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Betahistine exposure during pregnancy: A case series

Article  in  Reproductive Toxicology · April 2016

DOI: 10.1016/j.reprotox.2016.03.017

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Selin Acar Yusuf Cem Kaplan

Izmir Katip Celebi Universitesi Izmir Katip Celebi Universitesi
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Barış Karadaş
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 Abstracts / Reproductive Toxicology 60 (2016) 172–187
during gestation. Depending on the stereochemistry of specific
PBDEs, some may disrupt exposure to androgens during fetal devel-
opment. Previous work suggests that PBDEs are associated with
reduced AGD in rodent models (but not in all studies) and are
associated with other male reproductive anomalies, such as crypt-
orchidism. This is the first study conducted in Israel to investigate
this marker in newborns.
Methods and preliminary results: 295 mother–infant pairs were
recruited from the delivery rooms at the Assaf Harofeh Medical
Center (n = 226) and the Dana Childrens’ Hospital (n = 69) during
2013–2015. AGD was measured three consecutive times within
24 h of birth, and the mean of the three measures was used. In
males (n = 147), mean ± standard deviation (sd) (range) anoscrotal
distance was 24.05 ± 3.80 mm (115.1–33.7 mm), mean anopenile
distance was 45.01 ± 4.83 mm (26.8–61.2 mm) and mean penile
width was 10.5 ± 1.59 mm (3–13 mm). In females (n = 146), mean
anofourchette distance was 14.40 ± 2.99 mm (8.5–34.4 mm) and
mean anoclitoral distance was 34.70 ± 3.24 mm (27.5.5–42.9 mm).
PBDEs (BDE 47, 99, 100 and 153) and PCBs (PCB 118, 138, 153 and
180) were measured in maternal serum collected at the time of
delivery. In preliminary analyses of infants with both anogenital
and PCB measures, all PCBs were associated, albeit not statistically
significant, with reductions in anoscrotal and anopenile distance
and with reductions in penile width in boys. Likewise all PCBs
were associated with reduced anofourchette distance in the girls;
no associations were found for anoclitoral distance in girls. These
results suggest that endocrine disrupting compounds may be asso-
ciated with reductions in anogenital distance in newborns. Larger
samples sizes are needed to fully explore the associations, and we
are still collecting additional newborns.
This study is supported by the Environment and Health Fund
(EHF), Israel.
http://dx.doi.org/10.1016/j.reprotox.2016.03.016
Posters
Betahistine exposure during pregnancy: A case
series
Selin Acar 1,2,∗ , Yusuf C. Kaplan 1,2 , Gözde
Küçüksolak 1 , Barış Karadaş 1,2 , Tijen
Kaya-Temiz 1,2
1 Terafar – Izmir Katip Celebi University Teratology
Information, Training and Research Center, Izmir,
Turkey
2 Izmir Katip Celebi University School of Medicine,
Department of Pharmacology, Izmir, Turkey
Introduction: Betahistine is a histamine analogue used for the
treatment of Meniere disease. Preclinical rodent studies demon-
strated the lack of a teratogenic effect, however human experience
is limited. We, therefore, aimed to investigate the outcomes of
the pregnant women who contacted Terafar (Izmir Katip Celebi
Teratology Information, Research and Training Center) for risk
assessment regarding betahistine exposure during pregnancy.
Methods: Terafar records were searched between the years
2009–2014 to retrieve the pregnant women with a prospective
referral for the risk assessment regarding betahistine use during
pregnancy. A detailed form for each women including the demo-
graphics, medical and obstetric history were completed at the time
of referral. Follow-up telephone calls with mothers/families were
made in order to collect the information regarding the pregnancy
outcomes.
View publication stats
177
Results: Seventeen pregnancies with maternal betahistine expo-
sure were retrieved. All exposures occurred during the first
trimester. The mean maternal gestational age at admission was
9.0 ± 4.9. The median daily dose of betahistine was 24 mg/day and
the duration of exposure varied between 1 and 71 days. The route
of administration was oral in all of the pregnancies. Of the 15 preg-
nancies (one twin pregnancy) with known outcomes, 14 (87.5%)
resulted in live births and 2 (12.5%) resulted in elective termina-
tions. The age of the children at the time of follow-up was between
9 and 63 months. Of the 13 live births with known outcomes, there
was one case of major congenital malformation (7.7%) in which the
infant had an intestinal malrotation and died at the 11th day, post-
natally. In terms of perinatal complications, one premature infant
was diagnosed with gastroesophageal reflux of which symptoms
resolved at the 45 days of age. This infant demonstrated inadequate
physical growth and development. Among other premature infants,
one was presented with respiratory distress and feeding difficul-
ties while another had arrhythmias and hypoglycemia at birth. A
term infant was born with patent foramen ovale and diagnosed
with hypothyroidism on 10th day postnatally while another term
infant was diagnosed with iron deficiency (40th day) and goiter
(2nd month) and both of them were treated successfully.
Conclusions: Among 13 infants, there was only one major con-
genital malformation for which the causality with betahistine
exposure cannot be established. A previous case series reported
no major congenital malformations among 12 live births resulted
from 15 pregnancies with betahistine exposure [1]. Several infants
in our case series had perinatal complications most of which may
be associated with the prematurity and the chronic diseases in their
mothers. These results may be used to inform the pregnant women
after an inadvertent exposure until the data from larger prospective
studies are available.
Reference
[1] M.K. Duman, I. Erkoseoglu, D. Aykan, et al., Betahistine use in pregnant women
with vertigo, Reprod. Toxicol. 57 (2015) 225.
http://dx.doi.org/10.1016/j.reprotox.2016.03.017
Pregnancy outcome after in utero exposure to
oxybutynin
Delphine Beghin ∗ , Catherine Vauzelle-Gardier,
Elisabeth Elefant
Centre de Référence sur les Agents Tératogènes
(CRAT), Hôpital Trousseau, Hôpitaux universitaires
Est Parisien (AP-HP), Paris, France
Introduction: Requests about treatments for neurologic blad-
der, enuresis, and detrusor over-activity are in constant increase
in our TIS, mainly for paraplegic patients. As published data on the
medications used in these chronic conditions (anticholinergics and
alpha blockers) are lacking during pregnancy, self-catheterization
is the main option proposed to pregnant women, while inducing
a non-negligible risk of repeated urinary tract infections during
pregnancy. Oxybutynin, one of the oldest drug used in such cir-
cumstances, is an anticholinergic tertiary amine with spasmolytic
activity. It is teratogenic at very high doses in one species and to
date there are no data on its use in human pregnancies. Considering
an increasing number of calls for this drug in our TIS (n = 142) and
the need to explore alternate options to self-catheterization during
pregnancy, we investigated the outcomes of oxybutynin exposed
pregnancies.
Methods: Paris (France) TIS (CRAT) prospectively collected preg-
nancies exposed to oxybutynin between 4 and 12 weeks after LMP