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1.
Yakugaku Zasshi ; 140(10): 1199-1206, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999198

RESUMO

Potential risks to the fetus or infant should be considered prior to medication during pregnancy and lactation. It is essential to evaluate the exposure levels of drugs and their related factors in addition to toxicological effects. Epilepsy is one of the most common neurological complications in pregnancy; some women continue to use antiepileptic drugs (AEDs) to control seizures. Benzodiazepines (BZDs) are widely prescribed for several women who experience symptoms such as anxiety and insomnia during the postpartum period. In this review, we describe the 1) transport mechanisms of AEDs across the placenta and the effects of these drugs on placental transporters, and 2) the transfer of BZDs into breast milk. Our findings indicated that carrier systems were involved in the uptake of gabapentin (GBP) and lamotrigine (LTG) in placental trophoblast cell lines. SLC7A5 was the main contributor to GBP transport in placental cells. LTG was transported by a carrier that was sensitive to chloroquine, imipramine, quinidine, and verapamil. Short-term exposure to 16 AEDs had no effect on folic acid uptake in placental cells. However, long-term exposure to valproic acid (VPA) affected the expression of folate carriers (FOLR1, SLC46A1). Furthermore, VPA administration changed the expression levels of various transporters in rat placenta, suggesting that sensitivity to VPA differed across gestational stages. Lastly, we developed a method for quantifying eight BZDs in human breast milk and plasma using LC/MS/MS, and successfully applied it to quantify alprazolam in breast milk and plasma donated by a lactating woman.


Assuntos
Anticonvulsivantes/metabolismo , Benzodiazepinas/metabolismo , Transporte Biológico/genética , Aleitamento Materno , Gabapentina/metabolismo , Lactação/metabolismo , Lamotrigina/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/fisiologia , Troca Materno-Fetal , Leite Humano/metabolismo , Placenta/metabolismo , Ácido Valproico/metabolismo , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Linhagem Celular , Epilepsia/tratamento farmacológico , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Gabapentina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Humanos , Lamotrigina/efeitos adversos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Transportador de Folato Acoplado a Próton/genética , Transportador de Folato Acoplado a Próton/metabolismo , Ácido Valproico/efeitos adversos
2.
Mult Scler ; 26(10): 1137-1146, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32924838

RESUMO

Concerns regarding infection with the novel coronavirus SARS-CoV-2 leading to COVID-19 are particularly marked for pregnant women with autoimmune diseases such as multiple sclerosis (MS). There is currently a relative paucity of information to guide advice given to and the clinical management of these individuals. Much of the limited available data around COVID-19 and pregnancy derives from the obstetric literature, and as such, neurologists may not be familiar with the general principles underlying current advice. In this article, we discuss the impact of potential infection on the pregnant woman, the impact on her baby, the impact of the current pandemic on antenatal care, and the interaction between COVID-19, MS and pregnancy. This review provides a framework for neurologists to use to guide the individualised advice given to both pregnant women with MS, and those women with MS who are considering pregnancy. This includes evidence derived from previous novel coronavirus infections, and emerging evidence from the current pandemic.


Assuntos
Infecções por Coronavirus/imunologia , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Pneumonia Viral/imunologia , Complicações Infecciosas na Gravidez/imunologia , Complicações na Gravidez/tratamento farmacológico , Betacoronavirus , Aleitamento Materno , Assistência à Saúde , Parto Obstétrico , Suscetibilidade a Doenças , Feminino , Retardo do Crescimento Fetal , Humanos , Esclerose Múltipla/imunologia , Pandemias , Cuidado Pré-Concepcional , Gravidez , Complicações na Gravidez/imunologia , Nascimento Prematuro , Cuidado Pré-Natal , Recidiva
3.
Cochrane Database Syst Rev ; 9: CD009402, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32956536

RESUMO

BACKGROUND: Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, such cramps have no obvious underlying pathology, and so are termed idiopathic. Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this purpose remains unclear. This is an update of a Cochrane Review first published in 2012, and performed to identify and incorporate more recent studies. OBJECTIVES: To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps.   SEARCH METHODS: On 9 September 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED, and SPORTDiscus. We also searched WHO-ICTRP and ClinicalTrials.gov for registered trials that might be ongoing or unpublished, and ISI Web of Science for studies citing the studies included in this review. SELECTION CRITERIA: Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. We collected all data on adverse effects from the included RCTs. MAIN RESULTS: We identified 11 trials (nine parallel-group, two cross-over) enrolling a total of 735 individuals, amongst whom 118 cross-over participants additionally served as their own controls. Five trials enrolled women with pregnancy-associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). Another study enrolled 29 people with liver cirrhosis, only some of whom suffered muscle cramps. All trials provided magnesium as an oral supplement, except for one trial which provided magnesium as a series of slow intravenous infusions. Nine trials compared magnesium to placebo, one trial compared magnesium to no treatment, calcium carbonate or vitamin B, and another trial compared magnesium to vitamin E or calcium. We judged the single trial in people with liver cirrhosis and all five trials in participants with pregnancy-associated leg cramps to be at high risk of bias. In contrast, we rated the risk of bias high in only one of five trials in participants with idiopathic rest cramps. For idiopathic cramps, largely in older adults (mean age 61.6 to 69.3 years) presumed to have nocturnal leg cramps (the commonest presentation), differences in measures of cramp frequency when comparing magnesium to placebo were small, not statistically significant, and showed minimal heterogeneity (I² = 0% to 12%). This includes the primary endpoint, percentage change from baseline in the number of cramps per week at four weeks (mean difference (MD) -9.59%, 95% confidence interval (CI) -23.14% to 3.97%; 3 studies, 177 participants; moderate-certainty evidence); and the difference in the number of cramps per week at four weeks (MD -0.18 cramps/week, 95% CI -0.84 to 0.49; 5 studies, 307 participants; moderate-certainty evidence). The percentage of individuals experiencing a 25% or better reduction in cramp rate from baseline was also no different (RR 1.04, 95% CI 0.84 to 1.29; 3 studies, 177 participants; high-certainty evidence). Similarly, no statistically significant difference was found at four weeks in measures of cramp intensity or cramp duration. This includes the number of participants rating their cramps as moderate or severe at four weeks (RR 1.33, 95% CI 0.81 to 2.21; 2 studies, 91 participants; moderate-certainty evidence); and the percentage of participants with the majority of cramp durations of one minute or more at four weeks (RR 1.83, 95% CI 0.74 to 4.53, 1 study, 46 participants; low-certainty evidence). We were unable to perform meta-analysis for trials of pregnancy-associated leg cramps. The single study comparing magnesium to no treatment failed to find statistically significant benefit on a three-point ordinal scale of overall treatment efficacy. Of the three trials comparing magnesium to placebo, one found no benefit on frequency or intensity measures, another found benefit for both, and a third reported inconsistent results for frequency that could not be reconciled. The single study in people with liver cirrhosis was small and had limited reporting of cramps, but found no difference in terms of cramp frequency or cramp intensity. Our analysis of adverse events pooled all studies, regardless of the setting in which cramps occurred. Major adverse events (occurring in 2 out of 72 magnesium recipients and 3 out of 68 placebo recipients), and withdrawals due to adverse events, were not significantly different from placebo. However, in the four studies for which it could be determined, more participants experienced minor adverse events in the magnesium group than in the placebo group (RR 1.51, 95% CI 0.98 to 2.33; 4 studies, 254 participants; low-certainty evidence). Overall, oral magnesium was associated with mostly gastrointestinal adverse events (e.g. diarrhoea), experienced by 11% (10% in control) to 37% (14% in control) of participants. AUTHORS' CONCLUSIONS: It is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults experiencing skeletal muscle cramps. In contrast, for those experiencing pregnancy-associated rest cramps the literature is conflicting and further research in this population is needed. We found no RCTs evaluating magnesium for exercise-associated muscle cramps or disease-state-associated muscle cramps (for example amyotrophic lateral sclerosis/motor neuron disease) other than a single small (inconclusive) study in people with liver cirrhosis, only some of whom suffered cramps.


Assuntos
Magnésio/uso terapêutico , Cãibra Muscular/tratamento farmacológico , Músculo Esquelético , Complicações na Gravidez/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Estudos Cross-Over , Feminino , Humanos , Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cãibra Muscular/etiologia , Placebos/uso terapêutico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Medicine (Baltimore) ; 99(28): e21212, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664171

RESUMO

RATIONALE: Teriflunomide is a disease-modifying drug that has been approved for treatment of relapsing-remitting multiple sclerosis. Due to its teratogenic effect in animals, however, it is not recommended during pregnancy. For this reason, effective contraception must be used during its administration. When an unscheduled pregnancy occurs during therapy, patients must undergo a cholestyramine procedure for rapid flushing of the drug. PATIENT CONCERNS: We describe the case of a 35-year-old female patient suffering diagnosed with relapsing-remitting multiple sclerosis at the age of 20. The patient as a result of side effects of previous therapies started taking teriflunomide. DIAGNOSIS: Despite recommendations for the use of contraceptives, the patient became pregnant during drug therapy. Pregnancy occurred 12 months after initiating teriflunomide treatment. INTERVENTIONS: Therapy with teriflunomide was immediately suspended and cholestyramine was prescribed (8 g 3 times a day, for 11 days) to flush out any residual drug from the body. OUTCOMES: Despite an 8-week exposure to teriflumomide during gestation, the patient gave birth to healthy twin girls at 35 week. Controls carried out after birth did not reveal any malformation or genetic and chromosomal abnormality. At a 5-month pediatric specialist check both babies were healthy and growing regularly. CONCLUSION: This shows that even if there is evidence of teratogenic effects in animals, an 8-week exposure to teraflunomide >0.02 mg/L did not have effects on the newborn.


Assuntos
Resina de Colestiramina/uso terapêutico , Crotonatos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Gravidez de Gêmeos/efeitos dos fármacos , Toluidinas/uso terapêutico , Adulto , Feminino , Humanos , Recém-Nascido , Nascimento Vivo , Gravidez
5.
Nat Commun ; 11(1): 3593, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681096

RESUMO

During pregnancy, maternal endocrine signals drive fetal development and program the offspring's physiology. A disruption of maternal glucocorticoid (GC) homeostasis increases the child's risk of developing psychiatric disorders later in life. We here show in mice, that the time of day of antenatal GC exposure predicts the behavioral phenotype of the adult offspring. Offspring of mothers receiving GCs out-of-phase compared to their endogenous circadian GC rhythm show elevated anxiety, impaired stress coping, and dysfunctional stress-axis regulation. The fetal circadian clock determines the vulnerability of the stress axis to GC treatment by controlling GC receptor (GR) availability in the hypothalamus. Similarly, a retrospective observational study indicates poorer stress compensatory capacity in 5-year old preterm infants whose mothers received antenatal GCs towards the evening. Our findings offer insights into the circadian physiology of feto-maternal crosstalk and assign a role to the fetal clock as a temporal gatekeeper of GC sensitivity.


Assuntos
Relógios Circadianos/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Exposição Materna/efeitos adversos , Transtornos Mentais/etiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ansiedade , Comportamento/efeitos dos fármacos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido Prematuro/psicologia , Masculino , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Cuidado Pré-Natal , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
7.
J Reprod Immunol ; 141: 103168, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32603991

RESUMO

COVID-19 pandemic is affecting various areas of health care, including human reproduction. Many women with reproductive failures, during the peri-implantation period and pregnancy, are on the immunotherapy using immune modulators and immunosuppressant due to underlying autoimmune diseases, cellular immune dysfunction, and rheumatic conditions. Many questions have been raised for women with immunotherapy during the COVID-19 pandemic, including infection susceptibility, how to manage women with an increased risk of and active COVID-19 infection. SARS-CoV-2 is a novel virus, and not enough information exists. Yet, we aim to review the data from previous coronavirus outbreaks and current COVID-19 and provide interim guidelines for immunotherapy in women with reproductive failures.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Imunoterapia/métodos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Complicações na Gravidez/tratamento farmacológico , Feminino , Humanos , Pandemias , Gravidez , Saúde Reprodutiva
8.
PLoS One ; 15(7): e0236060, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649710

RESUMO

BACKGROUND: There are concerns about the quality of medicines available in low- and middle-income countries (LMIC) to manage hemorrhage, pre-eclampsia/eclampsia and sepsis. We aimed to identify, critically appraise, and synthesize the findings of studies on the quality of these three types of medicines available in LMIC. METHODS: This systematic review searched Medline, EMBASE and LILACS (from inception to 25 May 2020) for studies on the quality of selected medicines available in LMIC that provided at least the amount of active pharmaceutical ingredient. We contacted study authors for additional information. We excluded simulation studies. We used the MEDQUARG tool to assess study quality. The main outcome was the prevalence of failed samples. FINDINGS: We identified 9699 unique citations and included 34 studies (3159 samples from 40 countries) in the review. Most studies (65%) had low quality (scores <6/12). Overall, 48.9% of 1890 uterotonic samples (19 studies) failed quality tests; failures rates were 75% for ergometrine and nearly 40% each for oxytocin and misoprostol. The overall prevalence of failed injectable antibiotics (1090 samples, 18 studies) was 13.4%, ranging from 2.9% for injectable metronidazole (34 samples, 3 studies) to 16.0% for cefazolin (449 samples, 2 studies). The prevalence of low quality magnesium sulphate (179 samples, 2 studies) was 3.4%. We did not find any studies on the quality of carbetocin, tranexamic acid, or clindamycin. CONCLUSIONS: There is a widespread problem with the quality of medicines used to manage life-threatening maternal conditions in LMIC. This can be a contributing factor to high maternal mortality rates in these regions.


Assuntos
Países em Desenvolvimento/estatística & dados numéricos , Complicações na Gravidez/tratamento farmacológico , Qualidade da Assistência à Saúde , Feminino , Humanos , Gravidez
9.
Arch Womens Ment Health ; 23(5): 709-717, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32632522

RESUMO

Antidepressant treatment when facing a pregnancy is an important issue for many women and their physicians. We hypothesized that women with a greater burden of pre-pregnancy psychiatric illness would be more likely to re-initiate antidepressants following discontinuation of treatment during pregnancy. A register-based cohort study was carried out including 38,595 women who gave birth between the 1st of January 2007 and the 31st of December 2014, who had filled a prescription for an antidepressant medication in the year prior to conception. Logistic regressions were used to explore associations between maternal characteristics and antidepressant treatment discontinuation or re-initiation during pregnancy. Most women discontinued antidepressant treatment during pregnancy (n = 29,095, 75.4%), of whom nearly 12% (n = 3434, 11.8%) re-initiated treatment during pregnancy. In adjusted analyses, parous women (aOR 1.22, 95% CI 1.12-1.33), with high educational level (aOR 1.21, 95% CI 1.08-1.36); born within the EU (excluding Nordic countries, aOR 1.41, 95% CI 1.03-1.92) or a Nordic country (aOR 1.42, 95% CI 1.22-1.65); who more often reported prior hospitalizations due to psychiatric disorders (aOR 1.50, 95% CI 1.10-2.03, for three or more episodes); and had longer duration of pre-pregnancy antidepressant use (aOR 6.10, 95% CI 5.48-6.77, for >2 years antidepressant use), were more likely to re-initiate antidepressants than were women who remained off treatment. Women with a greater burden of pre-pregnancy psychiatric illness were more likely to re-initiate antidepressants. Thus, pre-pregnancy psychiatric history may be particularly important for weighing the risks and benefits of discontinuing antidepressants during pregnancy.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Complicações na Gravidez/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Gravidez , Sistema de Registros , Suécia , Adulto Jovem
10.
Arch Endocrinol Metab ; 64(3): 290-297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555996

RESUMO

OBJECTIVE: To evaluate the use of metformin for preventing cesarean deliveries and large-for-gestational-age (LGA) newborn (NB) outcomes in non-diabetic obese pregnant women. SUBJECTS AND METHODS: This is a randomized clinical trial with obese pregnant women, divided into 2 groups: metformin group and control group, with followed-up prenatal routine. The gestational age of participants was less than or equal to 20 weeks and were monitored throughout entire prenatal period. For outcomes of delivery and LGA newborns, absolute risk reduction (ARR) and the number needed to treat (NNT) were calculated with a 95% confidence interval (CI). RESULTS: 357 pregnant women were evaluated. From the metformin group (n = 171), 68 (39.8%) subjects underwent cesarean delivery, and 117 (62.9%) subjects from the control group (n = 186) had intercurrence (p < 0.01). As for the mothers' general characteristics, there was significance for marital status (p < 0.01). Maternal-fetal results presented reduced preeclampsia (p < 0,01). Primary prophylactic results presented an ARR of 23.1 times (95% CI: 13.0-33.4) with NNT of 4 (95% CI: 3.0-7.7) and no significant values for LGA NB (p > 0.01). Secondary prophylactic outcomes presented decreased odds ratio for preeclampsia (OR = 0.17, 95% CI: 0.10-0.41). CONCLUSION: The use of metformin reduced cesarean section rates, resulted in a small number of patients to be treated, but it did not reduce LGA NB. Administering a lower dosage of metformin from the early stages to the end of treatment may yield significant results with fewer side effects. Arch Endocrinol Metab. 2020;64(3):290-7.


Assuntos
Cesárea/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Obesidade/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Fatores Socioeconômicos
11.
PLoS One ; 15(6): e0232493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511256

RESUMO

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF`FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/terapia , Peptídeos/farmacologia , Complicações na Gravidez/tratamento farmacológico , Nascimento Prematuro/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/imunologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Complicações na Gravidez/imunologia , Nascimento Prematuro/imunologia
12.
J Clin Psychiatry ; 81(4)2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32558401

RESUMO

OBJECTIVE: The aim of this systematic review and meta-analysis was to determine the effect of antidepressant discontinuation on the risk of relapse of depression during pregnancy. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and PsycInfo were searched from the inception of each database through March 2019 using keywords such as antidepressants, pregnancy, preconception, discontinuation, stop, recurrence, reintroduction, and relapse. STUDY SELECTION: Original studies that involved pregnant women who discontinued antidepressants during preconception (ie, 3 months prior to pregnancy) or pregnancy and examined the relapse of depression during pregnancy (ie, the reemergence of depression or reintroduction of medication) and published in English were included. A total of 2,172 records were identified, and the full texts of 37 articles were reviewed. Eight studies met the inclusion criteria, 6 of which fulfilled the quality criteria, with 4 studies providing data for the meta-analysis. DATA EXTRACTION: Data were extracted using a data extraction form developed for the purpose of this study. The Cochrane Collaboration Review Manager software version 5.3 was used to conduct the meta-analysis. RESULTS: Pooled data did not show higher risk of relapse of depression during pregnancy for women who discontinued antidepressants than for those who continued antidepressants (risk ratio [RR] = 1.74; 95% CI, 0.97 to 3.10; P = .06). In the subanalysis based on the severity and recurrence of depression in the study populations, the risk of relapse was significantly higher for populations suggestive of severe or recurrent depression (RR = 2.30; 95% CI, 1.58 to 3.35) but not for populations suggestive of mild or moderate depression severity (RR = 1.59; 95% CI, 0.83 to 3.04). CONCLUSIONS: Women with severe or recurrent depression should be informed about the increased risk of relapse following antidepressant discontinuation, and those who discontinue antidepressants should be monitored for relapse.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Suspensão de Tratamento , Antidepressivos/uso terapêutico , Feminino , Humanos , Gravidez , Recidiva
13.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32513841

RESUMO

OBJECTIVES: To estimate the risk of neonatal outcomes from patterns of prenatal antidepressant use. METHODS: From the OptumLabs Data Warehouse, 226 932 singleton deliveries were identified. Antidepressant claims with coverage between the last menstrual period and 35 weeks' gestation were converted to fluoxetine equivalents, and a longitudinal cluster analysis was performed. Outcomes included major cardiac malformations (11.7 of 1000 births), preterm birth (75.7 of 1000 births), and newborn respiratory distress (54.2 of 1000 births). The lowest trajectory was the primary reference group, and depression and anxiety with no antidepressant claims served as secondary reference groups. RESULTS: From 15 041 (6.6%) pregnancies exposed to an antidepressant, use patterns were best described as (1) low use (∼10 mg/day) with first-trimester reduction, (2) low sustained use (∼20 mg/day), (3) moderate use (∼40 mg/day) with first-trimester reduction, (4) moderate sustained use (∼40 mg/day), and (5) high sustained use (∼75 mg/day). Moderate sustained use increased the risk of major cardiac malformations, although results included the null when compared with depression or anxiety reference groups. Moderate sustained (adjusted risk ratio [RR] 1.31; 95% confidence interval [CI] 1.16-1.49) and high sustained (adjusted RR 1.78; 95% CI 1.48-2.14) trajectories were associated with an increased risk of preterm birth. All 4 trajectories increased the risk of neonatal respiratory distress in a dose-response fashion (adjusted RRs 1.36 [95% CI 1.20-1.50] to 2.23 [95% CI 1.83-2.77]). CONCLUSIONS: Although findings support continuation of the lowest effective dose to treat depression or anxiety, which benefits the mother, they also highlight an increased risk for newborn respiratory distress in all groups and preterm birth at moderate to high sustained doses.


Assuntos
Antidepressivos/efeitos adversos , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Doenças do Recém-Nascido/induzido quimicamente , Doenças do Recém-Nascido/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Adulto , Antidepressivos/uso terapêutico , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
14.
Expert Opin Pharmacother ; 21(13): 1591-1602, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32521172

RESUMO

INTRODUCTION: Multiple sclerosis (MS) is a chronically progressive disease of the central nervous system. The relapsing form of the disease predominantly affects women with onset between the ages 20 to 40 years. Therefore, timing, choice, and treatment options should take pregnancy planning into consideration to accommodate both the needs and safety of the mother and health of the fetus. AREAS COVERED: In this review, the authors discuss and summarize the recent evidence of different pharmacotherapeutic possibilities in the treatment of women with MS. EXPERT OPINION: There is evidence that disease modifying therapy reduces the risk of relapses and diminishes disability progression in people with relapsing MS. The disease is often diagnosed in the childbearing years, and thus pregnancy planning can possibly be a part of the pharmacotherapeutic considerations. The management of women planning pregnancy requires a balancing of risks. The clinician must consider the risks related to treatment discontinuation versus the risk of exposing the developing fetus to drugs that are potential fetotoxic. Randomized controlled trials of medication safety - if used during pregnancy, are prohibited for ethical reasons; hence, the evidence is continuously gathered from observational data, post-authorization studies and pregnancy registries.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Progressão da Doença , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Esclerose Múltipla Recidivante-Remitente/imunologia , Gravidez , Complicações na Gravidez/imunologia , Resultado da Gravidez , Resultado do Tratamento , Adulto Jovem
15.
Rev. iberoam. fertil. reprod. hum ; 37(2): 3-11, abr.-jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193739

RESUMO

El uso de probióticos es un área de investigación traslacional en continuo progreso debido al creciente interés de los clínicos del área de fertilidad y sus pacientes. Por lo que el objetivo principal de este trabajo es recabar y resumir la información de la literatura científica relevante sobre los probióticos y su posible papel modulador efectivo en alteraciones relacionadas con la fertilidad y reproductivas. Para ello se describen los aspectos de interés relativos a: 1. La microbiota humana y sitios naturales de colonización relacionados con la salud reproductiva: microbiota vaginal, microbiota endometrial, microbiota y embarazo. 2. A continuación, hemos resaltado las disbiosis de los sitios de colonización y las repercusiones en fertilidad del estado de salud/enfermedad y por último 3. La hipótesis sobre los tratamientos efectivos con probióticos orales vs vaginales y sus vías fisiológicas de transferencia y actuación; que lleva asociado la descripción del concepto de translocación efectiva o llegada de los probióticos alsitio natural de colonización tras su administración como suplementos. La mayoría de probióticos utilizados en disbiosis relacionadas con la fertilidad pertenecen al género Lactobacillus. Se suelen administrar principalmente por vía oral a una concentración del orden de 1x109UFC/día y una duración de4-12 semanas, siendo diferencial en función de la disbiosis a tratar


The use of probiotics is an area of translational research in continuous progress due to the growing interest of fertility clinicians and their patients. Therefore, the main objective of this work is to collect and summarise relevant information from the available scientific literature on probiotics and their effective modulating role in fertility-related and reproductive disorders. To approach this objective, we have summarised the knowledge regarding the following pertinent aspects: 1. The human microbiota: intestinal microbiota already well studied, and other natural colonization sites related to reproductive health: vaginal microbiota, endometrial microbiota, pregnancy microbiota. 2. Next, we have highlighted the dysbiosis of the colonization sites and the repercussions on the state of health / disease and finally 3. The hypothesis that exists about effective treatments with oral probiotics and their physiological transfer and performance pathways and the associated concept of translocation or arrival at the natural site of colonization. Most probiotics used in fertility-related dysbiosis be-long to the genus Lactobacillus. They are mainly administered via oral at average concentrations of 1x109CFU/day during 4-12 weeks, being differential depending on the dysbiosis to be treated


Assuntos
Humanos , Feminino , Probióticos/administração & dosagem , Disbiose/tratamento farmacológico , Microbiota/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Endometriose/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico
16.
Int J Infect Dis ; 98: 138-143, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32592906

RESUMO

BACKGROUND: Few studies have focused on the treatment of tuberculosis (TB) during pregnancy. This study aimed to evaluate the risk of adverse events, particularly liver toxicity, in pregnant women during treatment for active TB. METHODS: We conducted a retrospective study on pregnant and age-matched non-pregnant women receiving treatment for active TB at four hospitals in Western Sweden between 1992 and 2017. RESULTS: A total of 135 women were included, 40 pregnant and 95 non-pregnant. The frequency of severe hepatotoxicity was 40% in pregnant women and 6% among non-pregnant women (p < 0.001) (odds ratio 9.9; 95% confidence interval 3.5-28.0). Temporary drug withdrawal due to elevated transaminase levels was more frequent for pregnant than non-pregnant women (40% vs 9.5%; p < 0.001) (odds ratio 6.4; 95% confidence interval 2.5-16.2). There was one fatal case of hepatotoxicity in a pregnant woman. CONCLUSION: Severe hepatotoxicity was significantly more frequent in pregnant women compared to non-pregnant women. Careful monitoring of liver transaminases while receiving TB treatment during pregnancy is mandatory, as well as ensuring adequate measures with adjustment of drug regimen and temporary drug withdrawals when a rise in liver enzymes is noted.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Complicações na Gravidez/tratamento farmacológico , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Feminino , Humanos , Testes de Função Hepática , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Suécia/epidemiologia , Suspensão de Tratamento , Adulto Jovem
17.
Am J Physiol Gastrointest Liver Physiol ; 319(2): G197-G211, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32597707

RESUMO

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment, and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 wk before mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. Because high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.NEW & NOTEWORTHY We used a mouse model of gestational hypercholanemia to investigate the use of obeticholic acid (OCA), a potent FXR agonist, as a treatment for the hypercholanemia of intrahepatic cholestasis of pregnancy (ICP). The results demonstrate that OCA can improve the fetal bile acid profile. This is relevant not only to women with ICP but also for women who become pregnant while receiving OCA treatment for other conditions such as primary biliary cholangitis and nonalcoholic steatohepatitis.


Assuntos
Ácidos e Sais Biliares/sangue , Ácido Quenodesoxicólico/análogos & derivados , Colestase Intra-Hepática/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Animais , Ácidos e Sais Biliares/metabolismo , Ceco , Ácido Quenodesoxicólico/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Dislipidemias/tratamento farmacológico , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , RNA Ribossômico 16S , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
18.
Arch Osteoporos ; 15(1): 94, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32583122

RESUMO

INTRODUCTION: The pregnancy and lactation-associated osteoporosis (PLO) is a rare disease whose precise pathophysiological mechanisms remain mostly unknown. CASE REPORT: We reported here a case of PLO that occurred in the early postpartum period and led to multiple compression fractures. Combination therapy with alendronate, calcium carbonate, and vitamin D was used to treat the patient and a marked but gradual increase in the density of bone mineral was observed. Moreover, no further fractures have occurred. CONCLUSION: PLO is a very rare type of osteoporosis associated with severe chronic back pain. Increased bone resorption significantly increases the risk of bone fractures in women with PLO. Early diagnosis, stopping breastfeeding, treatment of calcium and vitamin D, bisphosphonates, or other antiosteoporosis medicine and regular follow-ups of these cases are particularly important in the prevention of fractures and to increase the quality of life of patients.


Assuntos
Lactação , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Alendronato/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Carbonato de Cálcio/uso terapêutico , Quimioterapia Combinada , Feminino , Fraturas por Compressão/etiologia , Humanos , Osteoporose/etiologia , Gravidez , Qualidade de Vida , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico
20.
Am J Psychiatry ; 177(6): 506-517, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375539

RESUMO

OBJECTIVE: Observational studies of prenatal antidepressant safety are hindered by methodological concerns, including susceptibility to surveillance bias. Some studies address potential bias by using alternative strategies to operationalize study comparison groups. In a meta-analysis of the association between prenatal antidepressant exposure and autism risk, the authors examined the utility of comparison group operationalization in reducing surveillance bias. METHODS: A systematic search of multiple databases through August 2017 was conducted, selecting controlled observational studies of the association of prenatal antidepressant exposure with autism. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis produced summary effect measures with 95% confidence intervals stratified by comparator group composition, antidepressant class, and trimester of exposure. RESULTS: Fourteen studies were included, with 13 reporting results using a population-based comparison group, five using a psychiatric control group, and four using a discordant-sibling control group. Eight of the 14 studies were rated poor because of inadequate control for prenatal depression and maternal ethnicity. Autism risk estimates after prenatal exposure to any antidepressant were decidedly different for population-based designs (hazard ratio=1.42, 95% CI=1.18, 1.70; odds ratio=1.58, 95% CI=1.25, 1.99) compared with psychiatric control (hazard ratio=1.14, 95% CI=0.84, 1.53; odds ratio=1.24, 95% CI=0.93, 1.66) and discordant-sibling (hazard ratio=0.97, 95% CI=0.68, 1.37; odds ratio=0.85, 95% CI=0.54, 1.35) designs. Findings for prenatal exposure to selective serotonin reuptake inhibitors were similar. Meta-regression of population-based studies demonstrated that despite statistical adjustment, ethnicity differences remained a significant source of study heterogeneity. CONCLUSIONS: In this meta-analysis, neither psychiatric control nor discordant-sibling designs supported an association between prenatal antidepressant exposure and autism. Discordant-sibling designs effectively addressed surveillance bias in pharmacovigilance reports derived from national registries and other large databases.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Autístico/epidemiologia , Grupos Controle , Transtorno Depressivo/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Feminino , Humanos , Farmacovigilância , Gravidez , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Fatores de Risco , Irmãos
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