Search

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.

Objective. Reduced calciferol (vitamin D) levels in pregnant women have been associated with an increased risk to infant health. Progesterone sustains pregnancy and reduces the risk of premature birth through its metabolites affecting myometrial contractility. Sex hormone-binding globulin protein (SHBG) is a biomarker of premature birth. The present study aimed to find out if early pregnancy levels of vitamin D, SHBG, and progesterone metabolites may predict preterm birth risk. Methods. Five hundred pregnant women aged 18-43 years during their 2nd and 3rd trimesters from multiple civilian regional medical centers in Lahore participated in the study. Blood samples taken from participants were used to determine vitamin D, SHBG, 11-deoxycorticosterone (DOC), and 16α-hydroxyprogesterone (16α-OHP) levels using specific ELISA kits. Statistical analysis was performed by one-way ANOVA using the latest GraphPad Prism software. Results. A significant decrease in vitamin D, DOC, and SHBG levels (p<0.001, p<0.001, and p<0.05, respectively) in the preterm birth cohorts in the 2nd and 3rd trimester was found compared to the corresponding control groups. Furthermore, 16α-OHP levels in the preterm birth cohorts in the 2nd and 3rd trimesters were significantly increased (p<0.001 and p=0.0062, respectively) compared to their control cohorts. Conclusion. The results of our study confirm that calciferol deficiency in pregnant women is associated with an increased risk of premature birth and indicate that SHBG and progesterone metabolites may be useful biomarkers for the early identification and prediction of preterm birth., (© 2024 Sundas Akram et al., published by Sciendo.)

Background: Despite the global standardization of hemoglobin (Hb) testing in early pregnancy, the impact of first trimester Hb concentrations on pregnancy outcomes remains inadequately understood. Also, the early pregnancy Hb concentrations have not been well documented in Western China. Therefore, this study aimed to assess the Hb concentrations during early pregnancy and their associations with adverse pregnancy outcomes in Western China., Methods: This cross-sectional study used data from the Chengdu Maternal and Child Health Information System for pregnant women who delivered between January 1, 2019, and December 31, 2023. A total of 454,815 Chinese females aged 15 to 49 years with available first trimester Hb data, including those with singleton or multiple gestations, were included in the analysis. Multivariable logistic regression models were performed to estimate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between Hb categories and adverse pregnancy outcomes., Results: The average first trimester Hb concentration was 126.0 (SD 10.5) g/L, with 5.8% of pregnant women experiencing anemia during early pregnancy. Multivariable logistic regression analyses revealed significantly increased odds of developing gestational diabetes mellitus (GDM) and gestational hypertensive disorders (GHD) across increasing Hb concentration categories. Compared to Hb concentrations of 110-119 g/L, Hb ≥ 140 g/L was associated with elevated risk of GDM (aOR: 1.57, 95% CI: 1.52, 1.62) and GHD (aOR: 1.87, 95% CI: 1.79, 1.96). Moreover, both Hb ≤ 99 g/L (aOR: 1.15, 95% CI: 1.03, 1.29) and Hb ≥ 140 g/L (aOR: 1.20, 95% CI: 1.13, 1.26) were associated with higher odds of preterm birth compared to Hb concentrations of 110-119 g/L. In addition, the restricted cubic spline demonstrated a U-shaped relationship for cesarean delivery, low birthweight and small for gestational age (p < 0.001). However, no significant associations were found between first trimester Hb concentrations and the odds of stillbirth, Apgar score < 7 at 5 min, or Apgar score < 7 at 10 min (p > 0.05)., Conclusions: Our research findings suggest associations between first trimester Hb concentrations and various adverse pregnancy outcomes. We recommend interventions for early pregnancy anemia, particularly moderate to severe cases, and emphasize monitoring females with high Hb concentrations to reduce adverse outcomes., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital (approval number: 202285). Informed consent was waived because of the retrospective study design, and the data analyses used data containing no personally identifiable information. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Prenatal exposure to heavy metals such as Lead (Pb), arsenic (As), cadmium (Cd), and selenium (Se) is associated with various adverse pregnancy outcomes. This study examines the association between early pregnancy maternal blood levels of these metals and adverse pregnancy outcomes, while also addressing the differences between low-risk and high-risk groups based on having a history of preterm birth (PTB). This prospective cohort study recruited parous women during first trimester, categorized into low-risk and high-risk groups. Participants completed a questionnaire, and heavy metal levels were measured in blood samples. Pregnancy outcomes including PTB, low birth weight (LBW), gestational age at delivery, birth weight and head circumference were recorded following delivery. Multivariable analyses were conducted to evaluate the independent associations between heavy metal levels and pregnancy outcomes, while adjusting for maternal age, BMI, employment, smoking, fertility treatments and education. Among 404 participants, the mean (± SD) levels were Pb: 3.12 ± 1.82 µg/L, As: 0.41 ± 0.4 µg/L, Cd: 0.26 ± 0.34 µg/L, and Se: 119.84 ± 21.05 µg/L. Significant differences in Pb, Se, Cd and As levels were observed between the low-risk and high-risk groups, with higher levels in the low-risk group. However, no significant associations were found between heavy metal levels and any of the study outcomes in either univariable comparison or multivariable models. These findings highlight the need for further research to understand the potential impact of these metals on pregnancy, considering population-specific factors and exposure timing., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics declaration The study protocol was approved by the institutional review board (Soroka University Medical Center IRB committee, #0390-20-SOR). The study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments (Helsinki Declaration 1975, revision 2013). All participants gave signed informed consent at recruitment., (© 2024. The Author(s).)

Objective: To evaluate the association between continuous glucose monitoring in pregnant people with type 2 diabetes and perinatal outcomes., Methods: This was a retrospective cohort study of pregnant people with type 2 diabetes who received prenatal care and delivered singleton, nonanomalous neonates at a single academic tertiary care center from November 1, 2019, to February 28, 2023. The primary outcome was a composite of neonatal morbidity, including hypoglycemia, hyperbilirubinemia, shoulder dystocia, large for gestational age at birth, preterm birth, neonatal intensive care unit (NICU) admission, or perinatal death. Demographics and outcomes were compared by type of monitoring (continuous glucose monitoring vs intermittent self-monitoring of blood glucose), and multivariable logistic regression estimated the association between continuous glucose monitoring use and perinatal outcomes., Results: Of 360 pregnant people who met the inclusion criteria, 82 (22.7%) used continuous glucose monitoring. The mean gestational age at continuous glucose monitoring initiation was 21.3±6.4 weeks. The use of continuous glucose monitoring was associated with lower odds of the primary composite neonatal morbidity (65.9% continuous glucose monitoring vs 77.0% self-monitoring of blood glucose, adjusted odds ratio [aOR] 0.48, 95% CI, 0.24-0.94). Continuous glucose monitoring use was also associated with lower odds of preterm birth (13.4% vs 25.2%, aOR 0.48, 95% CI, 0.25-0.93) and NICU admission (33.8% vs 47.6%, aOR 0.36, 95% CI, 0.16-0.81)., Conclusion: In pregnant people with type 2 diabetes, continuous glucose monitoring use was associated with less neonatal morbidity, fewer preterm births, and fewer NICU admissions., Competing Interests: Financial Disclosure: The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: This study aimed to quantify adverse perinatal outcomes (APO), including small/large for gestational age (SGA/LGA) and preterm birth (PTB), in pregnant women with abnormal red cell distribution width (RDW) and explore the related mechanisms., Methods: This study included 11,659 pregnant women who delivered in a specialized hospital. At the time of admission, the lipid profiles and whole blood cell counts were assessed, and APO was analyzed., Results: Women with high RDW (>18.5% [the 97.5 th percentile]) in late pregnancy had a higher risk of LGA compared with those with low RDW (<12.3% [the 2.5 th percentile]), whereas women with low RDW had a higher risk of SGA and PTB, compared with those with high RDW. A 1% increase in RDW was associated with an increased risk of LGA and a decreased risk of SGA and PTB. Consistent associations were observed in sensitivity analysis among pregnant women of non-advanced age, non-obesity, non-pregnancy complications, and non-PTB (for SGA/LGA only). Increased RDW was significantly associated with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). Triglycerides and HDL-C significantly mediated 10.63 and 15.8% of RDW-associated LGA, 9.51% and 9.40 of RDW-associated SGA, and 8.44 and -8.25% of RDW-associated PTB, respectively., Conclusion: Abnormal RDW was associated with an increased risk of APO, and the RDW-associated APO risk could be partially mediated by triglycerides and HDL-C, suggesting that RDW may be a promising APO predictor., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Preterm birth (PTB) forms a heterogeneous group with possible genetic predisposition. 25(OH)-vitamin D3 plays a significant role during implantation, placentation, and the maintenance of normal pregnancy. The aim of our research was to examine whether FokI, Cdx2, and ApaI VDR gene variants, as well as serum concentrations of 25-hydroxy25(OH)-vitamin D3 in women and their newborns, might be predisposing factors for idiopathic spontaneous preterm birth. The patient group consisted of 44 pairs of women with ISPTB and their children, and the control group consisted of 44 pairs of women who delivered at term and their children. At the time of delivery, peripheral blood was collected from every woman, and after newborn delivery, umbilical cord blood was collected. For genotyping of the rs2228570 C/T, rs11568820 G/A, and rs7975232 T/G SNPs, a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used. Serum concentrations of 25(OH)-vitamin D3 were determined using high-performance liquid chromatography (HPLC). There were no statistically significant differences in the frequencies of VDR genotypes and alleles between women with ISPTB and control women. There was a statistically significant difference in the distribution of VDR Cdx-2 (rs11568820) genotypes between preterm-born children and controls, with the GG genotype and G allele being more prevalent among patients than controls ( p < 0.001). There were no statistically significant differences in mean values between women with ISPTB and control women, nor between preterm and full-term newborns, although the 25(OH)-vitamin D3 concentrations in preterm-born children were lower than in controls. Furthermore, there was a statistically significant correlation in 25(OH)-vitamin D3 concentrations between mothers and children both in the patient and in the control groups (b = 0.771, p < 0.001). The results of our study demonstrate a notable association between the VDR Cdx2 gene polymorphism and idiopathic spontaneous preterm birth (ISPTB) in a Caucasian population, but because of the small number of participants, further research is needed.

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared with those with uncomplicated births, perhaps related to prepregnancy inflammation, dysmetabolism, or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Using repeated measures analysis of variance, we estimated prepregnancy and postpregnancy biomarkers, as well as biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and term HDP groups had higher prepregnancy high-sensitivity C-reactive protein (hsCRP) (+0.37 [95% CI, 0.08-0.65]; +0.29 [95% CI, 0.04-0.55] log mg/L), higher leptin (+0.29 [95% CI, 0.09-0.50]; +0.37 [95% CI, 0.17-0.56] log ng/ml), and lower adiponectin (-0.25 [95% CI, -0.36 to -0.13); -0.11 [95% CI, -0.22 to -0.01] log ng/ml) values than those with uncomplicated births, and these profiles persisted in magnitude postpregnancy. Controlling for body mass index attenuated most profiles, except that lower prepregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower prepregnancy hsCRP and soluble intercellular adhesion molecule-1 (-0.31 [95% CI, -0.56 to -0.06] log mg/L; -0.05 [95% CI, -0.09 to -0.01] log ng/ml) and a larger leptin increase from before to after pregnancy (+0.20 [95% CI, 0.02-0.37] log ng/ml). Prepregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher body mass index. PTB may be related to adverse metabolic changes postpregnancy, although the unexpected endothelial biomarker profile warrants further study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite routine iron supplementation for pregnant women in South Africa, anaemia and iron deficiency (ID) in pregnancy remain a public health concern., Objective: To determine the associations between iron status and birth outcomes of pregnant women attending antenatal clinic at a regional hospital in Bloemfontein., Methods: In this cross-sectional study of 427 pregnant women, blood was taken to analyze biomarkers of anaemia (haemoglobin), iron status (ferritin and soluble transferrin receptor) and inflammation (C-reactive protein and α-1-acid glycoprotein). A questionnaire was used to collect information about birth outcomes (birth weight and gestational age at birth), HIV exposure, sociodemographics, iron supplement intake, and maternal dietary iron intake using a validated quantified food frequency questionnaire., Results: The median (Q 1 , Q 3 ) weeks of gestation of participants was 32 (26, 36) at enrolment. Anaemia, iron deficiency (ID), ID anaemia (IDA) and ID erythropoiesis (IDE) were present in 42%, 31%, 19% and 9.8% of participants, respectively. Median (Q 1 , Q 3 ) dietary and supplemental iron intake during pregnancy was 16.8 (12.7, 20.5) mg/d and 65 (65, 65) mg/d, respectively. The median (max-min) total iron intake (diet and supplements) was 81 (8.8-101.8) mg/d, with 88% of participants having a daily intake above the tolerable upper intake level of 45 mg/d. No significant associations of anaemia and iron status with low birth weight and prematurity were observed. However, infants born to participants in the third hemoglobin (Hb) quartile (Hb > 11.3-12.2 g/dL) had a shorter gestation by 1 week than those in the fourth Hb quartile (Hb > 12.2 g/dL) (p = 0.009). Compared to pregnant women without HIV, women with HIV had increased odds of being anaemic (OR:2.14, 95%CI: 1.41, 3.247), having ID (OR:2.19, 95%CI: 1.42, 3.37), IDA (OR:2.23, 95%CI: 1.36, 3.67), IDE (OR:2.22, 95%CI: 1.16, 4.22) and delivering prematurely (OR:2.39, 95%CI: 1.01, 5.64)., Conclusion: In conclusion, anaemia, ID, and IDA were prevalent in this sample of pregnant women, despite the reported intake of prescribed iron supplements, with HIV-infected participants more likely to be iron deficient and anaemic. Research focusing on the best formulation and dosage of iron supplementation to enhance iron absorption and status, and compliance to supplementation is recommended, especially for those living with HIV infection., (© 2024. The Author(s).)

Introduction: Preterm delivery (PTD) is the leading cause of death in children under 5 years of age. Cervical shortening detected by ultrasound can be used to predict PTD, but prediction is not perfect, and complementary diagnostic markers are needed. Recently, specific plasma microribonucleic acid (miRNAs) detected in early second trimester were shown to be associated with spontaneous PTD in high-risk women with a singleton pregnancy. The aim of this study was to explore to what extent these miRNAs are associated with spontaneous PTD and cervical length in a general population., Material and Methods: This study is a nested case-control study within the CERVIX study. The CERVIX study evaluated the ability of cervical length screening with transvaginal ultrasound to identify women at risk of PTD. In the present study, women who delivered spontaneously <34 weeks (n = 61) were compared with a control group of women who delivered at full term (39 + 0 to 40 + 6 gestational weeks, n = 205). Archived serum samples were analyzed with RT-qPCR for miRNA expression levels of let-7a-5p, miR-150-5p, miR-15b-5p, miR-185-5p, miR-191-5p, miR-19b-3p, miR-23a-3p, miR-374a-5p, and miR-93-5p. The mean relative expression was compared between the groups. Sub-analyses were performed for women delivering <32, <30, and <28 weeks vs the full-term group., Results: The analyzed miRNAs were not significantly differentially expressed in women delivering <34 weeks compared to those delivering at full term. MiR-191-5p and miR-93-5p were significantly overexpressed in women who delivered <32 weeks, and further increase in fold change was observed with decreasing gestational age at delivery. The level of miR-15b-5p was significantly higher in women delivering at <30 weeks compared to those delivering at full term., Conclusions: Our study shows that overexpression of miR-93-5p, miR-15b-5p, and miR-191-5p in serum at early gestation is associated with spontaneous PTD in a general population. Further research is needed to evaluate the potential of these miRNAs as future biomarkers for spontaneous PTD, as well as their pathophysiological role in spontaneous PTD., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Aims: Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes., Methods: Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA)., Results: Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20 mmol/mol]-4.4% [25 mmol/mol]), moderate-stable (range 4.6% [27 mmol/mol]-5.1% [32 mmol/mol]), and elevated-increasing (range 5.0% [31 mmol/mol]-5.6% [38 mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively., Conclusions: Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Exposure to certain heavy metals has been demonstrated to be associated with a higher risk of preterm birth (PTB). However, studies focused on the effects of other metal mixtures were limited. A nested case‒control study enrolling 94 PTB cases and 282 controls was conducted. Metallic elements were detected in maternal plasma collected in the first trimester using inductively coupled plasma‒mass spectrometry. The effect of maternal exposure on the risk of PTB was investigated using logistic regression, least absolute shrinkage and selection operator, restricted cubic spline (RCS), quantile g computation (QGC) and Bayesian kernel machine regression (BKMR). Vanadium (V) and arsenic (As) were positively associated with PTB risk in the logistic model, and V remains positively associated in the multi-exposure logistic model. QGC analysis determined V (69.42%) and nickel (Ni) (70.30%) as the maximum positive and negative contributors to the PTB risk, respectively. BKMR models further demonstrated a positive relationship between the exposure levels of the mixtures and PTB risk, and V was identified as the most important independent variable among the elements. RCS analysis showed an inverted U-shape effect of V and gestational age, and plasma V more than 2.18 μg/L was considered a risk factor for shortened gestation length. Exposure to metallic elements mixtures consisting of V, As, cobalt, Ni, chromium and manganese in the first trimester was associated with an increased risk of PTB, and V was considered the most important factor in the mixtures in promoting the incidence of PTB., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Preterm birth (PTB) remains a significant public health concern, and prediction is an important objective, particularly in the early stages of pregnancy. Many studies have relied on cervical characteristics in the mid-trimester, with limited results. It is therefore crucial to identify novel biomarkers to enhance the ability to identify women at risk. The complement pathway is implicated in the process of placentation, and recent proteomics studies have highlighted the potential roles of some complement proteins in the pathophysiology of PTB. To determine the association between the occurrence of spontaneous preterm birth (sPTB) and the concentration of complement C3, factor B, and factor H in the blood of pregnant women during the first trimester. This prospective cohort study included women with singleton pregnancies, both with and without a history of sPTB, from two health institutions in Bucaramanga, Colombia. The outcome was sPTB before 37 weeks. A blood sample was obtained between 11 + 0 to 13 + 6 weeks. ELISA immunoassay was performed to quantify the levels of C3, factor B, and factor H. A total of 355 patients were analyzed, with a rate of sPTB of 7.6% (27/355). The median plasma concentration for C3, factor B, and factor H were 488.3 μg/mL, 352.6 μg/mL, and 413.2 μg/mL, respectively. The median concentration of factor H was found to be significantly lower in patients who delivered preterm compared to patients who delivered at term (382 μg/mL vs. 415 μg/mL; p = 0.034). This study identified a significant association between low first-trimester levels of factor H and sPTB before 37 weeks. These results provide relevant information about a new possible early biomarker for sPTB. However, the results must be confirmed in different settings, and the predictive value must be examined.

Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2 µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95-1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16-5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33-9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures., (© 2024. The Author(s).)

Background: Maternal lipid metabolism has been implicated in elevating the risk of adverse pregnancy outcomes, which is a particularly significant concern in twin pregnancies. However, the precise relationship between early pregnancy dyslipidemia and the risk of preterm birth (PTB) in twin pregnancies remains unclear., Methods: This retrospective cohort study included women with twin pregnancies between January 2018 and December 2023. Early pregnancy blood lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), were examined. Dyslipidemia was diagnosed based on the diagnostic criteria outlined in the 2016 guidelines for the prevention and treatment of dyslipidemia in Chinese adults. PTB was defined as birth occurring before 37 weeks of pregnancy. Logistic regression models were used to evaluate the association of early pregnancy dyslipidemia with PTB in twin pregnancies., Results: A total of 613 women with twin pregnancies were included, and 141 women were complicated with dyslipidemia. The incidence of PTB < 37 weeks was significantly higher in the dyslipidemia group compared to the group without dyslipidemia (64.5% vs. 50.4%, P = 0.003). After adjusting for confounding factors, dyslipidemia was positively associated with PTB < 37 weeks (adjusted odds ratio: 1.71; 95% confidence interval: 1.13-2.58). However, these associations varied depending on the chorionicity and mode of conception of the twins. The positive associations between early pregnancy dyslipidemia and PTB < 37 weeks remained significant only in spontaneously conceived (SC) or dichorionic diamniotic (DCDA) twin pregnancies. No statistically significant associations were observed between dyslipidemia and the other secondary outcomes., Conclusion: Early pregnancy dyslipidemia was positively associated with PTB < 37 weeks in twin pregnancies, and this association remained significant in SC or DCDA twin pregnancies. Comprehensive lipid profile assessment in the first trimester may be beneficial for patients' monitoring and implementing interventions to mitigate adverse pregnancy outcomes., (© 2024. The Author(s).)

Background: Anemia in pregnancy has been associated with a number of adverse birth outcomes, such as low birth weight (LBW) or preterm birth (PTB). However, the evidence from primary studies on anemia in pregnancy with LBW and PTB is contentious. Moreover, a systematic review and meta-analysis to summarize these findings have not been conducted for Ethiopia. This study aimed to synthesize the best available evidence and quantify the strength and direction of the association of anemia in Ethiopia., Methods: This review examined women with singleton pregnancies with low birth weight (LBW) and preterm birth (PTB). We retrieved studies from PubMed, Wiley, Cochrane databases, and Google Scholar from inception to February 2, 2024. The World Health Organization (WHO) defines anemia in pregnancy as a low blood haemoglobin (Hgb) concentration below 11 g/dl or a hematocrit level of < 33%. When the newborn's weight was below 2500 g, LBW was considered. Preterm birth refers to the birth of a baby before 37 completed weeks of gestation. Meta-analysis was conducted using fixed and random effects models. The degree of heterogeneity, publication bias, and quality of the evidence of studies was assessed., Results: There were 35 and 8 studies, with 14,319 and 3,265 respondents included in the meta-analysis for LBW and PTB, respectively. Neonates born to women who had normal Hgb levels were less likely to be LBW [pooled odds ratio (POR) = 0.22, 95% CI: (0.17, 0.28); I2 = 80%] (low-quality evidence). Neonates born to women with normal Hgb levels had a lower risk of PTB [POR = 0.22, 95% CI: 0.18, 0.28; I2 = 19%] (very low-quality evidence). The effect size estimate remained significant after sub-group analysis based on study design and province, except in two retrospective cohort studies for LBW., Conclusion: The findings suggest major implications for strengthening the implementation of nutrition policies to prevent anemia during pregnancy in Ethiopia. Further research is warranted to assess interventions that are effective in combating maternal anemia to reduce rates of LBW and PTB., Competing Interests: The authors declared that they have no competing interests., (Copyright: © 2024 Beressa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis ( DROSHA , DICER , and AGO2 ) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.

Objective: To study the relationship between umbilical cord blood vitamin A (VA) and neonatal lung diseases and explore the impact of umbilical cord blood VA on neonatal lung diseases., Method: Umbilical vein blood was collected at birth, and its VA content was measured. According to the VA levels in umbilical cord blood, a VA deficiency (VAD) group, a marginal deficiency group and a normal group were created and followed up until 28 days after birth., Results: The umbilical cord blood VA level in the neonatal group with lung disease was 0.13 ± 0.05 mg/L, while the result for the VA level in the non-lung disease group was 0.15 ± 0.05 mg/L. The umbilical cord blood VA levels in the neonatal lung disease group were significantly lower than those in the non-lung disease group. The incidence of neonatal pulmonary diseases was highest in the VAD group, and the incidence decreased as the level of VA in umbilical cord blood increased. Umbilical cord blood VAD and premature birth were found to be independent risk factors for neonatal respiratory disease., Conclusion: Umbilical cord blood VAD and premature birth are independent risk factors for neonatal pulmonary diseases. The lower the level of VA in umbilical cord blood, the more susceptible infants will be to neonatal respiratory infections in the neonatal period., Competing Interests: Declaration of competing interest All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Preterm birth is the leading cause of neonatal mortality worldwide, and dyslipidemia is associated with preterm birth in observational studies. We use Mendelian randomization (MR) analyses to uncover the causal association between blood lipid levels and preterm birth., Methods: We extracted uncorrelated (R 2  < 0.001) single-nucleotide polymorphisms strongly associated (p < 5 × 10-8) with blood lipids from genome wide association studies of FinnGen database and UK Biobank participants. Inverse variance weighted method was the main MR analysis. Sensitivity analyses including genetic pleiotropy, heterogeneity, and directionality of causality were conducted., Results: The study included 115,082 participants with lipid measurements, 8,507 patients with preterm birth. Increasing apolipoprotein B (odds ratio (OR), 1.12[95 % CI, 1.02-1.23]; p = 0.019), low-density lipoprotein cholesterol (OR, 1.11[95 % CI, 1.00-1.22]; p = 0.040), non-high-density lipoprotein cholesterol (OR, 1.12[95 % CI, 1.01-1.24]; p = 0.026), remnant cholesterol (OR, 1.11[95 % CI, 1.00-1.23]; p = 0.047) and total free cholesterol (OR, 1.11[95 % CI, 1.01-1.23]; p = 0.037) were associated with increased risk of preterm delivery. Moreover, triglycerides in low-density lipoprotein were causally associated with the risk of PTB. Our sensitivity analysis yielded robust results, uncovering no evidence of horizontal pleiotropy or reverse causal relationships., Conclusion: Our investigation unveils the adverse impact of dyslipidemia on preterm birth, with a particular emphasis on the detrimental effect of elevated low-density lipoprotein cholesterol., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Elevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive., Objective: We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes., Methods: A large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 μmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB)., Results: sTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24-1.59]), SGA (aOR=1.31; [95 % CI: 1.18-1.46]), and PTB (aOR=1.27; [95 % CI: 1.15-1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %-63 %] for LBW, 24 % [95 % CI: 13 %-35 %] for SGA, and 34 % [95 % CI: 19 %-49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %-29 %], 4 % [-6%-14 %], 32 % [15 %-50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis., Conclusions: The substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Preterm delivery (PTD) is associated with severe adverse maternal and neonatal outcomes and higher medical costs. Therefore, PTD warrants more attention. However, predicting PTD remains a challenge for researchers. This study aimed to investigate potential prenatal predictors of PTD. We retrospectively recruited pregnant women who experienced either PTD or term delivery (TD) and underwent laboratory examinations at 32 weeks of gestation. We compared the test results between the two groups and performed logistic regression analysis and receiver operating characteristic (ROC) curve analysis to identify risk factors and predictive factors for PTD. Our investigation revealed that the PTD cohort exhibited statistically significant elevations in lymphocyte count, mean corpuscular hemoglobin concentration, calcium, uric acid, alkaline phosphatase, triglycerides, and total bile acids. Conversely, the PTD group demonstrated statistically significant reductions in mean corpuscular volume, homocysteine, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), neutrophils to (white blood cells-neutrophils) ratio (dNLR), and (neutrophils × monocytes) to lymphocyte ratio (SIRI). The ROC curve analysis revealed that calcium had an area under the curve (AUC) of 0.705, with a cut-off value of 2.215. Logistic regression analysis showed that premature rupture of membranes was an independent risk factor for PTD. Our study demonstrated that serum calcium levels, NLR, dNLR, and other laboratory tests conducted at 32 weeks of gestation can serve as predictors for PTD. Furthermore, we identified premature rupture of membranes as a risk factor for PTD., (© 2024. The Author(s).)

Purpose: To examine the effects of first-trimester HbA1c (HbA1c-FT) ≥ 37 mmol/mol on preterm birth (PTB) and large-for-gestational-age (LGA) babies in a retrospective cohort of South Asian pregnant women with gestational diabetes (GDM)., Methods: The cohort (n = 686) was separated into two groups based on HbA1c-FT values: Group A (n = 97) and Group B (n = 589), with values of 37-46 mmol/mol (5.5-6.4%) and < 37 mmol/mol (5.5%), respectively. HbA1c-FT's independent influence on PTB and LGA babies was examined using multivariable logistic regression in groups A and B women. The reference group (Group C) included 2031 non-GDM women with HbA1c-FT < 37 mmol/mol (< 5.5%). The effects of HbA1c-FT on PTB and LGA babies in obese women in Groups A, B, and C (designated as A-ob, B-ob, and C-ob, respectively) were re-analyzed using multivariable logistic regression., Results: Group A GDM women with greater HbA1c-FT had a higher risk for PTB (aOR:1.86, 95% CI:1.10-3.14) but not LGA babies (aOR:1.13, 95%: 0.70-1.83). The risk of PTB was higher for obese women in Group A-ob: aOR 3.28 [95% CI 1.68-6.39]. However, GDM women with normal HbA1c-FT exhibited no elevated risk for PTB: Groups B and B-ob had aORs of 1.30 (95% CI 0.86-1.98) and 1.28 (95% CI 0.88-1.85) respectively., Conclusions: South Asian GDM women with prediabetic HbA1c FT; 37-46 mmol/mol (5.5-6.4%) are more likely to deliver preterm babies despite treatment, while the risk for LGA babies was the same as non-GDM women., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess a panel of cytokines and placental insufficiency with the risk of preterm delivery (PTD)., Methods: Nested case-control study into the BRISA birth cohort. Eighty-two mother-infant-placenta pairs were selected at 20 +0 to 25 +6 weeks. Circulating biomarker levels were performed using Luminex flowmetric xMAP technology. Cytokines classified as Th1, Th2 or Th17 and other biomarkers were selected. The ratio between birth weight and placental weight (BW/PW) was used as a proxy for placental efficiency. Spearman correlation, univariate analyses and logistic regression models were calculated. Sensitivity, specificity, positive and negative likelihood ratios were calculated using the Receiver Operating Characteristic curve., Results: Mean gestational age was 250 days, 14,6% were small for gestational age, 4,8% large for gestational age and 13,4% stunted. Placental efficiency was higher for term newborns (p<0,001), and 18/22 (81%) preterm biomarker values were higher than the control group. Th1 cytokines were highly correlated, while the weakest correlation was observed in other biomarkers. Less education was associated with a higher risk of PTD (p = 0.046), while there was no appreciable difference in the risk of PTD for placental insufficiency. Biomarkers showed negligible adjusted OR of PTD (0.90 to 1.02). IL-6, IL-8, IL-1β, TNFβ, IL-4, IL-13, GCSF, MIP1A, VEGF, EGF, and FGF2 presented a higher sensitivity ranging from 75.56% to 91.11%., Conclusion: IL-8, IL-12p40, IL-4, IL-13, GCSF, MIP1B, and GMSF in asymptomatic pregnant women were associated with PTD. This finding suggests an activation of maternal inflammatory response., Competing Interests: Conflicts to interest: none to declare.

Background: In order to identify and possibly offer prophylactic treatment to women at risk for preterm birth (PTB), novel prediction models for PTB are needed. Our objective was to utilize high-sensitive plasma protein profiling to investigate whether early prediction of spontaneous PTB (sPTB) before 34 gestational weeks (gw) was possible in a low-risk population., Methods: A case-control study was conducted on 46 women with sPTB before 34 gw and 46 women with normal pregnancies and term deliveries. Prospectively collected plasma sampled at gw 11 (range 7-16) and gw 25 (range 23-30) was analyzed with a high-sensitivity Proximity Extension Assay for levels of 177 inflammation-associated proteins, and statistically processed with multivariate logistic regression analysis., Results: In the first trimester, higher levels of hepatocyte growth factor (HGF) were associated with sPTB <34 gw (OR 1.49 (1.03-2.15)). In the second trimester, higher levels of interleukin (IL)-10 (OR 2.15 (1.18-3.92)), IL-6 (OR 2.59 (1.34-4.99)), and the receptor activator of nuclear factor κB (RANK) (OR 2.18 (1.26-3.77)) were associated with sPTB <34 gw. The area under the curve for the prediction models including these proteins was 0.653 (0.534-0.759) in the first trimester and 0.854 (0.754-0.925) in the second trimester., Conclusion: A combination of inflammation-associated plasma proteins from the second trimester of pregnancy showed a good predictive ability regarding sPTB before 34 gw, suggesting it could be a valuable supplement for the assessment of the clinical risk of sPTB. However, although a high number (n=177) of plasma proteins were analyzed with a high-sensitivity method, the prediction of sPTB in the first trimester remains elusive., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Svenvik, Raffetseder, Brudin, Berg, Hellberg, Blomberg, Jenmalm and Ernerudh.)

In this investigation, we explored the correlation between first-trimester biochemical markers and the incidence of preterm birth (PTB), irrespective of the cause, spontaneous preterm birth (sPTB), and preterm premature rupture of membranes (pPROM) within a cohort comprising 1164 patients. It was discovered that diminished levels of Pregnancy-Associated Plasma Protein-A (PAPP-A) between 11 and 13 + 6 weeks of gestation significantly contributed to the risk of preterm deliveries both before 35 and 37 weeks, as well as to pPROM instances. Furthermore, women experiencing sPTB before the 37th week of gestation also exhibited lower concentrations of PAPP-A. Moreover, reduced first-trimester concentrations of free beta-human chorionic gonadotropin (fb-HCG) were identified as a risk factor for deliveries preceding 37 weeks, pPROM, and sPTB before 35 weeks of gestation. Despite these correlations, the area under the curve for these biochemical markers did not surpass 0.7, indicating their limited diagnostic potential. The most significant discriminatory capability was noted for PAPP-A levels, with a threshold of < 0.71 multiples of the median (MoM) predicting PTB before 37 weeks, yielding an odds ratio of 3.11 (95% Confidence Interval [CI] 1.97-4.92). For sPTB, the greatest discriminatory potential was observed for PAPP-A < 0.688, providing an OR of 2.66 (95% CI 1.51-4.66). The cut-off points corresponded to accuracies of 76.05% and 79.1%, respectively. In regression analyses, the combined predictive models exhibited low explanatory power with R 2 values of 9.2% for PTB and 7.7% for sPTB below 35 weeks of gestation. In conclusion, while certain biochemical markers demonstrated associations with outcomes of preterm birth, their individual and collective predictive efficacies for foreseeing such events were found to be suboptimal., (© 2024. The Author(s).)

Objective: To assess the utility of placental growth factor (PlGF) levels and the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA)., Design: Prospective, observational cohort study., Setting: Tertiary maternity hospital in Australia., Population: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32 +0  weeks) and 109 (30.0%) late FGR (≥32 +0  weeks)., Methods: Maternal serum PlGF and sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt-1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt-1/PlGF ratio to the time of birth or censoring., Main Outcome Measures: The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained., Results: The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt-1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt-1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt-1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt-1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48-175.46)., Conclusions: Low maternal PlGF levels and elevated sFlt-1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Purpose: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies., Methods: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used., Results: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks., Conclusion: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended., (© 2024. The Author(s).)

Purpose: To explore the value of measuring maternal serum PLGF in the prediction of the outcome of small for gestational age fetuses (SGA)., Methods: Singleton pregnancies referred with suspicion of SGA in the third trimester were included if they had: no indication for nor signs of imminent delivery, fetal abdominal circumference (AC) at or below the 10th centile and/or estimated fetal weight (EFW) at or below the 10th centile and/or umbilical artery pulsatility index (Umb-PI) at or above the 90th centile for gestation. Women with pre-eclampsia at presentation were excluded. Maternal blood was drawn at the first (index) visit and analyzed retrospectively., Results: Fifty-one fetuses were examined. Multiple regression analysis showed that family history of microsomia, index EFW and PLGF were significant predictors of the birthweight centile; index femur length centile and PLGF were significant predictors of pre-eclampsia; PLGF and index systolic blood pressure were significant predictors of iatrogenic preterm delivery < 37 weeks, whereas PLGF and index EFW were significant predictors of birthweight ≤ 5th centile and admission to the neonatal intensive care unit. For all outcomes, the addition of maternal-fetal parameters did not improve the prediction compared to PLGF alone. Using a cutoff of 0.3 MoM for PLGF would identify 94.1% of the pregnancies with iatrogenic preterm delivery and/or intra-uterine death and all of the cases that developed pre-eclampsia, for a screen positive rate of 54.9%. Women with PLGF ≤ 0.3 MoM had a poor fetal/maternal outcome (iatrogenic preterm delivery, pre-eclampsia, intra-uterine death) in 61.5% of cases., Conclusion: In pregnancies complicated by SGA, PLGF identifies a very high-risk group that may benefit from intense surveillance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk factor for preterm birth. However, there are currently no studies on the relationship of the related research in twin-pregnant women., Methods: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were measured in the first trimester(6-14 weeks), the second trimester(18-28 weeks) and the third trimester(after 28 weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/ApoA1 ratio and preterm birth., Results: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm. Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese dichorionic twin-pregnant women., Conclusions: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: A considerable amount of neonatal morbidity and mortality worldwide is caused by preterm birth. To date, the underlying etiology of preterm birth has not been fully clarified. Previous studies demonstrate that inflammation is one of the pathological factors that might cause preterm birth, and that there is a difference between primiparous and multiparous women in immune response to pregnancy. The objective of this prospective cohort study was to investigate the role of two inflammatory markers, ferritin and C-reactive protein (CRP) and preterm birth, in first trimester women, stratified for parity. In addition, a possible association between high ferritin and CRP, and a possible association between high ferritin and CRP and preterm birth were assessed., Material and Methods: A total of 2044 healthy, low-risk pregnant women from primary obstetric care in the Netherlands participated in this study. Their ferritin and CRP levels were evaluated at 12 weeks' gestation. Levels above the parity specific 95th percentile were defined as high. The main outcome of this study was to assess the presence of a possible association between parity specific high ferritin and CRP, and preterm birth. The secondary outcomes were the ferritin and CRP levels of women, stratified for parity, and the possible association between high ferritin and CRP levels. Logistic regression analysis was performed with preterm birth as a dependent variable and parity specific high ferritin and CRP as an independent variable, adjusting for age and history of preterm birth., Results: Ferritin levels decreased with increasing parity. Ferritin and CRP levels at 12 weeks' gestation were significantly higher in women with preterm birth. In primiparous women, high ferritin levels (OR: 2.5, CI: 1.14-5.38) and high CRP levels (OR: 5.0, CI: 2.61-9.94) were independently associated with preterm birth. In multiparous women, high ferritin levels (OR: 6.0, CI: 2.28-16.67) were independently associated with preterm birth while high CRP levels were not., Conclusions: First trimester parity specific ferritin and CRP levels could play a part in predictive models for preterm birth, and further research for their additive role in preterm birth is needed., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Problem: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L-arginine) in women with spontaneous PTB and term birth., Methods of the Study: The study was based on data from the population-based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF-R1 and TNF-R2 and GDF-15., Results: Women with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L-Arginine (p = 0.03). In addition, inflammation marker, TNF-R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP., Conclusions: These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: The effectiveness of MgSO4 for foetal neuroprotection is acknowledged, but the best time to provide it in relation to birth is a conundrum, and dose schedule is yet unknown. Understanding the determinants of the magnesium levels in cord blood aids in determining the appropriate timing and length of administration., Aim and Objective: To assess the cord blood magnesium concentration in relation to the timing of MgSO4 and delivery. To achieve ROC in relation to optimum level of cord blood magnesium concentration in relation to neonatal outcome variables., Study Design: A prospective observational study conducted in a tertiary care hospital over 2 years in women having preterm delivery from 26 weeks to 33 + 6 weeks, who received Neuroprophylaxis. Cord blood was collected for magnesium level estimation. Baby followed 24 h after delivery. ROC analysis performed for predicting an optimal cut-off for a continuous predictor predicting binary outcome., Results: 85 recruited cases divided into bolus group, bolus + infusion group. The mean cord blood magnesium (n = 85) was 3.8 mg/dl. The AUROC for Gestational Age at Administration predicting Baby Outcome: 0.699, It was statistically significant (p = 0.034). The AUROC for Cord Blood Mg predicting Baby Outcome: 0.606, It was not statistically significant (p = 0.262)., Conclusion: Mean cord blood magnesium levels served as a tool to determine the timing and duration of Neuroprophylaxis. Mean cord blood magnesium of 3.8 mg/dl should be achieved to serve the purpose of Neuroprotection. To achieve this, Bolus followed by Infusion should be administered for at-least 6 h prior to delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Conflicting findings have emerged regarding the levels of high mobility group box 1 (HMGB1) in individuals experiencing adverse pregnancy outcomes. Here we conducted a meta-analysis to assess the association between maternal blood HMGB1 levels and adverse pregnancy outcomes. Utilizing databases such as PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase and China National Knowledge Infrastructure (CNKI), a systematic literature search was conducted in January 2024. Eligible literature was screened according to inclusion and exclusion criteria. Quality assessment was evaluated using the Newcastle-Ottawa Scale (NOS). The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. 21 observational studies with a total of 2471 participants were included in this meta-analysis. Significantly higher peripheral blood levels of HMGB1 were associated with preeclampsia (PE) (SMD=1.34; 95% CI: 0.72-1.95; P < 0.0001) and gestational diabetes mellitus (GDM) (SMD=1.20; 95% CI: 0.31-2.09; P = 0.009). Additionally, HMGB1 levels in peripheral blood were significantly elevated in patients with unexplained recurrent spontaneous abortion (URSA) than those in pregnancy controls (SMD=4.22; 95% CI: 1.64-6.80; P = 0.001) or non-pregnancy controls (SMD=3.87; 95% CI: 1.81-5.92; P = 0.0002). Interestingly, higher blood HMGB1 levels were observed in women with preterm birth (PTB), however, the results did not reach a statistical difference (SMD=0.54; 95% CI: -0.36-1.44; P = 0.24). In conclusion, overexpressed maternal blood HMGB1 levels were associated with adverse pregnancy outcomes, including PE, GDM and URSA. Further studies should be conducted to validate the efficacy of HMGB1 as a biomarker for assessing the risk of adverse pregnancy outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Objectives: To identify and internally validate metabolites predictive of spontaneous preterm birth (sPTB) using multiple machine learning methods and sequential maternal serum samples, and to predict spontaneous early term birth (sETB) using these metabolites., Design: Case-cohort design within a prospective cohort study., Setting: Cambridge, UK., Population or Sample: A total of 399 Pregnancy Outcome Prediction study participants, including 98 cases of sPTB., Methods: An untargeted metabolomic analysis of maternal serum samples at 12, 20, 28 and 36 weeks of gestation was performed. We applied six supervised machine learning methods and a weighted Cox model to measurements at 28 weeks of gestation and sPTB, followed by feature selection. We used logistic regression with elastic net penalty, followed by best subset selection, to reduce the number of predictive metabolites further. We applied coefficients from the chosen models to measurements from different gestational ages to predict sPTB and sETB., Main Outcome Measures: sPTB and sETB., Results: We identified 47 metabolites, mostly lipids, as important predictors of sPTB by two or more methods and 22 were identified by three or more methods. The best 4-predictor model had an optimism-corrected area under the receiver operating characteristics curve (AUC) of 0.703 at 28 weeks of gestation. The model also predicted sPTB in 12-week samples (0.606, 95% CI 0.544-0.667) and 20-week samples (0.657, 95% CI 0.597-0.717) and it predicted sETB in 36-week samples (0.727, 95% CI 0.606-0.849). A lysolipid, 1-palmitoleoyl-GPE (16:1)*, was the strongest predictor of sPTB at 12 weeks of gestation (0.609, 95% CI 0.548-0.670), 20 weeks (0.630, 95% CI 0.569-0.690) and 28 weeks (0.660, 95% CI 0.599-0.722), and of sETB at 36 weeks (0.739, 95% CI 0.618-0.860)., Conclusions: We identified and internally validated maternal serum metabolites predictive of sPTB. A lysolipid, 1-palmitoleoyl-GPE (16:1)*, is a novel predictor of sPTB and sETB. Further validation in external populations is required., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction., Material and Methods: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth., Results: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68)., Conclusions: Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objectives: Preterm delivery abruptly separates a baby from the placental supply of nutrients which are mostly accreted during the third trimester. The study aimed to determine the relationship between plasma levels of vitamin D in mothers and their preterm infants within the first 24 hours of life in a Nigerian population and how this is related to the intrauterine growth pattern., Methods: This hospital-based panel study of 121 preterm infants and their mothers was carried out in three neonatal units in southwest Nigeria. The plasma levels of vitamin D were assayed in mothers and their corresponding singleton infants while anthropometric parameters of the babies were also recorded., Results: The prevalence of low plasma Vitamin D was 33.1% in the mothers and 43.8% in their preterm neonates. Plasma vitamin D levels in infants showed a moderately strong positive correlation with maternal plasma levels at birth (r = 0.517; p < 0.001). Mean maternal plasma Vitamin D was lowest in mothers whose babies were small for gestational age., Conclusion: Notably high proportions of Nigerian preterm infants and their mothers had low plasma Vitamin D around the period of birth and low maternal vitamin D is associated with delivery of small-for-gestational-age babies. Supplementation of Vitamin D in pregnant women and preterm babies is recommended., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Intrahepatic cholestasis of pregnancy (ICP) can lead to many adverse pregnancy outcomes, and the influencing factors remain unclear at present. This study retrospectively analyzed clinical data from 1815 pregnant women with ICP and evaluated the relationship between ICP subtypes, gestational age at onset, and pregnancy outcomes. The results of this study show that during pregnancy, the levels of biochemical indicators (TBA, DBIL and ALT) in the serum of pregnant women initially diagnosed with subtypes of ICP were noted to constantly change, and the subtype of ICP and its severity also changed. The incidence of adverse pregnancy outcomes [meconium-stained amniotic fluid (MSAF), NICU transfer, Apgar score ≤ 7 at 1 min, and preterm birth] in patients with ICP1 (icteric type) was significantly higher than for patients with ICP2, ICP3 or ICP4. The preterm birth rate of early-onset ICP was higher than that of late-onset ICP in ICP1 and ICP3 subtypes. In conclusion, the outcome of pregnancy in women with ICP is closely related to the serum TBA level and ICP subtype, which should be recognized in the clinic., (© 2024. The Author(s).)

Preterm labor, a condition associated with various risk factors such as a history of prior preterm birth (PTB) and multiple pregnancies, has recently seen an increasing focus on its potential link with dyslipidemia. This study aims to investigate the relationship between dyslipidemia in expectant mothers and the risks of PTB. We studied 6963 mothers who gave birth at the International Peace Maternal and Child Health Hospital of Shanghai Jiaotong University School of Medicine in 2020, among which, 437 women had PTB. We extracted clinical and lipid data from electronic records, using multivariable logistic regression and restricted cubic spline models to explore the link between lipid concentrations (by quartiles) in pregnancy stages and PTB risk. The PTB rate was 6.3%. Early pregnancy in the PTB group showed elevated ApoA, ApoB, CHOL, LDL, and TG levels compared to controls (all P < 0.05). Late pregnancy showed no notable lipid differences. Multivariable analysis revealed elevated ApoA, TG, higher age, BMI ≥ 28 kg/m 2 , hypertension, assisted reproductive technology and gestational diabetes as PTB risk factors (all P < 0.05). After adjustments, higher ApoA, ApoB, CHOL and TG levels correlated with increased PTB risk. Using the lowest quartile, the adjusted ORs for early pregnancy's highest quartile of ApoA, ApoB, CHOL and TG were 1.348, 1.442, 1.442 and 2.156, respectively. Our findings indicate that dyslipemia in early pregnancy, including elevated levels of ApoA, ApoB, CHOL and TG, are associated with PTB. Managing lipid abnormalities during pregnancy may help reduce the risk of PTB., (© 2024. The Author(s).)

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB., (© 2024. The Author(s).)

Objective: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Doppler indices (umbilical artery (UA) pulsatility index (PI) and uterine artery (UtA) PI) in various combinations for predicting preterm birth (PTB) in pregnancies complicated by fetal growth restriction (FGR)., Methods: This was a prospective observational cohort study, performed at Mater Mother's Hospital in Brisbane, Queensland, Australia, from May 2022 to June 2023, of pregnancies complicated by FGR and appropriate-for-gestational-age (AGA) pregnancies. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA-PI and UtA-PI were measured at 2-4-weekly intervals from recruitment until delivery. Harrell's concordance statistic (Harrell's C) was used to evaluate multivariable Cox proportional hazards regression models featuring various combinations of placental biomarkers and fetoplacental Doppler indices to ascertain the best combination to predict PTB (< 37 weeks). Multivariable Cox regression models were used with biomarkers as time-varying covariates., Results: The study cohort included 320 singleton pregnancies, comprising 179 (55.9%) affected by FGR, defined according to a Delphi consensus, and 141 (44.1%) with an AGA fetus. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio were associated with significantly shorter time to PTB. Low PlGF was a better predictor of PTB than was either sFlt-1/PlGF ratio or a combination of PlGF and sFlt-1/PlGF ratio (Harrell's C, 0.81, 0.78 and 0.79, respectively). Although both Doppler indices were significantly associated with time to PTB, in combination they were better predictors of PTB than was either UA-PI > 95 th centile or UtA-PI > 95 th centile alone (Harrell's C, 0.82, 0.75 and 0.76, respectively). Predictive utility for PTB was best when PlGF < 100 ng/L, UA-PI > 95 th centile and UtA-PI > 95 th centile were combined (Harrell's C, 0.88) (hazard ratio, 32.99; 95% CI, 10.74-101.32)., Conclusions: Low maternal serum PlGF level (< 100 ng/L) and abnormal fetoplacental Doppler indices (UA-PI > 95 th centile and UtA-PI > 95 th centile) in combination have the greatest predictive utility for PTB in pregnancies complicated by FGR. Their assessment may help guide clinical management of these complex pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency., Study Design: A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively., Results: Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p  = 0.097; LB: 37.6 vs. 98.1 pg/mL, p  = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB., Conclusion: In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB., Key Points: · Maternally circulating DLK1 is correlated with placental insufficiency.. · Maternally circulating DLK1 is not correlated with SB.. · DLK1 is a promising marker for placental insufficiency.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The determinants of preterm birth remain unknown. Excessive maternal inflammation during pregnancy may play an important role in the pathogenesis of preterm birth. Our objective was to describe the association of prenatal levels of proinflammatory C-reactive protein (CRP) and interleukin-8 (IL-8) with preterm birth in participants of the Vitamin D Antenatal Asthma Reduction Trial., Study Design: Five hundred and twenty-eight patients with available samples of both first- and third-trimester plasma were included in this analysis. CRP and IL-8 were measured from maternal prenatal samples. We examined the association between prenatal CRP and IL-8 with maternal health characteristics and the outcome of preterm birth. We also described the patterns of change in CRP and IL-8 from first to third trimester and their association with preterm birth. A subgroup analysis comparing only those with a spontaneous preterm birth phenotype to those with term birth was also performed., Results: Maternal characteristics including lower educational attainment, higher prepregnancy body mass index, gestational diabetes, lower vitamin D, and an unhealthy diet were associated with elevated levels of prenatal CRP and IL-8. Higher third trimester CRP and an increase in CRP from first to third trimester were associated with an increased odds of preterm birth when compared to lower levels of CRP (adjusted odds ratio [aOR] = 1.49, 95% confidence interval: 1.02, 2.23, p  = 0.04) or a decrease in CRP over pregnancy (aOR = 3.06, 95% CI = 1.31,7.55, p  = 0.01), after adjusting for potential confounders. These associations were strengthened when comparing only patients with spontaneous preterm birth ( n  = 22) to those with term births., Conclusion: Higher levels of the proinflammatory markers CRP and IL-8 are associated with indicators of poor maternal health and preterm birth. Prenatal CRP levels may reflect maternal prenatal health status and serve as a predictor of preterm birth, especially among those with spontaneous preterm birth., Key Points: · Elevated prenatal CRP is associated with poor maternal health.. · High prenatal CRP may predict premature birth, especially spontaneous premature birth phenotypes.. · Vitamin D insufficiency may be a modifiable risk factor for prenatal inflammation.., Competing Interests: A.A.L. has received author royalties from UpToDate, Inc. S.T.W. has received royalties from UpToDate, Inc. H.M. has received research support from NHLBI. K.L.-S., N.L., Y.S.C., R.S.K., and H.K. have nothing to disclose., (Thieme. All rights reserved.)

Objectives: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies., Methods: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5 %ile or >95 %ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test., Results: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5 %, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8 %, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8 %, p=0.04) and hypertension (66.7 vs. 21.4 %, p=0.03)., Conclusions: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background/aim: To evaluate whether there is a relationship between serum myosin-binding protein C (MyBP-C) levels measured in the first trimester and the timing of delivery, and, if a relationship is detected, the potential of this relationship in distinguishing between preterm and term labor., Materials and Methods: This prospective case-control study was conducted with 701 pregnant women who applied to the Obstetrics Outpatient Clinic of Gaziosmanpaşa Training and Research Hospital in the first trimester, between 11 and 14 gestational weeks. MyBP-C serum samples from the first trimester were stored under appropriate conditions until the time of delivery. Of these pregnant women, 628 completed the study. According to the delivery time, the pregnant women were divided into two groups, as those who delivered prematurely before 37 weeks and those who gave birth at term. The case group comprised 45 women who gave birth prematurely, while 583 women gave birth at term. A control group was formed with 45 pregnant women of the same age, who were selected by randomization using a simple random sampling method from the 583 pregnant women. The MyBP-C levels were measured and compared from the first-trimester serum materials of both groups., Results: The MyBP-C levels of the preterm delivery group were significantly higher than those of the term delivery control group (4.51 ± 1.69 vs. 3.09 ± 1.44 pg/mL, respectively; p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the MyBP-C levels in the first trimester with a cut-off value of 4.76 ng/dL indicated women with preterm delivery with a sensitivity of 42.22% and specificity of 95.56% (AUC: 0.734, 95% CI: 0.630-0.822). The overall differential diagnosis performance of the MyBP-C level for preterm delivery was determined as 73.4% (p < 0.001). The MyBP-C levels were found to be significantly higher both in the early preterm group compared with the late preterm group (p < 0.001), and in those with premature rupture of membranes (PROM) compared with those without (p < 0.001)., Conclusion: The preterm delivery group exhibited high serum MyBP-C levels in the serum samples taken in the first trimester. First-trimester serum MyBP-C levels seem to be a simple and easy way to exclude preterm delivery risk in a significant manner. In addition, levels are significantly higher for early preterm compared with late preterm and early PROM compared with intact membranes., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest., (© TÜBİTAK.)

Importance: Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy., Objective: To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia., Design, Setting, and Participants: Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants., Interventions: Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group)., Main Outcomes and Measures: Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%., Results: Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48% (7/473) in the intervention group and 1.73% (8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority., Conclusions and Relevance: Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio., Trial Registration: ClinicalTrials.gov Identifier: NCT03741179 and ClinicalTrialsRegister.eu Identifier: 2018-000811-26.

Background: Vitamin D deficiency has been associated with the severity of COVID-19. The role of vitamin D in pregnant women with COVID-19 has been poorly investigated to date. The aim of this study was to evaluate the influence of vitamin D in affecting some clinical features in pregnancy between SARS-CoV-2 positive and negative patients., Methods: Vitamin D pathway related polymorphisms and 25-hydroxyvitamin D levels were quantified in pregnant women followed from the first to the third trimester of pregnancy. Vitamin D deficiency was considered with values ≤ 30 ng/mL., Results: In total, 160 women were enrolled: 23 resulted positive for at least one SARS-CoV-2 related test (molecular swab or antibody tests). Vitamin D-associated polymorphisms were able to affect vitamin D levels in SARS-CoV-2 negative and positive subjects: remarkably, all the VDR TaqICC genotype patients were negative for SARS-CoV-2. In a sub-population (118 patients), vitamin D levels correlated with pregnancy-related factors, such as alpha-fetoprotein levels. Third-trimester vitamin D levels were lower in preterm births compared to full-term pregnancy: this trend was highlighted for SARS-CoV-2 positive patients., Conclusions: This is the first study demonstrating a role of vitamin D in affecting the clinical characteristics of pregnant women during the COVID-19 era. Further studies in larger and different cohorts of patients are required to confirm these findings., Competing Interests: The authors declare no potential conflict of interest.

Background: Abnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth., Methods: This case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE who delivered at < 37 and < 34 weeks of gestation, respectively., Results: There were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p < 0.0001), PlGF (0.76 vs 1.01, p < 0.0001) and free-β hCG (0.81 vs. 0.98, p < 0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p < 0.01) and PlGF (0.75 vs 1.02, p < 0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester. The corresponding DR was 58% for gestational hypertension and 36% for preterm birth cases., Conclusions: Maternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy. This combination was less accurate in predicting women who have gestational hypertension or preterm birth., (© 2022. The Author(s).)

Background: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy., Methods: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes., Results: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1-3.5)., Conclusion: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting., (© 2022. The Author(s).)