Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

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Antidepressant use During Pregnancy and the Risk of Major Congenital Malformations in a Cohort of Depressed Pregnant Women: A Re-analysis of the Quebec Pregnancy Cohort

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2019 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S155-S155

Author(s):

A. Bérard ◽

J.P. Zhao ◽

O. Sheehy

Keyword(s):

Pregnant Women ◽

Serotonin Reuptake ◽

Congenital Malformations ◽

Selective Serotonin Reuptake Inhibitors ◽

First Trimester ◽

Pregnancy Cohort ◽

Organ Specific ◽

Antidepressant Use ◽

Major Congenital Malformations ◽

First Year Of Life

ObjectiveTo quantify the association between first-trimester antidepressant exposure and the risk of major congenital malformations (MCM) in a cohort of depressed women.MethodData were obtained from the Quebec pregnancy cohort. All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and other antidepressants), and types were individually compared to non-exposure during the first-trimester (depressed untreated). MCM overall and organ-specific malformations in the first year of life were identified.ResultEighteen thousand four hundred and eighty-seven depressed pregnant women were included. Citalopram use during the first-trimester was increasing the risk of MCM (aOR 1.36, 95%CI 1.08, 1.73; 88 exposed cases). Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) were increasing the risk of certain organ specific defects: paroxetine was increasing the risk of cardiac defects (aOR 1.45, 95%CI 1.12, 1.88), and ventricular/atrial septal defects (aOR 1.39, 95%CI 1.00. 1.93); citalopram was increasing the risk of musculoskeletal defects (aOR 1.92, 95%CI 1.40. 2.62), and cranyosynostosis (aOR 3.95, 95%CI 2.08, 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95%CI 1.05, 5.72), and digestive defects (aOR 2.55, 95%CI 1.40. 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95%CI 1.07, 4.38).ConclusionAntidepressants with effects on serotonin reuptake during embryogenesis are increasing the risk of some organ specific malformations in a cohort of pregnant women with depression.Disclosure of interestCOI: Disclosures and acknowledgments: AB is a consultant for plaintiffs in litigations involving antidepressants and birth defects. All other authors report no financial relationships with commercial interests. All authors have completed the ICMJE uniform disclosure form.

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Real-world evidence on sodium-glucose cotransporter-2 inhibitor use and risk of Fournier’s gangrene

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000985 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000985 ◽

Cited By ~ 3

Author(s):

Jeff Yufeng Yang ◽

Tiansheng Wang ◽

Virginia Pate ◽

John B Buse ◽

Til Stürmer

Keyword(s):

Real World ◽

Fournier’S Gangrene ◽

Sensitivity Analyses ◽

Standardized Mortality Ratio ◽

Fournier's Gangrene ◽

Diagnosis Codes ◽

Sodium Glucose Cotransporter ◽

Real World Evidence ◽

Increased Risk ◽

The Impact

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier’s gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning.MethodsWe used data from IBM MarketScan (2013–2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions.ResultsWe identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51–0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04–1.74) to 1.14 (0.86–1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53–6.11) and inpatient diagnoses only (aHR 4.58; 0.99–21.21).ConclusionsNo evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG.Trial registration numberEUPAS Register Number 30018.

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

Clinical Infectious Diseases ◽

10.1093/cid/ciz1231 ◽

2020 ◽

Vol 70 (Supplement_1) ◽

pp. S37-S50 ◽

Cited By ~ 2

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.

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

American Journal of Perinatology ◽

10.1055/s-0039-1694005 ◽

2019 ◽

Vol 37 (01) ◽

pp. 008-013 ◽

Cited By ~ 4

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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Management of special situations in systemic lupus erythematosus

10.1093/med/9780198739180.003.0009 ◽

2016 ◽

Author(s):

April Jorge ◽

Rosalind Ramsey-Goldman

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Comprehensive Treatment ◽

Systemic Lupus ◽

Risk Factor Modification ◽

Safety Issues ◽

Increased Risk ◽

Treatment Considerations ◽

Pregnancy And Lactation ◽

Adverse Pregnancy

In caring for patients with systemic lupus erythematosus (SLE), there are several important treatment considerations. Since many patients with SLE are female and of childbearing potential, it is important to address conception planning, contraceptive options, and the maternal and fetal risks associated with pregnancy, which are increased when there is higher SLE disease activity. It is also pertinent to address medication safety issues throughout pregnancy and lactation, as some commonly used medications can increase risks of adverse pregnancy outcomes. Additionally, patients with SLE are at higher risk for cardiovascular disease (CVD) than the general population. Therefore, these patients must undergo aggressive risk factor modification. Patients with SLE are also at increased risk for osteoporosis, and bone health is an important treatment consideration. Routine cancer screening and vaccinations are also important elements of the comprehensive treatment of the patient with SLE.

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Cohort profile: targeted antenatal screening for haemoglobinopathies in Basel

BMJ Open ◽

10.1136/bmjopen-2019-035735 ◽

2020 ◽

Vol 10 (7) ◽

pp. e035735

Author(s):

Gabriela Amstad Bencaiova ◽

Franziska Geissler ◽

Irene Hoesli

Keyword(s):

High Risk ◽

Pregnant Women ◽

Risk Group ◽

Iron Status ◽

First Trimester ◽

High Risk Group ◽

University Hospital ◽

Pregnancy Cohort ◽

Haemoglobin Variant ◽

Adverse Pregnancy

PurposeThe pregnancy cohort was established to examine the prevalence and variety of haemoglobinopathies in a high-risk group of pregnant women.ParticipantsThe pregnancy cohort is located in the Department of Obstetrics and Antenatal Care, University Hospital of Basel. The pregnant women were recruited in the first trimester between June 2015 and May 2019. Family origin questionnaires were used to screen pregnant women for the risk of a haemoglobin variant. Based on the questionnaire, pregnant women were divided into two groups: women with a high risk and women with a low risk of a haemoglobin variant. In women with a high risk, red blood cell indices, iron status and chromatography were conducted.Findings to date1785 pregnant women were recruited. Out of the 1785 women, 929 were identified as a part of the high-risk group. Due to the missing data of 74 pregnant women with a high risk, the final analysis was conducted in the remaining 855 women. The prevalence of haemoglobinopathies in the high-risk group was 14.5% (124/855).Future plansThis cohort will be used to: (1) implement the screening in prenatal care in Basel; (2) recommend the screening among pregnant women with a high risk of a haemoglobin variant in Switzerland; (3) improve prenatal and neonatal care in patients with a haemoglobin variant; (4) examine adverse pregnancy outcomes in women with a haemoglobin variant and (5) reduce maternal and neonatal morbidity and mortality in the future.Trial registration numberClinicalTrials.gov Registry (NCT04029142).

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Case Report on Pregnancy with Lupus Nephritis Type IV with Hypothyroidism – A Clinical Vignette

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2021/52 ◽

2021 ◽

Vol 8 (05) ◽

pp. 272-274

Author(s):

Abirbhab Pal

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

First Trimester ◽

The Body ◽

Fetal Mortality ◽

Thyroid Disorder ◽

Multisystem Disease ◽

Mortality And Morbidity ◽

Multiple Systems ◽

Increased Risk

Lupus is a multisystem disease affecting almost all systems including the immune system of our body. Its aetiology is not known. Lupus involving kidneys causes lupus nephritis and adds more complications in the multisystem disease. Lupus or systemic lupus erythematosus (SLE) is a multifactorial chronic disease involving multiple systems of the body. It is autoimmune1 in nature. There is increase in maternal and fetal risk of mortality and morbidity in lupus with pregnancy. The rate of pregnancy loss is 1.7 %2 in active SLE during initial first trimester and the most common adverse morbidity causing factor of fetomaternal side.3 There can be an increase in fetal mortality and morbidity associated with lupus nephritis.4,5 There is increased risk of intrauterine growth restriction (IUGR) / neonatal lupus / gestational diabetes mellitus / osteoporosis / HELLP syndrome / preeclampsia. Associated thyroid disorder is increased with preterm pregnancy.

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Birth outcomes following antiretroviral exposure during pregnancy: Initial results from a pregnancy exposure registry in South Africa

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v20i1.971 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Ushma C. Mehta ◽

Cari Van Schalkwyk ◽

Prineetha Naidoo ◽

Arthi Ramkissoon ◽

Otty Mhlongo ◽

...

Keyword(s):

Birth Outcomes ◽

Congenital Malformations ◽

First Trimester ◽

First Year ◽

Increased Risk ◽

Bivariable Analysis ◽

Major Congenital Malformations ◽

Clinical Records ◽

Surface Examination ◽

The Impact

Background: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes.Objectives: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy.Method: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk.Results: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12–6.4; p = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3–37.9; p = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14–1.31; p 0.001]).Conclusion: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants.

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A COMPARATIVE STUDY OF MATERNAL OUTCOME IN FIRST-TRIMESTER VAGINAL BLEEDING IN THE DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, SMS MEDICAL COLLEGE, JAIPUR

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i7.2006 ◽

2021 ◽

Vol 5 (7) ◽

Author(s):

Savita Meena ◽

Suniti Verma ◽

R N Sehra ◽

Suman Choudhary

Keyword(s):

Gestational Age ◽

Vaginal Bleeding ◽

Adverse Pregnancy Outcome ◽

First Trimester ◽

Control Group ◽

Case Group ◽

Medical College ◽

Obstetrics And Gynaecology ◽

Increased Risk ◽

Adverse Pregnancy

Background: The outcome of ongoing pregnancies after first trimester vaginal bleeding is of relevance to women and obstetricians for planning antenatal care and clinical interventions in pregnancy. Hence, this study was conducted to identify the risks associated with first trimester bleed which may facilitate decision making regarding mode, place and timing of delivery during management, which may improve maternal and neonatal outcome. Methods: Hospital based comparative prospective study conducted at Department of Obstetrics and Gynaecology, SMS Medical College & associated Hospitals, Jaipur. Results: APH was found in 4 (8.00%) patients of case group and nil in control group. So, APH was found to be more in the case group than control group but was statistically not significant. Pre-eclampsia was found in 4 (8.00%) in case group and 3 (6.00%) in control group with statistically insignificant difference between the two groups. 26 (52.00%) delivered at the gestational age of ?37 weeks, whereas only 8 (16%) of control group delivered at ?37 weeks. So, the gestational age at delivery of control group subjects was found to be higher as compared to case group subjects and the difference was statistically significant (p=0.001). Conclusion: Threatened miscarriage in early pregnancy increases the risk of adverse pregnancy outcome. In our study, these patients were found to be at an increased risk of preterm delivery, PPROM. Keywords: PROM, Miscarriage, Gestational age

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