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pres.title = "First Trimester Pre-Eclampsia Screening";

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// ─── SLIDE 1: TITLE ───────────────────────────────────────────────────────
{
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  titleSlide(s,
    "First Trimester Pre-Eclampsia\nScreening",
    "A Comprehensive Clinical Overview — Pathophysiology · Biomarkers · Algorithms · Prevention"
  );
}

// ─── SLIDE 2: OVERVIEW OF PREECLAMPSIA ───────────────────────────────────
{
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  headerBodySlide(s, "Overview: What is Pre-Eclampsia?", [
    "New-onset hypertension (≥140/90 mmHg on two occasions ≥4 hours apart) after 20 weeks' gestation",
    "Accompanied by proteinuria (≥300 mg/24h, PCR ≥0.3, or dipstick 2+) OR evidence of end-organ dysfunction",
    "Proteinuria is NOT required if thrombocytopenia (<100,000/µL), elevated liver enzymes (>2× ULN), AKI (creatinine >1.1 mg/dL), pulmonary oedema, or new cerebral/visual disturbances are present",
    "Classified as: Pre-eclampsia (without severe features) vs. Pre-eclampsia with Severe Features",
    "ISSHP 2021 & ACOG: dropped the term 'mild'; all PE carries morbidity risk",
    "Incidence: ~3–5% of all pregnancies worldwide; affects ~8 million women per year",
    "Major cause of maternal and perinatal morbidity/mortality globally",
    "Early-onset PE (<34 weeks) = most severe form; late-onset PE (≥37 weeks) = most common form"
  ], "Source: Creasy & Resnik MFM, 8e; ISSHP 2021; ACOG Practice Bulletin");
}

// ─── SLIDE 3: EPIDEMIOLOGY & IMPACT ──────────────────────────────────────
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    { label: "Global incidence of PE", value: "3–5%" },
    { label: "Women affected globally/year", value: "8 million" },
    { label: "Maternal deaths attributable to PE/year", value: "~76,000" },
    { label: "Perinatal deaths attributable to PE/year", value: "~500,000" },
    { label: "Risk in twin pregnancies", value: "10–20%" },
    { label: "Risk reduction with aspirin (preterm PE)", value: "62%" },
  ]);
}

// ─── SLIDE 4: CLASSIFICATION & TIMING ────────────────────────────────────
{
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    "Classification of Pre-Eclampsia",
    [
      "Early-onset PE: delivery < 34 weeks",
      "Preterm PE: delivery < 37 weeks",
      "Late-onset / Term PE: delivery ≥ 37 weeks",
      "Early-onset: placental origin, shallow trophoblast invasion, severe phenotype",
      "Late-onset: maternal constitutional factors, obesity, chronic HTN, metabolic syndrome",
      "Superimposed PE: PE developing on pre-existing chronic hypertension",
    ],
    [
      "HELLP syndrome: Haemolysis, Elevated Liver enzymes, Low Platelets — variant/complication of PE",
      "Eclampsia: new-onset grand mal seizures in setting of PE without other neurological cause",
      "PE with severe features: SBP ≥160 or DBP ≥110; platelet <100k; creatinine >1.1; transaminases >2× ULN; pulmonary oedema; cerebral/visual symptoms",
      "Fetal growth restriction and proteinuria >5g are NO LONGER criteria for severe features (ACOG)",
    ],
    "Timing & Type", "Severe Features & Variants"
  );
}

// ─── SLIDE 5: PATHOPHYSIOLOGY — TWO-STAGE THEORY ─────────────────────────
{
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  headerBodySlide(s, "Pathophysiology: The Two-Stage Model", [
    { text: "STAGE 1 (1st Trimester, Subclinical — before 20 weeks):\n", options: { bold: true, color: GOLD, fontSize: 17, fontFace: "Calibri" } },
    { text: "Defective trophoblast invasion and impaired remodelling of spiral arteries → high-resistance, low-flow uteroplacental vasculature\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Failure of physiological conversion of spiral arteries from narrow muscular vessels to wide-bore, low-resistance conduits\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Results in chronic placental ischaemia and oxidative stress\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "STAGE 2 (2nd–3rd Trimester, Clinical — after 20 weeks):\n", options: { bold: true, color: GOLD, fontSize: 17, fontFace: "Calibri" } },
    { text: "Placental release of anti-angiogenic factors (sFlt-1) and pro-inflammatory mediators into maternal circulation\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "sFlt-1 antagonises VEGF and PlGF → generalised maternal endothelial dysfunction\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Clinical manifestations: hypertension, proteinuria, multi-organ dysfunction", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
  ], "Creasy & Resnik MFM 8e, Chapter 45 | Roberts & Hubel model");
}

// ─── SLIDE 6: ANGIOGENIC IMBALANCE ───────────────────────────────────────
{
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  twoColSlide(s,
    "Angiogenic Imbalance in Pre-Eclampsia",
    [
      "sFlt-1 (Soluble FMS-like Tyrosine Kinase-1): secreted splice variant of VEGF receptor",
      "Potent antagonist of VEGF and PlGF — neutralises circulating free forms",
      "Elevated in maternal serum weeks BEFORE clinical onset",
      "When injected in pregnant rodents → hypertension, proteinuria, glomerular endotheliosis",
      "sFlt-1/PlGF ratio >38: high risk of PE; <38: NPV 99% for excluding PE within 1 week",
      "Commercial assays: sensitivity/specificity ~90% for diagnosis and prognosis",
    ],
    [
      "PlGF (Placental Growth Factor): member of VEGF family",
      "Produced in large amounts by placenta; promotes vasodilation via NO and prostacyclin",
      "DECREASED in PE — precedes clinical diagnosis by 5–10 weeks",
      "Low PlGF (<100 pg/mL in 1st trimester) = high-risk marker",
      "PAPP-A (Pregnancy-Associated Plasma Protein-A): low levels in 1st trimester → impaired trophoblast invasion",
      "Combined sFlt-1/PlGF ratio: best single biomarker for established PE surveillance",
    ],
    "Anti-Angiogenic (sFlt-1)", "Pro-Angiogenic (PlGF & PAPP-A)"
  );
}

// ─── SLIDE 7: RISK FACTORS FOR PE ────────────────────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Risk Factors for Pre-Eclampsia",
    [
      "Previous history of PE (RR: 7–10×)",
      "Chronic hypertension (RR: 5×)",
      "Pre-existing renal disease",
      "Type 1 or Type 2 diabetes mellitus",
      "Autoimmune conditions (SLE, antiphospholipid syndrome)",
      "Multiple gestation (twin: 10–20%; triplet: 25–60%)",
      "Assisted reproductive technology (ART)",
    ],
    [
      "Nulliparity",
      "Age ≥35 years",
      "BMI >30 kg/m²",
      "Family history of PE (first-degree relative)",
      "Inter-pregnancy interval >10 years",
      "African-American/South Asian ethnicity",
      "Low socioeconomic status",
      "First pregnancy with a new partner",
    ],
    "High-Risk Factors (any single factor = high risk)", "Moderate-Risk Factors (≥2 required)"
  );
}

// ─── SLIDE 8: RATIONALE FOR 1ST TRIMESTER SCREENING ──────────────────────
{
  const s = pres.addSlide();
  headerBodySlide(s, "Why Screen in the First Trimester?", [
    "Pre-eclampsia originates in early placentation — pathological changes begin at 8–12 weeks (well before symptoms)",
    "Placental biomarkers of impaired trophoblast invasion are detectable at 11–13+6 weeks",
    "Low-dose aspirin is most effective when started BEFORE 16 weeks — early identification is key for intervention",
    "Risk-factor-only screening (NICE/ACOG approach): detection rate 39–41% for preterm PE at 10% FPR — insufficient",
    "FMF combined algorithm: detection rate 75–90% for preterm PE at 10% FPR — superior to risk-factor approach",
    "Only preterm PE screening has a proven intervention (aspirin); term PE has no effective prevention",
    "Optimal timing: 11+0 to 13+6 weeks — coincides with routine first trimester anomaly scan (nuchal translucency)",
    "Single universal screening visit for multiple conditions: aneuploidy, structural anomalies, PE, growth restriction",
  ], "Lee et al., Best Pract Res Clin Obstet Gynaecol 2024 | FIGO Initiative 2020");
}

// ─── SLIDE 9: FMF COMBINED ALGORITHM — COMPONENTS ────────────────────────
{
  const s = pres.addSlide();
  headerBodySlide(s, "FMF Combined First-Trimester Screening Algorithm", [
    { text: "Four Pillars of the FMF Algorithm (11+0 to 13+6 weeks):\n\n", options: { bold: true, color: GOLD, fontSize: 17, fontFace: "Calibri" } },
    { text: "1. Maternal Risk Factors: age, weight, ethnicity, obstetric history, conception method, smoking, chronic HTN, diabetes, SLE, APS\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 16, fontFace: "Calibri" } },
    { text: "2. Mean Arterial Pressure (MAP): automated sphygmomanometer, both arms; MAP = (SBP + 2×DBP)/3; expressed as MoM\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 16, fontFace: "Calibri" } },
    { text: "3. Uterine Artery Pulsatility Index (UtA-PI): transabdominal/transvaginal Doppler at 11–13+6 weeks; elevated PI = impaired trophoblast invasion; expressed as MoM\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 16, fontFace: "Calibri" } },
    { text: "4. Placental Growth Factor (PlGF): maternal serum; low PlGF = reduced placental angiogenesis; expressed as MoM\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 16, fontFace: "Calibri" } },
    { text: "\nOptional: PAPP-A (Pregnancy-Associated Plasma Protein-A) — further improves prediction, especially for early-onset PE", options: { bullet: { type: "bullet" }, color: LGRAY, fontSize: 14, fontFace: "Calibri" } },
  ], "Source: Poon et al., FIGO 2020 | Rolnik et al., NEJM 2017");
}

// ─── SLIDE 10: MAP MEASUREMENT ────────────────────────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Component 1: Mean Arterial Pressure (MAP)",
    [
      "Automated oscillometric sphygmomanometer — preferred over manual (reduces operator bias)",
      "Measurements taken from BOTH arms simultaneously or in sequence",
      "Patient seated, resting for ≥5 minutes, arm at heart level",
      "MAP = (SBP + 2×DBP) ÷ 3",
      "The HIGHER of the two readings is used for risk calculation",
      "Adjusted for gestational age, maternal weight, height, and ethnic origin — expressed as MoM",
      "High MAP MoM (>90th centile) → impaired maternal vascular adaptation in early pregnancy",
    ],
    [
      "Normal MAP in 1st trimester: approximately 80–90 mmHg",
      "Elevated MAP = earliest sign of impaired cardiovascular adaptation to pregnancy",
      "Women who later develop PE show higher MAP from as early as 8–10 weeks",
      "Angiotensin II sensitivity differences detectable as early as 14 weeks (Creasy & Resnik Ch.45)",
      "Standalone MAP: DR ~55% for preterm PE at 10% FPR",
      "Combined with PlGF and UtA-PI: DR improves to 75–90%",
    ],
    "Measurement Protocol", "Clinical Significance"
  );
}

// ─── SLIDE 11: UtA-PI DOPPLER ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Component 2: Uterine Artery Pulsatility Index (UtA-PI)",
    [
      "Colour-flow Doppler of uterine artery at the crossing of the external iliac artery (transabdominal or transvaginal)",
      "MEAN UtA-PI of both left and right uterine arteries used",
      "Performed at 11+0 to 13+6 weeks, CRL 45–84 mm",
      "Expressed as MoM corrected for gestational age and maternal characteristics",
      "Normal: progressive decrease in PI as trophoblast invasion remodels spiral arteries (2nd trimester further decreases)",
      "High UtA-PI = failed/incomplete physiological spiral artery transformation",
      "Notching in waveform = additional indicator of increased resistance",
    ],
    [
      "UtA-PI reflects the resistance of the uteroplacental circulation",
      "Elevated UtA-PI predates clinical PE by weeks — detects subclinical placental dysfunction",
      "Standalone UtA-PI: DR ~40–50% for preterm PE at 10% FPR",
      "Incremental value: adds significantly to maternal factors + MAP combination",
      "High PI in one artery only can still confer risk (asymmetric implantation)",
      "Used in the Bayes-theorem FMF model as a continuous distribution — NOT a binary cut-off",
    ],
    "Measurement Technique", "Clinical Interpretation"
  );
}

// ─── SLIDE 12: PlGF & PAPP-A ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Components 3 & 4: PlGF and PAPP-A",
    [
      "Placental Growth Factor (PlGF): member of VEGF superfamily; produced by syncytiotrophoblast",
      "Mediates angiogenesis, vasodilation (via NO and prostacyclin), and trophoblast invasion",
      "In PE: low PlGF reflects inadequate placental vascularisation from early 1st trimester",
      "Measured by chemiluminescent immunoassay (ELISA); expressed as MoM",
      "PlGF <100 pg/mL at 11–13 weeks = high-risk threshold (dependent on assay)",
      "Standalone PlGF: DR ~45% for early PE at 10% FPR",
      "Combined PlGF + MAP + UtA-PI: DR 90% for early PE; 75% for preterm PE at 10% FPR",
    ],
    [
      "PAPP-A (Pregnancy-Associated Plasma Protein-A): zinc metalloprotease; produced by trophoblasts",
      "Cleaves IGF-binding proteins → releases IGF → promotes trophoblast invasion",
      "Low PAPP-A MoM → impaired trophoblast invasion",
      "Routinely measured in 1st trimester combined aneuploidy screening — available without extra blood draw",
      "Low PAPP-A: DR ~35% for preterm PE at 10% FPR (standalone)",
      "Adds incremental value to MAP + UtA-PI + PlGF combination in some models",
      "Two-stage strategy: use maternal factors + MAP (stage 1); reserve PAPP-A + PlGF + UtA-PI for 30% (stage 2) → DR 71% at 10% FPR",
    ],
    "PlGF", "PAPP-A"
  );
}

// ─── SLIDE 13: PERFORMANCE STATISTICS TABLE ──────────────────────────────
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      { text: "Early PE (<34w)", options: { bold: true, color: WHITE, fill: MID } },
      { text: "Preterm PE (<37w)", options: { bold: true, color: WHITE, fill: MID } },
      { text: "Term PE (≥37w)", options: { bold: true, color: WHITE, fill: MID } },
    ],
    [
      { text: "Maternal Risk Factors Only (NICE)", options: { color: WHITE } },
      { text: "41%", options: { color: RED } },
      { text: "39%", options: { color: RED } },
      { text: "34%", options: { color: RED } },
    ],
    [
      { text: "Maternal Factors + MAP", options: { color: WHITE } },
      { text: "~60%", options: { color: GOLD } },
      { text: "~55%", options: { color: GOLD } },
      { text: "~38%", options: { color: GOLD } },
    ],
    [
      { text: "Maternal Factors + MAP + UtA-PI", options: { color: WHITE } },
      { text: "~70%", options: { color: GOLD } },
      { text: "~63%", options: { color: GOLD } },
      { text: "~40%", options: { color: GOLD } },
    ],
    [
      { text: "Maternal Factors + MAP + PlGF", options: { color: WHITE } },
      { text: "~80%", options: { color: TEAL } },
      { text: "~68%", options: { color: TEAL } },
      { text: "~42%", options: { color: TEAL } },
    ],
    [
      { text: "FMF FULL (MF + MAP + UtA-PI + PlGF)", options: { bold: true, color: GOLD } },
      { text: "90%", options: { bold: true, color: TEAL } },
      { text: "75%", options: { bold: true, color: TEAL } },
      { text: "41%", options: { bold: true, color: GOLD } },
    ],
    [
      { text: "Two-Stage Strategy (MF+MAP → +PlGF+UtA-PI)", options: { color: WHITE } },
      { text: "~85%", options: { color: TEAL } },
      { text: "71%", options: { color: TEAL } },
      { text: "~38%", options: { color: GOLD } },
    ],
  ];

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    valign: "middle",
  });
}

// ─── SLIDE 14: THE FMF BAYES MODEL & RISK CALCULATION ─────────────────────
{
  const s = pres.addSlide();
  headerBodySlide(s, "FMF Bayes-Theorem Risk Calculation Model", [
    "Bayesian method: a priori risk from maternal characteristics is multiplied by likelihood ratios derived from biophysical and biochemical markers",
    "Marker values converted to multiples of the median (MoM) — adjusted for gestational age, maternal weight, height, ethnicity, and method of conception",
    "A woman is considered HIGH RISK when risk ≥ 1:100 based on the full first-trimester combined test",
    "The FMF risk calculator is freely available on fmf.org.uk and as a mobile app",
    "Also integrated into commercial laboratory reporting systems (Astraia, Viewpoint, etc.)",
    "High-risk threshold (1:100) provides ~10% screen-positive rate in the general population",
    "Alternative cut-offs: 1:50 (higher sensitivity) or 1:150 (lower FPR) can be chosen based on local resource availability",
    "Two-stage protocol: all women screened with maternal factors + MAP at 11–13 weeks; PlGF + UtA-PI measured in 30% at screen-positive stage → DR 71% at 10% FPR",
    "FMF algorithm validated in >120,000 pregnancies across multiple prospective studies (FIGO 2020)",
  ], "Poon et al., Am J Obstet Gynecol 2020 | FIGO Initiative | FMF prospective cohorts 58,884–120,000 pregnancies");
}

// ─── SLIDE 15: COMPARISON ACROSS GUIDELINES ───────────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Guideline Comparison: FMF vs. NICE vs. ACOG",
    [
      "FMF/FIGO (2020, endorsed globally): Combined algorithm — maternal factors + MAP + UtA-PI + PlGF at 11–13+6 weeks; high risk = 1:100; HIGH DR, LOW FPR",
      "NICE (UK, 2019): Risk-factor based scoring; aspirin for ≥1 high-risk factor OR ≥2 moderate-risk factors; DR 39% for preterm PE at ~10% FPR",
      "WHO: Supports first-trimester screening; recommends low-dose aspirin for high-risk women; calcium supplementation in low-intake populations",
      "ISSHP 2021: Endorses FMF combined model as best practice; pragmatic alternative — use maternal factors + MAP where biomarkers not available",
    ],
    [
      "ACOG (2022/2024): Risk-factor based approach; aspirin 81 mg/day from 12 weeks for high-risk women; biophysical markers not yet routine in US practice",
      "ACOG 2024 Biomarker Guidance: Acknowledges sFlt-1/PlGF ratio utility for diagnosis/surveillance; supports PlGF-based testing",
      "USPSTF (2023): Grade B — low-dose aspirin 81 mg/day after 12 weeks for high-risk patients based on risk-factor screening",
      "SMFM: Endorses aspirin 81 mg/day (some guidelines state 150 mg in high-risk) from 12–16 weeks; supports combined screening where feasible",
      "Key gap: ACOG/USPSTF use less precise risk-factor-only approach vs. validated FMF Bayesian model",
    ],
    "FMF / FIGO / NICE / WHO / ISSHP", "ACOG / USPSTF / SMFM"
  );
}

// ─── SLIDE 16: SCREENING PROTOCOL — STEP BY STEP ──────────────────────────
{
  const s = pres.addSlide();
  headerBodySlide(s, "First Trimester Screening Protocol (11+0 to 13+6 Weeks)", [
    { text: "Step 1 — Gestational Age Confirmation:\n", options: { bold: true, color: GOLD, fontSize: 16, fontFace: "Calibri" } },
    { text: "Crown-rump length (CRL) 45–84 mm; gestational age established by CRL measurement\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Step 2 — Maternal History & Demographics:\n", options: { bold: true, color: GOLD, fontSize: 16, fontFace: "Calibri" } },
    { text: "Age, weight, height, ethnicity, smoking status, parity, previous PE history, conception method, chronic diseases (HTN, diabetes, autoimmune, renal), family history\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Step 3 — Biophysical Measurements:\n", options: { bold: true, color: GOLD, fontSize: 16, fontFace: "Calibri" } },
    { text: "Mean Arterial Pressure (both arms, automated, seated); Uterine Artery Doppler PI (bilateral, mean UtA-PI)\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Step 4 — Biochemical Markers:\n", options: { bold: true, color: GOLD, fontSize: 16, fontFace: "Calibri" } },
    { text: "Serum PlGF (and PAPP-A if combined aneuploidy screen); entered as MoM into risk calculator\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Step 5 — Risk Calculation & Counselling:\n", options: { bold: true, color: GOLD, fontSize: 16, fontFace: "Calibri" } },
    { text: "FMF Bayesian algorithm → risk score. High risk (≥1:100): counsel and initiate aspirin 150 mg/night before 16 weeks", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
  ], "FIGO 2020 | FMF.org | Creasy & Resnik MFM 8e");
}

// ─── SLIDE 17: INTERVENTION — ASPIRIN PROPHYLAXIS ─────────────────────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Intervention: Low-Dose Aspirin Prophylaxis",
    [
      "Aspirin inhibits COX-1/COX-2 → reduces thromboxane A2 (vasoconstrictor/platelet aggregator) while sparing prostacyclin (vasodilator)",
      "Corrects the prostacyclin:thromboxane imbalance characteristic of PE",
      "May improve trophoblast invasion and spiral artery remodelling when initiated early",
      "ASPRE Trial (Rolnik et al., NEJM 2017): aspirin 150 mg/night in FMF high-risk women → 62% reduction in preterm PE",
      "Effect is dependent on compliance: ≥90% compliance → 75% reduction in preterm PE",
      "Aspirin started BEFORE 16 weeks = significant benefit; after 16 weeks = minimal benefit",
      "Meta-analyses (>35,000 women): 10% overall reduction in PE; 17% reduction in preterm PE; 15% reduction in preterm birth",
    ],
    [
      "Dose: 150 mg nocte (FMF/FIGO recommendation); 81 mg/day (ACOG/USPSTF for US practice)",
      "Timing: initiate between 11–16 weeks of gestation; ideally by 13+6 weeks",
      "Duration: continue until 36 weeks of gestation",
      "Administration: nighttime dosing may be more effective (circadian variation in blood pressure)",
      "Safety: no increase in major bleeding; no increase in congenital malformations; safe in pregnancy",
      "PARIS Collaborative (individual patient data): NNT 500 for low-risk; NNT 50 for high-risk",
      "USPTF recommendation (Grade B): aspirin 81 mg after 12 weeks for risk-factor high-risk patients",
    ],
    "Mechanism & Evidence", "Dose, Timing & Safety"
  );
}

// ─── SLIDE 18: ADDITIONAL PREVENTIVE MEASURES ─────────────────────────────
{
  const s = pres.addSlide();
  headerBodySlide(s, "Additional Preventive Measures & What Doesn't Work", [
    { text: "EVIDENCE-BASED MEASURES:\n", options: { bold: true, color: TEAL, fontSize: 16, fontFace: "Calibri" } },
    { text: "Calcium supplementation (≥1g/day): WHO recommends for populations with LOW calcium intake; reduces PE and preterm birth in these populations; no benefit in high-calcium-intake populations\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Pravastatin: under investigation for preterm PE prevention in high-risk women (ongoing RCTs)\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Metformin: being studied in obese women; results awaited\n\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "NOT EFFECTIVE (Creasy & Resnik MFM):\n", options: { bold: true, color: RED, fontSize: 16, fontFace: "Calibri" } },
    { text: "Antioxidant vitamins C and E: initial small trial suggested benefit; larger RCTs showed NO benefit; possible harm (excess low-birth-weight infants in antioxidant group)\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Dietary sodium restriction: no benefit\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Bed rest: not recommended to prevent PE; not supported by RCTs\n", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
    { text: "Marine fish oils, magnesium, zinc, folic acid: insufficient evidence", options: { bullet: { type: "bullet" }, color: WHITE, fontSize: 15, fontFace: "Calibri" } },
  ], "Creasy & Resnik MFM 8e Ch.45 | WHO 2011 | Cochrane reviews");
}

// ─── SLIDE 19: SPECIAL POPULATIONS & MONITORING AFTER SCREENING ───────────
{
  const s = pres.addSlide();
  twoColSlide(s,
    "Special Populations & Post-Screening Monitoring",
    [
      "TWIN PREGNANCIES: Incidence 10–20% (dichorionic), 8–15% (monochorionic); FMF algorithm applicable to twins with adjustments; PE in twins occurs earlier and is more severe",
      "CHRONIC HYPERTENSION: 15–25% risk of superimposed PE; aspirin recommended regardless of 1st trimester screen result",
      "DIABETES (T1DM/T2DM): 2–4× increased risk; aspirin 60–162 mg/day from 12–28 weeks (ADA, ACOG, SMFM); HbA1c control reduces risk",
      "ANTIPHOSPHOLIPID SYNDROME: High risk; aspirin + heparin may be required; obstetric APS management protocol",
      "PREVIOUS PE: Aspirin regardless of screen; surveillance ultrasound from 20 weeks",
    ],
    [
      "POST-SCREEN HIGH-RISK MONITORING:",
      "Aspirin 150 mg nocte commenced by 16 weeks",
      "Serial blood pressure monitoring every 2–4 weeks from 20 weeks",
      "Serial uterine artery Doppler at 20–24 weeks",
      "Serial fetal growth scans (every 4 weeks from 24 weeks)",
      "sFlt-1/PlGF ratio if suspected PE develops",
      "PlGF-based testing (Triage PlGF, Elecsys): helps triage suspected PE in 2nd/3rd trimester",
      "Magnesium sulfate: seizure prophylaxis in severe PE (4 g IV loading dose, 1–2 g/hr maintenance)",
    ],
    "Special Populations", "Surveillance Protocol After High-Risk Screen"
  );
}

// ─── SLIDE 20: KEY TAKEAWAYS & CONCLUSIONS ────────────────────────────────
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  const points = [
    ["01", "Pre-eclampsia originates in the first trimester — impaired trophoblast invasion precedes clinical symptoms by weeks to months"],
    ["02", "The FMF combined algorithm (maternal factors + MAP + UtA-PI + PlGF) achieves 90% DR for early PE and 75% for preterm PE at 10% FPR — far superior to risk-factor-only screening"],
    ["03", "Low-dose aspirin (150 mg/night) initiated before 16 weeks in FMF high-risk women reduces preterm PE by 62% (ASPRE Trial, NEJM 2017)"],
    ["04", "Optimal screening window: 11+0 to 13+6 weeks — integrable with routine nuchal translucency scan"],
    ["05", "All pregnant women should be offered first-trimester PE screening using the Bayesian combined model (FIGO 2020 strong recommendation, high-quality evidence)"],
    ["06", "sFlt-1/PlGF ratio <38 has 99% NPV for ruling out PE within 1 week; useful for 2nd/3rd trimester triage"],
    ["07", "Guidelines diverge: FMF/FIGO/NICE endorse combined screening; ACOG/USPSTF still rely on risk factors — combined approach is more effective"],
  ];

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  s.addText("References: Creasy & Resnik MFM 8e | FIGO 2020 | ASPRE (Rolnik, NEJM 2017) | Lee et al., Best Pract Res 2024 | ACOG PB 222 | ISSHP 2021 | USPSTF 2023", {
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// ─── WRITE ─────────────────────────────────────────────────────────────────
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