Validation of Fetal Medicine Foundation charts for fetal growth in twins: nationwide Danish cohort study.

OBJECTIVE: To assess the validity of the Fetal Medicine Foundation (FMF) chorionicity-specific models for fetal growth in twin pregnancy. METHODS: This was an external validation study of the FMF models using a nationwide Danish cohort of twin pregnancies. The cohort included all dichorionic (DC) and monochorionic diamniotic (MCDA) twin pregnancies with an estimated delivery date between 2008 and 2018, which satisfied the following inclusion criteria: two live fetuses at the first-trimester ultrasound scan (11-14 weeks' gestation); biometric measurements available for the calculation of estimated fetal weight (EFW) using the Hadlock-3 formula; and delivery of two liveborn infants. Validation involved assessing the distributional properties of the models and estimating the mean EFW Z-score deviations. Additionally, the models were applied to pregnancies that delivered preterm and attended non-scheduled visits (complicated pregnancies). RESULTS: Overall, 8542 DC and 1675 MCDA twin pregnancies met the inclusion criteria. In DC twins, 17 084 fetuses were evaluated at a total of 95 346 ultrasound scans, of which 44.5% were performed at scheduled visits in pregnancies carried to 37 + 0 weeks or later. The median number of growth scans per DC twin fetus from 20 + 0 weeks onwards was four. The model showed good agreement with the validation cohort for scheduled visits in DC twins delivered at 37 + 0 weeks or later (mean EFW Z-score, -0.14 ± 1.05). In MCDA twins, 3350 fetuses underwent 31 632 eligible ultrasound scans, of which 59.5% were performed at scheduled visits in pregnancies carried to 36 + 0 weeks or later. The median number of growth scans per MCDA twin fetus from 16 + 0 weeks onwards was 10. The model showed favorable agreement with the validation cohort for scheduled visits in MCDA twins delivered at 36 + 0 weeks or later (mean EFW Z-score, -0.09 ± 1.01). Non-scheduled visits and preterm delivery before 37 + 0 weeks for DC twins and before 36 + 0 weeks for MCDA twins corresponded with smaller weight estimates, which was consistent with the study's definition of complicated pregnancy. CONCLUSIONS: The FMF models provide a good fit for EFW measurements in our Danish national cohort of uncomplicated twin pregnancies assessed at routine scans. Therefore, the FMF models establish robust criteria for subsequent investigations and potential clinical applications. Future research should focus on exploring the consequences of clinical implementation, particularly regarding the identification of twins that are small-for-gestational age, as they are especially susceptible to adverse perinatal outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quadruplet pregnancy outcome with and without fetal reduction: Danish national cohort study (2008-2018) and comparison with dichorionic twins.

OBJECTIVES: To perform a nationwide study of quadrichorionic quadriamniotic (QCQA) quadruplet pregnancies and to compare the pregnancy outcome in those undergoing fetal reduction with non-reduced quadruplets and dichorionic diamniotic (DCDA) twin pregnancies from the same time period. METHODS: This was a retrospective Danish national register-based study performed using data from the national Danish Fetal Medicine Database, which included all QCQA quadruplets and all non-reduced DCDA twin pregnancies with an estimated due date between 2008 and 2018. The primary outcome measure was a composite of adverse pregnancy outcomes, including pregnancy loss or intrauterine death of one or more fetuses. Secondary outcomes included gestational age at delivery, the number of liveborn children, preterm delivery before 28, 32 and 37 gestational weeks and birth weight. Data on pregnancy complications and baseline characteristics were also recorded. Outcomes were compared between reduced and non-reduced quadruplet pregnancies, and between DCDA pregnancies and quadruplet pregnancies reduced to twins. A systematic literature search was performed to describe and compare previous results with our findings. RESULTS: Included in the study were 33 QCQA quadruplet pregnancies, including three (9.1%) non-reduced pregnancies, 28 (84.8%) that were reduced to twin pregnancy and fewer than three (6.1%) that were reduced to singleton pregnancy, as well as 9563 DCDA twin pregnancies. Overall, the rate of adverse pregnancy outcome was highest in non-reduced quadruplets (66.7%); it was 50% in quadruplets reduced to singletons and 10.7% in quadruplets reduced to twins. The proportion of liveborn infants overall was 91.1% of the total number expected to be liveborn in quadruplet pregnancies reduced to twins. This was statistically significantly different from 97.6% in non-reduced dichorionic twins (P = 0.004), and considerably higher than 58.3% in non-reduced quadruplets. The rates of preterm delivery < 28, < 32 and < 37 weeks were decreased in quadruplets reduced to twins compared with those in non-reduced quadruplet pregnancies. Quadruplets reduced to twins did not achieve equivalent pregnancy outcomes to those of DCDA twins. CONCLUSION: This national study of QCQA quadruplets has shown that multifetal pregnancy reduction improves pregnancy outcome, including a decreased rate of preterm delivery and higher proportion of liveborn children. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Microbiological Quality of Ready-to-Eat Salad Products Collected from Retail and Catering Settings in England during 2020 to 2021.

ABSTRACT: Salad and other fresh produce were collected in England from retail and catering businesses during 2020 to 2021 and were tested for Salmonella, Shiga toxin-producing Escherichia coli (STEC), Listeria, Bacillus cereus, and E. coli. Of the 604 samples collected, 57% were from retail settings and 43% were from catering settings; 61% were either salad leaves or salad leaves mixed with other products. Equal numbers of samples were prepacked or loose, and 50% were refrigerated at the time of sampling. Combining results for all microbiological parameters, 84% were interpreted as satisfactory, 12% were interpreted as borderline, and 4% were interpreted as unsatisfactory. One sample (prepacked leaves, cucumber, and tomato from a caterer) was categorized as unacceptable and potentially injurious because of detection of STEC O76; no STEC from human infections in the United Kingdom matched this isolate. No Salmonella enterica was detected, but Listeria monocytogenes was recovered from 11 samples: 1 at 20 CFU/g and the remainder at <20 CFU/g. B. cereus was detected at borderline levels (103 to ≤105 CFU/g) in 9% of samples and at an unsatisfactory level (>105 CFU/g) in one sample. E. coli was detected in 3% of samples at borderline levels (20 to ≤102 CFU/g) and in 4% at unsatisfactory levels (>102 CFU/g). There was a significant association between detection of L. monocytogenes and borderline or unsatisfactory levels of E. coli. There were no specific risk profiles associated with products with the higher levels of B. cereus, STEC, or Listeria, but elevated levels of E. coli were predominantly confined to loose products from the United Kingdom collected from caterers in summer or autumn 2021 and may have resulted from relaxation of COVID-19 restrictions. Among the L. monocytogenes isolates, only one matched those from human cases and was recovered from a prepacked mixed salad from a catering business in 2021. This isolate was the same strain as that responsible for a multicountry outbreak (2015 to 2018) associated with Hungarian-produced frozen sweet corn; no link to the outbreak food chain was established.

Assessment of the Microbiological Quality and Safety of Unpasteurized Milk Cheese for Sale in England between 2019 and 2020.

ABSTRACT: Cheese made with unpasteurized milk has been associated with outbreaks of illness. However, there are limited data on the prevalence of Shiga toxin-producing Escherichia coli (STEC) in these products and a lack of clarity over the significance of E. coli as a general indicator of hygiene in raw milk cheeses. The aim of this study was to provide further data to address both of these issues, as well as assessing the overall microbiological quality of raw milk cheeses available to consumers in England. A total of 629 samples of cheese were collected from retailers, catering premises, and manufacturers throughout England. The majority (80%) were made using cow's milk, with 14% made from sheep's milk and 5% from goat's milk. Samples were from 18 different countries of origin, with the majority originating from either the United Kingdom (40%) or France (35%). When interpreted against European Union microbiological criteria and United Kingdom guidance, 82% were considered to be of satisfactory microbiological quality, 5% were borderline, and 12% were unsatisfactory. Four samples (0.6%) were potentially injurious to health due to the isolation of STEC from one, >104 CFU/g of coagulase-positive staphylococci in two, and >100 CFU/g of Listeria monocytogenes in the fourth sample. Indicator E. coli and Listeria species were detected more frequently in soft compared with hard cheese. Higher levels of indicator E. coli were significantly associated with a greater likelihood of detecting Shiga toxin genes (stx1 and/or stx2).

Prenatal cardiac biometry and flow assessment in fetuses with bicuspid aortic valve at 20 weeks' gestation: multicenter cohort study.

OBJECTIVE: To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. METHODS: This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. RESULTS: Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). CONCLUSIONS: Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Listeria monocytogenes in Cooked Chicken: Detection of an Outbreak in the United Kingdom (2016 to 2017) and Analysis of L. monocytogenes from Unrelated Monitoring of Foods (2013 to 2017).

ABSTRACT: In England and Wales, Public Health England applies whole genome sequencing to cultures of Listeria monocytogenes recovered from human cases of listeriosis, foods, and food production environments. Following the routine inspection of a small retailer in February and March 2016, two unopened packs of cooked chicken produced by the same manufacturer were found to be contaminated with L. monocytogenes at levels of 340 and 20 CFU/g. A public recall of this product was issued in March 2016. Early in 2017, a less than five single-nucleotide polymorphism single-linkage cluster was detected between the L. monocytogenes isolates from the two cooked chicken products and cultures from five cases of human listeriosis in England and Scotland with onsets of illness between March 2016 and February 2017. Epidemiological data provided further supportive evidence that this cluster was an outbreak linked to a manufacturer of cooked chicken whose products were supplied to the small retailer that initiated the outbreak investigation. Unrelated to this outbreak, 34 L. monocytogenes isolates recovered from routine food monitoring of 2,007 samples of cooked chicken during 2013 to 2017 were analyzed by whole genome sequencing. Previously undetected fewer than five single-nucleotide polymorphism single-linkage clusters were identified between cultures from cooked chicken and with those from two clusters and two sporadic cases of human listeriosis that were consistent with foodborne transmission. This analysis identified linkage of L. monocytogenes clusters within specific food chains more readily than traditional manual tracing. Linking of data associated with L. monocytogenes cultures from cases of listeriosis with those from unrelated food testing is a unique source of information for communicable disease risk assessment, epidemiological studies, and disease prevention and control. This report provides further evidence that should act as a reminder of the association between cooked chicken consumption and human listeriosis.

Microbiological quality of raw drinking milk and unpasteurised dairy products: results from England 2013-2019.

The aim of this study was to review microbiology results from testing >2500 raw drinking milk and dairy products made with unpasteurised milk examined in England between 2013 and 2019. Samples were collected as part of incidents of contamination, investigation of infections or as part of routine monitoring and were tested using standard methods for a range of both pathogens and hygiene indicators. Results from testing samples of raw cow's milk or cheese made from unpasteurised milk for routine monitoring purposes were overall of better microbiological quality than those collected during incident or investigations of infections. Results from routine monitoring were satisfactory for 62% of milks, 82% of cream, 100% of ice-cream, 51% of butter, 63% of kefir and 79% of cheeses, with 5% of all samples being considered potentially hazardous. Analysis of data from cheese demonstrated a significant association between increasing levels of indicator Escherichia coli with elevated levels of coagulase positive staphylococci and decreased probability of isolation of Shiga toxin-producing E. coli. These data highlight the public health risk associated with these products and provide further justification for controls applied to raw drinking milk and dairy products made with unpasteurised milk.

Factors affecting the species of Campylobacter colonizing chickens reared for meat.

AIM: To investigate factors influencing Campylobacter spp. colonization of broiler chickens. METHODS AND RESULTS: Campylobacters were isolated from caeca from 319 flocks of two different breeds (199 Cobb and 120 Hubbard), reared as standard (199), Freedom Food/corn fed (57), free-range (47) or organic (16). The standard category exclusively used Cobb birds slaughtered at 38-41 days. The Freedom Food/corn-fed and free-range Hubbard birds were slaughtered at 49-56 days and the organic flocks at 70 days. Campylobacters were picked at random from direct plates. Both breed of chicken (Hubbard) and age at slaughter were independently associated with increased likelihood of colonization by Campylobacter coli rather than Campylobacter jejuni, but breed could not be separated from other aspects of husbandry with the data available. CONCLUSIONS: Chickens are frequently colonized by C. jejuni and C. coli and most human infections originate from poultry. In most developed countries approximately 90% of human infections are caused by C. jejuni, but fewer than 10% by C. coli. This might be due to C. coli being less pathogenic than C. jejuni to humans, and/or to chicken meat carrying fewer C. coli than C. jejuni. More investigations are needed into these aspects before it can be concluded that slaughtering older birds from slower-growing breeds would reduce the risk of human Campylobacter disease. SIGNIFICANCE AND IMPACT OF THE STUDY: Meat from certain breeds of poultry are predominantly colonized by C. coli rather than C. jejuni. More research is needed to understand the impact this may have on the number and severity of human campylobacter infections.

Public health risks associated with Salmonella contamination of imported edible betel leaves: Analysis of results from England, 2011-2017.

Fresh betel leaves (Piper betle L.), imported into the UK are a traditional ready-to-eat food consumed by Asian populations. We report here the consolidation of routinely collected data to model the public health risks from consumption of this food. Amongst 2110 samples collected at Border Inspection, wholesale, catering or retail, Salmonella was detected in 488 (23%) of samples tested between 2011 and 2017 and was the most commonly Salmonella-contaminated ready-to-eat food examined by Public Health England during this period. Using data from multiple samples (usually 5) tested per consignment sampled at Border Inspection, contamination levels were calculated by most probable number: seasonal, temporal and country specific differences were detected. Quantitative contamination data was used to estimate the levels present at retail, and a ß-Poisson dose response model the probability of illness was calculated. Using data for products imported from India, the probability of acquiring infection following a single exposure (comprising of a single leaf) was estimated to be between 0.00003 (January-March) and 0.0001 (July-September). Using British Asian population data for individuals over 30 years of age in England in 2011, two estimates of consumption were modelled as 2.1 and 12.8 million servings per annum. Results from the model estimated 160 cases (range 102 to 242) and 960 cases (range 612 to 1456) per year in England for the two consumption estimates and equated to 34 (range 22 to 51) and 204 (range 130 to 310) salmonellosis cases per year reported to national surveillance. Salmonella from 475 of the contaminated samples were further characterised which showed a heterogeneous population structure with 46 S. enterica subsp. Enterica serovars, together with S. enterica subs diarizonae and salamae identified. Isolates from individual consignments were diverse and close genetic relationships between independent isolates were very rare except from within an individual consignment. There were no outbreaks detected as associated with betel leaf consumption. However analysis by whole genome sequencing of the 2014-17 data identified two cases where the clinical isolate had <5 single nucleotide polymorphism differences to isolates from betel leaves which is indicative of a likely epidemiological link and common source of contamination. Due to the diversity of the Salmonella contaminating this product, associations between salmonellosis cases and betel leaf consumption will appear sporadic and unlikely to be detected by current surveillance strategies based on outbreak detection.

Imported edible leaves collected at retail sale in England during 2017 with an emphasis on betel and curry leaves: microbiological quality with respect to Salmonella, Shiga-toxin-producing E. coli (STEC) and levels of Escherichia coli.

AIMS: To investigate the microbiological quality of imported fresh leaves on retail sale during 2017 with respect to Salmonella, Shiga-toxin-producing Escherichia coli (STEC) and levels of E. coli. METHODS AND RESULTS: Two hundred and seventy-nine samples of imported edible leaves (69 banana, 77 betel, 118 curry and 15 other types) were tested. Salmonella spp. were confirmed by whole-genome sequencing and isolated from 44 samples, 26% from curry leaves, 14% from betel and 2·4% from all other leaf types: 80% of all samples contained ≥102 , 44% ≥103 and 22% ≥104 CFU of E. coli CFU per g. All samples where Salmonella were detected also yielded ≥20 CFU of E. coli/g. 54 samples were tested for STEC which was detected in six samples and isolated from three: one was identified as STEC O157:H7. CONCLUSIONS: This report further highlights an ongoing problem of Salmonella contamination of imported fresh edible leaves. SIGNIFICANCE AND IMPACT OF THE STUDY: Among all food tested by Public Health England (approximately 11 000 per annum), curry leaves were the herb most commonly contaminated with Salmonella, and betel leaves were the most commonly contaminated ready-to-eat food. The high proportion with unsatisfactory E. coli levels and the detection of STEC suggests risks of contamination by multiple enteric pathogens.

Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes.

BACKGROUND: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. OBJECTIVES: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. METHODS: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. RESULTS: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. CONCLUSIONS: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children's health.

An assessment of the microbiological quality and safety of raw drinking milk on retail sale in England.

AIMS: This study aimed to review the microbiological results for raw drinking milk (RDM) samples submitted to Public Health England laboratories between 2014 and 2016 in order to produce up-to-date data on the microbiological safety of RDM and inform future risk assessments on its sale. METHODS AND RESULTS: A total of 902 samples of RDM were collected from retail sale in England for microbiological examination. Overall, 454 of 770 samples (59·0%) taken for routine monitoring were of a satisfactory quality, whilst eight (1·0%) were 'unsatisfactory and potentially injurious to health' due to the presence of Shiga toxin-producing Escherichia coli, Campylobacter or elevated levels of Listeria monocytogenes or coagulase-positive staphylococci. In contrast, 16 of 114 (14·0%) of samples taken in follow-up to a previous unsatisfactory result and 5 of 18 (27·8%) of samples related to illness were potentially injurious. A total of 229 of 902 samples (25·4%) gave unsatisfactory results due to elevated aerobic colony counts and/or coliforms, whilst 139 of 902 samples (15·4%) were of borderline quality due to coagulase-positive staphylococci. Listeria monocytogenes was detected at levels of <100 CFU per ml in 66 of 902 samples (7·3%) and other Listeria species in 44 of 902 samples (4·9%). CONCLUSIONS: Pathogens and/or indicators of poor hygiene were present in almost half of samples examined. Cows' milk samples gave a significantly greater proportion of unsatisfactory results compared to milk from other species (i.e. goat, sheep, buffalo, camel). SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate the importance of maintaining strict controls on the production and sale of this product.

Presence of benzophenones commonly used as UV filters and absorbers in paired maternal and fetal samples.

BACKGROUND: Previous studies have demonstrated widespread exposure of humans to certain benzophenones commonly used as UV filters or UV absorbers; some of which have been demonstrated to have endocrine disrupting abilities. OBJECTIVES: To examine whether benzophenones present in pregnant women pass through the placental barrier to amniotic fluid and further to the fetal blood circulation. METHODS: A prospective study of 200 pregnant women with simultaneously collected paired samples of amniotic fluid and maternal serum and urine. In addition, unique samples of human fetal blood (n=4) obtained during cordocentesis: and cord blood (n=23) obtained at delivery, both with paired maternal samples of serum and urine collected simultaneously, were used. All biological samples were analyzed by TurboFlow-liquid chromatography - tandem mass spectrometry for seven different benzophenones. RESULTS: Benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-methyl-benzophenone (4-MBP), and 4-hydroxy-benzophenone (4-HBP) were all detectable in amniotic fluid and cord blood samples and except 4-HBP also in fetal blood; albeit at a low frequency. BP-1 and BP-3 were measured at ~10-times lower concentrations in fetal and cord blood compared to maternal serum and 1000-times lower concentration compared to maternal urine levels. Therefore BP-1 and BP-3 were only detectable in the fetal circulation in cases of high maternal exposure indicating some protection by the placental barrier. 4-MBP seems to pass into fetal and cord blood more freely with a median 1:3 ratio between cord blood and maternal serum levels. Only for BP-3, which the women seemed to be most exposed to, did the measured concentrations in maternal urine and serum correlate to concentrations measured in amniotic fluid. Thus, for BP-3, but not for the other tested benzophenones, maternal urinary levels seem to be a valid proxy for fetal exposure. CONCLUSIONS: Detectable levels of several of the investigated benzophenones in human amniotic fluid as well as in fetal and cord blood calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of these compounds in order for better assessment of the risk to the developing fetus.

An assessment of the microbiological quality of lightly cooked food (including sous-vide) at the point of consumption in England.

This observational study aims to investigate the microbiological quality of commercially prepared lightly cooked foods with a major component of food of animal origin and collected as would be served to a consumer. A total of 356 samples were collected from catering (92%), retail (7%) or producers (1%) and all were independent of known incidents of foodborne illness. Using standard methods, all samples were tested for: the presence of Campylobacter spp. and Salmonella spp. and enumerated for levels of, Bacillus spp. including B. cereus, Clostridium perfringens, Listeria spp. including L. monocytogenes, Staphylococcus aureus, Escherichia coli, Enterobacteriacea and aerobic colony count (ACC). Results were interpreted as unsatisfactory, borderline or satisfactory according to the Health Protection Agency guidelines for assessing the microbiological safety of ready-to-eat foods placed on the market. Amongst all samples, 70% were classified as satisfactory, 18% were borderline and 12% were of unsatisfactory microbiological quality. Amongst the unsatisfactory samples, six (2%) were potentially injurious to health due to the presence of: Salmonella spp. (one duck breast); Campylobacter spp. (two duck breast and one chicken liver pâté); L. monocytogenes at 4·3 × 103 cfu (colony-forming units)/g (one duck confit with foie gras ballotin) and C. perfringens at 2·5 × 105 cfu/g (one chicken liver pâté). The remaining unsatisfactory samples were due to high levels of indicator E. coli, Enterobacteriaceae or ACC.