Myelomeningocele (Meningomyelocele) - A Neonatologist's Deep Dive

#!/usr/bin/env python3
"""
Myelomeningocele (MMC) - Interactive 2-column print-optimised PDF
Neonatologist/Paediatrician Reference
"""

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import mm, cm
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether, PageBreak
)
from reportlab.platypus.flowables import Flowable
from reportlab.lib.colors import HexColor, white, black
import io

# ─── Colour palette ────────────────────────────────────────────────────────────
C_NAVY    = HexColor("#1a3a5c")   # header / title bg
C_TEAL    = HexColor("#0e7c86")   # section heading bg
C_ORANGE  = HexColor("#e07b39")   # accent / alert
C_SKY     = HexColor("#daf0f5")   # alternate row / note bg
C_LIME    = HexColor("#e8f5e9")   # green note bg
C_YELLOW  = HexColor("#fff8e1")   # warning bg
C_RED     = HexColor("#b71c1c")   # danger text
C_GREY    = HexColor("#f5f5f5")   # table alt row
C_LGREY   = HexColor("#90a4ae")   # subtext
C_PURPLE  = HexColor("#6a1b9a")   # purple accent
C_DGREY   = HexColor("#37474f")   # body text

PAGE_W, PAGE_H = A4

# ─── Two-column layout constants ───────────────────────────────────────────────
MARGIN_OUTER = 12 * mm
MARGIN_INNER = 8  * mm
COL_GAP      = 6  * mm
COL_W        = (PAGE_W - 2*MARGIN_OUTER - COL_GAP) / 2  # ≈ 85 mm

# ─── Style registry ────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

# Base styles
BASE       = S("base",      fontName="Helvetica",      fontSize=7.2, leading=10, textColor=C_DGREY)
BODY       = S("body",      fontName="Helvetica",      fontSize=7.2, leading=10.5, textColor=C_DGREY, alignment=TA_JUSTIFY)
BODY_SML   = S("bodySmall", fontName="Helvetica",      fontSize=6.5, leading=9,  textColor=C_DGREY, alignment=TA_JUSTIFY)
BOLD       = S("bold",      fontName="Helvetica-Bold", fontSize=7.2, leading=10, textColor=C_DGREY)
ITALIC     = S("italic",    fontName="Helvetica-Oblique", fontSize=7, leading=9.5, textColor=C_LGREY)

# Headings
H_PAGE     = S("hPage",  fontName="Helvetica-Bold",  fontSize=10, leading=13, textColor=white,   alignment=TA_CENTER)
H_SEC      = S("hSec",   fontName="Helvetica-Bold",  fontSize=7.5,leading=10, textColor=white,   alignment=TA_LEFT)
H_SUB      = S("hSub",   fontName="Helvetica-Bold",  fontSize=7.2,leading=10, textColor=C_NAVY,  alignment=TA_LEFT)
H_MINI     = S("hMini",  fontName="Helvetica-Bold",  fontSize=6.8,leading=9,  textColor=C_TEAL,  alignment=TA_LEFT)

# Bullets / lists
BULLET     = S("bullet", fontName="Helvetica", fontSize=7, leading=10, textColor=C_DGREY,
                leftIndent=8, firstLineIndent=-6)
BULLET_RED = S("bulletRed", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_RED,
                leftIndent=8, firstLineIndent=-6)
BULLET_TEAL= S("bulletTeal", fontName="Helvetica", fontSize=7, leading=10, textColor=C_TEAL,
                leftIndent=8, firstLineIndent=-6)
NOTE       = S("note",   fontName="Helvetica-Oblique", fontSize=6.5, leading=9, textColor=C_PURPLE)
WARN       = S("warn",   fontName="Helvetica-Bold",    fontSize=7,   leading=10, textColor=C_RED, alignment=TA_CENTER)
SOURCE     = S("source", fontName="Helvetica-Oblique", fontSize=5.8, leading=8, textColor=C_LGREY)

# ─── Helper Flowables ──────────────────────────────────────────────────────────
class ColorRect(Flowable):
    """Full-width coloured rectangle used as section header bar."""
    def __init__(self, text, bg=C_TEAL, text_style=None, h=7*mm, icon=""):
        super().__init__()
        self.text  = icon + ("  " if icon else "") + text
        self.bg    = bg
        self.h     = h
        self.ts    = text_style or H_SEC
        self._w    = 0
    def wrap(self, aw, ah):
        self._w = aw
        return aw, self.h
    def draw(self):
        c = self.canv
        c.setFillColor(self.bg)
        c.roundRect(0, 0, self._w, self.h, 2, fill=1, stroke=0)
        p = Paragraph(self.text, self.ts)
        pw, ph = p.wrap(self._w - 4*mm, self.h)
        p.drawOn(c, 2*mm, (self.h - ph) / 2)

class AlertBox(Flowable):
    """Coloured alert / note box."""
    def __init__(self, text, bg=C_YELLOW, border=C_ORANGE, text_style=None, label=""):
        super().__init__()
        self.text   = text
        self.bg     = bg
        self.border = border
        self.ts     = text_style or BOLD
        self.label  = label
        self._w = self._h = 0
    def wrap(self, aw, ah):
        self._w = aw
        p = Paragraph(("<b>" + self.label + "</b> " if self.label else "") + self.text, self.ts)
        _, ph = p.wrap(self._w - 6*mm, 9999)
        self._h = ph + 4*mm
        return aw, self._h
    def draw(self):
        c = self.canv
        c.setFillColor(self.bg)
        c.setStrokeColor(self.border)
        c.setLineWidth(0.8)
        c.roundRect(0, 0, self._w, self._h, 2, fill=1, stroke=1)
        p = Paragraph(("<b>" + self.label + "</b> " if self.label else "") + self.text, self.ts)
        p.wrap(self._w - 6*mm, 9999)
        p.drawOn(c, 3*mm, 2*mm)

def sp(n=2): return Spacer(1, n)
def hr(color=C_TEAL): return HRFlowable(width="100%", thickness=0.5, color=color, spaceAfter=2)

# ─── Table helper ──────────────────────────────────────────────────────────────
def make_table(data, col_widths, header_bg=C_NAVY, alt_bg=C_GREY,
               header_text_color=white, font_size=6.5, leading=9):
    """Build a styled table with alternating rows."""
    styled_data = []
    for ri, row in enumerate(data):
        styled_row = []
        for ci, cell in enumerate(row):
            if ri == 0:
                styled_row.append(Paragraph(str(cell),
                    ParagraphStyle("th", fontName="Helvetica-Bold",
                        fontSize=font_size, leading=leading, textColor=header_text_color)))
            else:
                styled_row.append(Paragraph(str(cell),
                    ParagraphStyle("td", fontName="Helvetica",
                        fontSize=font_size, leading=leading, textColor=C_DGREY)))
        styled_data.append(styled_row)

    ts = TableStyle([
        ("BACKGROUND",  (0,0), (-1,0),  header_bg),
        ("TEXTCOLOR",   (0,0), (-1,0),  header_text_color),
        ("GRID",        (0,0), (-1,-1), 0.4, HexColor("#cfd8dc")),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [white, alt_bg]),
        ("TOPPADDING",  (0,0), (-1,-1), 2),
        ("BOTTOMPADDING",(0,0),(-1,-1), 2),
        ("LEFTPADDING", (0,0), (-1,-1), 3),
        ("RIGHTPADDING",(0,0), (-1,-1), 3),
        ("VALIGN",      (0,0), (-1,-1), "MIDDLE"),
    ])
    return Table(styled_data, colWidths=col_widths, style=ts, repeatRows=1)

# ─── Two-column builder ────────────────────────────────────────────────────────
def two_col(left_content, right_content, col_w=COL_W, gap=COL_GAP):
    """Wrap two lists of flowables into a side-by-side table."""
    from reportlab.platypus import KeepInFrame
    lf = KeepInFrame(col_w, 9999, left_content, mode='shrink')
    rf = KeepInFrame(col_w, 9999, right_content, mode='shrink')
    tbl = Table([[lf, rf]], colWidths=[col_w, col_w])
    tbl.setStyle(TableStyle([
        ("VALIGN",      (0,0), (-1,-1), "TOP"),
        ("LEFTPADDING", (0,0), (-1,-1), 0),
        ("RIGHTPADDING",(0,0), (-1,-1), 0),
        ("TOPPADDING",  (0,0), (-1,-1), 0),
        ("BOTTOMPADDING",(0,0),(-1,-1), 0),
        ("INNERGRID",   (0,0), (-1,-1), 0, white),
        ("BOX",         (0,0), (-1,-1), 0, white),
    ]))
    return tbl

# ─── Page frame / background decoration ───────────────────────────────────────
def page_header(canvas, doc):
    canvas.saveState()
    # Top navy bar
    canvas.setFillColor(C_NAVY)
    canvas.rect(0, PAGE_H - 8*mm, PAGE_W, 8*mm, fill=1, stroke=0)
    canvas.setFillColor(white)
    canvas.setFont("Helvetica-Bold", 7.5)
    canvas.drawCentredString(PAGE_W/2, PAGE_H - 5.5*mm,
        "MYELOMENINGOCELE (MMC)  |  Neonatologist & Paediatrician Reference")
    # Bottom footer
    canvas.setFillColor(C_NAVY)
    canvas.rect(0, 0, PAGE_W, 6*mm, fill=1, stroke=0)
    canvas.setFillColor(white)
    canvas.setFont("Helvetica", 5.5)
    canvas.drawString(MARGIN_OUTER, 2*mm,
        "Sources: Bradley & Daroff Neurology 8e | Miller's Anesthesia 10e | Creasy & Resnik MFM | The Developing Human | MOMS Trial")
    canvas.drawRightString(PAGE_W - MARGIN_OUTER, 2*mm, f"Page {doc.page}")
    # Teal left accent stripe
    canvas.setFillColor(C_TEAL)
    canvas.rect(0, 6*mm, 1.5*mm, PAGE_H - 14*mm, fill=1, stroke=0)
    canvas.restoreState()

# ─── CONTENT BLOCKS ────────────────────────────────────────────────────────────

def build_story():
    story = []

    # ══════════════════════════════════════════════════════
    # ▌ PAGE 1 – Cover banner + Anatomy + Embryology + Epidemiology
    # ══════════════════════════════════════════════════════

    # ── Title banner ──
    story.append(ColorRect("MYELOMENINGOCELE  (Meningomyelocele)", bg=C_NAVY, h=14*mm,
        text_style=ParagraphStyle("tt", fontName="Helvetica-Bold", fontSize=11,
            leading=14, textColor=white, alignment=TA_CENTER)))
    story.append(sp(1))
    story.append(Paragraph(
        "A comprehensive neonatologist/paediatrician reference — 2-column print edition",
        ParagraphStyle("sub", fontName="Helvetica-Oblique", fontSize=7, leading=9,
            textColor=C_TEAL, alignment=TA_CENTER)))
    story.append(sp(3))

    # ── Two-column: left = Anatomy spectrum, right = Embryology ──
    left = [
        ColorRect("1 · ANATOMY & SPECTRUM", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>The Spina Bifida Spectrum</b>", H_SUB),
        sp(1),
        make_table([
            ["Type", "What Herniates", "Neural?", "Deficit"],
            ["Spina bifida\nocculta", "Nothing\n(arch only)", "No", "None"],
            ["Meningocele", "Meninges+CSF", "No", "Rarely"],
            ["<b>Myelomening-\nocele</b>", "<b>Cord+roots\n+meninges</b>", "<b>YES</b>", "<b>Always</b>"],
            ["Myeloschisis", "Open cord,\nno sac", "Yes", "Severe"],
        ], col_widths=[22*mm, 24*mm, 14*mm, 16*mm]),
        sp(3),
        Paragraph("<b>Key Anatomical Fact</b>", H_SUB),
        sp(1),
        AlertBox(
            "The neural PLACODE (dysplastic spinal cord) lies exposed in or at the surface of the sac — directly bathed in amniotic fluid. This is why closure (prenatal or postnatal) is urgent.",
            bg=C_SKY, border=C_TEAL,
            text_style=ParagraphStyle("ab", fontName="Helvetica", fontSize=6.8, leading=10, textColor=C_NAVY)),
        sp(3),
        Paragraph("<b>Location of Defect</b>", H_SUB),
        sp(1),
        Paragraph("● <b>&gt;75%</b> lumbosacral region", BULLET),
        Paragraph("● Thoracic lesions — minority but worst deficit", BULLET),
        Paragraph("● Cervical lesions — rare", BULLET),
        sp(2),
        Paragraph("<b>Myelomeningocele vs Meningocele</b>", H_MINI),
        sp(1),
        Paragraph("If the sac contains nerve roots or spinal cord → <b>myelomeningocele</b>. If neural elements absent → <b>meningocele</b>. The distinction is clinical + MRI.", BODY_SML),
    ]

    right = [
        ColorRect("2 · EMBRYOLOGY", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>Timeline</b>", H_SUB),
        sp(1),
        make_table([
            ["Day", "Event"],
            ["Day 18", "Neural plate forms"],
            ["Day 22-23", "Neural folds begin fusing (cranial)"],
            ["Day 26", "Rostral neuropore closes"],
            ["<b>Day 26-28</b>", "<b>Caudal neuropore closes → FAILURE here = MMC</b>"],
        ], col_widths=[18*mm, 58*mm]),
        sp(3),
        Paragraph("<b>The Two-Hit Hypothesis</b>", H_SUB),
        sp(1),
        AlertBox(
            "<b>Hit 1:</b> Primary failure of neural tube closure at ~week 4 (genetic + environmental)\n\n"
            "<b>Hit 2:</b> Progressive secondary damage from chronic exposure of the open placode to neurotoxic amniotic fluid + mechanical trauma throughout gestation",
            bg=C_YELLOW, border=C_ORANGE,
            text_style=ParagraphStyle("twohit", fontName="Helvetica", fontSize=6.8, leading=10, textColor=C_DGREY)),
        sp(2),
        Paragraph("<i>This two-hit model is the entire scientific rationale for in-utero surgery — closing early stops Hit 2.</i>", NOTE),
        sp(3),
        Paragraph("<b>3 · EPIDEMIOLOGY</b>", H_SUB),
        sp(1),
        make_table([
            ["Parameter", "Data"],
            ["Incidence", "~1 in 3,000 live births (post-folate era)"],
            ["Folate effect", "~50% reduction in MMC; plateau reached"],
            ["Terminations", "25–40% of MMC pregnancies terminated after prenatal Dx"],
            ["Sex", "Slight female predominance"],
            ["Most common\nlevel", "Lumbosacral (>75%)"],
        ], col_widths=[24*mm, 52*mm]),
        sp(2),
        Paragraph("<b>Risk Factors</b>", H_MINI),
        sp(1),
        Paragraph("● Maternal folate/B12 deficiency (most important modifiable)", BULLET),
        Paragraph("● <b>Valproic acid</b> in 1st trimester → 1–2% NTD risk", BULLET_RED),
        Paragraph("● Carbamazepine, trimethoprim (folate antagonist)", BULLET),
        Paragraph("● Prior affected pregnancy (10× background risk)", BULLET),
        Paragraph("● Maternal obesity, diabetes, early hyperthermia", BULLET),
        Paragraph("● Family history of NTDs", BULLET),
    ]

    story.append(two_col(left, right))
    story.append(sp(4))
    story.append(hr())

    # ══════════════════════════════════════════════════════
    # Two-column: Prenatal Diagnosis | Associated Anomalies
    # ══════════════════════════════════════════════════════
    left2 = [
        ColorRect("4 · PRENATAL DIAGNOSIS", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>Screening Timeline</b>", H_SUB),
        sp(1),
        make_table([
            ["Test", "When", "Sensitivity"],
            ["MSAFP", "14–16 wks", "~85%"],
            ["Amnio AFP +\nAChE", "As indicated", "Higher specificity"],
            ["<b>2nd trimester USS</b>", "<b>18–20 wks</b>", "<b>&gt;90%</b>"],
            ["Fetal MRI", "19–25 wks", "Best detail"],
        ], col_widths=[24*mm, 22*mm, 30*mm]),
        sp(3),
        Paragraph("<b>Ultrasound Signs — The Classic Triad</b>", H_SUB),
        sp(1),
        make_table([
            ["Sign", "What You See", "Mechanism"],
            ["🍋 Lemon sign", "Frontal bone scalloping", "Chiari II pulling brain"],
            ["🍌 Banana sign", "Curved cerebellum", "Hindbrain herniation"],
            ["Splayed vertebrae", "U/V-shaped on axial", "Direct spinal defect"],
        ], col_widths=[26*mm, 28*mm, 22*mm]),
        sp(3),
        Paragraph("<b>Fetal MRI advantages</b>", H_MINI),
        sp(1),
        Paragraph("● Precise lesion level characterisation", BULLET),
        Paragraph("● Degree of hindbrain herniation", BULLET),
        Paragraph("● Cortical anomalies (polymicrogyria)", BULLET),
        Paragraph("● Ventricular size assessment", BULLET),
        sp(2),
        AlertBox("AFP is elevated because open neural defects allow CSF-AFP to leak into amniotic fluid → absorbed into maternal circulation. <b>Closed defects do NOT elevate AFP.</b>",
            bg=C_SKY, border=C_TEAL,
            text_style=ParagraphStyle("afp", fontName="Helvetica", fontSize=6.5, leading=9, textColor=C_DGREY)),
    ]

    right2 = [
        ColorRect("5 · ASSOCIATED ANOMALIES", bg=C_ORANGE, h=6*mm,
            text_style=ParagraphStyle("h5", fontName="Helvetica-Bold", fontSize=7.5, leading=10, textColor=white)),
        sp(2),
        AlertBox("THE TRIAD: Chiari II + Hydrocephalus + Neurogenic Bladder\nAll three need active management from Day 1.",
            bg=HexColor("#fff3e0"), border=C_ORANGE,
            text_style=ParagraphStyle("triad", fontName="Helvetica-Bold", fontSize=7.2, leading=10.5, textColor=C_NAVY)),
        sp(3),
        Paragraph("<b>A. Chiari II Malformation</b> — present in virtually 100%", H_SUB),
        sp(1),
        Paragraph("Downward traction of tethered cord pulls hindbrain through foramen magnum:", BODY_SML),
        sp(1),
        Paragraph("● Cerebellar vermis + caudal brainstem herniate through enlarged foramen magnum", BULLET),
        Paragraph("● Small posterior fossa, kinked medulla, polymicrogyria", BULLET),
        sp(1),
        Paragraph("<b>Neonatal/Infant Signs of Chiari II:</b>", H_MINI),
        sp(1),
        make_table([
            ["Sign", "Mechanism", "Severity"],
            ["Inspiratory stridor", "Vocal cord palsy (CN X)", "⚠ Common"],
            ["Apnea", "Central (brainstem) / obstructive", "⚠⚠ Serious"],
            ["Swallowing dysfunction", "Bulbar palsy → aspiration", "⚠⚠ Serious"],
            ["Central hypoventilation", "Brainstem compression", "⚠⚠⚠ Critical"],
            ["Opisthotonus", "Severe herniation", "⚠⚠⚠ Critical"],
        ], col_widths=[28*mm, 30*mm, 18*mm], header_bg=HexColor("#bf360c")),
        sp(2),
        AlertBox("Brainstem dysfunction = 35% mortality by 5 years even with repair.",
            bg=HexColor("#ffebee"), border=C_RED,
            text_style=ParagraphStyle("bsd", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_RED)),
        sp(3),
        Paragraph("<b>B. Hydrocephalus</b>", H_SUB),
        sp(1),
        Paragraph("● 64–85% of lumbosacral MMC need VP shunt", BULLET),
        Paragraph("● Higher lesion level → higher shunt risk", BULLET),
        Paragraph("● Mechanism: 4th ventricle CSF flow obstruction from Chiari II", BULLET),
        Paragraph("● Mean IQ with shunt ≈ 80 (low normal) vs without shunt = better", BULLET),
        sp(2),
        Paragraph("<b>C. Latex Allergy</b>", H_SUB),
        sp(1),
        AlertBox("10–40% of MMC patients develop latex allergy from repeated early exposures. LATEX-FREE from BIRTH — no exceptions.",
            bg=HexColor("#ffebee"), border=C_RED,
            text_style=ParagraphStyle("latex", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_RED)),
        sp(2),
        Paragraph("<b>Other associations:</b>", H_MINI),
        sp(1),
        Paragraph("● Tethered cord syndrome (post-repair)", BULLET),
        Paragraph("● Syringomyelia  ● Craniolacunia (Lückenschädel)", BULLET),
        Paragraph("● Orthopedic: scoliosis, kyphosis, hip Dx, clubfoot", BULLET),
        Paragraph("● Precocious puberty (hydrocephalus-related)", BULLET),
    ]

    story.append(two_col(left2, right2))
    story.append(PageBreak())

    # ══════════════════════════════════════════════════════
    # PAGE 2 – Lesion level | Neonatal assessment + management
    # ══════════════════════════════════════════════════════
    left3 = [
        ColorRect("6 · LESION LEVEL — FUNCTIONAL ANATOMY", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph(
            "The <b>motor level</b> predicts function. In MMC, functional level is often "
            "<b>better</b> than anatomic level. <b>Almost ALL patients have neurogenic bladder</b> regardless of level (sacral roots always involved).",
            BODY_SML),
        sp(2),
        make_table([
            ["Level", "Motor Preserved", "Ambulation", "Bladder/Bowel"],
            ["Thoracic", "Arms, partial trunk", "Wheelchair", "Neurogenic"],
            ["L1–L2", "Hip flexors (iliopsoas)", "Braces + WC", "Neurogenic"],
            ["L3–L4", "Knee extensors (quads)", "Walk with braces", "Neurogenic"],
            ["L4–L5", "Ankle dorsiflexors, knee flexors", "Walk with AFOs", "Partial neurogenic"],
            ["Sacral", "Intrinsic foot muscles", "Independent walk", "Variable"],
        ], col_widths=[14*mm, 30*mm, 24*mm, 08.5*mm]),
        sp(3),
        AlertBox(
            "Neurogenic bladder → urinary retention → upper tract damage (hydronephrosis, VUR, CKD). "
            "<b>Clean Intermittent Catheterisation (CIC) must be initiated within days of birth.</b> "
            "Baseline renal USS + urodynamics in first weeks.",
            bg=C_YELLOW, border=C_ORANGE,
            text_style=ParagraphStyle("nic", fontName="Helvetica", fontSize=6.8, leading=10, textColor=C_DGREY)),
        sp(3),
        Paragraph("<b>Dermatomes to Test at Delivery</b>", H_MINI),
        sp(1),
        make_table([
            ["Level", "Sensory Region"],
            ["L1", "Inguinal ligament"],
            ["L2", "Medial thigh"],
            ["L3", "Medial knee"],
            ["L4", "Medial leg"],
            ["L5", "Dorsum of foot"],
            ["S1", "Lateral foot, sole"],
            ["S2–S4", "Perineum, perianal"],
        ], col_widths=[16*mm, 60*mm]),
    ]

    right3 = [
        ColorRect("7 · NEONATAL PRESENTATION", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>Spot Diagnosis at Birth</b>", H_SUB),
        sp(1),
        make_table([
            ["Finding", "Significance"],
            ["Posterior midline sac (lumbosacral)", "Diagnostic"],
            ["Flaccid lower limbs / no voluntary movement", "Level of lesion"],
            ["Absent anal wink", "Sacral root involvement"],
            ["Macrocephaly / bulging fontanelle", "Hydrocephalus"],
            ["Inspiratory stridor", "Chiari II vocal cord palsy"],
            ["Intact sac vs exposed placode", "Surgical urgency"],
        ], col_widths=[44*mm, 32*mm]),
        sp(3),
        Paragraph("<b>Neurological Exam in the Delivery Room</b>", H_MINI),
        sp(1),
        Paragraph("● Spontaneous leg movement — observe with stimulation", BULLET),
        Paragraph("● Pin-prick dermatomal testing — sensory level", BULLET),
        Paragraph("● Anal wink reflex — S2–S4 integrity", BULLET),
        Paragraph("● Lower limb tone (passive) — LMN pattern: flaccid", BULLET),
        Paragraph("● OFC measurement — pre-existing hydrocephalus?", BULLET),
        Paragraph("● Fontanelle tension — raised ICP?", BULLET),
        Paragraph("● Respiratory pattern / cry quality — brainstem function", BULLET),
        sp(3),
        ColorRect("8 · IMMEDIATE NEONATAL ORDERS (First Hour)", bg=C_ORANGE, h=6*mm,
            text_style=ParagraphStyle("h8", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=white)),
        sp(2),
        make_table([
            ["#", "Action", "Rationale"],
            ["1", "LATEX-FREE protocol immediately", "10–40% latex allergy risk"],
            ["2", "Prone / lateral positioning on doughnut ring", "Protect sac; never supine on sac"],
            ["3", "Sterile moist saline gauze over defect", "Prevent desiccation + infection"],
            ["4", "Incubator + thermoregulation", "High insensible losses from exposed sac"],
            ["5", "IV access + ↑ maintenance fluids", "Compensate insensible fluid losses"],
            ["6", "Cranial USS", "Ventricular size, pre-existing hydrocephalus"],
            ["7", "Renal USS", "Baseline upper urinary tract"],
            ["8", "Urgent Neurosurgery consult", "Surgical closure planning"],
            ["9", "Urology consult", "CIC protocol, urodynamics plan"],
            ["10", "Hold oral feeds — assess swallow", "Aspiration risk from Chiari II"],
        ], col_widths=[6*mm, 42*mm, 28*mm]),
    ]

    story.append(two_col(left3, right3))
    story.append(sp(4))
    story.append(hr())

    # Two-column: Repair | Post-op care
    left4 = [
        ColorRect("9 · SURGICAL REPAIR", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>A. Postnatal Repair (Standard)</b>", H_SUB),
        sp(1),
        Paragraph("● Close within <b>24–72 hours</b> of birth", BULLET),
        Paragraph("● Reduces meningitis risk from open CSF exposure", BULLET),
        Paragraph("● Steps: placode separation → dural closure → fascial closure → skin closure", BULLET),
        sp(2),
        Paragraph("<b>Anaesthesia considerations:</b>", H_MINI),
        sp(1),
        Paragraph("● Prone intubation with doughnut under sac", BULLET),
        Paragraph("● Risk of brainstem herniation on induction", BULLET),
        Paragraph("● High insensible fluid + blood loss — underestimated", BULLET),
        Paragraph("● Vocal cord palsy (CN X) — stridor, intubation difficulty", BULLET),
        Paragraph("● Associated hydrocephalus — raised ICP", BULLET),
        sp(3),
        Paragraph("<b>B. In Utero Fetal Repair — The MOMS Trial</b>", H_SUB),
        sp(1),
        Paragraph("RCT, 2003–2010, n=183, 3 US centres. Open fetal repair vs postnatal repair.", BODY_SML),
        sp(1),
        Paragraph("<b>Benefits of Prenatal Repair (at 30 months):</b>", H_MINI),
        sp(1),
        Paragraph("● VP shunt needed: <b>40% vs 82%</b> (prenatal vs postnatal)", BULLET_TEAL),
        Paragraph("● Independent walking: <b>44.8% vs 23.9%</b> (p=0.04)", BULLET_TEAL),
        Paragraph("● Function ≥2 levels better than anatomic: 26.4% vs 11.4%", BULLET_TEAL),
        Paragraph("● Better Bayley MDI + Peabody Motor Scale", BULLET_TEAL),
        Paragraph("● Reversal of hindbrain herniation (Chiari II)", BULLET_TEAL),
        sp(2),
        Paragraph("<b>Costs of Prenatal Repair:</b>", H_MINI),
        sp(1),
        Paragraph("● Preterm birth / PPROM — significantly ↑", BULLET_RED),
        Paragraph("● Uterine dehiscence at delivery (~11%)", BULLET_RED),
        Paragraph("● Maternal laparotomy + hysterotomy scar", BULLET_RED),
        Paragraph("● 2 perinatal deaths in each group", BULLET_RED),
        sp(2),
        Paragraph("<b>Fetal surgery window:</b> 19–26 weeks gestation", BOLD),
        sp(1),
        Paragraph("<b>Strict eligibility:</b> singleton, T1–S1 lesion with hindbrain herniation, normal chromosomes, no other major anomalies.", BODY_SML),
        sp(2),
        AlertBox("Fetoscopic (minimally invasive) repair is increasingly explored but carries higher PPROM (91% vs 36%) and CSF leak rates vs open. Open remains the reference standard (2025 meta-analysis, PMID: 40492626).",
            bg=C_SKY, border=C_TEAL,
            text_style=ParagraphStyle("feto", fontName="Helvetica", fontSize=6.5, leading=9.5, textColor=C_DGREY)),
    ]

    right4 = [
        ColorRect("10 · POST-OP NEONATAL CARE", bg=C_TEAL, h=6*mm),
        sp(2),
        Paragraph("<b>Immediate Post-operative (First Week)</b>", H_SUB),
        sp(1),
        Paragraph("● Prone positioning for 5–7 days — protect wound", BULLET),
        Paragraph("● Daily OFC — monitor for hydrocephalus development", BULLET),
        Paragraph("● Serial cranial USS — ventricular size", BULLET),
        Paragraph("● Fontanelle checks — raised ICP?", BULLET),
        Paragraph("● Wound monitoring — CSF leak, infection, dehiscence", BULLET),
        Paragraph("● Respiratory monitoring — apnea, central hypoventilation", BULLET),
        Paragraph("● NG feeds initially — assess swallow before oral feeding", BULLET),
        Paragraph("● Initiate CIC (urology clears, typically day 1–3)", BULLET),
        sp(3),
        Paragraph("<b>VP Shunt Decision</b>", H_MINI),
        sp(1),
        AlertBox("64–85% of lumbosacral MMC will need VP shunt. Usually placed days–weeks after closure. Signs requiring urgent shunt: rapidly rising OFC, bulging fontanelle, setting-sun sign, apnea, worsening brainstem signs.",
            bg=C_SKY, border=C_TEAL,
            text_style=ParagraphStyle("vps", fontName="Helvetica", fontSize=6.8, leading=10, textColor=C_NAVY)),
        sp(3),
        Paragraph("<b>Before Discharge Checklist</b>", H_SUB),
        sp(1),
        make_table([
            ["Domain", "Required"],
            ["Neurosurgery", "Wound healed; shunt if indicated"],
            ["Urology", "CIC technique taught to parents"],
            ["Renal USS", "Baseline documented"],
            ["Ophthalmology", "Strabismus, papilledema screen"],
            ["Audiology", "Baseline hearing screen"],
            ["Physiotherapy", "Positioning, passive ROM taught"],
            ["Social work", "Family counselling, support services"],
            ["Neurodevelopment", "MDT follow-up plan in place"],
        ], col_widths=[28*mm, 48*mm]),
        sp(3),
        Paragraph("<b>11 · LONG-TERM COMPLICATIONS OVERVIEW</b>", H_SUB),
        sp(1),
        make_table([
            ["System", "Problem", "Onset"],
            ["CNS", "Shunt malfunction/infection", "Anytime"],
            ["CNS", "Tethered cord (progressive deficits)", "Childhood+"],
            ["Urological", "Neurogenic bladder, VUR, CKD", "Lifelong"],
            ["Orthopaedic", "Scoliosis, kyphosis, pressure sores", "Childhood+"],
            ["Cognitive", "Executive dysfunction, ADHD-like", "School age"],
            ["Allergy", "Latex anaphylaxis", "Lifelong"],
            ["Endocrine", "Precocious puberty", "Childhood"],
            ["Respiratory", "Central sleep apnea", "Any age"],
        ], col_widths=[22*mm, 36*mm, 18*mm]),
        sp(2),
        Paragraph("<b>Intellectual outcomes:</b> >70% IQ >80. Executive function, attention, processing speed disproportionately impaired. 46–75% of lumbosacral MMC walk.", BODY_SML),
    ]

    story.append(two_col(left4, right4))
    story.append(sp(4))
    story.append(hr())

    # ── Full-width prevention + quick ref strip ──
    story.append(ColorRect("12 · PREVENTION — FOLIC ACID", bg=C_NAVY, h=6*mm))
    story.append(sp(2))

    prev_left = [
        Paragraph("<b>All women of childbearing age:</b> 400 mcg (0.4 mg) folic acid daily — start BEFORE conception, continue through 1st trimester", BODY_SML),
        sp(1),
        Paragraph("<b>Prior NTD pregnancy / on AED:</b> 4 mg/day (10× dose) — start 1 month before conception", BODY_SML),
        sp(1),
        Paragraph("<b>Mechanism:</b> Folate essential for DNA synthesis + methylation → neural tube closure on days 18–28 (before most women know they are pregnant)", BODY_SML),
    ]
    prev_right = [
        Paragraph("<b>Drugs to AVOID in pregnancy (especially trimester 1):</b>", H_MINI),
        sp(1),
        Paragraph("● Valproic acid — 1–2% NTD risk (highest teratogen risk for NTDs)", BULLET_RED),
        Paragraph("● Carbamazepine", BULLET_RED),
        Paragraph("● Trimethoprim (folate antagonist)", BULLET_RED),
        Paragraph("● Methotrexate", BULLET_RED),
        sp(1),
        Paragraph("Grain/cereal fortification with folate reduced NTD prevalence by 30–50% at population level.", BODY_SML),
    ]
    story.append(two_col(prev_left, prev_right))
    story.append(sp(4))
    story.append(hr())

    # ── Quick Reference Summary box ──
    story.append(ColorRect("QUICK REFERENCE — BEDSIDE CARD", bg=HexColor("#1b5e20"), h=6*mm,
        text_style=ParagraphStyle("qr", fontName="Helvetica-Bold", fontSize=7.5, leading=10, textColor=white)))
    story.append(sp(2))

    qr_left = [
        Paragraph("<b>Spot Diagnosis (5 signs)</b>", H_SUB),
        sp(1),
        Paragraph("1  Posterior midline sac (lumbosacral)", BULLET),
        Paragraph("2  Flaccid lower limbs / no voluntary movement", BULLET),
        Paragraph("3  Absent anal wink", BULLET),
        Paragraph("4  Macrocephaly / bulging fontanelle", BULLET),
        Paragraph("5  Possible inspiratory stridor", BULLET),
        sp(2),
        Paragraph("<b>First 6 Steps in Delivery Room</b>", H_SUB),
        sp(1),
        Paragraph("① LATEX-FREE — from this moment", BULLET_RED),
        Paragraph("② Prone on doughnut, sterile moist gauze over sac", BULLET),
        Paragraph("③ Incubator — prevent heat + fluid loss", BULLET),
        Paragraph("④ IV access + extra fluids", BULLET),
        Paragraph("⑤ Cranial USS + Renal USS", BULLET),
        Paragraph("⑥ Urgent Neurosurgery + Urology consults", BULLET),
    ]

    qr_right = [
        Paragraph("<b>The 3 Mandatory Associations to Manage</b>", H_SUB),
        sp(1),
        AlertBox("1. CHIARI II — monitor for stridor, apnea, swallow dysfunction, central hypoventilation",
            bg=HexColor("#fff3e0"), border=C_ORANGE,
            text_style=ParagraphStyle("q1", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_DGREY)),
        sp(2),
        AlertBox("2. HYDROCEPHALUS — daily OFC, serial cranial USS, VP shunt in 64–85%",
            bg=C_SKY, border=C_TEAL,
            text_style=ParagraphStyle("q2", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_DGREY)),
        sp(2),
        AlertBox("3. NEUROGENIC BLADDER — CIC from day 1–3. Renal USS + urodynamics. Prevent upper tract damage.",
            bg=C_LIME, border=HexColor("#2e7d32"),
            text_style=ParagraphStyle("q3", fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=C_DGREY)),
        sp(2),
        Paragraph("<b>Surgical Closure Timing:</b> Within 24–72 hours postnatal. Ruptured/exposed sac = same-day emergency.", BODY_SML),
        sp(1),
        Paragraph("<b>Prenatal repair (MOMS Trial):</b> VP shunt need 40% vs 82%; independent walking 44.8% vs 23.9%", BODY_SML),
    ]

    story.append(two_col(qr_left, qr_right))
    story.append(sp(3))
    story.append(Paragraph(
        "Sources: Bradley & Daroff's Neurology 8e | Miller's Anesthesia 10e | Creasy & Resnik's MFM | "
        "The Developing Human (Moore & Persaud) | Medical Physiology (Boron & Boulpaep) | "
        "MOMS Trial (NEJM 2011) | Kunpalin et al. 2025 (PMID 40492626) | Oliveira et al. 2025 (PMID 40779058)",
        SOURCE))

    return story


# ─── BUILD PDF ─────────────────────────────────────────────────────────────────
def build_pdf(output_path):
    doc = SimpleDocTemplate(
        output_path,
        pagesize=A4,
        leftMargin=MARGIN_OUTER,
        rightMargin=MARGIN_OUTER,
        topMargin=10*mm,
        bottomMargin=8*mm,
        title="Myelomeningocele — Neonatologist Reference",
        author="Orris Medical AI",
        subject="MMC/Meningomyelocele Clinical Reference",
    )
    story = build_story()
    doc.build(story, onFirstPage=page_header, onLaterPages=page_header)
    print(f"PDF written → {output_path}")


if __name__ == "__main__":
    build_pdf("/home/daytona/workspace/mmc-pdf/Myelomeningocele_Neonatologist_Reference.pdf")

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/mmc-pdf/generate_mmc_pdf.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/mmc-pdf/generate_mmc_pdf.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/mmc-pdf/generate_mmc_pdf.py'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/mmc-pdf/generate_mmc_pdf.py'

#!/usr/bin/env python3
"""
MYELOMENINGOCELE — Full Neonatologist/Paediatrician Reference PDF
ALL content, ALL tables, ALL images, 2-column bookish layout
"""

import os, urllib.request, io
from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import mm
from reportlab.lib.styles import ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, KeepTogether, PageBreak, Image, KeepInFrame
)
from reportlab.platypus.flowables import Flowable
from reportlab.lib.colors import HexColor, white, black
from reportlab.graphics.shapes import Drawing, Rect, String
from PIL import Image as PILImage

PAGE_W, PAGE_H = A4

# ── Colours ──────────────────────────────────────────────────────────────────
NAVY   = HexColor("#1a3a5c")
TEAL   = HexColor("#0e7c86")
ORANGE = HexColor("#e07b39")
SKY    = HexColor("#daf0f5")
LIME   = HexColor("#e8f5e9")
YELLOW = HexColor("#fff8e1")
RED    = HexColor("#b71c1c")
GREY   = HexColor("#f5f5f5")
LGREY  = HexColor("#90a4ae")
PURPLE = HexColor("#6a1b9a")
DGREY  = HexColor("#37474f")
GREEN  = HexColor("#1b5e20")
LGREEN = HexColor("#2e7d32")
AMBER  = HexColor("#e65100")

# ── Margins / column geometry ─────────────────────────────────────────────────
ML = MR = 11*mm
MT = 11*mm
MB = 8*mm
GAP = 5*mm
COL = (PAGE_W - ML - MR - GAP) / 2   # ~87 mm per column

# ── Styles ────────────────────────────────────────────────────────────────────
def S(n, **k): return ParagraphStyle(n, **k)

BODY    = S("BODY",  fontName="Helvetica",       fontSize=7.2, leading=10.5, textColor=DGREY, alignment=TA_JUSTIFY)
BODYL   = S("BODYL", fontName="Helvetica",       fontSize=7.2, leading=10.5, textColor=DGREY, alignment=TA_LEFT)
BODS    = S("BODS",  fontName="Helvetica",       fontSize=6.7, leading=9.5,  textColor=DGREY, alignment=TA_JUSTIFY)
BOLDS   = S("BOLDS", fontName="Helvetica-Bold",  fontSize=7.2, leading=10.5, textColor=DGREY)
ITALIC  = S("IT",    fontName="Helvetica-Oblique",fontSize=6.8,leading=9.5,  textColor=LGREY)
CAPT    = S("CAPT",  fontName="Helvetica-Oblique",fontSize=6.5,leading=9,    textColor=LGREY, alignment=TA_CENTER)
NOTE_P  = S("NP",    fontName="Helvetica-Oblique",fontSize=6.8,leading=9.5,  textColor=PURPLE)
SOURCE  = S("SRC",   fontName="Helvetica-Oblique",fontSize=5.8,leading=8,    textColor=LGREY)

H1  = S("H1",  fontName="Helvetica-Bold", fontSize=12, leading=15, textColor=white, alignment=TA_CENTER)
H2  = S("H2",  fontName="Helvetica-Bold", fontSize=8,  leading=11, textColor=white, alignment=TA_LEFT)
H3  = S("H3",  fontName="Helvetica-Bold", fontSize=7.5,leading=10, textColor=NAVY,  alignment=TA_LEFT)
H4  = S("H4",  fontName="Helvetica-Bold", fontSize=7.0,leading=9.5,textColor=TEAL,  alignment=TA_LEFT)
H5  = S("H5",  fontName="Helvetica-Bold", fontSize=6.8,leading=9,  textColor=ORANGE,alignment=TA_LEFT)

BUL  = S("BUL", fontName="Helvetica",      fontSize=7, leading=10, textColor=DGREY, leftIndent=9,  firstLineIndent=-7)
BULB = S("BULB",fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=DGREY, leftIndent=9,  firstLineIndent=-7)
BULR = S("BULR",fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=RED,   leftIndent=9,  firstLineIndent=-7)
BULT = S("BULT",fontName="Helvetica",      fontSize=7, leading=10, textColor=TEAL,  leftIndent=9,  firstLineIndent=-7)
BULG = S("BULG",fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=LGREEN,leftIndent=9,  firstLineIndent=-7)

NUM  = S("NUM", fontName="Helvetica",      fontSize=7, leading=10, textColor=DGREY, leftIndent=12, firstLineIndent=-10)
NUMB = S("NUMB",fontName="Helvetica-Bold", fontSize=7, leading=10, textColor=NAVY,  leftIndent=12, firstLineIndent=-10)

# ── Spacing helpers ───────────────────────────────────────────────────────────
def sp(n=2):   return Spacer(1, n)
def hr(c=TEAL):return HRFlowable(width="100%", thickness=0.5, color=c, spaceAfter=2, spaceBefore=2)

# ── Coloured header bar ───────────────────────────────────────────────────────
class Bar(Flowable):
    def __init__(self, text, bg=TEAL, style=None, h=6.5*mm, r=2, icon=""):
        super().__init__()
        self.text=icon+("  " if icon else "")+text; self.bg=bg; self.h=h; self.ts=style or H2; self.r=r; self._w=0
    def wrap(self,aw,ah): self._w=aw; return aw,self.h
    def draw(self):
        c=self.canv; c.setFillColor(self.bg)
        c.roundRect(0,0,self._w,self.h,self.r,fill=1,stroke=0)
        p=Paragraph(self.text,self.ts); pw,ph=p.wrap(self._w-4*mm,self.h)
        p.drawOn(c,2*mm,(self.h-ph)/2)

# ── Alert / note box ──────────────────────────────────────────────────────────
class Box(Flowable):
    def __init__(self, text, bg=YELLOW, border=ORANGE, style=None, label="", r=2):
        super().__init__()
        self.text=text; self.bg=bg; self.border=border
        self.ts=style or BODS; self.label=label; self.r=r; self._w=self._h=0
    def wrap(self,aw,ah):
        self._w=aw
        txt=("<b>"+self.label+"</b> " if self.label else "")+self.text
        p=Paragraph(txt,self.ts); _,ph=p.wrap(self._w-6*mm,9999)
        self._h=ph+4*mm; return aw,self._h
    def draw(self):
        c=self.canv; c.setFillColor(self.bg); c.setStrokeColor(self.border); c.setLineWidth(0.8)
        c.roundRect(0,0,self._w,self._h,self.r,fill=1,stroke=1)
        txt=("<b>"+self.label+"</b> " if self.label else "")+self.text
        p=Paragraph(txt,self.ts); p.wrap(self._w-6*mm,9999); p.drawOn(c,3*mm,2*mm)

# ── Table builder ─────────────────────────────────────────────────────────────
def tbl(data, cw, hbg=NAVY, altbg=GREY, htc=white, fs=6.5, lead=9.5, vpad=2):
    rows=[]
    for ri,row in enumerate(data):
        r2=[]
        for cell in row:
            st=S(f"c{ri}", fontName="Helvetica-Bold" if ri==0 else "Helvetica",
                 fontSize=fs, leading=lead,
                 textColor=htc if ri==0 else DGREY)
            r2.append(Paragraph(str(cell),st))
        rows.append(r2)
    ts=TableStyle([
        ("BACKGROUND",(0,0),(-1,0),hbg),
        ("GRID",(0,0),(-1,-1),0.4,HexColor("#cfd8dc")),
        ("ROWBACKGROUNDS",(0,1),(-1,-1),[white,altbg]),
        ("TOPPADDING",(0,0),(-1,-1),vpad),("BOTTOMPADDING",(0,0),(-1,-1),vpad),
        ("LEFTPADDING",(0,0),(-1,-1),3),("RIGHTPADDING",(0,0),(-1,-1),3),
        ("VALIGN",(0,0),(-1,-1),"MIDDLE"),
    ])
    return Table(rows,colWidths=cw,style=ts,repeatRows=1)

# ── Two-column wrapper ────────────────────────────────────────────────────────
def two(L, R, cw=COL, gap=GAP):
    lf=KeepInFrame(cw,9999,L,mode='shrink')
    rf=KeepInFrame(cw,9999,R,mode='shrink')
    t=Table([[lf,rf]],colWidths=[cw,cw])
    t.setStyle(TableStyle([
        ("VALIGN",(0,0),(-1,-1),"TOP"),
        ("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0),
        ("INNERGRID",(0,0),(-1,-1),0,white),("BOX",(0,0),(-1,-1),0,white),
    ]))
    return t

# ── Full-width wrapper ────────────────────────────────────────────────────────
def full(content, cw=COL*2+GAP):
    f=KeepInFrame(cw,9999,content,mode='shrink')
    t=Table([[f]],colWidths=[cw])
    t.setStyle(TableStyle([("LEFTPADDING",(0,0),(-1,-1),0),("RIGHTPADDING",(0,0),(-1,-1),0),
        ("TOPPADDING",(0,0),(-1,-1),0),("BOTTOMPADDING",(0,0),(-1,-1),0)]))
    return t

# ── Remote image fetcher ──────────────────────────────────────────────────────
IMG_CACHE={}
def remote_img(url, width, caption=None):
    """Fetch a remote image, return [Image, caption_paragraph] or []"""
    items=[]
    try:
        if url not in IMG_CACHE:
            req=urllib.request.Request(url, headers={"User-Agent":"Mozilla/5.0"})
            data=urllib.request.urlopen(req, timeout=15).read()
            IMG_CACHE[url]=data
        data=IMG_CACHE[url]
        buf=io.BytesIO(data)
        pil=PILImage.open(buf)
        iw,ih=pil.size
        h=width*(ih/iw)
        buf.seek(0)
        img=Image(buf,width=width,height=h)
        items.append(img)
        if caption:
            items.append(Paragraph(caption,CAPT))
    except Exception as e:
        items.append(Paragraph(f"[Image: {caption or url[:60]}]",CAPT))
    return items

# ── Page decorations ──────────────────────────────────────────────────────────
def decor(canvas, doc):
    canvas.saveState()
    # top navy bar
    canvas.setFillColor(NAVY); canvas.rect(0,PAGE_H-9*mm,PAGE_W,9*mm,fill=1,stroke=0)
    canvas.setFillColor(white); canvas.setFont("Helvetica-Bold",7.5)
    canvas.drawCentredString(PAGE_W/2, PAGE_H-6*mm,
        "MYELOMENINGOCELE (MMC)  |  Neonatologist & Paediatrician — Complete In-Depth Reference")
    # bottom bar
    canvas.setFillColor(NAVY); canvas.rect(0,0,PAGE_W,6.5*mm,fill=1,stroke=0)
    canvas.setFillColor(white); canvas.setFont("Helvetica",5.5)
    canvas.drawString(ML, 2.3*mm,
        "Sources: Bradley & Daroff Neurology 8e | Miller's Anesthesia 10e | Creasy & Resnik MFM | The Developing Human | Medical Physiology | MOMS Trial")
    canvas.drawRightString(PAGE_W-MR, 2.3*mm, f"Page {doc.page}")
    # left accent
    canvas.setFillColor(TEAL); canvas.rect(0,6.5*mm,1.8*mm,PAGE_H-15.5*mm,fill=1,stroke=0)
    canvas.restoreState()

# ═════════════════════════════════════════════════════════════════════════════
# STORY BUILDER
# ═════════════════════════════════════════════════════════════════════════════
def story():
    S_=[]

    # ─────────────────────────────────────────────────────────────────────────
    # COVER BANNER
    # ─────────────────────────────────────────────────────────────────────────
    S_.append(Bar("MYELOMENINGOCELE  (Meningomyelocele)", bg=NAVY, h=16*mm,
        style=S("tt",fontName="Helvetica-Bold",fontSize=13,leading=16,textColor=white,alignment=TA_CENTER)))
    S_.append(sp(2))
    S_.append(Paragraph(
        "A complete neonatologist / paediatrician teaching reference — every section, table, diagram, and clinical pearl",
        S("sub",fontName="Helvetica-Oblique",fontSize=7.5,leading=10,textColor=TEAL,alignment=TA_CENTER)))
    S_.append(sp(2))
    S_.append(Paragraph(
        "<b>Terminology note:</b> The terms <i>myelomeningocele</i> (MMC) and <i>meningomyelocele</i> are used interchangeably. "
        "\"Myelomeningocele\" is the preferred modern term. It is a subset of open spina bifida and the most severe "
        "common form of neural tube defect (NTD) compatible with life.",
        BODS))
    S_.append(sp(3))
    S_.append(hr(NAVY))

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 1 — ANATOMY  |  SECTION 2 — EMBRYOLOGY
    # ─────────────────────────────────────────────────────────────────────────
    L1=[
        Bar("1 · THE ANATOMY — WHAT EXACTLY IS IT?", bg=TEAL),
        sp(2),
        Paragraph("Understand the spectrum first:", BODYL),
        sp(2),
        tbl([
            ["Type","What Herniates","Neural Elements?","Neurological Deficit"],
            ["Spina bifida occulta","Nothing — vertebral arch unfused only","No","Usually none"],
            ["Meningocele","Meninges + CSF only","No","Usually none"],
            ["MYELOMENINGOCELE","Meninges + spinal cord + nerve roots","YES","ALWAYS PRESENT"],
            ["Myeloschisis","Open spinal cord, no sac — exposed neural plate","Yes","Severe"],
        ], cw=[30*mm,34*mm,22*mm,COL-86*mm+0.5]),
        sp(3),
        Paragraph(
            "In MMC, the spinal cord itself (the <b>placode</b>) lies within or at the surface of the sac. "
            "The neural tissue is directly exposed to amniotic fluid — this is critical to understanding "
            "why postnatal (or prenatal) closure is urgent.", BODY),
        sp(3),
        Box(
            "The neural PLACODE (dysplastic spinal cord) lies exposed in or at the surface of the sac — "
            "directly bathed in amniotic fluid throughout gestation. This chronic chemical and mechanical "
            "trauma to exposed neural tissue is responsible for the progressive secondary neurological injury "
            "that occurs in utero.",
            bg=SKY, border=TEAL,
            style=S("bx1",fontName="Helvetica",fontSize=7,leading=10.5,textColor=NAVY)),
        sp(3),
        Paragraph("<b>Location of Defect:</b>", H4),
        sp(1),
        Paragraph("● <b>&gt;75%</b> of cases involve the <b>lumbar and sacral region</b>", BUL),
        Paragraph("● Most common: lumbosacral junction (L4–S1)", BUL),
        Paragraph("● Thoracic lesions — minority but associated with the worst deficit", BUL),
        Paragraph("● Cervical lesions — rare", BUL),
        sp(3),
        Paragraph("<b>Myelomeningocele vs Meningocele — The Critical Distinction:</b>", H4),
        sp(1),
        Paragraph(
            "If the sac contains nerve roots or spinal cord → <b>myelomeningocele</b>. "
            "If neural elements are absent from the sac → <b>meningocele</b>. "
            "These brain and spinal cord malformations may be associated with CSF leakage into "
            "adjacent structures, posing a risk of meningitis. Neurological deficits are directly "
            "related to the anatomical extent of the malformation and vary from insignificant to grave.",
            BODY),
    ]

    R1=[
        Paragraph("<b>Figure: Variations of Spina Bifida</b>", H4),
        sp(2),
    ]
    R1 += remote_img(
        "https://cdn.orris.care/cdss_images/90a054b0c539236e25b1af1dc6a9337fe0a9a0311a782e0a28ed71ed4eea9122.png",
        COL-2*mm,
        "Cross-section of myelomeningocele: displaced spinal cord and nerve roots herniated into the membranous sac through the unfused vertebral arch. (Medical Physiology, Fig. 10-7C)")
    R1+=[
        sp(3),
        Paragraph("<b>Figure: Sagittal view of MMC</b>", H4),
        sp(2),
    ]
    R1 += remote_img(
        "https://cdn.orris.care/cdss_images/a1bf442be94c61b32a6c1e6d754e3b9e9bcb00367a28ef2f90ae4de2d0d7e53c.png",
        COL-2*mm,
        "Sagittal anatomical diagram showing the spinal cord and nerve roots descending into the posterior sac at the lumbar level. (Bradley & Daroff's Neurology, Fig. 104.10)")
    R1+=[
        sp(3),
        Paragraph("<b>Spina Bifida Spectrum — Cross-Sections:</b>", H4),
        sp(2),
    ]
    R1 += remote_img(
        "https://cdn.orris.care/cdss_images/f34ba7fe0742075e679bc08c0b194dd10390a5a1b9d736a3e1ffbbc1a02af68f.png",
        COL-2*mm,
        "A = Spina bifida occulta with tuft of hair (unfused arch, no herniation). B = Meningocele (dura + arachnoid herniate, no neural tissue). Spinal cord and vertebral anatomy labelled. (Medical Physiology)")
    S_.append(two(L1,R1))
    S_.append(sp(4)); S_.append(hr())

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 2 — EMBRYOLOGY  |  SECTION 3 — EPIDEMIOLOGY
    # ─────────────────────────────────────────────────────────────────────────
    L2=[
        Bar("2 · EMBRYOLOGY — WHY DOES IT HAPPEN?", bg=TEAL),
        sp(2),
        Paragraph(
            "<b>Timeline:</b> Weeks 3–4 of gestation (days 18–28). This is <b>before most women "
            "know they are pregnant</b>.", BODY),
        sp(2),
        Paragraph(
            "The neural plate folds to form the neural tube through a process called "
            "<b>primary neurulation</b>. Failure of this closure — specifically the "
            "<b>caudal neuropore</b> (which closes last, around day 26–28) — results in open "
            "defects at lumbar/sacral levels.", BODY),
        sp(3),
        Paragraph("<b>Neural Tube Closure Timeline:</b>", H4),
        sp(1),
        tbl([
            ["Day","Embryological Event"],
            ["Day 18","Neural plate forms from ectoderm"],
            ["Day 22–23","Neural folds begin fusing (cranial neuropore)"],
            ["Day 26","Rostral (anterior) neuropore closes"],
            ["Day 26–28","Caudal neuropore closes — FAILURE HERE = MMC"],
        ], cw=[16*mm, COL-16*mm]),
        sp(3),
        Paragraph("<b>Neural Tube Defects Classification Table:</b>", H4),
        sp(1),
        tbl([
            ["Malformation","Characteristics"],
            ["Brain Defects",""],
            ["Anencephaly","Absence of brain, massive skull, meninges, scalp defects"],
            ["Cephalocele","Partial brain herniation through skull defect (cranium bifidum)"],
            ["Meningocele","Meningeal herniation through skull or spine defect"],
            ["Spina Bifida Defects",""],
            ["Spina bifida occulta","Vertebral arch defect only — no herniation"],
            ["Spina bifida cystica","Herniation of dura and arachnoid through vertebral defect"],
            ["Myelomeningocele","Herniation of spinal cord AND meninges through vertebral defect"],
        ], cw=[36*mm, COL-36*mm]),
        sp(3),
        Paragraph("<b>The Two-Hit Hypothesis</b> (Creasy & Resnik MFM, 2022):", H3),
        sp(2),
        Box(
            "<b>Hit 1 — Primary failure:</b> Failure of neural tube closure at ~week 4 "
            "(genetic + environmental determinants). This creates the anatomic malformation "
            "with abnormal development of the spinal cord and associated tissues.\n\n"
            "<b>Hit 2 — Secondary damage:</b> Progressive damage from chronic exposure of "
            "the open neural placode to neurotoxic agents in amniotic fluid AND direct "
            "mechanical trauma throughout the remainder of gestation. "
            "This secondary injury worsens neurological function progressively in utero.",
            bg=YELLOW, border=ORANGE,
            style=S("2hit",fontName="Helvetica",fontSize=7,leading=10.5,textColor=DGREY)),
        sp(2),
        Paragraph(
            "<i>This two-hit model is the entire scientific rationale for in-utero surgery — "
            "closing the defect early stops Hit 2 and isolates neural tissue from "
            "the intrauterine environment. Animal models have demonstrated improved neonatal "
            "neurologic function with fetal closure, and ultrasound assessment demonstrates "
            "that central and peripheral neurologic injury is progressive during gestation.</i>",
            NOTE_P),
    ]

    R2=[
        Bar("3 · EPIDEMIOLOGY", bg=TEAL),
        sp(2),
        tbl([
            ["Parameter","Data"],
            ["Incidence","~1 in 3,000 live births (post-folate supplementation era)"],
            ["Pre-folate era","~1 in 1,000 live births in some populations"],
            ["Folate effect","~50% reduction in MMC; plateau now reached without elimination"],
            ["Terminations","25–40% of MMC pregnancies terminated after prenatal diagnosis"],
            ["Sex","Slight female predominance"],
            ["Most common level","Lumbosacral (>75% of cases)"],
            ["5-yr mortality","~14% overall; 35% in those with brainstem dysfunction"],
        ], cw=[32*mm, COL-32*mm]),
        sp(3),
        Paragraph("<b>Risk Factors:</b>", H3),
        sp(2),
        Paragraph("<b>Modifiable:</b>", H4),
        sp(1),
        Paragraph("● <b>Maternal folate deficiency</b> — most important modifiable factor", BUL),
        Paragraph("● <b>Low maternal B12</b> — may significantly increase NTD risk", BUL),
        Paragraph("● <b>Valproic acid</b> in 1st trimester — 1–2% NTD risk (highest known teratogen risk for NTDs)", BULR),
        Paragraph("● <b>Carbamazepine</b> — NTD risk", BULR),
        Paragraph("● Trimethoprim (folate antagonist)", BUL),
        Paragraph("● Methotrexate", BUL),
        Paragraph("● Maternal obesity", BUL),
        Paragraph("● Maternal diabetes mellitus", BUL),
        Paragraph("● Maternal hyperthermia in early pregnancy", BUL),
        sp(2),
        Paragraph("<b>Non-modifiable:</b>", H4),
        sp(1),
        Paragraph("● Prior affected pregnancy (approximately 10× background risk)", BUL),
        Paragraph("● Family history of neural tube defects", BUL),
        Paragraph("● Gene–gene and gene–environment interactions (most cases are multifactorial)", BUL),
        sp(3),
        Paragraph("<b>Prevention — Folic Acid:</b>", H3),
        sp(1),
        Paragraph(
            "Food fortification with folic acid and folic acid supplements taken <b>before conception</b> "
            "and continued for at least 3 months during pregnancy reduce the incidence of NTDs. "
            "In 2015, the US CDC urged all women of childbearing age who can become pregnant to get "
            "<b>0.4 mg of folic acid every day</b> to help reduce the risk of NTDs.", BODY),
        sp(1),
        Paragraph(
            "Epidemiologic studies have also shown that low maternal B12 levels may significantly "
            "increase the risk of NTDs.", BODY),
        sp(2),
        tbl([
            ["Population","Dose","Timing"],
            ["All women of childbearing age","400 mcg (0.4 mg) daily","Start BEFORE conception, continue 1st trimester"],
            ["Prior NTD pregnancy / on AED","4 mg/day (10× dose)","Start 1 month before conception, continue for 3 months"],
            ["Women on total parenteral nutrition","Folic acid supplement","As part of TPN fluid"],
        ], cw=[30*mm,22*mm,COL-52*mm]),
        sp(2),
        Box("Grain/cereal fortification with folate has reduced NTD prevalence by 30–50% at population level.",
            bg=LIME, border=LGREEN,
            style=S("fol",fontName="Helvetica",fontSize=7,leading=10,textColor=DGREY)),
    ]

    S_.append(two(L2,R2))
    S_.append(sp(4)); S_.append(hr())

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 4 — PRENATAL DIAGNOSIS  |  SECTION 5 — ASSOCIATED ANOMALIES
    # ─────────────────────────────────────────────────────────────────────────
    L3=[
        Bar("4 · PRENATAL DIAGNOSIS", bg=TEAL),
        sp(2),
        Paragraph("<b>Screening Pathway:</b>", H3),
        sp(1),
        tbl([
            ["Test","When","Sensitivity / Notes"],
            ["Maternal serum AFP (MSAFP)","14–16 weeks","Elevated in ~85% of open NTDs"],
            ["Amniocentesis AFP + AChE","As indicated (↑ MSAFP)","AChE more specific than AFP alone"],
            ["2nd trimester ultrasound","18–20 weeks","Detects >90% of NTDs"],
            ["Fetal MRI","19–25 weeks","Best lesion characterisation"],
        ], cw=[30*mm,22*mm,COL-52*mm]),
        sp(2),
        Paragraph(
            "Pregnant women can be screened at 14–16 weeks for serum α-fetoprotein (AFP) levels, "
            "which are elevated about <b>85% of the time</b> when the fetus has neural closure defects. "
            "The level of AFP may also be elevated in maternal blood serum. Amniocentesis is usually "
            "performed on pregnant women with high levels of serum AFP for determination of AFP level "
            "in amniotic fluid. An ultrasound scan may reveal an NTD that has resulted in spina bifida "
            "cystica. The fetal vertebral column can be detected by ultrasound at 10–12 weeks, and if "
            "there is a defect in the vertebral arch, a meningeal cyst may be detected in the affected area.",
            BODY),
        sp(3),
        Paragraph("<b>Ultrasound Signs — The Classic Triad:</b>", H3),
        sp(2),
        tbl([
            ["Sign","What You See","Mechanism"],
            ["🍋 Lemon sign","Frontal bone scalloping — skull looks like a lemon","Chiari II traction pulling brain anteriorly"],
            ["🍌 Banana sign","Curved cerebellum wrapping around brainstem","Hindbrain herniation into spinal canal"],
            ["Splayed vertebrae","U-shaped or V-shaped vertebrae on axial view","Direct spinal bifida — posterior elements unfused"],
        ], cw=[24*mm,36*mm,COL-60*mm]),
        sp(2),
        Paragraph(
            "Ultrasound detects greater than <b>90% of neural tube defects at 18–20 weeks</b> "
            "(coupled with AFP >95% detection rate).", BODY),
        sp(3),
        Paragraph("<b>Fetal MRI Advantages (19–25 wks):</b>", H4),
        sp(1),
        Paragraph("● Precise lesion level characterisation (better than USS)", BUL),
        Paragraph("● Degree of hindbrain herniation", BUL),
        Paragraph("● Cortical anomalies (polymicrogyria)", BUL),
        Paragraph("● Ventricular size and hydrocephalus assessment", BUL),
        Paragraph("● Identify associated brain malformations", BUL),
        sp(2),
    ]
    L3+=remote_img(
        "https://cdn.orris.care/cdss_images/53dea4ec16a11fdae29a3a0e41a5ef8608eca95112bea082ae77127db45c0fb7.png",
        COL-4*mm,
        "Second-trimester ultrasound: (A) midsagittal lumbosacral view with low-lying conus medullaris. (B) Pathologic tethered cord. (C) Cystic mass protruding from lumbosacral vertebral bodies. (D) Transverse U-shaped splayed vertebrae with herniated sac. (Creasy & Resnik MFM, Fig. 34.16)")
    L3+=[
        sp(2),
        Box("AFP is elevated because open neural defects allow CSF-AFP to leak into amniotic fluid → absorbed into maternal circulation. <b>Closed defects do NOT elevate AFP.</b> A normal AFP does NOT rule out spina bifida occulta.",
            bg=SKY, border=TEAL,
            style=S("afpb",fontName="Helvetica",fontSize=7,leading=10,textColor=DGREY)),
    ]

    R3=[
        Bar("5 · ASSOCIATED ANOMALIES", bg=ORANGE,
            style=S("h5o",fontName="Helvetica-Bold",fontSize=8,leading=11,textColor=white)),
        sp(2),
        Box("THE TRIAD — All three need active management from Day 1:\n"
            "1. CHIARI II MALFORMATION\n"
            "2. HYDROCEPHALUS\n"
            "3. NEUROGENIC BLADDER",
            bg=HexColor("#fff3e0"), border=ORANGE,
            style=S("triad",fontName="Helvetica-Bold",fontSize=7.5,leading=11.5,textColor=NAVY)),
        sp(3),
        Paragraph("<b>A. Chiari II Malformation</b> — present in virtually 100% of MMC", H3),
        sp(1),
        Paragraph(
            "In Chiari II malformation, the cerebellar vermis and caudal brainstem descend through "
            "an enlarged foramen magnum. The extent of brainstem herniation is variable, including "
            "portions of the medulla or even the pons. The downward traction of the tethered cord "
            "pulls the hindbrain caudally.", BODY),
        sp(2),
        Paragraph("<b>Anatomy of Chiari II:</b>", H4),
        sp(1),
        Paragraph("● Cerebellar vermis + caudal brainstem (medulla, sometimes pons) herniate through enlarged foramen magnum", BUL),
        Paragraph("● Small posterior fossa", BUL),
        Paragraph("● Kinked medulla", BUL),
        Paragraph("● Polymicrogyria can be seen", BUL),
        Paragraph("● Hydrocephalus and syringomyelia are common accompanying features", BUL),
        sp(2),
        Paragraph("<b>Clinical Consequences of Chiari II in Neonates/Infants:</b>", H4),
        sp(1),
        tbl([
            ["Sign","Mechanism","Severity"],
            ["Inspiratory stridor","Vocal cord palsy — CN X dysfunction","⚠ Common"],
            ["Apnea","Central (brainstem) or obstructive","⚠⚠ Serious"],
            ["Swallowing dysfunction","Bulbar palsy → aspiration risk","⚠⚠ Serious"],
            ["Central hypoventilation","Brainstem compression / dysfunction","⚠⚠⚠ Critical"],
            ["Opisthotonus","Severe brainstem herniation","⚠⚠⚠ Critical"],
        ], cw=[28*mm,34*mm,COL-62*mm], hbg=HexColor("#bf360c")),
        sp(2),
        Box("Brainstem dysfunction = <b>35% mortality by 5 years</b> even after repair. Neonates with spina bifida have 14% mortality by 5 years overall, rising to 35% in those with known brainstem dysfunction and Chiari II.",
            bg=HexColor("#ffebee"), border=RED,
            style=S("bsd",fontName="Helvetica-Bold",fontSize=7,leading=10.5,textColor=RED)),
        sp(3),
        Paragraph("<b>B. Hydrocephalus</b>", H3),
        sp(1),
        Paragraph(
            "Either defect (myelomeningocele or meningocele) is often accompanied by hydrocephalus or "
            "Chiari II malformation. More than 90% of cases of meningomyelocele have associated "
            "hydrocephalus due to coexistence of an Arnold–Chiari malformation. Most patients require "
            "surgical diversion of CSF to avoid high intracranial pressure-related complications.", BODY),
        sp(1),
        Paragraph("● <b>64–85%</b> of children with lumbosacral MMC require a VP shunt", BUL),
        Paragraph("● Higher lesion level → higher risk of shunt-dependent hydrocephalus", BUL),
        Paragraph("● Mechanism: obstruction of CSF flow at the 4th ventricle from Chiari II", BUL),
        Paragraph("● Mean IQ with VP shunting = <b>80 (low normal)</b> — decreased vs those not requiring shunt", BUL),
        Paragraph("● Even with successful shunting: complications of central hypoventilation, vocal cord dysfunction, and swallowing difficulties can persist", BUL),
        sp(3),
        Paragraph("<b>C. Latex Allergy</b>", H3),
        sp(1),
        Box("10–40% of children with MMC develop latex allergy from repeated early latex exposures during multiple procedures. STRICT LATEX-FREE ENVIRONMENT from birth — use only latex-free gloves, catheters, and equipment for ALL procedures, first and every subsequent anaesthetic.",
            bg=HexColor("#ffebee"), border=RED,
            style=S("ltx",fontName="Helvetica-Bold",fontSize=7,leading=10.5,textColor=RED)),
        sp(3),
        Paragraph("<b>D. Other Associated Anomalies:</b>", H4),
        sp(1),
        Paragraph("● <b>Tethered cord syndrome</b> — progressive neurological deterioration post-repair as cord re-tethers with scarring", BUL),
        Paragraph("● <b>Syringomyelia</b>", BUL),
        Paragraph("● <b>Craniolacunia (Lückenschädel)</b> — defective development of calvaria with depressed, non-ossified areas on inner surfaces of flat bones", BUL),
        Paragraph("● <b>Spinal dermoid and epidermoid inclusion cysts</b> — risk after surgical repair", BUL),
        Paragraph("● <b>Orthopedic:</b> hip dislocation, clubfoot, scoliosis, kyphosis, pressure ulcers (insensate skin)", BUL),
        Paragraph("● <b>Neurogenic bowel and bladder</b> — virtually universal", BUL),
        Paragraph("● <b>Precocious puberty</b> — associated with hydrocephalus", BUL),
        Paragraph("● <b>Polymicrogyria</b> and other cortical dysplasias", BUL),
    ]

    S_.append(two(L3,R3))
    S_.append(PageBreak())

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 6 — LESION LEVEL FUNCTIONAL ANATOMY  |  SECTION 7 — NEONATAL PRESENTATION
    # ─────────────────────────────────────────────────────────────────────────
    L4=[
        Bar("6 · LESION LEVEL — FUNCTIONAL ANATOMY FOR NEONATOLOGISTS", bg=TEAL),
        sp(2),
        Paragraph(
            "The <b>motor level</b> predicts functional ability. In MMC, the functional level is often "
            "<b>better than the anatomic level</b>. Motor deficits and cognitive dysfunction are "
            "correlated with lesion level — higher levels are associated with greater morbidity. "
            "Improved motor function has been observed at 2 years of age in children with MMC who "
            "underwent caesarean delivery before labour onset compared to those delivered vaginally "
            "or by caesarean after onset of labour.", BODY),
        sp(2),
        tbl([
            ["Lesion Level","Motor Function Preserved","Ambulation Potential","Bladder/Bowel"],
            ["Thoracic","Arms, trunk partially","Wheelchair-dependent","Neurogenic"],
            ["L1–L2","Hip flexors (iliopsoas)","Braces + wheelchair","Neurogenic"],
            ["L3–L4","Knee extensors (quadriceps)","May walk with braces","Neurogenic"],
            ["L4–L5","Ankle dorsiflexors, knee flexors","Walk with AFOs","Neurogenic (partial)"],
            ["Sacral","Intrinsic foot muscles","Independent walking","Variable"],
        ], cw=[16*mm,32*mm,28*mm,COL-76*mm]),
        sp(3),
        Paragraph("<b>Neurogenic Bladder — Why It Matters Most in the Neonate:</b>", H3),
        sp(1),
        Paragraph(
            "Almost ALL patients with MMC have <b>neurogenic bladder</b> regardless of lesion level, "
            "due to involvement of sacral roots (S2–S4). This means urinary retention with overflow "
            "incontinence if untreated, and risk of upper urinary tract damage.", BODY),
        sp(2),
        Box("NEUROGENIC BLADDER → Urinary retention → back pressure → hydronephrosis → vesicoureteral reflux → progressive CKD and renal failure if untreated.\n\n"
            "CLEAN INTERMITTENT CATHETERISATION (CIC) must be started within days of birth.",
            bg=YELLOW, border=ORANGE,
            style=S("nb",fontName="Helvetica",fontSize=7,leading=10.5,textColor=DGREY)),
        sp(2),
        Paragraph("● Baseline renal USS in first days of life", BUL),
        Paragraph("● Urodynamic studies in first weeks of life", BUL),
        Paragraph("● Urology consult before discharge", BUL),
        Paragraph("● CIC technique taught to parents prior to discharge", BUL),
        sp(3),
        Paragraph("<b>Dermatomal Sensory Testing at Delivery:</b>", H4),
        sp(1),
        tbl([
            ["Level","Sensory Region Tested"],
            ["L1","Inguinal ligament / groin"],
            ["L2","Medial thigh"],
            ["L3","Medial knee"],
            ["L4","Medial leg and ankle"],
            ["L5","Dorsum of foot, great toe"],
            ["S1","Lateral foot and sole"],
            ["S2–S4","Perineum and perianal region"],
        ], cw=[16*mm, COL-16*mm]),
        sp(2),
        Paragraph(
            "<i>Note: Any existing myelopathic or radiculopathic neurological deficit is likely to "
            "persist after surgery. The goal of closure is to prevent further deterioration and "
            "infection, not to restore lost function.</i>", NOTE_P),
    ]

    R4=[
        Bar("7 · NEONATAL PRESENTATION AND INITIAL ASSESSMENT", bg=TEAL),
        sp(2),
        Paragraph("<b>At Delivery — What You See:</b>", H3),
        sp(1),
        Paragraph(
            "The neonate is born with a visible posterior midline mass, most commonly in the "
            "<b>lumbosacral region</b>. Spinal defects are often visible on examination of the back "
            "of the newborn.", BODY),
        sp(2),
        tbl([
            ["Finding","What It Tells You","Action"],
            ["Posterior midline sac","Diagnostic of spina bifida cystica","Document level, size"],
            ["Translucent intact sac","Relatively protected neural tissue","Still urgent closure"],
            ["Ruptured/exposed placode","Direct route for ascending infection","Same-day surgical emergency"],
            ["Flaccid lower limbs","Level of cord involvement","Assess dermatomal level"],
            ["Absent voluntary movement","Upper level of lesion","Document carefully"],
            ["Absent anal wink","S2–S4 root involvement","Neurogenic bladder certain"],
            ["Macrocephaly / bulging fontanelle","Pre-existing hydrocephalus","Urgent cranial USS"],
            ["Inspiratory stridor","Chiari II vocal cord palsy (CN X)","Respiratory monitoring"],
            ["Abnormal cry/voice","Vocal cord palsy / bulbar","Assess swallow safety"],
        ], cw=[28*mm,34*mm,COL-62*mm]),
        sp(3),
        Paragraph("<b>Neurological Examination in the Delivery Room:</b>", H3),
        sp(1),
        tbl([
            ["What to Assess","How","What It Tells You"],
            ["Spontaneous leg movement","Observe with and without stimulation","Level of motor function"],
            ["Response to pin-prick","Careful dermatomal testing (L1–S4)","Sensory level"],
            ["Anal wink reflex","Perianal stimulation","S2–S4 sacral root integrity"],
            ["Lower limb tone","Passive movement assessment","LMN injury = flaccid"],
            ["Head circumference (OFC)","Measurement with tape","Pre-existing hydrocephalus"],
            ["Fontanelle tension","Careful palpation","Raised ICP"],
            ["Respiratory pattern","Observation + SpO2","Brainstem / Chiari II function"],
            ["Cry and voice quality","Listen carefully","Vocal cord palsy"],
            ["Swallow assessment","Observe feeding attempts","Aspiration risk"],
        ], cw=[26*mm,28*mm,COL-54*mm]),
        sp(3),
        Bar("8 · IMMEDIATE NEONATAL ORDERS — FIRST HOUR", bg=ORANGE,
            style=S("h8",fontName="Helvetica-Bold",fontSize=7.5,leading=10,textColor=white)),
        sp(2),
        tbl([
            ["#","Action","Rationale"],
            ["1","LATEX-FREE protocol — immediately, no exceptions","10–40% latex allergy risk with repeated exposure"],
            ["2","Prone or lateral decubitus positioning on padded doughnut ring","Protect sac; NEVER supine directly on the sac"],
            ["3","Sterile moist normal saline gauze over defect (non-adherent)","Prevent desiccation and ascending infection"],
            ["4","Incubator — active thermoregulation","High insensible fluid + heat losses from exposed sac"],
            ["5","IV access + increase maintenance fluids","Compensate for insensible losses from sac"],
            ["6","Cranial ultrasound","Ventricular size; rule out acute hydrocephalus"],
            ["7","Renal ultrasound","Baseline upper urinary tract assessment"],
            ["8","Urgent Neurosurgery consultation","Surgical closure within 24–72 hours"],
            ["9","Urology consultation","CIC protocol + urodynamics plan"],
            ["10","Hold oral feeds; assess swallow safety","Aspiration risk from Chiari II bulbar dysfunction"],
        ], cw=[6*mm,44*mm,COL-50*mm]),
        sp(2),
        Paragraph(
            "<i>Note on fluid loss: Underestimating insensible fluid and blood loss is a common "
            "anaesthetic pitfall. The exposed sac results in significant evaporative and third-space "
            "losses that must be factored into fluid management.</i>", NOTE_P),
    ]

    S_.append(two(L4,R4))
    S_.append(sp(4)); S_.append(hr())

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 9 — SURGICAL REPAIR  |  SECTION 10 — POST-OP NEONATAL CARE
    # ─────────────────────────────────────────────────────────────────────────
    L5=[
        Bar("9 · SURGICAL REPAIR", bg=TEAL),
        sp(2),
        Paragraph("<b>A. Postnatal Repair (Standard of Care for Decades):</b>", H3),
        sp(1),
        Paragraph(
            "Initial surgical treatment in utero or in the neonatal period can provide cosmetic repair "
            "and decrease the risk for meningitis. If uncorrected in utero, surgical closure of the "
            "spinal defect must be performed within a few days after birth.", BODY),
        sp(2),
        Paragraph("● Timing: <b>within 24–72 hours</b> of birth", BUL),
        Paragraph("● Ruptured/exposed placode = <b>same-day emergency</b>", BULR),
        Paragraph("● Rationale for urgency: open defect = direct route for ascending infection; CSF leak", BUL),
        Paragraph("● Surgical steps: separation of placode from surrounding skin → dural closure → fascial closure → skin closure", BUL),
        sp(3),
        Paragraph("<b>Anaesthesia Considerations for MMC Closure:</b>", H4),
        sp(1),
        Paragraph("● Special positioning: defect placed on a 'doughnut' ring; towels under head for tracheal intubation", BUL),
        Paragraph("● Underestimating insensible fluid and blood loss is a common hazard", BULR),
        Paragraph("● Association with hydrocephalus — raised ICP must be considered during induction", BUL),
        Paragraph("● Cranial nerve (vocal cord) palsy may cause inspiratory stridor on intubation", BUL),
        Paragraph("● Potential for brainstem herniation during airway manipulation", BULR),
        Paragraph("● Latex allergy precautions for ALL anaesthetics — first and subsequent", BULR),
        Paragraph("● Patients with lumbosacral MMC typically deliver by caesarean section before labour onset to preserve motor function", BUL),
        sp(3),
        Paragraph("<b>B. In Utero (Fetal) Repair — The MOMS Trial Revolution:</b>", H3),
        sp(2),
        Paragraph(
            "The landmark <b>Management of Myelomeningocele Study (MOMS Trial)</b> was a randomised, "
            "prospective clinical trial completed between 2003 and 2010 at three US medical centres. "
            "It examined the risks, benefits, and outcome of open in utero repair for MMC compared "
            "with standard postnatal repair among <b>183 patients</b>.", BODY),
        sp(2),
        Paragraph("<b>Rationale for Fetal Surgery:</b>", H4),
        sp(1),
        Paragraph(
            "Initial human studies found that in utero repair reversed the hindbrain herniation of "
            "the Arnold–Chiari II malformation and decreased the requirement for VP shunt placement "
            "before 1 year of age. A 1999 series of 10 fetuses undergoing in utero MMC closure at "
            "22–25 weeks' gestation found improved lower extremity function among 6 of 9 fetuses "
            "compared with expected function based on level of lesion.", BODY),
        sp(3),
        Paragraph("<b>MOMS Trial Results — Benefits of Prenatal Repair (at 30 months):</b>", H4),
        sp(1),
        tbl([
            ["Outcome","Prenatal Repair","Postnatal Repair","Significance"],
            ["VP shunt needed","40%","82%","p < 0.001"],
            ["Independent walking","44.8%","23.9%","p = 0.04"],
            ["Function ≥2 levels better than anatomic level","26.4%","11.4%","Significant"],
            ["Hindbrain herniation reversal","YES","No","Significant"],
            ["Bayley Mental Dev. Index","Better","Lower","Significant"],
            ["Peabody Developmental Motor Scale","Better","Lower","Significant"],
        ], cw=[38*mm,20*mm,20*mm,COL-78*mm], hbg=HexColor("#1b5e20")),
        sp(2),
        Paragraph(
            "Long-term outcome from this trial is still ongoing, but a pretrial cohort of 54 patients "
            "undergoing fetal MMC repair reported improved functional, behavioural, and motor outcomes "
            "at age 10 years, especially among children who did not require VP shunting.", BODY),
        sp(3),
        Paragraph("<b>MOMS Trial — Costs of Prenatal Repair:</b>", H4),
        sp(1),
        tbl([
            ["Maternal Complication","Prenatal Group","Postnatal Group"],
            ["Preterm birth / PPROM","Significantly ↑","Lower"],
            ["Partial/complete uterine dehiscence","~11%","Lower"],
            ["Maternal laparotomy + hysterotomy scar","Required","Not required"],
            ["Need for caesarean in future pregnancies","YES (scar)","No"],
            ["Perinatal deaths","2","2"],
        ], cw=[40*mm,24*mm,COL-64*mm], hbg=HexColor("#bf360c")),
        sp(2),
        Box("Results of this trial should NOT be generalised to patients outside the inclusion criteria. "
            "This procedure should be offered only at medical facilities with the expertise, "
            "multidisciplinary teams, services, and facilities to provide the intensive care required.",
            bg=YELLOW, border=ORANGE,
            style=S("moms",fontName="Helvetica",fontSize=7,leading=10,textColor=DGREY)),
        sp(3),
        Paragraph("<b>Fetal Surgery Window and Eligibility Criteria:</b>", H4),
        sp(1),
        Paragraph("● Window: <b>19–26 weeks' gestation</b>", BUL),
        Paragraph("● Singleton pregnancy", BUL),
        Paragraph("● MMC between T1 and S1 with hindbrain herniation", BUL),
        Paragraph("● Gestational age 19–25+6 weeks at evaluation", BUL),
        Paragraph("● Normal chromosomes", BUL),
        Paragraph("● No other major fetal anomalies", BUL),
        Paragraph("● No maternal contraindications (BMI, uterine anatomy, etc.)", BUL),
        sp(3),
        Paragraph("<b>Fetoscopic (Minimally Invasive) Repair:</b>", H4),
        sp(1),
        Paragraph(
            "Endoscopic myelomeningocele repair is increasingly practiced. In theory, a minimally "
            "invasive approach may reduce complications for pregnant individuals and obviate the need "
            "for caesarean delivery. A 2018 meta-analysis of 11 studies found no difference in "
            "mortality or need for VP shunt among fetal patients treated with open vs endoscopic technique.", BODY),
        sp(1),
        tbl([
            ["Approach","PPROM Rate","Preterm Delivery","CSF Leak","Uterine Dehiscence"],
            ["Open fetal surgery","36%","81%","7%","11%"],
            ["Fetoscopic (percutaneous)","91%","96%","30%","0%"],
        ], cw=[30*mm,20*mm,22*mm,18*mm,COL-90*mm]),
        sp(2),
        Box("A 2025 systematic review and meta-analysis (PMID: 40492626) confirms open fetal surgery remains the reference standard. Fetoscopic repair remains promising but not yet perfected.",
            bg=SKY, border=TEAL,
            style=S("feto",fontName="Helvetica",fontSize=7,leading=10,textColor=DGREY)),
    ]

    R5=[
        Bar("10 · POST-OPERATIVE NEONATAL CARE", bg=TEAL),
        sp(2),
        Paragraph("<b>Immediate Post-operative Care (First Week):</b>", H3),
        sp(1),
        Paragraph("● <b>Positioning:</b> Prone for 5–7 days to allow wound healing; avoid pressure on repair site", BUL),
        Paragraph("● <b>Monitor for hydrocephalus:</b> Head circumference (OFC) daily", BUL),
        Paragraph("● <b>Serial cranial USS:</b> Monitor ventricular size closely", BUL),
        Paragraph("● <b>Fontanelle checks:</b> Tension, bulging — signs of raised ICP?", BUL),
        Paragraph("● <b>Wound monitoring:</b> CSF leak at repair site, infection, dehiscence", BUL),
        Paragraph("● <b>Respiratory monitoring:</b> Apnea, central hypoventilation from Chiari II", BUL),
        Paragraph("● <b>NG feeds initially:</b> Assess swallow function before oral feeds — risk of aspiration with Chiari II-related bulbar dysfunction", BUL),
        Paragraph("● <b>Initiate CIC:</b> Urology clears — typically within days 1–3 post-closure", BUL),
        sp(3),
        Paragraph("<b>VP Shunt Decision — When and Why:</b>", H3),
        sp(1),
        Box("64–85% of lumbosacral MMC will need VP shunt. Usually placed days to weeks after closure. "
            "Signs requiring urgent shunting: rapidly rising OFC, bulging fontanelle, "
            "setting-sun sign, apnea, worsening brainstem signs.",
            bg=SKY, border=TEAL,
            style=S("vps",fontName="Helvetica",fontSize=7,leading=10.5,textColor=NAVY)),
        sp(2),
        Paragraph(
            "Common indications for VP shunt include hydrocephalus occurring in association with "
            "meningomyelocele, neonatal intraventricular haemorrhage, and posterior fossa tumours. "
            "Open fontanelles seem to provide some margin for error in younger patients — but never "
            "be casual about the management of these patients.", BODY),
        sp(3),
        Paragraph("<b>Before Discharge — Comprehensive Checklist:</b>", H3),
        sp(1),
        tbl([
            ["Domain","Required Before Discharge"],
            ["Neurosurgery","Wound healed; VP shunt placed if indicated and functioning"],
            ["Urology","CIC technique taught to parents; urodynamics scheduled"],
            ["Renal USS","Baseline documented before discharge"],
            ["Ophthalmology","Strabismus screen, papilloedema check"],
            ["Audiology","Baseline hearing screen (SNHL can be associated)"],
            ["Physiotherapy","Positioning, passive ROM, stretching taught to parents"],
            ["Occupational therapy","Developmental stimulation guidance"],
            ["Social work","Family counselling, support services, community resources"],
            ["Neurodevelopment","MDT follow-up plan in place — first appointment booked"],
            ["Dietetics","Feeding plan; risk of overweight in wheelchair-bound children"],
        ], cw=[26*mm, COL-26*mm]),
        sp(3),
        Paragraph("<b>Paediatric Neurosurgery — Post-Closure Complications to Watch:</b>", H4),
        sp(1),
        Paragraph("● <b>CSF leak</b> at repair site → risk of meningitis", BUL),
        Paragraph("● <b>Wound infection</b> or dehiscence", BUL),
        Paragraph("● <b>Acute hydrocephalus</b> developing post-closure", BUL),
        Paragraph("● <b>VP shunt infection</b> — Staph epidermidis most common", BUL),
        Paragraph("● <b>Shunt obstruction</b> — re-present with signs of raised ICP", BUL),
        Paragraph("● <b>Tethered cord syndrome</b> — progressive motor/bladder deterioration", BUL),
        sp(3),
        Box("Some patients, especially infants with progressive brainstem dysfunction, are treated with decompression of the rostral spinal canal (Chiari decompression). Less than 30% of such patients survive beyond the first year.",
            bg=HexColor("#ffebee"), border=RED,
            style=S("bss",fontName="Helvetica",fontSize=7,leading=10,textColor=DGREY)),
    ]

    S_.append(two(L5,R5))
    S_.append(sp(4)); S_.append(hr())

    # ─────────────────────────────────────────────────────────────────────────
    # SECTION 11 — LONG-TERM COMPLICATIONS  |  SECTION 12 — OUTCOMES
    # ─────────────────────────────────────────────────────────────────────────
    L6=[
        Bar("11 · LONG-TERM COMPLICATIONS — THE LIFESPAN PERSPECTIVE", bg=TEAL),
        sp(2),
        Paragraph(
            "As a neonatologist, you are launching a child into a life of multidisciplinary care. "
            "Understand what lies ahead for the patient and family:", BODY),
        sp(2),
        tbl([
            ["System","Problem","Typical Onset"],
            ["CNS","Shunt malfunction / infection","Anytime"],
            ["CNS","Tethered cord syndrome (progressive neurological deterioration)","Childhood, adolescence"],
            ["CNS","Syringomyelia","Any age"],
            ["CNS","Chiari II decompensation","Any age"],
            ["Urological","Neurogenic bladder, recurrent UTIs, VUR, renal scarring, CKD","Lifelong from birth"],
            ["Urological","Neurogenic bowel (constipation, incontinence)","Lifelong from birth"],
            ["Orthopedic","Scoliosis, kyphosis","Childhood +"],
            ["Orthopedic","Hip dislocation, subluxation","Infancy +"],
            ["Orthopedic","Clubfoot, foot deformities","Present at birth"],
            ["Orthopedic","Pressure ulcers (insensate skin)","Any age"],
            ["Cognitive","Learning disabilities, executive function deficits","School age"],
            ["Cognitive","Attention problems (ADHD-like)","School age"],
            ["Allergy","Latex anaphylaxis","Lifelong"],
            ["Endocrine","Precocious puberty (hydrocephalus-related)","Childhood"],
            ["Respiratory","Central sleep apnea","Any age"],
            ["Sexual function","Dysfunction — depends on level","Adolescence+"],
        ], cw=[26*mm,46*mm,COL-72*mm]),
    ]

    R6=[
        Bar("12 · OUTCOMES AND PROGNOSIS", bg=TEAL),
        sp(2),
        Paragraph("<b>Intellectual Outcomes:</b>", H3),
        sp(1),
        Paragraph(
            "More than <b>70% of survivors with neural tube defects have an IQ greater than 80</b>. "
            "However, executive function, attention, and processing speed are disproportionately "
            "affected even with preserved overall IQ. With VP shunting, mean IQ is approximately "
            "<b>80 (low normal)</b> — decreased compared to those who do not require a shunt. "
            "Few patients with myelomeningocele are mentally normal, but most of those with lumbar "
            "meningocele (without neural involvement) are.", BODY),
        sp(2),
        Paragraph("<b>Ambulation Outcomes:</b>", H3),
        sp(1),
        Paragraph("● <b>46–75%</b> of children with lumbosacral MMC will walk (with or without assistive devices)", BUL),
        Paragraph("● Following MOMS fetal repair: 46% could ambulate independently at 30-month follow-up", BULT),
        Paragraph("● 46% had functional level at least two segments better than anatomic level", BULT),
        sp(3),
        Paragraph("<b>Survival:</b>", H3),
        sp(1),
        Paragraph("● Neonates with spina bifida have a <b>14% mortality rate by 5 years</b>", BUL),
        Paragraph("● <b>35% mortality rate</b> in those with known brainstem dysfunction and Chiari II", BULR),
        Paragraph("● 5-year mortality rate among patients with spina bifida undergoing neonatal repair: 79 per 1,000 births", BUL),
        sp(3),
        Paragraph("<b>Independence in Adulthood:</b>", H3),
        sp(1),
        Paragraph("● Only <b>37% can live independently as adults</b>", BUL),
        Paragraph("● Many have anal sphincteric dysfunction and lower extremity paralysis", BUL),
        Paragraph("● Sexual dysfunction is common depending on level", BUL),
        sp(3),
        Box("Cognitive outcomes are best in children who:\n"
            "1. Have sacral-level lesions (lower)\n"
            "2. Do NOT require VP shunting\n"
            "3. Undergo fetal repair (better Bayley scores)\n"
            "4. Have no shunt infections",
            bg=LIME, border=LGREEN,
            style=S("cog",fontName="Helvetica",fontSize=7,leading=10.5,textColor=DGREY)),
        sp(3),
        Paragraph("<b>Antenatal Counselling Points:</b>", H3),
        sp(1),
        Paragraph("● >70% will have IQ >80 — most are educable", BUL),
        Paragraph("● Most will require lifelong multidisciplinary follow-up", BUL),
        Paragraph("● Ambulation is possible for many lumbosacral cases", BUL),
        Paragraph("● Quality of life reported as good by many patients with MMC", BUL),
        Paragraph("● Fetal surgery option should be discussed — refer to a fetal surgery centre before 26 weeks", BULT),
        Paragraph("● Prenatal repair: better motor and intellectual outcomes but maternal risks must be weighed", BUL),
        sp(3),
        Paragraph("<b>Hemimyelomeningocele:</b>", H4),
        sp(1),
        Paragraph(
            "A 2026 systematic review and meta-analysis (PMID: 41511579) examined "
            "hemimyelomeningocele — a rare variant where only one half of the spinal cord is involved. "
            "This represents a distinct entity on the dysraphism spectrum with variable outcomes.", BODS),
    ]

    S_.append(two(L6,R6))
    S_.append(sp(4)); S_.append(hr(NAVY))
    S_.append(PageBreak())

    # ─────────────────────────────────────────────────────────────────────────
    # FULL-WIDTH: PREVENTION + QUICK REFERENCE BEDSIDE CARD
    # ─────────────────────────────────────────────────────────────────────────
    S_.append(Bar("12 · PREVENTION — FOLIC ACID AND DRUG AVOIDANCE", bg=NAVY, h=7*mm,
        style=S("pv",fontName="Helvetica-Bold",fontSize=8.5,leading=11,textColor=white,alignment=TA_CENTER)))
    S_.append(sp(3))

    PL=[
        Paragraph("<b>Folic Acid Supplementation — The Key Public Health Intervention:</b>", H3),
        sp(1),
        Paragraph(
            "Food fortification with folic acid and folic acid supplements taken <b>before conception</b> "
            "and continued for at least 3 months during pregnancy reduce the incidence of NTDs. "
            "The mechanism is that folate is essential for DNA synthesis, methylation reactions, and "
            "neural tube closure — and the critical window is days 18–28, <b>before most women know "
            "they are pregnant</b>.", BODY),
        sp(2),
        tbl([
            ["Population","Dose","Timing","Source"],
            ["All women of childbearing age","400 mcg (0.4 mg)/day","Start BEFORE conception, continue through 1st trimester","CDC 2015"],
            ["Prior NTD pregnancy OR on antiepileptic drugs","4 mg/day (10× dose)","Start 1 month before conception, continue for first 3 months","Evidence-based guideline"],
            ["On total parenteral nutrition","As part of TPN","Continuous","Clinical practice"],
        ], cw=[30*mm,24*mm,50*mm,COL-104*mm+GAP/2]),
        sp(2),
        Paragraph(
            "In women with a history of a pregnancy complicated by a neural tube defect, "
            "an even larger dose of <b>4 mg/day</b> has been recommended. "
            "There are two approaches to preventing NTDs: (1) educate women to supplement their "
            "diets with folic acid 1 month before conception continuing for 2 months after conception; "
            "(2) food fortification programmes.", BODY),
    ]

    PR=[
        Paragraph("<b>Drugs to Avoid in Pregnancy (Especially Trimester 1):</b>", H3),
        sp(1),
        Box("Valproic acid causes NTDs in 1–2% of pregnancies if taken during early pregnancy when "
            "the neural folds are fusing. This is one of the highest known teratogen risks for NTDs.",
            bg=HexColor("#ffebee"), border=RED,
            style=S("val",fontName="Helvetica-Bold",fontSize=7,leading=10.5,textColor=RED)),
        sp(2),
        tbl([
            ["Drug","Mechanism of NTD Risk"],
            ["Valproic acid","Direct NTD teratogen — 1–2% risk; folate antagonism"],
            ["Carbamazepine","NTD risk; enzyme inducing"],
            ["Trimethoprim","Folate antagonist — inhibits dihydrofolate reductase"],
            ["Methotrexate","Folate antagonist — direct anti-folate"],
        ], cw=[32*mm, COL-32*mm+GAP/2]),
        sp(2),
        Paragraph(
            "Grain/cereal fortification with folate has reduced NTD prevalence by <b>30–50%</b> "
            "at population level in countries that have implemented mandatory fortification programmes.", BODY),
    ]

    S_.append(two(PL,PR))
    S_.append(sp(4)); S_.append(hr())

    # ── QUICK REFERENCE BEDSIDE CARD ──────────────────────────────────────────
    S_.append(Bar("QUICK REFERENCE — BEDSIDE CARD FOR NEONATOLOGISTS", bg=GREEN, h=7*mm,
        style=S("qb",fontName="Helvetica-Bold",fontSize=8.5,leading=11,textColor=white,alignment=TA_CENTER)))
    S_.append(sp(3))

    QL=[
        Paragraph("<b>5 Signs That Spot MMC at Birth:</b>", H3),
        sp(1),
        Paragraph("1️⃣  Posterior midline sac — most commonly lumbosacral", NUMB),
        Paragraph("2️⃣  Flaccid lower limbs / no voluntary movement below lesion", NUMB),
        Paragraph("3️⃣  Absent anal wink reflex (S2–S4 involvement)", NUMB),
        Paragraph("4️⃣  Macrocephaly / bulging fontanelle (hydrocephalus)", NUMB),
        Paragraph("5️⃣  Possible inspiratory stridor (Chiari II vocal cord palsy)", NUMB),
        sp(3),
        Paragraph("<b>Your First 6 Steps in the Delivery Room:</b>", H3),
        sp(1),
        Box("① LATEX-FREE — from this exact moment. No exceptions.\n"
            "② Prone on doughnut ring — sterile moist saline gauze over sac\n"
            "③ Incubator — prevent heat and evaporative fluid loss\n"
            "④ IV access + increase maintenance fluids\n"
            "⑤ Cranial USS + Renal USS stat\n"
            "⑥ Urgent Neurosurgery + Urology consults",
            bg=LIME, border=LGREEN,
            style=S("qstep",fontName="Helvetica-Bold",fontSize=7.5,leading=12,textColor=NAVY)),
        sp(3),
        Paragraph("<b>Surgical Timing:</b>", H4),
        sp(1),
        Paragraph("● Postnatal closure: <b>within 24–72 hours</b> of birth", BUL),
        Paragraph("● Ruptured/exposed placode = <b>same-day emergency</b>", BULR),
        Paragraph("● Prenatal repair: 19–26 weeks' gestation at designated centre", BULT),
        sp(2),
        Paragraph("<b>MOMS Trial Key Numbers:</b>", H4),
        sp(1),
        Paragraph("● VP shunt: 40% (prenatal) vs 82% (postnatal)", BUL),
        Paragraph("● Walk independently: 44.8% vs 23.9%", BUL),
        Paragraph("● Function ≥2 levels better: 26.4% vs 11.4%", BUL),
    ]

    QR=[
        Paragraph("<b>The 3 Mandatory Associations — All Need Active Day-1 Management:</b>", H3),
        sp(2),
        Box("CHIARI II MALFORMATION\n"
            "Monitor for: stridor, apnea, swallowing dysfunction, central hypoventilation.\n"
            "Present in virtually 100% of MMC. Mortality 35% if brainstem dysfunction.",
            bg=HexColor("#fff3e0"), border=ORANGE,
            style=S("q1",fontName="Helvetica-Bold",fontSize=7,leading=11,textColor=DGREY)),
        sp(2),
        Box("HYDROCEPHALUS\n"
            "Daily OFC measurements. Serial cranial USS.\n"
            "VP shunt required in 64–85% of lumbosacral MMC.\n"
            "Mean IQ with shunt ≈ 80 (low normal).",
            bg=SKY, border=TEAL,
            style=S("q2",fontName="Helvetica-Bold",fontSize=7,leading=11,textColor=DGREY)),
        sp(2),
        Box("NEUROGENIC BLADDER\n"
            "CIC from days 1–3 post-closure.\n"
            "Renal USS + urodynamics in first weeks.\n"
            "Prevent upper tract damage → protect kidneys for life.",
            bg=LIME, border=LGREEN,
            style=S("q3",fontName="Helvetica-Bold",fontSize=7,leading=11,textColor=DGREY)),
        sp(3),
        Paragraph("<b>Don't Forget:</b>", H3),
        sp(1),
        Paragraph("● Latex allergy precautions — every procedure, every anaesthetic, for life", BULR),
        Paragraph("● Assess swallow before oral feeds (Chiari II bulbar dysfunction)", BULR),
        Paragraph("● Caesarean before labour onset — better motor outcomes for the baby", BUL),
        Paragraph("● Baseline OFC, cranial USS, renal USS before discharge", BUL),
        Paragraph("● Teach CIC to parents before discharge", BUL),
        Paragraph("● Multidisciplinary follow-up: neurosurgery, urology, orthopaedics, physiotherapy, neurodevelopment, ophthalmology, audiology", BUL),
        sp(2),
        Paragraph("<b>Recurrence Risk Counselling:</b>", H4),
        sp(1),
        Paragraph("● Background population risk: ~1 in 3,000", BUL),
        Paragraph("● After one affected child: ~10× background risk (2–3%)", BUL),
        Paragraph("● After two affected children: ~10–15% risk", BUL),
        Paragraph("● Folic acid 4 mg/day from 1 month pre-conception for high-risk women", BULG),
    ]

    S_.append(two(QL,QR))
    S_.append(sp(4)); S_.append(hr(NAVY))
    S_.append(sp(2))
    S_.append(Paragraph(
        "<b>Sources:</b> Bradley & Daroff's Neurology in Clinical Practice 8e | Miller's Anesthesia 10e | "
        "Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice | "
        "The Developing Human: Clinically Oriented Embryology (Moore & Persaud) | "
        "Medical Physiology (Boron & Boulpaep) | Medical Physiology (Guyton & Hall) | "
        "MOMS Trial — NEJM 2011 | Kunpalin et al. 2025 (PMID: 40492626) | "
        "Oliveira et al. 2025 (PMID: 40779058) | Adiyaman et al. 2026 (PMID: 41511579)",
        SOURCE))

    return S_


# ── BUILD ─────────────────────────────────────────────────────────────────────
def build():
    out="/home/daytona/workspace/mmc-pdf/MMC_Full_Neonatologist_Reference.pdf"
    doc=SimpleDocTemplate(
        out, pagesize=A4,
        leftMargin=ML, rightMargin=MR,
        topMargin=11*mm, bottomMargin=8*mm,
        title="Myelomeningocele — Complete Neonatologist Reference",
        author="Orris Medical AI",
        subject="MMC Complete Reference — All Sections, Tables, Images",
    )
    doc.build(story(), onFirstPage=decor, onLaterPages=decor)
    print(f"✓ PDF → {out}")

if __name__=="__main__":
    build()