Singleton Preterm Birth Research Articles

Achieving more with less: lessons from country-level analyses of caesarean delivery and perinatal outcomes in Europe

Abstract Background There is consensus that caesarean delivery (CD) is a lifesaving procedure for both mother and child in emergency situations and that CD without medical indication should be avoided. However, the rate that optimally balances the risks and benefits of CD is unresolved. In 1985, the World Health Organization concluded that the CD rate should be no more than 10-15%; subsequent reviews relating CD rates to infant mortality show no benefits at the country-level for rates higher than 15-19%. However, stillbirth has not been investigated because comparable international stillbirth data are not readily available. Methods We conducted an ecological study in 25 European countries from 2015 to 2019 utilizing data from routine birth data sources aggregated using the Euro-Peristat PHIRI federated data analysis protocol. We assessed country-level associations between CD rates and perinatal outcomes (singleton preterm birth, stillbirth at ≤ 24 weeks’ gestational age, neonatal death) for all years using Pearson correlations, adjusted for clustering of years within country. Correlations were also estimated between linear trends over time in the indicators. Results The median [range] of CD rates was 23.1% [16.2 to 56.9] in 21 participating countries, while these were 6.9% [5.3 to 11.9] for preterm birth, 3.3 per 1000 total births [1.8 to 7.6] for stillbirth and 1.9 per 1000 live births [0.7 to 6.1] for neonatal mortality. The CD rate was not associated with the stillbirth rate (cluster-adjusted rho: -.01, P=.94) or with the neonatal mortality rate (rho:.27, P=.27). However, there was a strong positive correlation with the preterm birth rate (rho:.81, P<.001). Results were similar in time trend analyses. Conclusions Higher CD rates were not associated with lower stillbirth or neonatal mortality rates, but were strongly correlated with higher preterm birth rates. This study suggests no benefits and indicates potential harms for higher CD rates in Europe.

Effects of gestational diabetes mellitus and assisted reproductive technology treatment on the risk of preterm singleton birth.

BackgroundAlthough assisted reproductive technology (ART) plays a critical role in reducing infertility, ART pregnant women are reported at higher risk of preterm birth (PTB). Besides, women undergoing ART encounter a higher risk of developing gestational diabetes mellitus (GDM). However, existing studies on the combined effect of ART treatment and GDM on PTB risk are sparse.MethodsThis population-based retrospective cohort study used nationwide birth certificate data from the US National Vital Statistics System 2015-2019. All mothers who had a singleton live birth without pre-pregnancy diabetes were included. Multivariable logistic regression models were used to estimate the odds ratio (OR) of PTB.ResultsWe finally included 18,140,241 American mother-infant pairs. The overall rate of PTB was 7.92% (n = 1,436,328). The PTB rate for non-ART mothers without GDM, ART mothers without GDM, non-ART mothers with GDM, and ART mothers with GDM were 7.67, 10.90, 11.23, and 14.81%, respectively. The incidence of GDM in ART mothers (10.48%) was significantly higher than in non-ART mothers (6.26%). After adjusting for potential confounders, compared with non-ART mothers without GDM, the PTB risk was significantly increased for ART mothers without GDM (AOR: 1.47, 95% CI 1.44-1.50), non-ART mothers with GDM (AOR:1.35, 95% CI 1.34-1.36) and ART mothers with GDM (AOR: 1.82, 95% CI 1.74-1.90) respectively, showing an increasing tendency. This phenomenon was stable among mothers in all groups of mothers older than 25 years.ConclusionTo prevent PTB, effective approaches for the prevention of GDM are crucial to mothers who conceived through ART.

The variation of antenatal corticosteroids administration for the singleton preterm birth in China, 2017 to 2018

BackgroundThe administration of antenatal corticosteroids (ACS) to women who are at risk of preterm birth has been proven to reduce not only the mortality, but also the major morbidities of the preterm infants. The rate of ACS and the risk factors associated with ACS use in Chinese population is unclear. This study aimed to investigate the rate of ACS use and the associated perinatal factors in the tertiary maternal centers of China.MethodsData for this retrospective observational study came from a clinical database of preterm infants established by REIN-EPIQ trial. All infants born at < 34 weeks of gestation and admitted to 18 tertiary maternal centers in China from 2017 to 2018 were enrolled. Any dose of dexamethasone was given prior to preterm delivery was recorded and the associated perinatal factors were analyzed.ResultsThe rate of ACS exposure in this population was 71.2% (range 20.2 – 92%) and the ACS use in these 18 maternal centers varied from 20.2 to 92.0% in this period. ACS exposure was higher among women with preeclampsia, caesarean section delivery, antibiotic treatment and who delivered infants with lower gestational age and small for gestational age. ACS use was highest in the 28–31 weeks gestational age group, and lowest in the under 26 weeks of gestational age group (x2 = 65.478, P < 0.001). ACS exposure was associated with lower odds of bronchopulmonary dysplasia or death (OR, 0.778; 95% CI 0.661 to 0.916) and invasive respiration requirement (OR, 0.668; 95% CI 0.585 to 0.762) in this population.ConclusionThe ACS exposure was variable among maternity hospitals and quality improvement of ACS administration is warranted.

Biopsychosocial factors influencing the occurrence and recurrence of preterm singleton births among Australian women: A prospective cohort study

IntroductionIn Australia, 8.6% of all births are premature, and this figure has relativelyincreased by 10% in the past decade. A range of biological, psychological, and socialfactors have previously been identified as predictors of preterm birth using cross sectionaldata; however, this lacks ascertainment of a cause-and-effect relationship.This study harnessed the power of longitudinal cohort data by investigating pretermbirth among women prospectively followed for 19 years using a comprehensiveframework that examines biological, psychological, and social factors concurrently. MethodsData from 5,292 women (11,256 newborns) who reported singleton birthsbetween 1996 and 2015 in the Australian Longitudinal Study on Women’s Health wereincluded. ResultsThe prevalence of preterm birth was 8.5% for first-births and 5.9% for allbirths.The recurrent preterm birth rate was 9.5% . Risk factors for first preterm birthswere chronic hypertension (OR 2.34; 95% CI: 1.67-3.27), gestational hypertension (OR2.87; 95% CI: 2.22-3.72), gestational diabetes (OR 1.66; 95% CI: 1.14-2.41),menarche before 12 years (OR 1.36; 95% CI: 1.02-1.82) and history of miscarriage(OR 1.35; 95% CI: 1.01-1.79). Risk factors for all preterm births were a history ofpreterm birth (OR 2.33; 95% CI: 1.46-3.70), menarche before 12 years (OR 1.33; 95%CI: 1.00-1.77), not being partnered (OR 1.31; 95% CI: 1.02-1.69), chronic hypertension(OR 2.02; 95% CI: 1.45-2.82), gestational hypertension (OR 3.22; 95% CI: 2.43-4.25),gestational diabetes (OR 1.67; 95% CI: 1.16-2.41), and asthma (OR 1.40; 95% CI:1.14-1.72). Premature birth was less likely for second or later births (OR 0.44; 95% CI:0.36-0.55) compared to first births. Premature birth was also less likely for women whocompleted a university degree compared to women with a high school certificate (OR0.73; 95% CI: 0.57-0.94). ConclusionFurther development of multi-sectoral policies for chronic diseaseprevention and reducing social inequalities is required to prevent preterm birth inAustralia.

The relationship between obstetrical interventions and the increase in U.S. preterm births, 2014-2019.

We examined the relationship between obstetrical intervention and preterm birth in the United States between 2014 and 2019. This observational study analyzed 2014–2019 US birth data to assess changes in preterm birth, cesarean delivery, induction of labor, and associated risks. Logistic regression modeled the odds of preterm obstetrical intervention (no labor cesarean or induction) after risk adjustment. The percentage of singleton preterm births in the United States increased by 9.4% from 2014–2019. The percent of singleton, preterm births delivered by cesarean increased by 6.0%, while the percent with induction of labor increased by 39.1%. The percentage of singleton preterm births where obstetrical intervention (no labor cesarean or induction) potentially impacted the gestational age at delivery increased from 47.6% in 2014 to 54.9% in 2019. Preterm interventions were 13% more likely overall in 2019 compared to 2014 and 17% more likely among late preterm births, after controlling for demographic and medical risk factors. Compared to non-Hispanic White women, Non-Hispanic Black women had a higher risk of preterm obstetric interventions. Preterm infants have higher morbidity and mortality rates than term infants, thus any increase in the preterm birth rate is concerning. A renewed effort to understand the trends in preterm interventions is needed to ensure that obstetrical interventions are evidence-based and are limited to those cases where they optimize outcomes for both mothers and babies.

The role of maternal age on the risk of preterm birth among singletons and multiples: a retrospective cohort study in Lombardy, Northern Italy

BackgroundAll over the world, especially in the developed countries, maternal age at birth is rising. This study aimed to assess the role of maternal age on the occurrence of preterm birth (PTB) in a large birth cohort of Lombardy Region, Northern Italy.MethodsThis population-based study used data from regional healthcare utilization databases of Lombardy to identify women who delivered between 2007 and 2017. PTBs were defined as births before 37 completed weeks of gestation and considered according to the gestational age (two categories: < 32 weeks and 32 to 36 weeks). Six maternal age groups were defined (< 20, 20–24, 25–29, 30–34, 35–39, ≥40 years). Logistic regression models were fitted to estimate the crude and adjusted odds ratio (aOR) and the corresponding 95% confidence interval (CI) for PTB among different maternal age groups. Analyses were separately performed according to type of pregnancy (singletons and multiples). Reference group was the age group with the lowest frequency of PTB.ResultsOverall, 49,759 (6.6%) PTBs were observed, of which 41,807 were singletons and 7952 were multiples. Rates of PTB were lowest in the women aged 25–29 years among singletons and in the 30–34 years old group among multiples. Our results described a U-shaped association between maternal age and risk of PTB. In particular, the risk of a singleton PTB between 32 and 36 weeks was significantly higher for women aged less than 20 years (aOR = 1.16, CI 95%: 1.04–1.30) and more than 40 years (aOR = 1.62 CI 95%: 1.54–1.70). The highest risk of a multiple delivery between 32 and 36 weeks was observed among women aged less than 25 years and more than 40 years (aOR = 1.79, CI 95%: 1.01–3.17, aOR = 1.47, CI 95%: 1.16–1.85 and aOR = 1.36, CI 95%: 1.19–1.55 respectively for < 20, 20–24 and > 40 age categories). PTB before 32 completed weeks occurred more frequently in the same age categories, except that among multiples no association with advanced maternal age emerged.ConclusionOur study suggested that, after adjustment for potential confounders, both advance and young maternal age were associated with an increased risk of PTB.

Latent class analysis of placental histopathology: a novel approach to classifying early and late preterm births

Neonatal morbidity attributable to prematurity predominantly occurs among early preterm births (<32 weeks) rather than late preterm births (32 to <37 weeks). Methods to distinguish early and late preterm births are lacking given the heterogeneity in pathophysiology and risk factors, including maternal obesity. Although preterm births are often characterized by clinical presentation (spontaneous or clinically indicated), classifying deliveries by placental features detected on histopathology reports may help identify subgroups of preterm births with similar etiology and risk factors. Latent class analysis is an empirical approach to characterize preterm births on the basis of observed combinations of placental features. To identify histopathologic markers that can distinguish early (<32 weeks) and late preterm births (32 to <37 weeks) that are also associated with maternal obesity and neonatal outcomes. Women with a singleton preterm birth at University of Pittsburgh Medical Center Magee-Womens Hospital (Pittsburgh, PA) from 2008 to 2012 and a placental evaluation (89% of preterm births) were stratified into early (n=900, 61% spontaneous) and late preterm births (n=3362, 57% spontaneous). Prepregnancy body mass index was self-reported at first prenatal visit and 16 abstracted placental features were analyzed. Placental subgroups (ie, latent classes) of early and late preterm births were determined separately by latent class analysis of placental features. The optimal number of latent classes was selected by comparing fit statistics. The probability of latent class membership across prepregnancy body mass indexes was estimated in early preterm births and in late preterm births by an extension of multinomial regression called pseudo-class regression, adjusting for race, smoking, education, and parity. The frequencies of severe neonatal morbidity (composite outcome: respiratory distress, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, periventricular leukomalacia, patent ductus arteriosus, and retinopathy of prematurity), small-for-gestational-age, and length of neonatal intensive care unit stay were compared across latent classes by chi-square and Kruskal-Wallis tests. Early preterm births were grouped into 4 latent classes based on placental histopathologic features: acute inflammation (38% of cases), maternal vascular malperfusion with inflammation (29%), maternal vascular malperfusion (25%), and fetal vascular thrombosis with hemorrhage (8%). As body mass index increased from 20 to 50kg/m2, the probability of maternal vascular malperfusion and fetal vascular thrombosis with hemorrhage increased, whereas the probability of maternal vascular malperfusion with inflammation decreased. There was minimal change in the probability of acute inflammation with increasing body mass index. Late preterm births also had 4 latent classes: maternal vascular malperfusion (22%), acute inflammation (12%), fetal vascular thrombosis with hemorrhage (9%), and low-risk pathology (58%). Body mass index was not associated with major changes in likelihood of the latent classes in late preterm births. Associations between body mass index and likelihood of the latent classes were not modified by type of delivery (spontaneous or indicated) in early or late preterm births. Maternal malperfusion and fetal vascular thrombosis with hemorrhage were associated with greater neonatal morbidity than the other latent classes in early and late preterm births. Obesity may predispose women to early but not late preterm birth through placental vascular impairment. Latent class analysis of placental histopathologic data provides an evidence-based approach to group preterm births with shared underlying etiology and risk factors.

Antenatal corticosteroids and neonatal outcomes in preterm birth in the United States.

To determine the impact of antenatal corticosteroids (ACS) on neonatal outcomes in a large United States population of preterm births. Retrospective cohort study utilizing the United States Natality Live Birth database from the Centers for Disease Control and Prevention (2016-2017). Women with singleton preterm births were eligible for inclusion. Out-of-hospital births, fetal anomalies, and cases where ACS exposure was unknown were excluded. Neonates from reported live births were divided into two groups based onwhether the mother received ACS before delivery or not.The incidence of several reported neonatal outcomes werecompared between the two groups at each gestational week. Subsequently, comparisons between three gestational age groups (23 0/7 to 27 6/7, 28 0/7 to 33 6/7, and 34 to 36 6/7weeks) were performed. Statistical analysis included use of Chi-squared test and multivariate logistic regression. Of the 588,077 live births included, 121,151 (20.6%) had been exposed to ACS. ACS use was associated with a significantly decreased odds of neonatal mortality and 5-min Apgar score <7, but an increased rate of several neonatal outcomes such as surfactant replacement therapy, prolonged ventilation, antibiotics for suspected neonatal sepsis, and neonatal intensive care unit (NICU) admissions. ACS administration prior to preterm birth is associated with a decrease in neonatal mortality and low Apgar scores, and increased odds of several adverse neonatal outcomes.

Association of Preterm Singleton Birth With Fertility Treatment in the US

Preterm birth is a global health issue. The association between fertility treatment and preterm singleton births has not been clarified. To examine the association between fertility treatment and preterm birth. This population-based cohort study used birth data that were submitted by 50 states and the District of Columbia to the National Vital Statistics System database. All mothers in the database who had a singleton live birth from January 1, 2016, to December 31, 2019, were included. Those who had preexisting hypertension or diabetes were excluded. Fertility treatment categorized as assisted reproductive technology (ART) or non-ART treatment. The main outcome was a diagnosis of preterm birth, which was defined as birth before 37 complete weeks (<259 days) of gestation. Gestational age was calculated by obstetric estimation at delivery and was collected from the database. The final sample consisted of 14 370 920 mothers (mean [SD] age, 28.79 [5.79] years) with singleton live births. Of these women, 122 944 (0.9%) conceived by ART and 71 176 (0.5%) received non-ART treatment. The prevalence of preterm birth was 7.6% (n = 1 071 994) in natural conception, 10.7% (n = 13 205) in ART, and 9.3% (n = 6629) in non-ART groups. Compared with neonates who were naturally conceived, newborns who were conceived with ART (adjusted risk difference [aRD], 3.10% [95% CI, 2.93%-3.27%]; adjusted odds ratio [aOR], 1.49 [95% CI, 1.46-1.52]; P < .001) and non-ART treatment (aRD, 2.22% [95% CI, 2.00%-2.44%]; aOR, 1.35 [95% CI, 1.31-1.38]; P < .001) had significantly higher risk for preterm birth after full adjustment. These associations were similar in subgroups of participants as defined by baseline characteristics. This study found that singleton neonates who were conceived by fertility treatment had higher rates of preterm birth. Further investigations are warranted into the association between ART or non-ART treatment and the risk of preterm birth in singleton neonates.

Attributable factors for the rising cesarean delivery rate over 3 decades: an observational cohort study

Cesarean delivery rates continue to rise globally, the reasons for which are incompletely understood. We aimed to characterize the attributable factors for the increasing cesarean delivery rates over a 30-year period within our health network. This was a planned observational cohort study across 2 hospitals (a large tertiary referral hospital and a metropolitan hospital) in Sydney, Australia using data from a previously published study. The following 2 time periods were compared: 1989-99 and 2009-16, between which the cesarean delivery rate increased from 19% to 30%. The participants were all women who had a cesarean delivery after 24 weeks' gestational age. The data were analyzed using multiple imputation and robust Poisson regression to calculate the differences in the adjusted and unadjusted relative risk of cesarean delivery and estimate the changes in the cesarean delivery rate attributable to maternal and clinical factors. The primary outcome was cesarean delivery. After 576 exclusions, 102,589 births were included in the analysis. Fifty-six percent of the increase in the rate of cesarean delivery was attributed to changes in the distribution of the maternal age, body mass index, and parity and to a history of previous cesarean delivery. An additional 10% of the increase was attributed to changes in the obstetrical management of the following high-risk pregnancies: multiple gestation, malpresentation (mainly breech), and preterm singleton birth. When prelabor cesarean deliveries for maternal choice, suspected fetal compromise, previous pregnancy issues, and suspected large fetus were excluded, 78% of the increase was attributed to either maternal factors or changes in the obstetrical management of these high-risk pregnancies. Most of the steep rise in the cesarean delivery rate from 19% to 30% was attributed to changes in the maternal demographic and clinical factors. This observation is relevant to developing preventative strategies that account for nulliparity, age, body mass index, and management of high-risk pregnancies.

Comparison between Cervical Ureaplasma spp. Colonization and the Intensity of Inflammatory Mediators in the Amniotic Fluid Retrieved during Cesarean Delivery in Preterm Birth

We investigated whether cervical Ureaplasma spp. colonization affects the intensity of inflammatory mediators in amniotic fluid retrieved during cesarean delivery in singleton preterm birth. One hundred fifty-three cases in singleton preterm birth with 24–34 weeks’ gestation were enrolled. The intensities of seven inflammatory mediators (interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and matrix metalloproteins (MMP)-8, MMP-9) of amniotic fluid were measured. We tested cervical swab specimens using real-time polymerase chain reaction assays to detect Ureaplasma spp. colonization. Histologic chorioamnionitis (HCA) was diagnosed when acute inflammation was observed in any of the placental tissues. Mean gestational age at delivery and birth weight were 30.9 ± 2.4 weeks and 1567 ± 524 g, respectively. Cervical Ureaplasma spp. colonization was detected 78 cases. The incidence of HCA was 32.3% (43/133). Although the intensities of all inflammatory mediators were significantly different according to presence or absence of HCA, there were no significant differences according to cervical Ureaplasma spp. colonization. In all 43 cases with HCA and 90 cases without HCA, there were no significant differences between cervical Ureaplasma spp. colonization and the intensity of inflammatory mediators. Cervical Ureaplasma spp. colonization did not affect the intensity of inflammatory mediators in the amniotic fluid retrieved during cesarean delivery.

Racial and sociodemographic disparities associated with singleton preterm births are increased in earlier gestational ages

Racial and ethnic minority groups, lower educational attainment, and the Medicaid program have all been linked to higher rates of preterm birth (PTB). We aimed to evaluate whether the association of these factors with PTB changes based on the gestational age at delivery.

Vaginal versus Intramuscular Progesterone for Prevention of Recurrent Preterm Birth (VIP): a randomized controlled trial

To determine whether vaginal progesterone is superior to intramuscular 17-hydroxyprogesterone caproate (17OHPC) in prevention of recurrent preterm birth (PTB) in singletons with prior spontaneous preterm birth (sPTB).

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

Joint Modeling of Singleton Preterm Birth and Perinatal Death Using Birth Registry Cohort Data in Northern Tanzania.

Understanding independent and joint predictors of adverse pregnancy outcomes is essential to inform interventions toward achieving sustainable development goals. We aimed to determine the joint predictors of preterm birth and perinatal death among singleton births in northern Tanzania based on cohort data from the Kilimanjaro Christian Medical Center (KCMC) zonal referral hospital birth registry between 2000 and 2017. We determined the joint predictors of preterm birth and perinatal death using the random-effects models to account for the correlation between these outcomes. The joint predictors of higher preterm birth and perinatal death risk were inadequate (<4) antenatal care (ANC) visits, referred for delivery, experiencing pre-eclampsia/eclampsia, postpartum hemorrhage, low birth weight, abruption placenta, and breech presentation. Younger maternal age (15–24 years), premature rupture of membranes, placenta previa, and male children had higher odds of preterm birth but a lessened likelihood of perinatal death. These findings suggest ANC is a critical entry point for delivering the recommended interventions to pregnant women, especially those at high risk of experiencing adverse pregnancy outcomes. Improved management of complications during pregnancy and childbirth and the postnatal period may eventually lead to a substantial reduction of adverse perinatal outcomes and improving maternal and child health.

Risk factors for neonatal encephalopathy in late preterm and term singleton births in a large California birth cohort.

The objective was to investigate maternal and pregnancy characteristics associated with neonatal encephalopathy (NE). We queried an administrative birth cohort from California between 2011 and 2017 to determine the association between each factor and NE with and without hypothermia treatment. From 3 million infants born at 35 or more weeks of gestation, 6,857 cases of NE were identified (2.3 per 1000 births), 888 (13%) received therapeutic hypothermia. Risk factors for NE were stronger among cases receiving hypothermia therapy. Substance-related diagnosis, preexisting diabetes, preeclampsia, and any maternal infection were associated with a two-fold increase in risk. Maternal overweight/obesity, nulliparity, advanced maternal age, depression, gestational diabetes or hypertension, and short or long gestations also predicted NE. Young maternal age, Asian race and Hispanic ethnicity, and cannabis-related diagnosis lowered risk of NE. By disseminating these results, we encourage further interrogation of these perinatal factors.

Acute chorioamnionitis and intra-amniotic inflammation are more severe according to outside-in neutrophil migration within the same chorio-decidua

ObjectiveNo information exists about whether acute histologic chorioamnionitis (acute-HCA) is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. The objective of current study is to examine this issue. Materials and methodsWe included 106 singleton preterm-births (gestational age at delivery: 20–34 weeks) due to either preterm-labor or preterm-PROM in the context of acute chorio-deciduitis. Study-population was divided into 3 groups according to outside-in neutrophil migration within chorio-decidua as follows: 1) group-1: ‘inflammation restricted to the decidua’ (n = 22); 2) group-2: ‘inflammation restricted to the MT of chorion and the decidua’ (n = 31); 3) group-3: ‘inflammation in the CT of chorion’ (n = 53). We examined the frequency of inflammation in each placental compartment beyond chorio-decidua (i.e., amnion, umbilical cord, and chorionic-plate), and total grade (1–8) of acute-HCA. Moreover, the frequency of intra-amniotic infection (defined as positive amniotic-fluid culture for aerobic and anaerobic bacteria and genital mycoplasmas) and intra-amniotic inflammation (defined as amniotic fluid WBC ≥ 19 cells/mm3), and an intra-amniotic inflammatory response gauged by amnioticfluid WBC count (cells/mm3) were examined in 50 amniotic fluid samples within 7 days of birth. ResultsAmnionitis, funisitis and chorionic plate inflammation were more frequent (each for P < 0.01) and median total grade of acute-HCA was increased (P < 0.001) according to outside-in neutrophil migration within chorio-decidua (group-1vs.group-2vs.group-3). Moreover, intra-amniotic infection and inflammation were more frequent (each-for P < 0.05) and median amniotic-fluid WBC count was increased (P < 0.01) according-to outside-in neutrophil-migration within chorio-decidua (group-1 vs. group-2 vs. group-3). ConclusionAcute-HCA is more advanced and severe, and intra-amniotic inflammation is more frequent and intense according to outside in neutrophil migration within the same chorio-decidua. This finding suggests that what is now acute chorio-deciduitis should be subdivided.

Neutrophil to Lymphocyte Ratio in Maternal Blood: A Clue to Suspect Amnionitis

There is no information about whether maternal neutrophil to lymphocyte ratios (NLRs) progressively increase with respect to the progression of acute histologic chorioamnionitis (acute-HCA) and increased maternal NLR is a risk factor for amnionitis, known as advanced acute-HCA, in pregnant women at risk for spontaneous preterm birth (PTB). The objective of the current study is to examine this issue. The study population included 132 singleton PTB (<34 weeks) due to either preterm labor or preterm-PROM with both placental pathology and maternal CBC results within 48 h before delivery. We examined maternal NLRs according to the progression of acute-HCA in extra-placental membranes (EPM) (i.e., group-0, inflammation-free EPM; group-1, inflammation restricted to decidua; group-2, inflammation restricted to the membranous trophoblast of chorion and the decidua; group-3, inflammation in the connective tissue of chorion but not amnion; group-4, amnionitis). Maternal NLRs significantly and progressively increased with the progression of acute-HCA (Spearman’s rank correlation test, γ = 0.363, p = 0.000019). Moreover, the increased maternal NLR (≥7.75) (Odds-ratio 5.56, 95% confidence-interval 1.26-24.62, p < 0.05) was a significant independent risk factor for amnionitis even after the correction for potential confounders. In conclusion, maternal NLRs significantly and progressively increased according to the progression of acute-HCA and the increased maternal NLR (≥7.75) was an independent risk factor for amnionitis in spontaneous PTB. The evaluation of the performance of NLR should clearly require a prospective description of this parameter in a cohort of patients with either threatened PTL or preterm-PROM.

Clinical risk models for preterm birth less than 28 weeks and less than 32 weeks of gestation using a large retrospective cohort.

To develop risk prediction models for singleton preterm birth (PTB) < 28 weeks and <32 weeks. Using a retrospective cohort of 267,226 singleton births in Ontario hospitals, we included variables from the first and second trimester in multivariable logistic regression models to predict overall and spontaneous PTB < 28 weeks and <32 weeks. During the first trimester, the area under the curve (AUC) for prediction of PTB < 28 weeks for nulliparous and multiparous women was 68.5% (95% CI: 63.5-73.6%) and 73.4% (68.6-78.2%), respectively, while for PTB < 32 weeks it was 68.9% (65.5-72.3%) and 75.5% (72.3-78.7%), respectively. AUCs for second-trimester models were 72.4% (95% CI: 69.7-75.1%) and 78.2% (95% CI: 75.8-80.5%), respectively, in nulliparous and multiparous women. Predicted probabilities were well-calibrated within a wide range around expected base prevalence for the study outcomes. Our prediction models generated acceptable AUCs for PTB < 28 weeks and <32 weeks with good calibration during the first and second trimester.

Fetal Growth Restriction and Subsequent Low Grade Fetal Inflammatory Response Are Associated with Early-Onset Neonatal Sepsis in the Context of Early Preterm Sterile Intrauterine Environment.

There is no information about whether fetal growth restriction (FGR) is an independent risk factor for low-grade fetal inflammatory response (FIR), and which is more valuable for the prediction of early-onset neonatal sepsis (EONS) between low-grade FIR or fetal inflammatory response syndrome (FIRS) in the context of human early preterm sterile intrauterine environment. We examined FIR (umbilical cord plasma (UCP) CRP concentration at birth) according to the presence or absence of FGR (birth weight < 5th percentile for gestational age (GA)) and EONS in 81 singleton preterm births (GA at delivery: 24.5~33.5 weeks) within 72 h after amniocentesis and with sterile intrauterine environment. A sterile intrauterine environment was defined by the presence of both a sterile amniotic fluid (AF) (AF with both negative culture and MMP-8 < 23 ng/mL) and inflammation-free placenta. Median UCP CRP (ng/mL) was higher in cases with FGR than in those without FGR (63.2 vs. 34.5; p = 0.018), and FGR was an independent risk factor for low-grade FIR (UCP CRP ≥ 52.8 ng/mL) (OR 3.003, 95% CI 1.024–8.812, p = 0.045) after correction for confounders. Notably, low-grade FIR (positive likelihood-ratio (LR) and 95% CI, 2.3969 (1.4141–4.0625); negative-LR and 95% CI, 0.4802 (0.2591–0.8902)), but not FIRS (positive-LR and 95% CI, 2.1071 (0.7526–5.8993); negative-LR and 95% CI, 0.8510 (0.6497–1.1145)), was useful for the identification of EONS. In conclusion, FGR is an independent risk factor for low-grade FIR, and low-grade FIR, but not FIRS, has a value for the identification of EONS in the context of the early preterm sterile intrauterine environment.