History Of Preterm Birth Research Articles

Clinical impact of respiratory syncytial virus infection on children hospitalized for pertussis

BackgroundAlthough Respiratory syncytial virus (RSV) is one of the common pathogens in children with pertussis and viral coinfection, the clinical impact of RSV infection on pertussis remains unclear. We compared clinical characteristics and sought differences between infants with single Bordetella pertussis (B. pertussis) infection and those with RSV coinfection.MethodsWe enrolled 80 patients with pertussis who were hospitalized in Shenzhen Children’s Hospital from January 2017 to December 2019. Respiratory tract samples were tested for B. pertussis with real-time polymerase chain reaction and respiratory viruses with immunofluorescence assay. Clinical data were obtained from hospital records and collected using a structured questionnaire.ResultsThirty-seven of 80 patients had B. pertussis infection alone (pertussis group) and 43 had RSV-pertussis coinfection (coinfection group). No significant differences were found with regard to sex, body weight, preterm birth history, pertussis vaccination, symptoms, presence of pneumonia, or lymphocyte count between the 2 groups. Univariate analysis showed patients with RSV coinfection were older (median, 4.57 months vs 4.03 months, p = 0.048); more commonly treated with β-lactam antibiotics (21% vs 5%, p = 0.044); had higher rates of wheezes (40% vs 14%, p = 0.009) and rales (35% vs 14%, p = 0.028) on chest auscultation, a higher rate of readmission (40% vs 11%, p = 0.004), and a longer hospital stay (median, 10 days vs 7 days, p = 0.002). In the further binary logistic regression analysis, patients with RSV coinfection had higher rates of wheezes (OR = 3.802; 95% CI: 1.106 to 13.072; p = 0.034) and readmission (OR = 5.835; 95% CI: 1.280 to 26.610; p = 0.023).ConclusionsRSV coinfection increases readmission rate in children hospitalized for pertussis. RSV infection should be suspected when wheezes are present on auscultation of the chest in these patients. Early detection of RSV may avoid unnecessary antibiotic use.

1090 Cervicovaginal fluid (CVF) TNFα as a biomarker for preterm birth

The prediction of preterm birth (PTB) is complex due to its multifactorial etiology. The inflammatory response through TNFα activation of the NFκB pathway is a proposed mechanism of preterm birth. TNFα can also be found in cervicovaginal fluid (CVF) in women who deliver preterm. We have demonstrated that cytokine profiles vary by obstetric history. The goal of our study was to examine CVF TNFα as a predictor of PTB in women discriminated by obstetric history. This was a secondary analysis of a longitudinal multicenter study of women with singleton gestations. Maternal CVF specimens were collected in the first (5w0d-13w6d) and second (14w0d-26w6d) trimester and assayed for cytokine concentrations (IL-1a, IL-1b, IL-6, IL-8, IL-10, TNFα, CRP and MMP-8) using a multiplex beadlyte assay on a Luminex IS-100. Women were grouped by obstetric history: nulliparous, multiparous with history of PTB and multiparous without history of PTB. Women were followed throughout pregnancy and outcomes were obtained by medical record review. ROC analysis was used to determine an optimal cutpoint, chosen to maximize the Youden’s distance and minimize the distance to the perfect (0,1), in predicting PTB. Analysis included 217 women: 102 nulliparas (47%), 46 (21%) multiparous with a history of PTB, and 69 (32%) multiparous without history of PTB. Thirteen (28%) of those with a history of PTB had a recurrent PTB. Only TNF-α was found to be a potentially useful predictor of PTB and only in the subpopulation of women with a history of PTB. A ROC curve for women with history of PTB (Figure 1) was constructed and the cutpoint maximizing the Youden’s index was 0.82 pg/ml; yielding a sensitivity of 92% and specificity of 63%. A ROC curve for women without a history of PTB was constructed for comparison (Figure 2). CVF TNFα can be used as a predictor of PTB in women with a history of PTB. A proposed cutpoint for CVF TNFα could be 0.82 pg/ml with a sensitivity of 92% and specificity of 63%. A large validation study is warranted to assess the value of this biomarker in this subpopulation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

978 Cerclage versus vaginal progesterone in low risk pregnant women with a short cervix

To compare vaginal progesterone to cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, incidentally found sonographic cervical length of <15 mm, and no history of preterm birth. A retrospective cohort study was conducted on 68 women who delivered at the University of Kansas Health System with a singleton gestation found to have a cervical length <15 mm on transvaginal ultrasound and no history of preterm birth. Women treated with vaginal progesterone (n=29) were compared to women who underwent cerclage placement (n=39). The primary outcome was the difference in average latency period. Secondary outcomes include preterm birth < 37, <34, and <28 weeks, and neonatal morbidities. Of the 268 patients who had a cervical length of <15 mm on transvaginal ultrasound, 68 participants met inclusion criteria and were included in the final analysis. Twenty-nine participants received vaginal progesterone and 39 participants received cervical cerclage. The average cervical length at initiation of therapy was greater in the progesterone cohort (10.5 mm vs 8.0 mm, p<0.01). All other baseline characteristics were similar between groups, including no difference in average gestational age at initiation of therapy (21.6 weeks vs. 21.5 weeks, p=0.87). Average latency after therapy did not differ between groups (100 days vs. 92.7 days p=0.43). The incidence of preterm birth at <37 weeks (41.4% vs. 51.3%), <34 weeks (27.6% vs. 35.9%), and <28 weeks (10.3% vs. 18%), did not differ significantly between groups. Additionally, no difference in neonatal morbidity was detected. At our institution we found no difference between vaginal progesterone and cerclage in the average latency period or risk of preterm birth among women with an incidental short cervix of < 15 mm and no history of preterm birth, despite the significantly shorter initial cervical length in the cerclage group. These findings suggest either vaginal progesterone or cerclage could be used to reduce the risk of preterm birth among this high risk population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

1079 Cervicovaginal fluid cytokine profiles vary by subpopulations stratified by obstetrical history

An association has repeatedly been demonstrated between pro-inflammatory cervicovaginal cytokines and preterm birth. Our objective was to evaluate the cervicovaginal milieu of women categorized by their obstetric history to determine whether subpopulations carried different risks. This was a secondary analysis of a longitudinal multicenter study of women with singleton gestations. Maternal cervicovaginal fluid (CVF) specimens were collected in the first and second trimesters. Cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, MMP-8, CRP) were measured using a multiplex beadlyte assay on a luminex IS-100. Women were stratified by obstetrical history into three groups: nulliparas, multiparas with a history of preterm birth, and multiparas without a history of preterm birth. Repeated measures modeling was used to examine group differences over time, adjusting for age, BMI and first trimester smoking status. Post-hoc analysis was accomplished using Fisher’s least significant differences (LSD) method for pairwise comparisons. Statistics were performed using SAS 9.4 with an alpha level of 0.05. 217 women were included in the analysis. The cytokine profiles varied significantly based on obstetric history. For all cytokines studied, the highest levels were identified in those with a history of preterm birth, followed by nulliparas, and lastly those without preterm birth. Univariate analysis demonstrated cytokine profiles of IL-6 and CRP varied significantly between subgroups, see Table 1. After controlling for age, BMI and smoking status, these relationships persisted and TNF-α also demonstrated significant differences between subgroups. Inflammatory cytokines differ significantly based on obstetrical history. If these cytokines are to be utilized as potential biomarkers for preterm birth, there sensitivity and specificity profiles should be evaluated in particular subpopulations based on obstetric history.

710 Mid-gestation cervicovaginal cytokines correlate with gestational age at delivery in women with prior preterm birth

Our objective was to identify if the baseline cervico-vaginal cytokine profile differed in women with a history of preterm birth in comparison to women with only term births and to determine if there are cytokine predictors for preterm delivery. This was a sub-analysis of a multicenter prospective observational trial comparing the pregnancy outcomes in women without and with a history of preterm birth. Women with a cervical length <25mm were excluded from the study. Cervicovaginal fluid was collected from the posterior fornix for baseline assessment prior to any treatments. Maternal and pregnancy characteristics were collected. We performed unbiased multiplex luminex profiling on 37 cytokines and compared women with a history of preterm birth to controls as well as pregnancy characteristics. Pregnancy characteristics including age, BMI, race did not differ between groups. Women with a prior preterm birth delivered at an earlier gestational age than controls (39.4 w compared to 37.6 w) p=0.0012. We found that several cervicovaginal fluid cytokines were different in women with a prior preterm birth than controls. IL-26 (p=0.04), IL-6R-beta (p=0.03), MMP-2 (p=0.02) were elevated in women with a prior preterm birth (Figure 1). We found no correlations in baseline cervicovaginal cytokine levels and gestational age at delivery in the combined cohort. In women with prior preterm birth, both IL-26 and IL-27 correlated with gestational age at delivery (Figure 2) We found that several cervicovaginal fluid cytokines were elevated in the second trimester in women with a prior preterm birth, suggesting aberrations in inflammatory pathways are important in the pathogenesis of recurrent preterm birth. Additionally, our data suggest that the cervicovaginal immune profile may predict risk of preterm birth in high risk women and suggests that further investigation into the immune modulation of cervicovaginal fluid is warranted.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

875 Cerclage in singletons with a short cervix (≤10mm) and no history of spontaneous preterm birth

To determine whether cervical cerclage is associated with an increased time interval to delivery in women with an asymptomatic short cervical length (CL ≤10mm) and no history of spontaneous preterm birth (sPTB). Multicenter retrospective cohort of women with CL ≤10mm between 16 and 23 weeks’ gestation from January 2014 to December 2019. Women with prior sPTB, symptoms of preterm labor, cervical dilation > 1cm, pessary or missing data were excluded. The primary outcome was time interval from diagnosis to delivery. Secondary outcomes included various PTB cut-offs and adverse neonatal outcomes. A sub-group analysis of all outcomes on patients already treated with vaginal progesterone in each group was also performed. Statistical analysis included Chi-squared and Wilcoxon rank-sum tests, as well as a multivariate Cox proportional hazard regression for time interval to delivery. Of the 90 patients included, 52 (57.8%, 35 already treated with progesterone) had cervical cerclage and 38 (42.2%, 21 already treated with progesterone) did not. Baseline characteristics of the two groups are displayed in Table 1. Cervical cerclage was associated with a longer time interval to delivery (14.5 weeks vs. 12.4 weeks; P = 0.02; Table 2) and lower likelihood of delivery (aHR 0.61, 95% CI 0.38-0.99; P = 0.04) compared to no cerclage, after accounting for gestational age and CL at diagnosis. In patients already treated with progesterone, cervical cerclage was also associated with a longer time interval to delivery (15.1 weeks vs. 11.3 weeks, P = 0.01; Table 2) and lower likelihood of delivery (aHR 0.47, 95% CI 0.26-0.87, P = 0.01) compared to no cerclage. Cervical cerclage was also associated with a lower rate of late PTB compared to no cerclage (11.5% vs. 31.6%, P = 0.03) (Table 2). Cervical cerclage should be considered in asymptomatic women with an extremely short CL (≤10mm) and no history of sPTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

1074 Cervical length nomogram in hispanic patients

Most of the studies have been done on the general population and none targeted special populations. The studies on transvaginal ultrasound cervical length (TVUCL) included patients with various ethnicities. There are reports that CL differs by race and ethnicity. The aim of this study was to develop a TVUCL normogram in low risk pregnant Hispanic women. All TVUCL measurements performed between December 2016 and December 2018 at a single tertiary care institution were reviewed. We included all patients who self-identified as Hispanic, were between the ages of 18 to 45 years, had singleton pregnancies, and underwent universal TVUCL between 16-24 weeks of gestation. We excluded patients with twin or higher order pregnancies, uterine anomalies or cerclage placement at time of screening or with history of preterm birth. We collected demographic data, gravidity, parity, gestational age at time of cervical length screen and cervical length. Cervical length across gestation was analyzed by the LMS method. A thousand patients were included in the analysis (Table 1). Nomogram is shown in Figure 1A. The 50th, 10th and 5th percentiles TVUCLs were 4.01 cm, 3.23 cm, and 3 cm, respectively (Table 2). Compared with those who delivered at term (>37 weeks), patients who had spontaneous preterm birth (sPTB) had shorter TVUCL (mean difference (MD): 0.57cm, 95%CI 0.25-0.89; Figure 1B), but those with medically indicated preterm delivery did not (MD: -0.06cm, 95%CI -0.25-0.13; Figure 1C). Among preterm deliveries, only deliveries below 28 weeks had significantly shorter cervix (MD: 0.99cm, 95%CI (0.21- 1.77)) compared to patients who delivered more than 28 weeks. Receiver operating characteristic curve analysis revealed that for a clinically relevant positive likelihood ratio, a TVUCL cutoff of 3.08cm was best in predicting sPTB (Table 3). The nomogram for TVUCL in Hispanic low risk pregnant women shows longer CL than previously reported. If validated in other studies, a higher cutoff may need to be used to define short cervix in Hispanics.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

947 Recurrence risk of short cervix in women with history of short cervix and term delivery

Little is known about the recurrence risk for short cervix in women with an obstetric history of short cervix with term delivery. The objective of our study was to determine the recurrence risk of short cervix in this population of women. We performed a cross-sectional study of women who delivered at a single tertiary care center from 1/1/2015–12/31/2019 with an obstetric history of short cervix - defined as a cervical length <2.5cm - who delivered at term in an index pregnancy. At our institution, universal transvaginal cervical length screening is performed at the anatomical survey between 16 and 24 weeks. Measurements were performed in compliance with the Cervical Length Education and Review program. Women were included if the index and subsequent pregnancies and deliveries were within our institution during the study period. Women with a history of preterm birth, multiple gestations, fetal anomalies, stillbirth and missing data were excluded. Data were collected via chart abstraction and compared between women with and without recurrent short cervix. 54 women met our inclusion criteria. 21 (39%) women had recurrent short cervix in the subsequent pregnancy. In unadjusted univariate analysis, women with short cervix diagnosed at ≥20 weeks in the index pregnancy were at increased risk of recurrent short cervix in the subsequent pregnancy (Table 1). This persisted after controlling for age, race, body mass index, and vaginal progesterone use during the index pregnancy (aOR 7.86, 95% CI 1.30-47.38) (Table 2). There was no difference in the overall and spontaneous preterm birth (PTB) rates between women with and without recurrent short cervix (overall PTB 9.52% vs 9.09%, p=0.99; spontaneous PTB 4.76% vs 3.03%, p=0.99). In women with an obstetric history of short cervix with a term birth, gestational age at diagnosis of short cervix in the index pregnancy was associated with an increased risk of recurrent short cervix in the subsequent pregnancy. However, there was no increased risk of preterm birth based on recurrent short cervix.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

85 Prevention of preterm delivery after fetoscopy for twin-twin transfusion: a multicenter prospective cohort study

Pre-operative short cervical length (CL) remains a major risk factor for preterm birth after laser surgery for twin-twin transfusion syndrome (TTTS). Interventions to prolong pregnancy remain elusive. The objective of the study is to compare various secondary preventive methods used in the setting of short CL at the time of laser surgery by the North American Fetal Treatment Network (NAFTNet) centers. A prospective cohort study of five NAFTNet centers was conducted from January 2013 to March 2020. Inclusion criteria was monochorionic diamniotic twins complicated by TTTS with pre-operative CL <30mm undergoing fetoscopic laser surgery. Treatments for short CL included no treatment (CRL), progesterone (PRG, prometrium 200 mg daily), pessary (PSR, Arabin, incontinence, Dish or cup-type), cerclage (CLG), or a combination (COM) of two or more treatments. Demographics, ultrasounds, operative records and outcomes were compared. The primary outcome was procedure to delivery interval. 255 women were included. Of these, 151 (59%) had CRL, 32 (13%) had PRG, 21 (8%) had PSR, 21 (8%) had CLG and 30 (12%) had COM. Selected variables and outcomes are listed in the Table. Overall, there were higher proportion of patients in the COM group with prior history of preterm birth compared to CRL. The preoperative cervical length was significantly shorter in the PSR, CLG and COM groups. There was no difference in the gestational age at intervention and stage of TTTS among groups. Preterm premature rupture of membranes (PPROM) was higher in the vaginal progesterone and cerclage group. There were no significant differences in gestational age at delivery, procedure-to-delivery interval, live birth and neonatal survivors among the groups (see Figure). A high percentage of patients had no additional treatment, and this group had longer CL. There were no differences in outcomes among treatments; however, there were significant difference in confounding variables, like history of preterm birth. A large randomized control trial is urgently needed to determine the effects of these treatments.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

555 Preterm birth rates with vaginal progesterone and cerclage for incidentally found shortened cervical length

Administration of vaginal progesterone to asymptomatic women with short cervical length (CL) decreases the risk of spontaneous preterm birth (PTB). Insufficient evidence exists to assess the additive effect of progesterone and cerclage. While most physicians use vaginal progesterone for incidentally found short CL, the benefit of continuing this after cerclage placement is unclear. Our objective was to determine if continuing vaginal progesterone with cerclage reduces rate of PTB and prolongs pregnancy latency when compared to cerclage alone in patients with incidentally found short CL and without history of PTB. IRB approved retrospective cohort study of singleton pregnancies who received cerclage for incidentally found short CL from October 2013 to June 2019. Institutional practice was to offer vaginal progesterone at CL<25mm and cerclage at CL<15mm. Primary outcome was gestational age (GA) at delivery. Secondary outcomes were CL and GA at diagnosis, delivery at <34 and <28 weeks, use of preoperative antibiotics, postoperative tocolysis, and genitourinary infection. Of 43 patients, 22(51.2%) continued vaginal progesterone after cerclage. Baseline demographics, preoperative antibiotics, postoperative tocolysis, suture type, genitourinary infection, delivery and neonatal outcomes were similar between groups. There was also no significant difference in GA, CL, and cervical dilation at cerclage placement. Delivery at <34 weeks and <28 weeks occurred in 27.3% and 13.6% in the combined group and 42.9% and 28.6% with cerclage alone, respectively. Median GA at delivery was 37.5 weeks (IQR 30.7-38.9) for the combined group and 35.9 weeks (IQR 27-39.1) for cerclage alone. These differences were not statistically significant (Table 1). In patients with cerclage for incidentally found short CL, there was no significant difference in GA at delivery between those who continued vaginal progesterone versus those who did not. However, our results indicate a potential pregnancy latency of one to two weeks with continued use of vaginal progesterone. This warrants future study.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

349 Understanding racial-ethnic disparities in preterm birth sub-types

To determine if there are racial-ethnic disparities in preterm birth (PTB) subtypes (spontaneous or medically indicated) after controlling for known risk factors. Retrospective cohort study including singleton pregnancies from 2011-2018 within Kaiser Permanente Northern California (KPNC). Women with missing data on gestational age at delivery or maternal race-ethnicity were excluded. Spontaneous PTB (sPTB) was defined as spontaneous onset of labor or preterm premature rupture of membranes less than 37 weeks gestation. Medically indicated PTB (mPTB) was defined as all other PTB that were not spontaneous. The primary outcome was PTB by subtype, and exposure was race-ethnicity. Covariates included demographic factors (maternal age at delivery, pre-pregnancy BMI, parity, insurance status), and PTB risk factors (diabetes, hypertension, history of PTB, cervical insufficiency, uterine anomalies, cervical shortening, smoking and illegal drug use during pregnancy). Bivariate and multivariate logistic regression analyses were performed. A total of 295,210 pregnancies met inclusion criteria. Overall PTB rate was 6.6% (N=19,357). Compared to White women (5.4%), Black women had almost double the risk of PTB at 9.5%, while Asian/Pacific Islander women had a 7% rate and Hispanic women had a 6.9% rate of overall PTB. Of all PTB, 44.2% were mPTB and 55.8% were sPTB. After adjusting for maternal demographics and medical conditions associated with PTB, all non-White racial-ethnic categories were independently associated with increased relative risks of both mPTB and sPTB (Table 1). Black race was associated with the highest relative risk of mPTB at 1.46 (95% CI 1.32-1.61, Table 1), while Asian/Pacific Islander race was associated with the highest relative risk of sPTB at 1.30 (95% CI 1.23-1.39, Table 1). There are racial and ethnic disparities in PTB within KPNC overall, and by PTB subtype. Further examination of the drivers of PTB disparities by subtype can help direct further efforts to reduce these disparities.

1082 Among women with preexisting diabetes, can preeclampsia or preterm delivery be predicted?

Women with preexisting diabetes (DM) are at increased risk of adverse perinatal outcomes. We aimed to develop multivariable predictive models to estimate the risk of preeclampsia or preterm birth (PTB) in this population. Patients with DM who delivered a live singleton fetus at a single tertiary care center between 2002 and 2013 were identified within a large, NIH-funded database of detailed pregnancy and delivery information extracted by trained research nurses. Candidate predictors for both preeclampsia and PTB were determined from prior literature. Fifteen candidate predictors were included in the initial predictive model for preeclampsia and 10 were included in the initial predictive model for PTB (defined as iatrogenic or spontaneous delivery <37 weeks’ gestation). Logistic regression with backward elimination and a p-value to stay of 0.15 was used to create a parsimonious model for each outcome. 521 eligible pregnancies were identified (190 with type 1 DM and 331 with type 2 DM). Preeclampsia occurred in 93 pregnancies (18%) and PTB occurred in 100 (19%). The final model for preeclampsia included 7 predictors with an increased likelihood of preeclampsia with type 1 versus type 2 DM, nulliparity, preexisting hypertension, increasing number of oral antihypertensive medications, absence of maternal renal disease, lower maternal age, and higher pre-pregnancy BMI, and had an area under the curve (AUC) of 0.74 (95% CI 0.68-0.80). The final model for PTB prediction maintained 5 candidate predictors with an increased likelihood of PTB with type 1 versus type 2 DM, higher first pregnancy A1c, preexisting hypertension, poor diabetes control requiring hospitalization, and history of PTB, and had an (AUC) of 0.67 (95% CI 0.61-0.73). After being validated externally and prospectively, the model for development of preeclampsia among women with DM could be used by clinicians to identify women with DM at highest risk for preeclampsia for whom additional interventions such as higher dose aspirin could be offered.

Risk Factors for Severe COVID-19 in Children.

There are limited pediatric data regarding severe COVID-19 disease. Our study aims to describe the epidemiology and identify risk factors for severe COVID-19 disease in children. This is a retrospective cohort study among children with positive SARS-CoV-2 PCR from March to July 2020 at Children's Hospital Colorado. Risk factors for severe disease were analyzed as defined by hospital admission, respiratory support, or critical care. Univariable and multivariable analyses were conducted. Among 454 patients identified with SARS-CoV-2, 191 (42.1%) were females, median age 11 years. Fifty-five percent of all patients identified as Hispanic compared with 29% among all hospital visits in 2019 (P < 0.0001). In multivariable analyses, age 0-3 months or >20 years [adjusted odds ratio (aOR), 7.85; P < 0.0001 and aOR, 5.1; P = 0.03, respectively], preterm birth history (aOR, 3.7; P = 0.03), comorbidities [including immunocompromise (aOR, 3.5; P = 0.004), gastrointestinal condition (aOR, 2.7; P = 0.009), diabetes (aOR, 6.6; P = 0.04), asthma (aOR, 2.2; P = 0.04)], and specific symptoms at presentation were predictors for admission. Age 0-3 months or >20 years, asthma, gastrointestinal condition, and similar symptoms at presentation were also predictors for respiratory support. Elevated C-reactive protein was associated with the need for critical care with median of 17.7 mg/dL (IQR, 5.3-22.9) versus 1.95 mg/dL (IQR, 0.7-5.5) among patients requiring critical versus no critical care (OR, 1.2; P = 0.02). Extremes of age, comorbid conditions, and elevated CRP are predictors of severe disease in children. Findings from this study can inform pediatric providers and public health officials to tailor clinical management, pandemic planning, and resource allocation.

819 Cervicovaginal microbiome and cytokine expression in twin versus singleton gestations

Second trimester cervicovaginal microbiome diversity and cytokine profiles have not been elucidated for twin gestations. We sought to explore differences in second trimester cervicovaginal microbiome diversity and cytokine profiles among women with twin versus singleton gestations. In this prospective cohort study, women with twin gestations were matched to singleton controls without a history of short cervix or preterm birth by gestational age ± 2 weeks and race. Cervicovaginal lavage samples were collected from 14 to 24 weeks gestation during prenatal visits with cervical length if indicated. Cervicovaginal microbiota were analyzed with 16S RNA gene sequencing and classified into community state types (CST) based on Lactobacillus species predominance. A broad survey cytokine multiplexed ELISA panel was performed to assess changes in immune responses. Cytokine profiles and microbiome diversity were compared between groups. 19 twins and 19 singletons had second trimester cervicovaginal microbiome and cytokine analysis performed. Gestational age at sample collection was similar among twins and singletons (19.7 ± 3.4 vs. 19.4 ± 2.9, p=.72). The groups were similar in maternal characteristics, including age, parity, body mass index, preterm birth history and comorbidities. 79% of twin gestations were dichorionic/diamniotic and 21% monochorionic/diamniotic. 3 twin pregnancies were complicated by short cervix compared with 1 singleton pregnancy (p=.6). The cytokine profiles of twins and singletons were not different. Of the 38 cytokines measured, only G-CSF was noted to be elevated in singleton gestations (46.3 [28.2-189.2] vs. 218.5 [47.3-1151] pg/mL, p=.054). CST I, III and V were more prevalent among twin gestations. CST II and IV were similar among the two groups. CST IV was the predominant type among microbiota profiles of twins (55%) and singletons (64%). Second trimester cervicovaginal cytokine profiles were similar among twins and singletons. CST types I, III and V were more prevalent among twins, while rates of CST II and IV were similar to singleton controls.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

964 Prior spontaneous preterm birth: subsequent pregnancy outcomes among women with PPROM vs spontaneous preterm labor

Women with a history of spontaneous preterm birth (sPTB) are at an increased risk for recurrent preterm birth. Preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) have potentially varying mechanisms and etiopathogenesis. The objective of our study was to evaluate the differential impact of history of PPROM vs sPTL on subsequent pregnancy management and perinatal outcomes. Retrospective review of women delivering at a single hospital from July 2018- November 2019 to identify women with a history of sPTB of singleton gestations. The cohort was divided into two groups based on a history of sPTL vs PPROM. Demographic data, pregnancy management, and perinatal outcomes were abstracted through a review of electronic medical records and compared across the 2 groups using student’s t test and chi squared/Fischer’s exact test for continuous and categorical data respectively. Out of 2,803 women, 168 women had a history of sPTB: 125 (74%) with a history of sPTL and 43 (23%) with a history of PPROM. Demographic characteristics were similar across groups. We found no significant differences in the pregnancy interventions (Table 1) and perinatal outcomes (Table 2) among study groups. Subgroup analyses were performed evaluating the impact of vaginal vs IM progesterone. While there were no significant differences noted in women with a history of PPROM, differences were noted among women with a history of sPTL. Women who received IM progesterone had longer cervical lengths (mean ± SD) [36.3mm ± 4.4; N=21 vs 20.5 ± 12.2; N=18 p<0.001] and delivered at a later gestational age (mean ± SD) (37.2 ± 1.6 weeks; N=28 vs 34.7 ± 5.6 weeks; N = 23) as compared to women receiving vaginal progesterone. In our cohort, similar outcomes were noted in subsequent pregnancies among women with history of PPROM and sPTL. However, subgroup analyses in women with a history of sPTL suggest a potential benefit of IM progesterone. Further research in a larger cohort is warranted to delineate the differential impact of the history of sPTB in the context of PPROM vs sPTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

744 Clinical factors associated with gestational latency in women with twins undergoing physical exam-indicated cerclage

A randomized trial demonstrated that, compared to expectant management, physical exam-indicated cerclage (PEIC) reduced preterm birth in twins with advanced cervical dilation < 24 weeks gestational age (GA). However, data are limited to personalize the expected gestational latency after PEIC placement. Thus, we assessed clinical factors associated with gestational latency among pregnant women with twin gestations undergoing PEIC. This single-site retrospective cohort study included all women with a twin gestation who underwent a PEIC and delivered between 2009 and 2018. PEIC was performed in the setting of painless cervical dilation ≥ 1 cm between 16 0/7 and 23 6/7 weeks GA. The primary outcome was gestational latency ≥ 28 days. Generalized linear models using a Poisson error distribution with robust error variances were created. A priori covariates included a history of preterm birth and use of perioperative antibiotics and indomethacin. Other clinical covariates were included based on statistical significance of p < 0.10 on bivariable analyses. Effect modification between clinical variables associated with gestational latency was evaluated using interaction variables. Subgroup analyses were performed for interaction variables significant on multivariable analysis at p < 0.05. 130 women were included. Women who achieved a gestational latency ≥ 28 days had a lower frequency of prolapsing membranes (36.6% v 64.9%, p = 0.003) and cervical dilation ≥ 2 cm (32.3% v. 62.2%, p = 0.002) when compared to those who did not (Table 1). On multivariable analysis, the interaction between prolapsing membranes and cervical dilation was significant (p=0.004). Women with cervical dilation ≥ 2 cm and prolapsing membranes had a lower risk of achieving a gestational latency ≥ 28 days than women with cervical dilation < 2 cm and no prolapsing membranes (aRR 0.51, 95% CI 0.32-0.80, Table 2). Both cervical dilation and prolapsing membranes are associated with gestational latency after PEIC in twin gestations and can be used to counsel women on anticipated clinical outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Time-to-pregnancy and risk of cardiovascular disease among men and women

A few studies indicate that women with prolonged time-to-pregnancy (TTP) have an increased risk of cardiovascular disease (CVD). This has not been studied in men. We evaluated CVD risk by self-reported TTP among parous women (n = 64,064) and men (n = 50,533) participating in the Norwegian Mother, Father and Child Cohort Study. TTP was categorized as 0–3 (reference), 4–12 and > 12 months. CVD diagnosed between 2008 and 2017 were available from the national patient and general practitioner databases. Risk of CVD by TTP was estimated using Cox regression adjusting for baseline age, education, BMI, smoking, diabetes, and number of offspring in both sexes, and history of endometriosis, ovarian cysts, preterm birth and pre-eclampsia for women. Mean age was 33 for women and 35 for men at baseline (years). The rate of any CVD was 24 per 1000 person years among women and 22 per 1000 person years among men. Longer TTP was associated with increased rate of CVD among women, with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.03, 1.09) for TTP 4–12 months and 1.14 (1.08, 1.20) for TTP > 12 months. Among men, respective HRs for CVD were 1.06 (1.00, 1.10) for TTP 4–12 months and 1.07 (1.01, 1.14) for TTP > 12 months. We observed sex-differences in the relationship with CVD subtypes but none were statistically significant. In conclusion, both men and women with a prolonged TTP had a small increased risk of CVD, clinical significance of which is unclear. Further studies are necessary to investigate in detail what underlying causes of prolonged TTP might be reflected in the increased risk of CVD. Longer follow-up is required to confirm these preliminary findings.

BACTERIAL INFECTION CAUSES OF PREGNANCY LOSS AND PREMATURE BIRTH IN THE WOMEN IN UKRAINE

The aim: To find out whether or not the presence of pregnancy loss and preterm birth was associated with the history of healthcare-associated infection (HAI) of women reproductive tract. Materials and methods: We performed a retrospective cohort study was based on surveillance data. This study included 1,027 fertile women aged 21-50 years admitted to 8 hospitals from 2017-2019 with complaints to pregnancy loss or preterm birth. Definitions HAI of women reproductive tract were used from the CDC/ NHSN. Results: Of 1,027 fertile women with complaints to pregnancy loss or preterm birth, 702 (68.4%) HAIs of reproductive tract were detected. The predominant HAIs were: postpartum endometritis (19.1), bacterial vaginitis (15.8%), chorioamnionitis (11.3%), vaginal cuff infection (9.1%), and parametritis (5.6%). According to the statistical data, a significant association between HAI of women reproductive tract and the history of pregnancy loss (p < 0.05) was determined. The presence of HAI had no effect on the first trimester miscarriage (p > 0.05), but HAI women reproductive tract had strongly affected the second trimester pregnancy losses (p < 0.05). Main causative agents of HAI were Escherichia coli (31.5%), Enterobacter spp. (18.4%), Klebsiella pneumoniae (12.5%), Enterococcus faecalis (11.6%),Staphylococcus aureus (10.2%), Pseudomonas aeruginosa (8.4%). Conclusions: This study identified a significant association between healthcare-associated infection of women reproductive tract and a history of miscarriage. However, there was no association between HAI and a history of preterm birth.

Pediatric resuscitation, emergencies in pediatrics. Various infusion methods for children

Background. Medical care for premature babies in Germany is divided into two levels. Perinatal centers of the first level provide care for infants with body weight at birth &lt;1500 g. Perinatal centers of the second level provide care for children whose body weight exceeds 1500 g. In order to be included in the list of first level institutions, the hospital must, among other, be able to pick up children from other institutions in the surrounding region. Mobile incubators are used for this purpose. Such an incubator is a kind of a mobile intensive care unit. In some cases, the incubator is delivered to the desired location by helicopter, but in most cases, specialized road transport is used.&#x0D; Objective. To describe neonatological medical care in Germany.&#x0D; Materials and methods. Analysis of own experience and available literature data on this issue.&#x0D; Results and discussion. In recent years, Germany experiences a decrease in the number of births, which causes the problem of professional training of doctors. Hospitals with the fewest births are closed due to lack of efficiency. Although there are some fluctuations from year to year, in general, the number of premature babies with extremely low birth weight remains approximately constant. Prematurity remains one of the most important problems of modern medicine, as it is accompanied by high mortality rates. The earlier the premature birth is and the lower the body weight is, the higher these rates are. Prematurity is caused by numerous risk factors. Multiple pregnancies are accompanied by the highest risk of premature birth. The presence of twins or triples increases this risk by 7.7 times. Other risk factors include vaginal bleeding in late pregnancy, preeclampsia, and a history of preterm birth. Over the past 20 years, the survival of children born before 32 weeks of pregnancy or weighing &lt;1500 g has increased by almost 20 %. The smallest premature baby born in our clinic is a baby born at 24 weeks of gestation with a body weight of 350 g. Nowadays in Germany, the survival rate of infants born after 24 weeks of gestation is almost 80 %, and after 29 weeks – almost 100 %. It should be noted that maintaining the life of a premature baby from birth to discharge costs 250-300 thousand euros. Bronchopulmonary dysplasia is an important problem of premature infants, especially in case of mechanical lung ventilation (MLV) or joining infections. Up to 40 % of children who die from complications of bronchopulmonary dysplasia can be saved. If possible, MLV and infections should be avoided, premature births should be prevented, so-called neuroprotective ventilation and nasal or mask devices that do not require intubation should be used. Surfactants have made great progress in the management of premature infants. The modern LISA (less invasive surfactant administration) method allows to inject a surfactant into a child’s lungs without intubation. In the early 20th century, 100 % oxygen was used in the resuscitation of newborns, but now we use air (21 % oxygen) or a mixture containing up to 30 % oxygen. To prevent necrotizing enterocolitis, premature infants are prescribed probiotics based on lyophilized lactic acid bacteria and bifidobacteria. Breast milk is an another way to prevent this complication of prematurity. There is a breast milk bank in Potsdam.&#x0D; Conclusions. 1. Prematurity remains one of the most important problems of modern medicine, as it is accompanied by high mortality rates. 2. Multiple pregnancies are accompanied by the highest risk of premature birth. 3. Nowadays in Germany, the survival rate of children born after 24 weeks of gestation is almost 80 %, and after 29 weeks – almost 100 %. 4. Surfactants and the LISA method have made great progress in the management of premature infants. 5. Probiotics and breast milk are prescribed to premature babies to prevent necrotizing enterocolitis.

Is real-time dynamic cervical shortening predictive of preterm birth?- A case control study

Objectives We aimed to assess the risk of preterm birth in those with real-time dynamic cervical shortening. Methods A retrospective matched case-control study. The study group comprised all women with dynamic cervical shortening (≥4 mm) noted from 24 to 34 weeks of gestation during 2010–2017 at a university hospital. Two control groups of women were established by matching the minimal and maximal cervical length measured, as well as age, parity, gestational age, history of spontaneous preterm birth, symptoms of preterm labor, and delivery year. Results Data from 339 women were analyzed, 113 with dynamic cervical shortening comprised the study group, and two groups with 113 women each, matched for the minimal and maximal cervical lengths measured comprised the control groups. Rates of spontaneous preterm birth rate at <37 weeks (32.7% vs. 15.9%; OR [95% CI]: 2.60 (1.36, 4.87), p = .004) and <35 weeks (15.9% vs. 5.3%; OR [95% CI]: 3.38 (1.29, 8.86), p = .013) were significantly higher among those with dynamic cervix than among the control group matched for the maximal cervical length, and comparable to the control group matched for the minimal cervical length. The negative predictive values of cervical length for preterm birth occurrence at various cutoff values were lower in those with dynamic cervix. Conclusions The minimal cervical length measured should be used to guide patient management when dynamic cervix is noted. In the setting of dynamic cervical change, the value of cervical length as a negative predictor of preterm birth is limited.