Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.

BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).

Unpredictable supplementation of vitamin D to infants in the neonatal intensive care unit: An experimental study.

AIM: Extremely premature infants receive nutrition and medication through nasogastric tubes. Breastmilk given accordingly is subject to fat loss. This study aimed to investigate whether this could also apply to vitamin D. METHODS: A questionnaire investigated vitamin D administration at a level III neonatal intensive care unit in Sweden in 2021. Feeding simulations with breastmilk and various vitamin D mixtures were done accordingly. After administration, vitamin D3 concentration was analysed using chromatography with mass spectrometry, followed by repeated simulations with vitamin D mixtures without breastmilk in 2023. RESULTS: The questionnaire was completed by 10 persons. Vitamin D was administered as drops using an enteral syringe and a nasogastric tube in conjunction with a breastmilk meal. In the feeding simulations, vitamin D3 concentration after administration was significantly higher using a syringe alone compared to standard administration. When vitamins were administered according to standard but without breastmilk, 100% of the vitamin D and 40% of the multivitamins were lost. The vitamins adhered to the material, mainly in the nasogastric tube. CONCLUSION: Our findings indicate that standard vitamin D supplementation in the neonatal intensive care unit may be unpredictable when administered by enteral syringe and nasogastric tube. We suggest using direct oral administration whenever possible.

Sodium supply from administered blood products was associated with severe intraventricular haemorrhage in extremely preterm infants.

AIM: The aim of this study was to investigate the associations between sodium supply, fluid volume, sodium imbalances and severe intraventricular haemorrhage (IVH) in extremely preterm (EPT) infants. METHODS: We used data from the EXtremely PREterm infants in Sweden Study (EXPRESS) cohort consisting of all infants born at 22 to 26 gestational weeks from 2004 to 2007 and conducted a nested case-control study. For every infant with severe IVH (grade 3 or peri-ventricular haemorrhagic infarction), one IVH-free control infant with the birthday closest to the case infant and matched for hospital, sex, gestational age and birth weight was selected (n = 70 case-control pairs). RESULTS: Total sodium supply and fluid volume were higher in infants with severe IVH compared with controls [daily total sodium supply until postnatal Day 2: mean ± SD (mmol/kg/day): 5.49 ± 2.53 vs. 3.95 ± 1.91, p = 0.009]. These differences were accounted for by sodium and fluid from transfused blood products. High plasma sodium concentrations or large sodium fluctuations were not associated with severe IVH. CONCLUSION: Our results suggest a relationship between sodium-rich transfusions of blood products and severe IVH in EPT infants. It is unclear whether this is an effect of sodium load, volume load or some other transfusion-related factor.

Amino acid infusions in umbilical artery catheters enhance protein administration in infants born at extremely low gestational age.

AIM: It is challenging to provide extremely low gestational age neonates (ELGANs) with adequate protein supply. This study aimed to investigate whether amino acid (AA) infusion in the umbilical artery catheter (UAC) in ELGANs is safe and enhances protein supply and growth. METHOD: A before and after study including infants born <27 weeks, treated in Uppsala, Sweden, during 2004-2007, compared those receiving normal saline/10% dextrose in water with those receiving AA infusion in the UAC. Data were retrieved from the Extremely Preterm Infants in Sweden Study, hospital records and the Swedish Neonatal Quality Register. Group comparisons, univariate and multivariate analyses were conducted. RESULTS: AA group (n = 41, females 39%) received on average approximately 0.3 g/kg/day more protein during the first postnatal week, compared to control group (n = 30, females 40%) (unstandardised coefficient (B) 0.26, p .001) but no difference was noted during 8-28 postnatal days. The type of infusion was not associated with growth variables. The incidence of neonatal morbidities and UAC-related thrombosis did not differ between the groups. CONCLUSION: AA infusions in the UACs in ELGANs is safe and enhances protein supply during the first postnatal week. However, this practice is not associated with growth during the first 28 postnatal days.

Parents experiences of feeding their extremely preterm children during the first 2-3 years - A qualitative study.

AIM: To describe parents of extremely preterm children experiences regarding feeding of their children during the first 3 years of the child's life. METHODS: This is a qualitative study involving interviews conducted with 12 parents of nine children who had been cared for at one neonatal intensive care unit in Sweden. The interviews were conducted between May and September 2018; the data were analysed using qualitative content analysis. RESULTS: All parents experienced some difficulties with their child's eating development and described feeding their child as sometimes both difficult and frustrating. Variation in when these difficulties arose made it hard for the parents to obtain the individual support they wanted and needed. Parents experienced a need for more support - from both staff members and parents with similar experiences - during and after their child's stay at the NICU. CONCLUSION: All parents participating in the study experienced difficulties during some phase of their child's feeding development. They expressed the need for more specialised support both during and after their child's time at the hospital.

Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks.

AIM: Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35 + 0 weeks. METHODS: A PubMed search-based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations. RESULTS: Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold-based screening and treatment protocol presented as a flow chart was developed. CONCLUSION: An updated and evidence-based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia-related long-term sequelae.

Postnatal growth in children born small for gestational age with and without smoking mother.

BACKGROUND: Maternal smoking impairs fetal growth; however, if postnatal growth differs between children born small for gestational age (SGA) with smoking and non-smoking mother is unknown. METHODS: Cohort-study of term born children born appropriate for gestational age with non-smoking mother (AGA-NS, n = 30,561), SGA (birthweight <10th percentile) with smoking mother (SGA-S, n = 171) or SGA with non-smoking mother (SGA-NS, n = 1761). Means of height and weight measurements, collected at birth, 1.5, 3, 4, and 5 years, were compared using a generalized linear mixed effect model. Relative risks of short stature (<10th percentile) were expressed as adjusted risk ratios (aRR). RESULTS: At birth, children born SGA-S were shorter than SGA-NS, but they did not differ in weight. At 1.5 years, SGA-S had reached the same height as SGA-NS. At 5 years, SGA-S were 1.1 cm taller and 1.2 kg heavier than SGA-NS. Compared with AGA-NS, SGA-S did not have increased risk of short stature at 1.5 or 5 years, while SGA-NS had increased risk of short stature at both ages; aRRs 3.0 (95% CI 2.6;3.4) and 2.3 (95% CI 2.0;2.7), respectively. CONCLUSIONS: Children born SGA-S have a more rapid catch-up growth than SGA-NS. This may have consequences for metabolic and cardiovascular health in children with smoking mothers.

Changing diagnostic criteria for gestational diabetes in Sweden - a stepped wedge national cluster randomised controlled trial - the CDC4G study protocol.

BACKGROUND: The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden ( www.cdc4g.se/en ) is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. METHODS: This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. DISCUSSION: The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child. TRIAL REGISTRATION: CDC4G is listed on the ISRCTN registry with study ID ISRCTN41918550 (15/12/2017).

High birthweight was not associated with altered body composition or impaired glucose tolerance in adulthood.

AIM: To investigate whether a high birthweight was associated with an increased proportion of body fat or with impaired glucose tolerance in adulthood. METHODS: Our cohort comprised 27 subjects with birthweights of 4500 g or more, and 27 controls with birthweights within ±1 standard deviation scores, born at Uppsala University Hospital 1975-1979. The subjects were 34-40 years old at the time of study. Anthropometric data was collected, and data on body composition was obtained by air plethysmography and bioimpedance and was estimated with a three-compartment model. Indirect calorimetry, blood sampling for fasting insulin and glucose as well as a 75 g oral glucose tolerance test were also performed. Insulin sensitivity was assessed using homoeostasis model assessment 2 and Matsuda index. RESULTS: There were no differences in body mass index, body composition or insulin sensitivity between subjects with a high birthweight and controls. CONCLUSION: In this cohort of adult subjects, although limited in size, those born with a moderately high birthweight did not differ from those with birthweights within ±1 standard deviation scores, regarding body composition or glucose tolerance.

Hyperglycemia in Extremely Preterm Infants-Insulin Treatment, Mortality and Nutrient Intakes.

OBJECTIVE: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants. STUDY DESIGN: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data. RESULTS: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05). CONCLUSIONS: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

Association Between Preterm Birth and Lower Adult Height in Women.

We examined whether being born preterm was associated with changes in adult anthropometry in women. We assessed data on 201,382 women (born in 1973-1988) from the Swedish Birth Register. The mean age was 26.0 years. Of the women in our cohort, 663 were born very preterm (<32 weeks of gestation), 8,247 were born moderately preterm (at least 32 weeks but <37 weeks), and 192,472 were born at term (37-41 weeks). Subgroup analyses were carried out among siblings and also after adjustment for maternal anthropometric data. Statistical tests were 2-sided. Decreasing gestational age was associated with lower height (-1.1 mm per week of gestation; P < 0.0001), so that women who were born very preterm were on average 12 mm shorter than women who were born moderately preterm (P < 0.0001) and 17 mm shorter than women born at term (P < 0.0001). Compared with women who were born at term, those who were born very preterm had 2.9 times higher odds of short stature (<155.4 cm), and those born moderately preterm had 1.43 times higher odds. Subgroup analyses showed no differences between women born moderately preterm and those born at term but accentuated differences from women born very preterm. Among siblings (n = 2,388), very preterm women were 23 mm shorter than those born at term (P = 0.003), with a 20-mm difference observed in subgroup analyses (n = 27,395) that were adjusted for maternal stature (P < 0.001). A shorter final height was associated with decreasing gestational age, and this association was particularly marked in women born very preterm.

Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants.

BACKGROUND: Hyper- and hyponatremia occur frequently in extremely preterm infants. Our purpose was to investigate plasma sodium (P-Na) concentrations, the incidence of hyper- and hyponatremia, and the impact of possible predisposing factors in extremely preterm infants. METHODS: In this observational study, we analyzed data from the EXtremely PREterm (< 27 wk.) infants in Sweden Study (EXPRESS, n = 707). Detailed nutritional, laboratory, and weight data were collected retrospectively from patient records. RESULTS: Mean ± SD P-Na increased from 135.5 ± 3.0 at birth to 144.3 ± 6.1 mmol/l at a postnatal age of 3 d and decreased thereafter. Fifty percent of infants had hypernatremia (P-Na > 145 mmol/l) during the first week of life while 79% displayed hyponatremia (P-Na < 135 mmol/l) during week 2. Initially, the main sodium sources were blood products and saline injections/infusions, gradually shifting to parenteral and enteral nutrition towards the end of the first week. The major determinant of P-Na and the risks of hyper- and hyponatremia was sodium supply. Fluid volume provision was associated with postnatal weight change but not with P-Na. CONCLUSION: The supply of sodium, rather than fluid volume, is the major factor determining P-Na concentrations and the risks of hyper- and hyponatremia.

Body Mass Index, Overweight, and Obesity in Swedish Women Born Post-term.

BACKGROUND: There is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. METHODS: Data were collected at first antenatal visit (~10-12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (≥43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110). RESULTS: Increasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2) . The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term. CONCLUSIONS: Post-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation.

Intakes of Micronutrients Are Associated With Early Growth in Extremely Preterm Infants.

OBJECTIVES: The aim of the study was to describe micronutrient intakes and explore possible correlations to growth during the first 70 days of life in extremely preterm infants. METHODS: Retrospective population-based study including extremely preterm infants (<27 weeks) born in Sweden during 2004-2007. Detailed nutritional and growth data were derived from hospital records. RESULTS: Included infants (n = 531) had a mean gestational age of 25 weeks and 2 days and a mean birth weight of 765 g. Estimated and adjusted intakes of calcium, phosphorus magnesium, zinc, copper, selenium, vitamin D, and folate were lower than estimated requirements, whereas intakes of iron, vitamin K, and several water-soluble vitamins were higher than estimated requirements. High iron intakes were explained by blood transfusions. During the first 70 days of life, taking macronutrient intakes and severity of illness into account, folate intakes were positively associated with weight (P = 0.001) and length gain (P = 0.003) and iron intake was negatively associated with length gain (P = 0.006). CONCLUSIONS: Intakes of several micronutrients were inconsistent with recommendations. Even when considering macronutrient intakes and severity of illness, several micronutrients were independent predictors of early growth. Low intake of folate was associated with poor weight and length gain. Furthermore, high iron supply was associated with poor growth in length and head circumference. Optimized early micronutrient supply may improve early growth in extremely preterm infants.

School performance after preterm birth.

BACKGROUND: An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. METHODS: We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. RESULTS: Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31-33 weeks was on average 3.85 (95% confidence interval = -4.36 to -3.35) centiles lower than for children born at 40 weeks. For births at 22-24 weeks, the corresponding figure was -23.15 (-30.32 to -15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. CONCLUSIONS: Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

Perioperative nutrition in extremely preterm infants undergoing surgical treatment for patent ductus arteriosus is suboptimal.

AIM: To evaluate perioperative nutrition in extremely preterm infants undergoing surgery for patent ductus arteriosus (PDA). METHODS: This is a population-based study of extremely preterm infants born in Sweden during 2004-2007 and operated on for PDA. Data on perioperative nutrition were obtained from hospital records. All enteral and parenteral nutrients and blood products were used to calculate daily nutritional intakes, starting 3 days before and ending 3 days after surgery. Data are mean (95% confidence intervals). RESULTS: Study infants (n = 140) had a mean gestational age (GA) of 24.8 weeks, and mean birth weight was 723 g. Energy and macronutrient intakes were below minimal requirements before, during and after PDA surgery. On the day of surgery, energy intake was 78 (74-81) kcal/kg/day, protein 2.9 (2.7-3.2) g/kg/day, fat 2.5 (2.3-2.7) g/kg/day and carbohydrate intake 10.7 (10.2-11.2) g/kg/day. Nutrition did not vary in relation to GA, but infants operated early (0-6 days after birth) received poorer nutrition than infants operated at older age. Fluid intake was 164 (159-169) mL/kg/day, and it did not vary during the week of surgery. CONCLUSION: Perioperative nutrition in extremely preterm infants undergoing PDA surgery in Sweden is suboptimal and needs to be improved. The significance of malnutrition for outcome after PDA surgery remains unclear and requires further investigation.

Combined maternal central adiposity measures in relation to infant birth size.

Improvement of prenatal identification of large-for-gestational-age (LGA) infants could lower the risk for adverse outcomes. Therefore, we sought to evaluate the association of a combination of maternal waist circumference (WC) and abdominal fat depths with infant birth size. A cohort study including 1240 women was performed between 2015 and 2018 at Uppsala University Hospital, Sweden. Maternal WC was measured at the first antenatal visit, and visceral (VF) and subcutaneous (SCF) fat depths by ultrasound at the second-trimester anomaly scan. Waist circumference, VF, and SCF were categorized as low or high (cut-offs WC ≥ 88 cm, VF ≥ 54 mm, SCF ≥ 21 mm). Outcomes were birth weight standard deviation score (BWSDS) and LGA (BWSDS > 90th and > 97th percentile). Secondary outcome was small-for-gestational-age (SGA, BWSDS < 10th and < 3rd percentile). Univariate analysis of variance and logistic regression analyses were performed adjusted for maternal weight, height, parity, smoking, country of birth, pregestational diabetes, and chronic hypertension. For both high and low WC, high VF was positively associated with BWSDS and LGA. There was no association with SGA. The results did not demonstrate any value of the combination of WC and fat depth measures in predicting infant birth size but suggested VF as a marker for large infants.

Differential gene expression in two consecutive pregnancies between same sex siblings and implications on maternal constraint.

The objective of this study was to investigate how placental gene expression differs in two consecutive pregnancies in same sex siblings, and its possible association with the "maternal constraint" hypothesis. Material was gathered from the BASIC study (Biological, Affect, Stress, Imaging, and Cognition in Pregnancy and the Puerperium), a population based prospective study that was started in 2009 in Uppsala. Over 900 specimens of placenta biopsies were collected and out of these 10 women gave birth twice, to the same sex child, and were included in this study. The total RNA was isolated and prepared from frozen villous tissue from the placenta and further analyzed by use of Ion AmpliSeq Human Transcriptome Gene Expression kit. A total of 234 genes differed significantly between the first and second pregnancy placentas, when adjusting for delivery mode, maternal BMI and gestational age. Of special interest was the down-regulated group of genes in the second pregnancy. Exemplified by Pentraxin 3, SRY-Box Transcription Factor 9, and Serum Amyloid A1, which all were associated with biological processes involved in the immune system and inflammation. Further, protein-protein interaction analysis visualized them as hub genes interacting with several of the other differentially expressed genes. How these altered gene expressions affect maternal constraint during pregnancy needs further validation in lager study cohorts and also future validation in functional assays.

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.

Mothers' acceptability of using novel technology with video and audio recording during newborn resuscitation: A cross-sectional survey.

OBJECTIVE: This study aims to assess the acceptability of a novel technology, MAchine Learning Application (MALA), among the mothers of newborns who required resuscitation. SETTING: This study took place at Bharatpur Hospital, which is the second-largest public referral hospital with 13 000 deliveries per year in Nepal. DESIGN: This is a cross-sectional survey. DATA COLLECTION AND ANALYSIS: Data collection took place from January 21 to February 13, 2022. Self-administered questionnaires on acceptability (ranged 1-5 scale) were collected from participating mothers. The acceptability of the MALA system, which included video and audio recordings of the newborn resuscitation, was examined among mothers according to their age, parity, education level and technology use status using a stratified analysis. RESULTS: The median age of 21 mothers who completed the survey was 25 years (range 18-37). Among them, 11 mothers (52.4%) completed their bachelor's or master's level of education, 13 (61.9%) delivered first child, 14 (66.7%) owned a computer and 16 (76.2%) carried a smartphone. Overall acceptability was high that all participating mothers positively perceived the novel technology with video and audio recordings of the infant's care during resuscitation. There was no statistical difference in mothers' acceptability of MALA system, when stratified by mothers' age, parity, or technology usage (p>0.05). When the acceptability of the technology was stratified by mothers' education level (up to higher secondary level vs. bachelor's level or higher), mothers with Bachelor's degree or higher more strongly felt that they were comfortable with the infant's care being video recorded (p = 0.026) and someone using a tablet when observing the infant's care (p = 0.046). Compared with those without a computer (n = 7), mothers who had a computer at home (n = 14) more strongly agreed that they were comfortable with someone observing the resuscitation activity of their newborns (71.4% vs. 14.3%) (p = 0.024). CONCLUSION: The novel technology using video and audio recordings for newborn resuscitation was accepted by mothers in this study. Its application has the potential to improve resuscitation quality in low-and-middle income settings, given proper informed consent and data protection measures are in place.