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The use of ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organization. However, this modality remains unavailable to many women in low‐income countries where trained practitioners are scarce. Although previous initiatives have demonstrated efficacy in training midwives and technicians to perform antenatal ultrasound, these programs have often been too long and too complex to be realistic within the specific constraints of this context, highlighting the need for a novel and pragmatic approach. We describe the development and piloting of a bespoke course to teach midwives 3 fundamental components of early antenatal ultrasound scanning: (1) to identify the number of fetuses, (2) to confirm fetal viability, and (3) to determine gestational age. Having established that 5 days is insufficient, we propose that the minimum duration required to train ultrasound‐naive midwives to competency is 10 days. Our completed program therefore consists of one and one‐half days of didactic teaching, followed by 8 and one‐half days of supervised hands‐on practical training in which trainees are assessed on their skills. This package has subsequently been successfully implemented across 6 sites in Malawi, where 28 midwives have achieved competency. By describing the processes involved in our cross‐continental collaboration, we explain how unexpected challenges helped shape and improve our program, demonstrating the value of preimplementation piloting and a pragmatic and adaptive approach. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB; defined as delivery before 37 weeks of pregnancy) is the leading cause of morbidity and mortality in infants and children aged <5 years, conferring potentially devastating short‐ and long‐term complications. Despite extensive research in the field, there is currently a paucity of medications available for PTB prevention and treatment. Over the past few decades, inflammation in gestational tissues has emerged at the forefront of PTB pathophysiology. Even in the absence of infection, inflammation alone can prematurely activate the main components of parturition resulting in uterine contractions, cervical ripening and dilatation, membrane rupture, and subsequent PTB. Mechanistic studies have identified critical elements of the complex inflammatory molecular pathways involved in PTB. Here, we discuss therapeutic options that target such key mediators with an aim to prevent, postpone, or treat PTB. We provide an overview of more traditional therapies that are currently used or being tested in humans, and we highlight recent advances in preclinical studies introducing novel approaches with therapeutic potential. We conclude that urgent collaborative action is required to address the unmet need of developing effective strategies to tackle the challenge of PTB and its complications. [ABSTRACT FROM AUTHOR]

The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In vivo, in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24 h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC‐1α, required for glucocorticoid‐induced maturation of primary mouse fetal cardiomyocytes in vitro, was also downregulated in fetal hearts at E17.5, 24 h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC‐1α were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility. Key points: Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart.In fetal cardiomyocytes in culture, glucocorticoids promote mitochondrial fatty acid oxidation, suggesting they facilitate the perinatal switch from carbohydrates to fatty acids as the predominant energy substrate.Administration of a synthetic glucocorticoid in late pregnancy in mice downregulates the glucocorticoid receptor and interferes with the normal increase in genes involved in fatty acid metabolism in the heart.In a sheep model of preterm birth, antenatal corticosteroids (synthetic glucocorticoid) downregulates the glucocorticoid receptor and the gene encoding PGC‐1α, a master regulator of energy metabolism.These experiments suggest that administration of antenatal corticosteroids in anticipation of preterm delivery may interfere with fetal heart maturation by downregulating the ability to respond to glucocorticoids. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth in twin pregnancy before 30 weeks of gestation.Material and Methods: In a prospective cohort study, we studied the accuracy of quantitative fetal fibronectin measured between 18 and 27+6 weeks of gestation in high-risk asymptomatic women with twin pregnancies, to predict spontaneous preterm birth before 30 weeks of gestation. Predefined fetal fibronectin thresholds were ≥10, ≥50 and ≥200 ng/mL. Predictive statistics were also calculated to evaluate accuracy of "early" tests, performed between 18 and 21+6 weeks and "standard" tests performed between 22+0 and 27+6 weeks of gestation in the same cohort. Subgroup analysis was performed according to cervical length measurement. In addition, we compared accuracy of prediction with quantitative fetal fibronectin measured during the standard test period in asymptomatic twin pregnancy with no additional risk factors, to twin pregnancies with one or more additional risk factors for spontaneous preterm birth.Results: Of 130 eligible women identified with quantitative fetal fibronectin tests undertaken during the standard testing period, 9% delivered before 30 weeks of gestation. Quantitative fetal fibronectin was significantly related to outcome before 30/40 (ROC curves of 0.8 [95% CI 0.7-1]). Early tests were not significantly predictive; ROC area 0.53 (95% CI 0.29-0.81). There was a trend towards better predictive accuracy when one or more additional risk factors for spontaneous preterm birth or cervical length were considered.Conclusions: Quantitative fetal fibronectin measured from 22 to 27+6 weeks of gestation accurately predicts spontaneous preterm birth at <30 weeks of gestation. Tests undertaken earlier are of limited value. Consideration of cervical length or prior history in addition to quantitative fetal fibronectin strengthens prediction. [ABSTRACT FROM AUTHOR]

Key content: Twin pregnancies are associated with a three‐fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation. The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons. Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm. The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies. There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply. Learning objectives: To review the burden of preterm birth in multiple pregnancy. To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one. To be aware of the use of the Arabin pessary. [ABSTRACT FROM AUTHOR]

Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to determine the prognostic value of the first urinary albumin/creatinine ratio ( ACR) for adverse maternal and neonatal outcomes and how it relates to other prognostic factors. Material and methods We performed a retrospective cohort study from December 2009 to February 2012 with analysis of demographic, clinical and biochemical data from two obstetric day assessment units in hospitals in Southeast Scotland. We included 717 pregnant women, with singleton pregnancies after 20 weeks' gestation, referred for evaluation of suspected preeclampsia and having their first ACR performed. The ability of ACR to predict future outcomes was assessed in both univariable and multivariable logistic regression models. The latter assessed its prognostic value independent of (adjusting for) existing prognostic factors. Primary outcome measures were maternal and neonatal composite adverse outcomes, and a secondary outcome was gestation at delivery. Results In all, 204 women (28.5%) experienced a composite adverse maternal outcome and 146 women (20.4%) experienced a composite adverse neonatal outcome. Multivariate analysis of log-transformed ACR demonstrated that a 1-unit increase in log ACR is associated with an increased odds of adverse maternal [odds ratio 1.60, 95% confidence interval ( CI) 1.45-1.80] and adverse neonatal (odds ratio 1.15, 95% CI 1.02-1.29) composite outcomes, and with reduced gestational age at delivery (coefficient: −0.46, 95% CI −0.54 to −0.38). Conclusions ACR is an independent prognostic factor for maternal and neonatal adverse outcomes in suspected preeclampsia. ACR may be useful to inform risk predictions within a prognostic model. [ABSTRACT FROM AUTHOR]

Problem Complement is a central defence against sepsis, and increasing complement insufficiency in neonates of greater prematurity may predispose to increased sepsis. Ureaplasma spp. are the most frequently cultured bacteria from preterm blood samples. Method of study A sheep model of intrauterine Ureaplasma parvum infection was used to examine in vivo Ureaplasma bacteraemia at early and late gestational ages. Complement function and Ureaplasma killing assays were used to determine the correlation between complement potency and bactericidal activity of sera ex vivo. Results Ureaplasma was cultured from 50% of 95-day gestation lamb cord blood samples compared to 10% of 125-day gestation lambs. Bactericidal activity increased with increased gestational age, and a direct correlation between functional complement activity and bactericidal activity (R2=.86; P<.001) was found for 95-day gestational lambs. Conclusions Ureaplasma bacteraemia in vivo was confined to early preterm lambs with low complement function, but Ureaplasma infection itself did not diminish complement levels. [ABSTRACT FROM AUTHOR]

Problem Functional complement activity is routinely measured utilizing rabbit antibody-sensitized sheep erythrocytes. Due to complement inhibitor expression on erythrocytes, the development of an alternative method to measure complement function in sheep serum was required. Method of study Several species of target erythrocyte and sensitizing antibody were investigated for improved measurement of complement function testing. Results and conclusion Guinea pig erythrocytes were identified as the optimal target, although sensitizing them with rabbit antiguinea pig erythrocyte antibody did not enhance the lysis by maternal sheep serum. In contrast, preterm neonatal sheep serum was unable to efficiently lyse guinea pig erythrocytes unless pre-sensitized with antibody. Further investigation revealed that maternal serum contained high levels of antibodies that cross-reacted with guinea pig and rabbit erythrocytes, while no cross-reacting antierythrocyte antibodies were found in preterm neonatal serum. Therefore, unlike primates, rabbits, and guinea pigs, no transplacental transfer of maternal IgG to foetal sheep occurs. Use of exogenous complement regulators is often used to dissect the contribution of complement to disease pathogenesis; however, we found that while full-length soluble human complement receptor 1 ( sCR1, CDX-1135) was able to inhibit lysis of guinea pig erythrocytes by human and rat serum, no inhibition of sheep serum could be observed. Investigation of complement contribution to disease pathogenesis in the future will require the identification of an inhibitor that is effective against sheep complement. [ABSTRACT FROM AUTHOR]