The Impact of Timing of Pertussis Vaccination During Pregnancy on Infant Antibody Levels at Birth: A Multi-Country Analysis.

Background: Pertussis vaccination during pregnancy is an effective strategy at reducing pertussis-related morbidity and mortality in infancy and is recommended across several countries. However, the optimal timepoint for vaccination in pregnancy to afford maximal protection to newborns is yet to be elucidated. This multi-country analysis aimed to model the impact of timing of vaccination during pregnancy on infant antibody titers at birth. Methods: A multi-country analysis on a cohort of mother-infant pairs (n=698) vaccinated between 19.6-37.1 weeks gestation was conducted. Data taken from four parent studies on pertussis vaccination during pregnancy were modelled using natural cubic splines and linear mixed models to study the association of both gestational age at vaccination and the interval between vaccination and delivery with pertussis-specific cord blood antibody levels after pertussis vaccination during pregnancy. Results: Term born infants on average achieve the highest antibody levels at birth if women are vaccinated before 31 weeks' gestation. When considering both term and preterm deliveries, an interval of at least 7.5 weeks between vaccination and delivery is required to achieve the highest cord blood antibody levels. The models show that vaccinating earlier than these timeframes will also provide the infant with equally high antibody levels at birth. Conclusions: Vaccinating in the second and early third trimester results in the highest antibody levels at birth. Vaccinating earlier within this window is needed to provide equal benefits to both term and preterm born infants.

Impact of Thyroid Function on Pregnancy and Neonatal Outcome in Women with and without PCOS.

Background: Women with polycystic ovary syndrome (PCOS) are more prone to autoimmune thyroiditis, and both disorders lead to subfertility and pregnancy-related complications. The aim of this study was to investigate whether mothers with and without PCOS and their offspring have comparable thyroid parameters at term and how thyroid parameters are associated with perinatal outcome in this population. Methods: This cross-sectional observational study was performed in a single academic tertiary hospital in Austria. Seventy-nine pregnant women with PCOS and 354 pregnant women without PCOS were included. Blood samples were taken from the mother and cord blood at birth. Primary outcome parameters were maternal and neonatal thyroid parameters at delivery. Secondary outcome parameters were the composite complication rate per woman and per neonate. Results: Thyroid dysfunction was more prevalent among PCOS women (p < 0.001). At time of birth, free triiodothyronine (fT3) levels were significantly lower in PCOS than in non-PCOS women (p = 0.005). PCOS women and their neonates had significantly higher thyreoperoxidase antibody (TPO-AB) levels (p = 0.001). Women with elevated TPO-AB had a significantly higher prevalence of hypothyroidism (p < 0.001). There was a significant positive correlation between maternal and neonatal free thyroxine, fT3 and TPO-AB levels. There were no significant differences in thyroid parameters between women or neonates with or without complications. Conclusions: Our results demonstrate a higher prevalence of thyroid dysfunction and autoimmunity in PCOS women, supporting a common etiology of both disorders. We were not able to show an association between complication rate and thyroid parameters.

Seroprevalence of IgG antibodies against SARS-CoV-2 - a serial prospective cross-sectional nationwide study of residual samples, Belgium, March to October 2020.

BackgroundTo control epidemic waves, it is important to know the susceptibility to SARS-CoV-2 and its evolution over time in relation to the control measures taken.AimTo assess the evolving SARS-CoV-2 seroprevalence and seroincidence related to the first national lockdown in Belgium, we performed a nationwide seroprevalence study, stratified by age, sex and region using 3,000-4,000 residual samples during seven periods between 30 March and 17 October 2020.MethodsWe analysed residual sera from ambulatory patients for IgG antibodies against the SARS-CoV-2 S1 protein with a semiquantitative commercial ELISA. Weighted seroprevalence (overall and by age category and sex) and seroincidence during seven consecutive periods were estimated for the Belgian population while accommodating test-specific sensitivity and specificity.ResultsThe weighted overall seroprevalence initially increased from 1.8% (95% credible interval (CrI): 1.0-2.6) to 5.3% (95% CrI: 4.2-6.4), implying a seroincidence of 3.4% (95% CrI: 2.4-4.6) between the first and second collection period over a period of 3 weeks during lockdown (start lockdown mid-March 2020). Thereafter, seroprevalence stabilised, however, significant decreases were observed when comparing the third with the fifth, sixth and seventh period, resulting in negative seroincidence estimates after lockdown was lifted. We estimated for the last collection period mid-October 2020 a weighted overall seroprevalence of 4.2% (95% CrI: 3.1-5.2).ConclusionDuring lockdown, an initially small but increasing fraction of the Belgian population showed serologically detectable signs of exposure to SARS-CoV-2, which did not further increase when confinement measures eased and full lockdown was lifted.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

Prevalence of anemia in pregnant women in Styria, Austria-A retrospective analysis of mother-child examinations 2006-2014.

BACKGROUND: Many women suffer from anemia during their pregnancy. Austria, a central European country, has an instituted mandatory prenatal care system and therein two anemia screening tests (before end of week 16 and in weeks 25-28) are scheduled. Epidemiological data on the prevalence of anemia in pregnant women in Austria are missing. METHODS: We analysed data from Styria, an Austrian federal state, to determine the prevalence of anemia diagnosed in pregnant women aged 15-45 years with at least one examination in the first and second time period using the cut-off hemoglobin (Hb) concentration of 11 g/dl as recommended by the World Health Organisation (WHO). Sensitivity analyses for cut-off values with 10.5 and 7 g/dl (severe anemia) were performed. The STROBE checklist was applied for this retrospective cohort study. RESULTS: The study included anemia screening tests from 25,922 women during 31,429 pregnancies from 2006-2014. Anemia was diagnosed in either time period in 13.7% (95% confidence interval (CI) 13.4-14.1) of pregnancies, in the first time period in 2.2% (95% CI 2.0-2.2), and in the second time period in 13.0% (95% CI 12.6-13.4). The annual age-adjusted anemia prevalence showed no change over time. Reducing the cut-off value to 10.5 g/dl resulted in an anemia prevalence in either time period of 5.6% (95% CI 5.3-5.8). The pattern of a higher prevalence in the second time period remained unchanged. Severe anemia (Hb <7 g/dl) was diagnosed in four pregnancies (0.01%). CONCLUSION: The estimated anemia prevalence of around 14% in pregnant women in Styria (Austria) is stable over the observed time window (2006-2014) and almost all are diagnosed in the second test period (in weeks 25-28). It seems that in a developed country like Austria the first examination (before week 16) is not mandatory for pregnancy care. However, in other countries where a high prevalence of anemia is common due to risk factors such as malaria and HIV, early screening in pregnancy might be very important.

Prevalence and incidence of toxoplasmosis: a retrospective analysis of mother-child examinations, Styria, Austria, 1995 to 2012.

In Austria, mandatory screening for the prevention of congenital toxoplasmosis stipulates a serological test for antibodies against Toxoplasma gondii as early as possible in pregnancy. In the case of a seronegative result, subsequent tests at intervals of 8 weeks are requested. We analysed serological data from Styria, an Austrian federal state, to determine the seroprevalence and incidence of Toxoplasma infections. The study included 353,599 tests from 103,316 women during 158,571 pregnancies from 1995 to 2012. The age-adjusted seroprevalence decreased from 43.3% in 1995 to 31.5% in 2012, with a yearly decline of 0.84% (95% confidence interval (CI): 0. 79 -0.88). The intergravid incidence showed an annual decrease of 4.2%. The average yearly incidence of intragravid and intergravid seroconversions was 0.52% (95% CI 0.45-0.61) and 0.72% (95% CI 0.67-0.77), respectively. If the difference between these rates (p < 0.001) can be explained by the effect of primary prevention such as avoiding raw meat and taking hygiene precautions when encountering cats or preparing vegetables, only ca two of seven (28%) infections were avoided by hygiene measures taken by pregnant women. Primary prevention may therefore have its limits.

Estimating Retinal Blood Flow Velocities by Optical Coherence Tomography.

IMPORTANCE: While optical coherence tomography (OCT) angiography has been considered to evaluate retinal capillary blood flow instead of fluorescein angiography, the reflectance pattern of blood vessels on structural OCT might also provide retinal capillary flow data in the absence of fluorescein angiography. This potential has been insufficiently explored, despite promising data concerning a possible relationship between the reflectance pattern of blood vessels and their perfusion velocity in a laboratory setting. OBJECTIVE: To evaluate the potential of retinal blood flow velocity estimation by structural OCT. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional observational study conducted from June to November 2015 at a tertiary clinical referral center. Sixty arteries (the superior and inferior temporal arteries) from 30 eyes of 30 patients (17 female, 13 male) were included in the study. MAIN OUTCOMES AND MEASURES: Based on the intraluminal contrast patterns of retinal arteries on OCT, 3 independent graders categorized the blood flow velocities as low, medium, or high. These results and the results from a software-based intraluminal contrast analysis were compared with the retinal blood flow velocities measured by video fluorescein angiography. RESULTS: Among the 30 eyes of 30 patients (mean [SD] age, 72.6 [12.3] years; 17 female, 13 male), 15 were controls without retinal occlusion, 6 had a branch retinal artery occlusion, and 9 had a central retinal artery occlusion. When discriminating between low flow velocities and medium or high flow velocities, the graders' sensitivity ranged from 88.2% to 100% (grader 1: 88.2%; 95% CI, 63.6%-98.5%; grader 2: 88.2%; 95% CI, 63.6%-98.5%; and grader 3: 100%; 95% CI, 69.8%-100%) and their specificity ranged from 97.6% to 100% (grader 1: 100%; 95% CI, 87.7%-100%; grader 2: 97.6%; 95% CI, 87.4%-99.9%; and grader 3: 100%; 95% CI, 87.7%-100%). The κ coefficients of the comparison between the 3 graders and the angiography were 0.77 (95% CI, 0.60-0.93; P < .001), 0.64 (95% CI, 0.44-0.83; P < .001), and 0.87 (95% CI, 0.74-0.99; P < .001). In the computer-based assessment, the contrast reduction of the intraluminal pattern could be numerically expressed in a specific coefficient in the model (I2, describing the angular change of the backscattering intensity in the model), which presented nonoverlapping intervals between low flow velocities and medium or high flow velocities (mean [SD] I2, 0.3 [5.3], 20.4 [6.4], and 21.7 [4.0], respectively). CONCLUSIONS AND RELEVANCE: This study suggests that a low retinal blood flow velocity reflects in a visually distinct contrast reduction of the intraluminal pattern of retinal vessels on OCT. Larger studies are required to assess the clinical benefits.

Circadian macular volume changes in the healthy human choroid.

PURPOSE: To investigate a potential circadian fluctuation of the choroidal volume in healthy adults by enhanced depth imaging (EDI) via spectral-domain optical coherence tomography (SD OCT). DESIGN: Prospective observational case series. METHODS: Thirty healthy eyes of 15 healthy subjects with a median age of 26 years (range 22-55) underwent EDI SD OCT scans for macular choroidal volume measurement every 3 hours within a 24-hour period at a single tertiary center. The mean ocular perfusion pressure was calculated for each eye at each of the 8 time points as 2/3(mean arterial pressure-intraocular pressure [IOP]). The circadian fluctuation of the macular choroidal volume as well as the association with axial length, mean ocular perfusion pressure, or IOP was assessed using a linear mixed model. RESULTS: Macular choroidal volume showed a significant circadian fluctuation (P < .05) and was lowest at midday (mean ± SD, 10.14 ± 2.62 mm(3)) and highest at 3 AM (mean ± SD, 10.66 ± 2.70 mm(3)). Of all factors tested, only mean ocular perfusion pressure showed a significant association with macular choroidal volume fluctuation (P = .016). CONCLUSIONS: Macular choroidal volume shows a significant circadian pattern with higher values at night and lower values during the day in young adults. Besides time, mean ocular perfusion pressure is significantly associated with this fluctuation.

Reinfection by untreated partners of people treated for Chlamydia trachomatis and Neisseria gonorrhoeae: mathematical modelling study.

OBJECTIVES: Reinfection after treatment for Chlamydia trachomatis or Neisseria gonorrhoeae reduces the effect of control interventions. We explored the impact of delays in treatment of current partners on the expected probability of reinfection of index cases using a mathematical model. METHODS: We used previously reported parameter distributions to calculate the probability that index cases would be reinfected by their untreated partners. We then assumed different delays between index case and partner treatment to calculate the probabilities of reinfection. RESULTS: In the absence of partner treatment, the medians of the expected reinfection probabilities are 19.4% (IQR 9.2-31.6%) for C trachomatis and 12.5% (IQR 5.6-22.2%) for N gonorrhoeae. If all current partners receive treatment 3 days after the index case, the expected reinfection probabilities are 4.2% (IQR 2.1-6.9%) for C trachomatis and 5.5% (IQR 2.6-9.5%) for N gonorrhoeae. CONCLUSIONS: Quicker partner referral and treatment can substantially reduce reinfection rates for C trachomatis and N gonorrhoeae by untreated partners. The formula we used to calculate reinfection rates can be used to inform the design of randomised controlled trials of novel partner notification technologies like accelerated partner therapy.

Insights into the timing of repeated testing after treatment for Chlamydia trachomatis: data and modelling study.

OBJECTIVES: The objective of this study was to determine the optimal time interval for a repeated Chlamydia trachomatis (chlamydia) test. METHODS: The authors used claims data for US women aged 15-25 years who were enrolled in commercial health insurance plans in the MarketScan database between 2002 and 2006. The authors determined the numbers of initial positive and negative tests that were followed by a repeated test and the positivity of repeated tests. The authors used a dynamic transmission pair model that reflects the partnership formation and separation processes in 15-25 year olds to determine the time course of repeated infections in women under different levels of notifying the current partner. The authors then explored the additional impact of repeated testing uptake on reducing chlamydia prevalence. RESULTS: 40% (4949/12 413) of positive tests were followed by a repeated test compared with 22% (89 119/402 659) of negative tests at any time. Positivity of repeated tests followed by an initial positive test was high: 15% (736) after a positive test versus 3% (2886) after a negative test. The transmission model showed a peak in repeated infections between 2 and 5 months after treatment. For a chlamydia testing uptake of 10% per year, the additional impact of repeated testing on reducing chlamydia population prevalence was modest. CONCLUSIONS: The mathematical model predictions support the recommended interval for repeat chlamydia testing. This study provides information that can be used to design randomised controlled trials to determine more effective interventions to prevent chlamydial reinfection.