Half Of Pregnancy Research Articles

Synthesis of cytokines during physiological pregnancy

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy. The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

A Multiscale Mathematical Model for the Fetal Blood Circulation of the Second Half of Pregnancy.

Doppler ultrasound is a commonly used method to assess hemodynamics of the fetal cardiovascular system and to monitor the well-being of the fetus. Indices based on the velocity profile are often used for diagnosis. However, precisely linking these indices to specific underlying physiology factors is challenging. Several influences, including wave reflections, fetal growth, vessel stiffness, and resistance distal to the vessel, contribute to these indices. Understanding these data is essential for making informed clinical decisions. Mathematical models can be used to investigate the relation between velocity profiles and physiological properties. This study presents a mathematical model designed to simulate velocity wave propagation throughout the fetal cardiovascular system, facilitating the assessment of factors influencing velocity-based indices. The model combines a one-fiber model of the heart with a 1D wave propagation model describing the larger vessels of the circulatory system and a lumped parameter model for the microcirculation. Fetal growth from 20 to 40 weeks of gestational age is incorporated by adjusting cardiac and circulatory parameter settings according to scaling laws. The model's results, including cardiac function, cardiac output distribution, and volume distribution, show a good agreement with literature studies for a growing healthy fetus from 20 to 40 weeks. In addition, Doppler indices are simulated in various vessels and agree with literature as well. In conclusion, this study introduces a novel closed-loop 0D-1D mathematical model that has been verified against literature studies. This model offers a valuable platform for analyzing factors influencing velocity-based indices in the fetal cardiovascular system.

Individual empowerment and community norm effects of engaging young husbands in reproductive health in rural India: findings from a pilot study

BackgroundDespite decades of a call to action to engage men in reproductive health, men are often left out of programs and interventions. In India, where half of pregnancies are reported as unintended, patriarchal gender norms and still dominant patterns of arranged marriages make engaging men in family planning and strengthening couples communication critical in increasing reproductive autonomy and helping young couples meet their reproductive goals. This study explores the feasibility and acceptability from the men’s perspective of the pilot of a gender transformative intervention for newly married couples in India.MethodsA pilot study was conducted of TARANG, a 4 month intervention for newly married women, with light touch engagement of husbands (4 sessions). A total of 41 husbands participated in the pilot, and we collected baseline knowledge and endline feasibility and acceptability data from them, along with in depth qualitative interviews with 13 men. The study was conducted in June 2023-January 2024.ResultsMen had low levels of knowledge about biology, family planning, with the majority of men reporting that no one had provided them information about these topics. Most men wanted to delay the first birth by at least 2 years, yet less than a quarter had discussed childbearing plans with their partner or engaged in family planning methods. While all men reported high acceptability (satisfaction and usefulness), feasibility (participation) was low, with only 43% attending 2 or more sessions. Main barriers to participation included commitments due to work and migration. Men reported that the intervention led to improvements in their relationships with their wives, gave them a sense of empowerment, and led them to become resources for other men in their community.ConclusionsMen in these rural communities are not receiving the information that they need to meet their reproductive goals, however, they greatly desire this information and ways to improve relationships with their new wives. Such an intervention appears to have the potential to help change norms and spread information in the community and provide men with positive, life affirming feelings. Providing information through technology could address barriers to in-person engagement.Trial registration clinicaltrials.gov 03/13/24.NCT06320964

Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology.

Low maternal urinary iodine concentration (UIC) during pregnancy is associated with adverse offspring neurodevelopment. Thyroglobulin (Tg) has been suggested as a more sensitive biomarker than UIC of long-term iodine status, but associations of Tg with neurodevelopment and the possible mediating role of thyroid function remain unknown. To study whether maternal Tg is associated with i) maternal and newborn thyroid function and ii) offspring IQ and brain morphology. Participants were selected from two population-based prospective cohorts: Generation R (the Netherlands, iodine-sufficient) and INfancia y Medio Ambiente (Spain, mildly iodine-deficient) with maternal Tg and thyroid function data in the first half of pregnancy or in cord blood, early childhood IQ (age 4.5 and 6 years), late childhood IQ (age 9 and 13), or brain morphology at 10 years. Associations of Tg with TSH, FT4, IQ and brain morphology were studied with multivariable linear regression. i) Tg was associated with lower TSH (-0.12[-0.16; -0.08]) and higher FT4 (0.08[0.05;0.12]) in pregnancy (N=4,367), but not with cord blood TSH or FT4 (N=2,008). ii) Tg was associated with lower IQ in early childhood (β[95% CI]:-0.06 [-0.10; -0.01], N=2,919), but not with IQ (N=2,503) or brain morphology (N=1,180) in later childhood. None of the associations of Tg with the studied outcomes differed by the iodine-to-creatinine ratio (i.e. effect modification) or changed when adjusted for thyroid function. Higher Tg is associated with lower IQ in early childhood and higher thyroid function during pregnancy, but not with IQ or brain morphology in later childhood. Further research should determine the value of Tg in addition to UIC for defining iodine status.

Placental Nanoparticle-mediated IGF1 Gene Therapy Corrects Fetal Growth Restriction in a Guinea Pig Model.

Fetal growth restriction (FGR) caused by placental insufficiency is a major contributor to neonatal morbidity and mortality. There is currently no in utero treatment for placental insufficiency or FGR. The placenta serves as the vital communication, supply, exchange, and defense organ for the developing fetus and offers an excellent opportunity for therapeutic interventions. Here we show efficacy of repeated treatments of trophoblast-specific human insulin-like 1 growth factor (IGF1) gene therapy delivered in a non-viral, polymer nanoparticle to the placenta for the treatment of FGR. Using a guinea pig maternal nutrient restriction model (70% food intake) of FGR, nanoparticle-mediated IGF1 treatment was delivered to the placenta via ultrasound guidance across the second half of pregnancy, after establishment of FGR. This treatment resulted in correction of fetal weight in MNR + IGF1 animals compared to sham treated controls on an ad libitum diet, increased fetal blood glucose and decreased fetal blood cortisol levels compared to sham treated MNR, and showed no negative maternal side-effects. Overall, we show a therapy capable of positively impacting the entire pregnancy environment: maternal, placental, and fetal. This combined with our previous studies using this therapy at mid pregnancy in the guinea pig and in two different mouse model and three different human in vitro/ex vivo models, demonstrate the plausibility of this therapy for future human translation. Our overall goal is to improve health outcomes of neonates and decrease numerous morbidities associated with the developmental origins of disease.

Embryonic and Fetal Mortality in Dairy Cows: Incidence, Relevance, and Diagnosis Approach in Field Conditions

Pregnancy loss (PL) in dairy cattle results in animal health and welfare disruption and has a great economic impact on farms, with decreases in fertility and increased culling. It can occur at any stage of embryonic or fetal development. Abortion occurring from the second half of pregnancy has a more negative impact on dairy farms. There are several infectious and non-infectious factors that can lead to PL and vary according embryonic or fetal stages. As this is a multifactorial or multi-etiological occurrence, it is important to identify the risk factors and the best diagnostic tools to approach these reproductive losses that can occur sporadically or by outbreaks. Reaching a final diagnosis can be challenging, especially when it occurs at a very early stage of pregnancy, where losses may not be detected and neonatal deaths may be related to alterations in the fetus in utero. Also, laboratorial results from animal samples should be interpreted according to the full clinical approach. This review aimed to highlight all these essential aspects, identifying the main infectious and non-infectious causes leading to PL, as well as the best veterinary practices for diagnosing it, mainly through transrectal palpation, ultrasound, and laboratory methods, in bovine dairy farms.

Potential teratogenic effect of prenatal dexamethasone administration on palate development: Experimental study in rats

BackgroundThe interaction of cell populations and synchronization of cell signaling pathways during craniofacial development can cause malformations such as facial clefts when interrupted by teratogenic agents including synthetic corticosteroids. Therefore, this study aimed to determine the potentially disturbing dexamethasone (Dex) effect on palatal shelf development in rat embryos and the possible reasons for this teratogenic potential in relation to fibroblast growth factor 10 (FGF10) as well as FGF10 receptor2 (FGFR2) signaling. MethodsThirty pregnant rats were used, which were then randomly categorized into three groups of ten animals each: the control group, where pregnant rats received no treatment, Sham group in which pregnant rats were injected subcutaneously with saline (0.4 mg/kg body weight) during the mid-pregnancy period at gestational day 9–14, and Dex-treated group, where pregnant rats received 0.4 mg/kg of Dex at mid-gestational period. Pregnant animals from all groups were sacrificed on day 20 of gestation before birth and the fetuses were removed for examination of the palatal shelves using a light microscope (LM). In addition, a real-time polymerase chain reaction and a reverse transcription-polymerase chain reaction (RT-PCR) were done to evaluate FGF10 and its receptor FGFR2 gene expression. ResultsThe cleft palate incidence rates in the groups of embryos were determined. Only the offspring in the Dex group showed a cleft palate. Moreover, the cleft palate incidence rate in the Dex group was significantly different compared to controls. Moreover, a significant decrease in FGF10 and FGFR2 expression levels was reported in the Dex group than in the controls. ConclusionsDex treatment in mid-gestation may increase the incidence of cleft palate development, which may be due to modulation of FGF signaling. This calls for caution when using this medication in the first half of pregnancy unless absolutely necessary and under close medical supervision.

Role of chronic kidney disease and risk factors in preeclampsia

BackgroundOur goal was to identify what impact chronic kidney disease (CKD) and its associated risk factors, such as body mass index (BMI), diabetes and hypertension, have on preeclampsia and other adverse pregnancy outcomes in the CKD population. MethodsThis was a population-based cohort study of women with CKD who had a pregnancy from 2010 to 2022 (n = 95). At the time of the woman’s pregnancy, data was collected on demographics, clinical measures, BMI, CKD etiology and other renal parameters. Outcomes included preeclampsia, pre-term delivery, and low birth weight. ResultsPre-pregnancy BMI increased over time in patients with CKD, with a median (interquartile range) BMI of 25 (22–29) prior to 2016 and 29 (25–34) after 2016 (p = 0.01). There were significant trends of increasing age at delivery and decreasing pre-pregnancy estimated glomerular filtration rate (eGFR) by delivery year. Preeclampsia affected nearly half of pregnancies in this cohort. In multivariate analyses, BMI and chronic hypertension did not impact the odds of preeclampsia, preterm delivery or low birth weight, though a CKD etiology of diabetes (19/20 with type I diabetes), was associated with a significant increase in preeclampsia risk (odds ratio (OR) 7.41 (95 % CI 2.1–26.1)). Higher pre-pregnancy eGFR was associated with a lower odds of preterm delivery (OR 0.81 (95 % CI 0.67–0.98)) per 10 ml/min/1.73 m2). ConclusionPre-pregnancy BMI significantly increased over time, similar to the general population. While preeclampsia was common in CKD patients, outcomes were associated with eGFR and CKD etiology as opposed to BMI and chronic hypertension.

Neonatal Thyrotoxicosis in Infants of Mothers with Graves' Disease Treated for Radioiodine-Induced Hypothyroidism: A Literature Review.

Fetal and neonatal thyrotoxicosis occurs in up to 5% of pregnancies in mothers with Graves' disease (GD). This condition is caused by stimulating antibodies against the thyrotropin receptor (TRAbs) that cross the placenta and may stimulate the fetal thyroid, typically in the second half of pregnancy. GD is often treated with radioiodine, resulting in hypothyroidism in most patients, but TRAbs can persist for several years. Even if a pregnant mother is hypothyroid after radioiodine therapy or surgery, her TRAbs can still, although rarely, induce fetal hyperthyroidism. In this review, we first present two cases of neonatal hyperthyroidism in mothers with GD who became hypothyroid after prior radioiodine therapy, identified through a 10-year analysis of the National Perinatal System in Slovenia. Based on these cases, we provide an overview of existing data on this rare clinical condition in neonates. We also discuss the underlying mechanisms and clinical outcomes based on currently available data. In conclusion, our review highlights the importance of careful monitoring during pregnancy in all women with GD, even in those well managed after radioiodine therapy or surgery.

Rhekiss-The German Register for Child Wish and Pregnancies in Inflammatory Rheumatic Diseases.

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs.

Progression of Gestational Subclinical Hypothyroidism and Hypothyroxinemia to Overt Hypothyroidism After Pregnancy: Pooled Analysis of Data from Two Randomized Controlled Trials.

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

In women with epilepsy, use of valproate in the second half of pregnancy was linked to autism in offspring.

Hernández-Díaz S, Straub L, Bateman BT, et al. Risk of autism after prenatal topiramate, valproate, or lamotrigine exposure. N Engl J Med. 2024;390:1069-1079. 38507750.

Association of pre-pregnancy anthropometric factors and mediterranean diet score with hyperemesis gravidarum: Results from a hospital-based case-control study

BackgroundHyperemesis gravidarum (HG) is the most widespread reason for admission to the hospital during the first half of pregnancy. HG etiology is not clear in many cases. However, maternal body composition and pre-pregnancy diet are suggested as possible factors. This hospital-based case-control study aims to determine the link between the Mediterranean diet score (MDS) and pre-pregnancy anthropometric indicators with Hyperemesis gravidarum. MethodsA total of 45 women with incident HG and 126 controls were entered into this case-control study between April 2020 and June 2021. A repeatable and accurate 168-item semi-quantitative food frequency questionnaire was used to define the MDS. The association between MDS and HG odds was examined through adjustment by possible confounders by the estimation of multivariate regression models. ResultsThe median (interquartile range) pre-pregnancy body mass index of participants was 22.7 (21.7-25.9) and 22.9 (21.4-25) Kg/m2 in cases and controls, respectively (P=0.284). The adjusted analyses found that the MDS was associated with a 25% reduced odds of HG (odds ratio (OR): 0.75, 95% confidence interval (95%CI): 0.24-0.91). Body mass index and waist circumference before pregnancy were not significantly associated with HG odds in both regression models. ConclusionsThe odds of HG during pregnancy are lower in women with a higher MDS before pregnancy. Also, a high intake of fruits and nuts, vegetables, legumes, and fish before pregnancy is liked with a lower HG odds.

Modern trends in the treatment of bacterial vaginosis in primigravida in the first half of gestation

Pregnancy with bacterial vaginosis (BV) is accompanied by a high risk of various obstetric and perinatal complications, including miscarriage, preterm birth, placental dysfunction, premature rupture of membranes, chorionamnionitis, polyhydramnios, etc. Screening for BV is carried out in the first half of pregnancy during the registration of a woman, however, taking into account the gestational age, many drugs with antimicrobial and antiseptic effects are categorically contraindicated, as they have an embryo- and fetotoxic effect.Timely detection and correction of microbiocenosis disorders of the birth canal is an extremely important element to prevent a number of obstetric and perinatal complications. A balanced approach in the treatment of vaginal dysbiosis consists in the use of modern combined antiseptic preparations for local treatment, which do not contain antibacterial components and are safe for use during pregnancy.The objective: to determine the effectiveness of the treatment of BV in primigravida women in the first half of pregnancy.Materials and methods. 126 primigravida women aged 18–35 years in the first half of pregnancy were examined during pregnancy registration. The participants were selected randomly.The main group included 36 primigravida women with a gestation period of up to 20 weeks with a diagnosis of BV according to the Amsel and Hay–Ison criteria, who were treated with a combined antiseptic drug (chlorhexidine and chlorophyllipt) – suppository vaginally twice a day, the course of treatment – 5 days. The control group included 30 primigravida women with a gestational age of up to 20 weeks with vaginal normocenosis.For all women the pH of vaginal secretions was determined, followed by microscopy of a native smear, stained according to Gram, and a cultural study was performed. Adherence to the Amsel criteria was also determined, followed by evaluation by the Hay–Ison criteria. The clinical effect was evaluated according to clinical examination data before and on the 6th day of treatment with a combined antiseptic drug (chlorhexidine and chlorophyllipt) using bacterioscopic and bacteriological methods.Results. A normal pH was observed only in every fifth part of examined pregnant woman (28 women – 22.2%), while in the rest patients the acidity of the vaginal environment was not normal. Normocenosis was observed only among 1/3 of primigravida women (37 women – 29.4%). A third of the patients were diagnosed with BV (36 women - 28.6%), every fifth pregnant woman – vulvovaginal candidiasis (28 women - 22.2%).In healthy pregnant women (control group, n=30), the main component of the microbiocenosis was Lactobacillus spp. with a small content of facultatively anaerobic microorganisms. In the main group Atopobium vaginae (38.9%), Gardnerella vaginalis (33.3%), Prevotella bivia (27.8%), Candida spp. (22.2%), as well as Lactobacillus spp. in low titers were dominated. Before the treatment all 36 pregnant women of the main group corresponded to the 3rd type according to the Hay–Ison criteria with the dominance of Gardnerella vaginalis and/or Mobiluncus morphotypes and a small number or complete absence of lactobacilli, which served as the basis for establishing the diagnosis of BV. After treatment type 1 (94.4%) was found in 34 pregnant women, and type 2 (5.6%) – in 2 pregnant women.The results of the microbiological study indicate the normalization of the content of the biotope with the predominance of Lactobacillus spp. in women of the main group, in whom the indicators were similar to the control group.Conclusions. Since pregnancy with BV is accompanied by a high risk of obstetric and perinatal complications, the premorbid background of which is laid already in the first half of pregnancy, there is an urgent need to carry out the birth canal sanitation. The drugs of choice for the BV in the first half of pregnancy are local combined agents of a wide spectrum of action.A universal antiseptic with an anti-inflammatory effect, which includes two components – chlorhexidine and chlorophyllipt, fully meets the recommendations for efficiency and safety and can be used for the BV in the first half of pregnancy.

Histological Observations of the Developing Human Fetal Humerus at Different Trimesters of Pregnancy

Background: Although femur length is the preferred method for fetal age assessment, the humerus is sometimes the right choice, especially in the second half of pregnancy. Fetal bone development significantly impacts adult bone quality and senescent bone disorders, including osteoporosis. Purpose of the study: The present study aimed to ascertain the histological changes in the human fetal humerus across the three trimesters. After the institutional ethical committee clearance and parent consent, the study was carried out on stillborn or medically terminated human fetuses from the 10th to the 32nd week of intrauterine life. Results: First trimester: The primary bone collar appeared with the primary ossification center, marked by more vascular invasion and a pool of mesenchymal cells. Trabeculations begin from the bony collar and insignificant periosteum. Second trimester: The changes showed longitudinal growth of periosteal bone towards the proximal and distal ends of the growing bone. Growth plate with distinguished zones and gradual fusion of epiphysis with growth plate were observed. Third trimester: Trabeculation number and thickness increase with calcification. Towards the third trimester, the marrow cavity with increased and prominent trabeculations is consistent. Conclusion: Understanding normal microstructural and cellular events chronologically is an ideal platform for future studies to develop cell-based or cell-targeted therapies for adult bone disorders, traumatic bone injuries, or bone engineering. KEYWORDS: Histology, Developing Bone, Humerus, Fetuses, Embryology.

Small RNAs in the pathogenesis of preeclampsia

Preeclampsia is a major contributor to maternal and fetal morbidity and mortality. The disorder can be classified into early- and late-onset subtypes, both of which evolve in two stages. The first stage comprises the development of pre-clinical, utero-placental malperfusion. Early and late utero-placental malperfusion have different causes and time courses. Early-onset preeclampsia (20 % of cases) is driven by dysfunctional placentation in the first half of pregnancy. In late-onset preeclampsia (80 % of cases), malperfusion is a consequence of placental compression within the confines of a limited uterine cavity. In both subtypes, the malperfused placenta releases stress signals into the maternal circulation. These stress signals trigger onset of the clinical syndrome (the second stage). Small RNA molecules, which are implicated in cellular stress responses in general, may be involved at different stages. Micro RNAs contribute to abnormal trophoblast invasion, immune dysregulation, angiogenic imbalance, and syncytiotrophoblast-derived extracellular vesicle signalling in preeclampsia. Transfer RNA fragments are placental signals known to be specifically involved in cell stress responses. Disorder-specific differences in small nucleolar RNAs and piwi-interacting RNAs have also been reported. Here, we summarise key small RNA advances in preeclampsia pathogenesis. We propose that existing small RNA classifications are unhelpful and that non-biased assessment of RNA expression, incorporation of non-annotated molecules and consideration of chemical modifications to RNAs may be important in elucidating preeclampsia pathogenesis.

Maternal early life and prenatal stress in relation to birth outcomes in Argentinian mothers.

Environmental influences before and during pregnancy significantly impact offspring development. This study investigates open research questions regarding the associations between maternal early life stress (ELS), prenatal psychosocial stress, prenatal hair cortisol (HC), and birth outcomes in Argentinian women. Data on ELS, prenatal life events, HC (two samples representing first and second half of pregnancy), and birth outcomes were collected from middle-class Argentinian women (N=69) upon delivery. Linear mixed models indicated that HC increased from the first half to the second half of pregnancy with considerable variability in the starting values and slopes between individuals. Mothers who experienced more ELS, were taller, or more educated, tended to show lower increases in HC. Older age was positively related to HC increases. Our data did not suggest an interaction between ELS and prenatal life events in relation to HC. We found that the change in HC was most likely negatively associated with birth weight. Our data are most compatible with either a weak or the absence of an association between ELS or prenatal life events and absolute values of HC. Mothers with stronger increases in hair cortisol tended to have newborns with slightly lower birth weight. Hence, ELS and birthweight may either have been related to changes in cortisol exposure during pregnancy or to factors that influence accumulation or retention of cortisol in hair.

Melatonin administration during the first half of pregnancy improves physiological response and reproductive performance of rabbits under heat stress conditions.

Context Melatonin may have a heat-stress-alleviating role during pregnancy. Aims To investigate the effects of melatonin administration during the first half of pregnancy on heat-tolerance capacity and pregnancy outputs of naturally heat-stressed rabbits. Methods Forty female rabbits were stratified equally into two experimental groups and daily received 1mg melatonin/kg body weight or not (control) for 15 consecutive days post-insemination. Heat tolerance indices, hormone profile, ovarian structures, and fetal loss were determined. Key results Treatment with melatonin significantly decreased respiration rate and rectal temperature, improved concentrations of nitric oxide, and tended to decrease malondialdehyde concentrations (P =0.064) compared to control. Melatonin treatment significantly increased concentrations of high-density lipoprotein, oestradiol, and progesterone compared to control. No significant differences in the numbers of visible ovarian follicles, corpora lutea, and total implantation sites on day 18 of pregnancy were observed between experimental groups. However, melatonin treatment significantly reduced the number of absorbed implantation sites and significantly improved amniotic fluid volume and conception rate compared to control. Conclusions Melatonin administration during the first half of pregnancy can improve reproductive performance of heat-stressed female rabbits. Implications Melatonin can improve fetal survivability via improving heat-tolerance capacity of does and steroidogenesis.

Individual empowerment and community norm effects of engaging young husbands in reproductive health in rural India: findings from a pilot study.

Despite decades of a call to action to engage men in reproductive health, men are often left out of programs and interventions. In India, where half of pregnancies are reported as unintended, patriarchal gender norms and still dominant patterns of arranged marriages make engaging men in family planning and strengthening couples communication critical in increasing reproductive autonomy and helping young couples meet their reproductive goals. This study explores the feasibility and acceptability from the men's perspective of the pilot of a gender transformative intervention for newly married couples in India. A pilot study was conducted of TARANG, a 4-month intervention for newly married women, with light touch engagement of husbands (4 sessions). A total of 41 husbands participated in the pilot, and we collected baseline knowledge and endline feasibility and acceptability data from them, along with in depth qualitative interviews with 13 men. The study was conducted in June-January, 2023. Men had low levels of knowledge about biology, family planning, with the majority of men reporting that no one had provided them information about these topics. Most men wanted to delay the first birth by at least 2 years, yet less than a quarter had discussed childbearing plans with their partner or engaged in family planning methods. While all men reported high acceptability (satisfaction and usefulness), feasibility (participation) was low, with only 43% attending 2 or more sessions. Main barriers to participation included commitments due to work and migration. Men reported that the intervention led to improvements in their relationships with their wives, gave them a sense of empowerment, and led them to become resources for other men in their community. Men in these rural communities are not receiving the information that they need to meet their reproductive goals, however, they greatly desire this information and ways to improve relationships with their new wives. Such an intervention appears to have the potential to help change norms and spread information in the community and provide men with positive, life affirming feelings. Providing information through technology could address barriers to in-person engagement. clinicaltrials.gov (NCT06320964), 03/13/24.