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Chorioamnionitis is present in up to 70% of spontaneous preterm births and is associated with poor maternal, fetal and neonatal outcomes.To explore the relationship between the neutrophil-to-lymphocyte ratio and histological chorioamnionitis in women who delivered preterm with no clinical signs or symptoms of infection.This was a retrospective analysis of a cohort of women who delivered spontaneously between 16 and 36169 women had available placental pathology and were included in the analysis. 70 % (118/169) had confirmed placental inflammation. The mean neutrophil-to-lymphocyte ratio was significantly raised in this group compared to those with normal (n = 24) or vascular (n = 27) pathology (inflammatory neutrophil-to-lymphocyte ratio 9.81 vs non-inflammatory neutrophil-to-lymphocyte ratio 6.53, p = 0.002. The delivery neutrophil-to-lymphocyte ratio had an area under the receiver operating characteristic curve of 0.69 (0.60 to 0.78) for predicting placental inflammation. A raised neutrophil-to-lymphocyte ratio (6) was associated with an odds ratio of 5.2 (95 % CI 2.55 to 10.56) for histological chorioamnionitis, with a sensitivity of 80 % and negative predictive value of 86 %. A higher cut-off of 9 had a negative predictive value of 79 % for fetal inflammatory response.A raised neutrophil-to-lymphocyte ratio is associated with a 5-fold increased risk of histological chorioamnionitis in women who delivered early without signs or symptoms of infection. It was also raised at the time of preterm labour compared to the first trimester. A full blood count is an almost universal investigation in women admitted in preterm labour, often repeated, making this inexpensive and non-invasive ratio a useful additional antenatal biomarker in women admitted in spontaneous preterm labour at risk of subclinical chorioamnionitis and its associated poor outcomes.

Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (HT) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of PROG include anti-apoptotic, anti-inflammatory and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema and excitotoxicity. In pre-clinical studies of neonatal HIE, progesterone (PROG) has neuroprotective properties, but has not been the subject of systematic review. Here our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria; Population: human neonates with HIE/Animal models of HIE, Intervention: PROG +/- other agents, Comparison: V.S. control, Outcome: pathological, neurobehavioural and mechanistic outcome measures. Medline, EMBASE and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and key words. Study inclusion, data extraction and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG had positive effects on neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) injury. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without HT.

The mechanical force of blood flow is a fundamental determinant of vascular homeostasis. This frictional stimulation of cells, fluid shear stress (FSS), is increasingly recognised as being essential to placental development and function. Here, we focus on the role of FSS in regulating fetoplacental circulatory flow, both in normal pregnancy and that affected by fetal growth restriction (FGR). The fetus is reliant on placental perfusion to meet its circulatory and metabolic demands. Failure of normal vascular adaptation and the mechanisms enabling responsive interaction between fetoplacental and maternal circulations can result in FGR. FSS generates vasodilatation at least partly through the release of endothelial nitric oxide, a process thought to be vital for adequate blood flow. Where FGR is caused by placental dysfunction, placental vascular anatomy is altered, alongside endothelial dysfunction and hypoxia, each impacting upon the complex balance of FSS forces. Identifying specific mechanical sensors and the mechanisms governing how FSS force is converted into biochemical signals is a fast-paced area of research. Here, we raise awareness of Piezo1 proteins, recently discovered to be FSS-sensitive in fetoplacental endothelium, and with emerging roles in NO generation, vascular tone and angiogenesis. We discuss the emerging concept that activating mechanosensors such as Piezo1 ultimately results in the orchestrated processes of placental vascular adaptation. Piecing together the mechanisms governing endothelial responses to FSS in placental insufficiency is an important step towards developing new treatments for FGR., Graphical abstract Image 1

ObjectivesTo describe the severity of maternal infection when the Omicron SARS-CoV-2 variant was dominant (15/12/21-14/01/22) and compare outcomes among groups with different vaccination status.DesignProspective cohort studySettingUK consultant-led maternity unitsParticipantsPregnant women hospitalised with a positive SARS-CoV-2 PCR test up to 7 days prior to admission and/or during admission up to 2 days after giving birth.Main outcome measuresSymptomatic or asymptomatic infection. Vaccination status. Severity of maternal infection (moderate or severe infection according to modified WHO criteria). Mode of birth and perinatal outcomes.ResultsOut of 1561 women admitted to hospital with SARS-CoV-2 infection, 449 (28.8%) were symptomatic. Among symptomatic women admitted, 86 (19.2%) had moderate to severe infection; 51 (11.4%) had pneumonia on imaging, 62 (14.3%) received respiratory support, and 19 (4.2%) were admitted to the intensive care unit (ICU). Three women died (0.7%). Vaccination status was known for 383 symptomatic women (85.3%) women; 249 (65.0%) were unvaccinated, 45 (11.7%) had received one vaccine dose, 76 (19.8%) had received two doses and 13 (3.4%) had received three doses. 59/249 (23.7%) unvaccinated women had moderate to severe infection, compared to 10/45 (22.2%) who had one dose, 9/76 (11.8%) who had two doses and 0/13 (0%) who had three doses. Among the 19 symptomatic women admitted to ICU, 14 (73.7%) were unvaccinated, 3 (15.8%) had received one dose, 1 (5.3%) had received two doses, 0 (0%) had received 3 doses and 1 (5.3%) had unknown vaccination status.ConclusionThe risk of severe respiratory disease amongst unvaccinated pregnant women admitted with symptomatic SARS-CoV-2 infection during the Omicron dominance period was comparable to that observed during the period the wildtype variant was dominant. Most women with severe disease were unvaccinated. Vaccine coverage among pregnant women admitted with SARS-CoV-2 was low compared to the overall pregnancy population and very low compared to the general population. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential.SUMMARY BOXWhat is already known on this topicIn non-pregnant adults, growing evidence indicates a lower risk of severe respiratory disease with the Omicron SARS-CoV-2 Variant of Concern (VOC).Pregnant women admitted during the periods in which the Alpha and Delta VOC were dominant were at increased risk of moderate to severe SARS-CoV-2 infection compared to the period when the original wildtype infection was dominant.Most women admitted to hospital with symptomatic SARS-CoV-2 infection have been unvaccinated.What this study addsOne in four women who had received no vaccine or a single dose had moderate to severe infection, compared with one in eight women who had received two doses and no women who had received three dosesThe proportional rate of moderate to severe infection in unvaccinated pregnant women during the Omicron dominance period is similar to the rate observed during the wildtype dominance periodOne in eight symptomatic admitted pregnant women needed respiratory support during the period when Omicron was dominant

Introduction There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. Material and methods This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. Results Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30–39 1.48, 95% confidence interval [CI] 1.20–1.83), be overweight or obese (aOR 1.73, 95% CI 1.34–2.25 and aOR 2.52 95% CI 1.97–3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17–3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09–1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61–11.83), a very or extreme preterm birth (28–31+ weeks’ gestation, aOR 18.97, 95% CI 7.78–14.85; Conclusions Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

Background Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. Objectives To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. Design This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Participants Thirty-three patients (who were Interventions Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. Main outcome measures The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Results Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. Limitations The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. Conclusions The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. Trial registration Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.

Background Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage, the procedure can be performed using either a monofilament (single-stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. Methods A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either a history of three or more previous mid-trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women who have taken part in C-STICH previously, are aged less than 18 years old at the time of presentation, require a rescue cerclage, and are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life), and secondary outcomes include the core outcome set for preterm birth trials. Discussion Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates. Trial registration ISRCTN 15373349. Registered before recruitment on 03 December 2014 prior to first recruit.

BackgroundIn the UK, the Alpha variant of SARS-CoV-2 became dominant in late 2020, rapidly succeeded by the Delta variant in May 2021. The aim of this study was to compare the impact of these variants on severity of maternal infection and perinatal outcomes within the time-periods in which they predominated.MethodsThis national, prospective cohort study collated data on hospitalised pregnant women with symptoms of confirmed SARS-CoV-2 infection and compared the severity of infection and perinatal outcomes across the Wildtype (01/03/20-30/11/20), Alpha (01/12/20-15/05/21) and Delta dominant periods (16/05/21-11/07/21), using multivariable logistic regression.FindingsOf 3371 pregnant women, the proportion that experienced moderate to severe infection significantly increased between Wildtype and Alpha periods (24.4% vs. 35.8%; aOR1.75 95%CI 1.48-2.06), and between Alpha and Delta periods (35.8% vs. 45.0%; aOR1.53, 95%CI 1.07-2.17). Compared to the Wildtype period, symptomatic women admitted in the Alpha period were more likely to require respiratory support (27.2% vs. 20.3%, aOR1.39, 95%CI 1.13-1.78), have pneumonia (27.5% vs. 19.1%, aOR1.65, 95%CI 1.38-1.98) and be admitted to intensive care (11.3% vs. 7.7%, aOR1.61, 95%CI 1.24-2.10). Women admitted during the Delta period had further increased risk of pneumonia (36.8% vs. 27.5%, aOR1.64 95%CI 1.14-2.35). No fully vaccinated pregnant women were admitted between 01/02/2021 when vaccination data collection commenced and 11/07/2021. The proportion of women receiving pharmacological therapies for SARS-CoV-2 management was low, even in those critically ill.InterpretationSARS-CoV-2 infection during Alpha and Delta dominant periods was associated with more severe infection and worse pregnancy outcomes compared to the Wildtype infection, which itself increased risk compared to women without SARS-CoV-2 infection.1 Clinicians need to be aware and implement COVID-specific therapies in keeping with national guidance. Urgent action to tackle vaccine misinformation and policy change to prioritise uptake in pregnancy is essential.FundingNational Institute for Health Research HS&DR Programme (11/46/12).

Background: Vaginal cerclage (a suture around the cervix) is commonly placed in women with recurrent pregnancy loss. These women may experience late miscarriage or extreme preterm delivery, despite being managed with cerclage. Transabdominal cerclage (TAC) has been advocated following failed cerclage, although its efficacy is unproven by randomised controlled trial (RCT). Methods: A multicentre RCT to compare TAC or high vaginal cerclage (HVC) to low vaginal cerclage (LVC), as a preventative strategy for spontaneous preterm birth (sPTB) in women with history of a failed cerclage was undertaken. Women were randomly assigned (1:1:1) to receive TAC, HVC or LVC, either prior to conception or before 14 weeks' gestation. Primary outcome was delivery before 32 completed weeks of pregnancy. Findings: 111/139 women recruited who conceived were analysed: 39 to TAC, 39 to HVC and 33 to LVC. Rates of sPTB

Background There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2. Methods and findings We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9–2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1–1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39–2.48) and aOR 2.07 (1.53–2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93–9.90), aOR 4.36, (3.19–5.95) and aOR 12.95, (4.93–34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32–2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80–426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97–3.42) and aOR 3.08, (1.99–4.77); asymptomatic aOR 2.02, (1.52–2.70) and aOR 1.84, (1.12–3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status. Conclusions We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18&ndash, 40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks&rsquo, gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 &micro, g/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 &micro, g/day (94, 196), with 49% &lt, UK reference nutrient intake (140 &micro, g/day). Women with Pakistani heritage had 129 &micro, g/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 &micro, g/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.

Background Maternal iodine requirements increase during pregnancy to supply thyroid hormones essential for fetal brain development. Maternal iodine deficiency can lead to hypothyroxinemia, a reduced fetal supply of thyroid hormones which, in the first trimester, has been linked to an increased risk of autism spectrum disorder (ASD) in the child. No study to date has explored the direct link between maternal iodine deficiency and diagnosis of ASD in offspring. Methods Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6955 mothers at 26–28 weeks gestation participating in the Born in Bradford (BiB) cohort. Maternal iodine status was examined in relation to the probability of a Read (CTV3) code for autism being present in a child’s primary care records through a series of logistic regression models with restricted cubic splines. Results Median (inter-quartile range) UIC was 76 μg/L (46, 120) and I:Cr was 83 μg/g (59, 121) indicating a deficient population according to WHO guidelines. Ninety two children (1·3%) in our cohort had received a diagnosis of ASD by the census date. Overall, there was no evidence to support an association between I:Cr or UIC and ASD risk in children aged 8–12 years (p = 0·3). Conclusions There was no evidence of an increased clinical ASD risk in children born to mothers with mild-to-moderate iodine deficiency at 26 weeks gestation. Alternative functional biomarkers of exposure and a wider range of conditions may provide further insight., BMC Pediatrics, 20 (1), ISSN:1471-2431

Background Full dilatation caesarean sections are associated with recurrent early spontaneous preterm birth and late miscarriage. The risk following first stage caesarean sections, are less well defined, but appears to be increased in late-first stage of labour. The mechanism for this increased risk of late miscarriage and early spontaneous preterm birth in these women is unknown and there are uncertainties with regards to clinical management. Current predictive models of preterm birth (based on transvaginal ultrasound and quantitative fetal fibronectin) have not been validated in these women and it is unknown whether the threshold to define a short cervix (≤25 mm) is reliable in predicting the risk of preterm birth. In addition the efficacy of standard treatments or whether benefit may be derived from prophylactic interventions such as a cervical cerclage is unknown. Methods There are three distinct components to the CRAFT project (CRAFT-OBS, CRAFT-RCT and CRAFT-IMG). CRAFT-OBS: Observational Study; To evaluate subsequent pregnancy risk of preterm birth in women with a prior caesarean section in established labour. This prospective study of cervical length and quantitative fetal fibronectin data will establish a predictive model of preterm birth. CRAFT-RCT: Randomised controlled trial arm; To assess treatment for short cervix in women at high risk of preterm birth following a fully dilated caesarean section. CRAFT-IMG: Imaging sub-study; To evaluate the use of MRI and transvaginal ultrasound imaging of micro and macrostructural cervical features which may predispose to preterm birth in women with a previous fully dilated caesarean section, such as scar position and niche. Discussion The CRAFT project will quantify the risk of preterm birth or late miscarriage in women with previous in-labour caesarean section, define the best management and shed light on pathological mechanisms so as to improve the care we offer to women and their babies. Trial registration CRAFT was prospectively registered on 25th November 2019 with the ISRCTN registry (10.1186/ISRCTN15068651).

Highlights • Low PlGF at presentation with suspected preeclampsia identifies a severe phenotype of disease. • The use of PlGF testing leads to a reduction in severe maternal adverse outcomes. • PlGF testing increases antenatal surveillance of women at risk of complications of preeclampsia. • PlGF testing does not appear to cause an increase in preterm delivery rates., Objective Placental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms. Study design This was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia. Main outcome measures Maternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration. Results 1006 women were included. PlGF

ObjectiveTo describe a national cohort of pregnant women hospitalised with SARS-CoV-2 infection in the UK, identify factors associated with infection and describe outcomes, including transmission of infection, for mother and infant.DesignProspective national population-based cohort study using the UK Obstetric Surveillance System (UKOSS).SettingAll 194 obstetric units in the UKParticipants427 pregnant women admitted to hospital with confirmed Sars-CoV-2 infection between 01/03/2020 and 14/04/2020. 694 comparison women who gave birth between 01/11/2017 and 31/10/2018.Main outcome measuresIncidence of maternal hospitalisation, infant infection. Rates of maternal death, level 3 critical care unit admission, preterm birth, stillbirth, early neonatal death, perinatal death; odds ratios for infected versus comparison women.ResultsEstimated incidence of hospitalisation with confirmed SARS-CoV-2 in pregnancy 4.9 per 1000 maternities (95%CI 4.5-5.4). The median gestation at symptom onset was 34 weeks (IQR 29-38). Black or other minority ethnicity (aOR 4.49, 95%CI 3.37-6.00), older maternal age (aOR 1.35, 95%CI 1.01-1.81 comparing women aged 35+ with those aged 30-34), overweight and obesity (aORs 1.91, 95%CI 1.37-2.68 and 2.20, 95%CI 1.56-3.10 respectively compared to women with a BMI2) and pre-existing comorbidities (aOR 1.52, 95%CI 1.12-2.06) were associated with admission with SARS-CoV-2 during pregnancy. 247 women (58%) gave birth or had a pregnancy loss; 180 (73%) gave birth at term. 40 (9%) hospitalised women required respiratory support. Twelve infants (5%) tested positive for SARS-CoV-2 RNA, six of these infants within the first 12 hours after birth.ConclusionsThe majority of pregnant women hospitalised with SARS-CoV-2 were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes and transmission of SARS-CoV-2 to infants was uncommon. The strong association between admission with infection and black or minority ethnicity requires urgent investigation and explanation.Study RegistrationISRCTN 40092247

Background Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent. Objectives To quantify the association between maternal iodine status and child educational outcomes. Methods Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26‐28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4‐7 years. Results Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively. Conclusions In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization–outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight., Paediatric and Perinatal Epidemiology, 35 (2), ISSN:0269-5022, ISSN:1365-3016

Background Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes. Methods Maternal iodine status was estimated from spot urine samples collected at 26–28 weeks’ gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score. Results There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies. Conclusion Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered., BMC Medicine, 18 (1), ISSN:1741-7015

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia., Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

STUDY QUESTION: Does the shear stress sensing ion channel subunit Piezo1 have an important mechanotransduction role in human fetoplacental endothelium?SUMMARY ANSWER: Piezo1 is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezo1 prevents the normal response to shear stress.WHAT IS KNOWN ALREADY: Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature.STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We investigated the relevance of Piezo1 to placental vasculature by studying human fetoplacental endothelial cells (FpECs) from healthy pregnancies. Endothelial cells were isolated from placental cotyledons and cultured, for the study of tube formation and cell alignment to shear stress. In addition, human placental arterial endothelial cells were isolated and studied immediately by patch-clamp electrophysiology.MAIN RESULTS AND THE ROLE OF CHANCE: The synthetic Piezo1 channel agonist Yoda1 caused strong elevation of the intracellular Ca2+ concentration with a 50% effect occurring at about 5.4 μM. Knockdown of Piezo1 by RNA interference suppressed the Yoda1 response, consistent with it being mediated by Piezo1 channels. Alignment of cells to the direction of shear stress was also suppressed by Piezo1 knockdown without loss of cell viability. Patch-clamp recordings from freshly isolated endothelium showed shear stress-activated single channels which were characteristic of Piezo1.LIMITATIONS, REASONS FOR CAUTION: The in vitro nature of fetoplacental endothelial cell isolation and subsequent culture may affect FpEC characteristics and PIEZO1 expression. In addition to Piezo1, alternative shear stress sensing mechanisms have been suggested in other systems and might also contribute in the placenta.WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that Piezo1 is an important molecular determinant of blood flow sensitivity in the placenta. Establishing and manipulating the molecular mechanisms regulating shear stress sensing could lead to novel therapeutic strategies to improve blood flow in the placenta.LARGE-SCALE DATA: Not applicable.STUDY FUNDING/COMPETING INTEREST(S): LCM was funded by a Clinical Research Training Fellowship from the Medical Research Council and by the Royal College of Obstetricians and Gynaecologists, and has received support from a Wellcome Trust Institutional Strategic Support Fund. JS was supported by the Wellcome Trust and a BHF Intermediate Research Fellowship. HJG, CW, AJH and PJW were supported by PhD Studentships from BHF, BBSRC and the Leeds Teaching Hospitals Charitable Foundation respectively. All authors declare no conflict of interest.

Background: In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. Methods: In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. Findings: Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79–0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. Interpretation: There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. Funding: National Institute for Health Research Health Technology Assessment Programme.

Reducing preterm birth is a priority for Maternity and Children’s services. In the recent UK Department of Health publication ‘Safer Maternity Care’ the Secretary of State for Health aimed to achieve the national maternity safety ambition by pledging to reduce the rate of preterm birth from 8% to 6%. It was proposed that specialist preterm birth services should be established in the UK in order to achieve this aim. In response the Preterm Clinical Network has written Commissioning Guidance aimed to establish best practice pathways and agreed models of care to reduce variation nationally. They have been developed by clinical experts in the field, from within the UK, to provide recommendations for commissioning groups and to recommend pathways to organisations with the aim of reducing the incidence of preterm birth. Three key areas of care provision are focused on: prediction, prevention and preparation of women at high risk of PTB. This Expert Opinion, will summarise the Commissioning Guidance. Keywords: Preterm birth, UK commissioning guidance, Safer maternity care

Fish is an important source of the essential fatty acids contributing to foetal growth and development, but the evidence linking maternal fatty fish consumption with birth outcomes is inconsistent. In the UK, pregnant women are recommended to consume no more than two 140 g portions of fatty fish per week. This study aimed to investigate the association between fatty fish consumption before and during pregnancy with preterm birth and size at birth in a prospective birth cohort. Dietary intake data were acquired from a cohort of 1208 pregnant women in Leeds, UK (CARE Study) to assess preconception and trimester-specific fatty fish consumption using questionnaires. Multiple 24-h recalls during pregnancy were used to estimate an average fatty fish portion size. Intake was classified as &le, 2, &gt, 2 portions/week and no fish categories. Following the exclusion of women taking cod liver oil and/or omega-3 supplements, the associations between fatty fish intake with size at birth and preterm delivery (&lt, 37 weeks gestation) were examined in multivariable regression models adjusting for confounders including salivary cotinine as a biomarker of smoking status.. The proportion of women reporting any fatty fish intake decreased throughout pregnancy, with the lowest proportion observed in trimester 3 (43%). Mean intakes amongst consumers were considerably lower than that recommended, with the lowest intake amongst consumers observed in the 1st trimester (106 g/week, 95% CI: 99, 113). This was partly due to small portion sizes when consumed, with the mean portion size of fatty fish being 101 g. After adjusting for confounders, no association was observed between fatty fish intake before or during pregnancy with size at birth and preterm delivery.

Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004&ndash, 2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks&rsquo, gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 &mu, g/L, 95% confidence intervals (CI): 126, 158) and London (130 &mu, g/L, 95% CI: 114, 177) and lowest in Leeds (116 &mu, g/L, 95% CI: 99, 135), but the proportion with UIC &lt, 50 &micro, g/L was &lt, 20% in all three cities. No evidence of an association was observed between UIC and birth weight centile (&minus, 0.2% per 50 &mu, g/L increase in UIC, 95% CI: &minus, 1.3, 0.8), nor with odds of spontaneous preterm birth (odds ratio = 1.00, 95% CI: 0.84, 1.20). Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes.

Objective To investigate compliance with risk-based screening for Gestational Diabetes Mellitus (GDM) in a nulliparous cohort. Design A retrospective analysis of nulliparous women recruited to a prospective cohort, the Screening for Pregnancy Endpoints (SCOPE) study, was performed. Population included 2428 healthy nulliparous women with singleton pregnancies, recruited within Cork, Ireland; and Manchester, Leeds and London, United Kingdom. Compliance with risk factor screening for GDM was assessed in relation to the following risk factors: obesity, family history of diabetes and increased ethnic risk. GDM was diagnosed using an oral Glucose Tolerance Test (GTT) with locally employed diagnostic criteria. Statistical analysis was performed using Statistical Packages for Social Sciences (SPSS V22). Descriptive statistics are presented for the various baseline characteristics using numbers and percentages. Cross tabulation was used to compare relevant groups. When comparing group distributions Chi-square test was used. p -value Results In the entire cohort of 2432 women, 27% (650 Women) had one or more identifiable risk factors as defined by National Institute of Health and Care Excellence (NICE) for GDM. Of those that had identifiable GDM risk factors according to the NICE guidelines, 395(60.8%) were appropriately screened. 253 (38.9%) had risk factors but were not screened. 261 (14.6%) had no GDM NICE risk factors but were screened with an oral GTT. Women with a risk factor that were screened with a GTT had an 8.9% ( n = 34) prevalence of GDM. Of those that were screened but did not have a risk factor 7.7% ( n = 20) were diagnosed with GDM. Overall, 2% (54 women) of the cohort had a diagnosis of GDM. Ethnicity was the risk factor most likely to be missed ( n = 55, 66.3%). The GTT test was completed within the recommended gestational window (24−28 weeks) 56.6% ( n = 371) of the time. Conclusion This study highlights poor compliance with risk factor screening for GDM in nulliparous women. Further investigation into the underlying reasons is warranted as well as the implications for pregnancy outcome. Trial registration number ACTRN12607000551493.

Background Small-for-gestational-age (SGA) is a significant cause of morbidity and mortality, and there are currently few preventive strategies. Aim The aim of this study was to investigate the relationship between maternal folic acid supplement (FAS) use pre-conception through to the second trimester, and small-for-gestational age (SGA) and birth size parameters. Study design Women were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) international prospective multi-centre cohort study: New Zealand, Australia, United Kingdom and Ireland. Information on FAS use pre-conception, during the first trimester and at 15 ± 1 weeks' gestation was collected via interview administered questionnaire. Participants were followed through to delivery. Pregnancy outcome data and birth measurements were collected within 72 h of birth. Multivariable regression analysis was used to investigate relationships between FAS and outcomes, adjusting for maternal sociodemographic and lifestyle factors. Subjects Nulliparous women with singleton pregnancies. Outcome measures SGA ( Results 5606 women were included. SGA prevalence was 11.3%. Pre-conception FAS was associated with a significantly lower risk of SGA: aOR = 0.82 (95% CI: 0.67–01.00 p = 0.047). Although the association between FAS at 15 weeks' gestation and SGA did not reach significance, FAS at 15 weeks was associated with a significantly higher customised birthweight centile (β 2.56 (95% CI: 0.87–4.26; p = 0.003). There was no significant effect of FAS on large-for-gestational-age births or head circumference. Conclusions In this international cohort, FAS was positively associated with fetal growth, without increasing risks associated with LGA. Further studies are required to confirm whether continuing FAS beyond the first trimester might lower the risk of SGA.

Objective: To ascertain the incidence of massive transfusion (MT) in obstetrics in the UK, and describe its management and clinical outcomes. Design: A population‐based cross‐sectional study conducted through the UK Obstetric Surveillance System (UKOSS). Settings: All UK hospitals with consultant‐led maternity units. Population: Any pregnant woman at ≥20 weeks of gestation receiving ≥8 units of red blood cells within 24 hours of giving birth, from July 2012 to June 2013. Methods: Prospective case identification through the monthly mailing of UKOSS. Results: We identified 181 women who had undergone MT, making the estimated incidence of MT associated with postpartum haemorrhage (PPH) 23 per 100 000 maternities (95% confidence interval 19–26) per year. The median estimated blood loss was 6 l (interquartile range 4.5–8.0 l). The majority of women presented outside working hours (63%), 40% had had previous caesarean sections and 3% had normal vaginal births without risk factors. The main cause for MT was uterine atony (40%) and the main mode of birth was caesarean section (69%). Of the 181 women, 15 received >20 units of red blood cells. In total, 45% of women underwent hysterectomy, and among all causes of PPH, placenta accreta had the highest hysterectomy rate. Two women died, 82% were admitted to intensive care/high‐dependency units, and 28% developed major morbidities. Conclusion: Massive transfusion due to PPH is associated with high rates of morbidity and hysterectomy. Clinical and research efforts should focus on approaches to recognise and optimise timely resuscitation and management of these severe cases. Tweetable abstract: Massive transfusion due to postpartum haemorrhage is associated with high rates of morbidity and hysterectomy.

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver–operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia.

Objective To determine the microarchitecture of the cervix using high resolution diffusion-tensor (DT) magnetic resonance imaging (MRI). Design Cross-sectional study. Setting Leeds, United Kingdom. Population or Sample Women undergoing hysterectomy for benign pathology. Methods Ex-vivo DT-MRI measurements were obtained using a 9.4T Bruker NMR on seven fixed human cervices obtained at hysterectomy. A deterministic fibre tracking algorithm was used to indirectly visualise underlying fibre organisation. Interregional differences in tissue structure were sought using quantitative measurements of diffusion. Main outcome measures Identification of an occlusive structure in the region corresponding to the internal cervical os. Results Fibre tracking demonstrated two regions: an outer circular and inner longitudinal layer. The total circumferential tract volume (TV) was greatest in the proximal region of the cervix (TV: proximal= 271 ± 198 mm3, middle= 186 ± 119 mm3, distal= 38 ± 36 mm3). Fractional anisotropy (FA) and apparent diffusion coefficient(ADC) measurements were significantly different between regions in all samples (P < 0.0005), indicating greater tract density and organisation towards the internal os. Conclusions Fibre tracking infers a system of dense, well-defined, encircling fibres in the proximal region of the cervix, corresponding to the location of the internal os. These findings may provide evidence of specific anatomic microarchitecture within the cervix able to resist intrauterine forces associated with pregnancy. This article is protected by copyright. All rights reserved.

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss

Background: evidence is conflicting regarding the relationship between low maternal alcohol consumption and birth outcomes. This paper aimed to investigate the association between alcohol intake before and during pregnancy with birth weight and gestational age and to examine the effect of timing of exposure.Methods: a prospective cohort in Leeds, UK, of 1303 pregnant women aged 18–45?years. Questionnaires assessed alcohol consumption before pregnancy and for the three trimesters separately. Categories of alcohol consumption were divided into ?2 units/week and >2 units/week with a non-drinking category as referent. This was related to size at birth and preterm delivery, adjusting for confounders including salivary cotinine as a biomarker of smoking status.Results: nearly two-thirds of women before pregnancy and over half in the first trimester reported alcohol intakes above the Department of Health (UK) guidelines of ?2 units/week. Associations with birth outcomes were strongest for intakes >2 units/week before pregnancy and in trimesters 1 and 2 compared to non-drinkers. Even women adhering to the guidelines in the first trimester were at significantly higher risk of having babies with lower birth weight, lower birth centile and preterm birth compared to non-drinkers, after adjusting for confounders (pConclusions: we found the first trimester to be the period most sensitive to the effect of alcohol on the developing fetus. Women adhering to guidelines in this period were still at increased risk of adverse birth outcomes. Our findings suggest that women should be advised to abstain from alcohol when planning to conceive and throughout pregnancy

To evaluate decafluoro-di-n-pentyl ether (DFPE) as a vitreous tamponade by examining ocular tolerance in rabbits' eyes.Thirteen rabbits were divided into 4 groups after mechanical vitrectomy and were followed up to 12 months. The tamponade remained in the eye for 6 months in group 1 (DFPE) and Group 3 (DFPE and silicone oil) and for 12 months in group 2 (DFPE). Group 4 served as control.In groups 1, 2, and 3, dispersion of the fluid appeared 2 weeks postoperatively. Posterior subcapsular cataracts appeared in rabbits' eyes with large fills of DFPE (50%). Histologic findings in groups 1 and 2 showed no detectable change in outer nuclear layer thickness. Except for some vacuolations, the inner retina was well preserved in all injected rabbits' eyes. On the electroretinography of injected rabbits' eyes, there was no effect on the a wave amplitude and b wave implicit time, but the b wave amplitude was elevated with statistical significance (P0.001) at 1, 3, and 6 months postoperatively but with no statistical significance (P0.05) after that period when compared with group 4 and unoperated fellow rabbits' eyes of each group.Decafluoro-di-n-pentyl ether demonstrated minimum adverse effects in retinal rabbits; further studies are needed before clinical use as short-term tamponade.

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (P Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.