Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

AIMS: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. METHODS: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. RESULTS: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. CONCLUSION: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.

Contact to perfluoroalkyl substances and thyroid health effects: A meta-analysis directing on pregnancy.

In vivo, in vitro, and epidemiological evidence suggests that perfluoroalkyl substances (PFAS) may alter thyroid function in human health, with negative effects on maternal and fetal development outcomes. However, data on the effects of PFAS on thyroid hormones remain controversial. Here, we conducted a meta-analysis of 13 eligible studies searched from Embase, PubMed, and Web of Science by July 10, 2022, to explore the relationship between maternal exposure to PFAS and thyroid health effects, including thyroid stimulating hormone (TSH), triiodothyronine (TT3), thyroxin (TT4), free T3 (FT3), and free T4 (FT4). The estimated values (ß) and the corresponding confidence intervals (95%CI) were extracted for analysis. The tests for heterogeneity, sensitivity and publication bias between studies were performed using Stata 15.0. The combined results showed a positive association between changes in TSH and exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), with no significant correlation observed between changes in other thyroid hormones and exposure to PFAS. This difference was attributed to sample size, region, sample type, body mass index (BMI), and gestational week. Our data recommend verifying the relationship between PFAS exposure and thyroid health effects in a large sample population cohort in future studies. In addition, health care should be taken into account in early and mid-pregnancy.

The associations of cola intake with adverse birth outcomes among pregnant women after assisted reproductive technology treatment and women naturally conceived: a birth cohort study.

The influence of cola intake on birth outcomes is unclear. This study sought to describe and compare the associations between cola intake and adverse birth outcomes among women following assisted reproductive technology (ART) and women spontaneously conceived (SC). Participants (736 ART women and 1,270 SC women) were from the Chinese National Birth Cohort collected in Anhui province. Cola intake was assessed by self-reported questionnaires at each trimester. Outcome measures including preterm birth (PTB) and low birth weight (LBW) were extracted from medical records. The association between cola intake during pregnancy and PTB was found using multivariable log-binomial regression in combined ART and SC women. Separately, for ART women, cola intake during pregnancy increased the risk of PTB (risk ratios were 2.10, 1.65, and 1.81 for all three trimesters, respectively, all p < 0.05), and cola intake in the 1st trimester increased the risk of LWB (risk ratio 2.58, 95% confidence interval 1.29 to 5.16). Cola intake during pregnancy was not associated with PTB or LBW for SC women. Our findings indicate a detrimental effect of cola intake during pregnancy on birth outcomes for ART women. Thus, avoidance of cola intake should be counselled by medical doctors in women prescribed with ART treatment.

Aspirin Inhibits the Inflammatory Response of Protease-Activated Receptor 1 in Pregnancy Neutrophils: Implications for Treating Women with Preeclampsia.

Neutrophils expressing cyclooxygenase-2 (COX-2) extensively infiltrate maternal blood vessels in preeclampsia, associated with vascular inflammation. Because pregnancy neutrophils also express protease-activated receptor 1 (PAR-1, F2R thrombin receptor), which they do not in non-pregnant subjects, they can be activated by proteases. We tested the hypothesis that aspirin at a dose sufficient to inhibit COX-2 would reduce inflammatory responses in preeclampsia neutrophils. Neutrophils were isolated from normal pregnant and preeclamptic women at approximately 30 weeks' gestation. Normal pregnancy neutrophils were treated with elastase, a protease elevated in preeclampsia, or elastase plus aspirin to inhibit COX-2, or elastase plus pinane thromboxane, a biologically active structural analog of thromboxane and a thromboxane synthase inhibitor. Preeclamptic pregnancy neutrophils were treated with the same doses of aspirin or pinane thromboxane. Confocal microscopy with immunofluorescence staining was used to determine the cellular localization of the p65 subunit of nuclear factor-kappa B (NF-κB) and media concentrations of thromboxane were measured to evaluate the inflammatory response. In untreated neutrophils of normal pregnant women, p65 was localized to the cytosol. Upon stimulation with elastase, p65 translocated from the cytosol to the nucleus coincident with increased thromboxane production. When neutrophils were co-treated with aspirin or pinane thromboxane, elastase was not able to cause nuclear translocation of p65 or increase thromboxane. In untreated neutrophils of preeclamptic women, the p65 subunit was present in the nucleus and thromboxane production was elevated, but when preeclamptic neutrophils were treated with aspirin or pinane thromboxane, p65 was cleared from the nucleus and returned to the cytosol along with decreased thromboxane production. These findings suggest that COX-2 is a downstream mediator of PAR-1 and demonstrate that PAR-1- mediated inflammation can be inhibited by aspirin. Given the extensive and ubiquitous expression of PAR-1 and COX-2 in preeclamptic women, consideration should be given to treating women with preeclampsia using a dose of aspirin sufficient to inhibit COX-2.

Granulocyte colony stimulating factor versus human chorionic gonadotropin for recurrent implantation failure in intra cytoplasmic sperm injection: a randomized clinical trial.

BACKGROUND: Repeated implantation failure (RIF) is defined as the case whereby the transferred embryos fail to implant after several attempts of In vitro fertilization (IVF) which causes a profound impact on the quality of life and financial burden. Some clinical studies have confirmed that Granulocyte colony-stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) can improve pregnancy outcomes and implantation rates. Hence, our study aims to compare the efficacy of G-CSF and HCG on pregnancy outcomes in RIF women who undergo intra-cytoplasmic sperm injection (ICSI). METHODS: This randomized, single-blinded study was conducted et al.-Azhar University Hospitals, Cairo, Egypt, between 10th October 2020 and 20th December 2020. The study included 100 women aged 20-43 years old undergoing ICSI cycles, with a history of RIF. Patients were divided randomly into two groups: group (1): included 50 patients injected with 500 IU of intrauterine HCG on embryo transfer day, and group (2): Included 50 patients injected with G-CSF on the embryo transfer day. RESULTS: In 100 RIF women, we found a significant improvement in pregnancy outcomes favoring G-CSF over HCG including implantation rate, chemical pregnancy, and clinical pregnancy (P < 0.0001, P = 0.0003, and P = 0.0006, respectively). CONCLUSION: For the first time, we demonstrated a significant improvement in pregnancy outcomes favoring G-CSF over HCG in terms of implantation rate, chemical pregnancy, and clinical pregnancy. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202010482774275 and was approved on 2nd October 2020.

Salud mental, abuso de sustancias y trastornos duales en el embarazo: Tasas de prevalencia y tratamiento en un país desarrollado / Substance use, mental health and dual disorders on pregnancy: Results of prevalence and treatment rates in a developed country

El tabaquismo y el consumo de sustancias durante el embarazo son importantes causas prevenibles de morbimortalidad, teniendo una relaciónbidireccional y deletérea con la salud mental de la madre y el niño.Como parte de la iniciativa WOMAP (Woman Mental Health and Addictions on Pregnancy), se estudiaron 2.014 embarazadas buscando describir la prevalencia de trastornos mentales y por uso de sustancias concurrentes, las tasas de tratamiento y los diagnósticos y la gravedad. Lasparticipantes fueron evaluadas con la escala AC-OK y se les preguntó sobre sus hábitos tabáquicos y uso de servicios de salud mental/sustancias.De las participantes, 170 mujeres resultaron positivas para un trastornomental y por uso de sustancias concurrentes (≥ 2 positivos a la subescalaAC-OK-Salud Mental, ≥ 1 positivos a la subescala AC-OK-Sustancias y/ofumar más de una vez al mes y no estar en tratamiento) y fueron evaluadas en profundidad mediante una batería de escalas (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Post-traumatic stress disorder Checklist [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] y Fagerström).En el último año, 614 mujeres (30,5%) fumaron tabaco (42,5% diariamente) y el 9,8% fueron positivas para problemas por uso de sustancias ysalud mental según la AC-OK. Solo el 11,1% había recibido tratamientoen los tres meses previos y solo un 13,6% tenía una cita en el siguientemes. De las 170 pacientes evaluadas secundariamente, 62(36,5%) presentaron al menos depresión moderada, 35(20,6%) al menos ansiedadmoderada, 32(18,8%) fueron positivas a la PCL-5, y 37 de las 88 quereconocieron uso de alcohol puntuaron por encima del umbral en AUDIT (≥ 3).En conclusión, la combinación de una prevalencia significativa junto conbajas tasas de tratamiento, remarcan la necesidad de mecanismos de detección efectivos en la atención habitual, permitiendo una intervencióntemprana. (AU)

Smoking and substance use during pregnancy are major preventablecauses of mortality and morbidity, having a bidirectional and deleterious relationship with the mental health of the mother and child.As part of the WOMAP (Woman Mental Health and Addictions onPregnancy) initiative, our study aimed to describe the prevalence ofco-occurring mental illness and substance use problems, diagnosesand severity of those considered at risk and rates of treatment.A screening of 2,014 pregnant women was done using the AC-OKscale and they were asked about their smoking habits and servicesuse for mental health/substance abuse. Of these, 170 women wereconsidered at risk of co-occurring mental illness and substance useproblems (≥ 2 positive responses to the AC-OK-Mental Health subscale, ≥ 1 positive response to the AC-OK-Substance Abuse subscaleand/or smoking more than once a month and no use of specialized services) and were assessed with a more extensive battery of measures(Patient Health Questionnaire [PHQ-9], General Anxiety Disorder[GAD-7], Posttraumatic stress disorder [PTSD] Checklist for DSM-5[PCL-5], Alcohol Use Disorders Identification Test [AUDIT], DrugAbuse Screening Test [DAST] and Fagerström).In the last year, 614 women (30.5%) smoked tobacco (42.5% daily) and9.8% were positive for both substance use and mental illness per theAC-OK. Only 11.1% of them received specific treatment in the previousthree months while another 13.6% were scheduled to attend services inthe following month. From the subsample assessed in depth, 62(36.5%)endorsed at least moderate depression, 35(20.6%) endorsed at leastmoderate anxiety, 32(18.8%) endorsed PTSD on the PCL, and 37 outof 88 alcohol users scored above the threshold in AUDIT (≥ 3).In conclusion, high prevalence and low treatment rates suggest thateffective detection mechanisms should be integrated into usual care,allowing for early interventions. (AU)

Tartary buckwheat flavonoids relieve the tendency of mammary fibrosis induced by HFD during pregnancy and lactation.

Mammary gland fibrosis is a chronic and irreversible disease. Tartary buckwheat flavonoids (TBF) are a natural product of flavonoid extracts from buckwheat and have a wide range of biological activities. The purpose of this experiment was to explore whether HFD during pregnancy and lactation induces fibrosis of the mammary tissue and whether TBF alleviates the damage caused by HFD, along with its underlying mechanism. The HFD significantly increased the levels of TNF-α, IL-6, IL-1ß, and MPO; significantly damaged the integrity of the blood-milk barrier; significantly increased the levels of collagen 1, vimentin and α-SMA, and reduced the level of E-cadherin. However, these effects were alleviated by TBF. Mechanistic studies showed that TBF inhibited the activation of AKT/NF-κB signaling and predicted the AKT amino acid residues that formed hydrogen bonds with TBF; in addition, these studies not only revealed that TBF promoted the expression of the tight junction proteins (TJs) claudin-3, occludin and ZO-1 and inhibited the activation of TGF-ß/Smad signaling but also predicted the Smad MH2 amino acid residues that formed hydrogen bonds with TBF. Conclusion: HFD consumption during pregnancy and lactation induced the tendency of mammary fibrosis. TBF alleviated the tendency of mammary fibrosis by inhibiting the activation of AKT/NF-κB, repairing the blood-milk barrier and inhibiting the activation of TGF-ß/Smad signaling.

El embarazo y los efectos que produce en la salud de las mujeres VIH positivas / Pregnancy and the effects it produces on the health of HIV positive women

INTRODUCCIÓN: Existen 35 millones de casos de infección por el virus de la inmunodeficiencia humana (VIH) en el mundo, y de ellos, 15 millones corresponden a mujeres en edad fértil. El embarazo en las mujeres seropositivas genera efectos relevantes que afectan la condición psicosocial y física. Los cambios que genera el embarazo en una mujer VIH positiva se relacionan con resultados perinatales adversos, como hemorragia posparto, sepsis puerperal, parto prematuro y mortalidad. OBJETIVO: Conocer los efectos físicos y psicosociales que tiene el embarazo en la evolución de la mujer portadora del VIH. MÉTODO: Revisión narrativa. Se realiza un análisis de contenido de fuentes primarias obtenidas mediante búsqueda en las bases de datos CINAHL, PubMed y SciELO. La búsqueda abarcó un periodo de 10 años, en idioma español e inglés. Para la presente investigación se incluyen 22 artículos, de los que se consideraron las secciones de resultados y conclusiones. RESULTADOS: Se seleccionaron inicialmente 318 artículos y 22 fueron elegibles para su inclusión. En esta revisión se plantean tres dimensiones de análisis psicosocial, fisiopatología y características clínicas, y tratamiento farmacológico. La literatura evidencia un efecto psicológico negativo en la población de estudio, y en cuanto al tratamiento se manifiesta un escaso porcentaje de eventos adversos frente a la terapia antirretroviral, por lo que los beneficios superan los riesgos. CONCLUSIONES: Las tres dimensiones planteadas se relacionan entre sí, definiendo los efectos del embarazo en mujeres VIH positivas y lo que conlleva esta condición en la salud de la madre. Se identificaron diversos problemas que afectan la salud de las mujeres seropositiva que se embarazan. Sin embargo, estas mujeres pueden embarazarse siguiendo un tratamiento óptimo, con atenciones de salud en periodos regulares, evitando así la mayoría de los efectos que pueden afectar su salud.

INTRODUCTION: There are 35 million cases of human immunodeficiency virus (HIV) worldwide, 15 million correspond to women of childbearing age. This pregnancy condition in seropositive women generates relevant effects that affect the psychosocial and physical condition. The changes generated by pregnancy in an HIV positive woman are related to adverse perinatal results such as postpartum hemorrhage, puerperal sepsis, premature delivery and mortality. OBJECTIVE: To know the physical and psychosocial effects that pregnancy has on the evolution of women with HIV. METHOD: Narrative review. Content analysis of primary sources obtained through searches in the CINAHL, PubMed and SciELO databases is performed. The search was carried out within a 10-year range, in Spanish and English. For the present investigation 22 articles are included. The sections for the analysis were results and conclusions. RESULTS: 318 articles were initially selected, 22 articles were eligible for inclusion. In this review, three dimensions of psychosocial analysis, pathophysiology and clinical characteristics, and pharmacological treatment are proposed. The literature shows the negative psychological effect in the study population, in terms of treatment there is a low percentage of adverse events compared to ART, so the benefits outweigh the risks. CONCLUSIONS: The three dimensions raised are related to each other, defining the effects of pregnancy in HIV positive women and what the condition entails on the mothers health. Various problems were identified that affect the health of an HIV-positive woman who becomes pregnant. However, these HIV positive women can become pregnant, following optimal treatment, with regular health care, thus avoiding most of the effects that can affect her health.

Prevención de la transmisión maternoinfantil del virus de la hepatitis B. directrices sobre la profilaxis con antivirales en el embarazo / Prevention of mother-to-child transmission of hepatitis B virus. guidelines on antiviral prophylaxis in pregnancy

Según estimaciones de la Organización Mundial de la Salud (OMS), en el 2015 257 millones de personas en el mundo tenían la infección crónica por el virus de la hepatitis B (VHB) y 900 000 fallecieron a causa de ella, en la mayor parte de los casos de cirrosis o carcinoma hepatocelular. La mayoría de las defunciones asociadas con el VHB en personas adultas obedecen a infecciones contraídas al nacer o en los cinco primeros años de vida. En mayo del 2016, la Asamblea Mundial de la Salud aprobó la Estrategia mundial del sector de la salud contra las hepatitis víricas 2016-2021, en la que se hace un llamado a eliminar las hepatitis virales como amenaza de salud pública ­definida como una reducción de 90% de la incidencia de infecciones y una reducción de 65% de la mortalidad­ para el 2030. La eliminación de la infección por el VHB como amenaza de salud pública conlleva la necesidad de reducir la prevalencia del antígeno de superficie del virus de la hepatitis B (HBsAg) a menos de 0,1% en los niños de 5 años de edad. Esta meta se puede lograr mediante la vacunación de todos los recién nacidos contra la hepatitis B y otras intervenciones orientadas a prevenir la transmisión maternoinfantil del VHB

Available medications used as potential therapeutics for COVID-19: What are the known safety profiles in pregnancy.

BACKGROUND: Medications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source. METHODS: Using the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998-2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations. RESULTS: Of the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11-3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31-1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01-4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41-2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25-4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00-1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51-4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02-2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02-1.19; 747 exposed cases) exposures were associated with MCM. CONCLUSIONS: Many available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.

Maternal and Fetal Pharmacokinetic Analysis of Cannabidiol during Pregnancy in Mice.

Cannabidiol (CBD), a major component of cannabis, has various effects, such as antiemetic and anxiolytic activities, and has recently been marketed as a supplement. The number of people using CBD during pregnancy is increasing, and there are concerns about its effects on the fetus. In addition, the scientific evidence supporting the fetal safety of CBD use during pregnancy is insufficient. To investigate CBD transfer from the mother to the fetus, a single intravenous dose of CBD was administered to pregnant mice in this study, and fetal pharmacokinetics (distribution and elimination) was analyzed. The transfer of CBD from the maternal blood to the fetus was rapid, and the compound accumulated in the fetal brain, liver, and gastrointestinal tract. Conversely, little CBD was transferred from the mother to the amniotic fluid. We analyzed the pharmacokinetics of CBD using a two-compartment model and found that the maternal and fetal half-lives of CBD were approximately 5 and 2 hours, respectively. Furthermore, we performed a moment analysis of the pharmacokinetics of CBD, observing a mean residence time of less than 2 hours in both the mother and fetus. These results suggest that once-daily CBD intake during pregnancy is unlikely to result in CBD accumulation in the mother or fetus. SIGNIFICANCE STATEMENT: CBD is currently marketed as a supplement, and despite its increasing use during pregnancy, little information concerning its fetal effects has been reported. In the present study, CBD was administered to pregnant mice, and the pharmacokinetics in the fetus was investigated using a two-compartment model and moment analysis. The results of these analyses provide important information for estimating the risk to the fetus if CBD is mistakenly consumed during pregnancy.

Synergistic action of estradiol and PGE2 on endometrial transcriptome in vivo resembles pregnancy effects better than estradiol alone†.

Successful pregnancy establishment in mammals depends on numerous interactions between embryos and the maternal organism. Estradiol-17ß (E2) is the primary embryonic signal in the pig, and its importance has been questioned recently. However, E2 is not the only molecule of embryonic origin. In pigs, prostaglandin E2 (PGE2) is abundantly synthesized and secreted by conceptuses and endometrium. The present study aimed to determine the role of PGE2 and its simultaneous action with E2 in changes in porcine endometrial transcriptome during pregnancy establishment. The effects of PGE2 and PGE2 acting with E2 were studied using an in vivo model of intrauterine hormone infusions, and were compared to the effects of E2 alone and conceptuses' presence on day 12 of pregnancy. The endometrial transcriptome was profiled using gene expression microarrays followed by statistical analyses. Downstream analyses were performed using bioinformatics tools. Differential expression of selected genes was verified by quantitative polymerase chain reaction. Microarray analysis revealed 2413 differentially expressed genes (DEGs) in the endometrium treated simultaneously with PGE2 and E2 (P < 0.01). No significant effect of PGE2 administered alone on endometrial transcriptome was detected. Gene ontology annotations enriched for DEGs were related to multiple processes such as: focal adhesion, vascularization, cell migration and proliferation, glucose metabolism, tissue remodeling, and activation of immune response. Simultaneous administration of E2 and PGE2 induced more changes within endometrial transcriptome characteristic to pregnancy than infusion of E2 alone. The present findings suggest that synergistic action of estradiol-17ß and PGE2 resembles the effects of pregnancy on endometrial transcriptome better than E2 alone.

The Influence of the Food and Drug Administration Pregnancy and Lactation Labeling Rule on Drug Information Resources.

BACKGROUND: Drug information resources are commonly used by health-care providers answering pregnancy-related medication questions. In 2015, the United States Food and Drug Administration approved a new pregnancy and lactation medication labeling content and format, removing the pregnancy category, and using a narrative. Despite labeling requirements changing, it is unknown if drug information resources updated monographs to reflect these changes. OBJECTIVE: The primary objective was to evaluate if commonly used drug information resources provide pregnancy information listed similar to the requirements of the Pregnancy and Lactation Labeling Rule (PLLR). Secondary analyses included evaluating the references and inclusion of the pregnancy category rating. METHODS: Pregnancy recommendations for 23 medications were evaluated in 9 drug information resources (Clinical Pharmacology, Drugs in Pregnancy and Lactation, Epocrates®, First Databank, LexiComp® Online, LexiComp® Online Pregnancy & Lactation, In-Depth, Medi-Span®, Micromedex®, and Multum®). The number of references per drug monograph and most recent reference publication year was obtained. RESULTS: LexiComp® Online Pregnancy & Lactation, In-Depth mimics the new PLLR structure and consistently had the highest number of and most recent references when the medication was included. Drugs in Pregnancy and Lactation was the next most similar in content with the PLLR and second in most references per monograph; however, the most recent reference was the textbook publication year. CONCLUSION AND RELEVANCE: LexiComp® Online Pregnancy & Lactation, In-Depth and Drugs in Pregnancy and Lactation provided pregnancy information in a format most similar to the PLLR. However, several drug information resources contained pregnancy categories ratings that were to be removed from medication labeling per the PLLR.

The overview of current evidence on the reproductive toxicity of dibutyl phthalate.

Over the past years, many legitimate concerns have been raised about the effects of dibutyl phthalate (DBP) as an endocrine disruptor, especially on reproduction. The aim of this publication is to critically review the literature related to the developmental and reproductive toxicity of DBP in animals. Several electronic databases were systematically searched until 2019. Studies were qualified for the review if they: linked exposure to DPB with reproduction, were published in English after 1990, and were conducted on animals. In the studies of the testicular effects of DBP on experimental animals, the most common effects of exposure included reduced fertility, atrophic changes in male gonads, degenerative changes in the epididymis, as well as a reduction in sperm count and motility, cryptorchidism, hypospadias, poor sperm quality and other genital defects (decreased testicular weight, delayed spermatogenesis, Leydig cell aggregation, impaired Sertoli cell maturation, and significant inhibitions of testicular enzymes). The embryotoxic effects of DBP on laboratory animals included mainly an increase in fetal resorption and a decrease in live births. The teratogenic effects of DBP also manifest as skeletal malformations in fetuses, malformations of male gonads and other genital effects. On the basis of the literature data, it is clearly demonstrated that DBP shows anti-androgenic effects; however, there are also reports confirming its weak estrogenic effect. Additionally, lower doses cause more adverse effects than the highest dose, which is an important fact because of the widespread environmental exposure to DBP. The studies clearly confirm that DBP is an endocrine disruptor. Int J Occup Med Environ Health. 2021;34(1):15-37.

Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring.

Folate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.

Iodine contrast prior to or during pregnancy and neonatal thyroid function: a systematic review.

OBJECTIVE: Thyroid dysfunction is a known side effect of iodinated contrast media. There is some evidence to suggest that iodinated contrast media administered to pregnant women may cause thyroid dysfunction not only in themselves but also in their offspring. Here, we systematically evaluated literature on the use of iodinated contrast media prior to or during pregnancy on the offspring's thyroid function. DESIGN: Systematic review of published literature. MATERIALS AND METHODS: Relevant studies were identified by PubMed, EMBASE and The Cochrane Library up to June 5, 2020. All study designs, reporting on the foetal or neonatal thyroid function after exposure to iodinated contrast media prior to or during pregnancy, were included. We undertook random effects meta-analysis and pooled the estimates as proportions with 95% CIs. RESULTS: We identified 402 articles, of which 26 were included. Six studies reported (n = 369) on exposure to iodinated contrast media prior to pregnancy by hysterosalpingography and 20 studies (n = 670) on exposure to these media during pregnancy by amniofetography, urography or CT. There was low to high risk of bias. The proportion of (transient) neonatal thyroid dysfunction was 0.0% (95% CI: 0.0-2.9% based on 3 studies) for hysterosalpingography, 2.25% (95% CI: 0.03-6.55% based on 2 studies) for amniofetography and 0.0% (95% CI: 0.0-0.02% based on 5 studies) for CT. There was a tendency towards an increased risk of thyroid dysfunction with higher amounts of contrast used. CONCLUSIONS: Exposure to iodinated contrast media prior to or during pregnancy may increase the risk of thyroid dysfunction in offspring. We recommend keeping the amount of contrast used as low as possible.