High risk pregnancies Flashcards
Epidemiology and aetiology of diabetes in pregnancy
- 0.5-5% of pregnancies
- Women of south Asian and African-Caribbean origin at greater risk
- Obesity increases risk of type 2 and gestational diabetes
How can gestational diabetes be prevented?
- Preconception advice and optimisation of glycaemic control prior to pregnancy
- Weight loss
Pathogenesis of gestational diabetes
- Placental hormones e.g. human placental lactogen, cortisol and growth hormone promote insulin resistance
- Normally beta cells can compensate but this is impaired in pregnancy so hyperglycaemia occurs
- The rate of complications increases with increasing HbA1c levels
Complications of diabetes in pregnancy
Maternal:
- Hyperglycaemia, ketoacidosis, increasing insulin requirements or need to start insulin, hypoglycaemia, nephropathy, retinopathy, pre-eclampsia, increased risk of caesarean section
Foetal:
- insulin resistance, vomiting in early pregnancy, microvascular disease, often related to iatrogenic intervention
Babies born to mothers with high blood glucose have high basal levels of insulin to cope and are at risk of hypoglycaemia after birth. This results in hypoxia and erythropoiesis occurs which can cause polycythaemia and jaundice
The complications listed are those that occur in diabetics with poor control
Diagnosis of diabetes during pregnancy
Previous GD: offer 2-hour 75g OGTT ASAP after booking (whether 1st/2nd trimester) and further test at 24-28w if the results of first are normal
Screening for gestational diabetes at 24-28 weeks in women at risk done with oral glucose tolerance test
Women at risk:
- BMI >30
- Previous big baby
- FHx of diabetes
- Previous hx of gestational diabetes
Investigations: 🎶 5,6,7,8 🎶
- Oral GTT after woman has fasted overnight
- Serum glucose measured and the test is repeated after 2hrs following drinking a solution containing 75g glucose. Gestational diabetes diagnosed if blood glucose is >5.6mmol/L after fasting or >7.8mmol/L after 2hrs
- Threshold values are lower than for diabetes outside of pregnancy due to increase risk
Management of diabetes during pregnancy
Newly diagnosed - seen in clinic within 7 days
- High levels of folic acid protect against glucose induced foetal anomalies
- Lifestyle changes initially then if no changes started on metformin
- Medication: metformin or glibencamide are safe to use
Add insulin if metforminor glibencamide does not control DM
- Insulin: requirements increase during pregnancy peaking around 36 weeks. A sudden increase in insulin requirements indicates placental insufficiency so delivery is induced to prevent stillbirth
- Delivery: induced at 38 weeks to prevent risk of late stillbirth. Macrosomic babies delivered by c-section to reduce risk of shoulder dystocia
- Post natal: insulin requirements rapidly decrease so women with gestational diabetes immediately stop medication and those with pre-existing diabetes go back to normal regimen
Ideal blood glucose levels: 3.5-5.9mmol/L fasted and <7.8mmol/L 1hr after food
Measure blood glucose 4x day
Diagnosed > joint diabetes and antenatal clinic within 1 week
- glucose > 7: insulin
- glucose 6-6.9 + symptomatic (macrosomia/ polyhydramnios): insulin
- glucose 6-6.9 + asymptomatic: exercise > metformin > insulin
- delivery: good control + no macrosomia: 38+6; recued movements: surveillance.
- delivery: good control + macrosomic: induce at 36 weeks
- delivery: non-reactive CTG: C-section
Define gestational diabetes
Defined as glucose intolerance with onset or first recognition during pregnancy. However, changing definition to being diagnosed in 24-28w of gestation that is clearly not overt diabetes
Epidemiology of gestational diabetes
Ep: affects 1/20 pregnancies
87.5% have GDM, 7.5% have T1DM, 5% have T2DM
Hypertension in pregnancy
Common, classified according to blood pressure
- Mild = 140-149/90-99 mmHg
- Moderate = 150-159/100-109 mmHg
- Severe = >160/110 mmHg
Severe hypertension can cause placental abrupt ion, foetal growth restriction, cerebrovascular accident and maternal and foetal death.
Terms used to describe HTN in pregnancy with or without proteinuria
- Without proteinuria = gestational hypertension
- With proteinuria = pre-eclampsia
Outline types of HTN in pregnancy
Chronic HTN: onset <20 weeks gestation, foetal growth restriction, super-imposed pre-eclampsia, en organ disease, placental abruption, PTB
Gestational HTN: >20 weeks gestation, no significant proetinuria, cause unknown but may be due to abnormal placentation, low risk of maternal or foetal complications
Pre-eclampsia: significant proetinuria, >20 weeks gestation, due to abnormal placentation, failure of invasion of he spinal arteries by trophoblasts, maternal BP increases to compensate for increased vascular resistance, endothelial damage causes proteinuria, causes IUGR, prematurity, eclampsia, HELLP, disseminate intravascular coagulation, maternal and foetal death
What is pre-eclampsia?
Hypertension developing after 20 weeks gestation in association with significant proteinuria
What is eclampsia?
- Onset of generalised seizures in a woman with pre-eclampsia
- Only 1/3 of women with eclampsia have hypertension and proteinuria before their first eclamptic seizure
- Caused by a loss of cerebral auto regulation which leads to increased blood flow, vessel permeability and oedema
Epidemiology of pre-eclampsia
- 10-15% pregnancies affected by hypertension
- Eclampsia affects 1% of women with pre-eclampsia in UK, <1% of cases are fatal
- Higher incidence in low and middle income countries
Women at risk of hypertension in pregnancy
- Hx of hypertension in pregnancy
- Diabetes
- CKD
- Autoimmune disease
- First pregnancy or >10yrs between pregnancies
- 40+
- BMI >35
- Multiple pregnancy
What medication is recommended for women at risk of HTN in pregnancy?
Aspirin is recommended from week 12
Inhibits the production of thromboxane A2 and reverses vasoconstriction that underlies hypertension and improves endothelial function
This reduces the risk of developing pre-eclampsia by 10%
Clinical features of pre-eclampsia
Hypertension usually asymptomatic so screening is vital
Symptoms and signs are related to increased vascular permeability and leakage of fluid into interstitial spaces: blurred vision, headaches, seizures, swollen face, epigastric pain, vomiting and others
Investigations for HTN in pregnancy
- Dipstick analysis to test for proteinuria
- Proteinuria in the context of new onset hypertension indicates pre-eclampsia
- Bloods: to identify end organ damage and HELLP syndrome
What is HELLP syndrome?
- Haemolysis
- Elevated liver enzymes
- Low platelets
Affects 15% of women with pre-eclampsia and has a 25% mortality rate. Mortality is related to liver rupture and cerebral oedema and haemorrhage
Other features of HELLP: renal function impaired, PT and APTT prolonged in the presence of disseminated intravascular coagulation
Clinical features of HELLP
RUQ pain
N&V
Headache
Malaise
- haemolysis (schistocytes, burr cells, polychromasia on smear are diagnostic),
- elevated liver enzymes (ALT > 70)
- low platelets (<100,000/microlitre).
Monitoring of HTN in pregnancy
- Chronic hypertension and mild - moderate gestational hypertension are managed in community. USS used to determine foetal growth and amniotic fluid volume at 28 & 32 weeks in cases of chronic hypertension.
- Severe hypertension and pre-eclampsia are monitored in hospital. Blood pressure checked 4x a day and bloods repeated every 3-4 days to detect HELLP syndrome
Timing of delivery in women with HTN
- Chronic and gestation hypertension have a good prognosis so delivery after 37 weeks
- Pre-eclampsia delivery after 34 weeks reduces risk of adverse events
Prognosis for foetus following eclamptic seizure
Foetal mortality 30% after eclamptic seizure
Medication used to treat eclamptic seizures?
Magnesium sulfate IV
Do not use diazepam, phenytoin or other anticonvulsants as an alternative to magnesium sulfate in women wit
Recommended blood pressure medication for women with pre-eclampsia
Labetolol 1st line
Nifedipine for those who cannot take abetolol
Methyldopa if the above are not suitable
Timing of birth in women with pre-eclampsia
Any adverse features such as
inability to control BP, maternals sats <90%, HELLP syndrome, neurological features, placental abruption, abnormal CTG or reversed end diastolic flow in the umbilical artery
Warrant planned early birth
Timing: <34 weeks continue surveillance unless delivery is absolutely necessary, 34-36 weeks is acceptable, 37 weeks+ initiate birth within 24-48hrs
What is obstetric cholestasis?
Liver disease unique to pregnancy, develops in third trimester, resolves after delivery
Slows or stops the normal flow of bile from the gallbladder causing jaundice
Pathogenesis of obstetric cholestasis
Increased oestrogen levels impair sulphation of bile acids and inhibit a bile acid export pump in hepatocytes.
This blocks excretion of bile salts and these are deposited in the skin which causes itching and damages hepatocytes.
This can also occur if women take the combined pill because it contains oestrogen
Clinical features of obstetric cholestasis
- Severe itching due to cholestasis, especially on palms and soles
- Skin excoriation due to scratching
- Dark urine
- Pale stools
- Jaundice
- Steatorrhoea
Diagnosis and investigations of obstetric cholestasis
Unexplained abnormalities in liver enzymes but other causes should be excluded
*symptoms can develop before LFTs are deranged so if symptoms are present, repeat bloods every 1-2 weeks
Investigations:
- LFTs: increased ALT and GGT, normal pregnancy adjusted ALP and bilirubin
- Bile acids: most specific test for obstetric cholestasis - raised
- Viral hepatitis screen to exclude othr causes
- Autoimmune hepatitis screen to exclude other causes
- Liver USS: exclude FLD and gallstones
- BP and urinalysis: exclude pre-eclampsia
What happens to ALP levels during pregnancy
Serum ALP levels are elevated in late pregnancy, usually in the third trimester. This increase is mainly due to the production of placental isoenzyme rather than elevation of hepatic isoenzyme
Levels in a pregnant woman can be as much as 2x the normal upper limit
What is acute fatty liver of pregnancy?
Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism
Often confused with HELLP
Causes hypoglycaemia, marked increase in serum iron acid conc. and coagulopathy
Managing obstetric cholestasis
Supportive, medication to relieve symptoms
Delivery of the baby is the only known cure
Medication:
- Topical emollients with menthol to block the action of histamine which is responsible for activating C fibres which transmit the sensation of itch
- Ursodeoxycholic acid 500mg 2-3x a day relieves itching and improves liver function by binding bile acids but not licensed for use in pregnancy
- If clotting abnormal: vitamin k
- Vitamin K given to babies when born to prevent haemorrhagic disease of the newborn
Delivery:
- Increased risk of meconium and foetal distress so women give birth in obstetric unit
- Delivery induced after 37 weeks because of the risk of stillbirth
Prognosis:
- Improves with delivery, can take time so repeat LFTs at least 10 days after delivery
- 90% risk of recurrence in future pregnancy
What is polyhydramnios?
Excess amniotic fluid
Affects 1% of pregnancies
Classification: according to single deepest pool depth
- Mild: 8-11cm
- Moderate polyhydramnios: 12-15cm
- Severe: >16cm
What causes polyhydramnios?
Mixture of maternal and foetal factors
Maternal
- Gestational diabetes
- Cardiac failure
- Haemolytic disease of the newborn
- Placental chorioangioma
- 80% unexplained
Foetal
- TORCH infections
- Oesophageal/ duodenal atresia
- Diaphragmatic hernia
- Anencephaly
- Twin to twin transfusion syndrone
- Chromosomal abnormalities
- Skeletal dysplasia
Clinical features of polyhydramnios
- Higher than expected symphysis fundal height
- Maternal abdo skin is stretched and shiny
- Tense uterus
- Difficult to palpate parts of the foetus
- Splinting of diaphragm by enlarged uterus causes SOB
Investigations into polyhydramnios
- USS to measure amniotic fluid pool depth
- Amniocentesis offered if generic anomaly suspected
- Maternal blood checked for evidence of TORCH infection
- Oral GTT to screen for diabetes
Management and prognosis of polyhydramnios
Management:
- Mild and asymptomatic cases managed expectantly - no intervention
- Medication: indometacin decreases volume of fluid by reducing urine production by the foetal kidneys but it causes premature closure of DA
- Surgery: amniocentesis but procedure carries risk of miscarriage and fluid builds up again
Prognosis:
- Risks of increased uterine stretch:
- Preterm labour
- Abruption
- Rupture of the membranes
- Post partum haemorrhage
- Unstable foetal lie
What is oligohydramnios?
Reduced amniotic fluid, <500ml at 32-36w
Causes of oligohydramnios
Foetal: urethral obstruction, bilateral renal agenesis, ARPKD, chromosomal abnormalities, multiple pregnancies
Maternal: late term, PROM, pre-eclampsia, placental insufficiency
What is Potter’s sequence?
Describes the typical physical appearance caused by pressure in utero due to oligohydramnios. It can occur in conditions such as infantile polycystic kidney disease, renal hypoplasia, and obstructive uropathy
Urine is not produced >> oligohydramnios >> baby is squashed in utero and does not develop properly
Investigations into oligohydramnios
Abnormal size for dates, ultrasound, Amniotic fluid index (<5cm)
What are the most common causes of perinatal infection?
TORCH organisms
Toxoplasmosis
Other: syphilis, varicella-zoster, parvovirus
Rubella
Cytomegalovirus
Herpes
Discuss perinatal toxoplasmosis infection
- Infection with toxoplasma gondii is asymptomatic in the mother in most cases but can present as flu with lymphadenopathy
- Infections can cause miscarriage especially if within the first 10 weeks of pregnancy
- Can cause hydrocephalus and intellectual disability in the foetus, cerebral calcification, chorioretinitis which can cause blindness later in life
Discuss perinatal infection with varicella-zoster
- Presents in the mother with fever, malaise and a maculopapular rash (chickenpox)
- No increased risk of miscarriage
- Can cause foetal varicella syndrome which presents with scarring in dermatomal distribution, eye defects, microcephaly, cortical atrophy, learning disability, bladder and bowel sphincter dysfunction
- Mortality rate of 30% in babies
Discuss perinatal parvovirus infection
- Asymptomatic in the mother in 20-30% of cases, otherwise presents with a non vesicular (slapped cheek) facial rash, malaise, sore throat, mild fever, arthropathy, anaemia and anaplastic crisis
- No increased risk of congenital abnormalities
- Hydrous fetalis (accumulation of fluid in two or more foetal compartments) is a complication of foetal anaemia and cardiac failure
Which virus causes slapped cheek sydrome?
Parvovirus 19
Discuss perinatal rubella infection
- Presents in mother with malaise, fever, conjunctivitis, coryzal symptoms, macular rash, arthropathy, post auricular lymphadenopathy
- Foetal complications: miscarriage, stillbirth, growth restriction, deafness, microcephaly, cataracts, cardiac defects
Discuss perinatal CMV infection
- Most cases asymptomatic in mother but can cause flu like symptoms and lymphadenopathy
- Foetal complications: hepatosplenomegaly, thrombocytopenia, intracranial calcification, hearing loss, chorioretinitis, microcephaly and learning disability, growth restriction and stillbirth
- Of the 5-15% of infected babies symptomatic at birth, 30% die and 80% have serious consequences. 10-15% of asymptomatic babies will develop auditory, visual or neurological defects
Discuss perinatal herpes infection
- Mother: painful genital ulcers, encephalitis, hepatitis and skin lesions if disseminated herpes
- No increased risk of miscarriage
- Morbidity <2% with antivirals
- 70% of cases there is disseminated disease with or without CNS involvement
Herpes can be contracted as the baby passes through birth canal causing baby to be irritable, blisters over body, difficulty breathing, jaundice and easy bleeding
Can be fatal if not treated with antivirals
Investigations for perinatal infection
- HIV+ women have viral load and CD4 levels checked once a trimester
- Women with hep C or B have viral load assessed early in pregnancy
- Positive immunoglobulin M antibodies to a TORCH organisms are diagnostic of a recent infection and increasing IgG confirms acute disease
- Amniocentesis and viral detection by PCR or culture confirm foetal infection
- Serial USS scans to screen for complications of infection
Management of perinatal infections
Aim is to reduce transmission
Termination offered to women with TORCH infections depending on the organism, gestation when infection occurred and presence of foetal abnormalities
Medication:
- HIV: women continue antiretrovirals throughout pregnancy. Cabergoline is used to suppress lactation. Some retrovirals cause gestational diabetes
- Hepatitis: antivirals used in third trimester for women with hep B and high viral load. No safe treatment for hep C in pregnancy
-
Toxoplasmosis: spiramycin given prophylactically to reduce risk of parasite transmission, doesn’t reduce risk of foetal anomalies. If foetus is infected, pyrimethamine and spiramycin are given to reduce severity.
- *pyrimethamine is teratogenic so not used in first trimester. It also antagonises folate so supplements are needed to prevent folate deficiency
- Parvovirus: no drug treatment available, intrauterine infusions to treat foetal anaemia
- Rubella: no drug treatment available, cochlear implants and cardiac surgery may be needed after birth
- CMV: antivirals given to babies with congenital infection to reduce risk of hearing loss
- Herpes: primary disease treated with aciclovir and given from 36 weeks to reduce need for c-section
Do all women with HIV have to have c-section?
No
HIV: viral load <50 RNA copies/mL at 36 weeks means woman can have vaginal delivery otherwise c-section. If load >1000 IV zidovudine is given
Woman has a primary herpes infection in 3rd trimester - how is delivery managed
Indication for c-section
Breastfeeding with perinatal infections
- HIV: avoid in high income countries
- Hep B and C: encouraged
- TORCH: all ok apart from CMV but even in CMV transmission is rare
What vaccinations are given to babies born to mothers with neonatal infection
- Babies born to mothers with hep B receive the first dose of the vaccine and a dose of hep B immunoglobulin within 12hrs birth
- Further doses of hep B vaccine given at 1 and 6mo
- No vaccinations against TORCH
Why do babies infected with parvovirus suffer with anaemia?
Parvovirus suppresses EPO
Treatment of perinatal parvovirus infection
No treatment
Pregnant woman has come into contact with varicella zoster virus - what is done?
VZV IgG antibodies:– if not immune (IgG negative give VZIG ASAP - effective up to 10d after exposure
Acyclocir within 24h of rash
Most common TORCH infection?
CMV - affects 1/100
What % of pregnant women in the UK have a BMI >30?
20%
What are the risks of maternal obesity?
To mother:
- Gestational diabetes
- Gestational HTN and pre-eclampsia
- Difficulty with epidurals
- Wound infection
- PPH
- VTE
To foetus:
- Miscarriage
- Foetal anomalies: neural tube defects, cardiac defects, omphalocele
- Stillbirth
- Prematurity
- Shoulder dystocia
- Childhood obesity
What advice, regarding weight, is given to obese pregnant women?
Advised to maintain weight neutral pregnancy meaning they don’t lose or gain weight but light exercise and diet modification is recommended
Pregnant woman is obese, what investigations are done?
- USS to screen for abnormalities, assess growth
- Blood pressure and urinalysis for pre-eclampsia
- Organ GTT for gestational diabetes
Management of epilepsy in pregnancy
- Balance between teratogenic risk of drugs and worsening seizure control
- Medication: many are teratogens and cause neural tube defects, cleft lip and palate, cardiac defects
- Sodium valproate has the highest rate of genetic abnormalities, twice that of other anti-epileptics
- Carmabazepine and lamotrigene have a 2-2.5% incidence of malformations
- Generally drugs should be continued because risk of seizure is higher than risk to foetus but women on sodium valproate are encouraged to switch to a different drug before pregnancy. If sodium valproate is the only drug that works, the dose is split over the day
- All anti-epileptics have the potential to cause foetal anticonvulsant syndrome
Clinical features of haemolytic disease of the newborn
- Anaemia
- Increased erythropoiesis and hepatosplenomegaly
- Jaundice arising from hyperbilirubinaemia
- Oedema and polyhydramnios as a consequence of high output heart failure
- In severe cases foetal death can occur
Discuss chronionicity and amnionicity
Refers to whether a multiple pregnacy shares amniotic sac and foetal part of placenta (chorion)
- Chorionicity - can be dichorionic or monochorionic - refers to whether the foetuses have one or two placenta between them
- The chorionicity and amnionicity of monozygotic twins is determined by the time at which the zygote splits, or cleaves. If the cleavage occurs by day 3, you will have two separate blastocysts, and therefore, two sites of implantation, resulting in dichorionic-diamniotic (di-di) twins
- This can be determined using USS before 14 weeks gestation
How is chorionicity diagnosed?
USS
Dichorionic = 2 placentas (in twin pregnancy) - accounts for 80%
Monochorionic = 1 shared placenta - 20% and higher risk
When does embryonic split occur in dichorionic, dizygotic twins?
Early on - at the morula stage before implantation has occurred and the the two separate blastocysts implant
When does the split occur in monochorionic diamniotic twins?
3-8 days after fertilisation
Single placenta but 2 amniotic sacs
When does the split occur in monochorionic monoamniotic twins?
8-13 days after fertilisation
Same amniotic sac, same placenta
What is twin to twin transfusion syndrome?
Caused by shared circulation in monochronionic twins
Affects 8-25% of monochorionic pregnancies
80% mortality of not treated
Caused by abberant vascular anastomosies in the placenta which redistibute foetal blood from one to the other but not in the opposite direction
One twin receives too much blood and the other too little
How is polyhydramnios categorised?
Single deepest amniotic pool depth
Mild: 8-11cm
Moderate: 12-15cm
Severe: >16cm
Volume of fluid classified at oligohydramnios?
<500mL at 32-36 weeks
Amniotic fluid index <5cm
Discuss syphillis infection in pregnancy
Treponema pallidum spirochaete bacterium - causes syphilis - can cross placenta
Can cause PTB, stillbirth and congenital syphilis
- 8th nerve deafness
- Saddle nose
- Sabre shins
Management: penicillin
