Medical Disorders of Pregnancy Flashcards
Define gestational diabetes
any degree of glucose intolerance with onset or first recognition during pregnancy
Pathophysiology of gestational diabetes
Body unable to produce enough insulin to meet needs of pregnancy
- progressive insulin resistance so higher volume of insulin needed
- woman with a borderline pancreatic reserve is unable to respond to the increased insulin requirements, resulting in transient hyperglycaemia
Risk factors for gestational diabetes
BMI > 30 Asian ethnicity Previous gestational diabetes 1st degree relative with diabetes PCOS Previous macrosomic baby
Clinical features of gestational diabetes
Mostly asymptomatic
Polyuria, polydipsia and fatigue
Foetal complications of gestational diabetes
Glucose but not insulin transported across placenta -> foetal hyperinsulinaemia
- Macrosomia – this can cause complications during labour, such as shoulder dystocia, obstructed/delayed labour, and/or higher rates of instrumental deliveries
- Organomegaly -particularly cardiomegaly
- Erythropoiesis -> polycythaemia
- Polyhydramnios
Increased rates of pre-term delivery
Investigations for gestational diabetes
Oral Glucose Tolerance Test
- a fasting plasma glucose is measured, then a 75g glucose drink is given – with a repeat plasma glucose measurement after 2 hours
- Fasting glucose > 5.6mmol/L
- 2hrs postprandial glucose > 7.8mmol/L
When is the OGTT offered
Booking – if previous gestational diabetes.
24 – 28 weeks’ gestation – if risk factors are present or in cases of previous gestational diabetes
Any point during pregnancy – if 2+ glycosuria on one occasion, or 1+ on two occasions
Management of gestational diabetes
Lifestyle advice
- diet and exercise
Medical
- Metformin – suitable in pregnancy and breast feeding.
- Glibenclamide – used if metformin is not tolerated (often due to GI side effects) and insulin has been declined
- Insulin
- Consider starting at diagnosis if the fasting glucose >7.0mmol/L.
- Or introduce later in pregnancy if
- (i) pre meal glucose > 6.0mmol/L
- (ii) post meal glucose >7.5mmol/L
- (iii) fetal AC (abdominal circumference) >95th centile
Delivery with gestational diabetes
Deliver at 37 to 38 weeks if they are on treatment
Delivery (induction of labour or caesarean section) before 40 weeks and 6 days if there is gestational diabetes managed by diet
Postnatal management of gestational diabetes
All anti-diabetic medication should be stopped immediately after delivery - BM taken at discharge to ensure normal levels
Fasting glucose tolerance test 6-13 weeks post-partum
Yearly tests should be offered because of the increased risk of developing diabetes in the future
In subsequent pregnancies, an OGTT should be offered at booking and at 24 – 28 weeks’ gestation
Definitions of anaemia in pregnancy
1st trimester = < 110g/l
2nd/3rd trimester = < 105g/l
Postpartum = < 100g/l
Plasma volume increases disproportionately to RBC -> haemodilution
Risk factors for anaemia in pregnancy
Haemoglobinopathies - thalassaemia - sickle cell disease Increasing maternal age Low socioeconomic status Poor diet Anaemia during previous pregnancy
Causes of anaemia
Microcytic - iron deficiency - thalassaemia - sideroblastic anaemia Normocytic - anaemia of chronic disease - marrow infiltration - haemolytic anaemia - CKD Macrocytic - B12/folate deficiency - alcohol consumption - reticulocytosis - hypothyroidism
Invetigations for anaemia
FBC - hb and MCV Serum ferritin Consider - haemoglobinopathy screening - serum folate - haemoglobin electrophoresis
Management of iron deficiency anaemia
Trial oral iron (100-200mg)
Parental iron infusion is compliance poor or evidence of malabsorption
Management of folate deficiency
Folate supplementation - 5mg once daily increased up to three times daily
Management of beta thalassaemia
Folate supplementation and blood transfusions as required - aim for Hb of 80g/L during pregnancy and 100g/L at delivery
Management of sickle cell disease
Folate supplementation and iron supplementation if lab evidence or iron deficiency
Define antiphospholipid syndrome
Autoimmune condition in which antibodies are targeted against phospholipid-binding proteins
Pathophysiology of antiphospholipid syndrome
In vivo antibodies induce procoagulant state
Obstetric complications due to
- inhibition of trophoblastic function and differentiation
- activation of complement pathways at maternal-foetal interface
- thrombosis of uteroplacental vasculature
Clinical features of antiphospholipid syndrome
Defined by thrombosis formation and/or recurrent pregnancy loss
Other manifestations include
- Livedo reticularis – red/blue/purple reticular pattern on skin of the trunk, arms or legs
- Valvular heart disease – particularly aortic and mitral regurgitation
- Renal impairment – ischaemia in the small vessels of the kidney can result in chronic kidney disease
- Thrombocytopaenia
Investigations of antiphospholipid syndrome
USS doppler for DVT
Anticardiolipin – detects antibodies that bind cardiolipin (a phospholipid)
Lupus anticoagulant – measures the clotting ability of the blood
Anti-B2-glycoprotein I – detects antibodies that binds B2-glycoprotein I (a molecule that binds with cardiolipin)
Management of antiphospholipid syndrome
Anticoagulation - LMWH or warfarin depending on presentation
Why does pregnancy increase risk of VTE
Changes to levels of proteins in clotting cascade - increased fibrinogen and decreased protein S
Become more pronounced as pregnancy progresses - highest risk post-partum
Risk factors for VTE in pregnancy
Pre-existing factors - Thrombophilia (e.g Antiphospholipid syndrome) - Medical co-morbidities (e.g cancer) - Age >35 years - BMI >30 kg/m2 - Parity >3 - Smoking - Varicose veins - Paraplegia Obstetric Factors - Multiple pregnancy - Pre-eclampsia - Caesarean section - Prolonged labour - Stillbirth - Preterm birth - PPH Transient Factors - Any surgical procedure in pregnancy of puerperium - Dehydration (e.g hyperemesis) - Ovarian hyperstimulation syndrome - Admission or immobility - Systemic infection - Long distance travel
Clinical features of VTE
DVT
- unilateral leg pain and swelling
- pyrexia, pitting oedema, tenderness and prominent superficial veins
- left leg most commonly affected
PE
- sudden onset dyspnoea
- pleuritic chest pain, cough and haemoptysis
Investigations for VTE
DVT - compression duplex USS PE - ECG and CXR - definitive diagnosis by CTPA or V/Q scan
Management of VTE in pregnancy
LMWH started immediately
- maintained until - weeks post-partum
Prophylaxis of VTE in pregnancy
Assessed for risk in early pregnancy
- offered thromboprophylaxis if have > risk factors in 1st+2nd trimester, > 3 in 3rd trimester and >2 post-partum
- continue till at least 6 weeks post-partum
10 day course of LMWH post C-section
Define hyperemesis gravidarum
Persistent and severe vomiting during pregnancy
- leads to weight loss, dehydration and electrolyte imbalances
Pathophysiology of hyperemesis gravidarum
Normally starts between 4-7 weeks gestation - reaches peak in 9th week and settles by 20th week
Thought to be due to rapidly increasing levels of beta hCG
- stimulates chemoreceptor trigger zone in brainstem which feeds into vomiting centre
Risk factors for hyperemesis gravidarum
First pregnancy Previous history Raised BMI Multiple pregnancy Hydatidiform mole
Clinical features of hyperemesis gravidarum
Pregnancy-Unique Quantification of Emesis (PUQE) score - 6 = mild - 7-12 = moderate - 13-15 = severe In the last 24 hours, for how long have you felt nauseated or sick to your stomach? - Not at all = 1 - 1 hour or less = 2 - 2-3 hours = 3 - 4-6 hours = 4 = More than 6 hours = 5 In the last 24 hours have you vomited or thrown up? - 7 or more times = 5 - 5–6 times = 4 - 3–4 times = 3 - 1–2 times = 2 - I did not throw up = 1 In the last 24 hours how many times have you had retching or dry heaves without bringing anything up? - No time = 1 - 1–2 times = 2 - 3–4 times = 3 - 5–6 times = 4 - 7 or more times = 5
Differential diagnosis of hyperemesis gravidarum
Gastroenteritis Cholecystitis Hepatitis Pancreatitis Chronic H. Pylori infection Peptic ulcers UTI or pyelonephritis Metabolic conditions Neurological conditions Drug-induced.
Investigations for hyperemesis gravidarum
Bedside Tests
- Weight
- Urine dipstick: quantify ketonuria (1+ ketones)
Laboratory Tests
- Mid-stream urine
- Full blood count: anaemia, infection, haematocrit (can be raised)
- Urea and Electrolytes: hypokalaemia, hyponatraemia, dehydration, renal disease
- Blood glucose: exclude diabetic ketoacidosis if diabetic
Refractory or Severe Cases
- Liver function tests: exclude liver disease e.g. hepatitis or gallstones, monitor malnutrition
- Amylase: exclude pancreatitis
- Thyroid function tests: hypo-/hyper-thyroid
- Arterial blood gas: exclude metabolic disturbances, monitor severity
Imaging
- Ultrasound scan: confirm viability, confirm gestation, exclude multiple pregnancy and trophoblastic disease.
Management of hyperemesis gravidarum
Mild – should be managed in the community with oral antiemetics, oral hydration, dietary advice and reassurance.
Moderate (or cases where community management has failed) – should be managed with ambulatory daycare. This involves IV fluids, parenteral antiemetics and thiamine. The patient should be managed until ketonuria resolves.
Severe – inpatient management.
Management of severe hyperemesis gravidarum
IV rehydration should be with 0.9% saline. Potassium chloride should be added as guided by electrolyte monitoring
H2 receptor antagonists or proton pump inhibitors: for reflux, oesophagitis or gastritis
Thiamine: for prolonged vomiting to prevent Wernicke’s encephalopathy
Thromboprophylaxis: for all women requiring admission
Antiemetics for hyperemesis gravidarum
First line - Cyclizine - Prochlorperazine - Promethazine - Chlorpromazine Second line - Metoclopramide (maximum 5 days due to risk of extrapyramidal side effects) - Domperidone - Ondansetron Third line - Hydrocortisone IV - once symptoms improve, convert to prednisolone PO and gradually reduce dose until lowest maintenance dose is reached
Define CMV
Cytomegalovirus
- member of herpesvirus family
Clinical features of CMV
Usually asymptomatic in immunocompetent individuals
Occasionally mild-flu like illness
Can cause mononucleosis syndrome -> fever, splenomegaly and impaired liver function
Investigations for CMV
Viral serology for CMV specific IgM and IgG performed
A positive test is signified if
- presence of CMV specific IgG in previously seronegative mother
- presence of CMV IgM and low IgG avidity
Management of CMV during pregnancy
Referred to foetal medicine specialist
Maternal
- if mother immunocompetent no treatment required
- licensed anti-CMV drugs have potential teratogenic effects so not recommended
Foetal
- diagnosed via amniocentesis and PCR of sample
- must be carried out after 21 weeks gestation as functioning kidneys required
- no effective therapy and termination of pregnancy offered
- if wishes to continue offer serial ultrasound scanning performed to assess for manifestations of congenital CMV
Features of congenital cytomegalovirus
Neonates born following intrauterine CMV infection can have several problems
- IUGR
- hepatosplenomegaly
- thrombocytopenic purpura
- jaundice
- microencephaly
- chorioretinitis
Define GBS
Group B streptococcus is commensal bacterium found in vagina or rectum of 25% or pregnant women
Pathophysiology of GBS
Streptococci are gram positive cocci which typically grow in chains
Streptococcus agalcatiae
Can cause GBS streptococcus of the newborn, chorioamniotis or endometritis
Risk factors for GBS infection in neonate
GBS infection in a previous baby
Prematurity <37 weeks
Rupture of membranes >24 hours before delivery
Pyrexia during labour
Positive test for GBS in the mother
Mother diagnosed with a UTI found to be GBS during pregnancy
Clinical features of GBS infection
UTI - frequency, urgency and dysuria
Chorioamnioitis - fever, lower abdominal/uterine tenderness, foul discharge, maternal/foetal tachycardia
Endometritis - fevers, lower abdominal pain, IMB, foul discharge
Investigations for group B strep infection
Swabs - single swab in vagina then rectum
- cultured or PCR
- maybe detected on urine cultures
Prevention of GBS disease of the newborn
High dose IV penicillins throughout labour if
- GBS positive swabs
- UTI caused by GBS
- previous baby with GBS infection
- pyrexia during labour
- labour onset < 37 weeks
- rupture of membranes > 189 hours
Define parvovirus B19 infection
Single stranded DNA virus transmitted by resp droplets or blood
- produces mild, self-limiting infection in adults but can cause spontaneous miscarriage or intrauterine death if transmitted to foetus
Clinical features of parvovirus B19 infection
Usually asymptomatic in adults In children - URTI - malaise - headaches - low-grade fever - erythema infectiosum
Investigations for parvovirus B19 infection
Viral serology
- parvovirus specific IgM antibodies indicate recent infection
- parvovirus specific IgG antibodies indicate past infection and therefore immunity
Management of parvovrius B19 infection
Referal to foetal medicine specialist
Maternal
- self-limiting - does not require treatment but can give antipyretics and analgesia
Foetal
- main risk is foetal hydrops - abnormal accumulation of fluid in two or more foetal compartments
- serial USS and doppler assessment - 4 weeks post infection repeated every 1-2 weeks until 30 weeks gestation
- intrauterine erythrocyte transfusion
Define foetal hydrops
Common manifestation of foetal parvovirus B19 infection
Diagnosed by USS - ascites, subcut oedema, pleural effusion, pericardial effusion, scalp oedema, polyhydramnios
Parvovirus B19 has an affinity for erythroid system and replicates within erythroid progenitor cells of liver and bone marrow
Induces severe anaemia -> high output cardiac failure
-> increased extrahepatic and hepatic erythropoiesis -> portal hypertension and hypoproteinaemia with ascites
Define rubella
German measles
Single stranded RNA virus
Transmitted by airborne droplets between close contacts
Clinical features of rubella
Often asymptomatic
Malaise, headache, coryza and lymphadenopathy
Diffuse fine maculopapular rash
Investigations for rubella
ELISA performed
- IgM antibody - acute infection
- IgG antibody - following infection or vaccination
Management of rubella
Referal to foetal medicine specialist
Maternal
- self limiting = no treatment
- antipyretics for fever
- informed infective - 7 days prior and 4 days post symptom
Foetal
< 12 weeks - high likelihood of defects - consider termination
- 12-20 weeks - prenatal diagnosis required - RT-PCR on amniotic fluid
> 20 weeks - no action required
Features of congenital rubella syndrome
Present at Birth
- Auditory Problems
- Sensorineural deafness
- Cardiac Defects
- Pulmonary Stenosis, Patent Ductus Arteriosus, Ventricular Septal Defect
- Ophthalmic Defects
- Retinopathy, Congenital Cataracts
- Central Nervous System Abnormalities
- Learning disabilities, Microencephaly
- Haematological
- Thrombocytopaenia, Blueberry Muffin Appearance
Late Onset
- Diabetes mellitus
- Thyroiditis
- Growth Hormone Abnormalities
- Behavioural DisordersDefine varicella zoster
DNA virus
Responsible for
- chicken pox - primary infection
- shingles - viral reactivation
Incidence of varicella zoster infection in pregnancy
90% seropositive IgG antibody due to previous exposure
If contracted during pregnancy there is an increased morbidity and mortality for both mother and foetus
Clinical features of varicella zoster infection
Fever, malaise and pruritic maculopapular rash
Incubation period is 10-21 days - infectious 48 hours prior
Associated with pneumonia, hepatitis and encephalitis
Investigations for varicella zoster infection
Clinical diagnosis
- immunofluorescence of basal epithelial cells scrapped from vesicle
- PCR for varicella zoster DNA
- IgM and IgG antibodies for immunity
Management of varicella zoster infection
Maternal suspected varicella contact
- if previous primary infection - assume immunity for no further action required
- no previous infection - varicella IgG to confirm immunity status
- if not immune given varicella zoster immunoglobulin within 10 days of contact
Maternal Chickenpox
- Aciclovir within 24 hours of rash onset if > 20 weeks gestation
- serial ultrasound examinations at 5 weeks post-infection for identify foetal abnormalities
Varicella Vaccination
- if seronegative for IgG pre-pregnancy or postpartum vaccination
Complications of varicella zoster infection
Varicella of the newborn - occurs within the last 4 weeks of pregnancy
- asymptomatic
- route of infection can be transplacental, vaginal and direct contact after birth
Foetal varicella syndrome - reactivation of virus in utero
- Skin scarring in a dermatomal distribution
- Eye defects
- Microphthalmia
- Choriorenitis
- Cataracts
- Optic atrophy
- Hypoplasia of the limbs
- Neurological Abnormalities
- Microcephaly
- Cortical and spinal cord atrophy
- Seizures
- Horner’s SyndromeDefine pre-eclampsia
Hypertensive disorder
Thought to be due to to poor placental perfusion, secondary to abnormal placentation
Pathophysiology of pre-eclampsia
In normal placentation
- trophoblast invades myometrium and spiral arteries of uterus destroying tunica muscularis media
In pre-eclampsia
- remodelling of spiral arteries is incomplete
- high resistance low flow uteroplacental circulation develop
Risk factors for pre-eclampsia
Moderate risk factors - Nuliparity - Maternal age ≥ 40 years - Maternal BMI ≥ 35 at initial presentation - Family history of pre-eclampsia - Pregnancy interval > 10 years - Multiple pregnancy High risk factors - Chronic hypertension HTN, pre-eclampsia or eclampsia in previous pregnancy - Pre-existing chronic kidney disease - Diabetes Mellitus. - Autoimmune diseases (e.g. SLE, antiphospholipid syndrome)
Pre-eclampsia prophylaxis
75mg aspirin
- women with 1 high or 2 moderate risk factors
- from 12 weeks gestation until birth
Clinical features of pre-eclampsia
Mainly asymptomatic
- Headaches (usually frontal)
- Visual disturbances e.g. blurred or double vision, halos, flashing lights
- Epigastric pain (due to hepatic capsule distension/infarction)
- Sudden onset non-dependent oedema
- Hyper-reflexia
Criteria for pre-eclampsia
Hypertension - on 2 occasions at least 4 hours apart
Significant proteinuria - >300mg
Classification of pre-eclampsia
Mild = BP 140/90-149/99 mmHg
Moderate = BP 150/100 – 159/109 mmHg
Severe = BP > 160/110 + proteinuria > 0.5 g/ day
or
BP > 140/90 mmHg + proteinuria + symptoms
Complications of pre-eclampsia
Onset of pre-eclampsia before 34 weeks is associated with poorer prognosis
- HELLP syndrome – haemolysis, elevated liver enzymes, low platelets
- Eclampsia
- AKI
- DIC
- ARDS
- Hypertension (4-fold ↑ risk post-partum)
- Cerebrovascular haemorrhage (1-2%)
- Death
Differential diagnosis of pre-eclampsia
Essential HTN – HTN prior to 20 weeks’ gestation
Pregnancy induced HTN (PIH) – new onset HTN presenting after 20 weeks’ gestation, without significant proteinuria
Eclampsia – Pre-eclampsia + seizures - obs emergency
Investigations for pre-eclampsia
Presence of hypertension and proteinuria
- detected on urine dipstick then quantified on 24 hour urinary collection
Management of pre-eclampsia
Prevent development of eclampsia
Minimise risk of complications for mother and foetus
- monitoring of maternal and foetal wellbeing - regular blood pressure measurements, urinalysis, blood tests, foetal growth scans and cardiotocography
VTE prevention - LMWH
Antihypertensives - reduce stroke risk
Delivery
Antihypertensives for pre-eclampsia
Labetalol (1st line)
- Beta-blocker
- Postural hypotension, fatigue, headache, nausea and vomiting, epigastric pain
Nifedipine
- Calcium channel blocker
- Peripheral oedema, dizziness, flushing, headache, constipation
Methyldopa
- Alpha-agonist
- Drowsiness, headache, oedema, GI disturbances, dry mouth, postural hypotension, bradycardia, hepatotoxicity
Post-natal care of women with pre-eclampsia
Still at risk of seizures for 24 hours
Blood pressure monitored for 2 days
Repasses hypertensives
Advised of risk of pre-eclampsia in future pregnancies
Pregnancy specific changes with thyroid
The half-life of thyroxine binding globulin increases - total thyroid hormone levels increase
hCG stimulates like TSH
Increased GRF and increased uptake of iodine into thyroid can deplete iodine -> iodine deficiency
Management of hypothyroidism in pregnacy
Maintain thyroxine dose and monitor regularly
Management of hyperthyroidism in pregnancy
Ensure euthyroidism
- propylthiouracil or carbimazole
Complications of hyperthyroidism in pregnancy
Maternal - thyroid storm - congestive cardiac failure - pre-eclampsia Foetal - foetal growth restriction - prematurity - stillbirth
