Maternal and fetal outcomes in pregnancy complicated by pre-existing lupus nephritis: Insights from a developing country Pakistan.

BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.

Anti-TPO-mediated specific features of the placenta immunohistochemical profile and possible mechanisms for fetal loss.

Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-ß, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P < .01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-ß was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.

Feto-maternal outcomes of pregnancies in women with SLE: Experience from a tertiary care center of Asia.

OBJECTIVE: We aim to quantify the risk of maternal and fetal complications in patients with SLE in order to identify the impact of SLE on pregnancy and of pregnancy on SLE. METHODS: This retrospective record review study was conducted in Aga khan university hospital, Karachi, from Jan 1998 to Dec 2019. All pregnant patients with SLE diagnosed and delivered during this time were included in the study. Categorical variables were analyzed by using chi-square test and fisher exact test. Whereas quantitative point estimate was estimated as mean and SD. We matched the data and computed crude odds ratio of pre-eclamptic patients with respect to age of conception, gravida, and body mass index in both case and control group. RESULTS: The SLE disease activity was monitored during pregnancy under SLEDAI-2K Scoring system. The patients with mild (25.6%) and moderate (25.6%) disease activity were prevalent and most antenatal patients (51.7%) had flare up in third trimester. Adverse maternal outcomes include pre-eclampsia (28.8%), eclampsia (3.2%), cesarean section (57.6%), and thrombocytopenia (9.6%), whereas perinatal outcomes includes intrauterine growth retardation (24%), preterm birth <34 weeks (19.2%) and <37 weeks (63.2%), APGAR Score < 7 at 1 min (5.6%), and neonatal death (5.6%) found to be statistically significant in between two groups There were more high-risk patients (42) with positive IgG (88%), IgM (83.3%), and lupus anticoagulant (33.3%) as compared to low-risk APS group. CONCLUSION: Planned pregnancy and less severe disease flares during pregnancy is associated with more favorable feto-maternal outcomes.

Open versus laparoscopic appendectomy for acute appendicitis in pregnancy: a population-based study.

BACKGROUND: Laparoscopic appendectomy (LA) is the standard treatment for acute appendicitis (AA) in general population. However, the safety of LA during pregnancy has remained a matter of debate. The purpose of this study was to compare surgical and obstetrical outcomes in pregnant women who underwent LA vs. open appendectomy (OA) for AA. We hypothesized that LA results in improved surgical and obstetric outcomes during pregnancy. METHODS: Using a nationwide claim-based database in Estonia, a retrospective review of all cases of pregnant women undergoing OA or LA for AA from 2010 to 2020 was performed. Patient characteristics, surgical and obstetrical outcomes were analyzed. Primary outcomes were preterm delivery, fetal loss and perinatal mortality. Secondary outcomes included operative time, hospital length of stay (HLOS) and 30-day postoperative complications. RESULTS: Overall, 102 patients were included of whom 68 (67%) underwent OA and 34 patients (33%) LA, respectively. Patients in LA cohort had a significantly shorter length of pregnancy in terms of gestational weeks when compared to OA cohort (12 weeks versus 17 weeks, p = 0.002). Most of the patients in their 3rd trimester pregnancy were subjected to OA. Operative time in LA cohort was shorter than in OA cohort (34 min. versus 44 min., p = 0.038). HLOS in LA cohort was shorter than in OA cohort (2.1 days versus 2.9 days, p = 0.016). There were no differences between OA and LA cohorts in terms of surgical complications or obstetrical outcomes. CONCLUSIONS: Laparoscopic appendectomy for acute appendicitis was associated with a significantly shorter operative time and a shorter hospital length of stay while open and laparoscopic appendectomy cohorts experienced comparable obstetrical outcomes. Our findings support the laparoscopic approach for acute appendicitis in pregnancy.

Association of Genetic Polymorphisms in Long Noncoding RNA HOTTIP with Risk of Idiopathic Recurrent Spontaneous Abortion.

The clustered homeobox gene family known as the Hox family plays a fundamental role in the morphogenesis of the vertebrate's embryo. A long noncoding RNA (lncRNA), known as HOTTIP (HOXA transcript at the distal tip), has been functionally characterized and contributed to the pathogenesis of various conditions. The current case-control study was undertaken to examine the gene frequencies and shared alleles of the HOTTIP  gene in Iranian participants with or without idiopathic recurrent spontaneous abortion (RSA). Both ARMS-PCR reaction and RFLP-PCR techniques were employed to detect three HOTTIP polymorphisms (rs2023843C/T, rs78248039A/T, and rs1859168C/A) in a DNA sample of 161 women with RSA and 177 healthy women. We found that the TT genotype of the HOTTIP rs2023843 C/T polymorphism was associated with a lower risk for idiopathic RSA. In contrast, the TT genotype of the HOTTIP rs78248039 A/T polymorphism was correlated with an enhanced risk of RSA. The presence of the A-allele for HOTTIP rs1859168 C/A polymorphism was associated with an increased risk for idiopathic RSA. Haplotype analysis showed that the T/T/A, C/T/A, T/T/C, and T/A/A haplotypes of rs2023843/rs78248039/rs1859168 enhanced RSA susceptibility. Computational analysis predicted that this lncRNA might act as a potential sponge for some microRNAs; therefore, affecting the expression of genes being targeted by them. In addition, both rs2023843 and rs1859168 variants could alter the local secondary structure of HOTTIP. Our results showed that HOTTIP rs2023843C/T, rs78248039A/T, and rs1859168C/A polymorphisms may confer genetic susceptibility to idiopathic RSA in an Iranian population.

Fetal Loss and Preterm Birth Caused by Intraamniotic Haemophilus influenzae Infection, New Zealand.

Invasive Haemophilus influenzae infection during pregnancy can cause preterm birth and fetal loss, but the mechanism is unclear. We investigated 54 cases of pregnancy-associated invasive H. influenzae disease in 52 unique pregnancies in the Auckland region of New Zealand during October 1, 2008‒September 30, 2018. Intraamniotic infection was identified in 36 (66.7%) of 54 cases. Outcome data were available for 48 pregnancies. Adverse pregnancy outcomes, defined as fetal loss, preterm birth, or the birth of an infant requiring intensive/special care unit admission, occurred in 45 (93.8%) of 48 (pregnancies. Fetal loss occurred in 17 (35.4%) of 48 pregnancies, before 24 weeks' gestation in 13 cases, and at >24 weeks' gestation in 4 cases. The overall incidence of pregnancy-associated invasive H. influenzae disease was 19.9 cases/100,000 births, which exceeded the reported incidence of pregnancy-associated listeriosis in New Zealand. We also observed higher rates in younger women and women of Maori ethnicity.

Performance of Ductus Venosus Doppler (at 11-13 + 6 Weeks) in Predicting Adverse Fetal Outcomes in Indian Population: Going Beyond Aneuploidies: Going Beyond Aneuploidies.

OBJECTIVES: The objective of this study is to examine the performance of Ductus venosus (DV) Doppler done at the routine first trimester screening (11-13 + 6 weeks) in predicting the adverse fetal outcomes in Indian population. METHODS: This observational study was conducted between 2013 and 2019, on 4340 singleton pregnancies. Ductus Doppler were considered abnormal if DV pulsatility index values were >95th centile for that gestation or with a reversed "a" wave. Anatomical survey was done to rule out other abnormalities. Women were followed up till delivery and outcomes were divided into 4 groups: 1) aneuploidies; 2) cardiac defects; 3) non-cardiac structural abnormalities; and 4) miscarriages before 24 weeks or fetal deaths after 24 weeks. RESULTS: Prevalence of abnormal DV Doppler is 5.12% (205/4004). There were significantly higher number of fetal losses (4.4 versus 0.3%), aneuploidies (10.2 versus 1.7%), fetal cardiac defects (5.9 versus 1.4%), and non-cardiac structural defects (5.4 versus 1.4%) among the pregnancies with abnormal DV Doppler in comparison to those with normal flow (P < .001). Logistic regression analysis has shown that significant contribution to fetal chromosomal abnormalities and cardiac defects was associated with abnormal DV. Other factors which were found to have a significant association with adverse fetal outcome were increased nuchal translucency and increased body mass index (BMI). CONCLUSION: DV Doppler in first trimester can be used as a screening tool for cardiac defects and fetal deaths. Women with abnormal DV Dopplers should be offered fetal echocardiography at 18-22 weeks and third trimester growth scans with Dopplers.

A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice.

Benzophenone-3 (BP-3) is widely used in a variety of cosmetics and is prevalent in drinking water or food, and women were under notable high exposure burden of BP-3. Reports show the associations between prenatal exposure to BP-3 and the risk of fetal loss, but its underlying mechanism remains largely unknown. Pregnant ICR mice were gavaged with BP-3 from gestational day (GD) 0 to GD 6 at doses of 0.1, 10 and 1000 mg/kg/day. The samples were collected on GD 12. Ultra-performance liquid chromatography coupled with mass spectrometry-based metabolomics was used to detect metabolome changes in fetal mice, the uterus and the placenta to identify the underlying mechanism. The results showed that the body weight and relative organ weights of the liver, brain and uterus of pregnant mice were not significantly changed between the control group and the treatment group. BP-3 increased fetal loss, and induced placental thrombosis and tissue necrosis with enhancement of platelet aggregation. Metabolomic analysis revealed that fructose and mannose metabolism, the TCA cycle, arginine and proline metabolism in the fetus, arginine and proline metabolism and biotin metabolism in the uterus, and arginine biosynthesis and pyrimidine metabolism in the placenta were the key changed pathways involved in the above changes. Our study indicates that exposure to BP-3 can induce placental thrombosis and fetal loss via the disruption of maternal and fetal metabolism in mice, providing novel insights into the influence of BP-3 toxicity on the female reproductive system.

Outcome of antenatal invasive diagnostic tests in a fetal medicine unit with low case load in North Wales, United Kingdom.

The aim of this retrospective cohort study was to review rate of miscarriage following antenatal invasive diagnostic procedures from a unit where relatively low annual numbers of procedures are undertaken. Data were analysed for 201 chorionic villous samplings (CVSs) performed between January 2007 and June 2019 and 511 amniocenteses performed between January 2008 and June 2019, in singleton pregnancies. The miscarriage rates after CVS was 0% at 48 hours, 0.6% at 2 weeks and 2.5% up to 24 weeks of gestation. All four miscarriages following CVS had significant inherent high-risk features, therefore, it would be inappropriate to attribute these losses solely to the procedure itself. None of the women who had an amniocentesis had a miscarriage during the study period. We did not find a causal association between number of invasive procedures performed by an operator and miscarriage rate in our setting even with low annual numbers of invasive procedures.Impact StatementWhat is already known on this subject? Royal College of Obstetricians and Gynaecologists (RCOG) of UK recommends a minimum of at least 30 CVSs or amniocenteses procedures per year for a practitioner in order to maintain skills. A centre performing more fetal invasive procedures has lower miscarriage rates due to more experience of practitioners.What the results of this study add? This study is the first long-term audit data from a smaller fetal medicine unit with relatively low annual case load, suggesting that miscarriage risk may actually be lower than the current understanding. No additional risk of miscarriage or pregnancy loss following fetal invasive procedures even with relatively low annual numbers than that recommended by the RCOG.What the implications are of these findings for clinical practice and/or further research? The findings of this study are important in the era of non-invasive prenatal testing which will see the overall number of fetal invasive procedures decline with time. Competence in safely undertaking antenatal invasive procedure can possibly be maintained with lower annual procedure numbers. Units undertaking low number of antenatal invasive procedure must continuously audit their practice to ensure satisfactory standards and outcomes. More research is needed from smaller units to corroborate or refute the findings of this study.

Pregnant patients requiring appendectomy: comparison between open and laparoscopic approaches in NY State.

INTRODUCTION: Even though acute appendicitis is the most common general surgical condition encountered during pregnancy, the preferred approach to appendectomy in pregnant patients remains controversial. Current guidelines support laparoscopic appendectomy as the treatment of choice for pregnant women with appendicitis, regardless of trimester. However, recent published data suggests that the laparoscopic approach contributes to higher rates of fetal demise. Our study aims to compare laparoscopic and open appendectomy in pregnancy at a statewide population level. METHODS: ICD-9 codes were used to extract 1006 pregnant patients undergoing appendectomy between 2005 and 2014 from the NY Statewide Planning and Research Cooperative System (SPARCS) database. Surgical outcomes (any complications, 30-day readmission rate, length of stay (LOS)) and obstetrical outcomes (antepartum hemorrhage, preterm delivery, cesarean section, sepsis, chorioamnionitis) were compared between open and laparoscopic appendectomy. Multivariable generalized linear regression models were used to compare different outcomes between two surgical approaches after adjusting for possible confounders. RESULTS: The laparoscopic cohort (n = 547, 54.4%) had significantly shorter LOS than the open group (median ± IQR: 2.00 ± 2.00 days versus 3.00 ± 2.00 days, p value < 0.0001, ratio = 0.789, 95% CI 0.727-0.856). Patients with complicated appendicitis had longer LOS than those with simple appendicitis (p value < 0.0001, ratio = 1.660, 95% CI 1.501-1.835). Obstetrical outcomes (p value = 0.097, OR 1.254, 95% CI 0.961-1.638), 30-day non-delivery readmission (p value = 0.762, OR 1.117, 95% CI 0.538-2.319), and any complications (p value = 0.753, OR 0.924, 95% CI 0.564-1.517) were not statistically significant between the laparoscopic versus open appendectomy groups. Three cases of fetal demise occurred, all within the laparoscopic appendectomy group. CONCLUSIONS: The laparoscopic approach resulted in a shorter LOS. Although fetal demise only occurred in the laparoscopic group, these results were not significant (p value = 0.255). Our large population-based study further supports current guidelines that laparoscopic appendectomy may offer benefits over open surgery for pregnant patients in any trimester due to reduced time in the hospital and fetal and maternal outcomes comparable to open appendectomy.

Comparison of pregnancy outcomes after second trimester amniocentesis between procedures performed by experts and non-experts.

OBJECTIVES: To compare the rate of fetal loss in pregnancy after second trimester amniocentesis between procedures performed by experts and non-experts and to assess other pregnancy complications as secondary outcomes. METHODS: A retrospective cohort study was performed on singleton pregnancies that underwent mid-trimester amniocenteses in a single institution. The fetal loss rates of procedures performed by experts and non-experts were collected and analyzed. Other adverse pregnancy outcomes were also examined. RESULTS: In total, 14,450 amniocenteses were performed during the study period. These included 11,357 (78.6%) procedures in the group expert operators and 3,093 (21.4%) procedures in the group non-expert operators. In the non-expert group, the fetal loss rate was slightly increased but not significantly (p=0.24).In addition, the higher number of spontaneous abortions was associated with blood-stained amniotic fluid sample (p<0.001; RR=9.28). Multiple needle insertions also increased in the non-expert group significantly. However, no difference in pregnancy outcomes was found between in single and multiple needle insertions. CONCLUSIONS: The amniocentesis procedures performed by the non-experts was not increase the fetal loss rate. However, the other adverse pregnancy outcomes, including preterm birth, low birth weight and fetal growth restriction were significantly increased in the non-expert group.

Fetal Genetic Diagnosis by Chorionic Villus Sampling: Evaluation of the Five-Year Experience from a Single Center.

OBJECTIVE: We summarized our five-year chorionic villus sampling (CVS) experience with indications, detected chromosomal abnormalities and pregnancy outcomes. Materials and Methods: This retrospective study examined 552 patients underwent CVS for prenatal diagnosis between 2014 and 2018. Results: The most frequent patients undergoing CVS indications were abnormal aneuploidy screening results, increased nuchal translucency, and cystic hygroma/edema. Of 552 CVS, 385 were normal, 141 abnormal. Eight were contaminated with maternal cells, 4 were mosaics, in 12 the culture failed, and in 2 there was inadequate sampling. The most frequent chromosomal abnormalities were trisomy 21, trisomy 18 and 45,X. Of 246 followed pregnancies, there were 165 live-births (67,1%), 58 pregnancy terminations (23,6%), and 23 pregnancy losses (9,3%). There were 5 procedure-related losses (2%), 3 of which were chromosomally normal. Conclusion: Although significant advances have been made in noninvasive methods such as NIPT, CVS is still a reliable technique for cytogenetic diagnosis in early gestation.

Prediction of pregnancy loss by early first trimester ultrasound characteristics.

BACKGROUND: Pregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed toward distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction. OBJECTIVES: To identify routinely measured features of the early first trimester ultrasound and the gestational age-specific cut-points that are most predictive of pregnancy loss. MATERIALS AND METHODS: This was a secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6 weeks 0 days and 8 weeks 6 days. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks, respectively, and 95% confidence intervals between jointly categorized low fetal heart rate, small crown-rump length, and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation. RESULTS: A total of 64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 women (88.5%) had a live birth. Low fetal heart rate and small crown-rump length (≤122, 123, and 158 bpm; ≤6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (relative risk, 2.08; 95% confidence interval, 1.24-2.91). The combination of low fetal heart rate and small crown-rump length was linked to a 16% (95% confidence interval, 9.1-23%) adjusted absolute increase in risk of subsequent loss, from 5.0% (95% confidence interval, 1.5-8.5%) to 21% (95% confidence interval, 15-27%). Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss. CONCLUSION: Identified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. The specified criteria should not be used to diagnose nonviability.

Vaginal bleeding and nausea in early pregnancy as predictors of clinical pregnancy loss.

BACKGROUND: Although nausea and vaginal bleeding are commonly experienced in early pregnancy, their prognostic value in predicting clinical pregnancy loss is not well understood. OBJECTIVE: This study aimed to understand whether timing of bleeding and nausea symptoms can be used to predict risk of pregnancy loss among women with ultrasound-confirmed pregnancies. STUDY DESIGN: A cohort of 701 women with clinically confirmed pregnancies and 1 to 2 previous pregnancy losses were preconceptionally enrolled in the Effects of Aspirin in Gestation and Reproduction trial (2006-2012). Participants completed daily symptom diaries from 2 to 8 weeks' gestation and were prospectively monitored for detection of pregnancy loss. The risk of pregnancy loss was estimated for each observed bleeding and nausea pattern, and positive and negative predictive values for each pattern were calculated. RESULTS: Among 701 women, 211 (30.1%) reported any vaginal bleeding, and 639 (91.2%) reported any nausea. Most bleeding experienced by women was spotting and contained within a single episode. Within 2 to <4, 4 to <6, and 6 to 8 weeks' gestation, vaginal bleeding occurred in 5.9% (41) (5.7% live birth, 7.1% clinical pregnancy loss), 14.6% (102) (13.9% live birth, 18.6% clinical pregnancy loss), and 20.8% (146) (18.4% live birth, 32.4% clinical pregnancy loss) of women, respectively. Within the same gestational periods, nausea was reported in 22.7% (159) (23.2% live birth, 20.4% clinical pregnancy loss), 65.9% (462) (67.5% live birth, 58.4% clinical pregnancy loss), and 87.0% (610) (90.6% live birth, 69.0% clinical pregnancy loss) of women. Women who had bleeding without nausea between 6 and 8 weeks' gestation (3.6% prevalance) had the greatest risk of clinical pregnancy loss (risk difference=56.1%; 95% confidence interval, 37.6-74.7), a positive predictive value of 68.0% (49.7%, 86.3%), negative predictive value of 85.8% (83.2%, 88.4%), positive likelihood ratio of 11.1 (2.04, 20.1), and negative likelihood ratio of 0.86 (0.79, 0.93). Nausea and bleeding are clinical factors that predicted clinical pregnancy loss (area under the curve, 0.87; 95% confidence interval, 0.81-0.88) similar to age, body mass index, blood pressure, and waist-to-hip ratio (area under the curve, 0.81; 95% confidence interval, 0.78-0.88) measured preconceptionally. CONCLUSION: Women experiencing bleeding without nausea between 6 and 8 weeks' gestation had an increased risk of clinical pregnancy loss. Bleeding and nausea were not predictive risk factors of clinical pregnancy loss prior to 6 weeks' gestation.

Adverse pregnancy outcomes among multi-ethnic systemic lupus erythematosus patients in Malaysia.

BACKGROUND: Despite the improvement in the live birth rate among patients with systemic lupus erythematosus (SLE), they are still at an increased risk of adverse pregnancy outcomes (APOs). OBJECTIVE: To determine the prevalence and factors associated with APOs in the multi-ethnic SLE populations in Malaysia.Methodology: This was a retrospective review of the consecutive SLE patients who attended the outpatient clinic in two major rheumatology centres from January 2016 until December 2019 with complete pre-pregnancy, antenatal and intra-partum records. APOs include pregnancy loss, prematurity, pre-eclampsia, intra-uterine growth restriction (IUGR) and maternal death. Univariate and multivariable logistic regression with generalised estimating equation (GEE) analyses were performed to determine the factors associated with APOs. RESULTS: A total of 153 patients with 240 pregnancies were included and the majority of the patients were Malay (69.9%), followed by Chinese (24.2%) and Indian (5.9%). The prevalence of APOs was 61.7% with the commonest complication being prematurity (28.3%), followed by pregnancy loss (24.6%) and pre-eclampsia (21.8%). Logistic regression model-based GEE analysis revealed that the independent predictors of APOs were active haematological system during pregnancy, pre-pregnancy active disease, Indian patients and positive lupus anticoagulant. Hydroxychloroquine use was associated with lower APOs including pre-eclampsia, prematurity and IUGR in the univariate analyses but it was no longer significant in the GEE analysis. CONCLUSION: The prevalence of APOs was high particularly among the Indian patients. Positive lupus anticoagulant and pre-pregnancy active disease were the factors strongly associated with APOs in our multi-ethnic cohort. Hydroxychloroquine may protect against APOs but further larger studies are needed to confirm this.

Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls. RESULTS: Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS. CONCLUSION: The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Riesgo de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas en un embarazo de gemelos: revisión sistemática y metaanálisis OBJETIVO: Evaluar la tasa de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas (BVC) en un embarazo de gemelos. MÉTODOS: Se hizo una búsqueda en las bases de datos MEDLINE, EMBASE y Cochrane de estudios que habían reportado complicaciones relacionadas con el procedimiento después de una amniocentesis o una BVC en un embarazo de gemelos. El resultado primario fue la tasa de pérdida del feto relacionada con el procedimiento. Los resultados secundarios fueron la pérdida del feto producida antes de las 24 semanas de gestación y la pérdida del feto producida dentro de las 4 semanas posteriores al procedimiento. Se utilizaron metaanálisis cara a cara para comparar cada resultado directamente, entre las mujeres que se sometieron a una amniocentesis y las que no se sometieron a ella, y entre las mujeres que se sometieron a una BVC y las que no se sometieron a ella, así como para calcular las diferencias de riesgo (DR) combinadas entre las mujeres expuestas y las no expuestas a cada procedimiento agresivo. Además, se utilizaron los metaanálisis de proporciones para estimar las tasas combinadas de cada uno de los tres resultados en las mujeres que se sometieron a amniocentesis o a BVC y en los controles. RESULTADOS: Se incluyeron 16 estudios (3.419 embarazos de gemelos sometidos a un procedimiento agresivo y 2.517 no sometidos). Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos sometidos y no sometidos a amniocentesis mostraron un mayor riesgo de pérdida general del feto en total en los sometidos a amniocentesis (Razón de Momios (RM), 1,46 (P=0,04); DR, 0,013 (P=0,04)), mientras que no hubo diferencias en el riesgo de pérdida del feto antes de las 24 semanas de gestación (RM, 1,59 (P=0,06); DR, 0,010 (P=0,11)) ni en el de las 4 semanas posteriores al procedimiento (RM, 1,38 (P=0,3); DR, 0,003 (P=0,8)). En general, la tasa conjunta de pérdida del feto fue del 2,4% (IC 95%, 1,4-3,6%) en los embarazos de gemelos sometidos a amniocentesis, en comparación con el 2,4% (IC 95%, 0,9-4,6%) en los que no se sometieron a amniocentesis. Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos que se sometieron y que no se sometieron a una BVC no mostraron diferencias significativas ni en la pérdida del feto en total (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)) ni en la pérdida del feto antes de las 24 semanas de gestación (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)). En general, la tasa combinada de pérdida del feto fue del 2,0% (IC 95%, 0,0-6,5%) de los embarazos de gemelos sometidos a BVC, comparada con el 1,8% (IC 95%, 0,3-4,2%) de los que no se sometieron a BVC. CONCLUSIÓN: El riesgo de pérdida del feto tras la amniocentesis y la BVC en gemelos es menor que lo reportado en el pasado y la tasa de pérdida del feto antes de las 24 semanas de gestación, o dentro de las 4 semanas posteriores al procedimiento, no difiere de la del riesgo de contexto en los embarazos de gemelos que no se someten a pruebas prenatales agresivas. Estos datos pueden servir de guía para el asesoramiento prenatal de los embarazos de gemelos que se someten a procedimientos agresivos.

Cordocentesis-associated fetal loss and risk factors: single-center experience with 6650 cases.

OBJECTIVES: To identify procedural risk factors associated with fetal loss following cordocentesis and to determine the rate of cordocentesis-related fetal loss associated with the current cordocentesis protocol used in our institution. METHODS: This was a retrospective cohort study of pregnancies that underwent midpregnancy cordocentesis in a single center (a tertiary hospital, teaching school), between 1992 and 2018, based on data retrieved from our prospective database. All consecutive cases were validated to retrieve those meeting the eligibility criteria, which included: singleton pregnancy without underlying maternal disease, normal fetus (no structural or chromosomal abnormality or severe disorder), gestational age between 16 and 24 weeks at the time of the procedure and availability of pregnancy outcome. Cases that resulted in termination of pregnancy were excluded. We assessed the effect of prior cordocentesis model training on the fetal-loss rate and procedure-related complications, and evaluated potential risk factors of fetal loss secondary to cordocentesis, including procedure difficulty, placenta penetration, prolonged bleeding, fetal bradycardia, puncture site and early gestational age at procedure. Pregnancy outcomes were compared between the study group and a control group of women, who did not undergo cordocentesis, selected randomly at a 1:1 ratio from our obstetric database. RESULTS: A total of 10 343 procedures were performed during the study period, of which 6650 met the eligibility criteria and were included in the analysis. The fetal-loss rate in the first 60 procedures (early practice) of six operators (n = 360 procedures), who did not have prior model training, was significantly higher than that during the early practice of 18 operators (n = 1080 procedures) with prior model training (6.9% vs 1.6%; P < 0.001); whereas the fetal-loss rate in the next 60 procedures of practice was comparable between the two groups. After excluding the first 360 procedures of the groups without prior model training, the overall fetal-loss rate in pregnancies that underwent cordocentesis was significantly higher than that in the control group (1.6% vs 1.0%; P < 0.001). Considering the fetal-loss rate in the normal controls as background loss, the incremental cordocentesis-associated fetal-loss rate was 0.6%. Penetration of the placenta (odds ratio (OR), 2.65 (95% CI, 1.71-4.10)), prolonged bleeding from the puncture site (OR, 10.85 (95% CI, 5.27-22.36)) and presence of fetal bradycardia (OR, 3.32 (95% CI, 1.83-6.04)) during cordocentesis were independent risk factors associated with fetal loss. CONCLUSIONS: Cordocentesis model training markedly reduces fetal loss during the early learning curve of practice. Thus, cordocentesis practice without prior model training should not be acceptable. Significant procedural risk factors for fetal loss secondary to cordocentesis are placental penetration, prolonged bleeding and fetal bradycardia. Cordocentesis-related fetal loss may be only 0.6%, much lower than the rate reported previously. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Increased nuchal translucency at 11-13 weeks' gestation and outcome in twin pregnancy.

OBJECTIVE: To investigate the value of increased fetal nuchal translucency thickness (NT) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major defects or chromosomal abnormalities, we examined the value of increased NT ≥ 95th percentile in one or both fetuses in the prediction of, first, miscarriage or death of one or both fetuses at < 20 and < 24 weeks' gestation in DC, MCDA and MCMA twin pregnancies, second, death of one or both fetuses or neonates at ≥ 24 weeks in DC, MCDA and MCMA twin pregnancies, third, development of twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) treated by endoscopic laser surgery at < 20 and ≥ 20 weeks' gestation in MCDA pregnancies, and, fourth, either fetal loss or laser surgery at < 20 weeks' gestation in MCDA pregnancies. RESULTS: The study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.5%) MCDA and 55 (0.9%) MCMA pregnancies. The incidence of NT ≥ 95th percentile in one or both fetuses in DC twin pregnancies was 8.3%; in MCDA twins the incidence was significantly higher (10.4%; P = 0.016), but in MCMA twins it was not significantly different (9.1%; P = 0.804) from that in DC twins. In DC twin pregnancies, the incidence of high NT was not significantly different between those with two survivors and those with adverse outcome. In MCMA twin pregnancies, the number of cases was too small for meaningful assessment of the relationship between high NT and adverse outcome. In MCDA twin pregnancies with at least one fetal death or need for endoscopic laser surgery at < 20 weeks' gestation, the incidence of NT ≥ 95th percentile was significantly higher than in those with two survivors (23.5% vs 9.8%; P < 0.0001). Kaplan-Meier analysis in MCDA twin pregnancies showed that, in those with NT ≥ 95th percentile, there was significantly lower survival at < 20 weeks' gestation than in those with NT < 95th percentile (P = 0.001); this was not the case for survival at ≥ 20 weeks (P = 0.960). The performance of screening by fetal NT ≥ 95th percentile for prediction of either fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation was poor, with a detection rate of 23.5% at a false-positive rate of 8.9%, and the relative risk, in comparison to fetal NT < 95th percentile, was 2.640 (95% CI, 1.854-3.758; P < 0.0001). In MCDA twin pregnancies, the overall rate of fetal loss or need for laser surgery at < 20 weeks' gestation was 10.7% but, in the subgroups with NT ≥ 95th and NT ≥ 99th percentiles, which constituted 10.4% and 3.3% of the total, the rates increased to 24.1% and 40.5%, respectively. CONCLUSIONS: In MCDA twin pregnancies with no major fetal abnormalities, measurement of NT at the 11-13-week scan is a poor screening test for adverse pregnancy outcome. However, the finding in one or both fetuses of NT ≥ 95th percentile, and more so ≥ 99th percentile, is associated with a substantially increased risk of fetal loss or need for endoscopic laser surgery at < 20 weeks' gestation. The extent to which closer monitoring and earlier intervention in the high-risk group can reduce these complications remains to be determined. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.