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 (2.6%) 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.
The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers.
Care providers from ...neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies.
Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance.
At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus.
At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aim
To describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers.
Methods
SNQ collects data for infants admitted to neonatal units ...during the first four postnatal weeks. Completeness and registers’ agreement were determined cross‐linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years.
Results
In total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24–34, completeness of SNQ was 98–99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near‐term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re‐admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic‐ischaemic encephalopathy) were often missing in the population registers.
Conclusion
SNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
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.
Aims/hypothesis
Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it ...is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered.
Methods
Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery.
Results
After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon.
Conclusions/interpretation
After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism.
Trial registration
ClinicalTrials.gov NCT01559779.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Approximately 2.6 million children live with HIV globally, and efavirenz (EFV) is one of the most widely used antiretroviral agents for HIV treatment in children and adults. There are concerns about ...the appropriateness of current EFV dosing and it has been discussed whether EFV dosing should be adapted according to genotype in children as suggested for adults.
To investigate if pediatric EFV dosing should be guided by genetic variation in drug metabolizing enzymes rather than by body weight.
EFV plasma concentrations measured for clinical purposes from all children less than 18 years old at Karolinska University Hospital, Stockholm, Sweden, treated with EFV were collected retrospectively. They were genotyped for eleven polymorphisms in genes coding for drug-metabolizing enzymes and P-glycoprotein, of potential importance for EFV disposition. Data on country of origin, sex, age, weight, HIV RNA, viral resistance patterns, CD4 cells, adherence to treatment, subjective health status and adverse events were collected from their medical records.
Thirty-six patients and 182 (mean 5 samples/patient) EFV plasma concentration measurements from children of African, Asian and Latin American origin were included. EFV plasma concentration varied 21-fold between measurements (n = 182) (0.85-19.3 mg/L) and 9-fold measured as mean EFV plasma concentration across the subjects (1.55-13.4 mg/L). A multivariate mixed-effects restricted maximum likelihood regression model, including multiple gene polymorphisms, identified CYP2B6*6 T/T (p < 0.0005), CYP2B6*11 G/G (p < 0.0005), CYP2A6*9 A/C (p = 0.001) genotypes, age at treatment initiation (p = 0.002) and time from treatment initiation (p < 0.0005) as independent factors significantly related to loge concentration/(dose/weight). The contribution of the model to the intra- and interindividual variation were 6 and 75%, respectively (Bryk/Raudenbush R-squared level).
Genetic polymorphisms in CYP2B6 and CYP2A6 explained a significant proportion of variability in EFV plasma concentration in HIV-infected children in a multi-ethnic outpatient clinic. Knowledge about individual variants in key drug metabolizing enzyme genes could improve clinical safety and genotype directed dosing could achieve more predictable EFV plasma concentrations in HIV-infected children.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AspireAssist® allows aspiration of ~30% of an ingested meal through a percutaneous gastrostomy tube thereby reducing caloric uptake. We evaluated the acute effects of aspiration therapy on ...postprandial glucose tolerance, responses of gluco-regulatory and appetite-regulating gut hormones, appetite sensations and food intake. Seven AspireAssist®-treated persons without diabetes (median IQR age 52 44;54 years; BMI 35.6 31.5;40.5 kg/m2) underwent two mixed meal tests on separate days with double-blinded aspiration (aspiration visit) and sham aspiration (sham visit), respectively. Seven age and BMI-matched controls (age 43 42;54; BMI 34.1 31.6;38.7 kg/m2) underwent one meal test (control visit). All mixed meal tests were followed by an ad libitum meal for evaluation of food intake. Compared to sham visits, postprandial glucose tolerance was improved on aspiration visits (median IQR baseline-subtracted area under the curve (bsAUC) 170 88;356 vs. 388 239;456 mmol/L × min, P = 0.025). Postprandial responses (bsAUCs) of C-peptide, cholecystokinin (CCK) and glucose-dependent insulinotropic polypeptide (GIP) were reduced during aspiration vs. sham visits (113 28;224 vs. 302 215;433 nmol/L × min, P = 0.014; 223 59.4;402 vs. 467 416;546 pmol/L × min, P = 0.005; and 4,634 1,488;9,044 vs. 15,382 9,588;18,850 pmol/L × min, P = 0.025). Glucagon, gastrin, ghrelin and peptide YY, respectively, were similar on aspiration and sham visits. Appetite sensations and ad libitum food intake were similar on aspiration and sham visits. Responses of plasma glucose, gut hormones, appetite sensations and food intake were similar on sham and control visits. In this study, aspiration therapy acutely improved postprandial glucose tolerance without causing a compensatory increase in appetite sensations or food intake at a subsequent ad libitum meal; pointing to acute beneficial metabolic effect of aspiration therapy in addition to the long-term bodyweight-lowering effect of this treatment.
Disclosure
I. Gether: None. M. M. Jensen: None. T. Jorsal: None. C. Nexøe-larsen: None. L. S. Gasbjerg: Stock/Shareholder; Self; Antag Therapeutics. L. P. S. Naver: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S.
Funding
Augustinus Fonden
The global spread of antibiotic resistance among
is largely due to multidrug resistance plasmids that can transfer between different bacterial strains and species. Horizontal gene transfer of ...resistance plasmids can complicate hospital outbreaks and cause problems in epidemiological tracing, since tracing is usually based on bacterial clonality. We have developed a method, based on optical DNA mapping combined with Cas9-assisted identification of resistance genes, which is used here to characterize plasmids during an extended-spectrum β-lactamase (ESBL)-producing
outbreak at a Swedish neonatal intensive care unit. The outbreak included 17 neonates initially colonized with ESBL-producing
(ESBL-KP), some of which were found to carry additional ESBL-producing
(ESBL-EC) in follow-up samples. We demonstrate that all ESBL-KP isolates contained two plasmids with the
gene located on the smaller one (~80 kbp). The same ESBL-KP clone was present in follow-up samples for up to 2 years in some patients, and the plasmid carrying the
gene was stable throughout this time period. However, extensive genetic rearrangements within the second plasmid were observed in the optical DNA maps for several of the ESBL-KP isolates. Optical mapping also demonstrated that even though other bacterial clones and species carrying
group 1 genes were found in some neonates, no transfer of resistance plasmids had occurred. The data instead pointed toward unrelated acquisition of ESBL-producing
(EPE). In addition to revealing important information about the specific outbreak, the method presented is a promising tool for surveillance and infection control in clinical settings.
This study presents how a novel method, based on visualizing single plasmids using sequence-specific fluorescent labeling, could be used to analyze the genetic dynamics of an outbreak of resistant bacteria in a neonatal intensive care unit at a Swedish hospital. Plasmids are a central reason for the rapid global spread of bacterial resistance to antibiotics. In a single experimental procedure, this method replaces many traditional plasmid analysis techniques that together provide limited details and are slow to perform. The method is much faster than long-read whole-genome sequencing and offers direct genetic comparison of patient samples. We could conclude that no transfer of resistance plasmids had occurred between different bacteria during the outbreak and that secondary cases of ESBL-producing
carriage were instead likely due to influx of new strains. We believe that the method offers potential in improving surveillance and infection control of resistant bacteria in hospitals.
Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and ...adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand.
Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.
In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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