Early Preterm Birth Research Articles

Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study

BackgroundPreimplantation genetic testing for aneuploidy (PGT-A) is widely used as an embryo selection technique in in vitro fertilization (IVF), but its effectiveness and potential beneficiary populations are unclear.MethodsThis retrospective cohort study included patients who underwent their first oocyte retrieval cycles at CITIC-Xiangya between January 2016 and November 2019, and the associated fresh and thawed embryo transfer cycles up to November 30, 2020. PGT-A (PGT-A group) and intracytoplasmic sperm injection (ICSI)/IVF (non-PGT-A group) cycles were included. The numbers of oocytes and embryos obtained were unrestricted. In total, 60,580 patients were enrolled, and baseline data were matched between groups using 1:3 propensity score matching. Sensitivity analyses, including propensity score stratification and traditional multivariate logistic regression, were performed on the original unmatched cohort to check the robustness of the overall results. Analyses were stratified by age, body mass index, ovarian reserve/responsiveness, and potential indications to explore benefits in subgroups. The primary outcome was cumulative live birth rate (CLBR). The other outcomes included live birth rate (LBR), pregnancy loss rate, clinical pregnancy rate, pregnancy complications, low birth weight rate, and neonatal malformation rate.ResultsIn total, 4195 PGT-A users were matched with 10,140 non-PGT-A users. A significant reduction in CLBR was observed in women using PGT-A (27.5% vs. 31.1%; odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.78–0.91; P < 0.001). However, women using PGT-A had higher first-transfer pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI 1.81–2.23; P < 0.001) and LBR (52.6% vs. 34.2%, OR = 2.13, 95% CI 1.92–2.36; P < 0.001) rates and lower rates of early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI 0.48–0.70; P < 0.001), preterm birth (8.6% vs 17.3%; P < 0.001), and low birth weight (4.9% vs. 19.3%; P < 0.001). Moreover, subgroup analyses revealed that women aged ≥ 38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefited from PGT-A, with a significant increase in first-transfer LBR without a decrease in CLBR.ConclusionPGT-A does not increase and decrease CLBR per oocyte retrieval cycle; nonetheless, it is effective in infertile populations with specific indications. PGT-A reduces complications associated with multiple gestations.

A nomogram for predicting prognosis of patients with cervical cerclage

IntroductionCervical insufficiency is an increased risk of midterm miscarriage and early preterm birth which increase the risk of fetal loss. This study aimed to construct a nomogram for patients with cervical insufficiency after cervical cerclage, which may assist clinicians to have individualized treatment for patients with cervical insufficiency. MethodsA study was done retrospectively from January 2013 through July 2022 in our hospital. The primary outcomes were delivered at more than 28, 30, 32, or 34 gestational weeks. Kaplan-Meier curves were applied to analyze 17 variables. All patients were randomly split (147:64) into development and validation cohorts. Based on the multivariate Cox regression analysis, a nomogram was constructed through the 'rms' package in R. ResultsA total of 211 patients with cervical insufficiency were enrolled: 121 had history-indicated cerclage; 58 had ultrasound-indicated cerclage and 32 had emergency cerclage. Times of gestations, times of miscarriages, IVF, abdominal pain, diagnostic classification, preoperative and postoperative management were demonstrated to impact overall extended days when delivering at more than 28 gestational weeks was set as the primary outcome. Except for preoperative and postoperative management, the above other five variables impacted the primary outcomes of delivering at more than 30, 32, or 34 gestational weeks. Postoperative tocolytics had an impact on the prognosis of patients who delivered at more than 30 gestational weeks. In development cohort data, a nomogram was established to predict overall extended days of patients with cervical cerclage. In present study, C-index was 0.662 in the development cohort and 0.687 in the validation cohort respectively, suggesting that the model presented some satisfied prediction. Moreover, the clinical decision curves for patients with delivering at more than 28, 30, 32 or 34 weeks set as primary outcomes also displayed that this nomogram demonstrated good clinical predictive usefulness. ConclusionsThe nomogram developed in this study may be a valuable tool assisting clinicians to evaluate outcomes of patients with cervical insufficiency after cervical cerclage, which helps them develop individualized management for the patients.

Neonatal outcomes of early preterm births according to the delivery indications

ObjectiveTo compare the neonatal outcomes of early preterm births according to delivery indications and determine the obstetric risk factors associated with adverse outcomes. MethodsWe retrospectively studied pregnancies delivered between 22 + 0 and 26 + 6 weeks at the tertiary center between April 2013 and April 2022. Stillbirths, elective termination of pregnancy, and multifetal pregnancies were excluded. Patients were classified into two groups according to delivery indications: spontaneous preterm birth (sPTB) due to premature rupture of membranes (PROM), preterm labor, or acute cervical insufficiency; and indicated preterm birth (iPTB). Obstetric and neonatal outcomes were compared between the groups. ResultsOf the 121 neonates, 73 % (88/121) underwent sPTB. The overall survival rates were 73 % and 49 % in the sPTB and iPTB groups, respectively (p = 0.017). Multivariate logistic regression analysis was performed with adjustment for gestational age at delivery, fetal growth restriction, cesarean section, histological chorioamnionitis, and funisitis. Moreover, in the 1-year follow-up, the proportion of body mass below the third percentile was significantly higher in the iPTB-group than in the sPTB-group (53 % vs. 20 %, p = 0.019). Furthermore, diagnoses of developmental delay and cerebral palsy were slightly higher in the iPTB-group (33 % and 20 %, respectively) than in the sPTB-group (27 % and 9 %, respectively); however, this difference was not statistically significant. ConclusionsIn early preterm births, iPTB was associated with a higher neonatal mortality than sPTB.

EP16.02: The association of placenta previa and early preterm birth in pregnancies complicated by placenta accreta spectrum

EP16.02: The association of placenta previa and early preterm birth in pregnancies complicated by placenta accreta spectrum

Preterm Doğum Öngörüsünde Birinci ve Üçüncü Trimester Tam Kan Sayımı Parametrelerinin Karşılaştırılması

Introduction: The complete blood count parameters and its combinations, such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and mean platelet volume (MPV), are inflammatory markers. In this study, we aimed to demonstrate the possible role of complete blood count parameters (NLR, PLR, and MPV) in predicting preterm birth.&#x0D; &#x0D; Material and Methods: The complete blood count parameters in the first and third trimesters were recorded, as well as the corresponding NLR, PLR, and MPV. The study population was categorized as preterm (n = 94) and term births (n = 953). The preterm birth group was further divided into early preterm (n = 11) and late preterm birth (n = 83) groups. The inflammatory markers were compared between the study groups for the first and third trimesters separately. The alterations between the first and third trimester values were also compared.&#x0D; &#x0D; Results: The first trimester values were similar across the study groups. Moreover, the MPV difference between the first and third trimesters was significantly lower in the preterm group than in the term group (0.0  1.1 vs. 0.2  1.1, p = 0.038). Furthermore, NLR values were higher in the early preterm subgroup than in the late preterm and term groups for the first and third trimesters (first trimester; 4.0  1.2 vs. 3.1  2.0 and 3.1  1.3, p = 0.005; third trimester; 5.3  1.2 vs. 4.0  1.5 and 4.4  2.9, p = 0.013).&#x0D; &#x0D; Conclusion: NLR and MPV predict preterm births in the first trimester and before birth. This enables physicians to take some precautions in preventing preterm delivery.

DHA, nutrient intake, and maternal characteristics as predictors of pregnancy outcomes in a randomised clinical trial of DHA supplementation

To investigate the relationships among docosahexaenoic acid (DHA) intake, nutrient intake, and maternal characteristics on pregnancy outcomes in a phase III randomised clinical trial designed to determine the effect of a DHA dose of 1000mg/day compared to 200mg/day on early preterm birth (<34 weeks gestation). A secondary aim of the phase III randomised trial was to explore the relationships among pregnancy outcomes (maternal red blood cell phospholipid (RBC-PL) DHA at delivery, preterm birth, gestational age at delivery, labor type, birth anthropometric measures, low birth weight, gestational diabetes, pre-eclampsia, and admission to a neonatal intensive care unit) in participants (n=1100). We used Bayesian multiple imputation and linear and logistic regression models to conduct an analysis of five general classes of predictor variables collected during the trial: a) DHA intake, b) nutrient intake from food and supplements, c) environmental exposure to tobacco and alcohol, d) maternal demographics, and e) maternal medical history. DHA supplementation lowered the risk of preterm birth and NICU admission, and increased gestation and birth weight as observed in the primary analysis. Higher maternal RBC-PL-DHA at delivery was associated with DHA supplementation and formal education of a bachelor's degree or higher. DHA supplementation and maternal age were associated with a higher risk of gestational diabetes. Total vitamin A intake was associated with longer gestation, while fructose and intake of the long chain omega-6 fatty acid, arachidonic acid, were associated with shorter gestation. Risk of preterm birth was associated with a history of low birth weight, preterm birth, pre-eclampsia, and NICU admission. Bayesian models provide a comprehensive approach to relationships among DHA intake, nutrient intake, maternal characteristics, and pregnancy outcomes. We observed previously unreported relationships between gestation duration and fructose, vitamin A, and arachidonic acid that could be the basis for future research. ClinicalTrials.gov (NCT02626299); December 10, 2015.

Accelerated epigenetic clock aging in maternal peripheral blood and preterm birth

Epigenetic clocks use CpG DNA methylation to estimate biological age. Acceleration is associated with cancer, heart disease, and shorter life span. Few studies evaluate DNA methylation age and pregnancy outcomes. AgeAccelGrim is a novel epigenetic clock that combines 7 DNA methylation components. This study aimed to determine whether maternal biological aging (via AgeAccelGrim) is associated with early preterm birth. A prospective cohort of patients with singleton pregnancies and at high risk of spontaneous preterm birth delivering at a tertiary university hospital were included in this study. Genome-wide CpG methylation was measured using the Illumina EPIC BeadChip (Illumina, Inc, San Diego, CA) from maternal blood samples obtained at <28 weeks of gestation. AgeAccelGrim and its 7 DNA methylation components were estimated by the Horvath DNA methylation age online tool. Positive values are associated with accelerated biological aging, whereas negative values are associated with slower biological aging relative to each subject's age. The primary outcome was preterm birth at <34 weeks of gestation (any indication). The secondary outcomes were preterm birth at <37 and <28 weeks of gestation. AgeAccelGrim was analyzed as a continuous variable and in quartiles. Exploratory analyses evaluated each of the 7 DNA methylation components included in the composite AgeAccelGrim. Data were analyzed by chi-square test, t test, rank-sum test, logistic regression (controlling a priori for maternal age, cell counts, low socioeconomic status, and gestational age at the time of sample collection), and Kaplan-Meier survival analyses. The log-rank test was used to test the equality of the survival functions. Overall, 163 patients met the inclusion criteria. Of the patients, 48%, 39%, and 21% delivered at <37, <34, and <28 weeks of gestation, respectively. The median AgeAccelGrim was-0.35 years (interquartile range,-2.24 to 1.31) for those delivering at term. Those delivering preterm had higher AgeAccelGrim values that were inversely proportional to delivery gestational age (preterm birth at <37 weeks of gestation:+0.40 years [interquartile range:-1.21 to+2.28]; preterm birth at <34 weeks of gestation:+0.51 years [interquartile range:-1.05 to+2.67]; preterm birth at <28 weeks of gestation:+1.05 years [interquartile range:-0.72 to+2.72]). Estimated DNA methylation of the 7 epigenetic clock component values was increased among those with preterm birth at <34 weeks of gestation, although the differences were only significant for DNA methylation of plasminogen activation inhibitor 1. In regression models, AgeAcccelGrim was associated with an elevated risk of preterm birth with increasing magnitude for increasing severity of preterm birth. For each 1-year increase in the AgeAccelGrim value (ie, each 1-year increase in biological age compared with chronologic age), the adjusted odds of preterm birth were 11% (adjusted odds ratio, 1.11; 95% confidence interval, 1.00-1.24), 13% (adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.26), and 18% (adjusted odds ratio, 1.18; 95% confidence interval, 1.04-1.35) higher for preterm birth at <37, <34, and <28 weeks of gestation, respectively. Similarly, individuals with accelerated biological aging (≥75th percentile AgeAccelGrim) had more than double the odds of preterm birth at <34 weeks of gestation (adjusted odds ratio, 2.36; 95% confidence interval, 1.10-5.08) and more than triple the odds of preterm birth at <28 weeks of gestation (adjusted odds ratio, 3.89; 95% confidence interval, 1.61-9.38). The adjusted odds ratio for preterm birth at <37 weeks of gestation was 1.73 but spanned the null (adjusted odds ratio, 1.73; 95% confidence interval, 0.81-3.69). In Kaplan-Meier survival analyses, those in the highest AgeAccelGrim quartile delivered the earliest (log-rank Pvalue of <.001). Accelerated biological aging was associated with preterm birth among high-risk patients. Future research confirming these findings and elucidating factors that slow biological aging may improve birth outcomes.

Umbilical cord thrombosis is more increased according to the progression of outside-in neutrophils migration in extra-placental membranes among early spontaneous preterm birth.

Umbilical cord thrombosis is more increased according to the progression of outside-in neutrophils migration in extra-placental membranes among early spontaneous preterm birth.

Short and long term consequences of early preterm birth: challenges in understanding

Short and long term consequences of early preterm birth: challenges in understanding

Residential greenspace counteracts PM2.5 on the risks of preterm birth subtypes: A multicenter study

BackgroundThe association between residential greenspace and preterm birth (PTB) risk remained inconclusive. The PTB subtypes have been ignored and the effect of co-exposure of PM2.5 on PTB risk is still unclear. ObjectiveTo investigate the independent, interactive, and mixed effects of residential greenspace and PM2.5 on the risk of PTB subtypes. MethodsA total of 19,900 singleton births from 20 hospitals in Shanghai, China, from 2015 to 2017 were included. The Normalized Difference Vegetation Index (NDVI) within 500 m and 1000 m buffers of the maternal residence and a combined geoscience-statistical model-derived PM2.5 and its six components were used as the exposure measures. PTB (<37 completed weeks of gestation) were divided into early PTB (24–33 weeks) vs. late PTB (34–36 weeks) and into spontaneous PTB (sPTB), preterm premature rupture of the fetal membranes (PPROM), and iatrogenic PTB. Multivariable logistic regression models were applied to assess the independent and interactive effects of NDVI and PM2.5 on PTB in each trimester. The quantile g-computation approach was employed to explore the mixture effect of PM2.5 components and greenspace across the pregnancy and to determine the main contributors. ResultsLevels of PM2.5 and greenspace were associated with increased [aOR (95%CI) ranging from 1.18 (1.07, 1.30) to 3.36 (2.45, 4.64)] and decreased risks [aORs (95%CI) ranging from 0.64 (0.53, 0.78) to 0.86 (0.73, 0.99)] of PTB subtypes, respectively. At the same PM2.5 level, higher residential greenspace was associated with lower risks, and vice versa. All these associations were more pronounced in late pregnancy. Early PTB and PPROM were the main affected subtypes, and the main drivers in PM2.5 were black carbon and ammonium. ConclusionsResidential greenspace may mitigate the PTB risks due to PM2.5 exposure during pregnancy.

Association between early preterm birth and maternal exposure to fine particular matter (PM10): A nation-wide population-based cohort study using machine learning.

Although preterm birth (PTB), a birth before 34 weeks of gestation accounts for only less than 3% of total births, it is a critical cause of various perinatal morbidity and mortality. Several studies have been conducted on the association between maternal exposure to PM and PTB, but the results were inconsistent. Moreover, no study has analyzed the risk of PM on PTB among women with cardiovascular diseases, even though those were thought to be highly susceptible to PM considering the cardiovascular effect of PM. Therefore, we aimed to evaluate the effect of PM10 on early PTB according to the period of exposure, using machine learning with data from Korea National Health Insurance Service (KNHI) claims. Furthermore, we conducted subgroup analysis to compare the risk of PM on early PTB among pregnant women with cardiovascular diseases and those without. A total of 149,643 primiparous singleton women aged 25 to 40 years who delivered babies in 2017 were included. Random forest feature importance and SHAP (Shapley additive explanations) value were used to identify the effect of PM10 on early PTB in comparison with other well-known contributing factors of PTB. AUC and accuracy of PTB prediction model using random forest were 0.9988 and 0.9984, respectively. Maternal exposure to PM10 was one of the major predictors of early PTB. PM10 concentration of 5 to 7 months before delivery, the first and early second trimester of pregnancy, ranked high in feature importance. SHAP value showed that higher PM10 concentrations before 5 to 7 months before delivery were associated with an increased risk of early PTB. The probability of early PTB was increased by 7.73%, 10.58%, or 11.11% if a variable PM10 concentration of 5, 6, or 7 months before delivery was included to the prediction model. Furthermore, women with cardiovascular diseases were more susceptible to PM10 concentration in terms of risk for early PTB than those without cardiovascular diseases. Maternal exposure to PM10 has a strong association with early PTB. In addition, in the context of PTB, pregnant women with cardiovascular diseases are a high-risk group of PM10 and the first and early second trimester is a high-risk period of PM10.

Extreme Temperature Exposure and Risks of Preterm Birth Subtypes Based on a Nationwide Survey in China.

Previous studies have reported that ambient temperature may affect perinatal outcomes. However, whether extreme temperature affects the risk of preterm birth (PTB) remains controversial. Studies on the associations of extreme temperature with PTB subtypes are lacking. We aimed to investigate the associations of extreme climate events with the risks of PTB and its subtypes, discerning possible modifiers. Data on all singleton deliveries were obtained from the China Labor and Delivery Survey (CLDS), a nationwide investigation implemented in 2015 and 2016. PTB was defined as gestational weeks and then categorized as early (24-34 wk) and late PTBs (35-36 wk), and clinical subtypes [spontaneous PTB, preterm premature rupture of the fetal membranes (PPROM), iatrogenic PTB]. Ambient temperature data were provided by the China National Weather Data Sharing System. Five heat indexes and five cold indexes were used to define heat waves and cold spells. Generalized linear mixed models with a random term by hospital unit were used to assess the associations of short-term prenatal extreme temperature exposure. The Cox proportional hazard regression model was applied to assess the nonlinear associations of low- or high-temperature exposure at the whole and different trimesters of pregnancy with the risk of PTB. Stratified analyses were conducted to assess the possible modification by geographic region and fetal sex. A total of 70,818 singleton births from 96 hospitals in China were included, among which 4,965 (7.01%) were PTBs. Exposure to extreme cold events 1 wk before delivery was associated with an increased PTB risk, with an adjusted odds ratio (aOR) [95% confidence intervals (CIs)] of 1.07 (95% CI: 1.04, 1.10) and 1.06 (1.04, 1.09) for the total days when the daily average temperature below the fifth percentile (fifth-days) and the 10th percentile (10th-days), 1.18 (1.04, 1.34) for the cold spells when the daily average temperature below the fifth percentile for two consecutive days (fifth-2D), 1.09 (1.03, 1.16) and 1.12 (1.06, 1.19) for the cold spells when the daily average temperature below the 10th percentile for three and two consecutive days (10th-3D and 10th-2D), respectively. Results of extreme temperature exposure during 2 weeks before delivery showed similarly significant associations. The association between cold spells and PTB tended to be stronger for late PTB than for early PTB. Cold spells were mainly associated with spontaneous PTB and late PPROM. A stratified analysis indicated that pregnant women in western and northern regions tended to be more sensitive to cold spells, and pregnant women with a female fetus appeared to be at a higher risk of PTB when exposed to cold spells. Pregnant women in late pregnancy were more susceptible to extreme temperatures. No significant or stable association was found between heat waves and preterm birth. Exposure to cold spells was associated with an increased risk of PTB, especially late, spontaneous PTB and PPROM. The associations appeared to be more pronounced in the north and west regions and in pregnancies with female fetuses. https://doi.org/10.1289/EHP10831.

Addressing a broken drug pipeline for preterm birth: why early preterm birth is an orphan disease

Preterm birth remains one of the most urgent unresolved medical problems in obstetrics, yet only 2 therapeutics for preventing preterm birth have ever been approved by the United States Food and Drug Administration, and neither remains on the market. The recent withdrawal of 17-hydroxyprogesterone caproate (17-OHPC, Makena) marks a new but familiar era for obstetrics with no Food and Drug Administration-approved pharmaceuticals to address preterm birth. The lack of pharmaceuticals reflects a broad and ineffective pipeline hindered by extensive regulatory hurdles, soaring costs of performing drug research, and concerns regarding adverse effects among a particularly vulnerable population. The pharmaceutical industry has historically limited investments in research for diseases with similarly small markets, such as cystic fibrosis, given their rarity and diminished projected financial return. The Orphan Drug Act, however, incentivizes drug development for "orphan diseases", defined as affecting <200,000 people in the United States annually. Although the total number of preterm births in the United States exceeds this threshold annually, the early subset of preterm birth (<34 weeks' gestation) would qualify, which is predominantly caused by inflammation and infection. The scientific rationale for classifying preterm birth into early and late subsets is strong given that their etiologies differ, and therapeutics that may be efficacious for one subset may not work for the other. For example, antiinflammatory therapeutics would be expected to be highly effective for early but not late preterm birth. A robust therapeutic pipeline of antiinflammatory drugs already exists, which could be used to target spontaneous early preterm birth, in combination with antibiotics shown to sterilize the amniotic cavity. New applications for therapeutics targeting spontaneous early preterm birth could categorize as orphan disease drugs, which could revitalize the preterm birth therapeutic pipeline. Herein, we describe why drugs targeting early preterm birth should qualify for orphan status, which may increase pharmaceutical interest for this vitally important obstetrical condition.

STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE ENDOMETRIUM AND OVARIAN TISSUE IN PATIENTS WITH IMPAIRED REPRODUCTIVE POTENTIAL AND OBESITY

According to the WHO, every second woman has a problem with excess weight, while about 23% of women indicate a pathological body mass index, and excess weight (the so-called “pre-obesity”) is noted in 25% of women.&#x0D; The aim of the research was to evaluate the structural and functional parameters of the endometrium and ovarian tissue and to optimize the diagnostic algorithm and monitoring of the endometrium in women with obesity and impaired reproductive function.&#x0D; Materials and methods. 110 patients of reproductive age with impaired reproductive health underwent a comprehensive clinical and laboratory examination within the framework of this research. The main group included 64 patients with overweight and class 1 obesity, and the comparison group consisted of 46 women with a normal body mass index. The proposed diagnostic algorithm included a sonographic study of the structural parameters of the endometrium and ovaries, as well as an assessment of the features of the blood supply to the pelvic organs and statistical processing of the results.&#x0D; Research results and their discussion. The presented results allow us to note a significant percentage of comorbidity of somatic and gynecological pathology in overweight and obese patients. Pregnancy is accompanied by a higher percentage of early reproductive losses (14.0%), preterm birth (10.9%), preeclampsia (42.2%), placental dysfunction (46.4%) and low birth weight (17.2%). The main clinical forms of endometrial pathology in the main group were polyposis (32.8%), endometrial hyperplasia (23.4%) and dyschronosis of morphological changes of the endometrium (28.1%). The combination of endometrial hyperplasia with/or uterine leiomyoma, adenomyosis, benign ovarian tumors and retention formations was noted in 53.6% of observations in both groups; in 46.4% of women the isolated form was noted. The morphological characteristics of endometrial polyposis allowed us to note the dominance of glandular-fibrous polyps (45.2%) and in the case of a combination with myoma or ovarian retention cysts - glandular forms (32.3%). The most frequent sonographic marker of dysfunction of the endometrial potential (inconsistency of the ultrasound image of the endometrium with the phase of the menstrual cycle) was revealed in more than half of the cases (62.5%). Sonographic evaluation of the structural parameters of the endometrium and ovarian tissue showed an increase in the anterior-posterior size of the uterus and the thickness of the endometrium by 2.8 times, the volume of the ovary – by 2.0 times. It should be noted that the patients of the main group had a greater proportion of cysts and endometriomas. According to dopplerometry data, significantly lower parameters of the vascular resistance index were confirmed in the ovarian arteries and in the arteries of the stroma; in almost half of the observations, varicose veins of the parametrium were noted.&#x0D; Conclusions. Changes in steroidogenesis against the background of lipid metabolism disorders are accompanied by an increase in the volume of the endometrium and ovarian tissue, growing proportion of cystic formations in the appendages, an increase in the hemodynamic imbalance of blood flow in pelvic organs, which requires optimization of the monitoring program at the stage of preconception preparation and elimination of risk factors for placental dysfunction.

The long-term mediation role of cytokines on the causal pathway from maternal gestational age to offspring eye diseases: Lifecourse-Network Mendelian randomization

BackgroundGestational duration has a significant impact on eye diseases. A large number of evidences suggest that cytokines are associated with gestational duration and eye diseases. However, the causal relationships among cytokines, maternal gestational impairment and offspring eye diseases remain unclear. MethodsWe performed lifecourse-network Mendelian randomization (MR) to explore the causal relationships between maternal gestational duration (from the Early Growth Genetics (EGG) Consortium and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study, N = 84,689), neonatal/adult cytokines (from the NHGRI-EBI Catalog, N = 764/4,618), and adult eye diseases (from FinnGen consotium, N = 309,154) using summary-level data from large genome-wide association studies. Multiplicative random effects inverse variance weighted (IVW) and multivariable-IVW methods were the main analysis methods, and the other 15 pleiotropy-robust methods, weak IV-robust methods, and outliers-robust methods were used as auxiliary methods. ResultsMaternal gestational age (early preterm birth, preterm birth, gestational duration, and post-term birth) had a causal relationship with 42 eye diseases. Four neonatal cytokines, Tumor Necrosis Factor-α(TNF-α), IL10, GROA, and CTACK, as well as four adult cytokines, CTACK, IL10, IL12p70 and IL6 are mediators in the causal relationships between early preterm birth and preterm birth in eight eye diseases. However, after adjusting for these mediators, a null direct causal effect of early preterm birth and preterm birth on eight eye diseases was found. In addition, there was no mediator in the causal relationship between gestational duration and post-term birth to eye diseases. ConclusionThe effects of maternal gestational duration on offspring eye diseases through cytokines are long-term and life-course effects.

Cervical sliding sign at second trimester in the prediction of early preterm birth in twin pregnancy.

To examine the cervical sliding sign (CSS) alongside cervical length (CL) in twin pregnancies to predict preterm birth (PB). Twin pregnancies (n = 37) with no known risk factor for PB were included in this prospective study. CSS was defined as the ultrasonographic finding in which the anterior lip of the cervix slides over the posterior lip with gentle and continuous pressure application. The CSS and CL measurements were held in the second trimester. Early PB was defined as the birth of the fetus before 32 weeks of gestation. The patients were divided into two groups as CSS-positive and CSS-negative. Whereas 11 (29.7%) of the twin pregnancies were CSS-positive, 26 (70.3%) were CSS-negative. CSS positivity had a sensitivity of 75.0%, a specificity of 82.2%, a positive predictive value of 54.5%, and a negative predictive value of 92.3% to predict early PB. Multivariate logistic regression analysis revealed that CSS positivity was the only significant independent factor related to early PB. CSS was shown to be superior to CL in providing a better insight to predict early PB. CSS evaluation should be performed in twin pregnancies.

Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol

BackgroundObesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. Methods and designInfants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT 02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DiscussionEffective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. Ethics and disseminationThe University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications.Trial registration: ClinicalTrials.gov ID: NCT03310983

Перинатальні наслідки інноваційної тактики лікування звичного невиношування вагітності при істміко-цервікальній недостатності

Purpose - to improve the effectiveness of the treatment of miscarriage due to isthmic-cervical insufficiency (ICI) by using improved management tactics for women at high risk of ICI. Materials and methods. A two-stage innovating tactic for the treatment of miscarriage caused by ICI was proposed, including the prediction of the ineffectiveness of vaginal cerclage and the implementation of transabdominal cerclage in certain groups of patients. Starting from the pregravid stage, 30 women at risk of ICI were examined, which were conducted according to the developed scheme. 2 patients with a history of failed vaginal cerclage had abdominal cerclage prior to pregnancy and had not yet become pregnant at the time of writing. In 28 remaining women, the course and results of pregnancy were monitored. 3 patients after trachelectomy for cervical cancer were given abdominal cerclage in early pregnancy. 23 pregnant women were subjected to vaginal cerclage prophylactically or for sonographic or physical indications, these women constituted the main group for evaluating the effectiveness of the proposed treatment regimen for miscarriage in ICI. The comparison group consisted of 80 women with intravaginal cerclage, who were managed according to the protocols of the Ministry of Health of Ukraine. Results. The effectiveness of the proposed tactics for the treatment of miscarriage caused by ICI reflects the frequency of miscarriage and its structure. No cases of late miscarriages were observed. The rate of preterm birth significantly decreased from 37.5% to 21.7% (p&lt;0.05), while no cases of early preterm birth (before 28 weeks) were observed. In the structure of miscarriage, 80.0% is the proportion of preterm births at 34-36 weeks of gestation (against 35.5%; p&lt;0.05). The frequency of premature rupture of membranes decreased by 4 times (8.7% vs. 36.3%; p&lt;0.05). The frequency of birth of children in a state of asphyxia decreased by more than 2 times (17.4% vs. 43.4%; p&lt;0.05), and there was not a single case of birth in a state of severe asphyxia. The incidence of complications in the early neonatal period decreased by 20% (43.5% vs. 63.2%; p&lt;0.05), mainly due to a decrease in the frequency of such dangerous complications as respiratory distress syndrome (13.0% vs. 31.6%; p&lt;0.05) and disorders of central nervous system (17.4% vs. 44.7%; p&lt;0.05). Conclusions. The use of the proposed tactics for the treatment of miscarriage caused by CI made it possible to significantly reduce the frequency of miscarriage and improve its structure, avoid cases of spontaneous miscarriages and neonatal deaths, improve the condition of newborns, which makes it possible to recommend the introduction of this tactic in the practical work of obstetric and gynecological institutions. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Development and internal validation of a non-invasive clinical tool to predict sufficient omega-3 levels in early pregnancy

BackgroundComplications from preterm birth (PTB) are the leading cause of death and disability in those under five years. Whilst the role of omega-3 (n-3) supplementation in reducing PTB is well-established, growing evidence suggests supplementation use in those replete may increase the risk of early PTB. Aim: To develop a non-invasive tool to identify individuals with total n-3 serum levels above 4.3% of total fatty acids in early pregnancy.MethodsWe conducted a prospective observational study recruiting 331 participants from three clinical sites in Newcastle, Australia. Eligible participants (n = 307) had a singleton pregnancy between 8 and 20 weeks’ gestation at recruitment. Data on factors associated with n-3 serum levels were collected using an electronic questionnaire; these included estimated intake of n-3 (including food type, portion size, frequency of consumption), n-3 supplementation, and sociodemographic factors. The optimal cut-point of estimated n-3 intake that predicted mothers with total serum n-3 levels likely above 4.3% was developed using multivariate logistic regression, adjusting for maternal age, body mass index, socioeconomic status, and n-3 supplementation use. Total serum n-3 levels above 4.3% was selected as previous research has demonstrated that mothers with these levels are at increased risk of early PTB if they take additional n-3 supplementation during pregnancy. Models were evaluated using various performance metrics including sensitivity, specificity, area under receiver operator characteristic (AUROC) curve, true positive rate (TPR) at 10% false positive rate (FPR), Youden Index, Closest to (0,1) Criteria, Concordance Probability, and Index of Union. Internal validation was performed using 1000-bootstraps to generate 95% confidence intervals for performance metrics generated.ResultsOf 307 eligible participants included for analysis, 58.6% had total n-3 serum levels above 4.3%. The optimal model had a moderate discriminative ability (AUROC 0.744, 95% CI 0.742–0.746) with 84.7% sensitivity, 54.7% specificity and 37.6% TPR at 10% FPR.ConclusionsOur non-invasive tool was a moderate predictor of pregnant women with total serum n-3 levels above 4.3%; however, its performance is not yet adequate for clinical use.Trial registrationThis trial was approved by the Hunter New England Human Research Ethics Committee of the Hunter New England Local Health District (Reference 2020/ETH00498 on 07/05/2020 and 2020/ETH02881 on 08/12/2020).

Association between season of conception, month of conception with preterm birth in China: a population-based retrospective cohort study

BackgroundSeasonal patterns of preterm birth were identified in previous studies, but the effect of conception season on preterm birth has not been extensively studied. Based on the notion that the etiological roots of preterm birth lie in the beginning of pregnancy, we did a population-based retrospective cohort study in Southwest China to examine the effects of season of conception and month of conception on preterm birth.MethodsWe did a population-based retrospective cohort study in women (aged 18–49) who participated in the NFPHEP from 2010 to 2018, and had a singleton livebirth in southwest China. According to the time of the last menstruation reported by the participants, month of conception and season of conception were then ascertained. We used multivariate log-binomial model to adjust the potential risk factors for preterm birth and obtained adjusted risk ratio (aRR) and 95% confidence intervals (95%CI) for conception season, conception month and preterm birth.ResultsAmong 194 028 participants, 15 034 women had preterm birth. Compared with pregnancies that were conceived in the summer, pregnancies that were conceived in the spring, autumn and winter had the higher risk of preterm birth (Spring: aRR = 1.10, 95% CI: 1.04–1.15; Autumn: aRR = 1.14, 95% CI: 1.09–1.20; Winter: aRR = 1.28, 95% CI: 1.22–1.34) and also had a higher risk of early preterm birth (Spring: aRR = 1.09, 95% CI: 1.01–1.18; Autumn: aRR = 1.09, 95% CI: 1.01–1.19; Winter: aRR = 1.16, 95% CI: 1.08–1.25). Pregnancies in December, and January had a higher risk of preterm birth and early preterm birth than pregnancies that were conceived in July.ConclusionsOur study found that preterm birth was significantly related to season of conception. Preterm and early preterm birth rates were the highest among pregnancies that were conceived in winter, and the lowest among pregnancies in summer.