Quality improvement efforts directed at optimal umbilical cord management in delivery room.

Delayed or deferred cord clamping (DCC) and umbilical cord milking (UCM) benefit all infants by optimizing fetal-neonatal transition and placental transfusion. Even though DCC is recommended by almost all maternal and neonatal organizations, it has not been universally implemented. There is considerable variation in umbilical cord management practices across institutions. In this article, we provide examples of successful quality improvement (QI) initiatives to implement optimal cord management in the delivery room. We discuss a number of key elements that should be considering among those undertaking QI efforts to implement DCC and UCM including, multidisciplinary team collaboration, development of theory for change, mapping of the current and ideal process and workflow for cord management, and creation of a unit-specific evidence-based protocol for cord management. We also examine important strategies for implementation and provide suggestions for developing a system for measurement and benchmarking.

Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Implementing Higher Phototherapy Thresholds for Jaundice in Healthy Infants 35 Plus Weeks.

OBJECTIVES: To determine the impact of higher bilirubin thresholds on testing and treatment of healthy infants during the neonatal period. METHODS: This quality improvement study included infants born at ≥35 weeks gestation and admitted to the well-baby nursery between July 2018 and December 2020. We assessed the transition from infants treated according to the 2004 AAP guidelines (pregroup) with those following the Northern California Neonatal Consortium guidelines (postgroup). We examined the proportion of infants receiving phototherapy and total serum bilirubin (TSB) assessments as outcome measures. We examined critical hyperbilirubinemia (TSB above 25 mg/dL or TSB within 2 mg/dL of threshold for exchange transfusion), exchange transfusion, and readmission for jaundice as balancing measures. We compared the differences in outcomes over time using Statistical Process Control p charts. Balancing measures between the pre and postgroups were compared using χ square tests and t-tests. RESULTS: In our population of 6173 babies, there was a significant shift in the proportion receiving phototherapy from 6.4% to 4%. There were no significant changes in incidences of bilirubin >25 mg/dL (0 of 1472 vs 7 of 4709, P = .37), bilirubin within 2 mg/dL of exchange transfusion thresholds (4 of 1472 vs 5 of 4709, P = .15), exchange transfusion (0 of 1472 vs 1 of 4709, P = .70) or readmission for phototherapy (2.9% versus 2.4%, P = .30), between the 2 groups. CONCLUSIONS: Higher thresholds for phototherapy treatment of neonatal hyperbilirubinemia can decrease the need for phototherapy without increasing critical hyperbilirubinemia or readmission rate.

Increased newborn NICU admission for evaluation of hypoxic-ischemic encephalopathy during COVID-19 pandemic in a public hospital.

Background: Prenatal and perinatal care of pregnant mothers has been adversely affected during the COVID-19 pandemic. Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal death and long-term neurological disabilities. Therapeutic hypothermia is effective for neonatal HIE. This study evaluated the effect of the pandemic on neonatal HIE. Methods: This retrospective single-center study compared neonatal HIE evaluation and hypothermia treatment between pre-COVID-19 pandemic (1 January 2018-31 December 2019) and COVID-19 pandemic (1 January 2020-31 December 2021) periods. Infants with abnormal neurological examination and or significant metabolic acidosis were admitted to NICU for evaluation of HIE and therapeutic hypothermia. Demographics, NICU admission and interventions, and neonatal outcomes were compared between infants born during the two periods using χ2, t-test, and Wilcoxon rank-sum test as appropriate. Statistical Process Control charts show the yearly proportion of infants evaluated for HIE and those treated with therapeutic hypothermia. Results: From the pre-pandemic to the pandemic period, the proportion of infants that met HIE screening criteria increased from 13% to 16% (p < 0.0001), the proportion of infants admitted to NICU for HIE evaluation increased from 1% to 1.4% (p = 0.02), and the maternal hypertension rates of the admitted infants increased from 30% to 55% (p = 0.006). There was no difference in the proportions of the infants diagnosed with HIE (0.7% vs. 0.9%, p = 0.3) or treated with therapeutic hypothermia (0.2% vs. 0.3%, p = 0.3) between the two periods. There were no differences in the HIE severity and outcomes of the infants treated with therapeutic hypothermia between the two periods. Conclusion: During the COVID-19 pandemic, we observed a significant increase in NICU admission for HIE evaluation. While we did not find significant increases in neonatal HIE and the need for therapeutic hypothermia, larger studies are needed for a comprehensive assessment of the impact of the COVID-19 pandemic on neonatal HIE.

Higher NICU admissions in infants born at ≥35 weeks gestational age during the COVID-19 pandemic.

Background: Increasing evidence has shown that the COVID-19 pandemic has had a profound negative impact on vulnerable populations and a significant effect on maternal and neonatal health. We observed an increase in the percentage of infants admitted to NICU from 8% to 10% in the first year of the pandemic. This study aimed to compare the delivery room outcomes, NICU admissions and interventions, and neonatal outcomes two years before and during the pandemic. Methods: This was a retrospective study in a public hospital between pre-COVID-19 (April 2018-December 2019) and COVID-19 (April 2020-December 2021). Data were obtained from all live births at ≥35 weeks gestation (GA). Maternal and neonatal demographics, delivery room (DR), and NICU neonatal outcomes were compared between the study periods using simple bivariable generalized estimating equations (GEE) regression. Multivariable GEE logistic regression analysis was performed to adjust for the effects of baseline differences in demographics on the outcomes. Results: A total of 9,632 infants were born ≥35 weeks gestation during the study period (pre-COVID-19 n = 4,967, COVID-19 n = 4,665). During the COVID-19 period, there was a small but significant decrease in birth weight (33 g); increases in maternal diabetes (3.3%), hypertension (4.1%), and Hispanic ethnicity (4.7%). There was a decrease in infants who received three minutes (78.1% vs. 70.3%, p < 0.001) of delayed cord clamping and increases in the exclusive breastfeeding rate (65.9% vs. 70.1%, p < 0.001), metabolic acidosis (0.7% vs. 1.2%, p = 0.02), NICU admission (5.1% vs. 6.4%, p = 0.009), antibiotic (0.7% vs. 1.7%, p < 0.001), and nasal CPAP (1.2% vs. 1.8%, p = 0.02) use. NICU admissions and nasal CPAP were not significantly increased after adjusting for GA, maternal diabetes, and hypertension; however, other differences remained significant. Maternal hypertension was an independent risk factor for all these outcomes. Conclusion: During the COVID-19 pandemic period, we observed a significant increase in maternal morbidities, exclusive breastfeeding, and NICU admissions in infants born at ≥35 weeks gestation. The increase in NICU admission during the COVID-19 pandemic was explained by maternal hypertension, but other adverse neonatal outcomes were only partly explained by maternal hypertension. Socio-economic factors and other social determinants of health need to be further explored to understand the full impact on neonatal outcomes.

Cord management strategies in multifetal gestational births.

Multifetal gestations are associated with high risks of neonatal mortality and morbidities primarily due to prematurity. Delayed cord clamping and cord milking facilitate the postnatal transition and improve outcomes. Limited evidence shows that delayed cord clamping for 30-60 s and cord milking are feasible without causing harm and potentially beneficial in uncomplicated multifetal deliveries. However, data on maternal bleeding from the limited studies are inconsistent. Based on current knowledge of the risk vs. benefits, it is reasonable to perform delayed cord clamping or cord milking (>28 weeks of gestation) in uncomplicated monochorionic and dichorionic multiples. Clearly defined criteria for suitable candidates, indications for clamping or milking the cord during delivery, and improved obstetric techniques in Cesarean deliveries are critical to minimize risks and optimize neonatal transition. Research is needed to identify safe and optimal cord-management strategies for improving survival and long-term outcomes in this high-risk population.

Screening and diagnosis of neonatal hypoglycaemia in at-risk late preterm and term infants following AAP recommendations: a single centre retrospective study.

BACKGROUND: There is a lack of consensus regarding the definition and treatment threshold for neonatal hypoglycaemia. The American Academy of Pediatrics (AAP) has a published clinical report making recommendations on practice guidelines. There is limited literature discussing the impact of these guidelines. In this study, we evaluated the screening and diagnosis of neonatal hypoglycaemia following the AAP guidelines. METHODS: Infants born ≥35 weeks gestational age and admitted to the well-baby nursery between January and December 2017 were included in this study. Our hypoglycaemia policy was based on the AAP clinical report for hypoglycaemia management in newborns. Chart review was done to obtain infant hypoglycaemia risk factors and blood glucose values in the first 24 hours. Data analysis was conducted using Stata V.14.2 (StataCorp). RESULTS: Of 2873 infants born and admitted to the well-baby nursery, 32% had at least one hypoglycaemia risk factor and 96% of them were screened for hypoglycaemia. Screened infants were more likely to be born at a lower gestational age, via C-section, and to a multiparous older mother. Screened infants and hypoglycaemic infants had lower exclusive breastfeeding rates compared with those who were not screened or not hypoglycaemic, respectively. Sixteen per cent of screened infants were diagnosed with hypoglycaemia; 0.8% of at-risk screened infants and 5% of hypoglycaemic infants were admitted to the NICU for treatment of hypoglycaemia. Thirty-one per cent of preterm infants, 15% of large for gestational age infants, 13% of small for gestational age infants and 15% of infants of diabetic mothers were hypoglycaemic. Hypoglycaemic infants were more likely to be born preterm and via C-section. CONCLUSION: Using the AAP time-based definitional blood glucose cut-off values, our incidence of hypoglycaemia found in those who were screened for risk factors was lower compared with other studies. Future long-term follow-up studies will be important.

Ondansetron to reduce neonatal opioid withdrawal severity a randomized clinical trial.

OBJECTIVE: To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS). STUDY DESIGN: A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days. RESULTS: Twenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p > 0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p = 0.02). A non-significant trend was noted for the duration of hospitalization. There was no difference in need for phenobarbital or clonidine therapy, or total dose of morphine in the first 15 days of NOWS treatment. CONCLUSIONS: Ondansetron treatment reduced the severity of NOWS symptoms; and there was an indication that it could reduce the length of stay. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01965704.

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.

Are preterm birth and very low birth weight rates altered in the early COVID (2020) SARS-CoV-2 era?

Objective: We evaluated the prevalence of preterm birth (PTB) and very low birth weight (VLBW) during Jan-Dec 2,020 (early COVID era) at 5 hospitals (2 in West Virginia, 3 in California) compared to Jan 2017-Dec 2019 (pre-COVID) inclusive of 2 regional perinatal centers (1 in Huntington, WV and 1 in San Jose, CA) and 3 community hospitals (1 each in Cabell, Los Angeles and Santa Clara counties). Design/methods: We examined PTB and VLBW rates of live births at 5 US hospitals from Jan 2017-Dec 2020. We compared PTB and VLBW rates in 2020 to 2017-2019 using Poisson regression and rate ratio with a 95% confidence interval. We stratified live births by gestational age (GA) (<37, 33-36, and <33 weeks) and birth weight (≤1,500 g, >1,001 g to ≤1,500 g, ≤1,000 g). We examined PTB rates at 4 of the hospitals during Jan-Dec 2020 and compared them to the prior period of Jan 2017-Dec 2019 using Statistical Process Control (SPC) for quarterly data. Results: We examined PTB and VLBW rates in 34,599 consecutive live births born Jan 2017-Dec 2019 to rates of 9,691 consecutive live births in 2020. There was no significant change in PTB (<37 weeks GA) rate, 10.6% in 2017-2019 vs. 11.0% in 2020 (p = 0.222). Additionally, there was no significant change when comparing VLBW rates in 2017-2019 to 2020, 1.4% in 2017-2019 vs. 1.5% in 2020 (p = 0.832). Conclusion: We found no significant change in the rates of PTB or VLBW when combining the live birth data of 5 US hospitals in 3 different counties.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants. DESIGN: A prospective observational study. SETTING: Public healthcare system in Santa Clara County (California, USA). PARTICIPANTS: Women with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p<0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared with <60 days (1.2 vs 0.6, p<0.0001). Infant IgG seroreversion rates over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4 of 48), 12% (3 of 25), and 38% (5 of 13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to 6 months of age. Two newborns showed seroconversion at 2 weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than 2 months before delivery. Maternally derived passive immunity may persist in infants up to 6 months of life. Neonates are capable of mounting a strong antibody response to perinatal SARS-CoV-2 infection.

Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study.

OBJECTIVE: To investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants. DESIGN: A prospective observational study. SETTING: A public healthcare system in Santa Clara County (CA, USA). PARTICIPANTS: Women with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021. OUTCOMES: SARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life. RESULTS: Of 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age. CONCLUSIONS: Maternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.

Practice Variations in Diagnosis and Treatment of Hypoglycemia in Asymptomatic Newborns.

OBJECTIVES: To describe variations in the practice of hypoglycemia screening and treatment in asymptomatic infants in the United States. METHODS: During the time period from February 2018 to June 2018, we surveyed representatives of hospitals participating in the Better Outcomes through Research for Newborns Network, a national research network of clinicians providing hospital care to term and late-preterm newborns. The survey included 22 questions evaluating practices related to hypoglycemia screening and management of asymptomatic infants. RESULTS: Of 108 network sites, 84 (78%) responded to the survey; 100% had a hypoglycemia protocol for screening at-risk infants in the well-baby nursery. There were wide variations between sites regarding the definition of hypoglycemia (mg/dL) (<45 [24%]; <40 [23%]; <40 [0-4 hours] and <45 [4-24 hours] [27%]; <25 [0-4 hours] and <35 [4-24 hours] [8%]), timing of first glucose check (<1 hour [18%], 1-2 hours [30%], 30 minutes post feed [48%]), and threshold glucose level for treatment (<45 [19%]; <40 [18%]; <40 [0-4 hours] and <45 [4-24 hours] [20%]; <25 [0-4 hours] and <35 [4-24 hours] [15%]). All respondents used breast milk as a component of initial therapy. Criteria for admission to the NICU for hypoglycemia included the need for dextrose containing intravenous fluids (52%), persistent hypoglycemia despite treatment (49%), and hypoglycemia below a certain value (37%). CONCLUSIONS: There is a significant practice variation in hypoglycemia screening and management across the United States.

Effect of Delayed Cord Clamping on Umbilical Blood Gas Values in Term Newborns: A Systematic Review.

OBJECTIVE: To compare the effect of delayed cord clamping on cord blood gas values in vaginally delivered, healthy, term singletons. DATA SOURCE: We used MEDLINE, CINAHL, CENTRAL, EMBASE, and ClinicalTrials.gov databases. METHODS OF STUDY SELECTION: Eligible studies included randomized controlled trials (RCTs) comparing cord blood gas values obtained from early compared with delayed cord clamping groups and observational studies using serial cord blood gas from the same umbilical cord. We described the difference in means of cord blood gas parameters and comparative descriptive statistics when a difference in means was not available. We used a domain-based risk bias tool to extract methodologic details and assess potential risk of bias. TABULATION, INTEGRATION, AND RESULTS: This review included two RCTs and three observational studies. These studies included a total of 234 newborns with early cord clamping and 218 newborns with delayed cord clamping. The observational studies showed that 45-90 seconds delayed cord clamping was associated with mean decreases in umbilical arterial pH (0.02-0.03), HCO3 (0.3-0.8 mmol/L) and increases in base deficit (0.3-1.3 mmol/L) compared with early cord clamping. One observational study showed that delayed cord clamping was associated with decreases in umbilical venous pH (0.01) and HCO3 (0.2 mmol/L) and increase in venous base deficit (0.1-0.3 mmol/L) compared with early cord clamping. These changes were not observed in the two RCTs. CONCLUSION: Delayed cord clamping up to 120 seconds has either no effect or only a small effect on cord blood acid-base balance; overall, the magnitude of these changes is not clinically significant in vaginally delivered, healthy, term singletons. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019135779.

Delayed Cord Clamping and Umbilical Cord Milking among Infants in California Neonatal Intensive Care Units.

OBJECTIVE: To assess the current practice of delayed cord clamping (DCC) and to determine patient and hospital factors that predict DCC. STUDY DESIGN: The California Perinatal Quality Care Collaborative (CPQCC) collects data on preterm and acutely ill infants. In 2016, 52 CPQCC neonatal intensive care units (NICUs) collected data on DCC. Hospital and patient characteristics were analyzed using multivariable logistic regression. RESULTS: Of 5,332 deliveries, 1,555 (29%) newborns received DCC. Hospital rates ranged from 0 to 74.5% and increased from 21 to 37% throughout 2016. Infants delivered at <32 weeks or with birth weight <1,500 g were more likely to receive DCC (odds ratio: 2.80; 95% confidence interval: 2.33, 3.36). Cesarean delivery was associated with less likelihood of DCC (odds ratio: 0.68; 95% confidence interval: 0.59, 0.79). After risk adjustment, 17 (33%) hospitals had higher than expected DCC rate. Hospitals with less than 50 NICU beds are more likely to practice DCC, whereas Level 3 American Academy of Pediatrics NICUs, nonprofit owned hospitals, and teaching institutions were less likely to practice DCC (p < 0.001). CONCLUSION: There are opportunities to implement quality improvement activities to increase DCC rates.

Haematocrit in <35 weeks preterm infants who received at least 60 seconds of delayed cord clamping: a retrospective observational study.

OBJECTIVE: To describe haematocrit at birth in preterm infants who received ≥60 s of delayed cord clamping (DCC). DESIGN: Retrospective observational study. SETTING: A California public hospital with an American Academy of Pediatrics level 4 neonatal intensive care unit, with 3500-4000 deliveries annually. PARTICIPANTS: 467 preterm infants born at <35 weeks' gestational age (GA) between January 2013 and December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Haematocrit reference ranges for 0-4 hours after birth and paired haematocrit differences between 0-4 and 4-24 hours. METHODS: Haematocrits were obtained when clinically indicated and collected from arterial, venous and capillary sources. Haematocrits obtained after packed red blood cell transfusions were excluded. We summarised the first available haematocrit between 0 and 4 hours by GA strata. We used mixed-effects linear regression to describe the associations between haematocrit and predictor variables including GA, male sex and hours after an infant's birth. We also compared paired haematocrits at 0-4 and 4-24 hours after birth. RESULTS: The median GA of the 467 included infants was 33.3 weeks, birth weight was 1910 g and DCC duration was 60 s. The mean (95% CI) first haematocrit at 0-4 hours was 46.6 (45.0% to 48.1%), 51.2 (49.6% to 52.8%), 50.6 (49.1% to 52.1%), 54.3 (52.8% to 55.8%) and 55.6 (54.6% to 56.6%) for infants 23-29, 30-31, 32, 33 and 34 weeks' GA strata, respectively. The subanalysis of 174 infants with paired haematocrits at 0-4 and 4-24 hours showed that for each additional hour after birth, the mean (95% CI) haematocrit increased by 0.2 (0.1% to 0.3%), 0.2 (0.1% to 0.4%) and 0.1 (0.0% to 0.2%) for infants in 23-29, 30-31 and 32 weeks' GA strata, respectively. The subanalysis showed no change between the paired haematocrits in the 33 and 34 weeks' GA strata. CONCLUSIONS: Our study describes haematocrit in preterm infants who received ≥60 s DCC as standard of care. Haematocrit during the first 0-4 hours in our study is higher than the previously described reference ranges prior to DCC becoming routine clinical practice. The paired second haematocrit at 4-24 hours is higher than haematocrit at 0-4 hours.

Neonatal outcomes in preterm multiples receiving delayed cord clamping.

OBJECTIVE: To compare neonatal outcomes in singletons versus multiples, first-born versus second-born multiples and monochorionic versus dichorionic/trichorionic multiples <33 weeks' gestational age (GA) who received delayed cord clamping (DCC). DESIGN: Retrospective, observational study of 529 preterm infants receiving ≥30 s DCC. Generalised estimating equations and mixed effects models were used to compare outcomes in singletons versus multiples and monochorionic versus dichorionic/trichorionic multiples. Wilcoxon signed-rank and McNemar tests were used to compare first-born versus second-born multiples. SETTING: Level III neonatal intensive care unit, California, USA. PATIENTS: 433 singletons and 96 multiples <33 weeks' GA, born January 2008-December 2017, who received DCC. RESULTS: 86% of multiples and 83% of singletons received DCC. Multiples had higher GA (31.0 weeks vs 30.6 weeks), more caesarean sections (91% vs 54%), fewer males (48% vs 62%) and higher 12-24 hour haematocrits (54.3 vs 50.5) than singletons. Haematocrit difference remained significant after adjusting for birth weight, delivery type and sex. Compared with first-born multiples, second-born multiples were smaller (1550 g vs 1438 g) and had lower survival without major morbidity (91% vs 77%). Survival without major morbidity was not significant after adjusting for birth weight. Compared with dichorionic/trichorionic multiples, monochorionic multiples had slightly lower admission temperatures (37.0°C vs 36.8°C), although this difference was not clinically significant. There were no other differences in delivery room, respiratory, haematological or neonatal outcomes between singletons and multiples or between multiples' subgroups. CONCLUSIONS: Neonatal outcomes in preterm infants receiving DCC were comparable between singletons and multiples, first and second order multiples and monochorionic and dichorionic/trichorionic multiples.

Patterned frequency-modulated oral stimulation in preterm infants: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the effect of patterned, frequency-modulated oro-somatosensory stimulation on time to full oral feeds in preterm infants born 26-30 weeks gestation. STUDY DESIGN: This is a multicenter randomized controlled trial. The experimental group (n = 109) received patterned, frequency-modulated oral stimulation via the NTrainer system through a pulsatile pacifier and the control group (n = 101) received a non-pulsatile pacifier. Intent-to-treat analysis (n = 210) was performed to compare the experimental and control groups and the outcomes were analyzed using generalized estimating equations. Time-to-event analyses for time to reach full oral feeds and length of hospital stay were conducted using Cox proportional hazards models. RESULTS: The experimental group had reduction in time to full oral feeds compared to the control group (-4.1 days, HR 1.37 (1.03, 1.82) p = 0.03). In the 29-30 weeks subgroup, infants in the experimental group had a significant reduction in time to discharge (-10 days, HR 1.87 (1.23, 2.84) p < 0.01). This difference was not observed in the 26-28 weeks subgroup. There was no difference in growth, mortality or morbidities between the two groups. CONCLUSIONS: Patterned, frequency-modulated oro-somatosensory stimulation improves feeding development in premature infants and reduces their length of hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01158391.

Eliminating Risk of Intubation in Very Preterm Infants with Noninvasive Cardiorespiratory Support in the Delivery Room and Neonatal Intensive Care Unit.

INTRODUCTION: Avoiding intubation and promoting noninvasive modes of ventilator support including continuous positive airway pressure (CPAP) in preterm infants minimizes lung injury and optimizes neonatal outcomes. Discharge home on oxygen is an expensive morbidity in very preterm infants (VPI) with lung disease. In 2007 a standardized bundle was introduced for VPI admitted to the neonatal care unit (NICU) which included delayed cord clamping (DCC) at birth and noninvasive ventilation as first-line cardiorespiratory support in the delivery room (DR), followed by bubble CPAP upon NICU admission. OBJECTIVE: Our goal was to evaluate the risk of (1) intubation and (2) discharge home on oxygen after adopting this standardized DR bundle in VPI born at a regional perinatal center and treated in the NICU over a ten-year period (2008-2017). MATERIALS AND METHODS: We compared maternal and neonatal demographics, respiratory care processes and outcomes, as well as neonatal mortality and morbidity in VPI (< 33 weeks gestation) and extremely low birth weight (ELBW, < 1000 g) subgroup for three consecutive epochs: 2008-2010, 2011-2013, and 2014-2017. RESULTS: Of 640 consecutive inborn VPI, 55% were < 1500 g at birth and 23% were ELBW. Constant through all three epochs, DCC occurred in 83% of VPI at birth. There was progressive increase in maternal magnesium during the three epochs and decrease in maternal antibiotics during the last epoch. Over the three epochs, VPI had less risk of DR intubation (23% versus 15% versus 5%), NICU intubation (39% versus 31% versus 18%), and invasive ventilation (37% versus 30% versus 17%), as did ELBW infants. Decrease in postnatal steroid use, antibiotic exposure, and increase in early colostrum exposure occurred over the three epochs both in VPI and in ELBW infants. There was a sustained decrease in surfactant use in the second and third epochs. There was no significant change in mortality or any morbidity in VPI; however, there was a significant decrease in pneumothorax (17% versus 0%) and increase in survival without major morbidity (15% versus 41%) in ELBW infants between 2008-2010 and 2014-2017. Benchmarked risk-adjusted rate for oxygen at discharge in a subgroup of inborn VPI (401-1500 g or 22-31 weeks of gestation) is 2.5% (2013-2017) in our NICU compared with > 8% in all California NICUs and > 10% in all California regional NICUs (2014-2016). CONCLUSION: Noninvasive strategies in DR and NICU minimize risk of intubation in VPI without adversely affecting other neonatal or respiratory outcomes. Risk-adjusted rates for discharge home on oxygen remained significantly lower for inborn VPI compared with rates at regional NICUs in California. Reducing intubation risk in ELBW infants may confer an advantage for survival without major morbidity. Prenatal magnesium may reduce intubation risk in ELBW infants.

Prevention of Prematurity: Advances and Opportunities.

Preterm birth (PTB) rate varies widely and has significant racial and ethnic disparities. Although causal mechanisms are ill understood, socioenvironment, phenotype, and genotype provide insight into pathways for preventing PTB. Data suggest varied response to current medical interventions is explicable Approved by underlying pharmacogenomics. Currently, prevention focuses on minimizing iatrogenic PTB and risk reduction especially in those with prior PTB using proven medical and public health strategies. In the future, preventive approaches will be based on better understanding of sociodemography, nutrition, lifestyles, and underlying individual genetic and epigenetic variation. Statistical approaches and "big-data" models are critical in future study.