Frequency of Leaks from Conical Centrifuge Tubes.

Introduction: Threaded conical centrifuge tubes are ubiquitous in biological laboratories and are frequently used for the storage/transport of potentially biohazardous samples. However, limited data are available on how frequently and from where these tubes leak. These data are valuable for laboratory biorisk management and to inform future studies on risks arising from the routine use of laboratory consumables. Methods: The frequency of leaks from threaded conical centrifuge tubes was tested using a Glo Germ solution as a tracer. Conical tubes (15 and 50 mL) from several brands were filled, inverted, and placed on their side on the benchtop. After 1 h, the presence or absence of leaks on the benchtop surface, tube threads, and exterior was recorded. Results: We observed that liquid leaked out of tubes that were apparently properly threaded in 2% of 15 mL tubes (confidence interval [95% CI] 1.4-2.6) and 1.4% of 50 mL tubes (95% CI 0.2-1.5). After opening, liquid was found on the threads on the outside of the tube in 20% of 15 mL tubes (95% CI 10-31) and 14% of 50 mL tubes (95% CI 1-28). We did not find sufficient evidence that differences in leak rates among brands were practically significant. Conclusions: The fact that leaks were not uncommonly observed from conical centrifuge tubes suggests that mitigations for any hazard posed by a leak should be a component of every biorisk management strategy for protocols involving the manipulation of hazardous substances in these tubes. Further research should be conducted on other activities that could cause tubes to leak (such as centrifugation or vortexing) and should be completed to understand the risks associated with this consumable. Research into the costs and benefits of mitigating the risk of leaks from conical tubes is recommended.

Safe Today, Unsafe Tomorrow: Tanzanian Households Experience Variability in Drinking Water Quality.

Measuring Escherichia coli in a single-grab sample of stored drinking water is often used to characterize drinking water quality. However, if water quality exhibits variability temporally, then one-time measurement schemes may be insufficient to adequately characterize the quality of water that people consume. This study uses longitudinal data collected from 193 households in peri-urban Tanzania to assess variability in stored water quality and to characterize uncertainty with different data collection schemes. Households were visited 5 times over the course of a year. At each visit, information was collected on water management practices, and a sample of stored drinking water was collected for E. coli enumeration. Water quality was poor for households, with 80% having highly contaminated (>100 CFU per 100 mL) water during at least one visit. There was substantial variability of water quality for households, with only 3% of households having the same category (low, medium, or high) of water quality for all five visits. These data suggest a single sample would inaccurately characterize a household's drinking water quality over the course of a year and lead to misestimates of population level access to safe drinking water.

Rate of Splashes When Opening Microfuge Tubes with Various Methods.

Introduction: Snap-cap microcentrifuge tubes are ubiquitous in biological laboratories. However, limited data are available on how frequently splashes occur when opening them. These data would be valuable for biorisk management in the laboratory. Methods: The frequency of splashes from opening snap-cap tubes using four different methods was tested. The splash frequency for each method was measured on the benchtop surface and on the experimenter's gloves and smock, using a Glo Germ solution as a tracer. Results: Splashes occurred very frequently when opening microcentrifuge snap-cap tubes, no matter which method was used to open the tube. The highest rate of splashes on all surfaces was observed with the one-handed (OH) opening method compared with two-handed methods. Across all methods, the highest rate of splashes was observed on the opener's gloves (70-97%) compared with the benchtop (2-40%) or the body of the researcher (0-7%). Conclusions: All tube opening methods we studied frequently caused splashes, with the OH method being the most error-prone but no two-handed method being clearly superior to any other. In addition to posing an exposure risk to laboratory personnel, experimental repeatability may be affected due to loss of volume when using snap-cap tubes. The rate of splashes underscores the importance of secondary containment, personal protective equipment, and good protocols for decontamination. When working with especially hazardous materials, alternatives to snap-cap tubes (such as screw cap tubes) should be strongly considered. Future studies can examine other methods of opening snap-cap tubes to determine whether a truly safe method exists.

Timing and Trends for Municipal Wastewater, Lab-Confirmed Case, and Syndromic Case Surveillance of COVID-19 in Raleigh, North Carolina.

Objectives. To compare 4 COVID-19 surveillance metrics in a major metropolitan area. Methods. We analyzed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater influent and primary solids in Raleigh, North Carolina, from April 10 through December 13, 2020. We compared wastewater results with lab-confirmed COVID-19 cases and syndromic COVID-like illness (CLI) cases to answer 3 questions: (1) Did they correlate? (2) What was the temporal alignment of the different surveillance systems? (3) Did periods of significant change (i.e., trends) align? Results. In the Raleigh sewershed, wastewater influent, wastewater primary solids, lab-confirmed cases, and CLI were strongly or moderately correlated. Trends in lab-confirmed cases and wastewater influent were observed earlier, followed by CLI and, lastly, wastewater primary solids. All 4 metrics showed sustained increases in COVID-19 in June, July, and November 2020 and sustained decreases in August and September 2020. Conclusions. In a major metropolitan area in 2020, the timing of and trends in municipal wastewater, lab-confirmed case, and syndromic case surveillance of COVID-19 were in general agreement. Public Health Implications. Our results provide evidence for investment in SARS-CoV-2 wastewater and CLI surveillance to complement information provided through lab-confirmed cases. (Am J Public Health. 2023;113(1):79-88. https://doi.org/10.2105/AJPH.2022.307108).

Dynamic growth changes in fetal growth restriction using serial ultrasonographic biometry and umbilical artery doppler: The multicenter PORTO study.

OBJECTIVE: To describe the growth dynamics of fetuses with initial fetal growth restriction (FGR) later outgrowing the 10th centile for estimated fetal weight with respect to perinatal outcomes and maternal factors. METHODS: A multicenter prospective study recruited 1116 patients for ultrasound surveillance between 2010 and 2012. All pregnancies were growth-restricted singleton gestations between 24 + 0 and 36 + 0 weeks. Biometry and Doppler analysis were carried out, and delivery and adverse perinatal outcomes were recorded. RESULTS: A total of 193 (17%) fetuses outgrew their diagnosis of initial FGR (surpassed the 10th centile) on their last sonogram before delivery. These fetuses were termed "growers," to compare with the true FGR group. The mothers of "growers" were less likely to be smokers (14% vs 25%, P = 0.0001) or affected by hypertensive pregnancy complications (5.2% vs 15%, P = 0.001). Of the growers, 49 (25%) had an abnormal umbilical artery Doppler; however, in most cases (33/49, 67%), this was a single episode of raised umbilical artery pulsatility index, which subsequently normalized. CONCLUSION: There were dynamic growth changes in FGR fetuses, with 17% outgrowing their original diagnosis. Positive growth spurts more commonly occurred in healthy mothers. Once a fetus had outgrown the 10th centile, antenatal surveillance could be decreased.

Onset and outcomes of spontaneous labour in low risk nulliparous women.

OBJECTIVES: The objective of this study was to: 1. Establish the median gestational age of spontaneous labour for low-risk nulliparas. 2. Examine the variation in mode of delivery and short-term neonatal outcomes with gestation at onset of spontaneous labour. STUDY DESIGN: This is a retrospective observational cohort study conducted at a tertiary obstetric unit. The study population was 12, 323 low risk nulliparous women with singleton pregnancies who experienced spontaneous onset of labour. The study period was over seven years, from Jan 1st 2011 to 31st Dec 2017. Exclusion criteria were multiparity, multi-fetal pregnancy, booking after 14 weeks gestation, antepartum or intrapartum death, or any obstetric or fetal indication for delivery with the exception of post-maturity. Gestation of onset of spontaneous labour, demographic variables and maternal and neonatal outcomes were collected. The primary outcome was median gestational age at onset of spontaneous labour and its distribution at term. Secondary outcomes were mode of delivery and neonatal outcomes including low-apgar score and NICU admission. RESULTS: 12, 323 patients were eligible for inclusion. Median gestation for onset of labour was 40.1 weeks gestation, with 80.5% of spontaneous labour occurs by 41 + 0 weeks gestation. The risk of assisted delivery (RR 1.32, 95% CI 1.23 - 1.42), caesarean section (RR 2.17, 95% CI 1.88-2.51) and low-apgar scores (RR 3.13 95% CI 1.50-6.55) increased significantly with spontaneous labour after 41 weeks' gestation. CONCLUSIONS: Nulliparous women with low-risk pregnancies are most likely to experience spontaneous labour between 40 + 0 and 40 + 6. 80.5% of spontaneous labour occurred by 41 + 0 weeks gestation. Assisted vaginal delivery, caesarean section and low-apgar scores were significantly more likely with spontaneous labour after 41 weeks' gestation.

Modeling Exposure to Fecal Contamination in Drinking Water due to Multiple Water Source Use.

The Joint Monitoring Programme estimated that 71% of people globally had access to "safely managed" drinking water in 2017. However, typical data collection practices focus only on a household's primary water source, yet some households in low- and middle-income countries (LMICs) engage in multiple water source use, including supplementing improved water supplies with unimproved water throughout the year. Monte Carlo simulations and previously published data were used to simulate exposure to fecal contamination (as measured by E. coli) along a range of supplemental unimproved source use rates (e.g., 0-100% improved water use, with the remainder made up with unimproved water). The model results revealed a statistically significant increase in annual exposure to E. coli when individuals supplement their improved water with unimproved water just 2 days annually. Additionally, our analysis identified scenarios-realistic for the data set study setting-where supplementing with unimproved water counterintuitively decreases exposure to E. coli. These results highlight the need for evaluating the temporal dynamics in water quality and availability of drinking water sources in LMICs as well as capturing the use of multiple water sources for monitoring global access to safe drinking water.

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.

BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6). CONCLUSION: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate.

Postgraduate training in Cancer Genetics-a cross-specialty survey exploring experience of clinicians in Ireland.

BACKGROUND: As genomic profiling of constitutional and tumour-derived DNA becomes increasingly critical in cancer risk estimation, prognostication and treatment, there is a growing need for clinicians involved in cancer care to up-skill in Cancer Genetics. In the Republic of Ireland (ROI), this is particularly crucial, given a paucity of vocationally trained Clinical Geneticists per capita compared to other European countries. AIMS: We aimed to assess the self-reported confidence of postgraduate medical/surgical trainees in ROI in requesting, interpreting, and managing genomic data in patients with cancer, and to assess their selfreported experience, and demand for future training in this area. METHODS: A cross-sectional survey of postgraduate trainees in four specialties (Medical and Radiation Oncology, Surgery, and Obstetrics and Gynaecology (O&G)), training in ROI, was undertaken. A bespoke electronic questionnaire was designed to capture data regarding preceding experience, and confidence across several hypothetical clinical scenarios involving genomic testing. The survey was circulated to eligible participants by training programme administrators, after relevant institutional ethical approval. Data was collected anonymously. RESULTS: The study cohort included 62 respondents. A paucity of cancer genetics training at every level was demonstrated, with "hardly any" or "none at all" reported by 47(76%), 62(100%), and 50(81%) during undergraduate, core specialty, and higher specialist training, respectively. A relative lack of confidence in all clinical scenarios was apparent, particularly among Surgery/O&G trainees. Most respondents would value more training in Cancer Genetics. CONCLUSIONS: This study demonstrates an unmet need in dedicated Cancer Genetics training for postgraduate specialty trainees in ROI.

The prediction of morbidity related to vaginal delivery in nulliparous women - A secondary analysis from the genesis multicenter trial.

OBJECTIVE: In the prospective multicenter Genesis study, we developed a prediction model for Cesarean delivery (CD) in term nulliparous women. The objective of this secondary analysis was to determine whether the Genesis model has the potential to predict maternal and neonatal morbidity associated with vaginal delivery. STUDY DESIGN: The national prospective Genesis trial recruited 2,336 nulliparous women with a vertex presentation between 39 + 0- and 40 + 6-weeks' gestation from seven tertiary centers. The prediction model used five parameters to assess the risk of CD: maternal age, maternal height, body mass index, fetal head circumference and fetal abdominal circumference. Simple and multiple logistic regression analyses were used to develop the Genesis model. The risk score calculated using this model were correlated with maternal and neonatal morbidity in women who delivered vaginally: postpartum hemorrhage (PPH), obstetric anal sphincter injury (OASI), shoulder dystocia, one- and five-minute Apgar score ≤ 7, neonatal intensive care (NICU) admission, cephalohematoma, fetal laceration, nerve palsy and fractures. The morbidities associated with spontaneous vaginal delivery were compared with those associated with operative vaginal delivery (OVD). The likelihood ratios for composite morbidity and the morbidity associated with OVD based on the Genesis risk scores were also calculated. RESULTS: A total of 1,845 (79%) nulliparous women had a vaginal delivery. A trend of increasing intervention and morbidity was observed with increasing Genesis risk score, including OVD (p < 0.001), PPH (p < 0.008), NICU admission (p < 0.001), low Apgar score at one-minute (p < 0.001) and OASI (p = 0.009). The morbidity associated with OVD was significantly higher compared to spontaneous vaginal delivery, including NICU admission (p < 0.001), PPH (p = 0.022), birth injury (p < 0.001), shoulder dystocia (p = 0.002) and Apgar score of<7 at one-minute (p < 0.001). The positive likelihood ratios for composite outcomes (where the OVD was excluded) increases with increasing risk score from 1.005 at risk score of 5% to 2.507 for risk score of>50%. CONCLUSION: In women who ultimately achieved a vaginal birth, we have shown more maternal and neonatal morbidity in the setting of a Genesis nomogram-determined high-risk score for intrapartum CD. Therefore, the Genesis prediction tool also has the potential to predict a more morbid vaginal delivery.

Multiple water source use in low- and middle-income countries: a systematic review.

The Joint Monitoring Programme (JMP) 2017 Update and Sustainable Development Goals (SDGs) Baselines report classified 71% of the global population as having access to 'safely managed' drinking water. Current global monitoring efforts to track access to safely managed drinking water rely on collecting information on the 'primary' source of drinking water. However, there is evidence that households often rely on multiple sources to meet their water needs in many low- and middle-income countries (LMICs). This systematic review was designed to compile the literature related to the practice of multiple water source use (MWSU) for drinking water in LMICs. A total of 5,318 studies were collected, and after abstract and full-text review, 74 articles were identified for inclusion. Studies reviewed reported from 4 to 100% of the study populations practicing MWSU. Additionally, the practice of supplemental unimproved source use was reported globally, representing households with improved primary source water also accessing unimproved water sources throughout the year. These findings expose gaps in current global water monitoring efforts, revealing potential inflation of reports of 'safe drinking water access' and unaccounted exposure to drinking water from unimproved sources.

A narrative literature review: the application of video games as therapeutic tools for psychological therapy.

OBJECTIVES: Video games (games played by electronically manipulating images produced by a computer programme on a screen) are being developed with a specific focus on treating mental health. This narrative review briefly discusses the history of video games and mental health. It then provides a critical discussion on the application of video games as therapeutic tools, then discusses the notion of 'serious games' (games designed for a primary purpose other than entertainment) and their applicability. CONCLUSIONS: Serious games have preliminary evidence to support their use practically in the clinical treatment of mental illness. Future randomised control trials are necessary to further explore their efficacy and potential areas of application.

Valsartan exposure in pregnancy with resultant anhydramnios and chronic kidney disease in a late preterm infant.

In utero exposure to angiotensin II receptor blockers (ARBs) has fetotoxic effects including renal failure, oligohydramnios and lung hypoplasia. We present the case of a 24-year-old woman who presented to the maternity services in the 34th week of her first pregnancy. She was taking valsartan for hypertension. Ultrasound showed a structurally normal fetus with anhydramnios. The patient was admitted and valsartan was discontinued. She had spontaneous preterm delivery at 35 weeks' gestation of a baby girl. The baby's urine output was minimal in the first week of life and she was transferred to a paediatric hospital for specialist nephrology input. At 6 months of age, she requires ongoing nephrology follow-up and she remains on treatment for hypertension and anaemia. This case demonstrates the serious adverse effects resulting from ARB exposure in utero, and highlights the importance of avoiding fetotoxic medications in women of childbearing age.

Human Gut Microbiota-associated Gastrointestinal Malignancies: A Comprehensive Review.

The human gastrointestinal tract houses trillions of microbes. The gut and various types of microorganisms, including bacteria, viruses, fungi, and archaea, form a complex ecosystem known as the gut microbiota, and the whole genome of the gut microbiota is referred to as the gut microbiome. The gut microbiota is essential for homeostasis and the overall well-being of a person and is increasingly considered an adjunct "virtual organ," with a complexity level comparable to that of the other organ systems. The gut microbiota plays an essential role in nutrition, local mucosal homeostasis, inflammation, and the mucosal immune system. An imbalanced state of the gut microbiota, known as dysbiosis, can predispose to development of various gastrointestinal malignancies through three speculated pathogenic mechanisms: (a) direct cytotoxic effects with damage to the host DNA, (b) disproportionate proinflammatory signaling inducing inflammation, and (c) activation of tumorigenic pathways or suppression of tumor-suppressing pathways. Several microorganisms, including Helicobacter pylori, Epstein-Barr virus, human papillomavirus, Mycoplasma species, Escherichia coli, and Streptococcus bovis, are associated with gastrointestinal malignancies such as esophageal adenocarcinoma, gastric adenocarcinoma, gastric mucosa-associated lymphoid tissue lymphoma, colorectal adenocarcinoma, and anal squamous cell carcinoma. Imaging plays a pivotal role in diagnosis and management of microbiota-associated gastrointestinal malignancies. Appropriate use of probiotics, fecal microbiota transplantation, and overall promotion of the healthy gut are ongoing areas of research for prevention and treatment of malignancies. Online supplemental material is available for this article. ©RSNA, 2021.

Correlation of maternal body mass index with umbilical artery Doppler in pregnancies complicated by fetal growth restriction and associated outcomes.

OBJECTIVE: To evaluate the correlation between umbilical artery (UA) Doppler and its feasibility across categories of maternal body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) in the presence of fetal growth restriction (FGR). METHODS: A total of 1074 singleton pregnancies with suspected FGR on ultrasound examination between 24+0 and 36+0 weeks of pregnancy were reviewed. Evaluation of the UA Doppler was performed at 1- to 2-weekly intervals. Abnormal UA Doppler findings and delivery outcomes were compared between the different maternal BMI categories. RESULTS: Increased UA pulsatility index (PI >95th centile) was reported in 81% of obese class II patients (BMI 35-39.9) compared with a 46% incidence in the remaining categories, normal (BMI <24.9), overweight (BMI 25-29.9), and obese class I (BMI 30-34.9) (P = 0.001). In absent or reversed end diastolic flow (AEDF/REDF) we found an increasing incidence across the BMI categories (4%-25%) (P < 0.001). Higher maternal BMI was associated with lower birthweights and higher cesarean section rates. Increasing maternal BMI did not affect successful assessment of UA Doppler. CONCLUSION: There is a positive correlation between increasing maternal BMI and abnormal UA Doppler findings in FGR. Maternal BMI may be considered as an additional risk factor when evaluating UA Doppler for placental insufficiency.

Inter-hospital comparison of Cesarean delivery rates should not be considered to reflect quality of care without consideration of patient heterogeneity: An observational study.

OBJECTIVE: Contemporary approaches to monitoring quality of care in obstetrics often focus on comparing Cesarean Delivery rates. Varied rates can complicate interpretation of quality of care. We previously developed a risk prediction tool for nulliparous women who may require intrapartum Cesarean delivery which identified five key predictors. Our objective with this study was to ascertain if patient heterogeneity can account for much of the observed variation in Cesarean delivery rates, thereby enabling Cesarean delivery rates to be a better marker of quality of care. MATERIALS AND METHODS: This is a secondary analysis of the Genesis study. This was a large prospective study of 2336 nulliparous singleton pregnancies recruited at seven hospitals. A heterogeneity score was calculated for each hospital. An adjusted Cesarean delivery rate was also calculated incorporating the heterogeneous risk score. RESULTS: A cut-off at the 90th percentile was determined for each predictive factor. Above the 90th percentile was considered to represent 'high risk' (with the exception of maternal height which identified those below the 10th percentile). The patient heterogeneous risk score was defined as the number of risk factors > 90th percentile (<10th percentile for height). An unequal distribution of high-risk patients between centers was observed (p < 0.001). The correlation between the Cesarean delivery rate and the patient heterogeneous risk score was high (0.76, p < 0.05). When adjusted for patient heterogeneity, Cesarean delivery rates became closer aligned. CONCLUSION: Inter-institutional diversity is common. We suggest that crude comparison of Cesarean delivery rates between different hospitals as a marker of care quality is inappropriate. Allowing for marked differences in patient characteristics is essential for correct interpretation of such comparisons.

Childbirth in Ireland's capital city over sixty years.

BACKGROUND: Ireland has changed over the past sixty years, and the dynamic practice of obstetrics and gynaecology has changed with it. STUDY DESIGN AND METHODS: To describe these changes, a review was performed of clinical reports of a tertiary referral teaching hospital over six decades. RESULTS: Since the 1960s, the hospital's total births per annum has risen (3050 to 8362 births). Teenage pregnancy is less common (4.7 to 2.0%, p < 0.001), with more women over age 40 at booking (2.6 to 6.4%, p < 0.001). There are more multiple pregnancies now (1.8 to 4.1%, p < 0.001) and less grand-multiparous woman (10.1 to 1.3%, p < 0.001). Eclampsia is less common (0.18 to 0.02%, p = 0.003), with a slight decrease in rate of preeclampsia (3.8 to 3.0%, p = 0.03). Induction of labour increased considerably (8.8 to 32.1%, p < 0.001). While the instrumental delivery rate remained stable, the instrument of choice has changed from forceps (11.3 to 5.4%, p = 0.001) to ventouse delivery (0.6 to 9.1%, p = 0.001). The caesarean section rate rose (5.9 to 29.7%, p < 0.001). Vaginal birth after caesarean section rate dropped (90.4 to 28.2%, p < 0.001) without significant change in rate of uterine rupture (0.4 to 0.7%, p = 0.1). The perinatal mortality rate improved (48.5 to 5.4 per 1000 births, p < 0.001). Preterm birth rate rose (4.9 to 6.6%, p = 0.001). Foetal macrosomia decreased in this time (2.5 to 1.7%, p = 0.007), despite a rise in the incidence of gestational diabetes mellitus. CONCLUSION: This study provides an intriguing glimpse into the changes in the practice of obstetrics and demonstrates how it adapts to the population it serves.

Concentrations of perfluoroalkyl substances in human milk from Ireland: Implications for adult and nursing infant exposure.

Concentrations of 10 perfluoroalkyl substances (PFASs) were measured in 16 pools of human milk from Ireland. Only four PFASs were detected (PFOA, PFNA, PFHxS and PFOS), with concentrations dominated by PFOA which was detected in all samples at a median of 0.10 ng/mL. Concentrations and the relative abundance of PFASs in human milk from Ireland are within the range reported for other countries. Estimated exposures for nursing infants to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) do not suggest a health concern. A one compartment pharmacokinetic model was used to predict the intakes of PFOS and PFOA required to support the observed concentrations in human milk. This suggests current adult exposure in Ireland to PFOS is below the provisional tolerable weekly intake (TWI) proposed by EFSA. In contrast, the model predicts that the maximum concentration detected in human milk in this study, implies a level of adult exposure that would exceed EFSA's provisional TWI for PFOA. As exposure of the Irish population to PFASs via drinking water, indoor air and dust is well-characterised, current understanding suggests that the major contributor to overall exposure of the Irish population is via the diet and/or less well-studied pathways like dermal uptake from PFAS-containing fabrics and cosmetics.

Emerging and legacy brominated flame retardants in the breast milk of first time Irish mothers suggest positive response to restrictions on use of HBCDD and Penta- and Octa-BDE formulations.

The brominated flame retardants (BFRs) hexabromocyclododecane (HBCDD), eight polybrominated diphenyl ethers (PBDEs), and decabromodiphenyl ethane (DBDPE) were measured in 16 pools of human milk from Ireland. Concentrations of BDEs-47, -99, -100, -153, and HBCDD were significantly lower (p < 0.05) than those in Irish human milk collected in 2011. In contrast, concentrations of BDE-209 in our study exceeded those in 2011, and while decabromodiphenyl ethane (DBDPE) was not detected in 2011 it was detected in 3 of our samples. This suggests increased use of DBDPE and that while restrictions on the Penta- and Octa-BDE formulations are reducing human exposure, those on Deca-BDE use have yet to reduce body burdens. Estimated exposures for nursing infants to all target BFRs do not suggest a health concern. A one compartment pharmacokinetic model was used to predict body burdens arising from BFR intakes via air, dust and diet. While for most targeted BFRs, predicted and observed body burdens derived from our human milk data compared reasonably well; predicted BDE-209 and DBDPE values were substantially lower than observed. This suggests exposure pathways not included in the model like dermal uptake from fabrics may be important, and highlights knowledge gaps about the human half-lives and bioavailability of these contaminants.

Investigating the role of early low-dose aspirin in diabetes: A phase III multicentre double-blinded placebo-controlled randomised trial of aspirin therapy initiated in the first trimester of diabetes pregnancy.

BACKGROUND: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. METHODS: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). DISCUSSION: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks' gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation.