Allergic disease, such as allergic rhinitis (hay fever) and asthma are common chronic conditions.
In the Netherlands, the prevalence of hay fever is estimated to be 1 in 5, or 20%, with a peak at young adulthood (allergiecentra.nl).
Hay fever is reported to be increasing, probably due to climate changes (Gezondheidseffecten van klimaatverandering, RIVM rapport).
Many people do not consult their GP for treatment of hay fever symptoms. Only 5.1% of men and 6.0% of women were registered at their GP practice as having allergic rhinitis in 2024 (Cijfers Ziekten op jaarbasis in Nederland - incidentie en prevalentie | Nivel).
Common over-the-counter treatments for hay fever include antihistamines. However, are they safe to be used during pregnancy? And what about prescribed nasal steroids?
Nasal sprays containing corticosteroids beclomethasone, budesonide and fluticasone are considered most safe of which fluticasone is most frequently prescribed under the brand name Flixonase® (GIPdatabank.nl). There is broad experience with inhaled steroids for treatment of asthma without evidence of teratogenic effects. The steroids triamcinolone and mometasone are probably safe, as well as sprays containing antihistamines azelastine or levocabastine. Azelastine is available over-the-counter under the names Carelastin® en Pollispray® in the Netherlands. It can be obtained on prescription in combination with the steroid fluticasone, also known under the brand name Dymista®.
Table 1 provides an overview of available information on the level of safety of oral antihistamines used for treatment of hay fever, based on information provided by Netherlands Pharmacovigilance Centre Lareb and Pharmacotherapeutic Compass (the Netherlands). Two of these drugs are also used to treat nausea during pregnancy: doxylamine and meclozine, the latter often in combination with pyridoxine (Vitamin B6), under the brand name Emesafene®.
Table 1. Reported safety of oral antihistamines (generic names)
| Most safe | cetirizine* loratadine* |
| Probably safe | desloratadine doxylamine fexofenadine* levocetirizine* meclozine* |
| Possible risk (third trimester) |
clemastine hydroxyzine promethazine |
| Do not use; insufficient data available on safety | acrivastine alimemazine chloorcyclizine/cinnarizine* dimetindene ebastine ketotifen mizolastine oxomemazine rupatidine |
| * also available over the counter; Source: based on information from websites LAREB and Pharmacotherapeutic Compass (the Netherlands) | |
Eurocat Northern Netherlands collects data on medication dispensed at pharmacies and on self-reported use of over-the-counter medication, based on a questionnaire.
From 1997-2023, 75% of mothers who participated used any medication in the first trimester of pregnancy, excluding folic acid and other vitamins.
Medication for treatment of allergic rhinitis was used by 5.0% of mothers in the first trimester of pregnancy; 2.6% used a nasal spray and 2.8% an oral antihistamine.
Only 3 mothers used an oral histamine that is advised not to be used in the first trimester of pregnancy. Another 11 mothers used any of these, but not in the first trimester.
Eurocat annually checks whether drugs taken by the mother in the first trimester of pregnancy are associated with specific types of congenital anomalies.
In Northern Netherlands, we have found a relatively high number of children with an anomaly of the urinary tract among mothers who used levocetirizine (Xyzal®) in the first trimester of pregnancy: 13 of 42 exposed children, where we would expect 6 (statistical p-value=0.0052).
However, due to the low numbers of children involved and the fact that the association cannot be replicated in the larger European EUROCAT database, we cannot draw any conclusions from this finding.
In a systematic review of 37 studies that included >50,000 pregnant women, the use of oral antihistamines for nausea or allergic disease during the first trimester was not associated with an increased risk of congenital anomalies.1 However, this finding cannot rule out increased risks for specific congenital malformations with the use of specific drugs.
A recently published EUROmediCAT paper reported a twofold risk of eye anomalies (congenital cataract and lens anomalies) with the use of oral antihistamines in the first trimester of pregnancy2, which emphasizes the need for more research.
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