Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth

Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks’ gestation) and preterm birth (less than 37 weeks’ gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12–20 weeks’ gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1β, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Cerclage for the Management of Cervical Insufficiency: A Review

Cervical insufficiency (CI) is classically characterized as painless dilation of the uterine cervix in the second trimester that results in delivery of the pregnancy, typically prior to 24 weeks’ gestation. Treatment of the condition has centered on prevention of recurrence in women with a history of CI or early preterm birth. Universal screening tools for CI in women without a history of prior PTB are lacking. Cervical change that is painless may occur with minimal symptoms such as increasing of vaginal discharge/mucous, vaginal pressure or fullness; many women and their providers can dismiss pathologic symptoms that would otherwise be benign in women without CI. The management of CI is categorized as surgical vs. nonsurgical. The cornerstone of surgical management is composed of cervical cerclage, and may be placed by a transvaginal or transabdominal approach depending on the obstetric history. Nonsurgical management includes pessary or activity restriction. For women who have experienced a midtrimester loss due to suspected cervical insufficiency, postnatal or preconception consultation is essential to identify modifiable risk factors, collect medical records of the delivery, and review pathology results if available.

Maternal risk factors associated with preterm birth after IVF/ICSI

In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).is associated with an increased risk of preterm (33rd - 37th gestational week), and early preterm birth (20th - 32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4,328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: a) early preterm birth group (n=66), b) preterm birth group (n=675 ) and c) full-term birth group (n=3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (>39) or younger (<25) maternal age (OR:1.504, 95%CI: 1.108-2.042,P=0.009; OR: 2.125, 95%CI: 1.049-4.304,P=0.036, respectively), multiple pregnancy (OR: 9.780, 95%CI: 8.014-11.935,P<0.001; OR: 8.588, 95%CI: 4.866-15.157,P<0.001, respectively), placenta previa (OR: 14.954, 95%CI: 8.053-27.767,P<0.001; OR: 16.479, 95%CI: 4.381-61.976,P<0.001, respectively), and embryo reduction (OR: 3.547, 95%CI: 1.736-7.249,P=0.001; OR: 7.145, 95%CI: 1.990-25.663,P=0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95%CI: 1.770-3.514,P<0.001), elevated triglycerides (OR: 1.120, 95%CI: 1.011-1.240,P=0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95%CI: 0.949-0.985,P<0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor.

СERVICAL INSUFFICIENCY AND GENITAL INFECTION

Despite the availability of diagnostics and modern methods of treatment, preterm birth with cervical insufficiency occurs in 44-57% of cases, while early preterm birth reaches 38,8%. To date, there is no doubt about the connection of premature labor and intraamnial inflammation, the frequency of which in cervical insufficiency reaches 80%. Most researchers are unanimous in the opinion that the ascending route of infection in intraamnial infection is a priority. It has been proven that a decrease in the absolute and relative amount of Lactobacillus spp., A change in the species composition of lactoflora or atypical vaginal colonization associated with premature birth and premature rupture of membranes. Conditionally pathogenic microorganisms of the vaginal biotope with an insufficient number of lactobacilli are capable of producing various proteases that destroy collagen, constituting the basis of connective tissue and determining the elasticity of the membranes, which allows us to consider cervicovaginal infections as one of the mechanisms of premature remodeling of the cervix and rupture of membranes. In that way, it is relevant to study the frequency and structure of genital infection in cervical insufficiency. The analysis of medical literature data, presented in the electronic libraries Elibrary and Pubmed for the last 10 years, devoted to the study of genital infection in cervical insufficiency. The issue of the relationship of cervicovaginal infections with premature remodeling of the cervix of the uterus was discussed, as well as studies on the role of intrauterine infection in the genesis of preterm labor. The results of scientific studies are presented, indicating both the direct influence of cervical incompetence on the risk of intraamnial infection and the root cause of genital infection in the pathogenesis of cervical insufficiency. Convincing data are given that timely diagnosis and treatment of violations of the vaginal biocenosis is one of the significant links in the prevention of premature birth. It is necessary to further study the pathogenetic relationship of cervicovaginal infections and cervical insufficiency.

Causes and clinical picture of very early preterm birth

The objective: the determination of the risk factors, causes and clinical features of very early preterm birth.Materials and methods. The data of anamnesis, the course of pregnancy, childbirth and perinatal outcomes in 166 women of reproductive age with very early preterm birth at 22–27 weeks of gestation were analyzed. The fact of childbirth at these terms of pregnancy is the main criterion of inclusion. The patients were divided into two groups depending on the criteria of live birth: 1 group — 79 women, whose labor was regarded as late miscarriage (retrospective study); 2 group — 87 women with very early preterm (prospective study). Exclusion criteria: congenital malformations of the fetus. Results. The main risk factors for the development of very early preterm labor are urogenital infections (83.7 % and 78.9 % in 1 and 2 groups, respectively). A combination of pathogens was found in almost half of the subjects (43 % in 1 group, 44 % in 2 group). The patients in both groups had a complicated general and obstetric anamnesis, in particular, a significant frequency of inflammatory processes of the genital organs (50.0 % – in 1 group and 59.2 % – in 2 group), surgical interventions (50.0 % and 59.2 %, respectively), as well as hormonal disorders and related diseases (ovarian dysfunction – 27.8 % and 27.6 %, uterine fibroids – 16.4 % and 17. 2%, ovarian cysts – 11.4 % in both groups). 35.4 % of patients in 1 group and 28.7 % of patients in 2 group had a history of chronic foci of infections, pathology of the urinary system – 30.3 % and 28.7 %, respectively, of the digestive tract – 24 % and 22.98 %, hypertension – 32.9 % and 31 %. The main complications of gestation in pregnant women in both groups in the II trimester were the threat of abortion (43 % and 30 %, respectively) and dysfunction of the fetoplacental complex (22.7 % and 21.8 %). This caused fetal growth retardation in both groups – 66 % and 63 % of newborns, respectively.Conclusions. Analysis of the general and obstetric history, the presence of infectious factor in combination with extragenital pathology confirm the polyetiology of the causes that leads to very early preterm birth. Considering the main risk factors of preterm birth, a complete examination for urogenital infections in women before and during pregnancy, followed by treatment and restoration of normal vaginal biocenosis, as well as the study of fetoplacental system function from early pregnancy is neseccary.Preventive measures and timely treatment of fetoplacental disorders should prolong pregnancy for the terms in which there is the best way to improve perinatal outcomes.