Challenges in obstetric prescription

Challenges in obstetric
prescription

Chairperson-Dr. Ragini
Agrawal
Food, Drug & Medico - 2009-2011
surgical committee

FOGSI

• 2009 • 2010
• President- • President-
• Dr C.N.Purandare • Dr Sanjay Gupte
• Vice president • Vice president
• Dr H.R. Patnaik • Dr Jaideep Malhotra

Editors
Dr Ragini Agrawal
Dr Tamkeen Rabbani

Contributors—
Challenges of obstetrics prescription –A
Dr Ragini Agrawal conceptual consideration

Dr Tamkeen Rabbani How To Prescribe Antibiotics In Pregnancy
Dr Seema Hakim Counseling for Prescribing in Pregnancy

Dr. Nasreen Noor Drug Abuse During Pregnancy
Dr Sabahat Rassool Teratology
Dr Shaheen Categorization of Drugs in Pregnancy

Dr Alami Zeba Safe Drugs for Common Diseases in Pregnancy

Dr Zehra Mohasin Vaccination In Pregnancy

Challenges of
obstetrics prescription
–A conceptual
consideration

Dr Ragini Agrawal , M.S.
Chairperson, FOGSI
(Food , Drug & Medico surgical committee )

• The aim of ante natal
care is to improve the
health of mother &
babies by preventing
birth defects, premature
birth and infant
mortality.

• Pregnancy is
most joyous
period of woman

• But It is a “stress test
for life” also

Perfect baby is
everyone’s dream

• The developing organism is unique in its
responsiveness to drugs and predictability of
therapeutic effectiveness based on the adult can lead
to grave consequences in the neonate and child. It
should be emphasized that fetal adverse drug effects
are not always manifested immediately as in the case
of maternal thalidomide ingestion. It is important to
note that fetal abnormalities can occur after several
months as seen with clonidine or in the case of DES
vaginal adenocarcinoma can take 20 years to develop.
Based on limited reported effects in humans and more
extensive studies with animals, drugs are classified as
to the risk of induction of fetal toxicity in categories
ranging from A (safe) to D (contraindicated in
pregnancy). A separate extremely toxic category X is
also used.
Int J Clin Pharmacol Ther. 1994 Jul;32(7):335-43.
• Fetal consequences and risks attributed to the use of prescribed and over-the-
counter (OTC) preparations during pregnancy.
• Kacew S, Department of Pharmacology, University of Ottawa, Faculty of

Very high doses of vitamin A, D and E in
pregnancy have been linked to birth defects.
Professor Owens said doctors should not
underestimate the dosage of vitamin
supplements that some pregnant women
consumed, particularly if they used high-
potency multivitamins.

Professor Julie Owens, from Adelaide
University's school of pediatrics and
reproductive health,

Immunosuppressant Drug Causes
Birth Defects
American Journal of Medical Genetics.

Insect repellent linked to birth defects

Pregnant women may wish to avoid insect
repellent after a study found a link to an
increasingly common birth defect, experts say

Some prescription meds can harm fetus
November 17, 2009
More than six percent of expectant mothers in
Quebec consume prescription drugs that are
known to be harmful to their fetuses,
according to a Université de Montréal
investigation published in the British Journal
of Obstetrics and Gynaecology.
.

Asthmatic children: Did mom use her pump
during pregnancy?
October 5, 2009
Expectant mothers who eschew asthma treatment during
pregnancy heighten the risk transmitting the condition to
their offspring, according to one of the largest studies of its
kind published in the European Respiratory
Journal. A research team from the Université de Montréal,
the Hôpital du Sacré-Cœur de Montréal and Sainte-Justine
University Hospitl Research Center found
that 32.6
percent of children born to mothers who
neglected to treat their asthma during
pregnancy developed the respiratory illness
themselves.

Sexually transmitted disease, urinary tract
infections
may be bad combination for birth defect
June 20, 2008
[B]Chances of gastroschisis increase fourfold in
babies whose moms have both infections[/B]
University of Utah researchers report
in the online British Medical Journal.

Epilepsy drug may increase risk of birth
defects
July 21, 2008
Taking the epilepsy drug topiramate alone or along
with other epilepsy drugs during pregnancy may
increase the risk of birth defects, according to
a study published in the July 22, 2008, issue
of Neurology, the medical of the American
Academy of Neurology

Local health investigation sheds light on
gastroschisis birth defect
November 6, 2009
Results of an investigation conducted by University of
Nevada, Reno researchers
, public health officials and area physicians published this
week in the Archives of Pediatrics & Adolescent
Medicine, indicate that Washoe County experienced a
cluster of a particular birth defect, gastroschisis, during the
period April 2007 - April 2008. This study added significant
support to the findings of other studies that
certain
infections, such as colds and sore throats;
use of cold medications, such as
pseudoephedrine; and some recreational
drugs, may be contributing factors in the
development of gastroschisis.

Concerns during
pregnancy
• Fear of teratogenesis
• Need to safeguard the smooth
progress of pregnancy and
delivery
• Need to prevent withdrawal
effects in the neonate
• Concerns about subtle effects
on the infant‘s
neurodevelopment

Concerns &
considerations
• congenital abnormalities caused
by human teratogenic drugs
accounts for less than 1% of
total congenital abnormalities.

• About 8% of pregnant women
need permanent drug treatment
due to various chronic diseases
and pregnancy-induced
complications.

Concerns &
considerations
• Moreover in India, due to easy
availability of drugs coupled
with inadequate health services,
increased proportions of drugs
are used as self medication (for
common complains and
infective conditions), as
compared to the prescribed
drugs.

Concerns &
considerations
• Woman always face the threat of
adverse drug reactions and drug
interactions between active
hidden ingredients of both
herbal and allopathic drugs.
• Un planned pregnancy is a
bigger issue as she is already on
potential teratogenic medicine
or had inadvertently during
early period of conception

Concerns &
considerations
• Careful consideration of
the benefit to the mother
and the risk to the fetus
is required while
prescribing drugs during
pregnancy

Concerns &
considerations
• Reducing medication errors and
improving patient safety are the
important areas of discussion

• The use of drugs during pregnancy
calls for special attention because in
addition to the mother, the health
and life of her unborn child is also at
stake.

Concerns &
considerations
• The drugs given to pregnant
mothers for therapeutic
purposes may cause serious
structural and functional
adverse effects in the developing
child .

Concerns &
considerations

• Since it is very difficult to
determine the effects on the
fetus before marketing new
drugs due to obvious ethical
reasons, most drugs are not
recommended to be used
during pregnancy

Concerns &
considerations
• Since there are numerous gaps
in knowledge about deleterious
consequences for the fetus,
prescription drug use by
pregnant women should be
viewed as a public health issue.
• Pharmaco-epidemiological
studies can measure the extent
of prescription and teratogenic
drug use in pregnant women.

Prescription drugs and
pregnancy.
• Prescribing drugs in pregnancy
is an unusual risk-benefit
situation.

• Drugs that may be of benefit or
even life-saving to the mother
can deform or kill the fetus.
However, the risk to the fetus
should not be exaggerated.

Important points
• There are only approximately 20
groups of drugs which are
known to cause birth defects in
humans.

• For one of these drugs to cause
birth defects, a number of
criteria must be fulfilled.

Important points
• The drug exposure must take
place at a critical stage of
pregnancy
• The dose must be high enough
to cause a threshold of exposure
for an appropriate duration of
time.
• For most of the known human
teratogens, > 90% of
pregnancies exposed during the

Important points
• Although only a few drugs are
known to cause birth defects in
humans, uncertainty about the
safety of the majority may lead
to under prescribing for
pregnant women and women of
childbearing age.

Important points
• Epidemiological studies of
pregnancy outcome after
specific drug exposures are
often superficially reassuring,
but most are severely limited in
their power to detect adverse
outcomes.

Important points
• Safety in animal studies may
also be reassuring but species
differences demand caution in
this interpretation.
• Concerns about prescription
drugs in the first trimester,
when they can cause birth
defects, are mostly quite
different to concerns about use
in the second and third

Important points
• As the fetal organ systems
mature, the fetus can be
affected by the pharmacological
activity of the drug in the same
way as the mother.
• Many drugs have
pharmacological effects on the
fetus in the second and third
trimesters but in most cases,
they are well recognised and can

Important points
• Communicating the risk-benefit
situation to the patient is always
a challenge for physicians with
limited time and sometimes
limited knowledge.

Important points
• Fear of litigation is an
unfortunate and an unwanted
parameter in the assessment.
• Better knowledge of the
parameters that determine
teratogenicity may allow
physicians to feel more
confident in assessing the risks
and benefits associated with
prescribing in pregnancy

Drug classification
• Although the pregnant mother may require
treatment of certain disorders, there are a number
of drugs which are absolutely contraindicated
including those agents in risk category X and the
socially unacceptable drugs of abuse.
• A limited use for drugs in category D under close
supervision may be necessary .
• .Prescribed drug use in pregnancy should be
dissuaded. Further ingestion of over-the-counter
(OTC) preparations should be limited and deemed to
be used with caution.
• It is generally accepted that the pregnant mother
provides a fetus an environment in which to
develop. However, drug exposure in utero is far
more deleterious than in the growing child as the
fetus lacks the ability to cope with pharmaceutical
agents entering its biosphere.

Objective For Discussion
• Rational use of drugs in
pregnancy
• Clear understanding of
Teratogens & birth defects
• Substance abuse effects on
pregnancy
• Role of Counselling for
Prescribing in Pregnancy
• Clear concept of Categorization
of Drugs in Pregnancy

Objective For Discussion

• Safe Drugs for Common
Diseases in Pregnancy

• Vaccination In Pregnancy

• To achieve
healthy mother
& healthy baby

Categorization of Drugs
in Pregnancy

Dr Shaheen
Assistant Professor Deptt of OBG
JNMC , AMC ,Aligarh

Introduction
• Pregnancy is a physiological
condition where drug treatment
presents a special concern.

• The concern has been influenced
by historical events, including
Thalidomide crisis in 1960‟s & Di-
ethyl stilboestrol in 1971.

Introduction contd.

• Hence in 1979 in the USA, Food &
Drug Administration (FDA)
developed a system that
determines the teratogenic risks
of drugs.

Introduction contd.
• There are other organizations such
as Australian Categorization of
Risk of drugs use in pregnancy.

• But the most widely used system
are the FDA & TERIS (Teratogen
information system) pregnancy risk
classifications.

The FDA Categorization of
Drugs in Pregnancy

• Category A- Controlled studies in
women fail to demonstrate a risk to
the fetus in the any trimester and
the possibility of fetal harm appears
remote

Drugs in Pregnancy
• Category B- Animal studies have
not demonstrated a fetal risk but
there are no controlled studies in
pregnant women,
or
Animal studies have shown an
adverse effect that was not
confirmed in controlled studies in
women in any trimester

Drugs in Pregnancy
• Category C- Studies in animals
have revealed adverse effects on
the fetus (teratogenic or
embryocidal or other) and there are
no controlled studies in women
or
studies in women and animals are
not available. Drugs should be
given only if the potential benefit
justifies the potential risk to the
fetus.

Drugs in Pregnancy
• Category D-
There is positive evidence of fetal
risk, but the benefits from use in
pregnancy may be acceptable
despite the risk
e.g. if the drug is needed in a life-
threatening situation for which safer
drugs cannot be used or are
ineffective.

Drugs in Pregnancy
• Category X-
Studies in animals or humans have
demonstrated fetal abnormalities, or
there is fetal risk based on human
experience or both, and the risk
clearly outweighs any possible
benefit.
The drug is contraindicated in
women who are or may become
pregnant.

Drug Safety System: the
problems
• Pregnant women are excluded from
pre-licensure clinical trial, for fear of
harming the mother or developing
fetus

• Most drugs are marketed with
limited information on their safety
during pregnancy and therefore are
not recommended for use by
pregnant women.

Drug Safety System: the
problems

• Passive mechanism of spontaneous
reporting of adverse drug effects
are inadequate for detecting drug
induced fetal risk or lack of such
risk

Drug Safety System : the
problems & solutions
• Therefore the U.S. FDA has
overhauled safety issues related to
drugs by provisions in the FDA
Amendments Act (FDAA)

• The legislation instructs FDA to
establish a system that can access
drug safety data on 25 million
patients by 2010 and 100 million by
2012

• The US FDA and the European
Medicine Agency recommend active
surveillance, such as the use of
Pregnancy Exposure Registers
(PERs)

• Another important component of the
sentinel system is a more modern
and expanded FDA Spontaneous
Adverse Event Reporting System
(AERS).

• The FDA is collaborating with the
Center for Disease Control and
Prevention (CDC) and the National
Institute of Health (NIH) on a
standard and common reporting
method of adverse events for all
FDA regulated products.

• The FDA also plans to combine
safety-signal detection and analysis
for drugs, biologics, medical
devices, and other regulated
products into an agency – wide FDA
Adverse Event Reporting System
(FAERS) and a user friendly
Medwatch plus portal

limitations
• Resources for routine pharmaco-
vigilance are rare and automated
data sources generally do not exist
in developing world

• In industrialized countries the drug
information can be derived from
medical records and automated
databases, including medical or
pharmacy insurance claims

limitations
• Troubling news about several high-profile
drugs saps confidence in the system for
assuring the supply of safe ones and
flushing out dangerous medicines

• No drug is ever fully safe. The safety net
isn't designed to catch rare side effects
until drugs reach the market.

• By then, regulators are often powerless
to spot mistakes

limitations
The massive import of drugs also
poses problems.

The FDA conducts inspections of
plants, amid explosive growth in
imports from India and China, to
ensure that the drugs are of high
quality.

limitations
The low level of follow up
inspection, combined with
the huge amount of
imports, greatly increases
the potential that
consumers will get
products that have
impurities or ineffective
ingredients.
Brant Zell pastchairman of the Bulk

• Rare harmful effects pop up only
with mass consumption. Doctors
are merely encouraged to report
them, and the FDA forces the
industry to carry out relatively few
studies of drugs on the market.

"If a plane crashes off the
coast of New York, we
don't leave the
investigation to the
controllers that were
controlling the plane and
the airline that was flying
it,"
Dr. Alastair Wood, a Vanderbilt
University pharmacologist and FDA
drug safety adviser.

New drug trials in
pregnancy:
A recent review found that only 17
medications for maternal health are
are being developed world wide,
and many advocates say that the
“drought” of new medications to
treat pregnant women is unlikely to
change any time soon,
USA today reports

This building is on very shaky ground.
Would I condemn it ? No but I would tell
people, ‘ you go in at your risk’

Dr Cathrine De Angel , Editor, JAMA

The answer to the problems is to
have an evidence based review
system for guiding prescribing in
pregnancy

Despite such limitations thousands of
Americans survive or lead better lives
thanks to effective and safe drugs.
• "Medicines that receive FDA
approval are among the safest in
the world,"
Acting Commissioner Lester Crawford
• The FDA has commissioned the
independent non-profit Institute of
Medicine to study drug safety and
recommend improvements.

Evidence Based Review
System
The FDA‟s evidence based review
system
• Identifies scientific studies that
evaluate the substance/disease
relationships
• Identifies surrogate endpoints of
disease risk
• Assesses the quality of scientific
studies

Evidence Based Review
System
• Evaluates the totality of the
scientific evidence
• Assesses SSA (significant scientific
agreement)
• Analyzes the specificity of the claim
language of a QHC (Qualified
health claim)
• Revaluates existing SSA claim and
existing QHCs

AHFS drug information

• AHFS DI is an attested and proven
source of comparative, unbiased
and evidence based drug
information for safe and effective
drug therapy

REPRORISK System
The single most comprehensive
compilation of Reproductive Risk
Information Databases

Benefits:
• Provides guideline for reducing
exposures.
• Helps to prevent possible medical
and legal complications

REPRORISK System
• Equips patients with information
needed to make informed decisions
and take preventive measures.

• Facilitates identification and
reporting of hazardous health
effects.

REPROTEXT
A Reproductive Hazard Reference

• Presents reviews on health effects of industrial
chemicals encountered in the work place.
• Describes effects on human reproduction of
acute and chronic exposures and reproductive,
carcinogenic, and genetic influences
• Includes unique dual health hazard ranking
system for general society and “grade card”
scale suggesting level of reproductive hazard.

REPROTEXT
• Covers physical agents including
heat, noise, and radiation.
• Helps set risk – reducing priorities
by combining hazard rankings with
exposure estimates.
• Assists with development of
program to improve employee
protection guidelines

REPROTOX
Reproduction Hazard
Information –
From the reproductive toxicology
centre, Bethesda, MD, covers the
impact of the physical and chemical
environment on human reproduction
and development.

Covers all aspects of reproduction
including fertility, male exposures
and lactation

REPROTOX
• Discusses reproductive influences
of industrial and environmental
chemicals, naturally occurring
radioactive materials, prescription
non-prescription, and recreational
drugs and nutritional agents

Includes the latest, most relevant
teratology articles

TERIS
• Teratogens Information System
developed by the university of
Washington.

• Provides current information on the
teratogenic effects of drugs and
environmental agents.

TERIS
TERIS documents include:

• Agent name and number.
• Summery of teratogenic effects
• Magnitude of risk
• Quality and quantity of data
• Comments
• References

Conclusion
• The most widely used system for
categorizing drug risk during
pregnancy in the United States are
the FDA and TERIS pregnancy
risk classification.

• Controlled data on using
medication during pregnancy and
lactation are lacking, making firm
recommendations more difficult.

Conclusion
• Only fair agreement on risk
category assignment exists when
comparing common pregnancy risk
classification systems within and
between countries

Conclusion
• Pregnancy risk categories should
be used as general guide lines to
help choose safer medications
alternatives.

• Useful print and internet resources
help guide national medication
selection during pregnancy and
lactation

Don't endanger your
baby by taking harmful
medication!

Counseling for Prescribing
in Pregnancy

Dr Seema Hakim
Professor Of Obstetrics & Gynaecology
J N Medical College,Aligarh Muslim University
Aligarh, U.P.

Introduction
• 40-90% women are exposed to
drugs in pregnancy

• The safety of more than 60% of
these drugs for the fetus and
the mother is unknown

• Known teratogens sometimes
are required for the pregnant
patient to treat life-threatening
conditions

The Problems:
• Some pregnant women are
exposed to drugs inadvertently
because they do not know they
are pregnant at the time of
intake

• Often women requesting
counseling for prenatal drug
exposure have misconceptions
regarding the risks

The Problems:
• The problem is compounded by
referral sources who exaggerate
the risk and offer termination.

• Inaccurate reports in the lay
press further cause panic.

• Most women report for
counseling only after exposure
rather than coming for prenatal
counseling

The Problems:
• The drug manufactures label
almost all drugs as unsafe in
pregnancy to avoid litigations

• Most women have no idea about
the background risk of
congenital anomalies

Why counseling:
• The health of the fetus and
concomitantly pregnant female‘s
health is at risk

• Patients are more receptive to
adverse effects if they are
already aware and well informed
about them

Effective counseling
Results in:
• Improved understanding
• Increased recall of information
• Reduced anxiety
• Decreased uncertainty
• Increased satisfaction
• Improved compliance

Concerns during
pregnancy
Pregnancy likely to unmask
occult chronic diseases e. g.
glucose intolerance,
hypertension
Pregnancy is a ―stress test for
life‖
Obstetric complications and
increasing maternal age will
add to overall rates of poor
outcome.

Prenatal Counseling

• Drugs may be needed for certain
conditions like epilepsy,
diabetes, hypertension which
predate pregnancy.

Prenatal Counseling
• Counseling should include both
the fetal risk from the drug as
well as the teratogenic risk of
the condition for which the drug
is being prescribed e.g epilepsy
and diabetes which are
associated with a higher
malformation rate per se.

Prenatal Counseling
• The manner in which the
information is given affects the
perception of the risk e.g.. Women
given negative information– such
as a 1-3% chance of having a
malformed baby are more likely to
perceive an exaggerated risk as
compared to women given positive
information– the 97-99% chance
of having a normal baby

Prenatal Counseling
• Most commonly used drugs can
be prescribed with relative
safety in pregnancy

• All women have a 3% chance of
having an abnormal baby

Prenatal Counseling

• Exposure to a known teratogen
may increase this risk, but it is
usually increased by only 1-2%,
or at the most doubled or
tripled.
• Counseling should emphasize
relative risk
• The concept of risk versus
benefit should also be

Counseling After
Exposure

• Counseling a woman exposed to
drugs specially during the critical
period of organogenesis is a
challenge.

Certain questions need
to be answered---
• Is the drug a known teratogen?
• What are its potential adverse
effects on the fetus and
neonate?
• What are the risks to the mother
if the drug is withheld?

Certain questions need
to be answered---
• What are the implications of the
disease itself for which the drug
is to be given regarding risk of
anomaly?

• What are available sources of
information about its use in
pregnancy and its effects on the
fetus?

How to proceed with
counseling---

• After looking for answers to
these questions proceed by
giving the following information
to the woman:-------

-----Etiology Of
Malformations
• Cause is unknown in 60-70% of
malformations

• It is estimated that----
- 20-25% are genetic
- 3-5% due to intra-uterine
infections
- 4% due to maternal disease
like diabetes, epilepsy

---fewer than 1% are due to
prescribed drugs!

• However patients, physicians,
lawyers often suspect that drugs
caused a malformation in any
exposed infant.

Next we should evaluate the risk
of teratogenicity.

Evaluating the Risk
• Few drugs are known teratogens but no
information is available for more than
60% of the drugs to allow an
assessment of the risk to the fetus

• Major text books, FDA categorization,
computerized data-bases such as
TERIS, REPROTOX etc. provide
information for assessment of potential
risks.

But are these methods appropriate
& adequate for risk evaluation?

Limitations of FDA
Categorization
• Hard to remember

• May be misleading
– Up to 60% of category X drugs
have no human data
– Few drugs listed in category A
e.g Ampicillin is category B

Limitations of FDA
Categorization
Rarely updated, does not reflect
current scientific data e.g oral pills
still in category X though
teratogenicity has been disproved

No information on degree of risk

The system bases drug ratings on
limited animal data or case reports.

Therefore should not be
considered as a primary
directive for prescribing in
pregnancy.

Counseling the Patient

• Detailed medical history and
physical examination required
before proceeding further with
counseling.

History
• LMP for accurate gestational
dating

• Detailed information regarding
class, dose, route of
administration, timing of
exposure according to
gestational age, disease being
treated

History
• Co-morbidities to be ruled out
which may affect risk of
malformations

• USG to be done for gestational
dating, as menstrual age and
gestational age have a difference
of 2 weeks

• The period of 2 weeks between
fertilisation and implantation follows
„all & none‟ law– either fetus aborts
or pregnancy continues without any
harm.

History
• it can be confirmed that the
exposure was before conception
or organogenesis then the
counseling may simply consist
of reassuring the patient.

• Determine whether the drug is
absorbed in circulation or has
only local effect and then will
not harm the fetus eg.

History
• Determine whether agent
crosses the placenta eg even
LMW Heparin does not cross
and so no fetal effects.

• For known teratogens eg.
Isotretinoin having established
risk of anomaly and when
exposure in a given period of
gestation has been documented

counseling
The counselor may explain the
risk as follows---

“ although a small risk cannot be
„ruled out‟, the risk of spontaneous
anomalies is probably greater than
any risk that can be estimated from
available information for most
medications that have been
studied.”

counseling
• Finally if the initiation of therapy for
a pregnant lady may be delayed for
the period of organogenesis without
risking her life then this may be
considered as an option.

counseling
• If delay is unsafe, treatment should
be started, even if risk is involved
and termination may be offered
after counseling e.g.chemotherapy
for acute leukemia should be
initiated as soon as diagnosis is
confirmed irrespective of gestational
age.

Prescribing in pregnancy
• Consider non drug options

• Avoid drugs if possible during
weeks 6-10

• Do not start any medication
unless clearly indicated

• Do not discontinue medicines
that successfully maintain the
maternal condition unless there
are clear indications to do so

• Ask about and document non-
prescription medicines

• Have a pregnancy medication
reference available

• Favor older medicines with
longer record of use

• Keep doses low before delivery if
possible

• Consult with pediatrician.
• Educate your patient
• Report adverse outcomes
• Always consider the effect of not
treating
• Remember that few drugs are
absolutely contraindicated

Avoid polypharmacy in
pregnancy
• Optimize non-pharmacologic
alternatives

• Determine whether each
medication:
– Is necessary
– Is effective
– Is at lowest effective dose
– Does not adversely alter other
medication effect

Rational management to
avoid polyfarmacy
Simple
– Use generics

– Use least frequent dosing
needed

– Tie to scheduled daily
activities, meals, sleep/wake

– Provide legible written
instructions

•Support
– Educate-- all medicines, even
over-the-counter have adverse
effects, report all products
used
– Encourage use of one
pharmacist
– Avoid seeing multiple
physicians
– Enlist help of family, friends,
caregivers
– Medication organization
equipment
• Survey
-Periodic review

5 `rights' of medication:
-- right patient
– right drug
– right dose
– right route
– right frequency

Process of Rational Prescribing
Define the patient’s problem

Specify the Therapeutic objective


Verify if treatment is suitable for this patient



Start the Treatment


Give information, instructions and warnings


Monitor and stop treatment

Conclusions
Constantly update your
knowledge

Give time to your patient

Evaluate the condition

Make a prudent decision

Wisdom
and
knowledge
are the key
to good
counseling
and
prescribing
in
pregnancy!

Teratology

Dr Sabahat Rasool, MBBS, MS
JNMC, AMU, Aligarh

Objectives
• To define teratology and
teratogens
• Evaluate potential teratogens
• Genetic mechanisms, including
Homeobox genes
• Physiological mechanisms
• Perinatal pharmacology

Teratology – A
Historical Perspective
• 15th & 16th centuries –
malformations caused by the
devil: mother & child killed
• 1900’s –malformations related
to genes
• 1941 –malformations linked to
rubella virus
• 1960’s – Thalidomide Tragedy
• 1970’s – Fetal Alcohol
Syndrome

Chemicals &
teratogenicity
• Approximately 80,000
chemicals listed by EPA in the
USA
• Most of them not tested for
developmental toxicity
• For example, High Production
Volume (HPV) chemicals
• Mercury & lead are good
examples

Teratology
• A Teratogen is any agent acting
during embryonic or fetal
development to produce a
permanent alteration of form or
function (Shepard, 1998)
• Teratogenesis is derived from
the Greek words gennan which
means to produce, and terata,
which means monster

Teratogen – Types
• Hadegen – named after the God
Hades, agent that interferes with
normal maturation and function of
organ
• Trophogen – an agent that alters
growth
• Teratogen – an agent that produces
structural abnormalities
• Most authors use the term
teratogens to describe all three:
hadegen, trophogen, and teratogen

Definitions
• Malformation- structural defect
from a localised error of
morphogenesis
• Disruption- specific
abnormality due to disruption of
normal developmental process
• Deformation- an alteration in
shape/ structure of a previously
normal organ
• Syndrome- a recognised pattern
of malformations with a specific
agent/ etiology

Teratogens--Classification
• Viruses (rubella, toxoplasma,CMV)
• Chemicals (methyl mercury,
pesticides, PCBs, alcohols)
• Environmental agents (alcohol,
tobacco, cocaine)
• Physical factors (radiation,
hyperthermia, atomic fallouts)
• Drugs (phenytoin, thalidomide,
retinoids, warfarin, DES)
• Maternal factors (hyperthermia,
diabetes)

Consequences of
Teratogen Exposure

• Death
• Malformation
• Growth restriction
• Functional defects

Evaluation of Potential
Teratogens

Wilson’s Six Principles
• 1. Susceptibility to
teratogens depends on the
genotype of the conceptus
and the manner in which
this interacts with adverse
environmental factors

2. Susceptibility to
teratogenesis varies with the
developmental stage at the
time of exposure.

3. Teratogenic agents act in
specific ways on developing
cells and tissues to initiate
sequences of abnormal
developmental events

4. The access of adverse
influences to developing
tissues depends on the nature
of the influence.

5. There are four manifestations
of deviant development
(Death, Malformation, Growth
Retardation and Functional
Defect)

• 6. Manifestations of deviant
development increase in
frequency and degree as dosage
increases from the No
Observable Adverse Effect Level
(NOAEL) to a dose producing
100% Lethality (LD100)

Criteria for Proof of
Human Teratogenicity
• Careful delineation of clinical
cases

• At least three reported cases of
rare environmental exposure
associated with rare defect

Shepard, 2001, Czeizel & Rockenbaeur, 1997 & Yaffe
and Briggs 2003)


• Proof that the agent acts directly
or indirectly on the embryo or
fetus

• Proven exposure to agent at a
critical time in prenatal
development

• A biologically plausible
association

• Consistent findings by two or
more high quality
epidemiological studies

• Teratogenicity in experimental
animals, especially primates

Timing of Organogenesis
Central Nervous System

Heart

Ears

Eyes

Limbs

Palate

External Genetalia

1 2 3 4 5 6 7 8 12 16 20 38
Implantation Emryonic period Fetal Period
Prenatal Physiological and Functional
Death Major Morphological abnormalities Defects

Timing of organogenesis
during the embryonic
development
• Pre-implantation period starts
from 2 weeks from fertilisation
to implantation

• Also known as the ‗all or none’
period

• Any insult at this stage leads to
embryonic death.

Timing of exposure- pre-
implantation stage

• Exposure of embryos to
teratogens during the pre-
implantation stage usually does
not cause congenital
malformations, unless the agent
persists in the body beyond this
period.

Embryonic period

• Embryonic period starts from
the 2nd week through the 8th
week following conception. This
is the most critical period
encompassing organogenesis.

Fetal Period
• Fetal period starts after 9
weeks post fertilisation till
term. Exposure during this
period will affect fetal growth
(e.g., intrauterine growth
restriction), the size of a specific
organ, or the function of the
organ. The term fetal toxicity is
commonly used to describe such
an effect .

Factors affecting drug
Transfer:

Transfer across placenta
depends on:

–Placental surface area
–Placental metabolism

Factors related to drugs
affecting drug transfer:

–Molecular weight
–Lipid solubility
–Ionization
–Protein binding
–Chemical Structure
–Size
–High blood concentration

The Thalidomide
Disaster

• Thalidomide introduced in 1956
as an anti-anxiety, sedative-
hypnotic and antiemetic
medication for use in the first
trimester

The Thalidomide
Disaster
• During late 50s and early 60s,
more than 10,000 children in 46
countries were born with
deformities such as
phocomelia, as a consequence
of thalidomide use.

• Withdrawn in 1961

• Thalidomide tragedy led to
stricter testing being required
for drugs before they can be

Thalidomide- The most
notorious teratogen

Lifelong effects of
Mercury

An example of a
mistake…DES

Genetic & Physiological
Mechanisms of
Teratogenecity
• Folic acid metabolism
disruption
• Toxic oxidative intermediates
• Fetal genetic makeup
• Homeobox genes
• Maternal diseases or paternal
exposures

Folic Acid
• Disruption of folic acid
metabolism may lead to neural
tube defects (NTDs), cleft lip &
palate, and even Down‘s
Syndrome

• Folic acid is needed for
production of methionine, and
methylation of proteins, lipids
and myelin

Anticonvulsants

• Anticonvulsants act as folic
acid antagonists, leading to oral
clefts, cardiac and urinary tract
defects

Oxidative Intermediates
Microsomes Drugs- Hydantoin Carbamazapine, Phenobarbital

Epoxides – Carcinogenic, Mutagenic
ADULT FETAL
Epoxide hydroxylase Epoxide hydroxylase - weak

Detoxified No detoxification

Epoxides
Accumulate

Fetal Genetic Makeup
• Interaction of environment and
certain altered genes may lead
to malformations

• MTHFR 677C → T mutation is
associated with NTDs, but only
when folate intake is inadequate

Hwang et al, 1995, Am J Epidemiol)

cigarette smokers

• Polymorphisms in gene for TGF-
1 are linked to producing
isolated cleft palate in cigarette
smokers

Homeobox Genes
• A homeobox is a DNA
sequence found within genes
that is involved in the regulation
of development
(morphogenesis) in animals

• These are regulatory genes
encoding nuclear proteins, and
controlling expression of
developmentally important

Mutations to homeobox genes can
produce easily visible phenotypic
changes
• Arrangement of the genes along
the chromosome corresponds to
the arrangement of the body
areas they control

• Genes at the 3-prime end of the
chromosome control the cranial
region and are expressed before
those at the 5-prime end, which
control the caudal region
(Faiella et al, 1994, Proc Natl Acad Sci USA)

Homeobox Genes and
Teratogens
• Some teratogens, (retinoids) activate
homeobox genes prematurely,
leading to chaotic expression at
different sensitive stages of
development, especially causing
abnormalities of limb buds and
hindbrain

• Valproate alters the expression of
Hox d8, d10 & d11 genes, preventing
normal closure of posterior
neuropore

Maternal diseases
• Interaction of maternal disease
with fetal genetic composition
determines some drug effects e.g
alcoholic mothers have
nutritional deficiencies and also
abuse other drugs. Fetuses
exposed to these combined
adverse effects will be at higher
risk of malformations.

Paternal exposures
• Paternal exposure to teratogens
can act by inducing gene/
chromosomal abnormality in
sperm.

• Another possibility is that a
drug in seminal fluid may
directly contact the fetus during
intercourse.

Drugs and the lactating
mother:
• The physiologic processes that
govern the excretion of drugs in
breast milk are the same as that
which determine the transfer of
drugs through placenta.
• Toxicity therefore depends on
pharmacological characteristics
of the drug

Conclusion
• Toxicity most of the time is reversible
and is related to prolonged and
continuous use of drug

• But there are exceptions where a
single dose may be associated with
fetal / newborn toxicity e.g narcotic
analgesics close to delivery may
cause sinusoidal fetal heart rate
pattern or respiratory depression of
newborn

Conclusion
• Therefore when a woman
requires drug therapy during
pregnancy or lactation,
particularly prolonged /
continuous use, the lowest
possible dose should be used
and monitoring should be done
to detect any signs of toxicity.

Safe Drugs for Common Diseases
in Pregnancy

Dr Alami Zeba
MBBS, MD, Aligarh

Introduction

 The safety of more than 60% of
the medications in pregnancy
remains unknown.
 40-90% pregnant women are
exposed to medications during
gestation.

Introduction
• 90-97% pregnant women take
medications prescribed by their
physician and two thirds take
over the counter medications
without medical advice.

Objectives
• To summarize the safest drug
for treating common conditions
in pregnancy

• To discuss the teratogenic
potential of drugs which
sometimes must be prescribed
in pregnancy to treat life-
threatening conditions.

Frequently used drugs in
pregnancy:

• Vitamins, anti-emetics,
analgesics, antipyretics,
sedatives, antibiotics, laxatives,
antacids, diuretics,
antihistamines

Medications used to manage
serious medical complications /
pregnancy complications:
• Hypertension, PIH, diabetes,
cardiac disease, bronchial
asthma, thyroid disease,
cancers, poly-hydramnios, pre-
term labor, general and local
anesthetics,coagulation
disorders, auto-immune
disorders, epilepsy etc.

Considerations
• Pharmokinetics are affected by
physiologic changes of
pregnancy and dose
adjustments are needed to
optimize the clinical outcome.
• Teratogenetic potential of the
drug should be considered while
prescribing
• Some may directly affect the
fetus, others may cause harm

Analgesics
Salicylate - Increase the risk of early
s and spontaneous abortion.
Acetamin
ophen
- 1st trimester use may cause
fetal gastroschisis.

- There is theoretical concern of
premature closure of ductus
arteriosus.
185

CLASP Study 1994

• Did not report any fetal anamoly
with low dose aspirin [60 mg]
given to pregnant women for
prevention of PIH and IUGR

Analgesics
• Indomethacin

• Used to treat hydramnios, and for
tocolysis. May casue premature
closure of ductus arteriosus and
pulmonary hypertension in neonate.
This effect is reversible if drug is not
given after 34 weeks. Other adverse
effects are – intraventricular
hemorrhage, necrotizing enterocolitis
and bronchopulmonary dysplasia

Analgesics cont…

Narcotic - Chronic maternal ingestion may
analgesics : cause neonatal withdrawal
syndrome.

morphine, - They may also cause neonatal
codine, respiratory depression and
meperidine, sinusoidal heart rate pattern in -
propoxyphene utero.

Not known to be teratogenic
188

Analgesics cont…
Ergotamine - Used for treatment of migraine
and headache.
sumatriptan:
- Use of ergotamine in 1st
trimester may cause neural
tube defect and leads to fetal
bradycardia due to uterine
contraction and decreased
uterine blood flow.
Sumatriptan does not cause fetal
anomalies and spares uterine vessels so
better during pregnancy
189

Antiemetics
Doxylamine : Non-teratogenic, safe in
pregnancy
Piperazine and : Not associated with anomalies.
phenothiazine
s
[Metoclopramid
e.
Chlorpromazine
]
Ondansetron : Reserved for treatment of
hyperemesis refractory to other
medications as no human
studies , [category B]. 190

Antacids
Aluminum, Calcium, Magnesium
Magaldrate, Sodium Bicoarbonate.
- These are not teratogenic safe if used in
moderation Long term high dose use may lead
to maternal or fetal hyper-calcacemia, hyper-
magnesemia or hypocalcaemia.
H2 receptor antagonists: (ranitidine)
- Not associated with congenital malformations
even if used in 1st trimester though cross the
placenta
Proton pump inhibitors: (Omeprazole)
- Can be used safely even in 1st trimester 191

Decongestants
Pseudoephedrine:
-The most preferred decongestant as proven to
be safe in pregnancy.

Phenylephrine and
phenylpropanolamine:
-Used in nasal sprays and eye drops.
-No increased risk of anomalies but may
interfere with uterine blood flow and should
be avoided in pregnancy with decreased
uterine blood flow (e.g.PIH) 192

Decongestants cont…

Oxymetazoline, Xylometazoline:

-used in long acting nasal sprays
-No increase in the frequency of
congenital malformations.

193

Antihistamines
• Ethanolamine, Piperidine,
Butyrophenone and
Piperazine derivatives :
All are non- teratogenic .

Parenteral use of ethylamine
derivatives [Clemastine,
Diphynhydramine] may have
oxytocic effect.

Antihistamines cont….
Non-sedating antihistamines:
- Loratadine: No study to address
its safety in pregnancy.
-Cetrizine: There is no risk of
congenital anomaly.
-Astemizole and Fexofenadine are
non teratogenic .
-Chromolyn Sodium: safe even in
1st trimester
195

Antitussives
Dextromethorphan:
Not associated with congenital anomalies if
used in first trimester.
Narcotic containing:
Neonatal withdrawal syndrome and
respiratory depression may occur on long
term use.
Alcohol containing:
Short term use has no adverse effect.
196

Expectorants
Guaifenesin:
- Most commonly used agent in
expectorants
- It does not increase the risk of
birth defects
Iodide containing expectorants:
- Should not be used after 10 weeks
as these may cause fetal goiter.
197

Cardiac Medications
Digoxin:
- Cardiac glycoside used to treat
heart failure, atrial fibrillation or
flutter and other supraventricular
tachycardias.
-Readily crosses the placenta but
has no adverse fetal effects,
-Successfully used to treat fetal
arrythmias also. 198

Cardiac Medications
cont…
Quinidine:
- Used as antiarrhythmic drug.
- Dose used to treat arrhythmia is
one tenth the dose used to treat
severe malaria and has not been
associated with fetal
abnormalities.

199

• Many local anesthetics are used
as anti-arrhythmics e.g
Lidocaine, Procainamide.
• These cross placenta but do not
increase congenital
malformations
• However short term use is
different from long term use to
treat arrhythmias as long term
studies not available but we
have to see risk-benefit ratio as
arrhythmias may be life

Cardiac Medications
cont…
Amiodarone:
Used for life-threatening arrhythmias

-Structurally similar to thyroxine

-May cause fetal and neonatal
hypothyroidism if given after 10
weeks. 201

Anti anginals:

Nitro-glycerine:
Is used during general
anesthesia in hypertensive and
cardiac patients.
No epidemiologic studies
available to confirm safety but
do not withhold in life-
threatening cases.

Verapamil:

Used as antianginal,
antihypertensive and for
arrhythmias.

Is associated with decreased
uterine flow, cardiac depression
and cardiac arrest in neonates so
give only if condition is life
threatening and other agents are
ineffective

Antihypertensives
Methyldopa:
- Most commonly used drug to treat
hypertension during pregnancy.
- Its many years of use attest its safety
Hydralazine:
- Used to treat hypertension in later half
of pregnancy without adverse fetal
effects.
204

Antihypertensives
cont….
Sodium Nitroprusside:
- Readily crosses the placenta.
- May lead to accumulation of
cyanide in fetal liver.

Clonidine:
- An α-adrenergic antagonist.
- Has no adverse fetal effects.
205

Antihypertensive
cont…
β-blockers:

- long term use possibly associated
with fetal growth restriction and
neonatal hypoglycaemia.
- May cause transient mild
hypotension and symptomatic β-
blockade in exposed newborns.
206

Antihypertensives
cont…
Calcium channel blockers:

- May block the calcium dependent
embryonic processes
theoretically.
- Nifedepine has been associated
with fetal loss in some studies

Antihypertensives
cont…
Verapamil:
- Associated with limb defects
and hypertrophic
cardiomyopathy.
- Causes cardiac depression
and arrest if used with digoxin.
Nifedipine:
- Associated with fetal limb
defects and pregnancy loss if
used in early pregnancy . 208

Antihypertensives
cont…
ACE inhibitors:
-Decrease fetal renal perfusion which
leads to oligohydramnios if used in II
and III trimester.
-Resulting oligohydramnios causes lung
hypoplasia and limb contractures
known as ACE inhibitor fetopathy
-Contra-indicated in pregnancy
209

Diuretics
Thiazides:
-May cause neonatal thrombocytopenia,
bleeding and electrolyte disturbances if given
near term.
Furosemide:
•-May increase incidence of PDA in preterm
newborns.
•Crosses placenta increasing fetal urine production.
• Increase utero-placental insufficiency and IUGR.
•Given only when benefits outweigh risks as in
pregnancy with heart disease or in pulmonary edema.

210

Diuretics cont…
Spironolactone:
-anti-androgenic and shown to cause
feminization of male rats and delayed
sexual maturation of female rats in-
utero. Not been studied widely in
pregnancy
Acetazolamide:
-Has been associated with limb defects
in rodents but not in primates or
humans. 211

Anticoagulants
Warfarin:
-Readily crosses the placenta.
-Exposure between sixth and ninth week
causes warfarin embryopathy characterized
by nasal and midface hypoplasia and
stippled vertebral and femoral epiphyses.
-Second and third trimester exposure causes
hemorrhage in several organs leading to
disharmonic growth and deformation.
-Contra-indicated in 1st trimester of
pregnancy 212

Anticoagulants cont…

Heparin:
Has large and highly polar
molecules that do not cross the
placenta and thus are not
associated with fetal anomalies,
low birth weight or stillbirth
May cause maternal osteopenia
Safe in pregnancy
213

Antiepileptics
Phenytoin:
-Fetal hydantion syndrome,10% of
infants exposed will have major defects
and 1/3rd will have minor defects.
Carbamazepine:
-Fetal hydantion syndrome and neural
tube defect risk is 1% as compared to
.1% for general population, but safest in
pregnancy as compared to other drugs
214

Valproate:
Used for petit mal seizures
Neural tube defects
1-2% risk of neural tube defects
which is 8-10 times more than the
general population

Trimethadone and
Paramethadone:
Craniofacial anomalies,
microcephaly, growth deficiency and
cardiac defects.

Antiepileptics cont…
Phenobarbital:
Clefts, cardiac anomalies, urinary tract
malformations.

Lamotrigine:
Lower teratogenic risk than other antifolate
anti convulsants.

Topiramate:
Should be avoided in pregnancy.
216

Asthma Medications

Epinephrine and Terbutaline:
- Not associated with adverse
fetal effects.

Theophylline:
- Safe in pregnancy, all
trimesters.

217

Asthma Medications
Beclomethasone and
Prednisone:
- Have no adverse fetal effects.
Given as inhalers for long
term use and short term,
parenteral for exacerbations.

Avoid Triamcinolone in
pregnancy as teratogen for
animals

Thyroid Disorder Drugs
Propylthiouracil:
- May cause fetal goiter and
hypothyroidism
- Clinically significant effects are
uncommon with the therapeutic
doses.
Methimazole:
- Associated with scalp defects,
esophageal and choanal
atresia. 219

Potassium Iodide & Sodium
Iodide:
can be used for short term e.g
for thyroid surgery or thyroid
crisis but long term use may
cause goitre in infant.

Thyroid Replacement drugs:
Thyroxin does not cross placenta
significantly and is not
associated with anamolies

Anti Neoplastic Drugs
- Breast carcinoma, melanoma
and Hodgkin‘s lymphoma are
the most common malignancies
in pregnant women.
- Most chemotherapeutic agents
impede cell growth and cell
division.
- Cause congenital anomalies and
growth retardation.

221

Anti Neoplastic Drugs

All are Category D drugs but
potentially life- saving therapy
cannot be withheld in
pregnancy

Hormones
Androgens:
- Masculinization of female fetus.

Testosterone and anabolic
steroids:
- First trimester exposure may
cause labio-scrotal fusion.
- Phallic enlargement may occur
in late exposure. 223

Hormones cont…
Medroxyprogesterone acetate:
- Virilization of female fetuses
and feminization of male fetuses
in rats but not in humans.

Norethindrone:
- Female fetus masculinization
in 1% exposures.
224

Hormones cont…
Danazole:
- Causes clitorimegaly, fused
labia and urogenital sinus
malformation.

Oral Contraceptives:
- Not associated with congenital
anomalies
225

Diethylstilbestrol:
- Vaginal clear cell
adenocarcinoma.
- Cervical ectropion and vaginal
adenosis.
- Hypoplastic, T-shaped uterine
cavity.
- Cervical collars, hoods, septa
and coxcombs.
- Exposed males may have
epididymal cysts, microphallus,
cryptorchidism, testicular
hypoplasia and hypospadias. 226

Psychotropics
Diazepam:
- Most widely used tranquilizer.
- Increased risk of cleft palate,
limb malformation and other
defects in rodents.
- It‘s teratogenic effects in
humans is controversial.
- Neonatal depression and
withdrawal symptoms on long
term use.
227

Psychotropics cont…
Lithium salts:
- Ebstein anomaly
- May also cause diabetes
insipidus, hypothyroidism and
hypoglycemia.
Selective Serotonine Reuptake
Inhibitors:
- Not associated with fetal losses
and malformations
- can be used safely as 228

Psychotropics cont…

Tricyclic Antidepressants:
- Safe in pregnancy.

Phenothiazines:
- Teratogenic potential is
minimal.

229

Immuno Suppressives
Azathioprine:
- Growth restriction, immune
suppression and pancytopenia
may occur in exposed neonates.
Should not be with held from
pregnant patients as given for
prevention of rejection in renal
transplant

230

Immuno Suppressives
cont…
Cyclosporine:
- Causes maternal nephro-toxicity
but safe for fetus, cannot be withheld
in pregnancy as prescribed for life-
threatening conditions
Tacrolimus:
- Cause abortions and anomalies in
animals but not in humans.
- May lead to preterm delivery,
hyperkalemia growth restriction and
nephrotoxicity. 231

Others
Antifungals:
Local agents like Clotrimazole
and Nystatin are safe.
Fluconazole parenteral in high
doses is associated with
anomalies like brachycephaly,
heart defects, cleft palate. Single
oral dose is not associated with
increased frequency of
anomalies.

Antivirals
• Ziduvidine for AIDS and a
Acyclovir for Herpes are safe in
pregnancy
• Ribavarin used for treating
resiratory viral infections as
aerosol is highly teratogenic.
• No human data available for
Idoxuridine, Gangcyclovir,
Indinavir, Lamivudine,
Nevirapine etc

Antiparasitic drugs
• Metronidazole for
Trichomoniasis and Amebiasis
safe even in 1st trimester
• Chloroquine used for Malaria is
safe
• Quinine for falciparum malaria
in large doses often used as
abortifacient increases risk of
congenital abnormalities or
when taken in 1st trimester.
• Mefloquine may cause stillbirth

Antiparasitic drugs
• Spiramycin, Pyremethamine,
Sulphadiazine used for
Toxoplasmosis are safe in
pregnancy but concurrent
administration of folic acid is
needed with Pyrimethamine
• Mabendazole and Pyrantel
pamoate safe in pregnancy

Herbal Preparations

• It is difficult to estimate the
risk of herbal remedies as the
quantity and quality of the
ingredients in these
preparations are not known.

• Pregnant mothers should
therefore be counseled to avoid
these.

Some known
teratogens:
• Alcohol
• Antiepileptics- phenytoin,
carbamazepine, valproate,
phenobarbital, trimethadione,
lamotragine
• Warfarin compounds
• ACE-inhibitors
• Retinoids
• Hormones- androgens, danazole,
anabolic steroids, DES, androgenic
progestogens

Some known teratogens:
• Antineoplastic drugs-
cyclophosphamide,
methotrexate,
• Antimicrobials - tetracyclins,
streptomycin, sulphonamides,
• Antifungals- griseofulvin,
fluconazole
• Antivirals- ribavirin
• Antimalarial- mefloquin

How To Prescribe
Antibiotics In Pregnancy

Dr. Tamkin Rabbani
MD, DNB, MICOG
Department of OBG, J.N. Medical College,
AMU Aligarh.

When I look upon the past, I can
only dispel the sadness which falls
upon me by gazing into that happy
future when infection will be
banished as a cause of maternal
death and disability.

Philip Sammuel Weiss

Infection
• Infection is the commonest
and single most important
problem encountered by
obstetricians during
pregnancy

• Sepsis still remains an
important cause of maternal
mortality and morbidity.

In a study of almost 9000
Medicaid prenatal patients
Piper and colleagues
(1987) reported that each
woman received an average
of 3.1 prescriptions of
drugs with antibiotics as
the commonest group.

Indian scenario is expected to
be grimmer due to:
-Lack of regulatory agencies ,
-Poor enforcement of existing
regulations, --Lack of
awareness of general
population about teratogenic
potential of various drugs.

It important that as
obstetricians we should
know how to prescribe
antibiotics correctly.

Spectrum of problems
• Common infections encountered
are cystitis, acute
pyelonephritis, upper and lower
respiratory tract infections,
amnionitis, septic abortion,
puerperal sepsis

• Typhoid, hepatitis, malaria and
TORCH group of infections
sometimes also present a
therapeutic dilemma for us!

• Surgical prophylaxis for cases
like ovarian cystectomy, Mc
Donald stitches, Bartholin
abscess, Cesarean section,
episiotomy etc. is required.
• Prevention of chorioamnionitis
in both term and PTL with
PROM also needs antibiotics
• Prophylaxis for prevention of
streptococcal infection of
neonates is needed.

Most of these infections
are straight forward to
treat but may become
life threatening if not
treated adequately.

Today we have a whole
array of antibiotics at our
disposal but despite this
sudden explosion in the
number of antibiotics an
obstetrician‘s choice is
limited because of the risk
of teratogenecity and
emergence of resistance
against the tried and tested

The problem is that almost every
drug we are using today has this
warning in the accompanying
insert----

• This drug has not been proven
safe for pregnant and
lactating women!

The infamous thalidomide
tragedy is the background
for these warnings.

This has made antibiotics
big business for lawyers.

Nobody, specially the
FDA wants a repeat of
the benedictin episode -
--- drug was withdrawn
not because it was a
teratogen but because
it was a LITOGEN!

• Predicting human
teratogenicity from animal
studies is difficult if not
impossible!

• Package inserts do not
provide guidance as to
whether termination is
indicated if a pregnant lady
has inadvertently ingested
that drug.

• Simply mentioning that a
particular drug crosses the
placenta does not indicate
potential fetal harm as:

-Drug may cross but may not
harm
-Drug may not cross but have
deleterious effects on fetus by
affecting maternal physiology

The present system of testing,
marketing and categorizing
drugs has created a population
of „therapeutic orphans’– the
pregnant and potentially
pregnant women.

We are supposed to make the
intelligent decisions!

----And responsibility
shifts to us, the
obstetricians to decide the
risk- benefit ratio
subjecting us to an unfair
and unrealistic burden.

Prescribing in pregnancy---
the obstetrician’s burden!

?
Whether to prescribe at all

When to prescribe

What to prescribe

For how long to prescribe

Commandments
• Discourage pregnant ladies from
self medication.
• Warn pregnant ladies against
smoking and drug abuse,
environmental factors etc.
• All prescriptions should be
evidence based.
• Avoid poly pharmacy in
pregnancy.

Antibiotics with potentially
adverse fetal effects
• Tetracyclins-
yellow-brown discoloration of
deciduous teeth
• Aminoglycosides-
oto-toxicity, 8th cranial nerve damage
and sensori-neural deafness in fetuses
reported with streptomycin given in
high doses for long-term use, risk of
damage is 1-2% which is 20 times
than that for general population

Tetracyclin induced teeth discoloration


Nitrofurantoin-
Transient hemolytic anemia in
newborn specially those with G-
6-PO4 Deficiency and others as
well.
Avoid near term.

Sulfonamides and
trimethoprim-
• Cross placenta and compete
with biliruben in fetus and in
late gestation cal lead to neo-
natal hyper-bilirubenemia.
• Avoid in pregnancy

• Fluroquinolones-
irreversible arthropathy in
animals, so use only for
resistant cases.

• N-methyl thio tetrazole
containing cephalosporins-
testicular hypopasia in rats ,
no human studies


Chloramphenicol-
• Crosses placenta in high levels
causing peri-natal problems
like ‗gray baby syndrome‘ in
newborn.
• Avoid in pregnancy

Safe antibiotics in
pregnancy
Penicillins-
Ampicillin, Penicillin, Amoxicillin are
safe.
Newer penicillins– Mezlocillin,
Piperacillin and those combined with
Clavulanic Acid and Sulbactum not
adequately studied in pregnancy so
should be avoided.
All cross placenta and achieve high
levels so used for treating fetal syphilis.

Safe antibiotics in
pregnancy

Cephalosporins-
All cross placenta and achieve
high levels in fetus.1st
generation cephalosporins and
cefoxitin from 2nd generation
cephalosporins are a better
choice as they do not contain
the side chain N-methyl thio
tetrazole

Safe antibiotics in
pregnancy
• Erythromycin-
does not cross placenta in
significant amount so does not
prevent congenital syphilis.
Azithromycin and
Clarithromycin are probably
safe and few studies available
do not show an increased risk
of anomalies if given in 1st
trimester

Safe antibiotics in
pregnancy
• Aztreonam-
• Monobactum with same
spectrum of activity as
aminoglycosides and given
category B in pregnancy by
FDA.

Safe antibiotics in
pregnancy
Clindamycin-
No human studies, but reaches
fetus in high levels so do not use
except for local tablets for
bacterial vaginosis. CDC states
that clindamycin vaginal
preparations should only be
used during the first half of
pregnancy.

But remember absence of
evidence is not evidence of
absence!

Because for most newer
antibiotics there are no
human studies.

Evidence based treatment of
some common infections in
pregnancy:
[WHO recommendations].
Asymptomatic bacteriuria:
- Amoxicillin 3gms stat or
- Ampicillin 2gms stat or
- Nitrofurantoin 200 mg stat or
- Cephalosporin 2gms stat or
Single dose treatment is as good
as a 3 day course

Cystits:
- Amoxicillin 500 mgs TDS 3days
- If treatment fails / recurs more
than 2-3
times send C/S and treat
accordingly.
- For prevention of further
attacks:
Co-trimaxazole / NFT 100
mgs/ Amox
250 mgs HS till delivery and
2 weeks of puerperium.

Acute pyelonephritis:
- Ampicillin 2g IVI 6 hrly
plus Gentamycin 5 mg /kg b wt
IVI OD till she is fever free for 48
hrs.
- If poor clinical response after 72
hours reevaluate and add anaerobic
coverage.
- After treatment give Amox 1gm
TDS 14 days,then
250 mgs HS till 2 weeks post
partum.

Amnionitis:
- Amp 2 gms IVI 6 hrly plus
GM 5 mgs /kg B WT OD.
- Discontinue if she delivers
vaginally.
- If delivers by c/s add
metronidazole and
stop antibiotics once fever free
for 48 hrs.

Pneumonia
Community acquired infection is
usually caused by pneumococcal,
Mycoplasma or Chlamydia so
DOC is:
-Erythromycin 500- 1000 mgs 6 hrly
x 7days orally or IVI depending on
severity.
If no response:
3rd generation cephalosporin to be
started
as cause may be Hemophilus or
staphylococcal infection.

Typhoid
- Ampicillin 1gm x 6 hourly or
Amoxycillin
1gm x 8 hourly for a total of 14
days.

- However, Cephalosporins may
be used as
first line drugs according to
local
sensitivity patterns.

Acute Gastro-enteritis
• Mostly self limiting
• Strict maintenance of fluid and
electrolyte balance is mandatory by oral
Re hydration therapy or Parenteral
fluids according to the condition of the
patient.

- Attempt should be made for a specific
diagnosis by simple stool examination
and cephalosporin or metronidazole
should be added accordingly.

Septic Abortion
-Ampicillin 2gm IVI x 6 hourly
plus Gentamycin 3-5 mg / kg
body weight/day plus
Metronidazole 500 mg IVI x 8
hourly till patient is fever free
for 48 hours.

-Surgical management
according to case.

Metritis
-Use combination of antibiotics
ampicillin plus gentamycin and
metronidazole till fever free for 48
hrs.

- surgical management for retained
products– D&C, laparotomy,
hysterectomy according to situation

Pregnancy with heart
disease
• Ampicillin 2 gm IVI plus
Gentamycin 1.5 mg per kg wt(
max.80 mg.) IVI / IMI ½ hour
prior to procedure followed by
Amp 1gm IVI 6 hours of initial
dose..
• Amoxicillin 3 gms orally stat
then 1.5 gms after 6 hrs in low
risk cases.

Preterm PROM
• Use amoxicillin and erythromycin
IVI for 48 hrs then orally for 7-10
days to prevent sepsis in mother.

• Do not use clavulanic acid as risk of
necrotising entero-colitis in neonate.

• Ampicillin 2g iv 6 hourly or Penicillin
G 2 m.u. IV 6 hourly for prevention
of group B streptococcal infection of
neonate.

Term PROM
Membranes ruptured >18 hours,
Ampicillin 2g IVI 6 hourly or Penicillin
G 2 M.U.IVI 6 hourly for prevention of
group B streptococcal infection of
neonate.
• Stop antibiotics if she delivers
normally and has no fever.
• Add metronidazole if she undergoes
c/s and continue antibiotics till she is
fever free for 48 hours

Summary of treatment
practices:
-As 1st line defence against serious
infections give a combination of
Amp 2gms 6 hrly plus Gentamycin
3-5 mg /kg b wt od and
metronidazole 500 mg 8 hrly.

-If infection is not serious start
Amoxicillin 500 mg 8 hrly plus
Metronidazole 500 mg tds orally.

If clinical response is poor
after 48 hrs ensure proper
dosage , look for another
cause of fever and change
antibiotic (according to
culture report) after 72 hrs.

-If staphylococcal infection
is suspected give Cloxacillin
1 gm 4 hrly.

-If clostridia or group A 
hemolytic is suspected give
Penicillin 2 million units ivi
4 hrly

-If above are not a possibility then
switch over to Ceftriaxone 2gm IVI
OD

-Continuation of antibiotics after
patient is fever free for 48 hrs has
not been proven to have any
additional benefit.

-Women with blood stream
infections however need antibiotics
for a minimum of 7 days.

Process of writing a
rational prescription—
1. Define the patient‘s problem.

2. Specify the therapeutic objective i.e.
what do you want to achieve with the
treatment.

3. Verify the suitability of your
treatment i.e. check effectiveness and
safety.

Process of writing a
rational prescription—
4. Start the treatment.

5. Give information instructions
and warning, ask the patient
to paraphrase.

6. Monitor the therapy and stop
if required.

While writing
the treatment
avoid
polypharmacy-
-

Give:
information,
instruction,
warning.

Keep uptodate

• Knowledge and ideas keep
changing.
• New drugs are developed and
experience with existing ones
expand.
• Side effects become better known.
• New indications are discovered.

Lack of
knowledge
can not be an
excuse for the
physician and
is liable to be
held
responsible, so
make good
use of internet
and library.

The most important type of
inefficiency in treatment is a
combination of two separate
groups, the use of ineffective
therapies and the use of
effective therapies at the wrong
time.

--Archibald Leman
Cochrane

To remain true to our
Hippocratic oath we
should remember our
promise to ourselves as we
entered the medical
school---
I will apply for the benefit of
the sick all measures that
are required , avoiding the
twin traps of over treatment
and therapeutic nihilism.

Drug Abuse During
Pregnancy

Dr. Nasreen Noor
Assistant Professor, Department of Obs. & Gynae
J.N.M.C.,

Why do people take drugs ?
• It’s pleasurable • Coping mechanism
• Experimentation • Escaping
• Introduction by • Overwhelming
partners family • Emotions.
or • Managing
friends depression or
• Low self esteem anxiety
• Mental Health • Managing trauma

A Major Reason People
Take a Drug is they Like
What It Does to Their Brains

The first use is usually voluntary

Impact of drug abuse

 Maternal dis-inhibition and
personality alteration can further
impair the welfare of the fetus.

Effects of Substance Use
During Pregnancy

What are the consequences of substance
use or exposure?

• Complications during birth

• Physical deformities

• Mental retardation

• Developmental Disorders

Women who use substances
may:
• Feel anxious about becoming a parent.
• Wonder what they can offer a child.
• Need to explore the impact of the
pregnancy on their life style.
• Have concerns about being stigmatised
or
judged in a hospital setting.

Four Factors in Parenting Negat ive
Dysfunction in Chemically Heritage
Dependent Women

Emotional
Instabilit y

Vulnerable Deficits in
Infant Social
Support

PARENTING

Alcohol
• Teratogen – risk of foetal alcohol
syndrome
• Not known what is ‗safe level‘ of
consumption, seems, binge drinking more
problematic.
• (2007) English Dept of Health guidelines
‗no alcohol is safe,so avoid if pregnant or
trying to conceive.
• Abstinence ‗ideal‘
• Breast feeding : alcohol enters breast milk
but not stored.

Fetal Alcohol Syndrome

• Low birth weight
• Central nervous system effects
• Facial dysmorphology

FASD

Fetal Alcohol Spectrum Disorders

― an umbrella term describing the
range of effects that can occur in an
individual whose mother drank
during pregnancy. These effects may
include physical, mental, behavioral,
and/or learning disabilities with
possible lifelong implications.‖
Bertrand et al, 2004

Microcephaly Epicanthal folds

Short palpebral Flat nasal bridge
fissures

Flattened midface Low set ears

Short, upturned nose
Flat philtrum

Thin upper lip Receding jaw

Tobacco
Increased likelihood of: miscarriage and
threatened miscarriage, prematurity, LBW,
accidental haemorrage & perinatal death
• Ask if woman smokes
• Advise (non confrontationally) to quit
• Assess stage of change, level of
dependence
• Assist (eg provide information, explore
persons doubts, tobacco cessation group)
• Arrange follow up (eg at next A/N visit)

Cocaine
• Associated with IUGR, placental
abruption and premature rupture of the
membranes
• Developmental problems observed.
• Advise cessation, harm minimisation,
offer counseling
• Breastfeeding: express and discard for
24hours after use

Amphetamines
• Appetite depressant – poor maternal
nutrition – low birth weight.
• If IV drug use – infection risks..
• Possible link with cerebral ischemic
lesions
• Advise cessation, counselling may be
of use
• Breast feeding: Express and discard for
24 hours

Maternal Effects of Amphetamine
During Pregnancy
• Increased maternal blood pressure
• Increased maternal heart rate
• Increased risk of premature birth
• Constricts blood flow in the placenta,
thereby impacting oxygen flow to the
fetus

Effects of Amphetamine on the
Developing fetus/infant
• Poor fetal growth—small for gestational
age
• Elevated fetal blood pressure (stroke)
• Birth defects (6 times the normal rate)
• Cleft palate/lip
• Heart disease
• Kidney disease
• Omphalocele
• Premature birth

Managing substance abuse in
pregnancy
Antenatal care -Goal is to stop or reduce use of
recreational drugs
• Detailed history including partner‘s drug use &
sexual history
• Consultation with a trainee in addiction
medicine
• Consultation with anaesthesist may be
beneficial for labour analgesia
• Specialist in USG to rule out structural
anomalies, defects and syndromes.

Intrapartum care

• Need constant intrapartum
monitoring
• Disturbances in fetal heart rate
and rhythm observed with some
drugs.

Postnatal Care
• Pediatricians should be informed detailed
history .
• Careful newborn examination for birth
defects or withdrawal effects
• Early liaison with social work team is
vital.
• Maternal withdrawal symptoms should be
looked for.
• Sedative or replacement therapy if
indicated.

Avoiding Relapse

It is also important to keep in mind
that substances can continue to cause
significant health problems to children
after birth…

• Transmission through breast milk

• Environmental exposure to smoke

Heroin
Short half life – mother and foetus
experience withdrawal – may increase
pre maturity, miscarriage associated with
IUGR
• Illicit – unknown additives
• If used IV – infection & life style issues .
• Detoxification not advised - very high risk
of relapse, preferred treatment: stabilise
women on methadone, counseling and
psychosocial support
• Breastfeeding: not recommended

Avoiding Relapse

• Many new mothers report that they
resuming substance use following
delivery

• Particularly true of tobacco products
and alcohol

A Strategy for Avoiding
Relapse

–Make a plan

–Return for follow-up

–Tell others you have quit

–Ask for help from family and
friends

Message
Care of women abusing recreational
substances can be exasperating, but
is worthwhile.

Although the mother‟s health needs
must be met,the well being and
development of the fetus must not
be neglected by her care taker.

Vaccination In
Pregnancy

Dr. Zehra Mohsin
Assistant Professor
JNMC, AMU, Aligarh

Introduction

• Vaccination is the single most
important public health
achievement of the 20th century.

• The word vaccination was first
coined by Edward Jenner from the
Latin word vacca for cow as the
first vaccine was derived from the
cowpox virus

• No evidence exists of risk from
vaccinating pregnant women
with inactivated vaccines or
toxoids.

• Benefits of vaccinating pregnant
women usually outweigh
potential risks when the
likelihood of disease exposure
is high.(1)

Killed Vaccines /
Toxoids
• Usually multiple doses are
required.
• Periodic booster required.
• May be given in pregnancy if
needed.
• No vaccine is recommended in
the 1st trimester.

Live Vaccines

• Provide long-lasting immunity.
Single dose required.
• Contraindicated in pregnancy as
they pose a theoretical risk of
infection to fetus.
• If inadvertently given in
pregnancy termination is not
indicated as yet no vaccine
related side effects are reported

• Tetanus Toxoid(TT)/
Tetanus + Diphtheria (Td)
Indian national immunization schedule
and WHO recommend 2 doses given
IM, 4 weeks apart in the 2nd trimester
(16-20 weeks)

In those who have been vaccinated,a
single booster is adequate if next
pregnancy is within 3 years (2).
•

• CDC recommends 3 doses of TD in
un-immunised women.

• First 2 doses, 4 weeks apart,
starting in 2nd trimester and 3rd
dose 6 months after 2nd dose
(postpartum).

• Single dose booster is
recommended for women who have
received TD vaccination within the
last 10 years.(3)

Hepatitis B Vaccine
• Purified HbsAg produced by
recombinant technique.

• Recommended in „at risk‟ women:
Having more than 1 sex partner
during the previous 6 months,
evaluated or treated for STD, IV
drug user or with a HbsAg +ve
partner.

• Dose : 3 doses at 0, 1 and 6 months,
IM (4).

Hepatitis B
Immunoglobulin
• Post exposure prophylaxis in
newborn along with hepatitis B
vaccine.

• To be given preferably within 12
hours of birth.

Influenza Vaccine
• Trivalent killed virus vaccine
recommended for women who
are pregnant in influenza
season (Oct-March) but live
attenuated influenza vaccine
is contraindicated (5).

• Single dose – IMI

• Also contra indicated in those
allergic to eggs

Meningococcal Vaccine
• Mpsv4 is quadrivalent
polysaccharide vaccine. Single dose
- subcutaneous, recommended for
those at risk for infection

• Mcv4 a quadrivalent conjugate
vaccine may be given but data
regarding safety is not available

MMR Vaccine

• Live virus vaccine

• Pregnancy contraindicated for upto
28 days after vaccination.

• Routine pregnancy testing before
vaccination in not necessary, if
given inadvertently termination not
recommended.

Varicella Vaccine
• Live attenuated viral vaccine

• Can cause congenital Varicella in
2% fetuses

• VZ IG should be strongly
considered for susceptible
pregnant women who have been
exposed

BCG Vaccine
Herpes Zoster Vaccine

• Not recommended in
pregnancy

HPV Vaccine
• The quadrivalent vaccine does not
contain live virus and is categorized as
category B drug by FDA

• If the woman is found to be pregnant
after vaccination the remaining of the 3
dose regimen are to be given after
delivery

Vaccines Recommended
in
Special Cases

Hepatitis A Vaccine
• Inactivated viral vaccine

• Two dose schedule 6 months
apart

• Pre-exposure and post-
exposure for women at risk of
infection

Rabies Vaccine

• Killed virus vaccine

• Post exposure prophylaxis can
be given.

• Pre exposure prophylaxis
might also be indicated in
those at risk of exposure.

Pneumococcal Vaccine
• Polyvalent polysaccharide vaccine
(ppv23) given in a single dose, SC or
IM , repeat dose after 6 years

• Recommended in women with :
Chronic lung disease, cardiovascular
disease, Diabetes mellitus, chronic liver
disease, chronic renal failure, asplenia
/ post spleenectomy,
immunosuppressive disease, cochlear
implants.

Yellow Fever Vaccine
• Live attenuated viral vaccine

• Dose: single ,subcutaneous

• To be administered only if travel
to an endemic area is
unavoidable

Anthrax Vaccine

• Prepared from cell free filtrate of
bacillus anthracis

• Recommended only for those
who work directly with
-animal hides
-Potentially infected animal

Typhoid Vaccine

• Killed vaccine given as 2 doses 4
weeks apart, SC.
• Recommended in women following
exposure or traveling to endemic
areas
• Not much data regarding safety
• Live oral vaccine ty21a not
recommended

Japanese Encephalitis
Vaccine

• Inactivated viral vaccine

• Not routinely recommended

• Only if traveling to endemic
areas or during outbreaks

Novel influenza A
[H1N1]

Both seasonal flu shots and
2009 H1N1 flu shots are
recommended for pregnant
women at any time during
pregnancy

drraginiagrawal@gmail.com
09711187176, 09311292012

Challenges in obstetric prescription

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Similar a Challenges in obstetric prescription

Similar a Challenges in obstetric prescription (20)

Más de Shambhu N

Más de Shambhu N (18)

Último

Último (20)

Challenges in obstetric prescription