Allergic Reactions in Pregnancy

Overview

• Tietz Textbook of Laboratory Medicine, 7th Ed., p. 3934

Immunological Basis

• The maternal-fetal interface maintains a Th2 + T-regulatory cytokine milieu (IL-4, -10, -13, TGF-β), suppressing Th1 responses against fetal antigens - essential to prevent rejection.
• A shift toward Th1 dominance is associated with spontaneous abortion, preeclampsia, and preterm labor.
• This Th2 bias can promote allergic sensitization. Maternal allergen exposure during pregnancy may establish IgE-mediated responses in the fetus, particularly when exposure occurs against a heightened Th2 background.
• Fetal allergen exposure occurs via: (1) swallowing allergen in amniotic fluid (e.g., Der p 1, ovalbumin detected in amniotic fluid), and (2) direct transplacental transfer of allergen-IgG complexes, especially in the third trimester.
• Tietz Textbook of Laboratory Medicine, 7th Ed., p. 3934-3935

Common Allergic Conditions in Pregnancy

1. Asthma

• Course is unpredictable: ~1/3 improve, ~1/3 stay the same, ~1/3 worsen.
• Improvement may relate to rising serum cortisol and progesterone (smooth muscle relaxant).
• Worsening factors include GERD, gestational rhinitis, smoking, obesity, viral infections.
• Triggers: dust mites, cockroach, pollens, molds, aspirin, cold air, exercise.
• Associated pregnancy complications: gestational diabetes, hypertension, preeclampsia, intrauterine growth restriction, preterm birth.
• Tietz Textbook of Laboratory Medicine, 7th Ed., p. 3971-3972; Creasy & Resnik's Maternal-Fetal Medicine

2. Allergic Rhinitis

• Affects quality of life and can worsen asthma.
• "Pregnancy rhinitis" is a distinct entity: nasal congestion lasting ≥6 weeks during pregnancy without infection or allergic cause, resolving within 2 weeks postpartum.
• Smoking and dust mite sensitization are risk factors.
• Oral decongestants (especially first trimester) are associated with gastroschisis - avoid.

3. Urticaria and Angioedema

• Can be new-onset in pregnancy (often resolves postpartum).
• Hereditary angioedema may worsen in pregnancy due to high estrogen levels.

4. Food Allergy, Drug Allergy, Atopic Dermatitis

• All can complicate pregnancy; management should balance maternal and fetal safety.

Anaphylaxis in Pregnancy

Epidemiology

• Estimated frequency: 1.5-3.8 per 100,000 pregnancies.
• Maternal mortality from anaphylaxis: ~0.05/100,000 live births.
• 49-74% of cases occur during caesarean section.
• Main culprits: beta-lactam antibiotics (58%), latex (25%), anesthetic agents (17%).
• Carra et al., J Allergy Clin Immunol Pract, 2021 [PMID: 34365055]

Diagnostic Challenges

• Baseline hypotension and tachycardia are normal in pregnancy.
• Cutaneous symptoms are less prominent during peripartum anaphylaxis.
• Uterine contractions and fetal distress may be the first signs.
• Normal vital sign ranges are shifted, making thresholds harder to apply.
• Kuder et al., Immunol Allergy Clin North Am, 2023 [PMID: 36410997]

Fetal Consequences

• Maternal hypotension reduces uteroplacental blood flow → fetal hypoxia.
• Anaphylaxis can trigger premature uterine contractions.
• Delayed treatment is associated with worse maternal and fetal outcomes.

Management

General Principles

• Diagnosis should rely on detailed history and symptom monitoring; avoid skin prick testing (SPT) and provocation testing in pregnancy (prefer in vitro sIgE testing or lymphocyte transformation test for type IV allergy).
• Allergen avoidance remains the primary strategy.
• Immunotherapy (allergen desensitization): do not initiate during pregnancy due to anaphylaxis risk; patients already on maintenance therapy may continue.
• Tietz Textbook of Laboratory Medicine, 7th Ed., p. 3971; Creasy & Resnik's, p. 1412

Anaphylaxis - Acute Management

• Intramuscular epinephrine 0.3-0.5 mg in the lateral thigh.
• A 2026 multidisciplinary review (Tanno et al., J Allergy Clin Immunol Pract [PMID: 42250901]) emphasizes the "safety and critical importance of prompt intramuscular epinephrine use as first-line therapy."

• High-flow oxygen (critical for fetal oxygenation)
• IV fluid resuscitation
• Continuous fetal monitoring if fetus is viable
• Obstetric team involvement

Medications for Ongoing Allergic Disease

• Second-generation antihistamines are preferred: loratadine (Claritin) and cetirizine (Zyrtec) are specifically recommended in pregnancy.
• First-generation antihistamines (diphenhydramine) are generally considered compatible but may cause sedation and have limited fetal safety data vs. second-generation.
• Creasy & Resnik's Maternal-Fetal Medicine

• Inhaled corticosteroids are the preferred controller therapy for asthma in pregnancy.
• Intranasal corticosteroids are first-line for allergic rhinitis (preferred over oral decongestants).
• Short courses of systemic corticosteroids may be used for severe exacerbations; weigh risk of oral clefts (very small absolute risk) against benefit.

• Inhaled short-acting beta-agonist (salbutamol/albuterol): safe, first-line for rescue.
• Inhaled corticosteroids (budesonide has best safety data): first-line controller.
• Long-acting beta-agonists: add-on when ICS insufficient.
• Monitor PEFR or FEV1 regularly; maintain asthma diary.

• Intranasal corticosteroids: first-line (safe throughout pregnancy).
• Loratadine or cetirizine: safe second-line antihistamines.
• Avoid oral decongestants in first trimester (gastroschisis association).
• Intranasal decongestants (short-course, ≤3 days) acceptable if needed.

Diagnostic Testing in Pregnancy

Fetal and Neonatal Implications

• Maternal allergic disease, especially poorly controlled asthma, is linked to IUGR, preterm birth, low birth weight, and increased perinatal morbidity.
• Th2 cytokine milieu during gestation may predispose the neonate to allergic sensitization in early infancy.
• Maternal dietary factors (n-3 PUFAs, antioxidants, vitamin D) may modulate fetal immune development and reduce later allergic disease risk.
• Gut microbiome diversity in the infant is a key switch from neonatal Th2 bias toward balanced immunity.

Key Takeaways

1. Never withhold epinephrine in anaphylaxis - it is the treatment of choice per ACOG.
2. Use left lateral positioning (not supine) during anaphylaxis or hypotension.
3. Loratadine and cetirizine are the safest antihistamines in pregnancy.
4. Inhaled corticosteroids are safe and effective for asthma control; avoid oral decongestants in the first trimester.
5. Do not start immunotherapy during pregnancy; maintenance therapy can continue.
6. Prefer in vitro sIgE testing over SPT for allergy workup.
7. Asthma is the most common allergic disease in pregnancy - aggressive management prevents maternal and fetal complications.

• Anaphylaxis and Epinephrine Use in Pregnancy (2026) - multidisciplinary review emphasizing prompt IM epinephrine as non-negotiable first-line therapy [PMID: 42250901]
• Anaphylaxis and Pregnancy: A Systematic Review (2021) - beta-lactams, latex, and anesthetics are the top culprits; management mirrors non-pregnant adults with epinephrine central [PMID: 34365055]
• Anaphylaxis in Pregnancy (2023) - cutaneous signs are often absent; diagnosis is clinically challenging [PMID: 36410997]