l unachievable at home. Metformin can be used in pregnancy. Monitor fetal growth & wellbein g by ultrasound and cardiotocography (p3). Delivery Deliver the baby where there are good n eonatal facilities. NICE recom- mends elective delivery at 38 weeks. \200 66 In labor: Avo id acidosis and monitor the fetus (p44). Avoid maternal hyperglycaemia (causes fetal hypogl ycaemia). Monitor glucose; prevent hyperglycaemia with extra insulin (may need 5U/h) if glu cocorticoids are used in preterm labor. Aim for vaginal delivery with labor of <12h. Beware shoulder dystocia with macrosomic babies. With elec- tive delivery, give normal insulin th e evening before induction. During labor give 1L of 5 \200\22310% glucose/8h IVI with 1 \200\2232U insulin/h via a pump. Aim for a blood glucose of 4.5 \200\2235.5mmol/L (check ho urly). Insulin needs fall as labor progress- es and immediately postpartum. Stop infusions at delivery. Return to pre-preg- nancy regimen. Do a cesarean section if labor is prolonged . Clamp cord early (polycythaemia risk). Postnatal \200 Encourage breastfeeding (metformi n and glibenclamide are com- patible with breastfeeding). \200 Encourage pre-pregnancy co unseling before next pregnancy (p2) to transfer to insulin if needed. \200 If preprolifer ative retin- opathy review ophthalmologically for 6 months. \200 Discuss contraception. G estational diabetes (OGTT glucose \211 7.8mmol/L, OHCM p198) Incidence: 3%. 67 For screeni ng and who to screen see p8. Monitor glucose if diagnosed. If levels not controlled by diet and exercise over 1 \200\2232 weeks consider oral hypoglycae- mics (metformin, glibenclami de \200\223note NICE and product characteristic sheets con \202 icting advice) or insulin. 50% get full DM, so give lifelong dietary advice and follow-up. 68 Check fasting glucose 6 weeks postpartum. \200\207Exercise, a good diet, and no smoking all help lower this risk. s c i r t e t s b O See diabetic care plan p3. 25 25 Thyroid disease in pregnancy (see also p15) \200\207Whenever a mother isn \200\231t quite right postpartum, check her TSH & free T4 \200\224 but note that any apparent hypothyroidis m may be transitory. Biochemical changes in normal pregnancy NB: normal pregnancy mimics hy perthyroidism (pulse \200\200, warm moist skin, slight goiter, anxiety). \200 Thyroid bi nding globulin & T4 output rise to maintain free T4 levels, p15. \200 High levels of HCG mimic thyroid stimulating hormone (TSH). \200 There is reduced availability of iodine (in iodine-limited localities). \200 TSH may fall below normal in the \201 rst trimester ( suppressed by HCG). \200 The best thyroid tests in pregnancy are free T4, free T3 , and T SH. Pre-pregnancy hyperthyroidism Treatment options include antithyroid drugs (but 60% rela pse on stopping treatment), radioactive iodine (contra- indicated in pregnancy or breastfee ding: avoid pregnancy for 4 months after use), or surgery. Fertility is reduced by hyperthy roidism. Hyperthyroidism in pregnancy (Usually Graves \200\231 disease.) There is \200\200 risk of prematurity, fetal loss, and, maybe, malformations. Severity of hyperthyroid- ism often falls in pregnancy. Transient exacerbations may occur (1st trimester & postpartum). P ropylthiouracil is the best treatment. 69 Keep dose as low as possible. Monitor \211 mont hly. Some advocate stopping antithyroid drugs in the last month of pregnancy. Propylthioura cil is preferred postpartum (less con- centrated in breast milk). If hyperthyroidism cannot be controlled by drugs, partial thyroidectomy can be done in the 2nd trimester. TRAb (TSH- receptor stimulating antibodies): \200\200levels can cause fetal hyperthyroidism after 24w ks causing premature delivery; craniosynostosis so intellectual impairment; goi- tre so pol yhydramnios; extended neck in labor. Note labor, delivery, surgery, and anesthesia can prec ipitate thyroid storm (fever, tachycardia, changed mental state \200\224agitation, psychosi s, coma) requiring urgent treatment. Hypothyroidism Associated with relative infertility, u ntreated hypothyroidism risks \200\200 rates of miscarriage, stillbirth, premature labor, and abnormality. Optimize T4 preconception (p2). Increase levothyroxine by 30% as soon as k nows pregnant. 70 Monitor replacement by T4 and TSH measurement 6-weekly. Aim for TSH \211 2.5mU/L. Use pre-pregnancy levothyroxine doses postpartum. Postpartum thyroiditis Prevalen ce: 5%. Hyperthyroidism is followed by hypo- thyroidism ( 4 months postpartum). The hyperth yroid phase does not usually need treatment as it is self-limiting. If treatment is require d \200 -blockers are usually suffi cient. Antithyroid drugs are ineff ective as thyrotoxic osis is from thyroid destruction releasing thyroxine, rather than increased synthesis. Moni - tor the hypothyroid phase for >6 months, and treat if symptomatic. Withdraw treatment aft er 6 \200\22312 months for 4 weeks to see if long-term therapy is re- quired. 90% have thyr oid antiperoxidase antibodies; 5% of antibody positive women become permanently hypothyroid each year so monitor annually. Hypothyroidism may be associated with postpartum depression , so check thy- roid status of women with postpartum depression. Neonatal thyrotoxicosis Se en in 1% of babies of women with past Graves \200\231 disease, as TRAb crosses the placenta . Signs: fetal tachycardia (>160/min) in late pregnancy intrauterine growth restriction. If mother has been on antithyroid drugs signs may not be manifest until the baby has metab olized the drug (7 \200\22310 days postpartum). Test thyroid function in aff ected babies f re- quently. Antithyroid drugs may be needed. It resolves spontaneously at 2 \200\2233 mont hs, but perceptual motor diffi culties, and hyperactivity can occur later in childhood. Thy roid antibodies Presence of these increase rates of miscarriage and pre- term delivery; ran domized studies suggest thyroxine treatment may reduce miscarriage in euthyroid women with antibodies. 71 s c i r t e t s b O Jaundice in pregnancy 26 \200 \200 \200\207Get expert help promptly. Jaundice in pregnancy may be lethal. Know exact- ly what drugs were taken and when (prescribed or over-the-counter). Where has she traveled to? Wha t lifestyle or occupational risks are there? Jaundice occurs in 1 in 1500 pregnancies. Viral hepatitis and gallstones may cause jaundice in pregnancy and investigation is similar to the non-pregnant. Those with Gilbert \200\231 s and Dubin \200\223Johnson syndrome (OHCM p714) do well in pregnancy (jaundice may be exac erbated with the latter). Tests Do all the usual tests (OHCM p250), eg urine tests for bile , serology, LFTs, and ultrasound. Intrahepatic cholestasis of pregnancy \200 72 Incidence: 0.1 \200\2231.5% pregnancies in Europe. There is pruritus, especially of palms and soles i n the second half of pregnancy. Liver transaminases are mildly \200\200 (<300U/L) in 60%, \200\200 bilirubin in 25%. Exclude viral hepatitis. There is risk of preterm labor, fetal distress, and stillbirth, so monitor fetal wellbeing. Give vitamin K 10mg PO/24h to the mot h- er, and 1mg IM to the baby at birth. Ursodeoxycholic acid reduces pruritus and abnormal LFTs. Symptoms resolve within days of delivery. It is a contraindica- tion to estrogen-cont aining contraceptive pills. It recurs in 40% pregnancies. Acute fatty liver of pregnancy In cidence: 1 : 6600 \200\22313,000 deliveries \200\224so it is rare but grave. The mother dev elops abdominal pain, jaundice, headache, vom- iting, thrombocytopenia and pancreatitis. There is associated pre-eclampsia in 30 \200\22360% ( postpartum). It usually occurs afte r 30 weeks. There is hepatic steatosis with micro-droplets of fat in liver cells. Deep jaun dice, uraemia, severe hypoglycaemia, and clotting disorder may develop causing coma and dea th. Monitor BP. Give supportive treatment for liver and renal failure and treat hypoglycaem ia vigorously (CVP line). Correct clotting disorders. Enlist hematologist \200\231s help. E xpedite delivery. Epidural and regional anesthesia are CI. Monitor postpartum. Beware PPH a nd neonatal hypoglycaemia. Mortality can be as low as 18% maternal and 23% fetal. Some othe r causes of jaundice in pregnancy \200 Viral hepatitis; ALT \200\200, eg >200U/L; matern al mortality \200\200 ( 20%) in E virus, \200 48 treatment is supportive. Hepatitis C is thought to aff ect <1% of women in the UK at present. Vertical transmission aff ects about 5% of babies. Elective cae- sarean delivery is only recommended for those with coexistent H IV. \200 48 Passive antibodies transferred from the mother wane by 18 months. Check baby f or HCV RNA at 2 \200\2233 months (& 12 months, and anti HCV antibody at 12 \200\22318 month s), refer baby to paedatric hepatologist if HCV RNA positive. 73 Currently screening is not planned. Refer infected women for specialist treatment to clear the viral infection after birth (OHCM p470). s c i r t e t s b O The jaundice of severe pre-eclampsia (hepatic rupture and infarction can oc- cur); ALT <500 U/L; bilirubin <86 mol/L. \200 Rarely, complicating hyperemesis gravidarum (can be fatal ); ALT <200U/L. \200 Hepatitis may occur if halothane is used for anesthesia (so avoid it ). \200 HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count). Inci dence in pregnancy: 0.1 \200\2230.6%; in pre-eclampsia: 4 \200\22312%. It causes upper abdo pain, malaise, vomiting, headache, jaundice, microangiopathic haemo- lytic anemia, DIC, LD H \200\200, ALT \200\200 <500U/L, bilirubin <86 mol/L. It recurs in 20%. Treatment: get expert help. Admit; deliver if severe. Hepatitis B Check HBsAG in all women with jaundice and look for IgM anti-HBc to detect acut e infection. Avoid contact with blood during delivery and be careful with disposal of \200 \230sharps \200\231. Babies need immunoglobulin and vaccination at birth (p151). Transplace ntal infection may be reduced by maternal lamivu- dine 74 (seek expert advice). Off er vacc ination to all the family. 27 Malaria in pregnancy In any woman who presents with odd behavior, fever, jaundice, sweating , DIC, fetal distress, premature labor, seizures, or loss of consciousness, always ask your self: \200\207Could this be malaria? If so, do thick and thin \201 lms. Con \201 rm (or exclude) pregnancy. Seek expert help, eg from Liverpool, below. \200 Falciparum malaria is dangerous (and complicated) in pregnancy, particu- larly in those wit h no malaria immunity. Cerebral malaria has a 50% mortality in pregnancy. 3rd-stage placent al autotransfusion may lead to fatal pulmonary oedema. Hypoglycaemia may be a feature (both of malaria itself and second- ary to quinine). There is increased susceptibility to sepsis . Women with coex- istent HIV have less good pregnancy outcomes (fetal and maternal). Other associations between falciparum malaria and pregnancy are anae- mia, miscarriage, sti llbirth, low birth weight, and prematurity. PPH is also more common. Hyperreactive malaria splenomegaly (occurs typically where malaria is holoendemic) may contribute to anemia via i ncreased haemolysis. Vivax malaria is less dangerous, but can cause anemia and \200\201 bi rth weight. Treating malaria \200\207OHCM p396; \200 cerebral malaria, OHCM p397. In seve re fal- ciparum artesunate 2.4mg/kg IV at 0, 12, & 24h then daily until can take oral artes unate+clindamycin is 1st line, if available (tel 08451 555000 tropical medi- cal registrar for advice/supply), or load with quinine 20mg/kg IVI over 4h in 5% glucose (max 1.4g) (do n ot load if on quinine/me \202 oquine). Then 10mg/kg IVI over 4h in 5% glucose every 8h wit h 450mg clindamycin/8h IV. Beware hypoglycaemia with quinine. Switch to artesunate regimen as soon as it is available. \200\22575 When severe treat on ITU. If haematocrit <20% give slow transfu- sion of packed cells, with 20mg furosemide. Include the volume of packed cell s in \202 uid balance calculations. Consider exchange transfusion. Beware hyper- pyrexia (fan, give paracetamol); renal failure; pulmonary oedema; and sepsis (if shock do blood cul tures give IV ceftriaxone). Get expert help. Uncomplicat- ed falciparum and resistant vivax are treated for 7 days with quinine 600mg with clindamycin 450mg/8h PO. Non-resistant viva x, ovale and malariae are treated with chloroquine orally over 3 days with weekly dose to p revent re- lapse during pregnancy. 3 months after delivery (and G6PD testing) primaquine is then given for ovale and vivax prevention of relapse. s c i r t e t s b O If infection peripartum, anticipate fetal distress, \202 uid-balance problems, and hypogl ycaemia in labor. Monitor appropriately. After any infection send pla- centa for histology and placental, cord, and baby blood (weekly \211\2104) for blood \201 lms to check if bab y infected (0.3 \200\2234% are), and treat baby if infected. Prevention in UK women Advise against visiting malarious areas. If it is una- voidable, give prophylaxis (OHCM p396). Emp hasize importance of preventive measures such as mosquito nets and insect repellents. Norma l dose chloro- quine and proguanil if P. falciparum strains are sensitive. With proguanil, give concurrent folic acid 5mg/day. If chloroquine resistance me \202 oquine is best. Me \202 oquine is recommended for 2nd and 3rd trimester use. 76 Heed strict contraindicati ons (eg epilepsy, neuropsychiatric disorder). If unsuitable, Malarone (atovaquone-proguan il, with folic acid) is an alternative in 2nd and 3rd trimester for chloroquine or me \202 oquine resistant areas. 1st trimester proph- ylaxis is a problem. Seek expert advice (eg t el 0845 602 6712). Mothers living in endemic areas Chemoprophylaxis improves birthweight (b y 250g, with fewer very low birthweight babies). Red cell mass also rises. WHO advises int ermittent preventive treatment (IPT) eg with 2 or 3 doses of sul- fadoxine-pyrimethamine (S P) during pregnancy, but monthly doses are better if HIV +ve. 78 But SP causes Stevens \200 \223Johnson syndrome in 1 in 7000, and resistance to SP has spread fast, so new IPT regimen s need urgent evaluation in pregnan- cy. 79 Dihydroartemisinin-piperaquine (Artekin ) is a good candidate. 80 \200\207If in doubt, phone an expert, eg, in the UK, at Liverpool (tel . 0151 705 3100). Renal disease in pregnancy 28 Note: Values considered normal when not pregnant may re \202 ect decreased renal function in pregnancy. Creatinine >75 mol/L and urea >4.5mmol/L merit further investigation. See p1 5. Glycosuria in pregnancy may re \202 ect altered re- nal physiology and not necessarily imply hyperglycaemia. \200\207Treat asymptomatic bacteriuria in pregnancy. Check that infe ction and bac- teriuria clear with treatment. Asymptomatic bacteriuria Found in 2% of sexua lly active women it is com- moner (up to 7%) during pregnancy \200\224especially in diabeti cs and in those with renal transplants. With the dilatation of the calyces and ureters that occurs in pregnancy, 25% will go on to develop pyelonephritis, which can cause fetal growt h restriction, fetal death, and premature labor. This is the argument for screening all wom en for bacteriuria at booking. If present on 2 MSUs treatment is given (eg amoxicillin 250m g/8h PO with a high \202 uid intake). Test for cure after 1 and 2 weeks. If the organism is not sensitive to amoxicillin, consider nitrofurantoin 50mg/6h PO with food. It recurs in 30% (so keep screening). 81 Pyelonephritis This may present as malaise with urinary freque ncy or as a more \202 orid picture with raised temperature, tachycardia, vomiting, and lo in pain. It is common at around 20 weeks and in the puerperium. Urinary infec- tions should always be carefully excluded in those with hyperemesis gravidar- um and those admitted wit h premature labor. Treatment is with bed rest and plenty of \202 uids. After blood and ur ine culture give IV antibiotics (eg ampicil- lin 500mg/6h IV, according to sensitivities) i f oral drugs cannot be used (eg if vomiting). Treat for 2 \200\2233 weeks. MSUs should be c hecked every fortnight for the rest of the pregnancy. 20% of women having pyelonephritis in pregnancy have underlying renal tract abnormalities and an IVU or ultrasound at 16 weeks \200\231 postpartum should be considered. In those who suff er repeated infection, ni- trof urantoin (100mg/24h PO with food) may prevent recurrences. Avoid if the glomerular \201 l tration rate is <50mL/min. SE: vomiting, peripheral neuropathy, pulmonary in \201 ltration , and liver damage. Chronic renal disease With mild renal impairment (pre-pregnancy creati- nine <125mmol/L) without hypertension there is little evidence that pregnancy accelerates renal disorders. Patients with marked anemia, hypertension, retinopathy, or heavy proteinur ia should avoid pregnancy as further deteriora- tion in renal function may be expected. Clo se collaboration between physi- cians and obstetricians during pregnancy in those with rena l disease is the aim. Induction of labor may become advisable in those with hypertension an d proteinuria, or if fetal growth is retarded. s c i r t e t s b O Pregnancy for those on dialysis is fraught with problems ( \202 uid overload, hypertension , pre-eclampsia, polyhydramnios). A 50% increase in dialysis is needed. Live birth outcome is 50 \200\22370%. Outcome is better for those with renal transplants, but up to 10% of mot hers die within 7 years from birth. Obstetric causes of acute tubular necrosis Acute tubula r necrosis may be a complication of any of the following situations: \200 Septicaemia (eg from miscarriage with infection, or pyelonephritis). \200 Haemolysis (eg sickling crisis , malaria). \200 Hypovolaemia, eg in pre-eclampsia; hemorrhage (APH, eg abruption, PPH, o r intrapartum); DIC; miscarriage \200\224or adrenal failure in those on steroids not receiv ing booster doses to cover labor. Whenever these situations occur, monitor urine output carefully (catheterize the bladder). Aim for >30mL/h output. Monitor renal function (U&E, creatinine). Dialysis may be needed (O HCM p304). 29 Epilepsy in pregnancy \200\207The key to successful pregnancy is access to good preconcept ion counseling (p2). Anti-epileptic drugs are normally specialist initiated; ask for a revi ew if pregnancy may be being considered. \200\207If seizures occur in pregnancy, think cou ld this be eclampsia? Epilepsy de novo is rare in pregnancy. Epilepsy aff ects 0.5% of wom en of childbearing age so a unit with 3000 deliveries per year has 15 pregnant epi- leptic women at any one time. Seizure rates worsen in most women having >1 seizure/month. Sleep d eprivation in the last month of pregnancy may contrib- ute to seizures. It is unusual for s eizures to recur in pregnancy when preceded by a long seizure-free period. Complications \200\224Maternal: \200\200 Risk of 3rd trimester vaginal bleeding. 1% con- vulse in labor. Fetal: \200 Haemorrhagic disease of newborn can occur with en- zyme inducers (below). \200 Congenital malformation (UK register suggests 6.2% aff ected with sodium valproate, 2 .2% with carbamazepine, 3.2% with lamo- trigine). 82 Malformation is commoner if \211 2 an ticonvulsants are used and with higher doses. Fetal valproate syndrome: Signs: major organ system anoma- lies autism small ears, small broad nose, a long upper lip, shallow phi ltrum & micro/retrognathia.1 Cleft lip: Associated with maternal epilepsy only, the relativ e risk for a fetus having clefts compared to the non-epileptic population is 1.0 if the mot her develops epilepsy after the pregnancy; 2.4 if she develops it after conception (but has no drugs); 4.7 if fetus is exposed to anticonvulsants. Phenytoin and phenobarbital cause c lefts and congenital heart disease. Neu- ral tube defects are commoner with valproate (& ca rbamazepine) so screen for these (p10). Reduced cognitive function is seen with valproate ( at age 3); 83 seen as lower intelligence quotient (also seen in the off spring of those hav ing frequent tonic clonic seizures in pregnancy). 84 Management \200\207Get expert help (r efer to epilepsy specialist to optimize and monitor medication: only make antiepileptic cha nges on expert advice). Car- bamazepine may be drug of choice in pregnancy. 85 Lamotrigine dose usually needs to be increased in pregnancy to maintain seizure control. Where anti- co nvulsants are needed keep the dose of the chosen drug as low as possible. Aim for 1 drug on ly. Give folic acid supplements, eg 5mg/24h PO from prior to conception. Give vitamin K 20m g/24h PO to the mother from 36 weeks if she is taking enzyme inducers, ie carbamazepine, et hosuximide, phenytoin, primi- done, phenobarbital (oxcarbazine and topiramate are subjects of debate). Screen for neural tube defects and heart disease if relevant (above). Treat sta - tus epilepticus as in the non-pregnant but monitor the fetus. It is associated with signi \201 cant fetal and maternal mortality. Deliver in hospital with resusci- tation faciliti es (1 \200\2232% epileptic women convulse in labor and the subsequent 48 hours) and avoid e arly discharge. Give baby vitamin K 1mg IM at birth. If sei- zures are likely, to avoid dro pping the baby during a seizure, advise changing the baby on mat on \202 oor, and feeding sitting on \202 oor supported by cushions; only bath the baby with supervision. Mothers showering, not bathing reduces risk of drowning. Mothers may breastfeed (phenobarbital can cause drowsi- ness in the baby). Ask for review of epilepsy drugs postnatally eg at 12 week s. Encourage mother to register pregnancy at www.epilepsyandpregnancy.co.uk. or s c i r t e t s b O tel 0800 389 1245. 1 Of those aff ected 62% had musculoskeletal abnormalities, 26% had cardiovascular abnormal ities, 22% had genital abnormalities, and 16% had pulmonary abnormalities.86 Connective tissue diseases in pregnancy 30 Rheumatoid arthritis is usually alleviated by pregnancy (but exacerbations may occur in the puerperium). Methotrexate use is contraindicated (terato- genic); sulfasalazine may be use d (give extra folate). Azathioprine use may cause intrauterine growth restriction and penic illamine may weaken fetal collagen. Non-steroidal anti-in \202 ammatories can be used in t he \201 rst and second trimesters but are not recommended in the third as they can cause premature closure of the ductus arteriosus and late in pregnancy have been associated with renal impairment in the newborn. Anti-tumor necrosis fac- tor TNF-alpha therapies have not shown problems; but experience is limited. 87 Congenital heart block is a rare fetal featur e. Deliver babies with heart block as below. Systemic lupus erythematosus SLE exacerbations are commoner in preg- nancy and the puerperium. Most are mild to moderate involving skin, but those with renal involvement and hypertension may deteriorate and are prone to pre-ecla mpsia. Of those with SLE glomerulonephritis and a creatinine >130 mol prior to conception only 50% achieve a live birth. Pre-eclampsia, oligohydramnios, and intrauterine growth rest riction may occur. Both hydrala- zine and methyldopa can be used in pre-eclampsia. s c i r t e t s b O Planned pregnancy should be embarked on after 6 months stable disease without requiring cy totoxic suppression. Disease suppression may be main- tained with azathioprine and hydroxyc hloroquine. Aspirin 75mg daily should be started prior to conception and continued througho ut pregnancy, and the fetus should be carefully monitored. Rarely, the fetus is aff ected by maternal antibodies that cause a self-limiting sunlight s ensitive rash (usually face and scalp) for which no treatment is re- quired; or anti-Ro or anti-La antibodies irreversibly damage the fetal heart conduction system causing congenital heart block ( 65% require a pacemak- er). Deliver by cesarean or monitor fetal blood gasse s in labor. Mothers requiring \211 7.5mg daily prednisolone in the 2 weeks before delivery should receive hydrocortisone 100mg/6h IV in labor. Antiphospholipid syndrome Those aff ect ed have antiphospholipid anti- bodies (lupus anticoagulant and/or anticardiolipin antibodie s on 2 tests taken >8 weeks apart) past arterial thrombosis, venous thrombosis, or recur rent pregnancy loss. It may be primary, or follow other connective tissue disorder (usually SLE in which it occurs in 10%). Outcome: Untreated, <20% of pregnan- cies proceed to a liv e birth due to 1st trimester loss or placental thrombosis (causes placental insuffi ciency, leading to intrauterine growth restriction and fetal death). Careful regular fetal assessment (Doppler \202 ow studies and ultrasound for growth) is r equired from 20 weeks as appropriate obstetric intervention can substantially increase the number of live-born babies. Management: Aff ected women are treated from conception with as pirin 75mg daily and heparin eg enoxaparin 40mg SC/24h from when fetal heart identi \201 e d ( 6 weeks) until 34 weeks. Those who have suff ered prior thrombo- ses receive heparin th roughout pregnancy. See p33. Postpartum use either heparin or warfarin (breastfeeding contraindicated with neither) as risk of thrombosis is high. Pregnancies in those with SLE (especially with renal disease) and antiphos- pholipid syndrome require specialist management. 31 Hypertension in pregnancy Chronic hypertension is hypertension predating pregnancy or devel oping be- fore 20 weeks \200\231 gestation. Gestational hypertension is that, without prote inu- ria, which develops after 20 weeks \200\231 gestation. Hypertension with proteinuria i s pre-clampsia see p48 \200\22349. Chronic hypertension Preconception: ACE inhibitors, A2A blockers and chlo- rothiazide risk congenital abnormality so change these pre-conception to more suitable preparation and encourage low sodium intake or use of salt substitute. Ateno lol, labetalol, metoprolol and methyldopa are licensed for use throughout pregnancy. Antena tal: Ensure suitable antihypertensive is being used (above). Aim for BP <150/90 (140/90 if end organ damage), but with diastolic \211 80. If hy- pertension is secondary to another d isorder involve a specialist in hypertensive disorders. Give aspirin 75mg/24h/PO from 12 we eks until the baby is born. At 28 \200\22330 and 32 \200\22334 weeks arrange ultrasound to assess fetal growth, amniotic \202 uid volume and umbilical artery velocity: if normal at 34 weeks do not repeat. If fetal activity is abnormal arrange cardiotocography (CTG). Duri ng labor, monitor BP hourly if BP <159/109, continuously if \211 160/100. If severe hypert ension does not respond to treatment advise operative delivery. Give oxytocin alone at 3rd stage of labor. Postnatally check BP on days 1, 2, and once on days 3 \200\2235 and at 2 we eks. Change methyldopa to another antihypertensive post delivery as risk of postnatal depre ssion. Avoid diuretics if breastfeeding (labetalol, atenolol, metoprolol, captopril, and en alapril are safe). Gestational hypertension needs assessment in secondary care, with urine testing for proteinuria with automated reagent strip readings or urine protein/ creatinine ratio testing. Check urine and BP weekly if mild (BP 140/90 \200\223149/99) but start treat ment eg with labetalol PO if >150/100 and check BP and urine twice weekly. If BP \211 160 /110 admit to hospital, measure BP 4 times daily and check urine daily and check FBC, U&E, AST/ALT and bilirubin at presentation and weekly. If BP is mild do ultrasound/CTG as above but do ultrasound fortnightly if BP se- vere. Repeat CTG if there is a PV bleed, abdominal pain, reduced fetal movements or maternal deterioration. Aim for delivery after 37 weeks un less pre-eclampsia (p49) supervenes. During labor continue antihypertensives, monitor BP ho urly (continuously if >160/110). If BP is outside target range (>160/110) advise opera- tiv e delivery. Continue antenatal hypotensives postnatally (as above), reducing treatment if B P <130/80. Review at 2 and 6 weeks. If treatment is still needed at 6 weeks arrange review with specialist in hypertensive disorders. s c i r t e t s b O Venous thromboembolism (VTE) in pregnancy 32 \200 \200\207Investigate any unexplained calf or chest symptoms today. Thrombo- embolism is a c hief UK cause of maternal death. VTE risk rises 6-fold in pregnan- cy ( 0.1 \200\2230.2% of pregnancies: 20 \200\22350% occur antenatally \200\224in any trimester). For those at spec ial risk see p16. 50% of those with 1st VTE have thrombophilia (p33), so check for this. Wh ere clinical suspicion is strong but tests negative, start treatment; stop only after repea t negative tests 1 week later. 88 Before starting heparin take blood for: FBC, U&E, LFTs, c oagulation screen. Pulmonary embolism Small emboli may cause unexplained pyrexia, syncope, cough, chest pain, and breathlessness. Pleurisy should be considered due to embolism unless there is high fever or much purulent sputum. Large emboli present as collapse with chest p ain, breathlessness, and cyanosis. There will be a raised JVP, third heart sound, and paras ternal heave. Tests: Do CXR (normal in 50%). Scan legs for venous thrombi (if thrombi seen V/Q and CTPA (below) not needed as treatment indicated). Blood gasses may be helpful (PaO2 \200\201; PaCO2 \200\201). If PE still suspected do V/Q scan, spiral CT, or CT pulmonary angiography (CTPA). Maternal breast radiation is higher with CTPA increasing lifetime breas t cancer risk by 13% but V/Q increases risk of child- hood cancer more, as fetal radiation is higher. Exclude neonatal hypothyroid- ism after CTPA as iodinated contrast medium is use d. Treatment: Massive emboli may require prolonged cardiac massage, thrombo- lysis, percuta neous catheter thrombus fragmentation or pulmonary embol- etomy. Give unfractionated hepari n eg 80U/kg IV stat then 18U/kg/h IVI in 0.9% saline by syringe pump. Omit the stat dose if thrombolysis has been used. Mon- itor APTT at 6h from stat dose and after dose changes, an d /24h. (Target value APTT 1.5 \200\2232.5.) Adjust dose as needed 89 (usual 1000 \200\2232 000U/h). After 3 \200\2237 days IV heparin maintain on longterm heparin (eg 10,000U/12h sc) with careful monitor- ing. Problems: maternal osteopenia (reversible on stopping); thrombo cytopenia; allergic skin rashes; alopecia. Monitor platelets every 2 \200\2233 days from da y 4. s c i r t e t s b O For less massive emboli, low molecular weight heparin (LMWH) eg enoxa- parin (see below) is good treatment. (Warfarin is teratogenic in pregnancy \200\224Conradi \200\223H nermann syndrome, p640 and is used antenatally up to 36 weeks only in those with arti \201 cial he art valves.) SC heparin is continued throughout pregnancy (see below). Treat for at least 6 weeks postpartum and 3 months from embolus. Some choose warfarin instead after 3 days post partum. Deep vein thrombosis (DVT) Suspect if leg pain/discomfort (especially left); swelli ng; oedema; \200\200 T ; \200\200 WCC; lower abdominal pain. Tests: Compression duplex u ltrasound. If iliac vein thrombosis suspected (back pain/entire limb swollen) do MRI or con trast venography. If iliac thrombosis consider use of inferior vena caval \201 lter perin atally. \200\22589 Treatment: Use class 2 compression stockings. Ini- tially elevate the l eg; then mobilize wearing stockings. Give heparin throughout pregnancy eg enoxaparin 1mg/kg /12h SC (based on early pregnancy weight). Check platelets every 2 \200\2234 days (2 \200 \22314 days if on LMWH). Stop injections at onset of labor, 24h before planned delivery. Do not use regional anesthesia until >24h since last dose LMWH. If cesarean section, use drai ns and wound clips or inter- rupted sutures in case of wound haematoma. Restart heparin 3h post-op (or >4h from epidural; do not remove epidural catheter within 12h of LMWH use). Postpartum enoxaparin can be reduced to 1.5mg/kg/24h. If warfarin chosen (after 3rd day) po stpartum, monitor INR meticulously. Treat for at least 6 weeks postpartum and 3 months from thrombosis. Compression stockings should be worn for 2 years (reduces post-thrombotic synd rome incidence from 23% to 11%). \200\22589 Both heparin and warfarin are \201 ne if bre astfeeding. Prophylaxis See p16. 33 Thrombophilia in pregnancy Thrombophilia is a tendency to increased clotting and many under lying causes are now known to contribute. Collectively, the conditions below aff ect at lea st 15% of Western populations, but are found in 50% of those with episodes of venous thromb oembolism. Conditions include: \200 Factor V Leiden mutation* decreases factor V breakdow n by protein C (ac- tivated protein C (APC) resistance). This aff ects 4% of the populatio n and increases thrombotic risk 5 \200\2238.3 times (heterozygotes). Homozygous individu- a ls have 10 \200\22334 times the risk of venous thromboembolism. Protein C de \201 ciency* (aff ects 0.3% of population; increasing thrombotic risk 2 \200\2234.8 times). \200 Protein S de \201 ciency* (aff ects 2% of population; \200 \200 thrombotic risk 3.2 times). \200 Antithrombin III de \201 ciency* (aff ects 0.02% o f population; thrombotic risk is s c i r t e t s b O increased 4.7 \200\22310 times). \200 Acquired thrombophilia. This is lupus anticoagulant cardiolipin antibody*. Women with lupus anticoagulant risk arterial and venous thrombos is; in atypical veins, eg portal or arm. G20210A mutation of the prothrombin gene (1% of the population). Thrombotic risk is increased 3 \200\22310 times for heterozygotes, 26.4 times in homozygotes Homozygosity for the thermolabile variant of methylene tetrahydrofolate reductase (C677T MT HFR), which leads to homocysteinaemia (10% of the population). No association was found bet ween venous thromboembolism and homozygosity for C677T MTHFR mutation, perhaps because plas ma homo- cysteine reduces in pregnancy and folic acid supplements ameliorate hyper- homocys teinaemia. Dys \201 brinogenaemia is rare, and the thrombotic risk variable. Pregnancy is an acquired risk factor for venous thromboembolism; the post- natal period being especially risky. The diffi culty is to know who has throm- bophilia, and what risk this poses to a pregnant wom an. Past thrombosis increases risk, as does family history so thromboprophylaxis is recomme nded for those with history of thromboembolism and known thrombophilia or fam- ily history of thromboembolism (p16) both antenatally and postnatally. Treat- ment is strati \201 ed a ccording to risk. For risks see p16. Women with asymptomatic thrombophilia: Women without p ast thrombo- embolic history but with the higher risk thrombophilias ie antithrombin de \201 - ciency, more than one thrombophilic defect (including homozygous factor V Leiden, ho mozygous G20210A mutation, and compound heterozygotes of factor V Leiden and G20210A mutati ons); and women with other thrombophilias but additional risk factors need expert advice as to whether antenatal thrombo- prophylaxis is required in addition to postnatal use on an i ndividual basis. Women with lower risk thrombophilias but no additional risk factors can ha ve careful surveillance antenatally and 7 days of postnatal low molecular weight heparin. It is not felt that all women should be screened for thrombophilia; although screening is r ecommended for those with a family history of thromboembo- lism and those with past history of idiopathic, or unprovoked thromboembo- lism (ie not estrogen or pregnancy related). Scr eening is also recommended in those with second-trimester pregnancy loss, severe or recurre nt eclampsia, and intrauterine growth restriction. Low molecular weight heparin is recommended for those with thrombo- philia and past history of thromboembolism (see p16). The thrombophilias marked * above, and acquired protein c re sistance are risk factors for develop- ing pre-eclampsia so aspirin 75mg/24h PO is recommen ded from 12 weeks until delivery. 90