.

2-3



3
1. Pre-embryonic period 17

teratogen all or nothing effect
teratogen

2. Embryonic period 18 60
(critical period)
terotogen
(organogenesis)


1
1

18-38

18-40
24-40
24-36
45-90
50-150

methotrexate,
cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, warfarin

3. Fetal period 60
280

metabolites
teratogen (cocaine)


(mental retardation)
(fetal alcohol syndrome)
(cognitive ability)

ethyl alcohol
thalidomide
threshold effect
(lipophilicity)

500 daltons

 1,000 daltons insulin

heparin
3
1.
teratogen (teratogenic
effect) 2
2

(Teratogenic effect)
Alcohol
Fetal alcohol syndrome
Angiotensin converting enzyme
Severe neonatal renal insufficiency, decrease skull
inhibitors
ossification
Anticholinergic drugs
Neonatal meconium ileus
Androgenic drugs
Musculinization of female fetus
Diethyl stilbestrol
Adenosis of the vagina of young women exposed in
utero
Iodine
Fetal thyroid agenesis (when exposed in early
gestation)
Goiter, hypothyroidism (when exposed in late
gestation)
Isotretinoin
Lithium
Ebsteins anomaly of fetal heart, fetal goiter,
fetal nephrogenic diabetes insipidus
Misoprostol
Mobieus sequence
NSAIDs
Constriction of ductus arteriosus, necrotizing
enterocolitis
Sedative-hypnotics
Neonatal withdrawal symptom
Tetracycline (especially weeks 24Teeth and bone anomalies
26)
Warfarin
Skeletal defect, central nervous system defect
2.
3

(Teratogenic effect)
Antineoplastic, Cytotoxics
Multiple congenital anomalies, intrauterine growth
retardation, stillbirth, abortion
Paramethadione
Multiple congenital anomalies
Sex hormone (ie. androgen,
Increase malformation, vaginal adenosis, hypotrophic
estrogen)
testis, epididymal cyst
Thalidomide
Severe deformity of the limb, blindness, deafness, cleft
palate, malformed internal organs
Trimathadione
Multiple congenital anomalies
3.
4
4

(Teratogenic effect)
Aminoglycoside
Ototoxicity
Anticonvulsant
Neural tube defect
Carbamazepine and Valproic acid
Central nervous system defect, growth retardation
Phenytoin
Antithyroid drugs
Neonatal goitor and hypothyroidism, aplasia cutis
Chloramphenicol
Gray baby syndrome
Corticosteriods
Central nervous system defect
Hypoglycemic drugs
Neonatal hypoglycemia
Methyldopa
Neonatal meconium ileus, reduced neonatal blood
pressure
Propanolol
Neonatal hypoglycemia, respiratory depression,
bradycardia
Reserpine
Nasal congestion, lethargy
Sulfonamides
Hyperbilirubinemia, hemolytic anaemia (in G-6-PD
deficiency),
Competition of albumin sites-neonatal kernicterus
Thiazide diuretics
Neonatal thrombocytopenia (rare)

teratogen
(variability in gene expression)
thalidomide 25


3-5
1

(route of medication)


thalidomide
1960 (USFDA)


.. 1979 USFDA

teratogenity 5
Category A


(multivitamin)
Category B

Category C

Category D


(tricyclic antidepressants)
Category X (contraindication) thalidomide,
DES





3
1.
(heart burn)
2.

3.

5
5 (Drug of choice)

Analgesics
Anticoagulants
Anticonvulsants

Acetaminophen
Heparin, preferably LMWH
Phenobarbital

Antidiabetics
Antihypertensives
Anti-infectives
Corticosteriods
Decongestants
GI protectants

Insulin
Methyldopa
Penicillin, cephalosporin
Prednisolone
Oxymetolazine drops/ spray
Magnesium hydroxide, calcium
carbonate, aluminium hydroxide,
ranitidine, sucralfate
Psyllium or docusate
Psyllium or docusate

Laxatives/Stool
softeners

Acetaminophen
Heparin, warfarin
Carbemazepine,
ethosuximide or valproic acid
Insulin, tolbutamide
ACEI or CCB
Penicillin, cephalosporin
Prednisolone
Oxymetolazine drops/ spray
Sucralfate or famotidine

80

4

morning sickness

HCG (Human Chorionic Gonadotrophin)

-

-
-



80
6
6

6 (pyridoxine) 6
50-200
6

6 (plasma pyridoxal 5
phosphate, PLP)


6
(p=0.0008)
6

Meclizine 25-100

teratogenic
Promethazine 25

teratogenic

Dimenhydrinate 50

,

Diphenhydramine 25

Metoclopramide 10

, Domperidone extrapyramidal side effect
10

 70

(relaxation of lower esophageal sphincter)
(increase pressure from the uterus onto the stomach)



6

(antacid)


Sucralfate

cimetidine, ranitidine, lansoprazole,

omeprazole metoclopramide
(indigestion) (flatulence)
simethicone

progesterone


-
( 25-30 )

- 10-12
- 20-30
3
-

2
- (bulk laxative) psyllium, methyl cellulose


- (stool softener) dioctyl sodium sulfosuccinate
lactulose

-

electrolyte imbalance
- mineral oil

bisacodyl, senna




(Hemorrhoids)

(increase
venous pressure)


sitz baths

50
paracetamol aspirin 2 3

intracranial
hemorrhage bleeding aspirin
prostaglandin
NSAIDs
pregnancy category B D 3

(migraine)
paracetamol NSAIDs
triptans
sumatriptan,
naratriptan, zolmitriptan, rizatriptan frovatriptan ergot alkaloids
ergotamine dihydroergotamine
pregnancy category X

beta-blockers
tricyclic antidepressants
sodium valproate, phenobarbital, phenytoin

(Leg cramps)

(nocturnal leg cramp)

 quinine
quinine magnesium citrate
magnesium citrate ( 300
magnesium salt) (diarrhea) (abdominal pain)
(Vaginal irritation)
Candida albicans

Trichomonas vaginalis
1 2
(chorioamniotitis)

Candida
albicans imidazole clotrimazole
fluconazole, itraconazole
(pregnacy category C)
Trichomonas vaginalis


T.vaginalis
metronidazole 200 3 7
2 metronidazole
(carcinogenic)
(mutagenic) metronidazole

(Urinary tract infection)

- penicillin, cephalosporin nitrofurantoin
- trimetroprim cotrimoxazole
- tetracyclines, quinolones

 (Common cold)

teratogen
(poly-pharmacy)

(antihistamine)
chlorpheniramine tripolidine brompheniramine

(2nd generation antihistamine) cetirizine, fexofenadine
loratadine pregnancy category B
cetirizine
active metabloite hydroxyzine

(decongestants)
(clubfoot) inguinal hernia
pseudoephedrine
topical
dextrometrophan, gauifenesin

Fetal Alcohol Syndrome (FAS)
(uterine growth restriction) (microencephaly)
(micropthalmia)

(Hypertension)

2
1. Pre-eclampsia 140/90
20 (
300 /24

100 /
2 6 )

/ (pathologic edema)
2.3 /
2. Eclampsia pre-eclampsia
pre-eclampsia
(multiple gestation) pre-eclampsia


pre-eclampsia
aspirin thromboxane A2 prostacyclin
12
aspirin
pre-eclampsia 19 7
16 pre-eclampsia

1
pre-eclampsia 31-67
pre-eclampsia

2
/ (diureitcs) 48

Pre-eclampsia 160/110
6
/
- 4 /24

- 2+ (dipstick)

-
- (visual disturbance)
- 400 /24

magnesium sulfate

4-7 mEq/L
patellar reflex 10 / (urine output)
25 /

(cerebrovascular accidents)
hydralazine 5-10 5-10 10-20
diastolic pressure 110
hydralazine (tachycardia)
(flushing) (headache) (tremor, palpitation)
propranolol hydralazine propranolol

pre-eclampsia methyldopa 250

2-3 clonidine hydralazine
methyldopa
Beta-adrenergic blocker

()
24-72

Calcium channel blocker

nifedipine
(hypoxia), (acidosis)

Angiotensin Converting Enzyme Inhibitor (ACEI) Angiotensin II Receptor Blocker
(ARB) congenital
hypocalvaria, renal anomalies, nephrotoxicity, neonatal anuria, oligohydramnios pulmonary
hypoplasia
pregnancy category X

 (diuretics)

thiazide
(neonatal hypoglycemia)
(electrolytes imbalance)
(Seizure disorder)

(anticonvulsant) 2-3

3
Phenytoin Fetal
Hydantoin Syndrome (FHS) 7-11
(mental retardation)
(congenital heart disease)
vitamin K
(Hemorrhagic Disease of New Born: HDN) vitamin K1
(phytonadione) 10
folic acid
carbamazepine (drowsiness) (ataxia)
(leukopenia) (mild hepatotoxicity)
(facial dysmorphism) (neural tube defect)
Phenobarbital (drowsiness) (ataxia)
(neonatal withdrawal)

Valproic acid (drowsiness) (ataxia) (alopecia)

(hepatotoxicity)
(facial
dysmorphism) (neural tube defect)


Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to
moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews
2007, Issue 1. Art. No.: CD002252. DOI: 10.1002/14651858.CD002252.pub2.
Alonso-Coello P, Guyatt G, Heels-Ansdell D, et al. Laxatives for the treatment of hemorrhoids.
The Cochrane Database of Systematic Reviews 2005;Issue 4:Art No CD004649.
Askie LM, Duley L, Henderson-Smart DJ, on behalf of the PARIS Collaborative Group.
Antiplatelet agents for the prevention of pre-eclampsia: a meta-analysis of individual
patient data. Lancet 2007; 369: 17918.
Baron TH, Ramirez B, Richter JE. Gastrointestinal motility disorders during pregnancy. Ann
Intern Med 1993; 118: 36675.
Bates S, Greer IA, Ginsberg J, Hirsh J. Use of antithrombotic agents during pregnancy. Chest
2004; 126(Suppl 3): 627s44s.
Bint AJ, Hill D. Bacteriuria in pregnancy an update on significance, diagnosis and
management. J Antimicrob Chemother 1994; 33(Suppl A): 937.
Bracken M, Holford TR. Exposure to prescribed drugs in pregnancy and association with
congenital malformations. Obstet Gynecol 1981; 58: 33644.
Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 7th edition. Baltimore:
Lippinott, Williams & Wilkins; 2005.
Broussard CN, Richter JE. Treating gastro-oesophageal reflux disease during pregnancy and
lactation: what are the safest therapy options? Drug Saf 1998; 19: 32537.
Chidress CH, Katz VL. Nifedipine and its indications in obstetrics and gynecology. Obstet
Gynecol 1994; 83: 61624.
CLASP Collaborative Group. Low dose aspirin in pregnancy and early childhood development:
follow-up of the collaborative aspirin study in pregnancy. Br J Obstet Gynaecol 1995; 102:
8618.
Dowswell T, Neilson JP. Interventions for heartburn in pregnancy. Cochrane Database of
Systematic Reviews 2008, Issue 4. Art. No.: CD007065. DOI:
10.1002/14651858.CD007065.pub2.
Garbis H, Elefant E, Diav-Citrin O, et al. Pregnancy outcome after exposure to ranitidine and
other H2-blockers. A collaborative study of the European Network of Teratology
Information Services. Reprod Toxicol 2005; 19: 4538.
Greer IA, Hunt BJ. Low molecular weight heparin in pregnancy: current issues. Br J Haematol
2005;128:593601.

Greer IA, Nelson-Piercy C. Low-molecular weight heparins for thromboprophylaxis and

treatment of venous thromboembolism in pregnancy: a systemic review of safety and
efficacy. Blood 2005;1 06(2): 4017.
Glmezoglu AM. Interventions for trichomoniasis in pregnancy. Cochrane Database of
Systematic Reviews 2002, Issue 3. Art. No.: CD000220. DOI:
10.1002/14651858.CD000220.
Hedgley CA, McElhatton PR, Thomas SHL. Outcome of pregnancy following maternal treatment
with proton pump inhibitors (PPIs). Clin Toxicol 2005; 43: 431.
Inman WH, Pearce G,Wilton L. Safety of fluconazole in the treatment of vaginal candidiasis. A
prescription-event monitoring study, with special reference to the outcome of pregnancy.
Eur J Clin Pharmacol 1994; 46: 1158.
Lee A, Schofield S. Drug use in pregnancy: 2. Common medical problems. Pharm J 1994; 252:
5760.
Marlettini MG, Crippa S, Morselli-Labate AN, et al. Randomized comparison of calcium
antagonists and -blockers in the treatment of pregnancyinduced hypertension. Curr
Ther Res 1990; 48(4): 68492.
Matthews A, Dowswell T, Haas DM, Doyle M, O'Mathna DP. Interventions for nausea and
vomiting in early pregnancy. Cochrane Database of Systematic Reviews 2010, Issue 9.
Art. No.: CD007575. DOI: 10.1002/14651858.CD007575.pub2.
Nelson-Piercy C. Treatment of nausea and vomiting. Drug Saf 1998; 19: 15564.
Pfaffenrath V, Rehm M. Migraine in pregnancy.What are the safest treatment options? Drug Saf
1998; 19: 3838.
Philipson A. Pharmacokinetics of antibiotics in pregnancy and labour. Clin Pharmacokinet 1979;
4: 297309.
Quijano CE, Abalos E. Conservative management of symptomatic and/or complicated
haemorrhoids in pregnancy and the puerperium. Cochrane Database of Systematic
Reviews 2005, Issue 3. Art. No.: CD004077. DOI: 10.1002/14651858.CD004077.pub2.
Ranchet G, Gangemi O, Petrone M. Sucralfate in the treatment of gravidic pyrosis. G Ital
Ostericia Ginecol 1990; 12: 116.
Reveiz L, Gyte GML, Cuervo LG. Treatments for iron-deficiency anaemia in pregnancy.
Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD003094. DOI:
10.1002/14651858.CD003094.pub2.
Rost van Tonningen M. Gastrointestinal and antilipidemic agents and spasmolytics. In: Schaefer
C (ed.), Drugs During Pregnancy and Lactation. Amsterdam: Elsevier Science; 2001.

Rubin PC. Aspirin and preeclampsia. Curr Obstet Gynaecol 1994; 4: 1669.
Schatz M, Pettiti D. Antihistamines and pregnancy. Ann Allerg Asthma Immunol 1997; 78: 157
9.
Sorensen HT, Nielsen GL, Olesen C, et al. Risk of malformations and other outcomes in
children exposed to fluconazole in utero. Br J Clin Pharmacol 1999; 48: 2348.
Stuart MJ, Gross SJ, Elrad H, Graeber JE. Effects of acetylsalicylic acid ingestion on maternal
and neonatal haemostasis. N Engl J Med 1982; 307: 90212.
Uknis A, Silberstein SD. Review article: migraine and pregnancy. Headache 1991; 31: 3724.
Van Thiel DH, Gavaler JS, Stremple J. Heartburn of pregnancy. Gastroenterology 1977; 72:
6668.
Weitz JL. Low molecular weight heparins. NEngl J Med 1997; 337: 68898.
Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Use of over-the-counter medications
during pregnancy. Am J Obstet Gynecol 2005; 193: 7717.
Wesseling J, van Driel D, Heymans HAS, et al. Coumarins during pregnancy: long-term effects
on growth and development of school-age children. Thromb Haemost 2001; 85(4): 577
755.
Whitelaw A. Maternal methyldopa treatment and neonatal blood pressure. Br Med J 1981; 283:
471.