Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016.

Importance: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective: To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants: All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures: Delivery at 22-26 weeks' gestational age. Main Outcomes and Measures: The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results: During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008). Conclusions and Relevance: Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age.

BACKGROUND: Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children. METHODS: A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels. RESULTS: After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up. CONCLUSION: Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass.

EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden.

AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions. METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.

IMPORTANCE: Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. OBJECTIVE: To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. MAIN OUTCOMES AND MEASURES: Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-lll), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. RESULTS: At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-lll assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). CONCLUSIONS AND RELEVANCE: Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth.

Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial.

OBJECTIVE: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). DESIGN: Prospective. SETTING: University hospital. PATIENT(S): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. INTERVENTION(S): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. MAIN OUTCOME MEASURE(S): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. RESULT(S): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. CONCLUSION(S): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

C-Peptide Suppression During Insulin Infusion in the Extremely Preterm Infant Is Associated With Insulin Sensitivity.

CONTEXT: Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants. OBJECTIVE: To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high-frequency sampling regimen in extremely preterm infants treated with insulin because of hyperglycemia. DESIGN: Prospective longitudinal cohort study. SETTING: Two university hospitals in Sweden between December 2015 and September 2016. PATIENTS AND INTERVENTION: Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose >10 mmol/L) at the start of insulin infusion, at 12, 24, and every 24 hours thereafter during ongoing infusion, and 12, 24, and 72 hours after the end of insulin infusion. MAIN OUTCOME MEASURES: Longitudinal serum concentrations of insulin and C-peptide and plasma glucose levels. RESULTS: During insulin infusion, the serum C-peptide concentrations decreased compared with at start of infusion (P = 0.036), and then increased after ending the infusion. Individual insulin sensitivity based on the nonfasting plasma glucose/insulin ratio at the start of insulin infusion correlated with the initial decrease in serum ΔC-peptide[after 12h] (P = 0.007) and the degree of lasting decrease in serum ΔC-peptide[after end of infusion] (P = 0.015). CONCLUSION: Exogenous insulin infusion suppressed the C-peptide concentration to individually different degrees. In addition, the effect of insulin infusion on ß cells may be linked to individual insulin sensitivity, where a low insulin sensitivity resulted in a more pronounced decrease in C-peptide during insulin infusion.

N-acetylcysteine administration during the first week of life does not improve lung function in extremely low birth weight infants.

Oxygen toxicity is thought to be an important factor involved in development of bronchopulmonary dysplasia (BPD) in the very preterm infant. Glutathione (GSH) plays a major role in the antioxidant defense system in the preterm lung and there are theoretical implications that N-acetylcysteine (NAC) treatment could improve its function. The purpose of this study was to investigate whether NAC treatment during the first week of life to preterm infants improved neonatal lung function as a measure of lung injury. The study was part of a multi-center Nordic controlled trial with prophylactic intravenous NAC treatment (16-32 mg/kg/day) for 6 days in newborn infants with birth weights 500-999 g. Lung mechanics, with calculations of compliance and resistance of the respiratory system, together with measurements of functional residual capacity and indices of gas mixing efficiency in the lung, were performed in 33 preterm infants (18 received NAC and 15 placebo) before discharge from the NICU. Median (range) gestational age was 25 (24-28) weeks in the NAC-treated infants and 25 (24-29) in the placebo group. Corresponding mean (SD) birth weights were 0.774 (0.11) and 0.761 (0.12) kg respectively. Lung function measurements did not show any significant differences between NAC-treated infants compared to placebo when examined before discharge from the NICU. We conclude that prophylactic NAC treatment to extremely low birth weight infants during the first week of life does not improve lung function at term.

N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial.

OBJECTIVE: To evaluate whether N-acetylcysteine (NAC) infusion during the first week of life reduces the risk of death or bronchopulmonary dysplasia (BPD) in infants with extremely low birth weight. Study design In a Nordic multicenter, double-blind trial, infants (n=391) weighing 500 to 999 g and on ventilator or nasal continuous positive airway pressure were randomized before the age of 36 hours to receive NAC 16 to 32 mg/kg/d (n=194) or placebo (n=197) intravenously for 6 days. Primary end points were death or BPD, defined as supplementary oxygen requirement at 36 weeks' gestational age. RESULTS: There was no difference in the combined incidence of the primary end points death or BPD, 51% vs. 49%, between the NAC group and control group. Also similar was the incidence of BPD in survivors at 36 weeks' gestational age, 40% vs. 40%, and the mean oxygen requirement at the age of 28 days, 31.2% vs. 30.7%, respectively. The severity of BPD was similar in both groups. CONCLUSIONS: A 6-day course of intravenous N-acetylcysteine at the dosage used does not prevent BPD or death in infants with extremely low birth weight.