New research on the global prevalence of female genital mutilation/cutting: Research, clinical, and policy implications.

In this perspective, Kerrie Stevenson and Brenda Kelly discuss new research on the prevalence of female genital mutilation/cutting alongside clinical and policy implications.

Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicenter study.

BACKGROUND: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies. OBJECTIVE: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance. STUDY DESIGN: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020. RESULTS: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%. CONCLUSION: This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins.

Communication with children and adolescents about the diagnosis of a life-threatening condition in their parent.

Many adults diagnosed with a life-threatening condition have children living at home; they and their partners face the dual challenge of coping with the diagnosis while trying to maintain a parenting role. Parents are often uncertain about how, when, and what to tell their children about the condition, and are fearful of the effect on their family. There is evidence that children are often aware that something is seriously wrong and want honest information. Health-care professionals have a key role in supporting and guiding parents and caregivers to communicate with their children about the diagnosis. However, the practical and emotional challenges of communicating with families are compounded by a scarcity of evidence-based guidelines. This Review considers children's awareness and understanding of their parents' condition, the effect of communication around parental life-threatening condition on their wellbeing, factors that influence communication, and the challenges to achieving effective communication. Children's and parents' preferences about communication are outlined. An expert workshop was convened to generate principles for health-care professionals, intended as practical guidance in the current absence of empirically derived guidelines.

Communication with children and adolescents about the diagnosis of their own life-threatening condition.

When a child is diagnosed with a life-threatening condition, one of the most challenging tasks facing health-care professionals is how to communicate this to the child, and to their parents or caregivers. Evidence-based guidelines are urgently needed for all health-care settings, from tertiary referral centres in high-income countries to resource limited environments in low-income and middle-income countries, where rates of child mortality are high. We place this Review in the context of children's developing understanding of illness and death. We review the effect of communication on children's emotional, behavioural, and social functioning, as well as treatment adherence, disease progression, and wider family relationships. We consider the factors that influence the process of communication and the preferences of children, families, and health-care professionals about how to convey the diagnosis. Critically, the barriers and challenges to effective communication are explored. Finally, we outline principles for communicating with children, parents, and caregivers, generated from a workshop of international experts.

Fifteen-minute consultation: perinatal palliative care.

Perinatal palliative medicine is an emerging subspecialty within paediatric palliative medicine, neonatal medicine, fetal medicine and obstetrics. It comprises patient-focused, non-judgemental shared decision making and aims to provide holistic multidisciplinary support for families. In this paper we define and describe one model for providing perinatal palliative care, drawing on the personal and professional experience of the authors.

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2-5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

Short-term exposure to exogenous lipids in premature infants and long-term changes in aortic and cardiac function.

OBJECTIVE: Intravenous lipid use is associated with an acute hyperlipidemia, but long-term consequences have not been studied. We investigated whether elevated lipids in humans during the critical period of preterm neonatal life have a long-term impact on aortic and myocardial function relevant to adult disease. METHODS AND RESULTS: We followed up 102 subjects born prematurely and now aged 23 to 28 years. Eighteen received intravenous lipids as neonates and were matched to controls with equivalent perinatal characteristics. Global and regional aortic stiffness and left ventricular function were assessed by cardiovascular magnetic resonance. Those who received intravenous lipids had greater aortic stiffness in early adulthood (P=0.0002), with greater stiffness in the abdominal aorta (P=0.012). The relationship was graded according to the elevation in neonatal cholesterol induced by intravenous lipids (P<0.0001) but not other metabolic parameters altered by the infusion. Peak systolic circumferential strain was also reduced in the lipid group (P=0.006), which, again, was proportional to neonatal cholesterol level (P<0.01). CONCLUSIONS: Aortic and myocardial function in young adulthood is associated with intralipid exposure during neonatal life for preterm infants, in a graded manner related to the rise in cholesterol. Circulating cholesterol during critical developmental periods may have long-term impacts on the human cardiovascular system.

Obstetrical opportunities: will pharmacy ever realize them?

Based on a survey of the American College of Clinical Pharmacy Women's Health Practice and Research Network and our own experience, the pharmacy profession has limited involvement in obstetric pharmacotherapy. We believe that such involvement in pregnancies with complicated conditions can result in significant improvement of pregnancy outcomes. Moreover, we believe this involvement would be welcomed by the physicians caring for these patients. This commentary documents current obstetrical pharmacy practices and proposes changes for the profession of pharmacy to consider.

Case of placental insufficiency and premature delivery in a Fontan pregnancy: physiological insights and considerations on risk stratification.

OBJECTIVES: The coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion. METHODS AND RESULTS: We analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings. CONCLUSION: Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.

Barriers to establishing shared decision-making in childbirth: Unveiling epistemic stereotypes about women in labour.

RATIONALE, AIMS, AND OBJECTIVES: The benefits for shared decision-making (SDM) in delivery of high-quality and personalized care are undisputed, but what is it about the dynamics of the delivery room that leads some to doubt that true SDM is possible? How difficult can it be to establish SDM as the norm when caring for a woman in labour? The discussion around SDM, autonomy, and rationality is timely and highly relevant to wider practice. METHOD: The concept of a person's autonomy in decision-making about their body and health is generally accepted and is indeed enshrined in law in many countries. This ought to lay the foundation for SDM in obstetrics. Yet, women's experience speaks to an uncomfortable truth, namely, that it is far from commonplace. We are interested in exploring this tension between the law and the practice. RESULTS: We examine a theory of female rationality and its application to women in labour, and juxtapose this with the view from the front line of care delivery. Is a woman in labour able to fully engage in an SDM process? In answering this question, associations in the discourses and practises around women's capacity during labour are revealed, which act as barriers, consciously or unconsciously, to establishing SDM as the norm in obstetrics and midwifery. CONCLUSION(S): The recent UN report advocating a human rights-based approach to end mistreatment and violence against women in reproductive health services has a particular focus on childbirth and obstetric violence. This paper contributes to the recognition of obstetric violence as a human rights violation. It offers conceptual tools to diagnose the impact of gender stereotypes during childbirth and to eliminate women's discrimination in the field of reproductive health.

A Deep Learning Solution for Automatic Fetal Neurosonographic Diagnostic Plane Verification Using Clinical Standard Constraints.

During routine ultrasound assessment of the fetal brain for biometry estimation and detection of fetal abnormalities, accurate imaging planes must be found by sonologists following a well-defined imaging protocol or clinical standard, which can be difficult for non-experts to do well. This assessment helps provide accurate biometry estimation and the detection of possible brain abnormalities. We describe a machine-learning method to assess automatically that transventricular ultrasound images of the fetal brain have been correctly acquired and meet the required clinical standard. We propose a deep learning solution, which breaks the problem down into three stages: (i) accurate localization of the fetal brain, (ii) detection of regions that contain structures of interest and (iii) learning the acoustic patterns in the regions that enable plane verification. We evaluate the developed methodology on a large real-world clinical data set of 2-D mid-gestation fetal images. We show that the automatic verification method approaches human expert assessment.

Sexually-dimorphic expression of tyrosine hydroxylase immunoreactivity in the brain of a vocal teleost fish (Porichthys notatus).

Vocal communication has emerged as a powerful model for the study of neural mechanisms of social behavior. Modulatory neurochemicals postulated to play a central role in social behavior, related to motivation, arousal, incentive and reward, include the catecholamines, particularly dopamine and noradrenaline. Many questions remain regarding the functional mechanisms by which these modulators interact with sensory and motor systems. Here, we begin to address these questions in a model system for vocal and social behavior, the plainfin midshipman fish (Porichthys notatus). We mapped the distribution of immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) in the midshipman brain. The general pattern of TH(+) cell groups in midshipman appears to be highly conserved with other teleost fish, with a few exceptions, including the apparent absence of pretectal catecholamine cells. Many components of the midshipman vocal and auditory systems were innervated by TH(+) fibers and terminals, including portions of the subpallial area ventralis, the preoptic complex, and the anterior hypothalamus, the midbrain periaqueductal gray and torus semicircularis, several hindbrain auditory nuclei, and parts of the hindbrain vocal pattern generator. These areas thus represent potential sites for catecholamine modulation of vocal and/or auditory behavior. To begin to test functionally whether catecholamines modulate vocal social behaviors, we hypothesized that male and female midshipman, which are sexually dimorphic in both their vocal-motor repertoires and in their responses to hearing conspecific vocalizations, should exhibit sexually dimorphic expression of TH immunoreactivity in their vocal and/or auditory systems. We used quantitative immunohistochemical techniques to test this hypothesis across a number of brain areas. We found significantly higher levels of TH expression in male midshipman relative to females in the TH cell population in the paraventricular organ of the diencephalon and in the TH-innervated torus semicircularis, the main teleost midbrain auditory structure. The torus semicircularis has been implicated in sexually dimorphic behavioral responses to conspecific vocalizations. Our data thus support the general idea that catecholamines modulate vocal and auditory processing in midshipman, and the specific hypothesis that they shape sexually dimorphic auditory responses in the auditory midbrain.

Prevention of vascular dysfunction after preeclampsia: a potential long-term outcome measure and an emerging goal for treatment.

Preeclampsia is increasingly being recognised as more than an isolated disease of pregnancy. In particular, preeclampsia has emerged as an independent risk factor for maternal cardiovascular disease and has recently been recognised as a risk factor for cardiovascular disease in children exposed in utero. Preeclampsia and cardiovascular disease may share important pathophysiological and molecular mechanisms and further investigation into these is likely to offer insight into the origins of both conditions. This paper considers the links between cardiovascular disease and preeclampsia and the implication of these findings for refinement of the management of patients whose care is complicated by preeclampsia.

Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review.

BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on 45,249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74-3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90-1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism. CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.

Antenatal glucocorticoid exposure and long-term alterations in aortic function and glucose metabolism.

OBJECTIVE: Animal studies have demonstrated long-term effects of in utero glucocortcoid exposure on vascular development and glucose metabolism. We hypothesized that there would be a similar impact in humans. METHODS: One hundred and two young adults born preterm aged 23 to 28 years, with prospective data collection from birth, and 95 adults born term after uncomplicated pregnancies underwent cardiovascular MRI. We compared cardiac and aortic structure and function, as well as cardiovascular risk profile, in a nested case-control study of 16 participants exposed to antenatal steroids and 32 who were not, but with otherwise similar perinatal care. Outcomes were compared with normal ranges in those born term. RESULTS: Adults whose mothers had received antenatal steroids had decreased ascending aortic distensibility (9.88 ± 3.21 vs 13.62 ± 3.88 mm Hg(-1) × 10(3), P = .002) and increased aortic arch pulse wave velocity (5.45 ± 1.41 vs 4.47 ± 0.91 m/s, P = .006). The increase in stiffness was equivalent to that of term adults a decade older. Those who had in utero exposure to antenatal steroids also had significant differences in homeostatic model assessments for ß-cell function (P = .010), but in multiple regression analysis this did not explain the impact of steroids on aortic function. CONCLUSIONS: Antenatal glucocorticoid exposure in preterm infants is associated with increased aortic arch stiffness and altered glucose metabolism in early adulthood.