-
American Journal of Obstetrics and... Dec 2023This study aimed to evaluate the association of placental fetal vascular malperfusion lesions with neonatal brain injury and adverse infant neurodevelopmental outcomes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the association of placental fetal vascular malperfusion lesions with neonatal brain injury and adverse infant neurodevelopmental outcomes.
DATA SOURCES
PubMed and Medline, Scopus, and Cochrane databases were searched from inception to July 2022.
STUDY ELIGIBILITY CRITERIA
We included cohort and case-control studies reporting the associations of fetal vascular malperfusion lesions with neonatal encephalopathy, perinatal stroke, intracranial hemorrhage, periventricular leukomalacia, and infant neurodevelopmental and cognitive outcomes.
METHODS
Data were analyzed by including fetal vascular malperfusion lesions as an exposure variable and brain injuries or neurodevelopmental impairment as outcomes using random-effects models. The effect of moderators, such as gestational age or study type, was assessed by subgroup analysis. Study quality and risk of bias were assessed by applying the Observational Study Quality Evaluation method.
RESULTS
Out of the 1115 identified articles, 26 were selected for quantitative analysis. The rates of neonatal central nervous system injury (neonatal encephalopathy or perinatal stroke) in term or near-term infants were more common among fetal vascular malperfusion cases (n=145) than among controls (n=1623) (odds ratio, 4.00; 95% confidence interval, 2.72-5.90). In premature deliveries, fetal vascular malperfusion lesions did not influence the risk of intracranial hemorrhage or periventricular leukomalacia (odds ratio, 1.40; 95% confidence interval, 0.90-2.18). Fetal vascular malperfusion-associated risk of abnormal infant neurodevelopmental outcome (314 fetal vascular malperfusion cases and 1329 controls) was modulated by gestational age being higher in term infants (odds ratio, 5.02; 95% confidence interval, 1.59-15.91) than in preterm infants (odds ratio, 1.70; 95% confidence interval, 1.13-2.56). Abnormal infant cognitive development and mental development were more common among fetal vascular malperfusion cases (n=241) than among controls (n=2477) (odds ratio, 2.14; 95% confidence interval, 1.40-3.27). The type of study (cohort vs case-control) did not influence the association between fetal vascular malperfusion and subsequent infant brain injury or abnormal neurodevelopmental outcome.
CONCLUSION
The findings of cohort and case-control studies indicate a considerable association between fetal vascular malperfusion placental lesions and increased risk of brain injury in term neonates, and neurodevelopmental impairment in both term and preterm infants. A diagnosis of placental fetal vascular malperfusion should be taken into consideration by both pediatricians and neurologists during the follow-up of infants at risk of adverse neurodevelopmental outcomes.
Topics: Infant, Newborn; Infant; Pregnancy; Female; Humans; Placenta; Infant, Premature; Leukomalacia, Periventricular; Intracranial Hemorrhages; Infant, Newborn, Diseases; Stroke; Brain Injuries; Morbidity; Observational Studies as Topic
PubMed: 37315755
DOI: 10.1016/j.ajog.2023.06.014 -
European Journal of Clinical Nutrition Aug 2023This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion.
METHODS
This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups.
RESULTS
No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05).
CONCLUSIONS
The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.
Topics: Infant, Newborn; Humans; Infant, Premature; Prospective Studies; Fat Emulsions, Intravenous; Soybean Oil; Olive Oil; Fish Oils; Cholestasis; Triglycerides; Bilirubin; Infant, Very Low Birth Weight
PubMed: 37138099
DOI: 10.1038/s41430-023-01288-6 -
Neuroradiology Feb 2024Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite...
PURPOSE
Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL.
METHODS
We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP.
RESULTS
There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect.
CONCLUSION
This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.
Topics: Child; Infant, Newborn; Humans; Cerebral Palsy; Leukomalacia, Periventricular; Glymphatic System; Retrospective Studies; Hand
PubMed: 38129651
DOI: 10.1007/s00234-023-03269-9 -
Minerva Pediatrics Oct 2023Some studies have shown increased risk for neonatal morbidity and mortality with increasing maternal age. The aim of this study was to assess the influence of a maternal...
BACKGROUND
Some studies have shown increased risk for neonatal morbidity and mortality with increasing maternal age. The aim of this study was to assess the influence of a maternal age of 35 years, and older, on the neonatal morbidities and mortality of very preterm infants.
METHODS
Obstetrical and neonatal data on mothers and preterm infants with gestational age 24 to 30 weeks, born during 2015 and 2016 after a surveilled pregnancy at 11 Portuguese level III centers were analyzed according to a mother's age <35 years versus ≥35. Statistical analysis was performed using IBM SPSS statistics 23 (IBM, Armonk, NY, USA) and a P value <0.05 was considered significant.
RESULTS
A total of 415 mothers and 499 infants were included; 340 (68.1%) infants were delivered to mothers <35 years old and 159 (31.9%) to mothers ≥35. There were no differences in birthweight, gestational age and gender in both groups of preterm infants. Rupture of membranes over 18 hours and chronic hypertension with superimposed preeclampsia were significantly more frequent in mothers ≥35 years. Cystic periventricular leukomalacia (cPVL) assessed by cranial ultrasound was significantly more prevalent in infants delivered to mothers ≥35 years. The multivariate analysis by logistic regression revealed an association between cPVL and a maternal age ≥35 years (OR=2.34, 95% CI: 1.20-4.54; P=0.012).
CONCLUSIONS
Our study revealed a significant association between a maternal age ≥35 years and echographic cPVL in preterm infants below 30 weeks of gestational age.
PubMed: 31621275
DOI: 10.23736/S0026-4946.19.05551-8 -
Journal of Child Neurology Aug 2023Periventricular leukomalacia occurs in up to 25% of very preterm infants resulting in adverse neurodevelopmental outcomes. In its acute phase, periventricular... (Review)
Review
Periventricular leukomalacia occurs in up to 25% of very preterm infants resulting in adverse neurodevelopmental outcomes. In its acute phase, periventricular leukomalacia is clinically silent. Although ultrasonography is widely available, its sensitivity in the early detection of periventricular leukomalacia is low. We identified a preterm infant with early diffusion-weighted imaging changes that later evolved to periventricular leukomalacia. Thirty-two cases of abnormal diffusion-weighted imaging reliably heralding severe periventricular leukomalacia in the preterm infant have been published in the literature. Notable features include the following: (1) infants were more mature preterm infants (29-36 weeks' gestation); (2) findings were often serendipitous with benign clinical courses; (3) diffusion-weighted imaging changes only were evident in the first weeks of life with later evolution to more classical abnormalities on conventional magnetic resonance imaging (MRI) or ultrasonography. Diffusion-weighted imaging in the first week of life may be a reliable early marker of severe periventricular leukomalacia injury in more mature preterm infants.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Leukomalacia, Periventricular; Diffusion Magnetic Resonance Imaging; Magnetic Resonance Imaging; Gestational Age
PubMed: 37464767
DOI: 10.1177/08830738231185688 -
American Journal of Perinatology Aug 2023The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity...
OBJECTIVE
The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP).
STUDY DESIGN
This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8-28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia.
RESULTS
Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9-3.7) and 2.5 (95% CI: 1.9-3.3), respectively; < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1-4.8], and 3.3 [95% CI: 2.3-4.7] respectively, < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3-3.4], and 1.9 [95% CI: 1.3-2.8] respectively, < 0.001) compared with infants without surgical NEC.
CONCLUSION
Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP.
KEY POINTS
· Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC.. · Increased ROP risk is seen in infants with both early- or later onset surgical NEC.. · Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC..
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Infant, Low Birth Weight; Enterocolitis, Necrotizing; Retinopathy of Prematurity; Gestational Age
PubMed: 34344041
DOI: 10.1055/s-0041-1733785 -
The Cochrane Database of Systematic... Nov 2023Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with... (Review)
Review
BACKGROUND
Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness.
OBJECTIVES
To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.
SEARCH METHODS
We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.
SELECTION CRITERIA
We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO range (MD 13.54%, 95% CI 11.69 to 15.39; I = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS
Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.
Topics: Humans; Infant; Infant, Newborn; Bronchopulmonary Dysplasia; Infant, Premature; Oxygen; Randomized Controlled Trials as Topic; Reproducibility of Results; Retinopathy of Prematurity
PubMed: 38032241
DOI: 10.1002/14651858.CD013294.pub2 -
Journal of Perinatal Medicine Jul 2023Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage...
Perinatal brain damage is still one of the leading contributors to perinatal death and postnatal disability worldwide. However, the term perinatal brain damage encompasses very different aetiological entities that result in an insult to the developing brain and does not differentiate between the onset, cause and severity of this insult. Hypoxic-ischemic encephalopathy (HIE), intraventricular haemorrhage, periventricular leukomalacia and perinatal stroke are often listed as the major aetiologies of perinatal brain damage. They differ by type and timing of injury, neuropathological and imaging findings and their clinical picture. Along the timeline of neurodevelopment , there appears to be a specific "window of vulnerability" for each type of injury, but clinical overlap does exist. In the past, peripartum acute hypoxia was believed to be the major, if not the only, cause of perinatal brain damage, but intrauterine inflammation, prematurity, chronic hypoxia/growth retardation and genetic abnormalities appear to be at least equally important contributors.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Obstetricians; Brain Injuries; Brain; Hypoxia-Ischemia, Brain; Hypoxia; Infant, Newborn, Diseases
PubMed: 36853861
DOI: 10.1515/jpm-2022-0523 -
Journal of Neonatal-perinatal Medicine Jun 2024Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental...
BACKGROUND
Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental histology, namely by the identification of funisitis (inflammation of the umbilical cord) and chorionic vasculitis (inflammation of fetal vessels within the chorionic plate). The aim of this study was to identify and evaluate associations between FIRS and neonatal outcomes in preterm neonates.
METHODS
We performed a retrospective cohort study at a level III neonatal intensive care unit (NICU), from January 1st 2008 to December 31st 2022, involving all inborn neonates with a gestational age below 30 weeks. We compared preterm neonates based on whether their placental histology described funisitis with chorionic vasculitis (FCV) or not.
RESULTS
The study included 113 preterms, 27 (23.9%) of those had FCV and 86 (76.1%) did not. After adjusting to gestational age, prolonged rupture of membranes and preeclampsia, FCV was independently associated with the development of early-onset sepsis (OR = 7.3, p = 0.021) and cystic periventricular leukomalacia (OR = 4.6, p = 0.004).
CONCLUSION
The authors identified an association between FIRS and the development of early-onset sepsis and cystic periventricular leukomalacia, highlighting the importance of early detection and management of this condition in order to improve long-term neonatal outcomes.
PubMed: 38905060
DOI: 10.3233/NPM-240017 -
American Journal of Perinatology Jul 2024The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may...
OBJECTIVE
The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may reduce the risk of IVH, although it has been a matter of debate. The aim of this study was to evaluate the influence of the mode of delivery (MOD) on the development of IVH and cystic periventricular leukomalacia (cPVL).
STUDY DESIGN
We analyzed an initial cohort of 11,023 very low birth weight (VLBW) infants born between January 2010 and December 2019. Infants with major malformations and gestational age <23 weeks and ≥32 weeks were excluded. A final cohort of 8,251 newborns was analyzed. Data was collected from Portuguese National very low birth weight registry. Cases were classified as vaginal delivery (VD) or CS. Outcome was assessed in univariate and logistic regression analyses.
RESULTS
The median gestational age was 29 weeks (IQR 3.3) and the median weight was 1,100 g (IQR 555). The prevalence of IVH was significantly higher in the VD group versus the CS group, across all grading levels:1,144 newborns had grade I IVH (16% VD vs. 14% CS, <0.01), 706 had grade II IVH (12% VD vs. 7.6% CS, <0.01), and 777 had grade III IVH (14% VD vs. 7.9% CS, <0.01). Post-hemorrhagic ventricular dilatation occurred in 457 newborns (8.3% VD vs. 4.6% CS, <0.01) and 456 newborns had periventricular hemorrhagic infarction (8.4% VD vs. 4.5% CS, <0.01). There was no association between MOD and cPVL. After applying a logistic regression analysis, including known risk factors for IVH and cPVL, VD was independently associated with an increased risk of IVH (odds ratio [OR] 1.600[1.423-1.799], <0.001) and its complications (OR 1.440[1.195-1.735], <0.001). MOD was not associated with an increased risk of cPVL.
CONCLUSION
Our study suggests that CS is associated with a reduced risk of IVH and its complications in preterm VLBW infants < 32 weeks of gestational age. A CS should be considered in this group of infants to prevent the development of IVH and its complications.
KEY POINTS
· IVH and cPVL are risk factors for neurological disabilities.. · CS may decrease the risk of IVH in preterms <32 weeks GA.. · There is no association between the MOD and cPVL..
Topics: Humans; Infant, Newborn; Infant, Very Low Birth Weight; Female; Cesarean Section; Male; Gestational Age; Leukomalacia, Periventricular; Delivery, Obstetric; Pregnancy; Risk Factors; Portugal; Cerebral Intraventricular Hemorrhage; Cerebral Hemorrhage; Logistic Models; Retrospective Studies; Registries
PubMed: 35378547
DOI: 10.1055/a-1815-1842