Impact of SARS-CoV-2 on incidence, treatment and outcome of very preterm born infants in Switzerland: a retrospective, population-based cohort study.

AIMS OF THE STUDY: To assess whether the COVID-19 pandemic caused by SARS-CoV-2 had an impact on incidence, treatment or major adverse short-term outcome of preterm-born infants in Switzerland. METHODS: Retrospective cohort study of preterm infants born in 2020 based on two independent data sources from the Swiss Federal Statistics Office (FSO) and SwissNeoNet. Based on FSO data, we calculated the odds ratios for extremely preterm (22-27 weeks gestation), very preterm (28-31 weeks gestation), and late preterm (32-36 weeks gestation) births during the pandemic. Based on SwissNeoNet data of infants born between 22 and 31 weeks gestation, we compared infants born during the Swiss lockdown period in 2020 with infants born during the same period between 2015 and 2019, all infants of 2020 with all infants between 2015 and 2019 and infants born to mothers tested SARS-CoV-2 positive and negative. Possible associations with the pandemic were tested using logistic regression adjusted for case-mix. As a control, we compared births of 2019 with those of 2015-2018. RESULTS: The FSO data revealed equivalent odds for extremely preterm births in 2020 (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.89-1.14), as well as somewhat lower odds ratios for very preterm (OR 0.9, 95% CI 0.82-1.00) and late preterm (OR 0.91, 95% CI 0.88-0.93) births in 2020. A comparison between 2019 and 2015-2018, however, revealed matching odds ratios rendering an association to the pandemic unlikely. In the SwissNeoNet data, 137 infants were born during lockdown in 2020 compared with 134 births per year during 2015-2019. When including all infants, 744 infants were compared to 845 births, respectively. The only difference observed in treatments and short term outcomes between 2020 and the reference years were a higher odds for respiratory distress syndrome (OR 1.6, 95% CI 1.08-2.37) and provision of continuous positive airway pressure (CPAP) (OR 1.39, 95% CI 1.05-1.84). CONCLUSIONS: Our Swiss population-based analysis did not identify the elsewhere reported association between the COVID-19 pandemic and a reduced preterm birth rate. However, we can confirm a possible link between the COVID-19 pandemic and higher odds of respiratory distress syndrome, possibly coupled with CPAP requirements. Further observation of potential effects of the pandemic on health and health care provision to newborns may however be indicated based on the literature available so far and that our data only covers the first 9 months of the current pandemic.

Retrospective validation of the postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria in a Swiss cohort.

BACKGROUND: Currently used screening criteria for retinopathy of prematurity (ROP) show high sensitivity for predicting treatment-requiring ROP but low specificity; over 90% of examined infants do not develop ROP that requires treatment (type 1 ROP). A novel weight gain-based prediction model was developed by the G-ROP study group to increase the specificity of the screening criteria and keep the number of ophthalmic examinations as low as possible. This retrospective cohort study aimed to externally validate the G-ROP screening criteria in a Swiss cohort. METHODS: Data from 645 preterm infants in ROP screening at Inselspital Bern between January 2015 and December 2019 were retrospectively retrieved from the screening log and analysed. The G-ROP screening criteria, consisting of 6 trigger parameters, were applied in infants with complete data. To determine the performance of the G-ROP prediction model for treatment-requiring ROP, sensitivity and specificity were calculated. RESULTS: Complete data were available for 322 infants who were included in the analysis. None of the excluded infants had developed type 1 ROP. By applying the 6 criteria in the G-ROP model, 214 infants were flagged to undergo screening: among these, 14 developed type 1 ROP, 9 developed type 2 ROP, and 43 developed milder stages of ROP. The sensitivity for predicting treatment-requiring ROP was 100% (CI, 0.79-1.00), and the specificity was 41% (CI, 0.35 -0.47). Implementing the novel G-ROP screening criteria would reduce the number of infants entering ROP screening by approximately one third. CONCLUSIONS: The overall prevalence of treatment-requiring ROP was low (2.15%). Previously published performance parameters for the G-ROP algorithm were reproducible in this Swiss cohort. Importantly, all treatment-requiring infants were correctly identified. By using these novel criteria, the burden of screening examinations could be significantly reduced.

Associations between Red Blood Cell and Platelet Transfusions and Retinopathy of Prematurity.

AIM: The aim of this study is to examine possible associations between the transfusion of RBC or platelets (PLTs) and the development of retinopathy of prematurity (ROP) in infants. METHODS: This retrospective, national, case-control study included all live births in Switzerland between 2013 and 2018. We investigated preterm infants at a gestational age of <28 weeks, who developed higher stage ROP (≥stage 2, n = 178). Each case infant was matched to another of the same sex who did not develop ROP (n = 178, control group). RESULTS: When compared with the control group, we observed higher numbers of RBC transfusions per infant and higher percentages of infants receiving PLT transfusions in the case group. An adjusted logistic regression analysis revealed that both RBC (odds ratio [OR] 1.081, 95% confidence interval [CI] 1.020-1.146) and PLT transfusions (OR = 2.502, 95% CI 1.566-3.998) numbers were associated with ROP development. CONCLUSIONS: Multiple RBC and PLT transfusions are associated with higher stage ROP development. Prospective studies are required to determine their potential as risk factors.

HIV Drug Efavirenz Inhibits CYP21A2 Activity with Possible Clinical Implications.

BACKGROUND: The HIV drugs lopinavir and ritonavir have recently been reported to cause transient adrenal insufficiency in preterm newborns. We, therefore, considered HIV drugs as a cause of transiently elevated 17-hydroxyprogesterone (17OHP) levels in a neonatal screening test for congenital adrenal hyperplasia in a preterm girl exposed to zidovudine, efavirenz, tenofovir, and emtricitabine. OBJECTIVE: So far, HIV drugs have not been tested for their effect on steroidogenesis and the steroidogenic enzyme activity of CYP21A2 specifically in an in vitro system. METHODS: We tested the effect of efavirenz, tenofovir, emtricitabine, and zidovudine on steroidogenesis of human adrenal H295R cells. Cells were treated with the drugs at different concentrations including concentrations in therapeutic use. The effect on CYP21A2 activity was assessed by testing the conversion of radiolabeled 17OHP to 11-deoxycortisol. Cell viability was tested by an MTT assay. In addition, recombinant human CYP21A2 protein was used to assess direct drug effects on CYP21A2 activity. RESULTS: We observed significantly decreased CYP21A2 activity in both in vitro testing systems after treatment with efavirenz at therapeutic concentrations. Moreover, efavirenz affected cell viability. By contrast, the other test drugs did not affect steroidogenesis. Follow-up of our patient revealed elevated 17OHP and androgen levels during the first weeks of life, but values normalized spontaneously. Genetic testing for CYP21A2 mutations was negative. Thus, it remains unsettled whether the transient 17OHP elevation in this baby was due to a drug effect. CONCLUSION: The HIV drug efavirenz inhibits CYP21A2 activity in vitro through direct interaction with enzyme catalysis at therapeutic concentrations. This may have clinical implications for HIV treatment in children and adults. However, so far, clinical data are scarce, and further studies are needed to be able to draw clinical conclusions.

Recommendations for term and late preterm infants at risk for perinatal bacterial infection.

Since publication of the initial guidelines for the prevention of group B streptococcal disease in 1996, the incidence of perinatal infection has decreased significantly. Intrapartum antibiotic prophylaxis together with appropriate management of neonates at increased risk for early-onset sepsis not only reduces morbidity and mortality, but also decreases the burden of unnecessary or prolonged antibiotic therapy. This article provides healthcare workers in Switzerland with evidence-based and best-practice derived guidelines for the assessment and management of term and late preterm infants (>34 weeks) at increased risk for perinatal bacterial infection. Management of neonates at increased risk for early-onset sepsis depends on clinical presentation and risk factors. Asymptomatic infants with risk factors for early-onset sepsis should be observed closely in an inpatient setting for the first 48 hours of life. Symptomatic neonates must be treated promptly with intravenous antibiotics. As clinical and laboratory signs of neonatal infection are nonspecific, it is mandatory to reevaluate the need for continued antibiotic therapy after 48 hours.

Discovery and development of exome-based, co-dominant single nucleotide polymorphism markers in hexaploid wheat (Triticum aestivum L.).

Globally, wheat is the most widely grown crop and one of the three most important crops for human and livestock feed. However, the complex nature of the wheat genome has, until recently, resulted in a lack of single nucleotide polymorphism (SNP)-based molecular markers of practical use to wheat breeders. Recently, large numbers of SNP-based wheat markers have been made available via the use of next-generation sequencing combined with a variety of genotyping platforms. However, many of these markers and platforms have difficulty distinguishing between heterozygote and homozygote individuals and are therefore of limited use to wheat breeders carrying out commercial-scale breeding programmes. To identify exome-based co-dominant SNP-based assays, which are capable of distinguishing between heterozygotes and homozygotes, we have used targeted re-sequencing of the wheat exome to generate large amounts of genomic sequences from eight varieties. Using a bioinformatics approach, these sequences have been used to identify 95 266 putative single nucleotide polymorphisms, of which 10 251 were classified as being putatively co-dominant. Validation of a subset of these putative co-dominant markers confirmed that 96% were true polymorphisms and 65% were co-dominant SNP assays. The new co-dominant markers described here are capable of genotypic classification of a segregating locus in polyploid wheat and can be used on a variety of genotyping platforms; as such, they represent a powerful tool for wheat breeders. These markers and related information have been made publically available on an interactive web-based database to facilitate their use on genotyping programmes worldwide.

The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review.

BACKGROUND: Neonates in a neonatal intensive care unit are exposed to a high number of painful procedures. Since repeated and sustained pain can have consequences for the neurological and behaviour-oriented development of the newborn, the greatest attention needs to be paid to systematic pain management in neonatology. Non-pharmacological treatment methods are being increasingly discussed with regard to pain prevention and relief either alone or in combination with pharmacological treatment. AIMS: To identify effective non-pharmacological interventions with regard to procedural pain in neonates. METHODS: A literature search was conducted via the MedLine, CINAHL, Cochrane Library databases and complemented by a handsearch. The literature search covered the period from 1984 to 2004. Data were extracted according to pre-defined criteria by two independent reviewers and methodological quality was assessed. RESULTS: 13 randomised controlled studies and two meta-analyses were taken into consideration with regard to the question of current nursing practice of non-pharmacological pain management methods. The selected interventions were "non-nutritive sucking", "music", "swaddling", "positioning", "olfactory and multisensorial stimulation", "kangaroo care" and "maternal touch". There is evidence that the methods of "non-nutritive sucking", "swaddling" and "facilitated tucking" do have a pain-alleviating effect on neonates. CONCLUSIONS: Some of the non-pharmacological interventions have an evident favourable effect on pulse rate, respiration and oxygen saturation, on the reduction of motor activity, and on the excitation states after invasive measures. However, unambiguous evidence of this still remains to be presented. Further research should emphasise the use of validated pain assessment instruments for the evaluation of the pain-alleviating effect of non-pharmacological interventions.

[The efficacy of non-pharmacological interventions in the management of pain in preterm and term neonates. A systematic literature review]. / Die Effektivität nicht-medikamentöser Interventionen in der Schmerzbehandlung von Früh- und Termingeborenen. Eine systematische Literaturübersicht.

Many diagnostic and therapeutic procedures performed in the neonatal intensive care unit are painful for the preterm or term infant. Pain is therefore a central issue in neonatal intensive care nursing. As significant side effects are associated with analgesics, non-pharmacological methods of pain prevention and relief are being favoured over pharmacological therapy. This development is very important for the nursing profession since non-pharmacological interventions are determined and carried out without an order from a physician. This review of the current literature investigates the efficacy of non-pharmacological nursing interventions in the management of pain in the neonatal intensive care unit. Despite certain methodological problems with some of the studies included in this review, the trend favours non-pharmacological interventions. Modulation of arousal and excitability during and after a painful stimulus as well as an effect on physiological and behavioural parameters have been described following non-pharmacological interventions. The studies reviewed suggest that neonates show fewer signs of pain and stress after non-pharmacological interventions for prevention and relief of pain.

C-reactive protein in vaginal fluid of patients with preterm premature rupture of membranes.

OBJECTIVE: To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation. METHODS: Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis. RESULTS: A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p < 0.001) and umbilical cord levels (r = 0.47, p < 0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p < 0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p < 0.01]. After adjustment for gestational age, vaginal fluid CRP concentration > 800 ng/mL remained a predictor of intraamniotic infection and funisitis. CONCLUSIONS: Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.

Aortic dissection in pregnancy: analysis of risk factors and outcome.

Aortic dissection during pregnancy is a life-threatening event. Recent studies have revealed similar histologic changes in the wall of the ascending aorta in patients with bicuspid aortic valve disease (BAVD). Based on a review of the literature, including the experience from two institutions, we looked at the patient's characteristics in patients with thoracic aortic dissection during pregnancy. We found that aortic root enlargement (> 4cm) or an increase of aortic root size during pregnancy in patients with BAVD, and Marfan syndrome is associated with a considerable risk for the occurrence of Type A dissection.

Evidence of fetal C-reactive protein urinary excretion in early gestation.

BACKGROUND: C-reactive protein has been measured in amniotic fluid in the second and third trimesters of gestation, and its elevated concentration has been found to be associated with adverse pregnancy outcome. It remains unexplained whether amniotic fluid C-reactive protein is of fetal origin. CASE: We report the measurement of C-reactive protein in fetal urine obtained by transabdominal vescicocentesis in a fetus at 15 weeks' gestation affected by obstructive uropathy. Using an enzyme-linked immunosorbent assay, C-reactive protein was detected at a concentration of 234 ng/mL. CONCLUSION: The fetal kidneys excrete C-reactive protein as early as 15 weeks' gestation.