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BACKGROUND: The partograph has been endorsed by World Health Organization (WHO) since 1994 which presents an algorithm for assessing maternal and foetal conditions and labor progression. Monitoring labour with a partograph can reduce adverse pregnancy outcomes such as prolonged labor, emergency C-sections, birth asphyxia and stillbirths. However, partograph use is still very low, particularly in low and middle income countries (LMICs). In Bangladesh the reported partograph user rate varies from 1.4% to 33.0%. Recently, an electronic version of the partograph, with the provision of online data entry and user aid for emergency clinical support, has been tested successfully in different settings. With this proven evidence, we conducted and operations research to test the feasibility and effectiveness of implementing an e-partograph, for the first time, in 2 public hospitals in Bangladesh.METHODS: We followed a prospective crossover design. Two secondary level referral hospitals, Jessore and Kushtia District Hospital (DH) were the study sites. All pregnant women who delivered in the study hospitals were the study participants. All nurse-midwives working in the labor ward of study hospitals were trained on appropriate use of both types of partograph along with standard labour management guidelines. Collected quantitative data was analyzed using SPSS 23 statistical software. Discrete variables were expressed as percentages and presented as frequency distribution and cross tabulations. Chi square tests were employed to test the association between exposure and outcome variables. Potential confounding factors were adjusted using multivariate binary logistic regression methods. Ethical approval was obtained from the institutional review board of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b).FINDINGS: In total 2918 deliveries were conducted at Jessore DH and 2312 at Kushtia DH during one-year study period. Of them, 1012 (506 in each facility) deliveries were monitored using partograph (paper or electronic). The trends of facility based C-section rates was downwards in both the hospitals; 43% to 37% in Jessore and from 36% to 25% in Kushtia Hospital. There was a significant reduction of prolonged labour with e-partograph use. In Kushtia DH, the prolonged labour rate was 42% during phase 1 with the paper version which came down to 29% during phase-2 with the e-partograph use. The similar result was observed in Jessore DH where the prolonged labour rate reduced to 7% with paper partograph from the reported 30% prolonged labour with e-partograph. The e-partograph user rate was higher than the paper partograph during both phases (phase 1: 3.31, CI: 2.04-5.38, p < .001 and in phase 2: 15.20 CI: 6.36-36.33, p < .001) after adjusting for maternal age, parity, gestational age, religion, mother's education, husband's education, and fetal sex.CONCLUSION: The partograph user rate has significantly improved with the e- partograph and was associated with an overall reduction in cesarean births. Use of the e-partograph was also associated with reduced rates of prolonged labour. This study has added to the growing body of evidence on the positive impact of e-partograph use. We recommend implementing e-partograph intervention at scale in both public and private hospitals in Bangladesh.TRIAL REGISTRATION: ClinicalTrials.gov NCT03509103.

Given the high rate of alcoholism throughout history, its effects on the fetus may have existed for millennia. But, the claim that Greeks and Romans were aware of fetal alcohol syndrome rests on incorrect citations. From 1725, maternal alcohol consumption was associated with retarded fetal growth and neurological anomalies. From 1809, scientists followed Lamarck’s theory that the disorders parents acquire during their lifetime are passed on to their offspring. Fetal effects were thought to be inherited mainly from the father. During the 19th century, parental alcoholism became associated with malformations. In 1915, Ballantyne distinguished genetic influence via germ cells from toxin’s effect on the embryo. Fetal alcohol syndrome was characterized by Rouquette [Influence de la toxicomanie alcoolique parentale sur le développement physique et psychique des jeunes enfants] in 1957 and Lemoine et al. [Ouest Medical. 1968;21:476–482] in 1968 as consisting of 4 features: (A) facial anomalies (narrow forehead, retracted upper lip, and cupped ears), (B) severe growth retardation (prenatal and postnatal), (C) malformations (limbs, cardiac, and visceral), and (D) central nervous system anomalies (hyperexcitability and mental retardation). But, their studies, written in French, remained disregarded. In 1973, Jones et al. [Lancet. 1973;302:999–1001] reported “the first association between maternal alcoholism and aberrant morphogenesis in the offspring.” The history of fetal alcohol syndrome reveals shortcomings in citation practice. Alleged quotations remained unverified, non-English publications neglected, and short quotations taken out of context. Prejudiced by religious and abstinence groups, reports on alcohol damage to the unborn were fraught with emotions, moralizing, social implications, and presentism, the interpretation of past events with present knowledge.

WHAT IS IT?: Fetal neonatal alloimmune thrombocytopenia (FNAIT), also known as neonatal alloimmune thrombocytopenia (NAIT) or fetomaternal alloimmune thrombocytopenia (FMAIT), is a rare condition which affects a baby's platelets. This can put them at risk of problems with bleeding, particularly into the brain. One baby per week in the UK may be seriously affected and milder forms can affect one in every 1000 births. HOW IS IT CAUSED?: Platelets are blood cells that are very important in helping blood to clot. All platelets have natural proteins on their surface called human platelet antigens (HPAs). In babies, half of these antigens are inherited from the mother and half from the father. During pregnancy, some of the baby's platelets can cross into the mother's bloodstream. In most cases, this does not cause a problem. But in cases of FNAIT, the mother's immune system does not recognise the baby's HPAs that were inherited from the father and develops antibodies, which can cross the placenta and attack the baby's platelets. These antibodies are called anti-HPAs, and the commonest antibody implicated is anti-HPA-1a, but there are other rarer antibody types. If this happens, the baby's platelets may be destroyed causing their platelet count to fall dangerously low. If the platelet count is very low there is a risk to the baby of bleeding into their brain before they are born. This is very rare but if it happens it can have serious effects on the baby's health. HOW IS IT INHERITED?: A baby inherits half of their HPAs from its mother and half from its father. Consequently, a baby may have different HPAs from its mother. As the condition is very rare, and even if the baby is at risk of the condition we have no way of knowing how severely they will be affected, routine screening is not currently recommended. WHAT CAN BE DONE?: FNAIT is usually diagnosed if a previous baby has had a low platelet count. The parents are offered blood tests and the condition can be confirmed or ruled out. There are many other causes of low platelets in babies, which may also need to be tested for. As the condition is so rare, expertise is limited to specialist centres and normally a haematologist and fetal medicine doctor will perform and interpret the tests together. Fortunately, there is an effective treatment for the vast majority of cases called immunoglobulin, or IVIg. This 'blood product' is given intravenously through a drip every week to women at risk of the condition. It may be started from as early as 16 weeks in the next pregnancy, until birth, which would be offered at around 36-37 weeks. Less common treatments that may be considered depending on individual circumstances include steroid tablets or injections, or giving platelet transfusions to the baby. WHAT DOES THIS PAPER TELL YOU?: This paper considers the latest evidence in relation to treatment options in the management of pregnancies at risk of FNAIT. Specifically, we discuss the role of screening, when IVIg should be started, what dose should be used, and what evidence there is for maternal steroids. We also consider in very rare selected cases, the use of fetal blood sampling and giving platelet transfusions to the baby before birth. Finally, we consider the approaches to blood testing mothers to tell if babies are at risk, which is offered in some countries, and development of new treatments to reduce the risk of FNAIT.

Objectives: Coarctation of the aorta (CoA) is an irreversible congenital heart defect. Its prenatal diagnosis is not rare a subject to false-positive conclusion. We present a novel hypothesis explaining the basis of this error. Methods: Ten cases of prenatal suspicion of the coarctation of the aorta (based on disproportion at the level of 4 chamber view and mediastinum) coincidenced with the umbilical cord wrapped around the fetal body were found in the Filemaker datebase of the Fetal Cardiology Department. Only single pregnancies were taken into account. In all cases another cardiac and extracardiac malformations were excluded. Results: The mean maternal age was 29,6 years. The mean gestational age was 33 7/8 weeks. All fetuses were in a good cardiovascular condition. The usual position of the umbilical cord was neck, but they were also location such as nucha, abdomen or lower limb. At birth, all newborns had normal anatomy of the heart. We conclude that the explanation of the false diagnosis was haemodynamic, resulting from the compression of the fetal neck by the umbilical cord that resulted in a disproportion of cardiac blood flow, “mimicking” CoA. Conclusions: 1. Functional disturbances can mimic prenatal CoA. 2. Umbilical cord position (specially enlacing the fetus neck) should be taken into consideration in suspected cases of fetal CoA.

An epidemic of early fetal loss (EFL), late fetal loss (LFL), fibrinous pericarditis, and unilateral uveitis which occurred during the spring of 2001, are together now known as the mare reproductive loss syndrome (MRLS). A similar epidemic with less intensity was reported during the same period of time from southern Ohio, West Virginia, and Tennessee. The same syndrome with lesser intensity recurred in 2002. The estimated economic loss from the syndrome in 2001 and 2002 together was approximately $500 million. Both EFL and LFL were characterized by the absence of specific clinical signs in aborting mares. Nonhemolytic Streptococcus spp. and Actinobacillus spp. accounted for 65% of the organisms isolated from fetuses submitted for a postmortem during the MRLS period in 2001 and 2002. The pathologic findings in fetoplacental units of LFL included bronchopneumonia and funisitis, and there were no findings in EFL. Epidemiologic studies conducted in 2001 suggested an association between the presences of eastern tent caterpillars (ETC) in pastures with MRLS. Experimental studies in pregnant mares by exposure to ETC, or administration by stomach tube or with feed material, reproduced EFL and LFL. Similar experimental studies in mouse, rats, and goats with ETC were unsuccessful. Currently, 2 hypotheses are proposed for MRLS. One hypothesis proposes that an ETC-related toxin with secondary opportunistic bacterial invasion of the fetus leads to MRLS. The second hypothesis suggests that a breach of gastrointestinal mucosal integrity by hairs of ETC leads to a bacteremia and results in MRLS. In 2004, a similar equine abortion storm was reported from Australia and caterpillar exposure was identified as a risk factor for the abortion. In 2006, the syndrome was observed in Florida and New Jersey.

Environmental Health Perspectives (EHP) established the Paper of the Year in 2008 (Tilson 2008) as a way of highlighting high-quality articles published in the journal. Until now, the Paper of the Year for any given year was selected on the basis of citations received over the preceding 60 months. Starting this year, this award will be known as the EHP Classic Paper of the Year. This award will be given to the most highly cited Research Article, Commentary, or Review Article over the preceding 60 months. A new award, the EHP Paper of the Year, will honor a Research Article published in the preceding year. Final selection of both awards will be subject to approval by the EHP Board of Associate Editors. The winner of the EHP Paper of the Year will be announced later in the calendar year. We are proud to announce that the 2011 EHP Classic Paper of the Year is “Maternal Genistein Alters Coat Color and Protects Avy Mouse Offspring from Obesity by Modifying the Fetal Epigenome” by Dana C. Dolinoy, Jennifer R. Weidman, Robert A. Waterland, and Randy L. Jirtle. This article was published in the April 2006 issue of EHP (Dolinoy et al. 2006) and has been cited more than 35 times per year since it was published. At the time the paper was written, it was increasingly recognized that exposure to nutritional, chemical, and behavioral factors could alter gene expression and affect health and disease not only by mutating promoter and coding regions of genes but also by modifying the epigenome. The epigenome comprises the heritable changes in gene expression that occur in the absence of changes to the DNA sequence itself, including DNA methylation and chromatin packaging. If the genome is compared to the hardware in a computer, the epigenome is the software that directs the computer’s operation. Dolinoy et al. (2006) argued that identifying epigenetic targets and defining how they are influenced by nutrition and the environment might lead to the development of innovative diagnostic, treatment, and prevention strategies that target the “epigenomic software” rather than the “genomic hardware.” Dolinoy et al. (2006) used the viable yellow agouti (Avy) mouse as an epigenetic biosensor to demonstrate that genistein, the major phytoestrogen in soy, increases DNA methylation of the Agouti gene, resulting in population-level decreased incidence of adult-onset obesity, diabetes, and cancer. At the inception of this study, epidemiological data suggested that increased dietary genistein plays a role in decreased incidence of cancer in Asians compared with Westerners. Thus, they hypothesized that early dietary exposures, including genistein, might be linked to adult health status via epigenetic mechanisms. These authors demonstrated that maternal dietary genistein supplementation of mice during gestation at levels comparable to humans consuming high soy diets shifted the coat color of heterozygous viable yellow agouti (Avy/a) offspring toward pseudoagouti. This phenotypic change was significantly associated with increased methylation of six cytosine–guanine sites in a retrotransposon upstream of the transcription start site of the Agouti gene. A significant finding was that genistein-induced hypermethylation persisted into adulthood, decreasing ectopic Agouti expression and protecting offspring from adult-onset obesity. Dolinoy et al. (2006) provided the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome. They also established the framework for future studies by showing that both genistein and methyl donors, such as folic acid, betaine, and choline, counteract DNA hypomethylation caused by bisphenol A, an endocrine-active agent used to make polycarbonate plastic. Their results showed that simple dietary changes can protect against the deleterious effects of environmental toxicants on the fetal epigenome (Dolinoy et al. 2007). EHP congratulates Dolinoy and colleagues for their contribution to the environmental health science literature. In addition to demonstrating that single-nucleotide polymorphisms can affect environmentally responsive genes, they demonstrated that early nutritionally and environmentally induced epigenetic modifications may be an alternative mechanism underlying individual susceptibilities to environmental agents.

Objective 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell‐free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples. Methods In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in‐situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0‐Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype. Results The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2–80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5–100%)). Conclusions The results of this large‐scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0–0.5%) false‐positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false‐positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., Linked article: There is a comment on this article by Jing and Li. Click here to view the Correspondence.

Objectives To characterize spatiotemporal growth differences of prenatal brainstem substructures and cerebellum, using linear biometry and planimetry on fetal magnetic resonance imaging (MRI). Methods In this retrospective study, we included fetuses with normal brain and a precise midsagittal T2‐weighted brain MRI sequence obtained between May 2003 and April 2019. The cross‐sectional area, rostrocaudal diameter and anteroposterior diameter of the midbrain, pons (basis pontis and pontine tegmentum), medulla oblongata and cerebellar vermis, as well as the transverse cerebellar diameter, were quantified by a single observer. The diameters were also assessed by a second observer to test inter‐rater variability. Results We included 161 fetuses with normal brain and a precise midsagittal MRI sequence, examined at a mean ± SD gestational age of 25.7 ± 5.4 (range, 14 + 0 to 39 + 2) weeks. All substructures of the fetal brainstem and the cerebellum could be measured consistently (mean ± SD interobserver intraclass correlation coefficient, 0.933 ± 0.065). We provide reference data for diameters and areas of the brainstem and cerebellum in the second and third trimesters. There was a significant quadratic relationship between vermian area and gestational age, and all other measured parameters showed a significant linear growth pattern within the observed period (P

Objective To describe the short‐ and long‐term outcomes of infants with early‐onset fetal growth restriction (FGR) and umbilical artery absent or reversed end‐diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively. Methods This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early‐onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level‐3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small‐for‐gestational‐age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non‐FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery. Results There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non‐FGR group. The FGR infants had a median birth weight of 630 g (range, 340–1165 g) and gestational age at birth of 187 days (range, 164–209 days), as compared with 950 g (range, 470–2194 g) and 185 days (range, 154–209 days), respectively, in the non‐FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non‐FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non‐FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent (P = 0.008, P

Objectives Increased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long‐term neurodevelopmental prognosis of infants who had isolated increased NT in utero. Methods This was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet–Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability. Results A total of 203 chromosomally normal infants were included in the increased‐NT group and 208 in the control group. The mean global DQ was significantly lower in the increased‐NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively. Conclusions Infants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objective Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID‐19 (PAN‐COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal–Perinatal Medicine (SONPM) National Perinatal COVID‐19 Registry. Methods This was an analysis of data from the PAN‐COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS‐CoV‐2 infection at any stage in pregnancy, and the AAP‐SONPM National Perinatal COVID‐19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS‐CoV‐2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN‐COVID results are presented overall for pregnancies with suspected or confirmed SARS‐CoV‐2 infection and separately in those with confirmed infection. Results We report on 4005 pregnant women with suspected or confirmed SARS‐CoV‐2 infection (1606 from PAN‐COVID and 2399 from AAP‐SONPM). For obstetric outcomes, in PAN‐COVID overall and in those with confirmed infection in PAN‐COVID and AAP‐SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (

Objectives To determine the diagnostic accuracy of postmortem magnetic resonance imaging (PM‐MRI) and postmortem ultrasound (PM‐US) for perinatal autopsy in the same patient cohort, and to determine whether PM‐US can provide the same anatomical information as PM‐MRI. Methods In this prospective, 5‐year (July 2014–July 2019) single‐center study, we performed 1.5‐T PM‐MRI and PM‐US in an unselected cohort of perinatal deaths. The diagnostic accuracies of both modalities were calculated, using autopsy as the reference standard. As a secondary objective, the concordance rates between the two imaging modalities for the overall main diagnosis and for five anatomical regions (brain, spine, thorax, heart and abdomen) were calculated. Results During the study period, 136 cases underwent both PM‐US and PM‐MRI, of which 88 (64.7%) also underwent autopsy. There was no significant difference in the rates of concordance with autopsy between the two modalities for overall diagnosis (PM‐US, 86.4% (95% CI, 77.7–92.0%) vs PM‐MRI, 88.6% (95% CI, 80.3–93.7%)) or in the sensitivities and specificities for individual anatomical regions. There were more non‐diagnostic PM‐US than PM‐MRI examinations for the brain (22.8% vs 3.7%) and heart (14.7% vs 5.1%). If an ‘imaging‐only’ autopsy had been performed, PM‐US would have achieved the same diagnosis as 1.5‐T PM‐MRI in 86.8% (95% CI, 80.0–91.5%) of cases, with the highest rates of agreement being for spine (99.3% (95% CI, 95.9–99.9%)) and cardiac (97.3% (95% CI, 92.4–99.1%)) findings and the lowest being for brain diagnoses (85.2% (95% CI, 76.9–90.8%)). Conclusion Although there were fewer non‐diagnostic cases using PM‐MRI than for PM‐US, the high concordance rate for overall diagnosis suggests that PM‐US could be used for triaging cases when PM‐MRI access is limited or unavailable. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

To compare the expression of microRNA-185-5p (miR-185-5p) in normal foetuses and in foetuses with late-onset growth restriction (FGR) and to determine the factors influencing this expression. In a prospective study, 40 foetuses (22 of them with late-onset FGR and 18 with normal growth) were scanned with Doppler ultrasound after week 35 and followed until birth. Subsequently, blood samples from umbilical cords were collected after delivery to evaluate the expression of miR-185-5p using real-time qPCR. Finally, multivariable regression analysis was applied to determine the clinical and ultrasonographic factors influencing miR-185-5p expression in both normal and late-onset FGR foetuses. In comparison with normal foetuses, late-onset FGR foetuses expressed upregulation of miR-185-5p (2.26 ± 1.30 versus 1.27 ± 1.03 2^-ddCt, P = 0.011). Multivariable regression analysis confirmed that cerebroplacental ratio (P

Maternal immune activation (MIA) in midpregnancy is a risk factor for neurodevelopmental disorders. Improper brain development may cause malformations of the brain; maldevelopment induced by MIA may lead to a pathology-related phenotype. In this study, a single intraperitoneal injection of 20 mg/kg polyriboinosinic–polyribocytidylic acid [poly(I:C)] was administered to C57BL/6J mice on embryonic day (E) 12.5 to mimic maternal viral infection. Histopathological analysis of neurogenesis was performed using markers for Pax6, Tbr2, and Tbr1. In these fetuses, significant increases were observed in the proportion of Pax6-positive neural progenitor cells and Pax6/Tbr2 double-positive cells 24 h after poly(I:C) injection. There were no differences in the proportion of Tbr1-positive postmitotic neurons 48 h after poly(I:C) injection. At E18.5, there were more Pax6-positive and Tbr2-positive neural progenitor cells in the poly(I:C)-injected group than in the saline-injected group. Gene ontology enrichment analysis of poly(I:C)-induced differentially expressed genes in the fetal brain at E12.5 demonstrated that these genes were enriched in terms including response to cytokine, response to decreased oxygen levels in the category of biological process. At E13.5, activating transcription factor 4 (Atf4), which is an effector of integrated stress response, was significantly upregulated in the fetal brain. Our results show that poly(I:C)-induced MIA at E12.5 leads to dysregulated neurogenesis and upregulates Atf4 in the fetal brain. These findings provide a new insight in the mechanism of MIA causing improper brain development and subsequent neurodevelopmental disorders., Highlights • MIA increases Pax6-positive and Tbr2-positive neural progenitor cells. • MIA impaired the process of neurogenesis from as early as the acute stage. • MIA upregulated Atf4, an effector of integrated stress response, in the fetal brain.

Preeclampsia is a complication of pregnancy characterized by high blood pressure and organ damage after 20 gestational weeks. It is associated with high maternal and fetal morbidity and mortality. However, at present, there is no effective prevention or treatment for this condition. Previous studies have revealed that plasma exosomal mirnas from pregnant women with preeclampsia could serve as biomarkers of pathogenic factors. However, the roles of plasma exosomal mirnas in preeclampsia with severe features (sPE), which is associated with poorer pregnancy outcomes, remain unknown. Thus, the aims of this study were to characterize plasma exosomal miRNAs in sPE and explore the related pathogenic mechanisms using bioinformatic analysis. Plasma exosomes were isolated using a mirVana RNA isolation kit. the exosomal miRNAs were detected using high-throughput sequencing and the mirnas related to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) terms were analyzed using the clusterprofiler package of R. Fifteen miRNAs exhibited increased expression and fourteen miRNAs exhibited reduced expression in plasma exosomes from women with sPE as compared to normal pregnant women. Further, gene set enrichment analysis revealed that the differentially expressed plasma exosomal miRNAs were related to the stress response and cell junction regulation, among others. In summary, this study is the first to identify the differentially expressed plasma exosomal miRNAs in sPE. These findings highlight promising pathogenesis mechanisms underlying preeclampsia.

In an article in an earlier edition of the Journal of Medical Ethics (1) Dr Iglesias bases her analysis upon the mediaeval interpretation of Platonic metaphysics and Aristotelian logic as given by Aquinas. Propositional forms are applied to the analysis of experience. This results in a very abstract analysis. The essential connection of events and their changing temporal relationships are ignored. The dichotomy between body and soul is a central concept. The unchanging elements in experience are assumed to be more real than the actual world of experienced process. Such a view makes the analysis of the temporal factors in experience impossible. Its abstractness is quite unsuitable for the analysis of the ontological structure and development of the neonate from fertilisation to birth. A N Whitehead made the notion of organism central to his philosophy. He refused to place human experience outside nature, or admit dualism. His philosophy of organism is an attempt to uncover the essential elements connecting human experience with the physical and biological sciences. Time, change and process are, in his view, more real than the static abstractions obtainable by the use of the fallacy of misplaced concreteness. Use of the latter negates the essential connectedness of events and the importance of temporarily and change (2). In this paper I argue that the embryo, being an organism, is not analysable in terms of thinghood. It is a process. To apply Aristotelian logical concepts to it is to distort the real nature of the datum.In an article on in vitro fertilization (IVF) published in the March 1984 issue of the Journal of Medical Ethics (Vol. 10, No. 1), Teresa Iglesias identified the moral and ontological status of the embryo as the basic issue raised by IVF. Rejecting self-consciousness as a criterion for personhood and contending that the embryo is a person at every stage of its development, she argued that we are obligated to treat embryonic life as inviolable from its very beginning. In her essay, Mill criticizes Iglesias's Aristotelian analysis as being too static and abstract to use in an ontological assessment of human structure and development from fertilization to birth. Employing Whitehead's organism-centered philosophy, Mill argues that the embryo is a process, the first stage of human development. She suggests that human characteristics first are manifested after implantation, which is the embryo's initial interaction with another person.

We investigated the influence of signal transducer and activator of transcription-3 (STAT3) on the spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we hoped to identify whether transfection of the STAT3 overexpression plasmid increases the survival of spinal cord transplantation in order to improve therapeutic efficacy. The fetal rat model of spina bifida aperta was established using retinoic acid and treated with a microsurgical injection of bone marrow mesenchymal stem cells (BMSCs). The animals were divided into either the blank control group, negative control group or the experimental group. The optical density (OD) value of BMSCs viability was determined using the Cell Counting Kit-8 (CCK-8). The expression of STAT3, phosphorylated STAT3 (pSTAT3), neural markers and apoptosis-related factors were evaluated using real-time PCR and Western blot. The OD value in the experimental group was highest at eight hours after transplantation using CCK-8. The expression of pSTAT3, glial fibrillary acidic protein, neuron-specific enolase, neurofilament and nestin in the experimental group was significantly higher compared to the blank control group and negative control group (P

Aim of the study Metabolic-associated fatty liver disease (MAFLD) is now the most prevalent chronic liver disease in the world. Its prevalence in women of reproductive age is approximately 10%. Due to its high prevalence in this specific population, it is important to investigate adverse maternal and fetal outcomes caused by MAFLD during pregnancy. We aimed to summarize the association between MAFLD and adverse maternal and fetal outcomes. Material and methods A search was conducted on PubMed and ProQuest from inception to April 1, 2021, for studies assessing the association between MAFLD and adverse maternal and fetal outcomes. The quality of included studies was assessed using the Newcastle-Ottawa scale (NOS). We analyzed the pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I2. Results Six studies comprising 20,535,994 (5,964 MAFLD) pregnant women were included. The quality of studies ranged from 6 to 8 stars. MAFLD was significantly associated with increased risk of dysglycemia (OR = 3.65, 95% CI = 2.47-5.39), pregnancy-associated hypertension (OR = 3.27, 95% CI = 2.75-3.88), cesarean section (OR = 2.78, 95% CI = 1.60-4.83), and preterm birth (OR = 1.70, 95% CI = 1.37-2.10) but not large for gestational age (OR = 1.69, 95% CI = 0.64-4.45). Conclusions The presence of MAFLD is associated with adverse maternal and fetal outcomes.

Summary The foetal pH values of eighty-eight cases delivered within 30 min after foetal blood sampling were correlated with the 1-min Apgar score. With a pH of 7·20 or above the error of prediction was 1·3%. The error in cases with pH below 7·20 was 54·5%. Significantly higher pH and lower δ base deficit were present in the low foetal pH group in vigorous, as opposed to depressed infants, suggesting that infusion acidosis was present in infants with a high Apgar score. The degree of correlation between the foetal pH and the Apgar score was not significantly influenced by shortening the sampling-delivery interval to 15 min or lengthening it to 3 hr. The most significant factor affecting the degree of correlation in the present study was the setting of the critical pH. If the criterion of the critical pH was taken as 7·13 there would have been no false positive results and the error of prediction in cases delivered within 30 min of foetal blood sampling would be reduced to 1·1%.

Objectives Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin–twin transfusion syndrome (TTTS). Secondary aims were to create gestational‐age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. Methods In the period 2015–2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four‐chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16–26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed‐effects multilevel regression. Inter‐rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within‐fetus variation was assessed in 16 such fetuses, in which multiple four‐chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as ‘pre‐TTTS’ when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the ‘non‐TTTS’ group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non‐TTTS and pre‐TTTS cases, matched for gestational age. Results Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre‐TTTS and 113 non‐TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28–220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2–26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non‐TTTS and 13/14 pre‐TTTS MCDA twin pregnancies 3.6% was found in eight of 13 pre‐TTTS pregnancies. In non‐TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P

Contains fulltext : 220734.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. METHODS: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. RESULTS: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter >/= 97.7(th) percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02-2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). CONCLUSIONS: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. (c) 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Objectives To determine the feasibility and tissue yield of a perinatal incisionless ultrasound‐guided biopsy procedure, the INcisionless Targeted Core Tissue (INTACT) technique, in the context of minimally invasive autopsy. Methods Cases of perinatal death in which the parents consented for minimally invasive autopsy underwent postmortem magnetic resonance imaging and an INTACT biopsy procedure, defined as needle biopsy of organs via the umbilical cord, performed under ultrasound guidance. In each case, three cores of tissue were obtained from seven target organs (both lungs, both kidneys, heart, spleen and liver). Biopsy success was predefined as an adequate volume of the intended target organ for pathological analysis, as judged by a pathologist blinded to the case and biopsy procedure. Results Thirty fetuses underwent organ sampling. Mean gestational age was 30 weeks (range, 18–40 weeks) and mean delivery‐to‐biopsy interval was 12 days (range, 6–22 days). The overall biopsy success rate was 153/201 (76.1%) samples, with the success rates in individual organs being highest for the heart and lungs (93% and 91%, respectively) and lowest for the spleen (11%). Excluding splenic samples, the biopsy success rate was 150/173 (86.7%). Histological abnormalities were found in 4/201 (2%) samples, all of which occurred in the lungs and kidneys of a fetus with pulmonary hypoplasia and multicystic kidney disease. Conclusions Incisionless ultrasound‐guided organ biopsy using the INTACT procedure is feasible, with an overall biopsy success rate of over 75%. This novel technique offers the ideal combination of an imaging‐led autopsy with organ sampling for parents who decline the conventional invasive approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Objectives First, to obtain measurement‐error models for biometric measurements of fetal abdominal circumference (AC), head circumference (HC) and femur length (FL), and, second, to examine the impact of biometric measurement error on sonographic estimated fetal weight (EFW) and its effect on the prediction of small‐ (SGA) and large‐ (LGA) for‐gestational‐age fetuses with EFW 90th percentile, respectively. Methods Measurement error standard deviations for fetal AC, HC and FL were obtained from a previous large study on fetal biometry utilizing a standardized measurement protocol and both qualitative and quantitative quality‐control monitoring. Typical combinations of AC, HC and FL that gave EFW on the 10th and 90th percentiles were determined. A Monte‐Carlo simulation study was carried out to examine the effect of measurement error on the classification of fetuses as having EFW above or below the 10th and 90th percentiles. Results Errors were assumed to follow a Gaussian distribution with a mean of 0 mm and SDs, obtained from a previous well‐conducted study, of 6.93 mm for AC, 5.15 mm for HC and 1.38 mm for FL. Assuming errors according to such distributions, when the 10th and 90th percentiles are used to screen for SGA and LGA fetuses, respectively, the detection rates would be 78.0% at false‐positive rates of 4.7%. If the cut‐offs were relaxed to the 30th and 70th percentiles, the detection rates would increase to 98.2%, but at false‐positive rates of 24.2%. Assuming half of the spread in the error distribution, using the 10th and 90th percentiles to screen for SGA and LGA fetuses, respectively, the detection rates would be 86.6% at false‐positive rates of 2.3%. If the cut‐offs were relaxed to the 15th and 85th percentiles, respectively, the detection rates would increase to 97.0% and the false‐positive rates would increase to 6.3%. Conclusions Measurement error in fetal biometry causes substantial error in EFW, resulting in misclassification of SGA and LGA fetuses. The extent to which improvement can be achieved through effective quality assurance remains to be seen but, as a first step, it is important for practitioners to understand how biometric measurement error impacts the prediction of SGA and LGA fetuses. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.