Water birth: a systematic review and meta-analysis of maternal and neonatal outcomes.

OBJECTIVE: This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth. DATA SOURCES: We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023. STUDY ELIGIBILITY CRITERIA: We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water. METHODS: Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes. RESULTS: Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76-1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38-2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58-0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42-0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43-0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45-0.70). CONCLUSION: When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely.

Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review.

Postpartum depression (PPD) is one of the three major categories on the spectrum of postpartum psychiatric syndromes. Postpartum psychiatric syndromes are classified as either postpartum blues, postpartum depression, or postpartum psychosis. Postpartum depression is important to recognize clinically because of the effect it can have on the mother-child bond. The neurosteroid allopregnanolone, a progesterone derivative, is important for its role in positively modulating GABAA receptors. GABA-mediated signaling has been previously implicated in major depressive disorder. Allopregnanolone-mediated signaling has been identified as an important therapeutic target. Treatment with an allopregnanolone-analog, brexanolone, has been shown to improve depression scores in trials for the treatment of PPD. Brexanolone is a positive allosteric modulator of GABAA and is the first drug approved by the FDA to treat postpartum depression. Brexanolone enhances the inhibitory effects of GABAA, restores dysfunctional GABAA transmembrane channels, and mimics a naturally produced progesterone metabolite that fluctuates during pregnancy and postpartum. One open-label study and two phase two studies have some significant reduction in HAM-D scores after treatment and that the effect was still there 30 days post-treatment. Per the data reported, intravenous infusion of brexanolone could be efficacious and safe for the treatment of women suffering from postpartum depression.

Phase I/II Manufacture of Lentiviral Vectors Under GMP in an Academic Setting.

In clinical gene transfer applications, lentiviral vectors (LV) have rapidly become the primary means to achieve permanent and stable expression of a gene of interest or alteration of gene expression in target cells. This status can be attributed primarily to the ability of the LV to (1) transduce dividing as well as quiescent cells, (2) restrict or expand tropism through envelope pseudo-typing, and (3) regulate gene expression within different cell lineages through internal promoter selection. Recent progress in viral vector design such as the elimination of unnecessary viral elements, split packaging, and self-inactivating vectors has established a significant safety profile for these vectors. The level of GMP compliance required for the manufacture of LV is dependent upon their intended use, stage of drug product development, and country where the vector will be used as the different regulatory authorities who oversee the clinical usage of such products may have different requirements. As such, successful GMP manufacture of LV requires a combination of diverse factors including: regulatory expertise, compliant facilities, validated and calibrated equipments, starting materials of the highest quality, trained production personnel, scientifically robust production processes, and a quality by design approach. More importantly, oversight throughout manufacturing by an independent Quality Assurance Unit who has the authority to reject or approve the materials is required. We describe here the GMP manufacture of LV at our facility using a four plasmid system where 293T cells from an approved Master Cell Bank (MCB) are transiently transfected using polyethylenimine (PEI). Following transfection, the media is changed and Benzonase added to digest residual plasmid DNA. Two harvests of crude supernatant are collected and then clarified by filtration. The clarified supernatant is purified and concentrated by anion exchange chromatography and tangential flow filtration. The final product is then diafiltered directly into the sponsor defined final formulation buffer and aseptically filled.

Stimuli-responsively porating gels by condensation.

A polyurethane (PU) resin derived from glycerol and hexamethylene diisocyanate and an imidazolium bromide ionic liquid chain terminator yield a stimuli-responsive resin that reversibly porates as a solvation response.