Despite widespread prevalence of vitamin D deficiency, there is a paucity of evidence on the appropriate supplemental dose in preterm infants. Various professional organizations empirically recommend different doses of vitamin D, ranging from 400 to 1000 IU per day.

Daily vitamin D supplementation at a dose of 800 IU compared with 400 IU significantly reduces the prevalence of vitamin D deficiency in preterm infants. The clinical significance of achieving vitamin D sufficiency needs to be studied in larger trials. (Read the full article)

Preterm infants must develop oral feeding skills before successfully transitioning to home. Pacifier-activated devices playing selected music can improve nonnutritive sucking in preterm infants. A mother’s voice is a positive auditory stimulus for infants.

A brief intervention with a pacifier-activated music player using mother’s voice can decrease tube feeding duration without adverse effects on stress or growth. Operant conditioning with positive reinforcement is an effective developmental strategy to improve preterm infants’ feeding skills. (Read the full article)

Although expert consensus and previous literature document the importance of early feeding and activity behaviors and practices in preventing obesity and the risks of early rapid weight gain, few studies have rigorously assessed obesity-related behaviors by caregivers of infants.

This study demonstrates the high prevalence of behaviors thought to increase risk for obesity in a diverse, large sample of parent/2-month-old dyads and finds that many behaviors vary by race and ethnicity, suggesting the potential for culturally tailored interventions. (Read the full article)

Rapid and reliable tools for the diagnosis of neonatal sepsis are still unavailable. No single biomarker studied has yielded conclusive results. Genome-wide expression profiles (GWEPs) have been successfully determined for the diagnosis of sepsis in pediatric and adult populations.

GWEPs are described for the first time in very low birth weight infants with proven bacterial sepsis. Our results suggest that GWEPs could be used for early discrimination of septic newborn versus nonseptic infants. (Read the full article)

Many young children are at risk for caries, which is the most common chronic disease of childhood. As primary teeth begin to develop in utero, prenatal influences are believed to affect the integrity of enamel and subsequent resistance to decay.

This study shows, for the first time, that maternal prenatal 25-hydroxyvitamin D levels may have an influence on the primary dentition and the development of early childhood caries. Specifically, lower levels are associated with increased risk of caries in infants. (Read the full article)

Urinary tract infection (UTI) is the most common bacterial infection in febrile infants aged 1 to 90 days. It is unclear if urine microscopy offers significant benefit beyond urine dipstick as a screening test for UTI in this population.

Dipstick may be an adequate screening test for UTI in infants aged 1 to 90 days with a negative predictive value (NPV) of 98.7%. Adding microscopy increases the NPV to 99.2% but results in 8 false-positives for every UTI missed by dipstick. (Read the full article)

Although a number of randomized controlled trials of erythropoietin administration to preterm infants have been performed, few studies have reported 2-year or longer neurodevelopmental outcomes, and no studies have evaluated neurodevelopmental outcomes of infants randomized to receive Darbepoetin.

This is the first prospectively designed study to evaluate the neurocognitive outcomes of preterm infants randomized to receive Darbepoetin or erythropoietin compared with placebo. Infants in the ESA groups had significantly higher cognitive scores compared with the placebo group. (Read the full article)

Prematurely born infants commonly have abnormal metabolic screens.

Both gestational and chronological age influence metabolic profiles used to screen for inborn errors of metabolism. (Read the full article)

Children born late and moderately preterm are at increased risk of developmental problems compared with term-born peers. Screening for developmental problems in the early years may thus aid in the early identification of children at risk for adverse outcomes.

The Parent Report of Children’s Abilities-Revised has good concurrent validity and 90% sensitivity and 76% specificity for identifying moderate/severe cognitive developmental delay in infants born late and moderately preterm. This parent questionnaire may be used as a clinical screening tool. (Read the full article)

Oral vaccine responses are low in children from less-developed countries perhaps as a result of intestinal dysbiosis. New high-throughput DNA-based methods allow characterization of intestinal microbiota as a predictor of vaccine responses.

High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and a larger thymus in Bangladeshi infants. Conversely, high abundance of Clostridiales, Enterobacteriales, and Pseudomonadales was associated with neutrophilia and lower vaccine responses. (Read the full article)

Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy.

Risk factors for sleep-related infant deaths may be different for different age groups. The predominant risk factor for younger infants is bed-sharing, whereas rolling to prone, with objects in the sleep area, is the predominant risk factor for older infants. (Read the full article)

Newborn infants who are predominantly breastfed are much more likely to develop prolonged hyperbilirubinemia than those fed formula, but the prevalence of prolonged hyperbilirubinemia in a largely white, North American, breastfed population is unknown.

Practitioners can be reassured that it is normal for 20% to 30% of predominantly breastfed infants to be jaundiced at age 3 to 4 weeks and for 30% to 40% of these infants to have bilirubin levels ≥5 mg/dL. (Read the full article)

Supplemented mother’s own milk is the preferred nutrition for very low birth weight infants.

Through targeted encouragement and guidance, most mothers are able to provide milk to their very low birth weight infants, both for early and prolonged feeding, in an open-bay NICU. (Read the full article)

Term MRI can assist in identifying the nature and extent of brain injury in preterm infants. However, brain injury detected by MRI does not fully account for neurodevelopmental impairments, particularly cognitive and behavioral impairments, common in preterm survivors.

In addition to brain injury, an assessment of brain growth by using one-dimensional measurements on MRI is helpful for predicting neurodevelopment. Two different patterns of impaired brain growth are observed that relate independently to early cognitive development in preterm infants. (Read the full article)

Messages emphasizing societal benefits of vaccines have been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children.

Findings suggest that health care providers should emphasize the direct benefits of MMR vaccination to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child. (Read the full article)

Prone sleeping is a major risk factor for sudden infant death syndrome (SIDS). Cerebral oxygenation and blood pressure are reduced in the prone sleeping position in healthy term infants. Preterm infants are at significantly increased risk of SIDS.

Preterm infants display reduced cerebral oxygenation compared with term infants, most prominently at 2 to 3 months corrected age in the prone position when blood pressure is concurrently reduced. This may contribute to the increased risk for SIDS among infants born preterm. (Read the full article)

Asymptomatic neonatal subdural hemorrhage (SDH) is common, resolves within 4 weeks, and is typically infratentorial or posterior when supratentorial. Subdural hemorrhages may occur after cardiac surgery in infancy. Some hypothesize a causal relationship between hypoxia and SDH in infancy.

Asymptomatic neonatal SDH is often supratentorial and over the convexities. Small infratentorial SDHs may persist for ≤90 days. In young infants with congenital heart disease, an association between hypoxia and SDH could not be demonstrated. (Read the full article)

The single-family room (SFR) NICU is a major response to improve care and reduce developmental morbidity in preterm infants. However, no studies have examined how and why this model is associated with changes in medical and neurobehavioral outcome.

This study shows improved medical and neurodevelopmental outcome in infants hospitalized in the SFR model of care. More important, improvements occurred specifically in relation to increases in maternal involvement and developmental support afforded by the SFR environment. (Read the full article)

Phototherapy decreases bilirubin concentration in skin more rapidly than in blood. During and after phototherapy, transcutaneous bilirubin measurements are considered unreliable and therefore discouraged.

Transcutaneous bilirubin underestimates total serum bilirubin by 2.4 mg/dL (SD, 2.1 mg/dL) during the first 8 hours after phototherapy. This gives a safety margin of ~7 mg/dL below the treatment threshold to omit confirmatory blood sampling. (Read the full article)

Prophylactic indomethacin in extremely low birth weight infants decreases severe intraventricular hemorrhage and patent ductus arteriosus but it is unknown whether concurrent enteral feeding and prophylactic indomethacin is associated with increased risk of spontaneous intestinal perforation.

The combination of prophylactic indomethacin and enteral feeding during the first 3 days after birth does not increase the risk of spontaneous intestinal perforation. (Read the full article)

White matter abnormality (WMA) on neuroimaging is considered a crucial link with adverse neurodevelopmental outcome in preterm infants. Brain MRI is more sensitive in detecting WMA than cranial ultrasound (CUS), but questions remain about timing and prognostic value of modalities.

Near-term CUS and MRI abnormalities were associated with adverse 18- to 22-month outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of later neuroimaging in this large, extremely preterm cohort surviving to near-term. (Read the full article)

Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalizations. Mortality rates associated with RSV hospitalizations are based on estimates from studies conducted decades ago. Accurate understanding of mortality is required for identifying high-risk infants and children.

Mortality associated with RSV is uncommon in the 21st century, with annual deaths far lower than previous estimates. The majority of deaths occurred in infants with complex chronic conditions or in those with life-threatening conditions in addition to RSV infection. (Read the full article)

Necrotizing enterocolitis is associated with high mortality and morbidity in premature infants. Anaerobic antimicrobial therapy has been associated with increased risk of intestinal strictures in a small randomized trial. Optimal antimicrobial therapy for necrotizing enterocolitis is unknown.

Anaerobic antimicrobial therapy was associated with increased risk of stricture formation. Infants with surgical necrotizing enterocolitis treated with anaerobic antimicrobial therapy had lower mortality. For infants with medical necrotizing enterocolitis, there was no added benefit associated with anaerobic antimicrobial therapy. (Read the full article)

Studies examining early postnatal discharge and readmission for jaundice report conflicting results. Infants born 37 to 38 weeks’ gestation have an increased risk for readmission for jaundice; however, the impact of early discharge on this group has not been investigated.

Early postnatal discharge was significantly associated with readmission for jaundice. Of the infants discharged early, those born 37 to 38 weeks’ gestation, born via vaginal delivery, born to Asian mothers, or were breastfed had the greatest risk for readmission. (Read the full article)

Immune-related bioactive proteins are highly concentrated in the colostrum of mothers who deliver preterm infants. Oropharyngeal administration was proposed as a safe and feasible alternative method of providing colostrum to immunocompromised premature infants.

Oropharyngeally administered colostrum during the first few days of life increased urinary secretory immunoglobulin A and lactoferrin, decreased urinary interleukin-1β, reduced salivary transforming growth factor-β1 and interleukin-8, and reduced the occurrence of clinical sepsis in extremely premature infants. (Read the full article)

Sustained lung inflation and positive end-expiratory pressure would permit lung recruitment immediately after birth, improving lung mechanics and reducing the need for respiratory support. Previous clinical studies in preterm infants provided promising results but have some limitations.

This randomized controlled study found that prophylactic sustained lung inflation and positive end-expiratory pressure in the delivery room decreased the need for mechanical ventilation in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome. (Read the full article)

Noninvasive ventilation (NIV) reduced the need of intubation in preterm infants with RDS. However, randomized studies comparing nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure are still lacking.

The present study shows no differences in short-term outcomes between 2 different NIV strategies, nasal synchronized intermittent positive pressure ventilation and bilevel continuous positive airway pressure, in preterm infants for the initial treatment of RDS. (Read the full article)

Preterm infants experience disproportionate growth failure postnatally and may be large weight for length despite being small weight for age by hospital discharge. There is no routinely used measure to quantify and monitor disproportionate growth in the NICU.

BMI differs across gender and gestational age. We provide a set of validated reference curves to track changes in BMI for prematurely born infants for use with weight-, length-, and head-circumference-for-age intrauterine growth curves. (Read the full article)

There is growing evidence reporting that moderately preterm, late preterm, and early term infants are at increased risk of developmental delay. The characteristics of this association are not well established in the literature.

In a sample of infants born between 32 and 41 weeks, there was an inverse and "dose response" relationship between gestational age and developmental delay risk using the ASQ at 8 and 18 months of corrected postnatal age. (Read the full article)

In a previous short-term physiologic randomized controlled trial, continuous positive airway pressure by helmet was feasible and efficient in improving gas exchange in pediatric acute respiratory failure due to bronchiolitis.

Continuous positive airway pressure administered by helmet reduces the rate of noninvasive respiratory support failure and provides longer application time with less sedation than a facial mask. In addition, it is safe to use and free from adverse events. (Read the full article)

Preterm infants are at an increased risk of infections; therefore, vaccination is of particular importance. Because immune response data reported for preterm infants may vary according to gestational age and vaccination timing, vaccine responses in this population warrant additional research.

This study evaluated 13-valent pneumococcal conjugate vaccine in preterm infants. Results suggest that this vaccine was well tolerated and immunogenic; most subjects achieved serotype-specific immunoglobulin G antibody levels and functional antibody responses likely to correlate with protection against invasive disease. (Read the full article)

Timely immunoprophylaxis and completion of the 3-dose hepatitis B vaccine series represents the cornerstone of perinatal hepatitis B prevention. Immunoprophylaxis for infants born to hepatitis B surface antigen–positive mothers reduces up to 95% of perinatal hepatitis B virus infections.

Despite recommended immunoprophylaxis, perinatal hepatitis B virus infection occurs among ~1% of infants. Infants born to mothers who are younger, hepatitis B e-antigen positive, or who have a high viral load or infants who receive <3 hepatitis B vaccine doses are at greatest risk of infection. (Read the full article)

Considerable differences in outcome after extremely preterm birth have been reported between centers and regions providing a comparative level of care, but the reasons for these variations have been poorly examined.

In extremely preterm fetuses alive at the mother’s admission for delivery, and in infants born alive, mortality up to 2.5 years is reduced in regions with a more active use of perinatal interventions without increased neurodevelopmental morbidity. (Read the full article)

Infants born extremely premature and infants born to adolescent mothers are at risk for adverse developmental and behavior outcomes. There is limited research on the dual risk imparted to infants born extremely premature to adolescent mothers.

Extremely premature infants of adolescent mothers have significantly increased rates of behavior problems. Nonwhite race and living in ≥3 places by 18 to 22 months of age are risk factors for adverse behavior outcomes among infants of adolescent mothers. (Read the full article)

Little is known about the prevalence or outcomes of infants with indeterminate diagnostic results after a positive cystic fibrosis (CF) newborn screen (CF transmembrane conductance regulator–related metabolic syndrome [CRMS]).

CRMS accounted for 15.7% of newborn screened diagnoses in the CF Patient Registry from 2010 to 2012 (CRMS:CF ratio = 5.0:1.0). Although most infants were healthy, some infants demonstrated clinical features concerning for CF. (Read the full article)

Newborn screening for critical congenital heart defects (CCHDs) has been implemented in many hospitals, yet there is uncertainty about the number of infants with CCHDs that might be detected through universal implementation of newborn CCHD screening in the United States.

We estimated that ~875 infants with CCHDs might be detected, and ~880 missed, annually through universal CCHD screening in the United States. Increases in prenatal diagnosis are unlikely to substantially impact the number of infants detected through CCHD screening. (Read the full article)

Suboptimal brain development and increased risk of cognitive deficits are well documented in very low birth weight children. Supplementation with docosahexaenoic acid and arachidonic acid has been associated with positive cognitive effects.

This follow-up study of a randomized controlled trial of supplementation with docosahexaenoic acid and arachidonic acid to very low birth weight infants is the first report on both cognition and brain macrostructure measured with MRI. No cognitive or neuroanatomical effects were detected at 8 years. (Read the full article)

The sensitivity of the urinalysis (UA) traditionally has been considered suboptimal in young infants. Whether the finding of a negative UA and a positive urine culture represents a false-negative UA versus a false-positive urine culture remains unclear.

In infants <3 months with bacteremic urinary tract infection, a condition that represents true infection, the UA sensitivity is higher than previously reported for urinary tract infection in general, suggesting that the UA is reliable even in young infants. (Read the full article)

Postnatal growth failure is common for very low birth weight infants. Although many of the major morbidities experienced by these infants during their initial NICU stays have decreased in recent years, it is unclear whether growth has improved.

For infants weighing 501 to 1500 g, average growth velocity increased and postnatal growth failure decreased from 2000 to 2013. Still, in 2013, half were discharged with a weight below the 10th percentile for postmenstrual age. (Read the full article)

Delayed cord clamping is recommended for all premature births, despite some studies suggesting a decreased placental transfusion at cesarean delivery.

Umbilical cord milking appears to improve systemic blood flow and perfusion in preterm infants delivered by cesarean delivery more efficiently than delayed cord clamping. (Read the full article)

Prenatal diagnosis may lead to benefits in outcomes for certain forms of critical congenital heart disease. Despite recognized benefits, single-center studies and focused regional efforts suggest that prenatal detection rates for congenital heart disease remain low in the United States.

We describe prenatal detection rates for a large cohort of neonates and infants undergoing heart surgery across a range of congenital heart defects. Additionally, this study adds new information by demonstrating geographic variability of prenatal detection rates across the United States. (Read the full article)

The routine childhood immunization schedule is crowded during the first 2 years, leading to deferred doses and limiting the addition of new vaccines. Combination vaccines can reduce the "shot burden" and improve coverage rates and timeliness.

Antibody response rates to antigens contained in an investigational hexavalent vaccine (DTaP5-IPV-Hib-HepB) were noninferior to licensed comparator vaccines when given as a 3-dose infant series. The safety profile was similar to control except for increased rates of mild-to-moderate, self-limited fever. (Read the full article)

Small-for-gestational-age neonates are at risk for thrombocytopenia during the first days and weeks after birth. However, the incidence, duration, severity, responsible mechanism, value of platelet transfusions, and risk of death from this variety of neonatal thrombocytopenia are unknown.

Ten percent of thrombocytopenic small-for-gestational-age neonates have a recognized cause for low platelets (aneuploidy, extracorporeal membrane oxygenation, disseminated intravascular coagulation); they have a high mortality rate (65%). Ninety percent have a moderate, transient (2 weeks), hyporegenerative thrombocytopenia with a low mortality rate (2%). (Read the full article)

Late preterm infants, compared with full-term infants, have less proficiency in reading and math at school age, with increased need for individualized educational plans and special education services. They also have lower cognitive performance on standardized IQ exams.

Late preterm infants have worse outcomes at school entry, and development is variable during the preschool years, so socioeconomic status, language spoken in the home, maternal education, maternal race, and being a late preterm infant have a large impact. (Read the full article)

Small for gestational age neonates (weight <10th percentile) are at risk for neutropenia during the first days after birth. However, the duration, responsible mechanism, and outcomes of this variety of neonatal neutropenia are not precisely known.

Six percent of small for gestational age neonates had neutrophils <1000/μL, with an average neutropenia duration of 7 days. Neutropenia was more closely linked with small for gestational age status than maternal hypertension. This neutropenia is associated with elevated nucleated red blood cell count and increased odds of necrotizing enterocolitis. (Read the full article)

Central apnea sometimes complicates bronchiolitis. Because apnea tends to occur early in the course of bronchiolitis, there is a danger that infants may be discharged from the emergency department only to subsequently develop apnea at home.

This study prospectively derived clinical decision rules to help emergency physicians admit infants at risk for apnea while discharging those not at risk. (Read the full article)

Abusive head trauma (AHT) remains a significant cause of morbidity and mortality in the pediatric population, especially in young infants. In the past decade, advancements in research have refined medical understanding of the epidemiological, clinical, biomechanical, and pathologic factors comprising the diagnosis, thereby enhancing clinical detection of a challenging diagnostic entity. Failure to recognize AHT and respond appropriately at any step in the process, from medical diagnosis to child protection and legal decision-making, can place children at risk. The American Academy of Pediatrics revises the 2009 policy statement on AHT to incorporate the growing body of knowledge on the topic. Although this statement incorporates some of that growing body of knowledge, it is not a comprehensive exposition of the science. This statement aims to provide pediatric practitioners with general guidance on a complex subject. The Academy recommends that pediatric practitioners remain vigilant for the signs and symptoms of AHT, conduct thorough medical evaluations, consult with pediatric medical subspecialists when necessary, and embrace the challenges and need for strong advocacy on the subject.

Graham A. Colditz
Jul 1, 1995; 96:29-35
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T. Michael O'Shea
Jul 1, 1999; 104:15-21
ARTICLES