Cerebral Palsy: A Current Perspective.

Cerebral palsy (CP) is the most common cause of motor disability in children. Insults to the brain at different times lead to diverse injuries. As a result, CP is an extremely heterogeneous clinical diagnosis, presenting differently in each individual and at various ages. With improving survival rates of preterm newborns, increasing active resuscitation of extremely preterm newborns, and widespread availability of extensive genetic testing soon after birth, it is imperative to focus on earlier diagnosis and long-term outcomes of CP. CP is primarily classified into 4 categories based on type of motor impairment, functional ability, distribution, and etiology. As the understanding of CP has evolved significantly in the last 2 decades, the methods of early detection of CP have consequently advanced. Appropriate diagnosis is essential for proper education and counseling of affected families, and introduction of therapeutic interventions as early as possible. In this review, we focus on early brain development and provide an overview of the etiology, classification, diagnosis, early therapeutic options, and prognosis of CP.

Effects of Infant Driven Feeding Program on Provision of Breast Milk in Very Low Birth Weight Infants.

Background: The ability to complete nipple feedings is one of the discharge criteria for most premature neonates. The Infant Driven Feeding (IDF) program suggests a system of objective promotion of oral feeds in premature infants. There is a lack of studies systematically studying the effects of IDF on the provision of breast milk. Methods: This was a retrospective study of all premature infants born before 33 weeks and birth weight of <1,500 g admitted to a level IV neonatal intensive care unit. Infants on IDF were compared with those not on IDF. Results: A total of 46 infants in the IDF group and 52 in the non-IDF group met the inclusion criteria. A higher number of infants in the IDF group breastfed at first oral attempt (54% versus 12%). Forty-five percent of IDF mothers completed a full 72 hours of protected breastfeeding at the start of oral feeds, and IDF infants had earlier removal of nasogastric (NG) tube. There was no difference in the provision of breast milk and/or breastfeeding on discharge between the two groups. There was no difference in the length of stay between the two groups. Conclusion: The IDF program attempts to streamline the promotion of oral feeds in very low birth weight infants. Higher incidence of breastfeeding at the start of oral feeds and earlier removal of NG tube did not translate into higher provision of breast milk on discharge in very low birth weight infants in the IDF group. Prospective randomized trials are needed to validate cue-based infant driven feeding programs and their effects on the provision of breast milk.

Outcome of Neonates Born to SARS-CoV-2-Infected Mothers: Tertiary Care Experience at US-Mexico Border.

BACKGROUND: SARS-CoV-2 has affected millions of people around the world. There is a need for data on the effects of this infection on neonates admitted to neonatal intensive care (NICU) units born to infected mothers. Here, we decided to analyze neonates born to mothers who tested positive for SARS-CoV-2 and admitted to NICU compared with neonates who remained with their mothers. METHODS: All pregnant mothers who tested positive for SARS-CoV-2 during pregnancy between 1 June 2020 and 30 June 2021, along with all neonates born to infected pregnant women, were included in this study. We then compared the neonates admitted to NICU with the neonates who remained with their mothers. RESULTS: Eighty-eight neonates were born to eighty-eight SARS-CoV-2-positive mothers. Fifteen of these neonates were admitted to the NICU. The mothers of the neonates admitted to the NICU were more likely to have received prenatal care outside of the USA. In addition, the neonates admitted to the NICU were more likely to have needed significant resuscitation at birth. Respiratory distress was the most common reason for NICU admission. None of the NICU-admitted neonates were SARS-CoV-2-positive. There were no differences between the values of the complete blood counts, morbidities at discharge, lengths of hospitalization, or rates of readmission to hospital in the first month of life observed between the two groups. CONCLUSIONS: The vertical transmission of the SARS-CoV-2 infection remains rare; there was no difference in the hospital outcomes in the neonates of infected mothers. Unlike other studies, which show an increased tendency toward preterm birth in SARS-CoV-2-positive mothers, our study indicates no such association.

Impact of the Coronavirus Pandemic on High-Risk Infant Follow-Up (HRIF) Programs: A Survey of Academic Programs.

OBJECTIVE: The impact of the COVID-19 pandemic on the functioning and services of academic high-risk infant follow-up (HRIF) clinics throughout North America. STUDY DESIGN: Prospective 25-question questionnaire survey through REDCAP links that was sent over 10 weeks, to 105 US and 10 Canadian programs. Finally, 59 of 105 US programs and 5 of 10 Canadian responses were analyzed using SAS version 9.4. RESULTS: In the US, 67% of programs reported closures between 1-5 months, whereas in Canada 80% of programs closed for 1-3 months. In the US 86% of programs provided telemedicine visits and only 42.5% provided multidisciplinary HRIF telemedicine visits. We enumerated innovative approaches specifically for the conduct of Telemedicine visits, the need for the standardization of various tests and services in a telemedicine setting, and to emphasize the urgent need for more government funding to improve follow-up and developmental services to this fragile group of newborns.

Supporting Breastfeeding in 2021 and Beyond-Lessons from the Pandemic.

The COVID-19 pandemic has affected maternal and infant health globally both directly from infection with the SARS-CoV-2 virus and indirectly from changes in health care resulting from social, economic, and health care policies unique to each country. The developing countries have to share the disproportionate burden on maternal and infant health. In this review, we discuss the uncertainties resulting from SARS-CoV-2 infection in pregnancy, vertical transmission of the virus, and its effects on breastfeeding of the newborn. The problems of families and communities caring for mothers with COVID-19 and its impact on breastfeeding in newborns are discussed. The challenges posed by the pandemic have forced us to think and devise innovative solutions, including telemedicine help for antenatal counseling, breastfeeding education, and lactation support. Optimal utilization of resources and technology to find creative solutions at the individual and the community level will help in facilitating maternal-infant bonding soon after birth. Appropriate health care policies to support pregnant and lactating mothers will go a long way in meeting healthy child development goals.

Discharging Preterm Infants Home on Caffeine, a Single Center Experience.

Background: Apnea of prematurity (AOP) affects preterm neonates. AOP, combined with intermittent hypoxemic (IH) events frequently prolongs the length of stay. Caffeine is the preferred medication to treat AOP and may help improve IH events. There is lack of information on the safety of discharging preterm neonates home on caffeine for AOP in the literature. Our objective was to assess safety and benefits, if any, of discharging preterm infants home on caffeine. Methods: After IRB approval, preterm infants discharged home from the neonatal intensive care unit (NICU) on caffeine were compared with those without a discharge prescription for the period of January 2013 to December 2017. Results: A total of 297 infants were started on caffeine, and of those, 87 infants were discharged home on caffeine. There was no difference in length of stay between two groups. Duration of caffeine at home was 31 (28-42) days. The average cost of apnea monitor and caffeine at home per 30 days was USD 1326 and USD 50. There was no difference in number or reasons for emergency department (ED) visits or hospitalizations between two groups. Conclusion: AOP affects almost all preterm infants and along with intermittent hypoxemic events, and is one of the most common reasons for prolonged hospital stay. Discharging stable preterm infants home on caffeine may be safe, especially in those who are otherwise ready to be discharged and are only awaiting complete resolution of AOP/IH events.

Improving timing of antibiotics in neonates with early onset sepsis - Quality improvement project.

BACKGROUND AND OBJECTIVES: Early onset sepsis (EOS) is an important cause of neonatal morbidity and mortality. Timely administration of antibiotics is crucial in management. We initiated a quality improvement project to improve timely administration of antibiotics. METHODS: Primary drivers of change identified by the team were improving delivery of antibiotics from pharmacy and improving time to admit in the electronic medical record (EMR) in order to improve overall timeliness of antibiotics administration. Timings of antibiotics administration was tracked by using a control chart. Timings of antibiotics and outcomes of pre-intervention (December 2016) were compared with post intervention of PDSA cycles (January 2017-November 2018). RESULTS: There was statistically significant improvement in time to admission in electronic medical records over the time periods of pre-intervention, PDSA I and PDSA II (p-value <  0.05) (Table 1). Also, time to delivery of antibiotics from pharmacy was significantly reduced between PDSA cycles from 21 minutes to 9 minutes with improvement in overall workflow. An average time to infusion of antibiotics decreased from 70 minutes to 48 minutes. There was also overall improvement in number of neonates receiving antibiotics under 1 hour of decision making from 37% to 77%. CONCLUSIONS: In our study we were able to successfully implement our "antibiotics under one hour" goal. The ability to achieve this objective can be met across multi-institutions rendering care to newborns if the approach is multidisciplinary. Deleting obstructions in the process that involve admission, registration and entry into the EMR effectively reduced time.

Estrogen Treatment Reverses Prematurity-Induced Disruption in Cortical Interneuron Population.

Development of cortical interneurons continues until the end of human pregnancy. Premature birth deprives the newborns from the supply of maternal estrogen and a secure intrauterine environment. Indeed, preterm infants suffer from neurobehavioral disorders. This can result from both preterm birth and associated postnatal complications, which might disrupt recruitment and maturation of cortical interneurons. We hypothesized that interneuron subtypes, including parvalbumin-positive (PV+), somatostatin-positive (SST+), calretinin-positive (CalR+), and neuropeptide Y-positive (NPY+) interneurons, were recruited in the upper and lower cortical layers in a distinct manner with advancing gestational age. In addition, preterm birth would disrupt the heterogeneity of cortical interneurons, which might be reversed by estrogen treatment. These hypotheses were tested by analyzing autopsy samples from premature infants and evaluating the effect of estrogen supplementation in prematurely delivered rabbits. The PV+ and CalR+ neurons were abundant, whereas SST+ and NPY+ neurons were few in cortical layers of preterm human infants. Premature birth of infants reduced the density of PV+ or GAD67+ neurons and increased SST+ interneurons in the upper cortical layers. Importantly, 17 ß-estradiol treatment in preterm rabbits increased the number of PV+ neurons in the upper cortical layers relative to controls at postnatal day 14 (P14) and P21 and transiently reduced SST population at P14. Moreover, protein and mRNA levels of Arx, a key regulator of cortical interneuron maturation and migration, were higher in estrogen-treated rabbits relative to controls. Therefore, deficits in PV+ and excess of SST+ neurons in premature newborns are ameliorated by estrogen replacement, which can be attributed to elevated Arx levels. Estrogen replacement might enhance neurodevelopmental outcomes in extremely preterm infants.SIGNIFICANCE STATEMENT Premature birth often leads to neurodevelopmental delays and behavioral disorders, which may be ascribed to disturbances in the development and maturation of cortical interneurons. Here, we show that preterm birth in humans is associated with reduced population of parvalbumin-positive (PV+) neurons and an excess of somatostatin-expressing interneurons in the cerebral cortex. More importantly, 17 ß-estradiol treatment increased the number of PV+ neurons in preterm-born rabbits, which appears to be mediated by an elevation in the expression of Arx transcription factor. Hence the present study highlights prematurity-induced reduction in PV+ neurons in human infants and reversal in their population by estrogen replacement in preterm rabbits. Because preterm birth drops plasma estrogen level 100-fold, estrogen replacement in extremely preterm infants might improve their developmental outcome and minimize neurobehavioral disorders.

Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC-HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of glycerol-induced IVH and analyzed autopsy samples from premature infants. We found that total HA levels were comparable in both preterm rabbit pups and human infants with and without IVH, but HA receptors--CD44, TLR2, TLR4--were elevated in the forebrain of both humans and rabbits with IVH. Hyaluronidase treatment of rabbits with IVH reduced CD44 and TLR4 expression, proinflammatory cytokine levels, and microglia infiltration. It also promoted OPC maturation, myelination, and neurological recovery. HC-HA and tumor necrosis factor-stimulated gene-6 were elevated in newborns with IVH; and depletion of HC-HA levels by HA oligosaccharide treatment reduced inflammation and enhanced myelination and neurological recovery in rabbits with IVH. Hence, hyaluronidase or HA oligosaccharide treatment represses inflammation, promotes OPC maturation, and restores myelination and neurological function in rabbits with IVH. These therapeutic strategies might improve the neurological outcome of premature infants with IVH. Significance statement: Approximately 12,000 premature infants develop IVH every year in the United States, and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The onset of IVH induces inflammation of the periventricular white matter, which results in arrested maturation of OPCs and myelination failure. HA is a major component of the extracellular matrix of the brain, which regulates inflammation through CD44 and TLR2/4 receptors. Here, we show two mechanism-based strategies that effectively enhanced myelination and neurological recovery in preterm rabbit model of IVH. First, degrading HA by hyaluronidase treatment reduced CD44 and TLR4 expression, proinflammatory cytokines, and microglial infiltration, as well as promoted oligodendrocyte maturation and myelination. Second, intraventricular injection of HA oligosaccharide reduced inflammation and enhanced myelination, conceivably by depleting HC-HA levels.

Management of preterm giant sacrococcygeal teratoma (GSCT) with an excellent outcome.

Infants born with a giant sacrococcygeal teratoma (GSCT; >10 cm) have high mortality. Risk factors for mortality include increased tumor vascularity, high cardiac output, rapid growth, diagnosis before 20-week gestation, delivery before 30-week gestation, hydrops, low birth weight, Apgar less than 7 at 5 min and polyhydramnios. We present the case of a 28-week infant born with a GSCT (15 × 12 × 16 cm) and all of these risk factors.

Hospital bath basins are frequently contaminated with multidrug-resistant human pathogens.

The hospital environment is increasingly recognized as a reservoir for hospital-acquired pathogens. During a 44-month study period, a total of 1,103 basins from 88 hospitals in the United States and Canada were sampled. Overall, 62.2% of the basins (at least 1 basin at each hospital) were contaminated with commonly encountered hospital-acquired pathogens.