Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation.

A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin ß (ß-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of ß-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations.

Primary entry trocar design and entry-related complications at laparoscopy in obese patients: meta-analysis.

BACKGROUND: Safe primary entry at laparoscopy could present challenges in obese patients. Various techniques have been proposed in previous studies, however, the characteristics of the actual device utilized may be more influential than the technique in achieving successful abdominal entry in patients with increased BMI. METHODS: This systematic review and meta-analysis included both randomized and non-randomized studies gathered with no date filters from MEDLINE, Embase, Scopus, Web of Science and Clinicaltrials.gov. PRISMA guidelines underpinned the conduct and reporting of the review. The meta-analysis of proportions was conducted using a generalized linear mixed model and analyses included random-effects models. The primary outcome was the proportion of first access vascular and visceral injuries incurred in the process of laparoscopic abdominal surgery in patients with a BMI >30 kg/m2. Subgroup analysis was performed for optical versus non-optically enabled devices. RESULTS: In total, 5403 patients were analysed across 13 observational studies with a mean BMI of 45.93 kg/m2. In 216 patients from two randomized studies, the mean BMI was 39.92 kg/m2. The overall incidence using a random-effects model was 8.1 per 1000 events of visceral and vascular injuries (95 per cent c.i. 0.003 to 0.024). Heterogeneity was statistically significant at I2 = 80.5 per cent (69.6 per cent; 87.5 per cent, P< 0.0001). In a subgroup analysis, a tendency towards reduced injuries when optical devices were employed was observed with one per 100 injuries in these trocars (95 per cent c.i. 0.001 to 0.018) versus four per 100 (95 per cent c.i. -0.019 to -0.102) in non-optically enabled devices. CONCLUSION: Injuries during primary laparoscopic entry undertaken in obese patient groups are uncommon. Due to considerable heterogeneity in the small number of examined studies, evidence was insufficient and largely of low quality to ascribe differences in the incidence of injuries to the characteristics of the primary entry trocar utilized.

Optimising timing of steroid administration in preterm pre-eclampsia.

Antenatal corticosteroids (ACS) are an established intervention to improve outcomes in preterm birth. ACS are optimally timed if the administration-to-birth interval is greater than 24 h and <7 days. Evidence has emerged suggesting harm associated with administration-to-birth intervals greater than seven days, or with repeated courses of ACS. Pre-eclampsia is a leading cause of iatrogenic preterm birth, as delivery of the fetus and placenta remains the only cure. This study investigated optimal ACS use in women delivering before 35 weeks' gestation in the United Kingdom with a diagnosis of preterm pre-eclampsia. Of 1,632 women with suspected pre-eclampsia, 250 delivered before 35 weeks' gestation with pre-eclampsia. 31 % (78/250) received optimally timed ACS, 49 % (122/250) received ACS more than seven days pre-delivery and 20 % (50/250) did not receive ACS. There were no significant differences in gestational age, mean birthweight, respiratory distress syndrome, neonatal unit admission or neonatal death between groups. There was a higher rate of intrauterine fetal death in the group of women who did not receive ACS (p < 0.05), and a corresponding increase in vaginal delivery and reduction in caesarean section (p < 0.05). Optimal ACS administration is poor in women delivering preterm with pre-eclampsia and the largest group of mistimed ACS administration were those given more than 7 days prior to birth. Clinicians should defer ACS until a decision for delivery has been made, at which point ACS should be prioritised. Judicious use of ACS may improve outcomes.

Mental health impact on Black, Asian and Minority Ethnic populations with preterm birth: A systematic review and meta-analysis.

BACKGROUND: Preterm birth (PTB) is one of the main causes of neonatal deaths globally, with approximately 15 million infants are born preterm. Women from the Black, Asian, and Minority Ethnic (BAME) populations maybe at higher risk of PTB, therefore, the mental health impact on mothers experiencing a PTB is particularly important, within the BAME populations. AIM: To determine the prevalence of mental health conditions among BAME women with PTB as well as the methods of mental health assessments used to characterise the mental health outcomes. METHODS: A systematic methodology was developed and published as a protocol in PROSPERO (CRD42020210863). Multiple databases were used to extract relevant data. I 2 and Egger's tests were used to detect the heterogeneity and publication bias. A trim and fill method was used to demonstrate the influence of publication bias and the credibility of conclusions. RESULTS: Thirty-nine studies met the eligibility criteria from a possible 3526. The prevalence rates of depression among PTB-BAME mothers were significantly higher than full-term mothers with a standardized mean difference of 1.5 and a 95% confidence interval (CI) 29%-74%. The subgroup analysis indicated depressive symptoms to be time sensitive. Women within the very PTB category demonstrated a significantly higher prevalence of depression than those categorised as non-very PTB. The prevalence rates of anxiety and stress among PTB-BAME mothers were significantly higher than in full-term mothers (odds ratio of 88% and 60% with a CI of 42%-149% and 24%-106%, respectively). CONCLUSION: BAME women with PTB suffer with mental health conditions. Many studies did not report on specific mental health outcomes for BAME populations. Therefore, the impact of PTB is not accurately represented in this population, and thus could negatively influence the quality of maternity services they receive.

A systematic review and meta-analysis of gestational diabetes mellitus and mental health among BAME populations.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with an increased risk of mental health (MH) disorders including antenatal and postnatal depression (PND), anxiety and post-traumatic-stress-disorder (PTSD). We hypothesized GDM and MH disorders will disproportionately affect individuals from Black, Asian and Minority Ethnic backgrounds. METHODS: A systematic methodology was developed, and a protocol was published in PROSPERO (CRD42020210863) and a systematic review of publications between 1st January 1990 and 30th January 2021 was conducted. Multiple electronic databases were explored using keywords and MeSH terms. The finalised dataset was analysed using statistical methods such as random-effect models, subgroup analysis and sensitivity analysis. These were used to determine odds ratio (OR) and 95% confidence intervals (CI) to establish prevalence using variables of PND, anxiety, PTSD and stress to name a few. FINDINGS: Sixty studies were finalised from the 20,040 data pool. Forty-six studies were included systematically with 14 used to meta-analyze GDM and MH outcomes. A second meta-analysis was conducted using 7 studies to determine GDM risk among Black, Asian and Minority Ethnic women with pre-existing MH disorders. The results indicate an increased risk with pooled adjusted OR for both reflected at 1.23, 95% CI of 1.00-1.50 and 1.29, 95% CI of 1.11-1.50 respectively. INTERPRETATION: The available studies suggest a MH sequalae with GDM as well as a sequalae of GDM with MH among Black, Asian and Minority Ethnic populations. Our findings warrant further future exploration to better manage these patients. FUNDING: Not applicable.

Anti-Infective Dosing in Special Populations: Pregnancy.

Substantial anatomical and physiological changes occur during pregnancy and labor, which impact on drug absorption, distribution, metabolism, and elimination. Reduced maternal concentrations may have a clinically important impact on the efficacy of anti-infectives for mother, fetus, and neonate, with potential dosing implications. However, there is a paucity of pregnancy-specific data examining this. Existing data on the pharmacokinetics of anti-infectives in pregnancy are summarized and evaluated, with emphasis on agents that are used in treatment of HIV, tuberculosis, malaria, and common bacterial infections. Limitations and challenges in achieving ideal study designs in pregnant populations are highlighted, and key quality considerations for the generation of the highest quality evidence are outlined. PubMed was searched for each chosen anti-infective. Pharmacokinetic studies which either compared pharmacokinetics from pregnant women against nonpregnant controls, or which assessed concentrations against a known minimum inhibitory concentration were included. Two independent reviewers extracted data from each study and appraised them using the 24-point ClinPK Checklist. The main finding was that there is a lack of published data for anti-infectives in pregnancy, despite their clinical importance. Of the studies identified, only those investigating cobicistat-boosted antiretroviral regimens firmly concluded that these should not be used in pregnancy. Most studies concluded either that further research was needed, or that there were significant pharmacokinetic differences between pregnant and nonpregnant participants which had uncertain clinical significance. Challenges in applying existing quality grading systems to these studies were noted, suggesting a development of a refined system for appraisal of pharmacokinetic studies in "special populations" may be warranted.

The characteristics and prevalence of phobias in pregnancy.

OBJECTIVE: The primary objective was to estimate the population prevalence of specific phobias (including pregnancy related specific phobias) and associated mental disorders. The secondary objective was to investigate the effectiveness of routinely collected screening tools (depression and anxiety screens, Whooley and GAD-2 respectively) in identifying specific phobias. Specific phobias are the most common anxiety disorder to occur during pregnancy, but studies on prevalence and clinical correlates of specific phobias, including pregnancy related specific phobias are lacking. DESIGN: Cross-sectional survey using a two-phase sampling design stratified according to being positive or negative on the Whooley questions routinely asked by midwives. Approaching all whooley positive women and drawing a random sample of Whooley negative women. Sampling weights were used to account for the bias induced by the stratified sampling. PARTICIPANTS: 545 pregnant women attending their first antenatal appointment. Language interpreters were used where required. SETTING: Inner-city maternity service, London, UK. MEASUREMENTS: The Structured Clinical Interview for DSM-IV Axis I Mental Disorders were administered to assess mental disorders and 544 women responded to the anxiety module on specific phobias. RESULTS: The maternity population prevalence estimate for specific phobias was 8.4% (95%CI: 5.8-12.1%) and for pregnancy related phobias was 1.5% (95%CI: 0.6-3.7%), most of which were needle phobias. The prevalence estimate of tokophobia was 0.032% (95%CI: 0.0044-0.23%). Over half (52.4%) the women with specific phobias had comorbid mental disorders. Routinely administered screening tools (Whooley and GAD-2) were not helpful in identifying phobias. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Phobias in pregnancy are common but pregnancy related phobias are rare, particularly tokophobia. As routinely administered screening tools were not helpful in identifying phobias, other indicators could be considered, such as avoidance of blood tests and requests for caesarean sections.

Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood.

Perinatal interventions for mothers and fathers who are survivors of childhood sexual abuse.

Childhood sexual abuse (CSA) is a worldwide problem with severe long-term consequences. A history of CSA can impact the childbearing experience of mothers and fathers; affecting their mental health, parenting skills and compromising infant development. Nonetheless, the perinatal period offers huge opportunity for intervention and hope. This literature review collates evidence for perinatal psychosocial interventions targeting both mothers and fathers who are survivors of CSA. Publications dating from 1970 to June 2016 were searched using Medline, Maternity and Infant Health, PsychINFO, PsychArticles, PubMed and the International Bibliography of the Social Sciences (IBSS). There were no perinatal interventions that considered the needs of survivor fathers. Sixteen publications on 9 psychosocial perinatal interventions for CSA survivors were identified. However, no sub-analyses specific to CSA survivors were reported. Trauma-specific perinatal interventions drew from a range of theoretical models and varied widely in format. Generally interventions were associated with improvements in maternal mental health, parenting competence, infant attachment security and positive public health outcomes. They were safe and feasible to implement, acceptable to parents and therapist, and therapists were able to implement protocols with adequate fidelity. Yet current data is hampered by small sample size, inconsistent reporting of CSA rates and outcome measures, scarcity of observational data and longer-term follow-up. Intervention modifications are proposed for CSA survivors in view of their unique childbearing experiences.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.