Cause Of Preterm Birth Research Articles

Хориоамнионит, спорные вопросы терминологии и диагностики

Chorioamnionitis is a common cause of preterm birth and can lead to poor maternal and neonatal outcomes, including severe fetal neurodevelopmental consequences. Chorioamnionitis is characterized by a combination of heterogeneous conditions associated with infection or inflammation, which has led to changes in the definition and basic concepts of this condition. The article provides an overview of current publications about chorioamnionitis and presents the concept of Triple I, which includes three concepts: isolated maternal fever, suspected infection / inflammation, confirmed infection and inflammation. Depending on this classification, a decision is made on the term of completion of pregnancy and further management of newborns. The article also highlights methods for diagnosing chorioamnionitis, including immunological and microbiological markers, with an assessment of their sensitivity and specificity.

Clinical audit of the management and outcomes of preterm pre-labour rupture of membranes at Aminu Kano Teaching Hospital

preterm pre-labour rupture of membranes (PPROM) is one of the important causes of preterm birth that can result in high perinatal morbidity and mortality along with maternal morbidity. The purpose of the study was to audit the management of women presenting with Preterm pre-labour rupture of membranes in Aminu Kano Teaching Hospital (AKTH). this was a retrospective audit on patients admitted with PPROM in AKTH over a period of 24 months. Data was analysed using SPSS version 22 and presented using percentages and compared with the audit standard. Chi-squared test was used to test for association (p-value <0.05). the mean gestational age was 33.27±2.42 weeks. Diagnosis was made on all patients through history and clinical examination. Almost all patients received a course of erythromycin (88%), corticosteroid (84%) and magnesium sulphate (86%). Vaginal delivery was achieved in 57%. About 60% of the neonates were premature, 78% had Apgar score >7 at 5 mins, 50% were admitted in the special care baby unit and 72% survived. Chorioamnionitis and puerperal sepsis occurred in 8% and 21.7% of the mothers. Prolonged PPROM of >24 hours was statistically significantly associated with puerperal sepsis (χ2=7.218; p = 0.007) and perinatal mortality (χ2= 11.505, p = 0.001). despite high fidelity to institutional clinical practice guidelines in Aminu Kano Teaching Hospital there seems to be poor maternal and neonatal outcome with high perinatal mortality. Thus the guidelines need to be reviewed in context of improving the outcome.

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of the membranes

Preterm birth is a leading cause of perinatal morbidity and mortality and Preterm premature rupture of the membranes (PPROM) is a major risk factor contributing to approximately one third of preterm deliveries. Vaginal infections are often associated with PPROM and are characterised by loss of lactobacillin normal vaginal flora and overgrowth of other pathogenic microorganisms. Probiotics appear to have an emerging role in prolonging pregnancy after PPROM. This trial compared the efficacy of a vaginal probiotic in combination with standard antibiotic prophylaxis versus only antibiotic in prolongation of latency period and on perinatal outcome in cases of PPROM between 24 and 34 weeks. Although no significant difference was observed in the mean latency period (p = 0.937) and mean gestational age at birth (p = 0.863) between the two groups, the overall neonatal outcome was better in the study group. There is need of further large-scale clinical trials to demonstrate effectiveness of probiotics. IMPACT STATEMENT What is already known on this subject? PPROM is an important cause of preterm birth. Prematurity leads significant global burden of neonatal morbidity and mortality. Antibiotics in PPROM have a proven benefit to prolong latency period from start of PPROM to birth. Probiotics have a role in improving vaginal flora and reducing infections and have been tried in PPROM. What do the results of this study add? The usefulness of probiotics in prolonging latency period and improving neonatal outcome has been reported in limited trials. In our study it has shown an improvement in neonatal outcome overall but not statistically significant compared to few studies which have reported significant beneficial effects. This might be due to existence of variation in the type of the vaginal microflora in different study population. What are the implications of these findings for clinical practice and/or further research? Preliminary results suggest that use of probiotic may benefit women with PPROM. This also implies need of multicentric larger scales trials with different types of probiotics so as to clarify whether any intervention in vaginal microflora can lead to any benefits in reducing the prematurity and its consequence, both on the neonate and heath care infrastructure.

Influence of Maternal Microbiome and Inflammatory Response in Preterm Birth: Recent Aspects of the Prevention of Preterm Birth

Preterm birth (PTB) is a global health issue and one of the most challenging problems affecting 12.9 million births worldwide. PTB is a multi-etiological disease and remains incompletely understood. The major cause of PTB is infection or inflammation and disruption of the vaginal microbiome, which affects the maternal immunologic response leading to PTB. The vaginal microbiome composition changes by a shift in the community are typically dominated by Lactobacillus during pregnancy. There are complex interactions between the maternal microbiome in pregnancy and the development of PTB, therefore, researchers have struggled to connect the maternal microbiome with the dysregulation of the maternal immune response in cases of PTB. The host microbiome affects alterations of the microorganisms with external stimuli such as disease, nutrition, immunity, and behavior. In this review, we discuss the complex association between the maternal microbiome and the risk of PTB and also focus on recent aspects of the prevention of PTB.

Lactobacillus rhamnosus reduces the cytotoxic effects of group B streptococcus on HeLa cells

Group B Streptococcus (GBS) is an opportunistic pathogen found in the vaginal tract and is a leading cause of preterm birth and neonatal illness. Aside from GBS, the vaginal tract is predominantly colonized by commensal Lactobacillus species that are thought to protect the vaginal tract from pathogens, including GBS. Studies that examined if, and how Lactobacilli modulate GBS pathogenicity remain limited. This study sought to investigate the potential protective role of Lactobacillus rhamnosus against GBS, using an in vitro model system. Immunofluorescence microscopy and Scanning Electron Microscopy (SEM) captured images of infected HeLa cells and were analyzed using the image analysis program ImageJ. Results indicate that GBS causes HeLa cell detachment unless L. rhamnosus is present. SEM images show that GBS reduces length and number of microvilli on HeLa cell surface, as well as size of secreted vesicles. L. rhamnosus partially inhibits GBS-dependent microvilli and vesicle disruption. GBS also disrupts HeLa cell F-actin fibers unless L. rhamnosus is present. These results reveal effects of GBS infection on the host cell cytoskeleton and implies a protective role of L. rhamnosus against GBS colonization.

Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study

Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc’s classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1–V2) from vaginal samples were sequenced and analyzed. Using a random forest algorithm, the bacterial species associated with CAM were identified, and a predictive CAM (PCAM) scoring method was developed. The α diversity was significantly higher in the CAM than in the non-CAM group (P < 0.001). The area under the curve was 0.849 (95% confidence interval 0.765–0.934) using the PCAM score. Among patients at < 35 weeks of gestation, the PCAM group (n = 22) had a significantly shorter extended gestational period than the non-PCAM group (n = 25; P = 0.022). Multivariate analysis revealed a significant difference in the frequency of developmental disorders in 3-year-old infants (PCAM, 28%, non-PCAM, 4%; P = 0.022). Analyzing vaginal microbiota can evaluate the risk of IAI. Future studies should establish appropriate interventions for IAI high-risk patients to improve perinatal prognosis.

Validation of low-coverage whole-genome sequencing for mitochondrial DNA variants suggests mitochondrial DNA as a genetic cause of preterm birth.

Preterm birth (PTB), or birth that occurs earlier than 37 weeks of gestational age, is a major contributor to infant mortality and neonatal hospitalization. Mutations in the mitochondrial genome (mtDNA) have been linked to various rare mitochondrial disorders and may be a contributing factor in PTB given that maternal genetic factors have been strongly linked to PTB. However, to date, no study has found a conclusive connection between a particular mtDNA variant and PTB. Given the high mtDNA copy number per cell, an automated pipeline was developed for detecting mtDNA variants using low‐coverage whole‐genome sequencing (lcWGS) data. The pipeline was first validated against samples of known heteroplasmy, and then applied to 929 samples from a PTB cohort from diverse ethnic backgrounds with an average gestational age of 27.18 weeks (range: 21–30). Our new pipeline successfully identified haplogroups and a large number of mtDNA variants in this large PTB cohort, including 8 samples carrying known pathogenic variants and 47 samples carrying rare mtDNA variants. These results confirm that lcWGS can be utilized to reliably identify mtDNA variants. These mtDNA variants may make a contribution toward preterm birth in a small proportion of live births.

618Is mode of first birth a risk factor for subsequent preterm birth?

Abstract Background Previous preterm birth is a strong predictor of subsequent preterm birth but less is known about the causes of preterm birth following a full-term pregnancy. Recent research highlighted previous caesarean as a potential risk factor and we aimed to further explore this risk. Methods This population-based record linkage study included all women in NSW, Australia who had a live singleton first birth at ≥ 37 weeks gestation, followed by a singleton second birth between 2005–2017. Relative risk (RR) and 95%CI of having a subsequent preterm birth, spontaneous preterm birth or preterm pre-labour caesarean was calculated using individual modified Poisson regression models, with mode of first birth as the exposure. Results Women who had an intrapartum (RR:1.26, 95%CI 1.19–1.32) or prelabour caesarean (RR:1.26,95%CI 1.18–1.35) first birth had a higher risk of subsequent preterm birth, than those who birthed vaginally. Those who had a pre-labour caesarean (RR:0.74, 95%CI 0.67–0.82) had a lower risk of subsequent spontaneous preterm birth. However, prior pre-labour caesarean also greatly increased the risk of subsequent preterm prelabour caesarean (RR:5.25, 95%CI 4.65–5.93). Conclusions Pre-labour and intrapartum caesareans have differing effects on the risk of subsequent spontaneous preterm birth and preterm pre-labour caesarean. Key messages The risk of subsequent preterm birth following a first birth caesarean depends on whether the caesarean occurred before or after the onset of labour and whether the subsequent preterm birth is spontaneous or a pre-labour caesarean.

The Role of Antimicrobial Peptides in Preterm Birth.

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

Chorioamnionitis and neonatal outcomes.

Chorioamnionitis or intra-uterine inflammation is a frequent cause of preterm birth. Chorioamnionitis can affect almost every organ of the developing fetus. Multiple microbes have been implicated to cause chorioamnionitis, but “sterile” inflammation appears to be more common. Eradication of micro-organisms has not been shown to prevent the morbidity and mortality associated with chorioamnionitis as inflammatory mediators account for continued fetal and maternal injury. Mounting evidence now supports the concept that the ensuing neonatal immune dysfunction reflects the effects of inflammation on immune programming during critical developmental windows, leading to chronic inflammatory disorders as well as vulnerability to infection after birth. A better understanding of microbiome alterations and inflammatory dysregulation may help develop better treatment strategies for infants born to mothers with chorioamnionitis.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Incidence, Risk Factors and Pregnant Outcomes of Premature Rupture of Membranes: A Cross Section Study

Abstract Background: Premature births are responsible for 27.0 per cent of annual child deaths globally, 70.0 per cent of prenatal mortality in developed countries and 50.0 per cent of neurological disorders. Obstetric risk factors include: Cer-vical incompetence, multiple gestation, limited birth cycles, history of abortion, premature membrane breakup, and prior preterm labour. In the meantime, pregnancy conditions such as respiratory disorders and hypertension are the most common direct causes of preterm birth. Bleeding during labour, poly-hydramnios or oligohydramnios, foetal abnormalities including, in particular, numerous organ systems and central nervous system abnormalities. Aim of Study: The purpose of this research was to measure the prevalence rate of PPROM among pregnant women in order to identify risk factors associated with PROM and fetal/neonatal outcomes. Patients and Methods: Is to calculate the incidence rate of PPROM among pregnant women attending Zagazig Uni-versity hospital, and to identify the fetal/neonatal outcome and potential factors associated with poor fetal/neonatal outcome.This is a cross-section study, performed at the ER Department of Zagazig University Hospitals for Vaginal Delivery, from July 2020 to January 2021, of 138 women with premature membrane abduction. Result: Risk factors for cases were 30 with no risk factor (21.7%), 16 with prior PROM (11.6%), 12 with multi-pregnancy (8.7%), 24 with Antepartum (17.4%). There was a statistically meaningful disparity between the outcomes of the infants in relation to the risk factors of the mothers. In the cases of the infants of strong APGAR there was a latent period of 8.89 (±6.64 SD) for cases where the infants required an O2 incubator there was a latent period of 9.73 (±5.69 SD). There was no statistically significant difference between the outcomes of the infants in relation to the latent period. Conclusion: From this study, it can be inferred that low socio-economic, younger, illiterate partitioning women have been shown to cause a rise in PPROM. Such hazards may impact both maternal and neonatal outcomes such as infection, maternal pain, foetal distress, increased surgical delivery, and the need for neonatal intensive care in more than 50 per cent of neonates.

Chorioamnionitis induces hepatic inflammation and time-dependent changes of the enterohepatic circulation in the ovine fetus

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h – 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.

Assessment of the hormonal levels in different management strategies for women with cervical insufficiency and a history of anovulatory infertility

Cervical insufficiency (CI) is one of the causes of preterm birth. The rate of CI is higher in women after in vitro fertilization treatment for infertility compared to the general population. The aim. To assess the hormonal level in women with CI and a history of anovulatory infertility in the second and third trimesters of pregnancy in different management strategies for CI. Materials and methods. 60 pregnant women with CI who conceived through in vitro fertilization treatment for anovulatory infertility were divided into two groups: in the I group (30 women), CI was corrected only with cervical cerclage / pessary in the II trimester of pregnancy, in the II group (30 persons), cervical cerclage / pessary was combined with vaginal progesterone 200 mg ones a day until 34 full weeks of gestation. 30 pregnant women without СІ or infertility with the physiological course of pregnancy were controls. The concentrations of estradiol, progesterone, placental lactogen, prolactin and cortisol were determined in the terms of 19–22 and 30–32 weeks of gestation in the maternal blood serum. Results. In the patients with CI at 19–22 gestational weeks, the estradiol and placental lactogen concentrations were slightly lower in the I and II groups than those in the control women, the level of progesterone was less in the I group by 13.44 %, in the II group – by 17.30 % (P &lt; 0.05) compared to the controls; the levels of prolactin and cortisol in the I and II groups were increased significantly (P &lt; 0.001). At 30–32 gestational weeks, the levels of estradiol (P &lt; 0.05), progesterone (a decrease of 23.10 %, P &lt; 0.001) and placental lactogen (a decrease of 10.74 %, P &lt; 0.05) were significantly less as compared to the physiological ranges, while these parameters in the II group patients were on the lower limit of normal. In the I group, the concentrations of prolactin and cortisol were higher by 41.70 % (P &lt; 0.001) and 27.36 % (P &lt; 0.001), respectively, than the controls, in the II group – only by 24.10 % (P &lt; 0.05) and 13.70 % (P &lt; 0.05), respectively. Conclusions. In the women with cervical insufficiency after in vitro fertilization treatment for anovulatory infertility, the levels of estradiol, progesterone and placental lactogen are not significantly different from physiological indices, but the prolactin and cortisol concentrations are much higher. Adjunctive vaginal progesterone treatment to cervical cerclage/pessary in the third trimester of pregnancy promotes the normalization of progesterone, estradiol and placental lactogen levels, the decrease in prolactin and cortisol indices at 30–32 gestational weeks compared to the women with cervical cerclage/pessary alone.

Study on the correlation between vaginal bleeding in first trimester and preterm birth: A birth cohort study in Lanzhou, China.

To investigate the correlation between first trimester vaginal bleeding and preterm birth (PB), and to offer suggestions on the perinatal health care and preterm birth prevention. A birth cohort study was conducted on 10 179 pregnant women. Unconditional logistic regression model was used to evaluate the associations between vaginal bleeding and preterm birth in sub-preterm groups. Of the 10 179 pregnant women included, a total of 1001 women suffered from vaginal bleeding during the first trimester, of which 119 suffered from PB. Any vaginal bleeding increased the risk of PB. Severe bleeding was a high-risk factor of PB, associated with 4.8-fold risk of very PB, 2.7-fold risk of spontaneous PB without PROM (premature rupture of membrane) and 4.6-fold risk of medical induced PB. Bleeding prolonged more than 1 week increased 66% risk of PB and 36% risk of PB on initial episode happened in 5-12 weeks of gestation age, especially in moderate PB, in medical-induced PB and in spontaneous PB with PPROM (preterm premature rupture of membrane which is one cause of PB). Mild bleeding or bleeding within 1 week or initial episode happened within 4 weeks of gestation age possibly had no influence on PB. Vaginal bleeding in the first-trimester was an independent risk factor for PB. The severity, duration and initial time of vaginal bleeding had different effects on different subtypes of PB.

Polymicrobial stimulation of human fetal membranes induce neutrophil activation and neutrophil extracellular trap release

Preterm birth is a major contributor to neonatal mortality and morbidity. While the causes of preterm birth remain incompletely understood, infection is a major risk factor, and chorioamnionitis is commonly observed. Chorioamnionitis is characterized by inflammation and neutrophil infiltration of the fetal membranes (FM). We recently reported that human FMs which had been exposed to low levels of bacterial lipopolysaccharide (LPS) recruit neutrophils and activate them, increasing their secretion of pro-inflammatory cytokines, degranulation of myeloperoxidase (MPO), and release of neutrophil extracellular traps (NETs). Herein, we demonstrate that conditioned media (CM) from viral dsRNA (Poly(I:C))-stimulated FMs also increased neutrophil migration, and induced the secretion of inflammatory IL-8 and the release of NETs. Furthermore, CM from FMs stimulated by a combination of bacterial LPS and Poly(I:C) augmented neutrophil NET release, compared to CM from FMs stimulated with either Poly(I:C) or LPS alone. NETs induced by FMs exposed to Poly(I:C), with or without LPS, were released and degraded quicker than those induced by resting or LPS-stimulated FM-CM. These findings indicate that FMs exposed to viral dsRNA promote neutrophil recruitment, activation and NET formation, similar to FMs exposed to bacterial LPS alone. However, in response to FM polymicrobial stimulation the levels and kinetics of NET release are augmented. This work builds upon our understanding of how infections at the maternal-fetal interface may affect neutrophil function.

STUDY OF MATERNALAND PERINATAL OUTCOME IN CASES OF PRETERM PREMATURE RUPTURE OF MEMBRANES

Background: Preterm premature rupture of membranes (PPROM) occurs in 3%to6% of pregnancies and is responsible for approximately one third of all preterm births. Aims &amp; Objective: of present study was to analyse the maternal and perinatal outcome of PPROM patients between 28 to 36 weeks +6days admitted in labour room of obs and gynae dept. of DMCH from January 2019 to April 2020. Material and Methods: It is hospital based prospective observational study of 100 patients of preterm premature rupture of membranes in between 28-36 weeks+6 days gestation with singleton pregnancy admitted in our tertiary care centre (Department of Obstetrics and Gynaecology, DMCH, Laheriasarai, Bihar). Results: In this study 42% patients went into spontaneous labour and 58% needed induction or augmentation. 68% patients had vaginal delivery and 23% required LSCS. The main indications for LSCS being malpresentation (26%) followed by foetal distress (22%). There was no maternal mortality; morbidity was found in 15% patients. Perinatal morbidity was seen in 40% and was mainly due to RDS, sepsis andhyperbilirubinaemia . Perinatal mortality was seen in 17% and was due to sepsis in 29.4%, RDS in 52.94% and birth asphyxia in 17.6%. Conclusion: PPROM is one of the important causes of preterm birth that can result in high perinatal morbidity &amp; mortality along with maternal morbidity. Looking after a premature infant puts immense burden on the family, economy and health care resources of the country. Therefore management of PPROM requires accurate diagnosis and evaluation of the risks and benets of continued pregnancy or expeditious delivery. An understanding of gestational age dependent neonatal morbidity and mortality is important in determining the potential benets of conservative management of preterm PROM at any gestation

Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study.

BackgroundThe pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants.Methods2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models.Results437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2–2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9–3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9–4.4).ConclusionVery preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor.Impact Late-onset sepsis risk differs according to the cause of preterm birth.Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis.Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.

Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications.

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d gestational age (GA). Gut inflammation, the number, distribution, and differentiation of goblet cells, ER stress, and apoptosis were measured. We found a biphasic reduction in goblet cell numbers 24 h–2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.