Prevalência de nascimentos prematuros como desfechos de infecções pela COVID-19 na gestação / Prevalence of Preterm Birth as an Outcome of COVID-19 Infections during Pregnancy / Prevalencia de nacimientos prematuros producto de la infección por COVID-19 durante el embarazo

Objetivo: estimar a prevalência de nascimento prematuro em gestantes infectadas pela Covid-19, comparar índices de prematuridade entre infectadas e não infectadas e elucidar fatores associados à prematuridade. Métodos: coorte retrospectiva, com coleta de dados por inquérito online, de abril a dezembro de 2022, com mulheres que estiveram gestantes durante a pandemia, com acesso à internet, idade superior a 18 anos e que preencheram o primeiro inquérito online. Protocolo de pesquisa aprovado pelo Comitê de Ética. Resultados: primeiro inquérito respondido por 304 gestantes/puérperas, e o segundo por 82 (27%), compondo a amostra final. O índice de prematuridade no primeiro inquérito foi de 7,2% (n=14), já no segundo, 8,5% (n=7). A infecção pela Covid-19 não foi associada à prematuridade. A prematuridade associou-se a baixo peso, à necessidade de internação em centros de terapia intensiva neonatal e internações após o nascimento. Conclusão: a infecção pela Covid-19 não influenciou no aumento de nascimentos prematuros.

Objective: to estimate the prevalence of preterm birth in pregnant women infected with Covid-19, compare prematurity rates between infected and non-infected, and elucidate factors associated with prematurity. Methods: a retrospective cohort study was conducted using online survey data collected from April to December 2022, involving women who were pregnant during the pandemic, had internet access, were over 18 years old, and completed the initial online survey. The research protocol was approved by the Ethics Committee. Results: the initial survey was completed by 304 pregnant/postpartum women, and the follow-up survey by 82 (27%), comprising the final sample. The preterm birth rate in the initial survey was 7.2% (n=14), and in the follow-up survey, it was 8.5% (n=7). Covid-19 infection was not associated with prematurity. Prematurity was associated with low birth weight, the need for neonatal intensive care unit admission, and postnatal hospitalizations. Conclusion: Covid-19 infection did not influence an increase in preterm births.

Objetivo: estimar la prevalencia de partos prematuros en gestantes infectadas por Covid-19, comparar las tasas de prematuridad entre gestantes infectadas y no infectadas y determinar los factores asociados a la prematuridad. Métodos: estudio de cohorte retrospectivo, con recolección de datos mediante encuesta online, de abril a diciembre de 2022, con mujeres que estuvieron embarazadas durante la pandemia, con acceso a internet, mayores de 18 años y que completaron la primera encuesta online. El protocolo de investigación fue aprobado por el Comité de Ética. Resultados: la primera encuesta fue respondida por 304 gestantes/puérperas, y la segunda por 82 (27%), que conformaron la muestra final. La tasa de prematuridad en la primera encuesta fue del 7,2% (n=14), en la segunda, del 8,5% (n=7). La infección por Covid-19 no se asoció con la prematuridad. La prematuridad se asoció con bajo peso, necesidad de internación en centros de cuidados intensivos neonatales e internaciones después del nacimiento. Conclusión: La infección por Covid-19 no influyó en el aumento de nacimientos prematuros.

Epigenetic scores derived in saliva are associated with gestational age at birth.

BACKGROUND: Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins. RESULTS: In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value < 8.3 × 10-3). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5, and hepatocyte growth factor-like protein (standardised estimates |0.06 to 0.13|, Bonferroni-adjusted p-value < 8.3 × 10-3). In a preterm subgroup (n = 217, median [range] GA 29.29 weeks [22.14 to 33.0 weeks]), SES-EpiScore associations did not remain statistically significant after adjustment for sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis. CONCLUSIONS: Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.

Preeclampsia and neonatal outcomes in pregnancies with maternal congenital heart disease: A nationwide cohort study from Norway.

INTRODUCTION: The prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease. MATERIAL AND METHODS: In a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs). RESULTS: Among 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD. CONCLUSIONS: Moderate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disorder characterized by impaired proximal airway and bronchoalveolar development in premature births. Secreted phosphoprotein 1 (SPP1) is involved in lung development and lung injury events, while its role was not explored in BPD. For establishing the in vivo models of BPD, a mouse model of hyperoxia-induced lung injury was generated by exposing neonatal mice to hyperoxia for 7 days after birth. Alveolar myofibroblasts (AMYFs) were treated with hyperoxia to establish the in vitro models of BPD. Based on the scRNA-seq analysis of lungs of mice housed under normoxia or hyperoxia conditions, mouse macrophages and fibroblasts were main different cell clusters between the two groups, and differentially expressed genes in fibroblasts were screened. Further GO and KEGG enrichment analysis revealed that these differentially expressed genes were mainly enriched in the pathways related to cell proliferation, apoptosis as well as the PI3K-AKT and ERK/MAPK pathways. SPP1 was found up-regulated in the lung tissues of hyperoxia mice. We also demonstrated the up-regulation of SPP1 in the BPD patients, the mouse model of hyperoxia-induced lung injury, and hyperoxia-induced cells. SPP1 deficiency was revealed to reduce the hyperoxia-induced apoptosis, oxidative stress and inflammation and increase the viability of AMYFs. In the mouse model of hyperoxia induced lung injury, SPP1 deficiency was demonstrated to reverse the hyperoxia-induced alveolar growth disruption, oxidative stress and inflammation. Overall, SPP1 exacerbates BPD progression in vitro and in vivo by regulating oxidative stress and inflammatory response via the PI3K-AKT and ERK/MAPK pathways, which might provide novel therapeutic target for BPD therapy.

Cyclostationary analysis of uterine EMG measurements for the prediction of preterm birth.

Preterm birth (gestational age < 37 weeks) is a public health concern that causes fetal and maternal mortality and morbidity. When this condition is detected early, suitable treatment can be prescribed to delay labour. Uterine electromyography (uEMG) has gained a lot of attention for detecting preterm births in advance. However, analyzing uEMG is challenging due to the complexities associated with inter and intra-subject variations. This work aims to investigate the applicability of cyclostationary characteristics in uEMG signals for predicting premature delivery. The signals under term and preterm situations are considered from two online datasets. Preprocessing is carried out using a Butterworth bandpass filter, and spectral correlation density function is adapted using fast Fourier transform-based accumulation method (FAM) to compute the cyclostationary variations. The cyclic frequency spectral density (CFSD) and degree of cyclostationarity (DCS) are quantified to assess the existence of cyclostationarity. Features namely, maximum cyclic frequency, bandwidth, mean cyclic frequency (MNCF), and median cyclic frequency (MDCF) are extracted from the cyclostationary spectrum and analyzed statistically. uEMG signals exhibit cyclostationarity property, and these variations are found to distinguish preterm from term conditions. All the four extracted features are noted to decrease from term to preterm conditions. The results indicate that the cyclostationary nature of the signals can provide better characterization of uterine muscle contractions and could be helpful in detecting preterm birth. The proposed method appears to aid in detecting preterm birth, as analysis of uterine contractions under preterm conditions is imperative for timely medical intervention.

Correlation of amniotic fluid inflammatory markers with preterm birth: a meta-analysis.

BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.

Laparoscopic Management of a 12-Week Pregnancy Loss in a Rudimentary Uterine Horn.

Unicornuate uterus with rudimentary horn is a rare structural uterine anomaly resulting from incomplete Mullerian duct development and/or fusion. Pregnancy in rudimentary horn is an uncommon presentation of a Mullerian anomaly and may lead to substantial morbidity and mortality due to high risk of uterine rupture with intraabdominal hemorrhage. Medical and/or surgical management may be undertaken; however, currently, no treatment guidelines exist. We describe the management of a 12-week rudimentary horn pregnancy in a 25-year-old multiparous patient with a prior spontaneous preterm breech vaginal delivery and one spontaneous early term cephalic vaginal delivery in whom this congenital uterine condition was previously unknown. The rudimentary horn, nonviable pregnancy, and contiguous ipsilateral fallopian tube were excised laparoscopically without complication. Given the infrequency of rudimentary horn pregnancies and the high risk for obstetric complications, a high index of suspicion should be maintained. We emphasize that a history of preterm birth or malpresentation should raise suspicion for maternal Mullerian anomaly, and that a minimally invasive approach can be feasible for treatment of a rudimentary horn pregnancy.

Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhages (grades 3,4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Prior randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born <28 weeks, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks. OBJECTIVE: To determine if the risk of severe intraventricular hemorrhage in infants delivered <28 weeks increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment prior to delivery decreases the rate of hemorrhage. STUDY DESIGN: Observational study examining the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk of delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equations techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who either delivered between 1-9 days (n=290) after the first 2-dose betamethasone course or delivered ≥10 days (and eligible for retreatment) (n=120). RESULTS: After adjusting for potential confounding variables, infants who delivered ≥10 days after a single betamethasone course had an increased risk of either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (OR (95%CI): 2.8 (1.2, 6.6)) compared with infants who delivered between 1-9 days after betamethasone. Among the 120 infants who delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second/retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second/retreatment course of betamethasone was similar to the rate in infants who delivered within 1-9 days and significantly lower than in those who delivered ≥10 days without retreatment (OR (95%CI): 0.10 (0.02, 0.65). Following the change in guidelines, the rate of retreatment in infants who delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%, p<0.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (p<0.001). In contrast, the rate of severe intraventricular hemorrhage in infants who delivered 1-9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSIONS: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course appears to restore its beneficial effects. Encouraging earlier retreatment of women at high risk of delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivering <28 weeks.

Aspirin 162 mg versus 81 mg for Preeclampsia Prophylaxis in High-risk Obese Individuals: A Comparative Effectiveness Open Label Randomized Trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Socioeconomic inequities during COVID 19 pandemic increase preterm birth and low birth weight in the most underprivileged.

BACKGROUND: The mitigation measures implemented to face the healthcare emergency brought by COVID 19 pandemic generated an increase in socioeconomic inequities in the most underprivileged population which is also the most threatened in their human rights. In Uruguay, this population is assisted in the public health care system. To analyze how these measures impacted on these mothers and their neonates we selected outcomes that most contributed to neonatal mortality. OBJECTIVE: To analyze the incidence of Preterm Birth (PB), Intrauterine Growth Restriction (IUGR) and Low Birth Weight (LBW) in the public health care system in Uruguay, during the period of time in which the strictest measures were adopted to mitigate the COVID 19 pandemic in 2020 (para-pandemic period) compared to the same period in 2019 (pre-pandemic). METHODS: A retrospective, cross sectional, descriptive study was performed to compare PB, IUGR and LBW from 15 March to 30 September 2019 (before COVID 19 pandemic) to the same period of 2020 (when COVID 19 pandemic bloomed), in the public health care subsystem. The analysis was performed with data from the national perinatal database system (SIP). RESULTS: In 2020, a significative increase in PB, RR: 1.14 (CI 95%: 1.03-1.25), and in LBW, RR: 1.16 (CI 95% 1.02-1.33), was registered compared to 2019 (pre-pandemic period). IUGR also showed an increase, but without statistical significance (4.6% in 2019 vs 5.2% in 2020, RR 1.13 CI 95% 0.98-1.31). The compared groups showed no differences in the distribution of biological confounding variables that could explain the increase in incidence of the main outcomes. CONCLUSIONS: In the absence of other factors that could explain the results we consider that social crisis associated to the restrictive measures implemented in the country to dwindle the effect of the pandemic exacerbated the adverse conditions that affect the reproductive process for those underprivileged women assisted in the public sector, increasing PB and LBW. It is important to consider the future impact of these results on neonatal and infant mortality and to implement social measures to reduce the damage as soon as possible.

Effect of maternal obsessive-compulsive disorder (OCD) on feto-maternal outcomes: A systematic review and meta-analysis.

BACKGROUND: Mental health disorders in pregnant women have been related to unfavorable obstetric and neonatal outcomes. Obsessive-compulsive disorder (OCD) significantly distresses mothers and affects the maternal-infant bond. OBJECTIVES: The present meta-analysis and systematic review aimed to assess the association of maternal OCD with adverse feto-maternal outcomes. SEARCH STRATEGY: A systematic search was undertaken in the five databases-Cochrane, Embase, ProQuest, Web of Science, and PubMed-on September 5, 2023. SELECTION CRITERIA: Studies that included pregnant women with OCD in whom the feto-maternal outcomes were reported were included in the systematic review. DATA COLLECTION AND ANALYSIS: Two pass screening ("title-abstract screening" followed by "full-text review"), and data extraction by two authors independently using the Nested-Knowledge Auto living semi-automated systematic review platform was carried out. The decision for selected studies was reviewed by a third author. Of the 360 studies identified, eight were included for the meta-analysis. Meta-analysis was conducted using R software. MAIN RESULTS: Of the 24 maternal and neonatal adverse outcomes assessed, 11 were found to be associated with maternal OCD, notably pre-eclampsia (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.19-1.57), antepartum hemorrhage or placental abruption (OR 1.32, 95% CI 1.13-1.54), postpartum hemporrhage (OR 1.19, 95% CI 1.08-1.31), cesarean section delivery (OR 1.32, 95% CI 1.23-1.41), emergency cesarean section (OR 1.22, 95% CI 1.15-1.30), preterm birth (OR 1.41, 95% CI 1.21-1.64), low birth weight (OR 1.41, 95% CI 1.28-1.54), low Apgar score at 5 min (OR 2.37, 95% CI 1.32-4.27), neonatal hypoglycemia (OR 1.37, 95% CI 1.23-1.53), neonatal respiratory distress (OR 1.77, 95% CI 1.44-2.16), and major congenital malformations (OR 1.37, 95% CI 1.08-1.74). CONCLUSION: OCD in pregnant women might be associated with multiple adverse feto-maternal outcomes.

Low fetal fraction and adverse pregnancy outcomes- systematic review of the literature and metanalysis.

PURPOSE: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies. METHODS: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966-2041), Scopus (2004-2024), Clinicaltrials.gov (2008-2024), EMBASE (1980-2024), Cochrane Central Register of Controlled Trials CENTRAL (1999-2024) and Google Scholar (2004-2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024. RESULTS: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%). CONCLUSION: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies.

Association between human papillomavirus and preterm delivery: A systematic review and meta-analysis.

INTRODUCTION: The lifetime prevalence of human papillomavirus infection (HPV) is estimated to be around 80% and it is the most common sexually transmitted infection. Despite being well known for its oncologic relevance, it has been associated with adverse pregnancy outcomes, though available evidence is contradicting. Previous meta-analyses involved articles which based HPV infection on Pap smear results, leading to a significant source of bias. Therefore, we aimed to assess the burden of genetically proven HPV infection on adverse pregnancy outcomes. MATERIAL AND METHODS: In our meta-analysis, pregnant women tested for HPV DNA were only considered eligible. We conducted a systematic search in three major databases (PubMed, Embase, and CENTRAL) on September 22, 2023. Cohort, cross-sectional, and case-control studies were eligible for the analysis. The exposed group consisted of HPV-infected patients. We assessed the odds ratios (OR) with a confidence interval (CI) of 95%. In order to reduce the heterogeneity, we performed subgroup analyses based on different strains (high risk HPV, HPV 16/18, study design). The study was prospectively registered on PROSPERO (CRD42022370228). RESULTS: Our study involved 14 articles with 7008 women. A significant association was found between preterm delivery and HPV infection (OR: 1.94, CI: 1.31-2.87). No significant association was found when separately examining high-risk HPV-infected women (OR: 1.94, CI: 0.82-4.59), and HPV 16 or 18-infected women (OR: 2.08, CI: 0.50-8.63) in terms of preterm delivery. No significant association was found between spontaneous abortion and HPV infection (OR: 1.02, CI: 0.16-6.31). CONCLUSIONS: Our analysis indicates an association between HPV infection and preterm delivery. It is imperative that future studies consider confounding variables more comprehensively. Additionally, the global implementation of HPV vaccination programs holds significance not only in oncology but also in obstetrics.

Uterocervical angle and cervical length measurements for spontaneous preterm birth prediction in low-risk singleton pregnant women: a prospective cohort study.

PURPOSE: Preterm birth is the leading cause of early neonatal morbidity and mortality. Strategies to predict preterm birth risk can help improve pregnancy outcomes. Even pregnant women without known risk factors for preterm birth can also experience it. This study aimed to evaluate the ability of the uterocervical angle and cervical length to predict spontaneous preterm birth in low-risk singleton pregnant women. METHODS: A prospective study on 1107 singleton pregnant women between 16+0 and 23+6 weeks gestation at low risk for spontaneous preterm birth who were treated at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, between September 2020 and September 2021 was conducted. A single sonographer assessed the cervical length and the uterocervical angle using transvaginal ultrasonography. The patients were followed up until delivery to determine the main pregnancy outcome (spontaneous preterm birth before 37 weeks gestation). The cut-off points for the uterocervical angle and cervical length were established by analyzing the receiver operating characteristic curve. The sensitivity, specificity, likelihood ratio, positive and negative predictive values, and accuracy of the uterocervical angle and cervical length for predicting spontaneous preterm birth were determined. RESULTS: A uterocervical angle ≥ 99° predicted spontaneous preterm birth at < 37 weeks, with a sensitivity and specificity of 91% and 76%, respectively. A cervical length ≤ 33.8 mm predicted preterm birth at < 37 weeks with a sensitivity and specificity of 25% and 66%, respectively. A uterocervical angle ≥ 99° combined with a cervical length ≤ 33.8 mm yielded the sensitivity, specificity, positive predictive value, likelihood ratio, and accuracy of spontaneous preterm birth prediction of 66%, 93%, 36%, 9, and 91%, respectively; thus provided a significant increase of specificity with an acceptable reduction of sensitivity as compared to cervical length alone. CONCLUSION: Besides the cervical length, the uterocervical angle can be considered a valuable ultrasound parameter for predicting spontaneous preterm birth in low-risk singleton pregnant women. Combining the uterocervical angle and cervical length yielded stronger spontaneous preterm birth prediction values.

Preterm Birth Research in Southeast Asia and its Association with Socioeconomic Determinants and Burden of Disease: A Bibliometric Analysis.

Objective: The aim of this study was to assess research productivity on preterm birth (PTB) in Southeast Asian (SEA) countries and its correlation with socioeconomic characteristics and burden of disease. Methods: A systematic review of preterm birth publications by SEA authors indexed in Scopus, PubMed, ClinicalTrials. gov, and Cochrane was done. Case reports, cohorts, control trials, reviews and cost analysis studies done by SEA researches involving pathophysiology, diagnosis, management, and complications of preterm birth was included in the study while published letters to editors were excluded. The correlation of bibliometric indices, namely Scopus citations, and PlumX metrics indices (citations, usage, captures, mentions, and social media), with socioeconomic status and burden of preterm birth in SEA countries were analyzed by computing for the correlation coefficient (r) and p-value at an alpha of 0.05. Results: Thailand had the highest number of publications and the highest count across all bibliometric indices among all countries in SEA. The percent gross domestic product (GDP) per capita allotted for research and development (R & D) had direct correlation with publications and captures while crude birth rates had indirect correlation with publications, citations, and captures. Neonatal mortality had indirect correlation with publications and captures. Conclusion: Support for research and development is essential to increase research productivity in SEA, which in turn may help in finding solutions to decrease the rate of preterm birth in the region.

Consistently lower volumes across thalamus nuclei in very premature-born adults.

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.

Gestational weight gain as a mediator of the relationship between pre-pregnancy body mass index and the risk of preterm birth: A four-way decomposition analysis.

OBJECTIVE: The aim of the present study was to examine and quantify whether the association between preterm birth (PTB) and pre-pregnancy body mass index (BMI) is mediated by gestational weight gain (GWG). METHODS: This is a secondary analysis of a large randomized community non-inferiority trial using a cohort design. The data of 26 101 pregnant women in their first trimester who sought prenatal care and met eligibility criteria were included. The four-way decomposition method was applied to screen for all types of association effects of pre-pregnancy BMI on the risk of PTB. These effects include the total, direct, and various indirect effects including pure mediation via GWG, interactive effects with GWG, and mediated interaction with GWG, all adjusted for potential confounders. RESULTS: Among the study participants, 24 461 (93.7%) had term deliveries, while 1640 (6.3%) experienced PTB. The results of the study showed that there was a positive association between pre-pregnancy BMI among those with BMI more than 25 kg/m2 and the risk of PTB and this association was negatively mediated and interacted by GWG, which differed quantitatively between those who had inadequate, adequate, or excessive GWG. The total association effect showed that the risk was lowest for those who had underweight pre-pregnancy BMI and adequate GWG (excess relative risk [RR]: 0.06, 95% CI: 0.01-0.11, P value: 0.022) and was highest for those who had obese pre-pregnancy BMI and excessive GWG (excess RR: 0.67, 95% CI: 0.35-1.00, P value <0.001). CONCLUSION: The findings of the present prospective population-based study demonstrated that pre-pregnancy BMI >25 kg/m2 is directly and positively associated with the risk of preterm birth. The highest risk of preterm birth was observed among individuals with an obese pre-pregnancy BMI who also experienced excessive GWG.

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine death is found to be more in group A (SLE with APS) (16.7% [12/72]) as compared to group B (SLE without APS) (5.7% [3/53]) with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

A cross-sectional analysis of preterm birth incidence and survival in Al Kharj, Saudi Arabia.

OBJECTIVES: To understand the prevalence and survival rates of preterm birth (PTB) is of utmost importance in informing healthcare planning, improving neonatal care, enhancing maternal and infant health, monitoring long-term outcomes, and guiding policy and advocacy efforts. METHODS: The medical records of preterm infants admitted to the Neonatal Intensive Care Unit (NICU) with a diagnosis of prematurity at the Maternity and Children's Hospital (MCH), Al Kharj, Saudi Arabia, were reviewed between January 2018 and December 2022. Data were collected on birth weight (BW), gender, number of live births, gestational age, mortality, nationality, APGAR score, length of stay in the NICU, and maternal details. RESULTS: A total of 9809 live births were identified between 2018 and 2022, of which 139 (3.9%) were born preterm. The overall mortality rate of the included sample was 7.19%, whereas the mortality rate according to BW was 38.4% of those born with extremely low birth weight (ELBW). The most common intrapartum complications were malpresentation (15.1%), placental complications (4.3%), and cord complications (3.6%). CONCLUSION: This study provides valuable insights into the prevalence of PTB in the country, particularly focusing on the vulnerability of extremely preterm babies.

A dynamic flow fetal membrane organ-on-a-chip system for modeling the effects of amniotic fluid motion.

Fetal membrane (amniochorion), the innermost lining of the intrauterine cavity, surround the fetus and enclose amniotic fluid. Unlike unidirectional blood flow, amniotic fluid subtly rocks back and forth, and thus, the innermost amnion epithelial cells are continuously exposed to low levels of shear stress from fluid undulation. Here, we tested the impact of fluid motion on amnion epithelial cells (AECs) as a bearer of force impact and their potential vulnerability to cytopathologic changes that can destabilize fetal membrane functions. A previously developed amnion membrane (AM) organ-on-chip (OOC) was utilized but with dynamic flow to culture human fetal amnion membrane cells. The applied flow was modulated to perfuse culture media back and forth for 48 h to mimic fluid motion. A static culture condition was used as a negative control, and oxidative stress (OS) condition was used as a positive control representing pathophysiological changes. The impacts of fluidic motion were evaluated by measuring cell viability, cellular transition, and inflammation. Additionally, scanning electron microscopy (SEM) imaging was performed to observe microvilli formation. The results show that regardless of the applied flow rate, AECs and AMCs maintained their viability, morphology, innate meta-state, and low production of pro-inflammatory cytokines. E-cadherin expression and microvilli formation in the AECs were upregulated in a flow rate-dependent fashion; however, this did not impact cellular morphology or cellular transition or inflammation. OS treatment induced a mesenchymal morphology, significantly higher vimentin to cytokeratin 18 (CK-18) ratio, and pro-inflammatory cytokine production in AECs, whereas AMCs did not respond in any significant manner. Fluid motion and shear stress, if any, did not impact AEC cell function and did not cause inflammation. Thus, when using an amnion membrane OOC model, the inclusion of a dynamic flow environment is not necessary to mimic in utero physiologic cellular conditions of an amnion membrane.