[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Socioeconomic disparities in changes to preterm birth and stillbirth rates during the first year of the COVID-19 pandemic: a study of 21 European countries.

BACKGROUND: Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. METHODS: The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015-2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. RESULTS: Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94-0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99-1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. CONCLUSIONS: PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.

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.

The role of bacterial genital infections in spontaneous preterm delivery: a case-control study.

Background: Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth. Methods: The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed. Results: The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of Chlamydia trachomatis, Neisseria gonorrhea, Listeria monocytogenes, and Mycoplasma genitalium infections was zero in both groups. The highest prevalence of Gardnerella vaginalis was 19 (19%) in the case group and Ureaplasma parvum 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between Gardnerella vaginalis bacteria and spontaneous preterm delivery. Conclusion: The results of our study showed that except for Gardnerella vaginalis bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers.

Women's experience of preterm birth in an East African context: a qualitative study.

Background: Approximately 15 million children are born each year prematurely, representing more than 10 percent of all childbirths worldwide. Prematurity is an acute event and the leading cause of death among newborns and children under five. Sixty percent of these premature deaths occur in Sub-Saharan Africa and Southeast Asia. Objective: The current study aimed to explore and understand women's experiences and perceptions regarding giving birth prematurely at the National Hospital of Muhimbili in Dar es Salaam, Tanzania. Method: A qualitative method, using Interpretive Phenomenological Analysis approach was chosen to understand and describe the women's experiences. A semi-structured guide was used during the interviews. All interviews were audio-recorded and transcribed verbatim. Findings: Eight in-depth interviews were conducted. The analysis revealed three superordinate themes: (a) Emotional turmoil: unmet expectations shattering maternal identity, emotional distress, and loss of hope; (b) Adapting to preterm birth and challenges: the unexpected situation, lack of proper care, strenuous breastfeeding routines, and socioeconomic challenges; (c) Significance of proper care and emotional support: good maternal care, mother-to-mother and family support. Conclusion: This study provided a deeper understanding of women's experiences and perceptions of premature childbirth. The current study indicated the importance of caregivers' awareness of the women's emotional distress, their need to adapt to a sudden unexpected situation, and the necessity of emotional support.

The use of antenatal corticosteroids in preterm labour for the prevention of perinatal mortality in hospitals in Tanzania.

Background: Antenatal corticosteroids (ACS) are given to pregnant women at risk of preterm delivery to hasten the maturation of the lungs, lowering the risk of newborn respiratory distress syndrome (RDS) and perinatal mortality. Objective: The aim of this study was to determine whether exposure to ACS was associated with lower rates of perinatal mortality and RDS in preterm infants delivered by women with preterm labour. Methods: This is a secondary analysis of data from four hospitals in Mwanza, Tanzania. All singletons and twins born to women who were in preterm labour between July 2019 and February 2020 and delivered in-hospital between 24 and 34 weeks of gestation were included. Data were recorded from participants' medical records and analysed using STATA Version 14. Results: Over an eight-month period, 588 preterm infants were delivered to 527 women. One hundred and ninety (36.1%) women were given ACS. Infants who were exposed to ACS in utero had a lower rate of perinatal mortality (6.8% vs 19.1%) and RDS (12.3% vs 25.9%) compared to those not exposed to ACS. In adjusted multivariable models, ACS exposure was related to a lower risk of perinatal mortality, aRR 0.23 (95% CI 0.13 - 0.39), and RDS, aRR 0.45 (95% CI 0.30 - 0.68). Conclusion: ACS significantly reduced the risk of perinatal mortality and RDS among preterm infants exposed to ACS in utero and delivered by women in preterm labour. The use of ACS should be encouraged in low-resource settings where preterm birth is prevalent to improve perinatal outcomes.

[Correlation between hepatitis B virus infection and adverse pregnancy outcomes-a systematic review and meta-analysis].

Objective: To systematically evaluate the effect of hepatitis B virus (HBV) infection on the risk of adverse pregnancy outcomes. Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases. Two researchers independently screened the literature, extracted data, and evaluated the quality. Meta-analysis and cumulative meta-analysis were performed using R4.4.1 software. Fixed/random effects models were used to analyze heterogeneous and non-heterogeneous results. Heterogeneous modifiers were identified by subgroup analysis. Funnel plots and Peters' test were used to analyze potential publication bias. Results: A total of 48 studies involving 92 836 HBsAg-positive pregnant women and 7 123 292 HBsAg-negative pregnant women were included. In terms of adverse pregnancy outcomes, HBV infection was significantly correlated with the occurrence of gestational diabetes mellitus [odds ratio (OR)=1.34, 95% confidence interval (CI): 1.17-1.53] and intrahepatic cholestasis (OR=2.48, 95%CI: 1.88-3.29), with statistically significant differences. In terms of adverse neonatal outcomes, HBV infection was significantly correlated with the occurrence of neonatal asphyxia (OR=1.49, 95%CI: 1.20-1.86) and preterm birth (OR=1.22, 95%CI: 1.12-1.33), with statistically significant differences. In addition, the cumulative meta-analysis demonstrated that the risk of gestational diabetes mellitus and preterm birth both tended to be stable in pregnant women with HBV infection following 2009 and 2010, respectively. The supplementary questions answered for repeated studies had limited significance. Conclusion: Intrahepatic cholestasis, gestational diabetes mellitus, neonatal asphyxia, and preterm birth occurrence risk can be raised with HBV infection in pregnant women.

Post-natal gestational age assessment using targeted metabolites of neonatal heel prick and umbilical cord blood: A GARBH-Ini cohort study from North India.

Background: Accurate assessment of gestational age (GA) and identification of preterm birth (PTB) at delivery is essential to guide appropriate post-natal clinical care. Undoubtedly, dating ultrasound sonography (USG) is the gold standard to ascertain GA, but is not accessible to the majority of pregnant women in low- and middle-income countries (LMICs), particularly in rural areas and small secondary care hospitals. Conventional methods of post-natal GA assessment are not reliable at delivery and are further compounded by a lack of trained personnel to conduct them. We aimed to develop a population-specific GA model using integrated clinical and biochemical variables measured at delivery. Methods: We acquired metabolic profiles on paired neonatal heel prick (nHP) and umbilical cord blood (uCB) dried blood spot (DBS) samples (n = 1278). The master data set consists of 31 predictors from nHP and 24 from uCB after feature selection. These selected predictors including biochemical analytes, birth weight, and placental weight were considered for the development of population-specific GA estimation and birth outcome classification models using eXtreme Gradient Boosting (XGBoost) algorithm. Results: The nHP and uCB full model revealed root mean square error (RMSE) of 1.14 (95% confidence interval (CI) = 0.82-1.18) and of 1.26 (95% CI = 0.88-1.32) to estimate the GA as compared to actual GA, respectively. In addition, these models correctly estimated 87.9 to 92.5% of the infants within ±2 weeks of the actual GA. The classification models also performed as the best fit to discriminate the PTB from term birth (TB) infants with an area under curve (AUC) of 0.89 (95% CI = 0.84-0.94) for nHP and an AUC of 0.89 (95% CI = 0.85-0.95) for uCB. Conclusion: The biochemical analytes along with clinical variables in the nHP and uCB data sets provide higher accuracy in predicting GA. These models also performed as the best fit to identify PTB infants at delivery.

Pregnancy outcomes of foetal reduction from twin to singleton gestation compared to ongoing twin gestations: a systematic review and meta-analysis.

BACKGROUND: Foetal reduction, which involves selectively terminating one or more foetuses in a multiple gestation pregnancy, has become more common. This systematic review and meta-analysis aims to assess and compare pregnancy outcomes of foetal reduction from twin to singleton gestation to ongoing twin gestations. METHODS: A comprehensive search of electronic databases (MEDLINE, EMbase, Cochrane Library, CINAHL and PsycINFO) was done for studies published until 15 April 2023. The outcomes analysed included gestational diabetes mellitus (DM), hypertension, caesarean delivery, foetal loss, perinatal death, preterm birth (PTB), intrauterine growth restriction (IUGR), preterm prelabour rupture of membranes (PPROM) and birth weight. RESULTS: A total of 13 studies comprising 1241 cases of twin to singleton foetal reduction gestation were compared to 20,693 ongoing twin gestations. Our findings indicate that foetal reduction was associated with a significantly lower risk of developing maternal gestational DM (odds ratio [OR] = 0.40, 95% confidence interval [CI] 0.27-0.59) and hypertension (OR = 0.36, 95% CI 0.23-0.57) compared to the control group. Incidence rate of caesarean delivery (OR = 0.65, 95% CI 0.53-0.81) after foetal reduction was significantly lower compared to ongoing twin gestations. There was a 63% lower chance of PTB before 37 weeks of pregnancy. However, there was no significant association between foetal reduction and outcomes such as foetal loss, perinatal death, IUGR and PPROM. CONCLUSIONS: Our findings suggest that foetal twin to singleton reduction entails potential benefits as compared to ongoing twin gestations. Further well planned studies are needed to explore underlying mechanisms to understanding of the outcomes associated with foetal reduction procedures and inform clinical decision-making for pregnant individuals and healthcare providers alike.

Foetal reduction, a procedure where one or more foetuses in a twin pregnancy are selectively terminated, has become more common. This study reviewed existing research to compare the outcomes of foetal reduction to singleton pregnancies with those of ongoing twin pregnancies. The study found that mothers who underwent foetal reduction had a lower risk of developing gestational diabetes and hypertension, and they were less likely to have a caesarean delivery. There was also a reduced chance of preterm birth before 37 weeks. However, foetal reduction did not appear to significantly impact outcomes like foetal loss, perinatal death, intrauterine growth restriction or preterm pre-labour rupture of membranes. It is important to note that there is some variation in the results among different studies, and more research is needed to fully understand these findings.

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.

Using Parametric g-Computation for Time-to-Event Data and Distributed Lag Models to Identify Critical Exposure Windows for Preterm Birth: An Illustrative Example Using PM2.5 in a Retrospective Birth Cohort Based in Eastern Massachusetts (2011-2016).

BACKGROUND: Parametric g-computation is an attractive analytic framework to study the health effects of air pollution. Yet, the ability to explore biologically relevant exposure windows within this framework is underdeveloped. OBJECTIVES: We outline a novel framework for how to incorporate complex lag-responses using distributed lag models (DLMs) into parametric g-computation analyses for survival data. We call this approach "g-survival-DLM" and illustrate its use examining the association between PM2.5 during pregnancy and the risk of preterm birth (PTB). METHODS: We applied the g-survival-DLM approach to estimate the hypothetical static intervention of reducing average PM2.5 in each gestational week by 20% on the risk of PTB among 9,403 deliveries from Beth Israel Deaconess Medical Center, Boston, Massachusetts, 2011-2016. Daily PM2.5 was taken from a 1-km grid model and assigned to address at birth. Models were adjusted for sociodemographics, time trends, nitrogen dioxide, and temperature. To facilitate implementation, we provide a detailed description of the procedure and accompanying R syntax. RESULTS: There were 762 (8.1%) PTBs in this cohort. The gestational week-specific median PM2.5 concentration was relatively stable across pregnancy at ∼7µg/m3. We found that our hypothetical intervention strategy changed the cumulative risk of PTB at week 36 (i.e., the end of the preterm period) by -0.009 (95% confidence interval: -0.034, 0.007) in comparison with the scenario had we not intervened, which translates to about 86 fewer PTBs in this cohort. We also observed that the critical exposure window appeared to be weeks 5-20. DISCUSSION: We demonstrate that our g-survival-DLM approach produces easier-to-interpret, policy-relevant estimates (due to the g-computation); prevents immortal time bias (due to treating PTB as a time-to-event outcome); and allows for the exploration of critical exposure windows (due to the DLMs). In our illustrative example, we found that reducing fine particulate matter [particulate matter (PM) with aerodynamic diameter ≤2.5µm (PM2.5)] during gestational weeks 5-20 could potentially lower the risk of PTB. https://doi.org/10.1289/EHP13891.

The influence of previous preterm birth with singleton pregnancy on the risk of recurrence in subsequent twin pregnancy: a meta-analysis.

BACKGROUND: Preterm birth is a significant obstetrical concern around the globe. With this study, we aimed to determine whether a prior singleton pregnancy preterm birth increases the likelihood of preterm birth in subsequent twin pregnancies. We designed his systematic review to provide valuable information for pregnant women and obstetricians during counselling and for individuals involved in the planning of preventive strategies. METHODS: We comprehensively searched the PubMed, Embase and Scopus databases to identify relevant studies published until October 2023 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We applied a random-effects meta-analysis to the data gathered from the selected studies. RESULTS: Among the 460 initially identified studies, only eight met the eligibility criteria. The analysis of incidence revealed an event rate of 9.5% (95% CI, 4.4-19.5%) for a history of preterm singleton birth in the cohort of women with subsequent twin pregnancies. Subgroup analyses focused on the risk of preterm twin births (<37 weeks, <34 weeks and <32 weeks) in women with prior preterm singleton births. Our results revealed a significantly elevated risk of subsequent preterm twin births associated with prior preterm singleton births at <37 weeks (OR, 2.94; 95% CI, 1.99-4.33; p < .001), <34 weeks (OR, 1.89; 95% CI, 1.67-2.14; p < .001) and <32 weeks (OR, 2.51; 95% CI, 1.58-3.99; p < .001), without heterogeneity in the included studies. CONCLUSIONS: Our systematic analysis indicates a consistent and statistically significant association between a history of preterm singleton births and preterm twin births at various gestational ages. These findings underscore the importance of the obstetric history during assessments to predict the risk of preterm births in twin pregnancies. Clinicians should monitor pregnancies with a history of preterm singleton births, as targeted interventions and improved prenatal care can mitigate the risk of preterm birth during twin pregnancies.

Preterm birth, a global concern, prompted a study examining whether a prior preterm singleton birth raises the risk of preterm birth in subsequent twin pregnancies. Conducting a systematic review of 460 studies, only eight met the eligibility criteria. The meta-analysis revealed a 9.5% incidence of preterm singleton births in subsequent twin pregnancies. Further analysis demonstrated a significantly elevated risk of preterm twin births at <32 weeks for those with a history of preterm singleton births. The study concludes that a consistent and statistically significant association exists between prior preterm singleton births and increased preterm twin birth risk at various gestational ages. This underscores the importance of considering obstetric history in assessing preterm birth risk in twin pregnancies. Clinicians are advised to closely monitor pregnancies with a history of preterm singleton births for interventions targeted and improved prenatal care.

Alteration of fractional anisotropy in preterm-born individuals: a systematic review and meta-analysis.

BACKGROUD: Neurological disorders are common in preterm (PT) born individuals. Diffusion tensor imaging (DTI) studies using tract-based spatial statistics (TBSS) effectively detect microstructural white matter (WM) abnormalities in the brain. We conducted this systematic review to integrate the findings of TBSS studies to determine the most consistent WM alterations in PT born individuals. METHODS: PubMed, Embase, Web of Science and Science Direct were searched. DTI studies using TBSS in PT born individuals were screened up to October 2022. The systematic review included studies reporting alterations in FA values for the entire brain in a stereotactic space, with three coordinates (x, y, z), according to the seed-based d mapping method. RESULTS: The search strategy identified seventeen studies that fulfilled our inclusion criteria, with a total of 911 PT-born individuals and 563 matched controls were analysed. Of the seventeen studies, eight were dedicated to 650 adults, five to 411 children and four to 413 infants. Ten studies recruited 812 individuals born very prematurely (GA <29 weeks), six studies recruited 386 moderately premature individuals (GA = 29-32 weeks) and one study recruited 276 individuals born late prematurely (GA >32 weeks). This meta-analysis of six studies including 388 individuals highlighted four brain regions in which fractional anisotropy (FA) was lower in PT group than in people born at term. The quantitative meta-analysis found that the most robust WM alterations were located in the corpus callosum (CC), the bilateral thalamus and the left superior longitudinal fasciculus (SLF) II. Significant changes in FA reflect WM abnormalities in PT born individuals from infant to young adulthood. CONCLUSIONS: Significant changes in FA reflect WM abnormalities in individuals born PT from infancy to young adulthood. The abnormal development of the CC, bilateral thalamus and left SLF may play a vital role in the neurodevelopment of PT individuals.

Neurological disorders are prevalent in preterm (PT) born individuals. The use of tract-based spatial statistics (TBSS) in diffusion tensor imaging (DTI) studies has proven effective in detecting microstructural abnormalities of the white matter (WM) of the brain. In order to determine the most consistent alterations in WM among those born prematurely, we have screened DTI studies using TBSS in this PT born population up until October 2022. The meta-analysis identified four brain regions where fractional anisotropy (FA) was lower in the PT group than in those born at term. The quantitative meta-analysis identified the corpus callosum, the bilateral thalamus and the left superior longitudinal fasciculus II. As the most robust WM alterations. Various studies have demonstrated the links between PT birth, intelligence quotient, gestational age and subject age.

Neutrophils and monocyte toll like receptors 2 and 4 expression in preterm versus term delivery.

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor.

Prenatal exposure to Benzo[a]pyrene affects maternal-fetal outcomes via placental apoptosis.

Prenatal exposure to Benzo[a]pyrene (BaP) has been suggested to increase the risk of adverse pregnancy outcomes. However, the role of placental apoptosis on BaP reproductive toxicity is poorly understood. We conducted a maternal animal model of C57BL/6 wild-type (WT) and transformation-related protein 53 (Trp53) heterozygous knockout (p53KO) mice, as well as a nested case-control study involving 83 women with PB and 82 term birth from a birth cohort on prenatal exposure to BaP and preterm birth (PB). Pregnant WT and p53KO mice were randomly allocated to BaP treatment and control groups, intraperitoneally injected of low (7.8 mg/kg), medium (35 mg/kg), and high (78 mg/kg) doses of 3,4-BaP per day and equal volume of vegetable oil, from gestational day 10.5 until delivery. Results show that high-dose BaP treatment increased the incidence of preterm birth in WT mice. The number of fetal deaths and resorptions increased with increasing doses of BaP exposure in mice. Notably, significant reductions in maternal and birth weights, increases in placental weights, and decrease in the number of livebirths were observed in higher-dose BaP groups in dose-dependent manner. We additionally observed elevated p53-mediated placental apoptosis in higher BaP exposure groups, with altered expression levels of p53 and Bax/Bcl-2. In case-control study, the expression level of MMP2 was increased among women with high BaP exposure and associated with the increased risk of all PB and moderate PB. Our study provides the first evidence of BaP-induced reproductive toxicity and its adverse effects on maternal-fetal outcomes in both animal and population studies.

Pregnancy outcomes and risk factors analysis in patients with systemic lupus erythematous.

BACKGROUND: The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. METHODS: A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. RESULTS: A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P < 0.0001), lupus nephritis (P = 0.0195), anti-SSB positivity (P = 0.0074) and hypocomplementemia (P = 0.0466) were related to ANOs. However, multivariate analysis showed that only disease activity during early pregnancy was an independent predictor for ANOs (OR = 7.053, 95% CI: 1.882 to 26.291, P = 0.004). In addition, 48 patients experienced AMOs during subsequent trimester, including 24 (19.0%) patients with disease flare and 23 (18.3%) patients with pre-eclampsia. Unplanned pregnancy (P = 0.010), active disease (P = 0.0004), new onset SLE (P = 0.0044) and lupus nephritis (P = 0.0009) were associated with AMOs in univariate analysis, while disease activity was identified as an independent risk factor for AMOs (OR = 2.553, 95% CI: 1.012-6.440, P = 0.047). CONCLUSION: Active disease in early pregnancy is associated with adverse pregnancy outcomes. For patients with high risk factor for ANOs and AMOs, more intensive treatment and follow-up should be a wise measure. Especially for those who suffer from active disease, they should be fully informed and given the option to terminate or continue their pregnancy.

Qualitative interview with mothers of moderately or late preterm infants in the UK: where are the care gaps?

INTRODUCTION: Preterm birth (<37 gestational weeks) accounts for an increasing proportion of global births each year, with moderately or late preterm birth (MLPT) (32+0/7-36+6/7 gestational weeks) comprising over 80% of all preterm births. Despite the frequency, MLPT births represent only a small fraction of prematurity research, with research exploring the parental experiences of having a child born MLPT particularly neglected. It is vital this perspective is considered to provide appropriate grounding for future research and service provision. METHODS: Six mothers from the UK of infants (aged between 18 and 36 months) born MLPT were invited to take part in a semistructured qualitative interview study. Reflexive thematic analysis was employed to explore the data and codes were then conceptualised through a process of inductive reasoning to identify patterns of meaning. RESULTS: Five themes are presented that are conceptualised from the data: (1) the moderate or later preterm 'label-does it matter?, (2) vulnerability within a new role, (3) coming home and wanting to start 'normal' life, (4) comparisons to provide a reference to experiences and (5) experience of professionals throughout the pregnancy, newborn and early years journey. CONCLUSIONS: Findings offer in-depth evidence surrounding mothers' experiences of healthcare throughout pregnancy and immediately after birth, perceptions of the 'preterm' label and thoughts on how mothers reflect on their experiences. Future research should show an awareness of the broader family context when interpreting findings and providing suggestions for future research avenues or service provision.

Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

INTRODUCTION: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality. METHODS AND ANALYSIS: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study.

BACKGROUND: Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth. METHODS: This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks' gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy. RESULTS: 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913 bp, p = 0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144 bp, p = 0.64) or in the Urban Cohort (6717 versus 6913, p = 0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p = 0.02). CONCLUSION: Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.

Biomarker Identification for Preterm Birth Susceptibility: Vaginal Microbiome Meta-Analysis Using Systems Biology and Machine Learning Approaches.

PROBLEM: The vaginal microbiome has a substantial role in the occurrence of preterm birth (PTB), which contributes substantially to neonatal mortality worldwide. However, current bioinformatics approaches mostly concentrate on the taxonomic classification and functional profiling of the microbiome, limiting their abilities to elucidate the complex factors that contribute to PTB. METHOD OF STUDY: A total of 3757 vaginal microbiome 16S rRNA samples were obtained from five publicly available datasets. The samples were divided into two categories based on pregnancy outcome: preterm birth (PTB) (N = 966) and term birth (N = 2791). Additionally, the samples were further categorized based on the participants' race and trimester. The 16S rRNA reads were subjected to taxonomic classification and functional profiling using the Parallel-META 3 software in Ubuntu environment. The obtained abundances were analyzed using an integrated systems biology and machine learning approach to determine the key microbes, pathways, and genes that contribute to PTB. The resulting features were further subjected to statistical analysis to identify the top nine features with the greatest effect sizes. RESULTS: We identified nine significant features, namely Shuttleworthia, Megasphaera, Sneathia, proximal tubule bicarbonate reclamation pathway, systemic lupus erythematosus pathway, transcription machinery pathway, lepA gene, pepX gene, and rpoD gene. Their abundance variations were observed through the trimesters. CONCLUSIONS: Vaginal infections caused by Shuttleworthia, Megasphaera, and Sneathia and altered small metabolite biosynthesis pathways such as lipopolysaccharide folate and retinal may increase the susceptibility to PTB. The identified organisms, genes, pathways, and their networks may be specifically targeted for the treatment of bacterial infections that increase PTB risk.