Overview
Maternal medical conditions are among the most significant contributors to adverse perinatal outcomes. The four conditions addressed here, diabetes mellitus, thyroid disease, epilepsy, and cardiac disease, require multidisciplinary antenatal care, pre-conception optimisation where possible, and condition-specific intrapartum and postnatal management strategies.
Diabetes Mellitus in Pregnancy
Classification and Diagnosis
- Pre-existing type 1 diabetes mellitus (T1DM)
- Pre-existing type 2 diabetes mellitus (T2DM)
- Gestational diabetes mellitus (GDM): diabetes occurring for the first time in pregnancy, clearly not pre-existing; usually diagnosed in the second or third trimester
GDM is diagnosed using a 75-g OGTT (single abnormal value sufficient). Australia follows IADPSG/WHO criteria:
| Parameter | IADPSG/WHO Threshold | NICE Threshold |
|---|---|---|
| Fasting plasma glucose | $\geq 5.1$ mmol/L | $\geq 5.6$ mmol/L |
| 1-hour plasma glucose | $\geq 10.0$ mmol/L | , |
| 2-hour plasma glucose | $\geq 8.5$ mmol/L | $\geq 7.8$ mmol/L |
Timing of OGTT:
- High-risk women (previous GDM, BMI $> 35$, maternal age $> 40$, first-degree family history of diabetes): fasting glucose or HbA1c at booking, OGTT at 14-20 weeks, repeat at 26-29 weeks if initial test is normal
- All other women: OGTT at 26-28 weeks
Not all diabetes presenting in pregnancy is gestational, screening may identify undiagnosed T2DM or monogenic diabetes.
Pathophysiology and Fetal Risks
Pregnancy induces progressive insulin resistance (mediated by placental lactogen, cortisol, progesterone), peaking in the third trimester; insulin requirements increase by 50-100% in T1DM. In late pregnancy, insulin absorption is delayed, women may need to extend the interval between short-acting insulin injection and meals. Maternal glucose crosses the placenta freely; insulin does not. Fetal hyperinsulinaemia causes macrosomia and, at cord clamping, rebound neonatal hypoglycaemia.
Rate of congenital malformations in pre-existing diabetes is at least doubled, directly related to glycaemic control during organogenesis. Anomalies include:
- Cardiac defects (most common)
- Skeletal malformations
- Neural tube defects
- Caudal regression syndrome (rare but specifically associated with diabetes)
Other fetal/neonatal risks: polyhydramnios, stillbirth, macrosomia, shoulder dystocia, birth injury, neonatal jaundice, respiratory distress, longer-term obesity and T2DM risk in offspring.
Maternal risks: pre-eclampsia, hypoglycaemia (early pregnancy awareness is impaired), worsening microvascular complications, retinopathy acceleration. Pregnancy can accelerate retinopathy, screen in the first and third trimesters, and in the second trimester if retinopathy is present at the outset.
Diabetic ketoacidosis (DKA): occurs at lower blood glucose thresholds than in non-pregnant individuals; carries a 40-50% fetal mortality rate. Ketone self-monitoring should be taught at the outset of pregnancy.
Pre-conception Counselling for Pre-existing Diabetes
- Optimise glycaemic control before conception (HbA1c $< 48$ mmol/mol [$6.5\%$] if achievable without excessive hypoglycaemia); congenital malformations can occur from 5-6 weeks after conception, underscoring the importance of pre-pregnancy counselling
- High-dose folic acid 5 mg/day from at least 3 months pre-conception
- Cease ACE inhibitors, ARBs, statins, GLP-1 receptor agonists, and oral antidiabetic drugs
- Screen for and manage microvascular complications (retinopathy, nephropathy, neuropathy)
- Structured diabetes education
Insulin Management in Pregnancy
T1DM: Basal-bolus multiple daily injection regimens or continuous subcutaneous insulin infusion (CSII/pump). In early pregnancy, nausea and impaired hypoglycaemia awareness increase hypoglycaemia risk (fetuses tolerate maternal hypoglycaemia relatively well). Target glucose ranges: fasting 4.0-5.3 mmol/L, 1-hour postprandial $< 7.8$ mmol/L.
T2DM: Initiate insulin antenatally; oral antidiabetic agents should be discontinued. Metformin may be continued in selected cases with informed consent regarding uncertain long-term metabolic effects in offspring (higher adiposity in children exposed in utero).
GDM:
- Initial: dietary and lifestyle modification, low glycaemic index carbohydrates, reduced sugar, appropriate portions, daily exercise
- If glycaemic targets not met within 1-2 weeks: commence pharmacological therapy
- Insulin is first-line; metformin is an alternative if insulin is declined or cannot be reliably taken
- Glyburide (glibenclamide) is not recommended in Australia
Intrapartum and Postnatal Management
- Fetal surveillance: growth scans and tests of fetal wellbeing in the third trimester; anomaly USS with four-chamber heart view and outflow tracts at 18-20 weeks; low-dose aspirin 150 mg/day from 12 weeks to reduce pre-eclampsia risk
- Timing of birth: most pre-existing diabetes delivered before term (induction or caesarean section); caesarean section reserved for estimated fetal weight $\geq 4500$ g or standard obstetric indications
- Intrapartum glycaemic control: variable-rate intravenous insulin infusion (VRIII); CSII increasingly used as alternative in specialist centres. Target intrapartum glucose 4.0-7.0 mmol/L (tight control minimises neonatal hypoglycaemia from fetal hyperinsulinaemia)
- Postnatal: insulin requirements fall rapidly to pre-conception levels within hours of delivery; breastfeeding may lower requirements further. Neonatal glucose monitoring; early feeding encouraged; breastfeeding preferred
- GDM follow-up: 75-g OGTT at 6-12 weeks postpartum to exclude persistent diabetes; HbA1c at 3 months postpartum also recommended to exclude pre-existing T2DM. Annual HbA1c thereafter; 50% risk of T2DM within 10 years (some sources cite 7-10-fold increased lifetime risk). Lifestyle modification reduces progression; uptake of postnatal screening and interventions remains low
Thyroid Disease in Pregnancy
Physiological Changes
Pregnancy increases thyroxine-binding globulin (TBG), raising total $T_4$ and $T_3$. hCG has TSH-like activity, suppressing TSH in the first trimester. Trimester-specific reference ranges must be used for all thyroid function tests.
Hypothyroidism
Affects approximately 1% of pregnancies (overt); subclinical hypothyroidism affects ~5% of the general population and is more common in females with antithyroid antibodies. Severe untreated hypothyroidism is associated with infertility, miscarriage, fetal loss, and impaired fetal neurodevelopment. Very little thyroxine crosses the placenta, maternal replacement does not cause fetal thyrotoxicosis.
Levothyroxine dose requirements increase by 25-50% during pregnancy, often from as early as week 5. Women with known hypothyroidism should have thyroid function tested at the first prenatal visit and each trimester.
TSH targets and treatment thresholds:
| Scenario | Action |
|---|---|
| TSH $< 4.0$ mU/L using pregnancy-specific range (after 7 weeks) | Usually no dose change required if previously euthyroid |
| TSH $> 4.0$ mU/L | Commence or increase levothyroxine |
| Subclinical hypothyroidism | Replace if TSH $> 4.0$ mU/L; evidence for benefit at lower thresholds is insufficient |
There is no evidence supporting the older recommendation of TSH $< 2.5$ mU/L as a universal pregnancy target.
Post-delivery: revert to pre-pregnancy levothyroxine dose; recheck TSH at 6 weeks postpartum.
Postpartum thyroiditis: prevalence 5-7%; more common with family history of hypothyroidism, thyroid peroxidase antibodies, and type 1 diabetes (3-fold increased risk). Typically presents 3-4 months postpartum. Transient hyperthyroid phase followed by hypothyroid phase. Most recover completely; a proportion progress to permanent hypothyroidism. High risk of recurrence in future pregnancies.
Hyperthyroidism and Graves' Disease
Graves' disease affects approximately 0.2% of pregnancies. Untreated hyperthyroidism is associated with miscarriage, fetal growth restriction, preterm delivery, and fetal/neonatal thyroid dysfunction. Disease often improves during pregnancy (TSI titres decline) but postpartum flare is common. Gestational thyrotoxicosis (hCG-mediated, particularly with hyperemesis gravidarum or multiple pregnancy) is a differential in the first trimester, thyrotropin receptor antibodies (TRAb) are the most useful test to establish Graves' disease.
Antithyroid drug (ATD) management by trimester:
| Drug | First Trimester | After 14-16 Weeks | Key Concerns |
|---|---|---|---|
| Propylthiouracil (PTU) | Preferred (lowest effective dose) | Switch to carbimazole (PTU hepatotoxicity risk) | Rare maternal liver failure; fetal hypothyroidism/goitre at high doses |
| Carbimazole/methimazole | Avoid (teratogenic) | Preferred | Aplasia cutis, choanal atresia, tracheoesophageal fistula (methimazole embryopathy) |
Recommended approach:
- PTU in the first trimester at the lowest effective dose; free $T_4$ maintained at or just above the upper limit of the pregnancy reference range (fetal thyroid is more sensitive to ATDs than maternal thyroid)
- Switch to carbimazole at 14-16 weeks at ratio 15-20 mg PTU : 1 mg methimazole
- For women euthyroid on low doses (carbimazole $< 5$-10 mg/day or PTU $< 100$-200 mg/day), consider discontinuation with close monitoring after evaluating TRAb, goitre size, duration of therapy, and recent TFTs
- High-dose ATD requirement ($> 20$ mg/day methimazole or $> 300$ mg/day PTU) risks fetal goitrous hypothyroidism
- ATD withdrawal is often possible in the third trimester as TSI decline; however, postpartum flare is common
- Switching from one ATD to the other before or during pregnancy is not otherwise recommended, as it risks compromising disease control without evidence of improved outcomes
- Breastfeeding is safe on low maintenance doses (carbimazole $< 15$ mg/day or PTU $< 150$ mg/day)
- Beta-blockers are safe for symptomatic control if required; labetalol is preferred, used at low doses for short periods
Radioiodine is absolutely contraindicated in pregnancy and breastfeeding.
TRAb/TSI and fetal thyrotoxicosis:
- Fetal/neonatal thyrotoxicosis occurs in 2-10% of Graves' pregnancies via transplacental passage of TRAb; neonatal mortality ~16%
- Complications: tachycardia ($> 160$ bpm), goitre, growth restriction, advanced bone age, craniosynostosis, intrauterine death
- Measure TRAb at the beginning of the third trimester (approximately 28-30 weeks), especially if ATD dose requirements are high
- If TRAb is elevated (TBII $\geq 40$ U/L or TSAb $\geq 300\%$), assess fetus for signs of thyrotoxicosis
- ATDs given to the mother treat the fetal thyroid and may be needed for 1-3 months after delivery until maternal antibodies clear from the neonate's circulation
- Previous neonate with hyperthyroidism: TRAb assay early in pregnancy
Epilepsy in Pregnancy
Overview
Epilepsy affects 0.6% of pregnant women. Seizure frequency increases in ~37%, decreases in ~13%, and is unchanged in ~50%. Women with poorly controlled epilepsy and those who stop medication are at highest risk of increased frequency. The fetus usually tolerates seizures without long-term sequelae, but status epilepticus carries a significant risk of fetal death.
Antiepileptic Drug (AED) Teratogenicity
Background rate of major congenital anomalies (MCAs) is ~2-3%; women with epilepsy on AEDs: ~4-9% (monotherapy). Women with epilepsy not on AEDs still have a higher baseline risk than the general population. Polypharmacy and higher doses substantially increase risk. Dividing doses to reduce peak blood levels may be beneficial.
| Antiepileptic Drug | Teratogenic Risk | Notable Concerns |
|---|---|---|
| Valproate | Highest ($\geq 10\%$ MCAs; neurodevelopmental risk even higher) | Neural tube defects, facial clefts, cardiac defects, fetal valproate syndrome, autism spectrum disorder, intellectual disability |
| Carbamazepine | Moderate | Neural tube defects (~1%), vitamin K deficiency (enzyme inducer) |
| Phenytoin | Moderate | Fetal hydantoin syndrome, vitamin K deficiency |
| Phenobarbitone | Moderate | Neonatal withdrawal, vitamin K deficiency |
| Topiramate | Moderate | Oral clefts, growth restriction |
| Lamotrigine | Low-moderate | Oral clefts at higher doses; generally preferred in women of reproductive age |
| Levetiracetam | Low (current evidence) | Limited long-term neurodevelopmental data |
Valproate must be avoided in women of childbearing potential unless no other effective treatment exists, with a formal pregnancy prevention programme documented.
Enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbitone, topiramate, oxcarbazepine) accelerate vitamin K metabolism, increasing risk of haemorrhagic disease of the newborn, administer neonatal vitamin K (phytomenadione) at birth.
Folic Acid Supplementation
All women with epilepsy on AEDs: high-dose folic acid 5 mg/day, commencing at least 3 months before conception and continuing throughout the first trimester (minimum). This reduces the risk of neural tube defects and some other structural anomalies.
Monitoring and Antenatal Care
- Pre-conception: review AED regimen; rationalise to monotherapy at lowest effective dose; any change ideally undertaken before pregnancy
- Lamotrigine clearance increases significantly in pregnancy (up to 50-100%), requiring dose escalation and therapeutic drug monitoring
- Anomaly USS at 18-20 weeks with detailed fetal survey
- Ideally all AEDs continued unless clear benefit to stopping; risk of stopping medication = increased seizure frequency
Seizure Management in Labour
- Continue AEDs throughout labour (oral or IV formulations as required)
- Avoid seizure triggers: hyperventilation, sleep deprivation, dehydration, prolonged fasting
- Breakthrough tonic-clonic seizure in labour: IV benzodiazepine (lorazepam 0.1 mg/kg or diazepam per unit protocol), exclude eclampsia if first seizure in pregnancy
- Epidural analgesia: reduces hyperventilation and fatigue; generally recommended in women with epilepsy
- Mode of delivery: vaginal birth appropriate in most; caesarean section for obstetric indications or refractory convulsive status epilepticus
- Increased midwifery supervision postpartum if mother is sedated; safe infant-care counselling regarding bathing and co-sleeping risks
Cardiac Disease in Pregnancy
Physiological Changes
Cardiac output increases 30-50% by 28-32 weeks (increased heart rate + stroke volume). Systemic vascular resistance falls. These haemodynamic changes significantly stress the diseased heart, with nadir of SVR at ~20-24 weeks and largest fluid shifts at delivery.
Risk Classification
WHO Modified Classification of Maternal Cardiovascular Risk (mWHO), the primary clinical framework:
| mWHO Class | Risk | Examples | Management |
|---|---|---|---|
| I | No detectable increased risk | Small ASD/VSD, repaired simple lesions, mild PS | Antenatal care with occasional specialist review |
| II | Small increased risk | Unrepaired ASD/VSD, repaired ToF, controlled arrhythmias | Specialist cardiac-obstetric review each trimester |
| II-III | Moderate risk | Mild LV impairment, Marfan syndrome without aortic dilation, moderate MS | Multidisciplinary team (MDT) care |
| III | Significantly increased risk; expert care required | Moderate-severe LV impairment, Fontan circulation, severe aortic dilation, mechanical prosthetic valves | Tertiary centre MDT; pregnancy may be inadvisable |
| IV | Extremely high risk; pregnancy contraindicated | Severe PAH/Eisenmenger syndrome, severe systemic ventricular dysfunction (EF $< 30\%$), severe symptomatic AS, PPCM with residual impairment | Pregnancy strongly advised against; termination discussed |
CARPREG II score provides quantitative risk prediction for adverse maternal cardiac events; predictors include prior cardiac events or arrhythmia, NYHA class $> 2$ or cyanosis, mechanical valve, pulmonary hypertension, coronary artery disease, high-risk valve disease, and late pregnancy assessment. Score $\geq 4$ predicts ~40% event rate.
Mechanical Heart Valves and Anticoagulation
All mechanical valves require continuous anticoagulation throughout pregnancy; no regimen is without risk.
| Anticoagulation Option | Benefits | Risks |
|---|---|---|
| Warfarin throughout | Lowest maternal thromboembolic risk | Warfarin embryopathy (weeks 6-12): nasal hypoplasia, stippled epiphyses, CNS defects; fetal haemorrhage |
| Warfarin $\leq 5$ mg/day | Embryopathy risk substantially reduced | May be inadequate in higher-risk valve positions |
| LMWH with anti-Xa monitoring | Avoids warfarin embryopathy | Higher maternal valve thrombosis risk; requires rigorous monitoring |
| Unfractionated heparin (UFH) | Reversible; used peripartum | Highest thromboembolic risk if used throughout pregnancy |
Current recommendations (ESC/RANZCOG):
- Warfarin dose $\leq 5$ mg/day: continue warfarin throughout including first trimester; switch to LMWH or UFH from 36 weeks
- Warfarin dose $> 5$ mg/day: switch to LMWH weeks 6-12 (peak embryopathy period), then resume warfarin second trimester onward
- LMWH must be dose-adjusted and monitored with anti-Xa levels (target 0.8-1.2 U/mL for mechanical mitral valve, 4 hours post-dose)
- Switch to UFH at 36 weeks for ease of reversal at delivery
- Stop warfarin and commence UFH once labour begins
High-Risk Lesions: Peripartum Management
- Pulmonary arterial hypertension (PAH)/Eisenmenger syndrome: maternal mortality 30-50%; pregnancy contraindicated (mWHO IV); if pregnancy continues, deliver at 32-34 weeks in tertiary centre with intensive haemodynamic monitoring
- Severe aortic stenosis: avoid tachycardia and vasodilation; balloon valvuloplasty may be considered pre-delivery in severe symptomatic cases
- Peripartum cardiomyopathy (PPCM): new LV systolic dysfunction (EF $< 45\%$) in the last month of pregnancy or within 5 months postpartum without prior cardiac disease; management includes bromocriptine (to inhibit prolactin-mediated myocardial damage), standard heart failure therapy (avoid ACE inhibitors/ARBs antenatally; use postnatally), and prophylactic anticoagulation
- Marfan syndrome with aortic root $\geq 45$ mm: elective caesarean section recommended; surgical repair before pregnancy preferred if root $\geq 45$ mm
- Intrapartum principles for high-risk lesions: epidural analgesia to reduce sympathetic surges and preload; avoid prolonged active second stage (passive descent + assisted delivery); invasive haemodynamic monitoring as required; MDT including obstetric anaesthesia, cardiology, and neonatology present at delivery
Summary Counselling Points
| Condition | Key Counselling Messages |
|---|---|
| Pre-existing diabetes | Pre-conception HbA1c optimisation; folic acid 5 mg pre-conception; cease teratogenic medications; anomaly USS 18-20 weeks; DKA risk; stillbirth risk; timing of birth |
| GDM | Dietary/lifestyle first; insulin preferred if pharmacotherapy needed; 50% lifetime T2DM risk; postnatal OGTT at 6-12 weeks; annual HbA1c; lifestyle modification |
| Hypothyroidism | Increase levothyroxine early (from week 5); TSH target $< 4.0$ mU/L (no evidence for $< 2.5$ mU/L); safe breastfeeding; revert to pre-pregnancy dose postpartum |
| Graves' disease | PTU first trimester then switch to carbimazole; ATD teratogenicity; TRAb monitoring third trimester; fetal hyperthyroidism signs; postpartum flare; radioiodine contraindicated |
| Epilepsy | Valproate avoidance; folic acid 5 mg pre-conception; monotherapy at lowest effective dose; AED teratogenicity data; vitamin K for neonate; do not stop AEDs without specialist review |
| Cardiac disease | mWHO classification determines intensity of care; contraception for mWHO IV; MDT tertiary planning; anticoagulation risks (maternal vs. fetal); mode and timing of delivery |
Medicolegal and Ethical Considerations
- Valproate: Prescribers must document counselling regarding teratogenicity and neurodevelopmental risk (autism, intellectual disability), ensure a pregnancy prevention programme is in place, and obtain informed consent for continuation. TGA and RANZCOG have issued specific mandatory guidance.
- Mechanical valve anticoagulation: Informed consent must document maternal thromboembolic risk versus fetal embryopathy risk for each anticoagulation strategy. Shared decision-making with detailed documentation is essential; both pathways carry inherent irreducible risk.
- Cardiac disease and pregnancy contraindication: For mWHO class IV, the clinician must clearly communicate the risk of maternal mortality. If the patient continues the pregnancy, tertiary referral and intensive MDT involvement are mandatory. Termination of pregnancy must be offered without coercion.
- GDM over-diagnosis: Use of IADPSG criteria substantially increases GDM prevalence (estimates 15-20% of pregnancies in some populations), with implications for medicalisation, patient anxiety, and healthcare resource allocation, an ongoing area of clinical and ethical debate within RANZCOG.
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