Inotropic Therapy in Newborns, A Population-Based National Registry Study.

OBJECTIVE: To describe the use of inotropic drugs and the characteristics of neonates receiving such treatment in a national cohort of patients admitted to neonatal ICUs in Norway. DESIGN: A national registry study of patients included in the Norwegian Neonatal Network database 2009-2014. Demographic and treatment data, including the use of inotropic drugs (dopamine, dobutamine, epinephrine, norepinephrine, milrinone, and levosimendan) and outcomes, were retrieved and analyzed. SETTING: Neonatal ICUs in Norway. PATIENTS: All patients admitted to Norwegian neonatal ICUs 2009-2014 with a postmenstrual age of less than 310 days at admission, corresponding to a postnatal age of less than 28 days for a child born at term (n = 36 397). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Inotropic drugs were administered to 974 of 361,803 live born infants (0.27%) in the study period, representing 2.7% of the neonatal ICU patient population. The relative proportion of neonatal ICU patients receiving inotropes decreased with increasing gestational age, yet 41% of the patients receiving inotropes were born at term. Of note, 89.8% of treated patients received dopamine. Use of inotropes was particularly prevalent in patients with necrotizing enterocolitis (72.4%) and pulmonary hypertension (42.1%) and in patients with gestational age less than 28 weeks (28.2%). Inotropic treatment initiated in the first week of life (84.2%) was associated with birth asphyxia and pulmonary hypertension, whereas treatment initiated after the first week of life was associated with extremely preterm birth, neonatal surgery, neonatal sepsis, cardiac disease, and necrotizing enterocolitis. CONCLUSIONS: This comprehensive epidemiologic study indicates that less than 0.3% of newborns receive inotropic support in the neonatal period. Dopamine was the most commonly used drug. Relating inotrope use to clinical condition, gestational age, and postnatal age may be useful for clinicians and helpful in delineating relevant patient populations for future clinical trials.

Associations between unit workloads and outcomes of first extubation attempts in extremely premature infants below a gestational age of 26 weeks.

Objective: The objective was to explore whether high workloads in neonatal intensive care units were associated with short-term respiratory outcomes of extremely premature (EP) infants born <26 weeks of gestational age. Methods: This was a population-based study using data from the Norwegian Neonatal Network supplemented by data extracted from the medical records of EP infants <26 weeks GA born from 2013 to 2018. To describe the unit workloads, measurements of daily patient volume and unit acuity at each NICU were used. The effect of weekend and summer holiday was also explored. Results: We analyzed 316 first planned extubation attempts. There were no associations between unit workloads and the duration of mechanical ventilation until each infant's first extubation or the outcomes of these attempts. Additionally, there were no weekend or summer holiday effects on the outcomes explored. Workloads did not affect the causes of reintubation for infants who failed their first extubation attempt. Conclusion: Our finding that there was no association between the organizational factors explored and short-term respiratory outcomes can be interpreted as indicating resilience in Norwegian neonatal intensive care units.

Breastfed Infants With Spells, Tremor, or Irritability: Rule Out Vitamin B12 Deficiency.

BACKGROUND: In Norway, 5-10% of neonates and infants have biomarkers suggesting vitamin B12 deficiency from newborn screening tests and unselected clinical screening, respectively. AIMS: The aims were to identify risk factors and describe presenting symptoms and biochemical profiles in infants diagnosed with vitamin B12 deficiency. METHODS: In this case-control study, we searched hospital medical records for infants younger than one year born in 2011-2018, diagnosed with vitamin B12 deficiency. We compared 85 cases with a control group of 252 infants aged 3-7 months. Parents completed questionnaires. RESULTS: Of the 85 cases with vitamin B12 deficiency, 80% presented with spells (37%) of apneas, motor seizures, or absences within the first two months of life. Tremor (29%) and irritability (18%) were the most common findings at the first examination. Serum total homocysteine ≥10 µmol/L was found in 77% of cases compared to 28% of controls (P < 0.001). None of the mothers were vegetarians, but 25% reported a previous history of vitamin B12 deficiency and 7% had celiac disease. The dose of nitrous oxide given during labor was significantly associated with infant serum total homocysteine level at diagnosis (r = 0.37, 95% confidence interval = 0.16-0.55, P < 0.001) for cases, but not for controls. CONCLUSION: Spells, tremor, and irritability are common findings in early infant vitamin B12 deficiency. Nitrous oxide given during labor is proposed as a contributing risk factor to the development of early infant vitamin B12 deficiency.

Predictors of extubation success: a population-based study of neonates below a gestational age of 26 weeks.

OBJECTIVE: The aim of the study was to investigate first extubation attempts among extremely premature (EP) infants and to explore factors that may increase the quality of clinical judgement of extubation readiness. DESIGN AND METHOD: A population-based study was conducted to explore first extubation attempts for EP infants born before a gestational age (GA) of 26 weeks in Norway between 1 January 2013 and 31 December 2018. Eligible infants were identified via the Norwegian Neonatal Network database. The primary outcome was successful extubation, defined as no reintubation within 72 hours after extubation. RESULTS: Among 482 eligible infants, 316 first extubation attempts were identified. Overall, 173 (55%) infants were successfully extubated, whereas the first attempt failed in 143 (45%) infants. A total of 261 (83%) infants were extubated from conventional ventilation (CV), and 55 (17%) infants were extubated from high-frequency oscillatory ventilation (HFOV). In extubation from CV, pre-extubation fraction of inspired oxygen (FiO2) ≤0.35, higher Apgar score, higher GA, female sex and higher postnatal age were important predictors of successful extubation. In extubation from HFOV, a pre-extubation FiO2 level ≤0.35 was a relevant predictor of successful extubation. CONCLUSIONS: The correct timing of extubation in EP infants is important. In this national cohort, 55% of the first extubation attempts were successful. Our results suggest that additional emphasis on oxygen requirement, sex and general condition at birth may further increase extubation success when clinicians are about to extubate EP infants for the first time.

The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants.

BACKGROUND: Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. AIMS: To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 µmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. METHODS: In a prospective study we clinically examined 252 infants aged 3-7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. RESULTS: Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. CONCLUSION: We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.

Neonatal Morbidity and 1-Year Survival of Extremely Preterm Infants.

OBJECTIVE: To determine 1-year survival and major neonatal morbidities (intracranial hemorrhage grade >2, cystic periventricular leukomalacia, retinopathy of prematurity grade >2, necrotizing enterocolitis, severe bronchopulmonary dysplasia) among extremely preterm infants in Norway in 2013-2014, and to compare the results to the first Norwegian Extreme Prematurity Study 1999-2000 and similar contemporary European population-based studies. METHODS: Population-based study of all infants born at 22 through 26 weeks' gestation in Norway in 2013-2014. Prospectively collected data were obtained by linking data in the Norwegian Neonatal Network to the Medical Birth Registry of Norway. RESULTS: Of 420 infants (incidence 3.5 per 1000 births), 145 were stillborn (34.5%), 275 were live-born (82.3% of the 334 fetuses alive at admission for obstetrical care), and 251 (91.3% of live-born infants) were admitted to a neonatal unit. The survival among live-born infants was 18% at 22 weeks, 29% at 23 weeks, 56% at 24 weeks, 84% at 25 weeks and 90% at 26 weeks (for each week increment in gestational age: odds ratio 3.3; 95% confidence interval, 2.4-4.4). Among infants surviving to 1 year of age, major neonatal morbidity was diagnosed in 55%. Decreasing gestational age was moderately associated with rates of major morbidity (odds ratio 1.6; 95% confidence interval, 1.2-2.2). CONCLUSIONS: Compared to the previous 1999-2000 cohort, the rate of stillbirth before admission to an obstetrical unit increased, whereas the survival rate among live born infants was similar in our 2013-2014 cohort. Neonatal morbidity rates remain high among extremely preterm infants.