Maternal Cardiovascular Responses to Position Change in Pregnancy.

The maternal cardiovascular-circulatory system undergoes profound changes almost from the conception of a pregnancy until the postpartum period to support the maternal adaptions required for pregnancy and lactation. Maintenance of cardiovascular homeostasis requires changes in the cardiovascular autonomic responses. Here, we present a longitudinal study of the maternal cardiovascular autonomic responses to pregnancy and maternal position. Over a normal gestation, in the left lateral position there are significant changes in both time and frequency domain parameters reflecting heart rate variability. We show that cardiovascular autonomic responses to physiological stressors (standing and supine positions in late pregnancy) became significantly different with advancing gestation. In the third trimester, 60% of the subjects had an unstable heart rate response on standing, and these subjects had a significantly reduced sample entropy evident in their heart rate variability data. By 6 weeks, postpartum function returned to near the non-pregnant state, but there were consistent differences in high-frequency power when compared to nulligravid cases. Finally, we review complementary evidence, in particular from magnetic resonance imaging, that provides insights into the maternal and fetal impacts of positioning in pregnancy. This demonstrates a clear relationship between supine position and maternal hemodynamic parameters, which relates to compression of the inferior vena cava (p = 0.05). Together, these studies demonstrate new understanding of the physiology of physiological stressors related to position.

The effect of maternal position on placental blood flow and fetoplacental oxygenation in late gestation fetal growth restriction: a magnetic resonance imaging study.

Fetal growth restriction (FGR) and maternal supine going-to-sleep position are both risk factors for late stillbirth. This study aimed to use magnetic resonance imaging (MRI) to quantify the effect of maternal supine position on maternal-placental and fetoplacental blood flow, placental oxygen transfer and fetal oxygenation in FGR and healthy pregnancies. Twelve women with FGR and 27 women with healthy pregnancies at 34-38 weeks' gestation underwent MRI in both left lateral and supine positions. Phase-contrast MRI and a functional MRI technique (DECIDE) were used to measure blood flow in the maternal internal iliac arteries (IIAs) and umbilical vein (UV), placental oxygen transfer (placental flux), fetal oxygen saturation (FO2 ), and fetal oxygen delivery (delivery flux). The presence of FGR, compared to healthy pregnancies, was associated with a 7.8% lower FO2 (P = 0.02), reduced placental flux, and reduced delivery flux. Maternal supine positioning caused a 3.8% reduction in FO2 (P = 0.001), and significant reductions in total IIA flow, placental flux, UV flow and delivery flux compared to maternal left lateral position. The effect of maternal supine position on fetal oxygen delivery was independent of FGR pregnancy, meaning that supine positioning has an additive effect of reducing fetal oxygenation further in women with FGR, compared to women with appropriately grown for age pregnancies. Meanwhile, the effect of maternal supine positioning on placental oxygen transfer was not independent of the effect of FGR. Therefore, growth-restricted fetuses, which are chronically hypoxaemic, experience a relatively greater decline in oxygen transfer when mothers lie supine in late gestation compared to appropriately growing fetuses. KEY POINTS: Fetal growth restriction (FGR) is the most common risk factor associated with stillbirth, and early recognition and timely delivery is vital to reduce this risk. Maternal supine going-to-sleep position is found to increase the risk of late stillbirth but when combined with having a FGR pregnancy, maternal supine position leads to 15 times greater odds of stillbirth compared to supine sleeping with appropriately grown for age (AGA) pregnancies. Using MRI, this study quantifies the chronic hypoxaemia experienced by growth-restricted fetuses due to 13.5% lower placental oxygen transfer and 26% lower fetal oxygen delivery compared to AGA fetuses. With maternal supine positioning, there is a 23% reduction in maternal-placental blood flow and a further 14% reduction in fetal oxygen delivery for both FGR and AGA pregnancies, but this effect is proportionally greater for growth-restricted fetuses. This knowledge emphasises the importance of avoiding supine positioning in late pregnancy, particularly for vulnerable FGR pregnancies.

The effect of needle length and skin to deltoid muscle distance in adults receiving an mRNA COVID-19 vaccine.

BACKGROUND: The mRNA COVID vaccines are only licensed for intramuscular injection but it is unclear whether successful intramuscular administration is required for immunogenicity. METHODS: In this observational study, eligible adults receiving their first ComirnatyTM/BNT162b2 dose had their skin to deltoid muscle distance (SDMD) measured by ultrasound. The relationship between SDMD and height, weight, body mass index, and arm circumference was assessed. Three needle length groups were identified: 'clearly sufficient' (needle exceeding SDMD by >5 mm), 'probably sufficient' (needle exceeding SDMD by ≤ 5 mm), and 'insufficient' (needle length ≤ SDMD). Baseline and follow-up finger prick blood samples were collected and the primary outcome variable was mean spike antibody levels in the three needle length groups. RESULTS: Participants (n = 402) had a mean age of 34.7 years, BMI 29.1 kg/m2, arm circumference 37.5 cm, and SDMD 13.3 mm. The SDMD was >25 mm in 23/402 (5.7%) and >20 mm in 61/402 (15.2%) participants. Both arm circumference (≥40 cm) and BMI (≥33 kg/m2) were able to identify those with a SDMD of >25 mm, the length of a standard injection needle, with a sensitivity of 100% and specificities of 71.2 and 79.9%, respectively. Of 249/402 (62%) participants with paired blood samples, there was no significant difference in spike antibody titres between needle length groups. The mean (SD) spike BAU/mL was 464.5 (677.1) in 'clearly sufficient needle length' (n = 217) compared with 506.4 (265.1) in 'probably sufficient' (n = 21, p = 0.09), and 489.4 (452.3) in 'insufficient needle length' (n = 11, p = 0.65). CONCLUSIONS: A 25 mm needle length is likely to be inadequate to ensure vaccine deposition within the deltoid muscle in a small proportion of adults. Vaccine-induced spike antibody titres were comparable in those vaccinated with a needle of sufficient versus insufficient length suggesting deltoid muscle deposition may not be required for an adequate antibody response to mRNA vaccines.

New research questions identified for Cochrane reviews: a cross-sectional study of a specialized register: part one: gynecology.

OBJECTIVES: The aim of this project was to identify gaps and research waste in the dissemination of gynecology evidence in Cochrane systematic reviews (CSRs). STUDY DESIGN AND SETTING: A cross-sectional study of the Cochrane Gynecology and Fertility (CGF) Group's specialized register of randomized controlled trials (RCTs). We included trials on benign gynecological conditions, published in 2010 and 2011. These trials were matched, by the condition and treatment, to existing Cochrane reviews. Unmatched trials were analysed to prioritize new review titles. RESULTS: After exporting 740 trials from the CGF specialized register, we found that 192 (26%) could be included in an existing CSR if it was updated, whereas 230 trials (32%) were not matched to any review title, and from these, we developed 21 new review titles. The topic with the largest number of associated 'unused' trials was 'Plant and herbal extracts for symptoms of menopause'. CONCLUSIONS: We found that a third of the benign gynecology trials published in 2010 and 2011 had no associated CSR. After identifying new topics from unmatched trials, we developed new CSR titles. This study identified the gaps in the evidence for women with gynecological problems.

Progressive corneal ectatic disease in pregnancy.

Pregnancy influences ocular changes which may exacerbate existing or develop new pathology. This review summarises the existing evidence on the association between pregnancy and progressive keratoconus or iatrogenic keratectasia. Ten online databases were searched systematically. Eligible studies were published in English and reported objective ophthalmic outcomes for women with evidence of (i) a new diagnosis of keratoconus, (ii) keratoconus progression or (iii) iatrogenic keratectasia following refractive surgery; during or within one year of pregnancy. Strength of evidence was assessed using the Oxford Centre for Evidence-Based Medicine levels of evidence. Seventeen articles have reported 33 peripartum women with new-onset or progressive ectasia, evident by signs of corneal hydrops or protrusion (n = 8); steepening on topography imaging (n = 20); a mean decline in best corrected visual acuity by +0.20 logMAR (95% CI -0.01 to +0.40, n = 23); a mean increase in maximum keratometry by 2.18 D (95% CI 1.44 to 2.91, n = 42); a mean decline in spherical equivalent refraction by -1.33 D (95% CI -1.73 to -0.93, n = 41); and a mean increase in astigmatism by -1.61 D (95% CI -2.46 to -0.75, n = 19). Pregnancy is associated with progressive ectasia in some women including those with previously stable keratoconus, or a history of laser-assisted in situ keratomileusis surgery or no history of corneal ectasia. This review highlights the heterogeneity in limited existing evidence, the need for a standardised definition of ectasia progression and further prospective studies for clinical guidelines. Closely monitoring women at risk may assist in early intervention with collagen cross-linking and prevent peripartum vision loss.

Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults.

Purpose of Review: Antipsychotics are the standard of care when it comes to the treatment of Schizophrenia, and they are often used in Bipolar as well. Their use can come with adverse effects such as extrapyramidal movements, metabolic complications as well as cardiovascular complications such as a prolonged QT interval. Treatment for these side effects ranges from the treatment of the complications up to the cessation of the medication, which could come at the expense of the user's stability. Both schizophrenia and bipolar disorder have an increased risk of suicide and increased morbidity. The purpose of this review presents the background, evidence, and indications for the use of the new second-generation antipsychotic Cariprazine, which has a primary function as a D3 and D2 partial agonist, with higher selectivity for the D3 receptor type. Recent Findings: Schizophrenia is currently teated by dopamine antagonists and/or 5HT modulators, each with their own set of side effects. Bipolar disorder is mostly treated with mood stabilizers. Studies looking at the efficacy and safety of cariprazine have shown in two phase II trials and phase III trials the decrease in PANSS scores in schizophrenia. The most common adverse effects were akathisia, insomnia, constipation, and other extrapyramidal side effects. A unique side effect of Cariprazine caused bilateral cataract and cystic degeneration of the retina in the dog following daily oral administration for 13 weeks and/or 1 year and retinal degeneration in rats following daily oral administration for 2 years. Another study showed that cariprazine had significant efficacy in preventing relapse in patients with schizophrenia. The time to the loss of sustained remission was significantly longer (P = .0020) for cariprazine compared to placebo (hazard ratio = 0.51) during the double-blind treatment. 60.5% of patients treated with cariprazine and 34.9% of patients treated with placebo sustained remission through the final visit (odds ratio [OR] = 2.85; P = .0012; number needed to treat [NNT] = 4. Another Phase IIIb study looked at negative symptoms and used the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and it found that the use of cariprazine, from baseline to week 26, led to a greater least-squares mean change in PANSS-FSNS than did risperidone. Another study looked at the quality of life years with the treatment of cariprazine and showed those treated with cariprazine had superior quality of life compared to those treated with risperidone. In terms of bipolar disorder, it showed a decrease in depressive symptoms as measured by decreased MADRs scores with a dose of 3.0mg/day. A phase II study looked at the use of cariprazine in mania or mix states and showed cariprazine significantly decreased YMRS scores compared to placebo, least-square mean difference of -6.1 (p < 0.001). The metabolic parameters demonstrated comparable changes except for fasting glucose in which cariprazine was associated with elevations in glucose levels compared to placebo (p < 0.05). Another phase III study showed significant differences in YMRS total score mean change between cariprazine versus placebo-treated group. Changes in metabolic profiles in all mentioned studies were minimal. Summary: Cariprazine, in recent studies, has shown some promise in being able to treat both bipolar disorder in manic, depressed, and mixed states as well as schizophrenia. Side effects noted as adverse events in these studies are similar in profile to the medications that were developed in the past. With better relapse prevention, cariprazine could be a reasonable alternative clozapine.