Perinatal outcomes of twin emergency cerclage: comparison with expectant treatment and singleton emergency cerclage.

The present study aimed to evaluate the perinatal outcomes and influencing factors in twin pregnancies undergoing emergency cervical cerclage. The present retrospective cohort study included clinical data that were recorded between January 2015 and December 2021 at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (China). The study included data from 103 pregnancies (26 twin and 77 singleton pregnancies) that underwent emergency cerclage and 17 twin pregnancies that underwent expectant treatment. The median gestational age of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but higher than that of expectant treatment (28.5, 34.0 and 24.0 weeks, respectively). The median interval to delivery of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but significantly higher than that of expectantly treated twin pregnancies (37.0, 78.0 and 7.0 days, respectively).IMPACT STATEMENTWhat is already known on this subject? An important cause of premature birth is cervical insufficiency. Cervical cerclage extends the gestational period of women with cervical insufficiency. According to 2019 SOGC's No. 373-Cervical Insufficiency and Cervical Cerclage, both twin and single pregnancies benefit from emergency cerclage. However, there is minimal information about the pregnancy outcomes of emergency cerclage in twin pregnancies.What the results of this study add? This study shows that the outcomes of pregnancy in twin pregnancies undergoing emergency cerclage were better than that of expectant treatment but worse than that in singleton pregnancies undergoing emergency cerclage.What the implications are of these findings for clinical practice and/or further research? In this study, pregnant women with cervical insufficiency in twin pregnancies can benefit from emergency cerclage, we should treat those pregnant women as early as possible.

The effects of intrauterine growth on physical and intellectual development of one-year-old infants: a study on monochorionic twins with selective intrauterine growth restriction.

This study aimed to evaluate physical and intellectual development of one-year-old infants of monochorionic twins with selective intrauterine growth restriction (sIUGR). A total of 31 pairs of sIUGR twins ageing 1 year old were included in the study. Each pair of sIUGR twins was divided into low birthweight-twin group (L-twin group) and high birthweight-twin group (H-twin group) according to twins' birthweight. The differences in height, weight, head circumstance and body mass index (BMI) in each stage were statistically significant for all measures from birth until 1 year old (p < .05), and there was a disappointed catch-up growth in lighter twins. Psychomotor development index (PDI) and mental development index (MDI) at 1 year old were significantly different between the two groups (p < .05). Stepwise regression analysis showed that the effects of weight on both PDI and MDI were statistically significant (p < .05). Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development.Impact StatementWhat is already known on this subject? Selective intrauterine growth restriction in monochorionic twins increases the risks of intrauterine foetal demise, preterm birth, caesarean delivery and adverse neonatal outcomes, especially in the smaller foetus.What do the results of this study add? Previous studies have concentrated on the clinical management of sIUGR, while little attention has been paid to the growth and development of twins after birth. Given the adverse neurobiological effects of suboptimal nutrition on the brain development, it is important to determine whether IUGR causes long-term cognitive deficits and physical retardation. The current study has assessed the physical and intellectual development of one-year-old infants of monochorionic twins with sIUGR.What are the implications of these findings for clinical practice and/or further research? Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development. Further research on the longer-term effects of sIUGR is needed.

Physical growth and intelligence development of discordant dizygotic twins from birth to preschool age: a prospective cohort study.

BACKGROUND: The majority of studies are limited to adverse perinatal outcomes and poor cognitive abilities in the short term in discordant monochorionic twins. METHODS: To determine whether small and large discordant dizygotic twins differ in physical growth and intelligence development and weight and height from birth up to 6 years of age were measured in 34 dizygotic twin pairs with ≥ 20% birth weight discordance. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated at 1 year, while the Wechsler Intelligence Scale for Children-IV (WISC-IV) full-scale intelligence quotient (IQ) was assessed at the age of 6. RESULTS: The difference in height and weight in each stage differed significantly from birth to 72-months-old (P < 0.05), although there was disappointing catch-up growth in smaller twins. PDI but not MDI at 1 year of age was significantly different between the two groups (P < 0.05), and smaller twins experienced higher psychomotor retardation rates (P < 0.05). Also, the influence of height and weight on PDI was statistically significant (P < 0.05). No significant difference was detected in the WISC-IV full-scale IQ at the age of 6; however, the full-scale IQ may be affected by the history of suffocation and the S/D value (P = 0.011, P = 0.022). CONCLUSIONS: Intrauterine fetal growth and development lead to birth weight differences in twins and sustain an impact on the children's physical growth in height and weight from birth to preschool age, causing psychomotor developmental differences at 1 year of age. However, the differences in psychomotor development decrease gradually by the age of 6.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring.

Background: The adverse impact of maternal negative TPOAb of gestational subclinical hypothyroidism (SCH-TPOAb-) on the development of the offspring has not yet been clearly identified. A lingering controversy exists over the treatment of SCH-TPOAb- diagnosed during pregnancy. Therefore, this study was designed to evaluate the intellectual development of children of mothers who had SCH-TPOAb-. Methods: A number of 139 children were recruited; 112 children were born to SCH TPOAb- and 27 children were born to euthyroid TPOAb- mothers. Based on the mothers' thyrotropin (TSH) levels during pregnancy and whether or not they received levothyroxine (LT4) treatment, the children were assigned to four groups: Group A (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 31) and Group B (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 26), whose mothers were treated with LT4 before eight gestational weeks, and Group C (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 27) and Group D (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 28), whose mothers received no treatment. A total number of 27 children whose mother's serum TSH was <2.5 mIU/L and were TPOAb- during their pregnancy served as the control group (Group E). The intellectual development of two-year-old children was assessed and compared using the Gesell Development Diagnosis Scale. Results: The developmental quotient (DQ) in Group D was 8.67 lower than this in Group E (p < 0.001). More specifically, gross motor quotient, fine motor quotient, adaptability quotient (ABQ), language quotient (LQ), and individual social behavior quotient (ISBQ) of DQ in Group D were significantly lower than those in Group E. No significant differences were observed in DQ among Group A, Group B, Group C, and Group E (p > 0.05). Spearman's rank correlation analysis showed that DQ, FMQ, ABQ, LQ, and ISBQ were significantly negatively correlated with the TSH level (r = -0.417, -0.253, -0.273, -0.436, and -0.272; p < 0.05). In addition, multivariate logistic regression analysis revealed that mothers' education (short education), mothers' education (medium education), and TSH level (4.0 mIU/L < TSH ≤10.0 mIU/L) were both risk factors affecting the intellectual development of the offspring (p < 0.05). Conclusion: The effects of the intellectual development of the offspring with SCH-TPOAb- are related to the level of TSH. Standardized treatment for SCH-TPOAb- pregnant women before eight gestational weeks, whose TSH level was from 4.0 to 10.0 mIU/L, may significantly improve the intellectual development levels of the approximately two-year-old offspring. Although our study was a historical cohort study, the data analyzed provide the foundation for further investigation. Further prospective intervention trials with large numbers of participants are needed to confirm our conclusions. The Clinical Trial Registration number is 2021-K-84-02.

Kiwi Root Extract Inhibits the Development of Endometriosis in Mice by Downregulating Inflammatory Factors.

PURPOSE: To determine whether the kiwi root extract inhibits the development of endometriosis in mice by suppressing inflammatory factors. MATERIALS AND METHODS: The mouse model of endometriosis was induced by surgery after which the mice were continuously injected with the drug for 14 days. On the 14th day, the mice were sacrificed, and the peritoneal fluid was obtained for enzyme-linked immunosorbent assay. Endometrial ectopic tissue was weighed and analyzed by tissue immunochemistry, RT-PCR, western blotting, and gelatin zymography experiment. RESULTS: Kiwi root extract significantly reduced endometriotic lesion volume and downregulated the proinflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α, as well as the angiogenic factor VEGF-A. It also inhibited the mRNA and protein expression of COX-1 and COX-2, IL-6, TGF-ß1, EP2 receptor, and ER-ß in endometriotic lesions but did not affect the expression of MMP-9 and MMP-2. CONCLUSIONS: Kiwi root extract could significantly inhibit the growth of surgery-induced endometriosis in mice. Our results suggest that the kiwi root extract may inhibit the development and progression of ectopic endometrium through disruption of neovascularization and reducing inflammation, which may be beneficial in treating this common gynecological disease.

Formyl-peptide receptor 2 suppresses proliferation, migration and invasion in human extravillous trophoblastic cells.

Although FPR2 receptor is distributed in the endometrium and placenta, its function in human extravillous trophoblastic (TEV-1) cells still remains enigmatic. In this study, overexpression of FPR2 was performed in TEV-1 cells. Then, CCK8 transwell and wound healing assays were used to assess the cell proliferation, migration and invasion, respectively. The results showed that FPR2 overexpression significantly inhibited proliferation, invasion and migration in TEV-1 cells. In addition, FPR2 overexpression significantly decreased mRNA and protein levels of integrin-linked kinase (ILK), nuclear factor-kappa B (NF--κB), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) in TEV-1 cells. These findings indicated that FPR2 overexpression alters proliferation, migration and invasion in human extravillous trophoblastic cellsthrough the ILK/NF-κB signaling pathway; ideal FPR2 levels are important for TEV-1 cells functions.

Lipoxin A4 interferes with embryo implantation via suppression of epithelial-mesenchymal transition.

PROBLEM: To test whether lipoxin A4 (LXA4) interferes with embryo implantation via suppression of epithelial-mesenchymal transition (EMT). METHOD OF STUDY: We developed a mouse model of LXA4 blocking embryo implantation and detected the indicators of EMT to confirm that LXA4 inhibits EMT might be a mechanism of interfering with the embryo implantation. We detected integrin-linked kinase (ILK), N-formylpeptide receptor 2 (FPR2), vascular endothelial growth factor, matrix metalloproteinases (MMPs), Akt, GSK3ß, NF-ĸB, twist, vimentin, fibronectin, and ß-catenin mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; localized protein expression using immunohistochemistry and Western blotting assay; MMPs activity assay by gelatin zymography; and the status of implantation in pregnant animals assessed by pontamine blue reaction test. RESULTS: Preimplantation administration of LXA4 resulted in implantation failure. LXA4 has a time- and dose-dependent effect on embryo implantation. Day 0.5 after fertilization is the most effective time to use LXA4 to block embryo implantation. (a) LXA4 reduced endometrial stroma edema; (b) LXA4 inhibited the activity of MMP9 and significantly upregulated the expression of ß-catenin, and downregulated the expression of vimentin, fibronectin, twist, NF-κB, Akt, and Gsk-3ß in the endometrium and TEV-1 cells; (c) LXA4 upregulated the expression of FPR2, and downregulated the expression of ILK; FPR2-overexpressing had an inhibitory effect on ILK in TEV-1 cells. CONCLUSION: LXA4 inhibits EMT which attenuates ILK action by enhancing FPR2; therefore, this might be a mechanism of interfering with embryo implantation.

Preeclampsia is associated with a deficiency of lipoxin A4, an endogenous anti-inflammatory mediator.

OBJECTIVE: To test whether lipoxin A4 (LXA4) deficiency results in preeclampsia. DESIGN: Prospective experimental study. SETTING: Patient and animal research facilities. ANIMAL(S): Sprague-Dawley rats. INTERVENTION(S): We measured LXA4 and its biosynthetic enzymes, blocked the LXA4 signaling pathway, treated experimental rats with preeclampsia with LXA4, and detected inflammatory factors, FPR2/ALX, and 11ß-HSD2 to systematically test whether lack of LXA4 results in preeclampsia. MAIN OUTCOME MEASURE(S): We measured serum levels of LXA4 and inflammatory factors using enzyme-linked immunosorbent assay; detected LXA4 biosynthetic enzymes, inflammatory factors, FPR2/ALX, and 11ß-HSD2 mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; and localized protein expression using immunohistochemistry. RESULT(S): FPR2/ALX and LXA4 and its biosynthetic enzymes were found to be decreased in women with preeclampsia. Replenishing LXA4 improved the symptoms of lipopolysaccharide-induced rats with preeclampsia, while blocking LXA4 signaling resulted in preeclampsia. LXA4 significantly reduced interleukin-6 (IL-6), tumor necrosis factor-α, and IFN-γ but increased IL-10, LXA4 up-regulated 11ß-HSD2. CONCLUSION(S): A deficiency of LXA4 may result in preeclampsia, which might be ascribed to a reduction in inflammation response, oxidative stress, and regulation of 11ß-HSD2.

Lipoxin A4: The double-edge sword in mice pregnancy.

PROBLEM: To evaluate the role for LXA4 in the pregnancy. METHOD OF STUDY: We detected the changes of LXA4 and LXA4 biosynthetic enzymes in the mice's pregnancy, blocked LXA4 signaling pathway, managed LXA4 level, and treated LPS-induced mouse abortion model to systematically determine how LXA4 impact pregnancy. RESULTS: The concentrations of LXA4 in serum and uterus were lowest on Days 4.5 of pregnancy and in labor as compared to Day 12.5 of pregnancy (270.2 ± 33.2, 277.5 ± 23.7 versus 457.1 ± 40.9 pg/mL). Inhibition of the LXA4 signaling pathway did not affect pregnancy during the peri-implantation period of pregnancy, but induced abortion when administered after implantation of blastocysts. High levels of LXA4 interfered with implantation, but protected mice from aborting in response to LPS. CONCLUSION: LXA4 might be involved in the process of pregnancy, and LXA4 might act as the double-edge sword in pregnancy: the anti-implantation effect in the stage of peri-implantation and the anti-abortion affect after blastocyst implantation.