Association of Growth During Infancy With Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z-score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n=1400). Growth during infancy was calculated as change in weight z-score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z-score <-1.67; very high weight gain was a change in weight z-score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z-score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% confidence interval: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% confidence interval: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% confidence interval: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

Neuroactive metabolites and bile acids are altered in extremely premature infants with brain injury.

The gut microbiome is associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigate the fecal and plasma metabolome of samples obtained from a cohort of 51 extremely premature infants at several time points, using liquid chromatography (LC)-high-resolution mass spectrometry (MS)-based untargeted metabolomics and LC-MS/MS-based targeted analysis for investigating bile acids and amidated bile acid conjugates. The data are integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor, and T cell profiles. We find an early onset of differentiation in neuroactive metabolites between infants with and without brain injury. We detect several bacterially derived bile acid amino acid conjugates in plasma and feces. These results provide insights into the early-life metabolome of extremely premature infants.

Effect of breast milk intake volume on early behavioral neurodevelopment of extremely preterm infants.

BACKGROUND: This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks). METHODS: The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum. RESULTS: The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups. CONCLUSIONS: Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system.

Quality improvement interventions to increase the uptake of magnesium sulphate in preterm deliveries for the prevention of cerebral palsy (PReCePT study): a cluster randomised controlled trial.

OBJECTIVE: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO4 ) uptake in preterm births for the prevention of cerebral palsy. DESIGN: Unblinded cluster randomised controlled trial. SETTING: Academic Health Sciences Network, England, 2018. SAMPLE: Maternity units with ≥10 preterm deliveries annually and MgSO4 uptake of ≤70%; 40 (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO4 uptake). METHODS: The National PReCePT Programme (NPP) gave maternity units QI materials (clinical guidance, training), regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching. MAIN OUTCOME MEASURES: MgSO4 uptake was compared using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative interviews. RESULTS: MgSO4 uptake increased in all units, with no evidence of any difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% CI -5.03 to 3.35). The probability of enhanced support being cost-effective was <30%. NPP midwives gave more than their funded hours for implementation. Units varied in their support needs. Enhanced support units reported better understanding, engagement and perinatal teamwork. CONCLUSIONS: PReCePT improved MgSO4 uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further.

Effect of additional dead space using end-tidal CO2 measurement on ventilating preterm infants: An experimental study.

BACKGROUND: Dead space is the part of the airway where no gas exchange takes place. Any increase in dead space volume has a proportional effect on the required tidal volume and thus on the risk of ventilation-induced lung injury. Inserts that increase dead space are therefore not used in small preterm infants. This includes end-tidal CO2 measurement. OBJECTIVE: The aim of this study was to investigate the effect of the end-tidal CO2 measurement adapter on ventilation. METHODS: In an experimental setup, an end-tidal CO2 measurement adapter, three different pneumotachographs (PNT-A, PNT-B, PNT-Neo), and a closed suction adapter were combined in varying set-ups. The time required for CO2 elimination by a CO2-flooded preterm infant test lung was measured. RESULTS: PNT-A prolonged CO2 elimination time by 0.9 s (+3.3%), Neo-PNT by 3.2 s (+11.6%) and PNT-B by 9.0 s (+32.7%). The end-tidal CO2 measurement adapter prolonged the elimination time by an additional second without the pneumotachograph (+3.6%) and in combination with PNT-A (+3.1%) and PNT-Neo (+3.1%). In conjunction with PNT-B, the end-tidal CO2 measurement adapter reduced the elimination time by 0.3 seconds (-1%). The use of a closed suction adaptor increased the CO2 elimination time by a further second with PNT-Neo (+3.1%) and by an additional two seconds with no flow sensor (+6.9%), with PNT-A (+6.4%) and with PNT-B (+5.5%). CONCLUSION: The flow sensor had the greatest influence on ventilatory effort, while end-tidal CO2 measurement had only a moderate effect. The increased ventilatory effort levied by the CO2 measurement was dependent on the flow sensor selected. The use of closed suctioning more negatively impacted ventilatory effort than did end-tidal CO2 measurement.

Changes in perinatal management and outcomes of extremely preterm infants born below 26 weeks of gestation in a tertiary referral hospital in Sweden: Comparison between 2004-2007 and 2012-2016.

INTRODUCTION: Perinatal management of extremely preterm births in Sweden has changed toward active care from 22-23 gestational weeks during the last decades. However, considerable regional differences exist. This study evaluates how one of the largest perinatal university centers has adapted to a more active care between 2004-2007 and 2012-2016 and if this has influenced infant survival. MATERIAL AND METHODS: In this historical cohort study, women admitted with at least one live fetus and delivered at 22-25 gestational weeks (stillbirths included) at Karolinska University Hospital Solna during April 1, 2004-March 31, 2007, and January 1, 2012-December 31, 2016, were compared regarding rates of obstetric and neonatal interventions, and infant mortality and morbidity. Maternal, pregnancy and infant data from 2004-2007 were obtained from the Extreme Preterm Infants in Sweden Study while data from 2012-2016 were extracted from medical journals and quality registers. The same definitions of interventions and diagnoses were used for both study periods. RESULTS: A total of 106 women with 118 infants during 2004-2007 and 213 women with 240 infants during 2012-2016 were included. Increases between the study periods were seen regarding cesarean delivery (overall rate 14% [17/118] during 2004-2007 vs. 45% [109/240] during 2012-2016), attendance of a neonatologist at birth (62% [73/118] vs. 85% [205/240]) and surfactant treatment at birth in liveborn infants (60% [45/75] vs. 74% [157/211]). Antepartum stillbirth rate decreased (13% [15/118] vs. 5% [12/240]) and the proportion of live births increased (80% [94/118] vs. 88% [211/240]) while 1-year survival (64% [60/94] vs. 67% [142/211]) and 1-year survival without major neonatal morbidity (21% [20/94] vs. 21% [44/211]) among liveborn infants did not change between the study periods. At 22 gestational weeks, interventions rates were still low during 2012-2016, most obvious regarding antenatal steroid treatment (23%), attendance of a neonatologist (51%), and intubation at birth (24%). CONCLUSIONS: Both obstetric and neonatal interventions at births below 26 gestational weeks increased between 2004-2007 and 2012-2016 in this single center study; however, at 22 gestational weeks they were still at a low level during 2012-2016. Despite more infants being born alive, 1-year survival did not increase between the study periods.

Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Rationale: Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. Objectives: To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA. Methods: The Prematurity-related Ventilatory Control (Pre-Vent) study was an observational multicenter prospective cohort study including infants born at <29 weeks of gestation with continuous cardiorespiratory monitoring. The primary outcome was either "favorable" (alive and previously discharged or inpatient and off respiratory medications/O2/support at 40 wk PMA) or "unfavorable" (either deceased or inpatient/previously discharged on respiratory medications/O2/support at 40 wk PMA). Measurements and Main Results: A total of 717 infants were evaluated (median birth weight, 850 g; gestation, 26.4 wk), 53.7% of whom had a favorable outcome and 46.3% of whom had an unfavorable outcome. Physiologic data predicted unfavorable outcome, with accuracy improving with advancing age (area under the curve, 0.79 at Day 7, 0.85 at Day 28 and 32 wk PMA). The physiologic variable that contributed most to prediction was intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <90%. Models with clinical data alone or combining physiologic and clinical data also had good accuracy, with areas under the curve of 0.84-0.85 at Days 7 and 14 and 0.86-0.88 at Day 28 and 32 weeks PMA. Intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <80% was the major physiologic predictor of severe bronchopulmonary dysplasia and death or mechanical ventilation at 40 weeks PMA. Conclusions: Physiologic data are independently associated with unfavorable respiratory outcome in extremely preterm infants.

Early death, morbidity and pharmacotherapy in extremely premature and very premature in neonatal intensive care units / Morte precoce, morbidade e farmacoterapia em prematuros extremos e muito prematuros em unidades de terapia intensiva neonatal

Abstract Objectives: to evaluate the evolution of extremely preterm and very preterm infants admitted to neonatal intensive care units, regarding the use of ventilatory support, morbidities, medication use, death, survival and viability. Methods: a non-concurrent cohort study, with 163 very premature and extreme newborns hospitalized in three neonatal intensive care units, during 2016 and 2017. A descriptive analysis of the data obtained from the medical records was performed. The outcomes studied were the use of ventilatory support, morbidities, medication use, death and causes of death. A survival curve was constructed and a viability limit was defined. Results: in the study, 28.2% were extreme and 71.8% were very premature. In this order of subgroups, the need for mechanical ventilation was higher for the extremes (65.2% and 41.0%) and the main diagnosis was early sepsis (78.6% and 82.6). Off-label (60.5% and 47.9%) and off-license (25.3% and 29.0%) medications were used. Most deaths (57.8%) occurred between the extremes, mainly due to septic shock. Survival was lower for the lowest gestational ages and the limit of viability was between 26 and 27 weeks. Conclusions: the main morbidities were from the respiratory system, with high use of off-label and unlicensed medications. Extremes had a greater demand for intensive care in addition to needing more drugs and progressing more to death.

Resumo Objetivos: avaliar a evolução dos prematuros extremos e muito prematuros internados em unidades de terapia intensiva neonatais, quanto ao uso de suporte ventilatório e de medicamentos, óbito, sobrevida e viabilidade. Métodos: estudo de coorte não concorrente, com 163 recém-nascidos muito prematuros e extremos internados em três unidades de terapia intensiva neonatais, durante 2016 e 2017. Realizou-se análise descritiva dos dados obtidos dos prontuários. Os desfechos estudados foram o uso de suporte ventilatório, morbidades, uso de medicamentos, óbito e causas de óbito. Foi construída curva de sobrevivência e delimitado um limite de viabilidade. Resultados: no estudo, 28,2% eram extremos e 71,8% muito prematuros. Nessa ordem de subgrupos, a necessidade de ventilação mecânica foi maior para os extremos (65,2% e 41,0%) e o principal diagnóstico foi sepse precoce (78,6% e 82,6).Medicamentos off-label (60,5% e 47,9%) e sem-licença (25,3% e 29,0%) foramutilizados. A maioria dos óbitos (57,8%) ocorreu entre os extremos, principalmente por choque séptico. A sobrevivência foi menor para as menores idades gestacionais e o limite de viabilidade ficou entre 26 e 27 semanas. Conclusões: as principais morbidades foram do sistema respiratório, com alto uso de medicamentos off-label e sem licença. Extremos tiveram maior demanda de cuidados intensivos além de necessitarem de mais medicamentos e evoluírem mais ao óbito.

Development and validation of a risk prediction model for low Apgar scores in extremely premature infants / 中国新生儿科杂志

Objective:To establish a risk prediction model for the occurrence of low 1 min Apgar scores in extremely premature infants (EPIs).Methods:From January 2017 to December 2021, EPIs delivered at our hospital were retrospectively analyzed and randomly assigned into training set group and validation set group in a 7∶3 ratio. 17 clinical indicators were selected as predictive variables and low Apgar scores after birth as outcome variables. Lasso regression and multi-factor logistic regression were used within the training set group to select the final predictors for the final model, and the calibration, distinguishability and clinical decision making curves of the final model were evaluated in the validation set group.Results:A total of 169 EPIs were enrolled, including 117 in the training set group and 52 in the validation set group. 4 indicators including gender, fetal distress, assisted conception and delivery time were selected as the final predictors in the final model. Both the training set group and the validation set group had good calibration curves. The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.731, the sensitivity was 72.2%, the specificity was 60.5% and the AUC of the external validation curve was 0.704. The clinical decision making curve showed that the model had a greater benefit in predicting the occurrence of low Apgar score in EPIs within the threshold of 2% to 75%.Conclusions:The clinical prediction model established in this study has good distinguishability, calibration and clinical accessibility and can be used as a reference tool to predict low Apgar scores in EPIs.

Regular lung recruitment maneuvers during high-frequency oscillatory ventilation in extremely preterm infants: a randomized controlled trial.

BACKGROUND: Lung recruitment maneuvers (LRMs) improve lung volume at initiation of high-frequency oscillatory ventilation (HFOV), but it is unclear when to repeat LRMs. We evaluated the efficiency of scheduled LRMs. METHODS: In a randomized controlled trial, extremely preterm infants on HFOV received either LRMs at 12-hour intervals and when clinically indicated (intervention) or only when clinically indicated (control). The primary outcome was the cumulative oxygen saturation index (OSI) over HFOV time, limited to 7 days. Additionally, LRMs were analyzed with respect to OSI improvement. RESULTS: Fifteen infants were included in each group. The mean (SD) postmenstrual age and weight at HFOV start were 23 + 6 (0 + 5) weeks and 650 (115) g in the intervention group and 24 + 4 (0 + 6) weeks (p = 0.03) and 615 (95) g (p = 0.38) in the control group. The mean (SD) cumulative OSI amounted to 4.95 (1.72) in the intervention versus 5.30 (2.08) in the control group (p = 0.61). The mean (SD) number of LRMs in 12 h was 1.3 (0.2) in the intervention versus 1.1 (0.5) in the control group (p = 0.13). Performing LRM when FiO2 > 0.6 resulted in a mean OSI reduction of 3.6. CONCLUSION: Regular versus clinically indicated LRMs were performed with equal frequency in preterm infants during HFOV, and consequently, no difference in lung volume was observed. LRMs seem to be most efficient at high FiO2. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04289324 (28/02/2020).

Hyperglycemia and Lactic Acidosis Associated with Linezolid Therapy in an Extremely Premature Infant.

The use of linezolid is relatively safe for all age categories, including premature infants. The case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid is reported. A 350-g male infant was born at 24 weeks by cesarean section. His Apgar scores were 1 and 1 at 1 and 5 min, respectively. On the day of life (DOL) 7, linezolid was started at a dose of 10 mg/kg/dose every 8 h for a catheter-related blood stream infection caused by methicillin-resistant coagulase-negative Staphylococci. After linezolid was given, serum lactate and glucose levels increased gradually. After discontinuation of linezolid on DOL 16, hyperglycemia and lactic acidosis improved immediately. In conclusion, a rare case of an extremely premature infant with hyperglycemia and lactic acidosis associated with linezolid was reported. It is crucial to monitor glucose levels along with lactate and pH levels during linezolid therapy.

Long-term follow-up of self-reported mental health and health-related quality of life in adults born extremely preterm.

BACKGROUND: Survival of extremely preterm (EP) birth is increasing, but long-term consequences are still largely unknown as their high survival rates are recent achievements. AIMS: To examine self-reported mental health, and health related quality of life (HRQoL) in a cohort of adults born EP in the early 1990s and individually matched term-born controls, and to describe development through the transition from teenager to adults. METHODS: Thirty-five eligible subjects were born at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g during 1991-1992 in this population-based cohort from Western Norway. We assessed mental health using Youth Self-Report (YSR) at 18 years of age, and Adult Self-Report (ASR) at 27 years, and HRQoL by RAND-36 at 27 years. Data were analysed by unadjusted and adjusted mixed effects models with time by group as interaction term. RESULTS: At 27 years, 24 (69 %) EP-born and 26 (74 %) term-born controls participated. Scores for internalising problems, and syndrome scale anxious/depressed and withdrawn were higher among EP-born compared to term-born controls. For HRQoL, scores were similar in EP-born and term-born groups, except the domain physical functioning where EP-born scored lower. Development over time from 18 to 27 years showed increasing (i.e. deteriorating) scores for internalising, anxious/depressed, somatic complaints, and attention problems in the EP born group. For the term-born, scores for anxious/depression increased over time. CONCLUSIONS: At 27 years of age, EP-born adults reported more internalising problems than term-born controls, while HRQoL was relatively similar except physical functioning. Mental health problems in the EP-born increased from adolescence to adulthood.

Predictive ability of neonatal illness severity scores for early death in extremely premature infants.

BACKGROUND: The predictive ability of neonatal illness severity scores for mortality or morbidity in extremely premature infants has not been extensively studied. We aimed to evaluate the ability of neonatal illness severity scores [Clinical Risk Index for Babies II (CRIB II), Score for Neonatal Acute Physiology II (SNAP-II), and SNAP-Perinatal Extension II (SNAPPE-II)] in predicting mortality and short-term morbidity of extremely premature infants. METHODS: This retrospective study involved 171 infants with gestational age (GA) between 22 and 27 weeks who were admitted to the NICU during 2010-2017. Predictive ability of neonatal illness severity scores for mortality and short-term morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and gastrointestinal perforation) was assessed by comparing their area under the receiver operating characteristic curve. RESULTS: The overall mortality rate was 11.1%. Mortality at 23 weeks' gestation was higher than that at 24-27 weeks' gestation (p < .01, adjusted residual 4.5). Neonatal illness severity scores were significantly higher in infants who died than in those who survived (p < .01). CRIB II (AUC 0.93, 95% CI 0.85-1.00), SNAP-II (AUC 0.90, 95% CI 0.76-1.00), and SNAPPE-II (AUC 0.95, 95% CI 0.91-0.99) appeared to be excellent predictors and were superior to birth weight (AUC 0.88, 95% CI 0.80-0.95) or GA (AUC 0.84, 95% CI 0.72-0.96) alone in predicting early death (died on <28th postnatal day). CRIB II, SNAP-II, and SNAPPE-II were better predictors of early death than mortality in extremely premature infants. Neonatal illness severity score and short-term morbidity were not strongly associated. CONCLUSIONS: The neonatal illness severity scores were excellent predictors of early death in extremely premature infants and might be useful for selecting extremely preterm infants who need intervention.

Skincare practices in extremely premature infants: A survey of tertiary neonatal intensive care units from Australia and New Zealand.

AIM: To investigate skincare practices in the first 2 weeks of life in extremely premature infants across tertiary neonatal intensive care units (NICUs). METHODS: A web-based secure survey invite was emailed to the medical directors of tertiary NICUs. The survey included questions on various aspects of skincare practices in the first 2 weeks of life in extremely premature infants (born before 28 weeks gestation). The person most familiar with local skincare practices was asked to complete the survey and only one response per unit was requested. We performed a descriptive analysis. RESULTS: We received responses from 30 out of 32 NICUs (response rate 93%). Twenty-five NICUs (89%) reported offering resuscitation and intensive care to infants born at ≥23 weeks gestation. All NICUs reported occurrences of skin breakdown, including medical adhesive-related skin injury (30%), abrasion/friction-associated skin injury (46%), perineal skin breakdown (55%), pressure site injury (47%) and diaper dermatitis (60%). A high level of consensus (≥75%) was observed for certain practices, such as the use of polyethylene occlusive plastic wraps at birth and aqueous chlorhexidine solution for sterile procedures, but a low level of consensus (<25%) was observed for many other practices, including the skin risk assessment tool used. CONCLUSIONS: Skin injuries in extremely premature infants are common and skincare practices vary considerably amongst NICUs. Clinical practice improvement projects and further clinical research will help improve consistency amongst NICUs. Further research is needed to assist the development of evidence-based guidelines and benchmarking for skincare practices in these vulnerable infants.

Noninvasive ventilation for respiratory distress syndrome is a potential risk factor for retinopathy of prematurity : Single Slovenian tertiary center study.

Retinopathy of prematurity (nROP) among extremely low gestational age newborns (ELGAN) in Slovenia has increased in recent years. At the same time mortality has further decreased and less invasive approaches for treatment of respiratory distress syndrome have been established. With the aim to study the possible association between the incidence of ROP and the duration of noninvasive ventilation, this retrospective study comprised ELGANs born during the first period (2010/2011), when invasive respiratory support was the prevalent method and in the second period (2015/2016), when noninvasive respiratory support was adopted. The results showed that the duration of noninvasive ventilation is a potential risk factor for ROP. Controlling for known risk factors for ROP and then adjusting for gestational age, number of transfusions and fraction of inspired oxygen (FiO2), the odds of ROP were 1.22 times greater (95% confidence interval, CI 1.01-1.48) with every additional week of noninvasive ventilation (p = 0.03).

Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review.

OBJECTIVES: To conduct a systematic literature review to evaluate the global incidence of intraventricular hemorrhage grade 2-4 among extremely preterm infants. METHODS: We performed searches in MEDLINE and Embase for intraventricular hemorrhage and prematurity cited in English language observational studies published from May 2006 to October 2017. Included studies analyzed data from infants born at ≤28 weeks' gestational age and reported on intraventricular hemorrhage epidemiology. RESULTS: Ninety-eight eligible studies encompassed 39 articles from Europe, 31 from North America, 25 from Asia, five from Oceania, and none from Africa or South America; both Europe and North America were included in two publications. The reported global incidence range of intraventricular hemorrhage grade 3-4 was 5-52% (Europe: 5-52%; North America: 8-22%; Asia: 5-36%; Oceania: 8-13%). When only population-based studies were included, the incidence range of intraventricular hemorrhage grade 3-4 was 6-22%. The incidence range of intraventricular hemorrhage grade 2 was infrequently documented and ranged from 5-19% (including population-based studies). The incidence of intraventricular hemorrhage was generally inversely related to gestational age. CONCLUSIONS: Intraventricular hemorrhage is a frequent complication of extremely preterm birth. Intraventricular hemorrhage incidence range varies by region, and the global incidence of intraventricular hemorrhage grade 2 is not well documented.

Antenatal magnesium sulfate and intestinal morbidities in preterm infants with extremely low gestational age.

BACKGROUND: Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants. METHODS: This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate. RESULTS: Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170-0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589-0.997). In the <26 weeks of gestational age subgroup, the use of antenatal magnesium sulfate was significantly associated with decreased intestinal morbidities requiring surgery (adjusted OR 0.234, 95% CI 0.060-0.922). CONCLUSION: Antenatal magnesium sulfate use appears to have a protective effect on intestinal morbidities requiring surgery in preterm infants in a duration-dependent manner. Association of antenatal magnesium sulfate use and decreased intestinal morbidities requiring surgery was more distinct in preterm infants <26 weeks of gestational age.

Cystic dysplasia of the kidneys in extremely preterm infants following acute kidney injury.

BACKGROUND: Various perinatal morbidities may adversely affect postnatal nephrogenesis in preterm infants. Kidney ultrasonographic findings following acute kidney injury (AKI) have not been well described in preterm infants. Herein, we describe three cases of extremely preterm infants who showed abnormal kidney ultrasonographic findings resembling dysplasia of the kidneys following AKI. CASE-DIAGNOSIS/TREATMENT: Their median gestational age and birth weight were 25+6 (range 23+3-26+6) weeks and 620 (480-840) g, respectively. All infants suffered severe AKI during their third to seventh week of life. Their kidney function recovered with conventional management. Kidney ultrasonographies performed after AKI revealed increased kidney echogenicity, loss of corticomedullary differentiation, and multiple cortical cysts, which were similar to cystic dysplasia of the kidneys and were absent in previous kidney imaging. Three infants eventually developed at least one of the long-term kidney sequelae following AKI, including proteinuria, hypertension, and elevated levels of serum creatinine or cystatin C as determined during the last follow-up at the corrected age of 9-18 months. CONCLUSIONS: Based on these cases, we can infer that AKI occurring during the early postnatal period may result in dysplasia of the kidneys with cortical cysts in extremely preterm infants, which may lead to chronic kidney disease in their later life. It is useful to follow up not only laboratory parameters but also kidney ultrasonographic findings in extremely preterm infants who suffered AKI during their early postnatal periods.

"En Caul" Cesarean Delivery for Extremely Premature Fetuses: Surgical Technique and Anesthetic Options.

The risks and technical difficulties at the cesarean delivery for extremely premature infant under 1,000g are as follows: (1) a premature infant is very weak for pressure of uterine wall or human hands, (2) skin of infant is really premature and weak, (3) uterine wall is thick and difficult to incise at lower segment of uterus, (4) classical vertical incision or reverse T-shape incision are at risk for future uterine rupture, and (5) at the timing of rupture of membrane, uterine wall may contract drastically and the infant is trapped the uterine wall, so called "hug-me-tight-uterus". To resolve the problems, we use the technique of "En Caul" cesarean delivery with nitroglycerin. Intravenous injection of nitroglycerin just before uterine incision made the rapid and sufficient relaxation of uterine muscle. After getting adequate uterine relaxation, U- or J-shaped incision is made to lower segment of the uterus; however, we never incise the membrane before the infant was delivered. The baby is delivered with wrapped amniotic fluid and the membrane, which protect the infant against the pressure of uterine wall or surgeon's hands. The infant is gently handled to neonatologist by "En Caul" with the placenta. Neonatologist can make the membrane ruptured and resuscitation. Own blood transfusion can be made through the umbilical cord and placenta, if the infant was anemic or hypovolemic.