Use of drug during pregnancy and associated precautions

1. DRUG THERAPYDRUG THERAPY
DURING PREGNANCYDURING PREGNANCY

2. Drugs that a pregnant woman takes canDrugs that a pregnant woman takes can
affect theaffect the fetus in several ways:fetus in several ways:
 1- They can act directly on the fetus causing damage1- They can act directly on the fetus causing damage
or abnormal development leading to birth defects oror abnormal development leading to birth defects or
death.death.
 Drugs can also alter the function of the placentaDrugs can also alter the function of the placenta
usually by constricting blood vessels and reducing theusually by constricting blood vessels and reducing the
blood supply of oxygen and nutrients to the fetus fromblood supply of oxygen and nutrients to the fetus from
mother and thus resulting in a baby that is underweightmother and thus resulting in a baby that is underweight
and underdevelopedand underdeveloped..
 Moreover they can cause the muscles of the uterus toMoreover they can cause the muscles of the uterus to
contract forcefully; indirectly injuring the fetus bycontract forcefully; indirectly injuring the fetus by
reducing the blood supply or triggering pre-term laborreducing the blood supply or triggering pre-term labor
and delivery.and delivery.

3. PHARMACOKENETICS OFPHARMACOKENETICS OF
DRUGS DURINGDRUGS DURING
PREGNANCYPREGNANCY
 ABSORPTION- DECREASED GIABSORPTION- DECREASED GI
MOTILITY CAUSES INCREASED DRUGMOTILITY CAUSES INCREASED DRUG
ABSORPTION.ABSORPTION.
 DISTURBUTION- PROTIEN BINDING ISDISTURBUTION- PROTIEN BINDING IS
DECREASED CAUSES INCREASEDDECREASED CAUSES INCREASED
FREE DRUG TO BE AVAILABLE.FREE DRUG TO BE AVAILABLE.
 METABOLISM-INCREASED HEPATICMETABOLISM-INCREASED HEPATIC
METABOLISM OCCURS FOR SOMEMETABOLISM OCCURS FOR SOME
DRUGSDRUGS

4. PHARMACOKENETICSPHARMACOKENETICS
 EXCRETION- IN THE 3RD TRIMESTEREXCRETION- IN THE 3RD TRIMESTER
INCREASED RENAL BLOOD FLOW &INCREASED RENAL BLOOD FLOW &
GFR CAUSES SOME DRUGS TOGFR CAUSES SOME DRUGS TO
CLEAR THE BODY FASTER.CLEAR THE BODY FASTER.

5. DRUG THERAPY IN THEDRUG THERAPY IN THE
CHILDBEARING CLIENTCHILDBEARING CLIENT
 REQUIRES SPECIALREQUIRES SPECIAL
CONSIDERATIONSCONSIDERATIONS
 IS CHALLENGING TOIS CHALLENGING TO
PROVIDEPROVIDE
EFFECTIVEEFFECTIVE
Treatment WHILETreatment WHILE
AVOIDING HARM TOAVOIDING HARM TO
EMBRYO, FETUS OREMBRYO, FETUS OR
NEONATENEONATE
 CENTERED ONCENTERED ON
RISK/BENEFITRISK/BENEFIT
RATIORATIO
 EFFECTS OFEFFECTS OF
DRUGS NOTDRUGS NOT
ALWAYS KNOWNALWAYS KNOWN

6. ANY DRUG TAKEN BY
THE PREGNANT ORTHE PREGNANT OR
BREAST FEEDINGBREAST FEEDING
CLIENT HAS THECLIENT HAS THE
POTENTIAL TOPOTENTIAL TO
REACH THE FETUSREACH THE FETUS
BY WAY OFBY WAY OF
MATERNALMATERNAL
CIRCULATION ORCIRCULATION OR
NEONATE BY WAY OFNEONATE BY WAY OF
BREASTMILKBREASTMILK

7. EFFECTS OF DRUGSEFFECTS OF DRUGS
ON THE EMBRYO,ON THE EMBRYO,
FETUS, OR NEONATEFETUS, OR NEONATE
 MAY VARY---MAY VARY---
 NO EFFECT.NO EFFECT.
 LITTLELITTLE
 SERIOUS- FETAL TOXICITYSERIOUS- FETAL TOXICITY
 SPONTANEOUS ABORTIONSPONTANEOUS ABORTION
 DEATHDEATH
 FETAL MALFUNCTIONFETAL MALFUNCTION
 FETAL MALFORMATIONS.FETAL MALFORMATIONS.

8. RECENT STUDIESRECENT STUDIES
 75% OF PREGNANT CLIENTS USE75% OF PREGNANT CLIENTS USE
3-10 DIFFERENT DRUGS3-10 DIFFERENT DRUGS
(PRESCRIPTION OR OTC’S) OTHER(PRESCRIPTION OR OTC’S) OTHER
THAN VITAMINS/MINERALTHAN VITAMINS/MINERAL
SUPPLEMENTS DURING THEIRSUPPLEMENTS DURING THEIR
PREGNANCY.PREGNANCY.
 OTC’S WERE USED 4 TIMES THATOTC’S WERE USED 4 TIMES THAT
OF PRESCRIPTION DRUGS.OF PRESCRIPTION DRUGS.

9. TYPES OF DRUGSTYPES OF DRUGS
USED BY PREGNANTUSED BY PREGNANT
CLIENTSCLIENTS
 DIETARYDIETARY
SUPPLEMENTSSUPPLEMENTS
 ANTIEMETICSANTIEMETICS
 ANTACIDSANTACIDS
 TRANQUILIZERSTRANQUILIZERS
 HYPNOTICSHYPNOTICS
 ANTIBIOBIOTICSANTIBIOBIOTICS
 ANTIHISTAMINESANTIHISTAMINES
 ANALGESICSANALGESICS
 DIURETICSDIURETICS
 ETOHETOH
 CNSCNS
DEPRESSANTSDEPRESSANTS
 CNS STIMULANTSCNS STIMULANTS

10. DRUG LEVELS IN THEDRUG LEVELS IN THE
FETUS REACHED 50-FETUS REACHED 50-
100% OF THE100% OF THE
MATERNAL BLOODMATERNAL BLOOD
LEVELSLEVELS

11. SELF TREATMENTSELF TREATMENT
WITH DRUGS DURINGWITH DRUGS DURING
PREGNANCYPREGNANCY
 SELF Treatment OF MINORSELF Treatment OF MINOR
ILLNESSES OR DISCOMFORTSILLNESSES OR DISCOMFORTS
SHOULD BE DISCOURAGEDSHOULD BE DISCOURAGED
 *SELF TREATMENT OF ANY*SELF TREATMENT OF ANY
ILLNESSES SHOULD BEILLNESSES SHOULD BE
DISCOURAGEDDISCOURAGED
 WOMEN SHOULD BE INSTRUCTEDWOMEN SHOULD BE INSTRUCTED
TO KEEP A COMPLETE RECORD OFTO KEEP A COMPLETE RECORD OF
ALL MEDICATIONS TAKEN .ALL MEDICATIONS TAKEN .

13.  CANNOT OR SHOULD NOT BECANNOT OR SHOULD NOT BE
AVOIDED BECAUSE THE HEALTH OFAVOIDED BECAUSE THE HEALTH OF
THE FETUS DEPENDS ON THETHE FETUS DEPENDS ON THE
HEALTH OF THE MOTHER.HEALTH OF THE MOTHER.
 FOR EXAMPLE: SEIZURES, DM,FOR EXAMPLE: SEIZURES, DM,
asthma, SLE, OR INFECTIONS.asthma, SLE, OR INFECTIONS.

14. BIRTH DEFECTSBIRTH DEFECTS
 INCIDENCE OF MAJOR STRUCTURALINCIDENCE OF MAJOR STRUCTURAL
DEFECTS (ABNORMALITIES) ISDEFECTS (ABNORMALITIES) IS
ABOUT 6% OF ALL PREGNANCIES.ABOUT 6% OF ALL PREGNANCIES.
 3% ARE CAUSED BY DRUGS OR3% ARE CAUSED BY DRUGS OR
ENVIRONMENTALENVIRONMENTAL
fACTORS/EXPOSUREfACTORS/EXPOSURE
 3% HAVE UNKNOWN CAUSES3% HAVE UNKNOWN CAUSES

15. BIRTH DEFECTSBIRTH DEFECTS
 1/2 OF THE BIRTH DEFECTS ARE1/2 OF THE BIRTH DEFECTS ARE
OBVIOUS AT BIRTH.OBVIOUS AT BIRTH.
 1/2 OF THE BIRTH DEFECTS1/2 OF THE BIRTH DEFECTS
AREN’T DISCOVERED UNTIL LATERAREN’T DISCOVERED UNTIL LATER
IN LIFE OR DISCOVERED DURINGIN LIFE OR DISCOVERED DURING
AN AUTOPSYAN AUTOPSY
 INCIDENCE OF MINORINCIDENCE OF MINOR
STRUCTURAL ABNORMALIES ISSTRUCTURAL ABNORMALIES IS
NOT KNOWN.NOT KNOWN.

16. TERATOGENICTERATOGENIC
TERATOGENESISTERATOGENESIS
 TERAS-”MONSTER”TERAS-”MONSTER”
 GENSIS-”PRODUCING”GENSIS-”PRODUCING”
 BIRTH DEFECTS/DISTORTION OFBIRTH DEFECTS/DISTORTION OF
GROSS ANATOMY.GROSS ANATOMY.
 EXAMPLES- CLEFT LIP/PALATE,EXAMPLES- CLEFT LIP/PALATE,
CLUBFOOT, NEURAL TUBALCLUBFOOT, NEURAL TUBAL
DEFECTS, MISSING ORDEFECTS, MISSING OR
MALFORMED LIMBS/FINGERS.MALFORMED LIMBS/FINGERS.

17. TERATOGENICTERATOGENIC
 ALSO-BEHAVORIAL AND/ ORALSO-BEHAVORIAL AND/ OR
BIOCHEMICAL ABNORMALITIES.BIOCHEMICAL ABNORMALITIES.
 TERATOGENESIS MAYBE DIRECTTERATOGENESIS MAYBE DIRECT
MALFORMATIONS OFMALFORMATIONS OF
STRUCTURESSTRUCTURES
 OR INDIRECT-SUCH ASOR INDIRECT-SUCH AS
INTERFERING WITH OINTERFERING WITH O22 OROR
NUTRIENTS.NUTRIENTS.

18. TERATOGENICTERATOGENIC
EXAMPLE OF KNOWN TERATOGENICEXAMPLE OF KNOWN TERATOGENIC
AGENTS:AGENTS:
ONE TIME EXPOSURE:ONE TIME EXPOSURE:
THALIDOMIDE CAUSES MISSINGTHALIDOMIDE CAUSES MISSING
LIMBS; phocomelia.LIMBS; phocomelia.
CONTinued OR PROLONGedCONTinued OR PROLONGed
EXPOSURE IS ethanol -CAUSES fetalEXPOSURE IS ethanol -CAUSES fetal
alcohol syndrome (FAS.alcohol syndrome (FAS.

19. FETAL EFFECTS FROMFETAL EFFECTS FROM
DRUGS DEPEND ONDRUGS DEPEND ON
SEVERAL FACTORSSEVERAL FACTORS
 TIME- WHEN DRUG IS TAKEN INTIME- WHEN DRUG IS TAKEN IN
PREGNANCY.PREGNANCY.
1.1. PREIMPLANTATIONPREIMPLANTATION PERIOD; fromPERIOD; from
CONCEPTION TO 2 WEEKCONCEPTION TO 2 WEEK
 HIGH DOSE- MAYBEHIGH DOSE- MAYBE
LETHAL/DEATH/ABORTIONS.LETHAL/DEATH/ABORTIONS.
 LOW DOSE-MAYBE NOTHING.LOW DOSE-MAYBE NOTHING.

20. 2.2. EMBRYONIC PERIOD-3-8EMBRYONIC PERIOD-3-8 WEEKSWEEKS
*FIRST TRIMESTER* 2-9 weeks*FIRST TRIMESTER* 2-9 weeks
GROSS MALFORMATIONSGROSS MALFORMATIONS
3.3. FETAL PERIODFETAL PERIOD 9-40 WEEKS (TERM)9-40 WEEKS (TERM)
FUNCTION PROBLEMS RATHERFUNCTION PROBLEMS RATHER
THAN GROSS ANATOMYTHAN GROSS ANATOMY
 LEARNING DEFICITS and ORLEARNING DEFICITS and OR
BEHAVORIAL ABNORMALIESBEHAVORIAL ABNORMALIES

22. WHY ISWHY IS
IDENTIFICATION OFIDENTIFICATION OF
TERATOGENIC AGENTSTERATOGENIC AGENTS
SOMETIMESSOMETIMES
DIFFICULT?DIFFICULT?

23.  INCIDENCE OF CONGENITALINCIDENCE OF CONGENITAL
ANOMALIES IS GENERALLY LOW.ANOMALIES IS GENERALLY LOW.
 ANIMAL TESTS MAY NOT BEANIMAL TESTS MAY NOT BE
RELIABLERELIABLE
 PROLONGED OR INCREASEDPROLONGED OR INCREASED
EXPOSURE MAYBE REQUIRED.EXPOSURE MAYBE REQUIRED.
 EFFECTS MAYBE DELAYED OR NOTEFFECTS MAYBE DELAYED OR NOT
RECONIZED.RECONIZED.
 BEHAVIORAL EFFECTS AREBEHAVIORAL EFFECTS ARE
DIFFICULT TO DOCUMENT.DIFFICULT TO DOCUMENT.
 CONTOLLED EXPERIMENTSCONTOLLED EXPERIMENTS
CANNOT BE DONE ON HUMANS.CANNOT BE DONE ON HUMANS.

24.  DOCUMENTATION IS INCOMPLETEDOCUMENTATION IS INCOMPLETE
 ONLY IN A LIMITED NUMBER OFONLY IN A LIMITED NUMBER OF
DRUGS IS THE TERATOGENICDRUGS IS THE TERATOGENIC
EFFECTS KNOWN OR PROVEN.EFFECTS KNOWN OR PROVEN.
 LACK OF PROOF OFLACK OF PROOF OF
TERATOGENICITY DOES NOT MEANTERATOGENICITY DOES NOT MEAN
A DRUG IS SAFE IN PREGNANCYA DRUG IS SAFE IN PREGNANCY

25. PLACENTAL DRUGPLACENTAL DRUG
TRANSFERTRANSFER
 THE PLACENTA IS NOT ATHE PLACENTA IS NOT A
COMPLETE BARRIER.COMPLETE BARRIER.
 SOME DRUGS ARE STOPPED.SOME DRUGS ARE STOPPED.
 SOME DRUGS (IN FACT MOST) ARESOME DRUGS (IN FACT MOST) ARE
NOT.NOT.
 WAYS DRUGS ARE TRANSFERedWAYS DRUGS ARE TRANSFERed
ACROSS- SIMPLE DIFFUSION-ACROSS- SIMPLE DIFFUSION-
ACTIVE TRANSPORT.ACTIVE TRANSPORT.

26. TRANSFER DEPENDSTRANSFER DEPENDS
ON SEVERAL FACTORSON SEVERAL FACTORS
 CHEMICAL PROPERTY OF THECHEMICAL PROPERTY OF THE
DRUGDRUG
 MOLECULAR WEIGHT.MOLECULAR WEIGHT.
 PROTEIN BINDING CAPABILITIES.PROTEIN BINDING CAPABILITIES.
 CHEMICAL CONFIQURATION.CHEMICAL CONFIQURATION.
 LIPID SOLUBILITY.*LIPID SOLUBILITY.*
 PERIOD OF TIME DRUG REMAINSPERIOD OF TIME DRUG REMAINS
IN MATERNAL BLOODSTREAMIN MATERNAL BLOODSTREAM

27. TRANSFER DEPENDSTRANSFER DEPENDS
ON SEVERAL FACTORSON SEVERAL FACTORS
 CONT.CONT.
 AMOUNT OF THE DRUG.AMOUNT OF THE DRUG.
 PATHOLOGICAL PROCESSES OFPATHOLOGICAL PROCESSES OF
THE PLACENTA.THE PLACENTA.
 WHEN IN THE PREGNANCY-WHEN IN THE PREGNANCY-
INCREASED BLOOD FLOW TO THEINCREASED BLOOD FLOW TO THE
PLACENTA IN LAST PART OFPLACENTA IN LAST PART OF
PREGNANCY.PREGNANCY.

28. MOST DRUGSMOST DRUGS
TRANSFER AND ARETRANSFER AND ARE
AT 50-100% THAT OFAT 50-100% THAT OF
THE MATERNALTHE MATERNAL
LEVELSLEVELS
* SOME DRUG LEVELS* SOME DRUG LEVELS
ARE MORE THAN THEARE MORE THAN THE
MATERNAL LEVELSMATERNAL LEVELS

29.  DRUGS THAT TRANSFER EASILYDRUGS THAT TRANSFER EASILY
ARE LIPID SOLUBLE.ARE LIPID SOLUBLE.
 DRUGS THAT ARE DIFFICULT/HARDDRUGS THAT ARE DIFFICULT/HARD
TO TRANSFER ARE IONIZEDTO TRANSFER ARE IONIZED
DRUGS-HIGHLY POLAR-ORDRUGS-HIGHLY POLAR-OR
PROTEIN BOUND.PROTEIN BOUND.

30. Known TeratogensKnown Teratogens
 Alcohol (Ethanol)Alcohol (Ethanol)
 CarbamazepineCarbamazepine
 CytotoxicCytotoxic
chemotherapychemotherapy
 DESDES
 Isotretinoin andIsotretinoin and
EtretinateEtretinate
 LithiumLithium
 MethimazoleMethimazole
 MisoprostolMisoprostol
 PhenytoinPhenytoin
 ThalidomideThalidomide
 TrimethoprimTrimethoprim
 Valproic AcidValproic Acid
 WarfarinWarfarin

36. Breast feeding drugBreast feeding drug
administrationadministration
 Most drugs that go into the body will also go into theMost drugs that go into the body will also go into the
milk.milk.
 so before any medication is taken, consideration ofso before any medication is taken, consideration of
its effect on baby and whether or not it has anyits effect on baby and whether or not it has any
effects on lactation needs to be done.effects on lactation needs to be done.
 While most medications are safe to take whileWhile most medications are safe to take while
breastfeeding, it’s wise to talk to the doctor beforebreastfeeding, it’s wise to talk to the doctor before
taking.taking.
 Some drugs do not harm the baby, but may affectSome drugs do not harm the baby, but may affect
the milk volume by suppressing the milk-makingthe milk volume by suppressing the milk-making
hormones.hormones.

37.  On the other hand, some conditions (i.e.,On the other hand, some conditions (i.e.,
hypothyroidism) can interfere with ability tohypothyroidism) can interfere with ability to
make milk, and medications to treat themake milk, and medications to treat the
problem will improve milk production.problem will improve milk production.
 There are three issues to consider whenThere are three issues to consider when
considering taking medication whileconsidering taking medication while
breastfeeding viz. is the drug needed, will thebreastfeeding viz. is the drug needed, will the
drug affect baby, will the drug affect ability todrug affect baby, will the drug affect ability to
make milk.make milk.

38. The effect of the drug willThe effect of the drug will
depend on:depend on:
••The route of administration:The route of administration:
Your baby is always exposed through the GI tract,Your baby is always exposed through the GI tract,
but drugs can enter your system several differentbut drugs can enter your system several different
ways: orally, intravenously, intramuscularly, topically,ways: orally, intravenously, intramuscularly, topically,
or through inhalation.or through inhalation.
Topical medications (skin creams) and medicationsTopical medications (skin creams) and medications
inhaled or applied to the eyes or nose reach the milkinhaled or applied to the eyes or nose reach the milk
in lesser amounts and more slowly than other routesin lesser amounts and more slowly than other routes
and are almost always safe for nursing mothers.and are almost always safe for nursing mothers.
oral medications take longer to get into the milk thanoral medications take longer to get into the milk than
IV and IM routesIV and IM routes

39. ••The amountThe amount taken: The higher the dosage, thetaken: The higher the dosage, the
more the drug transfers into milk.more the drug transfers into milk.
How often you take the drug:How often you take the drug: Medications taken 30Medications taken 30
to 60 minutes before you feed are likely to be ato 60 minutes before you feed are likely to be a
peak blood levels when your baby nurses.peak blood levels when your baby nurses.
Your baby’s age and health:Your baby’s age and health: Premature infantsPremature infants
have immature kidney and liver functions and mayhave immature kidney and liver functions and may
have trouble processing and eliminating even smallhave trouble processing and eliminating even small
quantities of drugs that might not cause problemsquantities of drugs that might not cause problems
for larger, full-term infantsfor larger, full-term infants
however, even full-term baby’s protective metabolichowever, even full-term baby’s protective metabolic
systems are not fully developed for the first week ofsystems are not fully developed for the first week of
life.life.

40. Babies who are seriously ill, especially those withBabies who are seriously ill, especially those with
immune system disorders, may have less ability toimmune system disorders, may have less ability to
metabolize the same amount of medication than ametabolize the same amount of medication than a
healthy baby.healthy baby.
••The frequency and volume of feedings:The frequency and volume of feedings: The baby whoThe baby who
is nursing once or twice a day, and is supplemented theis nursing once or twice a day, and is supplemented the
rest of the time, will receive less of a drug than the babyrest of the time, will receive less of a drug than the baby
who is exclusively breastfed and may nurse 11 times awho is exclusively breastfed and may nurse 11 times a
day.day.
••Duration of drug therapy:Duration of drug therapy: A medication taken for weeksA medication taken for weeks
or months may have a greater impact on nursing thanor months may have a greater impact on nursing than
one taken for just a few days.one taken for just a few days.

41. ••The type of medication:The type of medication: Characteristics such as theCharacteristics such as the
molecular weight, how fat soluble the drug is, andmolecular weight, how fat soluble the drug is, and
how long it takes for it to be eliminated from yourhow long it takes for it to be eliminated from your
system, or it’s half-life, all affect how much of thesystem, or it’s half-life, all affect how much of the
drug is transferred into your milk.drug is transferred into your milk.
Anti-cancer drugs - cause diarrhea and reducedAnti-cancer drugs - cause diarrhea and reduced
immunity in the fetusimmunity in the fetus
 Androgens – can affect sexual development ofAndrogens – can affect sexual development of
fetus and suppress milk production in the motherfetus and suppress milk production in the mother
 Aspirin in large doses – May cause bleeding orAspirin in large doses – May cause bleeding or
Reye’s syndrome in theReye’s syndrome in the fetusfetus
 Chloramphenicol – Can cause diarrhea, boneChloramphenicol – Can cause diarrhea, bone
marrow suppression and gray baby syndromemarrow suppression and gray baby syndrome

42.  Estrogens - May reduce milk production and causeEstrogens - May reduce milk production and cause
increase breast size in male childincrease breast size in male child
 Ergotamine – May suppress lactationErgotamine – May suppress lactation
 Iodine – Can cause low thyroid hormone levels andIodine – Can cause low thyroid hormone levels and
goiter in the babygoiter in the baby
 Lithium – Can cause abnormal heart rhythmLithium – Can cause abnormal heart rhythm
 Metformin – Can cause low blood sugar and lacticMetformin – Can cause low blood sugar and lactic
acidosis in the babyacidosis in the baby
 Tetracycline: yellowish discoloration of teethTetracycline: yellowish discoloration of teeth
 Sulfonamides: kerinectrusSulfonamides: kerinectrus

43. Drugs considered to be safeDrugs considered to be safe
 AcetaminophenAcetaminophen
 AntacidsAntacids
 Inhaled corticosteroidsInhaled corticosteroids
 InsulinInsulin
 IbuprofenIbuprofen
 Folic acidFolic acid
 HeparinHeparin
 LidocaineLidocaine
 Penicillins and CephalosporinsPenicillins and Cephalosporins
 SalbutamolSalbutamol
 ThyroxineThyroxine

44. Management of selected cases inManagement of selected cases in
pregnancypregnancy

45. Pregnancy and epilepsyPregnancy and epilepsy
 Women with epilepsy need to plan their pregnanciesWomen with epilepsy need to plan their pregnancies
carefully, as changes in Anti Epileptic Drugs (AED)carefully, as changes in Anti Epileptic Drugs (AED)
regimens might be beneficial.regimens might be beneficial.
 Ideally, women should be prescribed the mostIdeally, women should be prescribed the most
effective and best-tolerated AED regimen at theeffective and best-tolerated AED regimen at the
lowest possible dose before becoming pregnant.lowest possible dose before becoming pregnant.
 Changing medication once pregnant is not alwaysChanging medication once pregnant is not always
practical—lamotrigine therapy, for example, cannotpractical—lamotrigine therapy, for example, cannot
be initiated quickly—and might subject the motherbe initiated quickly—and might subject the mother
and developing fetus to additional risks as aand developing fetus to additional risks as a
secondary consequence of seizures.secondary consequence of seizures.
 .[2.[2

46.  If possible, women on polytherapy should beIf possible, women on polytherapy should be
switched to monotherapy, as data indicate thatswitched to monotherapy, as data indicate that
polytherapy is associated with a higher risk ofpolytherapy is associated with a higher risk of
teratogenic abnormalities.teratogenic abnormalities.
 If a woman has not had a seizure in 2 years or more,If a woman has not had a seizure in 2 years or more,
tapering off medication can be an option.tapering off medication can be an option.
 Because folic acid fortification in cereal grains hasBecause folic acid fortification in cereal grains has
significantly decreased the rates of neural tubesignificantly decreased the rates of neural tube
defects in the US and Canada, the Americandefects in the US and Canada, the American
Academy of Neurology recommends that all womenAcademy of Neurology recommends that all women
of childbearing age take folic acid supplementation atof childbearing age take folic acid supplementation at
a dose of 0.8-4.0 mg/day.a dose of 0.8-4.0 mg/day.
 No definitive proof exists, however, that folic acid hasNo definitive proof exists, however, that folic acid has
protective effects in children whose mothers takeprotective effects in children whose mothers take
AEDsAEDs

47.  Controlling seizures during pregnancy is vital, asControlling seizures during pregnancy is vital, as
seizures are likely to have an adverse effect on theseizures are likely to have an adverse effect on the
developing fetus.developing fetus.
 Generalized TONIC-CLONIC SEIZURES mightGeneralized TONIC-CLONIC SEIZURES might
cause hypoxia, leading to damage of the CNS ascause hypoxia, leading to damage of the CNS as
well as of other organ systems, and sustainedwell as of other organ systems, and sustained
hypoxia can result in fetal death.hypoxia can result in fetal death.
 In addition to hypoxia, a generalized tonic-clonicIn addition to hypoxia, a generalized tonic-clonic
seizure could result in trauma to the mother orseizure could result in trauma to the mother or
fetus.fetus.
 Maternal death rates might also be higher inMaternal death rates might also be higher in
women with epilepsywomen with epilepsy

48.  pregnancy pharmacokinetic alterations canpregnancy pharmacokinetic alterations can
affect AED concentrations, and are mostaffect AED concentrations, and are most
important for AEDs that are highly protein-important for AEDs that are highly protein-
bound, hepatically metabolized or renallybound, hepatically metabolized or renally
cleared. Both total and free levels of highlycleared. Both total and free levels of highly
protein-bound AEDs, including phenytoin andprotein-bound AEDs, including phenytoin and
valproate, should be monitoredvalproate, should be monitored..

49.  Vitamin K prophylaxis is recommended in the lastVitamin K prophylaxis is recommended in the last
few weeks of pregnancy, starting at approximatelyfew weeks of pregnancy, starting at approximately
week 36.week 36.
 The incidence of hemorrhagic disease in theThe incidence of hemorrhagic disease in the
newborn child has been reported to be increased innewborn child has been reported to be increased in
infants exposed to AEDs during pregnancy—ininfants exposed to AEDs during pregnancy—in
particular, AEDs that induce the CYTOCHROMEparticular, AEDs that induce the CYTOCHROME
P450 ENZYME SYSTEM.P450 ENZYME SYSTEM.
 Cytochrome P450 enzyme-inducing AEDs,Cytochrome P450 enzyme-inducing AEDs,
including phenobarbital, primidone, phenytoin,including phenobarbital, primidone, phenytoin,
carbamazepine and, to a lesser extent,carbamazepine and, to a lesser extent,
oxcarbazepine and topiramate, induce fetaloxcarbazepine and topiramate, induce fetal
microsomal enzymes, which degrade vitamin Kmicrosomal enzymes, which degrade vitamin K

50.  If mothers receiving ethosuximide, phenobarbital orIf mothers receiving ethosuximide, phenobarbital or
primidone choose to breastfeed, they shouldprimidone choose to breastfeed, they should
exercise caution and closely monitor the infant forexercise caution and closely monitor the infant for
sedation, lethargy and any significant clinicalsedation, lethargy and any significant clinical
findings.findings.
 phenytoin, carbamazepine and valproate arephenytoin, carbamazepine and valproate are
probably safe.probably safe.
 These AEDs are all moderately to highly protein-These AEDs are all moderately to highly protein-
bound, and are not transferred in highbound, and are not transferred in high
concentrations in breast milk.concentrations in breast milk.

51.  A small study of four infants indicates thatA small study of four infants indicates that
lamotrigine might be transferred to the infantlamotrigine might be transferred to the infant
through breast milk in concentrations similarthrough breast milk in concentrations similar
to those seen in the mother, as lamotrigine isto those seen in the mother, as lamotrigine is
extensively metabolized by glucuronidation,extensively metabolized by glucuronidation,
which is immature in infants.[50] Given thesewhich is immature in infants.[50] Given these
findings, infants who are breastfed byfindings, infants who are breastfed by
mothers receiving lamotrigine should bemothers receiving lamotrigine should be
monitoredmonitored

52. Pregnancy and diabetesPregnancy and diabetes
 Diabetes mellitus increases the risk of importantDiabetes mellitus increases the risk of important
adverse outcomes of pregnancy.adverse outcomes of pregnancy.
 In women with type 1 diabetes mellitus who areIn women with type 1 diabetes mellitus who are
poorly controlled at the time of conception andpoorly controlled at the time of conception and
during the early weeks of gestation, the incidenceduring the early weeks of gestation, the incidence
of spontaneous abortion and major congenitalof spontaneous abortion and major congenital
malformations are increased.malformations are increased.
 Glucose crosses the placenta by facilitatedGlucose crosses the placenta by facilitated
diffusion and, therefore, the concentration indiffusion and, therefore, the concentration in
maternal blood determines the level in the fetus.maternal blood determines the level in the fetus.
Insulin does not cross the placenta.Insulin does not cross the placenta.

53.  In the second trimester, maternal hyperglycemiaIn the second trimester, maternal hyperglycemia
produces fetal hyperglycemia, causing stimulationproduces fetal hyperglycemia, causing stimulation
of the fetalof the fetal ββ cells and fetal hyperinsulinemia.cells and fetal hyperinsulinemia.
 Insulin is the major fetal growth hormone andInsulin is the major fetal growth hormone and
produces excessive fetal growth particularly in fat,produces excessive fetal growth particularly in fat,
the most insulin-sensitive tissue.the most insulin-sensitive tissue.
 The fetus of the poorly controlled diabetic mother isThe fetus of the poorly controlled diabetic mother is
not only more likely to weigh more than 4000 g butnot only more likely to weigh more than 4000 g but
to be disproportionately large about the shouldersto be disproportionately large about the shoulders
and chest.and chest.
 These large fetuses are also at greater risk forThese large fetuses are also at greater risk for
intrauterine fetal death during the lastintrauterine fetal death during the last 4–6 weeks4–6 weeks

54.  Oral hypoglycemic using patientsOral hypoglycemic using patients
should be shifted to insulinshould be shifted to insulin
 Insulin releasing pumps moreInsulin releasing pumps more
succesful for managementsuccesful for management
 Insulin requirments may increaseInsulin requirments may increase

55.  TheseThese anomalies can be prevented by excellentanomalies can be prevented by excellent
control of maternal glycemia before gestation andcontrol of maternal glycemia before gestation and
during the early weeks of pregnancy.during the early weeks of pregnancy.
 Today, women with diabetes mellitus who receiveToday, women with diabetes mellitus who receive
excellent medical care can look forward to aexcellent medical care can look forward to a
pregnancy outcome that approaches that of womenpregnancy outcome that approaches that of women
without diabetes mellitus.without diabetes mellitus.
 Finally, the goal of our educational programs shouldFinally, the goal of our educational programs should
be not only to improve pregnancy outcome but alsobe not only to improve pregnancy outcome but also
to promote healthy lifestyle changes for the motherto promote healthy lifestyle changes for the mother
that will last long after deliverythat will last long after delivery

56. Asthma and pregnancyAsthma and pregnancy
 In fact, severe and/or poorly controlled asthma hasIn fact, severe and/or poorly controlled asthma has
been associated with numerous adverse perinatalbeen associated with numerous adverse perinatal
outcomes, including the following:outcomes, including the following:
 Preeclampsia Pregnancy-inducedPreeclampsia Pregnancy-induced
hypertensionhypertension
 Uterine hemorrhage Preterm laborUterine hemorrhage Preterm labor
 Premature birth Congenital anomaliesPremature birth Congenital anomalies
 Fetal growth restriction Low birth weightFetal growth restriction Low birth weight
 Neonatal hypoglycemia, seizures, tachypnea, andNeonatal hypoglycemia, seizures, tachypnea, and
neonatal intensive care unit (ICU) admissionneonatal intensive care unit (ICU) admission

57.  Almost all antiasthma drugs are safe to use inAlmost all antiasthma drugs are safe to use in
pregnancy and during breastfeeding.pregnancy and during breastfeeding.
 In fact, undertreatment of the pregnant patient is aIn fact, undertreatment of the pregnant patient is a
frequent occurrence, because such patients arefrequent occurrence, because such patients are
worried about medication effects on the fetus.worried about medication effects on the fetus.
 Corticosteroids can be used in the acute andCorticosteroids can be used in the acute and
outpatient setting and have been shown to beoutpatient setting and have been shown to be
relatively safe in pregnancy.relatively safe in pregnancy.
 The intravenous, intramuscular, and oralThe intravenous, intramuscular, and oral
preparations can be used for acute exacerbations,preparations can be used for acute exacerbations,
whereas the inhaled preparations are reserved forwhereas the inhaled preparations are reserved for
outpatient maintenance therapy. Recent data onoutpatient maintenance therapy. Recent data on
inhaled glucocorticoids support its relative safetyinhaled glucocorticoids support its relative safety
although there is the potential risk for offspringalthough there is the potential risk for offspring

58. Hyperthyroidism andHyperthyroidism and
pregnancypregnancy
 thioamide drugs are the first-line treatment inthioamide drugs are the first-line treatment in
pregnancy. PTU, methimazole (MMI), andpregnancy. PTU, methimazole (MMI), and
carbimazole (CMI) are equally effective.carbimazole (CMI) are equally effective.
 A controversial association exists betweenA controversial association exists between
MMI and fetal scalp defects, aplastic cutis,MMI and fetal scalp defects, aplastic cutis,
and choanal and/or esophageal atresia.and choanal and/or esophageal atresia.
Therefore, PTU tends to be the first choice inTherefore, PTU tends to be the first choice in
this class of drugs.this class of drugs.

59.  the US Food and Drug Administration (FDA)the US Food and Drug Administration (FDA)
had added a boxed warning, the strongesthad added a boxed warning, the strongest
warning issued by the FDA, to the prescribingwarning issued by the FDA, to the prescribing
information for propylthiouracil. The boxedinformation for propylthiouracil. The boxed
warning emphasizes the risk for severe liverwarning emphasizes the risk for severe liver
injury and acute liver failure, some of whichinjury and acute liver failure, some of which
have been fatal.have been fatal.

60.  Doses of ATDs should be maintained at theDoses of ATDs should be maintained at the
lowest dose needed to keep the mother's FT4lowest dose needed to keep the mother's FT4
level in the high-normal range.level in the high-normal range.
 Weight gain, pulse rate, FT4 results, and TSHWeight gain, pulse rate, FT4 results, and TSH
levels should be monitored monthly.levels should be monitored monthly.
 Beta-blockers (eg, atenolol, nadolol,Beta-blockers (eg, atenolol, nadolol,
propranolol) are valuable adjuncts to ATDs.propranolol) are valuable adjuncts to ATDs.
These drugs effectively alleviate symptoms ofThese drugs effectively alleviate symptoms of
hypermetabolic states. With prolonged use,hypermetabolic states. With prolonged use,
beta-blockers are associated with fetalbeta-blockers are associated with fetal
morbidity. Therefore, these drugs should bemorbidity. Therefore, these drugs should be
used for only a short period (ie, 2 wk) whileused for only a short period (ie, 2 wk) while
one waits for the ATDs to take effect.one waits for the ATDs to take effect.

61. Hypothyroidism andHypothyroidism and
pregnancypregnancy
 if hypothyroidism is diagnosed duringif hypothyroidism is diagnosed during
pregnancy, the thyroid medication should bepregnancy, the thyroid medication should be
titrated rapidly to achieve TSH levels of lesstitrated rapidly to achieve TSH levels of less
than 2.5 mcg. During pregnancy, the fullthan 2.5 mcg. During pregnancy, the full
replacement dosage of T4 is approximatelyreplacement dosage of T4 is approximately
2.0-2.4 mcg/kg/d.2.0-2.4 mcg/kg/d.
 Results of thyroid function tests (TFTs) shouldResults of thyroid function tests (TFTs) should
be checked within 30 days after the dosage isbe checked within 30 days after the dosage is
changed. TFTs should be repeated until thechanged. TFTs should be repeated until the
results return to normal. Afterward, levels mayresults return to normal. Afterward, levels may
be checked 6-8 weeks.be checked 6-8 weeks.

62.  Patients with subclinical hypothyroidismPatients with subclinical hypothyroidism
should be treated to normalize maternal TSHshould be treated to normalize maternal TSH
levels. Women with thyroid antibodies inlevels. Women with thyroid antibodies in
pregnancy who are euthyroid should bepregnancy who are euthyroid should be
monitored with TFTs because of their highmonitored with TFTs because of their high
risk of developing hypothyroidism.risk of developing hypothyroidism.
 After delivery, the dosage of thyroidAfter delivery, the dosage of thyroid
medication usually needs to be decreasedmedication usually needs to be decreased
over 4 weeks.over 4 weeks.