Severe Neurodevelopmental Impairment Research Articles

No change in neurodevelopment at 11 years after extremely preterm birth

ObjectiveTo determine whether improvements in school age outcomes had occurred between two cohorts of births at 22–25 weeks of gestation to women residents in England in 1995 and 2006.DesignLongitudinal national...

Neurodevelopmental Outcomes after Bevacizumab Treatment for Retinopathy of Prematurity: A Meta-analysis

To evaluate neurodevelopmental outcomes after intravitreal bevacizumab (IVB) therapy in retinopathy of prematurity (ROP) infants compared with those not exposed to IVB. The primary concern regarding IVB treatment of ROP is the potential systemic side effects, especially the risk of causing severe neurodevelopmental impairment (sNDI). Results regarding neurodevelopmental outcomes after IVB therapy are conflicting. We conducted a meta-analysis and searched PubMed, Embase, and Web of Science for related publications from inception through March 12, 2020. The eligibility criteria were as follows: comparative studies of ROP patients that (1) included IVB as a treatment arm, (2) included a control group without bevacizumab treatment, and (3) reported on at least 1 neurodevelopmental outcome, such as sNDI, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), composition scores, or cerebral palsy (CP). The primary outcome was sNDI, with the odds ratio (OR) calculated. Secondary outcomes were mean differences (MDs) for cognitive, language, and motor scores (Bayley III) and OR for CP. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation approach. Eight studies, 6 including laser-controlled ROP infants and 2 including ROP infants not requiring treatment, were included. The weighted OR for sNDI in the IVB group was 1.39 (95% confidence interval [CI], 0.98-1.97). The weighted MDs were -1.92 (95% CI, -4.73 to 0.88), -1.32 (95% CI, -4.65 to 1.99), and -3.66 (95% CI, -6.79 to -0.54) for cognitive, language, and motor scores in Bayley III, respectively. The OR for CP was 1.20 (95% CI, 0.56-2.55). No differences were observed between the preset subgroups comprising laser-controlled ROP infants and ROP infants not requiring treatment. The current quality of evidence was rated as low (sNDI and all Bayley III scores) to very low (CP). Risk of sNDI was not increased in ROP patients after IVB treatment. Bayley III scores were similar in the IVB and control groups, except for a minor difference in motor performance. These findings suggest that the risk of additional sNDI after IVB treatment is low. Randomized trials are warranted to provide a higher quality of evidence.

Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity. OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and mortality and morbidity invery preterm or very low birth weight infants. We searched Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library; MEDLINE Ovid (1946 to 17 Feb 2020), Embase Ovid (1974 to 17 Feb 2020), Maternity & Infant Care Database Ovid (1971 to 17 Feb 2020), the Cumulative Index to Nursing and Allied Health Literature (1982 to 18 Feb 2020). Wesearched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs comparing probiotic supplementation with placebo or no probiotics in very preterm or very low birth weight infants. We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on NEC, all-cause mortality, late-onset infection, and severe neurodevelopmental impairment. Weincluded 56trials in which 10,812 infants participated. Most trials were small (median sample size 149). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were the main potential sources of bias in about half of the trials.Trials varied by the formulation of the probiotics. The most commonly used preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus spp. alone or in combinations. Meta-analysis showed that probiotics may reduce the risk of NEC: RR 0.54, 95% CI 0.45 to 0.65 (54 trials, 10,604 infants; I² = 17%); RD -0.03, 95% CI -0.04 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 25 to 50. Evidence was assessed as low certainty because of the limitations in trials design, and the presence of funnel plot asymmetry consistent with publication bias. Sensitivity meta-analysis of trials at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55 to 0.89 (16 trials, 4597 infants; I² = 25%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100. Meta-analyses showed that probiotics probably reduce mortality (RR 0.76, 95% CI 0.65 to 0.89; (51 trials, 10,170 infants; I² = 0%); RD -0.02, 95% CI -0.02 to -0.01; NNTB 50, 95% CI 50 to 100), and late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; (47 trials, 9762 infants; I² = 19%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100). Evidence was assessed as moderate certainty for both these outcomes because of the limitations in trials design. Sensitivity meta-analyses of 16 trials (4597 infants) at low risk of bias did not show an effect on mortality or infection. Meta-analysis showed that probiotics may have little or no effect on severe neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26 (five trials, 1518 infants; I² = 0%). The certainty on this evidence is low because of limitations in trials design and serious imprecision of effect estimate. Few data (from seven of the trials) were available for extremely preterm or extremely low birth weight infants. Meta-analyses did not show effects on NEC, death, or infection (low-certainty evidence). Given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, and particularly for extremely preterm or extremely low birth weight infants, further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice.

Using different definitions affected the reported prevalence of neurodevelopmental impairment in children born very preterm.

We investigated the impact of varying definitions on the prevalence of neurodevelopmental impairment (NDI) in children born very preterm at 6.5years of age. Cognitive development and neurosensory impairments were assessed in 91 children (40/51 girls/boys) born <32 gestational weeks, in 2004-2007 in Uppsala county, Sweden. The results were compared with data from a reference group of 67 children born full term. The prevalence of NDI in the present cohort was reported according to definitions used by seven contemporary studies of children born very or extremely preterm. The prevalence of severe NDI varied from 2% to 23% depending on the definition used. The prevalence of cognitive impairment varied from 2% (-3 SD according to test norms) to 16% (-2 SD according to control group), the prevalence of cerebral palsy from 0% (severe) to 9% (any) and the prevalence of severe visual impairment from 0% (blindness) to 1% (visual acuity<0.3). There were no children with severe hearing impairment. A high variability in definitions affects the reporting of the prevalence of NDI in long-term follow-up studies of very or extremely preterm born children. There is a need for a better consensus to enable comparisons across studies.

Twin Anemia Polycythemia Sequence: Knowledge and Insights After 15 Years of Research

Abstract Twin anemia polycythemia sequence (TAPS) is a chronic form of unbalanced feto-fetal transfusion through minuscule placental anastomoses in monochorionic twin pregnancies, leading to anemia in the donor twin and polycythemia in the recipient twin. TAPS can occur spontaneously in up to 5% of monochorionic twins or can arise in 2%–16% of cases after incomplete laser surgery for twin-twin transfusion syndrome. TAPS can develop across the entire second and third trimester. Antenatal diagnosis for TAPS is reached via Doppler measurement of the fetal middle cerebral artery peak systolic velocity, showing an increased velocity in the donor, combined with a decreased velocity in the recipient. Treatment options for TAPS include expectant management, preterm delivery, intrauterine blood transfusion with or without a partial exchange transfusion, fetoscopic laser surgery and selective feticide. The best treatment option is unclear and is currently being investigated in an international multicenter randomized trial (the TAPS trial). Spontaneous fetal demise occurs in 5%–11% of TAPS twins, more often in donors (8%–18%) than in recipients (2%–5%). Severe long-term neurodevelopmental impairment is seen in 9% of TAPS twins, with donors having an increased risk for cognitive impairment and hearing problems (15%).

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

The International Liaison Committee on Resuscitation Neonatal Life Support Task Force reviewed evidence for the duration of cardiopulmonary resuscitation (CPR) for newborns immediately after birth. To summarize evidence for ongoing CPR on the outcomes of survival, neurodevelopment, and the composite of survival without moderate or severe neurodevelopmental impairment (NDI). Medline, Embase, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scientific Electronic Library Online were searched between inception and February 29, 2020. Two independent reviewers selected studies of newborns with at least 10 minutes of asystole, bradycardia, or pulseless electrical activity for which CPR is indicated. Two independent reviewers extracted data and appraised the risk of bias. In 16 eligible studies, researchers reported outcomes of 579 newborns born between 1982 and 2017. Within individual studies, 2% to 100% of infants survived to last follow-up (hospital discharge through 12 years). Summarized across studies, 237 of 579 (40.9%) newborns survived to last follow-up. In 13 studies, researchers reported neurodevelopmental outcomes of 277 newborns. Of these, 30 of 277 (10.8%) survived without moderate or severe impairment, and 240 of 277 (87%) met the composite outcome of death or NDI (191 died and 49 survived with moderate or severe impairment). There was very low certainty of evidence because of risk of bias and inconsistency. Infants with ongoing CPR at 10 minutes after birth are at high risk for mortality and neurodisability, but survival without moderate or severe NDI is possible. One specified duration of CPR is unlikely to uniformly predict survival or survival without neuroimpairment.

26 Not What Clinicians Thought: Decisional Regret in Parents of Extremely Preterm Children

Abstract Background Preterm birth is associated with higher risk of death and severe neurodevelopmental impairment. There is an increased risk in extremely preterm infants, raising questions among ethicists and clinicians as to whether providing active care to infants born at the lower extreme is worth the outcomes, and if these outcomes are a source of decisional regrets for parents. Objectives Explore decisional regrets in parents of extremely preterm children. Design/Methods We consecutively recruited all parents of infants born &amp;lt;29 weeks’ gestational age, aged between 18 months corrected age and 7 years, and seen for neonatal follow-up at a single tertiary center over a one-year period. We asked the following question: “Knowing what you know now, is there anything you would have done differently?” Answers were analyzed independently by two reviewers using qualitative methodology, and discrepancies were resolved by a third reviewer. Mixed methods were used to examine the frequency of each theme and associate parental answers to demographic and clinical factors. Results Responses were obtained from 249 parents (98% participation rate). The following main themes emerged: (1) Nothing – I did what I could or was told to do: 53%; (2) Regrets about self-care: 31%; “I would listen to the nurses’ advice to sleep more” (3) Guilt related to the impression preterm labor could have been prevented by them or the medical team: 19%; “I would have pushed for better care and monitoring during pregnancy. I felt as though I wasn’t listened to when I thought I was in labour when sure enough I was” (4) Regrets about parental role in decision-making: 15%; “I would speak up more at the beginning of the hospitalisation”. None of the parents reported on regretting any life-and-death decisions they made at birth and in the neonatal unit. Conclusion In our cohort, more than half of parents of surviving preterm infants did not have any regrets associated to their NICU experience. However, lessons can be learned to improve parental support, self-care and solutions to improve their role as parents. Unlike what can be stated using “opinion-based medicine”, limiting or forgoing intensive care is not a solution to eliminate decisional regrets in parents.

An alternative approach to developing guidelines for the management of an anticipated extremely preterm infant.

Objectives To identify the probability of survival and severe neurodevelopmental impairment (sNDI) at which perinatal physicians would or would not offer or recommend resuscitation at birth for extremely preterm infants. Methods A Delphi process consisting of five rounds was implemented to seek consensus (>80% agreement) amongst British Columbia perinatal physicians. The first-round consisted of neonatal and maternal-fetal-medicine Focus Groups. Rounds two to five surveyed perinatal physicians, building upon previous rounds. Draft guidelines were developed and agreement sought. Results Based on 401 responses across all rounds, consensus was obtained that resuscitation should not be offered if survival probability<5%, not recommended if survival probability 5 to<10%, resuscitation recommended if survival without sNDI probability>70 to 90% and resuscitation standard care if survival without sNDI>90%. Conclusions This physician consensus-based, objective framework for the management of an anticipated extremely preterm infant is a transparent alternative to existing guidelines, minimizing gestational-ageism and allowing for individualized management utilizing up-to-date data. Further input from other key stakeholders will be required prior to guideline implementation.

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5years.

This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5years. Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow-up data, born in 2004-2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full-scale intelligence quotient (FSIQ) at 6.5years. The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28-2.06) and a lower adjusted mean difference FSIQ of -7.1 (95% CI -11 to -3.2). Surgery at less than 10days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20days. Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.

Neurodevelopmental Outcome After Fetoscopic Laser Surgery for Twin-twin Transfusion Syndrome: A Systematic Review of Follow-up Studies from the Last Decade

Abstract Objective: To review the literature on long-term neurodevelopmental outcome after fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Methods: A literature search in PubMed, Embase, Emcare, Web of Science, Cochrane library, and Academic Search Premier was performed. Inclusion criteria were studies between 2009 and 2019 in TTTS-survivors treated with fetoscopic laser surgery and followed-up after the neonatal period with cognitive developmental tests and neurologic exams. Exclusion criteria were non-English articles and reviews, case reports, letters, and guidelines. Results: Nineteen articles were included. Long-term severe neurodevelopmental impairment (NDI) was reported by seven and ranged from 4.0% to 18.0% with a mean of 9.7% (95% confidence interval (CI): 7.8–11.5). The prevalence of cerebral palsy ranged from 1.6% to 18.2%, with a mean of 5.1% (95% CI: 4.1–6.2). The mean prevalence of minor impairment was 13.7% (95% CI: 11.4–16.0). However, only 78.9% (15/19) studies used a validated neurodevelopmental test. As studies lack uniform definitions of primary outcome, timing of follow-up, inclusion criteria, and methods, adequate comparison is hampered. Conclusion: The prevalence of severe NDI and cerebral palsy after fetoscopic laser surgery for TTTS in the last decade remains stable around 9.7% and 5.1%, respectively. International agreements on primary outcomes, methods, and follow-up are necessary to improve the knowledge of NDI in TTTS-survivors.

Loss of Wwox Perturbs Neuronal Migration and Impairs Early Cortical Development.

Mutations in the WWOX gene cause a broad range of ultra-rare neurodevelopmental and brain degenerative disorders, associated with a high likelihood of premature death in animal models as well as in humans. The encoded Wwox protein is a WW domain-containing oxidoreductase that participates in crucial biological processes including tumor suppression, cell growth/differentiation and regulation of steroid metabolism, while its role in neural development is less understood. We analyzed the exomes of a family affected with multiple pre- and postnatal anomalies, including cerebellar vermis hypoplasia, severe neurodevelopmental impairment and refractory epilepsy, and identified a segregating homozygous WWOX mutation leading to a premature stop codon. Abnormal cerebral cortex development due to a defective architecture of granular and molecular cell layers was found in the developing brain of a WWOX-deficient human fetus from this family. A similar disorganization of cortical layers was identified in lde/lde rats (carrying a homozygous truncating mutation which disrupts the active Wwox C-terminal domain) investigated at perinatal stages. Transcriptomic analyses of Wwox-depleted human neural progenitor cells showed an impaired expression of a number of neuronal migration-related genes encoding for tubulins, kinesins and associated proteins. These findings indicate that loss of Wwox may affect different cytoskeleton components and alter prenatal cortical development, highlighting a regulatory role of the WWOX gene in migrating neurons across different species.

Association of Antenatal Corticosteroids and Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm Children.

To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone. This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics. Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups. In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone. ClinicalTrials.gov, NCT00063063.

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up.

This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only). This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age. Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420-583) versus 547 (473-640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33-2.20). Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants. · Intravitreal bevacizumab therapy for retinopathy of prematurity may be safe in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase mortality rate in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase adverse neurodevelopmental outcome in periviable infants..

Fetal therapies for cytomegalovirus: What we tell prospective parents.

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.

Bringing Statistics to Life: Developing “Lived-Experience” Family Videos for a Periviable Decision-Support Tool [06K

INTRODUCTION: To develop and incorporate ‘lived-experience’ videos of families describing their lives following periviable delivery into the Periviable GOALS (Getting Optimal Alignment around Life Support) decision-support tool. METHODS: Through patient-engaged research methodology, patient-partners advocated ‘bringing statistics to life’ by including videos into the tool (IRB-approved). Five videos were created; each contained two families’ stories reflecting: death following comfort care, non-survival following resuscitation, or survival with mild, moderate, or severe neurodevelopmental impairment (NDI). Diverse families represented the spectrum of NDI, using different scripts for bereavement versus survival. Professional videographers filmed and edited the segments (3-5 minutes), which were embedded into the GOALS tool. Focus groups were conducted with pregnant women (20-26 weeks) and women who have delivered periviably to assess the videos’ acceptability. RESULTS: Ten families participated in the ‘lived-experience’ videos. Half were African American and half were white; children were age 16 months to 4 years. Bereaved parents were asked about end-of-life experiences and support after loss, while survivor segments described typical days, on-going medical care, and family adjustment. The videos were rated “excellent” (41.7%) or “good” (25%) by focus group participants (n=12). Most (91.7%) thought the tool provided sufficient information and would be useful in helping families make treatment decisions. CONCLUSION: Videos provide context for families to make meaning of complex prognostic information on long-term outcomes. They must be developed with caution due to their potential to introduce anchoring, conformity, or optimistic biases. Stakeholder engagement and diverse representation across the spectrum of outcomes and decisions may help to mitigate potential biases.

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.

Because most studies regarding neurodevelopment in retinopathy of prematurity (ROP) are small and single-center studies, we commend the authors for this retrospective multicenter analysis of prospectively collected data comparing anti–vascular endothelial growth factor (VEGF) with laser treatment.1 Although they found no difference in their primary outcome of severe neurodevelopmental impairment (NDI) or death, when examined separately, they found a higher rate of death but not of NDI. Unfortunately, as a nonrandomized study, it suffers from imbalance in baseline characteristics, which limits robustness. First, as the authors acknowledge, infants who received bevacizumab were smaller and sicker. At baseline, infants treated with bevacizumab had lower median birth weight ( P = .02), gestational age ( P = .05), and … E-mail: gnatara{at}med.wayne.edu

Antenatal imaging and clinical outcome in congenital CMV infection: A field-wide systematic review and meta-analysis

ObjectivesPostnatal outcome in fetuses with congenital cytomegalovirus infection (cCMV) varies from asymptomatic infection to severe neurodevelopmental impairment. Αntenatal biomarkers of long-term clinical outcome, have yet to be established. Α systematic review and meta-analysis was performed to examine whether prenatal cerebral ultrasonography (US) and magnetic resonance imaging (MRI) findings in cCMV fetuses may predict clinical outcome. MethodsPubMed and the Web of Science were systematically searched to identify studies reporting on any prenatal US and/or MRI imaging of fetuses with cCMV as well as their postnatal clinical outcome. All reported associations between imaging and postnatal clinical outcome were systematically extracted. Where appropriate, the reported associations were quantitatively synthesized within Bayesian random-effects meta-analyses. ResultsA total of 1336 studies were screened to identify 26 eligible observational studies. Overall, 4181 fetuses were studied, of which 1518 had been diagnosed with cCMV. All studies performed fetal US while in 14 (54%) MRI was also performed. Studies substantially varied in timing of fetal imaging, reporting of abnormalities, definition of poor outcome and statistical analysis. Among studies reporting on statistical significance, 6/6 for US and 3/4 for MRI identified significant associations between imaging findings and outcome. In our meta-analyses, within isolated abnormalities, only microcephaly had greater than 95% probability of being associated with poor outcome (OR 26.7; 95% CI, 1.44–1464.5; I2, 19%). Effect sizes for US were higher than those for MRI findings. ConclusionsAlthough studies displayed significant heterogeneity in both methodology and analytical decisions, it became evident that when both prenatal cerebral US and MRI are normal the negative predictive value of poor outcome is high. This is important for clinicians when consulting pregnant women. Need to standardize practices and definitions become evident. FundingThere was no source of funding.

Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes.

Objective:To determine the associations between age at first postnatal corticosteroids (PNS) exposure and risk for severe bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI).Study Design:Cohort study of 951 infants born <27 weeks gestational age at NICHD Neonatal Research Network sites who received PNS between 8 days of life (DOL) and 36 weeks’ postmenstrual age was used to produce adjusted odds ratios (aOR).Results:Compared to infants in the reference group (22–28 DOL-lowest rate), aOR for severe BPD was similar for children given PNS between DOL 8–49 but higher among infants treated at DOL 50–63 (aOR 1.77, 95% CI 1.03–3.06), and at DOL ≥64 (aOR 3.06, 95% CI 1.44–6.48). The aOR for NDI did not vary significantly by age of PNS exposure.Conclusion:For infants at high risk of BPD, initial PNS should be considered prior to 50 DOL for the lowest associated odds of severe BPD.

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants

BackgroundHigh-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.MethodsIn this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.ResultsA total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P=0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.ConclusionsHigh-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.)

High risk of long-term neurodevelopmental impairment in donor twins with spontaneous twin anemia-polycythemia sequence.

To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome between donors and recipients, and to investigate potential risk factors for neurodevelopmental impairment (NDI). This was a retrospective study of a consecutive cohort of spontaneous-TAPS survivors delivered between 2005 and 2017 at the Leiden University Medical Center, The Netherlands. Neurological, motor, cognitive and behavioral development were assessed at a median age of 4 years. The primary outcome was NDI, which was a composite outcome of cerebral palsy, deafness, blindness and motor and/or cognitive delay. NDI was subdivided into two grades of severity: mild-to-moderate and severe NDI. Outcome was compared between surviving donor and recipient twins. Logistic regression analysis was used to assess risk factors for NDI. Forty-nine twin pregnancies complicated by spontaneous TAPS were eligible for inclusion. The perinatal survival rate was 83% (81/98) of twins. Neurodevelopmental assessment was performed in 91% (74/81) of surviving twins. NDI occurred in 30% (22/74) of TAPS survivors, and was found more often in donors (44%; 15/34) than in recipients (18%; 7/40) (odds ratio (OR), 4.1; 95% CI, 1.8-9.1; P = 0.001). Severe NDI was detected in 9% (7/74) of survivors and was higher in donors compared with recipients (18% (6/34) vs 3% (1/40)), although the difference did not reach statistical significance; P = 0.056). Donors demonstrated lower cognitive scores compared with recipients (P = 0.011). Bilateral deafness was identified in 15% (5/34) of donors compared with 0% (0/40) of recipients (P = 0.056). Parental concern regarding development was reported more often for donor than for recipient twins (P = 0.001). On multivariate analysis, independent risk factors for NDI were gestational age at delivery (OR, 0.7; 95% CI, 0.5-0.9; P = 0.003) and severe anemia (OR, 6.4; 95% CI, 2.4-17.0; P < 0.001). Surviving donor twins of pregnancies complicated by spontaneous TAPS have four-fold higher odds of NDI compared with recipient cotwins, are at increased risk of cognitive delay and have a high rate of deafness. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.