Cerebral gray matter injuries in infants with intraventricular hemorrhage

While intraventricular hemorrhage (IVH) predominantly damages the periventricular white matter, it induces substantial injury to the cerebral gray matter. IVH destroys the germinal matrix, suppresses neurogenesis, and disrupts corticogenesis, thereby reducing the number of neurons in the upper cortical layer and volume of the cerebral gray matter. The pathogenesis of gray matter injury is attributed to IVH-induced oxidative stress, inflammation, and mass effect damaging the germinal matrix as well as to post-hemorrhagic ventricular dilation (PHVD). The IVH-induced cerebral gray matter injury and PHVD contribute to cognitive deficits and neurobehavioral disorders. Neuroimaging has enhanced our understanding of cerebral gray matter injury and is a valuable predictor of neurodevelopmental outcomes. Evidence from therapies tested in preclinical models and clinical trials suggests that strategies to promote neurogenesis, reduce cerebral inflammation and oxidative stress, and remove blood clots from the ventricles might enhance the outcome of these infants. This review offers an integrated view of new insights into the mechanisms underlying gray matter injury in premature infants with IVH and highlights the imminent therapies to restore neurodevelopmental dysfunction in IVH survivors.     

Ethical considerations in the management of infants with severe intraventricular hemorrhage

Intrinsic and extrinsic factors unique to neonatal care can complicate predictions of neurological outcomes for infants who suffer from severe intraventricular hemorrhage. While care decisions are driven by the same bioethical principles used in other domains, neurological prognostication can challenge concepts of futility, require careful examination of parental values, uncover biases and/or potentially compromise the best interests of the future child. In the following chapter we will review bioethical principles and relevant concepts, explore challenges to decision-making surrounding diagnoses of severe intraventricular hemorrhage and conclude with a brief review of practical approaches for counseling parents about neurodevelopmental impairment given the constraints of prognostic uncertainty and assumptions related to quality of life. We will argue that neurological findings alone, even in the setting of severe intraventricular hemorrhage, often do not constitute enough evidence for redirection of care but can be permissible when the entire neonatal condition is considered.     

The impact of prematurity and associated comorbidities on clinical outcomes in neonates with congenital heart disease

Prematurity is a common risk factor in children, affecting approximately 10% of live births, globally. It is more common in children with critical congenital heart disease (CCHD) and carries important implications in this group of patients. While outcomes have been improving over the years, even late preterm birth is associated with worse outcomes in children born with critical congenital heart disease compared to those without. Infants with both prematurity and CCHD are at particularly high risk for important comorbidities, including: necrotizing enterocolitis, intraventricular hemorrhage, white matter injury, neurodevelopmental anomalies and retinopathy of prematurity. Lesion-specific intensive care management of these infants, interventional and peri-operative management specifically tailored to their needs, and multidisciplinary care all have the potential to improve outcomes in this challenging group.     

Parental voice - what outcomes of preterm birth matter most to families?

Neonatal follow-up studies traditionally report on long-term neurodevelopmental outcomes as a metric of success of neonatal intensive care. Research endpoints are also typically deficit-based, assessing whether disabilities, such as cerebral palsy, cognitive impairment, deafness or blindness, are present or not. These historical approaches have resulted in neonatal follow-up programs that narrowly focus on the early identification of neurodevelopmental problems, possibly to the detriment of other outcomes that matter to parents. This focus on neurodevelopmental disability may also contribute to the negative stereotypes associated with extreme preterm birth. In this article, we discuss parental perspectives regarding important long-term outcomes. We examine limitations with current definitions of outcomes and propose a strength-based approach to generate meaningful findings both for clinicians and families.     

The cost of preterm birth and cesarean section as a result of infertility and its treatment: A review

Infertility, irrespective of receipt of fertility treatment, is associated with an increased risk of adverse pregnancy outcomes, including cesarean section (CS) and preterm birth (PTB). These complications are associated with significant physical, mental, emotional, social, and financial costs to individuals, healthcare systems, and society at large. Although multiple pregnancy is one of the most significant contributors to the elevated CS and PTB rates in women receiving fertility treatment, singleton pregnancy is also at an increased risk of these outcomes. Single embryo transfer policies through publicly funded in vitro fertilization programs have demonstrated beneficial health outcomes and cost savings. Low-dose aspirin prophylaxis may be considered for PTB reduction in patients with infertility. Finally, upstream prevention strategies such as lifestyle modification and social policies to address the underlying needs for fertility treatment may also beneficially impact both CS and PTB rates.     

Effects of ketone supplements on blood β-hydroxybutyrate,glucose and insulin: A systematic review and three-level meta-analysis

BackgroundEffects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial.ObjectiveThis study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects.MethodsMedline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression.ResultsThe meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = −0.3796, 95% CI [-0.4550, −0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30–60 min; >120 min) and insulin (30–60 min; 90–120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450–550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350–550 mg/kg).ConclusionDose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication.Registry and registry numberPROSPERO (CRD42022360620).     

A novel approach in the management of placenta accreta spectrum disorders: A single-center multidisciplinary surgical experience at Tu Du Hospital in Vietnam

ObjectivePlacenta accreta spectrum disorders (PASD) are the leading cause which results in highly maternal mortality during pregnancy. Although hysterectomy has been the gold standard for PASD, the recent study along with our experience has been demonstrated that the association between uterine myometrial resection and transverse B-Lynch suture in conservative management might be effective in the appropriate patients, thus we hereby attempted to determine this issue.Materials and methodsA retrospective observational study enrolled 65 patients at Tu Du Hospital in Vietnam between January 2017 and December 2018. This study included all pregnant women above 28 weeks of gestational age, who had undergone cesarean delivery due to PASD diagnosed preoperatively by ultrasound or upon laparotomy. Additionally, all patients who desired uterine preservation underwent modified one-step conservative uterine surgery (MOSCUS), avoiding peripartum hysterectomy.ResultsOverall, the rate of successful preservation was 93.8%. Other main outcomes such as average operative blood loss was 987 mL, mean blood transfusion was 831 ± 672 mL; mean operative time was 135 ± 31 min and average postoperative time was 5.79 days. Postoperative complications included six out of 65 cases due to intraoperative bleeding and postoperative infection, requiring hysterectomy in 4 patients.ConclusionMOSCUS was associated with less operative blood loss and blood transfusion amount. Its success rate of uterine preservation was approximately 94% in our study. Thus, this method can be acceptable in PASD management at our maternity health care center. Further studies might be necessary to evaluate the long-term effects of this method in PASD management.     

Environmental toxicants and male fertility

Semen quality has declined especially among Western men. Experimental and epidemiological studies have shown potential links between exposure to environmental toxicants and poor male fertility. Some environmental exposures in utero can disrupt fetal testicular function and result in cryptorchidism, low semen quality, low serum testosterone levels, and low fertility. Environmental exposure in childhood and adulthood can also adversely affect germ cells, Sertoli cells, Leydig cells, or the hypothalamic-pituitary-testicular axis, resulting in impaired male fertility. In this review, we report the latest results from human studies that investigated the role of endocrine disrupting chemicals, heavy metals, tobacco smoking, alcohol drinking, and use of marijuana in low semen quality and impaired male fertility. Current evidence suggests the relationship between these environmental factors and low male fertility; however, some factors showed conflicting results which need further investigation.     

Maternal blood concentration of tadalafil in pregnancy: Comparison of pregnant and non-pregnant women

ObjectiveIn this study, the drug kinetics of tadalafil were compared between pregnant and non-pregnant women to determine the ideal dosage to promote uterine blood flow.Materials and methodsWe recruited five pregnant and five non-pregnant women, all of which were administered tadalafil (20 mg/day). The blood concentration of tadalafil was measured 1, 2, 4, 6, 8, and 24 h after administration. We investigated the side effects within 4 days of tadalafil administration and compared the cumulative frequency between the two groups.ResultsThe mean area under the concentration–time curve and maximum blood concentration of tadalafil were not different between the pregnant and non-pregnant groups. Time to maximum blood concentration was delayed by 1 min on average in the pregnant group compared with the non-pregnant group. The cumulative frequency of side effects was significantly lower in the pregnant group than in the non-pregnant group (P = 0.026). No side effects were observed in either group after the fifth day of the tadalafil administration.ConclusionAlthough there was no difference in maximum blood concentration between non-pregnant and pregnant women, the rate of side effects was lower in pregnant women than in non-pregnant women. Therefore, pregnant women may tolerate tadalafil better.     

Guideline No. 441: Antenatal Fetal Health Surveillance

ObjectiveTo summarize the current evidence and to make recommendations for antenatal fetal health surveillance (FHS) to detect perinatal risk factors and potential fetal decompensation in the antenatal period and to allow for timely intervention to prevent perinatal morbidity and/or mortality.Target populationPregnant individuals with or without maternal, fetal, or pregnancy-associated perinatal risk factors for antenatal fetal decompensation.OptionsTo use basic and/or advanced antenatal testing modalities, based on risk factors for potential fetal decompensation.OutcomesEarly identification of potential fetal decompensation allows for interventions that may support fetal adaptation to maintain well-being or expedite delivery.Benefits, harms, and costsAntenatal FHS in pregnant individuals with identified perinatal risk factors may reduce the chance of adverse outcomes. Given the high false-positive rate, FHS may increase unnecessary interventions, which may result in harm, including parental anxiety, premature or operative birth, and increased use of health care resources. Optimization of surveillance protocols based on evidence-informed practice may improve perinatal outcomes and reduce harm.EvidenceMedline, PubMed, Embase, and the Cochrane Library were searched from inception to January 2022, using medical subject headings (MeSH) and key words related to pregnancy, fetal monitoring, fetal movement, stillbirth, pregnancy complications, and fetal sonography. This document represents an abstraction of the evidence rather than a methodological review.Validation methodsThe authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).Intended audienceAll health care team members who provide care for or education to obstetrical patients, including maternal fetal medicine specialists, obstetricians, family physicians, midwives, nurses, nurse practitioners, and radiologists.SUMMARY STATEMENTS

• 1.Accurate and ongoing early identification of risk factors for potential fetal decompensation allows care providers to develop an individualized care plan to optimize fetal well-being (moderate).
• 2.The nonstress test (NST) may be used in conjunction with a review of the total clinical picture to assess fetal well-being. An NST should be used only in the presence of a clear indication or finding associated with increased risk of fetal hypoxemia (moderate).
• 3.Sonography can evaluate amniotic fluid, estimated fetal weight, biophysical profile/modified biophysical profile, and Doppler blood flows to provide information regarding fetal well-being in pregnancies at risk of fetal morbidity (moderate).
• 4.Interprofessional team communication and documentation should be clear, using accepted and defined terminology (high).

RECOMMENDATIONS

• 1.Care providers should review and document perinatal risk factors (prior pregnancy, fetal, maternal, familial) at the initial visit and update factors throughout pregnancy (strong, moderate).
• 2.Pregnant individuals should be advised of local resources and/or the need for transfer of care based on pregnancy risk factors (strong, moderate).
• 3.Regular prenatal visits should include assessment and documentation of the presence of fetal heart tones, uterine size, pregnancy concerns or risk factors, the plan of care, and the discussion with the pregnant individual (strong, moderate).
• 4.All pregnant individuals should be advised to regularly monitor fetal movements starting at 26 weeks gestation (conditional, low).
• 5.If a reduction of fetal movements is identified, regardless of the technique used to assess fetal movements, pregnant individuals should be advised to present to their care provider or local obstetrical unit immediately for further evaluation (strong, low).
• 6.The nonstress test (NST) should be administered and interpreted by appropriately trained health professionals (strong, high).
• 7.A ≥2 cm × 1 cm pocket of fluid by transabdominal sonography should be used as the criterion for the amniotic fluid component of the biophysical profile (strong, moderate).
• 8.To ensure patient safety, care providers should develop clear protocols locally to communicate and document changes in fetal status identified during antenatal fetal surveillance and escalation of care (strong, moderate).
• 9.Care providers should use non-routine antenatal fetal health surveillance modalities, such as an NST, biophysical profile, or fetal Doppler sonography, only in the presence of a clear indication or finding associated with increased risk of fetal hypoxemia (strong, moderate).

     

Association between the number of oocytes and cumulative live birth rate: A systematic review

The available literature is controversial regarding the association between the number of oocytes retrieved and the cumulative live birth rate (CLBR). Although some authors report a continuous increase in the CLBR with the number of oocytes retrieved, others have found a plateau. A systematic review was conducted, including all eligible studies published until June 2022, to determine the optimal number of oocytes retrieved to maximize the CLBR. We found a positive association between the number of oocytes and the CLBR. However, this association varies according to patients’ age. While in patients younger than 35 years, little benefit is derived from increasing the number of oocytes above 25–30, in patients older than 35 years, the number of oocytes seems to improve the CLBR until the extreme of reproductive age is reached. In women aged 44 years or older, the CLBR will be consistently low, independent of the number of oocytes retrieved.     

Bleeding-related outcomes of low-risk total placenta previa are equivalent to those of partial/marginal placenta previa

ObjectiveTo clarify whether “low-risk total PP” patients bleed more than partial/marginal PP patients.Materials and methodsThe retrospective cohort study was performed involving patients with PP between April 2006 and December 2018. The placental position was determined by ultrasound. From medical charts, the backgrounds as well as obstetric and neonatal outcomes of PP patients were retrieved.ResultsThis study included 349 patients with PP, which was classified into three types according to the distance between the placenta and internal ostium: total (n = 174), partial (n = 52), and marginal (n = 123) PP. In total PP patients, three factors (prior CS, anterior placenta, and placental lacunae on ultrasound) significantly increased blood loss at CS, the need for hysterectomy, homologous transfusion (≥10 U), and ICU admission. No significant difference was observed in bleeding-related poor outcomes (rate of blood loss ≥2000 mL, amount of homologous transfusion, need for hysterectomy, and ICU admission) between total PP patients without all three factors: “low-risk total PP patients” and partial/marginal PP patients (19.8 vs. 17.1%; p = 0.604, 3.7 vs. 1.1%; p = 0.330, 1.2 vs. 1.1%; p = 1.000, and 1.2 vs. 1.1%; p = 1.000, respectively).ConclusionPrior CS, anterior placenta, and placental lacunae on ultrasound were risk factors for a bleeding-related poor outcome in total PP patients. Total PP patients without these three factors showed the same bleeding-related poor outcome as partial/marginal PP patients.     

Right ventricular outflow tract anomalies: Neonatal interventions and outcomes

Right ventricular outflow tract (RVOT) anomalies comprise a wide spectrum of congenital heart disease, typically characterized by obstruction to flow from the right ventricle to pulmonary arteries. This review highlights important considerations surrounding management strategy as well as clinical outcomes for the neonate with RVOT anomaly, including: pulmonary atresia with intact ventricular septum, congenital pulmonary valve stenosis, tetralogy of Fallot, and Ebstein anomaly with anatomic or physiologic RVOT obstruction.     

Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1

IntroductionStatins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.MethodsAt E14.5, untreated pregnant wild-type (WT, n=13–18), untreated HO-1^+/− (Het, n=6–9), and Het mice treated with pravastatin (Het+Pravastatin, n=12–14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.ResultsCompared with WT, HO activity in Het livers (65±18%, P<0.001) and placentas (74±7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0±2.2) compared with WT (9.1±1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0–73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83±7% and 87±14%, respectively). The number of viable fetuses per dam increased to 7.7±2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2–5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.DiscussionPravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.     

Efficacy of myofascial therapy and kinesitherapy in improving function in shoulder pathology with prolonged immobilization: A randomized,single-blind,controlled trial

BackgroundThe best physiotherapeutic approach in shoulder pathology that generates prolonged immobilization is still uncertain. Kinesitherapy remains the most widely used option. Myofascial therapy is a therapeutic approach in which the aim is to release fascial tension and regain mobility although its efficacy in shoulder pathology has not been sufficiently studied. This Prospective, single-blind randomized controlled trial in a university hospital setting aimed to compare the efficacy of myofascial therapy and kinesitherapy in improving function in shoulder pathology with prolonged immobilization.MethodsPatients were randomly assigned to a control group or to the intervention group.Both groups completed a therapeutic exercise program. Main Outcome Measures: The QuickDash questionnaire was the primary outcome, Pain Visual Analog Scale and the Range Of Motion of the shoulder were the secondary outcomes. The outcomes were evaluated at baseline (T0), at 4 (T2), 8 (T2), and 12 weeks (T3)Results44 participants were included. In the analysis of evolution over time, a significant improvement in functionality and range of motion measurements was observed in both groups (p < 0.05), although at 12 weeks only Myofasical Group achieved a clinically and statistically significant reduction in pain. Comparative analysis at 12 weeks revealed no statistically significant differences between the two therapies in the variables explored.ConclusionsBoth, myofascial therapy and kinesitherapy can improve function, mobility, and pain in patients with painful shoulder associated with prolonged immobilization, with no significant differences between therapies, although in the medium term only myofascial therapy achieves a clinically and statistically significant improvement in pain.Trial registrationTrial registration: ClinicalTrials.gov NCT04944446.     

Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial

BackgroundMenopausal symptoms have negative effects on the aspects of quality of life and impose a high cost on the health system. In traditional Persian medicine, pomegranate is recommended to alleviate menopausal symptoms.Material and methodsA randomized double-blind placebo-controlled trial was performed among 78 healthy women. Participants were interviewed three times: Before receiving the supplement/placebo, after completing the treatment, and after 3 weeks with no intervention. They filled out the demographic information sheet, modified-Kupperman index, and Menopause-Specific Quality of Life (MENQOL) questionnaires.ResultsThe mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001).ConclusionThis study demonstrated that 4 weeks' treatment with the pomegranate supplement significantly ameliorates the irritating symptoms of menopause and improves the quality of life in menopausal women even after 4 weeks' medicine deprivation.     

The Launch of A Girl&#x27;s First Period Study: Demystifying Reproductive Hormone Profiles in Adolescent Girls

Limited data exist on the reproductive hormone dynamics that govern the transition from menarche to the establishment of the mature ovulatory cycles of a fertile young woman. It is also unclear how environmental and lifestyle factors could modulate this transition in contemporary girls. Here, we introduce A Girl's First Period Study, an ambitious longitudinal study aimed at charting the early post-menarchal course of a cohort of healthy girls in the Triangle region of North Carolina.     

Prospective feasibility study of a mindfulness-based program for breast cancer patients in the southeastern US

BackgroundMindfulness interventions can improve psychological distress and quality of life (QoL) in cancer survivors. Few mindfulness programs for cancer recovery exist in Southeastern U.S. The primary objective of this study was to assess the feasibility of a modified mindfulness-based stress reduction (MBSR) program for breast cancer patients in Birmingham, Alabama. The secondary objective was to explore potential program effects on mindfulness skills and QoL.MethodsThis study was a prospective, quasi-experimental feasibility study conducted over 10 months at a university hospital. Feasibility was achieved if 80% of eligible patients screened enrolled in the study and 70% of enrolled patients attended all 8 program sessions. Effectiveness was estimated by changes in mindfulness and QoL indicators measured with validated scales administered at 3 time points and assessed with a non-parametric Friedman test. Sessions included meditation, yoga, and an attention practice called body scan. There were 3 groups of 2–5 patients.ResultsThe sample totaled 12 patients. Forty-four percent (12/27) of eligible patients enrolled in the study, and two out of 12 enrolled patients completed 8 program sessions, resulting in 16.7% (2/12) retention. However, more than half (66.7%) of participants completed at least 7 sessions. Between baseline and 8-week follow-up, patients demonstrated statistically significant improvements in distress, general wellbeing, and fatigue-related QoL.ConclusionsFeasibility objectives were not achieved. However, a majority of participants (66.7%) completed 7 of 8 program sessions. Program effects were promising for distress, fatigue, and wellbeing. Results warrant further research on MBSR-like programs for breast cancer patients in Alabama.