Risk Of Adverse Neurodevelopmental Outcomes Research Articles

Abnormal Interhemispheric Connectivity in Neonates with D-Transposition of the Great Arteries Undergoing Cardiopulmonary Bypass Surgery

Neonates with severe CHD require CPB within the first days of life. White matter injury can occur before surgery, and this may impair the long-term neurodevelopmental and psychosocial outcome. The purpose of this study was to assess the microstructural development of the CC in infants with CHD before and after CPB for transposition of the great arteries. Fifteen patients with CHD and 11 age-matched HC were recruited. We separately quantified the parallel (E1) and perpendicular (E23) diffusions, the ADC, and FA of the genu of the CC and splenium of the CC before and after surgery. In presurgical measures of the genu of the CC, higher E23 (P = .018), higher ADC (P = .026), and lower FA (P = .033) values were measured compared with those in HC. In the postsurgery scans, the genu of the CC had higher E23 (P = .013), higher ADC (P = .012), and lower FA (P = .033) values compared with those in HC. There was no significant difference in any DTI indices between the pre- and postsurgical groups. We report abnormal microstructural development in the genu of the CC of infants with d-TGA before and after CPB. High E23, high ADC, and low FA values in the genu of the CC may be explained by abnormal axonal pruning, thinner myelin sheaths, smaller axonal diameters, or more oligodendrocytes. It appears that the genu of the CC is more vulnerable than the splenium of the CC in patients with CHD and may serve as a biomarker to identify infants at highest risk for adverse neurodevelopmental outcome.

AdaPT: An adaptive preterm segmentation algorithm for neonatal brain MRI

Advances in neonatal care have improved the survival of infants born prematurely although these infants remain at increased risk of adverse neurodevelopmental outcome. The measurement of white matter structure and features of the cortical surface can help define biomarkers that predict this risk. The measurement of these structures relies upon accurate automated segmentation routines, but these are often confounded by neonatal-specific imaging difficulties including poor contrast, low resolution, partial volume effects and the presence of significant natural and pathological anatomical variability. In this work we develop and evaluate an adaptive preterm multi-modal maximum a posteriori expectation-maximisation segmentation algorithm (AdaPT) incorporating an iterative relaxation strategy that adapts the tissue proportion priors toward the subject data. Also incorporated are intensity non-uniformity correction, a spatial homogeneity term in the form of a Markov random field and furthermore, the proposed method explicitly models the partial volume effect specifically mitigating the neonatal specific grey and white matter contrast inversion. Spatial priors are iteratively relaxed, enabling the segmentation of images with high anatomical disparity from a normal population. Experiments performed on a clinical cohort of 92 infants are validated against manual segmentation of normal and pathological cortical grey matter, cerebellum and ventricular volumes. Dice overlap scores increase significantly when compared to a widely-used maximum likelihood expectation maximisation algorithm for pathological cortical grey matter, cerebellum and ventricular volumes. Adaptive maximum a posteriori expectation maximisation is shown to be a useful tool for accurate and robust neonatal brain segmentation.

Should we resuscitate newborn infants in developing countries?

There has been concern among primary caregivers in developing countries that the need for resuscitation after birth indicates brain injury and high risk for subsequent neurodevelopmental impairment. These beliefs have impaired widespread uptake of newborn resuscitation procedures. The study by Carlo et al in this issue of The Journal provides important information to negate that belief. They demonstrate that resuscitation of the newborn, without severe encephalopathy, is not associated with an increased risk for adverse neurodevelopmental outcome. These findings will greatly assist in supporting appropriate training for resuscitation of the term born infant resulting in increased survival without major neurodevelopmental impairment. Article page 781▶

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

BackgroundRandomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.Methods/DesignThe SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.DiscussionThis trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.Trial registration numberNetherlands Trial Register (NTR): NTR2768

Maternal prenatal anxiety and downregulation of placental 11β-HSD2

Raised maternal anxiety during pregnancy is associated with increased risk of adverse neurodevelopmental outcomes for her child. The mechanisms underlying this are not known but animal studies suggest prenatal stress may alter the function of the placenta. Here we determined whether maternal prenatal anxiety was associated with a downregulation of placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the enzyme which metabolises cortisol. We recruited mothers the day before delivery by elective caesarean, and gave them the Spielberger Trait and State anxiety and Edinburgh Depression self-rating scales. Placentae were collected and aliquots stored for later analysis. Prenatal Trait anxiety was negatively correlated with placental 11β-HSD2 mRNA expression (r=-0.40, p<0.01, n=56). Results were similar with male and female fetuses (r=-0.39, p=0.04, n=28; r=-0.40, p=0.03, n=28) respectively. Results were also significant with State anxiety (r=-0.27, p=0.05, n=56) but somewhat weaker for depression (r=-0.20, p=0.13, n=56). Preliminary analyses on a subset of cases (n=25) suggested parallel results for enzyme activity. These findings provide evidence for an association between prenatal maternal mood and downregulation of placental 11β-HSD2. Results are consistent with raised maternal anxiety being associated with increased fetal exposure to maternal cortisol, and support the hypothesis that this may be one mechanism underlying fetal programming by prenatal stress.

Impact of Preterm PROM and its Complications on Long-term Infant Outcomes

There is increasing evidence that preterm premature rupture of membranes (PPROM) is associated with increased risk for adverse neurodevelopmental outcomes through multiple mechanisms, including preterm birth and its antecedent etiologies. Intrauterine infection is a particularly important risk factor for adverse neurodevelopmental outcomes after PPROM. This review focuses on the long-term neurodevelopmental outcomes after PPROM, the possible etiologic mechanisms of neurological injury, and the effect of antenatal and perinatal interventions using available evidence.

Early development of children with major birth defects requiring newborn surgery

To describe neurodevelopmental outcomes of neonates following cardiac or non-cardiac surgery for major birth defects. From 1 June 2002 to 31 July 2004, infants born ≥ 33 weeks gestation who underwent major birth defect surgery were enrolled prospectively. Infants were assessed at a mean corrected age of 24 months (standard deviation (SD) = 8 months, range 18-36 months) using the Bayley Scales of Infant Development: Second Edition. Of the 118 study infants, 79 (66%) were male, the mean gestation was 38.5 weeks (SD 1.9 weeks) and mean birthweight was 3194 g (SD 653 g). Forty-five infants (47%) had undergone general surgery for non-cardiac defects. The majority of infants (73%) performed below average in cognitive and language skills. Mental delay was found in 41% of infants; 16% were significantly delayed. Fine and gross motor skills were below average in 60% of infants. Twenty-six percent of infants had motor delay; 9% were significantly delayed. Both the mean Mental Development Index (M = 88, SD = 19.8) and mean Psychomotor Development Index (M = 93, SD = 19.3) were significantly below the normative mean (d = 0.8, P < 0.001 and d = 0.5, P < 0.001, respectively). One in five children had global developmental delay. There was no significant difference in outcome between the cardiac and general surgery groups. The majority of infants performed below average on a standardised test of infant development. Our results show that infants requiring newborn surgery for major birth defects are at high risk of adverse neurodevelopmental outcomes. We recommend that follow-up programmes include systematic multidisciplinary developmental monitoring and early intervention.

Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors

Background Very premature infants occasionally have neurodevelopmental disabilities. However, there have been quite limited data on prenatal risk factors associated with their neurodevelopmental outcomes. Aim To clarify the relationship between prenatal risk factors and neurodevelopmental outcomes of very premature infants. Study design The study design is a retrospective review. Subjects One hundred seventy Japanese women with a singleton pregnancy and their infants whose birth weight being less than 1500 g were included. We classified those infants into 118 appropriate for gestational age (AGA) and 52 small for gestational age (SGA) infants. Outcome measures Infants' neurodevelopmental outcomes at 18 months of corrected age were evaluated by the Kyoto Scale of Psychological Development 2001 (KSPD). We analyzed and compared the infants' outcomes and prenatal risk factors between two groups. Results Mortality and rate of infants unevaluable by KSPD because of severe impairment were not significantly different between those groups. However, the developmental quotient score of the cognitive–adaptive area in SGA infants born between 25 and 31 weeks of gestation was significantly lower than that in AGA infants randomly selected as gestation-matched controls. More advanced gestational age and heavier birth weight protected against adverse neurodevelopmental outcomes in both groups. Moreover, male infants were related to the excess risk of adverse neurodevelopmental outcomes in the SGA group. Conclusion In view of the neurodevelopment of the infants, it seems that the most efficient obstetric strategy for improving prognosis of premature infants should be targeted to prolong the pregnancy period as long as the reassuring fetal status and maternal stable health condition are being confirmed.

Analysis of compliance, morbidities and outcome in neurodevelopmental follow-up visits in urban African-American infants at environmental risk.

The objectives of this study were to determine compliance rate in a uniform, urban African-American patient population at environmental risk for adverse neurodevelopmental outcome and to define risk factors for non-compliance with neurodevelopmental follow-up. A retrospective chart review was performed which included 481 infants with birth weight (BW) of 495-4195 g and gestational ages (GAs) between 23 and 42 weeks born at our hospital. Statistical analysis was performed using the Jonckheere-Terpstra test for ordinal variables. For 2 × 2 tables, χ 2 test and Fisher's exact test (P < 0.05) were used. To determine significant predictive variables, data were analyzed by multiple logistic regression with one independent variable at a time. Infants compliant with follow-up had significantly more morbidities in the very low BW category (⩽1500 g) than infants with larger BW. The highest compliance rate (70%) was found among the smallest and most immature (GA ⩽28 weeks) infants. Based on this finding, we postulate that the number of infants with severe disability is not likely to be underestimated. The significantly more frequent developmental anomalies found in the largest BW (⩽2500 g) category raises significant concern, though findings in this subset of infants may not be representative of the whole population. There was no significant difference between the compliant and non-compliant groups regarding socio-economic status. Severe or multiple morbidities and prolonged hospital stay may provide parents with greater opportunity to learn and understand about the infant's condition which may lead to greater compliance.

Brain Maturity and Brain Injury in Newborns With Cyanotic Congenital Heart Disease

Patients with congenital heart disease (CHD) are at high risk for adverse neurodevelopmental outcomes. The aim of this work was to assess brain maturity and brain injury in newborns with cyanotic CHD using proton magnetic resonance spectroscopy (MRS). The study included 38 newborns with cyanotic CHD (study group) and 20 healthy full-term newborns (control group) matched together regarding gestational age and sex. Three-dimensional MRS showed that the mean ratio of N-acetylaspartate to choline (Ch) was significantly lower in newborns with cyanotic CHD (0.55±0.08) compared with controls (0.67±0.11) (p<0.001). However, the mean ratio of lactate to Ch metabolite was significantly higher in the studied cases (0.14±0.04) compared with controls (0.09±0.04) (p<0.001). The mean value for average diffusivity was 1.41±0.06 in newborns with cyanotic CHD compared with 1.27±0.07 in control newborns (p<0.001), and the mean value for white-matter fractional anisotropy was 0.19±0.03 in cyanotic newborns and 0.25±0.08 in controls (p<0.001). Newborns with cyanotic CHD are at increased risk of cerebral white matter injury as well as poor brain maturity. MRS provides a surrogate marker for early detection of such brain abnormalities.

Open-Label Glucocorticoids Modulate Dexamethasone Trial Results in Preterm Infants

Open-label glucocorticoids (OLGs) were often used in trials that investigated postnatal dexamethasone treatment in ventilated preterm infants. To determine if OLG use modulates the dexamethasone treatment effect on mortality, bronchopulmonary dysplasia (BPD), and neurodevelopmental outcome. Electronic databases, abstracts from the Pediatric Academic Societies, and results of manual reference searches were used as data sources. Fifteen randomized controlled trials comparing dexamethasone with placebo in 721 ventilated preterm infants older than 7 days were identified. The interaction between dexamethasone treatment effect and OLG use was assessed by meta-regression analysis and subgroup meta-analysis according to the percentage of OLG use in the placebo group. Trials with a moderately early (7- to 14-day) or delayed (>3-week) treatment onset were analyzed separately. Moderately early, but not delayed, dexamethasone treatment significantly reduced mortality rates in trials with OLG use at <30% in the placebo arm. Meta-regression analysis revealed that this reduction was inversely related to OLG use. Increasing OLG use strengthened the positive effect of dexamethasone on BPD in the moderately early trials but attenuated the effect in the delayed-treatment trials. In trials with <30% OLG use, dexamethasone increased the risk for cerebral palsy in the delayed, but not the moderately early, treatment trials. When OLG use is taken into account moderately early dexamethasone treatment reduced mortality rates and the combined outcome mortality and BPD without increasing the risk of adverse neurodevelopmental outcome in ventilated preterm infants. A large randomized controlled trial is needed to confirm or refute these findings.

Cot-side electroencephalography for outcome prediction in preterm infants: observational study

ObjectiveTo assess the use of two-channel electroencephalographical (EEG) recordings for predicting adverse neurodevelopmental outcome (death or Bayley II mental developmental index/psychomotor developmental index < 70) in extremely preterm infants and...

Seizures in Extremely Low Birth Weight Infants Are Associated with Adverse Outcome

To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants. A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables. Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19). ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors.

Looking inside the newborn brain

Neonatal intensive care is a rapidly growing discipline within paediatrics due to the increasing numbers of admissions and survivors of preterm and complex-term birth. As these survivors have grown older, the fact that they face a high risk of adverse neurodevelopmental outcomes is becoming increasingly recognised. The basis for these adverse outcomes seems to be mediated both by unique forms of brain injury (eg, intraventricular haemorrhage) and altered brain development. Neonatal Cerebral Investigation fulfils a key role in educating the neonatologist caring for any infant at high risk of such neurological complications.

Heart rate characteristics and neurodevelopmental outcome in very low birth weight infants

Background:Sepsis in very low birth weight (VLBW) infants has been associated with an increased risk of adverse developmental outcome. We have identified abnormal heart rate characteristics (HRCs) that are predictive of impending sepsis, and we have developed a summary measure of an infant's abnormal HRCs during the neonatal hospitalization that we refer to as the cumulative HRC score (cHRC).Objective:In this study, we tested the hypothesis that increasing cHRC is associated with an increasing risk of adverse neurodevelopmental outcome in VLBW infants.Method:Data were collected on 65 VLBW infants whose HRCs were monitored while in the neonatal intensive care unit and who were examined at 12 to 18 months adjusted age. Using the Bayley Scale of Infant Development-II, we identified delays in early cognitive function (i.e., Mental Developmental Index <70) and psychomotor development (i.e., Psychomotor Developmental Index <70). Cerebral palsy (CP) was diagnosed using a standard neurological examination.Result:Increasing cHRC score was associated with an increased risk of CP (odds ratio per 1 standard deviation increase in cHRC: 2.6, 95% confidence limits: 1.42, 5.1) and delayed early cognitive development [odds ratio: 2.3 (1.3; 4.3)]. These associations remain statistically significant when adjusted for major cranial ultrasound abnormality. There was an association of increasing cHRC and delayed psychomotor development, which did not reach statistical significance [odds ratio: 1.7 (1.0, 3.0)].Conclusion:Among VLBW infants, the cumulative frequency of abnormal HRCs, which can be assessed non-invasively in the neonatal intensive care unit, is associated with an increased risk of adverse neurodevelopmental outcome.

Insults to the developing brain and impact on neurodevelopmental outcome

Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more subtle injury may result in disruption of critical neural pathways. There also appears to be an important relationship between brain injury in the cortex and the growth and developing cerebellum. Although the survival rate for premature has improved over the past decade, researchers remain concerned about the risk for adverse neurocognitive functioning in these early childhood, including an increased risk for cerebral palsy, cognitive impairment, speech and language delay and sensory dysfunction. Learning outcomes After this activity, the learner will be able to (1) identify potential causes of brain injury in the premature infant, (2) understand that the maturational process for the human brain continues throughout gestation, (3) identify risk factors for adverse neurocognitive functioning in premature infants, and (4) identify abnormalities on central nervous system neuroimaging studies that correlate with an increased risk for adverse neurodevelopmental outcome in premature infants.

Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials

Postnatal dexamethasone therapy reduces the incidence of bronchopulmonary dysplasia in preterm infants but may be associated with an increased risk for adverse neurodevelopmental outcome. Our goal was to determine if the effects of dexamethasone on mortality and pulmonary and neurodevelopmental sequelae in preterm infants are modified by the cumulative dose given. Randomized, controlled trials comparing dexamethasone with placebo in ventilated preterm infants >7 days old were identified by searching the electronic databases and the abstracts from the Pediatric Academic societies and by performing manual reference searches. Two reviewers independently assessed eligibility and quality of trials and extracted data on study design, patient characteristics, and relevant outcomes. Original trialists were asked to provide additional data. Sixteen trials including 1136 patients were analyzed by using meta-analysis and metaregression. Additional data were provided by 12 original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3-week) postnatal treatment onset were analyzed separately. Higher dexamethasone doses reduced the relative risk for the combined outcome, mortality or bronchopulmonary dysplasia, with the largest effect in trials that used a cumulative dose of >4 mg/kg. No effect was found of doses on the risk of neurodevelopmental sequelae in the delayed treatment studies, but in the moderately-early-treatment studies the risk of mortality or cerebral palsy decreased by 6.2%, and the risk of a Mental Developmental Index below -2 SDs decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose. Higher cumulative dexamethasone doses administered after the first week of life may decrease the risk for bronchopulmonary dysplasia without increasing the risk for neurodevelopmental sequelae in ventilated preterm infants. A large randomized trial is needed to confirm or refute these findings.

Two-year general and neurodevelopmental outcome after neonatal complex cardiac surgery in patients with deletion 22q11.2: A comparative study

Neonatal complex cardiac surgery carries a significant risk for adverse neurodevelopmental outcome. We hypothesized this risk to be higher in patients with deletion 22q11.2. From 1996 to 2004, neonates who had complex cardiac surgery at age 6 weeks or less had multisite, multidisciplinary health and neurodevelopmental outcomes (Bayley Scales of Infant Development II; mental and psychomotor developmental indices [MDI, PDI] as mean [SD] and delay [<70]) assessed at 18 to 24 months of age. All 16 patients with deletion 22q11.2 (group 1) were compared with 16 patients without deletion 22q11.2 (group 2) having undergone neonatal complex cardiac surgery at the same center and matched for cardiac lesion, socioeconomic status, and year of operation. Outcomes were compared by univariate and multivariate analyses. Heart lesions in each group consisted of 6 (37.5%) cases of interrupted aortic arch, 6 (37.5%) cases of truncus arteriosus, and 4 (25%) cases of tetralogy of Fallot. Outcomes were available for all survivors. Mortality was 3 (19%) and 1 (6%) in groups 1 and 2, respectively (P = .6). MDI and PDI scores were 66.1 (10.6) and 55.0 (9.4) for group 1 and 86.3 (14.6) and 82.3 (14.3) for group 2 (P < .001). Only deletion 22q11.2 was significant in stepwise multiple regression to predict MDI and PDI scores. Mental delay occurred in 8 (61.5%) of 13 in group 1 and 2 (13.8%) of 15 in group 2 (P = .016). Psychomotor delay occurred in 11 (84.6%) of 13 in group 1 and 1 (6.7%) of 15 in group 2 (P < .001). Neonates affected by deletion 22q11.2 and having neonatal complex cardiac surgery have significantly worse neurodevelopmental outcome than do those without deletion 22q11.2.

Neonatal MRI to Predict Neurodevelopmental Outcomes in Preterm Infants

Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive delay (odds ratio, 3.6; 95 percent confidence interval, 1.5 to 8.7), motor delay (odds ratio, 10.3; 95 percent confidence interval, 3.5 to 30.8), cerebral palsy (odds ratio, 9.6; 95 percent confidence interval, 3.2 to 28.3), and neurosensory impairment (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.3). Gray-matter abnormalities (present in 49 percent of infants) were also associated, but less strongly, with cognitive delay, motor delay, and cerebral palsy. Moderate-to-severe white-matter abnormalities on MRI were significant predictors of severe motor delay and cerebral palsy after adjustment for other measures during the neonatal period, including findings on cranial ultrasonography. Abnormal findings on MRI at term equivalent in very preterm infants strongly predict adverse neurodevelopmental outcomes at two years of age. These findings suggest a role for MRI at term equivalent in risk stratification for these infants.

237 Reducing The CMV Infectivity of Mother's Own Breast Milk

Background: Infants can acquire primary postnatal CMV infection from the breast milk of their CMV infected mothers(1). About 60% of Australian mothers are CMV positive. Most of these will eventually excrete CMV into their breast milk(1). CMV transmission has been documented in 37% of preterm infants of CMV infected mothers(1) -symptomatic infection such as neutropenia, thrombocytopenia, hepatopathy, sepsis-like deterioration occurred in about half of these (1). The infants most at risk of symptomatic infection are the extremely low birth weight infants and those who acquire CMV early(2). An increased risk of adverse neurodevelopmental outcome in low-birth weight infants who acquired CMV early has been suggested (3). Preventing CMV transmission in extremely preterm infants from maternal milk is a clinical problem. Methods that reliably remove CMV such as heating also remove beneficial properties of breast milk. Freezing is not harmful to the protective effects of breast milk. Previous small studies of freezing (to −20°C) breast milk with naturally acquired CMV showed a reduction in CMV titres, or elimination of CMV. These studies used a culture method with a low sensitivity.