Chronic medical disorders in pregnancy

• Pregnancy worsens some chronic diseases and chronic disease worsens pregnancy; outcomes are best when disease is controlled before conception, ideally with a planned pregnancy and a multidisciplinary team.
• Most drugs used for long-term disease are continued in pregnancy when the disease itself is the bigger risk; only a few are strictly contraindicated.
• Epilepsy: aim for seizure control on the smallest effective dose of a safer drug (lamotrigine or levetiracetam, or carbamazepine for generalised? see below), take folic acid 5 mg/day before and during pregnancy, and avoid polytherapy especially with valproate.
• Thyroid disease: treat overt hypothyroidism with levothyroxine to a trimester-adjusted TSH; in 2017 the American Thyroid Association (ATA) raised the non-local TSH upper limit in early pregnancy to 4.0 mIU/L.
• Asthma is not "cured" in pregnancy; about a third of women worsen; continue inhaled corticosteroids, because uncontrolled asthma is the greater danger.
• Systemic lupus erythematosus (SLE) should be quiet (inactive) before conception; hydroxychloroquine is continued, methotrexate and mycophenolate are stopped.
• Antiphospholipid syndrome (APS) is treated with low-dose aspirin, plus heparin when there is thrombosis or prior obstetric APS.

By the end of this page you should be able to:

1. Explain why planned pregnancy and preconception counselling improve outcomes in chronic disease.
2. Choose an antiepileptic drug and folate dose for a woman planning pregnancy, and say why valproate is avoided.
3. State the TSH targets and treatment approach in pregnancy hypothyroidism and gestational hyperthyroidism.
4. Manage asthma in pregnancy, including which drugs are safe and how to treat an exacerbation.
5. Assess a woman with SLE or APS before pregnancy, and outline immune therapy, monitoring, and antithrombotic treatment.
6. Recognise red flags in these conditions and when to involve specialists.

This page is a hub for chronic medical disorders that accompany pregnancy. It does not replace disease-specific topics; it focuses on what changes when each condition meets pregnancy, on the drugs that may or may not be used, and on the targets (for example thyroid stimulating hormone, TSH) that are different in pregnancy than at other times. It covers four groups that account for a large share of consultations: epilepsy, thyroid disease, asthma, and autoimmune disease with lupus (SLE) and antiphospholipid syndrome (APS). Regional notes indicate where guidelines differ.

The common thread is that pregnancy changes physiology (blood volume, hormones, glomerular filtration, clotting) and changes how drugs are handled. The safest default is usually to treat the mother's disease actively and to avoid stopping drugs out of fear of the fetus, because untreated disease usually harms both mother and fetus more than well-understood treatment.

A planned pregnancy improves outcomes in almost every chronic disease. Before conception, review the diagnosis, activity, medications, comorbidities, and the woman's own wishes; optimise control; switch away from teratogenic drugs with enough lead time; start folate where relevant; and check vaccines and cervical screening. During pregnancy, keep the patient on the lowest effective dose of the safest drug, monitor more often than in a non-pregnant adult, and keep a low threshold for involving the physician who knows the disease (neurologist, endocrinologist, respirologist/rheumatologist) alongside obstetrics.

A few general drug principles recur across all four groups:

• Continue low-risk treatment rather than stop it. Doses should not be reduced below effectiveness only because of pregnancy.
• Some drugs are strictly contraindicated: methotrexate, mycophenolate, and cyclophosphamide in pregnancy; valproate carries such high teratogenic and neurodevelopmental risk that it should not be started in women of childbearing potential; and carboprost is contraindicated in asthma (see below).
• Timing of change matters. Stopping immunomodulators such as methotrexate needs 1 to 3 months' lead time; mycophenolate at least 6 weeks; all of this is planned, not emergency, medicine.
• Folate: 400 micrograms daily for most women; 5 mg daily for anyone at raised risk, including women taking anti-epileptic medicines, for at least the first 12 weeks.^[2]
• Low-dose aspirin is broadly used in pregnancy for preeclampsia prevention (in SLE, APS, and chronic hypertension), started early in pregnancy.

Epilepsy is the most common serious neurological disorder in pregnancy. In women with epilepsy, seizure frequency rises in roughly 15% to 37% of pregnancies, usually in the first or second trimester, and tonic-clonic seizures carry a small but real risk of fetal hypoxia, intracranial haemorrhage, and fetal loss.^[1] Children exposed to anti-epileptic drugs (AEDs) in utero have roughly a two- to three-fold increase in major malformations compared with the general population.^[1] The aim of management is therefore not to remove all medication, which itself increases risk, but to control seizures with the smallest dose of the safest drug, in monotherapy, with adequate folate.^[1]

Lamotrigine and levetiracetam have the most reassuring pregnancy safety data and are preferred as first-line for most women; carbamazepine is also used, though it carries higher teratogenic and enzyme-inducing liabilities. The crucial rule is that sodium valproate should not be initiated in women or girls of childbearing potential unless no other option exists, and a pregnancy prevention programme is in place. Valproate is associated with major malformations in about 1 in 10 exposed pregnancies, and with postnatal neurodevelopmental problems including lower IQ, delayed speech, and autism-spectrum features in up to 4 in 10 children exposed in utero.^[1] Phenobarbitone and phenytoin are also avoided because of teratogenicity and neurodevelopmental risk.^[1]

Practical points:

• Review the drug before conception, not after the test is positive.
• Aim for monotherapy at the lowest effective dose. Polytherapy in the first trimester is associated with higher major-malformation rates than monotherapy.^[1]
• Lamotrigine levels commonly fall in pregnancy because clearance rises; check levels and raise the dose proactively, then reduce after delivery. Levetiracetam and carbamazepine levels may also need monitoring.
• Enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbitone, and others) interact with hormonal contraception and with lamotrigine.
• An acute tonic-clonic seizure is more dangerous to the fetus than modern AEDs; do not stop treatment.

All women with epilepsy planning pregnancy should take folic acid 5 mg daily, starting before conception where possible and continuing through at least the first 12 weeks.^[1][2] The higher dose is used because AEDs affect folate metabolism and the risk of neural tube and other congenital malformations is increased. Several guidelines cited 400 micrograms for women without extra risk factors, but 5 mg is advised for anyone taking anti-epileptic medicines.^[2]

The Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guideline No. 68 (2016) recommends 5 mg/day before conception and throughout pregnancy for women with epilepsy, alongside avoidance of valproate, phenobarbitone, and phenytoin, and preference for lamotrigine and carbamazepine.^[1] Vitamin K is not recommended routinely for the mother during pregnancy, but every baby born to a woman taking an enzyme-inducing AED should receive 1 mg of intramuscular vitamin K at birth.^[1]

• A detailed fetal anomaly scan at 18 to 20 weeks' gestation is offered; ultrasound opportunities are also used to screen for structural problems.^[1]
• Therapeutic drug monitoring is not routinely required, but is reasonable when seizure control worsens, when non-adherence is suspected, or when toxicity is a concern, particularly with phenytoin or lamotrigine.^[1]
• Labour and delivery: tonic-clonic seizures in labour are rare but managed with intravenous benzodiazepines; levetiracetam is preferred if intravenous anti-epileptic therapy is needed. Physiological changes and drug level changes postpartum require prompt reassessment. Women with epilepsy may have somewhat higher rates of induction and caesarean section than controls.^[1]
• Preterm and low-birth-weight risks are modestly increased; good seizure control improves them.

• A convulsion lasting over 5 minutes, repeated seizures, or status epilepticus.
• New seizure types, especially if the woman has only ever had non-convulsive seizures.
• Stopping or changing AEDs without advice.
• Poor concordance, or drug interactions with antibiotics, antimalarials, or oral contraceptives.

The American Thyroid Association's 2017 guidelines (ATA 2017) and the American College of Obstetricians and Gynecologists' Practice Bulletin No. 223 (2020) frame the management of thyroid disease in pregnancy.^[3][10] Pregnancy raises thyroxine-binding globulin and human chorionic gonadotropin (hCG), which in the first trimester lowers TSH; the normal range therefore shifts, and the diagnosis of hypo- and hyperthyroidism in pregnancy cannot use non-pregnant cut-offs directly.

Overt hypothyroidism in pregnancy is treated with levothyroxine to normalise maternal TSH. The goal is adequacy, not luxury: untreated overt disease is linked to miscarriage, anaemia, pre-eclampsia, placental problems, postpartum haemorrhage, and impaired fetal brain development.^[4]

Practical management:

• Women with established hypothyroidism should increase their levothyroxine dose by 20 to 30% as soon as pregnancy is diagnosed, roughly two extra tablets a week, and have TSH checked promptly. Requirements rise by 25 to 50% over pregnancy.^[4]
• Check TSH every 4 weeks during the first half of pregnancy, and again after any dose change.^[4]
• Levothyroxine and prenatal vitamins (iron, calcium) must be separated by at least 4 hours, because iron and calcium reduce absorption.^[4]
• After delivery, return to the prepregnancy dose.
• Iodine: the WHO recommends 250 micrograms daily in pregnancy; the ATA recommends 150 micrograms daily for US women planning or in pregnancy. Pregnant women in iodine-sufficient countries usually do not need more than a standard prenatal. Severe iodine deficiency itself causes goitre and cretinism.^[4]

For subclinical hypothyroidism, ACOG and ATA 2017 make TSH thresholds that depend on TPO-antibody (TPOAb) status and on whether a local, assay-specific, trimester-specific reference range exists:

• TSH above 10 mIU/L in the first trimester: treat.^[4]
• TSH 2.5 or less: do not treat.^[4]
• TSH between 2.5 and 10: treat if TPOAb positive and TSH above 4 (consider if between 2.5 and 4); if TPOAb negative, treatment only "may be considered" because the evidence is weaker.^[4]

When a local trimester-specific TSH reference range is available, use it. When it is not:

• ATA 2017 lowers the non-pregnant TSH reference range by about 0.5 mIU/L in the first trimester, so the practical upper limit for the first trimester is 4.0 mIU/L, with a gradual return towards the non-pregnant range in the second and third trimesters.^[3]
• The 2011 ATA/Endocrine Society limits of 2.5 mIU/L (first trimester) and 3.0 mIU/L (second and third) were largely replaced by ATA 2017 for this reason, although some groups still apply the older, stricter limits, and outcomes data in the 2.5 to 4.0 range are still being refined.^[3]
• Approximately 2.5% of pregnant women have a TSH slightly above 6 mIU/L and 0.4% have a TSH above 10 mIU/L.^[4]

Where sources differ, state both numbers rather than picking one.

Most hyperthyroidism in pregnancy is Graves disease or gestational transient thyrotoxicosis (from hCG stimulation) in the first trimester.

• Gestational transient thyrotoxicosis: usually mild, resolves as hCG falls; generally no antithyroid drug is needed; treat only if severe.
• Graves disease: the woman should ideally be euthyroid before conception. If antithyroid drugs are needed, propylthiouracil (PTU) is usually preferred in the first trimester because of concerns about methimazole and embryopathy; many then switch to carbimazole/methimazole in the second and third trimesters because PTU carries a risk of severe hepatotoxicity. If methimazole embryopathy is a specific concern, PTU is continued. Either way, the goal is the lowest effective dose to keep free T4 at the upper end of or slightly above the normal range; avoiding fetal hypothyroidism matters as much as controlling the mother.
• Women with a history of Graves disease treated with radioiodine or surgery need their TSH-receptor antibodies (TRAb) checked early in pregnancy, with follow-up at 18 to 22 weeks and again at 30 to 34 weeks if raised, to assess risk of fetal and neonatal thyrotoxicosis.^[4]
• Postpartum thyroiditis occurs in the first year after delivery; it can present as transient hyper- or hypothyroidism and is a reminder to re-check TSH postpartum in women at risk.

Thyroid nodules found in pregnancy are evaluated as outside pregnancy (ultrasound, with fine-needle aspiration if indicated), but biopsies and surgery are usually deferred to the second trimester when possible, and thyroid cancer treatment in pregnancy is planned individualistically. The 2015 ATA adult thyroid nodule guidelines inform this, but the specifics belong to an endocrine and surgical review rather than this page.

Asthma affects about 3 to 6% of pregnancies and is one of the most common chronic diseases to complicate gestation.^[5] Its natural course is highly variable: roughly one third of women worsen, one quarter improve, and one third stay the same, with the same pattern tending to recur in later pregnancies.^[5] For many women the course mirrors their pre-pregnancy severity so long as treatment is continued.^[5]

The danger in asthma in pregnancy is not the drugs but the uncontrolled disease: asthma is associated with preterm birth, low birth weight, pre-eclampsia, placental abruption, and maternal ICU admission, with complications more common in moderate-to-severe disease.^[5] About 50% of exacerbations occur before 20 weeks, and severe first-trimester exacerbations may be linked to congenital malformations.^[5]

Most women have a diagnosis already. In a breathless pregnant woman without a diagnosis, asthma must be separated from normal pregnancy dyspnoea (common, especially in the first and second trimesters), upper respiratory infection, gastro-oesophageal reflux, pulmonary embolism, and pulmonary oedema. Forced expiratory volume in 1 second (FEV1) and forced vital capacity do not change with normal pregnancy, so spirometry and bronchodilator reversibility can be used. Severity is classified using daytime and night-time symptoms plus spirometry, using the framework of the National Asthma Education and Prevention Program (NAEPP) Working Group on Asthma and Pregnancy, which is the same approach referenced in ACOG Practice Bulletin No. 90 (2008).^[5][6]

Follow up includes symptom review, peak expiratory flow, and spirometry at prenatal visits, ideally with validated questionnaires such as the Asthma Control Test. Fractional exhaled nitric oxide (FeNO)-guided management reduced exacerbations in at least one prospective study, but is still being investigated.^[5]

The bottom line is continue the controller. Inhaled therapy during pregnancy has not been shown to be associated with congenital heart defects, cleft lip, stillbirth, neonatal hospitalisation, or respiratory distress syndrome in observational data.^[5]

• Inhaled corticosteroids (ICS) are first-line controller therapy and are safe. Inhaled corticosteroids do not appear to affect fetal adrenal function.^[5]
• Short-acting beta-2 agonists (SABA) are the reliever for all asthma in pregnancy.
• Long-acting beta-2 agonists (LABA) are added as in non-pregnant asthma when ICS alone is insufficient.
• Leukotriene receptor antagonists may be continued; evidence in pregnancy is more limited and individualised.
• Biologics such as omalizumab (and anti-IL-5 or dupilumab) may be continued if started before pregnancy; current guidelines advise not to start them during pregnancy because prospective data are limited.^[5]
• Allergen immunotherapy may be continued if started before conception, but should not be initiated in pregnancy because of anaphylaxis risk.^[5]

ACOG's immune-modulating therapeutics framework is consistent in spirit: low-risk medicines are continued or started when needed, higher-risk ones are avoided, and the decision rests on the balance of maternal and fetal risk.^[9]

Treatment is as for non-pregnant adults: oxygen to maintain maternal saturation above 95%, short-acting beta-agonist, inhaled ipratropium when needed, systemic glucocorticoids (oral or intravenous), and, for poor response, magnesium sulfate and terbutaline.^[5] Interpret arterial blood gases with caution: because pregnancy is a state of respiratory alkalosis, a normal partial pressure of carbon dioxide can mask exhaustion. Maintaining oxygenation is the priority.

Continue asthma therapy through labour. Hydration and good analgesia help. Avoid carboprost and other prostaglandin F2-alpha analogues (they can cause bronchoconstriction) and, for pain control, avoid morphine and meperidine (histamine release).^[5]

• Peak flow under 50% of personal best, or rising supplemental oxygen needs.
• Silent chest, cyanosis, drowsiness, or rising carbon dioxide on blood gas.
• Admission or any prior intubation or near-fatal attack.
• Poor adherence, ongoing smoking, or untreated comorbidities (rhinitis, reflux, obesity).

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects women of childbearing age and can involve kidneys, joints, skin, haematology, and nerves. Most women with SLE can have successful pregnancies, but the best outcomes come from planning conception in a quiet phase of disease and managing the pregnancy with both maternal-fetal medicine and rheumatology.^[8]

• Disease should be inactive before conception; active SLE, especially active lupus nephritis, strongly predicts flare, pre-eclampsia, growth restriction, and preterm birth.^[8][7]
• Review autoantibody profile (anti-dsDNA, complement, aPL), renal function and proteinuria, blood pressure, and any end-organ damage.
• Women with severe maternal risk (active nephritis; severe pulmonary, cardiac, renal, or neurologic disease; recent stroke; pulmonary hypertension) are generally advised against pregnancy.^[7]
• Baseline risks in SLE pregnancy (with or without APS): prematurity 25 to 35%, pre-eclampsia 10 to 15%, and HELLP 1.0 to 1.5%.^[8]
• Women with aPL or APS carry additional risks (see below).

• Hydroxychloroquine (HCQ) is recommended preconception and throughout pregnancy in SLE. It is associated with better disease control and fewer flares, and may reduce the risk of congenital heart block in anti-Ro/SSA-positive women.^[8][7]
• Low-dose aspirin is given from about 12 weeks' gestation to delivery for preeclampsia prophylaxis, preferably started by 16 weeks, especially in lupus nephritis or aPL-positive women.^[8][7]
• Glucocorticoids, azathioprine, ciclosporin A, and tacrolimus can be used to prevent or treat flares. Moderate-to-severe flares may need pulse intravenous steroids, intravenous immunoglobulin, or plasmapheresis.^[8]
• Methotrexate, mycophenolate, and leflunomide must be stopped before conception because of teratogenicity. Methotrexate 1 to 3 months before, mycophenolate at least 6 weeks before.^[7][8]
• Immune-modulating therapy decisions (biologics) are individualised with rheumatology.^[7][9]
• Blood pressure is controlled; ACOG's general framework is that low-risk immune drugs are continued, and higher-risk ones avoided.^[9]

• Supplemental fetal surveillance (umbilical and uterine Doppler, growth) particularly in the third trimester, to detect placental insufficiency and fetal growth restriction.^[8]
• Fetal echocardiography when anti-Ro/SSA or anti-La/SSB antibodies are positive, because of the ~0.7 to 2% risk of congenital heart block (16% recurrence if a previously affected child).^[8]
• Antenatal testing and serial growth scans.^[7]
• Disease activity is monitored with C3/C4, anti-dsDNA, renal function parameters, and validated SLE activity scores. Assessment of decreased complement and rising anti-dsDNA can distinguish a flare from pre-eclampsia.^[8]

These antibodies are associated with neonatal lupus and a low but serious risk of congenital heart block, worse in women who already have a child affected. Serial fetal echocardiography between 16 and 26 weeks is used in sensitised women. Fluorinated steroids are not routinely recommended for treatment of fetal heart block given unproven benefit and known maternal/fetal risks.^[7][8]

APS is an autoimmune disorder defined by clinical events (thrombosis and/or specific pregnancy morbidity) together with persistently positive antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta-2 glycoprotein I). In pregnancy APS presents predominantly as recurrent early pregnancy loss, fetal death in utero, or preterm delivery due to severe pre-eclampsia or placental insufficiency.

• High-risk aPL profile: lupus anticoagulant, multiple antibodies, or moderate-to-high titres.
• Coexisting SLE, prior thrombosis (arterial or venous), and previous adverse pregnancy outcomes increase risk.^[8]
• In primary or SLE-associated APS, pregnancy and preeclampsia rates approximate 25 to 35% and 10 to 20% (HELLP 3 to 5%).^[8]

• Obstetric APS without prior thrombosis: combination of low-dose aspirin plus prophylactic unfractionated or low-molecular-weight heparin (LMWH) reduces the risk of adverse pregnancy outcomes.^[7][8] LMWH is preferred in practice for ease of use and has shown comparable efficacy to unfractionated heparin.^[8]
• Thrombotic APS (prior thrombosis): therapeutic-dose unfractionated or LMWH is recommended, with low-dose aspirin.^[7][8]
• SLE with aPL but no APS (no clinical event): low-dose aspirin alone.^[7][8]
• High-risk or refractory cases: additional regimens such as prednisolone 10 mg/day in the first trimester, intravenous immunoglobulin, or plasmapheresis can be considered in selected women (for example previous thrombosis, triple positivity).^[8]
• Women with aPL without any events may in some classifications receive aspirin alone, or no treatment, depending on titre and risk; low-dose aspirin alone is a reasonable default for aPL-positive women without APS.^[7][8]

• Start aspirin and heparin early (as soon as pregnancy is confirmed, or preconceptionally for heparin where indicated).
• Stop heparin at least 12 hours before delivery or procedures; resume after.
• Hydroxychloroquine may help in SLE-associated APS pregnancies, but data are insufficient to recommend it routinely for primary APS.^[8]
• Keep close fetal and placental surveillance (Doppler, growth, blood pressure) because of high rates of fetal growth restriction and late loss.

• Epilepsy: folate 5 mg is cheap and effective and should be given to every woman with epilepsy planning pregnancy. Where drug choice is limited, avoid valproate, use the safest available agent at the lowest dose, and arrange preconception counselling with the physician who knows the patient.
• Thyroid: a TSH test is widely available and is the single most useful test; treat overt hypothyroidism with levothyroxine, increase the dose in pregnancy, and re-check TSH at 4 to 6 weeks. In iodine-deficient regions, iodised salt and targeted iodine are the public-health priority.
• Asthma: inhaled low-dose ICS and a SABA are the minimum; teaching inhaler technique and adherence prevents more harm than any one drug choice. Peak-flow meters and spacer devices are cheap and underused.
• SLE/APS: renal function, urine dipstick, blood pressure, and fetal growth scans are the backbone. Hydroxychloroquine and low-dose aspirin are inexpensive; heparin costs more but matters most in thrombotic or obstetric APS. Where rheumatology and high-resolution ultrasound are unavailable, refer early for the highest-risk women.

• Planned pregnancy with preconception counselling improves outcomes in epilepsy, thyroid disease, asthma, and SLE/APS.
• Epilepsy: prefer lamotrigine or levetiracetam, avoid valproate and usually phenobarbitone/phenytoin; monotherapy at the lowest dose; folic acid 5 mg/day; 1 mg intramuscular vitamin K to the neonate if an enzyme-inducing AED is used.
• Thyroid: treat overt hypothyroidism with levothyroxine; increase dose by 20 to 30% early, re-check TSH every 4 weeks in early pregnancy, separate from iron/calcium by 4 hours; use local trimester-specific TSH ranges, or an upper limit of 4.0 mIU/L first trimester (ATA 2017). Treat TSH above 10; do not treat at 2.5 or less; between 2.5 and 10 depends on TPO-antibody status. ^[4]
• Asthma: about a third of women worsen; continue inhaled corticosteroids; SABA as reliever; treat exacerbations as in non-pregnant adults; avoid carboprost, morphine, and meperidine.
• SLE: aim for remission before conception; continue hydroxychloroquine; stop methotrexate (1 to 3 months) and mycophenolate (at least 6 weeks) before conception; low-dose aspirin from 12 weeks; fetal surveillance for growth restriction; fetal echocardiography if anti-Ro/SSA is positive. ^[7]
• APS: low-dose aspirin plus heparin (prophylactic for obstetric APS, therapeutic for thrombotic APS); aspirin alone for aPL-positive women without APS.
• Most low-risk drugs are continued in pregnancy; high-risk drugs are stopped before conception.
• SLE carries 25 to 35% prematurity and 10 to 15% pre-eclampsia; APS similar prematurity with higher pre-eclampsia and HELLP rates.

• Obstetric conditions in pregnancy
• Epilepsy and anti-epileptic drugs (pharmacology)
• Thyroid disorders and levothyroxine (endocrinology)
• Asthma diagnosis and stepwise treatment (respirology)
• Systemic lupus erythematosus (rheumatology)
• Antiphospholipid syndrome (haematology/rheumatology)
• Pre-eclampsia and hypertensive disorders of pregnancy
• Folic acid and neural tube defects