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Advances in ventilation strategies for infants in the NICU have led to increased survival of extremely preterm infants. More than 75% of infants born at less than or equal to 27 weeks’ gestation require initial mechanical ventilation for survival due to developmental immaturity of their lungs and respiratory drive. Various ventilators using different technologies and involving multiple management strategies are available for use in this population. Centers across the world have successfully used conventional, high-frequency oscillatory and high-frequency jet ventilation to manage respiratory failure in extremely preterm infants. This review explores the existing evidence for each mode of ventilation and the importance of individualizing ventilator management strategies when caring for extremely preterm infants.

OBJECTIVE: This study evaluates the 24 month follow up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score

Objective Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks.Study Design Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants Results The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort.Conclusion Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born

After birth, breastfeeding is the exclusive source of hormonal signaling between mother and infant. Hospitalized infants often receive donor milk when their own mother’s milk is unavailable. The presence of insulin, leptin, cortisol, progesterone, and testosterone was examined in samples from milk bank donors and mothers of preterm infants. We further investigated the effect of Holder pasteurization (HoP) on hormone levels. Comparing nonpasteurized samples, leptin levels were nearly threefold higher in milk from mothers of preterm infants versus donated milk, and regardless of milk source, leptin levels were significantly decreased by HoP. Insulin concentrations were also decreased by HoP, and among mothers of preterm infants, obesity was associated with significantly higher content of leptin and insulin. While combined use of donor milk and HoP was associated with cortisol levels nearly threefold higher than those in nonpasteurized own mother’s milk, progesterone and testosterone content did not differ by source or pasteurization. The hormonal composition of breast milk is impacted by HoP and maternal obesity. Compared to nonpasteurized maternal milk, use of pasteurized donor milk dramatically decreases the intake of leptin while increasing the intake of cortisol. Further research is necessary to define optimal breast milk processing practices.

The approach to clinical care of infants born at 22 weeks’ gestation must be consistent and well-designed if optimal results are to be expected. Publications from several international centers have demonstrated that, although there may be variance in aspects of care in this vulnerable population, treatment should be neither random nor inconsistent. In designing a standardized approach, careful attention should be paid to the unique anatomy, physiology, and biochemistry of this vulnerable patient population. Emerging evidence, suggesting a link between cardiopulmonary health and longer-term sequela, highlights the importance of understanding the relationship between cardiorespiratory illnesses of the 22-week infant, treatments provided, and subsequent cardiopulmonary development. In this review we will provide an overview to our approach to cardiopulmonary assessment and treatment, with a particular emphasis on the importance of early recognition of atypical phenotypes, timely interventions with evidence-based treatments, and longitudinal monitoring.

Survival of preterm newborn infants have increased steadily since the introduction of surfactant treatment and antenatal steroids. In the absence of randomized controlled trials on ventilatory strategies in extremely preterm infants, we present ventilatory strategies applied during the initial phase and the continued ventilatory care as applied in three centers with proactive prenatal and postnatal management and well documented good outcomes in terms of mortality and morbidity in this cohort of infants.

OBJECTIVE: To determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18–22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage (adjusted relative risk [aRR] = 1.0; 95% confidence interval [CI]: 0.87–1.14). A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (p = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR=0.81; 95% CI: 0.64 to 1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference

Background: Cord blood leptin increases with advancing gestation. Preterm delivery leads to premature separation from the maternal and placental leptin source predisposing infants to postnatal leptin deficiency, but this has not been fully described. Method: Blood leptin levels were measured for infants born before 33 weeks gestation daily for the first 2 days, then weekly until 36 weeks postmenstrual age (PMA). Cord blood was obtained to provide gestational age (GA)-specific standards. Results: Cord blood leptin levels were positively associated with GA at birth, maternal body mass index (BMI) and pregnancy weight gain (all P

OBJECTIVES To compare survival and short-term respiratory outcomes of infants weighing

Pasteurized donor human milk is in wide use for preterm infants in neonatal intensive care units when maternal milk is unavailable. Pasteurization of donor milk is required to prevent bacterial contamination, and multiple methods are used in the non-profit and commercial milk banking industries. Pasteurization results in changes in the nutrient and bioactive components in donor milk compared to unpasteurized human milk, and these changes vary by the type of pasteurization process. Other milk bank practices including freezing of milk, pooling of milk from multiple donors and use of pre-processing macronutrient analysis also affect the nutritional composition of donor milk. This review compiles evidence regarding three common pasteurization techniques for donor milk: Holder pasteurization, vat pasteurization, and retort pasteurization and their effects on the nutritional content and bioactive factors in human milk. It also includes review of literature investigating the impact of freezing and storage, and best practices for multi-donor milk pooling.

Antenatal steroids (ANS) are used widely for women at risk of preterm delivery. Evidence on the effects of ANS on thyroid hormone function in preterm infants is limited. To determine effects of ANS on thyroid hormone function in preterm infants. A retrospective cohort study of preterm infants born before 30 weeks of gestation. Infants were divided into no ANS, partial ANS, and complete ANS groups. Thyroid function tests at day of life 30 were compared. 260 Infants were included. A significantly higher proportion of patients were started on levothyroxine (LT4) in no ANS group and partial ANS group compared to complete ANS group. Logistic regression analysis revealed that infants in no ANS group are more likely to have TSH > 6 μIU ml−1 and started on LT4 compared to complete ANS group. Infants in no ANS group are more likely to have thyroid dysfunction compared to complete ANS group.

OBJECTIVE: Hypothermia occurs frequently in the first minutes after birth in preterm infants. Hyperthermia also occurs, often as a consequence of efforts to provide thermal support. Both hypothermia and hyperthermia are potentially harmful. Our objective was to examine the distribution of admission temperatures of very low birth weight (VLBW) infants, the effect of gestational age on admission temperatures, and the time required for correction of low temperatures. METHODS: Admission axillary temperatures were retrieved from the medical records for all VLBW infants born in our hospital during a 5-year period. The temperatures were classified as severe (

AIM To characterise the relationship between bronchopulmonary dysplasia (BPD) severity and cognition in the post-surfactant era. METHODS This was a single-centre retrospective analysis of a cohort of infants born 2009-2012. Inclusion criteria were as follows: admission within 48 hours of birth, gestational age 22-0/7-31-6/7 weeks, birthweight 400-1500 g and Bayley Scales of Infant and Toddler Development-III testing at 18-26 months corrected age. Infants (n = 151) were classified by BPD severity with the NIH Workshop definition. Generalised linear modelling and multivariate logistic regression were performed. RESULTS Bayley cognitive score was not associated with BPD severity in univariate (p = 0.053) or multivariate (p = 0.503) analysis. About 27% of infants with no/mild BPD, 33% of infants with moderate BPD and 40% of infants with severe BPD had a cognitive score

BackgroundWe examined changes in the causes and circumstances of death in our neonatal intensive care unit (NICU) over 20 years.MethodsFor 551 infants who died between 1993 and 2013, the principal cause of death was recorded. Circumstances of death were assigned to one of the following four categories: death following cardiopulmonary resuscitation (CPR), death while being mechanically ventilated without CPR, death after withholding life-support interventions, and death after withdrawal of life support. Data were compared across four 5-year epochs.ResultsThe mortality rate decreased from 5.9% in the first epoch to 3.0% in the last epoch (P

OBJECTIVE: To evaluate the effects of early treatment with CPAP on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (24–0/7 to 27–6/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks’ postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks’ PMA and follow-up outcomes at 18–22 months’ corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: 810 of 1316 infants enrolled in SUPPORT (414 in intervention group, 396 in control group) had growth data analyzed. Median gestational age was 26 weeks and mean birthweight was 839 grams. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between groups. In a regression model, growth rates between birth and 36 weeks’ PMA as well as growth rates during multiple intervals from birth to day 7, day 7 to14, day 14 to 21, day 21 to 28, day 28 to 32 weeks’ PMA, and 32 weeks’ PMA to 36 weeks’ PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of Bayley III cognitive score

ObjectiveBreast-feeding initiation rates have increased in the USA; however, maintenance of breast-feeding for recommended durations is low. The objective of the present study was to identify factors that may facilitate breast-feeding for longer durations among first-time mothers, including physiological and social experiences and changes in maternal perceptions.DesignSurvival analysis and linear regression methods were used to explore the relationship between experiences and breast-feeding duration, and the possible mediating effect of changes in maternal perceptions.SettingSecondary data from the Infant Feeding Practices Study II, conducted in the USA between 2005 and 2007.SubjectsData from 762 first-time mothers who ever breast-fed were analysed.ResultsExperiencing trouble with baby’s latch, problems with milk flow/supply and painful breast-feeding were significantly associated with breast-feeding duration (64, 26 and 36 % shorter duration, respectively). Meanwhile, positive changes in perception with respect to breast-feeding self-efficacy, opinion about infant feeding and belief about breast milk were associated with 16–27 % longer duration. Furthermore, changes in perception were observed to partially mediate the impact of physiological experiences on breast-feeding duration.ConclusionsPerceptions of breast-feeding self-efficacy, beliefs and opinions can change over time and are influenced by breast-feeding experiences. The combined effect of experience and perception plays a key role in influencing breast-feeding duration. Future research should explore interventions to maintain or improve these perceptions while accounting for physiological experiences to support breast-feeding for recommended durations among first-time mothers.

Objective We compared an infrared temporal artery thermometer with our clinical standard axillary thermometer for temperature measurements in neonatal patients. Study Design We measured temporal artery (Tta), axillary (Tax, clinical standard), and rectal (Tr, gold standard) temperatures of 49 infants. The difference between Tr and Tta was compared with that between Tr and Tax, and the data were analyzed based on bed type and postmenstrual age. Results The mean Tta, Tax, and Tr were 37.16 (SD 0.36) °C, 36.61 (SD 0.30) °C, and 36.82 (SD 0.30) °C, respectively. The measurements by these methods were all significantly different. The mean Tr-Tax was 0.21 (SD 0.26) °C, and the mean Tr-Tta was −0.34 (SD 0.37) °C, indicating that Tax was closer to Tr than was Tta (p Conclusion Compared with the gold standard, Tr, Tta is not more accurate than Tax. The temporal artery thermometer was less accurate for infants in incubators than for infants in cribs. The accuracy of temporal artery temperature increased with postmenstrual age.

OBJECTIVE: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision. STUDY DESIGN: For infants born at

To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P .001) and pervasive developmental problems (P .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values .05).BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Objective To assess the outcomes in actively managed extremely preterm infants after admission to a neonatal intensive care unit. Study design Retrospective cohort of 255 infants born at 22-25 weeks of gestation between 2006 and 2015 at a single study institution. Infants were excluded for congenital anomaly, death in delivery room, or parental request for palliation (n = 7). Neurodevelopmental outcomes were analyzed for 169 of 214 survivors (78.9%) at 18-22 months of corrected age. Outcomes were evaluated using the Mann-Whitney U, χ2, or Fisher exact test, where appropriate. In addition, cognitive scores of the Bayley Scales of Infant-Toddler Development (3rd edition) were assessed using generalized estimating equations. Results Seventy infants born at 22-23 weeks of gestation (22 weeks, n = 20; 23 weeks, n = 50) and 178 infants born at 24-25 weeks of gestation (24 weeks, n = 79; 25 weeks, n = 99 infants) were included. Survival to hospital discharge of those surviving to NICU admission was 78% (55/70; 95% CI, 69%-88%) at 22-23 weeks and 89% (159/178; 95% CI, 84%-93% at 24-25 weeks; P = .02). No or mild neurodevelopmental impairment in surviving infants was 64% (29/45; 95% CI, 50%-77%) at 22-23 weeks and 76% (94/124; 95% CI, 68%-83%; P = .16) at 24-25 weeks. Conclusions Although survival was lower in infants born at 22-23 weeks than at 24-25 weeks of gestation, the majority of survivors in both groups had positive outcomes with no or mild neurodevelopmental impairments. Further evaluation of school performance is warranted.

Background. Pasteurized donor human milk (DHM) use for healthy newborns is increasing; however, no studies have explored its effect on breastfeeding outcomes. Patients and Methods. We enrolled 60 healthy, term breastfeeding newborns with ≥4.5% weight loss in the first 36 hours in a randomized controlled trial. Thirty newborns were randomly assigned to early limited-volume DHM supplementation and 30 newborns to exclusive breastfeeding. Mothers were surveyed at 1 week and 1, 2, and 3 months regarding the mode of infant feeding. Comparing infants randomized to DHM supplementation with those exclusively breastfeeding, there was no significant difference in the proportion using formula at 1 week (21% vs 7%, P = .15), nor in the proportion of any breastfeeding (79% vs 90%, P = .30) or breastfeeding without formula at 3 months (62% vs 77%, P = .27). Conclusion For newborns with ≥4.5% weight loss in the first 36 hours, early limited-volume supplementation with DHM is unlikely to have a significant favorable impact on breastfeeding outcomes.

Background: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the USA. We have previously shown in preclinical studies that sertraline exposure impacts cardiomyocyte development, leading to reductions in left ventricular size and cardiac function. Objectives: We hypothesized that in utero SSRI exposure will lead to reduced left ventricular dimensions and cardiac function on echocardiography immediately after birth. Methods: Twenty term infants with and 21 term infants without in utero exposure to SSRIs underwent echocardiograms to assess cardiac size and function. The exclusion criteria for infants were prematurity, small or large for gestational age, any respiratory or cardiovascular support needed after birth, and any major congenital malformation. Results: Infants exposed to in utero SSRIs had significantly reduced right ventricular dimensions in the diastole (controls 1.0 cm [0.86, 1.20], SSRI 0.89 cm [0.730, 1.05], p = 0.03), and left ventricular lengths in the diastole and systole (diastole: controls 3.4 cm [3.25, 3.65], SSRI 3.25 cm [3.10, 3.45], p = 0.03; systole: controls 2.9 cm [2.65, 3.05], SSRI 2.6 cm [2.50, 2.85], p = 0.01). No differences were observed in cardiac function. Importantly, there were no differences in maternal conditions or infant birth weight, body surface area, or gestational age. Conclusions: Our findings suggest an association between in utero exposure to SSRIs and ventricular size in infants. Given the increasing use of SSRIs during pregnancy and the importance of early life programming on future cardiovascular health, larger studies need to be completed to determine if in utero SSRI exposure impacts ventricular size.

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking versus delayed cord clamping among infants

Objective To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. Study design Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. Results Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. Conclusions MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia–ischemia. Trial registration Clinicaltrials.gov: NCT00614744 .

Moderate preterm infants are the largest group of preterm infants but are an understudied population. Care practices are adapted from studies of full term infants or extremely preterm infants. Studies are needed to tailor treatments for this vulnerable population. The NRN began investigation in this population with a registry of characteristics, and neonatal outcomes of these infants. This work compares outcomes of MPR with those of full term infants reported in the literature.

Our aims were to investigate the presence of pituitary glycoprotein hormones in preterm and donor milk, and to examine the effects of Holder pasteurization and refrigeration on the levels of these hormones. We measured follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) in milk samples from mothers who delivered prematurely (n = 27) and in samples of mothers who delivered at term and donated milk to the Mother&rsquo, s Milk Bank of Iowa (n = 30). The gonadotropins and TSH were present in similar amounts within human milk produced for preterm and term infants. FSH increased 21% after refrigeration (p &lt, 0.05), while LH declined by 39% (p &lt, 0.05). Holder pasteurization decreased LH by 24% (p &lt, 0.05) and increased TSH by 17% (p &lt, 0.05). Holder pasteurization followed by refrigeration resulted in a 21% increase in FSH and a 41% decrease in LH (both p &lt, 0.05), resulting in more than a 3-fold increase in donor milk FSH:LH ratios (p &lt, 0.05 versus fresh donor milk). Despite structural similarities, the gonadotropins are differentially impacted by Holder pasteurization and refrigeration, and this results in marked alterations in the relative amount of FSH and LH that may be administered to preterm infants, potentially swinging hormonal balance towards ovarian hyperstimulation in females and hypogonadism in males.

Objective To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. Study design A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. Results Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. Conclusions Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. Trial registration ClinicalTrials.gov NCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study)

ObjectiveTo assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight.Study designThis trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight

BACKGROUND AND OBJECTIVES: Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value. METHODS: A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) RESULTS: A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0–129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1–6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6–111) were associated with FSIQ CONCLUSIONS: Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes.

BACKGROUND: Oral feeding skills of moderately preterm infants are not mature at birth. AIMS: To establish the relationship between postmenstrual age at introduction of first oral feeding and attainment of full oral feeding and hospital discharge for moderately preterm infants. STUDY DESIGN: Multicenter retrospective analysis of a prospective cohort of moderately preterm infants admitted to a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospital. SUBJECTS: 6146 infants born at 29-33 weeks’ gestation from January 2012 to November 2013. OUTCOME MEASURES: Postmenstrual age at full oral feeding and at hospital discharge. RESULTS: The median postmenstrual age at first oral feeding was 33.9 weeks (interquartile range 33.1-34.3). For each week earlier at first oral feeding, full oral feeding occurred 4.5 days earlier (p

Objective To investigate associations in toddlers born extremely preterm ( Study design Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ2 test. We computed correlations between BITSEA and Bayley-III scores. Results Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores Conclusions Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention. Trial registration ClinicalTrials.gov : NCT00063063 and NCT00233324 .

Background: Maternal overweight and obesity are associated with decreased breastfeeding duration. Objective: This study aimed to identify barriers to breastfeeding continuation among overweight and obese mothers. Methods: A retrospective cohort study examining breastfeeding continuation barriers was conducted using results of the Centers for Disease Control and Prevention Pregnancy Risk Assessment Monitoring System survey from Illinois, Maine, and Vermont from 2004 to 2008. SAS Complex Survey version 9.3 was used for analysis. Results: Of 19 145 mothers surveyed, 3717 (19%) were obese and 4367 (23%) were overweight. Overall, 14 731 women initiated breastfeeding, and 6467 discontinued breastfeeding prior to survey completion, around 4 months postpartum. The most common reasons that mothers reported for discontinuing breastfeeding were insufficient milk supply, infant not satisfied with breast milk alone, and breastfeeding difficulty. Overweight and obese women, compared with women of normal weight, had higher odds of discontinuing breastfeeding because their babies were not satisfied by breast milk alone (overweight: odds ratio [OR] = 1.39, 95% confidence interval [CI], 1.16-1.68; obese: OR = 1.26, 95% CI, 1.03-1.54). Obese mothers, compared with normal weight mothers, had lower odds of discontinuing breastfeeding because it felt like the right time (OR = 0.64, 95% CI, 0.47-0.88) and higher odds of discontinuing due to breastfeeding difficulties (OR = 1.29, 95% CI, 1.05-1.58) and infant jaundice (OR = 1.81, 95% CI, 1.26-2.60). Conclusion: Obese and overweight mothers were significantly more likely to discontinue breastfeeding due to infant dissatisfaction with breast milk alone. Obese mothers had higher odds than normal weight mothers of discontinuing breastfeeding due to breastfeeding difficulties and infant jaundice. Breastfeeding education and support should be enhanced for this at-risk population.

Donor milk usage in the United States has increased substantially over the past 10 years. Between 2007 and 2011, donor milk use in level 3 and 4 neonatal ICUs increased from 25 to 45%.Most centers have written protocols based on birth weight or gestational age, and give donor milk in an effort to prevent necrotizing enterocolitis. The evidence for protection against necrotizing enterocolitis using bovine-fortified donor milk vs. formula is limited, although the exclusive human milk diet seems to offer protection compared to diets containing formula. Adequate growth can be achieved with donor milk fortified with either bovine or human milk-derived fortifiers, but use of additional fortification and protein supplementation may be required. Several randomized trials of donor milk vs. formula are ongoing in the very low birth weight population in North America that can answer important questions.Further research is needed before donor milk and the exclusive human milk diet are considered the standard of care.

Importance Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. Objective To characterize the outcomes of extremely preterm neonates younger than 27 weeks’ gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks’ postmenstrual age. Design, Setting, and Participants This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks’ gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks’ postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. Main Outcomes and Measures The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Results Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ. Conclusions and Relevance Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.

We sought to determine the impact of changes in breastfeeding rates on population health.We used a Monte Carlo simulation model to estimate the population-level changes in disease burden associated with marginal changes in rates of any breastfeeding at each month from birth to 12 months of life, and in rates of exclusive breastfeeding from birth to 6 months of life. We used these marginal estimates to construct an interactive online calculator (available at www.usbreastfeeding.org/saving-calc ). The Institutional Review Board of the Cambridge Health Alliance exempted the study.Using our interactive online calculator, we found that a 5% point increase in breastfeeding rates was associated with statistically significant differences in child infectious morbidity for the U.S. population, including otitis media (101,952 cases, 95% confidence interval [CI] 77,929-131,894 cases) and gastrointestinal infection (236,073 cases, 95% CI 190,643-290,278 cases). Associated medical cost differences were $31,784,763 (95% CI $24,295,235-$41,119,548) for otitis media and $12,588,848 ($10,166,203-$15,479,352) for gastrointestinal infection. The state-level impact of attaining Healthy People 2020 goals varied by population size and current breastfeeding rates.Modest increases in breastfeeding rates substantially impact healthcare costs in the first year of life.

Objective The evidence on the role of early pulmonary vascular disease (PVD) in the development of late pulmonary hypertension (PH) in the extremely preterm infants is limited. Objectives were to determine the incidence of early and late PH in extreme preterm infants and to evaluate the role of early PH as a risk factor for development of clinically detected late PH. Methods It was a retrospective analysis of early echocardiograms (day of life 5–14) in preterm infants, 22 to 27 weeks' gestation, admitted to the University of Iowa NICU between July 01, 2012 to June 30, 2015. Late echocardiograms performed for clinical suspicion of PH were also analyzed. Results A total of 154 infants were included in the study. Early PH was diagnosed in 31 (20%) infants. Twenty-four (16%) infants were evaluated for clinically suspected PH. Eight (5%) infants were diagnosed with late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of late PH (p = 0.99). Conclusion Early PH is common among extremely preterm infants (20%). Five percent of infants had clinically detected late PH. Infants with early PH had echocardiograms performed earlier than infants without the evidence of early PH. Early PH was not associated with the development of clinically detected late PH.

Objectives To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. Study design This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. Results WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. Conclusions Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. Trial registration ClinicalTrials.gov : NCT00063063 .

OBJECTIVES: To describe the frequency and findings of cranial imaging in moderately preterm (MPT) infants (born at 29 0/7–33 6/7 weeks of gestation) across centers, and to examine the association between abnormal imaging and clinical characteristics. STUDY DESIGN: We used data from the Neonatal Research Network MPT Registry, including the most severe early (≤28 days) and late (>28 days) cranial imaging. Stepwise logistic regression and CART analysis were performed after adjustment for gestational age (GA), antenatal steroids and center. RESULTS: Among 7,021 infants, 4,184 (60%) underwent cranial imaging. These infants had lower GAs and birth weights and higher rates of birth weight small-for-gestation, outborn birth, cesarean delivery; neonatal resuscitation and treatment with surfactant, compared with those without imaging (P < .0001). Imaging abnormalities noted in 15% of the infants included any intracranial hemorrhage (13.2%), grades 3–4 intracranial hemorrhage (1.7%), cystic periventricular leukomalacia (2.6%) and ventriculomegaly (6.6%). Histological chorioamnionitis [OR 1.47; 95% C.I.:1.19–1.83], GA [0.95; 95% C.I.: 0.94–0.97], antenatal steroids [OR 0.55; 95% C.I.: 0.41–0.74] and cesarean delivery [OR 0.66; 95% C.I.: 0.53–0.81] were associated with abnormal imaging. The center with the highest rate of cranial imaging, compared with the lowest, had a higher risk of abnormal imaging [OR 2.08; 95% CI: 1.10–3.92]. On the CART model, cesarean delivery, center, antenatal steroids and chorioamnionitis, in that order, predicted abnormal imaging. CONCLUSIONS: Among the 60% of MPT infants with cranial imaging, 15% had intracranial hemorrhage, cystic periventricular leukomalacia or late ventriculomegaly. Further correlation of imaging and long-term neurodevelopmental outcomes in MPT infants is needed.

To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT,29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants.Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared.MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P .01), including the percentage36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality.Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

Introduction Multiparas tend to initiate breastfeeding less than primiparas. While mothers often repeat the feeding method used for their first child with their second child, the way in which experiences and maternal perceptions related to breastfeeding one's first child may influence breastfeeding initiation with a second child remain underexplored. The objective of this study was to investigate whether physiological or social experiences, and related psychological factors, reported at the end of breastfeeding one's first child influence breastfeeding initiation with a second child. Methods Data from 174 multiparas who participated in the Infant Feeding Practices Study II, breastfed their first child, and completed the Year 6 Follow Up were analyzed using exact logistic regression. Results Mothers who reported experiencing trouble with the first baby's suck or latch had lower odds of initiating breastfeeding (OR 0.15, 95% CI 0.04-0.56) than those who did not report this experience, whereas mothers who agreed that breastfed children are less likely to become obese had greater odds of initiating breastfeeding with a second child (OR 11.49, 95% CI 1.56-513.18) than those who did not agree. Discussion Efforts to facilitate breastfeeding initiation among multiparas may consider mothers' previous experiences and beliefs associated with breastfeeding. Strategies to facilitate initiation may focus on addressing barriers mothers experienced while breastfeeding their first child and increasing awareness about how breastfeeding may prevent childhood obesity. Future research should explore how such approaches may impact breastfeeding outcomes with subsequent children.

Importance Birth weight (BW) is an important predictor of mortality and morbidity. At extremely early gestational ages (GAs), BW may influence decisions regarding initiation of resuscitation. Objective To characterize outcomes of liveborn infants with a BW less than 400 g. Design, Setting, and Participants This retrospective multicenter cohort study analyzed extremely preterm infants born between January 2008 and December 2016 within the National Institute of Child Health and Human Development Neonatal Research Network. Infants with a BW less than 400 g and a GA of 22 to 26 weeks were included. Active treatment was defined as the provision of any potentially lifesaving intervention after birth. Survival was analyzed for the entire cohort; neurodevelopmental impairment (NDI) was examined for those born between January 2008 and December 2015 (birth years with outcomes available for analysis). Neurodevelopmental impairment at 18 to 26 months’ corrected age (CA) was defined as a Bayley Scales of Infant and Toddler Development, Third Edition, cognitive composite score less than 85, a motor composite score less than 85, moderate or severe cerebral palsy, gross motor function classification system score of 2 or greater, bilateral blindness, and/or hearing impairment. Data were analyzed from September 2017 to October 2018. Exposures Birth weight less than 400 g. Main Outcomes and Measures The primary outcome was survival to discharge among infants who received active treatment. Analysis of follow-up data was limited to infants born from 2008 to 2015 to ensure children had reached assessment age. Within this cohort, neurodevelopmental outcomes were assessed for infants who survived to 18 to 26 months’ CA and returned for a comprehensive visit. Results Of the 205 included infants, 121 (59.0%) were female, 133 (64.9%) were singletons, and 178 (86.8%) were small for gestational age. Almost half (101 of 205 [49.3%]) received active treatment at birth. A total of 26 of 205 infants (12.7%; 95% CI, 8.5-18.9) overall survived to discharge, and 26 of 101 actively treated infants (25.7%; 95% CI, 17.6-35.4) survived to discharge. Within the subset of infants with a BW less than 400 g and a GA of 22 to 23 weeks, 6 of 36 actively treated infants (17%; 95% CI, 6-33) survived to discharge. Among infants born between 2008 and 2015, 23 of 90 actively treated infants (26%; 95% CI, 17-36) survived to discharge. Two infants died after discharge, and 2 were lost to follow-up. Thus, 19 of 90 actively treated infants (21%; 95% CI, 13-31) were evaluated at 18 to 26 months’ CA. Moderate or severe NDI occurred in 14 of 19 infants (74%). Conclusions and Relevance Infants born with a BW less than 400 g are at high risk of mortality and significant morbidity. Although 21% of infants survived to 18 to 26 months’ CA with active treatment, NDI was common among survivors.

Background Neurally adjusted ventilatory assist (NAVA) has distinct advantages when used invasively compared with conventional ventilation techniques. Evidence supporting the use of noninvasive NAVA is less robust, especially in the very low birth weight (VLBW) population. Objective To determine whether synchronized noninvasive ventilation via neurally adjusted ventilatory assist (NIV NAVA) supports ventilation postextubation in premature infants. Methods A retrospective analysis of a cohort of twenty-four former VLBW (

The aim of this study was to quantify the excess cases of pediatric and maternal disease, death, and costs attributable to suboptimal breastfeeding rates in the United States. Using the current literature on the associations between breastfeeding and health outcomes for nine pediatric and five maternal diseases, we created Monte Carlo simulations modeling a hypothetical cohort of U.S. women followed from age 15 to age 70years and their children from birth to age 20years. We examined disease outcomes using (a) 2012 breastfeeding rates and (b) assuming that 90% of infants were breastfed according to medical recommendations. We measured annual excess cases, deaths, and associated costs, in 2014 dollars, using a 2% discount rate. Annual excess deaths attributable to suboptimal breastfeeding total 3,340 (95% confidence interval [1,886 to 4,785]), 78% of which are maternal due to myocardial infarction (n=986), breast cancer (n=838), and diabetes (n=473). Excess pediatric deaths total 721, mostly due to Sudden Infant Death Syndrome (n=492) and necrotizing enterocolitis (n=190). Medical costs total $3.0 billion, 79% of which are maternal. Costs of premature death total $14.2 billion. The number of women needed to breastfeed as medically recommended to prevent an infant gastrointestinal infection is 0.8; acute otitis media, 3; hospitalization for lower respiratory tract infection, 95; maternal hypertension, 55; diabetes, 162; and myocardial infarction, 235. For every 597 women who optimally breastfeed, one maternal or child death is prevented. Policies to increase optimal breastfeeding could result in substantial public health gains. Breastfeeding has a larger impact on women's health than previously appreciated.

Congenital hypothyroidism (CH) with delayed thyroid-stimulating hormone (TSH) elevation is a common form of thyroid dysfunction among premature infants. Routine newborn screening (NBS) may miss infants with CH with delayed TSH elevation. The objective of the study is to determine the prevalence of CH with delayed TSH elevation in premature infants and to identify associated risk factors. Retrospective analysis of serum thyroid function screening (TFS) at day of life 30 in premature infants

BACKGROUND AND OBJECTIVES: Late preterm birth (at 34–36 6/7 weeks’ gestation) is a risk factor for early breastfeeding cessation. The objective of this study was to determine barriers to and facilitators of breastfeeding continuation among late preterm infants (LPI) and to compare the barriers faced by LPI admitted to the well nursery versus the NICU. METHODS: The SAS Complex Survey was used to perform multivariable logistic regression analysis by using data from the Centers for Disease Control and Prevention’s Pregnancy Risk Assessment Monitoring System. Data from 3 states (Illinois, Maine, and Vermont) for the years 2004 to 2008 were used. RESULTS: A total of 2530 mothers of LPI were surveyed. Odds of breastfeeding initiation were similar among LPI admitted to the NICU versus the well nursery (adjusted odds ratio, 1.24 [95% confidence interval, 0.88–1.73]; P = .209). Odds of breastfeeding for ≥10 weeks were no different between LPI admitted to the NICU versus those admitted to the well-nursery (adjusted odds ratio, 1.02 [95% confidence interval, 0.73–1.43]; P = .904). Factors associated with increased odds of breastfeeding for ≥10 weeks among LPI were higher maternal education, mother being married, and normal maternal BMI. Regardless of NICU admission, the top reasons cited by mothers of LPI for early breastfeeding discontinuation were perceived inadequate milk supply and nursing difficulties. CONCLUSIONS: Among LPIs, NICU admission was not associated with early breastfeeding cessation. Mothers of LPIs with lower odds of sustaining breastfeeding for at least 10 weeks were single mothers, those with a high school education only, and those who were obese. Breastfeeding support should be enhanced for LPIs and should address perceived maternal milk supply concerns and nursing difficulties.

BACKGROUND AND OBJECTIVE: Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months’ corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. METHODS: Infants 22 to 28 weeks’ gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006–2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. RESULTS: Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17–2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07–1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00–1.79]). Among survivors evaluated at 18 to 22 months’ corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. CONCLUSIONS: In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference.

IMPORTANCE: Previous studies of myo-inositol in preterm infants with respiratory distress found reduced severity of retinopathy of prematurity (ROP) and less frequent ROP, death, and intraventricular hemorrhage. However, no large trials have tested its efficacy or safety. OBJECTIVE: To test the adverse events and efficacy of myo-inositol to reduce type 1 ROP among infants younger than 28 weeks’ gestational age. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial included 638 infants younger than 28 weeks’ gestational age enrolled from 18 neonatal intensive care centers throughout the United States from April 17, 2014, to September 4, 2015; final date of follow-up was February 12, 2016. The planned enrollment of 1760 participants would permit detection of an absolute reduction in death or type 1 ROP of 7% with 90% power. The trial was terminated early due to a statistically significantly higher mortality rate in the myo-inositol group. INTERVENTIONS: A 40-mg/kg dose of myo-inositol was given every 12 hours (initially intravenously, then enterally when feeding; n = 317) or placebo (n = 321) for up to 10 weeks. MAIN OUTCOMES AND MEASURES: Type 1 ROP or death before determination of ROP outcome was designated as unfavorable. The designated favorable outcome was survival without type 1 ROP. RESULTS: Among 638 infants (mean, 26 weeks’ gestational age; 50% male), 632 (99%) received the trial drug or placebo and 589 (92%) had a study outcome. Death or type 1 ROP occurred more often in the myo-inositol group vs the placebo group (29% vs 21%, respectively; adjusted risk difference, 7% [95% CI, 0%-13%]; adjusted relative risk, 1.41 [95% CI, 1.08-1.83], P = .01). All-cause death before 55 weeks’ postmenstrual age occurred in 18% of the myo-inositol group and in 11% of the placebo group (adjusted risk difference, 6% [95% CI, 0%-11%]; adjusted relative risk, 1.66 [95% CI, 1.14-2.43], P = .007). The most common serious adverse events up to 7 days of receiving the ending dose were necrotizing enterocolitis (6% for myo-inositol vs 4% for placebo), poor perfusion or hypotension (7% vs 4%, respectively), intraventricular hemorrhage (10% vs 9%), systemic infection (16% vs 11%), and respiratory distress (15% vs 13%). CONCLUSIONS AND RELEVANCE: Among premature infants younger than 28 weeks’ gestational age, treatment with myo-inositol for up to 10 weeks did not reduce the risk of type 1 ROP or death vs placebo. These findings do not support the use of myo-inositol among premature infants; however, the early termination of the trial limits definitive conclusions.

OBJECTIVE: To identify rates of overweight (BMI ≥85(th) percentile) and obesity (BMI ≥95(th) percentile) at 6-7 years of age and associated risk factors among extremely preterm infants born at < 28 weeks of gestation. STUDY DESIGN: Anthropometrics, blood pressure, and active and sedentary activity levels were prospectively assessed. Three groups were compared, those with BMI≥85(th) percentile (overweight or obese for age, height and sex) and ≥95(th) percentile (obese) versus 85(th) percentile), central fat (waist circumference> 90(th) percentile), spent more time in sedentary activity (20.5 versus 18.2 versus 16.7 hours/week), and had either systolic and/or diastolic hypertension (24% versus 26% versus 14 %) respectively. Post discharge weight gain velocities from 36 weeks postmenstrual age (PMA) to 18 months, and 18 months to 6-7 years were independently associated with BMI ≥85(th) percentile whereas weight-gain velocity from 18 months to 6-7 years was associated with obesity. CONCLUSIONS: One in five former extremely preterm infants is overweight or obese and has central obesity at early school age. Post discharge weight gain velocities were associated with overweight and obesity. These findings suggest the obesity epidemic is spreading to the most extremely preterm infants. Trial registration ClinicalTrials.gov NCT00063063 and NCT0000

Objectives To describe the frequency and extent of delivery room resuscitation and evaluate the association of delivery room resuscitation with neonatal outcomes in moderately preterm (MPT) infants. Study design This was an observational cohort study of MPT infants delivered at 290/7 to 336/7 weeks' gestational age (GA) enrolled in the Neonatal Research Network MPT registry. Infants were categorized into 5 groups based on the highest level of delivery room intervention: routine care, oxygen and/or continuous positive airway pressure, bag and mask ventilation, endotracheal intubation, and cardiopulmonary resuscitation including chest compressions and/or epinephrine use. The association of antepartum and intrapartum risk factors and discharge outcomes with the intensity of resuscitation was evaluated. Results Of 7014 included infants, 1684 (24.0%) received routine care and no additional resuscitation, 2279 (32.5%) received oxygen or continuous positive airway pressure, 1831 (26.1%) received bag and mask ventilation, 1034 (14.7%) underwent endotracheal intubation, and 186 (2.7%) received cardiopulmonary resuscitation. Among the antepartum and intrapartum factors, increasing GA, any exposure to antenatal steroids and prolonged rupture of membranes decreased the likelihood of receipt of all levels of resuscitation. Infants who were small for GA (SGA) had increased risk of delivery room resuscitation. Among the neonatal outcomes, respiratory support at 28 days, days to full oral feeds and length of stay were significantly associated with the intensity of delivery room resuscitation. Higher intensity of resuscitation was associated with increased risk of mortality. Conclusions The majority of MPT infants receive some level of delivery room resuscitation. Increased intensity of delivery room interventions was associated with prolonged respiratory and nutritional support, increased mortality, and a longer length of stay.