Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ

Background

Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.

Methodology/Principal Findings

We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.

Conclusion/Significance

Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.     

Perinatal Clinical Antecedents of White Matter Microstructural Abnormalities on Diffusion Tensor Imaging in Extremely Preterm Infants

Objective

To identify perinatal clinical antecedents of white matter microstructural abnormalities in extremely preterm infants.

Methods

A prospective cohort of extremely preterm infants (N = 86) and healthy term controls (N = 16) underwent diffusion tensor imaging (DTI) at term equivalent age. Region of interest-based measures of white matter microstructure - fractional anisotropy and mean diffusivity - were quantified in seven vulnerable cerebral regions and group differences assessed. In the preterm cohort, multivariable linear regression analyses were conducted to identify independent clinical factors associated with microstructural abnormalities.

Results

Preterm infants had a mean (standard deviation) gestational age of 26.1 (1.7) weeks and birth weight of 824 (182) grams. Compared to term controls, the preterm cohort exhibited widespread microstructural abnormalities in 9 of 14 regional measures. Chorioamnionitis, necrotizing enterocolitis, white matter injury on cranial ultrasound, and increasing duration of mechanical ventilation were adversely correlated with regional microstructure. Conversely, antenatal steroids, female sex, longer duration of caffeine therapy, and greater duration of human milk use were independent favorable factors. White matter injury on cranial ultrasound was associated with a five weeks or greater delayed maturation of the corpus callosum; every additional 10 days of human milk use were associated with a three weeks or greater advanced maturation of the corpus callosum.

Conclusions

Diffusion tensor imaging is sensitive in detecting the widespread cerebral delayed maturation and/or damage increasingly observed in extremely preterm infants. In our cohort, it also aided identification of several previously known or suspected perinatal clinical antecedents of brain injury, aberrant development, and neurodevelopmental impairments.     

Lower Transplacental Antibody Transport for Measles,Mumps, Rubella and Varicella Zoster in Very Preterm Infants

Background

Maternal antibodies, transported over the placenta during pregnancy, contribute to the protection of infants from infectious diseases during the first months of life. In term infants, this protection does not last until the first recommended measles-mumps-rubella vaccination at 14 months in the Netherlands, while these viruses still circulate. The aim of the study was to investigate the antibody concentration against measles, mumps, rubella and varicella (MMRV) in mothers and preterm infants or healthy term infants at birth.

Methods

Antibody concentrations specific for MMRV were measured in cord blood samples from preterm (gestational age <32 weeks and/or birth weight <1500 g) and term infants, and matched maternal serum samples, using a fluorescent bead-based multiplex immune-assay.

Results

Due to lower placental transfer ratios of antibodies against MMRV in 96 preterm infants (range 0.75–0.87) compared to 42 term infants (range 1.39–1.65), the preterm infants showed 1.7–2.5 times lower geometric mean concentrations at birth compared to term infants. Maternal antibody concentration is the most important determinant of infant antibody concentration against MMRV.

Conclusions

Preterm infants benefit to a lesser extent from maternal antibodies against measles, mumps, rubella and varicella than term infants, posing them even earlier at risk for infectious diseases caused by these still circulating viruses.     

Time Course Study of Blood Pressure in Term and Preterm Infants Immediately after Birth

Objective

To describe temporal changes in systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively) in term and preterm infants immediately after birth.

Methods

Prospective observational two-center study. In term infants SBP, DBP, and MBP were assessed non-invasively every minute for the first 15 minutes, and in preterm infants every minute for the first 15 minutes, as well as at 20, 25, 30, 45, and 60 minutes after birth. Regression analyses were performed by gender and respiratory support in all neonates; and by mode of delivery, cord clamping time, and development of ultrasound-detected brain injury in preterm neonates.

Results

Term infants (n = 54) had a mean (SD) birth weight of 3298 (442) g and gestational age of 38 (1) weeks, and preterm infants (n = 94) weighed 1340 (672) g and were 30 (3) weeks gestation. Term infants’ SBP, DBP and MBP within the first 15 minutes after birth were independent of gender or respiratory support. Linear mixed regression analysis showed that preterm infants, who were female, born vaginally, had delayed cord clamping and did not require positive pressure ventilation nor develop periventricular injury or ventriculomegaly, had significantly higher SBP, DBP, and MBP at some measurement points within the first hour after birth.

Conclusions

We present novel reference ranges of BP immediately after birth in a cohort of term and preterm neonates. They may aid in optimization of cardiovascular support during early transition at all gestations.     

Association of Gestational Age at Birth with Reasons for Subsequent Hospitalisation: 18 Years of Follow-Up in a Western Australian Population Study

Background

Preterm infants are at a higher risk of hospitalisation following discharge from the hospital after birth. The reasons for rehospitalisation and the association with gestational age are not well understood.

Methods

This was a retrospective birth cohort study of all live, singleton infants born in Western Australia between 1^st January 1980 and 31^st December 2010, followed to 18 years of age. Risks of rehospitalisation following birth discharge by principal diagnoses were compared for gestational age categories (<32, 32–33, 34–36, 37–38 weeks) and term births (39–41weeks). Causes of hospitalisations at various gestational age categories were identified using ICD-based discharge diagnostic codes.

Results

Risk of rehospitalisation was inversely correlated with gestational age. Growth-related concerns were the main causes for rehospitalisation in the neonatal period (<1 month of age) for all gestational ages. Infection was the most common reason for hospitalisation from 29 days to 1 year of age, and up to 5 years of age. Injury-related hospitalisations increased in prevalence from 5 years to 18 years of age. Risk of rehospitalisation was higher for all preterm infants for most causes.

Conclusions

The highest risks of rehospitalisation were for infection related causes for most GA categories. Compared with full term born infants, those born at shorter GA remain vulnerable to subsequent hospitalisation for a variety of causes up until 18 years of age.     

Decreased Bone Mineral Density in Adults Born with Very Low Birth Weight: A Cohort Study

Background

Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood.

Methods and Findings

The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults'' shorter height and lower self-reported exercise intensity.

Conclusions

Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors'' Summary     

Macrophage Phenotype Is Associated with Disease Severity in Preterm Infants with Chronic Lung Disease

Background

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.

Objectives

To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.

Methods

Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.

Results

Preterm birth was associated with an increase in the proportion of non-classical CD14+/CD16+ monocytes on the day of delivery (58.9±5.8% of total mononuclear cells in preterm vs 33.0±6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36⁺ macrophages compared with the CLD group (70.3±5.3% in RDS vs 37.6±8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14⁺ mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.

Conclusions

These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.     

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

Background

Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age.

Methods

42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling.

Results

After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes.

Conclusions

In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.     

Preterm Birth,Age at School Entry and Educational Performance

Objective

To investigate if the lack of gestational age correction may explain some of the school failure seen in ex-preterm infants.

Design

A cohort study based on the Avon Longitudinal Study of Parents and Children (ALSPAC). The primary outcome was a low Key Stage 1 score (KS1) score at age 7 or having special educational needs (SEN). Exposure groups were defined as preterm (<37 weeks gestation, n = 722) or term (37–42 weeks, n = 11,268). Conditional regression models were derived, matching preterm to term infants on date of birth (DOB), expected date of delivery (EDD) or expected date of delivery and year of school entry. Multiple imputation was used to account for missing covariate data.

Results

When matching for DOB, infants born preterm had an increased odds of a low KS1 score (OR 1.73 (1.45–2.06)) and this association persisted after adjusting for potential confounders (OR 1.57 (1.25–1.97)). The association persisted in the analysis matching for EDD (fully adjusted OR 1.53 (1.21–1.94)) but attenuated substantially after additionally restricting to those infants who entered school at the same time as the control infants (fully adjusted OR 1.25 (0.98–1.60)). A compatible reduction in the population attributable risk fraction was seen from 4.60% to 2.12%, and year of school entry appeared to modify the association between gestational age and the risk of a poor KS1 score (p = 0.029).

Conclusions

This study provides evidence that the school year placement and assessment of ex-preterm infants based on their actual birthday (rather than their EDD) may increase their risk of learning difficulties with corresponding school failure.     

Post-neonatal mortality, morbidity, and developmental outcome after ultrasound-dated preterm birth in rural Malawi: a community-based cohort study

Background

Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.

Methods and Findings

This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09–2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.

Conclusions

During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings. Please see later in the article for the Editors'' Summary     

IgM-Antibodies against Phosphorylcholine in Mothers and Normal or Low Birth Weight Term Newborn Infants

Objective

To determine levels of athero-protective IgM antibodies against phosphorylcholine in mothers and term-born normal or low birth weight infants.

Approach

Twenty three mother-infant pairs were studied, of whom 16 infants were within the normal weight range for gestational age (NGA; 3652[504] g) and 7 were small for gestational age (SGA; birth weight: 2715[255] g), the latter <2SD below the Swedish reference data mean for normal fetal growth. All infants were born at term (mean±SD 40.5±1.1 weeks). Serum was available from 6 mothers with SGA and 14 with NGA infants. Participating mothers were aged 34.0±3.9 years (no difference between groups). Fourteen neonates were boys and seven were girls. Levels of anti-PC IgM were determined by ELISA.

Results

Neonatal IgM anti-PC levels were low (undetectable in 8 infants out of which 3 were SGA) with a median of 76[range 0–2.51] U/ml. Maternal IgM anti-PC levels were significantly higher (median 7198[range: 25.32–656.0]) U/ml) and the proportion of mothers in highest quartile (>75th percentile) was larger in mothers of NGA-infants (43%) vs. those of SGA-infants (0%, p = 0.032).

Conclusions

IgM anti-PC levels are low at birth, which suggests that these antibodies do not play a “housekeeping” role in immune function during fetal life/development, but arise predominately on exposure to external antigens after birth. Furthermore, low maternal IgM anti-PC levels may play a role in placental insufficiency, contributing to poor fetal growth and a small-for-date baby. This preliminary observation may have implications for the future risk of atherosclerosis/cardiovascular disease development in pregnant women and their offspring.     

Birth Weight Reference Percentiles for Chinese

Objective

To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese.

Methods

Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged ≥28 weeks of gestation without birth defects during 2006–2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves.

Results

Gestational age-specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants.

Conclusion

There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes.     

Monitoring Lung Aeration during Respiratory Support in Preterm Infants at Birth

Background

If infants fail to initiate spontaneous breathing, resuscitation guidelines recommend respiratory support with positive pressure ventilation (PPV). The purpose of PPV is to establish functional residual capacity and deliver an adequate tidal volume (V_T) to achieve gas exchange.

Objective

The aim of our pilot study was to measure changes in exhaled carbon dioxide (ECO₂), V_T, and rate of carbon dioxide elimination (VCO₂) to assess lung aeration in preterm infants requiring respiratory support immediately after birth.

Method

A prospective observational study was performed between March and July 2013. Infants born at <37 weeks gestational age who received continuous positive airway pressure (CPAP) or PPV immediately after birth had V_T delivery and ECO₂ continuously recorded using a sensor attached to the facemask.

Results

Fifty-one preterm infants (mean (SD) gestational age 29 (3) weeks and birth weight 1425 (592 g)) receiving respiratory support in the delivery room were included. Infants in the CPAP group (n = 31) had higher ECO₂ values during the first 10 min after birth compared to infants receiving PPV (n = 20) (ranging between 18–30 vs. 13–18 mmHg, p<0.05, respectively). At 10 min no significant difference in ECO₂ values was observed. V_T was lower in the CPAP group compared to the PPV group over the first 10 min ranging between 5.2–6.6 vs. and 7.2–11.3 mL/kg (p<0.05), respectively.

Conclusions

Immediately after birth, spontaneously breathing preterm infants supported via CPAP achieved better lung aeration compared to infants requiring PPV. PPV guided by V_T and ECO₂ potentially optimize lung aeration without excessive V_T administered.     

Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective

To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA).

Study design

In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10^th percentile using the Canadian reference charts.

Results

Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDS_Canada (p<0.001), and SGA_Canada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDS_Sweden, OR = 0.80 vs 0.56; and BWSDS_Canada, OR = 0.72 vs 0.41).

Conclusions

Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant''s degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.     

Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

Background

Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain.

Objective

Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years.

Design/Methods

The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning.

Results

At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk.

Conclusions

Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.     

Bone Mineral Density of the Spine in 11,898 Chinese Infants and Young Children: A Cross-Sectional Study

Background

Bone mineral density (BMD) increases progressively during childhood and adolescence and is affected by various genetic and environmental factors. The aim of this study was to establish reference values for lumbar BMD in healthy Chinese infants and young children and investigate its influencing factors.

Methods and Findings

Healthy children aged 0 to 3 years who underwent regular physical examinations at the Child Health Care Clinic of Hubei Maternal and Child Health Hospital (N = 11,898) were recruited for this study. We also chose 379 preterm infants aged 0 to 1 years to preliminarily explore the development of BMD in this special population. BMD (g/cm²) measurements of the lumbar spine (L2–L4) were carried out with dual-energy X-ray absorptiometry and a questionnaire was administered to full-term children''s parents to gather information on various nutritional and lifestyle factors as well as mothers'' nutritional supplement use during pregnancy. Lumbar BMD significantly increased with age among both boys and girls (p<0.05), with fastest growth observed during the first postnatal year. There was no significant difference in lumbar BMD between boys and girls of similar age (p>0.05), either among healthy reference children or preterm infants. However, BMD values in preterm infants were significantly lower than those in term infants 3 to 8 months old (p<0.05) after adjustment for gestational age. Multivariable linear regression analysis indicated significant positive associations between lumbar BMD of healthy children and the child''s age and current weight, mother''s weight gain during pregnancy, birth weight, children''s outdoor activity duration and children''s physical activity duration.

Conclusion

Our study provides reference values of lumbar BMD for healthy Chinese children aged 0 to 3 years and identifies several influencing factors.     

Sequential Cranial Ultrasound and Cerebellar Diffusion Weighted Imaging Contribute to the Early Prognosis of Neurodevelopmental Outcome in Preterm Infants

Objective

To evaluate the contribution of sequential cranial ultrasound (cUS) and term-equivalent age magnetic resonance imaging (TEA-MRI) including diffusion weighted imaging (DWI) to the early prognosis of neurodevelopmental outcome in a cohort of very preterm infants (gestational age [GA] <31 weeks).

Study design

In total, 93 preterm infants (median [range] GA in weeks: 28.3 [25.0–30.9]) were enrolled in this prospective cohort study and underwent early and term cUS as well as TEA-MRI including DWI. Early cUS abnormalities were classified as normal, mild, moderate or severe. Term cUS was evaluated for ex-vacuo ventriculomegaly (VM) and enlargement of the extracerebral cerebrospinal fluid (eCSF) space. Abnormalities on T1- and T2-weighted TEA-MRI were scored according to Kidokoro et al. Using DWI at TEA, apparent diffusion coefficients (ADCs) were measured in four white matter regions bilaterally and both cerebellar hemispheres. Neurodevelopmental outcome was assessed at two years’ corrected age (CA) using the Bayley Scales of Infant and Toddler Development, third edition. Linear regression analysis was conducted to explore the correlation between the different neuroimaging modalities and outcome.

Results

Moderate/severe abnormalities on early cUS, ex-vacuo VM and enlargement of the eCSF space on term cUS and increased cerebellar ADC values on term DWI were independently associated with worse motor outcome (p<.05). Ex-vacuo VM on term cUS was also related to worse cognitive performance at two years’ CA (p<.01).

Conclusion

These data support the clinical value of sequential cUS and recommend repeating cUS at TEA. In particular, assessment of moderate/severe early cUS abnormalities and ex-vacuo VM on term cUS provides important prognostic information. Cerebellar ADC values may further aid in the prognostication of gross motor function.     

Personality in Adults Who Were Born Very Preterm

Aim

To investigate the personality in very preterm individuals (VPT; gestational age, GA, <32 weeks) at adult age in two cohorts born in 1974–76 and 1980–82, respectively, and to illuminate the effect of increased survival rates and the clinical implications of deviations in personality.

Method

Demographic data were extracted for all individuals born in Denmark in 1974–76 and 1980–82. From each period one index-group each comprising 150 individuals with the lowest gestational age was selected. Thereafter two control groups born at term were matched by gender, age and residential area. Personality was assessed with the short version of NEO PI-R, and psychiatric diagnoses were obtained from the Danish Psychiatric Central Research Register.

Results

Of all the individuals born <32 weeks of gestation in 1980–82 67% were alive in 2006 vs. 43% of those born in 1974–76 (p<0.0001). A total of 433 individuals participated in the study, 76% of the VPT groups (n = 227, mean GA = 27.9) and 69% of the control groups (n = 206). There were no significant differences on personality scores between the two VPT groups. Compared to the control groups, the combined VPT groups scored higher on neuroticism (p = 0.005) and agreeableness (p = 0.012), but lower on extraversion (p = 0.002). Psychiatric disorder was strongly associated with higher scores on neuroticism and lower scores on extraversion.

Interpretation

Improved survival of VPT infants was not associated with increased deviances in the personality as adults. The personality traits in VPT individuals differ moderately from those of term born controls. High scores in neuroticism and low scores in extraversion were associated with increased risk psychiatric disorders. VPT adults also showed signs of positive adaptation in the form of an agreeable and confident attitude towards others.

What this paper adds

The much improved survival rate in very preterm infants during the early years of active neonatology was not associated with increased risk of personality deviation. There are signs of positive adaptation in the form of increased agreeableness in young adults born very preterm.     

Changes in Birth Weight between 2002 and 2012 in Guangzhou,China

Background

Recent surveillance data suggest that mean birth weight has begun to decline in several developed countries. The aim of this study is to examine the changes in birth weight among singleton live births from 2002 to 2012 in Guangzhou, one of the most rapidly developed cities in China.

Methods

We used data from the Guangzhou Perinatal Health Care and Delivery Surveillance System for 34108 and 54575 singleton live births with 28–41 weeks of gestation, who were born to local mothers, in 2002 and 2012, respectively. The trends in birth weight, small (SGA) and large (LGA) for gestational age and gestational length were explored in the overall population and gestational age subgroups.

Results

The mean birth weight decreased from 3162 g in 2002 to 3137 g in 2012 (crude mean difference, −25 g; 95% CI, −30 to −19). The adjusted change in mean birth weight appeared to be slight (−6 g from 2002 to 2012) after controlling for maternal age, gestational age, educational level, parity, newborn''s gender and delivery mode. The percentages of SGA and LGA in 2012 were 0.6% and 1.5% lower than those in 2002, respectively. The mean gestational age dropped from 39.2 weeks in 2002 to 38.9 weeks in 2012. In the stratified analysis, we observed the changes in birth weight differed among gestational age groups. The mean birth weight decreased among very preterm births (28–31 weeks), while remained relatively stable among other gestational age subcategories.

Conclusions

Among local population in Guangzhou from 2002 to 2012, birth weight appeared to slightly decrease. The percentage of SGA and LGA also simultaneously dropped, indicating that newborns might gain a healthier weight for gestational age.