Spatial and cumulative organochlorine and mercury exposure assessments in Steller Sea lions of Alaska: Emphasizing pups.

Steller sea lions (SSL) are sentinels for monitoring environmental contaminants in remote areas of the Aleutian Islands, Alaska. Therefore, concentrations of several organochlorines (OCs) were measured in blood from 123 SSL pups sampled from 3 regions; the western Aleutian Islands (WAI), central Aleutian Islands (CAI), and the central Gulf of Alaska. Blood, blubber, and milk from 12 adult female SSL from WAI, CAI and southeast Alaska also were analyzed. Findings included the following. SSL pups had higher concentrations of some OCs and mercury (Hg) on rookeries in the WAI than those more easterly. Pups had significantly higher blood concentrations of many OC classes than adult females sampled within the same region; some pups had PCB concentrations exceeding thresholds of concern (∑PCBs >8600 ng/g lw). ∑PCB concentration in pup whole blood was positively correlated with the trophic marker, δ15N within the regions sampled, along with two PCB congeners (PCB138 and PCB153). This suggests that the dams of pups with higher ∑PCBs, PCB138, and PCB153 concentrations were feeding on more predatory prey. Adult female blubber ∑DDT and hexachlorocyclohexane concentrations were also positively correlated with δ15N values. Several pups (mostly from WAI) had blood Hg concentrations and/or blood PCB concentrations (surrogate for overall OC exposures) of concern. The finding that WAI SSL pups have been exposed to multiple contaminants calls for future investigation of their cumulative exposure to a mixture of contaminants especially their transplacental and then transmammary exposure routes.

Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy.

BACKGROUND: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. OBJECTIVE: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. STUDY DESIGN: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks' gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. RESULTS: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. CONCLUSION: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. CLINICALTRIALS: gov (NCT02626299).

Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.

BACKGROUND: Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE: To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN: This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS: Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION: The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.

Key predictors and burden of meticillin-resistant Staphylococcus aureus infection in comparison with meticillin-susceptible S. aureus infection in an Australian hospital setting.

BACKGROUND: Staphylococcus aureus is associated with significant mortality and increased burden on the healthcare system. Relatively few reliable estimates are available regarding the impact of meticillin-resistant S. aureus (MRSA) infection compared with meticillin-susceptible S. aureus (MSSA) infection. AIMS: To compare patients with MRSA infection and MSSA infection to identify differences in inpatient mortality, length of stay and costs of hospital services, and identify predictors of MRSA as a cause of S. aureus infection. METHODS: An analytical, retrospective, longitudinal study using non-identifiable linked data on adults admitted to hospitals of a health district in Australia with a diagnosis of S. aureus infection over a 10-year period. The main outcome measure was 30-day inpatient mortality. Secondary endpoints included total overnight stays, all-cause inpatient mortality, and hospitalization costs within 1 year of index admission. FINDINGS: Inpatient mortality at 30, 100 and 365 days was estimated to be significantly greater for patients with MRSA infection. The mean additional cost of MRSA infection when controlling for additional factors was $5988 and 4 nights of additional hospital stay per patient within 1 year of index admission. Key predictors of MRSA infection were: date of index admission; higher comorbidity score; greater socio-economic disadvantage; admission to hospital other than via the emergency department; older age; and prior admission to hospital within 28 days of index admission. CONCLUSIONS: MRSA infection is associated with increased inpatient mortality, costs and hospital length of stay compared with MSSA infection. Efforts are required to alleviate the additional burden of MRSA infection on patients and healthcare systems.

Piloting a novel cancer care pathway: socioeconomic background as a barrier to access.

BACKGROUND: The multidisciplinary diagnostic clinic (MDC) model for 'non-specific' symptoms has been piloted in the UK. We aimed to assess the degree to which the MDC pathway was influenced by socioeconomic factors. METHODS: We collected data for all patients referred to the MDC from 01 January 2017 - 28 March 2019. Indices of multiple deprivation (IMD) scores were matched to patients' postcodes and referring general practitioner (GP) location. Socioeconomic data for MDC patients was compared with all other cancer patients diagnosed in the MDC's base hospital, Airedale General Hospital (AGH), in 2018. Statistical significance was tested using the Mann-Whitney U test and Spearman's rank correlation. RESULTS: No significant difference was found between MDC pathway and the rest of AGH when comparing social deprivation of patients.There was a moderate negative correlation between the IMD associated with the location of GP premises and the number of referrals; practices in more deprived locations referred fewer patients (p≤0.025). CONCLUSION: The MDC pathway referral rate seems to be affected by social deprivation in a similar manner to other cancer diagnosis pathways. Our work highlights the importance of engaging GP practices with socially deprived populations as the MDC programme is rolled out across the UK.

Validation of an abbreviated food frequency questionnaire for estimating DHA intake of pregnant women in the United States.

Docosahexaenoic acid (DHA) intake was estimated in pregnant women between 12- and 20-weeks' gestation using the National Cancer Institute's (NCI) Diet History Questionnaire-II (DHQ-II) and a 7-question screener designed to capture DHA intake (DHA Food Frequency Questionnaire, DHA-FFQ). Results from both methods were compared to red blood cell phospholipid DHA (RBC-DHA) weight percent of total fatty acids. DHA intake from the DHA-FFQ was more highly correlated with RBC-DHA (rs=0.528) than the DHQ-II (rs=0.352). Moreover, the DHA-FFQ allowed us to obtain reliable intake data from 1355 of 1400 participants. The DHQ-II provided reliable intake for only 847 of 1400, because many participants only partially completed it and it was not validated for Hispanic participants. Maternal age, parity, and socioeconomic status (SES) were also significant predictors of RBC-DHA. When included with estimated intake from the DHA-FFQ, the model accounted for 36% of the variation in RBC-DHA.

Utility of a 7- question online screener for DHA intake.

The secondary analyses of two large, recently completed randomized clinical trials of DHA supplementation in pregnancy found that women with a low baseline DHA status benefited from randomization to a higher dose (800 vs 0 and 1000 vs 200 mg/day DHA). To obtain DHA status, it is necessary to obtain a blood sample and conduct an analysis using gas chromatography (GC) or GC-mass spectrometry (GCMS), both barriers to clinics where pregnant women receive advice on nutrition. Participants consuming less than 150 mg/day of DHA at baseline in our recent trial had a lower risk of early preterm birth and preterm birth when assigned to 1000 vs 200 m/day DHA. DHA intake was determined using a 7-question food frequency questionnaire administered by a trained nutritionist. Because the need for trained personnel to administer the questionnaire would be a barrier to implementing this finding in clinical management of pregnancy, the goal of this study was to determine if an online version of the questionnaire could be validly completed without assistance.

Requests from primary care for chest X-ray and CA125 measurements during the COVID-19 emergency: An observational study.

During the first 3 months of 2020, as the COVID-19 pandemic developed, it was noticed that requests from primary care for investigations were decreasing, including those that form part of the diagnostic process for cancers. We therefore obtained data on the requests from primary care for chest X-rays (CXRs) and CA125 measurement our hospital received in the first half of 2020 and compared them with 2019. The number of CXRs declined by 93% in April 2020 compared with 2019, with the decline being greater for patient living in outlying areas. Requests from the emergency department also declined. Requests for CA125 measurement similarly fell by 77% from all areas. The requests increased in June, CA125 more than CXR. If this phenomenon is widespread it may have an impact on diagnosis of major conditions, particularly cancers and tuberculosis.

Age at menarche and risk of vasomotor menopausal symptoms: a pooled analysis of six studies.

OBJECTIVE: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association. DESIGN: A pooled analysis of six cohort studies. SETTING: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE). POPULATION: 18 555 women from the UK, USA and Australia. METHODS: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects. MAIN OUTCOME MEASURES: Hot flushes and night sweats. RESULTS: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS. CONCLUSIONS: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk. TWEETABLE ABSTRACT: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche.

Geographical access to GPs and modes of cancer diagnosis in England: a cross-sectional study.

BACKGROUND: Poor geographical access to health services and routes to a cancer diagnosis such as emergency presentations have previously been associated with worse cancer outcomes. However, the extent to which access to GPs determines the route that patients take to obtain a cancer diagnosis is unknown. METHODS: We used a linked dataset of cancer registry and hospital records of patients with a cancer diagnosis between 2006 and 2010 across eight different cancer sites. Primary outcomes were defined as 'desirable routes to diagnosis' [screen-detected and 2-week wait (TWW) referrals] and 'less desirable routes' [emergency presentations and death certificate only (DCO)]. All other routes (GP referral, inpatient elective and other outpatient) were specified as the reference category. Geographical access was measured as travel time in minutes from patients to their GP, and multinomial logistic regression was used to estimate relative risk ratios (RRR). RESULTS: Longer travel was associated with increased risk of diagnosis via emergency and DCO, but decreased risk of diagnosis via screening and TWW. Patients travelling over 30 minutes had the highest risk of a DCO diagnosis, which was statistically significant for breast, colorectal, lung, prostate, stomach and ovarian cancers (compared with patients with travel times ≤10 minutes: RRR 5.89, 7.02, 2.30, 4.75, 10.41; P < 0.01 and 3.51, P < 0.05). DISCUSSION: Poor access to GPs may discourage early engagement with health services, decreasing the likelihood of screening uptake and increasing the likelihood of emergency presentations. Extra effort is needed to promote early diagnosis in more distant patients.

The association between vascular complications during pregnancy in women with Type 1 diabetes and congenital malformations.

AIMS: To assess the association between vascular complications of diabetes and the risk of congenital malformations in pregnant women with Type 1 diabetes. METHODS: We conducted an observational retrospective cohort study in women with Type 1 diabetes who received care consecutively from three tertiary care diabetes-in-pregnancy clinics in Calgary, Alberta, Canada. Multivariable logistic regression was used to assess the association between vascular complications (retinopathy, nephropathy and pre-existing hypertension) and congenital malformations in offspring of women with Type 1 diabetes. RESULTS: Of 232 women with Type 1 diabetes, 49 (21%) had at least one vascular complication and there were 52 babies with congenital malformations. Maternal age (31.8 ± 5.0 vs. 29.4 ± 4.7 years, P < 0.01), diabetes duration (20.9 ± 6.7 vs. 11.2 ± 7.4 years, P < 0.01) and pre-eclampsia rate (12.5% vs. 1.3%, P < 0.01) were higher in mothers with vascular complications than in those without. Multivariable analyses showed that vascular complications were not associated with an increased risk of congenital malformations (odds ratio 1.16, 95% confidence interval 0.46 to 2.88). CONCLUSIONS: Vascular complications are common, occurring in one-fifth of pregnant women with Type 1 diabetes, and in this study do not appear to be associated with an increased risk of congenital malformations in children.