Allergic Diseases in Pregnancy

Allergic disease accounts for a prevalence during pregnancy of about 20%, and thus represents the most common disease present during pregnancy.

In particular asthma is the most important of the disorders because of its prevalence and potential risk for the mother and foetus.

Pregnancy may modify the natural history through functional, hormonal and immunologic changes.

Points of view of the different specialists involved in the care of the Pregnant Allergic woman:

The Gynaecological Standpoint

Discussion should start with gynaecologist and Allergist possibly before pregnancy.

  • Asthma: It is said that about a third of asthma patients get worse during pregnancy (usually the severe ones). On the other hand, about a third of asthma patients improve during pregnancy, especially if their disease was mild before they became pregnant. Another third experience no change. If the asthma gets worse, it will most likely to occur during 24 to 36 weeks of pregnancy. Only about 1 in 10 women with asthma have symptoms during delivery.
  • Vasomotor Rhinitis (non-allergic) caused by nasal vascular pooling, secondary to the increased circulatory blood volume and possibly enhanced by the vasodilator effect of progesterone
  • Anaphylaxis: The incidence in pregnancy is probably extremely low. The foetus appears protected from this event because of placental production and secretion of histaminase, which could catalyse histamine. However, management would be no different from the non-pregnant state.
  • Urticaria & Angioedema may occasionally occur during pregnancy only, as a possible allergic reaction to progesterone. As gestational pruritic (itchy) dermatoses are relatively common a thorough differential diagnosis must be performed
  • Atopic dermatitis is not or minimally affected by pregnancy.
  • Drug allergy in pregnancy is considerably lower than in the nonpregnant state, probably because of the remarkably reduced use of drugs in pregnancy. The only drugs which warrant additional comment include: penicillin (oral desensitisation in skin test positive subjects permits relatively safe administration of this drug to pregnant women with penicillin allergy and serious infections); insulin (its use is relatively common because oral hypoglycemics are contraindicated in pregnancy, and so preference must be given to human insulin;

The Pulmonary Standpoint

There is overwhelming evidence, which suggest that the prevalence of asthma has increased in all industrialized countries during the last 20 years. For this reason asthma is considered one of the most common disease during pregnancy (about 1-4%)

Several studies show that severe under treated asthma during pregnancy is associated with:

  • Increase in preterm birth
  • Low birth weight
  • Neonatal hypoxia
  • Mortality from hyperemesis gravidarum
  • Vaginal haemorrhage
  • Toxaemia

The Dermatological Standpoint

From data regarding systemic absorption of topical steroids and those concerning the use of systemic steroids during pregnancy we can state that topical formulation can be prescribed to pregnant women with atopic eczema and contact dermatitis. Studies done with 1% hydrocortisone ointment and elocon showed no effect on adrenal suppression when given for 21 days. The use of potent topical steroids is not advisable in pregnancy, it is better to use steroids with moderate potency that cab be applied without occlusion once daily for no longer than 2 weeks.

Topical antihistamines: No data are available regarding their innocuousness during pregnancy; also, they are not useful in allergic dermatoses.

The Allergist Standpoint

Rhinitis can be difficult to treat during pregnancy and many treatment failures occur. This is partly due to the physician who tends to be too conservative in pregnancy and partly due to the condition, which is refractory.

DRUG THERAPY DURING PREGNANCY

To help guide therapy the FDA has developed a classification for the safety of drugs during pregnancy as follows:

Class A: Drugs that have undergone controlled studies in pregnant patients and have been found to be safe. Unfortunately, no allergy or asthma medications fall into this category.

Class B: These drugs have not undergone rigorous testing in pregnant patients, but adverse effects have not been detected in either animal or human studies. Several asthma medication fall into this category, including ipratropium, salmeterol, terbutaline, cromolyn sodium, nedocromil, zileuton, and zafirlukast.

Class C: Adverse effects have been detected in animal studies, but not yet in human studies. The corticosteroids: prednisone, beclomethasone, flunisolide, fluticasone, and triamcinalone, as well as the bronchodilators: theophylline, albuterol, bitolterol fall into this category.

Class D: These drugs have well demonstrated adverse effects on human foetal health. These drugs should not be used in pregnant patients.

Class X: These drugs are contraindicated in pregnancy.

Antihistamines
Oral Antihistamines: systemic antihistamines should not be prescribed during the first quarter of pregnancy. After this period, second generation (such as non sedating) antihistamines are preferred.

Topical antihistamines, chromones and topical steroids should be considered first choice of drugs because of their low dosage and their rapid action (few minutes for topical antihistamines, some hours or days for chromones and topical steroids)

Cromolyn: is a mast cell stabilizer. The nose and eye drops take about 2 to 5 days to produce clinical effects. No severe systemic or severe Transient burning and stinging is attributed to the preservative. Nedocromil appears to be more potent than cromolyn.

Lodoxamide (Lomide)is an antiallergy compoundanda potent mast cell stabilizer, initially produced for asthma, but now only used in eye drops. It exerts its anti allergy properties within half an hour of administration.

Topical antihistamines: Levocabastine (Livostin) eye drops and nasal solutions are at least as effective and in some cases more effective than, sodium cromoglycate. Levocabastine is well tolerated.

Because the safety profile of these compounds is very favourable since the nasal and/or conjunctival absorption is almost absent. These pharmacologic properties should promote these compounds to the forefront in the strategy for allergy treatment of rhinitis and conjunctivitis during pregnancy. The onset of action is also very fast.

Steroids
They are without teratogenic effects. Systemic steroids should be prescribed only for the most serious allergic disorders. Topical steroids (at the recommended dose for treating asthma and skin conditions) should be the first choice. One the basis of safety profile the newer ones should be preferred due to their reduced or almost absent absorption.

Chromones
As these compounds are almost without side effects, they can be used during pregnancy without significant problems.

Theophylline
They can pass through the placenta barrier, causing foetal arrhythmias.

Anticholinergics
They are without teratogenic effects, but the cost benefit ratio is not very favourable.

Adrenergics
Vasoconstrictors should be used only for a few days; Bronchodilator must be used as needed.

Allergen immunotherapy during pregnancy

Allergen immunotherapy is now recognised as an efficacious means of treating patients affected by rhinitis and/or allergic asthma. The literature confirms that when Immunotherapy is carefully implemented it can yield significant results and notable improvements in symptoms. Immunotherapy has proved to be efficacious in the treatment of rhinitis and asthma in the pregnant patient as well. The safety concerns of the mother and the newborn, the incidence of miscarriages, foetal and neonatal deaths, congenital malformations, and toxaemia have not been seen to be any higher than in control groups of untreated pregnant patients and the general population. Even in the few cases in which immunotherapy caused systemic reactions, when these have been promptly treated, no miscarriages or foetal abnormality have been caused.

On the basis of these findings, it can be concluded that immunotherapy can be continued in women already under treatment before pregnancy, if they meet the following requirement:

  • They are in the maintenance phase or
  • On high doses if in the initial incremental phase
  • They have benefited before from this therapy
  • They have not shown any increased risk to systemic reactions

It is usually advisable to reduce the dose in order to further reduce the risk of systemic reactions, and since the highest incidence of systemic reactions, and since the highest incidence of systemic reactions is seen in the phase of increasing doses, caution suggests that immunotherapy should be suspended if the treatment is in the initial stages when pregnancy is discovered. It is not, therefore, advisable to initiate immunotherapy during pregnancy for the following reasons:

  • The risk of untoward systemic reactions, which are more frequent in the initial incremental dosage stage
  • The lack of benefit from the first low dosage administration of immunotherapy;
  • And the difficulty of foreseeing which patients will benefit from the therapy, especially in the case of asthma.

Summary of the Profile of allergy drugs used during pregnancy

Drug category Pregnancy category*

Steroids C

Antihistamines B

Chromones B

Adrenergics C

Theophylline C

Anticholinergics C

* FDA category B = no evidence of risk in humans; FDA category C = risk cannot be ruled out

Considering toxicities of drugs, the following principles should guide drug therapy:

  • Optimise non-drug treatment, such as environmental controls and avoidance of asthma triggers before giving drugs
  • Use minimum dose necessary to control symptoms and avoid foetal hypoxia. Dosages should be decreased if asthma improves in pregnancy
  • Achieve asthma control and make changes in medication before conception, if possible
  • Aerosolised (inhaler) therapy, particularly inhaled steroids, is the preferred method of drug delivery due to the decreased systemic effects. Inhaled triamcinolone is teratogenic and should never be used.
  • If oral steroids are required for asthma control, prednisone or methylprednisolone are the preferred preparations since they cross the placenta poorly. Every effort should be made to decrease the dosage of oral steroids, alternate day dosing is preferred over daily dosing
  • Inhaled beta2-agonists (Ventolin and albuterol) are generally safe during pregnancy. Due to the risk of congenital malformations, adrenaline should be avoided during pregnancy. Systemic beta agonists should be avoided near labour, as they may inhibit or prolong labour.
  • Dosages of theophylline may need to be adjusted due to the changing pharmacokinetics as pregnancy progresses. Theophylline readily crosses the placenta and may cause jitteriness in the newborn.
  • Cromolyn appears to be a safe drug in pregnancy and is an increasingly popular drug for pregnant asthmatics.
  • Immunotherapy (desensitisation), if already started can be safely continued in pregnancy, but it should never be started. The dose should probably be reduced in very sensitive patients to avoid any systemic side effects
  • Skin tests, especially intradermal should be avoided in pregnancy. Do RAST instead.

PREFERRED ASTHMA DRUGS IN PREGNANCY

(From the National Asthma Education Program’s Working group on Asthma and Pregnancy)

Inhaled Steroids
  • Beclomethasone, 2-5 puffs b.i.d. to q.i.d. for asthma and/or 2 sprays in each nostril b.i.d. to control allergic rhinitis
Oral Steroids
  • Prednisone burst courses of 40mg/day in single or divided doses for 1 week and then taper for 1 week. If prolonged therapy is necessary, a single morning dose of prednisone on alternate days may help to minimise side effects.
Cromolyn sodium
  • 2 puffs q.i.d for asthma and /or 2 sprays in each nostril b.i.d to q.i.d to control allergic rhinitis
Inhaled Beta Agonists (Ventolin, Terbutaline)
  • Two puffs every 4 hours as needed
Theophylline
  • Oral sustained-release preparations to reach serum concentrations of 8-12 ug/ml.
Antihistamines
  • Chlorpheniramine, 4 mg up to q.i.d or 8-12 sustained release b.i.d
  • Tripelennamine 25-50 mg up to q.i.d or 100 mg sustained release b.i.d.
Decongestants
  • Pseudoephedrine, 60 mg up to q.i.d or 120 mg sustained release b.i.d
  • Oxymetazoline, intranasal spray or drops up to 5 days for rhinosinusitis
Cough Medications
  • Guaifenesin with or without dextrometorphan, 22 teaspoon q.i.d

The Australian Drug Evaluation Committee 4th Edition of Prescribing medicines in pregnancy

Categorisation consists of the following categories

Category A

Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

Category C

Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

Category B1

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed

Studies in animals have not shown evidence of an increased occurrence of fetal damage.

Category B2

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency malformation or other direct or indirect harmful effects on the human fetus having been observed.

Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

Category B3

Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.

Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

Category D

Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

Category X

Drugs which may have a high risk of causing permanent damage to the fetus that they should not be used in pregnancy or when there is a possibility of pregnancy

Commonly used drugs in Allergy and their Categorisation

Antitussives

Opium alkaloids and derivatives: codeine, dextromethorphan A
Expectorants and Mucolytics
 

Acetylcysteine (inhaled)

B2

Ammonium chloride, bromhexine, emetine, guaiphenesin,
Ipecacuanha, saponins
A
Decongestants
 

Phenylephrine, phenylpropanolamine, pseudoephedrine B2

Inhalent Agents

The agents that contain norflurane as the propellant have had limited human exposure. Norflurane has been shown to be safe in animals. The prescriber should consult the full pi for more information.

Bronchospasm relaxants

 

Eformoterol, salmeterol

B3

Ephedrine, fenoterol, isoprenaline, orciprenaline, rimiterol, salbutamol
Terbutaline, theophylline derivatives

A
Ipratropium bromide B1
Preventative aerosols and inhalations
 

Beclomethasone, budesonide, fluticasone, salmeterol B3

The benefits of asthma control outweigh any potential for an adverse pregnancy outcome.
 

Nedocromil

B1

Sodium cromoglycate A
Other Respiratory Agents
 

Acetylcysteine

B2

Dornase alfa, montelukast, zafirlukast B1
Antihistamines
 

Azatadine, cetirizine, diphenylpyraline, fexofenadine, methdilazine, Terfenadine

B2

Brompheniramine, chlorpheniramine, clemastine, cyproheptadine, Dexchlorpheniramine, diphenhydramine, diphenylamine, doxylamine, Pheniramine, triprolidine

A

Chlorcyclizine, cyclizine, hydroxyzine

A
Levocabastine B3

Inadvertent short term exposure during the first trimester is unlikely to cause a hazard to the fetus but it has been shown to be deratogenic in two species of animals and until human data are available, it should be expected of being teratogenic

 

Loratadine

B1
Trimeprazine, promethazine C

When given in high doses during late pregnancy, phenothiazines have caused prolonged neurological disturbances in the infant.

 
 

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