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Retrospective Assessment of the Use of Pharmacotherapeutic Agents in Pregnancy with Potential Impact on Neonatal Health Cover

Retrospective Assessment of the Use of Pharmacotherapeutic Agents in Pregnancy with Potential Impact on Neonatal Health

Open Access
|Aug 2022

Figures & Tables

Figure 1

The most frequently used therapeutic agents classified to particular code of Anatomical Therapeutic Chemical (ATC) classification system. ATC first level classification was used. P1–P22 represents Patient 1–Patient 22. Each patient could have used more than one therapeutic agent.
The most frequently used therapeutic agents classified to particular code of Anatomical Therapeutic Chemical (ATC) classification system. ATC first level classification was used. P1–P22 represents Patient 1–Patient 22. Each patient could have used more than one therapeutic agent.

Figure 2

Health conditions of newborns from a total of 22 adult female patients after being exposed to therapeutic agents. UN = unspecified information about newborn; SA = spontaneous abortion; CD = congenital defect or malformation; IL = illness of newborn; HL = healthy newborn.
Health conditions of newborns from a total of 22 adult female patients after being exposed to therapeutic agents. UN = unspecified information about newborn; SA = spontaneous abortion; CD = congenital defect or malformation; IL = illness of newborn; HL = healthy newborn.

Figure 3

View on foetal risk summary according to outcomes per therapeutic agent usage during pregnancy.
View on foetal risk summary according to outcomes per therapeutic agent usage during pregnancy.

Overview on therapeutic agents with confirmed foetal risk and their outcomes_

Drugs with confirmed foetal riskLevel of confirmed foetal risk-guide to foetal and neonatal risk (Briggs et al., 2017; Schaefer et al., 2015)Minimizing the potential risk for given therapeutic agentsStage of pregnancy during medication usage, dose, and duration of treatmentNumber of patients (N = 22)Outcome of pregnancy
Valproic acid2 to 3 times increased risk of congenital anomaliesHuman data suggest riskAntiepileptic polytherapy with valproate is not preferred (State Institute for Drug Control [ŠÚKL] 2018c).To minimize the risk, use of the lowest effective dose divided into several doses during the day is recommended (ŠÚKL 2018c). Preventive usage of folic acid before pregnancy and during pregnancy to lower neural tube defects and creation of congenital malformations is recommended (ŠÚKL 2018c).5th–6th week (2nd month, 1st trimester), 300 mg, previous long-term treatment1Spontaneous abortion
EletriptanNo clinical data, no harmful effect in animal dataNo human data; animal data suggest moderate riskTo minimize the risk, the lowest effective dose is recommended (Briggs et al., 2017).2nd–5th week (1st month, 1st–2nd trimester), 20 mg, 2–3 weeks1Healthy newborn
Venlafaxine hydrochlorideAnimal studies show reproductive toxicityHuman data suggest risk in 3rd trimesterPreferred is monotherapy and usage of the lowest but most effective dosing.If possible, it is recommended to discontinue the drug treatment 1–2 weeks before birth (Seifertová et al., 2007).Ø, 75 mg 1× a day, 1 week1Healthy newborn
Interferon ß-1aIncreased risk of spontaneous abortions Initiation of treatment is contraindicatedLimited human data; animal data suggest moderate riskThe injection site for the intramuscular injection must be changed weekly (ADC ČÍSELNÍK, 2018).Before the application of the injection and after 24 hours after injection, it is recommended to give antipyretic analgesic agents to relieve the flu-like symptoms that occur with inteferon ß-1a. These symptoms usually appear during the first few months of treatment (ADC ČÍSELNÍK, 2018).Time of conception, 30 μg, patient used Avonex regularly1Birth defect (unspecified)
Methylprednisolon sodium succinateIn animal studies foetal malformation was observed Risk of low birth weightHuman data suggest riskThe risk of low birth weight is dose-dependent and can be minimized by administering lower doses of corticosteroids (ŠÚKL 2018d).Time of conception, 40 mg, 2 weeks1Birth defect (unspecified)
BudesonideTeratogenic potential in animal studiesCompatible (inhaled/nasal); no human data; animal data suggest riskThere is no more detailed information, but adequate maintenance treatment of asthma during pregnancy is important (Liekinfo 2018a).3rd week (1st month, 1st trimester), 200 μg–400 μg, 2 days1Illness (Wilm's tumour)
DuloxetineAnimal studies show reproductive toxicitySSRI in advance stage may increase the risk of PPHNHuman data suggest risk in the 3rd trimesterMonotherapy is preferred.To minimize the risk, use of the lowest effective dose is recommended.If possible, it is recommended to discontinue the drug treatment 2 weeks before birth (Seifertová et al., 2007).8th week (2nd month, 1st trimester), 30 mg /60 mg in the morning, 4 weeks1Healthy newborn
MoclobemideSafety for pregnant woman has not been establishedØMonotherapy is preferred.To minimize the risk, usage of the lowest effective dose is recommended.If possible, it is recommended to discontinue the drug treatment 2 weeks before birth (Seifertová et al., 2007).8th week (2nd month, 1st trimester), 300 mg in the morning, 6 weeks1Healthy newborn
ClonazepamMay cause birth defectsAs an anticonvulsive agent, it can be teratogenicHuman data suggest low risk Potential toxicity if combined with other CNS depressantsThere is no more detailed information.8th week (2nd month, 1st trimester), 2 mg, 8 weeks1Healthy newborn
CiprofloxacinNeither animal nor human studies indicate malformative or foetal/neonatal toxicityDrug can cause damage to articular cartilage in the foetusContraindicated; used only if no other alternativesThere is no more detailed information.1. 2nd–3rd week (1st month, 1st trimester), 500 mg, 10 days2. 1st–2nd week (1st month, 1st trimester), 500 mg, every 12 hrs, 1 week3. 1st–3rd week (1st month, 1st trimester), 250 mg, 2 weeks31. Healthy newborn2. Healthy newborn3. Healthy newborn
DoxycyclineIn foetus and children, dental decay and reversible retardation of skeletal development may occurContraindicated in 2nd and 3rd trimestersThere is no more detailed information.1. 1st–2nd week (1st month, 1st trimester), 200 mg, 1× a day, 20 days2. 5th–6th week (2nd month, 1st trimester), 100 mg, 1× a day, 10 days3. 1st–2nd week (1st month, 1st trimester), 200 mg, 1 week31. Healthy newborn, born in 8th month2. Healthy newborn3. Healthy newborn
Amoxicillin, clavulonic acidAnimal studies do not indicate the harmful effect Human studies do not show an increased risk of congenital malformationsHuman data suggest risk in 1st and 3rd trimestersThere is no more detailed information.Ø, 125 mg, 2 weeks before conception1Healthy newborn
Betahistine dihydrochlorideAnimal studies are inadequate Potential risk to humans is unknownNo documented experiences are available for the histamine analogue betahistine.There is no more detailed information.5th–6th week (2nd month, 1st trimester), 24 mg, 2× a day, 3 weeks1Healthy newborn
Norethisterone acetateAdversely affects the development of the foetusContraindicatedThere is no more detailed information.5th week (2nd month, 1st trimester), 5 mg, 7 days1Spontaneous abortion
Bisulepine hydrochlorideSafety has not been verifiedIt is not recommended to use, especially during 1st trimesterNo human dataThere is no more detailed information.1st week (1st month, 1st trimester), 2 mg, 1 week1Healthy newborn
Monohydrate sodium salt of metamizoleThere is no evidence that drug damages the foetusPossible to use in the 2nd trimesterØThere is no more detailed informationØ, 500 mg, 3 days1Illness (heart murmur)
TetrazepamUsage should be avoided in the first three monthsMedication should be used occasionallyHuman data suggest risk in 1st and 3rd trimestersIt is recommended to avoid the use of benzodiazepines during the first three months of pregnancy.Increased doses should not be used during the last three months of pregnancy, as neonatal hypotension and respiratory disorders may occur in neonates (Liekinfo 2018b).2nd–4th week (1st month, 1st trimester), 50 mg, 1× every night, 8 days1Healthy newborn
Piroxicam β-cyclodext rineContraindicatedSafety has not been establishedHuman data suggest risk in 1st and 3rd trimestersThere is no more detailed information.2nd–4th week (1st month, 1st trimester), 20 mg, 1× every morning, 7 days1Healthy newborn
PrednisoneNot suitable, signs of hypoadrenalism in newbornsHuman data suggest riskThere is no more detailed information.Ø, 20 mg, Ø1Unspecified information (patient overcame 3 SABs and is planning pregnancy)
AllopurinolAnimal studies show teratogenic potentialIn human studies without apparent adverse effectsContraindicatedThere is no more detailed information.Ø, 300 mg, Ø1
NadroparinNo teratogenic or foetotoxic effects were observed in animal studiesLimited human clinical dataØThere is no more detailed information.Ø, Ø, Ø1
FluvastatinCan cause foetal harmContraindicated during pregnancyContraindicated in the 1st trimesterThere is no more detailed information on how to minimalize risk. Using of this agent is contraindicated during pregnancy (ŠÚKL, 2018b).Ø, 80 mg, 6 weeks1
Chlorprothixene chlorideNewborns exposed to antipsychotics during the third trimester are at risk of extrapyramidal symptomsReproduction studies in animals have not shown an increased incidence of foetal harmHuman data suggest risk mainly in the 3rd trimesterIf medication cannot be discontinued, it is possible to reduce the antipsychotic dose to the minimum effective level, especially in the first trimester.Monotherapy is preferred. We do not discontinue the antipsychotic even before delivery (Seifertová et al., 2007).In maintenance therapy, it is better to administer a minimal dose of an antipsychotic continuously than to administer high doses intermittently to decompensate the condition (Seifertová et al., 2007).Beginning of 2nd month, (1st trimester), 50 mg, 2 weeks1Healthy newborn
IbuprofenMay adversely affect pregnancy and/or embryonal or foetal developmentHuman data suggest risk in the 1st and 3rd trimestersThe risk is expected to increase with the dose and duration of treatment. Ibuprofen should not be used during 1st and 2nd trimesters unless clearly necessary. If ibuprofen is used by a woman trying to become pregnant or during the 1st and 2nd trimesters of pregnancy, she should take low doses, and the treatment should be as short as possible (ŠÚKL, 2018a).Beginning of 2nd month (1st trimester), 400 mg, 8 weeks1Healthy newborn
Language: English
Page range: 17 - 25
Submitted on: Mar 3, 2022
Accepted on: Jun 20, 2022
Published on: Aug 23, 2022
Published by: Comenius University in Bratislava, Faculty of Pharmacy
In partnership with: Paradigm Publishing Services
Publication frequency: 2 issues per year
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© 2022 K. Podolská, D. Mazánková, M. Göböová, published by Comenius University in Bratislava, Faculty of Pharmacy
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