Ulipristal acetate and pregnancy outcome—an observational study

Abstract STUDY QUESTION Is the failure of the selective progesterone receptor modulator ulipristal acetate (UPA) as emergency contraception (EC; 30 mg, single) or inadvertent exposure for myoma treatment (5 mg/d) in pregnancy associated with a higher risk of birth defects, spontaneous abortion (SAB) or elective termination of pregnancy (ETOP)? SUMMARY ANSWER We did not find an increased risk for birth defects, SABs or ETOPs after UPA exposure during implantation and early embryogenesis. WHAT IS KNOWN ALREADY Pregnancy outcome data after exposure to UPA are very limited. In cases of EC failure or unplanned pregnancy during myoma treatment, women need well-grounded risk assessment to minimize anxiety and prevent unjustified termination of pregnancy. STUDY DESIGN, SIZE, DURATION Observational study of prospectively ascertained pregnancies from the German Embryotox institute with UPA exposure (EC, n = 95; myoma, n = 7). Four retrospectively reported pregnancy outcomes were evaluated separately. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 226 requests on ulipristal were directed to the German Embryotox institute during the study period 2010–2018. Outcomes of pregnancies exposed—(i) precycle, (ii) preconceptional or (iii) first trimester—were ascertained using standardized questionnaires. Descriptive statistics were applied. MAIN RESULTS AND THE ROLE OF CHANCE Failed EC with UPA resulted in 95 prospectively ascertained pregnancies, of which 56 had completed follow-up: 37 live births, 7 SABs and 12 ETOPs. There was no major birth defect. Just 34% of women had taken UPA during the fertile window. Seven prospectively enrolled pregnancies were treated for myoma and had known pregnancy outcomes: five healthy live births and two SABs. Among the four retrospectively reported pregnancies after EC, there was one child diagnosed with Beckwith-Wiedemann syndrome (BWS). LIMITATIONS, REASONS FOR CAUTION Our limited sample size does not allow concluding safety of UPA use in pregnancy. WIDER IMPLICATIONS OF THE FINDINGS We provide a preliminary basis for reassuring women who wish to carry their pregnancy to term after EC or myoma treatment with UPA. However, because of the report of a BWS after UPA exposure, a possible epigenetic effect could not be excluded and requires further evaluation. STUDY FUNDING/COMPETING INTEREST(S) This work was performed with financial support from the German Federal Institute for Drugs and Medical Devices (BfArM). All authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER Registered with the German Clinical Trial Register (DRKS00015155).

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Pregnancy outcome following first trimester exposure to sumatriptan

Neurology ◽

10.1212/wnl.51.2.581 ◽

1998 ◽

Vol 51 (2) ◽

pp. 581-583 ◽

Cited By ~ 62

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.

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Prediction of Healthy Pregnancy Outcomes in Women with Overweight and Obesity: The Role of Maternal Early-Pregnancy Metabolites

Metabolites ◽

10.3390/metabo12010013 ◽

2021 ◽

Vol 12 (1) ◽

pp. 13

Author(s):

Rama J. Wahab ◽

Vincent W. V. Jaddoe ◽

Romy Gaillard

Keyword(s):

Pregnancy Outcome ◽

Early Pregnancy ◽

Pregnancy Outcomes ◽

Gestational Hypertension ◽

Characteristic Curve ◽

Overweight And Obesity ◽

Large For Gestational Age ◽

Maternal Characteristics ◽

Healthy Pregnancy ◽

Increased Risk

Women with obesity receive intensified antenatal care due to their increased risk of pregnancy complications, even though not all of these women develop complications. We developed a model based on maternal characteristics for prediction of healthy pregnancy outcomes in women with obesity or who are overweight. We assessed whether early-pregnancy metabolites improved prediction. In a population-based cohort study among a subsample of 1180 Dutch pregnant women with obesity or who are overweight, we developed a prediction model using 32 maternal socio-demographic, lifestyle, physical and pregnancy-related characteristics. We determined early-pregnancy amino acids, nonesterifed fatty acids, phospholipids and carnitines in blood serum using liquid chromatography-tandem mass spectrometry. A healthy pregnancy outcome was the absence of fetal death, gestational hypertension, preeclampsia, gestational diabetes, caesarian section, preterm birth, large-for-gestational-age at birth, macrosomia, postpartum weight retention and offspring overweight/obesity at 5 years. Maternal age, relationship status, parity, early-pregnancy body mass index, mid-pregnancy gestational weight gain, systolic blood pressure and estimated fetal weight were selected into the model using backward selection (area under the receiver operating characteristic curve: 0.65 (95% confidence interval 0.61 to 0.68)). Early-pregnancy metabolites did not improve model performance. Thus, in women with obesity or who are overweight, maternal characteristics can moderately predict a healthy pregnancy outcome. Maternal early-pregnancy metabolites have no incremental value in the prediction of a healthy pregnancy outcome.

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Sleep disorders in pregnancy and their association with pregnancy outcomes: a prospective observational study

Sleep And Breathing ◽

10.1007/s11325-015-1188-9 ◽

2015 ◽

Vol 20 (1) ◽

pp. 87-93 ◽

Cited By ~ 44

Author(s):

S. K. Sharma ◽

A. Nehra ◽

S. Sinha ◽

M. Soneja ◽

K. Sunesh ◽

...

Keyword(s):

Observational Study ◽

Sleep Disorders ◽

Pregnancy Outcomes ◽

Prospective Observational Study ◽

In Pregnancy

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P599 Trimester exposure and pregnancy outcomes in women exposed to golimumab: Results from the company pharmacovigilance database

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.727 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S500-S501

Author(s):

S Esslinger ◽

M Otero-Lobato ◽

S Gabriel ◽

M Clark ◽

P Sheridan ◽

...

Keyword(s):

Pregnancy Outcome ◽

Birth Outcomes ◽

Pregnancy Outcomes ◽

Spontaneous Abortions ◽

Live Births ◽

Elective Abortion ◽

Induced Abortions ◽

Pharmacovigilance Database ◽

Inflammatory Bowel ◽

Twin Pregnancies

Abstract Background Rheumatologic disorders and inflammatory bowel disease can affect women of childbearing potential. Golimumab (GLM) is approved for several rheumatological indications and ulcerative colitis (UC). To characterise pregnancy outcomes in patients treated with GLM, data obtained from maternal exposure to GLM are presented. Methods These dataset includes individual patient cases reported to the manufacturer through 06 April 2019. Cases included in the analysis were medically confirmed cases of maternal exposures to GLM during pregnancy or within 3 months prior to conception, and a reported pregnancy outcome. Both prospectively reported (ie, pregnancy outcome not known when first reported) and retrospectively reported cases (ie, pregnancy outcome known when first reported) were included. Cases originated from various sources, including spontaneous reporting, clinical studies, and registries. Results Two hundred eight pregnancy cases (131 rheumatological; 43 UC; and 34 other) with 211 reported birth outcomes were identified. Three cases reported twin pregnancies. Of the 208 pregnancy cases, 119 were prospective and 89 were retrospective (Table 1). Average maternal age was 31.9 years. Of the 119 prospectively reported pregnancy cases, 89 (74.8%) resulted in live births, 19 (16.0%) resulted in spontaneous abortion (of these, 42.1% (8/19) received GLM in combination with methotrexate [MTX]), 10 (8.4%) resulted in induced/elective abortion, and 1 (0.8%) resulted in ectopic pregnancy. Overall, 9 congenital anomalies were reported (2 prospective/7 retrospective cases). For 183 of the 208 pregnancy cases with-reported outcomes, the trimester of exposure to GLM was known (Table 2). Among the 110 prospectively reported cases, 82 (74.5%) were exposed during trimester 0 or 1. Of these, 19 had concomitant exposure to MTX, with the following birth outcomes: 8 live births, 8 spontaneous abortions, 3 elective/induced abortions. Eighteen of the prospectively reported cases (16.4%) were exposed to GLM throughout pregnancy (first, second and third trimester) and all resulted in live births. Conclusion The rates of congenital malformations and spontaneous abortions were consistent with published background rates for the general population. Persistent exposure throughout pregnancy was rare, but not associated with apparent clinical sequelae. Limitations of this analysis include the lack of a direct comparison group, the variable amount of data available in the reports, and the possible bias towards reporting more negative outcomes in retrospective cases.

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The Spectrum of Adverse Pregnancy Outcomes Based on Kidney Disease Diagnoses: A 20-Year Population Study

American Journal of Nephrology ◽

10.1159/000499965 ◽

2019 ◽

Vol 49 (5) ◽

pp. 400-409 ◽

Cited By ~ 4

Author(s):

Alyssa Fitzpatrick ◽

Kamalesh Venugopal ◽

Wendy Scheil ◽

Stephen P. McDonald ◽

Shilpanjali Jesudason

Keyword(s):

Preterm Birth ◽

Caesarean Section ◽

Pregnancy Outcomes ◽

Clinical Care ◽

Vesicoureteric Reflux ◽

Population Level ◽

Diagnostic Code ◽

Benign Condition ◽

Increased Risk ◽

In Pregnancy

Background and Objectives: Kidney disorders in pregnancy may be under-recognized and have variable impact on outcomes depending on diagnosis. Population-level data are limited, particularly for Australia, and comparison of impact of different kidney disorders on pregnancy has rarely been assessed. This study examined the prevalence and outcomes of varied kidney disorders using population-level perinatal data from a large cohort. Methods: Women with singleton pregnancies > 20 weeks’ gestation from the South Australian Pregnancy Outcomes Unit (1990–2012). Women with a kidney disorders diagnostic code were grouped into categories (immunological, cystic/genetic, urological, vesicoureteral reflux (VUR), pyelonephritis and “other”). Key pregnancy outcomes were assessed, with adjustment for demographic variables. Results: Kidney disorders were reported in 1,392 (0.3%) of 407,580 births. These pregnancies had increased risk of pregnancy-induced hypertension (OR 2.16, 95% CI 1.82–2.56), induction of labor (RRR vs. spontaneous birth 2.10, 95% CI 1.87–2.36), all Caesarean section (OR 1.31, 95% CI 1.17–1.47) as well as Caesarean section without labor (RRR 1.82, 95% CI 1.57–2.10), preterm birth (< 37 weeks; 2.76, 95% CI 2.40–3.18), low birth weight (< 2,500 g) infants (OR 2.43, 95% CI 2.07–2.84), and neonatal intensive care admission (OR 2.64, 95% CI 2.12–3.29). Diagnostic subgroups demonstrated differing patterns of adverse outcomes, enabling the development of a matrix of risk. Women with immunological renal conditions and VUR had greatest risk overall, and only women with immunological diseases had increased risk of small-for-gestational age < 10th centile (OR 2.36, 95% CI 1.26–4.42). Women with nonchronic urological conditions and pyelonephritis had increased risk of preterm birth, but not other adverse events. VUR conferred particularly increased risk of Caesarean section and induced labor. Conclusions: In a cohort of > 1,300 women with varied kidney disorders, increased adverse obstetric and perinatal events were observed, and the nature and magnitude of risk differed according to diagnosis. In particular, vesicoureteric reflux is not a benign condition in pregnancy. Women with nonchronic conditions still had increased risk of preterm birth. We confirm that women with kidney disorders warrant vigilant and tailored prepregnancy care and clinical care in pregnancy.

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Impact of Inherited Bleeding Disorders on Maternal Bleeding and Other Pregnancy Outcomes: A Population-Based Cohort Study

Blood ◽

10.1182/blood-2021-149673 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 493-493

Author(s):

Arafat Ul Alam ◽

Cynthia M. Wu ◽

Venu Jain ◽

Haowei Linda Sun

Keyword(s):

Cohort Study ◽

Pregnancy Outcomes ◽

Research Funding ◽

Population Based ◽

Diagnostic Code ◽

Bleeding Disorders ◽

Live Births ◽

Increased Risk ◽

Significant Change

Abstract Introduction: Increasing rate of postpartum hemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Given that bleeding disorders contribute to the risk of PPH, it is important to identify the current trend in PPH in the last decade and assess the impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes. Methods: This is a retrospective population-based cohort study using the Alberta Pregnancy Birth Cohort. The creation of this cohort using multiple linked administrative databases has been previously described. Number of deliveries per year in Alberta, Canada was determined by Vital Statistics birth registry from 2010 to 2018 and was linked with Discharge Abstract Database (DAD) to identify cases of PPH and other pregnancy outcomes. PPH was defined as a blood loss of ≥500 ml following vaginal delivery or ≥1000 ml following Caesarean section, or as a diagnosis noted by a health care provider. All diagnoses and procedures were identified by International Classification of Diseases (ICD)-10 codes and Canadian Classification of Interventions (CCI) codes, respectively. Previous validation study of diagnostic code for PPH in DAD showed high sensitivity and specificity. Inherited bleeding disorders including von Willebrand disease, hemophilia carriers, platelet function disorder, and hereditary deficiencies of other coagulation factors were identified by presence of at least two ICD codes. All analyses were restricted to hospitalized deliveries with live births. Temporal trend of PPH rate was assessed by Mann-Kendall test. Univariate logistic regression analyses were used to compute odds of pregnancy outcomes among women with inherited bleeding disorders compared with those without at their index pregnancies during the study period. Results: Between 2010 to 2018, 311,657 women had a total of 452,846 pregnancies with live births. The mean age of the study cohort was 29 years. Most (90%) of them reached term pregnancies. The total number of PPH was 47,602 (10.5 per 100 deliveries). The rate of PPH did not have any significant change from 10.3 in 2010 (95% confidence interval [CI] 10.0-10.6) to 10.8 (95% CI 10.6 -11.1) in 2018 (P for trend =0.28) [Figure 1]. Among 311,657 women, 345 (0.1%) had a diagnosis of inherited bleeding disorders [Table 1]. Women with bleeding disorders were more likely to experience PPH (odds ratio [OR] 1.4; 95% CI 1.1-1.9), antepartum hemorrhage (OR 4.3; 95% CI 2.9-6.4) and had a 3-fold increased risk of undergoing hysterectomy (OR 3.1; 95% CI 1.8-5.2). The bleeding cohort had 3.8 (95% CI: 2.4-6.0) times greater risk of being transfused with blood products. We observed a trend towards higher odds of caesarean delivery in women with bleeding disorders compared with those without (OR 1.2, 95% CI 0.9-1.5), albeit not statistically significant. However, there was no significant difference in prolonged labor, obstetric hematoma, low birth weight baby and induced labour. Conclusion: Despite a rise in the rate of PPH between 2003-2010, we observed no significant change in the rate of PPH in Alberta between 2010-2018. Women with inherited bleeding disorders are at an increased risk of bleeding events during pregnancy and childbirth. Further investigation into quality of care among this patient population is ongoing to identify areas for improvement. Figure 1 Figure 1. Disclosures Wu: BMS-Pfizer: Honoraria, Research Funding; Leo Pharma: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Bayer: Research Funding; Daiichi-Sankyo: Research Funding. Sun: Pfizer: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Octapharma: Consultancy, Research Funding; Shire: Consultancy.

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Prevalence of individual brain and eye defects potentially related to Zika virus in pregnancy in 22 U.S. states and territories, January 2016 - June 2017

10.21203/rs.3.rs-1189990/v1 ◽

2022 ◽

Author(s):

Augustina Delaney ◽

Samantha M. Olson ◽

Nicole M. Roth ◽

Janet D. Cragan ◽

Shana Godfred-Cato ◽

...

Keyword(s):

Birth Defects ◽

Zika Virus ◽

Cortical Atrophy ◽

Zikv Infection ◽

Live Births ◽

Prevalence Estimates ◽

Surveillance Programs ◽

Prevalence Ratios ◽

Cerebral Cortical Atrophy ◽

In Pregnancy

Abstract During the Centers for Disease Control and Prevention’s Zika Virus Response, birth defects surveillance programs adapted to monitor birth defects potentially related to Zika virus (ZIKV) infection during pregnancy. Pregnancy outcomes occurring during January 2016-June 2017 in 22 U.S. states and territories were used to estimate the prevalence of those brain and eye defects potentially related to ZIKV. Jurisdictions were divided into three groups: areas with widespread ZIKV transmission, areas with limited local ZIKV transmission, and areas without local ZIKV transmission. Prevalence estimates for selected brain and eye defects and microcephaly per 10,000 live births were estimated. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression for areas with widespread and limited ZIKV transmission compared to areas without local ZIKV transmission. Defects with significantly higher prevalence in areas of widespread transmission were pooled, and PRs were calculated by quarter, comparing subsequent quarters to the first quarter (January – March 2016). Nine defects had significantly higher prevalence in areas of widespread transmission. The highest PRs were seen in intracranial calcifications (PR=12.6, 95% CI [7.4, 21.3]), chorioretinal abnormalities (12.5 [7.1, 22.3]), brainstem abnormalities (9.3, [4.7, 18.4]), and cerebral/cortical atrophy (6.7, [4.2, 10.8]). The PR of the nine pooled defects was significantly higher in three quarters in areas with widespread transmission. The largest difference in prevalence was observed for defects consistently reported in infants with congenital ZIKV infection. Birth defects surveillance programs could consider monitoring a subset of birth defects potentially related to ZIKV in pregnancy.

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Insulin Glulisine in Pregnancy – Experience from Clinical Trials and Post-marketing Surveillance

European Endocrinology ◽

10.17925/ee.2015.11.01.17 ◽

2015 ◽

Vol 11 (1) ◽

pp. 17 ◽

Cited By ~ 9

Author(s):

Zoran Doder ◽

Demi Vanechanos ◽

Manfred Oster ◽

Wolfgang Landgraf ◽

Stephen Lin ◽

...

Keyword(s):

Diabetes Mellitus ◽

Clinical Trials ◽

Congenital Malformations ◽

Safety Data ◽

Live Births ◽

Post Marketing Surveillance ◽

Increased Risk ◽

Post Marketing ◽

Insulin Glulisine ◽

In Pregnancy

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (ApidraR, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.

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74. Maternal Dolutegravir (DTG) Use During Pregnancy and Birth Outcomes: The Antiretroviral Pregnancy Registry (APR)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.074 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S48-S49

Author(s):

Vani Vannappagari ◽

Jessica Albano ◽

Leigh Ragone ◽

Taylor Cook ◽

Angela Scheuerle ◽

...

Keyword(s):

Birth Defects ◽

Descriptive Analysis ◽

The United States ◽

Neonatal Outcomes ◽

Congenital Defects ◽

Think Tank ◽

Research Support ◽

Independent Contractor ◽

Live Births ◽

Increased Risk

Abstract Background The APR is prospective exposure-registration cohort study, monitoring for early warning signals of major teratogenic effects of antiretrovirals (ARV) used during pregnancy. This analysis aimed to assess maternal demographics, pregnancy and neonatal outcomes including birth defects among infants with periconception and prenatal exposure to DTG using APR data. Methods Descriptive analysis with frequency tabulation of pregnancy and neonatal outcomes is reported. Periconception is defined as any exposure within two weeks prior to or through 28 days after conception. Results There were 1010 prospectively reported pregnancies with exposure to DTG through 31January2021, with 526 periconception exposures, 105 exposed later during 1st trimester, 260 during 2nd trimester and 119 during 3rd trimester. Maternal median age at conception was 30 years and 77.0% of pregnancies were reported from the United States. At the time of reporting, 46.6% had CD4 count ≥500 cells/µL, 31.8% had 200-499 cells/µL, 12.5% had < 200 cells/µL and 9.1% unknown. The 1010 DTG exposed pregnancies resulted in 1036 outcomes: 956 (92.3%) live births (26 twin pairs), 12 (1.2%) stillbirths, 28 (2.7%) induced abortions, and 38 (3.7%) spontaneous abortions. Among live births, 39 (4.1%) reported birth defects. For 1st trimester exposures, overall defect prevalence was 3.3% (19/576, 95% CI:2.0-5.1) and for 2nd/3rd trimester exposures defect prevalence was 5.3% (20/380, 95% CI:3.2-8.0). One neural tube defect (NTD) case of anencephaly with periconception DTG exposure was reported. Among the 873 singleton, live births without birth defects, 92 (10.5%) were preterm (< 37 weeks of gestation); 103 (11.8%) had low birth weight (lbw) < 2500 grams including 22 (2.5%) < 1500 (very lbw) grams. Conclusion APR data do not demonstrate an increased risk of overall birth defects with DTG use above the population expected rate of defects (2.72 to 4.17 per 100 live births from Metropolitan Atlanta Congenital Defects Program [MACDP] and Texas Birth Defects Registry [TBDR] respectively). The number of periconception exposure outcomes is not yet sufficient to evaluate potential association of DTG with NTD. The Registry continues to closely monitor birth defects, including NTDs in pregnancies exposed to DTG and other integrase inhibitors. Disclosures Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee) Jessica Albano, PhD, MPH, Syneos Health (Employee, Shareholder) Leigh Ragone, MS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Taylor Cook, BS, Syneos Health (Employee) Angela Scheuerle, MD, ViiV (Independent Contractor) William R. Short, MD, Gilead Sciences (Individual(s) Involved: Self): Consultant; ViiV (Individual(s) Involved: Self): Consultant Claire Thorne, MSc, PhD, MSD (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Other Financial or Material Support, Contributor to Think Tank)

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