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Pharmacotherapy during Pregnancy, Childbirth and Lactation

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Women's Health".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 37892

Special Issue Editor

1. Department of Development and Regeneration, KU Leuven, Leuven, Belgium
2. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
3. Department of Clinical Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands
Interests: perinatal pharmacology; neonatal clinical pharmacology; PBPK in special populations; newborn; infant; lactation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmacotherapy is a very powerful tool to improve the medical outcome of pregnant women and their newborns. As little as 5% of available drugs have been properly monitored, tested and labeled for use in pregnancy and lactation. Pregnant or lactating women are usually excluded from clinical trials, while product development for diseases specific to pregnancy or perinatal indications is very limited. However, in real life, pregnant women get ill, and ill women get pregnant. Pregnant or lactating women and their caregivers are left in the dark about risks they cannot oversee, and they need to take responsibility for this uncertainty.

This Special Issue on perinatal clinical pharmacology aims to focus on various methods that can be applied and tailored to pregnancy and lactation, including but not limited to pharmacokinetic modeling, pharmaco-epidemiology, in vitro models (such as placental transfer), lactation and pharmacovigilance. Papers on pharmacotherapy on diseases related to pregnancy (preterm labor, pre-eclampsia, fetal anomalies, postpartum hemorrhage) and diseases that occur during pregnancy (depression, oncological diseases, peri-operative care, infectious diseases) are very welcome.

Prof. Dr. Karel Allegaert
Guest Editor

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Keywords

  • pharmacovigilance
  • pharmaco-epidemiology
  • pharmacokinetics
  • lactation, childbirth
  • pregnancy

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Published Papers (14 papers)

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Editorial

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5 pages, 677 KiB  
Editorial
Pharmacotherapy during Pregnancy, Childbirth, and Lactation
Int. J. Environ. Res. Public Health 2022, 19(18), 11336; https://doi.org/10.3390/ijerph191811336 - 09 Sep 2022
Cited by 1 | Viewed by 2059
Abstract
Pharmacotherapy is a very powerful approach to truly improve outcomes for pregnant women and their newborns [...] Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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Research

Jump to: Editorial, Review, Other

16 pages, 2024 KiB  
Article
Early Postnatal Outcome and Care after in Utero Exposure to Lithium: A Single Center Analysis of a Belgian Tertiary University Hospital
Int. J. Environ. Res. Public Health 2022, 19(16), 10111; https://doi.org/10.3390/ijerph191610111 - 16 Aug 2022
Cited by 5 | Viewed by 1720
Abstract
Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of [...] Read more.
Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36–39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56–0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87–1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8–12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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14 pages, 352 KiB  
Article
Information Needs and Counseling Preferences among Potential Users of the Future Teratology Information Service in Belgium: A Cross-Sectional Study Involving the Public and Healthcare Professionals
Int. J. Environ. Res. Public Health 2022, 19(14), 8605; https://doi.org/10.3390/ijerph19148605 - 14 Jul 2022
Cited by 2 | Viewed by 1416
Abstract
A Teratology Information Service (TIS) does not exist in Belgium yet but will hopefully be established soon. To prepare for this, we aimed to provide insight into the information needs and counseling preferences of the Belgian public and healthcare professionals (HCPs) regarding medication [...] Read more.
A Teratology Information Service (TIS) does not exist in Belgium yet but will hopefully be established soon. To prepare for this, we aimed to provide insight into the information needs and counseling preferences of the Belgian public and healthcare professionals (HCPs) regarding medication use in pregnancy and breastfeeding. A cross-sectional study using two anonymous, online surveys disseminated via social media, websites, and newsletters addressing Dutch and French-speaking individuals (≥18 years) and licensed HCPs was performed between June and September 2020. Ethics approval and informed consent were obtained. In total, 1508 public survey respondents (98% women) and 702 HCPs participated. Information needs on perinatal medication use were ubiquitous among both groups, and for which they often relied on patient information leaflets or the product information and online fora. Conflicting information on this topic regularly occurs and complicates HCPs’ duties. Women and HCPs assigned an important role to a TIS, both in terms of providing evidence-based information (via a website or app) and being accessible to be contacted in case of questions (by phone or via e-mail or chat). In conclusion, a TIS would be warmly welcomed by women and HCPs in Belgium and should ideally be established soon to address current information needs regarding perinatal medication use and to contribute to research in this field. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
16 pages, 664 KiB  
Article
Self-Reported Medication Use among Pregnant and Postpartum Women during the Third Wave of the COVID-19 Pandemic: A European Multinational Cross-Sectional Study
Int. J. Environ. Res. Public Health 2022, 19(9), 5335; https://doi.org/10.3390/ijerph19095335 - 27 Apr 2022
Cited by 12 | Viewed by 2371
Abstract
Information on medication utilization among pregnant and postpartum women during the pandemic is lacking. We described the prevalence and patterns of self-reported medication use among pregnant and postpartum women during the third wave of the pandemic (June–August 2021). An online questionnaire was distributed [...] Read more.
Information on medication utilization among pregnant and postpartum women during the pandemic is lacking. We described the prevalence and patterns of self-reported medication use among pregnant and postpartum women during the third wave of the pandemic (June–August 2021). An online questionnaire was distributed in five European countries between June–August 2021. Pregnant women or women who had delivered in the three preceding months, and ≥18 years old, could participate. The prevalence of overall medication use, self-medication, and changes in chronic medication use were determined. A total of 2158 women out of 5210 participants (41.4%) used at least one medication. Analgesics (paracetamol), systemic antihistamines (cetirizine), and drugs for gastric disorders (omeprazole) were the three most used classes. Anti-infectives were less prevalent than during pre-pandemic times. Antidepressants and anxiety related medication use remained similar, despite a higher prevalence of these symptoms. Self-medication was reported in 19.4% of women, and 4.1% of chronic medication users reported that they changed a chronic medication on personal initiative due to the pandemic. In conclusion, medication use patterns in our cohort were mostly similar to those of the first COVID-19 wave and the pre-pandemic period. More studies are needed to explore factors associated with self-medication and changes in chronic medication use due to the pandemic in this perinatal population. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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14 pages, 322 KiB  
Article
Validity of Administrative Data for Identifying Birth-Related Outcomes with the End Date of Pregnancy in a Japanese University Hospital
Int. J. Environ. Res. Public Health 2022, 19(8), 4864; https://doi.org/10.3390/ijerph19084864 - 16 Apr 2022
Cited by 7 | Viewed by 1822
Abstract
This study aimed to develop and validate claims-based algorithms for identifying live birth, fetal death, and cesarean section by utilizing administrative data from a university hospital in Japan. We included women who visited the Department of Obstetrics at a university hospital in 2018. [...] Read more.
This study aimed to develop and validate claims-based algorithms for identifying live birth, fetal death, and cesarean section by utilizing administrative data from a university hospital in Japan. We included women who visited the Department of Obstetrics at a university hospital in 2018. The diagnosis, medical procedures, and medication data were used to identify potential cases of live birth, fetal death, and cesarean section. By reviewing electronic medical records, we evaluated the positive predictive values (PPVs) and the accuracy of the end date of pregnancy for each claims datum. “Selected algorithm 1” based on PPVs and “selected algorithm 2” based on both the PPVs and the accuracy of the end date of pregnancy were developed. A total of 1757 women were included, and the mean age was 32.8 years. The PPVs of “selected algorithm 1” and “selected algorithm 2” were both 98.1% for live birth, 99.0% and 98.9% for fetal death, and 99.7% and 100.0% for cesarean section, respectively. These findings suggest that the developed algorithms are useful for future studies for evaluating live birth, fetal death, and cesarean section with an accurate end date of pregnancy. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
13 pages, 756 KiB  
Article
Experiences and Perspectives of Marketing Authorisation Holders towards Medication Safety Monitoring during Pregnancy: A Pan-European Qualitative Analysis
Int. J. Environ. Res. Public Health 2022, 19(7), 4248; https://doi.org/10.3390/ijerph19074248 - 02 Apr 2022
Cited by 5 | Viewed by 1843
Abstract
Although marketing authorisation holders (MAHs) are involved in monitoring medication safety, it was unclear how they experience their role and current monitoring activities in pregnancy. Therefore, a qualitative study using online focus groups with MAHs and the Belgian umbrella organisation of MAHs was [...] Read more.
Although marketing authorisation holders (MAHs) are involved in monitoring medication safety, it was unclear how they experience their role and current monitoring activities in pregnancy. Therefore, a qualitative study using online focus groups with MAHs and the Belgian umbrella organisation of MAHs was conducted in June–July 2021. In total, 38 representatives of nine organisations participated. Overall, participants reported multiple difficulties with data collection, including underreporting, collection of incomplete information, and loss to follow-up. The limited number of high-quality data collected, the unknown denominator and the lack of comparator data complicate MAHs’ data processing activities, preventing them to timely provide evidence in the pregnancy label. Three ‘conflicts’ inherent to the specific position of MAHs were identified explaining the difficulties they experience, i.e., (1) mistrust from patients and healthcare professionals (HCPs); (2) MAHs’ legal obligations and regulatory framework; (3) MAHs’ position outside the healthcare context. To overcome these barriers, MAHs suggested that data registration should occur in close collaboration with patients and HCPs, organised within the healthcare context and performed by using a user-friendly system. In conclusion, the reported difficulties and underlying conflicts of MAHs highlight the need for more effective, collaborative data collection strategies to generate new evidence on this topic. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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11 pages, 957 KiB  
Article
Drug Prescriptions among Italian and Immigrant Pregnant Women Resident in Italy: A Cross-Sectional Population-Based Study
Int. J. Environ. Res. Public Health 2022, 19(7), 4186; https://doi.org/10.3390/ijerph19074186 - 01 Apr 2022
Cited by 3 | Viewed by 2018
Abstract
Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence [...] Read more.
Ensuring drug safety for pregnant women through prescription drug monitoring is essential. The aim of this study was to describe the prescription pattern of medicines among pregnant immigrant women from countries with high migratory pressure (HMPCs) compared to pregnant Italian women. The prevalence of drug prescriptions among the two study populations was analysed through record linkage procedures applied to the administrative databases of eight Italian regions, from 2016 to 2018. The overall prevalence of drug prescription was calculated considering all women who received at least one prescription during the study period. Immigrants had a lower prevalence of drug prescriptions before (51.0% vs. 58.6%) and after pregnancy (55.1% vs. 60. 3%). Conversely, during pregnancy, they obtained a slightly higher number of prescriptions (74.9% vs. 72.8%). The most prescribed class of drugs was the blood and haematopoietic organs category (category ATC B) (56.4% vs. 45.9%, immigrants compared to Italians), followed by antimicrobials (31.3% vs. 33.7%). Most prescriptions were appropriate, while folic acid administration 3 months before conception was low for both study groups (3.9% immigrants and 6.2% Italians). Progesterone seemingly was prescribed against early pregnancy loss, more frequently among Italians (16.5% vs. 8.1% immigrants). Few inappropriate medications were prescribed among antihypertensives, statins and anti-inflammatory drugs in both study groups. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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12 pages, 353 KiB  
Article
The Contraindications to Combined Oral Contraceptives among Reproductive-Aged Women in an Obstetrics and Gynaecology Clinic: A Single-Centre Cross-Sectional Study
Int. J. Environ. Res. Public Health 2022, 19(3), 1567; https://doi.org/10.3390/ijerph19031567 - 29 Jan 2022
Cited by 3 | Viewed by 3765
Abstract
This study aimed to determine the estimated proportion of contraindications among women taking combined oral contraceptives (COCs) and to assess the risk factors associated with their contraindications. This study was cross-sectional. Reproductive-aged women (18–49 years) on any COCs between 2018 and 2020 were [...] Read more.
This study aimed to determine the estimated proportion of contraindications among women taking combined oral contraceptives (COCs) and to assess the risk factors associated with their contraindications. This study was cross-sectional. Reproductive-aged women (18–49 years) on any COCs between 2018 and 2020 were recruited from one obstetrics–gynaecology clinic in a university-affiliated hospital and were included. Contraindications were defined using the World Health Organization (WHO) Medical Eligibility Criteria (MEC) for Contraceptive Use. Data were collected from electronic medical records for all included women, as well as a standardised, pretested, structured survey for one-third of the women. In this cross-sectional study, 380 women using COCs were included. Their mean age was 31.645 ± 7.366 years. Among them, 131 (34.5%) participated via a survey and electronic records, while the other 249 (65.5%) participated via electronic records only. The majority of the participants had a Bachelor’s degree (59.0%) and were married (62.1%). The overall estimated proportion of patients with at least one contraindication to COCs according to category 3 (relative contraindications) or 4 (absolute contraindications) was 31.3% (95% CI 26.63–35.99). The most common contraindications observed were controlled hypertension, category 3 (12.1%); major surgery with prolonged immobilisation, category 4 (4.7%); migraine with aura at any age, category 4 (4.2%); breastfeeding from six weeks to less than six months postpartum, category 3 (4.0%); and diabetes mellitus with complications, category 4 (3.2%). Significant factors associated with contraindications to COCs were married women (OR 2.19, 95% CI 1.38–3.46), those aged 35 years or more (OR 2.33, 95% CI 1.49–3.66), and those with one or more live births (OR 2.19, 95% CI 1.38–3.46). Ensuring proper assessment prior to prescribing and considering alternatives suitable for long-term use among women taking an oral contraceptive regularly is recommended. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
25 pages, 1296 KiB  
Article
Use of Prescribed Drugs to Treat Chronic Diseases during Pregnancy in Outpatient Care in Switzerland between 2014 and 2018: Descriptive Analysis of Swiss Health Care Claims Data
Int. J. Environ. Res. Public Health 2022, 19(3), 1456; https://doi.org/10.3390/ijerph19031456 - 27 Jan 2022
Cited by 3 | Viewed by 2801
Abstract
Evidence on the use of drugs during pregnancy in Switzerland is lacking. We aimed to evaluate the utilisation of drugs to treat chronic diseases during pregnancy in Switzerland. We identified all pregnancies (excluding abortions) in Swiss Helsana claims data (2014–2018). In those, we [...] Read more.
Evidence on the use of drugs during pregnancy in Switzerland is lacking. We aimed to evaluate the utilisation of drugs to treat chronic diseases during pregnancy in Switzerland. We identified all pregnancies (excluding abortions) in Swiss Helsana claims data (2014–2018). In those, we identified all claims for drugs to treat a chronic disease, which typically affects women of childbearing age. Potentially teratogenic/fetotoxic drugs were evaluated during specific risk periods. Results were demographically weighted relative to the Swiss population. We identified claims for ≥1 drug of interest during 22% of 369,371 weighted pregnancies. Levothyroxine was most frequently claimed (6.6%). Antihypertensives were claimed during 5.3% (3.9% nifedipine in T3). Renin–Angiotensin–Aldosterone System (RAAS) inhibitors were dispensed to 0.3/10,000 pregnancies during trimester 2 (T2) or trimester 3 (T3). Insulin was claimed during 3.5% of pregnancies, most frequently in T3 (3.3%). Exposure to psychotropic drugs was 3.8% (mostly Selective serotonin reuptake inhibitors (SSRIs)) and to drugs for obstructive airway diseases 3.6%. Traditional immunosuppressants (excluding corticosteroids) were claimed during 0.5% (mainly azathioprine and hydroxychloroquine), biologic immunosuppressants (Tumour necrosis factor-alpha (TNF-alpha) inhibitors and interleukin inhibitors) during 0.2%, and drugs to treat multiple sclerosis during 0.09% of pregnancies. Antiretrovirals were claimed during 0.15% of pregnancies. Patterns of drug claims were in line with treatment recommendations, but relatively rare events of in utero exposure to teratogenic drugs may have had severe implications for those involved. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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13 pages, 366 KiB  
Article
Self-Reported Medication Use among Pregnant and Breastfeeding Women during the COVID-19 Pandemic: A Cross-Sectional Study in Five European Countries
Int. J. Environ. Res. Public Health 2022, 19(3), 1389; https://doi.org/10.3390/ijerph19031389 - 26 Jan 2022
Cited by 14 | Viewed by 4039
Abstract
Insight into the epidemiology of perinatal medication use during the COVID-19 pandemic is scarce. Therefore, a cross-sectional study using an anonymous web survey was performed in Ireland, Norway, Switzerland, The Netherlands, and United Kingdom (UK) to investigate the prevalence and type of medications [...] Read more.
Insight into the epidemiology of perinatal medication use during the COVID-19 pandemic is scarce. Therefore, a cross-sectional study using an anonymous web survey was performed in Ireland, Norway, Switzerland, The Netherlands, and United Kingdom (UK) to investigate the prevalence and type of medications used by pregnant and breast-feeding women during the first pandemic wave. Factors associated with medication use were estimated by logistic regression. In total, 8378 women participated (i.e., 3666 pregnant and 4712 breastfeeding women). Most responses were collected in Norway (34%) and The Netherlands (28%), followed by Switzerland (19%), Ireland (17%) and UK (2%). Participants were more often professionally active and more often had a higher educational level compared to the general birthing population in each country. Overall, approximately 60% of women reported having used at least 1 medication in the preceding 3 months. Daily and occasional use was reported by 34% and 42% of pregnant and 29% and 44% of breastfeeding women. The most prevalent ATC (Anatomical Therapeutic Chemical) categories were the nervous system, the respiratory system, the alimentary tract/metabolism, and the musculo-skeletal system. Paracetamol, ibuprofen, antacids, and cetirizine were the most frequently used medications. The rate of antibacterial use was lower than previously reported. Having a chronic illness, country, maternal age, SARS-CoV-2 testing, professional status and time since delivery were associated with medication use. In conclusion, perinatal medication use was highly prevalent during the first pandemic wave, underlining the importance of maintaining counseling efforts on medication use, even in times of disrupted healthcare services and/or limited resources. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
11 pages, 634 KiB  
Article
Development and Pilot Use of a Questionnaire to Assess the Knowledge of Midwives and Pediatric Nurses on Maternal Use of Analgesics during Lactation
Int. J. Environ. Res. Public Health 2021, 18(21), 11555; https://doi.org/10.3390/ijerph182111555 - 03 Nov 2021
Cited by 1 | Viewed by 2300
Abstract
There is a need to assess the knowledge of healthcare providers on the use of maternal analgesics during lactation; however, valid instruments are not yet available. This study aimed to develop and test a valid questionnaire on the knowledge of analgesics (acetaminophen, ibuprofen, [...] Read more.
There is a need to assess the knowledge of healthcare providers on the use of maternal analgesics during lactation; however, valid instruments are not yet available. This study aimed to develop and test a valid questionnaire on the knowledge of analgesics (acetaminophen, ibuprofen, aspirin, tramadol, codeine, oxycodone) during lactation, using a structured, stepwise approach. As a first step, literature was screened to generate a preliminary version consisting of a pool of item subgroups. This preliminary version was subsequently reviewed during two focus groups (midwives: n = 4; pediatric nurses: n = 6), followed by a two-round online Delphi with experts (n = 7) to confirm item and scale content validity. This resulted in an instrument consisting of 33 questions and 5 specific clinical case descriptions for both disciplines. Based on the assumption of an a priori difference in knowledge between midwives and pediatric nurses related to their curricula (known-groups validity), high construct validity was demonstrated in a pilot survey (midwives: n = 86; pediatric nurses: n = 73). We therefore conclude that a valid instrument to assess knowledge on lactation-related exposure to analgesics was generated, which could be further validated and used for research and educational purposes. As these pilot findings suggest suboptimal knowledge for both professions on this topic, adaptations to their curricula and postgraduate training might be warranted. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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Review

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15 pages, 3260 KiB  
Review
Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations
Int. J. Environ. Res. Public Health 2022, 19(18), 11207; https://doi.org/10.3390/ijerph191811207 - 06 Sep 2022
Cited by 8 | Viewed by 2842
Abstract
Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for [...] Read more.
Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for using sildenafil during the second and third trimester of pregnancy include maternal pulmonary hypertension, preeclampsia, preterm labor, fetal growth restriction, oligohydramnios, fetal distress, and congenital diaphragmatic hernia. For most indications, the rationale for administering prenatal sildenafil is based on limited, equivocal data from in vitro studies and rodent disease models. Clinical studies report mild maternal side effects and suggest good fetal tolerance and safety depending on the underlying pathology. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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23 pages, 3028 KiB  
Review
The Function of the Kynurenine Pathway in the Placenta: A Novel Pharmacotherapeutic Target?
Int. J. Environ. Res. Public Health 2021, 18(21), 11545; https://doi.org/10.3390/ijerph182111545 - 03 Nov 2021
Cited by 17 | Viewed by 3000
Abstract
(L-)tryptophan is metabolized via the kynurenine pathway into several kynurenine metabolites with distinct functions. Dysfunction of the kynurenine pathway can lead to impairments in vascular regulation, immune regulation, and tolerance. The first and rate limiting enzyme of this pathway, indoleamine 2,3-dioxygenase [...] Read more.
(L-)tryptophan is metabolized via the kynurenine pathway into several kynurenine metabolites with distinct functions. Dysfunction of the kynurenine pathway can lead to impairments in vascular regulation, immune regulation, and tolerance. The first and rate limiting enzyme of this pathway, indoleamine 2,3-dioxygenase (IDO), is highly expressed in the placenta and reduced in placentas from complicated pregnancies. IDO is essential during pregnancy, as IDO inhibition in pregnant mice resulted in fetal loss. However, the exact function of placental IDO, as well as its exact placental localization, remain controversial. This review identified that two isoforms of IDO; IDO1 and IDO2, are differently expressed between placental cells, suggesting spatial segregation. Furthermore, this review summarizes how the placental kynurenine pathway is altered in pregnancy complications, including recurrent miscarriage, preterm birth, preeclampsia, and fetal growth restriction. Importantly, we describe that these alterations do not affect maternally circulating metabolite concentrations, suggesting that the kynurenine pathway functions as a local signaling pathway. In the placenta, it is an important source of de novo placental NAD+ synthesis and regulates fetal tryptophan and kynurenine metabolite supply. Therefore, kynurenine pathway interventions might provide opportunities to treat pregnancy complications, and this review discusses how such treatment could affect placental function and pregnancy development. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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Other

43 pages, 10108 KiB  
Systematic Review
The Risk for Neonatal Hypoglycemia and Bradycardia after Beta-Blocker Use during Pregnancy or Lactation: A Systematic Review and Meta-Analysis
Int. J. Environ. Res. Public Health 2022, 19(15), 9616; https://doi.org/10.3390/ijerph19159616 - 04 Aug 2022
Cited by 5 | Viewed by 3981
Abstract
Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed [...] Read more.
Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed to evaluate the potential increased risk for hypoglycemia and bradycardia in neonates exposed to beta-blockers in utero or during lactation. A systematic search of English-language human studies was conducted until 21 April 2021. Both observational studies and randomized controlled trials investigating hypoglycemia and/or bradycardia in neonates following beta-blocker exposure during pregnancy and lactation were included. All articles were screened by two authors independently and eligible studies were included. Pair-wise and proportion-based meta-analysis was conducted and the certainty of evidence (CoE) was performed by standard methodologies. Of the 1.043 screened articles, 55 were included in this systematic review. Our meta-analysis showed a probable risk of hypoglycemia (CoE—Moderate) and possible risk of bradycardia (CoE—Low) in neonates upon fetal beta-blocker exposure. Therefore, we suggest the monitoring of glucose levels in exposed neonates until 24 h after birth. Due to the limited clinical implication, monitoring of the heart rate could be considered for 24 h. We call for future studies to substantiate our findings. Full article
(This article belongs to the Special Issue Pharmacotherapy during Pregnancy, Childbirth and Lactation)
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