Block 11 week 3 Flashcards
Teratogenicity
Teratogenicity is the ability to cause defects in a developing fetus. It is a potential side effect of many drugs such as thalidomide.
There is a background risk of congenital malformations of about 2-3% of births to normal young fit and health mothers
Risk is increased if
Teratogen
an agent is a teratogen if its administration to thepregnant mother directly or indirectly causes structural orfunctional abnormalities in the foetus or in the child afterbirth, which may not be apparent until later in life”
Common Teratogens
- Infections
- Physical agents
- chemicals
-Medicines
-alcohol - tobacco
-cocaine
Behavioral teratology
- drinking alcohol
FASD can cause problems with:
movement, balance, vision and hearing
learning, such as problems with thinking, concentration, and memory
managing emotions and developing social skills
hyperactivity and impulse control
communication, such as problems with speech
the joints, muscles, bones, and organs, such as the kidneys and heart
There is no particular treatment for FASD, and the damage to a child’s brain and body cannot be reversed. But an early diagnosis and support can make a big difference.
Transplacental carcinogenicity
No adverse effects on mother but cancer in offspring
Example is diethylstilboestrol (DES)
Doctors and obstetricians commonly prescribed DES to women who had fertility problems or who were at risk of miscarriage, usually as a pill.
DES mothers more likely to have breast cancer
Some common DES-induced problems in DES sons include:
-undescended testicles
-underdeveloped testicles
-cysts on the testicles
-lowered sperm count.
DES daughters:
- you have a higher chance of developing vaginal and cervical cancers
- Clear-cell cancer, or adenocarcinoma, is a rare cancer of the vagina or cervix associated with DES daughters. If this cancer is discovered at an early stage, doctors can treat it successfully.
- but a 2006 study indicated that DES daughters may have a slightly increased risk of developing breast cancer after the age of 40
- vaginal adenosis - where parts of the vagina and cervix secrete mucus ( become glandular)
- altered shape of uterus and cervix
- You should have a special DES check-up every year, along with annual breast examination by your GP and mammography every two years, once you have reached 40 years of
Germ cell mutations
A germ cell mutagen is a chemical that may cause mutations in the germ cells of humans that can be transmitted to the progeny
Somatic mutation
A somatic mutation describes any alteration at the cellular level in somatic tissues occurring after fertilization. These mutations do not involve the germline and consequently do not pass on to offspring.
Previous obstetric history
Previous obstetric history is an important factor in determining whether a woman is more likely to have a baby with malformation
For many malformations there is a high recurrence rate
There are 2 major types of inheritance:
- Mendelian inheritance (monogenic) - recognizable patterns
- Multifactorial or polygenic - degree of sensitivity is variable
Multifactorial inheritance
Multifactorial inheritance is when more than 1 factor causes a trait or health problem, such as a birth defect or chronic illness.
Genes can be a factor, but other things that aren’t genes can play a part, too. These may include:
- Nutrition
-Lifestyle
-Alcohol and tobacco
-Some medicines
-An illness
-Pollution
Multifactorial conditions tend to run in families. This is because they are partly caused by genes. Your risk for a multifactorial trait or condition depends on how close you are to a family member with the trait or condition.
For example, you’re at higher risk for a trait or disorder if your brother or sister has it. You’re at lower risk if a cousin has it.
Types of multifactorial traits and disorders:
Birth defects such as neural tube defects and cleft palate
Cancers of the breast, ovaries, bowel, prostate, and skin
High blood pressure and high cholesterol
Diabetes
Alzheimer disease
Schizophrenia
Bipolar disorder
Arthritis
Osteoporosis
Skin conditions such as psoriasis, moles, and eczema
Asthma and allergies
Multiple sclerosis and other autoimmune disorders
SPINA BIFIDA
Cause multifactorial inheritance: The causes of this disorder are heterogeneous and include chromosome abnormalities, single gene disorders, and teratogenic exposures.
- Up to 70% can be prevented by mother taking folic acidsupplements during pregnancy
Dose response relationships
A hypothetical dose-response curve has features that vary (see figure Hypothetical Dose-Response Curve ):
-Potency (location of curve along the dose axis)
-Maximal efficacy or ceiling effect (greatest attainable response)
-Slope (change in response per unit dose)
Small babies lecture
Intrauterine Growth Restriction (IUGR)
- Full fetal growth is not completed during gestation - which increases morbidity
(being unhealthy) and mortality (death) risk - AKA fetal growth restriction
Intrauterine growth restriction (IUGR) is a disorder in which a baby’s weight is below the 10th percentile for babies of the same gestational age and sex.
Intrauterine growth restriction can be caused by problems with the placenta, the baby’s genes, or mother’s health issues. Intrauterine growth restriction babies are at risk for many health problems, including low birth weight, premature birth, and death.
Types
Symmetric and Asymmetric
Symmetric:
- begins early in gestation
- Most commonly caused by intrinsic factors (infection, chromosomal abnormality)
- uniform effect (all organ system )
- Body/head circumference, length, weight restricted proportionally.
Asymmetric:
- affects the fetus in the late second/third trimester
- Commonly caused by decreased nutritional delivery to the fetus ( limits glyogen, fat storage, brain sparing)
- Head circumference (normal), length (near normal), weight (significantly affected)
What causes IUGR ?
Fetal factors:
- genetic ( e.g. aneuploidy, single gene mutations)
- infections ( cytomegalovirus, toxoplasmosis, rubella)
- multiple gestation ( e.g. nutrient competition by more than one foetus)
Placental factors:
- Ischemic placental disease ( preeclampsia)
- Structural anomalies (e.g. single umbilical artery)
Maternal factors:
- Chronic disease (e.g. renal, cardiac, pulmonary disease)
- Substance use ( alcohol, cigarettes, illicit drugs)
- Poor nutritional status, inadequate weight gain)
Environmental factors:
- teratogen exposure, pollution
- certain maternal therapeutic medication
Complications of IUGR
- Preterm birth, related sequelae (e.g. necrotizing enterocolitis, respiratory distress syndrome)
- Intrauterine asphyxia. Chronic intrauterine asphyxia affects placental blood flow, and placental infarction adversely affects fetal growth. In cases of chronic intrauterine asphyxia, labor may be poorly tolerated and neonatal resuscitation may be necessary.
- impaired thermoregulation
- Hypoglycemia
- Polycythemia - chronic hypoxia
- Impaired immune function
- Increased mortality risk
Diagnosis
- Doppler velocimetry
- Ultrasound biometry
- Lab results
CRL
- Crown Rump Length
- Crown-rump length (CRL) is an ultrasound measurement that is used during pregnancy. The baby is measured, in centimeters, from the top of their head (crown) to the bottom of their buttocks (rump).
-The limbs and yolk sac are not included in the measurement.
- The CRL can be measured starting around six or seven weeks of pregnancy up until 14 weeks.
What is Crown Rump Length ?
CRL may be useful in calculating gestational age. With this gestational age, doctors can estimate your potential due date. The earlier the first ultrasound is performed, the more accurate the baby’s gestational age will be.
Once the fetus has developed past 14 weeks, head circumference, biparietal diameter, and femur length measurements are used to determine how the baby is progressing.
The length of the umbilical cord is typically the same as the CRL throughout pregnancy.
Average baby weight
- At 37 weeks your pregnancy is considered full term
- The average baby weighs around 3-4kg
- Term - baby born between 37 and 42 weeks
- Pre - term: babies born alive before 37 weeks of pregnancy are completed
Post - term: babies born after 42 weeks gestation - they have a decreased weight because placenta doesn’t work properly
- At 32 weeks a baby can survive well ( at around 2kg)
- A babies weight increases by around 0.2kg/week from 32 weeks onwards
What are the 3 phases of foetal growth ?
3 phases of foetal growth:
- Cellular hyperplasia (0-14 weeks)
-An increase in the number of cells in all organs - Continued hyperplasia and hypertrophy (15-32 weeks)
-Cell multiplication and organ growth - Cell hypertrophy is the dominant feature of growth (32 weeks onwards)
-An increase in cell size
-Fat deposition
- Weight increases by 200g/week
Hormones necessary for foetal growth
- Insulin like Growth factor 2 is nutritional independent and is dominant in the first trimester
- Insulin like growth factor 1 is nutrient dependent and dominates in trimester 2 and 3.
- Leptin - produced by placenta itself - helps baby to grow
- epidermal and transforming not as important for foetal growth as insulin and insulin like growth factor.
- babies growth is used to tell you the gestational age of the baby and lets you estimate the due date of the baby.
- you can use the crown lump length to date pregnancies between 6-13 weeks.
- The first scan to date the pregnancy is between 11 weeks and 2 days and 14weeks + 1
- When you do this you can see the gestational age, you can see chronicity ( whether babies share placenta or if they have their own placenta), rule out multiple pregnancy and carry out screening.
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Monochorionic
Dichorionic
- Monochorionic - babies share a placenta and are always identical
- Dichorionic - babies each have their own placenta. They are more likely to be non-identical but can still be identical.
Describe tests of foetal growth and their limitations
- dating scan
- other options if you miss your dating scan are below:
- LMP - last menstrual period date - can be used to estimate due date however it is - highly inaccurate
- Developmental criteria: can give you an estimation of foetal age.
Fetal wellbeing:
- if foetus is moving well generally a good indicator that baby is okay
- biochemical test bHCG if its going up like doubling in 48hrs it can indicate early pregnancy issues
- regular measurements of uterine expansion - symphysis fundal height. Is relatively unreliable, but is non-invasive and cheap.
- Fundus of the uterus is palpable at 22 weeks
- a symphysis fundal height less than the 10th percentile identifies a fetus in further need of assessment
- ultrasound scan - best way to check fetal well being.
- safe
- can be used early in pregnancy to calculate age - can rule out ectopic, number of foetuses
- routinely carried at 20 weeks to asses foetal growth and fetal anomalies
- hCG
- hPL
- oestriol
- a-fetoprotein
- can detect poor endocrine function
Doppler analysis
- umbilical artery doppler is flow from the placenta into baby.
- you should get flow into the placenta and umbilical cord during each heartbeat. Flow being systolic and diastolic
- the decrease in pressure is a good sign as it indicates unobstructed blood flow
Decompensation cascade
- A raised umbilical artery pulsatility index and absent end diastolic flow are early sign of foetal hypoxia
- Late signs are REVERSED end diastolic flow is a late sign
- A good doppler has high volume diastolic flow
Describe pathogenesis of intrauterine growth restriction (IUGR)
If the decidual reaction is suboptimal it can lead to a range of adverse pregnancy outcomes:
- Placental insufficieny and pre eclampsia
- TORCH:
- acronym for a group of diseases that cause congenital (present at birth) conditions if a foetus is exposed to them in the uterus.
-Toxoplasmosis
- Others ( syphillis, varciella, mumps, parrovirus and HIV)
- Rubella
- Cytomegalovirus
- Herpes simplex virus
Milestones
Development: An increase in the complexity of the organism due to maturation of the nervous system.
Changes include:
- physical
- functional
- emotional
-psychological
-social
Areas of development:
- Gross motor - E.g. crawling, walking
-Fine motor - E.g. picking things up
- Speech - E.g. actual sounds
- Language - E.g. content of speech
- Hearing
- Vision
- Social skills and behavior’s
-50% of children walk by first birthday
Milestones
6 weeks:
- good head control - raise head to 45 degree when on tummy
- social smile (visual problem if not)
6 months:
- sit without support
- roll (prone) from their tummy to their back (supine)
- babble
- respond to noise
- reach for bottle/breast
9 moths:
- stands holding on
- straight back sitting
- respond to their own name
- stranger fear (6-9months - 2yrs)
- hold and bite food
12months:
- most can walk ( 9 - 18 months)
- show an understanding of nouns (‘wheres mummy?’)
- drink from beaker with lid
- play by themselves if someone familiar is nearby
18 months:
- run (16month)
- jump (18month)
- show understanding of nouns ‘ show me the xxx’
- imitates every day activities
2 years:
- tiptoe
- walk upstairs both feet each step
- 2 words joined together (50 words)
- eat skillfully with spoon
4 years: basically a mini adult
- children should be able to walk by 18 months or it can suggest something is wrong
Sensorineural hearing loss:
- Sensorineural hearing loss is a type of hearing loss from damage to the inner ear, the place of origin of the nerve that runs from the ear to the brain (auditory nerve)
Developmental surveillance
-Neonatal examination
- 6-8 week check by GP
- 1 year check by Healthcare visitor
- 2- 2.5 year check by the HV
Developmental red flags
Growth
josies notes
- physical milestones
FTT ( failure to thrive)
- Most FTT = inadequate intake
- Most do not need investigating but will need observing, extra calories, behavior changes
Congenital anomalies and their scientific basis
- Congenital anomalies occur when normal embryonic development is disrupted.
- Deformation: you had a normal structure then something later on has led to a mechanical impact that has led to a deformation
- Disruption: the blueprint for creating the embryo is fine but some external factor disrupts the formation of the embryo/fetus
- Malformation - something has gone wrong with the blueprint. Primary disturbance of embryogenesis
Classification:
Congenital anomalies can be classified by
- CAUSE: aetiological basis
- TIMING: more ‘explanatory’ of the problem. Tells us when the insult happend so explains the problem but does not help us to understand it
Aetiology - understanding the basis for congenital defects
Teratogens
Classify by timing
2-4 weeks:
- polytopic field defect
- Scattered pattern
4-8 weeks:
- Monotopic field effect
- Localised effect - effect on particular structure
- e.g. upper limbs develop a few days before lower limbs so you can have a congenital defect effecting only the upper limbs depending on the timing of that insult
9 weeks onwards:
- organogenesis
- organs are affected
Examples of deformation:
- Talipes - club foot
- Congenital hip dislocation
Examples of disruption:
- Aminotic band syndrome - Amniotic bands strip off the amniotic sac and can get twisted around developing structures and constrict fingers, limbs and other body parts
- Poland anomaly - the developmental blueprint for the development of the pectoralis major muscle is fine. However you have interruption of the subclavian artery that supplies the pectoralis muscle so the muscle doesn’t develop. So you end up with a unilateral absence of the pectoralis major muscle.
Sequence - you have an initial effect which then has a domino effect leading to a number of other events happening
Examples of sequence:
- Potter sequence
- Pierre Robin Sequence
Potter sequence:
- renal agenesis
- Olgiohydramnios
Pierre Robin Sequence:
- mechanical theory
- start with mandibular hypoplasia (smaller mandible or lower jaw)
- We need the mandible to grow sufficiently to increase the volume of the developing oral cavity to allow the developing toungue to move out of the way of the developing secondary palate.
- so first thing that goes wrong is the development of the jaw which effects the development of the tounge, then development of the secondary palate.
Chromosomal abnormalities:
- Downs syndrome
- Di George Syndrome
Charge Syndrome
- another collection of anomalies which are linked by a single error
Spina Bfiida
- From caudal neuropore has not closed
- Folic acid needed for the normal development of the neural tube
Fetal Alcohol Syndrome
- Alcohol crosses the placenta really easily.
Congenital Rubella Syndrome
- much less common because of vaccines
Congenital Rubella Syndrome symptoms:
- Microcephaly
- PDA
- Cataracts
Screening for congenital anomalies
Diagnosing Congenital Anomalies
Growth and Development
Growth Hormone
Principal mediators of growth
Achondroplasia
Acromegaly
