Glycemic control assessed by continuous glucose monitoring during pregnancy in women with type 1 diabetes and its association with preeclampsia, an observational Swedish cohort study.

INTRODUCTION: Women with type 1 diabetes have an increased risk of preeclampsia (PE), but it is not fully understood if degree of glycemic control is associated with this risk. The aim of this study was to assess glycemic control during pregnancy analyzed by continuous glucose monitoring (CGM) in women with and without PE and to investigate if glycemic control is associated with increased risk of PE. MATERIAL AND METHODS: A total of 120 pregnant Swedish women with type 1 diabetes using CGM were included. Background factors and pregnancy outcomes were collected from medical records. CGM data were collected via the internet-based platform Diasend. Mean glucose, standard deviation of mean glucose, percentage of time in target, time below target, and time above target were presented for each trimester in women who did or did not develop PE. Associations between CGM-derived metrics and PE were analyzed with logistic regression and adjusted for confounders. RESULTS: Twenty-two women (18.3%) developed PE. There were no significant differences in maternal characteristics between women with and without PE. Glycemic control improved in each trimester but was suboptimal in both groups. Time in target increased from 59% in the non-PE group and 54% in the PE group in the first trimester to 65% in both groups in the third trimester. There were no significant associations between glycemic control and PE after adjustment for confounders. CONCLUSIONS: Degree of glycemic control during pregnancy assessed by CGM was not associated with development of PE in women with type 1 diabetes. However, more research is needed to understand the role of glycemic control in relation to development of PE.

Ultra-high-frequency ultrasound (48-70 MHz) is a promising tool for improved gastrointestinal diagnostics in infants.

AIM: To investigate the clinical feasibility of ultra-high-frequency abdominal ultrasound (UHFUS) scans of preterm and term infants. METHODS: Prospectively, 19 healthy term newborn infants were examined with conventional ultrasound (CUS) (Toshiba, Aplio i700, linear probe 14L5) and UHFUS (Visualsonics VevoMD, linear probes UHF48 and UHF70) according to a standardised protocol. Measurements of wall thickness were performed for; stomach, small intestine, colon and peritoneum. Five preterm infants, with or without suspected necrotising enterocolitis (NEC), were also examined with UHF48. Of these, only one was later diagnosed with NEC. RESULTS: Differences between CUS and UHFUS (UHF48) were found in measurements of thickness; for peritoneum 0.25 versus 0.13 mm (p < 0.001), small intestine 0.76 versus 0.64 mm (p = 0.039) and colon 0.7 versus 0.47 mm (p < 0.001) in healthy term infants. Gaining frequency from 46 to 71 MHz showed a mean reduction in measurements of peritoneum from 0.13 to 0.09 mm (p < 0.001). One preterm infant with NEC showed a fivefold and twofold increase in peritoneal and gastrointestinal wall thickness respectively, compared to healthy preterm infants. CONCLUSION: UHFUS was a clinically feasible, promising method with potential to improve gastrointestinal diagnostics in infants. Lower peritoneum thickness and gastrointestinal wall thickness were demonstrated with UHFUS compared to CUS, suggesting an overestimation by CUS.

Body composition and bone mass among 5-year-old survivors of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) affects the intestine of preterm infants. Preterm infants risk inadequate bone mineralization. This risk may increase if the intestinal uptake of minerals is affected after NEC. METHODS: This is a study of growth, bone mineral density (BMD), bone mineral content (BMC), and body composition at 5 years of age among Swedish children born before gestational week 37 + 0 with a history of NEC, minimum stage IIA, compared to matched controls. Fifty children, 25 NEC cases and 25 controls, were examined with dual energy X-ray absorptiometry (DXA) and DXA with laser. RESULTS: The NEC cases had lower weight, -1.3 SDS vs -0.7 SDS, a lower fat mass and fat percent, 23.4 vs 29.1%, compared to the controls. NEC cases had lower BMC total body head excluded, 355.6 g vs 416.7 g. BMD Z-scores were lower among NEC cases in total body head excluded, -0.7 vs -0.1, and in lumbar spine. CONCLUSIONS: Preterm NEC survivors at 5 years of age had reduced growth, an altered body composition, and indications of a lower bone mass compared to matched controls. The study suggests that preterm infants diagnosed with NEC need special attention during childhood regarding growth and bone health. IMPACT: A follow-up longitudinal study of growth, bone health, and body composition at 5 years of age among children born preterm with a history of NEC compared to matched controls. The NEC cases had lower weight than controls. NEC cases had an altered body composition with lower fat mass compared to controls. The DXA results showed that the NEC cases had lower bone mineral content and a tendency to lower bone mineral density. The study suggests that preterm infants diagnosed with NEC need special attention at follow-up regarding growth and bone health compared to preterm infants without NEC.

Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden.

In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe.

Stabilisation and resuscitation with intact cord circulation is feasible using a wide variety of approaches; a scoping review.

AIM: This scoping review identified studies on approaches to intact cord resuscitation and/or stabilisation (ICR/S) for neonates delivered by Caesarean section (C-section). METHODS: A systematic literature search was carried out using the PubMed, Web of Science, Scopus, Cochrane and CINAHL databases to identify papers published in English from inception to 14 November 2022. RESULTS: We assessed 2613 studies and included 18 from 10 countries, covering 1-125 C-sections: the United States, the United Kingdom, Australia, India, Italy, China, France, The Netherlands, New Zealand and Taiwan. The papers were published from 2014 to 2023, and the majority were randomised controlled trials and observational studies. Different platforms, equipment and staff positions in relation to the operating table were described. Options for resuscitation and stabilisation included different bedding and trolley approaches, and maintaining aseptic conditions was mainly addressed by the neonatal team scrubbing in. Hypothermia was prevented by using warm surfaces, polythene bags and radiant heaters. Equipment was kept easily accessible by mounting it on a trolley or a separate mobile pole. CONCLUSION: We could not reach definitive conclusions on the optimal method for performing ICR/S during a C-section, due to study variations. However, a number of equipment and management options appeared to be feasible approaches.

Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.

INTRODUCTION: Anorexia nervosa (AN) increases the risk of impaired bone health, low areal bone mineral density (aBMD), and subsequent fractures. This prospective study investigated the long-term effects of bone and mineral metabolism on bone and biomarkers in 22 women with AN. MATERIALS AND METHODS: Body composition and aBMD were measured by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography. Total and free 25-hydroxyvitamin D (25OHD), C-terminal collagen cross-links (CTX), osteocalcin, bone-specific alkaline phosphatase (BALP), leptin, sclerostin, and oxidized/non-oxidized parathyroid hormone (PTH) were analyzed before and after 12 weeks of intensive nutrition therapy and again 3 years later. An age-matched comparison group of 17 healthy women was recruited for the 3-year follow-up. RESULTS: Body mass index (BMI) and fat mass increased from baseline to 3 years in women with AN. Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss. CTX was elevated at baseline and after 12 weeks but decreased over 3 years. BALP increased during nutrition therapy and stabilized over 3 years. Free 25OHD was stable during treatment but decreased over 3 years. Non-oxidized PTH was stable during treatment but increased over 3 years. Trabecular volumetric BMD in AN patients decreased during the first 12 weeks and over 3 years despite stable BMI and bone biomarkers implying increased BMD. CONCLUSION: Our findings highlight the importance of early detection and organized long-term follow-up of bone health in young women with a history of AN.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

Impaired renal clearance among Swedish adolescents born preterm.

AIM: To determine whether adolescents born before 28 gestational weeks have an increased risk for renal impairment. METHODS: Swedish infants, born before 28 gestational weeks in 2001 and 2002, were identified from a local register. A total of 16 children, 12 females and 4 males, were examined at 16-17 years of age with 51 Cr-EDTA clearance. A comparison group (n = 26) was used. RESULTS: Most study participants (n = 13) had normal blood pressure; one individual had hypertension stage 1. All study participants had results within the reference interval for ionised calcium, parathyroid hormone, intact fibroblast growth factor-23 and for urinary albumin-to-creatinine ratio. Four out of 16 participants (25%) had a 51 Cr-EDTA clearance less than 90 ml/min/1.73 m2 , indicating a reduced kidney function. Measured 51 Cr-EDTA clearance values were significantly lower in the study group than in the comparison group (p = 0.0012). Five study participants (31%) were referred for further investigations. CONCLUSION: Swedish children born before 28 gestational weeks have an increased risk of renal impairment later in life, suggesting that the kidney function in these individuals should be assessed, at least once, during adolescence.

Dramatic changes in blood protein levels during the first week of life in extremely preterm infants.

BACKGROUND: Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life. METHODS: We have performed in-depth analysis of the protein profiles of 14 extremely preterm infants using longitudinal sampling. Medical variables were integrated with extensive profiling of 448 unique protein targets. RESULTS: The preterm infants have a distinct unified protein profile in blood directly at birth regardless of clinical background; however, the pattern changed profoundly postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Clusters of proteins depending on temporal trend were identified. CONCLUSION: The protein profiles and the temporal trends here described will contribute to the understanding of the physiological changes in the intrauterine-extrauterine transition, which is essential to adjust early-in-life interventions to prone a normal development in the vulnerable preterm infants. IMPACT: We have performed longitudinal and in-depth analysis of the protein profiles of 14 extremely preterm infants using a novel multiplex protein analysis platform. The preterm infants had a distinct unified protein profile in blood directly at birth regardless of clinical background. The pattern changed dramatically postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Certain clusters of proteins were identified depending on their temporal trend, including several liver and immune proteins. The study contributes to the understanding of the physiological changes in the intrauterine-extrauterine transition.

Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy - Pump vs multiple daily injections, a secondary analysis of an observational cohort study.

INTRODUCTION: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes. MATERIAL AND METHODS: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real-time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders. RESULTS: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real-time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly. CONCLUSIONS: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.

The effects of exposure to HIV in neonates at a referral hospital in South Africa.

BACKGROUND: Fewer infants are infected with HIV through mother-to-child transmission, making HIV-exposed but uninfected (HEU) infants a growing population. HIV-exposure seems to affect immunology, early growth and development, and is associated with higher morbidity and mortality rates. Currently, there is a lack of information regarding the clinical effects of HIV-exposure during the neonatal period. OBJECTIVES: To identify a possible difference in mortality and common neonatal morbidities in HEU neonates compared to HIV-unexposed neonates. METHODS: This was a retrospective, descriptive study of all neonates admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital between 1 January 2017 and 31 December 2018. HEU neonates were compared to HIV-unexposed neonates. RESULTS: There were 3236 neonates included, where 855 neonates were HEU. The HEU neonates had significantly lower birth weight and gestational age. The HEU neonates had higher rates of neonatal sepsis (19.8% vs 14.2%, OR 1.49, p <  0.001), specifically for late onset sepsis, and required more respiratory support. NCPAP and invasive ventilation was more common in the HEU group (36.3% vs 31.3% required NCPAP, p = 0.008, and 20.1% vs 15,0% required invasive ventilation, p <  0.001). Chronic lung disease was more common among HIV-exposed neonates (12.2% vs 8.7%, OR 1.46, p = 0.003). The difference in mortality rates between the study groups was not significant (10.8% of HEU neonates and 13.3% of HIV-unexposed). CONCLUSIONS: HEU neonates had higher rates of neonatal sepsis, particularly late-onset sepsis, required more respiratory support and had higher rates of chronic lung disease. Mortality of HEU neonates was not different HIV-unexposed neonates.

Low false-positive rate of perfusion index as a screening tool for neonatal aortic coarctation.

AIM: Adding perfusion index (PI) to pulse oximetry screening (POS) may increase neonatal detection of CoA (aortic coarctation). A cut-off <0.7% has been suggested but is associated with a high rate of false positives. We aimed to evaluate the specificity of PI when using repeated instead of single measurements. METHODS: A pilot study was conducted in 50 neonates. PI was recorded in right hand and a foot by pulse oximeter. If PI was <0.7%, the measurement was immediately repeated up to 3 times. If all three measurements were <0.7% in hand and/or foot the screen was positive and echocardiography was performed. There were 3/50 false-positive screens. The protocol was therefore modified requiring 30 min intervals between measurements. RESULTS: An additional 463 neonates were included using the modified protocol at a median age of 18 h. There were no false positives. The only neonate with CoA had a negative screen (PI hand 1.2% and foot 0.8%). The measurement required on average an extra 3 min and 30 s compared with POS only. CONCLUSION: The false-positive rate of PI was reduced by using repeated PI measurements. The sensitivity for CoA using this protocol should be evaluated in large-scale prospective studies.

C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis. METHODS: The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016-2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019). Laboratory and clinical data were analysed. RESULTS: There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37-62) in period 1 and 42 mg/L (31-56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p < 0.001) and hospital stay (Median: seven vs. five days, p < 0.001) as well as healthcare costs (decreased by €122,000/year) was reduced in the group who met the criteria after the introduction of the guidelines. CONCLUSION: C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants. TRIAL REGISTRATION: Trial registration number: ISRCTN29535824 . Date of registration: 28 May 2020. Retrospectively registered.

Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies.

AIMS/HYPOTHESIS: The aim of this study was to analyse patterns of continuous glucose monitoring (CGM) data for associations with large for gestational age (LGA) infants and an adverse neonatal composite outcome (NCO) in pregnancies in women with type 1 diabetes. METHODS: This was an observational cohort study of 186 pregnant women with type 1 diabetes in Sweden. The interstitial glucose readings from 92 real-time (rt) CGM and 94 intermittently viewed (i) CGM devices were used to calculate mean glucose, SD, CV%, time spent in target range (3.5-7.8 mmol/l), mean amplitude of glucose excursions and also high and low blood glucose indices (HBGI and LBGI, respectively). Electronic records provided information on maternal demographics and neonatal outcomes. Associations between CGM indices and neonatal outcomes were analysed by stepwise logistic regression analysis adjusted for confounders. RESULTS: The number of infants born LGA was similar in rtCGM and iCGM users (52% vs 53%). In the combined group, elevated mean glucose levels in the second and the third trimester were significantly associated with LGA (OR 1.53, 95% CI 1.12, 2.08, and OR 1.57, 95% CI 1.12, 2.19, respectively). Furthermore, a high percentage of time in target in the second and the third trimester was associated with lower risk of LGA (OR 0.96, 95% CI 0.94, 0.99 and OR 0.97, 95% CI 0.95, 1.00, respectively). The same associations were found for mean glucose and for time in target and the risk of NCO in all trimesters. SD was significantly associated with LGA in the second trimester and with NCO in the third trimester. Glucose patterns did not differ between rtCGM and iCGM users except that rtCGM users had lower LBGI and spent less time below target. CONCLUSIONS/INTERPRETATION: Higher mean glucose levels, higher SD and less time in target range were associated with increased risk of LGA and NCO. Despite the use of CGM throughout pregnancy, the day-to-day glucose control was not optimal and the incidence of LGA remained high.

Increased risk of rickets but not fractures during childhood and adolescence following necrotizing enterocolitis among children born preterm in Sweden.

BACKGROUND: The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age. METHODS: All infants born in Sweden between 1987 and 2009 with a gestational age <32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed. RESULTS: In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007). CONCLUSIONS: This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.

Caffeine exposure during pregnancy, small for gestational age birth and neonatal outcome - results from the Norwegian Mother and Child Cohort Study.

BACKGROUND: Maternal caffeine intake has repeatedly been linked to babies being born small for gestational age (SGA). SGA babies are known to be at increased risk for adverse neonatal outcomes. The aim of this study was to explore the associations between prenatal caffeine exposure and neonatal health. METHODS: The study is based on 67,569 full-term singleton mother-infant pairs from the Norwegian Mother and Child Cohort Study. Caffeine consumption from different sources was self-reported in gestational week 22. Neonatal compound outcomes, namely (1) morbidity/mortality and (2) neonatal intervention, were created based on the Medical Birth Registry of Norway. Adjusted logistic regression was performed. RESULTS: Caffeine exposure was associated to SGA (OR = 1.16, 95%CI: 1.10; 1.23) and being born SGA was significantly associated with neonatal health (OR = 3.09, 95%CI: 2.54; 3.78 for morbidity/mortality; OR = 3.94, 95%CI: 3.50; 4.45 for intervention). However, prenatal caffeine exposure was neither associated with neonatal morbidity/mortality (OR = 1.01, 95%CI: 0.96; 1.07) nor neonatal intervention (OR = 1.02, 95%CI: 1.00; 1.05 for a 100 mg caffeine intake increase). Results did not change after additional adjustment for SGA status. CONCLUSIONS: Moderate prenatal caffeine exposure (< 200 mg/day) does not seem to impair neonatal health, although prenatal caffeine exposure is associated with the child being born SGA and SGA with neonatal health. We suggest diversity in neonatal outcomes of SGA infants according to the underlying cause of low birth weight.

Changes in incidence and etiology of early-onset neonatal infections 1997-2017 - a retrospective cohort study in western Sweden.

BACKGROUND: The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997-2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975. METHODS: Observational epidemiological, retrospective study on infants 0-6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997-2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975. RESULTS: The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997-2007 to 0.9/1000 LB in 2008-2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997-2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987-1996 to 0.45/1000 live births 1997-2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge. CONCLUSION: There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area. KEY NOTES: This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study.

AIM: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS) METHODS: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004-2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC. RESULTS: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%. CONCLUSION: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

Population-based study showed that necrotising enterocolitis occurred in space-time clusters with a decreasing secular trend in Sweden.

AIM: This study investigated space-time clustering of neonatal necrotising enterocolitis over three decades. METHODS: Space-time clustering analyses objects that are grouped by a specific place and time. The Knox test and Kulldorff's scan statistic were used to analyse space-time clusters in 808 children diagnosed with necrotising enterocolitis in a national cohort of 2 389 681 children born between 1987 and 2009 in Sweden. The municipality the mother lived in and the delivery hospital defined closeness in space and the time between when the cases were born - seven, 14 and 21 days - defined closeness in time. RESULTS: The Knox test showed no indication of space-time clustering at the residential level, but clear indications at the hospital level in all the time windows: seven days (p = 0.026), 14 days (p = 0.010) and 21 days (p = 0.004). Significant clustering at the hospital level was found during 1987-1997, but not during 1998-2009. Kulldorff's scan statistic found seven significant clusters at the hospital level. CONCLUSION: Space-time clustering was found at the hospital but not residential level, suggesting a contagious environmental effect after delivery, but not in the prenatal period. The decrease in clustering over time may reflect improved routines to minimise the risk of contagion between patients receiving neonatal care.

Very low birthweight infants face an increased risk of bloodstream infections following the removal of umbilical catheters.

AIM: This study examined whether there was a temporal association between removing umbilical catheters and bloodstream infections (BSI) in a neonatal intensive care unit, as this is an area of research that has not received sufficient attention. METHODS: We carried out a retrospective study of all neonates receiving umbilical catheters during 2011 and 2012 in the neonatal intensive care unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The time from umbilical catheter removals to the first subsequent BSI was recorded. RESULTS: A total of 372 infants had umbilical catheters inserted and 146 of these had a birthweight of <1500 g. Antibiotics were discontinued when umbilical catheters were removed in 67 of these low birthweight infants and 20 of them needed to be retreated for BSI within 72 hours. We found that very low birthweight infants had a significantly increased risk of developing BSI if antibiotics were discontinued at the same time as umbilical catheters were removed, rather than being continued after removal (p < 0.001). CONCLUSION: This NICU study demonstrated a temporal association between removing umbilical catheters and BSI in very low birthweight infants weighting <1500 g.