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Introduction: Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like tyrosine kinase receptor-1 (sFlt-1) to placental growth factor (PlGF) can be used to evaluate placental dysfunction in cases of preeclampsia and FGR. A need for delivery within 2 days has been recommended for sFlt-1/PlGF ratios > 655 (normal ratio < 38) measured before 34 weeks' gestation. However, few studies have assessed this recommendation in a real-world setting and there remains a need for further evidence-based guidance on the use of the ratio in delivery timing planning in this situation., Aim: To assess the need for delivery within 2 days associated with sFlt-1/PlGF ratios > 655 before 34 weeks' gestation., Methods: A retrospective audit of all sFlt-1/PlGF ratio test results obtained at a single maternity hospital between September 2016 and November 2022. The primary outcome was time to delivery after recording a ratio > 655 in patients with a pregnancy between 20 + 0 and 33 + 6 weeks' gestation. Statistical analysis was performed using IBM SPSS Statistics v29.0.0.0., Results: During the study period a total of 33 patients with suspected or confirmed preeclampsia and/or FGR recorded sFlt-1/PlGF ratios > 655 before 34 + 0 weeks' gestation. Amongst cases with ratios > 655, median time to delivery was 4 days (IQR 1.0-9.0), with 14 (42.4%) delivering in ≤ 2 days, 8 (24.2%) delivering between 2 and 7 days and 11 (33.3%) delivering after 7 days. A significant inverse correlation was observed between time to delivery and gestational age at the time of ratio testing ( r s = -0.484, p  = 0.004)., Discussion: This study provides updated recommendations on the use of the sFlt-1/PlGF ratio in predicting the risk of imminent delivery amongst those with high ratios > 655 measured before 34 weeks' gestation. Our results suggest that the risk of imminent delivery can be stratified based on ratio level and gestational age, which in combination with the results of other clinical assessments, can be used to plan delivery timing and allow for considerations of fetal lung maturing corticosteroid and neuroprotective magnesium sulfate therapies prior to delivery.

Background: To investigate the association between gestational weight gain (GWG) and preterm birth (PTB) according to pre-pregnancy body mass index (pp-BMI) and glycated haemoglobin (HbA1c) within the normal range., Methods: We conducted a population-based retrospective cohort study between July 2017 and January 2020 at Women's Hospital, Zhejiang University School of Medicine. Women were classified into three groups (inadequate GWG, appropriate GWG, and excessive GWG). In addition, women were divided into different subgroups according to pp-BMI and HbA1c. We estimated the odds ratios (OR) with 95% confidence intervals (CI) to assess the associations between GWG and the risk of PTB. Meanwhile, we adjusted for possible confounding factors, including maternal age, infant sex, family history of diabetes, education, pregnancy mode, delivery mode, parity, and gravidity., Results: The study involved 23,699 pregnant women, of which 1124 (4.70%) were PTB. Women who had inadequate GWG were found to have a significantly higher risk of PTB compared to women with appropriate GWG. In contrast, women with excessive GWG had a reduced risk of PTB. Similarly, GWG and PTB had similar risk associations in the HbA1c and pp-BMI subgroups. Among women with pp-BMI <18.5 kg/m 2 , women with inadequate GWG had a significantly increased risk of PTB compared with women in the control group (HbA1c 4.6-5.0%, appropriate GWG), and the risk increased with increasing HbA1c levels. Similar results were observed in women with normal pp-BMI., Conclusions: There was a significant association between GWG and the risk of PTB, but the risk varied by pp-BMI and HbA1c levels. Reasonable weight gain during pregnancy is essential to prevent PTB. Furthermore, while HbA1c is within the normal range, the higher levels should be noticed.

Preeclampsia patients have frequently been found to experience hyperuricaemia and this may result in poor outcomes compared to those with normal uric acid levels. This study aimed to determine the relationship of hyperuricaemia in pre-eclampsia patients with foetal and maternal outcomes. This prospective cohort study involved 79 patients in a tertiary centre from year 2016 to 2018. Blood samples were taken antenatally and at the 6th week, post-delivery for renal function including serum uric acid level. Our findings indicate that there was a higher incidence of poor maternal and foetal outcomes in the hyperuricaemia group than the normal uric acid group. Serum uric acid has been shown to be a significant predictor for low birth weight and premature delivery in preeclampsia patients. It was also found that there was a significant negative correlation between uric acid level and antenatal creatinine clearance ( r s  = -0.338, p  = .002). The assessment of the serum uric acid level seems to be important to ensure better outcomes in patients with preeclampsia.Impact statement What is already known on this subject? Preeclampsia is a serious pregnancy-related complication and remains as one of the most important cause of maternal and foetal morbidity and mortality, affecting 2-8% in all pregnancy. Many studies have established the association between hyperuricaemia and preeclampsia. Besides, numerous studies have found that hyperuricaemia contributed to adverse maternal and foetal outcomes. What the results of this study add? There was a significant increase in adverse foetal and maternal outcomes in the hyperuricaemia group compared to the normal uric acid group. This study revealed that serum uric acid remains a significant predictor for low birth weight and premature delivery in preeclampsia patients. What the implications are of these findings for clinical practice and/or further research? Hyperuricaemia does not merely become an indicator for the severity of disease in preeclampsia patients but also indicates adverse foetal outcomes. Large population-based studies are required to establish the absolute maternal and foetal outcomes in patients with hyperuricaemia. Besides, further studies are recommended on long-term implication of hyperuricaemia which is not limited to only during antenatal period.

Background: Women that previously had preterm labor are at an increased risk for heart disease. Because spontaneous preterm birth is an adverse pregnancy outcome that affects millions of children worldwide, our objective was to review and analyze studies that have examined associations between maternal total cholesterol (TC), LDL-C, and HDL-C concentrations during pregnancy and the risk of preterm birth to potentially define biomarkers or targets for treatment. Method: A search was performed and 22 articles were found that examined the association of maternal plasma cholesterol concentrations and preterm birth. A meta-analysis was performed on 10 of the articles, those that used maternal lipid concentrations as the outcome and presented results as means plus variables, and a qualitative review was performed on all 22 articles. Results: The meta-analysis showed no relationship between maternal TC, LDL-C, or HDL-C and increased risk of preterm birth, although, a near significant relationship between low maternal HDL-C concentration and preterm birth ( p  = .055). Importantly, associations increased when cholesterol concentrations were combined with inflammatory markers or metabolic syndrome factors. Conclusions: The relationship between maternal cholesterol levels and preterm birth is heterogeneous. Associations are strengthened when maternal cholesterol concentrations are combined with other factors that may be related to more recently defined lipoprotein functions.

Objective: To examine the association between progesterone concentration in early pregnancy and duration of pregnancy and risk of preterm delivery. Methods: Women enrolled in the Born in Guangzhou Cohort Study from 2013-2014, with a singleton pregnancy, who had serum progesterone measured at least one time between 4 and 10 weeks of gestation were included. The association between progesterone concentration both continuous and as categorical variable (quartile) and the risk of preterm delivery was assessed with Cox proportional hazards regression. Differences of length of gestation in four progesterone concentration quartiles were assessed using the Log-rank test. Results: We studied 1860 mother-newborn pairs. The mean overall progesterone concentration was 65.7 ± 21.3 nmol/L, with mean progesterone concentrations in the four quartiles of 42.4 ± 6.2 nmol/L ( n  = 463), 56.2 ± 3.3 nmol/L ( n  = 462), 68.9 ± 4.5 nmol/L ( n  = 470), and 95.1 ± 15.3 nmol/L ( n  = 465). There was no significantly difference in duration of gestation in four progesterone concentration groups ( p =.511). There was no relation between progesterone level and preterm delivery (adjusted hazard ratio (HR) per 10 nmol/l progesterone level 1.00 (95% confidence interval (CI) 0.90, 1.11)). After adjusting for potential confounders, the HR of any preterm delivery for quartiles 1, 2 and 3 versus the highest quartile of progesterone level (> 77.3 nmol/L) was 1.04 (95% CI 0.52, 2.07), 1.17 (95% CI 0.60, 2.28), and 1.46 (95% CI 0.76, 2.78), respectively. When analysis was done for spontaneous preterm delivery only, also no association with first trimester progesterone was found. Conclusion: Lower first trimester serum progesterone concentration is not associated with reduction of length of gestation or increased risk of preterm delivery.

Objective: To examine the relationship between the first-trimester serum biomarker levels (pregnancy-associated plasma protein A:PAPP-A; and free beta-human chorionic gonadotropin: b-hCG) and preterm birth; and to create the predictive models for preterm birth in case of strong correlation. Methods: Secondary analysis on a large prospective database of singleton pregnancies undergoing first-trimester serum screening with complete follow-up for pregnancy outcomes. The multiples of medians (MoM) of the biomarkers were compared between the group of term and preterm/early preterm birth. Predictive models were developed based on adjusted MoMs and logistic regression analysis, and then diagnostic performances in predicting preterm birth were assessed. Results: Of 24,611 pregnancies eligible for analysis, 1908 (7.8%) and 500 (2.0%) had preterm and early preterm birth, respectively. Medians MoMs of both biomarkers were significantly lower in preterm and early preterm birth group. The predictive models were constructed. Performance in predicting preterm birth of these models yielded the area-under-ROC-curve of 0.560, 0.652, and 0.653 for b-hCG, PAPP-A, and combined biomarkers, respectively. In predicting early preterm birth, the areas-under-the-curve were found to be 0.551, 0.675, and 0.674 for b-hCG, PAPP-A, and combined biomarkers, respectively. Conclusion: The routine first-trimester serum screening of fetal Down syndrome could also be used as a tool of risk identification of preterm birth. We could take advantage of the screening by incorporating the predictive models into the Down syndrome screening software to report the preterm risk in the same test without extra effort and extra cost.

Background: Identification of vascular pathologies in delivered placentas and their associations with biomarkers measured during pregnancy may elucidate mechanisms of adverse pregnancy outcomes and inform early detection and intervention strategies. Objectives: To examine associations of placental vascular pathology with birth size and timing of parturition, and to evaluate maternal midpregnancy serum corticotropin-releasing hormone (CRH) levels as a marker of the above associations. Study design: The pregnancy outcomes and community health (POUCH) Study enrolled women at 16-27 weeks of pregnancy from five Michigan communities. Histological assessments of delivered placentas and assays of CRH in maternal blood sampled at enrollment were performed in a subcohort of 1152 participants. Five placental vascular pathology constructs were formulated: Maternal-Vascular-Obstructive (MVO), Fetal Vascular-Obstructive (FVO), Maternal Vascular-disturbance of Integrity (MVI), Fetal Vascular-disturbance of Integrity (FVI), and Maternal Vascular-Developmental (MVD). A four-level outcome variable combined small for gestational (SGA) yes/no and delivery timing preterm/term; the non-SGA/term served as the referent group. In multinomial logistic regression models, the five vascular pathology groups were evaluated in relation to the outcome variable and effect sizes were compared before versus after exclusion of participants with high CRH (top quartile). Results: Adjusted odds ratios (aOR) for MVO among SGA/term and SGA/preterm were 4.1 (95% CI: 2.2, 7.9) and 8.8 (95% CI: 3.3, 23.5) respectively. Among SGA/preterm births, the aOR was attenuated by ∼40%, i.e. 5.4 (95% CI: 1.1, 26.2) after removing high CRH pregnancies. MVI and FVO were each associated with SGA/preterm, aOR = 3.7 (95% CI: 1.3, 10.3) and 10.5 (95% CI: 3.6, 30.8) respectively. Removal of high CRH pregnancies reduced the OR estimates by nearly half, i.e. MVI aOR = 1.9 (95% CI: 0.34, 10.9), FVO aOR = 6.0 (95% CI: 1.3, 28.6). MVI, FVI and MVD were each associated with greater odds of non-SGA/preterm, but the aORs showed little change after removing high CRH pregnancies. Conclusions: Obstructive placental vascular pathologies in maternal or fetal vessels are associated with SGA. High CRH levels coincided with a portion of pregnancies that share these complications, particularly among pregnancies that also ended prematurely.

Objectives : To evaluate if midtrimester maternal serum contains microbial DNA and whether it differs between women with spontaneous preterm birth (SPTB) and those delivering at term. Study design : In this retrospective case-control study, we identified 20 healthy nulliparas with SPTB at 24-33 weeks of a nonanomalous singleton in 2014. Each case was matched by race/ethnicity to a control delivering at 39-40 weeks. Serum samples, collected at 15-20 weeks and stored at -80 C, were thawed and DNA extracted. PCR with primers targeting the 16S rDNA V4 region were used to prepare an amplicon library, sequenced using Illumina MiSeq, and analyzed using quantitative insight into microbial ecology (QIIME). Taxonomy was assigned using Ribosomal Database program (RDP) Classifier (threshold 0.8) against a modified Greengenes database. Differences in number of observed species, microbial alpha-diversity and beta-diversity, and taxa level analyses were undertaken. Results: All 40 samples were included. Women with SPTB had more unique observed species ( p  = .046) and higher mean alpha-diversity by Shannon index (but not Chao1 or Simpson) ( p  = .024). Microbial composition was different between groups by Bray-Curtis clustering ( p  = .03) but not by weighted ( p  = .13) or unweighted Unifrac ( p  = .11). Numerous taxa in the Firmicutes, Proteobacteria, and Actinobacteria phyla differed between groups ( p  < .05). Conclusions: SPTB is associated with distinct microbial DNA changes detected in midtrimester maternal serum.

Background: The Bilicare™ is a new device that measures transcutaneous bilirubin (TcB) level at the ear pinna. There are only few studies which have evaluated its accuracy in clinical practice. Objective: This study aims to determine the accuracy of Bilicare™ as a predischarge screening tool in late preterm and term neonates and to define the optimal cutoff point for determining the need to measure total serum bilirubin (TSB). Methods: The 35 weeks' gestation or more and healthy neonates who underwent predischarge TSB measurement were enrolled. Bilicare™ TcB was measured within 30 minutes of blood sampling. Paired TcB and TSB data were analyzed. Results: We collected 214 paired samples. Mean age (SD) at TcB measurement was 57.17 (7.47) hours. Mean TSB (SD) was 9.79 (2.83) mg/dL. TcB showed a significant correlation with TSB ( r  = 0.84, r 2  = 0.7). The mean difference (SD) between TcB and TSB was 0.7 (0.21) mg/dL (95%CI 0.49-0.91). TcB tended to overestimate TSB level at the TSB values of <12 mg/dL but underestimate at the higher TSB level. The accuracy of using TcB values to detect neonates who required phototherapy was 92.5%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 78.3, 94.2, 62.1, and 97.3%, respectively. If TcB +3 mg/dL was applied as a cutoff point, the sensitivity, specificity, PPV, and NPV were 100, 53.9, 20.7, and 100%, respectively. Conclusions: Bilicare™ TcB and TSB measurements were well correlated. The TcB level +3 mg/dL could detect all neonates who had significant hyperbilirubinemia requiring phototherapy during their birth hospitalization.

The purpose of this study was to analyse the relationship between preterm delivery and maternal anaemia. This retrospective cohort study was completed with 483 women; 294 of them had a normal delivery and 189 had a preterm delivery. The haemoglobin (Hb) values of all the women participating in the study were measured in the first and second trimesters, and the average Hb values were calculated. The pregnant women participating in the study were divided into three groups, according to their Hb level: those with Hb level <10 g/dl, those with Hb level between 10 and 11 g/dl and those with Hb level >11 g/dl. In crude analysis, women with low Hb levels had an increased rate of preterm delivery (odds ratio, 2.42; 95% CI, 1.07-5.49). Our study provides data that low Hb level is effective in preterm delivery. Impact statement What is already known on this subject? Serum Hb levels have inconsistent associations with a risk of preterm delivery. What the results of this study add? Compared with term delivery Hb levels are lower in preterm delivery. It is necessary to take into account the Hb levels of both the first and second trimester of the pregnancy when describing the pregnancy anaemia. What the implications are of these findings for clinical practice and/or further research? Given these results, physicians should take into account anaemia in pregnancy when considering the risk of a preterm delivery.

Objective: To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Objective: A meta-analysis was performed to study the relationship between serum relaxin and preterm delivery in women with singleton pregnancies without estrogen stimulation. Methods: Cohort and case-control studies were identified through searching databases (PubMed, Embase, Ovid, CBM, Wan fang, VIP, and CNKI). We carried out a continuous variable meta-analysis. The outcome was preterm delivery (gestation age <37 weeks). Results: Fifteen studies were included, involving 1607 women with a singleton pregnancy. The pooled standard mean deviation (SMD) of 15 studies was 0.559 (95%CI: 0.002-1.196) and the heterogeneity was 96.6%. To reduce the heterogeneity, we chose random effects model and made subgroup analysis according to gestational age at sample testing (<18 weeks and ≥18 weeks) and race of included pregnant women. The pooled SMD of gestational age at sample testing ≥18 weeks and Chinese were 1.19 (95%CI: 0.63-1.75) and 1.61 (95%CI: 0.82-2.41) and the heterogeneity values (measured by I 2 ) were 93.5% and 76.5%, respectively. Conclusions: Elevated maternal serum relaxin of later than 18 weeks of gestational age is associated with singleton preterm birth in Chinese women. It might be an important information to prevent singleton preterm delivery in Chinese women. What's already known about this topic? Previous reports reveal that there is a relationship between elevated maternal serum relaxin and preterm birth. However, the included articles contained twin pregnancies and estrogen stimulation, which obviously resulted in higher relaxin concentrations. What does this study add?

Objective: To compare maternal blood endotoxin activity (EA) in women with preterm premature rupture of membranes (PPROM) with gestational age (GA) matched controls; to evaluate serial EA till birth in PPROM and its correlation with latency to delivery. Methods: We followed singleton preterm pregnancies from admission with PPROM until birth. Uncomplicated, GA-matched pregnancies served as controls. Demographics, birth and neonatal outcomes were collected. EA (EAA™) was assessed serially in PPROM and at study entry in controls. EA was compared using Mann Whitney and Wilcoxon tests, p value <.05 was considered significant. Results: We recruited 20 cases of PPROM and 20 controls. Demographics were similar between groups. Mean GA of PPROM was 29.0 ± 2.2 weeks and median latency was 7.5 (IQR 14.1) weeks. Median EA at admission following PPROM was significantly elevated over controls (0.43 (0.18) versus 0.36 (0.2); p  < .02). Overall there was no difference in median EA at admission and in labor (0.43 (0.18) versus 0.33 (0.21); p  = .2) following PPROM. However, on comparing cases with latency to delivery ≤7 days ( n  = 10) versus >7 days ( n  = 10), there was a significant drop in EA in the latter group (0.44 (0.2) versus 0.34 (0.2); p  < .004). Conclusions: EA in PPROM represents a promising biomarker in predicting the clinical evolution of preterm birth.

Objective: Increased inflammation is considered as a risk factor and a promoter of preterm birth (PTB). Monocytes and neutrophils are the main sources of cytokines in the early inflammatory phase. So far, very few studies have indicated CD14/TLR4 and TREM-1 on the monocytes and neutrophils as important targets in PTB. Materials and methods: TLR4 and TREM-1 on CD14 + maternal and cord blood monocytes and neutrophils were detected using flow cytometry in 48 normal term women, 48 PTB with chorioamnionitis (CCA) women, and 40 PTB without CCA women. In the fetal membranes, mRNA and protein levels of the CD14/TLR4-TREM-1 signaling pathway, CD14, TLR4, NF-κBp65, and TREM-1 were analyzed by qRT-PCR and western blot. ELISA was further used to detect TLR4 and TREM-1 levels in maternal and cord serums. Results: Compared with the normal term and PTB without CCA women, we found that (1) TLR4 and TREM-1 levels on CD14 + maternal and cord blood monocytes and neutrophils in the PTB with CCA group were elevated ( p  < .001); (2) the protein and mRNA expressions of CA14, TLR4, NF-κBp65, and TREM-1 of the PTB with CCA group were upregulated ( p  < .001); (3) Maternal and cord serum concentrations of TLR4 and TREM-1 in the PTB with CCA group were greater ( p  < .001). Conclusions: The high levels of TLR4 and TREM-1 surface expression were observed on CD14 + maternal and cord blood monocyte and neutrophils, confirming their proinflammatory profiles in PTB with CCA. TLR4 and TREM-1 on monocyte and neutrophils might have a role in infection-related PTB.

Background: During pregnancy, maternal thyroid hormone supply is crucial for fetal development. Preterm infants often present with hypothyroxinemia. Preterm birth, either spontaneous or medically indicated, is always the result of a complicated pregnancy. We hypothesized that in preterm birth, the maternal transplacental thyroid hormone supply is influenced by the pregnancy complication and we questioned whether maternal and placental compensatory mechanisms are activated to increase thyroid hormone transfer., Methods: Observational case-control study in mother-infant-dyads with complicated pregnancies ending in spontaneous preterm birth (n = 31) or indicated preterm birth due to vascular complications (n = 45) and normal pregnancies (healthy term controls; n = 41). At delivery, maternal and cord blood and placenta samples were collected. Cord and maternal plasma concentrations of thyroid stimulating hormone (TSH), total T4, fT4/FTI, total T3, and T4 binding globulin (TBG), and maternal serum concentrations of thyroid peroxidase (TPO)-antibodies were measured. Placental maturity was evaluated histologically and mRNA and/or protein levels of thyroid hormone deiodinases (DiO) 1, 2 and 3, and transporters (MCT8, MCT10, and OATP1c1) were quantified., Results: In indicated and spontaneous preterm births, cord plasma T4 concentrations were lower than in healthy term controls (p ≤ .001), whereas T3 was only decreased in spontaneous preterm birth (p ≤ .001). Compared with spontaneous preterm births and healthy term controls, indicated preterm birth was characterized by higher maternal plasma TSH (p ≤ .05), earlier placental maturation, higher placental DiO2 gene and MCT10 protein levels and lower DiO3 gene levels (all p ≤ .01)., Conclusions: Low T4 was observed in preterm infants irrespective of the cause of preterm birth, while maternal (TSH) and placental (DiO2, DiO3, and MCT10) compensatory responses were only activated in indicated preterm birth due to vascular complications. This may have mediated the normal fetal T3 availability in preterm infants born after indicated preterm birth but not after spontaneous preterm birth.

Background: Poor maternal vitamin D status and elevated circulating corticotropin-releasing hormone (CRH) are associated with preterm birth. It is not known if these risk factors are independent or interrelated. Both are associated with inflammation., Methods: We measured maternal circulating 25-hydroxyvitamin D (25-OH-D) and CRH from 97 samples collected from 15 early-preterm, 31 late-preterm, 21 early-term, and 30 term births. The potential involvement of vitamin D in the regulation of inflammation was evaluated by Q-PCR in human uterine smooth muscle (UTSM) cell line., Results: Maternal 25-OH-D was lowest in early-preterm births (22.9 ± 4.2 ng/ml versus 34.4 ± 1.4 ng/ml; p = .029). Circulating CRH was high in early-preterm births (397 ± 30 pg/ml). Late-preterm (304 ± 13 pg/ml) and early-term births (347 ± 17 pg/ml) were not different from term births (367 ± 19 pg/ml), after accounting for gestational age. Maternal circulating 25-OH-D and CRH were not associated in term births. In preterm births, 25-OH-D below 30 ng/ml was associated with higher CRH. Vitamin D treatment of UTSM significantly reduced mRNA for leptin and IL-6 receptors. Deletion of vitamin D receptor from UTSM promoted the expression of the cox2 inflammatory marker., Conclusion: Early-preterm birth showed a syndrome of high maternal CRH and low vitamin D status.

Purpose: To investigate the relationship between maternal serum homocysteine (Hcy) levels in the late stage of pregnancy and preterm birth. Other relevant biochemical parameters were measured to establish the normal reference interval of serum Hcy in both women in the late stage of pregnancy and neonates., Materials and Methods: The nested case-control study included 300 singleton pregnant women with preterm births between June 2013 and May 2015 and their premature delivered babies as a preterm group. Blood sample within three days before delivery was collected. Simultaneously, 300 healthy pregnant women admitted during the same time, and singleton mature neonates who had gestational week-matched blood sample were age-matched as a control group., Results: Maternal serum levels of Hcy, total triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), free fatty acids (FAA) and superoxide dismutase (SOD) were all higher in the preterm group than in the control group except high-density lipoprotein cholesterol (HDL-C). Serum levels of Hcy, TC, LDL-C, UA, FAA and SOD were higher in prematurely delivered neonates than in the control group except for HDL-C. The body weight of prematurely delivered neonates was negatively correlated with the maternal serum levels of Hcy and UA before delivery., Conclusions: Higher maternal serum Hcy levels were associated with preterm birth and neonatal body weight. Elevated maternal serum levels of Hcy might serve as a biomarker for preterm birth prediction.

Objectives: The aim of the study is to investigate differences in visfatin concentrations between mothers with term and preterm birth (PTB) and between mothers who delivered within seven days and after more than seven days following admission for PTB/preterm premature rupture of membranes (PPROMs)., Methods: Maternal peripheral blood and cord blood were collected from 56 mothers with PTB (31 with PPROM) and 71 mothers with term delivery (three with PPROM)., Results: Maternal visfatin concentration was significantly higher for given gestational age in PTBs compared to term deliveries (p = .021) and also in mothers who delivered within seven days after admission for PTB or PPROM, compared to those who delivered after more than seven days (p = .027; p = .039). Cord blood visfatin concentration was found to be decreased in preterm compared to term infants (p = .007)., Conclusions: Visfatin in both maternal and fetal circulation may play an important role in the pathogenesis of PTB/PPROM and could be used to distinguish between women who will deliver in a short period of time after clinical presentation of PTB/PPROM and those who deliver later. Nevertheless, additional research is necessary in order to identify its direct involvement in PTB/PPROM.

Objective: To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs)., Materials and Methods: Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n = 16) and without (n = 14) preterm premature rupture of membranes (PPROM)., Results: Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p = .015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established., Conclusions: High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.

The aim of this study was to assess whether serum markers would be useful as a new predictor of preterm birth in patients with spontaneous, late preterm labour. Patients diagnosed with late preterm labour were divided into preterm delivery (229 patients) and term delivery (178 patients) groups. The two groups were compared in terms of clinical characteristics and levels of serum markers (leukocyte subtypes, platelet, C-reactive protein [CRP], neutrophil to lymphocyte ratio [NLR] and platelet to lymphocyte ratio [PLR]), which were obtained at admission. The levels of leukocyte (p < .001), neutrophil (p < .001), CRP (p = .001), NLR (p < .001) and PLR (p = .003) were significantly higher, whereas lymphocytes (p = .012) were significantly lower in the preterm delivery group, compared to the term delivery group. On multivariate regression analysis, NLR positive was the most powerful predictive variable (OR = 1.41; 95%CI: 1.32-1.51; p = .005). NLR had the highest area under curve (0.711; 95%CI 0.662-0.760) in predicting preterm birth and a NLR >6.2 had the highest sensitivity (65.1%) and specificity (62.5%). High NLR at admission is an independent predictor of preterm birth in patients with spontaneous, late preterm labour. Impact statement What is already known on this subject: Preterm birth accounts for 5-12% of all births, and is a major factor associated with perinatal morbidity and mortality worldwide. However, more than 70% of preterm births occur at late preterm between 34 0/7 and 36 6/7 weeks of gestation. The central role of systemic and subclinical infections in preterm labour is well documented. Intrauterine infection leading to delivery can be measured by using a variety of laboratory parameters. What do the results of this study add: Neutrophil to lymphocyte ratio is an inexpensive, easily interpretable and promising haematologic parameter that is widely available. This study explored the association of high neutrophil to lymphocyte ratio with the risk of preterm birth in women with preterm labour between 34 and 37 weeks of gestation. What are the implications of these findings for clinical practice and/or further research: Neutrophil to lymphocyte ratio could be used in combination with existing markers to improve detection rates of preterm birth. Concomitant use of markers could be more powerful than measuring any of the individual markers alone.

Objective: To identify all systematic reviews investigating the role of maternal and fetal biomarkers for predicting spontaneous preterm birth (SPTB)., Methods: Medline and Web of Sciences databases were searched electronically. Studies exploring the association between maternal biomarkers and spontaneous delivery were considered suitable for inclusion. A synthesis of the systematic reviews was performed with the umbrella methodology. Statistical measures of association (Odd ratio, OR, relative risk, RR) and predictive accuracy (sensitivity, specificity, positive and negative likelihood ratios were used to synthesize results of the included studies., Results: 21,614 articles were identified, 542 were assessed with respect to their eligibility for inclusion and 14 systematic reviews included. Cervical fibronectin was the biomarkers which showed the highest strength of association with the occurrence of SPTB (delivery within 24 h OR 7, 95%CI 3-17; delivery <7 days (OR 12, 95%CI 8-16). Maternal serum alpha fetoprotein, was associated with an OR of 4 and 3 for early and late SPTB. C-reactive protein had an OR of 2 (95%CI 1-2) and 8 (95%CI 4-16) when detected in maternal plasma and amniotic fluid, respectively. Among cytokines, interleukin-6 had an OR and an LR + for SPTB of 2 and 12 when detected in maternal serum., Conclusions: Cervical fetal fibronectin, alpha fetoprotein, C- reactive protein and interleukin 6 can have an overall good diagnostic accuracy in identifying pregnancies at risk of SPTB. Large prospective studies in different sub-set of women are needed to ascertain whether the combination of different serological and imaging marker can improve antenatal prediction of this condition.

Purpose: To assess the utility of maternal serum calponin 1 level in the prediction of delivery within 7 days among pregnancies complicated with threatened preterm labor., Materials and Methods: Eligible women who presented at 24-34 weeks of gestation with threatened preterm labor underwent sampling for serum calponin 1 level and cervical length measurement. They were followed up until delivery prospectively and the perinatal outcomes of the patients were recorded., Results: Of 73 women included in the study, 36 women delivered within 7 days and 37 women delivered beyond 7 days after admission. The maternal serum calponin 1 level was significantly high in women who delivered within 7 days (p: 0.031). The threshold value of 2 ng/mL for maternal serum calponin 1 predicted delivery within 7 days with 61.1% sensitivity and 62.2 specificity (area under curve, 0.658, confidence interval 0.53-0.79). The general accuracy values for maternal cervical length measurement (≤25 mm), serum calponin 1 level (>2 ng/mL) and the combination of two tests to predict delivery within 7 days was found to be 64.4%, 61.6% and 72.1%, respectively., Conclusions: The maternal serum calponin 1 level may be a useful biomarker in short-term prediction of preterm birth among pregnancies complicated with threatened preterm labor, in addition to cervical length measurement.

Objective: There is little follow-up data in preterm infants from mothers with systemic lupus erythematosus (SLE). The aim of this study was to determine maternal outcomes and compare neonatal outcomes in preterm and term infants born to mothers with SLE., Methods: This study is a prospective study in a tertiary medical care center and clinical research center for rheumatoid arthritis. Demographic data, clinical features, laboratory findings, treatment and complications in 77 pregnant SLE patients were prospectively evaluated from 2007 to 2013., Results: Ninety-two infants (44 males and 48 females including four sets of twins) from 77 mothers with SLE were enrolled. Multivariate logistic analysis indicated that flares were significantly associated with antiphospholipid antibodies of lupus anticoagulant during pregnancy (p = 0.009) and preterm birth (p = 0.017). Compared with term infants, preterm infants had significantly higher antinuclear antibodies (ANA) positivity (p = 0.001) at 12 months of age in multivariate logistic analysis., Conclusion: Preterm birth is associated with maternal flares and persistent ANA positivity at 12 months of life in infants born to mothers with SLE.

Objective: We aimed to determine the potential value of maternal serum levels of acute phase reactants in the prediction of preterm delivery in women with threatened preterm labor (TPL)., Methods: Ninety-one pregnant women diagnosed with TPL and 83 healthy pregnant women as a control group were included in this prospective controlled study. All the pregnant women were followed until delivery and obstetric data and the serum levels of acute phase reactants were recorded for each participant. The study group was further divided into two groups according to the gestational age at delivery, which include women delivering prematurely and the ones who gave birth at term., Results: Serum albumin levels were significantly lower and mean serum ferritin levels were significantly higher in the study groups when compared the control group., Conclusion: Although an association between decreased serum albumin level and TPL, also between increased serum ferritin levels and preterm birth and low birth weight were demonstrated, more extensive studies are needed to clarify the potential use of the acute phase reactants in the prediction of preterm birth.

Objective: To investigate whether mannose-binding lectin (MBL) gene polymorphisms and low levels of second-trimester plasma MBL were significant risk factors for preterm birth in Taiwanese women., Methods: We conducted a prospective longitudinal study to explore the associations of MBL2 gene single nucleotide polymorphisms and plasma MBL levels between preterm birth and term controls. Blood samples were collected at 16-23 weeks of gestation, and were divided into 51 mothers with preterm births and 255 term controls after delivery. Blood samples were further collected at delivery from 11 mothers with term delivery and 9 with preterm births. DNA was isolated, and polymorphisms in exon 1, the promoter untranslated regions of MBL2 were determined by polymerase chain reaction. The plasma concentrations of MBL were measured by enzyme-linked immunosorbent assay., Results: There is a positive correlation between SNP genotypes and second-trimester plasma MBL levels. Among mothers with preterm births, a higher frequency of specific genotypes with low MBL levels was not observed. The second-trimester plasma MBL levels were not significantly different between mothers with preterm births (N = 51) and term deliveries (N = 255). However, among mothers (N = 11) with term pregnancies, the MBL plasma level significantly increased from the second trimester to delivery, whereas in mothers (N = 9) who developed preterm delivery, the MBL level did not significantly change., Conclusion: Genotypes associated with low levels of plasma MBL during pregnancy did not increase the risk of preterm births. A low second-trimester plasma MBL level is therefore not a predictor for the development of preterm birth.

Objective: The objective of this study is to determine if BPA exposure, as measured by maternal plasma (MP) and amniotic fluid (AF) BPA concentrations is associated with an increased risk of spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM)., Methods: In this nested case-control study, MP samples from women in term labor (n = 30), preterm labor that ended with preterm delivery (n = 25), or who had pPROM (n = 30) and amniotic fluid samples from term labor (n= 45), preterm labor (n = 60), and pPROM (n = 35) were assayed for BPA by enzyme immunoassay., Results: BPA was detectible in 100% of MP and AF samples. Women with MP BPA concentrations in the fourth quartile were at increased risk of PTB (cOR = 4.12, 95% CI = 1.32-12.87; aOR = 4.78, 95% CI = 1.14-20) but not pPROM. High (fourth quartile) AF BPA values also tended to increase the risk of pPROM (cOR = 2.47, 95% CI = 0.96-6.37) but results were not statistically significant., Conclusions: Increased BPA concentration is associated with an increased risk for PTB or pPROM depending on the maternal-fetal compartment(s) affected. High MP plasma BPA concentrations are associated with PTB with intact membranes but high AF BPA concentrations may weakly be associated with pPROM.

Objective: To identify associations between second-trimester serum inflammatory biomarkers and preterm birth among obese women., Methods: In this nested case-control study, we compared 65 serum inflammatory biomarkers in obese women whose pregnancies resulted in early spontaneous preterm birth (<32 weeks gestation, n = 34) to obese women whose pregnancies resulted in term birth (n = 34). These women were selected from a larger population-based California cohort. Random forest and classification and regression tree techniques were employed to identify biomarkers of importance, and adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using logistic regression., Results: Random forest and classification and regression tree techniques found that soluble vascular endothelial growth factor receptor-3 (sVEGFR3), soluble interleukin-2 receptor alpha-chain (sIL-2RA) and soluble tumor necrosis factor receptor-1 (sTNFR1) were related to preterm birth. Using multivariable logistic regression to compare preterm cases and term controls, decreased serum levels of sVEGFR3 and increased serum levels of sIL-2RA and sTNFR1 were associated with increased risk of preterm birth among obese women, aOR = 3.2 (95% CI: 1.0-9.9), aOR = 2.8 (95% CI: 0.9-9.0), and aOR = 4.1 (95% CI: 1.2-14.1), respectively., Conclusions: In this pilot study, we identified three serum biomarkers indicative of inflammation to be associated with spontaneous preterm birth among obese women: sVEGFR3, sIL-2RA and sTNFR1.

We conducted a study of markers of endothelial dysfunction and angiogenesis regulation, as well as the identification of the main lymphocyte populations, activated CD3  +  CD95 + -cells and cytokine-producing CD4  +  IFN-γ + -, CD4  +  IL-4 +  -lymphocytes in the 1st trimester of gestation in women with ART-induced pregnancy and spontaneous pregnancy. We used the same indicators to assess the immune status of ELBW infants at birth and at the post-conceptual age of 38-40 weeks. It was determined that the risk factors of very early preterm delivery are: threatened miscarriage, chronic placental insufficiency, endothelial dysfunction, increased spontaneous production of intracellular cytokines. Adverse perinatal outcomes in ELBW infants from ART-induced pregnancy are associated with lower anthropometric measures, low Apgar scores high level of inflammatory infections (pneumonia), grade II intraventricular hemorrhage, movement disorders in the form of lower paraparesis. Immune status of those infants is characterized by the increase in the number of CD8 + - and CD3 - CD16  +  CD56 +  -lymphocytes, the expression level of Fas-receptor by T-cells, and the increased production of intracellular and serum IFNγ against the decrease in the number of CD4 + -cells, which indicates enhancing of cytotoxic effector potential and proinflammatory orientation of cell responses.

This historical cohort study aimed to assess the relationship between antenatal maternal C-reactive protein (CRP) level and neonatal outcome preterm premature rupture of membranes (PPROM). We reviewed the records of 70 singleton pregnancies with PPROM between 24 and 34 weeks. Maternal CRP levels of neonates with respiratory distress syndrome, neonatal sepsis, grade 3-4 intraventricular haemorrhage and stage 2-3 necrotizing enterocolitis, perinatal mortality were compared with those without these complications. Administration of corticosteroid, tocolysis for two days and prophylactic antibiotics (intravenous ampicillin/sulbactam, and oral azithromycin) were the standard management protocol. The mean age at PPROM was 29 weeks 2 days (±3 weeks), the mean age at birth was 30 weeks 5 days (±20 days). CRP levels were not different between groups. Uni/multivariate analysis showed that maternal CRP levels were not related with neonatal outcomes. Neonatal complications in PPROM are related with the degree of prematurity and maternal WBC counts.

This prospective study aimed to evaluate pregnancy outcome and complications in women with recurrent pregnancy loss (RPL) and protein S (PS) deficiency, who received low dose aspirin (LDA) or LDA plus heparin (LDA/H) therapies. Clinical characteristics, pregnancy outcome and complications of 38 women with two or more RPL and <60% of plasma free PS antigen were compared among three groups: antiphospholipid antibody (aPL)-negative women who received LDA (group A), aPL-negative women who received LDA/H (group B) and aPL-positive women who received LDA/H (group C). Gestational weeks (GW) at delivery in group C (median 32 GW) were earlier than 40 GW in group A and 38.5 GW in group B (p < 0.05). The birth weight in group C (median 1794 g) was less than 2855 g in group B (p < 0.05). The incidences of fetal growth restriction (37.5%), pregnancy-induced hypertension (37.5%), and preterm delivery (62.5%) in group C were higher than those (4.5%, 0%, and 4.5%, respectively) in group B (p<0.05). Women with RPL, PS deficiency, and positive aPL had high risks for adverse pregnancy outcome and complications, even when they received LDA/H therapy. Among women with RPL, PS, and negative aPL, there was no difference in these risks between LDA alone and LDA/H therapies.

Objective: To determine (1) whether maternal plasma concentrations of angiogenic and anti-angiogenic factors can predict which mothers diagnosed with "suspected small for gestational age fetuses (sSGA)" will develop pre-eclampsia (PE) or require an indicated early preterm delivery (≤ 34 weeks of gestation); and (2) whether risk assessment performance is improved using these proteins in addition to clinical factors and Doppler parameters., Methods: This prospective cohort study included women with singleton pregnancies diagnosed with sSGA (estimated fetal weight <10th percentile) between 24 and 34 weeks of gestation (n = 314). Plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin (sEng) and placental growth factor (PlGF) were determined in maternal blood obtained at the time of diagnosis. Doppler velocimetry of the umbilical (Umb) and uterine (UT) arteries was performed. The outcomes were (1) subsequent development of PE; and (2) indicated preterm delivery at ≤ 34 weeks of gestation (excluding deliveries as a result of spontaneous preterm labor, preterm pre-labor rupture of membranes or chorioamnionitis)., Results: (1) The prevalence of PE and indicated preterm delivery was 9.2% (n = 29/314) and 7.3% (n = 23/314), respectively; (2) the area under the receiver operating characteristic curve (AUC) for the identification of patients who developed PE and/or required indicated preterm delivery was greater than 80% for the UT artery pulsatility index (PI) z-score and each biochemical marker (including their ratios) except sVEGFR-1 MoM; (3) using cutoffs at a false positive rate of 15%, women with abnormal plasma concentrations of angiogenic/anti-angiogenic factors were 7-13 times more likely to develop PE, and 12-22 times more likely to require preterm delivery than those with normal plasma MoM concentrations of these factors; (4) sEng, PlGF, PIGF/sEng and PIGF/sVEGFR-1 ratios MoM, each contributed significant information about the risk of PE beyond that provided by clinical factors and/or Doppler parameters: women who had low MoM values for these biomarkers were at 5-9 times greater risk of developing PE than women who had normal values, adjusting for clinical factors and Doppler parameters (adjusted odds ratio for PlGF: 9.1, PlGF/sEng: 5.6); (5) the concentrations of sVEGFR-1 and PlGF/sVEGFR-1 ratio MoM, each contributed significant information about the risk of indicated preterm delivery beyond that provided by clinical factors and/or Doppler parameters: women who had abnormal values were at 8-9 times greater risk for indicated preterm delivery, adjusting for clinical factors and Doppler parameters; and (6) for a two-stage risk assessment (Umb artery Doppler followed by Ut artery Doppler plus biochemical markers), among women who had normal Umb artery Doppler velocimetry (n = 279), 21 (7.5%) developed PE and 11 (52%) of these women were identified by an abnormal UT artery Doppler mean PI z-score (>2SD): a combination of PlGF/sEng ratio MoM concentration and abnormal UT artery Doppler velocimetry increased the sensitivity of abnormal UT artery Doppler velocimetry to 76% (16/21) at a fixed false-positive rate of 10% (p = 0.06)., Conclusion: Angiogenic and anti-angiogenic factors measured in maternal blood between 24 and 34 weeks of gestation can identify the majority of mothers diagnosed with "suspected SGA" who subsequently developed PE or those who later required preterm delivery ≤ 34 weeks of gestation. Moreover, incorporation of these biochemical markers significantly improves risk assessment performance for these outcomes beyond that of clinical factors and uterine and umbilical artery Doppler velocimetry.

Objective: To compare adipokinins between women experiencing preterm labor (PTL) and prior preterm deliveries (PTD)., Study Design: In this prospective observational cohort, 110 women with a singleton <35 weeks at increased risk of PTD were studied. Serum leptin, adiponectin, and resistin were obtained at three times (23-34 weeks, 35-36 weeks, at delivery) and analyzed via enzyme-linked immunosorbent assay. The adipokinins were compared across time and between PTL (n = 59) and prior PTD (n = 51) groups using generalized estimated equation models., Results: There were no differences in leptin, adiponectin, or resistin levels over the three times between the PTL and PTD groups. There was a trend toward higher leptin levels (p = 0.06 unadjusted analysis, p = 0.09 adjusted analysis) at 23-34 weeks. When stratified by body mass index (BMI), there were differences in leptin (p < 0.001 for BMI < 30; p = 0.77 for BMI ≥ 30) and adiponectin (p = 0.04 for BMI < 30; p = 0.09 for BMI ≥ 30), but not in resistin over the three times between the PTL and prior PTD groups., Conclusion: There were no significant differences in adipokinins in women with PTL and a prior PTD. The trends toward higher leptin levels at 23-34 weeks in women with PTL may represent a compensatory response and require further evaluation in the study of treatments for PTL.

Problem: To evaluate the association between serum presepsin (soluble CD14 antigen subtype, sCD14-ST) levels soon after the appearance of signs of preterm delivery and preterm delivery within 48 h, before the 34th and 37th gestational weeks and the possible additional value of concurrently evaluated ultrasound vaginal cervicometry with serum presepsin measurement., Methodology: A total of 60 females were included. Serum presepsin was measured by a chemiluminescent immunoassay. Sonographic evaluation of cervical length in all females was conducted by transvaginal ultrasound., Results: Patients who delivered within 48 h after analysis showed significantly higher presepsin concentrations compared to females with later deliveries. Higher presepsin was proven also for deliveries before/after weeks 34 and 37. A combined finding of cervical length shortening below 18 mm and presepsin level increasing above 623.5 pg/mL could point to the significantly high risk of preterm delivery., Conclusion: Elevated maternal serum concentration of sCD14-ST could be an independent and relevant risk factor for preterm delivery.

Objective: We sought to estimate the association between cervical length (CL) and fetal fibronectin (fFN) and each pathway leading to preterm birth in twin pregnancies., Methods: Cohort study of 560 patients with twin pregnancies who underwent routine serial CL and fFN screening from 22 to 32 weeks in one maternal fetal medicine practice during 2005-2013. We calculated the association between a short CL (≤20 mm) or positive fFN with overall preterm birth <32 weeks, and then subdivided the analysis into preterm birth <32 weeks from preterm labor, preterm premature rupture of membranes (PPROM) and indicated causes. We excluded cases of monochorionic-monoamniotic placentation, vasa previa, twin-twin transfusion and patients with cerclage., Results: The overall rate of preterm birth <32 weeks was 6.9% (3.9% from preterm labor, 1.6% from PPROM and 1.4% indicated). A short cervix was associated with preterm birth <32 weeks arising from preterm labor (12.4% versus 2.0%, p < 0.001), but not PPROM (1.9% versus 1.3%, p = 0.651). Positive fFN was associated with preterm birth <32 weeks both from preterm labor (17.0% versus 2.4%, p < 0.001) as well as from PPROM (5.7% versus 1.0%, p = 0.034). Neither was significantly associated with preterm birth <32 weeks from indicated causes., Conclusions: The mechanism leading toward preterm influences the accuracy of screening tests chosen to assess risk in twin pregnancies. A shortened cervical length and positive fFN is associated with spontaneous preterm labor and birth <32 weeks. However, PPROM does not appear to be preceded by a short cervix, but is preceded by a positive fFN. Neither test is associated with an indicated preterm birth.

Background: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits., Aim: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life., Method: This prospective study looked at 117 mothers and their extremely premature babies (born before 28 weeks' gestation). The relationship between neonatal thyroid hormone status and maternal factors (gestation, route of delivery, exogenous maternal glucocorticoid administration, maternal free T4 (FT4), presence or absence of maternal chorioamnionitis, maternal smoking status, maternal body mass index (BMI) index, maternal thyroid peroxidase antibody status (TPO) and maternal haemoglobin levels) were evaluated. Multiple linear regression was used to study independent factors affecting neonatal thyroid function., Results: Mean gestational age was 25(+5) ± 1.3 weeks (range 22(+0) to 27(+6)). Neonatal FT4 strongly correlated with gestation, with a greater severity of hypothyroxinaemia associated with lower gestation (r = 0.6, p < 0.0001). Multiple regression found gestation to be the only independent factors affecting thyroid status (beta coefficient = 0.08, p = 0.01), and no maternal factors were found to be associated with neonatal thyroid status., Conclusion: Neonatal thyroid status in extreme preterm infants is independently affected by gestation and not maternal factors such as route of delivery, exogenous maternal glucocorticoid administration, third trimester maternal FT4, presence or absence of chorioamnionitis, smoking status, BMI, TPO status or haemoglobin levels. The severity of neonatal hypothyroxinaemia increases with lower gestational age.

Objective: Preterm birth is a major cause of neonatal morbidity and mortality in the developed world. In order to better understand the pathophysiological pathway of this condition, the role of genetic factors and/or inflammation-associated molecules, as well as of socioeconomic parameters, is therefore under intense investigation. The purpose of this review study was to examine the potential role of maternal serum relaxin levels in the etiology of preterm birth., Methods: Electronic databases (Pubmed, Embase, Cochrane Library) were searched for previously published research studies that investigated the biological role of relaxin and the mechanisms in which this hormone is involved during pregnancy and labor., Results: It is evident that while relaxin is an essential endometrial/decidual angiogentic factor playing a vital role in maternal accommodation of pregnancy, elevated levels of this hormone could well be associated with preterm birth., Conclusions: There are strong indications that maternal serum hyperrelaxinemia correlates with an increased risk of preterm birth.

Objective: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery., Methods: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth., Results: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM > 2, as opposed to 6.23% of >34 week deliveries (p = 0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery., Conclusions: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.

In this study, we investigated whether the concentrations of pregnancy-associated plasma protein-A (PAPP-A) or free β-hCG (fβhCG) in the first trimester can identify women at increased risk of subsequent preterm delivery in the absence of hypertensive disorders. Preterm and early preterm deliveries are defined as those deliveries before completing 37 and 34 weeks, respectively. A total of 868 women were enrolled into this study. According to the level of the markers, the patients were evaluated in three groups: 1 - maternal serum level ≤ 5 th percentile, 2 - between 5th and 95th percentiles, 3 - ≥ 95 th percentile. In the group of patients with a PAPP-A level ≤ 5 th percentile [≤ 0.35 multiples of the median (MoM)], mean gestational age (GA) at delivery, mean birth weight and the number of the cases with early preterm delivery were significantly lower than the others. Mean level of PAPP-A was significantly lower in cases with early preterm than term deliveries (0.58 ± 0.32 versus 1.09 ± 0.69; p = 0.01). Maternal serum level of fβhCG did not show significant difference between these groups (0.84 ± 0.45 versus 1.17 ± 0.77; p = 0.15). Low levels of maternal serum PAPP-A (≤ 0.35 MoM) (Odds ratio = 7; 95% confidence interval 1.8-27.7; p = 0.0048) significantly predicted early preterm delivery in normotensive pregnancies. Women with low levels of PAPP-A at first trimester have a higher risk of early preterm delivery even in the absence of hypertensive disorders.

Objective: To investigate whether blood cytokines during the perinatal period predict the risk of cerebral palsy (CP) in preterm infants., Methods: This prospective cohort study comprised 169 children born before 32 weeks of gestation. Cord blood was drawn at birth, and 109 cytokines were analyzed using microarrays. Eleven cytokines were further measured from both cord and peripheral blood on days 1 and 7. Cerebral palsy was confirmed at 5 years of age., Results: Cerebral palsy was diagnosed in 19 children. Five clusters of cord blood cytokines were scored using factor analysis. According to logistic regression analysis, the scores of factors 1 and 2 independently predicted the risk of CP. These cytokines included several growth factors and chemokines, and they all tended to be higher in children with CP than in children without CP. Inflammatory cytokine levels were associated with CP risk on days 1 and 7 after birth., Conclusion: The high blood concentrations of various cytokines during the perinatal period may relate to CP, and these cytokines may influence the pathways leading to early insult in the central nervous system. The risk profile of inflammatory cytokines is different at birth than during the first week after birth.

Objective: To examine whether an association exists between platelet (PLT) count in the first trimester of pregnancy and the risk for hypertensive disorders or other obstetric complications., Methods: The study population included all registered births with available PLT count from the first trimester of pregnancy during 2000-2010. Thrombocytopenia was defined as PLT count below 100,000/μL. A comparison was performed between women with and without thrombocytopenia. Multiple logistic regression models were used to control for confounders., Results: The study population included 33,890 deliveries; of these, 119 (0.35%) were with thrombocytopenia. Women with thrombocytopenia had significantly higher rates of preterm delivery (16.0% vs. 9.4%; p = 0.015). There was no significant difference between the groups regarding hypertensive disorders., Conclusions: Hypertensive disorders cannot be predicted based on PLT count during the first trimester of pregnancy. Nevertheless, thrombocytopenia during the first trimester is a risk factor for preterm delivery.

Objective: The differential diagnosis between preterm and false labour remains one of the most challenging issues in perinatal medicine., Aim: To assess the prognostic importance of the selected biochemical markers in predicting preterm labour., Material and Methods: 74 patients hospitalized due to threatening preterm labour. 51 women gave birth prematurely; the remaining 23 were diagnosed with false labour. We used ELISA arrays to study 13 proteins: IGFBP-1, IGFBP-2, BDNF, L-Selectin, E-Selectin, ICAM-1, PECAM, VCAM-1, MIP-1 delta (MIP-1d) MIP-3β (MIP-3b), Eotaxin-1, Eotaxin-2, BLC., Results: An increased risk of preterm labour should be expected when the serum concentration for: IGFBP-1 > 158.83 pg/ml (sens. 0.608, sp. 0.609, p < 0.0001); MIP-1d < 27.66 pg/ml (sens. 0.627, sp. 0.627, p = 0.021); BDNF >36.54 pg/ml (sens. 0.630, sp. 0.647, p = 0.002); BLC >25.46 pg/ml (sens. 0.588, sp. 0.609, p < 0.001); Eotaxin-1 >1.16 pg/ml (sens. 0.633, sp. 0.652)., Conclusion: There have been reported statistically significant differences in serum concentrations of selected proteins in women with preterm labour and false labour.

Objective: To examine the potential value of maternal serum level of C-reactive protein (CRP) in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery., Methods: Maternal serum concentration of high-sensitivity CRP at 11-13 weeks' gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks, with 15 cases presenting with contractions and 15 cases presenting with preterm premature rupture of membranes, and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum CRP in the two outcome groups was compared., Results: The median serum CRP MoM was not significantly different in the spontaneous early preterm delivery group compared to the term delivery group (1.101, IQR = 0.572-1.985 vs. 0.975, IQR = 0.577-1.923; p = 0.813). The prevalence of CRP MoM above the 75th percentile was not significantly different between the early preterm delivery group compared to the term delivery group (26.7 vs. 24.4%; p = 0.811). In the preterm delivery group, the median serum CRP MoM in those presenting with contractions was not significantly different from those presenting with PPROM (1.175, IQR = 0.403-2.122 vs. 1.027, IQR = 0.659-1.940; p = 0.713). High-sensitivity CRP did not significantly improve prediction for preterm delivery over regular CRP., Conclusions: Measurement of maternal serum CRP at 11-13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.

Objective: Determine whether elevated second trimester maternal serum α-fetoprotein (AFP) is associated with clinical and histopathologic markers of inflammation at preterm delivery., Methods: 105 women <32 weeks' gestation were included. AFP levels were dichotomized at 2.0 multiples of the median (MoM). Rates of neonatal morbidities, clinical chorioamnionitis, cord blood IL-6 level, and placental inflammatory findings were compared., Results: Thirteen (12.4%) had elevated AFP. Fewer women with AFP ≥ 2 MoM had histologic placental or membrane rupture site inflammation, funisitis, or placental culture positive for Mycoplasma and Ureaplasma species, compared to those with normal AFP. Neonatal death was increased in the elevated AFP group (23.1% vs. 2.27%, RR 10.6). Elevated AFP was associated with a nonsignificant increase in indicated birth (54% vs. 35%; p = 0.225). Virtually all inflammatory findings were confined to the spontaneous delivery group., Conclusion: Elevated midtrimester AFP conveyed significant risk of neonatal death, but was negatively associated with clinical or histopathologic inflammation in preterm infants.

Objective: Soluble fms-like tyrosine kinase 1 (sFlt1) is an antiangiogenic protein that is associated with a number of disorders of placental angiogenesis. It has been hypothesized that disruption of placental angiogenesis may contribute to the pathophysiology of preterm delivery (PTD). However, the relationship of PTD risk to variation in sFlt1 levels is not well known. We investigate the relationship between longitudinal variation in maternal serum concentrations of sFlt1 and risk of PTD., Methods: Data were collected in a longitudinal cohort study involving 278 pregnant women. Maternal serum sFlt1 concentrations were measured at 6-10, 10-14, 16-20, 22-26, and 32-36 weeks gestation. Data analyses used longitudinal regression models using repeated measures that allow robust inferences from our modest sample size. The outcome was birth prior to 37 weeks gestation., Results: sFlt1 concentrations were higher in first trimester for preterm compared to term deliveries. This relationship reversed in second trimester because sFlt1 concentrations increased more rapidly across gestation for term deliveries. In Cox proportional hazards analyses, a 2 ng higher sFlt1 concentration across gestation was associated with a hazard ratio of 1.3 (95% CI: 1.1, 1.5) for PTD suggesting the importance of levels in early pregnancy., Conclusion: Elevated maternal serum sFlt1 concentration during pregnancy is associated with increased risk of PTD.

Objective: To examine the potential value of maternal serum level of ferritin in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery., Methods: Maternal serum concentration of ferritin at 11-13-week gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum ferritin in the two outcome groups was compared., Results: The median serum ferritin MoM was not significantly different in the spontaneous early preterm delivery group compared with the term delivery group (1.143, interquartile range [IQR] 0.578-2.383 vs. 1.059, IQR 0.641-1.644, p = 0.725)., Conclusions: Measurement of maternal serum ferritin at 11-13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.

Objective: The objective of the study was to investigate whether concentrations of chemokines in the umbilical cord blood of neonates are affected by delivery via cesarean section., Study Design: Umbilical cord blood was obtained from 116 singleton late-preterm and full-term neonates without infections, born to healthy pregnant women. Concentrations of chemokines - MIP-1α (CCL3), MIP-1β 1 (CCL4), RANTES (CCL5), GRO-α (CXCL1) and ENA-78 (CXCL5) - were measured by ELISA. Logistic regression was used to investigate regression relationships between the occurrence of neonatal chemokines concentrations in umbilical cord blood and mode and time of delivery., Results: Concentrations of CXC chemokines in late-preterm neonates were the same as those in term neonates. RANTES concentrations in late-preterm cord blood were significantly lower than concentrations in term cord blood. Concentrations of the CC chemokine - RANTES (CCL5) - were noted to be lower in neonates born to cesarean section than in neonates born vaginally. Any anesthetic taken by the mothers during cesarean section did not affect CC chemokine production in the cord blood of full-term neonates. In a logistic regression model including gestational age as a variable, late-preterm delivery was associated with RANTES concentrations (OR = 3.8). After adjustment for variable mode of delivery in regression model, RANTES concentration (OR = 4.75)., Conclusion: Both late-preterm and cesarean delivery are essential risk factors of low RANTES (CCL5) concentrations in the umbilical cord blood.

Objective: Our primary objective was to determine whether there was an association between levels of antenatal maternal serum soluble RAGE (sRAGE), drawn at the time of presentation with preterm labor (PTL), and subsequent preterm birth (PTB). Secondary objectives were to determine whether levels of sRAGE - analyzed from both antenatal maternal serum (MS) and postpartum umbilical cord serum (CS) - were associated with neonatal sepsis., Methods: Nested case-control analyses were performed within a prospective cohort of patients at risk for PTB. MS was obtained at enrollment and CS at delivery. The sRAGE levels were analyzed. Non-parametric calculations and receiver-operator analyses were performed., Results: Overall, 39.8% of patients delivered < 37 weeks (n=498) and 15% had neonatal sepsis (n=193). In comparing cases and controls, sRAGE was significantly lower in those with than those without an adverse event (PTB: median MS-sRAGE 771.79 versus 948.485 pg/mL, p=0.004; neonatal sepsis: 25-centile CS-sRAGE 1220.49 versus 2244.41 pg/mL, p=0.0013). Adding MS-sRAGE to models of clinical variables significantly enhanced the ability of the model to predict both PTB (area under the curve [AUC] 0.71 versus 0.79, p=0.004) and neonatal sepsis (AUC 0.65 versus 0.75, p=0.04). The negative predictive value of CS-sRAGE for neonatal sepsis was very strong (NPV=0.91)., Conclusions: The sRAGE can be used to help predict adverse perinatal outcomes. Patients with higher levels of sRAGE - who therefore may have an enhanced capability to regulate their immune response - appear less likely to experience PTB and neonatal sepsis.

Objective: To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM)., Methods: Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24-34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umbilical cord was studied. The data were analyzed using t test and χ(2) test., Results: IL-6 levels ≥ 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM., Conclusion: Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity.

Objective: To determine whether mid-pregnancy levels of angiogenic markers were associated with increased risk of preterm delivery (PTD)., Methods: We studied a subcohort from the Pregnancy Outcomes and Community Health Study for whom mid-pregnancy angiogenic markers (soluble fms-like tyrosine kinase-1 [sFlt-1], soluble endoglin [sEng] and placental growth factor [PlGF]) and covariate data were available (N = 1301). Angiogenic marker levels were grouped as high/not high (sFlt-1 and sEng), low/not low (PlGF) and high/intermediate/low (sFlt-1). Associations between levels of angiogenic markers and PTD/PTD subtype were determined for women who were nonsmokers during pregnancy (N = 933)., Results: Low PlGF and high sEng were associated with medically-indicated PTD and PTD <35 weeks, largely due to preeclampsia (PE). Excluding PE and small-for-gestational-age infants, low sFlt-1 was positively associated with medically-indicated PTD., Conclusions: Among nonsmokers, mid-pregnancy levels of angiogenic markers may mark multiple pathways leading to PTD, only one attributable to PE.

Preterm delivery (PTD) and pre-eclampsia (PE) represent the main "obstetric syndromes," caused by multiple conditions, and characterized by complex pathogenesis. Nonetheless, recent evidences attest that deregulation of the immune system and exaggeration of inflammatory processes, taking place in the feto-placental unit, represent common central mechanisms occurring in both diseases. Tertiary prevention represents the only intervention to prevent PTD, but its incidence is still increasing. Advances in secondary prevention, focusing on risk factors and possible markers, are necessary.