Elective Termination Of Pregnancy Research Articles

3006 – SINGLE CELL MAP OF THE EMERGENCE OF HUMAN HEMATOPOIETIC STEM CELLS FROM HEMOGENIC ENDOTHELIUM

Hematopoietic stem cells (HSCs) capable of sustaining life-long multilineage hematopoiesis are formed in the human embryo between 4 and 5 weeks of development. HSCs emerge from hemogenic endothelium (HE) in the aorta-gonad mesonephros (AGM) region in a process called endothelial-to-hematopoietic transition (EHT). EHT has been mainly studied in in vitro human pluripotent stem cell models, which do not fully recapitulate in vivo HSC specification. Thus, the precise molecular identity and source of the HSC-forming HE and the molecular programs governing EHT in human remain elusive. This is crucial, as the embryo and extraembryonic tissues also harbor HE that generates non-HSC hematopoietic progenitors. Here, we conducted single-cell RNA-sequencing on purified cells (CD34+/CD31+) from the AGM region of 4.5-5-week human embryos from elective pregnancy terminations. Trajectory inference analyses revealed a distinct cluster of nascent HSCs with a unique expression profile (RUNX1+HLF+HOXA+MLLT3+SPINK2+) and a closely associated putative arterial HE population with a molecular signature that distinguishes it from other arterial endothelium (ALDH1A1+COL23A1+AGTR2+DKK1+KCNK17+). We also identified a novel arterial population (IL33+SULF1+ALDH1A1+AGTR2+), herein termed pre-HE, that is largely non-proliferative and metabolically quiescent and precedes the HSC-forming HE. Pseudotime analyses showed that acquisition of hemogenic properties in endothelium is concomitant to the downregulation of Notch, TGFb and Wnt signaling, and to the induction of hematopoietic transcription factors and genes associated with autophagy, identifying key regulatory switches during EHT. Comparison of HSC-forming HE (4.5-5-week AGM) to earlier, non-HSC-forming HE (3-4-week AGM) informed that ALDH1A1, COL23A1, AGTR2 and DKK1 are HSC lineage-specific markers, while KCNK17 is a pan hemogenic marker also induced during progenitor development from HE. Altogether, these findings provide a high-resolution map of the cell types and molecular switches involved in human HSC formation from endothelium, and can ultimately enable the recapitulation of HSC development in vitro for therapeutic purposes.

Periconceptional exposure to lopinavir, but not darunavir, impairs decidualization: a potential mechanism leading to poor birth outcomes in HIV-positive pregnancies.

Periconceptional exposure to lopinavir, but not darunavir, impairs decidualization: a potential mechanism leading to poor birth outcomes in HIV-positive pregnancies.

Outcomes of haemoglobin Bart’s hydrops fetalis following intrauterine transfusion in Ontario, Canada

ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart’s hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive.DesignTo evaluate the long-term outcome of affected fetuses with and without IUT...

Elective Termination of Pregnancy in Autoimmune Rheumatic Diseases: Experience From Two Databases.

To provide reference data regarding the frequency and safety of elective termination of pregnancy in women with autoimmune rheumatic diseases followed up in 2 referral databases. Two large databases, one from an autoimmune rheumatic disease referral clinical practice with a known interest in pregnancy (the Barbara Volcker Center for Women and Rheumatic Disease [BVC]), and one from an observational study of systemic lupus erythematosus- and antiphospholipid antibody-associated pregnancies (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus [PROMISSE]), were interrogated for histories of prior elective termination of pregnancy and complications related to incident pregnancy termination. Of women who had had prior pregnancies, 21.7% of 1,307 in the BVC database and 25.3% of 297 in the PROMISSE database gave histories of 1-5 prior elective terminations of pregnancy; BVC patients reported no flares or hospitalizable complications due to pregnancy termination. Of 674 incident pregnancies, termination for fetal or maternal reasons was recommended for 15 (2%); of these, 2 fetuses died before the procedure was carried out and 1 woman declined termination and, though gravely ill, successfully delivered. She died of cardiomyopathy 3 years later. Many patients with autoimmune rheumatic disease undergo elective termination of pregnancy; few report complications. In medically indicated termination of pregnancy, there are no adverse signals of unusual complications or disease flare.

Association between contraceptive method chosen after induced abortion and incidence of repeat abortion in Northern Portugal

Objectives In Portugal, a country with strong Catholic roots, elective termination of pregnancy at women’s request is still stigmatised, especially if it is a repeat abortion. The objectives of this study were to determine the incidence of repeat abortion, taking into account the contraceptive method chosen after the index abortion event, and characterise the risk factors for repeat abortion. Methods This was a retrospective cohort study of 988 women who requested termination of pregnancy during 2015 in a Portuguese tertiary care public hospital. Contraception was given free of charge after the index event. The occurrence of a repeat induced abortion was evaluated during a 24 month follow-up period. Results Forty-nine (5.0%) of the 988 women had a repeat abortion. Users of long-acting reversible contraception (LARC) had fewer repeat abortions compared with users of non-LARC methods. Overall repeat abortion was 0.8% in subcutaneous contraceptive implant users, 1.5% in intrauterine contraceptive device (IUCD) users, 2.8% in vaginal ring users and 5.8% in oral contraceptives users (p < 0.05). Cox hazards ratio (HR) analysis showed that method choice after abortion correlated significantly with the probability of repeat abortion (p < 0.05). Using women choosing oral contraception as the reference group, the HRs (95% CIs) for repeat abortion were as follows: IUCD 0.282 (0.084, 0.942), contraceptive implant 0.142 (0.019, 1.050), vaginal ring 0.508 (0.175, 1.477). Conclusion Even though highly effective contraceptive methods are freely accessible in Portugal, other challenges must be managed to improve outcomes, such as a timely, patient-centred counselling approach.

Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families

BackgroundThe causes for thousands of individually rare recessive diseases have been discovered since the adoption of next generation sequencing (NGS). Following the molecular diagnosis in older children in a family, parents could use this information to opt for fetal genotyping in subsequent pregnancies, which could inform decisions about elective termination of pregnancy. The use of NGS diagnostic sequencing in families has not been demonstrated to yield benefit in subsequent pregnancies to reduce recurrence. Here we evaluated whether genetic diagnosis in older children in families supports reduction in recurrence of recessive neurogenetic disease.MethodsRetrospective study involving families with a child with a recessive pediatric brain disease (rPBD) that underwent NGS-based molecular diagnosis. Prenatal molecular testing was offered to couples in which a molecular diagnosis was made, to help couples seeking to prevent recurrence. With this information, families made decisions about elective termination. Pregnancies that were carried to term were assessed for the health of child and mother, and compared with historic recurrence risk of recessive disease.ResultsBetween 2010 and 2016, 1172 families presented with a child a likely rPBD, 526 families received a molecular diagnosis, 91 families returned to the clinic with 101 subsequent pregnancies, and 84 opted for fetal genotyping. Sixty tested negative for recurrence for the biallelic mutation in the fetus, and all, except for one spontaneous abortion, carried to term, and were unaffected at follow-up. Of 24 that genotyped positive for the biallelic mutation, 16 were electively terminated, and 8 were carried to term and showed features of disease similar to that of the older affected sibling(s). Among the 101 pregnancies, disease recurrence in living offspring deviated from the expected 25% to the observed 12% ([95% CI 0·04 to 0·20], p = 0·011).ConclusionsMolecular diagnosis in an older child, coupled with prenatal fetal genotyping in subsequent pregnancies and genetic counselling, allows families to make informed decisions to reduce recessive neurogenetic disease recurrence.

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

BackgroundThe crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies reported that autophagy can induce immune tolerance at the maternal fetal interface, while the mechanism remains unclear.MethodsAutophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. After co-cultured with trophoblast cells pretreated with 3-MA or rapamycin, NK cells were collected and the expression of killer receptors was detected by flow cytometry (FCM). The invasiveness of trophoblasts was tested by Cell invasion assay.ResultsCompared with elective pregnancy termination patients, the level of autophagy in the villi of RSA patients was significantly decreased. Inducing the autophagy level in trophoblast cells with rapamycin could significantly inhibit the cytotoxicity of NK cells in the co-culture system, and supplement of IGF-2 could rectify this effect. Meanwhile, autophagy suppression of trophoblasts reduced the level of Paternally Expressed Gene 10 (PEG10), leading to the impairment of trophoblast cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. In pregnant mice model, injection with 3-MA promoted the cytotoxicity of uterine NK cells, and increased the embryo absorption rate.ConclusionAutophagy suppression of trophoblasts increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.D8gv_yNUxy6MbMWPNKGsqRVideo Abstarct

Ulipristal acetate and pregnancy outcome-an observational study.

Is the failure of the selective progesterone receptor modulator ulipristal acetate (UPA) as emergency contraception (EC; 30mg, single) or inadvertent exposure for myoma treatment (5mg/d) in pregnancy associated with a higher risk of birth defects, spontaneous abortion (SAB) or elective termination of pregnancy (ETOP)? We did not find an increased risk for birth defects, SABs or ETOPs after UPA exposure during implantation and early embryogenesis. 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. 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. 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. 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). Our limited sample size does not allow concluding safety of UPA use in pregnancy. 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. 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. Registered with the German Clinical Trial Register (DRKS00015155).

Decidual NK cell-derived conditioned medium from miscarriages affects endometrial stromal cell decidualisation: endocannabinoid anandamide and tumour necrosis factor-α crosstalk.

What are the effects of endocannabinoid anandamide (AEA) in uterine natural killer (unK) cells from miscarriage decidua, regarding their cytokine profile and endometrial stromal cell (ESC) crosstalk? uNK-conditioned media from miscarriage samples present high TNF-α levels which inhibit ESC decidualisation. AEA plasma levels are higher in women who have suffered a miscarriage. Moreover, AEA inhibits ESC proliferation and differentiation, although the levels and impact on the uNK cell cytokine profile at the feto-maternal interface remain elusive. This laboratory-based study used human primary uNK cells which were isolated from first-trimester decidua (gestational age, 5-12weeks) derived from 8 women with elective pregnancy termination and 18 women who suffered a miscarriage. The first-trimester placental tissues were assayed for AEA levels by UPLC-MS/MS and respective enzymatic profile by western blot. The uNK cells were isolated and maintained in culture. The expression of angiogenic markers in uNK cells was examined by quantitative PCR (qPCR). The uNK-conditioned medium was analysed for IFN-γ, TNF-α and IL-10 production by enzyme-linked immunosorbent assay, and the impact on ESC differentiation was assessed by measuring decidual markers Prl, Igfbp-1 and Fox01 mRNA expression using qPCR. AEA levels were higher in miscarriage decidua compared with decidua from elective terminations. The uNK cell-conditioned medium from the miscarriage samples exhibited high TNF-α levels and interfered with the decidualisation of ESCs. Exacerbated inflammation and elevated TNF-α levels at the feto-maternal interface may trigger AEA signalling pathways that, in turn, may impact decidualisation and the angiogenic ability of uNK cells. N/A. Primary uNK cell responses are based on a simple in vitro model. Thus, in complex microenvironments, such as the feto-maternal interface, the mechanisms may not be exactly the same. Also, the inflammatory events of miscarriage that, in this study, have happened prior to processing of the samples may cause different responses to that observed. In addition, the magnitude of the inflammatory response, required to trigger the AEA pathways that impact decidualisation and the uNK angiogenic ability in vivo, is still unclear. The endocannabinoid AEA is a modulator of reproductive competence. AEA not only may contribute to neuroendocrine homeostasis but also can take part in uterine changes occurring during early pregnancy. The work was supported by UID/MULTI/04378/2019 with funding from Fundação para a Ciência e a Tecnologia (FCT)/MCTES through national funds and PORTUGAL 2020 Partnership Agreement, NORTE-01-0145-FEDER-000024. S.C. Cunha acknowledges FCT for the IF/01616/2015 contract. There are no conflicts of interest.

Placental transporter-mediated drug interactions and offspring congenital anomalies.

AimsP‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) are efflux transporters expressed in the placenta, limiting their substrates from reaching the foetus. Our aim was to investigate if concomitant prenatal exposure to several substrates or inhibitors of these transporters increases the risk of congenital anomalies.MethodsThe national Drugs and Pregnancy database, years 1996–2014, was utilized in this population‐based birth cohort study. In the database, the Medical Birth Register, the Register on Induced Abortions, the Malformation register and the Register on Reimbursed Drug Purchases have been linked. The University of Washington Metabolism and Transport Drug Interaction Database was used to identify substrates and inhibitors of P‐gp and BCRP. We included singleton pregnancies ending in birth or elective termination of pregnancy due to foetal anomaly. Known teratogens were excluded. We identified women exposed 1 month before pregnancy or during the first trimester to P‐gp/BCRP polytherapy (n = 21 186); P‐gp/breast cancer resistance protein monotherapy (n = 97 906); non‐P‐gp/BCRP polytherapy (n = 78 636); and unexposed (n = 728 870). We investigated the association between the exposure groups and major congenital anomalies using logistic regression adjusting for several confounders.ResultsThe prevalence of congenital anomalies was higher in the P‐gp/BCRP polytherapy group (5.5%) compared to the P‐gp/BCRP monotherapy (4.7%, OR 1.13; 95% CI 1.05–1.21), the non‐P‐gp/BCRP polytherapy (4.9%, OR 1.14; 95% CI 1.06–1.22), and to the unexposed groups (4.2%, OR 1.23; 95% CI 1.15–1.31).ConclusionThe results suggest a role of placental transporter‐mediated drug interactions in teratogenesis.

Latencia al parto tras cerclaje de emergencia en gestación múltiple

IntroductionCurrent guidelines support the use of physical-examination indicated cerclage (PEIC) as a treatment for cervical insufficiency and membrane exposure in single pregnancies. However, PEIC in twin pregnancies is a controversial issue as no data from random clinical trial are available to demonstrate its efficacy. Few studies suggest that PEIC may prolong pregnancy also in twin pregnancies. The aim of this study was to evaluate the results of twin pregnancies that underwent a PEIC in our health centre. Material and methodsA retrospective review was performed on women that underwent a PEIC from 2007-2016 in our centre. Women were not eligible if they were carrying foetuses with major foetal anomalies, more than two foetuses or monochorionic-monoamniotic pregnancies, or three or more foetuses or requesting an elective termination of pregnancy. Primary outcomes: latency to spontaneous delivery and gestational age (GA) at delivery. Secondary outcomes: neonatal mortality and Neonatal Intensive Care Unit admission, preterm premature rupture of membranes (PPROM), chorioamnionitis and cerclage displacement. ResultsThe study included a total of 17 women. The median (inter-quartile range) gestational age at delivery was 27.1 (24.5-32.3) weeks, and median (inter-quartile range) latency, from cervical cerclage to delivery, was 43 (21-64) days. There were 4/17 (23.5%) cases of delivery before 24 weeks of pregnancy, and 2/26 (7.7%) cases of neonatal death. DiscussionThese results suggest that latency to delivery after PEIC in twins is remarkable. Therefore, it could be considered as an optional management. Nevertheless, evidence based on random clinical trial is required to make firm recommendations on its formal use.

Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden.

BackgroundOur aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD).MethodsThis cohort study used Finnish (1996–2014) and Swedish (2005–2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity.ResultsAmong 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31–0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06–2.78).ConclusionIn this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

761: Reversal of intention for elective termination of pregnancy is associated with inadequate prenatal care utilization

More than half of all pregnancies in the U.S. are unintended; 18% result in elective termination of pregnancy (TOP). Some women seek TOP but ultimately elect for pregnancy continuation. This subset is more likely to have delayed entry into care and less likely to attend a postpartum visit. Data is limited about their utilization of routine prenatal care. The purpose of this study was to determine if reversal of intention for TOP is associated with differences in prenatal care (PNC) utilization. Retrospective cohort study of subjects presenting for obstetrical dating ultrasound (US) from 2011-2017 at academic medical center offering TOP until 24 weeks. “Contemplators” (CON) were subjects completing US with intention of TOP who instead continued the same pregnancy to live birth. A 2:1 group of non-contemplators (NCON) were selected who completed US and continued to live birth. Primary outcome was difference in PNC utilization; adequate PNC defined as “Adequacy of Prenatal Care Utilization Index” (API) score ≥14 points. Secondary outcomes included median API score, adverse pregnancy outcomes, and postpartum contraception plan. There were 93 CON and 186 NCON. Significant demographic differences noted between groups (Table 1). Inadequate PNC utilization was more common in CON compared to NCON (47.3% vs 71.0%; OR 0.70 (0.57-0.86); p< 0.01). Significance remained after adjusting for differences in maternal characteristics (aOR 0.48 (0.28-0.90)). CON had significantly lower scores on API (median 13 (2-18) vs 15 (5-18), p< 0.01). No differences in adverse pregnancy outcomes between groups (Table 2). A post-partum contraception plan was significantly higher in CON (aOR 4.16 (1.83-9.47); p< 0.01). Reversal of intention for TOP is associated with inadequate PNC utilization. The study was underpowered to detect a difference in adverse pregnancy outcomes. Focus towards interventions to address this health care disparity in this population is imperative.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

BackgroundMedical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains.ObjectivesTo examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries.MethodsWe conducted an observational study, using data from 24 population‐ and hospital‐based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution.ResultsBetween years 2001 and 2012, the overall first‐week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first‐week mortality occurred on the first day of life. In programmes where information on long‐term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%‐96% in Europe, and 86%‐96% in North America.ConclusionsOur multi‐country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.

Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

Genome amplification and cellular senescence are hallmarks of human placenta development

These authors studied human placental and decidual tissues obtained from elective pregnancy terminations (6–12 weeks gestation). Placental extravillous trophoblasts (EVTs), the cells that rapidly invade the mother’s endometrium, undergo an initial stage of genomewide amplification leading to a ‘tetraploid’ chromosomal state (XXYY or XXXX) followed by cellular senescence. By contrast, cells from androgenic complete hydatidiform moles (CHM) fail to show normal senescence.

Congenital anomalies and associated risk factors in a Saudi population: a cohort study from pregnancy to age 2 years

ObjectiveTo assess the three key issues for congenital anomalies (CAs) prevention and care, namely, CA prevalence, risk factor prevalence and survival, in a longitudinal cohort in Riyadh, Saudi Arabia.SettingTertiary care...

Prediction of Adverse Pregnancy Outcomes in Women with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease associated with major obstetrical complications such as gestational loss, preterm delivery, fetal growth restriction (FGR) and preeclampsia. Published literature is not consensual regarding the main risk factors for each of these outcomes. Our goal with this study was to determine the most important predictors for each of the main adverse pregnancy outcomes in this population. We conducted a retrospective cohort study of unifetal pregnancies of women with the diagnosis of SLE followed in our unit between January 1994 and December 2016. We excluded elective terminations of pregnancy and cases lost to follow-up and we analyzed 157 pregnancies (128 women). Multiple logistic regression models for the outcomes gestational loss, preterm delivery, fetal growth restriction, and preeclampsia were built. Two-sided p-values of < 0.05 were used to determine statistical significance, and two-sided confidence intervals of 95% are reported. In our cohort, the main risk factors for gestational loss were maternal age and the presence of antiphospholipid antibodies. Lupic nephritis was predictive of a preterm delivery and preeclampsia. Renal involvement and lupus flares during pregnancy were risk factors for FGR. Overall, the main risk factor for an adverse pregnancy outcome were lupus flares during pregnancy. Despite optimal pregnancy monitoring, women with SLE are still at risk for adverse pregnancy outcomes. Risk stratification for each of these outcomes is crucial for an effective counselling and tailored monitoring.

En bloc hysterectomy for treatment of symptomatic cervical varix in the early second trimester

The authors present a case of a cervical varix with morbidly adherent placentation treated with total abdominal hysterectomy. A 38-year-old presented at 15 weeks gestation with heavy painless vaginal bleeding and was found to have complete placenta previa and a cervical varix. After recurrent episodes of heavy bleeding requiring transfusion, she elected pregnancy termination. She underwent en block total abdominal hysterectomy with the fetus in utero at 18 weeks gestation. Pathology revealed dilated vessels at the cervical os and placenta percreta. The authors conclude that en bloc abdominal hysterectomy may be a reasonable management option to reduce hemorrhage risk in patients with a symptomatic cervical varix in the setting of a morbidly adherent placenta.

Hypospadias Prevalence and Trends in International Birth Defect Surveillance Systems, 1980–2010

BackgroundHypospadias is a common male birth defect that has shown widespread variation in reported prevalence estimates. Many countries have reported increasing trends over recent decades. ObjectiveTo analyze the prevalence and trends of hypospadias for 27 international programs over a 31-yr period. Design, setting, and participantsThe study population included live births, stillbirths, and elective terminations of pregnancy diagnosed with hypospadias during 1980–2010 from 27 surveillance programs around the world. Outcome measurements and statistical analysisWe used joinpoint regression to analyze changes over time in international total prevalence of hypospadias across programs, prevalence for each specific program, and prevalence across different degrees of severity of hypospadias. Results and limitationsThe international total prevalence of hypospadias for all years was 20.9 (95% confidence interval: 19.2–22.6) per 10000 births. The prevalence for each program ranged from 2.1 to 39.1 per 10000 births. The international total prevalence increased 1.6 times during the study period, by 0.25 cases per 10000 births per year (p<0.05). When analyzed separately, there were increasing trends for first-, second-, and third-degree hypospadias during the early 1990s to mid-2000s. The majority of programs (61.9%) had a significantly increasing trend during many of the years evaluated. Limitations include known differences in data collection methods across programs. ConclusionsAlthough there have been changes in clinical practice and registry ascertainment over time in some countries, the consistency in the observed increasing trends across many programs and by degrees of severity suggests that the total prevalence of hypospadias may be increasing in many countries. This observation is contrary to some previous reports that suggested that the total prevalence of hypospadias was no longer increasing in recent decades. Patient summaryWe report on the prevalence and trends of hypospadias among 27 birth defect surveillance systems, which indicate that the prevalence of hypospadias continues to increase internationally.