Drugs In Pregancny And The Newborn Flashcards
What kind of causes are there for birth defects
- chromosomal aberrations: such as Edward’s and Patau and down’s (3-5%)
- background risk of congenital malformations 2-3%
- known genetic transmission 20%
- infectious accounts = rubella most common agent (2-3%))
- drugs and chemical (4-6%)
- maternal metabolic disorders (1-2%)
- unknown (70%)
What is a teratogen
Agent if administered causes directly or indirectly structural or functional abnormalities in the foetus or in child after birth (may not be apparent until later in life)
What can teratogens cause
Resorption or abortion of the early embryo
Structural malformations
Intrauterine growth retardation
Mental retardation
Foetal death
What are common teratogens
Infections
‘
Physical agents/ chemicals
Medicines
Alcohol, tobacco or cocaine
What is behavioural teratology
Effect on the behaviour or functional adaptation of the offspring to its environment
What is transplacental carcinogenicity
Has no effect on the mother but results in cancer in the offspring
What causes vaginal/testicular cancer in the offspring
Diethylstilboestrol DES
How can mutagenicity result in infertility or cancer
Mutations in germ lines = sex cells are defective causing reduced fertility or complete infertility
Mutations of somatic cells can result in cancer induction
How does smoking result in defects
Causes hypoxia and vasoconstriction —> spontaneous abortion
Cocaine can cause placental issues indirectly and directly same as above leading to stillbirth
With regard to teratogens having any effect what are the some of the most important considerations
- time of exposure is critical
- teratogenicity is usually dose dependent
- susceptibility to some teratogens is genetically determined
However risk may altered through individual metabolism of drug
Behavioural teratology: alcohol use: how does it present
Use of alcohol is associated with increased risk of spontaneous abortion and reduced birth weight by 1kg
Foetal alcohol syndrome associated with binge drinking
Facial features: microcephaly, small chin, short nose, low set ears, flat mid face
However above physical features may not be as recognisable so other key indicators include attention span and academic ability as development of brain and CNS hindered
Strong link for children to have secondary comorbidities such as behavioural abnormalities
How is foetal alcohol spectrum disorders FASD different to FAS
In FASD not all symptoms of FAS are present
What are patterns of alcohol consumption in women of child-bearing age
Overall alcohol consumption has fallen
Younger women are drinking less frequently than older women but are more likely to participate in binge drinking
What are the two types of inheritance and how do they explain recurrence risks
Mendelian/ monogenic inheritance = recognisable patterns in inheritance
Multi factorial/ polygenic = degree of sensitivity is variable
Eg spina bifida
For many malformations there is a high recurrence rate and chromosomal abnormalities can result in disease
What is spina bifida
Failure of the caudal end of the neural tube to fuse
What are some of the causes of spina bifida
Chromosomal abnormalities
Single gene disorders
Teratogenic exposures
What % of spina Bifida can be prevented in mother takes folic acid
70%
What are risk factors for spina bifida
History of previous affected pregnancy with same partner
Inadequate maternal intake of folic acid
Pre-gestational diabetes
Valproate and carbamazepine use
Maternal obesity
Strong family history
Teratogenic damage is dependent on the dose relationship curve. What would a steep curve indicate
Small increments in dose show large increases in effect
What is the concept of synergy in relation to teratogenic damage
Work together to increase the harm done to the foetus. For example administering a second drug that enhances the teratogenicity of the first drug
So the general rule is to avoid poly pharmacy when possible
Placental transfer of drugs occurs via which 3 mechanisms
- passive diffusion
- facilitated diffusion through pores of the chorionic membrane
- active transport via enzymes or protein carriers
Drug transfer is influenced by which of the 5 factors
1) molecular weight
2) lipid solubility
3) ionisation
4) protein binding
5) chemical structure
Large molecular weight drugs such as ____________, _________, _________ do not cross the placenta
- heparin’s
- insulins
- iron dextran
Does a drug need to cross the placenta to affect the foetus
No! Eg insulin
Th glucose produced during episodes of maternal hyperglycaemia may pass across causing the foetus to produce insulin that it cannot clear
A molecular weight of ________ daltons will allow drug to enter the placenta
1000 or less
What is the main determinant of the conc in the foetus
The concentration in the mothers blood
How may physiological changes affect drug transfer to the placenta
Can modify blood flow to placenta
Can modify placental surface area available for transfer
What pharmacokinetic changes occur during pregnancy
- increase in maternal liver function so there is an increase in metabolism
- increase in maternal excretion due to increased renal flow eg Li
- there is a decrease in albumin which leads to a higher concentration of free unbound drug in the foetal circulation
- decrease in GI motility
Why is detecting teratogenic effects so difficult
- requires large number of infants exposed in utero to study them
But since it is advised to not take drugs in pregnancy and testing is not carried on women of childbearing age
= lack of data
And most birth defects occur rarely
Difference between gestational age and embryonic age
Gestational age = pregnancy is dated from the last menstrual period
Embryonic age = post conception so difference of two weeks in dating
What is the most critical time period
In the first trimester
What major structures form in the first trimester
Spine
Head
Arms
Legs
Organ development
Lungs
Heart
Stomach
What are the greatest risks in the 2nd trimester
Harmful exposures in the 2nd trimester may result in growth problems and minor birth defects
Functional defects such as learning problems
Brain and CNS
How may the use of androgenic steroids impact development if administered in the first 13 weeks
May masculinise a developing female foetus through clitoromegaly and labial fusion
What is transposition of the great vessels
Rare but serious disorder that requires surgical treatment
Group of congenital defects in which position of major blood vessels of heart are switched around. Rarely even chambers may be switched around
What is a cleft lip
Gap/split in the upper lip or roof of mouth. Occurs because part of the baby’s face did not join together properly
Most common facial birth defect
What is a ventricular septal defect
Hole in the heart which causes oxygen rich blood to get pumped back to the lungs causing the heart to work harder
Small VSDs may repair on own but larger ones may require intervention
What is syndactyly
Joined digits
May also involve webbing of the skin or fusion of the bones
What is hypospadiasis
Congenital birth defect in which the opening of the urethra is on the underside of the penis instead of at the tip.
Corrective surgery ensures normal appearance, urination and reproduction
1st trimester: what may oestrogens do to the foetus
Feminisation of the male foetus
Effects of warfarin in the T1
Nasal hypoplasia
Skeletal defects
Effects of retinoids in T1
Craniofacial, cardiovascular and CNS defects
Effects of diethylstilboestrol in T1
Uterine lesions
Transplacental carcinogen (vaginal and testicular cancer in the offspring)
Effects of anti-epileptics in T1
Facial defects
Mental retardation
Neural tube defects
Use of narcotics after T1 may result in
Neonatal respiratory depression
Use of warfarin after T1:
Foetal haemorrhage
CNS abnormalities
Use of anti-depressant after T1
Neonatal withdrawal symptoms
Use of benzodiazepines after T1
Floppy infant syndrome,
Neonatal respiratory depression
Withdrawal symptoms
Use of ACE inhibitors after T1
Olighydraminous (deficient amniotic fluid —> severe growth restriction)
Growth retardation
Lung and kidney hypoplasia
Hypocalvaria (cranial bones are hypoplastic (incomplete or arrested development)
Neonatal convulsions
Hypotension
Anuria
What kind of defects timing is unknown
Neurodevelopmental defects
What happens if you take NSAIDS in last 9 weeks of pregnancy
Premature closing of the ductus arteriosus. Is a foetal blood vessel that connects the aorta and pulmonary artery
May result in pulmonary hypertension and death
Possible paternal exposure to agents may include
Chemotherapeutic agents such as methotrexate
Industrial chemicals
Metals such as lead pesticides
Steroids
Recommended if exposed to mutagenic agent should wait 6 months/ 2 sperm cycles before attempting conception
As may impact on fertility/chance of getting pregnant and in some cases chromosomal aberrations
As a result of the thalidomide scandal post marketing surveillance introduced which regulatory measures
- MHRA yellow card
- congenital malformation registries
- UK teratology information service UKTIS
- UK epilepsy and pregnancy register and other national registers
Changes to the packaging and warning labels
Congenital disability act 1977
What could potentially be a risk to the foetus
- risks from the maternal illness
- risks from the treatment
- risks from failing to treat the mother
What are the critical factors in assessing risk factors to the foetus
Stage of the pregnancy
Drug and chemical exposure
Clinical condition of the mother or patient
Previous obstetric history (history of malformations or recurrent abortions)
What are the main principles of prescribing in pregnancy
Only give drug when necessary and make sure to carry out a risk vs benefit assessment
Use the lowest effective dose for the shortest amount possible
Consider the stage of pregnancy
Avoid all drug treatment in the first trimester wherever possible
Avoid new drugs
Avoid poly-pharmacy
Where to seek advice and information when it comes to prescribing in pregnancy
Safety in pregnancy SPS
UKMI UK medicines information
UKTIS UK teratology information service
RCOG royal college of obstetricians and gynaecologists
NHS medicines A-Z library
NHS evidence/ NICE
DoH green book - vaccine information
How is pain usually treated in pregnancy
- normally paracetamol or codeine if former not effective
- NSAIDS but not after week 20
- risk of opioid use near delivery associated with respiratory depression
- prolonged used of opioids related to neonatal withdrawal
Non pharmacological treatments - physiotherapy, hot and cold packs, TENS
How is nausea and vomiting treated in pregnancy
Step 1 = non pharmacological: small high carb, low fat frequent meals
Use of ginger or acupuncture
Step 2 = pharmacological
1st choice = cyclizine, promethazine or doxylamine
2nd choice = ondansetron or domperidone
Treatment for hyperemesis gravidarum
Hospitalisation
Fluid and electrolyte replacement
Consider corticosteroids (if severe)
Thiamine and pyridoxine if required
What are the treatments for constipation in pregnancy
Step 1 = non-pharmacological
Increased fibre
Increased fluid
Increased exercise
Step 2:
Bulk-forming laxatives isphagol
Osmotic laxatives = lactulose or macrogol
Senna
Glycerol suppository
What causes constipation in pregnancy
Affects 40% of women
Progesterone induced intestinal smooth muscle relaxation
Treatment of hay fever in pregnancy
Non-pharmacological interventions such as allergen avoidance
Topical therapy in form of intranasal corticosteroids
Non sedating anti-histamines such as certirizine and loratadine
Sedating anti-histamines = chhlorphenamine
What is the ruling on use of valproate in pregnancy
Valproate must not be given to women and girls of childbearing age and especially not pregnant women unless conditions of pregnancy prevention programme are met
What other drugs should be avoided in pregnancy
Anti-seizure medication such as leviteracetum
Topiramate
Isotretinoin
What did the baroness cumberledge report find
Reported on 3 clinical areas where harm has occurred
1) primodos
2) sodium valproate
3) surgical mesh for female incontinence
Patient voice is dismissed, parents are living with guilt and failure of informed consent
