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Objective: The objective of this study was to evaluate a lifestyle intervention implemented into routine antenatal care to optimize gestational weight gain (GWG) and outcomes using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework., Methods: This study was an embedded pragmatic behavioral intervention delivered by a health coach and supported by a physician over five sessions for women with a prepregnancy BMI between 25 and 43 kg/m 2 who were <23 weeks' gestation in an Australian maternity service. Both intervention and standard care received routine antenatal care. The primary outcome was effectiveness in reducing excess GWG, and the secondary outcomes were reach, adoption, implementation, and maintenance and maternal and neonatal outcomes using the RE-AIM framework., Results: For the "Reach" aspect, 90% of eligible women were included (N = 404; n = 202 intervention and n = 202 standard care). For the "Efficacy" aspect, there were no differences in proportion exceeding GWG recommendations or mean GWG between groups. Secondary analysis excluding women with gestational diabetes showed that a lower proportion of women in the intervention group had GWG above recommendations (β coefficient 0.51, 95% CI: 0.27 to 0.97; p = 0.04), with less GWG (β coefficient -1.93 kg, 95% CI: -3.63 to -0.24; p = 0.03). For the "Adoption" aspect, qualitative analysis of staff/participants demonstrated strong support for service. For the "Implementation" aspect, strong fidelity (implementation according to study plan) and staff/participant acceptability were observed. Finally, for the "Maintenance" aspect, the program has continued for 4 years with plans/funding for scale-up., Conclusions: Lifestyle intervention did not alter the overall proportion with excess GWG or total GWG. Secondary analysis, excluding women with gestational diabetes mellitus, showed less GWG. This demonstrates implementation and maintenance of the intervention in routine antenatal care, generating new knowledge within the RE-AIM framework., (© 2024 The Obesity Society.)

Objective: The aim of this study was 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 to 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: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%., Conclusions: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment., Competing Interests: The authors report no conflict of interests., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Maternal obesity is associated with health risks for women and their babies and is exacerbated by excess gestational weight gain. The aim of this study was to describe women's experiences and perspectives in attending a Healthy Pregnancy Service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity., Methods: An explanatory sequential mixed methods study design utilised two questionnaires (completed in early and late pregnancy) to quantify feelings, motivation and satisfaction with the service, followed by semi-structured interviews that explored barriers and enablers of behaviour change. Data were analysed separately and then interpreted together., Results: Overall, 49 women attending the service completed either questionnaire 1, 2 or both and were included in the analysis. Fourteen women were interviewed. Prior to pregnancy, many women had gained weight and attempted to lose weight independently, and reported they were highly motivated to achieve a healthy lifestyle. During pregnancy, diet changes were reported as easier to make and sustain than exercise changes. Satisfaction with the service was high. Key factors identified in qualitative analysis were: service support enabled change; motivation to change behaviour, social support, barriers to making change (intrinsic, extrinsic and clinic-related), post-partum lifestyle and needs. On integration of data, qualitative and quantitative findings aligned., Conclusions: The Healthy Pregnancy service was valued by women. Barriers and enablers to the delivery of an integrated model of maternity care that supported healthy lifestyle and recommended gestational weight gain were identified. These findings have informed and improved implementation and further scale up of this successful service model, integrating healthy lifestyle into routine antenatal care of women with obesity., Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry (no.12620000985987). Registration date 30/09/2020, retrospectively registered. http://www.anzctr.org.au/., (© 2021. The Author(s).)

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 <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed., Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40)., Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: The aim of this study is to evaluate the feasibility, safety, and efficacy of discharge with supplemental nasogastric tube (NGT) feeds in medically complex infants., Study Design: Cohort study of 400 infants enrolled in the Transitional Medical Home (TMH) program at Duke University Level IV neonatal intensive care unit from January 2013 to 2017., Results: Among 400 infants enrolled in the TMH, 57 infants were discharged with an NGT. A total of 45 infants with a variety of diagnoses and comorbidities were included in final analysis. Among 45 infants, 5 obtained a gastrostomy tube (GT) postdischarge. Median (25-75th percentile) length of use of NGT in 40 infants was 12 days (4-37). Excluding four outliers who used NGT for ≥140 days, the median length of use was 8 days (3-24). This extrapolates to a median of 288 hospital days saved for the remaining 36 infants. There were only three emergency room visits related to parental concern for incorrect NGT placement. There was no statistically significant difference in percent oral feeding predischarge or growth in first month postdischarge between infants who orally fed versus those who obtained GTs., Conclusion: Discharge with supplemental NGT feeds is safe and feasible utilizing a standardized protocol and close postdischarge follow-up. This practice can decrease length of stay and prevent need for GT., Key Points: · Discharge with nasogastric tube (NGT) supplementation is safe.. · Discharge with NGT supplementation decreases cost.. · Discharge with NGT can decrease neonatal intensive care unit length of stay.. · Medical home model facilitates safe discharge.., Competing Interests: D.D.M.S., R.F.G., and W.F.M. report grants from Duke Endowment during the conduct of the study. R.G.G. reports other from Feihe International outside the submitted work., (Thieme. All rights reserved.)

We investigated the effect of 12 months of functional electrical stimulation-assisted rowing with and without zoledronic acid (ZA) on computationally estimated bone strength and stiffness in individuals with spinal cord injury. We found that rowing with ZA, but not rowing alone, improved stiffness at the distal femur, but not the proximal tibia., Introduction: People with spinal cord injury (SCI) have high fracture risk at the knee after the injury. Therapies that prevent bone loss or stimulate an anabolic response in bone have been proposed to reduce fractures. Zoledronic acid (ZA) is a potent bisphosphonate that inhibits osteoclastic resorption. Functional electrical stimulation (FES)-assisted rowing is a potentially osteogenic exercise involving mechanical stimulation to the lower extremities. Here, we investigated the effect of FES-assisted rowing with and without ZA on bone strength and stiffness in individuals with SCI., Methods: Twenty individuals from a cohort of adults with SCI who participated in a clinical trial were included in the study. CT scans of their knees before and after the intervention were converted to finite element models. Bone failure strength (T ult ) and stiffness were calculated at the proximal tibia and distal femur., Results: T ult at the distal femur increased 4.6% among people who received rowing + ZA and decreased 13.9% among those with rowing only (p < 0.05 for group). Torsional and compressive stiffness at the femur metaphysis increased in people with rowing + ZA (+ 3 to +4%) and decreased in people with rowing only (- 7 to -8%; p < 0.05). T ult in the proximal tibia decreased in everyone, but the loss was attenuated in the rowing + ZA group. People with initially stronger bone tended to lose more strength., Conclusion: Overall, we observed increases in bone strength at the distal femur but not the proximal tibia, with FES-assisted rowing combined with ZA treatment. Rowing alone did not significantly prevent bone loss at either site, which might be attributed to insufficient mechanical loading.

Objective: To test associations between grades 3 or 4 (severe) intraventricular hemorrhage (IVH) and single nucleotide polymorphisms (SNPs) associated with coagulation, inflammation, angiogenesis, and organ development in an exploratory study., Study Design: Extremely low-birthweight (ELBW) infants enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's (NRN) Cytokines Study were included if they had cranial ultrasound (CUS) and genotyping data available in the NRN Anonymized DNA Repository and Database. Associations between SNPs and IVH severity were tested with multivariable logistic regression analysis., Result: One hundred thirty-nine infants with severe IVH and 687 infants with grade 1 or 0 IVH were included. One thousand two hundred seventy-nine SNPs were genotyped. Thirteen were preliminarily associated with severe IVH including five related to central nervous system (CNS) neuronal and neurovascular development., Conclusion: Genetic variants for CNS neuronal and neurovascular development may be associated with severe IVH in premature infants.

Maternal obesity is associated with health risks for women and their babies, exacerbated by excess gestational weight gain. We describe health professionals' perspectives in the provision of a Healthy Pregnancy service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. Semi-structured interviews were conducted with health professionals. Questions were based on the Theoretical Domains Framework (TDF) and deductive thematic analysis was performed. A total of 14 multidisciplinary staff were interviewed. Six themes were identified: 1. health professionals view themselves as part of a team; 2. health professionals reported having necessary skills; 3. experience generated confidence in discussing gestational weight gain; 4. gestational weight gain is considered of variable importance; 5. health professionals want women to be comfortable; 6. the environmental context and resources presented some barriers. Staff were supportive of the Healthy Pregnancy service and valued developing teamwork with staff and rapport with women. Most felt relatively comfortable discussing weight gain with women. Barriers included ability to navigate sensitive topics with women, limited awareness of the intervention among new staff, communication between teams, and waiting time for women. Barriers and enablers to the delivery of an integrated model of maternity care were identified. These findings should inform and improve implementation of service models integrating healthy lifestyle in the antenatal care of women with obesity.

Aim: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW)., Method: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0-14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP., Results: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates., Interpretation: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP., What This Paper Adds: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy., (© 2019 Mac Keith Press.)

Objective: To assess the frequency of gastrostomy tube (GT) placement in extremely low birth weight (ELBW) infants, associated comorbidities, and long-term outcomes., Study Design: Analysis of ELBW infants from 25 centers enrolled in the National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-up Registry from 2006 to 2012. Frequency of GT placement before 18-22 months, demographic and medical factors associated with GT placement, and associated long-term outcomes at 18-22 months of corrected age were described. Associations between GT placement and neonatal morbidities and long-term outcomes were assessed with logistic regression after adjustment for center and common co-variables., Results: Of the 4549 ELBW infants included in these analyses, 333 (7.3%) underwent GT placement; 76% had the GT placed postdischarge. Of infants with GTs, 11% had birth weights small for gestational age, 77% had bronchopulmonary dysplasia, and 29% severe intraventricular hemorrhage or periventricular leukomalacia. At follow-up, 56% of infants with a GT had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems. After adjustment, small for gestational age, bronchopulmonary dysplasia, intraventricular hemorrhage/periventricular leukomalacia, poor growth, and NDI were associated with GT placement. Thirty-two percent of infants with GTs placed were taking full oral feeds at follow-up., Conclusions: GT placement is common in ELBW infants, particularly among those with severe neonatal morbidities. GT placement in this population was associated with poor growth, NDI, and chronic respiratory and feeding problems at follow-up. The frequency of GT placement postneonatal discharge indicates the need for close nutritional follow-up of ELBW infants., Trial Registration: ClinicalTrials.gov: NCT00063063., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Premature and critically ill term infants are often discharged from the neonatal intensive care unit (NICU) with ongoing medical problems, including respiratory problems; growth, nutrition and feeding problems; and neurologic injury. At discharge, they may also be dependent on technology such as supplemental oxygen, tracheostomy, mechanical ventilation, feeding tube, and monitors. Primary care physicians must have special knowledge and understanding of the medical complications of NICU graduates to coordinate post-discharge care. We examine the most common post-discharge medical problems in premature and critically ill term infants and inform the primary care provider about expected outcomes and possible new problems., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation- (FES-) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES-rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES-rowing alone with FES-rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV ( p  = 0.05 to 0.006), the CTI ( p  = 0.009), and the BR ( p  = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing-only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia ( p  = 0.05). A subgroup analysis of the rowing-only arm showed that gains in the CSI at the tibial metaphysis varied in a dose-dependent fashion based on the total amount of exercise performed ( p  = 0.009). These findings demonstrate that the osteogenic response to FES-rowing is dose-dependent. Combination therapy with ZA and FES-row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Background: Therapeutic hypothermia reduces the risk of death, or moderate to severe neurodevelopmental impairment (NDI) in term infants with hypoxic-ischemic encephalopathy (HIE). Reports of its safety and efficacy in preterm infants are scarce., Objective: Report short and long-term outcomes of preterm infants with HIE who received therapeutic hypothermia., Methods: A retrospective cohort analysis of all preterm infants <36 weeks' gestation with HIE who received whole body hypothermia in a single center from January 2007 to April 2015. The primary outcome was death or moderate to severe NDI defined by moderate or severe cerebral palsy, severe hearing or visual impairment, or cognitive score < 85 on the Bayley Scales of Infant Development III (BSID III) at 18-24 months' adjusted age., Results: 30 infants with a median gestational age and birthweight of 35 weeks' (range; 33-35) and 2575 g (1850-4840) and a median first postnatal blood pH of 6.81 (6.58-7.14). Complications included coagulopathy (50%), early clinical seizures (43.3%), arterial hypotension (40%), persistent metabolic acidosis (37%) and thrombocytopenia (20%). Four infants died before or soon after discharge (18.2%). Eighteen surviving infants (69.2%) had follow up data; 7 of them had moderate to severe NDI (38.9%). Cognitive, motor and language mean composite BSID III scores were 84 (54-110), 83 (46-118), and 78 (46-112). Death or moderate to severe NDI occurred in 11/22 (50%) infants with known outcomes., Conclusion: Large randomized trials on efficacy and safety are needed in this highly vulnerable population as the incidence of complications and the combined outcome of death and NDI is concerning., (Copyright © 2018. Published by Elsevier B.V.)

Background: The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions., Methods: Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes., Results: Overall, 5874 studies were identified and 23 were included (n = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes., Conclusions: Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

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) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors., 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 <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging., 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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Purpose: The purpose of this study was to determine effectiveness of a midliner positioning system (MPS, Tortle Midliner) for preventing dolichocephaly., Methods: This was a nonrandomized, prospective study of 30 premature infants (study cohort, SC) using an MPS compared with a retrospective study cohort (RSC) of 65 infants who received standard of care intervention., Results: RSC baseline cranial index (CI) of 80% and final CI of 77% significantly decreased over an average 5.5 weeks (P < .0001). The SC baseline CI and the final CI were both 79% over an average 5.7 weeks, indicating no significant difference between CI measures (P = .6). Gestational age, birth weight, reflux, time on continuous positive airway pressure, and time in a supine position were not associated with dolichocephaly., Conclusions: The SC developed less cranial molding (ie, had greater CI), compared with the RSC. A larger randomized study is needed to recommend routine use of MPS for prevention and/or treatment of cranial molding in premature infants.

Importance: Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with theIOM guidelines and pregnancy outcomes is unclear., Objective: To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI 18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI ≥30]) and maternal and infant outcomes., Data Sources and Study Selection: Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain., Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data., Main Outcomes and Measures: Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus., Results: Of 5354 identified studies, 23 (n = 1 309 136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, -2% [-10% to -6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, -2% [-3% to -1%]); cesarean delivery showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [-2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, -3%; [-4% to -2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, -2% [-2% to -1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data., Conclusions and Relevance: In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.

Objective  The purpose of this study was to determine when dolichocephaly develops in preterm infants, to establish factors that contribute to its development, and to determine its association with adverse motor outcomes. Study Design  This study was a retrospective review of data collected from preterm infants born at < 32 weeks' gestation. The cranial index was measured by a physical therapist (PT) at three time points during hospitalization. Demographic data, neonatal morbidities, and motor outcomes at outpatient follow-up were collected. Results  Overall, 54% of infants developed dolichocephaly during hospitalization. The presence of dolichocephaly was highest in infants between 32 and 34 weeks' postmenstrual age (PMA) (39%). Birth weight, gestational age, bronchopulmonary dysplasia, gastroesophageal reflux disease, and severe intraventricular hemorrhage were not associated with dolichocephaly. Infants with dolichocephaly at 32 to 34 weeks' PMA were more likely to either be receiving PT services or be referred to PT services by outpatient follow-up ( p  = 0.05). Conclusion  The presence of dolichocephaly was highest in infants between 32 and 34 weeks' PMA and was associated with increased need for PT services in early infancy. Findings support early developmental intervention at < 32 weeks' PMA to prevent and/or treat cranial molding deformity and improve early motor outcomes., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes., Methods: We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 [epoch 1], 2004-2007 [epoch 2], and 2008-2011 [epoch 3]). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death., Results: Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (P<0.001). The percentage of infants who survived without neurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% [207 of 1391] in epoch 1 and 16% [211 of 1348] in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 [95% confidence interval {CI}, 1.01 to 1.59] and 1.59 [95% CI, 1.28 to 1.99], respectively)., Conclusions: The rate of survival without neurodevelopmental impairment increased between 2000 and 2011 in this large cohort of periviable infants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT00063063 and NCT00009633 .).

Background: Infants born near the limit of viability are at high risk for death or adverse neurodevelopmental outcomes. It is unclear whether these outcomes have improved over the past 15 years., Aim: To determine if death and neurodevelopmental impairment have declined over the past 15 years in infants born at 22 to 24 weeks' gestation., Study Design: Retrospective cohort study., Subjects: We identified infants born at 22 to 24 weeks' gestation in our center in two epochs: 1998-2004 (Epoch 1) and 2005-2011 (Epoch 2)., Outcome Measures: The primary outcome, death or neurodevelopmental impairment, was evaluated at 17-25 months' corrected gestational age with neurologic exams and Bayley Scales of Infant Development. Perinatal characteristics, major morbidities, and outcomes were compared between epochs., Results: Birth weight and gestational age were similar between 170 infants in Epoch 1 and 187 infants in Epoch 2. Mortality was significantly lower in Epoch 2, 55% vs. 42% (p=0.02). Among surviving infants, late-onset sepsis (p<0.01), bronchopulmonary dysplasia (p<0.01), and surgical necrotizing enterocolitis (p=0.04) were less common in Epoch 2. Neurodevelopmental impairment among surviving infants declined from 68% in Epoch 1 to 47% in Epoch 2, p=0.02. Odds of death or NDI were significantly lower in Epoch 2 vs. Epoch 1, OR=0.31 (95% confidence interval; 0.16, 0.58)., Conclusion: Risk of death or neurodevelopmental impairment decreased over time in infants born at 22 to 24 weeks' gestation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Amplitude-integrated electroencephalography (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated., Study Design: Inborn infants 23(0/7) to 28(6/7) weeks gestation or birth weight 401 to 1000 g were eligible. Serial, 6-h aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed., Result: A total of 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality., Conclusion: Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff.

Objective: To evaluate satisfaction with diagnosis, risk perceptions, and health beliefs among women with gestational diabetes mellitus (GDM)., Methods: In a cross-sectional questionnaire-based study, participants with GDM diagnosed after 26weeks of pregnancy were recruited from hospital-based services at Monash Health (Melbourne, VIC, Australia) and through newspaper advertisements between 2008 and 2010. Eligible participants-aged at least 18years and able to read English-completed a questionnaire., Results: Among 46 women who completed the questionnaire, 38 (83%) were satisfied with the explanation of the GDM screening test and 31 (67%) felt that the results were explained well. Generally, women were satisfied with the information provided about lifestyle management (29 [81%] of 36) and medical therapy (26 [72%] of 36). Most women (41 [89%]) associated poor GDM control with perinatal complications. Additionally, many participants thought that insulin (35 [76%]) and lifestyle changes (30 [65%]) could reduce macrosomia. A total of 37 (82%) of 45 women perceived that they were at risk of future GDM, and 33 (73%) thought they had an increased risk of type 2 diabetes. Most women believed that they could change these risks (29 [64%] and 37 [82%] of 45, respectively)., Conclusion: Women were largely positive about their experience of GDM diagnosis. Explanation of the screening test and provision of information could be improved. Risk perception was reasonable., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: To evaluate the association between cystoid macular edema (CME) observed in very preterm infants and developmental outcomes at 18 to 24 months corrected age., Design: Cohort study., Participants: Infants born at or less than 1500 g or at or less than 30 weeks postmenstrual age who underwent screening for retinopathy of prematurity (ROP) in an intensive care nursery., Methods: Bedside handheld spectral-domain optical coherence tomography (SD OCT; Envisu, Bioptigen, Inc, Research Triangle Park, NC) imaging was obtained from preterm infants who were being screened for ROP and graded for presence of CME, central foveal thickness (CFT), inner nuclear layer thickness, and foveal-to-parafoveal thickness ratio. At 18 to 24 months corrected age, the children were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition., Main Outcome Measures: Scores on the Bayley cognitive, language, and motor subscales., Results: Among 77 children with SD OCT imaging, 53 were evaluated with the Bayley Scales. Compared with children who did not have CME as infants (n=22), the mean score for children who had CME (n=31) was 7.3 points (95% confidence interval [CI], -15.5 to 0.9; P=0.08) lower on the cognitive subscale, 14.1 points (95% CI, -22.7 to -5.5; P=0.002) lower for the language subscale, and 11.5 points (95% CI, -21.6 to -1.3; P=0.03) lower for the motor subscale. Differences were maintained after adjusting for gestational age and birth weight. Severity of CME, as assessed by foveal-to-parafoveal thickness ratio, within the CME group correlated with poorer cognitive (R2=0.16, P=0.03) and motor (R2=0.15, P=0.03) development., Conclusions: Cystoid macular edema observed on SD OCT in very preterm infants screened for ROP is associated with poorer language and motor skills at 18 to 24 months corrected age. Evaluation of the retina with SD-OCT may serve as an indicator of neurodevelopmental health for very preterm infants in the intensive care nursery., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age., Methods: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors., Results: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes., Conclusions: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging., (Copyright © 2015 by the American Academy of Pediatrics.)

Purpose: To evaluate effects of prematurity on early optic nerve (ON) development and the usefulness of ON parameters as indicators of central nervous system (CNS) development and pathology., Design: Prospective, cross-sectional, longitudinal study., Participants: Forty-four preterm infants undergoing retinopathy of prematurity (ROP) screening and 52 term infants., Methods: We analyzed ON from portable handheld spectral-domain optical coherence tomography (SD-OCT) images (Bioptigen, Inc, Research Triangle Park, NC) of 44 preterm and 52 term infants. The highest-quality ON scan from either eye was selected for quantitative analysis. Longitudinal analysis was performed at 31-36 weeks and 37-42 weeks postmenstrual age (PMA). Preterm ON parameters also were assessed for correlation with indicators of cognitive, language, and motor development and CNS pathology., Main Outcome Measures: Vertical cup diameter (vCD), vertical disc diameter (vDD), vertical cup-to-disc ratio (vCDR), cup depth, and indicators of neurocognitive development and CNS pathology., Results: At 37-42 weeks PMA, preterm infants had larger vCD and vCDR than term infants (908 vs. 700 μm [P<0.001] and 0.68 vs. 0.53 μm [P<0.001], respectively), whereas cup depth and vDD were not significantly different. Longitudinal changes (n = 26 preterm eyes; mean interval, 4.7 weeks) in vDD and in vCDR were an increase of 74 μm (P = 0.008) and decrease of 0.05 (P = 0.015), respectively. In preterm infants (n = 44), periventricular leukomalacia was associated with larger vCD (1084 vs. 828 μm; P = 0.005) and vCDR (0.85 vs. 0.63; P<0.001), posthemorrhagic hydrocephalus was associated with shallower cup (331 vs. 456 μm; P = 0.030), and clinical magnetic resonance imaging was associated with larger vCDR (0.73 vs. 0.64; P = 0.023). In 23 preterm infants with Bayley Scales of Infant Development scores, larger vCDR was associated with lower cognitive scores (P = 0.049)., Conclusions: This is the first analysis of ON parameters in premature infants using SD-OCT. It demonstrated that by age of term birth, vCD and vCDR are larger in preterm infants who were screened for ROP than in term infants. In this prospective pilot study, ON parameters in these preterm infants associate weakly with CNS pathology and future cognitive development. Future prospective studies with larger numbers are necessary before further conclusions can be made., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant., Study Design: The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention., Results: One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P<.05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P<.05) by 18-22 months CA., Conclusion: Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Selenium is effective in improving quality of life and reducing the progression of active Graves' orbitopathy. The effect of correcting relative selenium deficiency on improving Graves' orbitopathy is unknown, as baseline selenium levels have not previously been measured. The study aims to determine whether serum selenium levels are reduced in patients with Graves' disease with orbitopathy (GO) compared with without orbitopathy (GD)., Design: A prospective, case-control study performed between 2009 and 2012 at endocrine and ophthalmology clinics in Australia., Patients: A total of 198 patients with Graves' disease participated in the study: 101 with Graves' orbitopathy and 97 without Graves' orbitopathy., Measurements: Serum selenium levels in both groups., Results: Mean serum selenium levels were significantly lower in GO (1·10 ± 0·18 μm) than in GD (1·19 ± 0·20 μm) (P = 0·001). Mean selenium levels appeared to decrease in parallel with increasing severity of GO; selenium level was 1·19 ± 0·20 μm in GD, 1·10 ± 0·19 μm in moderate-to-severe GO and 1·09 ± 0·17 μm in sight-threatening GO (P = 0·003). Serum selenium levels remained significantly lower in GO after adjusting for age, smoking status, thyroidectomy, radioactive iodine treatment and residential location., Conclusion: Serum selenium levels are lower in patients with GO compared with GD in an Australian study population with marginal selenium status. Relative selenium deficiency may be an independent risk factor for orbitopathy in patients with Graves' disease., (© 2013 John Wiley & Sons Ltd.)

Objective: To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE)., Study Design: We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells., Results: Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85., Conclusions: Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE)., Methods: We conducted a cohort study of infants who survived HIE and had 18-22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/-, and e2/-., Results: A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the e3/e3 genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29% among those with and without the e4 allele, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups., Conclusion: Disability was not associated with the APOE genotype in this cohort of HIE survivors.

Objective: Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH., Study Design: Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI)., Result: Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI., Conclusion: Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.

Objective: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status., Study Design: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study., Results: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047)., Conclusions: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: Determine predictors of neurocognitive outcome in early school age congenital diaphragmatic hernia (CDH) survivors., Study Design: Prospective study of infants with CDH at Duke University Medical Center. Neurocognitive delay (NCD) at school age (4 to 7years) was defined as a score<80 in any of the following areas: Verbal Scale IQ, Performance Scale IQ, Expressive Language, or Receptive Language. Logistic regression, Fisher's exact, and the Wilcoxon rank sum test were used to examine the relationship between NCD at early school age and 6 demographic and 18 medical variables., Results: Of 43 infants with CDH, twenty seven (63%) survived to hospital discharge, and 16 (59%) returned for school age testing at a median age of 4.9years. Seven (44%) of the children evaluated had NCD. Patch repair (p=0.01), extracorporeal membrane oxygenation (ECMO; p=0.02), days on ECMO (p=0.01), days of mechanical ventilation (p=0.049), and post-operative use of inhaled nitric oxide (p=0.02) were found to be associated with NCD at early school age., Conclusions: CDH survivors are at risk for neurocognitive delay persisting into school age. Perinatal factors such as patch repair and ECMO treatment may aid in identifying CDH survivors at high risk for continued learning difficulties throughout childhood., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Study Question: What is the prevalence of insulin resistance (IR) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria?, Summary Answer: We report novel clamp data in Rotterdam diagnosed PCOS women, using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR, strengthening the evidence for an aetiological role of IR in both National Institutes of Health (NIH) and Rotterdam diagnosed PCOS in lean and overweight women., What Is Known Already: PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes., Study Design, Size, Duration: Using a cross-sectional study design, 20 overweight and 20 lean PCOS (Rotterdam criteria), 14 overweight and 19 lean body mass index (BMI)-matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill., Materials, Setting, Methods: In an academic clinic setting, glucose infusion rate (GIR) on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity., Main Results and the Role of Chance: PCOS women were more IR than BMI-matched controls (main effect for BMI and PCOS; P < 0.001). IR was present in 75% of lean PCOS, 62% of overweight controls and 95% of overweight PCOS. Lean controls (mean ± SD; GIR 339 ± 76 mg min⁻¹ m⁻²) were less IR than lean PCOS (270 ± 66 mg min⁻¹ m⁻²), overweight controls (264 ± 66 mg min⁻¹ m⁻²) and overweight PCOS (175 ± 96 mg min⁻¹ m⁻²). The negative relationship between BMI and IR reflected by GIR was more marked in PCOS (y = 445.1 - 7.7x, R² = 0.42 (P < 0.0001) than controls (y = 435.5 - 4.6x, R² = 0.04 (P < 0.01))., Limitations, Reasons for Caution: The study did not use glucose tracer techniques to completely characterize the IR, as well as the lack of matching for body composition and age., Wider Implications of the Findings: IR is exacerbated by increased BMI, supporting intrinsic IR in PCOS. BMI impact on IR is greater in PCOS, than in controls, irrespective of visceral fat, prioritizing lifestyle intervention and the need for effective therapeutic interventions to address intrinsic IR and prevent diabetes in this high-risk population., Study Funding/competing Interest(s): This investigator-initiated trial was supported by grants from the National Health & Medical Research Council (NHMRC) Grant number 606553 (H.J.T., N.K.S. and S.K.H.) as well as Monash University and The Jean Hailes Foundation. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. A.E.J. is a Jean Hailes and NHMRC scholarship holder. The authors declare that there is no conflict of interest associated with this manuscript.

Objective: To determine whether death and/or neurodevelopmental impairment (NDI) after severe intracranial hemorrhage (ICH; grade 3 or 4) differs by gestational age (GA) at birth in extremely low birth weight (ELBW) infants., Study Design: Demographic, perinatal and neonatal factors potentially contributing to NDI for ELBW infants (23 to 28 weeks gestation) were obtained retrospectively; outcome data came from the ELBW Follow-up Study. NDI was defined at 18 to 22 months corrected age as moderate/severe cerebral palsy, Bayley Scales of Infant Development II cognitive or motor score <70, and/or blindness or deafness. Characteristics of younger versus older infants with no versus severe ICH associated with death or NDI were compared. Generalized linear mixed models predicted death or NDI in each GA cohort., Result: Of the 6638 infants, 61.8% had no ICH and 13.6% had severe ICH; 39% of survivors had NDI. Risk-adjusted odds of death or NDI and death were higher in the lower GA group. Lower GA increased the odds of death before 30 days for infants with severe ICH. Necrotizing enterocolitis (particularly surgical NEC), late onset infection, cystic periventricular leukomalacia and post-natal steroids contributed to mortality risk. NDI differed by GA in infants without ICH and grade 3, but not grade 4 ICH. Contributors to NDI in infants with severe ICH included male gender, surgical NEC and post-hemorrhagic hydrocephalus requiring a shunt., Conclusion: GA contributes to the risk of death in ELBW infants, but not NDI among survivors with severe ICH. Male gender, surgical NEC and need for a shunt add additional risk for NDI.

Background: Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses., Methods: Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age., Results: The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P=0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P=0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P=0.046)., Conclusions: We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute; SUPPORT ClinicalTrials.gov number, NCT00233324.).

Objectives: To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development's Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2)., Study Design: Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates., Results: Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P < .001)., Conclusion: Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available., Methods: In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70., Results: Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80)., Conclusions: The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

Background: Necrotizing enterocolitis (NEC) and periventricular hemorrhagic infarction (PVHI) are complications of prematurity associated with poor neurodevelopmental outcomes., Objectives: We characterized temporal and causal associations between NEC and type of PVHI as well as associations with outcomes., Methods: This was a multicenter retrospective study of infants with birth weight <1,500 g and diagnosis of PVHI by a pediatric radiologist at 3 neonatal intensive care units in North Carolina, USA, between January 1998 and December 2004. NEC was confirmed using radiological and surgical pathology findings. Infants were assessed by 3 years using the Bayley Scales of Infant Development, second edition., Results: 35 of 112 (31%) of study patients developed NEC. NEC was diagnosed subsequent to PVHI by a median of 16.6 days (95% CI [9.5, 24.9], p < 0.0001). Indomethacin use and the presence of bilateral PVHI were associated with an increased risk of subsequent NEC (OR 2.8, 95% CI [1.1, 7.2] and OR 2.4, 95% CI [1.1, 5.7], respectively). Having bilateral versus unilateral PVHI was associated with a 2.34-fold increased risk of death (95% CI [1.27, 4.33], p = 0.007). NEC was not associated with worse motor outcomes in this population. Overall, the probability of a mental development index >70 was greatest for infants with unilateral PVHI versus bilateral PVHI, although the presence of NEC was associated with worse cognitive outcomes in both groups., Conclusions: Premature infants with PVHI often subsequently develop NEC, especially if they have bilateral PVHI and are exposed to indomethacin. While NEC results in worse neurodevelopmental outcomes, PVHI severity appears more important to the outcome of these infants., (Copyright © 2010 S. Karger AG, Basel.)

Objective: Determine associations between left vocal cord paralysis (LVCP) and poor respiratory, feeding and/or developmental outcomes in extremely low birth weight (ELBW) infants following surgical closure of a patent ductus arteriosus (PDA)., Study Design: ELBW infants who underwent PDA ligation between January 2004 and December 2006 were identified. We compared infants with and without LVCP following ligation to determine relationships between LVCP and respiratory morbidities, feeding and growth difficulties and neurodevelopmental impairment at 18 to 22-month follow-up. Student's t-test, Fisher's exact test and multivariable regression analyses were used to determine associations., Result: In all, 60 ELBW infants with a mean gestational age of 25 weeks and mean birth weight of 725 g had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with LVCP post-operatively. Infants with LVCP were significantly more likely to develop bronchopulmonary dysplasia (82 vs 39%, P=0.002), reactive airway disease (86 vs 33%, P<0.0001), or need for gastrostomy tube (63 vs 6%, P<0.0001)., Conclusion: LVCP as a complication of surgical ductal ligation in ELBW infants is associated with persistent respiratory and feeding problems. Direct laryngoscopy should be considered for all infants who experience persistent respiratory and/or feeding difficulties following PDA ligation.

Misfolded proteins destined for the cell surface are recognized and degraded by the ERAD [ER (endoplasmic reticulum) associated degradation] pathway. TS (temperature-sensitive) mutants at the permissive temperature escape ERAD and reach the cell surface. In this present paper, we examined a TS mutant of the CFTR [CF (cystic fibrosis) transmembrane conductance regulator], CFTR DeltaF508, and analysed its cell-surface trafficking after rescue [rDeltaF508 (rescued DeltaF508) CFTR]. We show that rDeltaF508 CFTR endocytosis is 6-fold more rapid (approximately 30% per 2.5 min) than WT (wild-type, approximately 5% per 2.5 min) CFTR at 37 degrees C in polarized airway epithelial cells (CFBE41o-). We also investigated rDeltaF508 CFTR endocytosis under two further conditions: in culture at the permissive temperature (27 degrees C) and following treatment with pharmacological chaperones. At low temperature, rDeltaF508 CFTR endocytosis slowed to WT rates (20% per 10 min), indicating that the cell-surface trafficking defect of rDeltaF508 CFTR is TS. Furthermore, rDeltaF508 CFTR is stabilized at the lower temperature; its half-life increases from <2 h at 37 degrees C to >8 h at 27 degrees C. Pharmacological chaperone treatment at 37 degrees C corrected the rDeltaF508 CFTR internalization defect, slowing endocytosis from approximately 30% per 2.5 min to approximately 5% per 2.5 min, and doubled DeltaF508 surface half-life from 2 to 4 h. These effects are DeltaF508 CFTR-specific, as pharmacological chaperones did not affect WT CFTR or transferrin receptor internalization rates. The results indicate that small molecular correctors may reproduce the effect of incubation at the permissive temperature, not only by rescuing DeltaF508 CFTR from ERAD, but also by enhancing its cell-surface stability.

Objectives: Our goals were (1) to determine the use of medications to treat gastroesophageal reflux in extremely low birth weight infants (birth weight of < 1000 g) at discharge; (2) to identify risk factors associated with the use of medications to treat gastroesophageal reflux at discharge; and (3) to assess the contribution of gastroesophageal reflux medication use at discharge to growth and development at corrected ages of 18 to 22 months., Methods: This retrospective cohort analysis included extremely low birth weight infants enrolled at National Institute of Child Health and Human Development Neonatal Research Network Centers between 2002 and 2003 who survived to follow-up evaluations at corrected ages of 18 to 22 months. Analyses were used to identify factors associated with discharge with antireflux medications and poor growth or neurodevelopmental impairment after discharge., Results: A total of 1598 infants were included in the analyses; 24.8% were discharged from the hospital with medications to treat gastroesophageal reflux. A total of 19.3% of the 1287 infants discharged at postmenstrual age of < or = 42 weeks were discharged with antireflux medications. For those infants, center, lower gestational age, and race had significant effects on the use of antireflux medications at discharge. A total of 47.6% of the 311 infants discharged at postmenstrual age of > 42 weeks were discharged with antireflux medications. For those infants, no tested variables were associated with treatment with antireflux medications at discharge. Use of antireflux medications at discharge was not associated with either poor growth or neurodevelopmental impairment at corrected ages of 18 to 22 months., Conclusions: Use of antireflux medications at the time of discharge seems to be common for extremely low birth weight infants, especially those discharged at postmenstrual age of > 42 weeks, but does not seem to have effects on growth or development at the time of follow-up evaluations.

We compared outcomes in infants with methicillin-resistant and methicillin-sensitive Staphylococcus aureus bacteremia. Infants with methicillin-resistant S. aureus infection had a longer median duration of bacteremia (4.5 versus 1 day, P = 0.01), but no difference in length of hospital stay, mortality, or neurodevelopmental impairment.