Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV)

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, life-threatening lung development disorder that begins before birth. In a healthy newborn, countless tiny air sacs (alveoli) are lined with a dense web of microscopic blood vessels (capillaries). Oxygen passes easily from the air into these capillaries, and carbon dioxide passes out for exhalation. In ACD/MPV, this matching system is built incorrectly. There are too few capillaries near the alveoli, many of them are placed too far from the air spaces, and small pulmonary veins are in the wrong location (they “misalign”) alongside arteries. Because of this faulty design, oxygen cannot move well into the blood, leading to very low oxygen levels, severe pulmonary hypertension (high pressure in the lung circulation), and breathing failure in the first hours or days of life. Most cases are linked to changes in a single gene called FOXF1, which guides how the fetal lung circulation forms. MedlinePlus+1

ACD/MPV is a rare, serious lung development problem that starts before birth. In this condition, the baby’s tiny air sacs (alveoli) and the tiny blood vessels (capillaries) that should touch each other for gas exchange do not line up or form normally. Some veins also run in the wrong place (misalignment), and the small lung arteries are often thicker and tighter than normal. Because of these changes, oxygen cannot pass well from the air into the blood. Newborns develop severe low oxygen and high blood pressure in the lungs (pulmonary hypertension) very soon after birth. Most babies get very sick in the first hours to days of life. MedlinePlus+2Orpha+2

Other names

Doctors and families may see several labels that mean the same condition: “ACD/MPV,” “alveolar capillary dysplasia,” and “congenital alveolar capillary dysplasia.” All refer to a congenital (present at birth) problem in the structure and placement of the tiny lung blood vessels and the small pulmonary veins. MedlinePlus

How the disease develops

During fetal life, the lung’s tiniest vessels grow under the guidance of master “instruction” genes. In ACD/MPV these instructions are disrupted—most often by a change affecting FOXF1 or its long-range control region—so the capillary bed forms sparsely and away from the air spaces. Small pulmonary veins are found abnormally next to arteries in the walls surrounding the airways (the bronchi), and the alveolar walls (“septa”) can look thick or simplified. This structural mismatch causes severe, oxygen-resistant hypoxemia and persistent pulmonary hypertension of the newborn (PPHN). PMC+1

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Types

1. Classic, early-onset ACD/MPV
   The most common pattern. Babies are born at term, seem well at first, and then rapidly develop deep cyanosis and severe PPHN in the first hours of life despite high oxygen and full intensive care. Genetic Rare Disease Center

2. Atypical or late-onset ACD/MPV
   A smaller group has milder or “patchy” disease. Symptoms may appear later—over days or even weeks—and may briefly improve with standard therapies before worsening again. Genetic testing and lung pathology often still show FOXF1-related disease. PubMed

3. Patchy (mosaic) ACD/MPV
   Some infants have areas of relatively normal lung mixed with abnormal areas. This can reflect post-zygotic (somatic) mosaicism or partial involvement and may explain slower progression in a few cases. PMC

4. FOXF1 coding-variant ACD/MPV
   Disease driven by a damaging change inside the FOXF1 gene itself (for example, nonsense, frameshift, splice-site, or critical missense variants). BioMed Central

5. FOXF1 enhancer-deletion ACD/MPV
   Disease caused by deletion of a distant, noncoding enhancer upstream of FOXF1 at 16q24.1 (often involving lncRNA LINC01081). These deletions frequently arise on the maternal chromosome because the locus shows parent-of-origin effects. PMC+1

6. ACD/MPV with multiple congenital anomalies
   Many infants also have intestinal malrotation or other gastrointestinal, cardiac, or genitourinary anomalies, reflecting the broad developmental role of FOXF1. MedlinePlus

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Causes

Most cases are genetic, usually new (de novo) in the child and not inherited from either parent. Below are the known and suspected mechanisms explained in simple terms.

1. FOXF1 loss-of-function variant
   A damaging change removes or disables one working copy of FOXF1. One copy is not enough for normal lung vessel development (haploinsufficiency). PubMed

2. FOXF1 nonsense variant
   A “stop early” change truncates the FOXF1 protein so it cannot do its job regulating downstream developmental genes. BioMed Central

3. FOXF1 frameshift variant
   Small insertions/deletions shift the reading frame and create a faulty protein, again causing loss of function. BioMed Central

4. FOXF1 splice-site variant
   Changes at intron–exon boundaries disrupt proper RNA splicing and lead to unstable or nonfunctional protein. BioMed Central

5. FOXF1 critical missense variant (forkhead domain)
   A single-letter change in the DNA-binding (“forkhead”) domain can block FOXF1’s ability to control target genes and impair endothelial growth signaling. ATS Journals

6. Deletion of the FOXF1 coding region
   A small chromosomal deletion removes the gene entirely from one chromosome 16, leaving only one working copy. ScienceDirect

7. Deletion of the distal FOXF1 enhancer (16q24.1)
   Long-range control sequences that switch FOXF1 on in fetal lung are missing, so the gene is under-expressed even if the coding part is intact. PMC

8. Disruption of lncRNA LINC01081 within the enhancer
   Some deletions specifically cut through LINC01081, a long non-coding RNA within the enhancer region, disturbing FOXF1 regulation. PubMed

9. Structural rearrangements at 16q24.1
   Translocations, inversions, or duplications near FOXF1 can disconnect the gene from its enhancer (“position effect”) and lower expression. PMC

10. Maternal-allele deletions (imprinting effect)
    The enhancer region shows parent-of-origin effects; deletions on the maternal chromosome are especially harmful, consistent with imprinting at the locus. PubMed

11. De novo (new) FOXF1 mutation
    Many cases are brand-new changes that arise in egg or sperm or shortly after conception; parents test negative. Lippincott Journals

12. Parental germline mosaicism
    A small fraction of a parent’s reproductive cells carry the change even though blood testing is negative; recurrence, while uncommon, is possible. PMC

13. Child’s post-zygotic (somatic) mosaicism
    The mutation occurs after the first cell divisions, creating a mixture of normal and abnormal lung tissue (“patchy” disease). PMC

14. Epigenetic silencing of the FOXF1 region
    Abnormal DNA methylation at the enhancer or promoter can reduce FOXF1 activity even without a DNA sequence change. BioMed Central

15. Altered SHH–FOXF1 signaling axis
    FOXF1 integrates upstream morphogen signals (e.g., sonic hedgehog). Disruption of this pathway can contribute to the developmental error. (Mechanistic model in human and animal studies.) PMC

16. Perturbation of endothelial growth signaling (e.g., STAT3 downstream of FOXF1)
    Specific missense changes (such as S52F) can blunt STAT3 signaling, hindering capillary formation. ATS Journals

17. Large contiguous 16q24.1 deletions
    Bigger deletions that include FOXF1 and neighboring genes can produce ACD/MPV with additional malformations. ScienceDirect

18. Copy-number variants that spare the gene but alter long-range chromatin loops
    Some duplications/deletions change the 3-D DNA folding so the enhancer cannot contact FOXF1 efficiently. PMC

19. Unknown genetic cause (FOXF1-negative cases)
    A minority have no identifiable FOXF1 coding or enhancer change with current tests; other regulatory mechanisms are suspected. BioMed Central

20. Systems-level developmental vulnerability
    Because FOXF1 also helps form the fetal gut and heart vessels, broader embryologic disturbances can accompany ACD/MPV, though they are associations rather than direct external causes. MedlinePlus

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Symptoms and signs

Most babies are full-term and look healthy at birth. Symptoms often appear quickly and are severe.

1. Rapid breathing (tachypnea)
   The infant breathes very fast in an effort to move more air, but oxygen still remains low because the capillary network is sparse. Genetic Rare Disease Center

2. Grunting and nasal flaring
   These are classic signs of respiratory distress as the baby tries to keep alveoli open and improve gas exchange. Genetic Rare Disease Center

3. Chest retractions
   Skin pulls in between the ribs or above the breastbone because breathing muscles are working hard against poorly functioning lungs. Genetic Rare Disease Center

4. Cyanosis (blue lips/skin)
   Low oxygen in the blood makes the skin or lips bluish; this often does not improve much with extra oxygen. Genetic Rare Disease Center

5. Severe, persistent pulmonary hypertension of the newborn (PPHN)
   High pressure in lung arteries develops because blood cannot flow easily through the abnormal capillary bed. National Organization for Rare Disorders

6. Poor response to oxygen and ventilators
   Even maximal NICU support usually fails to raise oxygen to safe levels, a key clinical clue to ACD/MPV. National Organization for Rare Disorders

7. Poor response to inhaled nitric oxide
   iNO normally relaxes lung vessels in PPHN. In ACD/MPV, there are too few reachable capillaries, so benefit is limited or absent. SpringerOpen

8. Low blood pressure or shock
   Severe hypoxemia strains the heart and can lead to poor perfusion and low blood pressure. Genetic Rare Disease Center

9. Feeding difficulty or abdominal distension
   Co-existing gut malformations (like malrotation) are common; feeds may worsen distress. MedlinePlus

10. Heart murmur or signs of right-sided strain
    The right ventricle works against very high resistance; exam and tests may show stress on the right side of the heart. Genetic Rare Disease Center

11. Hypoxemia shortly after normal pregnancy scans
    Prenatal ultrasounds may be unrevealing; problems emerge postnatally when the lungs must exchange gas. PubMed

12. Periods of seeming improvement followed by sudden worsening
    In patchy/atypical cases, symptoms may fluctuate before rapidly declining. PubMed

13. Metabolic acidosis
    Tissues switch to anaerobic metabolism in low oxygen, producing acid and raising lactate. Genetic Rare Disease Center

14. Liver enlargement or dysfunction
    Severe hypoxemia and right-heart strain can cause congestion and organ stress. Genetic Rare Disease Center

15. Low urine output
    Poor oxygen delivery and low blood pressure can reduce kidney perfusion, lowering urine output. Genetic Rare Disease Center

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Diagnostic tests

There is no single bedside test that proves ACD/MPV early. Doctors put together the story from clinical clues, rule-out tests, imaging, genetics, and—in some cases—lung pathology. Genetic testing has become the most helpful way to confirm the diagnosis in life-threatening cases.

A) Physical examination

1. Observation of breathing effort
   Fast breathing, grunting, nasal flaring, and retractions show serious respiratory distress that is disproportionate to routine newborn lung problems. This mismatch raises early suspicion for a structural vascular disorder like ACD/MPV. Genetic Rare Disease Center

2. Color and oxygenation clues
   Central cyanosis and low pulse-oximeter readings persist despite supplemental oxygen—an important bedside red flag. Genetic Rare Disease Center

3. Cardiac exam
   A loud second heart sound or right-sided gallop suggests high lung arterial pressure (PPHN), which is expected in ACD/MPV and helps guide further testing. National Organization for Rare Disorders

4. Screen for associated anomalies
   Careful check for abdominal distension, feeding issues, or other congenital differences is important because extra-pulmonary anomalies often coexist with ACD/MPV. MedlinePlus

B) Manual/bedside clinical tests

5. Hyperoxia (100% oxygen) test
   The baby breathes 100% oxygen while clinicians watch for PaO₂ to rise. In ACD/MPV, oxygenation often improves little or not at all, supporting a severe diffusion–perfusion problem rather than simple lung collapse. Genetic Rare Disease Center

6. Pre-ductal vs post-ductal oxygen saturation
   Simultaneous right-hand (pre-ductal) and foot (post-ductal) pulse-oximetry shows a gradient in PPHN; a large, persistent difference despite therapy suggests profound pulmonary vascular disease. Genetic Rare Disease Center

7. Respiratory distress scoring (e.g., Silverman-Anderson)
   A standardized bedside score tracks severity over time; very high scores despite aggressive support strengthen concern for a non-responsive condition like ACD/MPV. Genetic Rare Disease Center

8. Oxygenation Index (OI) / A–a gradient calculations
   Simple calculations using ventilator settings and blood gases quantify how severe the oxygenation failure is and help decide on urgent genetic testing or advanced support. Genetic Rare Disease Center

C) Laboratory and pathological tests

9. Arterial blood gas (ABG)
   Shows severe hypoxemia and often acidosis despite high inspired oxygen—an essential early data point that signals the need to search for ACD/MPV in the right clinical setting. Genetic Rare Disease Center

10. Genetic testing: FOXF1 sequencing
    Rapid, targeted sequencing can detect pathogenic FOXF1 variants within a clinically meaningful timeframe and is increasingly used when refractory PPHN raises suspicion for ACD/MPV. ScienceDirect

11. Copy-number analysis (chromosomal microarray or targeted CNV testing)
    Detects deletions of the distant FOXF1 enhancer or larger 16q24.1 deletions that disrupt regulation of FOXF1. Finding such a deletion confirms the diagnosis. PMC

12. Infection work-up (blood cultures, CRP, etc.)
    Sepsis can mimic severe respiratory failure; negative infection studies support a noninfectious, developmental cause when clinical features fit ACD/MPV. Genetic Rare Disease Center

13. Lactate level
    Elevated lactate reflects poor oxygen delivery to tissues during severe hypoxemia and helps monitor overall severity, though it is not specific to ACD/MPV. Genetic Rare Disease Center

14. Lung pathology (surgical biopsy or autopsy when performed)
    Under the microscope, the hallmark picture shows paucity of alveolar capillaries, thickened septa, and misaligned small pulmonary veins alongside arteries. This is the traditional gold standard, but many infants are too unstable for biopsy. PMC+1

D) Electrodiagnostic tests

15. Continuous pulse-oximetry (plethysmography waveform)
    Continuous monitoring quantifies persistent, severe hypoxemia and pre-/post-ductal differences. The pleth waveform can also suggest poor perfusion during PPHN crises. Genetic Rare Disease Center

16. Electrocardiogram (ECG)
    May show signs of right-ventricular strain from sustained pulmonary hypertension; though nonspecific, it supports the overall picture. Genetic Rare Disease Center

17. Electrical impedance tomography (EIT) where available
    A bedside, radiation-free monitor that maps regional ventilation. In ACD/MPV it may show global ventilation with poor oxygenation, highlighting the perfusion mismatch; it is supportive, not diagnostic. SpringerOpen

E) Imaging tests

18. Echocardiography (heart ultrasound)
    Key test to document severe PPHN, right-ventricular pressure overload, and to exclude structural heart defects that could otherwise explain hypoxemia. Lack of a cardiac cause plus refractory PPHN keeps ACD/MPV high on the list. SpringerOpen

19. Chest X-ray
    May appear surprisingly nonspecific or show only mild haziness despite dangerous hypoxemia. This “clinical-radiologic mismatch” is another clue to a vascular development disorder. PMC

20. High-resolution CT / CT angiography (when feasible)
    Can suggest reduced peripheral vascularity and exclude other lung disorders, but findings are not definitive; genetic testing and/or pathology remain necessary for confirmation. Prenatal ultrasound and fetal echocardiography are usually normal, which is why symptoms often surprise families after birth. SpringerOpen+1

Non-pharmacological treatments (therapies & others)

Notes: These are supportive measures used in neonatal intensive care. They aim to stabilize breathing, improve oxygen delivery, and protect the lungs and heart while the team evaluates genetics/biopsy and considers advanced options. They do not cure ACD/MPV but can buy time or make the baby more comfortable.

1. Gentle ventilation strategy
   Description: Use the lowest breaths/pressures that maintain acceptable oxygen and carbon dioxide levels.
   Purpose: Limit ventilator-caused lung injury.
   Mechanism: Reduces over-stretching and inflammation in fragile lungs with poor capillary contact.

2. High-frequency ventilation (HFOV/HFJV)
   Description: Very small, very fast breaths with constant lung inflation.
   Purpose: Improve oxygenation without large pressure swings.
   Mechanism: Keeps alveoli open more evenly, which may help gas exchange in poorly formed units.

3. Careful oxygen titration
   Description: Provide enough oxygen to maintain target saturations; avoid both hypoxemia and hyperoxia.
   Purpose: Optimize tissue oxygen while preventing oxygen toxicity.
   Mechanism: Balances oxygen as a vasodilator of lung vessels with the risk of oxidative damage.

4. Inhaled nitric oxide trial (as a test of reactivity)
   Description: Short, closely monitored trial to see if oxygenation improves.
   Purpose: Determine if any reversible vessel constriction exists.
   Mechanism: Selective pulmonary vasodilation; however, benefit is typically transient in ACD/MPV. PubMed

5. Prone positioning (and careful positioning in general)
   Description: Place baby on tummy with monitoring.
   Purpose: Improve ventilation-perfusion matching and comfort.
   Mechanism: Alters chest and diaphragm mechanics to improve aeration.

6. Thermoregulation and minimal handling
   Description: Keep temperature neutral; cluster care.
   Purpose: Reduce oxygen demand and stress.
   Mechanism: Lowers metabolic needs and catecholamine surges that worsen pulmonary pressure.

7. Targeted fluid management
   Description: Avoid excess fluids; support blood pressure with judicious volume and vasoactive infusions if needed.
   Purpose: Prevent lung edema and keep organs perfused.
   Mechanism: Reduces capillary leak and interstitial fluid in stiff lungs.

8. Nutritional support (TPN and/or fortified breast milk)
   Description: Provide adequate calories, protein, and micronutrients.
   Purpose: Support growth and healing; prepare for possible transplant.
   Mechanism: Adequate nutrition supports lung tissue, immune function, and recovery.

9. Early genetic testing and counseling
   Description: Rapid FOXF1 sequencing/CNV analysis; family counseling.
   Purpose: Confirm diagnosis quickly; guide decisions about invasive steps.
   Mechanism: Identifies pathogenic variants or enhancer deletions linked to ACD/MPV. ScienceDirect

10. Bedside echocardiography guidance
    Description: Frequent heart ultrasounds to track right-heart strain and lung pressures.
    Purpose: Tailor support and detect complications.
    Mechanism: Non-invasive monitoring of pulmonary hypertension physiology.

11. Judicious sedation and analgesia
    Description: Use comfort measures and minimal sedation.
    Purpose: Reduce oxygen demand and ventilator dyssynchrony.
    Mechanism: Lowers stress response that can worsen pulmonary hypertension.

12. Infection prevention bundles
    Description: Hand hygiene, line care, ventilation bundles.
    Purpose: Avoid sepsis that can rapidly destabilize the baby.
    Mechanism: Reduces inflammatory triggers of pulmonary hypertension.

13. ECMO (veno-venous or veno-arterial) as a bridge
    Description: Heart–lung bypass support in refractory hypoxemia.
    Purpose: Stabilize gas exchange and right-heart load while evaluating for transplant.
    Mechanism: Oxygenates blood outside the body, bypassing diseased lungs; often a bridge, not a cure. PMC

14. Care conference and palliative care integration
    Description: Multidisciplinary family meetings early.
    Purpose: Align goals, explain prognosis, support family.
    Mechanism: Shared decision-making improves care quality and reduces suffering.

15. Physiotherapy as comfort care
    Description: Gentle positioning, skin-to-skin (when safe), and developmental care.
    Purpose: Support comfort and neurodevelopment.
    Mechanism: Low-stimulus environment reduces stress hormones that raise pulmonary pressures.

16. Ductal patency management strategy (team decision)
    Description: Consider keeping the ductus arteriosus open in select cases to offload the right ventricle.
    Purpose: Improve systemic oxygen delivery.
    Mechanism: Right-to-left shunt can bypass high-pressure lungs; must be individualized with echo guidance.

17. Avoidance of over-ventilation and respiratory alkalosis
    Description: Accept slightly higher CO₂ (“permissive hypercapnia”) if safe.
    Purpose: Prevent reduced brain blood flow and lung injury.
    Mechanism: Gentle ventilation reduces barotrauma in fragile lungs.

18. Transport to transplant-capable center
    Description: Early referral/transfer to a pediatric lung transplant program with neonatal capability.
    Purpose: Maximize eligibility and timing.
    Mechanism: Experienced centers can assess candidacy and bridge strategies. American Journal of Pathology

19. Prenatal counseling for future pregnancies
    Description: Discuss genetic risks and testing options.
    Purpose: Early detection and delivery planning at a tertiary center.
    Mechanism: FOXF1 testing and targeted enhanced ultrasounds may help detect associated anomalies. MDPI

20. Strict avoidance of unnecessary invasive procedures
    Description: Limit procedures that add risk without benefit.
    Purpose: Reduce instability, bleeding, and infection risks.
    Mechanism: Procedural stress can worsen pulmonary pressures and oxygen needs.

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Drug treatments

Safety first: Doses below are typical neonatal starting ranges used under expert NICU supervision and must be individualized by weight, organ function, echo findings, response, and local protocols. ACD/MPV often shows poor or only transient response to pulmonary vasodilators; these medicines are usually supportive or diagnostic rather than curative. PubMed

1. Inhaled Nitric Oxide (iNO) — Pulmonary vasodilator
   Dose/Time: Start 20 ppm by inhalation; short trial; wean if no response.
   Purpose/Mechanism: Selective dilation of lung vessels; tests reactivity.
   Side effects: Methemoglobinemia, NO₂ formation, rebound PH on sudden stop. Note: Improves oxygenation but not survival in ACD/MPV. PubMed

2. Sildenafil — PDE-5 inhibitor
   Dose/Time: IV infusion (e.g., 0.35–1.6 mg/kg/day) or PO 0.5–2 mg/kg every 6–8 h.
   Purpose/Mechanism: Increases cGMP to relax pulmonary arteries.
   Side effects: Hypotension, flushing, GI upset; careful titration.

3. Milrinone — PDE-3 inhibitor/inodilator
   Dose/Time: 0.33–0.75 mcg/kg/min continuous IV (without a large bolus in neonates).
   Purpose/Mechanism: Improves right-ventricle function and lowers pulmonary resistance.
   Side effects: Hypotension, arrhythmias.

4. Prostacyclin (epoprostenol, inhaled or IV) — Pulmonary vasodilator
   Dose/Time: Inhaled or IV titration in ng/kg/min per institutional protocol.
   Purpose/Mechanism: cAMP-mediated vasodilation and anti-platelet effects.
   Side effects: Hypotension, bleeding risk, jaw pain (older pts), line risks if IV.

5. Bosentan — Endothelin-receptor antagonist
   Dose/Time: Oral; neonatal dosing is specialist-guided.
   Purpose/Mechanism: Blocks endothelin-mediated vasoconstriction.
   Side effects: Elevated liver enzymes, edema; drug interactions.

6. Iloprost (inhaled) — Prostacyclin analogue
   Dose/Time: Frequent inhaled doses via ventilator circuit as per protocol.
   Purpose/Mechanism: Short-acting pulmonary vasodilator.
   Side effects: Cough, hypotension.

7. Prostaglandin E1 (alprostadil) — Ductal dilator
   Dose/Time: 0.01–0.05 mcg/kg/min IV.
   Purpose/Mechanism: Keeps the ductus arteriosus open to offload right heart.
   Side effects: Apnea, hypotension, fever; intubation readiness needed.

8. Dobutamine — Inotrope
   Dose/Time: 5–15 mcg/kg/min IV.
   Purpose/Mechanism: Improves right-ventricle squeeze and cardiac output.
   Side effects: Tachycardia, arrhythmias, hypotension.

9. Dopamine — Vaso-inotrope
   Dose/Time: 5–10 mcg/kg/min IV.
   Purpose/Mechanism: Supports systemic blood pressure/perfusion.
   Side effects: Tachyarrhythmias, increased afterload at higher doses.

10. Norepinephrine — Vasopressor
    Dose/Time: 0.05–0.2 mcg/kg/min IV.
    Purpose/Mechanism: Raises systemic vascular resistance to improve coronary and systemic perfusion.
    Side effects: Peripheral ischemia, arrhythmias.

11. Vasopressin — Vasopressor
    Dose/Time: 0.0003–0.0007 units/kg/min IV.
    Purpose/Mechanism: V1-mediated vasoconstriction without direct pulmonary vasoconstriction.
    Side effects: Hyponatremia, decreased urine output.

12. Furosemide — Diuretic
    Dose/Time: 0.5–1 mg/kg IV; repeat per status.
    Purpose/Mechanism: Reduces lung edema to improve gas exchange.
    Side effects: Electrolyte loss, ototoxicity (high/repeat doses).

13. Hydrocortisone (stress-dose, select cases) — Steroid
    Dose/Time: e.g., 1 mg/kg IV every 6–8 h short-term if adrenal insufficiency or refractory shock suspected.
    Purpose/Mechanism: Supports blood pressure; not a cure for ACD/MPV.
    Side effects: Hyperglycemia, infection risk.

14. Surfactant (trial if RDS overlap suspected) — Lung surfactant
    Dose/Time: 100–200 mg/kg intratracheal per product.
    Purpose/Mechanism: Lowers surface tension in alveoli.
    Side effects: Transient desaturation/bradycardia during dosing.

15. Heparin (with ECMO) — Anticoagulant
    Dose/Time: Continuous infusion titrated by ACT/anti-Xa during ECMO.
    Purpose/Mechanism: Prevents circuit clotting.
    Side effects: Bleeding, thrombocytopenia.

16. Broad-spectrum antibiotics (if sepsis not excluded) — Antimicrobials
    Dose/Time: e.g., ampicillin + gentamicin per neonatal dosing.
    Purpose/Mechanism: Treats possible infection that can mimic/worsen PH.
    Side effects: Renal toxicity (aminoglycosides), allergy.

17. Sedation/analgesia (fentanyl, morphine) — Opioid analgesics
    Dose/Time: Low continuous infusion with careful titration.
    Purpose/Mechanism: Reduces stress and ventilator fighting.
    Side effects: Respiratory depression, tolerance.

18. Midazolam (select centers) — Benzodiazepine
    Dose/Time: 0.05–0.1 mg/kg/h IV (institution-specific).
    Purpose/Mechanism: Anxiolysis, synchrony.
    Side effects: Hypotension, tolerance.

19. Inhaled epoprostenol (if available) — Pulmonary vasodilator
    Dose/Time: Device-dependent ng/kg/min via ventilator circuit.
    Purpose/Mechanism: Selective pulmonary vasodilation similar to iNO effect pathway (via cAMP).
    Side effects: Hypotension if systemic absorption; bleeding risk lower than IV.

20. Extravasation/line care medications (hyaluronidase, etc.)
    Purpose/Mechanism: Support safe delivery of the many infusions needed; prevent complications.
    Note: Supportive but essential to maintain therapy safely.

(Collectively, these medications come from the neonatal pulmonary-hypertension toolkit; studies and reviews show that while oxygenation can sometimes improve, iNO and other vasodilators do not change the poor overall survival in classic ACD/MPV, reinforcing the need for accurate diagnosis and transplant evaluation.) PubMed+1

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Dietary / molecular supplements

Important: In newborns, all nutrition and supplements must be prescribed by the NICU team. Evidence for supplements in ACD/MPV is indirect and aimed at general neonatal lung/vascular support, not disease cure.

1. Human milk (preferably mother’s milk)
   Function: Best overall nutrition and immune factors.
   Mechanism: Antibodies and bioactive lipids support mucosal defenses and recovery.

2. Human-milk fortifier / protein supplementation
   Function: Meet high calorie and protein needs during critical illness.
   Mechanism: Supplies amino acids and calories for growth and lung repair.

3. Vitamin D (e.g., 400 IU/day when enteral feeds established)
   Function: Bone, immune, and lung development support.
   Mechanism: Nuclear receptor signaling influencing epithelial and immune pathways.

4. DHA/ARA (long-chain omega-3/omega-6)
   Function: Anti-inflammatory membrane lipids.
   Mechanism: Modulates eicosanoids/cell signaling in lung tissue.

5. Zinc (NICU-guided dosing)
   Function: Enzyme function, wound healing, immune support.
   Mechanism: Cofactor for many enzymes; supports growth.

6. Selenium (NICU-guided dosing)
   Function: Antioxidant via glutathione peroxidase.
   Mechanism: Reduces oxidative stress from high oxygen exposure.

7. Carnitine (if deficient)
   Function: Fatty-acid transport; energy production.
   Mechanism: Mitochondrial β-oxidation support.

8. Glutamine (parenteral formulations only if indicated)
   Function: Gut and immune cell fuel.
   Mechanism: Nitrogen donor; antioxidant precursor.

9. Iron (only when indicated by labs; often delayed early on)
   Function: Hemoglobin building; oxygen transport.
   Mechanism: Cofactor for erythropoiesis; must avoid overload.

10. L-citrulline / L-arginine (research/center-specific use)
    Function: Substrates for nitric oxide production.
    Mechanism: May support endogenous NO; evidence in ACD/MPV is limited.

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Immunity-booster / regenerative / stem-cell” drugs

Honest status: There are no approved regenerative or stem-cell drugs for ACD/MPV. Use is experimental and not standard of care. Below are research concepts only—no established dosing.

1. Mesenchymal stem cells (MSC) or MSC-derived extracellular vesicles
   Function/Mechanism: Experimental lung repair and immunomodulation; studied in other neonatal lung diseases (e.g., BPD). Not established for ACD/MPV.

2. Endothelial progenitor cell therapy
   Function/Mechanism: Attempts to rebuild capillary networks; preclinical concept only.

3. Gene-directed therapies targeting FOXF1 pathways
   Function/Mechanism: Future idea to correct enhancer/gene dysfunction. No clinical dosing. Nature

4. Stat3 pathway modulators (research)
   Function/Mechanism: Based on animal work showing FOXF1 mutations affecting STAT3 signaling. Not a therapy today. ATS Journals

5. Pro-angiogenic growth-factor strategies
   Function/Mechanism: Hypothetical support of vessel development; safety concerns in neonates; not used clinically.

6. Cell-free gene editing (future)
   Function/Mechanism: Theoretical enhancer repair; currently in lab models only. Nature

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Surgeries / invasive procedures

1. Bilateral lung transplantation
   Procedure: Replace both lungs with donor lungs in a pediatric transplant center.
   Why it’s done: The only definitive option to restore normal lung structure. Selected infants (often atypical presentations) have undergone transplant with outcomes similar to other neonatal indications at experienced centers. Wiley Online Library+1

2. Extracorporeal Membrane Oxygenation (ECMO) cannulation
   Procedure: Surgical placement of cannulas in large vessels for veno-venous or veno-arterial ECMO.
   Why it’s done: Bridge to diagnosis and potential transplant when ventilation/vasodilators fail. PMC

3. Surgical lung biopsy
   Procedure: Small piece of lung is removed for pathology under controlled settings.
   Why it’s done: Provides definitive histologic diagnosis when the baby is stable enough; informs care decisions. PMC

4. Tracheostomy (rare, case-by-case)
   Procedure: Create a breathing opening in the neck.
   Why it’s done: Considered in rare atypical survivors needing prolonged ventilation.

5. Gastrostomy tube placement (supportive)
   Procedure: Feeding tube placed directly into the stomach.
   Why it’s done: Ensures safe nutrition during long support or post-transplant recovery.

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Preventions

1. Genetic counseling for the family—understand FOXF1 findings and recurrence risks. MedlinePlus

2. Prenatal genetic testing options in future pregnancies when a familial variant is known. MDPI

3. Detailed targeted prenatal imaging at a high-risk center if history suggests risk. MDPI

4. Plan delivery at a tertiary NICU with ECMO and transplant referral pathways. American Journal of Pathology

5. Avoid smoking/alcohol during pregnancy; optimize maternal health (general fetal benefits).

6. Manage maternal illnesses (diabetes, hypertension) to reduce overall perinatal risk.

7. Infection prevention in pregnancy (vaccinations per guidelines).

8. Early postnatal monitoring if any prenatal concern for anomalies.

9. Rapid escalation if hypoxemia is refractory—early echo, genetics, and transfer if needed. ScienceDirect

10. Family support networking (e.g., NORD resources, ACDMPV advocacy) for education and planning. National Organization for Rare Disorders

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When to see doctors

• During pregnancy: If scans show multiple anomalies or severe growth issues—ask for genetic counseling and targeted testing. MDPI

• Right after birth: If your baby has fast breathing, blue color, needs high oxygen, and does not improve with usual therapies, seek immediate higher-level care; ask the team about ACD/MPV work-up with FOXF1 testing. National Organization for Rare Disorders

• Anytime: If your baby on support has worsening oxygen levels, signs of infection, or feeding problems, call the care team at once.

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What to eat and what to avoid

• For the baby: When medically safe, human milk is preferred; the NICU may add fortifier for extra protein and calories. Avoid unapproved supplements or herbal products—newborn dosing is not safe without medical orders.

• For breastfeeding parents: Eat a balanced diet rich in protein, fruits/vegetables, whole grains, and healthy fats (with DHA sources). Avoid alcohol and nicotine. Stay well hydrated.

• For formula use: Follow the NICU plan exactly (type, mixing, sterilization). Do not change formula or add powders/oils unless instructed.

• For everyone: Focus on hygiene (handwashing) to reduce infections during critical illness and recovery.

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Frequently Asked Questions

1. Is ACD/MPV the same as PPHN?
   No. It causes severe pulmonary hypertension, but the lung structure itself is abnormal, so typical PPHN treatments rarely work. Genetic Rare Disease Center

2. What gene is involved?
   Often FOXF1, including changes in far-away enhancer regions that control the gene. MedlinePlus+1

3. Can an inhaled nitric oxide trial cure it?
   No. It may briefly improve oxygen levels but does not improve survival in classic ACD/MPV. PubMed

4. How is the diagnosis confirmed?
   By a combination of FOXF1 genetic testing and, when possible, lung biopsy pathology. MedlinePlus

5. Can babies outgrow ACD/MPV?
   Classic disease does not “go away.” A few atypical cases present later or milder, but they are uncommon. PMC

6. Is lung transplant the only cure?
   Yes—transplant replaces the abnormal lungs. Suitability depends on stability, size, and center expertise. American Journal of Pathology

7. Does ECMO fix the disease?
   No. ECMO buys time as a bridge to diagnosis or transplant consideration. PMC

8. Are there prenatal signs?
   Sometimes there are associated anomalies; genetic testing can identify some cases before birth when a familial change is known. MDPI

9. How rare is ACD/MPV?
   Very rare; reported numbers are in the low hundreds worldwide. National Organization for Rare Disorders

10. Are steroids helpful?
    They may help shock or adrenal insufficiency but do not treat the underlying lung vessel malformation.

11. Can special diets or vitamins cure it?
    No. Nutrition supports growth and healing but does not fix the malformed lung vessels.

12. What is the outlook?
    Without transplant, the outlook is poor. Early accurate diagnosis helps families and teams make the best plan. American Journal of Pathology

13. Can families get support?
    Yes—NORD and ACD/MPV family groups provide education and connections. National Organization for Rare Disorders

14. If we had one child with ACD/MPV, what about future pregnancies?
    Ask for genetic counseling; options may include targeted prenatal testing when a familial variant is known. MDPI

15. Why do standard pulmonary hypertension drugs fail?
    Because the core problem is structural: too few and misaligned capillaries and veins, and thickened arteries—not just vessel spasm. BioMed Central

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 14, 2025.

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