposure at any time during the 2 months prior to
conception could result in a mutation.
 During intercourse a drug in seminal fluid could
directly contact the foetus.
 Paternal germ cell exposure to drugs or
environmental agents may alter gene expression

23.  Alcohol
 Angiotensin-converting enzyme inhibitors and
angiotensin-receptor blockers
 Aminopterin
 Androgens
 Bexarotene
 Bosentan
 Carbamazepine
 Chloramphenicol
 Chlorbiphenyls
 Cocaine
 Corticosteroids (High doses)
 Cyclophosphamide

24.  Danazol
 Diethylstilbestrol (DES)
 Efavirenz
 Etretinate
 Isotretinoin
 Leflunomide
 Lithium
 Methimazole
 Methyl mercury
 Methotrexate
 Misoprostol
 Mycophenolate
 Paroxetine
 Penicillamine

25.  Phenobarbital
 Phenytoin
 Radioactive iodine
 Ribavirin
 Streptomycin
 Tamoxifen
 Tetracycline
 Thalidomide
 Tobacco
 Toluene
 Tretinoin
 Valproate
 Warfarin

26. Trimethadione and Paramethadione-Category D

28. Anticonvulsant
B C D
Mg sulphate Carbamazepine Phenytoin (Dilantin):
Metharbital (tegretol): Hydantoin syndrome
carbamazepin Phenobarbital,
syndrome Valporic acid:
Clonazepam valporic syndrome,
(Clonopin) Trimethadione
barbiturates

29. Fetal anticonvulsant
syndrome
Craniofacial abnormalities
Broad nasal bridge
Epicanthal fold
Limb defects
Growth deficiency
Mental Deficiency

32. Cardiovascular disorders
Antihypertensives
C D
Methyldopa Angiotensin converting
Hydralazine, ß blockers, enzyme inhibitors:
Nifedipine (Captopril)
Clonidine Nitroprusside
Prazosin Reserpine
Diazoxide
Captopril: oligohydramnios, pulmonary hypoplasia, IUGR
ß blockers: propranolol (inderal), atenolol (tenormin),
labetolol (trandate)

33. Diuretics
B C D
Amiloride Furosemide Thiazide: thrmbocytopenia
Ethacrynic Spironolactone:
acid antiandrogenic
Acetazolamide: limb
abnormalities
Others
B C
Lidocaine Digoxin, Quinidine, Procainamide

34. Oligohydromnios
Renal anomalies
Neonatal renal failure
Pulmonary hypoplasia
Hypoclavaria
Growth restriction
Death

35. DIURETICS: Reduced placental perfusion
and fetal compromise ,
thrombocytopenia and
hyponatremia
IUGR
SPIRONOLACTONE(ANTI-ANDROGEN)
 Feminisationof male fetus (short phallus and
bifid scrotum)
 Amiodaron –Category D (hypothyroidism)

36. Fetal-contradi syndrome
 skeletal and facial abnormalities
 optic atrophy
 Microcephaly
 chondrodysplasia puncta.

39. VITAMIN A
•avoid doses higher than the recommended daily
allowance of 5000 IU
BEXAROTENE
•contraindicated during pregnancy.
•eye and ear abnormalities.
• cleft palate and incomplete ossification.
•male patients who have partners who could become
pregnant are advised to use condoms during sexual
intercourse if they are taking bexarotene and for one
month after discontinuing therapy

40. ISOTRETENOIN(used in acne)
•first-trimester exposure- high rate of foetal loss
•malformations (26 fold)
•microtia or anotia
-agenesis or stenoses of the external ear canal
-cleft palate and maldevelopment of the facial bones and
cranium
-cardiac anomalies
-hydrocephalus
- thymic abnormalities

42. ETRETINATE -TERATOGENECITY
SIMILAR TO ISORETINOIN
-anomalies are observed
even when conception
occurs after
discontinuation (2yrs)
TRETINOIN first-trimester topical use
results in fetal defects
similar to those
associated with
isotretinoin

44. Infections
1. Antibacterial
B C D
Penicillin, Erythromycin, Trimethoprime Tetracyclins
Ampicillin, augmentin. Chloramphenicol Tobramycin
Cephalosporin, Gentamycin, Streptomycin
clindamycin, azithromycin Neomycin, Kanamycin
spectinomycin, spiramycin Amikacin,
Nitrofurantoin, nalidexic Vancomycin
acid Quinolones
Metronidazole
Polymyxin, Aztreonam

47. DRUGS SIDE EFFECTS AND COMPLICATIONS
Aminoglycosides –Category D Auditory or vestibular damage and
nephrotoxicity
Quinolones Arthropathy in animal studies
Anti Fungal- Griseofulvin Central nervous system and skeleton
anomalies in animals
Fluconazole and Itraconazole: skull abnormalities, cleft palate,
Category C humeral-radial fusion, and other arm
abnormalities
ANTILEPROBIC DRUGS Dapsone to be avoided in third
trimester.

48. DRUGS FETAL OR NEONATAL AFFECTION AND
COMMENT
Long acting Neonatal hemolysis,jaundice and
sulphonamides kernicterus
Nitrofurantoin Hemolysis In newborn if used at term
Metronidazole No evidence of foetal or neonatal
toxicity, high dose regimen should be
avoided

49. DRUGS SIDE EFFECTS AND COMPLICATIONS
Aminoglycosides Auditory or vestibular damage and
nephrotoxicity
Quinolones Arthropathy in animal studies
Sulphonamides Hyperbilirubinemia and neonatal
jaundice when used in 3rd trimester

50.  MEFLOQUINE- 5 fold increased risk of still
births
 chloroquine,quinineand quinidine are
generally considered safe in pregnancy in
therapeutic doses
 Quinine Category D drug

51. Amantadine , efavirenz and rabavarin are in
category x- Hydrocephalus and limb
abnormalities in rodents
Anti retrovirals
eg.lamivudine, nelfinavir, nevirapine, stavudi
ne, or zidovudine are Category C drugs

52. Antimalarial
B C D
Proguanil Chloroquine, primaquine, Quinine
Pyrimethamine, Dapsone,
Quinacrine, quinidine
Antihelminthic
B C
Piperazine Mebendazole, thiabendazole
Pyrantel, pyrvinium, quinacrine,
Gentian violet

53. Amebicides
B C D
Metronidazole Chloroquine, Carbarsone
iodoquinol,
paromomycin
Antiviral
B C X
Didanosine Acyclovir, Ribavirin
Famciclovir Ganciclovir,
Ritonavir Zidovudine

54. Antituberculosis
B C
Ethmbutol Rifampicin, INH, PAS,
Ethionamide, Cycloserin, pyrazinamide
Antifungal
B C
Miconazole, Griseofulvin, fluconazole,
clotrimazole itraconazole, ketoconazole,
Amphotericin, miconazole, teraconazole
Nystatin 5 flucytosine, gentian violet

56. Analgesic
B C D
Acetaminophen Aspirin Ibuprofen, indomethacin,
Ibuprofen, Codiene naproxin, pentazocine
indomethacin, Mepridine, morphine,
naproxin, Sulindac {premature closure
pentazocine of D. arteriosus
Mepridine, Asprin, Codien (if used at
morphine term)
Sulindac

57. COX-2 INHIBITORS,ASPIRIN- safe in low doses
(HIGH DOSE)
- impairment of blastocyst implantation
- increase risk of neonatal haemorrhage
- oligohydromnios
- premature closure of ductus arteriosus
- persistent pulmonary hypertension and
-kernicterus in newborn

60.  pyrimidine-synthesis inhibitor
 used to treat rheumatoid arthritis
 currently contraindicated in pregnancy.
 CAUSES- hydrocephalus,
 eye anomalies
 skeletal abnormalities
 embryo death

61. Vitamins
A C D X
Vitamins, multiple ßCarotene, Tretinoin Etretinate
Folic acid/C, Niacin/C, Leucovorin, systemic Isotretinoin
Niacinamide/C, Menadione/X,
Pantothenic acid/C, Phytonadione,
Pyridoxine/C, Riboflavin/C, Tretinoin
Thiamin/C, Vitamin B12/C, topical
Vitamin C/C, Vitamin E/C
Calcefediol/D, calcitriol/D,
Cholecalciferol/D,
Dihydrotachysterol/D
Vitamin D/D, Vitamin A/X

62. Antineoplastic
B C D X
Prednisone Cytosine, Methotrexate, 5 Aminopterin
arabinoside flurouracil, 6M.P Leuprolide
Dactinomycin Doxorubicin,
Interferon daunorubicin,
alfa bleomycin
Cyclophosphamide,
melphalan, busulphan,
Cisplatin, vincristin,
vinblastin, Etopside

63. CORTICOSTEROIDS -CAUSES FETAL AND NEONATAL
(PREDNISOLONE, ADRENAL SUPPRESSION
HYDROCORTISONE)- HIGH DOSES -IUGR(PROLONGED USE)
MYCOPHENOLATE MOFETIL -CATEGORY D
CAUSES
-bilateral microtia
-anotia
-atresia of the external auditory
canals
- oral clefts

64. CYCLOPHOSPHAMIDE -missing and hypoplastic digits,
-cleft palate
- single coronary artery
-imperforate anus
- fetal-growth restriction -
microcephaly
METHOTREXATE AND -growth restriction
AMINOPTERIN -failure of calvarial ossification, -
craniosynostosis
- hypoplastic supraorbital ridges,
-small posteriorly rotated ears, --
micrognathia
- severe limb abnormalities
TAMOXIFEN Category D
(Human data awaited)

66.  Extreme and
irreversible virilization
 Liver dysfunction
 Mood and libido
disorders
 Exposure of a female fetus results in
virilization, (labioscrotal fusion after first-
trimester exposure and phallic enlargement
from later fetal exposure )

69. T shaped uterus of
DES

70. RADIOACTIVE IODINE
- Highdoses ablates the foetal thyroid and
increases the future risk for childhood thyroid
cancer

72. Category D Drugs
TryclyclicAntidepressant-Imipramine,
Nortriptyline,Amitryptyline
Benzodiazepines-Alprazolam, Chlordiazepoxide-
Category D
Diazepam-Category D
Midazolam –Category D
LITHIUM –EBSTEIN ANOMALY –from first trimester
exposure
NARCOTICS : CNS depression , apnea , bradycardia
hypothermia

74. Psychotropic
B C D
Selective Monoamine oxidase Tricyclic
serotonin inhibitors: antidepressants:
reuptake isocarboxazid, phenelzine, amitriptylin,
inhibitors: tranylcypromine amoxapine,
fluoxetine, Tricyclic antidepressants: imipramine
paroxetine, desipramine, doxepin clomipramine,
sertraline Antipsychotics: nortriptyline
Antipsychotic: chlorpromazine, thioridazine, Benzodiazipines:
Clozapine perphenazine alprazolam,
Bupropion Benzodiazipines: diazepam
clonazepam, lorazepam, lithium
oxazepam

78. All live viral vaccines are potentially
dangerous to the foetus
 RELATIVE CONTRINDICATED DRUGS
BIOLOGICS eg
etanercept
infliximab
adalimumab

79.  most notorious human teratogen
 Bone defects- abnormal shape or size to total absence of a
bone or limb segment—phocomelia.
 upper limb phocomelia after exposure during days 27 to 30
days
 Lower limb phocomelia was associated with exposure during
days 30 to 33
 gallbladder aplasia at 42 to 43 days
 duodenal atresia at 40 to 47days

81. Phocomelia (limb reduction defects)
Bone defects
Anomalies of ear, CVS

82. AMPHETAMINES Methamphetamine - associated with
symmetrical fetal-growth restriction (NO
TERATOGENECITY)
COCAINE -vascular disruption within the embryo,
foetus, or placenta, highest after the first
trimester
-stillbirth
-skull defects ,microcephaly,behaviour
problems
-limb reduction
-urinary tract defects
-ileal atresia
-cardiac anomalies,
-visceral infarcts
-seizures
-hyperthermia and sudden death

83. HEROIN -foetal-growth restriction
-perinatal death
-withdrawal symptoms such as tremors,
irritability, sneezing, vomiting, fever, diarrhea,
and occasionally seizures are observed in 40 to
80 percent of newborns born to heroin-addicted
women
-postnatal growth -normal in most cases
may be mild developmental delay and
behavioural disturbances
METHADONE -low birth weight babies
-withdrawal symptoms similar to heroin but
more frequent and prolonged(upto 3wks)

84. TOBACCO •foetal growth restriction
•abortions
•pre term delivery
•placenta previa and abruption
•subfertility
•clefts
MARIJUANA -low birth weight
-teratogenic in high doses

85.  Pregnancy Category X
 Oxytocic properties could cause IUGR by
vascular disruption or increased uterine
tone
 Chronic exposure is contraindicated

86.  CategoryC
 Limited human data exists, sumatriptan has
been associated with VSDs in several cases

88. DRUGS COMMENTS
Pethidine (Meperidine) Pethidine does not inhibit uterine
contraction so has less adverse
effects on baby.
Fentanyl serious respiratory depression.
So require continuous pulse
oximetry monitoring and close
nursing surveillance
Butorphanol (Stadol). Causes drowsiness and dizziness.
Less nausea and vomiting.
Less respiratory depression

89.  PROBLEMS
 pruritus (60-100%).
 nausea (25-60%).
 urinary retention (10-35%).

90.  Most commonly used mixture is Entonox (an
equal mixture of NO & Oxygen).
 Provides quick with short duration of effect.
 Not suitable for prolonged use from early
labor, so most suitable is late in labor or while
awaiting epidural analgesia.
 Adverse effects include nausea & light
headedness.

91.  chemical properties of drug
 Molecular weight
 lipid solubility of the drug
 the mechanism of transport,
 the degree of ionization, and
 change in plasma pH
 degree of protein binding the plasma pH
 Drug concentration
 Exposure time

92. MATERNAL MEDICATION EFFECTS ON LACTATION AND THE
NEONATE
Oral pill Suppression of lactation
Bromocriptine Suppression of lactation
Ergot Suppression of lactation
Metronidazole Anorexia, blood dyscrasias
,irritability
Anti-thyroid drugs,radio active iodine Hypothyroidism,goitre,
granulocytosis
Warfarin Safe in therapeutic doses
Cytotoxic drugs Risk of immune suppression.Risks
may outweight the benefits
depending on individual drug
Lithium Lethargy, hypotonia, lithium toxicity

93.  Minimum therapeutic dose to be given for
shortest duration.
 Welltried drugs preferable to newer
alternatives
 Drugs
should be avoided for first 71 days of
pregnancy.
 Patient must be counseled about the
beneficial effects of the drugs and potential
risk to the foetus.