Leflunomide use during pregnancy and the risk of adverse pregnancy outcomes

2017 ◽  
Vol 77 (4) ◽  
pp. 500-509 ◽  
Author(s):  
Anick Bérard ◽  
Jin-Ping Zhao ◽  
Irene Shui ◽  
Susan Colilla
Keyword(s):  
Spontaneous Abortion ◽  
First Trimester ◽  
Spontaneous Abortions ◽  
Third Trimester ◽  
Increased Risk ◽  
First Trimester Of Pregnancy ◽  
Exposure During Pregnancy ◽  
Trimester Exposure ◽  
Adverse Pregnancy ◽  
Generalised Estimating Equations

ObjectivesLeflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans.MethodsFrom a cohort of 289 688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions. Also second or third-trimester leflunomide exposures were examined for associations with prematurity and LBW. Logistic regression model-based generalised estimating equations were used.Results51 pregnancies were exposed to leflunomide during the first trimester, and 21 during the second/third trimesters. Adjusting for potential confounders, use of leflunomide during the first trimester of pregnancy was not associated with the risk of MCM (adjusted OR (aOR) 0.97, 95% CI 0.81 to 1.16; 5 exposed cases). No association was found between second/third-trimester exposure to leflunomide and the risk of prematurity (aOR 4.03, 95% CI 0.91 to 17.85; 7 exposed cases) nor LBW (aOR 1.06, 95%CI 0.90 to 1.25; 8 exposed cases). Pregnancy exposure to leflunomide was also not associated with the risk of spontaneous abortion (aOR 1.09, 95% CI 0.90 to 1.32; 11 exposed cases).ConclusionsMaternal exposure to leflunomide during pregnancy was not associated with statistically significant increased risk of MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively few women were exposed to leflunomide during pregnancy in this cohort, caution remains warranted.

scholarly journals Safety of Antimicrobials During Pregnancy: A Systematic Review of Antimicrobials Considered for Treatment and Postexposure Prophylaxis of Plague

2020 ◽  
Vol 70 (Supplement_1) ◽  
pp. S37-S50 ◽  
Author(s):  
Patricia A Yu ◽  
Emmy L Tran ◽  
Corinne M Parker ◽  
Hye-Joo Kim ◽  
Eileen L Yee ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Case Reports ◽  
Case Series ◽  
First Trimester ◽  
Neonatal Outcomes ◽  
Primary Sources ◽  
Limited Data ◽  
Postexposure Prophylaxis ◽  
Increased Risk ◽  
Adverse Pregnancy

Abstract Background The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy. Methods We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes. Results Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2–28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2–4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9–4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4–4.3), spontaneous abortion (OR 3.5, 95% CI 2.3–5.6), preterm birth (OR 1.5, 95% CI 1.1–2.1), and small for gestational age (OR 1.6, 95% CI 1.2–2.2). No other statistically significant associations were reported. Conclusions For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.

scholarly journals Air pollution exposure during pregnancy and spontaneous abortion and stillbirth

2018 ◽  
Vol 33 (3) ◽  
pp. 247-264 ◽  
Author(s):  
Alexandra Grippo ◽  
Jun Zhang ◽  
Li Chu ◽  
Yanjun Guo ◽  
Lihua Qiao ◽  
...  
Keyword(s):  
Air Pollution ◽  
Spontaneous Abortion ◽  
Air Pollutants ◽  
Pregnancy Loss ◽  
Third Trimester ◽  
The Third ◽  
Increased Risk ◽  
Air Pollution Exposure ◽  
Exposure During Pregnancy ◽  
Pollution Exposure

Abstract The developing fetus is particularly susceptible to environmental pollutants, and evidence has shown adverse effects of air pollutants on pregnancy and birth outcomes. Pregnancy loss, including spontaneous abortion (miscarriage) and stillbirth, is the most severe adverse pregnancy outcome. This review focuses on air pollution exposure during pregnancy in relation to spontaneous abortion and stillbirth. A total of 43 studies are included in this review, including 35 human studies and eight animal studies. Overall, these studies suggest that exposure to air pollutants such as particulate matter (PM), carbon monoxide (CO) and cooking smoke may be associated with higher risk for stillbirth and spontaneous abortion. PM10 exposure during an entire pregnancy was associated with increased risk of spontaneous abortion, and exposure to PM2.5 and PM10 in the third trimester might increase the risk of stillbirth. CO exposure during the first trimester of pregnancy was associated with an increased risk of spontaneous abortion and exposure during the third trimester was associated with an increased risk of stillbirth. Cooking smoke was found to increase the risk of stillbirths, and the evidence was consistent. Insufficient and conflicting evidence was found for various other pollutants, such as NO2 and SO2. Studies did not show clear evidence for associations between pregnancy loss and others pollutants such as heavy metals, organochlorine compounds, PAH and total dust count. Further research is warranted to better understand the relationship between air pollution exposure and pregnancy loss.

Pregnancy outcome following first trimester exposure to sumatriptan

Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 581-583 ◽  
Author(s):  
S. Shuhaiber ◽  
A. Pastuszak ◽  
B. Schick ◽  
D. Matsui ◽  
G. Spivey ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Birth Defects ◽  
First Trimester ◽  
Spontaneous Abortions ◽  
Live Births ◽  
Increased Risk ◽  
Trimester Exposure

We prospectively compared pregnancy outcome after exposure to sumatriptan with that of disease-matched controls and nonteratogen controls. There were no differences in the rates of live births, spontaneous abortions, therapeutic abortions, or major birth defects among the three groups. This first prospective report suggests that the use of sumatriptan during organogenesis is not associated with an apparent increased risk of major birth defects.

scholarly journals A Case of Intertwin Membrane Hemorrhage with Spontaneous Resolution

2019 ◽  
Vol 2019 ◽  
pp. 1-3
Author(s):  
Lily Criscione ◽  
Kristen Elmezzi ◽  
Saioa Torrealday ◽  
Barton C. Staat ◽  
Kimberly Hickey
Keyword(s):  
Vaginal Bleeding ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Final Diagnosis ◽  
Spontaneous Resolution ◽  
Multiple Gestation ◽  
Spontaneous Abortions ◽  
Third Trimester ◽  
The Third ◽  
Increased Risk

Vaginal bleeding during pregnancy places women at increased risk of spontaneous abortion. Etiologies for threatened and spontaneous abortions have been well studied, but there is little information on intertwin membrane hemorrhage. We present a patient with a multiple gestation pregnancy who experienced first trimester vaginal bleeding with visualization and subsequent rapid resolution of an intertwin membrane hemorrhage. The patient had an otherwise normal pregnancy until the third trimester when she developed preeclampsia with severe features and elected for a primary cesarean section at 35 + 5 weeks. The implications of an intertwin membrane hemorrhage are not well understood, although there could be a possible correlation between the hemorrhage and the ultimate progression to preeclampsia with severe features. Despite the final diagnosis, the patient did not have any noticeable complications due to the hemorrhage both when it was discovered and in the weeks following its discovery.

Correlations Between the Values of Maternal Glycemia from the Last Trimester of Pregnancy and Fetal Birth Weight

2013 ◽  
Vol 20 (3) ◽  
pp. 259-265
Author(s):  
Monica Vereş ◽  
Aurel Babeş ◽  
Szidonia Lacziko
Keyword(s):  
First Trimester ◽  
Mean Value ◽  
Fetal Macrosomia ◽  
Entire Group ◽  
Third Trimester ◽  
The Third ◽  
Group I ◽  
Fetal Birth Weight ◽  
First Trimester Of Pregnancy ◽  
The Mean

Abstract Background and aims: Gestational diabetes represents a form of diabetes diagnosed during pregnancy that is not clearly overt diabetes. In the last trimester of gestation the growth of fetoplacental unit takes place, thus maternal hyperglycemia will determine an increased transplacental passage, hyperinsulinemia and fetal macrosomia. The aim of our study was that o analyzing the effect of maternal glycemia from the last trimester of pregnancy over fetal weight. Material and method: We run an observational study on a group of 46 pregnant women taken into evidence from the first trimester of pregnancy, separated in two groups according to blood glucose determined in the third trimester (before birth): group I normoglycemic and group II with hyperglycemia (>92mg/dl). Results: The mean value of third trimester glycemia for the entire group was of 87.13±22.03. The mean value of the glycemia determined in the third trimester of pregnancy was higher in the second group (109.17 mg/dl) in comparison to the first group (74.,21 mg/dl). The ROC curve for third trimester glycemia as fetal macrosomia appreciation test has an AUC of 0.517. Conclusions: Glycemia determined in the last trimester of pregnancy cannot be used alone as the predictive factor for fetal macrosomia.

TSH/miR‐17‐5p/ZNF367 axis is related to spontaneous abortion in patients with TSH above 2.5 mIU/L

2021 ◽  
Author(s):  
Yang Yang ◽  
Jiashu Li ◽  
Yingying Zhou ◽  
Wen Dai ◽  
Weiping Teng ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Spontaneous Abortion ◽  
Biological Function ◽  
Zinc Finger Protein ◽  
First Trimester ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Chorionic Villi ◽  
Increased Risk

Elevated thyroid stimulating hormone (TSH) is associated with an increased risk of spontaneous abortion (SA); however, the associated mechanism remains unclear. This study aimed to investigate the expression of microRNAs (miRNAs) and pathogenesis in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. The chorionic villi were collected from pregnant women in the first trimester with TSH > 2.5 mIU/L with or without SA, as well as TSH < 2.5 mIU/L with or without SA to determine the level of miRNA expression. Differentially expressed miRNAs were confirmed by qRT-PCR in a total of 92 subjects. Cell counting kit-8 (CCK8), wound healing, transwell assays, and Western blotting were used to measure cellular biological functions and related protein in HTR-8/SVneo cells. The potential mechanisms were determined using a Luciferase reporter assay and rescue experiment. Compared with normal pregnant women, miR-17-5p was decreased and zinc finger protein 367 (ZNF367) was upregulated in the chorionic villi of TSH > 2.5 mIU/L-related SA patients. Using HTR-8/SVneo cells, we demonstrated that elevated TSH inhibited miR-17-5p expression, as well as trophoblast migration and invasion. The overexpression of miR-17-5p targeted and inhibited ZNF367 expression promoting the biological function of trophoblasts. Further studies confirmed that ZNF367 interference partially reversed the biological function of the miR-17-5p inhibitor on HTR-8/SVneo cells. Taken together, our results showed that miR-17-5p promoted biological function of trophoblasts by suppressing ZNF367.

scholarly journals Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon

2021 ◽  
Vol 15 (4) ◽  
pp. e0009390
Author(s):  
Jamille Gregório Dombrowski ◽  
André Barateiro ◽  
Erika Paula Machado Peixoto ◽  
André Boler Cláudio da Silva Barros ◽  
Rodrigo Medeiros de Souza ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Pregnancy Outcomes ◽  
Multivariate Logistic Regression Analysis ◽  
Brazilian Amazon ◽  
First Trimester ◽  
Inflammatory Factors ◽  
Anthropometric Measures ◽  
First Trimester Of Pregnancy ◽  
Adverse Pregnancy ◽  
Angiopoietin 2

Background Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon. Methods and findings We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn’s anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69–24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29–9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes. Conclusions This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections.

First Trimester Hemoglobin A1 and Risk for Major Malformation and Spontaneous Abortion

2021 ◽  
pp. 13-19
Author(s):  
Rachel Blake ◽  
Chloe Zera
Keyword(s):  
Spontaneous Abortion ◽  
Clinical Case ◽  
First Trimester ◽  
Spontaneous Abortions ◽  
Major Malformation ◽  
Fetal Malformations ◽  
Study Population ◽  
Hemoglobin A1 ◽  
Location Study

This chapter summarizes a landmark study on the association of first trimester hemoglobin A1 values with risk for spontaneous abortions and major fetal malformations during pregnancy in women with pregestational diabetes. Is there a correlation between glycemic control during the first trimester and risk for spontaneous abortion and major malformations? Starting with this question, it describes the basics of the study, including study location, study population, amount of patients, study design, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.

High Fetal Fraction on First Trimester Cell-Free DNA Aneuploidy Screening and Adverse Pregnancy Outcomes

2019 ◽  
Vol 37 (01) ◽  
pp. 008-013 ◽  
Author(s):  
Lydia L. Shook ◽  
Mark A. Clapp ◽  
Penelope S. Roberts ◽  
Sarah N. Bernstein ◽  
Ilona T. Goldfarb
Keyword(s):  
Preterm Birth ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
First Trimester ◽  
Hypertensive Disorders Of Pregnancy ◽  
Aneuploidy Screening ◽  
Hypertensive Disorders ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
Fetal Fraction

Abstract Objective To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. Study Design This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th–95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Results A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant <fifth percentile, with an adjusted odds ratio of 2.4 (95% confidence interval: 1.1–4.8, p = 0.039). There was no significant association between high FF and either preterm birth or hypertensive disorders of pregnancy. Conclusion Women with a high FF in the first trimester are at increased risk of delivering a small for gestational age infant <fifth percentile. Further investigation into the clinical implications of a high FF is warranted.

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