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Psychedelic and psychedelic-adjacent substances, including 3,4-methylenedioxymethamphetamine (MDMA) and classic serotonergic hallucinogens, are undergoing renewed therapeutic investigation and remain in non-medical use. Inadvertent exposure during early, unrecognized pregnancy is clinically plausible, yet pregnancy-specific safety evidence is limited. To map and synthesize the extent, characteristics, and limitations of primary human evidence on prenatal exposure to MDMA, psilocybin, and classic hallucinogens (lysergic acid diethylamide (LSD), mescaline/peyote, and N,N-dimethyltryptamine (DMT)/ayahuasca), and to identify clinically relevant evidence gaps for perinatal counseling and pharmacovigilance. Peer-reviewed primary human studies (cohort, case-control, cross-sectional, case series, case reports, and brief reports) describing prenatal exposure with reported maternal, obstetric, neonatal, congenital anomaly, or child neurodevelopmental outcomes were included. Animal and preconception-only studies were excluded. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were searched from inception to March 2025. Supplementary methods included Google Scholar screening and citation tracking. Data were charted in duplicate using a standardized form and synthesized descriptively by substance and outcome domain. Consistent with scoping methodology, no formal risk-of-bias assessment or meta-analysis was undertaken. Twenty-three primary human sources (1968-2020) met inclusion criteria: MDMA (n = 11), LSD (n = 11), and mescaline/peyote (n = 1). No eligible primary human pregnancy outcome studies were identified for psilocybin or DMT/ayahuasca. The evidence base was heterogeneous and predominantly comprised small cohorts, teratology service follow-up reports, and case-based publications, frequently limited by self-reported exposure, polysubstance confounding, and inconsistent outcome definitions. Human evidence on prenatal psychedelic exposure remains sparse and methodologically constrained. Absence of data for several substances should not be interpreted as evidence of safety. Clinicians should counsel with explicit acknowledgment of uncertainty while supporting harm reduction and appropriate follow-up. Structured perinatal pharmacovigilance and ethically designed evidence-generation strategies are needed as therapeutic psychedelic research expands. What we know about psychedelic drug exposure during pregnancy Some people may be exposed to psychedelic drugs such as MDMA (“ecstasy”), LSD, or psilocybin during pregnancy, often before they realize they are pregnant. As interest in psychedelic therapies grows, clinicians are increasingly asked about possible risks to pregnancy and child development. In this review, we examined all available human studies that reported pregnancy or child outcomes following exposure to psychedelic or psychedelic-related substances. We found that the human evidence base is very limited and mostly consists of small observational studies, case reports, and follow-up data from teratology information services. Most available studies focus on MDMA or LSD, while there is little to no direct human pregnancy outcome data for substances such as psilocybin or ayahuasca. Because the available evidence is sparse and highly variable, it is not possible to reliably estimate the risks of miscarriage, birth defects, or long-term child development following psychedelic exposure during pregnancy. This review highlights important gaps in current knowledge and explains why careful, individualized clinical counselling is needed when such exposures occur. The findings are relevant for clinicians, patients, and researchers involved in drug safety and pregnancy care.

Etanercept is a tumor necrosis factor inhibitor frequently used to control ankylosing spondylitis (AS) in women of reproductive age, yet data on its safety during breastfeeding are limited. We report a case of an infant who developed somnolence, hypotonia, feeding difficulties, and a concomitant infection temporally associated with maternal etanercept therapy during lactation and discuss implications for breastfeeding. A 33-year-old woman with AS delivered a healthy female infant by cesarean section at 36 + 5 weeks' gestation and began exclusive breastfeeding. At 11 weeks postpartum, she initiated etanercept 25 mg subcutaneously once weekly for her active disease. During treatment, the infant developed prolonged sleep, somnolence, feeding difficulty, and hypotonia, followed within a week by low-grade fever, cough, and nasal congestion. After three doses, etanercept was discontinued, and she was referred to our teratology information service. Approximately 2 weeks after the last dose, the infant's respiratory symptoms worsened, and diarrhea developed, prompting emergency admission. Laboratory evaluation showed leukocytosis, elevated C-reactive protein, and a nasopharyngeal swab, which was positive for rhinovirus/enterovirus. Symptoms resolved with supportive care and azithromycin by treatment days 4-5. At 9 months of age, the infant has had no other health issues. This case illustrates the difficulty of interpreting adverse events in breastfed infants exposed to maternal biologic medications. Although current evidence suggests no clinically severe adverse effects, minimal infant exposure, and a low risk of clinically relevant immunosuppression with etanercept during breastfeeding, individualized counseling and careful monitoring of exposed infants remain essential.

Although regulatory responses to safety signals have been studied, pregnancy-specific data and their dissemination to medical professionals remain unclear. This study examined the characteristics and temporal trends of teratological safety signals prompting the European Medicines Agency to implement risk minimization measures. A secondary aim was to investigate how information on these signals, independent of regulatory communication, was disseminated to medical professionals in the Netherlands. Teratological safety signals from 2002 to 2022 were retrieved from the European Pharmacovigilance Issues Tracking Tool. For each signal, we recorded the dates of market authorization, first spontaneous report, scientific publication, regulatory decision and dissemination through the Teratology Information Service (TIS) and Dutch professional journals. The source of the signal (spontaneous reports, scientific literature or otherwise) was assessed. Time intervals between events were calculated and visualized. Twenty-four safety signals pertaining to fetal teratogenesis were identified. At the time of regulatory action, medicines had been on the market for a median of 23.9 years (range 3.2-59.3). Cases or studies published in the scientific literature were the origin for most (n = 18, 75%) teratological safety signals. Amendments of the product information was a regulatory action for all signals; eight (33%) also triggered Direct Healthcare Professional Communications. Apart from these regulatory communications, information may have reached healthcare professionals through scientific literature or other channels, sometimes before and sometimes alongside regulatory decisions. Teratological safety signals are predominantly scientific literature-driven and often arise decades after marketing. Scientific publications and TIS may provide early guidance, frequently preceding regulatory decisions.

Since 2008, the open-access internet portal "Embryotox" has provided evidence-based information on drug safety during pregnancy and breastfeeding. The German website, designed for health care professionals, comprises fact sheets about 400 drugs and is maintained by the Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy at the Charité - Universitätsmedizin Berlin. In 2024, it was accessed more than 5 million times. This study aimed to evaluate who is using the website, how it is being used, and to what extent it meets users' needs. Data were collected between 2022 and 2023 through a sequential mixed methods design incorporating explanatory and exploratory elements. Online questionnaire 1 contained questions on user characteristics, clinical specifics of use, comprehensibility, and changes in risk assessment or drug therapy following fact sheet use. Qualitative data were generated through semistructured phone interviews, with interviewees sampled from the main user groups identified in questionnaire 1 (patients, physicians, pharmacists, and midwives). Kuckartz's content analysis was used to analyze data on users' trust and the functions of website use for different stakeholder groups. Online questionnaire 2 collected data from the main user groups on their decision-making based on Embryotox fact sheets. This questionnaire was developed based on the findings from semistructured interviews on the functions of website use. Answers in both questionnaires included multiple-choice options or ratings on a Likert scale from 0 (not at all) to 10 (fully); data were analyzed using descriptive statistics. Questionnaire 1 was completed by 14,562 users, including 10,860 patients, 1676 physicians, 550 pharmacists, and 364 midwives. Of the physicians, 27.2% (456/1676) were obstetricians and gynecologists, and 22.7% (381/1676) were general practitioners. For physicians, the mean of comprehensibility ratings was 9.39 (pharmacists 9.25; midwives 9.14), and for patients 8.80. Following fact sheet use, 66.6% (9694/14,562) of all users changed their risk perception, and 22.3% (2252/10,083) of users in a specific treatment setting considered changing drug treatment. Qualitative content analysis revealed that users highly trusted the information in the fact sheets for a number of reasons, including recommendations from other users, the scientific basis of the website, and the authority of the Embryotox Center as a university-based specialist department for drug safety in pregnancy and lactation. Functions of fact sheet use differed depending on the stakeholder group. A total of 793 users, mostly physicians and patients, fully completed questionnaire 2, specifying typical clinical situations and benefits of fact sheet use for shared decision-making. Benefits included facilitating the decision-making process and increasing confidence in it. The information provided in the Embryotox fact sheets was generally perceived as both comprehensible and trustworthy, supporting and facilitating the decision-making process. Embryotox is used successfully by health care providers and patients in routine health care settings, helping to improve drug safety for pregnant and breastfeeding women.

The evidence gap relating to the risk of congenital anomalies (CA) associated with first trimester medication exposure in pregnancy is well recognized. We describe the EUROmediCAT network and databases, and the methodological approach to pregnancy pharmacovigilance. Multidisciplinary expertise includes CA diagnosis and epidemiology, pharmacoepidemiology, pharmacology and teratology. The EUROmediCAT central database comprises standardized data from 19 EUROCAT CA registries in 14 countries, including more than 40 000 CA cases 1995-2021 with first trimester medication exposure data recorded, and a population coverage of 14.6 million births, growing by more than 650 000 births per year. The distributed database enables federated data analysis across eight countries which can link data from CA registries to electronic healthcare data, with population coverage of up to 900 000 births per year for linkage to maternal prescriptions, of which 300 000 births per year for linkage also to data on all births. The databases have enabled a variety of study designs: case-malformed control studies, cohort studies, disease cohort studies, signal detection studies, prevalence and ecological studies, and medication utilization studies. A key strength is that studies of CA risk can address accurately the specificity of risk by type of CA. EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy. There is a well‐recognized need for more evidence about the safety of medication use in early pregnancy to guide optimal medication choice. This paper describes the EUROmediCAT network and its databases, and how these databases can be used to generate evidence about medication safety in pregnancy. A single central database includes data from congenital anomaly registries in 14 countries of Europe, with information on medication exposure of each case. This covers a population of 14.6 million births 1995–2021, and is growing by more than 650 000 births per year. Databases accessible in eight countries link congenital anomaly registries to prescription data (covering over 900 000 births per year), and to all births (covering over 300 000 births per year). These data can also be shared for large scale research. A key strength of the EUROmediCAT network and databases is that particular attention is paid to accurate information on the risk of specific types of congenital anomaly. EUROmediCAT presents a unique data and expert resource for tackling the enormous evidence gap regarding the safety of medication during pregnancy.

Autosomal-dominant polycystic kidney disease (ADPKD) remains refractory to curative therapy partly due to the lack of human models that recapitulate its adult-onset nature, genetic context, and multi-segment origin. Here, we established expandable, multi-lineage adult renal organoids (MAROs) directly from surgical specimens of ADPKD patients and healthy donors, creating a three-dimensional (3D) high-content screening platform. Patient-derived MAROs faithfully reproduced hallmark cystogenic features, including elongated primary cilia, polarity disruption, and elevated Rho GTPase/planar cell polarity (PCP) signaling. Single-cell transcriptomics of PKD1/PKD2-mutant organoids revealed genotype-specific alterations. Genetic ablation of IFT88 disrupted cilia and selectively attenuated Rho/PCP activity in mutant backgrounds, supporting a cilia-dependent cyst-activating (CDCA) mechanism in cystogenesis. Microfluidic perfusion accelerated cyst expansion and amplified Rho/PCP signaling. A high-throughput drug screen identified Rho GTPase inhibitors, including ML141, as effective cyst-reducing agents across genotypes without compromising viability. Our findings establish a patient-derived organoid platform that captures ADPKD pathology and nominates Rho pathway modulation as a therapeutic strategy.

Preventing cancer recurrence after surgical removal, while preserving breast cosmesis and restoring function, remains challenging. Traditional scaffold-based approaches are often restricted by their inadequate integration with natural tissues and unmatched rate of material degradation to tissue development. Here we report an anticancer drug secretion system based on engineered mammary organoids for inhibiting post-surgical tumour recurrence and promoting tissue reconstruction. By inducing the lactation of mammary organoids, cytoplasmic lipid droplets form intracellularly. A pH-responsive prodrug, comprising all-trans retinal and the chemotherapeutic agent doxorubicin, is readily encapsulated in these lipid droplets. Upon lactation, milk fat globules, enriched with these drug-loaded lipid droplets, are released to residual tumour cells through the contractile actions of myoepithelial cells. Both mouse and human-induced pluripotent stem cell-derived mammary organoids were engineered as drug-secreting depots and demonstrated their effectiveness in inhibiting tumour recurrence (96% regression) in a mouse post-surgical breast cancer model. In addition, the organoids could be self-adaptively integrated with mammary glands and contribute to their reconstruction, ultimately restoring lactational capacity in the recipient mice.

Prenatal alcohol exposure (PAE) can disrupt development, leading to alterations in physical, health, and behavioral outcomes, referred to as fetal alcohol spectrum disorders (FASD). Although alcohol likely impacts fetal development through many mechanisms, PAE could impact metabolism of choline, an essential nutrient that is important for brain development and function. Importantly, both preclinical and clinical studies show that choline supplementation can improve performance on hippocampal-dependent behavioral tasks, even when administered postnatally. However, the mechanisms by which choline mitigates prenatal alcohol-induced neurocognitive deficits are not well understood. Thus, the present study examined whether PAE leads to long-lasting changes in choline metabolism in the hippocampus and plasma of adolescent animals and if effects are modified by choline. From postnatal day (PD) 4-9, rat pups were given ethanol (EtOH; 5.25 g/kg/day) or sham intubations. From PD 10-30, subjects received s.c. choline chloride (100 mg/kg/day) or saline. Plasma and hippocampus were collected on PD 35 and choline metabolite levels were analyzed. Neither EtOH nor choline led to long-lasting changes in choline levels. However, EtOH-exposed females had reduced hippocampal betaine and plasma betaine:choline ratios. Plasma cystathionine was elevated in EtOH-exposed females treated with choline, suggesting choline activates anti-oxidative stress and anti-inflammation pathways among EtOH-exposed subjects. Choline alone increased homocysteine among females. In contrast, choline supplementation increased plasma SAM:SAH ratios in EtOH-exposed males, suggesting choline is modifying DNA methylation. Overall, these results provide insights to sex-specific mechanisms of action in which choline supplementation alters choline metabolic pathways in FASD.

One of the fundamental questions in developmental biology is how the organ size is controlled. While apoptosis, a type of programmed cell death, has been shown to restrict growth in proliferating tissues such as Drosophila wing imaginal disc, its key effectors, executioner caspases, paradoxically exhibit pro-growth functions. Executioner caspases are activated in some wing disc cells without triggering apoptosis. How non-apoptotic and apoptotic executioner caspase activation (ECA) are coordinated to regulate wing size remains poorly understood. In this study, we utilize two different executioner caspase reporters to monitor the dynamics of apoptotic and non-apoptotic ECA. We show that apoptotic and non-apoptotic ECA exhibit distinct spatiotemporal patterns during wing disc development, with non-apoptotic ECA prevalent in the proximal region of younger discs and apoptosis enriched in the distal region of older discs. Furthermore, we demonstrate that the non-apoptotic and apoptotic ECA are regulated by different pro-apoptotic genes. Non-apoptotic ECA depends on reaper (rpr), while apoptosis requires head involution defective (hid). In younger discs, rpr-induced non-apoptotic ECA promotes wing growth. As the disc ages, hid triggers strong ECA that leads to apoptosis, thereby refining the final wing size. Our work elucidates the mechanism regulating divergent cell fates following ECA and how they are coordinated to control organ size.

Cochlear hair cells are the mechanosensitive receptor cells responsible for detecting sound information. They are characterized by their apical F-actin-filled stereocilia that are essential for mechano-electrical transduction. Previously, we and other groups reported that RNA Binding Motif Protein 24 (RBM24) plays pivotal roles in stereocilia development and maintenance by regulating pre-mRNA alternative splicing and mRNA stability. In the present work, we show that exon 4 of the mouse Rbm24 gene is subjected to alternative splicing. Inclusion of exon 4 in Rbm24 mRNA results in premature translational stop, giving rise to a short isoform of RBM24 (RBM24-S). Notably, while sharing the same RNA-recognition motif, the canonical RBM24 long isoform (RBM24-L) and RBM24-S can bind different mRNA targets to affect their splicing and/or stability. Deletion of Rbm24 exon 4 in mice abolishes the expression of Rbm24(+e4) transcripts that encode for RBM24-S, and both homozygote and heterozygote mice suffer from severe hearing loss. Further investigations revealed that Rbm24 exon 4 deletion leads to stereocilia disorganization and eventually hair cell loss. Moreover, overexpression of RBM24-L in the hair cells leads to significant stereocilia deficits as well as profound hearing loss. Finally, we identified several RBM24 targets such as Strc, whose dysregulation contributes to stereocilia disorganization as well as hearing loss in Rbm24 deficient mice. Taken together, our present data suggest that Rbm24 is subjected to alternative splicing and appropriate RBM24 expression levels are important for stereocilia integrity and hearing function.

The Fildes Peninsula (maritime Antarctica) is greatly affected by global warming and local human impacts since it is in one of the Antarctic regions with the highest intensity of human activity. To establish the effect of human activities on Fildes Peninsula lakes, we compared trends in diatom assemblages, bacterial communities and metal concentrations in sediment cores from two lakes close to human infrastructure with those in a more remote lake. In the two lakes close to stations and the airport, we found heavy metal enrichments and diatom teratologies, as well as notable changes in diatom assemblages in one of these lakes, roughly coincident with the time when the first two stations were built (~ 1970). Due to the known association between diatom teratologies and metal enrichment, metal stress is a convincing explanation for these changes. Certain bacterial taxa determined to be indicators of pollution were also found to be more abundant in the impacted lakes in recent sediments (i.e., Hungateiclostridiaceae, OPB41, Anaerovorax and Leptolinea). Metal, diatom and bacteria changes observed in the lake more distant to infrastructure were more subtle and are likely related to climate change alone. Given the proximity of the affected lakes to the airport and roads, our data suggests that transportation infrastructure and activity on Fildes Peninsula is likely a key cause of contamination in the region's ecosystems. This study provides important insights into how human activities and climate change have affected Fildes Peninsula aquatic ecosystems and how they may respond to future stressors.

The stimulator of interferon genes (STING) is a critical mediator of innate immunity against cytosolic DNA pathogens, requiring precise regulation to balance antiviral defense and immune tolerance. While lipid metabolism influences immune signaling, the role of stearoyl-CoA desaturase 1 (SCD1), a key enzyme converting saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs), in STING activation remains unexplored. Here, we identify SCD1 as a metabolic checkpoint that licenses STING activation through biophysical membrane remodeling. Mechanistically, SCD1-generated MUFAs incorporate into endoplasmic reticulum (ER) phospholipids, enhancing membrane curvature and fluidity. This biophysical remodeling facilitates cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) binding to STING and promotes its dimerization, enabling downstream TBK1-IRF3 signaling and type I interferons (IFNs) production. Consequently, Scd1 deficiency or pharmacological inhibition impairs STING activation, attenuates antiviral responses against herpes simplex virus-1 (HSV-1), and exacerbates viral replication in vitro and in vivo. Conversely, MUFAs supplementation rescues STING activation in Scd1-deficient models. Our findings establish SCD1-mediated lipid desaturation as a fundamental regulator of STING-driven immunity, highlighting its therapeutic potential for disorders of aberrant STING activation.

Atherosclerosis is now widely recognized as a chronic inflammatory condition driven by the recruitment of leukocytes, with CXCR4 playing a critical role in plaque inflammation and disease progression. In this study, we report the development and initial assessment of five novel 68Ga-labeled small-molecule CXCR4 radiotracers ([68Ga]Ga-SDNUM08-12), engineered on an aniline-benzylamine scaffold with varying PEG linker lengths (PEG1 vs PEG2) and bridging amino acids (glutamic vs aspartic acid). Notably, [68Ga]Ga-SDNUM11, incorporating dual PEG2 units and glutamic acid, exhibited optimal hydrophilicity, rapid blood clearance, excellent stability and high binding affinity. In a turpentine-induced sterile muscle inflammation mouse model, [68Ga]Ga-SDNUM11 emerged as the lead radiotracer with optimal imaging efficacy. Subsequently, in a rat common carotid artery (CCA) atherosclerosis model, it exhibited focal uptake colocalizing with CXCR4-positive plaques. These findings establish [68Ga]Ga-SDNUM11 as a promising CXCR4-targeted radiotracer for PET imaging of atherosclerotic plaque inflammation and cardiovascular risk stratification.

Pain management during pregnancy poses a considerable challenge in everyday clinical practice. The relief of maternal discomfort must be weighed against the potential risks of using medication (nonsteroidal anti-inflammatory drugs, paracetamol, steroids, opioids, gabapentinoids). The current data on congenital anomalies, complications during pregnancy, neonatal adaptation or withdrawal symptoms, and long-term psychomotor developmental disorders in children exposed in utero must be taken into account. However, refraining from treating chronic maternal pain during pregnancy can also cause problems for the child's development. Given the limited research findings, prescribing physicians must clarify the advantages and disadvantages of treatment strategies through informed, joint decision-making with their patients. This overview is intended to serve as an evidence-based guide for optimizing pain management during pregnancy while minimizing risks to offspring. Die Schmerztherapie während der Schwangerschaft stellt eine erhebliche Herausforderung im klinischen Alltag dar. Die Linderung der Beschwerden der Mutter muss gegen die potenziellen Risiken einer Anwendung von Medikamenten (nichtsteroidale Antiphlogistika, Paracetamol, Steroide, Opioide, Gabapentinoide) abgewogen werden. Dabei ist die aktuelle Datenlage zu angeborenen Anomalien, Komplikationen im Schwangerschaftsverlauf und neonatalen Anpassungs- bzw. Entzugssymptomen, aber auch zu langfristigen psychomotorischen Entwicklungsstörungen der intrauterin exponierten Kinder zu berücksichtigen. Auch der Verzicht auf eine Therapie chronischer Schmerzen in der Schwangerschaft kann Probleme für die Entwicklung des Kindes mit sich bringen. Angesichts der begrenzten Forschungsergebnisse müssen die verordnenden ÄrztInnen die Vor- und Nachteile von Behandlungsstrategien durch eine informierte gemeinsame Entscheidungsfindung mit den Patientinnen klären. Diese Übersicht soll als evidenzbasierter Leitfaden der Optimierung der Schmerzbehandlung während der Schwangerschaft bei gleichzeitiger Minimierung der Risiken für die Nachkommen dienen.

Leydig cells play a crucial role in male development, fertility, and overall health through hormone production. Brahma-related gene 1 (BRG1), the catalytic subunit of the mammalian SWI/SNF complex, is a key regulator of chromatin accessibility and governs the development and function of diverse tissues. However, its role in Leydig cells remains unclear. In this study, we first characterized the expression pattern of PR-Cre in the testes, as this Cre mouse line has been widely used for gene targeting in the female reproductive system, but its activity in the testis has never been systematically reported. We found that PR-Cre drives recombination in multiple testicular cell types, including stem/progenitor adult Leydig cells (ALCs), peritubular myoid cells, and elongated spermatids. Using PR-Cre to conditionally delete BRG1 in ALCs, we observed no detectable abnormalities in ALC development, spermatogenesis, or male fertility. Similar results were obtained using the Cyp17a1-iCre mouse line and AAV8-iCre viral delivery for BRG1 deletion. Collectively, this work demonstrates that BRG1 is dispensable for ALC development and function, while providing a comprehensive characterization of PR-Cre as a valuable new tool for male reproductive research.

Clinical lactation studies are valuable to guide pharmacotherapy during breastfeeding, but are not easy to conduct. This paper reports on challenges and mitigation strategies while conducting the UmbrelLACT study, a prospective observational lactation study. The UmbrelLACT study includes breastfeeding women taking a relevant medicine (eg, absence of safety evidence during lactation) and after feasibility verification (eg, access to bioanalytical assay). Participants collect human milk samples at home over 24 hours. Optionally, maternal and infant blood samples are collected, together with self-reported questionnaires on clinical maternal and child variables. Medicine concentrations and estimated infant exposure (eg, daily and relative infant dose) are determined. Regarding informed consent, study objectives should be carefully phrased to prevent pharmacotherapy avoidance due to a lack of safety information. On sample collection, the study team should provide all necessary materials if not available at home, including an electric breast pump. Due to the milk expressions over 24 hours, the infant might miss soothing moments. This can be mitigated by giving the breast after expressing the milk for study purposes, creating alternative soothing moments. Sample handling might be complicated by additional steps needed for certain compounds. A bioanalysis method should be available or developed for the milk matrix. Finding the assay might be challenging, but it can be facilitated by a network of specialised labs. In the UmbrelLACT study, pharmacokinetic values are collected fragmentarily. This results in the need for data pooling with data from the literature. In contrast, at-home sampling and multidisciplinary collaboration are clear strengths. It is feasible to tailor the approach to each participant and compound, to minimise the burden on the patient and their family. While there are limitations related to the pragmatic design, the opportunities of this lactation study outweigh the challenges to result in clinically significant scientific observations. NCT06042803.

Maternal fever is a common occurrence during pregnancy, but evidence increasingly links even transient hyperthermia to adverse fetal outcomes. This review examines data from animal and human studies on the association between maternal hyperthermia and structural birth defects, neurodevelopmental disorders, fetal growth restriction, and pregnancy loss. A narrative review of published literature evaluating maternal hyperthermia and pregnancy outcomes was conducted, including both experimental animal models and observational human studies. The teratogenic effects appear to be dose- and timing-dependent, with greatest vulnerability during the first trimester. Reported associations including neural tube defects, craniofacial anomalies, and congenital heart defects as well as neurodevelopmental disorders, fetal growth restriction, and pregnancy loss. Proposed mechanisms include heat-induced cellular stress and maternal immune activation, both of which can disrupt embryonic development. Folic acid supplementation and antipyretic use are associated with reduced risk. Although the evidence is derived from observational studies and limited by difficulty of measuring temperatures, the consistency of findings from different models support the biologic plausability of a teratogenic effect of maternal fever. The variability in exposure assessment and confounding factors, including maternal comorbidities, remain important limitations. Maternal fever is a potentially modifiable risk factor for advere pregnancy outcomes. Preventative strategies that include preconception folic acid supplementation and maternal fever management are supported by the current literature. Further research is needed to define critical exposure windows and the impact of materanal comorbidities.

This exploratory pilot study evaluated whether subchronic late-gestational oral nicotine exposure alters postpartum maternal behavior in Wistar rats. Twelve pregnant Wistar rats were obtained in three successive intake batches and randomly assigned to experimental or control groups. Control animals received a 2% saccharin solution; experimental animals received nicotine (nominal 200 μg/mL) in 2% saccharin solution ad libitum from gestational day 7 through parturition. The initial concentration of 200 μg/mL produced two maternal deaths and one embryonic reabsorption in the first experimental batch; the solution was diluted approximately 1:3 to ∼50 μg/mL for the third experimental batch. Postpartum maternal behavior was scored from 15-min light-phase video samples (three 5-min blocks at 5-s instantaneous sampling) on each of the 14 postpartum days. Dependent variables were daily frequency counts of 19 ethogram behaviors organized into proximal, nest-related, motor, and self-maintenance categories. Primary analyses were 2 × 14 mixed repeated-measures ANOVAs. Fluid consumption, litter parameters, and cohort attrition are also reported. Experimental dams reduced solution consumption by approximately 81% relative to their pre-nicotine water baseline, indicating that actual nicotine exposure was substantially below the nominal concentration. Among the three surviving dams per group, proximal maternal behaviors showed no reliable group differences on either parametric or non-parametric tests. The clearest between-group difference was in eating frequency (controls > experimentals; F(1, 4) = 48.96, p = .002, ηp2 = 0.92). A significant Day × Group interaction was observed for locomotion, concentrated on postpartum days 11-12. In this small pilot, subchronic late-gestational nicotine exposure did not produce consistent alterations in core proximal maternal behaviors among surviving dams, but was associated with substantial gestational losses, reduced maternal fluid intake, a qualitative low-pup-birth-weight observation, and a postpartum eating-frequency difference that cannot be unambiguously attributed to nicotine pharmacology. The findings are hypothesis-generating and motivate adequately powered replication with cotinine verification and gravimetric pup-weight measurement.