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To determine the effect of gestational age at delivery on maternal and neonatal outcomes in preterm prelabor rupture of membranes (PPROM) and assess various predictors of neonatal and infant mortality in these pregnancies. United States birth data from CDC-National Center for Health Statistics natality database for years 2004–2008 was used to identify singleton pregnancies with PPROM and delivery from 32 0/7 to 36 6/7 weeks. Controls were singletons at 37–40 weeks, without PPROM. Maternal and neonatal complications reported by all states were analyzed along with neonatal outcomes such as chorioamnionitis and hyaline membrane disease, reported by a subgroup of states. OR (95% CI) were calculated after adjusting for preeclampsia, diabetes, chronic hypertension, maternal race, and infant sex. There were 134,502 PPROM cases and similar number of controls. There was a significant decrease in need for prolonged ventilation, hyaline membrane disease, 5 min Apgar score <7, and NICU admission with advancing gestational age. Placental abruption decreased and chorioamnionitis and cord prolapse were not different between 34 and 37 weeks. We found reductions in early death, neonatal death, and infant mortality with advancing gestational age (p<0.001 for each). Gestational age at delivery was the strongest predictor for early death, neonatal death, and infant mortality in PPROM. These differences persisted after adjusting for antenatal steroid use. We provide population-based evidence showing a decrease in neonatal complications and death with advancing gestational age in PPROM. Gestational age at delivery in pregnancies with PPROM is the strongest predictor of mortality risk. [ABSTRACT FROM AUTHOR]

The article examines soft markers, which are commonly identified during the secondtrimester anatomical scan. It reviews softt markers' clinical impacts when it comes to aneuploidy risk and potential associations with other abnormalities that may manifest in fetal or postnatal life. An approach is provided for counselling and management based on a consensus report from the 2012 National Institute of Child Health and Human Development Conference on Fetal Imaging.

Objective: Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. Method: A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied. Results: A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. Conclusion: This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function. [ABSTRACT FROM AUTHOR]

Objective: The molecular basis of failure to progress in labor is poorly understood. This study was undertaken to characterize the myometrial transcriptome of patients with an arrest of dilatation (AODIL). Study design: Human myometrium was prospectively collected from women in the following groups: (1) spontaneous term labor (TL; n=29) and (2) arrest of dilatation (AODIL; n=14). Gene expression was characterized using Illumina® HumanHT-12 microarrays. A moderated Student's t-test and false discovery rate adjustment were used for analysis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of selected genes was performed in an independent sample set. Pathway analysis was performed on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). The MetaCore knowledge base was also searched for pathway analysis. Results: (1) Forty-two differentially expressed genes were identified in women with an AODIL; (2) gene ontology analysis indicated enrichment of biological processes, which included regulation of angiogenesis, response to hypoxia, inflammatory response, and chemokine-mediated signaling pathway. Enriched molecular functions included transcription repressor activity, heat shock protein (Hsp) 90 binding, and nitric oxide synthase (NOS) activity; (3) MetaCore analysis identified immune response chemokine (C-C motif) ligand 2 (CCL2) signaling, muscle contraction regulation of endothelial nitric oxide synthase (eNOS) activity in endothelial cells, and triiodothyronine and thyroxine signaling as significantly overrepresented (false discovery rate <0.05); (4) qRT-PCR confirmed the overexpression of Nitric oxide synthase 3 ( NOS3); hypoxic ischemic factor 1A ( HIF1A); Chemokine (C-C motif) ligand 2 ( CCL2); angiopoietin-like 4 ( ANGPTL4); ADAM metallopeptidase with thrombospondin type 1, motif 9 ( ADAMTS9); G protein-coupled receptor 4 ( GPR4); metallothionein 1A ( MT1A); MT2A; and selectin E ( SELE) in an AODIL. Conclusion: The myometrium of women with AODIL has a stereotypic transcriptome profile. This disorder has been associated with a pattern of gene expression involved in muscle contraction, an inflammatory response, and hypoxia. This is the first comprehensive and unbiased examination of the molecular basis of an AODIL. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. Study design: A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. Results: 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1–34.7 vs. 35.4 weeks, IQR: 33.9–36.9; P=0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008) than those without IAI. Conclusions: Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h. [ABSTRACT FROM AUTHOR]

Objective. To assess the demographic characteristics, risk factors and perinatal outcomes among maternal intensive care unit (ICU) admissions in New Jersey from 1997 to 2005. Methods. Data were obtained from a perinatal linked database from MCH epidemiology programme in New Jersey. Chi-square test was used for bivariate analysis and stepwise logistic regression was used to assess the influence of the potential risk factors and pregnancy complications. Results. There were 15 447 (1.54%) ICU admissions and 23 maternal deaths (0.15%) among the 1 004 116 pregnancies. Analysis of demographic factors revealed that maternal age, race and smoking were significantly associated with ICU admission. Regression analysis adjusting for maternal age, parity, gravida, race, smoking status, maternal education and place of delivery found the following predictors for ICU admission, preeclampsia (odds ratio (OR): 2.8, 95% confidence interval (CI): 2.6-3.0), eclampsia (OR: 6.8, 95% CI: 5.4-8.6), placenta previa (OR: 3.0, 95% CI: 2.7-3.4), abruption (OR: 8.9, 95% CI: 8.3-9.6), multifetal pregnancy (OR: 4.2, 95% CI: 4.1-4.4), diabetes (OR: 3.1, 95% CI: 2.7-3.5), acute renal failure (OR: 22.1, 95% CI: 13.3-36.6) and cesarean delivery (OR: 1.9, 95% CI: 1.5-2.4). Infants born to ICU admitted mothers had higher rates of NICU admission, neonatal intubations and lower Apgar scores compared with infants born to non-ICU admitted mothers. Conclusion. Pregnancy complications are predictive of ICU admission amongst pregnant patients after adjusting for demographic factors. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate the associations of electronic fetal heart rate monitoring (EFM) patterns and adverse neonatal outcomes Study design: From 2013 to 2016; 12,067 term, singleton deliveries in labor ≥2 h with abnormal EFM defined as absent accelerations, variable, late or prolonged decelerations, tachycardia, bradycardia, or minimal variability were analyzed as any documentation during labor, in first hour and last hour of labor. Outcomes were composite neonatal adverse outcomes, neonatal intensive care unit (NICU) admission, neonatal hypoxia, neonatal hypoglycemia, umbilical artery pH, and base excess. Independent associations were ascertained using regression analysis. Results: Significant independent associations occurred between any abnormal EFM during the last hour and five adverse neonatal outcomes; between abnormal EFM at any time and one adverse neonatal outcome while there was none with the first hour of labor. In the last hour, accelerations had significant negative associations with three adverse neonatal outcomes, while prolonged decelerations, late decelerations, tachycardia, and bradycardia had significant positive associations with three adverse neonatal outcomes. Throughout labor, increasing accelerations events were significantly negatively correlated with all adverse neonatal outcomes, while increasing frequency of late, variable, and prolonged decelerations were positively associated with five adverse neonatal outcomes. Hierarchical analysis showed that bradycardia/tachycardia contributed only 0.8%, while all EFM periodic changes contributed 1%; the addition of the frequencies of abnormal EFM events contributed 0.6% to the variance in umbilical artery pH and base excess. Conclusions: Terminal EFM patterns are independently associated with neonatal outcomes. Accelerations are protective of adverse neonatal outcomes. Increasing frequency of EFM patterns overtime contributes to neonatal outcome. [ABSTRACT FROM AUTHOR]

Objective: Given concerns amongst physicians and other maternity providers for increased maternal blood loss with delayed cord clamping, our objective was to determine the impact of routine delayed clamping with term cesarean section on maternal blood loss metrics. Study design: A retrospective cohort study evaluated the impact of delayed cord clamping in term cesareans at our tertiary care center following protocol implementation. The pre-protocol group (PRE) ranged 1 October 2015 to 31 March 2016. The post-protocol (POST) group ranged 1 October 2017 to 31 March 2018. The primary outcome was maternal estimated blood loss (EBL) during cesarean section. Secondary outcomes included maternal transfusion, hemorrhage (EBL > 1,000 mL), and changes in hemoglobin (Hgb) and hematocrit (HCT). Neonatal outcomes were APGAR scores at 1 and 5min. Results: 733 subjects were included, (PRE = 416, POST = 317). Overall 44.7% reported prior cesarean section. Preop differences included only platelets k/mL (222 vs. 211, p=.015), Hgb g/dL (11.7 vs. 11.9, p=.002) and HCT% (36.2 vs. 35.2, p=.027), with Hgb and HCT differences in opposite clinical directions. EBL actually decreased after the delayed cord clamping protocol (p=.04). The median [interquartile range] was the same (700 [600-800]), but the PRE group had higher proportions of EBL 800-1,000 (16% vs. 11%) and EBL > 1,000 (4.3% vs 3.7%) comprising this statistical difference. There was no difference in maternal transfusion (2.2%), hemorrhage (11.1%), or change in Hgb (D = -1.6 g/dL) or HCT (D = -4.6%), (all p>.05). APGAR scores were slightly lower in the POST group at 1 min (8 [8-9] vs. 9 [8-9], p=.035) but similar by 5 min (9 [9-9], p=.38). Conclusion: Concerns for increased maternal blood loss during cesarean delivery after implementing a routine delayed cord clamping protocol were not supported. While EBL was lower with delayed cord clamping, all differences between groups appear to lack clinical significance. This offers reassuring evidence there is no negative impact on maternal hematologic characteristics including blood loss from the delayed cord clamping protocol. [ABSTRACT FROM AUTHOR]

Objective. Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia. Study design. This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups ( p < 0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group ( r = 0.48, p = 0.04). Conclusion. Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate. [ABSTRACT FROM AUTHOR]

Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design. Maternal plasma was obtained from patients with fetal death ( n = 59) and normal pregnant women ( n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term ( n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women ( p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women ( p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4–7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group ( p < 0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5–164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). Conclusion. Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus. [ABSTRACT FROM AUTHOR]

Objective. Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death ( n = 35) and controls ( n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained ( n = 25); (2) preeclampsia and/or placental abruption ( n = 5); and (3) chromosomal/congenital anomalies ( n = 5). The control group consisted of patients with preterm labor (PTL) who delivered at term ( n = 92) and women at term not in labor ( n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group ( p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth ( p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations. [ABSTRACT FROM AUTHOR]

Objective. Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition. Study design. This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) ( n = 48); (2) preterm labor (PTL) leading to term delivery ( n = 143); (3) PTL resulting in preterm delivery with ( n = 72) and without IAI ( n = 100); (4) preterm PROM with ( n = 46) and without IAI ( n = 42); (5) term in labor ( n = 48); and (6) term not in labor ( n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term ( p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95%CI 1.4–2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 ( p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations ( p > 0.05 for each comparison). Conclusion. (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm. [ABSTRACT FROM AUTHOR]