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Pre-Conception Counselling — PDCC Review

Note: Williams Obstetrics is not available in this library. The content below is drawn from Creasy & Resnik's MFM — the gold-standard MFM reference used alongside Williams in postgraduate training — supplemented by medical genetics texts.

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🔴 Review Page 1 — THALASSEMIA

Background

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Carrier Frequencies (High-Risk Ethnicities)

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Preconception Counselling Points

• All women from high-prevalence populations (Mediterranean, Middle Eastern, Southeast Asian, West Indian, African) — offer carrier screening before pregnancy
• CBC + RBC indices first; if MCV <80 fL with normal iron → proceed to Hb electrophoresis / HPLC
• Both partners should be screened sequentially (concurrent if time-constrained)

• β-Thalassaemia major: lifelong transfusion dependence or haematopoietic stem cell transplant (HSCT) — only cure
• Hb Bart's hydrops fetalis: typically lethal in utero or shortly after birth; associated with severe maternal morbidity (pre-eclampsia, PPH)
• Thalassaemia trait/HbH disease: generally compatible with normal life

• Prenatal diagnosis (CVS at 10–13 weeks or amniocentesis at 15–20 weeks) for at-risk couples
• Pre-implantation Genetic Testing (PGT-M) via IVF — allows selection of unaffected embryos
• Donor gametes
• Accept risk and continue pregnancy with prenatal testing

• CBC, peripheral blood film, serum ferritin (exclude iron deficiency before interpreting MCV)
• Hb electrophoresis / HPLC for both partners
• DNA mutation analysis if HPLC ambiguous (confirms α0 deletion genotype — critical for Hb Bart's risk)
• Liver iron assessment if patient has thalassaemia major (on transfusions): MRI T2*

• Cardiac MRI T2* (iron-related cardiomyopathy — high-risk in pregnancy)
• LFTs, viral hepatitis screen (transfusion-associated)
• Endocrine assessment: thyroid, glucose tolerance, fertility (hypothalamic-pituitary dysfunction from iron)
• Stop chelation (deferoxamine/deferasirox) pre-conception: teratogenic
• Splenectomy status → thrombotic risk in pregnancy
• Folate 5 mg/day

• Thalassaemia major: increased risk of cardiac failure, gestational diabetes, intrauterine growth restriction (IUGR), caesarean delivery
• Thalassaemia trait: essentially normal obstetric outcome

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🔴 Review Page 2 — SICKLE CELL DISEASE (SCD)

Background

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Carrier Frequency

• African-American: 1 in 20 for HbS carrier (sickle cell trait — HbAS)
• Carrier state (HbAS) confers malaria protection — founder advantage
• HbSS affects ~1 in 400 African-Americans

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Preconception Counselling Points

• All women of African, Mediterranean, Middle Eastern, South/Southeast Asian descent
• CBC + Hb electrophoresis (not just solubility test — misses HbC, β-thal)
• If patient is HbAS → screen partner

• Generally benign; does NOT carry the pregnancy risks of HbSS
• Increased risk of UTI and haematuria in pregnancy
• Counsel that trait ≠ disease

• Painful vaso-occlusive crises (often worsen in pregnancy)
• Acute chest syndrome — leading cause of maternal mortality in SCD
• Pulmonary hypertension (pre-existing) — high maternal mortality; screen with echocardiogram
• Pre-eclampsia, IUGR, preterm labour, stillbirth (all significantly elevated)
• Infections: pneumococcal, osteomyelitis, pyelonephritis
• Venous thromboembolism

• Echocardiogram — pulmonary hypertension (TRV ≥2.5 m/s = high risk)
• CBC, reticulocyte count, LDH, bilirubin (haemolytic baseline)
• Renal function (sickle nephropathy in 30%)
• Urinalysis and urine culture
• Ophthalmology — sickle retinopathy
• Iron studies (if on chronic transfusion — assess iron overload)
• Hepatitis B, C, HIV (transfusion-related)
• Pulmonary function if history of acute chest syndrome

• Stop hydroxyurea at least 3 months before conception (teratogenic in animal studies; limited human data, but standard practice is to discontinue)
• Folic acid 5 mg/day (chronic haemolysis → folate depletion)
• ACE inhibitors/ARBs (for nephropathy) — STOP, teratogenic
• Update pneumococcal, meningococcal, Hib, influenza vaccines
• Penicillin prophylaxis should be continued

• Prenatal diagnosis (CVS or amniocentesis)
• PGT-M via IVF
• Cord blood banking at delivery (HSCT — only cure)

• Maternal mortality remains elevated but has improved significantly with specialised care
• SCD is NOT an absolute contraindication to pregnancy
• Requires multidisciplinary team: obstetrician, haematologist, MFM specialist

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🔴 Review Page 3 — CYSTIC FIBROSIS (CF)

Background

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Carrier Frequencies

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Preconception Counselling Points

• ACOG: offer CF carrier screening to ALL women considering pregnancy regardless of ethnicity (pan-ethnic)
• Standard panel: 23 ACMG-recommended pathogenic variants (detects most common alleles)
• Expanded panels available but increase variants of uncertain significance (VUS)

• A negative carrier screen reduces risk but does NOT eliminate it (not all >1300 alleles are on panels)
• Residual carrier risk after negative: ~1 in 200 (Caucasian) to 1 in 476 (Asian)
• Important counselling point — must be communicated

• Pulmonary function: FEV₁ <50% predicted — significantly increased maternal mortality risk; strongly advise against pregnancy
• FEV₁ 50–70%: intermediate risk, proceed only after thorough counselling
• FEV₁ >70%: generally tolerable
• Pulmonary hypertension: assess with echocardiogram (high mortality)
• Nutritional status: BMI, fat-soluble vitamins (A, D, E, K), pancreatic enzyme replacement
• Diabetes (CF-related diabetes — CFRD): assess HbA1c, glucose tolerance
• Renal function (aminoglycoside nephrotoxicity history)
• Hepatic involvement (cirrhosis, portal hypertension)
• Cardiac function (cor pulmonale)

• Ivacaftor/lumacaftor/elexacaftor (CFTR modulators) — limited safety data in pregnancy; discuss risk/benefit
• Tobramycin inhaled: monitor carefully
• Colistin: use only if necessary
• ADEK vitamins should be continued (fat-soluble vitamin deficiency risk)
• Folic acid supplementation

• Males with CF: ~98% have congenital bilateral absence of vas deferens (CBAVD) → obstructive azoospermia → infertility (but sperm can be retrieved via TESE/PESA)
• Females with CF: reduced fertility (thickened cervical mucus, anovulation in severe disease), but majority are fertile
• Partner of a CF patient: screen for CFTR mutations; if male partner has CBAVD, test for CFTR mutations even if no CF diagnosis

• Prenatal diagnosis (CVS, amniocentesis)
• PGT-M
• Adoption

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🔴 Review Page 4 — DIABETES MELLITUS (PRE-GESTATIONAL)

Background

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Preconception Counselling Points

• Target HbA1c <6.5% (ideally ≤6%) before conception
• HbA1c >10%: pregnancy is strongly discouraged until glycaemia is optimised
• Poor control is directly associated with:
  • Congenital anomalies (neural tube defects, cardiac defects, sacral agenesis — caudal regression syndrome pathognomonic; risk ↑ 3–5× above background)
  • Miscarriage (risk proportional to HbA1c)
  • Stillbirth

• Metformin: acceptable in pregnancy (Type 2) — can continue or switch to insulin
• Insulin: preferred agent in pregnancy; switch from oral agents if on sulphonylureas
• ACE inhibitors / ARBs (diabetic nephropathy): STOP — teratogenic (renal dysgenesis, oligohydramnios)
• Statins: STOP — teratogenic (animal data); switch to bile acid sequestrants if hyperlipidaemia needs treatment
• SGLT2 inhibitors: STOP — safety data in pregnancy insufficient
• GLP-1 agonists: STOP before conception

• Folic acid 5 mg/day (high-dose, given ↑ neural tube defect risk) — start at least 3 months before conception
• Vitamin D assessment and correction

• Congenital malformations (cardiac, NTD, caudal regression) — 3–5× general population
• Macrosomia → shoulder dystocia, operative delivery
• Pre-eclampsia: 4–10× increased risk
• Polyhydramnios
• Preterm labour
• Stillbirth (especially if poor control in third trimester)
• Neonatal hypoglycaemia, respiratory distress, hypocalcaemia, polycythaemia

• Severe ischaemic heart disease (MI in past 6–12 months, unstable angina)
• Severe pulmonary hypertension
• Renal failure on dialysis (relative — can proceed with ESRD if transplanted)

• Fasting glucose: 3.5–5.9 mmol/L
• 1-hour post-prandial: <7.8 mmol/L
• HbA1c: aim <6.5% (monitor every trimester)

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🔴 Review Page 5 — CHRONIC KIDNEY DISEASE (CKD)

Background

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Preconception Counselling Points

• Pre-eclampsia: up to 30–40% (even higher with proteinuria/hypertension)
• Fetal growth restriction (IUGR): related to reduced uteroplacental perfusion
• Preterm delivery: 50–70% in Stage 4–5
• Permanent renal function loss: ~10% of Stage 3 patients lose significant GFR; up to 40% in Stage 4
• Neonatal outcomes: prematurity-related morbidity proportional to maternal GFR

• Target BP: <140/90 mmHg (ideally <130/80 in proteinuric CKD)
• Stop ACE inhibitors/ARBs (first choice in CKD — but teratogenic; causes fetal renal tubular dysplasia, skull ossification defects, oligohydramnios)
• Switch to: methyldopa, labetalol, nifedipine (pregnancy-safe antihypertensives)

• Baseline 24-hour protein (or spot PCR) essential before pregnancy — becomes reference for pre-eclampsia surveillance
• Significant proteinuria (>1 g/day) is an independent risk factor for worse outcome
• Stopping ACEi/ARB → proteinuria will increase; counsel patient

• Counsel to wait ≥1–2 years post-transplant before conception
• Stable graft function (creatinine <1.5 mg/dL, minimal proteinuria)
• Immunosuppression review: stop MMF, switch to azathioprine
• Rejection risk slightly increased in pregnancy
• Outcomes generally good if above criteria are met

• Folic acid 5 mg/day
• Iron and EPO if anaemia (EPO is safe in pregnancy)
• Vitamin D correction
• Calcium supplementation if on dialysis

• Active nephritis/lupus flare in past 6 months
• Uncontrolled hypertension
• eGFR <30 mL/min and deteriorating (accelerated loss of remaining nephrons likely)
• Severe anaemia not corrected

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Quick Reference Summary Table

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