A Population-Based Test-Negative Matched Case-Control Analysis of SARS-CoV-2 Vaccine Effectiveness Among Pregnant People in Ontario, Canada.

OBJECTIVE: Pregnancy is a risk factor for severe SARS-CoV-2 infection, which can result in adverse pregnancy outcomes, thus making understanding vaccine effectiveness (VE) in this population important. This study aimed to assess the VE of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in pregnant people. METHODS: Population-based matched test-negative case-control study of pregnant people aged 18-49 years, of 12 or more weeks gestation in Ontario, Canada, symptomatic with possible SARS-CoV-2 infection, and having at least 1 positive (n = 1842) or negative (n = 8524) real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 test between December 14, 2020, and December 31, 2021. The exposure was receipt of ≥1 dose of mRNA COVID-19 vaccine versus no vaccination. Exposure was further stratified by number and recency of doses. The primary outcome was a positive SARS-CoV-2 RT-PCR test. As a secondary outcome, VE for COVID-19-related hospitalization was assessed. RESULTS: In the primary outcome analysis, there were 1821 positive cases, matched to 1821 negative controls. The mean (SD) maternal age was 31 (5) years. When compared to those unvaccinated, receipt of ≥1 dose was associated with an estimated VE of 39% (95% CI 29%-48%) for symptomatic infection, and 85% (95% CI 72%-92%) for COVID-19 hospitalization. VE estimates demonstrated waning with increased time since last vaccination. CONCLUSIONS: mRNA COVID-19 vaccines provide protection against symptomatic COVID-19 illness and are highly effective at preventing severe illness in pregnant people. The observed effect of vaccine waning highlights the importance of booster doses to provide optimal protection for pregnant people.

Correlations of Placental Histopathology, Neonatal Outcome, and Cardiotocogram Baseline Variability and Acceleration Patterns in the Growth Restricted Preterm Population.

OBJECTIVE: To evaluate the possible connections of cardiotocography (CTG) signs with neonatal outcome and placental histopathology between growth restricted preterms. MATERIALS AND METHODS: Placental slides, baseline variability, and acceleration patterns of cardiotocograms, and neonatal parameters were studied retrospectively. Placental histopathological changes were diagnosed according to the Amsterdam criteria; percentage of intact terminal villi and capillarization of villi were also studied. 50 cases were analyzed: 24 were early-onset fetal growth restriction (FGR), 26 were late-onset FGR. RESULTS: Reduced baseline variability was related to poor neonatal outcome; lack of accelerations similarly had associations with poor outcomes. Maternal vascular malperfusion, avascular villi, VUE, and chorangiosis were more common in the background of reduced baseline variability and absence of accelerations. Lower percentage of intact terminal villi was significantly associated with lower umbilical artery pH, higher lactate levels, and reduced baseline variability on CTG; absence of accelerations was correlated with decreased capillarization of terminal villi. CONCLUSIONS: Baseline variability and absence of accelerations seem to be useful and reliable markers in predicting poor neonatal outcome. Maternal and fetal vascular malperfusion signs, decreased capillarization, and lower percentage of intact villi in placenta could contribute to pathologic CTG signs and poor prognosis.

Placental Pathology and Its Associations With Clinical Signs in Different Subtypes of Fetal Growth Restriction.

OBJECTIVE: We evaluated placental alterations in different subtypes of fetal growth restriction (FGR) to determine any clinical associations. METHODS: FGR placentas classified according to the Amsterdam criteria were correlated with clinical findings. Percentage of intact terminal villi and villous capillarization ratio were calculated in each specimen. Correlations of placental histopathology and perinatal outcomes were studied. 61 FGR cases were studied. RESULTS: Early-onset-FGR was more often associated with preeclampsia and recurrence than late-onset-FGR; placentas from early-onset-FGR often had diffuse maternal (or fetal) vascular malperfusion and villitis of unknown etiology. Decreased percentage of intact terminal villi was associated with pathologic CTG. Decreased villous capillarization was associated with early-onset-FGR and birth weight below the second percentile. Avascular villi and infarction were more common when femoral length/abdominal circumference ratio was >0.26, and perinatal outcome was poor in this group. CONCLUSION: In early-onset-FGR and preeclamptic FGR, altered vascularization of villi may have a key role in pathogenesis, and recurrent FGR is associated with villitis of unknown etiology. There is an association between femoral length/abdominal circumference ratio >0.26 and histopathological alterations of placenta in FGR pregnancies. There are no significant differences in the percentage of intact terminal villi between different FGR subtypes by onset or recurrency.

German obstetrician's self-reported attitudes and handling in threatening preterm birth at the limits of viability.

OBJECTIVES: Antenatal treatment and information influences the course of pregnancy and parental decision-making in cases of threatened prematurity on the borderline of viability. Numerous studies have shown significant interprofessional differences in assessing ethical boundary decisions; hence, this study aimed to evaluate obstetricians attitudes, practices and antenatal parental counseling regarding threatened preterm birth in Germany. METHODS: An anonymous online questionnaire was administered to 543 obstetricians at tertiary perinatal centers and prenatal diagnostic centers in Germany. The survey contained questions on basic ethical issues assessed using the Likert scale and a case vignette regarding the practical procedures of an imminent extreme premature birth at 23 1/7 gestational weeks. RESULTS: In the case of unstoppable preterm birth, 15 % of clinicians said they would carry out a cesarean section; however, specialists from centers with a high number of very low birth weight infants would do so significantly more often. Among respondents, 29.8 % did not take any therapeutic measures without discussing the child's treatment options with their parents, 19.9 % refused to offer actionable advice to the parents, and 57 % said they would advise parents to seek intensive care treatment for the child with the option of changing treatment destination in the event of serious complications. Moreover, 84 % said they would provide information together with neonatologists. CONCLUSIONS: Joint counseling with neonatologists is widely accepted. The size of the perinatal center significantly influences the practical approach to threatened preterm births. Respect for parents' decision-making autonomy regarding the child's treatment options is central and influences therapy initiation.

Placental pathology of preeclampsia from a clinical point of view: Correlation between placental histopathology, clinical signs of preeclampsia and neonatal outcome.

AIM: To evaluate the associations between placental histopathology (signs of maternal and fetal vascular malperfusion, delayed villous maturation, villitis of unknown etiology) and subtypes of preeclampsia by onset, clinical aspects of the disease and neonatal outcome. METHODS: Placental slides from preeclamptic pregnancies were retrospectively reviewed according to a uniform scheme. Information regarding obstetrical anamnesis, clinical data and perinatal outcome was collected from charts, and statistical analysis was performed in order to demonstrate associations between microscopic placental alterations and different aspects of preeclampsia. RESULTS: A total of 49 cases were studied. Diffuse signs of maternal vascular malperfusion and avascular villi were more common in early-onset-preeclampsia associated with worse prognosis. Preeclampsia with fetal growth restriction had more often diffuse signs of maternal and fetal vascular malperfusion and villitis of unknown etiology. Recurring preeclampsia was associated with more common perivasculitis. Umbilical and uterine artery Doppler indices were associated with medial hypertrophy and/or acute atherosis of maternal decidual vessels. Large foci of avascular villi correlated with extent of maternal 24-h-proteinuria which itself correlated with outcome of preeclampsia. Rate of capillarisation of villi was significantly lower in case of hypertension requiring a three-drug combination of antihypertensive medications versus hypertension treated with one or two drugs, preeclampsia with growth restriction, and stillbirth versus live birth. CONCLUSIONS: Early- versus late-onset-preeclampsia showed a markedly different profile of histopathological features and perinatal outcome, reflecting their distinguished pathogenesis and prognosis; preeclampsia complicated with fetal growth restriction also had distinctive features. Qualitative and quantitative changes define placental pathology of preeclampsia.

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Since the global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020, the virus has been evolving through mutations to acquire enhanced infectivity but reduced virulence. With a wide vaccination coverage among Chinese population, China is entering a new stage of SARS-CoV-2 infection control. The Working Group for the Prevention and Control of Neonatal SARS-CoV-2 Infection in the Perinatal Period of the Editorial Committee of Chinese Journal of Contemporary Pediatrics released the first and second editions of perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection in January and March 2020, respectively. In order to follow up new prevention and control needs, it is necessary to update the management plan to better guide clinical practice. Therefore, the Working Group formulated the 3rd-edition plan.

Adapting obstetric and neonatal services during the COVID-19 pandemic: a scoping review.

BACKGROUND: The provision of care to pregnant persons and neonates must continue through pandemics. To maintain quality of care, while minimizing physical contact during the Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV2) pandemic, hospitals and international organizations issued recommendations on maternity and neonatal care delivery and restructuring of clinical and academic services. Early in the pandemic, recommendations relied on expert opinion, and offered a one-size-fits-all set of guidelines. Our aim was to examine these recommendations and provide the rationale and context to guide clinicians, administrators, educators, and researchers, on how to adapt maternity and neonatal services during the pandemic, regardless of jurisdiction. METHOD: Our initial database search used Medical subject headings and free-text search terms related to coronavirus infections, pregnancy and neonatology, and summarized relevant recommendations from international society guidelines. Subsequent targeted searches to December 30, 2020, included relevant publications in general medical and obstetric journals, and updated society recommendations. RESULTS: We identified 846 titles and abstracts, of which 105 English-language publications fulfilled eligibility criteria and were included in our study. A multidisciplinary team representing clinicians from various disciplines, academics, administrators and training program directors critically appraised the literature to collate recommendations by multiple jurisdictions, including a quaternary care Canadian hospital, to provide context and rationale for viable options. INTERPRETATION: There are different schools of thought regarding effective practices in obstetric and neonatal services. Our critical review presents the rationale to effectively modify services, based on the phase of the pandemic, the prevalence of infection in the population, and resource availability.

Maternal, Fetal, and Neonatal Outcomes of Elective Fetal Reduction Among Multiple Gestation Pregnancies: A Systematic Review.

OBJECTIVE: To review the existing literature on fetal and maternal health outcomes following elective pregnancy reduction. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Trials Register. STUDY SELECTION: Studies involving women pregnant with dichorionic twins, trichorionic triplets, or quadra-chorionic quadruplets who underwent elective fetal reduction of 1 or more fetuses to reduce the risks associated with multiple gestation pregnancies. DATA EXTRACTION: The main fetal health outcomes measured were gestational age at delivery, preterm birth, miscarriage, birth weight, and small for gestational age at delivery. The main maternal health outcomes measured were gestational diabetes, hypertensive disorders of pregnancy, and cesarean delivery. DATA SYNTHESIS: Of 7678 studies identified, 24 were included (n = 425 dichorionic twin pregnancies, n = 2753 trichorionic triplet pregnancies, and n = 111 quadra-chorionic quadruplet pregnancies). Fifteen studies (62.5%) did not report maternal health outcomes, while every study reported at least 1 fetal health outcome. Fetal reduction was associated with higher gestational age at birth, lower preterm birth, higher birth weight, and lower rates of small for gestational age infants and intrauterine growth restriction. No consistent pattern was observed for miscarriage and neonatal mortality rates. Following fetal reduction, cesarean delivery rates were lower in most studies. There were no appreciable trends with respect to gestational diabetes or hypertensive disorders of pregnancy. CONCLUSION: Fetal reduction reliably optimizes gestational age at birth and neonatal birth weight. Miscarriage rates and other adverse procedural outcomes did not increase following transabdominal reduction. Further research on maternal outcomes is needed given a paucity of information in the literature.

Contributions of Artificial Intelligence Reported in Obstetrics and Gynecology Journals: Systematic Review.

BACKGROUND: The applications of artificial intelligence (AI) processes have grown significantly in all medical disciplines during the last decades. Two main types of AI have been applied in medicine: symbolic AI (eg, knowledge base and ontologies) and nonsymbolic AI (eg, machine learning and artificial neural networks). Consequently, AI has also been applied across most obstetrics and gynecology (OB/GYN) domains, including general obstetrics, gynecology surgery, fetal ultrasound, and assisted reproductive medicine, among others. OBJECTIVE: The aim of this study was to provide a systematic review to establish the actual contributions of AI reported in OB/GYN discipline journals. METHODS: The PubMed database was searched for citations indexed with "artificial intelligence" and at least one of the following medical subject heading (MeSH) terms between January 1, 2000, and April 30, 2020: "obstetrics"; "gynecology"; "reproductive techniques, assisted"; or "pregnancy." All publications in OB/GYN core disciplines journals were considered. The selection of journals was based on disciplines defined in Web of Science. The publications were excluded if no AI process was used in the study. Review, editorial, and commentary articles were also excluded. The study analysis comprised (1) classification of publications into OB/GYN domains, (2) description of AI methods, (3) description of AI algorithms, (4) description of data sets, (5) description of AI contributions, and (6) description of the validation of the AI process. RESULTS: The PubMed search retrieved 579 citations and 66 publications met the selection criteria. All OB/GYN subdomains were covered: obstetrics (41%, 27/66), gynecology (3%, 2/66), assisted reproductive medicine (33%, 22/66), early pregnancy (2%, 1/66), and fetal medicine (21%, 14/66). Both machine learning methods (39/66) and knowledge base methods (25/66) were represented. Machine learning used imaging, numerical, and clinical data sets. Knowledge base methods used mostly omics data sets. The actual contributions of AI were method/algorithm development (53%, 35/66), hypothesis generation (42%, 28/66), or software development (3%, 2/66). Validation was performed on one data set (86%, 57/66) and no external validation was reported. We observed a general rising trend in publications related to AI in OB/GYN over the last two decades. Most of these publications (82%, 54/66) remain out of the scope of the usual OB/GYN journals. CONCLUSIONS: In OB/GYN discipline journals, mostly preliminary work (eg, proof-of-concept algorithm or method) in AI applied to this discipline is reported and clinical validation remains an unmet prerequisite. Improvement driven by new AI research guidelines is expected. However, these guidelines are covering only a part of AI approaches (nonsymbolic) reported in this review; hence, updates need to be considered.

A case of corpus callosum dysplasia with different development of the corpus callosum in the right and left brain hemispheres.

The corpus callosum (CC) is a thick band of nerve fibers that divides the cerebral cortex lobes into the left and right hemispheres. Prenatal diagnosis of corpus callosum agenesis (partial/total) has been described frequently in the literature. In this case report, a case of corpus callosum dysplasia with different development of the halves of the corpus callosum in the right and left brain hemispheres, which was not previously discussed in the literature, will be described. Whenever we have any doubts about CC, axial, coronal, and sagittal scans of the fetal brain should be performed with TVUSG (transvaginal ultrasonography) or TAUSG (transabdominal ultrasonography) according to the position of the fetal head, and both length and thickness should be measured.

Placental abruption in immigrant women in Norway: A population-based study.

INTRODUCTION: Placental abruption is a serious complication in pregnancy. Its incidence varies across countries, but the information of how placental abruption varies in immigrant populations is limited. The aims of this study were to estimate the incidence of placental abruption in immigrant women compared with non-immigrants by maternal country and region of birth, reason for immigration, and length of residence. MATERIAL AND METHODS: We conducted a nationwide population-based study using data from the Medical Birth Registry of Norway and Statistics Norway (1990-2016). The study sample included 1 558 174 pregnancies, in which immigrant women accounted for 245 887 pregnancies and 1 312 287 pregnancies were to non-immigrants. Crude and adjusted odds ratios with 95% CI for placental abruption in immigrant women compared with non-immigrants were estimated by logistic regression with robust standard error estimations (accounting for within-mother clustering). Adjustment variables included year of birth, maternal age, parity, multiple pregnancies, chronic hypertension, and level of education. RESULTS: The incidence of placental abruption decreased during the study period for both immigrants (from 0.68% to 0.44%) and non-immigrants (from 0.80% to 0.34%). Immigrant women from sub-Saharan Africa had an adjusted odds ratio of 1.35 (95% CI 1.15-1.58) compared with non-immigrants for placental abruption, whereas immigrant women from Ethiopia had an adjusted odds ratio of 2.39 (95% CI 1.67-3.41). We found a small variation in placental abruption incidence by other countries or regions of birth, length of residence, and reason for immigration. CONCLUSIONS: Immigrant women from sub-Saharan Africa, especially Ethiopia, have increased odds for placental abruption when giving birth in Norway. Reason for immigration and length of residence had little impact on the incidence of placental abruption.

Risk of adverse perinatal outcomes in infants born to mothers with mental health conditions.

INTRODUCTION: Maternal mental health conditions have been shown to affect perinatal outcomes negatively. However, knowledge on the impact of different types and severities of maternal mental health conditions is needed. The objective of this study was to determine the association between maternal mental health status and perinatal health outcomes in the infant. MATERIAL AND METHODS: This register-based cohort study included all live-born infants in Denmark born between 2000 and 2016. Exposed infants were grouped based on whether the mothers received mental health care in primary care settings only (minor conditions) or required specialized psychiatric intervention (moderate-severe conditions) within 12 months before childbirth. Modified Poisson regression analyses were applied to produce adjusted risk ratios (aRRs) for each perinatal outcome of interest. The primary outcomes were neonatal mortality, 5-minute Apgar scores <7 and <4 and newborn hospital admission during the neonatal period. Secondary outcomes included several neonatal morbidities such as respiratory distress syndrome and abstinence syndrome. RESULTS: A total of 952 071 infants were included in the analysis; 4.0% had mothers with minor mental health conditions and 2.9% had mothers with moderate-severe conditions. The risk of neonatal death in exposed infants was aRR 1.08 (95% CI 0.93-1.27) for minor mental health conditions and aRR 0.93 (95% CI 0.78-1.11) for moderate-severe conditions. Both exposure groups had increased risks of 5-minute Apgar scores <7 (minor: aRR 1.28, 95% CI 1.16-1.41; moderate-severe: aRR 1.49, 95% CI 1.34-1.66); 5-minute Apgar scores <4 (minor: aRR 1.10, 95% CI 0.93-1.30; moderate-severe: aRR 1.18, 95% CI 0.98-1.43), and hospital admission during the neonatal period (minor: aRR 1.20, 95% CI 1.17-1.23; moderate-severe: aRR 1.22, 95% CI 1.19-1.26) along with several neonatal morbidities. An explicit high risk was seen for abstinence syndrome (minor: aRR 10.30, 95% CI 8.40-12.63; moderate-severe: aRR 12.13, 95% CI 10.17-15.67). CONCLUSIONS: Infants of mothers with moderate-severe and minor mental health conditions were at increased risks of multiple adverse perinatal outcomes. Effective supportive interventions to improve outcomes in both groups are needed.

Indirect effects of COVID-19 in referring women to gynecologic oncology, perinatology and gynecology clinics in Iran.

PURPOSE: COVID-19 has captured the world. We hypothesized that this pandemic reduced referral of other non-COVID-19 patients to the hospitals or clinics, including gynecological and perinatological referrals. Women can be at risk in limited use of health services. METHODS: In this retrospective study, referrals from gynecologic oncology, perinatology, and gynecology clinics in a large teaching hospital of Tehran University of Medical Sciences (TUMS) were compared from February 20 to May 20, 2020, with the same period in 2019. Finally, referral trends in 2020 were compared with the COVID-19 admission pattern. RESULTS: Total admissions to all three clinics declined 63% in 2020 compared to 2019. There was a significant relationship between the number of visits to three clinics during these2  years (p < 0.001). The reduction in referrals to the gynecology clinic was more than gynecologic oncology and perinatology. The COVID-19 referral pattern was conversely linked to gynecology-related admissions. CONCLUSION: As the pandemic situation makes patients hesitant to go to the hospitals or not, health policymakers should consider other non-COVID issues, including maternal and fetal concerns. Providing safe places for other patients to visit is a goal that can be achieved through developing guidelines for nosocomial hygiene and training informed healthcare staff. Moreover, non-urgent visits should be avoided or postponed. This issue calls for new strategies, including telemedicine in situations similar to the current pandemic to both identify and manage such conditions.

Tuberculosis in pregnant women and neonates: A meta-review of current evidence.

Pregnant women and their infants are a vulnerable but neglected population in tuberculosis (TB) control efforts. Recent advances in TB prevention, diagnosis and treatment have implications for their care, despite their frequent exclusion from research. We have conducted a meta-review of current evidence and clinical guidelines for TB prevention, diagnosis and management in pregnant women and neonates, focusing on review articles published since 2010. The actual burden of TB in pregnancy is unmeasured, but has been estimated at 216,500 cases per year. Although the effect of pregnancy on TB risk is uncertain and controversial, two large whole-of-population studies found that pregnancy was associated with a two- to three-fold increase in risk of TB. Congenital TB is rare but extremely serious. Neonates exposed to TB after delivery will be at high risk of disease, and preventive therapy is recommended once disease has been ruled out. At present, there is limited evidence regarding the performance of different screening strategies for pregnant women, appropriate drug dosing for either pregnant women or neonates, and the safety of most second-line drugs in pregnancy. High quality evidence on these topics is needed, as are detailed guidelines to inform efforts by TB control programs and clinicians working with pregnant women and their infants.

Can a probiotic supplement in pregnancy result in transfer to the neonatal gut: A systematic review.

INTRODUCTION: The establishment of the neonatal gut microbiome is a crucial step that may have lifelong health implications. We aimed to systematically review evidence on maternal probiotic supplementation during pregnancy and vertical transfer of the corresponding strain to the infant gut. MATERIAL AND METHODS: Medline, CINAHL, Embase, Web of Science, and OVID were searched from inception to September 2018. Studies of maternal probiotic supplementation for a minimum duration of 2 weeks and analyses of neonatal stool samples were included. The primary outcome was presence of the specific probiotic strain in the infant stool. Electronic databases were searched for relevant studies and references were cross-checked. Risk of bias among included studies was assessed and data were extracted independently by two authors. RESULTS: Three studies were included in the review. Only one study was identified involving prenatal maternal probiotic supplementation alone. Neonatal colonization with the maternally administered probiotic was not demonstrated but supplementation with the probiotic influenced levels of a bacterial strain other than that found in the probiotic product. The other two studies identified included both prenatal and postnatal supplementation of either mother or infant. All three studies reported employing strain-specific isolation methodology to isolate the supplemented bacterial strain in infant stool but none used whole metagenome shotgun sequencing. CONCLUSIONS: Few studies investigating transfer of a specific probiotic bacterial strain from mother to infant were identified, showing inconclusive evidence of vertical transfer.

Epigenetic programming-The important first 1000 days.

The perinatal period is a time of fast physiological change, including epigenetic programming. Adverse events may lead to epigenetic changes, with implications for health and disease. Our review covers the basics of clinical epigenetics and explores the latest research, including the role of epigenetic processes in complex disease phenotypes, such as neurodevelopmental, neurodegenerative and immunological disorders. Some studies suggest that epigenetic alterations are linked to early life environmental stressors, including mode of delivery, famine, psychosocial stress, severe institutional deprivation and childhood abuse. CONCLUSION: Epigenetic modifications due to perinatal environmental exposures can lead to lifelong, but potentially reversible, phenotypic alterations and disease.

Clinical guidance and perinatal care in the era of coronavirus disease 2019 (COVID-19).

Pregnant women may be at risk for more severe manifestations and sequelae of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At this time, there remain significant evidence gaps to allow for comprehensive counseling of pregnant women and their families, specifically regarding the risks of gestational-age specific maternal outcomes and potential risks of intrauterine or peripartum viral transmission to the fetus or newborn. As maternal fetal medicine providers and consultants, we are uniquely positioned to mitigate the risks associated with maternal infection and to guide the care for infected pregnant women by being able to provide the most current evidence-based recommendations. Such care requires incorporating the rapidly evolving data regarding this virus and its impact on pregnancy, as well as taking a stand to advocate for best scientific and clinical practices to optimize both women's health and public health during this pandemic.

The choice of amniotic fluid in metabolomics for the monitoring of fetus health - update.

Introduction: In recent years, several studies have highlighted the promising role of metabolomics in the analysis of amniotic fluid (AF), to describe and characterize the interactions occurring between the mother and the fetus during prenatal development. Among the available biological fluids, AF represents an ideal substrate to provide dynamic information regarding fetal organogenesis and metabolism through pregnancy, since it originates from both maternal and fetal tissues and contains substances derived from placenta, fetal skin, lungs, gastric fluid, and fetal urine. Areas covered: In this paper, we provide an update reporting the most recent results on AF metabolomics in the assessment of feto-maternal health, regarding physiological pregnancies but even fields such as prematurity, bronchopulmonary dysplasia, fetal malformations, chromosomopathies, maternal diseases, placental inflammation or infections, maternal diet or exposure to exogenous substances, according to the literature found on MEDLINE since 2015. Expert opinion: Metabolomics shows a promising role in describing both physiology and disease; the goal would be the identification of biomarkers able to precociously and efficaciously detect pathological conditions, allowing the identification of complicated pregnancy and improving their management. However, this field is under development and its reliability still needs to be clarified, especially through more numerous and accurate studies.

Single dose v two-dose antenatal anti-D prophylaxis: a randomised controlled trial.

OBJECTIVE: To compare rates of detectability of circulating Rh(D)-immunoglobulin (anti-D) at delivery with single and two-dose antenatal anti-D prophylaxis (RAADP) regimens; to compare compliance with the two regimens. DESIGN: Open label, randomised controlled trial between May 2013 and November 2015. SETTING, PARTICIPANTS: 277 women who attended a tertiary obstetric referral hospital in Perth for antenatal care and were at least 18 years of age, less than 30 weeks pregnant and yet to receive RAADP, Rh(D)-negative (negative antibody screen), and who intended to deliver their baby at the hospital. Exclusion criteria were prior anti-D sensitisation, any contraindication of anti-D administration, and a history of isolated IgA deficiency. INTERVENTIONS: One 1500 IU anti-D dose at 28 weeks of pregnancy (single dose regimen); two doses of 625 IU each at 28 and 34 weeks of pregnancy (two-dose regimen). MAIN OUTCOME MEASURES: The primary outcome was the proportion of women with detectable anti-D levels at delivery; the secondary outcome was compliance with the allocated RAADP regimen. RESULTS: Circulating anti-D was detectable at delivery in a greater proportion of women in the two-dose group (111 of 129, 86%) than in the single dose group (70 of 125, 56%; P < 0.001). Compliance was not significantly different between the single dose (86 of 138, 61%) and two-dose groups (70 of 139, 50%; P = 0.06). CONCLUSIONS: The two-dose RAADP schedule currently recommended in Australia provides better protection against Rh(D) sensitisation than a one-dose regimen. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12613000661774).

Clinical decision analysis and model-based economic evaluation studies in perinatology: A systematic review.

INTRODUCTION: Perinatology, the study of two individuals that constitute the mother-fetus dyad, poses unique challenges to the conduct of clinical decision analysis (CDA) and economic evaluation (EE) studies. Our objective was systematically to review CDA and model-based EE studies in pregnant women to better understand how these studies have been conducted and reported in perinatology. MATERIAL AND METHODS: MEDLINE, Embase, Scopus, Web of Science and clinicaltrials.gov were searched as of October 2018. The indexing terms "pregnancy", "decision trees", "Markov models" and "economic models" were used. The search was limited to human data and the English language. Two reviewers independently screened titles and abstracts. Data extraction and assessment of reporting quality were performed in duplicate for 10% of studies and reached 100% agreement. The remainder was carried out by a single reviewer. The study protocol was registered with PROSPERO (CRD 42016047206). RESULTS: Seventy-seven studies met eligibility criteria and fulfilled between 40% and 91% of relevant attributes on the checklist for critical appraisal of CDA models. There was considerable variation in study reporting. A total of 53% of studies included maternal and offspring outcomes, 14% described using weighted means, meta-analyses or health administrative databases to estimate probabilities and 13% considered outcomes over the lifetime of mother and offspring. Patient preferences (utilities) were used in 47% of the studies. Of these, 10% were elicited from healthcare providers alone and not from pregnant women or the public. Of the EE studies, 25% described a societal analytic perspective. Where relevant, 42% described discounting for costs and benefits, and 30% reported using probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Despite long-term implications of perinatal decisions to mother and offspring, CDA and model-based EE studies in perinatology frequently do not consider lifetime horizons and patient-preferences for outcomes related to mother and offspring. They also often fail to adhere to guidelines regarding conduct and reporting.