Week 9 Flashcards
Antenatal care ANC
Is a planned examination and observation of the woman from conception till the birth
Antenatal care is a perfect example of preventative medicine
what are we trying to prevent “maternal and perinatal mortality and morbidity”
Maternal mortality is the health indicator that shows the greatest differential between developing and industrialised countries
The lifetime risk of death as a result of pregnancy or childbirth is estimated at one in 23 for women in some countries in Africa compared with about one in 7000 for women in Northern Europe
Importance of antenatal care
To ensure that the pregnancy woman and her fetus are in the best possible health
Pregnancy is a physiological state
To detect early and treat properly complications
-identify women at risk
-low risk- midwife care
-high risk- obstetrician care
Offering education for parenthood
To prepare the woman for labour, lactation and care of her infant
Why mothers die
Thromboembolism
Pre eclampsia and eclampsia
Cardiac disease
Maternal mortality decreased rapidly after 1940: skilled attendants, antibiotics, banked blood, surgical improvements
We collect info about all women
Put them through comprehensive preconception and antenatal and newborn pathway
Eg screening for diabetes and Down syndrome
ANC pathyway in NHS
Antenatal care
Routine care for all pregnant women
Women needing additional care
-women with pre existing conditions or risk factors
-women who has problems in previous pregnancy
-diabetes in pregnancy pathway
-hypertension in pregnancy
-multiple pregnancy pathway
-pregnancy and complex social factors pathway
-interventional procedures for some complications in pregnancy
pregnancy care booklet
First few pages assess mother for risk during pregnancy
This allows you to make a decisions on whether-
-low risk: suitable for midwife care
-high risk: required obstetrician care
Social assessment booking partner details: women who have partners are at lower risk
High risk when mothers smoke, drug, alcohol and ethnic origin
Medical history and mental health also play important role
Family history of hypertension and DM have big influence
Outcomes from previous birth
Basic principles of antenatal care
Midwives and GPs should care for women with an uncomplicated pregnancy providing continuous care though out pregnancy. Obstetricians and specialist team should be involved where additional care is needed
Antenatal appointments should take place in location that women can easily access.
Maternity records should be structures, standardised, national maternity records, held by women
In an uncomplicated pregnancy 10 appointments for nulliparous women and 7 for parous women
Each antenatal appointment should have structure and. Focus. Appointments in early pregnancy should be longer to provide info and time for discussion about screening so that women can make informed decisions
If possible incorporate routine tests into the appointments to minimise inconvenience
Women should feel able to discuss sensitive issues and disclose problems. Be alert to the symptoms and signs of domestic abuse
NICE guidelines
Schedule of appointments
First contact with HCP:
-folic acid supplements
-food hygiene including how to reduce risk of food acquired infection
-lifestyle including smoking cessation, recreational drug use and alcohol consumptions
-all antenatal screening including risks, benefits, limitations of the screening tests
Vitamin D 10mcg/day
Booking appointment ideally by 10 weeks
Identify women need additional care
Measure height and weight and calculate BMI
Blood pressure test urine proteinuria
Risk factors preeclampsia and GDM
Blood tests, blood group, RhD, anaemia
Asymptomatic bacteriuria
Chlamydia
Screening Down’s syndrome
Early US for gestational age assessment and structural anomalies
FGM
Several mental illness or psychiatric treatment
Mood to identify possible depression
Occupational risks
Screening pregnancy
Screening for haematological conditions: sickle cell, thalassaemias
Screening for foetal anomalies:
Anomaly scan 18-20 weeks:
-if woman chooses US should be performed between 18 (0 days)-20 weeks(6 days) to detect structural anomalies
-for a woman whose placenta extends across the internal cervical os offer another scan at 32 weeks
Women needing additional care
Cardiac disease incl hypertension
Renal disease
Endocrine disorders or diabetes requiring insulin
Psychiatric disorders
Haematological disorders
Autoimmune disorders
Epilepsy requiring anticonvulsant durgs
Malignant Disease
Severe asthma
Use of recreational drugs
HIV or HBV infection
Obesity
Higher risk complications women over 40, smoke
Women who are particularly vulnerable- teenagers or who lack social support
Additional care women who experienced this in previous pregnancies
Recurrent miscarriage 3 or more
Preterm birth
Severe preeclampsia, HELLP syndrome or eclampsia
Rhesus
Uterine surgery inclu c section
Antenatal or postpartum haemorrhage on 2 occasions
Puerperal psychosis
Grand multiparity 4 or more
Stillbirth or neonatal death
SGA infant
LGA infant
Baby weighing below 2.5kg or above 4.5kg
Baby with congenital abnormality
16 weeks examination
Screening tests
BP and test urine proteinuria
Hb below 11g/100ml consider iron supplements
Routine anomaly scan specific info
25 weeks for nulliparous women
Measure bp and proteinuria
Symphysis-fundal height
28 weeks
BP and proteinuria
Second screening for anaemia and atypical red cell alloantibodies
Hb level below 10.5g/100ml consider iron
Anti-D prophylaxis RhD-
Symphysis fundal height
31 weeks for nulliparous women
Screening tests at 28 weeks discuss
Bp and urine test
Symphysis- fundal height
34 weeks
Screening test discuss
BP and urine test
Second dose of anti-D prophylaxis RhD-
Symphysis- fundal height
Specific info on prep labour and birth, birth plan, recognising active labour and coping with pain
36 weeks
Bp and urine test
Symphysis-fundal height
Position of baby, if breach offer external cephalic version
Info: breastfeeding, care new baby, VitK prophylaxis , newborn screening tests, postnatal self care, awareness of baby blues and postnatal depression
38 weeks
BP and urine
Symphysis fundal height
Info: options of management for prolonged pregnancy
40 weeks nulliparous women
BP and urine test
Symphysis fundal height
Discussion management prolonged pregnancy
41weeks
Who haven’t given birth yet:
-offer membrane sweep
-offer induction of labour
-BP and test urine
-measure symphysis fundal height
From 42 weeks offer women who decline induction of labour increased monitoring (at least twice weekly cardiotocography and US exam of max amniotic pool depth
Lifestyle advice
Work: occupational risk, safe to keep work, maternity rights and benefits
Nutritional supplements: folic acid before conception and first 12 weeks, vit D pregnancy and breastfeeding, don’t recommend routine iron supplements, risk for brith defects associated with vit A and to avoid vit A and liver products
Avoiding infection: reduce risk listeriosis and salmonella and how to avoids toxoplasmosis infection
Medicines: prescribe as few medicines as possible
Complementary therapies: use few
Exercise: no risk but avoid sports with abdominal trauma, falls or excessive joint strain, scuba diving
Sexual intercourse:L safe
Alcohol: avoid
Smoking: avoid
Cannabis: avoid
Air travel: increase risk venous thrombosis
Car travel: seatbelt above and below bump
Travel abroad: discuss flying, vaccinations and travel insurance with midwife or doctor
How ANC works: example preeclampsia
Unique to pregnancy
Associated with:
-raised blood pressure >140/90,mmHg
-proteinuria (at least 1+ urine dipstick)
Presents after 20 weeks gestation but mainly 3rd trimester
What happens in pre eclampsia
Vasospasm
Increased BP, headaches
Reduced organ perfusion
Coagulation
Kidneys: reduced urine output, proteinuria, hyperuricemia
Liver: raised liver enzymes, liver capsule stretch
Placenta: IUGR, abruption, fetal death
Brain: occipital lobe, ischaemia, convulsions
Management preeclampsia
Antihypertensives eg labetalol, nifedipine, methyldopa, hydralazine
Fluid restrict (85mls/hour)
Magnesium sulphate to prevent and treat seizures
Delivery- balance between achieving best outcomes for mother and fetus
ANC diabetes
Important issue in pregnancy
Requires MDT care in combined clinic
Pre-existing type 1 or type 2
Gestational diabetes
DM affects all systems in body- actual or effective insulin deficiency
3-4 per 1000 pregnancies
Before insulin 40% women died during pregnancy
Remainder died within 2 years of delivery
Fetal loss rate >50%
With insulin maternal mortality fell to 2-3%
Now deaths very rare
Fetal loss rates remained high
Initially concentrated on reducing stillbirth but PNMR high
Optimisation of maternal control and fetal surveillance lead to PNMR close to non diabetic
Factors leading to poor antenatal care
Poverty
Illiteracy
Population explosion
Low socioeconomic Status
Poor health facilities
Poor social status of woman
Lack of political will
Reduce death women
Stop bleeding
Stop infection
Training
Transport
Making a human
The correct number of genes working correctly to give the correct gene dosage in the correct tissues at the correct time
In a supportive intra-uterine environment
chromosomes, genes, DNA and heredity
Humans have over 20000 protein coding genes
A chromosome is made of a single molecule of DNA
A specific stretch of DNA where the sequence contains genetic instructions is a gene
Genes are arranged one after the other along the DNA of a chromosomes with stretches of non-coding DNA between them
Each chromosome has hundreds of genes
Meiosis
Function:
-reduction division (23 chromosomes per gamete)
-reassortment of genes: independent segregation of chromosomes crossing over
Mechanism:
-each homologue replicates to give 2 chromatids
-homologous pair
-exchange of material between non sister chromatids. Crossing over, recombination
-chiasmata (visible cytologically) are the physical manifestations of crossing over
How could errors in DNA replication and Meiotic cell division cause human disease
DNA replication: new mutations (copying errors)
Meiotic cell division: anomalies of chromosome number (non disjunction), anomalies of chromosomes structure (unequal crossing over)
As the gamete contains the genetic anomaly resulting from an error in meiosis the zygote will have the anomaly in all body cells
Main classes of genetic disorders
Mutations in single genes
Common complex/ Multifactorial diseases
Chromosome imbalance causes change in gene dosage
Mitochondrial disorders- generally affect organ systems with high energy requirement
Basic genetics- chromosomes
Numerical: aneuploidy, polyploidy. Monosomy, trisomy, triploidy
Structural: translocations (reciprocal, Robertsonian(centric fusion)). Deletions, duplications, inversions
Different cell lines: mosaicism
Most frequent numerical anomalies in liveborns:
Autosomes:
-Down syndrome (trisomy 21:47, XX +21)
-Edwards’s syndrome (trisomy 18:47, XX,+18)
-Patau syndrome (trisomy 13:47, XX +13)
Sex chromosomes:
-turner syndrome 45 X
-Klinefelter syndrome 47 XXY
All chromosomes:
-triploidy 69 chromosomes
How do we identify if a pregnancy is at increased risk of genetic condition
Through genetic diagnosis in a relative
Through the pattern of affected people in the family
From the results of screening or scans in the pregnancy
From the results of genetic testing in a pregnancy
Taking a family history and drawing a pedigree may help in assessing probability
Previous child with a single gene disorder
Family history of a single gene disorder
A parent with a chromosomal anomaly
Parental ages
Drawing a family pedigree
Build up the tree from the bottom starting with affected child and siblings. Record names, dates of birth and maiden names
Choose one parent ask about siblings and their children then parents
Add info other side of family
Colour in symbol is person affected
Sloping line through symbol if person died
Ask for miscarriages, stillbirths, deaths in each partnership
Children with other partners, divorce
Double line joins union of consanguineous couple
Diagonal line for twins with line between if identical
What might we find out from the pedigree
Family history of genetic disorder eg in a previous sibling
Parental consanguinity
Population ancestry
Elevated maternal age
Elevated paternal age
Environmental exposure affecting DNA
Is my baby at risk of developing cystic fibrosis
CF is inherited in autosomal recessive manner
Autosomal recessive inheritance. 1/4 affected
Increased probability of a genetic disorder in a child parental consanguinity
Consanguineous: where two people are related by blood ie share a common ancestor
Translocations
Chromosome anomalies can be inherited and give distinctive patterns in the family
Robertsonian translocation: centric fusion. Breakage of 2 acrocentric chromosomes (13,14, 15,21,22) at or close to their centromere with subsequent fusion of their long arms- short arms are lost
Reciprocal translocation: breakage of 2 non-homologous chromosomes with exchange of fragments
Multiple miscarriages, children with congential anomalies in multiple generations
Balanced reciprocal translocation carrier
Meiosis
Fertilisation by normal gamete
-normal: no risk to children
-balanced carrier: normal but risk to children of having unbalanced translocation
-partial trisomy and partial monosomy: miscarriage, congenital malformation, developmental delay, intellectual disability
-partial monosomy and partial trisomy: miscarriage, congenital malformation, developmental delay, intellectual disability
Unbalance reciprocal translocation
Increased probability of a genetic disorder in a child: population ancestry
Afro-Caribbean
Ashkenazi Jewish
Mediterranean
Northern Europe
Increased probability of a genetic disorder in a child: elevated maternal age
Incidence of trisomy 21 at time of CVS (11 weeks) amniocentesis (16 weeks) and term
Increases with maternal age
Oocytes and meiosis
22 cell divisions by 5 months gestation- stock of oocytes each remains in maturation arrests until ovulation
Each month one is ovulated
Meiosis I completed at ovulation
Meiosis II competed at fertilisation
There may a lengthy interval between onset and completion of meiosis
Accumulating effects on the primary oocyte may damage the cells spindle formation and repair mechanisms predisposing to non-disjunction
Trisomies appear to be associated with increase in maternal age
Eggs held at crossing over stage in meiosis from approx 6 months gestation
So “wear and tear” with increasing maternal age in machinery for cell division thought to be major component
The trisomy 21 type of Down syndrome is the result of an error in meiosis and has a recurrence risk of about 1 in 100
Trisomy 21 is the result of an error in meiosis, Meiotic non disjunction, has recurrence risk of about 1 in 100
Increased probability of a genetic disorder in a child: elevated paternal age
The number of cell divisions required to produce a human sperm
Spermatogonium every 16 days from puberty 4 spermatozoa
This spermatogonium maintains the stock of spermatogonia and continues to divide
New mutations increase with paternal age
Higher mutation rates in males are likely to be related to the greater number of germ cell divisions
(The DNA in a particular sperm is the result of hundred of rounds of replication)
Why make a diagnosis in a pregnancy
To provide options for management of the pregnancy eg termination of pregnancy if fetus shown to be affected with severe condition
To guide management in the new born period eg metabolic/endocrine conditions where immediate treatment might be needed
For parents information
Perinatal genetic testing
Pregnancy known to be at risk of genetic disorder (eg identified through prior family history)
-no pregnancies, adoption, donor gametes
-screening via imaging, targeted genetic testing invasive, targeted genetic testing, noninvasive
-preimplantation genetic diagnosis PGD
Pregnancy not thought to be at prior risk but affected with anomalies
Prenatal diagnosis- ultrasound scanning
Detects structural abnormalities
Routine screening of low risk pregnancies
-12 weeks dating scan
-20 weeks structural anomaly scan
High resolution scanning for specific disorder (eg cardiac/fetal MRI)
Safe and non invasive
Diagnostic limitations
Prenatal diagnosis invasive
Targeted genetic test where baby is high risk of a genetic condition
-eg gene testing for CF
-chromosome testing for familial translocation
Have to know the genetic diagnosis in the family before being able to offer a targeted genetic test
Amniocentesis may also be offered after structural abnormalities have been picked up in a pregnancy eg suspicion of Down syndrome
Invasive test carries a risk of miscarriage
Chorionic villus sampling CVS
From 11 weeks gestation
Under US guidance
Chromosome analysis-direct or cultured cells
DNA analysis- uncultured cells- result 1-2 weeks
Miscarriage rate ~1%
Associated with limb reduction defects if performed before 9 weeks
Amniocentesis
From 15 weeks gestation
Under US guidance
Trans-abdominal
Chromosome analysis- cultured cells
DNA analysis- cultured cells- results 2-3 weeks
Miscarriage rate ~0.5-1%
Vaginal termination
Prenatal non invasive genetic testing
Blood test from the mother to diagnose a genetic condition in the fetus
-free fetal DNA circulating in maternal blood
-measurable from 8-9 weeks
Fetal sexing- for X linked conditions eg DMD
NIPT- screening test for trisomy 21,18,13
NIPD- diagnostic test for certain conditions eg DMD,SMA, CF/bespoke
Earlier in pregnancy
No risk miscarriage
NIPT-screening not diagnostic test
Not available for all conditions
Pre-implantation genetic diagnosis PGD
PGD genetically testing an embryo before it is placed into the uterus that has been diagnosed as being free of a specific genetic condition
Highly specialised service
Involved IVF
Only for licensed conditions
How PGD is performed
Ovarian stimulation IVF
Blastomere biopsy of day 3
Genetic analysis
Transfer unaffected embryo
Clinically normal baby
Abnormal scan in a low risk pregnancy
2-5% pregnancies
Significant mortality and morbidity
Challenges: non specific, difficult to assess, limited phenotype
Testing approach: rare specific tests for specific phenotypes, otherwise broad approach
Stepwise genetic testing:
-QF-PCR detects chromosomal aneuploidy
-microarray detects copy number disorders
-trio exome detects monogenic
Rapid exome testing in pregnancies
Exome: coding regions of 20000 genes approx 2% genome
Genome: all 3 billion base pairs
Very fast turn around of exome testing in pregnancies with multiple malformations where there is:
-a strong likelihood of a genetic result
-the result will impact management in pregnancy
Complex
Demanding of resources
Time sensitive
Lots data to analyse
Need to limit result that are directly relevant to pregnancy
Life changing decisions
MDT approach needed
Genetic counselling
Making an accurate diagnosis
Describing the consequences of the disorder
Advising on the probability of having an affected child
Discussing the ways in which this can be treated or prevented
