Introduction
Up to 90% of women experience symptoms of nausea and/or vomiting during
pregnancy.1 Hyperemesis gravidarum (HG) is a severe
complication of pregnancy affecting around 1% of pregnancies
globally.2 HG can cause significant physical and
psychological morbidity for mothers.3 The majority of
women experiencing severe NVP/HG require one or more medications to
assist with symptom control.4 Ondansetron is an
effective antiemetic that is being widely used as a second-line
treatment option for severe nausea and vomiting of pregnancy (NVP) in
accordance with clinical guidelines.5-8
Currently, the increasing use of ondansetron was observed world-wide to
treat NVP and HG. In the US, ondansetron use increased from less than
1% of pregnancies before 2001 to as high as 13–25% in 2014, resulting
in approximately 500,000 to 1 million ondansetron exposed gestations out
of 4 million pregnancies a year.9-11 In Australia and
New Zealand, 25 and 75% of physicians prescribed ondansetron for NVP
and HG, respectively.12 In Norway, Prescriptions for
ondansetron were filled in 0.3% of pregnancies, with 76.9% being
initially filled in the first trimester.13 In France,
prescriptions of ondansetron only concerned 53 women (0.1%) between
2004 and 2017 in Haute-Garonne, contrary to other countries, like the
United States.14
In November 2019, the European Medicines Agency (EMA) Pharmacovigilance
Risk Assessment Committee (PRAC) released an updated comprehensive
assessment report which state that ondansetron should not be used during
the first trimester of pregnancy.15 A review about
0ndansetron in pregnancy revisited do not support the conclusion of
EMA/PRAC assessment report and this section of the SmPC, and the
regulatory authorities should consider deleting this sentence from the
SmPC.16 Indeed, the safety of ondansetron hasn’t
concluded a decision now. Some studies did not observe an increased risk
of abnormal pregnancy outcome in women who took ondansetron early in
pregnancy,17-18 but others reported an increased risk
of diaphragmatic hernia, hypoplastic left heart and respiratory system
anomalies.19-20 One recent meta-analysis has been
published in 2020 which search was conducted by authors until November
2019, so this meta-analysis does not take into account the five latest
published studies,21-25 which include three largest
ever published studies, including respectively 456,963/33, 677/1,880,594
pregnant women exposed to ondansetron. And three of the five studies
focus on not only the risk of malformations, but also other abnormal
pregnancy outcome.21-22,25
Therefore, this systematic review and meta-analysis was aim to quantify
the association between exposure to ondansetron during pregnancy and the
risk of abnormal pregnancy outcomes.