‫اﻟﻤﺮﺣﻠﺔ اﻟﺮاﺑﻌﺔ‬
Obstetrics
‫ ﺟﺎﻣﻌﺔ ﺑﺎﺑﻞ‬⁄ ‫ﻛﻠﯿﺔ اﻟﻄﺐ‬
‫ ﻧﺴﺮﯾﻦ ﻣﺎﻟﻚ‬-‫د‬
Medication in pregnancy:-
Each pregnancy carries a risk of major anomalies of 2-3 ٪ , and 2-3 ٪ of these are due to drugs
exposure.
In addition to prescription medication , many pregnant women also take over- the- counter
medication (OTCs), and others take medication before their realization of pregnancy.
Comonally used drugs are analgesics, antibiotics, antiemetics, antacids, antihypertensives,
tranqualizers, hypnotics, and diuretics.
Given the fact that half of pregnancies are unplanned. It is important to minimize exposure to
unnecessary medications in reproductive age women regardless of their plan for pregnancy.
Physiological changes in pregnancy that may affect drug metabolism:Continuous morphological and physiological changes in pregnancy affect drug pharmacokinetics and make
it difficult to predict the time course of drug concentration. These changes must be recognized when
prescribing in pregnancy:-
1-Gastrointestinal system:-In early pregnancy most women suffer from nausea and vomiting , and
later heartburn, all of which may result in poor compliance. During pregnancy, the acid content of
the stomach reduced and gastric emptying slows. Drugs which are absorbed in stomach or which
need to pass into the small bowel for absorption may therefore be affected.
The reduction in intestinal activity during pregnancy prolonged the transient time .Prolonged contact
with the intestinal surface may result in a more complete absorption .In contrast , if a drug is
metabolized in the gut wall , less of the parent drug may reach the systemic circulation and therefore
the bioavailability will be reduced.
2-Pulmonary system:- During pregnancy there is increase in the ventilation, so diffusion will be
increased, this is a characteristic of substances such as nitrous oxide used for analgesia in labour.
3- Skin and mucous membranes:- In pregnancy, blood flow to the skin is increased significantly ,
and this result in more rabid absorption of drugs from the skin surface and mucous membranes.
Although similar changes occur in the vagina , there is no evidence to indicate that the absorption
from the vagina is improved.
4- Central nervous system:- There is an increase in the vascularity of the epidural space .Opiates
placed in this space are more rapidly absorbed in pregnant than in non pregnant women .This
facilitates the rapid establishment of analgesia in labour.
5- Blood and plasma volume:- During pregnancy the body water increase by 6-8 L , the plasma
volume increase by 50 per cent by the third trimester and the red cell volume increase by 18
per cent in pregnancy. These physiological changes increase the area of distribution for water soluble
drugs.
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6- Plasma proteins:-The concentration of plasma albumin falls in the first half of pregnancy from
about 35 g\L to 25 g\L. This result in a decrease in the bound fraction of the drugs that bound to the
albumin, and corresponding increase in the free fraction.
7- The urinary system :- The kidneys are an important rout for the metabolism and excretion of
drugs . Physiological changes in pregnancy such as an increase in the renal plasma blood flow and
glomerular filtration rate may therefore affect the concentration and elimination of these drugs from the body,
and consequently alter their efficacy.
Teratogen:-Is any agent or factor to which the
alteration in form and \or function of the offspring.
embryo or fetal exposure produce a prominent
Factors that determine the teratogenic effect of agents on a fetus during pregnancy:1- Type of the agent (molecular weight, lipid solubility, physiological handling of the agent by both
the pregnant woman and the fetus).
2- Dose of the agent.
3- Genetic predisposition.
4- Timing of the agent exposure.
Pregnancy is divided into 3 periods:1-The germinal period:-from fertilization to implantation.
2- the embryonic period:-from 3-8 weeks of gestation, this is the period for organogenesis , and this
is the most vulnerable period.
3-Fetal period:- when there is only growth of the fetus (9 weeks till delivery).
The critical period for organogenesis or the classic teratogenic period is from 31- 71 days after the
last menstrual period in a normal 28 days menstrual cycle.
Timing of exposure is the key to the malformation pattern noted at birth. Administration of drugs
early in the period of organogenesis will lead to defect in the neural tube or heart which form early ,
whereas exposure later in the period may lead to abnormalities such as cleft palate.
Exposure to a teratogen prior to day 31 produces an all – or none effect .This means that the
exposure leads to abortion of the conceptus dose not survive , or there is survival without congenital
anomalies.
An important aspect in teratogenecity is that drug administered beyond the vulnerable period
usually will not cause structural malformation.
The US Food and Drug Administration (F.D.A) has five categories of labeling for drug use in
pregnancy:A
Controlled studies show no risk.
Adequate, well-controlled studies in pregnant women have failed to demonstrate risk to
the fetus in any trimester of pregnancy.
B
No evidence of risk in humans .
Either animal findings show risk (but human findings do not) or, if no adequate human
studies have been done, animal findings are negative.
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C
Risk cannot be ruled out.
Human studies are lacking and animal studies are either positive for fetal risk or lacking
as well. However, potential benefits may justify the potential risk.
D
Positive evidence of risk .
Investigational or post-marketing data show risk to fetus. Nevertheless,
potential benefits may outweight the risk.
X
Contraindicated in pregnancy.
Studies in animals or humans, or investigational or post-marketing reports have
shown fetal risk which clearly outweighs any possible benefit to the patient.
Antimicrobials:1-Antibacterial agents:-
Penicillin and its derivatives are some of the safest antimicrobials in pregnancy .Although they
may cross the placenta, they are not teratogenic.
The combination of the penicillins with the beta-lactamase inhibitor clavulanic acid
(Augmentin) has been demonstrated to induce significant side effects in the fetus, although
there may not associated with congenital malformations.It is therefore advisable to avoid
Augmentin in pregnancy.
Macrolides :-are large molecules and not cross the placenta .These agents are also considered
safe in pregnancy. The most common member of this family is erythromycin , this drug is
useful for patients who are allergic to penicillines .The main disadvantage of these agents is
that if the fetus needs treatment , they will be ineffective . For example , patient with syphilis.
The only satisfactory treatment for penicillin-allergic pregnant patients with syphilis is
desensitization for penicillin followed by penicillin therapy.
Erythromycin ethylsuccinate is safe in pregnancy , while erythromycin estoalte is contraindicated
during pregnancy due to risk of hepatotoxicity.
Cephalosporins:Second and third generation cephalosporins contain the N-methylthiotetrazole(MTT) side
chain that has been associated with testicular hypoplasia in animals. Although no similar effect
has been demonstrated in humans , these drugs should be use with caution in pregnancy ,
especially in the first trimester.
Aminoglycosides:-are teratogenic . When administered to the pregnant women , they cross
into the embryo\ fetus at significant levels. Streptomycin , a member of this family , has been
associated with sensorineural defness (eighth cranial nerve damage ).
Tetracycline:- Tetracycline and its derivatives are broad spectrum antibiotics , they should be
avoided during pregnancy and breast feeding because they are associated with discoloration of
the deciduous teeth .
Sulphonamides:- they interfere with folic acid metabolism (there is theoretical risk in early
pregnancy), and they are cross the placenta and may compete with the binding of the bilirubin
in the fetus , resulting in neonatal jaundice .
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Cloramphenicol:-Should be avoided during pregnancy , although it is not recognized to cause
specific congenital malformations ; it is associated with the neonatal gray baby syndrome.
Nitrofurantoin:-Is a drug use for uncomplicated UTI.is safe in pregnancy , but better to be
avoided in third trimester or 4 weeks before expected delivery as it may cause hemolysis in
neonate with G6PD.
Vancomycin:-a drug that use for prophylaxis of endocarditis in penicillin allergic patients , it
cross the placenta and cause ototoxicity .
Fluoroquinolones:-Ciprofloxacin is associated with congenital arthropathy in dogs (not
demonstrated in humans),so it is better avoided in pregnancy.
Anti tuberculosis:-Isoniazid INH is frequently used and considered safe in pregnant patients.
Excretion in breast milk is thought to be minimal, and the risk of adverse events to the infant of
a nursing mother receiving INH is generally considered to be low. There are two major adverse
reactions to INH: neurologic and INH-induced hepatotoxicity .
Rifampin and Pyrazinamide PZA can probably be used safely during pregnancy and is
recommended by the World Health Organization (WHO) and the International Union against
Tuberculosis and Lung Disease (IUATLD).
Ethambutol cause optic neuritis,so it use with caution .
2-Antifungal agents:-
Clotrimazole, Miconazole ,and Nystatin (Mycostatin) are topical antifungl are safe to use
during pregnancy.
Oral antifungai like Fluconazole (Diflucan) 150 mg oral tablet single dose, and others like
Amphotericin B , Ketoconazole ,Itraconazole and Griseofulvin are contraindicated in
pregnancy.
Griseofulvin has a possible association with conjoined twins in humans.
3- Anti viral agents:- Acyclovir has been assigned to pregnancy category B in which there
is no clear evidence of risk in humans .
Ganciclovir:- (group C )in the long animal studies have demonstrated carcinogenic and
teratogenic effects, and inhibition of spermatogenesis.
Zidovudine:- (group C ) Zidovudine crosses the placenta. The use of zidovudine reduces the
maternal-fetal transmission of HIV by ~70% and should be considered for antenatal and
intrapartum therapy whenever possible.
Zalcitabine:- (group C )It is not known if zalcitabine crosses the human placenta. Animal
studies have shown zalcitabine to be teratogenic, developmental toxicities were also observed.
Cases of lactic acidosis have been reported in pregnant women receiving nucleoside analogue
drugs.
Alfa -interferone(group C ) safety and efficacy for use during pregnancy have not been
established. Interferon alpha has been shown to decrease serum estradiol and progesterone
levels in humans. Menstrual irregularities and abortion have been reported in animals.
Effective contraception is recommended during treatment.
Amantadin:- (group C)Teratogenic effects were observed in animal studies; limited data in
humans. Impaired fertility has also been reported during animal studies and during human in
vitro fertilization.
Ribavirin:- (group X )Is contraindicated in pregnancy.it has been found to cause hydrocephaly
in animals.
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4-Antiprotozoal agents:-
Metroidazole:- (group B\C ) Crosses the placenta , it is carcinogenic in rats, mutagenic in
bacteria, contraindicated during the first trimester of pregnancy, unless alternative treatment is
inadequate. Until safety and efficacy for other indications have been established, use only
during pregnancy when the benefit to the mother outweighs the potential risk to the fetus.
Tinidazole:- (group C ) Tinidazole crosses the placenta and enters the fetal circulation. Use
during the first trimester is contraindicated.
Mefloquine:- (group C ) Mefloquine crosses the placenta and is teratogenic in animals. There
are no adequate and well-controlled studies in pregnant women, however, clinical experience
has not shown teratogenic or embryotoxic effects; use with caution during pregnancy if travel
to endemic areas with malaria cannot be postponed.
Chloroquine:- (group C ) There are no adequate and well-controlled studies using
chloroquine during pregnancy. However, based on clinical experience and because malaria
infection in pregnant women may be more severe than in nonpregnant women, chloroquine
prophylaxis may be considered in areas of chloroquine-sensitive P. falciparum malaria.
Pregnant women should be advised not to travel to areas of P. falciparum resistance to
chloroquine.
Quinine:- (group C\X ) Teratogenic effects have been reported in some animal studies. Optic
nerve hypoplasia, and deafness have been reported in the infant following maternal use of very
high doses; however, therapeutic doses used for malaria are generally considered safe. Quinine
may also cause significant hypoglycemia when used during pregnancy.
Lindane:- (group C ) Pediculocide,scabicidal agent.There are no well-controlled studies in
pregnant women.
Spiramycin:-spiramycin has been used safly to treat Toxoplasma gondii to prevent
transmission from mother to fetus.
Pyremethamine:- (group C ) There are no adequate or well-controlled studies in pregnant
women. Teratogenicity has been reported in animal studies .Is folate antagonist , better to be
avoided during pregnancy.
5-Antihelmintics:-
Albendazole:- (group C ) has been shown to be teratogenic in laboratory animals and should
not be used during pregnancy, if at all possible. Women should be advised to avoid pregnancy
for at least 1 month following therapy. Discontinue if pregnancy occurs during treatment.
Mebendazole:- (group C ).
Thiabendazole:- (group C ).Cleft palate and skeletal defects were observed in some animal
studies. There are no adequate and well-controlled studies in pregnant women.
Cardiovascular drugs:-
1-Antiarrhythmic agents:-
Adenosine:- (group C ) Reports of administration during pregnancy have indicated no adverse
effects on fetus or newborn attributable to adenosine.
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Amiodarone:- has unique characteristics that mandate cautious use in pregnancy. Among the
complications that can occur are hypothyroidism in fetus because of the iodine in amiodarone,
fetal bradycardia, fetal QT interval prolongation, premature labor, and low birth weight infants.
Flecainide:- (group C )It can use for treatment of fetal arrhythmia .
Quinidine:- (group C )It use for treatment of SVT and VT, and use for treatment of fetal
tachycardia.
Verapamil:- (group C ) Use in pregnancy only when clearly needed and when the benefits
outweigh the potential risk to the fetus. Crosses the placenta. One report of suspected heart
block when used to control fetal supraventricular tachycardia. May exhibit tocolytic effects.
Propranolol:- Propranolol crosses the placenta. Beta-blockers have been associated with
bradycardia, hypotension, IUGR, and neonatal hypoglycemia .
Propafenone:-There are no adequate and well-controlled studies in pregnant women; use only
if potential benefit to the mother justifies potential risk to the fetus.
2-Antihypertensive agents:-
Methyldopa:- (group B ) Available evidence suggests safe use during pregnancy.
Side effects include hypotension , dizziness , fatigue , insomnia, anxiety, depression,
nausea/vomiting, systemic lupus erythematosus like syndrome , nephrotic syndrome,
thrombocytopenia. Neonatal paralytic ileus with very high doses , and there may be false
positive Coombs test in the neonate.
Hydralazine:- (group C ) Crosses the placenta. One report of fetal arrhythmia; transient
neonatal thrombocytopenia and fetal distress reported following late 3rd trimester use. A large
amount of clinical experience with the use of this drug for management of hypertension during
pregnancy is available. Available evidence suggests safe use during pregnancy.
Nefidipine:- (group C ) Ca++ channel blocker ,cause hypokalemia, uterine relaxation and
PPH.
ACE:-Captopril:- (group C ) in 1st trimester, (group D ) in 2nd and 3rd trimesters.
It decrease placental blood flow, low birth weight, fetal hypotension, preterm delivery, and
fetal death have been noted with the use of some ACE inhibitors (ACEIs) in animal studies.
Neonatal hypotension, skull hypoplasia, anuria, renal failure, oligohydramnios (associated with
fetal limb contractures, craniofacial deformities, hypoplastic lung development), prematurity,
intrauterine growth retardation, and patent ductus arteriosus have been reported with the use of
ACEIs, primarily in the 2nd and 3rd trimesters
Sodium Nitroprusside: (group C\D ) Accumulation of cyanide in the fetal liver.
Diuretics:- (group C ).
Loop diuretics( furosemide, bumetanide) Crosses the placenta. Increased fetal urine
production, electrolyte disturbances reported. Generally, use of diuretics during pregnancy is
avoided due to risk of decreased placental perfusion. Diuretics should not be used during
pregnancy in the presence of reduced placental perfusion (eg, pre-eclampsia, intrauterine
growth restriction).
Thiazides:-Hydrochlorothiazide:-Although there are no adequate and well-controlled studies
using hydrochlorothiazide in pregnancy, thiazide diuretics may cause an increased risk of
congenital defects. Hypoglycemia, hypokalemia, hyponatremia, jaundice, and
thrombocytopenia are also reported as possible complications to the fetus or newborn.
Spironolacion:- (group C\D )The antiandrogen effects of spironolactone have been shown to
cause feminization of the male fetus in animal studies.
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3-Anticoagulant:-
Heparin:- (group B )Is safe , not cross the placenta.
warfarin:- (group D\X) Cross the placenta.There is convincing evidence that warfarin
administration between the sixth and ninth weeks of gestation is potentially teratogenic , affect
bone and cartilage; these simulate chondromalacia punctata, with stippled epiphyses and nasal
and limb hypoplasia.
CNS abnormalities (including optic atrophy, microcephaly, mental retardation, spasticity, and
hypotonia) ,and associated with higher rates of spontaneous abortion and stillbirth .
Fetal or neonatal hemorrhage if used in third trimester.
The teratogenic effect appears to be dose related, with doses less than 5 mg/day providing the
highest margin of safety .
Streptokinase:- (group C ) Thrombolytic agent . No study on fetal affect , high risk if used
during pregnancy in relation to maternal condition.
Drugs of asthma:Beta 2 Agonist:- Salbutamol (group C ) Crosses the placenta; tocolytic effects, fetal
tachycardia, fetal hypoglycemia secondary to maternal hyperglycemia with oral or intravenous
routes reported. Available evidence suggests safe use during pregnancy.
Epinephrine(adrenaline) (group C ) Crosses placenta.
Aminophyllin:- Theophylline (group C ) Crosses the placenta; adverse effects may be seen in
the newborn. Theophylline metabolism may change during pregnancy; monitor serum levels.
Glucocorticoids :- (group C ) The most commonly used glucocorticoids are the short acting
agents, prednisone, prednisolone, and methylprednisolone, and the longer acting
dexamethasone and betamethasone. Radiolabeled prednisone and prednisolone can cross the
placenta and appear in small amounts in cord blood. In comparison, dexamethasone and
betamethasone reach higher concentrations in the fetus because they are less efficiently
metabolized by the placenta.
Experimental studies in rodents have shown that maternal administration of glucocorticoids
can result in cleft palates in the offspring . Cases of cleft palate, mental retardation, and fatal
adrenal hypoplasia have also been described in humans after in utero corticosteroid exposure .
Antihistamines:-
Diphenhydramine, chlorphenamine:- (group B )
Anti acid and peptic ulcer healing drugs:Alkali:-thought to be safe in pregnancy .
Omeprazole:- (group C ) Crosses the placenta; congenital abnormalities have been reported
sporadically following omeprazole use during pregnancy.
Ranitidine:- (groupB ) Ranitidine crosses the placenta, teratogenic effects to the fetus have not
been reported in animal studies. Use with caution during pregnancy.
Cimetidine:-Teratogenic events were not observed in animal studies. It better to avoid as may
have anti-androgenic effect.
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Antiemetic drugs:-
Metoclopramide: (group B )Crosses the placenta; available evidence suggests safe use during
pregnancy.
Prochlorperazine: Crosses the placenta. Isolated reports of congenital anomalies. Jaundice,
extrapyramidal signs, hyper-/hyporeflexes have been noted in newborns. Available evidence
with use of occasional low doses suggests safe use during pregnancy.
Thalidomide:- (group X )casues phocomelia (limbs reduction or absence).
Antiepileptics:- (group D )All Antiepileptics carry a high risk for fetal malformations.
The mecanisim may be related to folate deficiency,or due to metabolic insult to the cells during
drug metabolism by immature cells of the body. Some author suggest a fetal genetic
predisposition.
Carbamazepine:-Crosses the placenta. Dysmorphic facial features, cranial defects, cardiac
defects, spina bifida, IUGR, and multiple other malformations reported.
Phenytoin:- Craniofacial anomalies ,cleft lip, broad nasal bridge, ,hypoplasia of distal
phalanges,IUGR, mental retardation.Isolated cases of malignancies (including neuroblastoma)
and coagulation defects in the neonate following delivery have also been reported.
Phenobarbital:-Crosses the placenta. Cardiac defect reported; hemorrhagic disease of
newborn due to fetal vitamin K depletion may occur; may induce maternal folic acid
deficiency; withdrawal symptoms observed in infant following delivery.
Valproic acid and derivatives:- Valproic acid crosses the placenta. Neural tube defect,
cardiac, facial (characteristic pattern of dysmorphic facial features), skeletal, and other multiple
defects were reported.
Diazepam:-Teratogenic effects have been reported in animal studies. In humans, diazepam
crosses the placenta. An increased risk of fetal malformations has been associated with
diazepam and other minor tranquilizers; epilepsy itself may also increase the risk. Hypotonia,
hypothermia, withdrawal symptoms, respiratory and feeding difficulties have reported in the
infant following maternal use of benzodiazepines near time of delivery.
Antidepressants:-
1-Selective serotonin reuptake inhibitors:fluoxetine (Prozac®):-(group C )Fluoxetine crosses the placenta. Nonteratogenic effects
including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding
difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability,
constant crying, and tremor have been reported in the neonate immediately following delivery
after exposure to SSRIs late in the third trimester. Exposure to SSRIs late in pregnancy has also
been associated with persistent pulmonary hypertension of the newborn (PPHN). Adverse
effects may be due to toxic effects of SSRI or drug discontinuation.
Sertraline:- (group C )
Citalopram:- (group C )
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2- Tricyclic antidepressants :-
Amitriptyline :- (group C )Teratogenic effects have been observed in animal studies.
Amitriptyline crosses the human placenta; CNS effects, limb deformities and developmental
delay have been noted in case reports.
Paroxetine :- (groupD )Teratogenic effects were not observed in animal studies.
imipramine (Tofranil®):-(groupD ).
3- Monoamine oxidase (MAO) inhibitors:-
Tranylcypromine, Phenelzine:- (group C )
4-Lithium:- (group D ) used for bipolar disorders.Cardiac malformations in the infant,
including Ebstein's anomaly, are associated with use of lithium during the first trimester of
pregnancy. Nontoxic effects to the newborn include shallow respiration, hypotonia, lethargy,
cyanosis, diabetes insipidus, thyroid depression, and nontoxic goiter when lithium is used near
term.
Antipsychotic Agent:-
Chlorpromazine:- (group C ) May cause congenital malformation.
Endocrine:-
1-Diabetes mellitus treatment:-
Insulin:- Does not cross the placenta. Insulin is the drug of choice for control of diabetes
mellitus during pregnancy.
Oral hypoglycemic agents:Sulfonylurea (Glyburide):- (group C ).Glyburide was not found to significantly cross the
placenta in vitro. Studies have shown glyburide to be an acceptable alternative to insulin when
treatment is needed for gestational diabetes. However, one retrospective study comparing
glyburide to insulin noted an increased risk of preeclampsia in women taking glyburide and a
higher rate of phototherapy in neonates.
Biguanides( Metformin):- cross the placenta , cause hypoglycemia, and associated with
increase of perinatal mortality.
2-Antithyroid drugs:-
Propylthiouracil:- (group D) Crosses the placenta and may induce goiter and hypothyroidism
in the developing fetus (cretinism). May need to monitor infant's thyroid function periodically.
Methimazole:- (group D) Hypothyroidism and congenital defects (rare) may occur.
Carbimazole:- (group D) Crosses the placenta and may induce goiter and hypothyroidism, and
may cause aplasia cutis.
Analgesics:-
1-Nonsteroidal Anti-inflammatory Drug (NSAID):Aspirin:- (group C \ D) Salicylates have been noted to cross the placenta and enter fetal
circulation. Adverse effects reported in the fetus include mortality, intrauterine growth
retardation, salicylate intoxication, bleeding abnormalities, and neonatal acidosis. Use of
aspirin close to delivery may cause premature closure of the ductus arteriosus. Adverse effects
reported in the mother include anemia, hemorrhage, prolonged gestation, and prolonged labor.
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Aspirin has been used for the prevention of pre-eclampsia; however, the ACOG currently
recommends that it not be used in low-risk women.
Indomethacin:- (group C \D) in 3rd trimester. Cause intrauterine growth retardation, use of it
after 32 weeks of gestation may cause premature closure of the ductus arteriosusm , renal
failure, oligohydramnios.
Acetaminophen:-Paracetamol (group B ) .
2- opioids:-
Tramadol:- (group C ) Tramadol has been shown to cross the placenta. Postmarketing reports
following tramadol use during pregnancy include neonatal seizures, withdrawal syndrome,
fetal death and stillbirth. Not recommended for use during labor and delivery.
Codeine:- (group C \ D) in prolonged use or high doses at term.
Diamorphine( Heroin):- (group C \ D).
Morphine:-(group C \ D) Crosses the placenta. The frequency of congenital malformations
has not been reported to be greater than expected in children from mothers treated with
morphine during pregnancy. Reduced growth and behavioral abnormalities in offspring have
been observed in animal studies. Neonates born to mothers receiving chronic opioids during
pregnancy should be monitored for neonatal withdrawal syndrome.
Methadone:- (group C \ D) Teratogenic effects have been observed in some, but not all,
animal studies.
Pethidine (Meperidine):- (group C \ D) in prolonged use or high doses at term.
Meperidine is known to cross the placenta, which may result in respiratory or CNS depression
in the newborn.
Anasthesia:-
Halothane:- (group C )May has teratogenic effect, and cause abortion in animals.
All general anesthetics may cause fetal hypoxia.
Substance abuse:-
Alcohol:-Fetal alcoholic syndrome FAS include The typical FAS face has short palpebral
fissures, a thin upper lip, an abnormal philtrum, and a hypoplastic midface, IUGR, stillbirth,
post natal growth retardation, and mental retardation.
Tobacco smoking:- Placental abruption/placenta previa, preterm premature rupture of
membranes, IUGR, stillbirth, and congenital malformations.
Marijuana:- (group C ) IUGR.
Cocaine:-Abruptio placenta.
Amphetamine:- (group C ) Teratogenic and embryocidal effects have been observed in animal
studies. Infants may deliver prematurely and suffer withdrawal symptoms. There are no
adequate and well-controlled studies in pregnant women.
Antineoplastic drugs:-
Cyclophosphamide:- (group D\X ) most commonly associated with missing or hypoplastic
digits on the hands and feet.
Methotrexate:- (group X ) is embryotoxic in early pregnancy and causes skeletal
abnormalities and cleft palate , hydrocephalus, congenital stenosis of tubular long bones,
abnormal facial features (low-set ears, micrognathia), and delayed ossification .
Chlorambucil:- (group D\X) Carcinogenic and mutagenic in humans.There is little data on the
effect of chlorambucil on human pregnancy. There are case reports of renal agenesis.
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Immunosuppressants:-
Glucocorticoids :- (group C ).
Azathioprine:- (group D ) can cause fetal absorption and death, while lower doses do not
interfere with normal implantation and fetal development.
Cyclosporine:- (group C ) there are conflicting reports on the transfer of cyclosporine across
the human placenta: some reports have found little or no transfer, while others found
cyclosporine levels in the placenta that were equivalent to those in maternal blood, premature
births and low birth weight were consistently observed.
Vitamins:-
Multiple vitamins (prenatal):- (group A )
Vitamin A:- (group A/X) according to the dose. Excessive use of vitamin A shortly before and
during pregnancy could be teratogenic.
Vitamin D:- (group C )There may be skeletal abnormalities in high doses regimen.
Isotretinoin:- (group X) Major fetal abnormalities (both internal and external), spontaneous
abortion, premature births and low IQ scores in surviving infants have been reported. Females
of childbearing potential should not become pregnant during therapy or for 1 month following
discontinuation of isotretinoin. It cause severe congenital malformations; including cleft palate,
congenital heart malformations, thymic, eye , and brain anomalies, and mental retardation.
Etretinate:- (group X) For treatment of psoriasis, detected in serum 2 years after cessation of
treatment. Cause CNS, and craniofacial malformations.
Topical tretinoin:- (group C ) Tretinoin does not appear to be teratogenic when used topically
since it is rapidly metabolized by the skin; however, there are rare reports of fetal defects. Use
for acne only if benefit to mother outweighs potential risk to fetus.
Hormones:-
Danazol:- (group X) May cause androgenic effects to the female fetus; clitoral hypertrophy,
labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been
reported.
Also Enters breast milk/contraindicated.
Diethylstilbestrol(DES):- (group X) Is a nonsteroidal synthetic estrogen There may be a
small increase in risk of breast cancer in women who took DES during pregnancy,
In-utero exposure to DES has been associated with several potential effects in female offspring (DES
daughters): Cervicovaginal clear cell adenocarcinoma ,congenital anomalies and epithelial changes of
the reproductive tract , Earlier age at menopause . Testicular hypoplasia in the male fetus.
Oral contraception pills:- (group X ) OC receive this category due to luck of benefit and not
due to significant fetal risk. Inadvertent OC administration during early pregnancy has not
been associated with an increase in risk of congenital anomalies. A possible exception is
congenital urinary tract abnormalities, the frequency of which was increased in one study .
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Vaccines:-
Live attenuated virus vaccine:-Are contraindicated during pregnancy. Like measles, mumps,
rubella vaccine, yellow fever, BCG ,oral polio vaccine.
Killed vaccines and toxoids:- are safe in pregnancy. Like Typhoid, typhus, influenza vaccine,
cholera, plaque, and killed polio vaccine .
Hepatitis A virus and recombinant hepatitis B virus vaccine:- (group C ).
Effect of ionizing radiation:-
There are no significant fetal effects from exposure to ultrasound or the magnetic fields related
to magnetic resonance imaging .
The potential deleterious consequences of ionizing radiation can be divided into four
categories : Intrauterine fetal death, malformation, disturbances of growth and development,
mutagenic and carcinogenic effects.
Preimplantation :- The embryo is most sensitive to the effects of ionizing radiation during
the preimplantation period (implantation begins 5.5 to six days after ovulation). During this
period, the exposed embryo will survive undamaged or will be resorbed (termed the "all or
none" phenomenon).
For human exposure, the best estimate of the threshold for preimplantation death is more than
(10 rads) . A fetal dose of 1 Gy (100 rads) will likely kill 50 percent of embryos; the dose
necessary to kill 100 percent of human embryos or fetuses before 18 weeks of gestation is
about 5 Gy (500 rads).
If injury to these cells occurs during a critical stage of organogenesis (usually the first 12
weeks of fetal development) , impairment, agenesis, or deformity of the developing organ can
occur. As an example, microcephaly develops when a large number of differentiating central
nervous system cells are injured.
Mental retardation occur when the exposure during 8 to 15 weeks after conception .
Growth restriction was most pronounced when the exposure occurred in the first trimester, and
3 to 4 percent reduction in height at age 18 occurred when the dose was greater than 1 Gy (100
rads).
Genetic effects :-Radiation may increase the frequency of naturally occurring mutations, (about
10 percent), recessive mutations take several generations to become apparent, and autosomal
dominant mutations are rare .
The average fetal exposure from a single chest X-ray (PA and lateral) < 0.1 mrad.
The average fetal exposure from a single abdominal radiograph is 100 mrad.
The average of radiation to the uterus during CT of the abdomen is 3 rad.
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