Adverse Fetal Outcomes Research Articles

Abnormal microRNA expression profile at early stages of gestation in pregnancies destined to develop placenta previa

BackgroundPlacenta previa is the abnormal implantation of the placenta into the lower segment of the uterus, is associated with adverse maternal and fetal outcomes such as placenta accreta spectrum disorders, antepartum and postpartum hemorrhage, fetal growth restriction, prematurity, stillbirth and neonatal death, thrombophlebitis, and septicemia. The aim of the study was to assess retrospectively how the later onset of placenta previa affects the microRNA expression profile in the whole peripheral blood during the first trimester of gestation.MethodsRegarding the occurrence of the association between aberrant microRNA expression profiles at early stages of gestation and later onset of various pregnancy-related complications, we selected for the study pregnancies developing placenta previa as the only pregnancy-related disorder. In total, 24 singleton pregnancies diagnosed with placenta previa that underwent first-trimester prenatal screening and delivered on-site within the period November 2012–May 2018 were included in the study. Overall, 80 normal pregnancies that delivered appropriate-for-gestational age newborns after completing 37 weeks of gestation were selected as the control group based on the equality of the length of biological sample storage.ResultsDownregulation of multiple microRNAs (miR-20b-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-103a-3p, miR-130b-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-210-3p, miR-342-3p, and miR-574-3p) was observed in pregnancies destined to develop placenta previa. The combination of seven microRNAs (miR-130b-3p, miR-145-5p, miR-155-5p, miR-181a-5p, miR-210-3p, miR-342-3p, and miR-574-3p) showed the highest accuracy (AUC 0.937, p < 0.001, 100.0% sensitivity, 83.75% specificity) to differentiate, at early stages of gestation, between pregnancies with a normal course of gestation and those with placenta previa diagnosed in the second half of pregnancy. Overall, 75% of pregnancies destined to develop placenta previa were correctly identified at 10.0% FPR.ConclusionConsecutive large-scale analyses must be performed to verify the reliability of the proposed novel early predictive model for placenta previa occurring as the only pregnancy-related disorder.

Would the utilization of sFlt-1/PlGF ratio in clinical practice prevent unnecessary hospital admissions of cases with preeclampsia?

ABSTRACT Objectives Preeclampsia (PET) is a serious pregnancy complication with potential adverse maternal and fetal outcomes. Recent research has examined the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio for predicting PET. The study aimed to assess the efficacy of the sFlt-1/PlGF ratio in ruling out unnecessary hospital admission and PET. Methods sFlt-1/PlGF ratio was performed in patients as clinically indicated. Results The sFlt-1/PlGF ratio at a cutoff value of 51 predicted hospital admission with AUC, PPV, NPV, sensitivity, and specificity of 85%, 44%, 98%, 88%, and 85%, respectively. Additionally, at a cutoff value of 38, the sFlt-1/PlGF ratio predicted the short-term development of PET with PPV, NPV, sensitivity, and specificity of 42%, 100%, 100%, and 81%, respectively. The PlGF alone at a cutoff value of 193.36 predicted hospital admission with AUC, PPV, NPV, sensitivity, and specificity of 87%, 80%, 97%, 67%, and 98%, respectively. Moreover, at a cutoff value of 51.35, the PlGF alone predicted the development of PET with PPV, NPV, sensitivity, and specificity of 54%, 98%, 88%, and 90%, respectively. There was a significant association between a high sFlt-1/PlGF ratio and developing PET. Conclusion The sFlt-1/PlGF ratio and PlGF are promising for ruling out PET and hospital admission in pregnant women.

Adverse Fetomaternal Outcomes in Obese Pregnant Women with Gestational Hypertension

Objective: To determine the incidence of adverse fetomaternal outcomes of gestational hypertension in pregnant obese women. Methodology: The six-month descriptive observational study at Liaqat Memorial Hospital, Kohat, with 127obesepregnantwomenaged15-45.Participantswere selectedbasedonsingletonpregnancy more than 24 weeks gestation according to scan or LMP and a blood pressure of >140/90 mmHg on two different occasions without proteinuria, or a single reading of BP of 160/110mmHg with a BMI over 30 kg/m². Baseline data (maternal age, parity, BMI gestational age, education, socioeconomic status, family income, and residence) were collected. Fetomaternal complications were recorded by following up the patients till delivery. Results: The study included obese pregnant women with an average age of 33.2± 1.5 years and a mean BMI of 31.2 ± 5.6. Most participants had a median parity of 3, with a majority belonging to urban areas (51.1%) , having middle socioeconomic status (48.8% ). The adverse fetal outcomes ranged from preterm birth (16.4%),fetal growth restriction (12.6%),fetal hypoxia (8.9%)andlastlyperinataldeath(5.2%).Theadversematernaloutcomeswerepostpartumhemorrhage (16.4%), placental abruption (8.3%) , ecclempsia (7.2%) , HELLPsyndrome (4.1%) and maternal mortality (3.1%). Adverse maternal and fetal outcomes preterm labor postpartum hemorrhage, eclampsia, and placental abruption, fetal growth restriction and intrauterine fetal death outcomes being significantly higher in moderate gestational hypertension compared to mild gestational hypertension p=0.023, p=0.030, p=0.020, p=0.011, p=0.035 and p=0.022) respectively and adverse outcome placental abruption, eclampsia, and fetal growth restriction being significantly higher in class II obesity when compared to class I (p value= p=0.045 p=0.041 p=0.038)respectively Conclusion: Adverse fetomaternal outcomes are significantly affected by the severity of gestational hypertension andclass of obesity.Prenatal identification ofrisk factors in these women couldlowermaternal and fetal morbidity and mortality rates, underscoring the importance of an effective prenatal care system. Keywords: Obesity, Maternal Health, Fetal Growth Retardation, Pre- Eclampsia, Premature Birth

Maternal and fetal outcomes in those with autoimmune connective tissue disease.

Autoimmune CTDs like systematic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA)predominantly affect women during reproductive years and are linked to maternal and fetal complications. We conducted a population-based, retrospective cohort study using the national inpatient data sample to compare maternal and fetal outcomes in patients with and without CTD delivering between October 2015 and December 2020. Regression analysis was performed and adjusted for multiple patient characteristics to compare outcomes. Our study comprised of 18,866,050 deliveries, of which 50,450 (0.02%) had autoimmune CTD, including 25,340 with SLE, 23,945 with RA, and 1,165 with SSc. Patients with CTDs had significantly higher odds of maternal death (aOR 3.898; 95% CI: 1.462-10.389, p = 0.007), hypertensive disorders (aOR 1.554; 95% CI: 1.456-1.659, p < 0.001), acute kidney injury (aOR 4.886; 95% CI: 3.934-6.069, p < 0.001), blood transfusions (aOR 1.853; 95% CI: 1.628-2.109, p < 0.001), peripartum cardiomyopathy (aOR 2.709; 95% CI: 1.492-4.917, p = 0.001), sepsis (aOR 2.112; 95% CI: 1.430-3.119, p < 0.001), and ARDS (aOR 1.623; 95% CI: 1.076-2.449, p = 0.021). Fetal outcomes were also worse, with higher odds of small for gestational age fetuses (aOR 1.926; 95% CI: 1.779-2.086, p < 0.001), stillbirth (aOR 1.644; 95% CI: 1.352-2.000, p < 0.001), and preterm labor (aOR 1.702; 95% CI: 1.574-1.841, p < 0.001). Patients with RA, SS, and SLE experience varying degrees of complications. Our study shows that pregnant patients with autoimmune CTDs have worse maternal and fetal outcomes compared to those without CTDs. The rates of adverse outcomes varies among CTD subtypes. Comprehensive preconception counseling and tailored management strategies are essential for optimizing outcomes in these patients. Key Points • Increased Maternal Complications: Patients with autoimmune CTDs had significantly higher odds of maternal death, hypertensive disorders, acute kidney injury, blood transfusions, peripartum cardiomyopathy, sepsis, and ARDS. • Adverse Fetal Outcomes: Higher odds of small for gestational age fetuses, stillbirth, and preterm labor were observed in patients with CTDs compared to those without. • CTD Subtype Variations: Complication rates varied among CTD subtypes, with SLE, RA, and SSc each presenting varying risks and outcomes.

Serial evaluation of morphological and biophysical placental attributes in women with normal outcome and preeclampsia.

The study's aim was to perform serial placental biometry and Doppler assessments in antenatal women and compare the characteristics of preeclampsia (PE) and normal outcome. This prospective cohort study was carried out after ethical clearance. Placental length (PL), thickness, and plavental volume (PV), along with the uterine artery (Ut), middle cerebral artery (MCA), and umbilical artery (UA) blood flow were evaluated serially at 11-14, 20-24, and 28-32 weeks of gestation. The women were followed until delivery, those with PE were considered cases, and those with no other adverse outcome were controls. The placental attributes between cases and controls were compared. A total of 135/1008 (13.4%) had hypertensive disorders of pregnancy (HDP) and 44/1008 (4.4%) had PE, and no maternal or fetal adverse outcomes were seen in 600 (59.5%) women. The PL and PV were significantly less in those with PE (P = 0.005) than in controls. The ratios of PL/Ut A PI and PV/Ut A PI were significantly lower in cases than in controls in all trimesters (P <0.001). In the first trimester, the area under the curve (AUC), sensitivity, and specificity of PV/Ut A PI for PE prediction were 0.801, 81.8%, and 70.5%, respectively. The sensitivity and specificity of the PL/Ut PI ratio was 81.8% and 70.5%, whereas that at 28-32 weeks was 73.3% & 70.7%. Placental parameters were significantly lower in PE than in normal outcome, and the ratios of PL/Ut A PI and PV/Ut A PI proved to be promising markers.

Remote blood pressure monitoring in women at risk of or with hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Remote blood pressure monitoring refers to an organized framework that either allows clinicians to review home-based blood pressure readings and institute management, or provide participants with clear instructions for contacting care teams when blood pressure readings are out of prespecified targets. With widespread uptake of telemonitoring and mobile health in recent years, such models of care have been increasingly described in the literature. This study aimed to review remote blood pressure monitoring in pregnant and postpartum women who are at high-risk for or have an established diagnosis of hypertensive disorders of pregnancy, and its effect on maternal and fetal outcomes, healthcare utilization and psychosocial outcomes. PubMed, Medline, Embase, Cochrane Library, Web of Science and CINAHL databases were searched electronically in June 2024 to their inception. Included studies compared remote blood pressure monitoring with standard care. Remote blood pressure monitoring was pre-defined as any framework for measuring blood pressure remotely in pregnancy, with organized review by clinicians. Published full-text and study abstracts describing randomized controlled trials and observational studies were included. The study population was pregnant women at high-risk for developing pre-eclampsia or postpartum (<6 weeks) women with an established diagnosis of a hypertensive disorder of pregnancy. Remote blood pressure monitoring undertaken in the antenatal and postnatal periods were analyzed separately. This systematic review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement. Screening of records and data extraction were independently performed. Data were extracted and analyzed using Review Manager software (version 5.4; Cochrane Collaboration, Copenhagen, Denmark). Risk of bias and quality assessment was performed independently using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) assessment tool and the Cochrane Risk of Bias 2 (RoB2) tool. A total of 18 studies with 28 094 patients were included. Antenatal remote blood pressure monitoring reduces antenatal outpatient visits, antenatal hospital admissions for any cause, and antenatal hospital admissions specifically for hypertension. Importantly, there was no increase in adverse maternal and fetal outcomes, including the likelihood of cesarean section deliveries or induction of labor due to hypertension, composite maternal outcome, growth restriction, neonatal intensive care unit admissions, gestational age at delivery and the composite fetal outcome. Psychosocial outcomes were also not significantly different between the remote blood pressure monitoring and usual care groups. Postpartum remote blood pressure monitoring in women with an established hypertensive disorder of pregnancy led to greater compliance with blood pressure follow-up within 10 days, with no increase in unscheduled hypertension-related presentations, postpartum readmissions or outpatient antihypertensive prescription. Utilizing a model of remote blood pressure monitoring which incorporates organized review and management by clinicians, may reduce antenatal outpatient visits and admissions, without increasing adverse fetal and maternal outcomes, in pregnant women who require frequent monitoring of their blood pressure. In postpartum women with a hypertensive disorder of pregnancy, remote blood pressure monitoring can improve guideline recommended follow-up within 10 days. However, the meta-analysis was hampered by study heterogeneity and a paucity of high-quality evidence. Further randomized controlled trials are needed to confirm the findings of this review and provide recommendations.

Distribution of Polybrominated Diphenyl Ethers (PBDEs) in Placental Tissues of Maternal and Fetal Origin in Exposed Wistar Rats and Associations with Thyroid Hormone Levels.

In utero exposure to polybrominated diphenyl ethers (PBDEs) is linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase out, PBDEs are still commonly detected in newborn cord blood. While PBDEs can cross the placenta, few studies have separately assessed PBDEs or THs in the maternal and fetal placental tissues. Additionally, no studies have separately assessed THs in these tissues across mid- and late gestation, during the onset of fetal TH synthesis. To address these gaps, we conducted a study with Wistar rats and examined PBDE accumulation in the maternal and fetal placenta. Pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose PBDE mixture. At GD15 and 20, dams were sacrificed and placental tissues were collected. Tissues were analyzed for PBDEs, T3, rT3, and T4 using mass spectrometry. BDE-47, -99, -100, and -209 were frequently detected in both the fetal and maternal placenta. At GD15, higher concentrations of BDE-99, -100, and -209 were measured in the fetal placenta; however, this trend reversed by GD20, with higher maternal placental concentrations. Placental T3 and T4 were significantly impacted by exposure, tissue, and exposure x tissue at GD15, with significant reductions in both THs following low dose exposure in the maternal placenta. By GD20, maternal placental T3 was only significantly reduced in the high exposure groups and there was no effect on placental T4. Overall, these results highlight the rapid developmental changes that occur throughout gestation between the maternal and fetal placenta, and the differential impacts of gestational PBDE exposure on placental T3 and T4 across mid- and late-gestation.

Prevalence and factors associated with placental malaria in Lira District, Northern Uganda: a cross-sectional study

BackgroundMalaria has a stable perennial transmission across Uganda. Placental malaria is associated with adverse maternal, fetal, and neonatal outcomes. The factors associated with placental malaria are poorly understood in the study setting. The aim of the study was to assess the prevalence of placental malaria and to determine its associated factors among parturient women in Lira District, Uganda.MethodsThis was a cross-sectional study among 366 pregnant women who delivered at Lira Regional Referral Hospital. Data were collected from December 2018 to February 2019 using an interviewer-administered questionnaire. The variables were socio-demographic, obstetric characteristics, and malaria preventive practices. Standard Diagnostic Bioline Rapid Diagnostic Tests were used to detect placental malaria present in placental blood. Microscopy was used to quantify the grade of placental malaria parasitaemia. Logistic regression was used to assess factors associated with placental malaria.ResultsThe mean age of the participants was 25.34 years (standard deviation [SD] 5.73). The prevalence of placental malaria was [4.4% (16/366) 95% CI (2.5 to 7.0)]. Of these, only 7/16 were positive on microscopy, with 2/7 having moderate parasitemia and 5/7 having mild parasitaemia. Women aged less than 20 years [AOR 3.48, 95% CI (1.13 to 10.72)], and those not taking iron supplements during pregnancy [AOR = 3.55, 95% CI (1.02 to 12.31)] were associated with an increased likelihood of having placental malaria.ConclusionThe prevalence of placental malaria was low in this setting. This may have reflected the low malaria transmission rates following intensive indoor residual spraying. Placental malaria infection was associated with younger age and not taking iron supplements during pregnancy. Public health measures need to scale up and emphasise adherence to malaria preventive measures during pregnancy especially among teenage mothers.

Relationship Between Clinical and Laboratory Parameters at Admission and Pregnancy Outcomes in Cases of Preterm Premature Rupture of Membranes

Abstract Background: Preterm premature rupture of membranes (PPROM) is a significant complication in pregnancy, often associated with adverse maternal and fetal outcomes. Understanding the relationship between clinical and laboratory parameters at admission and pregnancy outcomes in PPROM cases is essential for effective management and intervention. Methods The study was conducted retrospectively to examine the relationship between clinical and laboratory parameters at the time of admission and the latent period in pregnant women with PPROM. Records of pregnant women diagnosed with PPROM between 2015-2017 in the obstetrics department of a university hospital were reviewed. The patients were grouped according to gestational weeks, clinical parameters at admission were recorded, and their relationships with the latent period were analyzed. Results When the data obtained in the study were analyzed, it was shown that cervical length (p = 0.008) and the gestational week at the time of admission had an effect on the latent period (p

Evaluating neuronal damage biomarkers at birth for predicting neurodevelopmental risks in foetal growth restriction.

This study was based on the need to predict neurodevelopmental outcomes of children with foetal growth restriction. The aim was to systematically review the correlation between biomarkers of neural injury in children with foetal growth restriction and their neurodevelopment. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the review included studies on growth-restricted foetuses that measured biomarkers of postpartum brain injury and assessed neurodevelopment in childhood. Studies published between 1 January 2014 and 31 March 2024 were identified through PubMed and Embase, with the study protocol registered in PROSPERO (CRD42024520254). Only five met the inclusion criteria. Results showed that urinary S100B levels were significantly elevated in foetal growth restriction, negatively correlating with neurological development at 7 days of life. Neuron-specific enolase negatively correlated with cognitive, motor and socio-emotional development. Urinary nerve growth factor levels were significantly lower in neonates with foetal growth restriction, correlating with poor neurodevelopment. No alterations in BDNF levels were observed. Tau protein levels were lower in children with foetal growth restriction and adverse outcomes. The study emphasised the need for further research on biomarkers and predictive models of neurodevelopment in children with foetal growth restriction.

Association between gestational diabetes mellitus diagnostic criteria and adverse pregnancy outcomes—a systematic review and meta-analysis of adjusted effect sizes from studies using current diagnostic criteria

ObjectivesTo quantify the association between Gestational Diabetes Mellitus (GDM) and adverse pregnancy outcomes and primarily compare the associations between diagnostic criteria following the International Association of Diabetes and Pregnancy Study...

Managing diabetic chronic kidney disease in pregnancy: Current clinical practice and uncertainties.

Pre-gestational diabetes occurs in approximately 1% of pregnancies in the UK and increases the risk of adverse maternal and fetal outcomes. More women with type 2 than type 1 diabetes are now becoming pregnant and tend to have higher rates of obesity and other multi-morbidities. Chronic kidney disease (CKD) affects approximately 5%-10% of pregnant women with type 1 diabetes and about 2%-3% with type 2 diabetes. Diabetic chronic kidney disease (DCKD) increases the risk of preeclampsia, preterm birth, Caesarean section, small for gestational age (SGA) infant and infant admission to neonatal intensive care unit (NICU), and risks are higher compared to those with diabetes without CKD and those with CKD from other causes. Definitions of CKD in pregnancy are not standardised, and studies are generally small, observational, heterogenous, mainly include women with type 1 diabetes and often predate modern diabetes management such as continuous glucose monitoring and insulin pumps. Therefore, there is a lack of robust data to guide practice and clinical guidelines offer conflicting advice, without precise detail. We present our approach to caring for women with diabetes and CKD in pregnancy based on available guidelines and clinical experience. Our practice is to aim for intensive targets for blood pressure and glycaemic control pre and during pregnancy, lower than suggested in many guidelines. The importance of multidisciplinary team work and patient centred care is emphasised. Using standardised prospective data collection to better understand the prevalence and outcomes of diabetes and CKD in contemporary pregnancy populations, is recommended to drive future improvements in care.

Using an experience-based co-design approach to develop strategies for implementing an intravenous iron intervention to treat moderate and severe anemia in pregnancy in Malawi

BackgroundIn low- and middle-income countries, women experiencing anemia during pregnancy are recommended to take 30 mg to 60 mg of oral iron daily throughout pregnancy. However, oral iron tablets are often poorly tolerated and slow in correcting anemia, resulting in low adherence, prolonged anemia, and increased risk of adverse maternal and fetal outcomes. An alternative to oral iron is intravenous (IV) iron, commonly used in high-income countries to restore the body’s iron stores rapidly. A randomized controlled trial was conducted to investigate the effectiveness and safety of IV iron compared to standard-of-care oral iron supplementation for pregnant women with moderate and severe anemia in the third trimester in Malawi (REVAMP-TT). Using an experience-based co-design approach, our study aimed to identify barriers and facilitators to IV iron use to treat anemia in pregnancy in the primary healthcare system of Malawi, and develop mitigating strategies for the successful implementation of REVAMP-TT.MethodologyThe co-design process involved two phases: i) We conducted an information-gathering exercise to identify barriers and facilitators to IV iron use to treat anemia in pregnancy in the primary healthcare system of Malawi. We interviewed key informants (n = 53) including the policymakers, government partners, healthcare managers, and healthcare providers. We also gathered previous research findings from a formative qualitative study on the perceptions and experiences of IV iron treatment for pregnant women experiencing anemia in Malawi (n = 29). ii) We conducted two co-design workshops with end-users (n = 20) and healthcare providers (n = 20) to confirm and identify the key barriers and facilitators and developed mitigating strategies to inform the successful implementation of the REVAMP-TT trial. We mapped the emerging barriers to the Consolidated Framework for Implementation Research 2.0 (CFIR 2.0) and matched the mitigating strategies to the corresponding Expert Recommendations for Implementing Change (ERIC) compilation.ResultsThe following were identified as key barriers to IV iron use to treat anemia in pregnancy in the primary healthcare system of Malawi: the cost of IV iron, the lack of available resources and knowledge, local attitudes including myths and misconceptions about IV iron and keeping pregnancy a secret, local conditions, the lack of political will and buy-in from high-level leaders, the lack of capability of healthcare providers to deliver IV iron, and the lack of male involvement to support pregnant women's access to antenatal care. The proposed strategies to mitigate the barriers for the successful implementation of the REVAMP TT trial included providing financial strategy, developing stakeholder relationships, training and educating stakeholders, supporting clinicians, and engaging end-users.ConclusionThe use of the experience-based co-design approach in our study provided a valuable method to expose the potential barriers and facilitators to IV iron use and develop mitigating strategies to successfully implement the REVAMP-TT trial. Engaging both the key informants and end users promoted ownership and consensus among stakeholders and ensured a collaborative environment for sharing deeply rooted real-world experiences and insights. Not only do these findings address the needs of this study, but they also, lay a groundwork for the possible integration of IV iron into routine care in Malawi and provide knowledge for policymakers to make informed decisions on the management of anemia in the primary healthcare systems of Malawi.

Methylphenidate and Atomoxetine in Pregnancy and Possible Adverse Fetal Outcomes

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders, and it afflicts about 7% of young people. As a consequence, many young women might be pregnant while taking medication for ADHD, but data about safety have not yet been strictly examined. To examine adverse effects in offspring of mothers receiving treatment with atomoxetine and methylphenidate during pregnancy. Electronic databases (PubMed, Embase, and PsycINFO) were searched for articles published through December 31, 2023, with the following search terms: (atomoxetine OR methylphenidate) AND (pregnancy). Observational studies (eg, cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) that reported offspring outcomes in pregnancy with atomoxetine and/or methylphenidate and in mothers with ADHD but unexposed to ADHD treatment during pregnancy or from the general population were included. Ten studies of 656 records satisfied criteria. Two independent reviewers performed data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses were conducted based on reported odds ratios (ORs) and corresponding 95% CIs using a linear random effects model. Each study was inversely weighted by the reported variance of the estimators. Risk of publication bias and analysis of heterogeneity through univariate and multivariate metaregressions were also rated. Data were analyzed from January to March 2024. Study outcomes included miscarriages and congenital anomalies. Ten studies involving 16 621 481 pregnant women, 30 830 of them affected by ADHD, were included. Congenital anomalies or miscarriages were not more frequent in offspring of mothers receiving treatment with methylphenidate or atomoxetine during pregnancy compared with unexposed offspring (OR, 1.14; 95% CI, 0.83-1.55; P = .41; I2 = 8% for congenital anomalies; OR, 1.01; 95% CI, 0.70-1.47; P = .96; I2 = 0% for miscarriages) or compared with the general population (OR, 1.19; 95% CI, 0.93-1.53; P = .16; I2 = 74% for congenital anomalies; OR, 1.05, 95% CI, 0.81-1.37; P = .70; I2 = 0% for miscarriage). Evidence from this meta-analysis, which involves a substantial sample of pregnant women with and without ADHD, suggests the maintenance of methylphenidate or atomoxetine during pregnancy is safe, given that congenital anomalies and miscarriages did not appear to significantly increase. Further studies are recommended to support and confirm these findings.

Adverse maternal and fetal outcomes among tribal pregnant women suffering from sickle cell disease: A retrospective cohort study in a community-based hospital situated in a tribal block of Gujarat, India.

The study presents the risk of the maternal-fetal morbidity and mortality among one of the largest cohort of sickle cell disease (SCD) pregnancies in India and reports the epidemiology of the maternal morbidity. This was a retrospective cohort study conducted at Kasturba Maternity Hospital, SEWA Rural, in the tribal area of Gujarat, India. All pregnant women admitted to the Hospital between 2016 and 2021 were screened for SCD, and their maternal-fetal morbidities were recorded throughout the pregnancy. We quantified risk of maternal-fetal morbidity and mortality among SCD, trait and normal pregnancies after adjusting for potential confounders using Poisson and logistic regression. A total of 24 256 delivered during the study period, with 354 (1.5%) and 4216 (17.4%) suffering from SCD and trait, respectively. After adjusting for potential confounders, the women with SCD pregnancy had higher risk of maternal death (adjusted-odds-ratio [AOR] 13.7, 95% CI: 4.5-42.7), anemia (AOR 6.8, 95% CI: 4.5-10.2), severe anemia (AOR 4.3, 95% CI: 3.3-5.6), preterm delivery (AOR 4.5, 95% CI: 3.6-5.7), cesarean section (AOR 5.5, 95% CI: 4.7-7.0), stillbirth (AOR 3.4, 95% CI: 2.3-5.3), and low birth weight (AOR 3.1, 95% CI: 2.4-39) compared to normal pregnancies. Maternal morbidities occurred throughout the pregnancy; however, the risk was highest during the last month of pregnancy. Pregnant women who had severe manifestation of SCD before the pregnancy were at higher risk of developing maternal morbidities. We concluded that SCD might be an independent risk-factor for developing maternal-fetal morbidities. The SCD pregnancies with prior severe manifestations must be carefully managed during the last month of pregnancy when the risk is highest.

Evaluation of the clinical utility of NIPT-plus and analysis of adverse pregnancy outcomes.

To evaluate the performance of NIPT-plus in detecting fetal aneuploidies and CNVs and analyze the factors influencing adverse pregnancy outcomes. The retrospectively analyzed 8726 pregnant women who underwent NIPT-plus for fetal screening were classified into low- (who tested voluntarily) and high-risk (women with advanced age, abnormal ultrasound, abnormal serological screening, or a combination of indications) groups. Basic maternal information, prenatal findings, and pregnancy outcomes were recorded. NIPT-plus performance was assessed for various chromosomal abnormalities and the association between the fetal fraction and adverse pregnancy outcomes. Thirty-six (0.4%) patients had failed tests; 144 (1.65%) positive cases were detected, of which, 107 (74.31%) opted for invasive testing, and 51 were verified as true positives. The total positive predictive value was 45.45% and 48.65% in the low- and high-risk groups, respectively, and the difference was not significant. Among the subsequent cases with abnormal ultrasound monitoring, two false-negative cases were identified, and pathogenic CNV diagnosis was confirmed through amniocentesis, resulting in pregnancy termination. Fetal fraction was not associated with an increased adverse pregnancy outcome risk; however, ethnic differences may affect pregnancy outcomes. NIPT-plus technology use is no longer restricted to high-risk pregnant women, and it may produce false-positive results. The stakeholders should be aware of this limitation. The uncertainties and potential risks of the test results should be explained to the test takers to enable informed decision making and to minimize unnecessary anxiety and concerns. Ethnicity may influence adverse pregnancy outcomes in local multiracial settings.

Mid-late gestation leptin infusion induces placental mitochondrial and endoplasmic reticulum unfolded protein responses in a mouse model of preeclampsia

IntroductionPreeclamptic patients, both lean and obese, present with elevated leptin levels which are associated with the development of maternal endothelial dysfunction and adverse fetal outcomes, such as growth restriction, leading to low birth weight. Recent studies in pregnant mice demonstrate that mid-late gestation leptin infusion induces clinical characteristics of preeclampsia, including elevated maternal blood pressure, maternal endothelial dysfunction and fetal growth restriction. However, whether leptin triggers placental stress responses that contribute to adverse fetal outcomes as in preeclampsia is unknown. MethodsIn the current study we measured the expression of proteins involved in the endoplasmic reticulum (UPRer) and mitochondrial (UPRmt) unfolded protein responses in placentas of wild-type sham normal pregnant and leptin-infused preeclamptic mice. ResultsThe data show that mid-late gestation leptin infusion induced activation of indices of placental UPRer and UPRmt, while reducing placental repair mechanisms to UPRmt in preeclamptic mice. Mid-late gestation infusion with leptin upregulated markers of placental oxidative stress, reduced the placental expression levels of mitochondrial electron transport chain complexes I and II and increased the expression of placental endothelin-1 (ET-1) in preeclamptic mice. The leptin-induced activation of several placental UPRmt markers as well as ET-1 levels correlated with fetal growth restriction and impaired maternal endothelial function in preeclamptic mice. DiscussionCollectively, these data indicate that elevated levels of leptin in mid-late pregnancy in mice promote placental stress responses, akin to those in pregnant women with preeclampsia.

Safety of hepatitis E vaccine in pregnancy: an emulated target trial following a mass reactive vaccination campaign in Bentiu internally displaced persons camp, South Sudan

Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people. In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator. Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9). No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy. Médecins Sans Frontières.

Risk of invasive pneumococcal disease during pregnancy and postpartum and association with adverse maternal and foetal outcomes: a prospective cohort study, England, 2014-19

BackgroundPneumococcal infections are associated with significant morbidity and mortality, especially at the extremes of age and in those with underlying conditions. Little is known about the risks, presentations or outcomes of invasive pneumococcal disease (IPD) during pregnancy or the postpartum period. MethodsThe UK Health Security Agency conducts enhanced national surveillance of IPD in England. We used national surveillance data to calculate IPD risk and outcomes in pregnant, postpartum and non-pregnant women of childbearing age with IPD over a five-year period in England. FindingsThere were 1,701 IPD cases in women aged 15-44 years between 1 July 2014 and 30 June 2019, including 123 (7.2%) pregnant, 38 (2.1%) postpartum and 1,540 (90.7%) non-pregnant women. IPD incidence in pregnant women (0.048/1,000 woman-years) was not significantly different compared to non-pregnant women (0.041/1,000 woman-years; Incidence Rate Ratio [IRR]: 1.17; 95%CI 0.96-1.40; p=0.11). When stratified by trimester, however, women in their third trimester had a 2.27-fold (95%CI 1.79-2.85, p<0.001) increased risk of IPD, compared to non-pregnant women (IRR 2.27, 95%CI 1.78-2.85, p<0.001), while those in the first (IRR 0.49, 95%CI 0.28-0.80) and second trimester (IRR 0.71, 95%CI 0.47-1.04) had a lower risk, albeit only statistically significant for the first trimester. Postpartum women (0.144 per 1,000 woman-years), on the other hand, had a 3.49-fold (95%CI 2.46-4.81, p<0.001) higher IPD risk than non-pregnant women.Most pregnant women developed IPD during their third trimester (80/123, 65.0%), with all but one pregnancy resulting in a live birth. IPD in the second trimester was associated with live birth in 77.8% cases (21/27), while 22.2% experienced a miscarriage (5/27, 18.5%) or stillbirth (1/27, 3.7%). IPD in the first trimester was associated with live birth in 41.7% cases (5/12), miscarriages in 41.7% (5/12), and termination in 16.7% (2/12) cases. Only three neonates (3/142) had confirmed IPD. There were no deaths in pregnant women with IPD compared to 5.5% (85/1,540) in non-pregnant women. InterpretationWhile pregnant women overall did not appear to have an increased risk of IPD compared to non-pregnant women, those infected in third trimester appeared to have more than three times the incidence. Most pregnant and postpartum women had a live birth and subsequent neonatal infection was rare, occurring in 2% live births.

Asymptomatic bacteriuria screening for developing countries using a modified water quality test kit.

Between 2% and 15% of pregnant women unknowingly experience asymptomatic bacteriuria (ASB), defined as ≥105 CFU per milliliter of urine in the absence of symptoms. ASB increases the risk of adverse pregnancy outcomes including pyelonephritis, preterm labor, and low-birth weight infants. While pregnant women in the United States are routinely screened for ASB, those in developing countries with limited resources and funding lack an accurate mechanism for ASB screening. Aquagenx water quality test kits detect Escherichia coli, the most common causative agent of ASB, and total coliform bacteria in drinking water via colorimetric and fluorescent indicators. We found that the Aquagenx system is compatible with human urine and then proceeded to develop an ASB screening protocol using disposable inoculating loops. Our protocol diagnosed artificial ASB- samples (104 CFU/mL E. coli) with a false positive (FP) rate of 33% (n = 18) and ASB+ (105 CFU/mL E. coli) with a false negative (FN) rate of 5.6% (n = 18). Clinical sample testing with our protocol revealed a FP rate of 0% in ASB- samples (n = 28) and a FN rate of 0% in ASB+ samples caused by coliforms (n = 13). Aquagenx did not detect ASB in nine clinical samples with non-coliform etiological agents due to the limitations of the technology. However, with very high accuracy for detection of E. coli and other causative agents that collectively account for 90.1% of ASB cases, these kits could be used as a diagnostic ASB screening tool in developing countries in which there is currently no alternative to urine culture.IMPORTANCEAsymptomatic bacteriuria (ASB) affects 2%-15% of pregnant women and can result in adverse maternal and fetal outcomes if left undetected and untreated. In the United States and other developed nations, pregnant women are regularly screened for ASB via urine culture. However, in low-resource countries where bacterial culture is not available, dipstick testing is used. Although accurate in cases of symptomatic bacteriuria, dipstick detection is ineffective for detecting ASB. Here, we made use of an existing water quality field test for ASB urine screening, which would be readily deployable in low-resource settings. We optimized a dilution protocol for sampling patient urine within the detection limits of the Aquagenx kit technology. Overall, we were able to detect ASB samples with Gram-negative pathogens that collectively account for 90% of all ASB cases. Utilization of this repurposed technology for proactive medical screening may help prevent adverse pregnancy and birth outcomes due to ASB.