Evaluating the depression state during perinatal period by non-invasive scalp EEG.

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.

Maternal alcohol consumption up to mouse organogenesis disrupts fetal-placental interface at mid-gestation associated with dysregulation of AQP3 immunoexpression.

Adequate trophoblast development during placentation involves the AQP3 regulation. The link between potential placental fetal-maternal interface abnormalities and AQP3 expression after perigestational alcohol intake was not explored yet. Female mice were treated (TF) with 10 % ethanol in drinking water before and up to day 10 of gestation, and control females (CF) with ethanol-free water. At gestational day 13, TFs showed increased fetal/placental weight ratio and reduced histological placental thickness compared to CFs. TF-placentas had disorganized fetal face layers, increased junctional zone (JZ), and decreased labyrinth (Lab). Concomitantly, immunoexpression of cleaved caspase-3 significantly increased in TF-JZ and Lab vs controls. Consistent with placental changes, AQP3 expression was higher in junctional trophoblast giant cells (TGCs), glycogen cells (GCs), spongiotrophoblasts (spg), and lab-syncytiotrophoblasts compared to CF-placentas. This study reveals, for the first time, that perigestational alcohol consumption up to organogenesis causes abnormal placental development associated with dysregulation of AQP3 expression.

Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy.

Pregnancy is characterized by longitudinal maternal, physiological adaptations to support the development of a fetus. One of the cardinal maternal adaptations during a healthy pregnancy is a progressive increase in uterine artery blood flow. This facilitates sufficient blood supply for the development of the placenta and the growing fetus. Regional hemodynamic changes in the uterine circulation, such as a vast reduction in uterine artery resistance, are mainly facilitated by changes in uterine artery reactivity and myogenic tone along with remodeling of the uterine arteries. These regional changes in vascular reactivity have been attributed to pregnancy-induced adaptations of cell-to-cell communication mechanisms, with an emphasis on the interaction between endothelial and vascular smooth muscle cells. Perivascular adipose tissue (PVAT) is considered the fourth layer of the vascular wall and contributes to the regulation of vascular reactivity in most vascular beds and most species. This review focuses on mechanisms of uterine artery reactivity and the role of PVAT in pregnancy-induced maternal vascular adaptations, with an emphasis on the uterine circulation.

The evolution of gestation length in eutherian mammals.

Eutherian mammals exhibit considerable variation in their gestation lengths, which has traditionally been linked to variation in other traits, including body mass and lifespan. To understand how gestation length variation, including its association with body mass and lifespan variation, changed over mammalian evolution, we conducted phylogeny-informed analyses of 845 representative extant species. We found that gestation length substantially differed in both whether and how strongly it was associated with body mass and lifespan across mammals. For example, gestation length was not associated with lifespan or body mass in Chiroptera and Cetacea but was strongly associated only with body mass in Carnivora. We also identified 52 evolutionary shifts in gestation length variation across the mammal phylogeny and 14 shifts when we jointly considered variation of all three traits; six shifts were shared. Notably, two of these shifts, both positive, occurred at the roots of Cetacea and Pinnipedia, respectively, coinciding with the transition of these clades to the marine environment, whereas a negative shift occurred at the root of Chiroptera, coinciding with the evolution of flight in this clade. These results suggest that the relationship between gestation length and the two other traits has varied substantially across mammalian phylogeny.

High fat diet-induced obesity and gestational DMBA exposure alter folliculogenesis and the proteome of the maternal ovary†.

Obesity and ovotoxicant exposures impair female reproductive health with greater ovotoxicity reported in obese relative to lean females. The mother and developing fetus are vulnerable to both during gestation. 7,12-dimethylbenz[a]anthracene (DMBA) is released during carbon combustion including from cigarettes, coal, fossil fuels, and forest fires. This study investigated the hypothesis that diet-induced obesity would increase sensitivity of the ovaries to DMBA-induced ovotoxicity and determined impacts of both obesity and DMBA exposure during gestation on the maternal ovary. Female C57BL/6 J mice were fed a control or a High Sugar High Fat (45% kcal from fat; 20% kcal from sucrose) diet until ~30% weight gain was attained before mating with unexposed males. From gestation Day 7, mice were exposed intraperitoneally to either vehicle control (corn oil) or DMBA (1 mg/kg diluted in corn oil) for 7 d. Thus, there were four groups: lean control (LC); lean DMBA exposed; obese control; obese DMBA exposed. Gestational obesity and DMBA exposure decreased (P < 0.05) ovarian and increased liver weights relative to LC dams, but there was no treatment impact (P > 0.05) on spleen weight or progesterone. Also, obesity exacerbated the DMBA reduction (P < 0.05) in the number of primordial, secondary follicles, and corpora lutea. In lean mice, DMBA exposure altered abundance of 21 proteins; in obese dams, DMBA exposure affected 134 proteins while obesity alone altered 81 proteins in the maternal ovary. Thus, the maternal ovary is impacted by DMBA exposure and metabolic status influences the outcome.

Temporal involvement of phosphatidylinositol 4-phosphate 5-kinase γ in differentiation of Z-bands and myofilament bundles as well as intercalated discs in mouse heart at mid-gestation.

Considering the occurrence of serious heart failure in a gene knockout mouse of PIP5Kγ and in congenital abnormal cases in humans in which the gene was defective as reported by others, the present study attempted to localize PIP5Kγ in the heart during prenatal stages. It was done on the basis of the supposition that phenotypes caused by gene mutation of a given molecule are owed to the functional deterioration of selective cellular sites normally expressing it at significantly higher levels in wild mice. PIP5Kγ-immunoreactivity was the highest in the heart at E10 in contrast to almost non-significant levels of the immunoreactivity in surrounding organs and tissues such as liver. The immunoreactivity gradually weakened in the heart with the prenatal age, and it was at non-significant levels at newborn and postnatal stages. Six patterns in localization of distinct immunoreactivity for PIP5Kγ were recognized in cardiomyocytes: (1) its localization on the plasma membranes and subjacent cytoplasm without association with short myofibrils and (2) its localization on them as well as short myofibrils in association with them in cardiomyocytes of early differentiation at E10; (3) its spot-like localization along long myofibrils in cardiomyocytes of advanced differentiation at E10; (4) rare occurrences of such spot-like localization along long myofibrils in cardiomyocytes of advanced differentiation at E14; (5) its localization at Z-bands of long myofibrils; and (6) its localization at intercellular junctions including the intercalated discs in cardiomyocytes of advanced differentiation at E10 and E14, especially dominant at the latter stage. No distinct localization of PIP5Kγ-immunoreactivity of any patterns was seen in the heart at E18 and P1D. The present finding suggests that sites of PIP5Kγ-appearance and probably of its high activity in cardiomyocytes are shifted from the plasma membranes through short myofibrils subjacent to the plasma membranes and long myofibrils, to Z-bands as well as to the intercalated discs during the mid-term gestation. It is further suggested that PIP5Kγ is involved in the differentiation of myofibrils as well as intercellular junctions including the intercalated discs at later stages of the mid-term gestation. Failures in its involvement in the differentiation of these structural components are thus likely to cause the mid-term gestation lethality of the mutant mice for PIP5Kγ.

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

OBJECTIVE: A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. DESIGN: Retrospective cohort study. PARTICIPANTS: Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. MEASUREMENTS: Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aß). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. RESULTS: Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aß 0.62, 95% CI: 0.51-0.76) and higher fT4 (aß 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aß 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aß 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). CONCLUSIONS: In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

OBJECTIVE: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. DESIGN: Cross-sectional study. PARTICIPANTS: Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. MEASUREMENTS: Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). RESULTS: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). CONCLUSION: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Cord blood cytokine profiles in children later diagnosed with autism spectrum disorder: Results from the prospective MARBLES study.

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies - Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1ß, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations.

Implications of pregnancy on MCN of the pancreas: A multicentric case-control study.

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas express estrogen and progesterone receptors. Several case reports describe MCN increasing in size during gestation. The aim of this study is to assess if pregnancy is a risk factor for malignant degeneration of MCN. METHODS: All female patients who underwent pancreatic resection of a MCN between 2011 and 2021 were included. MCN resected or diagnosed within 12 months of gestation were defined perigestational. MCN with high grade dysplasia or an invasive component were classified in the high grade (HG) group. The primary outcome was defined as the correlation between exposure to gestation and peri-gestational MCN to development of HG-MCN. RESULTS: The study includes 176 patients, 25 (14 %) forming the HG group, and 151 (86 %) forming the low grade (LG) group. LG and HG groups had a similar distribution of systemic contraceptives use (26 % vs. 16 %, p = 0.262), and perigestational MCN (7 % vs 16 %, p = 0.108). At univariate analysis cyst size ≥10 cm (OR 5.3, p < 0.001) was associated to HG degeneration. Peri gestational MCN positively correlated with cyst size (R = 0.18, p = 0.020). In the subgroup of 14 perigestational MCN patients 29 % had HG-MCN and 71 % experienced cyst growth during gestation with an average growth of 55.1 ± 18 mm. CONCLUSIONS: Perigestational MCN are associated to increased cyst diameter, and in the subset of patients affected by MCN during gestation a high rate of growth was observed. Patients with a MCN and pregnancy desire should undergo multidisciplinary counselling.

Adverse pregnancy outcomes and effect of treatment in Wilson disease during pregnancy: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Wilson disease (WD) is a rare disorder of copper metabolism, leading to liver and neurological disease. Existing literature on WD in pregnancy is scarce, limiting preconception and obstetrical counselling. In this systematic review with meta-analysis, we determine the prevalence of various adverse pregnancy and neonatal outcomes in WD, as well as evaluate the impact of WD treatment on these outcomes. METHODS: Scopus, MEDLINE and EMBASE were searched until 12 May 2023, for studies of pregnant individuals with WD and at least one pregnancy or neonatal outcome of interest. Meta-analysis of single proportions was conducted to pool prevalence data for each outcome. Outcome rates were compared between treated and untreated groups in a meta-analysis of dichotomous events. RESULTS: Sixteen studies, published from 1975 to 2022, were included in the systematic review. Thirty-seven percent of pregnancies reported at least one adverse pregnancy outcome. Spontaneous abortions (20%), liver diseases of pregnancy (4.5%) and preterm births (2%) were the most frequent adverse pregnancy outcomes in patients with WD. The prevalence of spontaneous abortions was significantly lower in pregnant individuals with WD who received treatment during pregnancy (OR: .47, 95% CI: 35%-63%). The prevalence of any adverse pregnancy outcome was also significantly lower with treatment (OR: .53, 95% CI: .37-.76), which appears to be mostly driven by the reduction of spontaneous abortions. CONCLUSIONS: There is low to moderate quality evidence to suggest that preconception and obstetrical counselling for patients with WD should include a discussion on the potentially high frequency of adverse pregnancy outcomes in this population, as well as the importance of continuing WD treatment during pregnancy to ensure satisfactory pregnancy course and potentially minimize the risk of spontaneous abortions.

Prescription medication use during pregnancy in the United States from 2011 to 2020: trends and safety evidence.

BACKGROUND: Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications. OBJECTIVE: This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications. STUDY DESIGN: We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk. RESULTS: Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy. CONCLUSION: There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients.

SMFM Consult Series #70: Management of short cervix in individuals without a history of spontaneous preterm birth.

Most deliveries before 34 weeks of gestation occur in individuals with no previous history of preterm birth. Midtrimester cervical length assessment using transvaginal ultrasound is one of the best clinical predictors of spontaneous preterm birth. This Consult provides guidance for the diagnosis and management of a short cervix in an individual without a history of preterm birth. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend that all cervical length measurements used to guide therapeutic recommendations be performed using a transvaginal approach and in accordance with standardized procedures as described by organizations such as the Perinatal Quality Foundation or the Fetal Medicine Foundation (GRADE 1C); (2) we recommend using a midtrimester cervical length of ≤25 mm to diagnose a short cervix in individuals with a singleton gestation and no previous history of spontaneous preterm birth (GRADE 1C); (3) we recommend that asymptomatic individuals with a singleton gestation and a transvaginal cervical length of ≤20 mm diagnosed before 24 weeks of gestation be prescribed vaginal progesterone to reduce the risk of preterm birth (GRADE 1A); (4) we recommend that treatment with vaginal progesterone be considered at a cervical length of 21 to 25 mm based on shared decision-making (GRADE 1B); (5) we recommend that 17-alpha hydroxyprogesterone caproate, including compounded formulations, not be prescribed for the treatment of a short cervix (GRADE 1B); (6) in individuals without a history of preterm birth who have a sonographic short cervix (10-25 mm), we recommend against cerclage placement in the absence of cervical dilation (GRADE 1B); (7) we recommend that cervical pessary not be placed for the prevention of preterm birth in individuals with a singleton gestation and a short cervix (GRADE 1B); and (8) we recommend against routine use of progesterone, pessary, or cerclage for the treatment of cervical shortening in twin gestations outside the context of a clinical trial (GRADE 1B).

Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia in women at risk, whereas the NICE guidelines in the United Kingdom recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommended doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared with 81 mg in decreasing the rate of preeclampsia with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12-20 weeks of gestational age with a body mass index ≥30 kg/m2 at the time of enrollment and at least 1 of 3 high-risk factors: history of preeclampsia in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pregestational diabetes or gestational diabetes diagnosed before 20 weeks of gestational age were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin because of other indications, or contraindication to aspirin. The primary outcome was preeclampsia with severe features (preeclampsia or superimposed preeclampsia with severe features; eclampsia; or hemolysis, elevated liver enzymes, low platelet count syndrome). Secondary outcomes included rates of preterm birth because of preeclampsia, small for gestational age, postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Approximately 220/343 (64.1%) individuals were randomized. The primary outcome was available for 209/220 (95%) individuals. Baseline characteristics were similar between groups, with the median gestational age at enrollment being 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment before 16 weeks occurred in 55 of 110 of those assigned to 162 mg and 58 of 110 of those assigned to 81 mg of aspirin. The primary outcome occurred in n of d individuals (35%) in the 162 mg aspirin group and n of d individuals (40%) in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared with 81 mg aspirin dose. Rates of indicated preterm birth because of preeclampsia (21% vs 21%), small for gestational age (6.5% vs 2.9%), abruption (2.8% vs 3.0%), and postpartum hemorrhage (10.0% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was a 78% probability of benefit that 162 mg aspirin compared with 81 mg will decrease the rate of preeclampsia with severe features. With the best estimate of a 12% reduction when using 162 mg of aspirin compared with 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Randomized controlled trial of twin-twin transfusion syndrome laser surgery: the sequential trial.

BACKGROUND: Intraoperative blood transfer between twins during laser surgery for twin-twin transfusion syndrome can vary by surgical technique and has been proposed to explain differences in donor twin survival. OBJECTIVE: This trial compared donor twin survival with 2 laser techniques: the sequential technique, in which the arteriovenous communications from the volume-depleted donor to the volume-overloaded recipient are laser-occluded before those from recipient to donor, and the selective technique, in which the occlusion of the vascular communications is performed in no particular order. STUDY DESIGN: A single-center, open-label, randomized controlled trial was conducted in which twin-twin transfusion syndrome patients were randomized to sequential vs selective laser surgery. Nested within the trial, a second trial randomized patients with superficial anastomoses (arterioarterial and venovenous) to ablation of these connections first (before ablating the arteriovenous anastomoses) vs last. The primary outcome measure was donor twin survival at birth. RESULTS: A total of 642 patients were randomized. Overall donor twin survival was similar between the 2 groups (274 of 320 [85.6%] vs 271 of 322 [84.2%]; odds ratio, 1.12 [95% confidence interval, 0.73-1.73]; P=.605). Superficial anastomoses occurred in 177 of 642 cases (27.6%). Donor survival was lower in the superficial anastomosis group vs those with only arteriovenous communications (125 of 177 [70.6%] vs 420 of 465 [90.3%]; adjusted odds ratio, 0.33 [95% confidence interval, 0.20-0.54]; P<.001). In cases with superficial anastomoses, donor survival was independent of the timing of ablation or surgical technique. The postoperative mean middle cerebral artery peak systolic velocity was lower in the sequential vs selective group (1.00±0.30 vs 1.06±0.30 multiples of the median; P=.003). Post hoc analyses showed 2 factors that were associated with poor overall donor twin survival: the presence or absence of donor twin preoperative critical abnormal Doppler parameters and the presence or absence of arterioarterial anastomoses. Depending on these factors, 4 categories of patients resulted: (1) Category 1 (347 of 642 [54%]), no donor twin critical abnormal Doppler + no arterioarterial anastomoses: donor twin survival was 91.2% in the sequential and 93.8% in the selective groups; (2) Category 2 (143 of 642 [22%]), critical abnormal Doppler present + no arterioarterial anastomoses: donor survival was 89.9% vs 75.7%; (3) Category 3 (73 of 642 [11%]), no critical abnormal Doppler + arterioarterial anastomoses present: donor survival was 94.7% vs 74.3%; and (4) Category 4 (79 of 642 [12%]), critical abnormal Doppler present + arterioarterial anastomoses present: donor survival was 47.6% vs 64.9%. CONCLUSION: Donor twin survival did not differ between the sequential vs selective laser techniques and did not differ if superficial anastomoses were ablated first vs last. The donor twin's postoperative middle cerebral artery peak systolic velocity was improved with the sequential vs the selective approach. Post hoc analyses suggest that donor twin survival may be associated with the choice of laser technique according to high-risk factors. Further study is needed to determine whether using these categories to guide the choice of surgical technique will improve outcomes.

Parturition at term: induction, second and third stages of labor, and optimal management of life-threatening complications-hemorrhage, infection, and uterine rupture.

Childbirth is a defining moment in anyone's life, and it occurs 140 million times per year. Largely a physiologic process, parturition does come with risks; one mother dies every two minutes. These deaths occur mostly among healthy women, and many are considered preventable. For each death, 20 to 30 mothers experience complications that compromise their short- and long-term health. The risk of birth extends to the newborn, and, in 2020, 2.4 million neonates died, 25% in the first day of life. Hence, intrapartum care is an important priority for society. The American Journal of Obstetrics & Gynecology has devoted two special Supplements in 2023 and 2024 to the clinical aspects of labor at term. This article describes the content of the Supplements and highlights new developments in the induction of labor (a comparison of methods, definition of failed induction, new pharmacologic agents), management of the second stage, the value of intrapartum sonography, new concepts on soft tissue dystocia, optimal care during the third stage, and common complications that account for maternal death, such as infection, hemorrhage, and uterine rupture. All articles are available to subscribers and non-subscribers and have supporting video content to enhance dissemination and improve intrapartum care. Our hope is that no mother suffers because of lack of information.

Effect of chronic maternal L-Glu intake during gestation and/or lactation on oxidative stress markers, AMPA Glu1 receptor and adenosine A1 signalling pathway from foetal and neonatal cerebellum.

L-Glutamate (L-Glu) is an amino acid present in the diet that plays a fundamental role in the central nervous system, as the main excitatory neurotransmitter participating in learning and memory processes. In addition, the nucleoside adenosine has a crucial role in L-Glu metabolism, by regulating the liberation of this neurotransmitter through four different receptors: A1, A2A, A2B and A3, which activate (A2A and A2B) or inhibit (A1 and A3) adenylate cyclase pathway. L-Glu at high concentrations can act as a neurotoxin and induce oxidative stress. The study of the oxidative stress correlated with an excess of L-Glu consumption during maternity is key to understand its effects on foetuses and neonates. Previous studies have shown that there is a change in the receptor levels in the brain of pregnant rats and their foetuses when mothers are administered L-Glu during gestation; however, its effect on the cerebellum is unknown. Cerebellum is known to be responsible for motor, cognitive and emotional functions, so its possible involvement after L-Glu consumption is an important issue to study. Therefore, the aim of the present work was to study the effect of L-Glu exposure during gestation and lactation on oxidative stress biomarkers and neurotransmitter receptors from the cerebellum of foetuses and neonates. After maternal L-Glu intake during gestation, oxidative stress was increased, as the ionotropic L-Glu receptors, and GluR1 AMPA subunit levels were altered in foetuses. A1 adenosine receptor suffered changes after L-Glu treatment during gestation, lactation or both, in lactating neonate cerebellum, while adenylate cyclase activity remain unaltered. Further studies will be necessary to elucidate the importance of L-Glu intake and its possible excitotoxicity in the cerebellum of Wistar rats during the pregnancy period and their involvement in long-term neurodegeneration.

Modulation of cell-mediated immunity during pregnancy in wild bonobos.

During pregnancy, the mammalian immune system must simultaneously protect against pathogens while being accommodating to the foreign fetal tissues. Our current understanding of this immune modulation derives predominantly from industrialized human populations and laboratory animals. However, their environments differ considerably from the pathogen-rich, resource-scarce environments in which pregnancy and the immune system co-evolved. For a better understanding of immune modulation during pregnancy in challenging environments, we measured urinary neopterin, a biomarker of cell-mediated immune responses, in 10 wild female bonobos (Pan paniscus) before, during and after pregnancy. Bonobos, sharing evolutionary roots and pregnancy characteristics with humans, serve as an ideal model for such investigation. Despite distinct environments, we hypothesized that cell-mediated immune modulation during pregnancy is similar between bonobos and humans. As predicted, neopterin levels were higher during than outside of pregnancy, and highest in the third trimester, with a significant decline post-partum. Our findings suggest shared mechanisms of cell-mediated immune modulation during pregnancy in bonobos and humans that are robust despite distinct environmental conditions. We propose that these patterns indicate shared immunological processes during pregnancy among hominins, and possibly other primates. This finding enhances our understanding of reproductive immunology.

Different neurocognitive controls modulate obstacle avoidance through pregnancy.

Understanding why falls during pregnancy occur at over 25% rate over gestation has clinical impacts on the health of pregnant individuals. Attention, proprioception, and perception of the environment are required to prevent trips and falls. This research aimed to understand how the changes to these neurocognitive processes control obstacle avoidance through gestation. Seventeen pregnant participants were tested five times in 6-week intervals. Participants walked an obstacle course (OC), and we analyzed the crossings over obstacles that were set to 10% of participants' body height. Participants also performed an attentional network test (ANT: performance of specific components of attention), an obstacle perception task (OP: ability to visually define an obstacle and translate that to a body posture), and a joint position sense task (JPS: ability to recognize and recreate a joint position from somatosensation). In the OC task, average leading and trailing foot crossing heights significantly reduced by 13% and 23% respectively, with no change in variation, between weeks 13 and 31 of pregnancy, indicating an increased risk of obstacle contact during this time. The variability in minimum leading foot distances from the obstacle was correlated with all three neurocognition tasks (ANT, OP, and JPS). Increased fall rates in the second and third trimesters of pregnancy may be driven by changes in attention, with additional contributions of joint position sense and environmental perception at various stages of gestation. The results imply that a holistic examination on an individual basis may be required to determine individual trip risk and appropriate safety modifications.

Body image and pelvic floor dysfunction in pregnancy and postpartum: A prospective one-year follow-up cohort study.

OBJECTIVE: To determine the prevalence of pelvic floor dysfunction (PFD) among pregnant women, their clustering and their association with body image disturbance (BID) up to 1 year postpartum. DESIGN: Monocentric prospective cohort study. SETTING: University Hospitals Leuven. POPULATION: Pregnant women attending for pregnancy care, first assessed prior to 14 weeks of gestation and agreeing to follow-up until 1 year postpartum. METHODS: Standardised questionnaires reporting on PFD and BID at 12-14 and 28-32 weeks of gestation, and again at 6-8 weeks and 1 year postpartum. We calculated the prevalence of PFD, how the cases clustered and how the cases correlated with BID using a linear mixed-model analysis. A minimum of 174 women with complete follow-up were required. MAIN OUTCOME MEASURES: The questionnaires used were the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF), St. Mark's Incontinence Score (SMIS), Patient Assessment of Constipation Symptoms (PAC-SYM), Pelvic Organ Prolapse Distress Inventory (POPDI), Pelvic Organ Prolapse/Incontinence Sexual Questionnaire IUGA Revised (PISQ-IR) and the Body Image Disturbance Questionnaire (BIDQ). RESULTS: Out of 208 women, 92.8% reported one or multiple symptoms of PFD at 28-32 weeks of gestation, dropping to 73.6% by 1 year postpartum. The most common symptoms were constipation (65.3% at 28-32 weeks of gestation and 42.8% at 1 year postpartum) and urinary incontinence (56.8% at 28-32 weeks of gestation and 35.1% at 1 year postpartum). After correcting for body mass index, parity and mode of delivery, the severity of BID was associated with the ICIQ-UI SF score (ß = 0.016, range 0.007-0.024), the PAC-SYM score (ß = 0.006, range 0.002-0.011) and the POPDI score (ß = 0.009, range 0.005-0.012), but not with the SMIS score (ß = 0.015, range -0.001 to 0.031) or the PISQ-IR score, in sexually active women. CONCLUSIONS: Urinary incontinence, constipation and symptoms of prolapse have a measurable impact on BID.