Adverse Maternal-fetal Outcomes Research Articles

Quantitative Modeling to Characterize Maternal Inflammatory Response of Histologic Chorioamnionitis in Placental Membranes.

The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal-fetal outcomes. MIR is staged 1-3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1-2. Hematoxylin and eosin (H&E)-stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand-annotated and machine learning-identified cells. Overall cell class-level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross K-function. Clinical data were compared to neutrophil density and distribution. The classification model achieved a test-set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53073 cells from healthy and MIR1-2 placental membranes, we found that (1) MIR1-2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis. This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR.

Umbilical Artery Doppler and Adverse Outcomes in Severe Preeclampsia Without Fetal Growth Restriction: A Retrospective Cohort Study.

Background and objective Severe preeclampsia may be managed expectantly before 34 weeks gestation with close surveillance.Utilized in fetal growth restriction (FGR), evidence supports umbilical artery (UA) Dopplerpreventing neonatal morbidity from hypertensive disease and predicting adverse outcomes in preeclampsia. We evaluated the association of abnormal UA Doppler waveforms with early delivery (before 34 weeks gestation) and adverse maternal-fetal outcomes in patients with early severe preeclampsia without FGR. Methodology This is a retrospective cohort study of singleton pregnancies with International Classification of Diseases (ICD) Ninth or Tenth Revision, defined severe preeclampsia diagnosed before 34 weeks gestation without FGR from January 1, 2018, through January 27, 2023, at a large tertiary care center where S/D ratios were calculated from UA Doppler interrogation of a free loop of cord at least once weekly. This study was approved by the IRB (ID:00002216) and granted a full Health Insurance Portability and Accountability Act (HIPAA) waiver of consent. Exclusion criteria were major congenital anomalies, congenital infection, aneuploidy, leaving against medical advice >24 hours, and patient instability on admission defined as condition(s) precluding expectant management by the American College of Obstetrics and Gynecology. The primary outcome was delivery before 34 weeks gestation. Secondary outcomes were the mode of delivery and maternal/fetal complications. Patient characteristics and outcomes for normal versus abnormal UA Doppler groups were compared with chi-square, t-tests, and Fisher's exact test. Odds ratios and relative risks were calculated to compare outcomes. Results Of 194 patients with severe preeclampsia, 107 met inclusion criteria. Thirty-four patients had abnormal UA Doppler studies. There were no differences in demographic and clinical data between patients with normal and abnormal UA Doppler studies. Patients with abnormal UA Doppler studies were more likely to deliver before 34 weeks (OR=3.91; 95%CI 1.24-12.33) for worsening severe features (OR=3.85; 95% CI 1.42-10.41), and were less likely to deliver vaginally (OR=0.12; 95% CI 0.03-0.54). Abnormal UA Doppler studies were associatedwith an increased risk of neonatal complications (OR=6.46; 95% CI 1.42-29.42) and respiratory distress syndrome (RDS) (OR=4.75; 95%CI 1.32-17.16). Abnormal UA Doppler subgroups were divided into patients with elevated S/D >95% Acharya (N=22) and absent end-diastolic flow (EDF) (N=10). The elevated S/D group tended to deliver before 34 weeks gestation for worsening severe features (OR=3.71, 95% CI 1.144-12.050) and had a higher risk of neonatal complications (RR 1.404; 95% CI 1.213-1.624). The absent EDF subgroup was more likely to deliver before 34 weeks (RR=1.52; 95%CI 1.29-1.79) for abnormal fetal testing (OR=6.92; 95%CI 1.71-28.08) and undergo primary cesarean delivery (OR=7.23; 95%CI 1.43-36.61). Conclusion Pregnancies with severe preeclampsia without FGR displayed a high incidence of abnormal UA Doppler waveforms associated with loss of clinical stability and adverse fetal outcomes. The groups with more impedance to umbilical artery flow tended to deliver earlier, and as the Doppler shifted from elevated S/D to absent end-diastolic flow, the mode of delivery shifted to cesarean delivery with increased risk of abnormal fetal testing. These results support the utility of UA Doppler surveillance in severe preeclampsia.

Pre-gestational counselling for women living with CKD: starting from the bright side.

Pregnancy in women living with chronic kidney disease (CKD) was often discouraged due to the risk of adverse maternal-fetal outcomes and the progression of kidney disease. This negative attitude has changed in recent years, with greater emphasis on patient empowerment than on the imperative 'non nocere'. Although risks persist, pregnancy outcomes even in advanced CKD have significantly improved, for both the mother and the newborn. Adequate counselling can help to minimize risks and support a more conscious and informed approach to those risks that are unavoidable. Pre-conception counselling enables a woman to plan the most appropriate moment for her to try to become pregnant. Counselling is context sensitive and needs to be discussed also within an ethical framework. Classically, counselling is more focused on risks than on the probability of a successful outcome. 'Positive counselling', highlighting also the chances of a favourable outcome, can help to strengthen the patient-physician relationship, which is a powerful means of optimizing adherence and compliance. Since, due to the heterogeneity of CKD, giving exact figures in single cases is difficult and may even be impossible, a scenario-based approach may help understanding and facing favourable outcomes and adverse events. Pregnancy outcomes modulate the future life of the mother and of her baby; hence the concept of 'post partum' counselling is also introduced, discussing how pregnancy results may modulate the long-term prognosis of the mother and the child and the future pregnancies.

Pregnancy in Glomerular Disease: From Risk Identification to Counseling and Management.

Background: Pregnancy involves complex hemodynamic and immune adaptations to support the developing fetus. The kidney assumes a pivotal role in orchestrating these mechanisms. However, renal disease poses a potential risk for adverse maternal-fetal outcomes. While kidney function, hypertension, and proteinuria are recognized as key influencers of risk, the mere presence of glomerular disease, independent of these factors, may wield significant impact. Methods: A brief review of the existing literature was conducted to synthesize current knowledge regarding the interplay between glomerulonephritis and pregnancy. Results: The review underscores the centrality of the kidney in the context of pregnancy and highlights the role of glomerular disease, particularly when active. It emphasizes multifaceted risk modulators, including kidney function, hypertension, and proteinuria. Conclusion: Understanding the dynamics between pregnancy and glomerulonephritis is crucial for optimizing maternal and fetal outcomes. Preconception counseling and collaborative nephro-gynecological management emerge as pivotal components in addressing the unique challenges posed by this medical interplay.

Assessment of severity and feto-maternal outcomes among COVID-19 infected pregnant females hospitalized at tertiary care center in western Nepal

Objective: There is a paucity of data assessing the severity of coronavirus disease 2019 (COVID-19) infection and feto-maternal outcomes in pregnant women in Nepal, especially during the third wave of the pandemic with the Delta variant. This study aimed to severity as well as maternal-fetal outcomes among pregnant women with COVID-19 infection. Methods: In this cross-sectional study carried out amongst COVID-19 positive pregnant women visiting our institution for 6 months from January through June 2022, data surrounding COVID-19 severity and fetal outcomes were collected in a structured questionnaire. Disease severity was categorized based on the NIH (National Institutes of Health) severity classification. Descriptive statistics were used to describe the outcomes. Results: A total of 105 pregnant females infected with COVID-19 during the third wave were included in our study. The participants ranged from 16 through 40 years, mean gestational age being 36.6 weeks. Most of the women (40.55%) belonged to Brahmin and Chhetri ethnic backgrounds. About half (48.55%) of females were asymptomatic and four patients had severe disease requiring intensive care management. Only 13 pregnant females underwent vaccination. Of the 91 females that underwent delivery at our center, 77 (84.62%) were term. The rate of cesarean delivery was slightly higher (51.65%) than normal delivery. None of the babies born to COVID-positive pregnant females tested positive for COVID-19 and there were no stillbirths or any congenital anomalies. The majority of babies (68.14%) had normal fetal weight. Conclusion: Severe COVID-19 infection and adverse maternal-fetal outcomes during the third wave of COVID-19 infection with the Delta variant in Nepal were less than in other regions of the world despite low rates of vaccination.

Assessing adverse pregnancy outcomes in women with uncontrolled asthma vs. mild asthma: a retrospective comparative analysis.

The aim of this study was to evaluate perinatal outcomes between the uncontrolled asthma group and the mild asthma group and to reveal the relationship between disease severity and adverse maternal-fetal outcomes in this study. This retrospective cohort study analyzed 180 pregnant women diagnosed with asthma, hospitalized, and delivered at our center between September 1, 2019, and December 1, 2021. We compared two groups: 160 with mild asthma and 20 with uncontrolled asthma. Data encompassed maternal characteristics, obstetrical complications, medication use, emergency department admissions for exacerbations, smoking status, and neonatal outcomes. In the uncontrolled asthma group, hospitalization rates, use of inhaled short-acting β-agonist (SABA), and systemic corticosteroids were significantly higher compared to the mild asthma group (p < 0.01). Maternal and fetal complications were more prevalent in the uncontrolled group, including asthma exacerbations (45% vs. 1.2%), anemia (10% vs. 4.4%), prematurity (25% vs. 9.6%), and intrauterine fetal demise (IUFD) (10% vs. 0.6%). Neonatal outcomes in the uncontrolled group showed higher rates of admission to the neonatal intensive care unit (NICU) (50% vs. 25%), respiratory distress syndrome (RDS) (30% vs. 14%), and intraventricular hemorrhage (IVH) (5% vs. 0%) compared to the mild asthma group. Uncontrolled asthma during pregnancy is associated with higher adverse maternal-fetal and neonatal outcomes compared to mild asthma.

DENGUE IN PREGNANT WOMEN: A POTENTIAL THREAT TO MATERNAL-FETAL OUTCOMES?

INTRODUCTION: Dengue is an acute febrile disease caused by the DENV virus and transmitted mainly by the Aedes mosquito. It is an endemic disease mainly in countries in Asia and America. The clinical course is usually divided into three phases: febrile, critical and recovery, with fever being the initial symptom, sometimes accompanied by anorexia, vomiting, diarrhea and maculopapular rash. The critical phase is characterized by increased capillary permeability, which results in hemorrhage, shock and organ dysfunction due to fluid accumulation, gradually reabsorbed in the recovery phase. The diagnosis of dengue is made based on the detection of the NS1 antigen; the genome, by RT-PCR; or IgM or IgG antibodies. Treatment is only symptomatic. During pregnancy, studies suggest that there is an increase in adverse maternal-fetal outcomes due to DENV infection, in addition to the challenging diagnosis, due to the physiological adaptations of pregnancy. In this context, this systematic review aims to analyze how dengue behaves in pregnant women and the outcome of the infection. METHOD: searches were performed in PubMed, using the keywords “dengue pregnancy”, in LILACS, using “dengue pregnancy” and “dengue embarazo”, and in Scielo, using “dengue pregnancy”. A total of 188, 18, 21 and 1 results were obtained, respectively, and after exclusion by title and abstract, and by full text, 32 articles were included. RESULT: of the maternal outcomes, severe thrombocytopenia and death were the most cited in the articles, followed by postpartum hemorrhage, more severe forms of the disease, need for cesarean section and preeclampsia. The most prevalent fetal repercussion was prematurity, in addition to stillbirths, neonatal deaths, low birth weight and oligohydramnios. DISCUSSION: The articles analyzed suggest that dengue during pregnancy increases the risk of severe forms of the disease, postpartum hemorrhage, maternal death, miscarriage, stillbirths, fetal growth restriction, prematurity, and oligohydramnios, especially in cases of infections acquired in the third trimester of pregnancy. Vertical transmission also increases at the end of pregnancy. CONCLUSION: This review highlights that dengue is especially relevant during pregnancy, with a significant negative impact on maternal and fetal outcomes. However, further studies are still needed for greater depth, since there is no consensus.

Adverse Maternal-Fetal Outcomes in Pregnant Women with CKD on Hemodialysis: A Single-Center Experience

Adverse Maternal-Fetal Outcomes in Pregnant Women with CKD on Hemodialysis: A Single-Center Experience

Outcomes of Laparotomic Myomectomy during Pregnancy for Symptomatic Uterine Fibroids: A Prospective Cohort Study.

Background: The incidence of pregnant women with uterine fibroids is increasing. As they are reactive to hormonal stimuli, in some cases, uterine fibroids tend to grow during pregnancy and potentially generate symptoms with different levels of severity, causing maternal-fetal complications. In very select cases, when other treatment strategies fail to manage symptoms and there is a substantial risk of adverse pregnancy outcomes, a surgical approach during pregnancy may be considered. Methods: From 2016 to 2021, the data from 28 pregnant women with symptomatic uterine fibroids who underwent laparotomic myomectomy during pregnancy were prospectively collected, and operative and maternal-fetal outcomes were analyzed (ClinicalTrial ID: NCT06009562). Results: The procedure was carried out between 14 and 16 weeks of pregnancy. Four (14.3%) patients had intraoperative complications (miscarriages) and nine (32.1%) had postoperative complications (threatened preterm birth). Overall, 24 (85.7%) women delivered at full term (mean: 38.2 gestational weeks), more than half (n = 13; 54.2%) by vaginal delivery, with normal fetal weights and 1 and 5 min Apgar scores. Conclusions: Laparotomic myomectomy during pregnancy can be considered in selected cases for uterine fibroids with severe symptoms when other treatment options have failed and there is high risk of adverse maternal-fetal outcomes.

Effect of COVID-19 vaccination and booster on maternal–fetal outcomes: a retrospective cohort study

COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine's potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes. This was a retrospective multicentre cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people who delivered (n=106 428) at Providence St Joseph Health across seven western US states from Jan 26, 2021 to Oct 26, 2022. Cohorts were defined by vaccination status at delivery: vaccinated (n=35 926; two or more doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), unvaccinated (n=55 878), unvaccinated propensity score matched (n=16 771), boosted (n=10 927; three or more doses), vaccinated unboosted (n=13 243; two doses only), and vaccinated unboosted with propensity score matching (n=4414). We built supervised machine learning classification models, which we used to determine which people were more likely to be vaccinated or boosted at delivery. The primary outcome was maternal SARS-CoV-2 infection. COVID-19 vaccination status at delivery, COVID-19-related health care, preterm birth, stillbirth, and very low birthweight were evaluated as secondary outcomes. Vaccinated people were more likely to conceive later in the pandemic, have commercial insurance, be older, live in areas with lower household composition vulnerability, and have a higher BMI than unvaccinated people. Boosted people were more likely to have more days since receiving the second COVID-19 vaccine dose, conceive earlier in the pandemic, have commercial insurance, be older, and live in areas with lower household composition vulnerability than vaccinated unboosted people. Vaccinated pregnant people had lower rates of COVID-19 during pregnancy (4·0%) compared with unvaccinated matched people (5·3%; p<0·0001). COVID-19 rates were even lower in boosted people (3·2%) compared with vaccinated unboosted matched people (5·6%; p<0·0001). Vaccinated people were also less likely to have a preterm birth (7·9%; p<0·0001), stillbirth (0·3%; p<0·0002), or very low birthweight neonate (1·0%; p<0·0001) compared with unvaccinated matched people (preterm birth 9·4%; stillbirth 0·6%; very low birthweight 1·5%). Boosted people were less likely to have a stillbirth (0·3%; p<0·025) and have no differences in rates of preterm birth (7·6%; p=0·090) or very low birthweight neonates (0·8%; p=0·092) compared with vaccinated unboosted matched people (stillbirth 0·5%; preterm birth 8·4%; very low birthweight 1·1%). COVID-19 vaccination protects against adverse maternal-fetal outcomes, with booster doses conferring additional protection. Pregnant people should be high priority for vaccination and stay up to date with their COVID-19 vaccination schedule. National Institute for Child Health & Human Development and the William O and K Carole Ellison Foundation.

Placental Area in the Lower Uterine Segment, Cervical Length, and Clinical Outcome in Pregnancies With Complete Placenta Previa.

Complete placenta previa is associated with a higher percentage of adverse clinical outcomes and magnetic resonance imaging (MRI) is widely used in the preoperative examination of patients with placenta previa. To evaluate the effectiveness of the placental area in the lower uterine segment and cervical length in identifying the adverse maternal-fetal outcomes in women with complete placenta previa. Retrospective. A total of 141 pregnant women (median age, 32; age range, 24-40 years) with complete placenta previa were examined by MRI to evaluate the uteroplacental condition. A 3 T with T1 -weighted imaging (T1 WI), T2 -weighted imaging (T2 WI), and half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence. The association of the placental area in the lower uterine segment and cervical length measured using MRI with the risk of massive intraoperative hemorrhage (MIH) and maternal-fetal perinatal outcomes were determined. The adverse neonatal outcomes (preterm delivery, respiratory distress syndrome [RDS], admission to neonatal intensive care unit [NICU]) were analyzed in different groups. The t-test, Mann-Whitney U test, Chi-square, Fisher's exact test, and receiver operating characteristic (ROC) curve were used, and a P < 0.05 indicated a statistically significant difference. The mean operation time, intraoperative blood loss, and intraoperative blood transfusing were significantly higher in patients with large placental area and short cervix than in patients with the small placental area and long cervix, respectively. The incidence of adverse neonatal outcomes was significantly higher in the large placenta area group and short cervix group than in the small placenta group area and long cervix group, respectively, such as preterm delivery, RDS, and NICU. By combining placental area with cervical length sensitivity and specificity increased to 93% and 92%, respectively, for the identification of MIH > 2000 mL with area under the receiver operating curve (AUC) 0.941. Large placental area and short cervical length may be associated with a high risk of MIH and adverse maternal-fetal perinatal outcomes in patients with complete placenta previa. 2.

The relationship between social determinants of health and postpartum weight retention based on the World Health Organization model: path analysis

BackgroundPostpartum weight retention (PPWR) causes obesity, chronic diseases, and occurring adverse maternal-fetal and neonatal outcomes. Given the social factors’ effect on health and disease and considering the lack of information on social determinants of health (SDH) effects on PPWR, this study was conducted to survey the relationship between SDH and PPWR based on the World Health Organization (WHO) model.MethodsA cross-sectional study was performed on 400 women six months after delivery in 2020. Twelve health centers were randomly selected from the three universities of Medical Sciences in the city of Tehran, Iran. Participants were selected by convenience method and based on eligibility. Questionnaires used included: Lifestyle Profile Health Promoting II, Short Form Postpartum Quality of Life Questionnaire, Multidimensional Scale of Perceived Social Support, Postpartum Social Support, Depression Anxiety Stress Scales, and questionnaires designed by reviewing the literature about breastfeeding, sleep, contraceptive, child health, unhealthy behaviors, postpartum nutritional awareness/beliefs, body satisfaction, access to postpartum care, socioeconomic status, demographic, and obstetric questionnaire. Data analysis was performed in SPSS-23, and the relationship model was examined using the path analysis method in LISREL-8.8.ResultsPath analysis indicated the direct effect of six intermediate factors on PPWR including: gestational weight gain (β = 0.42), access to postpartum care (β = 0.11), postpartum nutritional awareness/beliefs (β=-0.17), anxiety (β = 0.09), sleep duration (β=-0.09), pre-pregnancy body mass index (β = 0.09). Among the structural factors, woman’s education and socioeconomic status had an indirect negative effect on PPWR. The model fit indices showed good fit (RMSE = 0/05, GFI = 0.92, CFI = 0.92, χ2/df = 2.17).ConclusionThe results indicate the effect of structural and intermediate determinants of health on PPWR. It is recommended to use the proposed model as an appropriate framework in the research, design, and implementation of programs to prevent and control PPWR.

Plasmodium vivax and SARS-CoV-2 co-infection in Venezuelan pregnant women: a case series

BackgroundMalaria‐endemic areas are not spared from the impact of coronavirus disease 2019 (COVID-19), leading to co-infection scenarios where overlapping symptoms impose serious diagnostic challenges. Current knowledge on Plasmodium spp. and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co‐infection in pregnant women remains limited, especially in Latin America, where Plasmodium vivax infection is highly prevalent.MethodsThis is a case series of five pregnant women with P. vivax and SARS-CoV-2 co-infection hospitalized in two main malaria referral centers of the Capital District and Bolivar state, Venezuela between March 13, 2020 and December 31, 2021.ResultsClinical and laboratory data from five pregnant women with a mean age of 22 years were analyzed; three of them were in the third trimester of pregnancy. Comorbidities included obesity in two cases, hypertension in one, and asthma in one. Three out of five patients had severe to critical COVID-19 disease. Dry cough, fever, chills, and headache were the most frequent symptoms reported. Laboratory analyses showed elevated aspartate/alanine aminotransferase and creatinine levels, thrombocytopenia, and severe anemia as the most relevant abnormalities. The mean period between symptom onset and a positive molecular test for SARS-CoV-2 infection or positive microscopy for Plasmodium spp. was 4.8 ± 2.5 days and 2.8 ± 1.6 days, respectively. The mean hospital stay was 5.4 ± 7 days. Three women recovered and were discharged from the hospital. Two women died, one from cerebral malaria and one from respiratory failure. Three adverse fetal outcomes were registered, two miscarriages and one stillbirth.ConclusionThis study documented a predominance of severe/critical COVID-19 disease and a high proportion of adverse maternal–fetal outcomes among pregnant women with malaria and COVID-19 co-infection. More comprehensive prospective cohort studies are warranted to explore the risk factors, management challenges, and clinical outcomes of pregnant women with this co-infection.

A case of overt hyperthyroidism: A forgotten cause of poor maternal-fetal outcome in low-resource settings

Introduction: Overt hyperthyroidism during pregnancy is uncommon, occurring in only 0.7% to 0.9% of pregnancies. The grave disease is the most common cause, accounting for 90–95% of cases. It is characterized by low Thyroid Stimulating Hormone (TSH) and Elevated Levels of Free Thyroxine (T4) and Triiodothyronine (T3). Due to the normal changes in a woman’s body during pregnancy and the different levels of thyroid-stimulating hormones in each trimester, overt hyperthyroidism is difficult to diagnose. Overt hyperthyroidism is associated with adverse maternal-fetal outcomes, including low birth weight, recurrent pregnancy loss, congenital abnormalities, preterm birth, intrauterine growth restriction, preeclampsia, abruptio placenta, and lastly, thyroid storm. Therefore, treatment is required for the management of overt hyperthyroidism during pregnancy, and it is essential to maintain euthyroid status to lessen the severity of the symptoms. Priority should be given to preconception care and achieving euthyroid is recommended prior to conception. Depending on the underlying cause, this can be accomplished through medical management such as antithyroid medication or surgery.

Health Care Workers’ Experiences, Challenges of Obstetric Referral Processes and Self-Reported Solutions in South Western Uganda: Mixed Methods Study

IntroductionIn resource limited settings, the highest burden of adverse maternal-fetal outcomes at referral hospitals is registered from emergency obstetric referrals from lower health facilities. Implementation of referral protocols has not been optimally successful possibly attributed to lack of understanding of profile of obstetric referrals and local challenges faced during implementation process.ObjectiveThis study described the profile of emergency obstetric referrals, challenges faced in implementation of obstetric referral processes and explored self-reported solutions by health workers.MethodsThis was a mixed methods study done at Mbarara Regional Referral Hospital (MRRH) and health centre IVs in South-Western Uganda. We consecutively recruited emergency obstetric referrals from Isingiro district for delivery at MRRH. Using a pre-tested questionnaire, we collected demographics, obstetric and referral characteristics. We described the profile of referrals using frequencies and proportions based on demographics, obstetric and referral characteristics. We conducted focus group discussions and in-depth interviews with health workers using discussion/interview guides. Using thematic analysis, we ascertained the challenges and health worker self-reported solutions.ResultsWe recruited 161 referrals: 104(65%) were below 26 years, 16(10%) had no formal education, 11(7%) reported no income, 151(94%) had no professional-escort, 137(85%) used taxis, 151(96%) were referred by midwives. Common diagnoses were previous cesarean scar (24% [n=39]) and prolonged labour (21% [n=33]). There was no communication prior to referral and no feedback from MRRH to lower health facilities. Other challenges included inconsistencies of ambulance and anesthesia services, electric power, medical supplies, support supervision, and harassment by colleagues. Self-reported solutions included the use of phone call technology for communication, audit meetings, support supervision and increasing staffing level.ConclusionMost referrals are of poor social-economic status, use taxis, and lack professional-escort. Health workers suffer harassment, lack of communication and shortage of supplies. We need to experiment whether mobile phone technology could solve the communication gap.

Impact of progesterone on innate immunity and cell death after influenza A virus H1N1 2009 infection of lung and placental cells in vitro.

The influenza A virus (IAV) 2009 H1N1 pandemic was associated with an increased risk of maternal mortality, preterm birth, and stillbirth. The underlying mechanism for severe maternal lung disease and stillbirth is incompletely understood, but IAV infection is known to activate innate immunity triggering the release of cytokines. Elucidating the impact of progesterone (P4), a key hormone elevated in pregnancy, on the innate immune and inflammatory response to IAV infection is a critical step in understanding the pathogenesis of adverse maternal-fetal outcomes. IAV H1N1 pdm/09 was used to infect cell lines Calu-3 (lung adenoma) and ACH-3P (extravillous trophoblast) with or without P4 (100 nM) at multiplicity of infections (MOI) 0, 0.5, and 3. Cells were harvested at 24 and 48 hours post infection (hpi) and analyzed for cytopathic effects (CPE), replicating virus (TCID50), cytotoxicity (Lactate Dehydrogenase (LDH) assay), and NLRP3 inflammasome activation (caspase-1 activity, fluorometric assay). Activation of antiviral innate immunity was quantified (RT-qPCR, Luminex) by measuring biomarker gene and protein expression of innate immune activation (IFIT1, IFNB), inflammation (IL6), interferon signaling (MXA), chemokines (IL-8, IL-10). Both Calu-3 and ACH-3P were highly permissible to IAV infection at each timepoint as demonstrated by CPE and recovery of replicating virus. In Calu-3, progesterone treatment was associated with a significant increase in cytotoxicity, increased gene expression of IL6, and increased protein expression of IFN-β, IL-6, and IL-18. Conversely, in ACH-3P, progesterone treatment was associated with significantly suppressed cytotoxicity, decreased gene expression of IFNB, IL6 and IL1B, and increased protein expression of IFN-β and IL-6. In both cell lines, caspase-1 activity was significantly decreased after progesterone treatment, indicating NLRP3 inflammasome activation was not underlying the higher cell death in Calu-3. In summary, these data provide evidence that progesterone plays a dual role by ameliorating viral infection in the placenta but exacerbating influenza A virus-associated injury in the lung through nongenomic modulation of the innate immune response.

Improved maternal–fetal outcomes among emergency obstetric referrals following phone call communication at a teaching hospital in south western Uganda: a quasi-experimental study

BackgroundEmergency obstetric referrals develop adverse maternal–fetal outcomes partly due to delays in offering appropriate care at referral hospitals especially in resource limited settings. Referral hospitals do not get prior communication of incoming referrals leading to inadequate preparedness and delays of care. Phone based innovations may bridge such communication challenges.We investigated effect of a phone call communication prior to referral of mothers in labour as intervention to reduce preparation delays and improve maternal–fetal outcome at a referral hospital in a resource limited setting.MethodsThis was a quasi-experimental study with non-equivalent control group conducted at Mbarara Regional Referral Hospital (MRRH) in South Western Uganda from September 2020 to March 2021. Adverse maternal–fetal outcomes included: early neonatal death, fresh still birth, obstructed labour, ruptured uterus, maternal sepsis, low Apgar score, admission to neonatal ICU and hysterectomy. Exposure variable for intervention group was a phone call prior maternal referral from a lower health facility. We compared distribution of clinical characteristics and adverse maternal–fetal outcomes between intervention and control groups using Chi square or Fisher’s exact test. We performed logistic regression to assess association between independent variables and adverse maternal–fetal outcomes.ResultsWe enrolled 177 participants: 75 in intervention group and 102 in control group. Participants had similar demographic characteristics. Three quarters (75.0%) of participants in control group delayed on admission waiting bench of MRRH compared to (40.0%) in intervention group [p = < 0.001]. There were significantly more adverse maternal–fetal outcomes in control group than intervention group (obstructed labour [p = 0.026], low Apgar score [p = 0.013] and admission to neonatal high dependency unit [p = < 0.001]). The phone call intervention was protective against adverse maternal–fetal outcome [aOR = 0.22; 95%CI: 0.09—0.44, p = 0.001].ConclusionThe phone call intervention resulted in reduced delay to patient admission at a tertiary referral hospital in a resource limited setting, and is protective against adverse maternal–fetal outcomes. Incorporating the phone call communication intervention in the routine practice of emergency obstetric referrals from lower health facilities to regional referral hospitals may reduce both maternal and fetal morbidities.Trial registrationPan African Clinical Trial Registry PACTR20200686885039.

221-OR: Safety and Effectiveness of Insulin Aspart vs. Other Bolus Insulins in Women with Preexisting Type 1 Diabetes during Pregnancy: A Post Hoc Analysis of the EVOLVE Study

Aims: This post hoc analysis of the real-world EVOLVE study investigated safety and effectiveness of insulin aspart (IAsp) vs. other bolus insulins in pregnant women with pre-existing type 1 diabetes. Methods: Maternal, pregnancy and infant outcomes were assessed in women receiving bolus insulins on enrolment and during pregnancy in a prospective cohort, by estimating risk differences following adjustment for potential confounders using propensity score matching. Results: Insulin treatment in early pregnancy and maternal, pregnancy and infant outcomes are presented (Table) . In total, 1434 women were treated with IAsp and 4with other bolus insulins on enrolment. Significantly lower mean A1c values in the third trimester were observed with IAsp vs. other bolus insulins (adjusted % point difference -0.16% [95% CI -0.28;-0.05]; p=0.005) . No significant differences were seen with IAsp vs. other bolus insulins in the risk of adverse maternal-fetal outcomes including major maternal hypoglycemia, abortion, pre-term delivery, pre-eclampsia, birthweight large for gestational age, major congenital malformations and perinatal or neonatal death, in the matched dataset. Conclusion: Compared with other bolus insulins, IAsp was associated with significantly lower A1c during the third trimester and a similar risk of adverse pregnancy outcomes. Disclosure E.Mathiesen: Consultant; Novo Nordisk A/S, Speaker's Bureau; Novo Nordisk A/S. On behalf of the evolve study group: n/a. A.Alibegovic: Employee; Novo Nordisk A/S, Novo Nordisk A/S. G.Anil: Employee; Novo Nordisk Global Business Services. F.P.Dunne: None. T.Halasa: Employee; Novo Nordisk A/S. M.Ivanisevic: None. D.R.Mccance: None. R.Baastrup nordsborg: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. P.Damm: Advisory Panel; Novo Nordisk A/S. Funding Novo Nordisk A/S

Optimal delivery time for patients with diet-controlled gestational diabetes mellitus: a single-center real-world study

BackgroundTo determine the optimal delivery time for women with diet-controlled gestational diabetes mellitus by comparing differences in adverse maternal–fetal outcome and cesarean section rates.MethodsThis real-world retrospective study included 1,050 patients with diet-controlled gestational diabetes mellitus who delivered at 35–42 weeks’ gestation. Data on patient characteristics, maternal–fetal outcomes, and cesarean section rate based on fetal gestational age were collected and analyzed. Differences between deliveries with and without iatrogenic intervention were also analyzed.ResultsThe cesarean section rate at ≥ 41 weeks’ gestation was significantly higher than that at 39–39 + 6 weeks (56% vs. 39%, p = 0.031). There were no significant differences in multiple adverse maternal or neonatal outcomes at delivery before and after 39 weeks. Vaginal delivery rates were increased significantly at 39–39 + 6 weeks due to iatrogenic intervention (p = 0.005) and 40–40 + 6 weeks (p = 0.003) in patients without and with spontaneous uterine contractions, respectively.ConclusionsIt’s recommended that optimal delivery time for patients with diet-controlled gestational diabetes mellitus should be between 39- and 40 + 6 weeks’ gestation. Patients who have Bishop scores higher than 4 can undergo iatrogenic intervention at 39–39 + 6 weeks. However iatrogenic interventions are not recommended for patients with low Bishop scores.

Rituximab related non-infectious lung injury complicating treatment of severe TTP in pregnancy – literature review and case-report

Background: Thrombotic thrombocytopenic purpura (TTP) in pregnancy is a rare but potentially life-threatening condition. Management of severe, refractory TTP during pregnancy is challenging and includes multidisciplinary approach. The prognosis of cases with a variety of hematological and autoimmune diseases, including TTP has changed profoundly after the rituximab therapy was introduced into clinical practice. However, adverse pregnancy outcomes associated with biological agents should be kept in mind and the decision to treat should be weighed by measurement of potential risks vs benefits. Case report: We reported the first documented case of noninfectious lung toxicity in pregnancy related to rituximab use for TTP treatment. 26 y/o patient at 23 weeks gestation initially presented to ED secondary to numbness, headache, and slurred speech with negative brain imaging. Her laboratory findings revealed severe deficiency of platelets, hemoglobin and ADAMT13 activity. She underwent multiple therapeutic interventions including plasmapheresis, intravenous immunoglobulins (IVIG), prednisone, and eventually required more often hospitalizations. Ultimately, the decision was made to proceed with rituximab therapy. After the third infusion of rituximab, she developed non-infectious lung injury without evidence of SARS-CoV-2 or other infections, pulmonary edema, or pulmonary embolism. The maternal condition worsened acutely resulting in significant desaturation that required intubation and eventual emergent premature delivery at 31-weeks’ gestation via C-section. Conclusion: Rituximab therapy for TTP management in pregnancy may be associated with significant adverse maternal-fetal outcomes. Risks and benefits of treatment should be discussed with each patient and during multidisciplinary communications. Physicians should maintain high index of suspicion for non-infectious lung injury associated with rituximab treatment in order to be able to diagnose this complication early and start treatment to avoid severe mortality and morbidity.