A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

PURPOSE: To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016. METHODS: A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency. RESULTS: We identified 357 infants with GPB-BSI, representing an incidence of 1.47/1000 live births (LB). Group B streptococcus (GBS) was the most common pathogen causing BSI in full-term infants and early-onset sepsis (EOS) (0.20/1000 LB), while coagulase-negative staphylococci (CoNS) were predominant in infants born very preterm and in late-onset sepsis (LOS) (0.79/1000 LB). There were no fatal GBS BSI cases, but 10.2% developed meningitis. The GPB case fatality rate was 9.5% and the sepsis fatality rate 2.8%. In GPB-BSI, 1/10 did not have an elevated C-reactive protein level. Staphylococcus aureus (S. aureus) BSI increased during the study period, but no methicillin or vancomycin resistant strains were found. The antimicrobial resistance (AMR) rate was highest in CoNS isolates. CONCLUSION: GPB-BSI was four times more common than Gram-negative BSI in neonates but resulted in lower mortality rate. GBS was the most common pathogen in full-term infants and in EOS. CoNS was the most common pathogen in LOS and infants born very preterm, and the AMR rate was high in these isolates. The increasing trend of S. aureus BSI indicates a need of further investigation.

Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial.

Background: Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death. We aimed to investigate whether supplementation with human milk-based fortifier (HMBF), as compared to bovine milk-based fortifier (BMBF), reduced the incidence of the composite outcome of necrotising enterocolitis (NEC), sepsis, and mortality in extremely preterm infants exclusively fed human milk. Methods: In this multicentre, randomised controlled trial at 24 neonatal units in Sweden, extremely preterm infants born between gestational week 22 + 0 and 27 + 6 fed exclusively human breast milk (mother's own and/or donor milk), were randomly assigned (1:1) to receive targeted fortification with either HMBF or BMBF. Randomisation was conducted before the enteral feeds reached 100 mL/kg/day, and was stratified by enrolment site, gestational age, singleton/twin, and sex. The allocation was concealed before inclusion, but after randomisation the study was not blinded for the clinical staff. For the NEC diagnosis, the study group was masked to an independent radiologist, and the final assessment of NEC and culture-proven sepsis was done by a blinded consensus panel review. The primary outcome was the composite of NEC stage II-III, culture-proven sepsis, and mortality from inclusion to discharge, no longer than postmenstrual week 44 + 0, in the intention-to-treat population (ClinicalTrials.gov, NCT03797157). Findings: Between February 21st, 2019, and May 21st, 2021, 229 neonates were randomly assigned (115 HMBF, 114 BMBF). After exclusion of one infant due to parents' withdrawal of consent, 228 infants were included in the intention-to-treat analysis. Of the 115 infants assigned to HMBF, 41 (35.7%) fulfilled the criteria of either NEC, sepsis, or death, compared with 39 (34.5%) of 113 infants assigned to BMBF (OR 1.05, 95% CI 0.61-1.81, p = 0.86). Adverse events did not differ significantly between groups. Interpretation: Supplementation with HMBF, as compared with BMBF, did not reduce the incidence of the composite outcome of NEC, sepsis, or death. Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk. Funding: ALF grant, Prolacta Bioscience, Swedish Research Council, and Research Council for Southeast Sweden.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy.

Importance: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. Objective: To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Design, Setting, and Participants: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Exposure: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Main Outcomes and Measures: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Results: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. Conclusions and Relevance: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

Growth, weight gain and BMI in virally suppressed children on antiretroviral therapy with specific reference to dolutegravir.

BACKGROUND: Pediatric HIV infection cause retardation in height and weight. However, effective antiretroviral therapy (ART) result in desirable weight gain. Concerns have emerged regarding excessive weight gain related to the integrase inhibitor dolutegravir in adults but knowledge about the circumstances in children/adolescents is limited. We studied if dolutegravir containing ART or switch to dolutegravir affected body mass index (BMI) and described height development in the Stockholm pediatric/adolescent HIV cohort. METHODS: A retrospective cohort study of height, weight and BMI in relation to ART in 94 children/adolescents living with HIV. RESULTS: At last documented visit 60/94 children/adolescents were on dolutegravir, 50 had switched from a protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Height standard deviation score (SDS) increased between first and last visit from mean height SDS -0.88 (16 had SDS < -2 and 6 SDS < -3) to -0.32 (four had SDS < -2). Mean BMI SDS increased from -0.15 to 0.62 in girls, but not (-0.20 to 0.09) in boys. The number of girls ≥ 12 years with BMI SDS ≥ 2 increased significantly from 0/38 to 8/38 and totally 9/50 (18%) girls and 4/44 (9%) boys had BMI SDS ≥ 2 at last visit. There was no difference in height or weight gain between different ART regimens. BMI SDS remained stable in 22/50 children switching to dolutegravir, decreased in 13 and increased in 15. CONCLUSION: Adolescent girls gained weight to a greater extent than expected but independently of ART. We found no association between dolutegravir alone or combined with tenofovir alafenamide fumarate (TAF) and excessive weight gain. Height development was within normal range.

Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, Setting, and Participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main Outcomes and Measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and Relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

Human visceral and subcutaneous adipose stem and progenitor cells retain depot-specific adipogenic properties during obesity.

Abdominal obesity associates with cardiometabolic disease and an accumulation of lipids in the visceral adipose depot, whereas lipid accumulation in the subcutaneous depot is more benign. We aimed to further investigate whether the adipogenic properties where cell-intrinsic, or dependent on a depot-specific or obesity-produced microenvironment. We obtained visceral and subcutaneous biopsies from non-obese women (n = 14) or women living with morbid obesity (n = 14) and isolated adipose stem and progenitor cells (ASPCs) from the stromal vascular fraction of non-obese (n = 13) and obese (n = 13). Following in vitro differentiation into mature adipocytes, we observed a contrasting pattern with a lower gene expression of adipogenic markers and a higher gene expression of immunogenic markers in the visceral compared to the subcutaneous adipocytes. We identified the immunogenic factor BST2 as a marker for visceral ASPCs. The effect of obesity and insulin resistance on adipogenic and immunogenic markers in the in vitro differentiated cells was minor. In contrast, differentiation with exogenous Tumor necrosis factor resulted in increased immunogenic signatures, including increased expression of BST2, and decreased adipogenic signatures in cells from both depots. Our data, from 26 women, underscore the intrinsic differences between human visceral and subcutaneous adipose stem and progenitor cells, suggest that dysregulation of adipocytes in obesity mainly occurs at a post-progenitor stage, and highlight an inflammatory microenvironment as a major constraint of human adipogenesis.

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit.

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU.

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand.

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.

Gastric Aspiration Improves Postprandial Glucose Tolerance Without Causing a Compensatory Increase in Appetite and Food Intake.

INTRODUCTION: AspireAssist® allows aspiration of ~30% of an ingested meal through a percutaneous gastrostomy tube, reducing caloric uptake. We evaluated the acute effects of gastric aspiration on postprandial glucose tolerance, responses of gluco-regulatory and appetite-regulating hormones, appetite sensations, and food intake. METHODS: Seven AspireAssist®-treated individuals underwent two separate experimental days each involving a mixed meal test (MMT) with double-blinded aspiration and sham aspiration, respectively. Seven age and body mass index (BMI)-matched controls underwent one MMT. MMTs were followed by an ad libitum meal. RESULTS: Postprandial glucose tolerance was improved during aspiration vs. sham visits (median [interquartile range] baseline-subtracted area under the curve (bsAUC) 170 [88.4;356] vs. 388 [239;456] mmol/L × min, p = 0.025). Reduced responses (bsAUCs) of C-peptide (113 [28.4;224] vs. 302 [215;433] nmol/L × min, p = 0.014), cholecystokinin (223 [59.4;402] vs. 467 [416;546] pmol/L × min, p = 0.005), glucose-dependent insulinotropic polypeptide (4.63 [1.49;9.04] vs. 15.4 [9.59;18.9] nmol/L × min, p = 0.025), and glucagon-like peptide 1 (532.8 [274.5;1,278] vs. 1,296 [746.2;1,618] pmol/L × min, p = 0.032) were observed during aspiration vs. sham visits. Responses of glucagon, gastrin, ghrelin and peptide YY, appetite sensations, and ad libitum food intake were unaffected by aspiration. Responses of plasma glucose, gut hormones, appetite sensations, and food intake were similar during sham and control visits. CONCLUSION: Gastric aspiration improved postprandial glucose tolerance without causing compensatory increases in appetite or food intake, pointing to acute beneficial metabolic effects of aspiration therapy together with previously reported body weight-lowering effects.

Talking to children about their HIV diagnosis: a discussion rooted in different global perspectives.

An online meeting was arranged with four professionals representing four countries to debate current practices and future steps in naming HIV to children (disclosing HIV status). This article considers the evidence and reports on the commentary and debate from the meeting. Naming HIV to children remains a challenge. Although studies identify some of the facilitators and barriers to informing children of their HIV diagnosis, further review of practice is required. This article presents a global perspective of naming practices from different settings. The article comprises commentary and a report of the online debate, along with supporting evidence. The four participating authors concluded that health professionals must work in collaboration with families to support early naming of HIV to children or having an open discussion about HIV in clinics. Naming when a child is younger reduces self-stigma and empowers children and young people to adhere to their medication, make informed decisions and share their own diagnosis appropriately. The authors concluded that health professionals play a key role in educating colleagues and the public to reduce stigma and discrimination. Professionals working with children and families living with HIV require support and resources to instil confidence in naming and facilitate naming of HIV status to a child.

Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

BACKGROUND: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered. RESULTS: Among 884 abstracts identified, 90 randomised controlled trials (RCTs) were included in this review. Only 30 manuscripts explicitly stated the primary and/or secondary outcomes. A total of 88 distinct outcomes were recorded across all 90 studies included. These were then assigned to seven different domains in line with the taxonomy for classification proposed by the COMET initiative. The most frequently reported outcome was survival with 74% (n = 67) of the studies reporting an outcome within this domain. CONCLUSIONS: This systematic review constitutes one of the initial phases in the protocol for developing a COS in neonatal sepsis. The paucity of standardised outcome reporting in neonatal sepsis hinders comparison and synthesis of data. The final phase will involve a Delphi Survey to generate a COS in neonatal sepsis by consensus recommendation. IMPACT: This systematic review identified a wide variation of outcomes reported among published RCTs on the management of neonatal sepsis. The paucity of standardised outcome reporting hinders comparison and synthesis of data and future meta-analyses with conclusive recommendations on the management of neonatal sepsis are unlikely. The final phase will involve a Delphi Survey to determine a COS by consensus recommendation with input from all relevant stakeholders.

Children living with HIV in Europe: do migrants have worse treatment outcomes?

OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. RESULTS: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96-2.38, p = 0.072). CONCLUSIONS: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring.

Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial.

INTRODUCTION: The mortality rate of extremely low gestational age (ELGA) (born

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

A decade of neonatal sepsis caused by gram-negative bacilli-a retrospective matched cohort study.

This study is to determine the incidence and outcome of neonatal gram-negative bacilli (GNB) sepsis in Stockholm, Sweden, and describe bacterial characteristics. This is a retrospective cohort study. All infants with GNB-sepsis between 2006 and 2016 were included and matched with two control groups, with suspected sepsis and uninfected neonates, respectively. Outcome was death before discharge, risk of death within 5 days after sepsis onset, and morbidity. The resistance pattern from all GNB was collected, and all available isolates were subjected to genome typing. All neonates with GNB-sepsis (n = 107) were included, and the cumulative GNB-sepsis incidence was 0.35/1000 live born. The in-hospital mortality was 30/107 (28%). GNB late-onset sepsis (LOS) was associated with an increase in mortality before discharge compared to uninfected controls (OR = 3.9; CI 1.6-9.4) but not versus suspected sepsis. The suspected LOS cases did not statistically differ significantly from uninfected controls. The case fatality rate (CFR) at 5 days was 5/33 (15%) in GNB early-onset sepsis (EOS) and 25/74 (34%) in GNB-LOS. The adjusted hazard for 5 days CFR was higher in GNB-LOS versus uninfected controls (HR = 3.7; CI 1.2-11.2), but no significant difference was seen in GNB-LOS versus suspected sepsis or in suspected sepsis versus controls. ESBL production was seen in 7/107 (6.5%) of the GNB isolates. GNB-LOS was associated with a higher 5 days CFR and in-hospital mortality compared to uninfected controls but not versus suspect sepsis. The incidence of both GNB-EOS and GNB-LOS was lower than previously reported from comparable high-income settings. The occurrence of antibiotic resistance was low.

Contagiousness in treated HIV-1 infection.

BACKGROUND: Effective antiretroviral treatment of HIV-1, defined as continuously undetectable virus in blood, has substantial effects on the infectiousness and spread of HIV. AIM: This paper outlines the assessment of the Swedish Reference Group for Antiviral Therapy (RAV) and Public Health Agency of Sweden regarding contagiousness of HIV-infected persons on antiretroviral therapy (ART). Results and Conclusion: The expert group concludes that there is no risk of transmission of HIV during vaginal or anal intercourse if the HIV-infected person fulfils the criteria for effective ART. Summary: The effective antiretroviral therapy (ART) for HIV-1 infection has dramatically reduced the morbidity and mortality among people who live with HIV. ART also has a noticeable effect on the infectiousness and on the spread of the disease in society. Knowledge about this has grown gradually. For ART to be regarded effective, the level of the HIV RNA in the plasma should be repeatedly and continuously undetectable and the patient should be assessed as continually having high adherence to treatment. Based on available knowledge the Swedish Reference Group for Antiviral Therapy (RAV) and the Public Health Agency of Sweden make the following assessment: There is no risk of HIV transmission during vaginal or anal intercourse if the HIV positive person fulfils the criteria for effective treatment. This includes intercourse where a condom is not used. However, there are a number of other reasons for recommending the use of condoms, primarily to protect against the transmission of other STIs (sexually transmitted infections) and hepatitis, as well as unwanted pregnancy. The occurrence of other STIs does not affect the risk of HIV transmission in persons on effective ART. It is plausible that the risk for transmission of HIV infection between people who inject drugs and share injection equipment is reduced if the individual with HIV is on effective ART, but there are no studies that directly show this. The risk of transmission from mother to child during pregnancy, labour and delivery is very low if the mother's treatment is initiated well before delivery and if the treatment aim of undetectable virus levels is attained. This is dependent on healthcare services being aware of the mother's HIV infection at an early stage. In most contacts with health and medical care, including dental care, the risk of transmission is not significant if the patient is on effective treatment, but the risk may remain, although considerably reduced, in more advanced interventions such as surgery. When an incident with risk of transmission occurs, the patient must always inform those potentially exposed about his or her HIV infection.

Synthetic Versus Biological Mesh in Laparoscopic and Open Ventral Hernia Repair (LAPSIS): Results of a Multinational, Randomized, Controlled, and Double-blind Trial.

OBJECTIVE: The aim of this study was to investigate the approach (open or laparoscopic) and mesh type (synthetic or biological) in ventral hernias in a clean setting.Summary of Background Data: The level of evidence on the optimal surgical approach and type of mesh in ventral hernia repair is still low. METHODS: Patients with a ventral abdominal hernia (diameter 4-10 cm) were included in this double-blind randomized controlled trial across 17 hospitals in 10 European countries. According to a 2 × 2-factorial design, patients were allocated to 4 arms (open retromuscular or laparoscopic intraperitoneal, with synthetic or Surgisis Gold biological mesh). Patients and outcome assessors were blinded to mesh type used. Major postoperative complication rate (hernia recurrence, mesh infection, or reoperation) within 3 years after surgery, was the primary endpoint in the intention-to-treat population. RESULTS: Between September 1st, 2005, and August 7th, 2009, 253 patients were randomized and 13 excluded. Six of 61 patients (9.8%) in the open synthetic mesh arm, 15 of 66 patients (22.7%) in the open biological mesh arm, 7 of 64 patients (10.9%) in the laparoscopic synthetic mesh arm and 17 of 62 patients (27.4%) in the laparoscopic biological mesh arm had a major complication. The use of biological mesh resulted in significantly more complications (P = 0.013), also after adjusting for hernia type, body mass index, and study site. The trial was prematurely stopped due to an unacceptable high recurrence rate in the biological mesh arms. CONCLUSIONS: The use of Surgisis Gold biological mesh is not recommended for noncomplex ventral hernia repair. TRIAL REGISTRATION: This trial was registered at controlled-trials.com (ISRCTN34532248).