Early Human Development

Editorial Board

2010-02-01

Asymmetric dimethylarginine, an endogenous NO synthase inhibitor, in human breast milk

Hirokazu Tsukahara, Hironori Nagasaka — 2010-02-01

Asymmetric dimethylarginine (ADMA), a methylated arginine metabolite, is an endogenous NO synthase inhibitor . Recently, we and others found that umbilical blood ADMA levels are significantly higher and that umbilical blood NO levels are significantly lower than maternal levels when delivery occurs at term or preterm . Vida et al. also reported that blood ADMA levels decreased significantly by the second postnatal day in neonates. These observations present one possibility: high ADMA levels counteract NO functions, thereby playing a role in cardiopulmonary adaptation in neonates.

Is smoking in pregnancy an independent predictor of academic difficulties at 14years of age? A birth cohort study

2010-02-01

Abstract: Background: Studies of the effects of maternal smoking during pregnancy have reported inconsistent findings in relation to measures of offspring cognitive functioning. Few studies, however, have examined learning outcomes in adolescents, as opposed to IQ.Aim: To examine the association between maternal smoking during pregnancy and academic performance among adolescent offspring.Study design: Population-based birth cohort study.Subjects: 7223 mothers and children were enrolled in the Mater-University of Queensland Study of Pregnancy in Brisbane (Australia) from 1981 to 1984. Analyses were restricted to the 4294 mothers and children for whom all information was reported at 14-year follow-up.Outcome measures: Reports of academic performance of 14-year-old offspring in English, Science and Mathematics with different patterns of maternal smoking (never smoked, smoked before and/or after pregnancy but not during pregnancy, or smoked during pregnancy).Results: Low academic achievement was more common only in those whose mothers had smoked during pregnancy. Effect sizes were, however, small. The adjusted mean difference in total learning score for smoking before and/or after pregnancy but not during pregnancy, and for smoking during pregnancy were −0.18 (−0.58, 0.22) and −0.40 (−0.69, −0.12). Similarly, the adjusted odds ratios were 0.9 (0. 65, 1.24) and 1.35 (1.07, 1.70).Conclusion: Maternal smoking during pregnancy is a preventable prenatal risk factor associated with small decrements in offspring academic performance that continue into adolescence.

Heart rate variability in infants with central coordination disturbance

2010-02-01

Abstract: Despite a remarkable medical progress in the field of Developmental Medicine and Child Neurology, early identification of infants at risk for permanent motor disabilities still presents challenge for both clinicians and researchers.As an indicator of cardiac autonomic control, it was shown that heart rate variability (HRV) might reflect not only sympathetic or parasympathetic activity but also functional integrity of the central nervous system (CNS). Furthermore a pattern of HRV was demonstrated to correlate with motor developmental outcome in high risk infants.The purpose of this study was to analyze the clinical usefulness as well as predictive value of time-domain HRV parameters in infants with central coordination disturbance.The study included 35 infants with central coordination disturbance and 37 healthy age and sex-matched controls. Time-domain HRV indices were analyzed from 24-h electrocardiography recordings.We found significantly lower values of SDNN, SDANN and RMSSD parameters in infants with central coordination disturbance compared to controls. Additionally, logistic regression analyses demonstrated independent predictive value of parameters SDNN and SDANN in infants who subsequently developed cerebral palsy (CP). By performing receiver operating characteristic (ROC) analyses, the optimal cut-off value of SDNN<=48ms predicted CP with a sensitivity of 68.7% (95% CI 41.4–88.9) and specificity of 84.2% (95 CI 60.4–96.4) while the optimal cut-off value of SDANN<=41ms predicted CP with a sensitivity of 87.5% (95% CI 61.6–98.1) and specificity of 57.9% (95 CI 33.5–79.7).We are in opinion that time domain HRV analysis could be helpful clinically as well as a prognostic tool in infants with central coordination disturbance.

General movements in the perinatal period and its relation to echogenicity changes in the brain

2010-02-01

Abstract: Background: In preterm born infants abnormal general movements (GMs) generally normalize before three months post term, but may persist when perinatal brain injury is present.Aims: To assess the continuity of GM quality from fetal to early neonatal period and its relation to brain echogenicity changes.Study design: Prospective study examining GMs and three vulnerable brain areas before and 7days after birth. The quality of GMs was classified as normal or abnormal by Gestalt-perception. The brain was examined for moderate echogenicity changes (periventricular: brighter than choroid plexus, intraventricular: filling equal or more than 50% of the ventricle, and locally increased basal ganglia/thalami).Subjects: 94 fetuses from pregnancies complicated by preterm hypertensive disorders or labour at a gestational age between 26 and 34weeks.Outcomes measures: Correlations of fetal GMs, echogenicity changes, and clinical parameters (e.g. gestational age, parity, hypertensive disorders or preterm labour, oligohydramnios and fetal growth restriction) with neonatal GMs.Results: Fetal GMs were abnormal in 64%, normalizing in 68% within 7days after birth. Fetal GMs were significantly related to postnatal GMs (p=0.045). Moderate fetal brain echogenicity changes and clinical parameters were not significantly related to neonatal GM.Conclusions: In this population of pregnancies compromised by hypertensive disorders or preterm labour fetal GMs correlated with neonatal GMs. Presence of moderate echogenicity changes in the fetal brain was not related to neonatal GMs.

Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus

2010-02-01

Abstract: Aim: To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA).Methods: We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen.Results: Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2wksd) in early (median CRIB 6 and 5, respiratory distress >2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage >2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0wksd) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24months corrected age.Conclusion: Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.

Bilateral loss of cortical somatosensory evoked potential at birth predicts cerebral palsy in term and near-term newborns

A. Suppiej, A. Cappellari, M. Franzoi, A. Traverso, M. Ermani, V. Zanardo — 2010-02-01

Abstract: Bilateral loss of cortical somatosensory evoked potential (SEP) is considered the single best indicator of adverse outcome in acute encephalopathy of adult patients and older children. This study determines whether the presence or absence of the neonatal cortical SEP can predict cerebral palsy at two years in survivors of neonatal encephalopathy scored according to Sarnat criteria. We also compare SEPs with visual evoked potentials (VEPs), the EEG and neonatal neurological status.Fifty-nine neonates admitted to the neonatal intensive care unit had SEP, VEP and EEG recordings analysed according to the presence (n=37, 63%) or absence (n=22, 37%) of neonatal encephalopathy (score ≥1).Cortical SEP was always present in the perinatal period in those surviving without major neurological disability, while it was bilaterally absent in all but one patient with a subsequent diagnosis of cerebral palsy. Multivariate analysis using the logistic regression model showed that bilateral loss of cortical SEP and Sarnat Score correctly classified the neurological outcome in all patients.Bilateral absence of cortical SEP indicates early identification of neonates at risk of cerebral palsy indicating that EPs have a clinical role in the workup of neonatal encephalopathy.

Antenatal fetal VEGF therapy to promote pulmonary maturation in a preterm rabbit model

2010-02-01

Abstract: Aim: To assess the effects of fetal tracheal administration of VEGF on pulmonary maturation in a preterm rabbit model.Methods: On day 26 (term=31days), fetal rabbits received recombinant rat VEGF (30µg in 70µL normal saline) or placebo (normal saline 70µL) intratracheally, with or without subsequent tracheal occlusion. Non-operated littermates served as internal controls. Fetuses were harvested on day 28 for morphometric study of the lungs or for mechanical ventilation and measurement of lung mechanics. In total, 96 fetuses from 42 does were used, 47 for ventilation and 49 for morphometry.Results: In fetuses receiving intratracheal VEGF, an increase in immunoreactivity for Flk-1 was observed throughout the lung parenchyma. Tracheal occlusion (TO) adversely affected pulmonary mechanics as compared to un-occluded controls. That effect is partly reversed by intratracheal VEGF. Intratracheal injection of VEGF without tracheal occlusion improves lung mechanics but no more than what was observed in placebo injected controls.Conclusion: Antenatal intratracheal VEGF administration was associated with an increase in Flk-1 immunoreactivity. It also improves lung mechanics, however more so when the trachea is occluded. Without TO, the effects were comparable to placebo controls.

Fetal general movements and brain sonography in a population at risk for preterm birth

2010-02-01

Abstract: Background: General movements (GMs) assessed three months post term are related to brain injury and neurological outcome.Aims: To study GMs in fetuses and their predictive value for echogenicity changes in the fetal brain.Study design: Prospective study of fetal GMs (classified as normal or abnormal) and echogenicity changes in the periventricular, basal ganglia/thalami area, and ventricular system (classified as absent, mild or moderate).Subjects: 121 fetuses from pregnancies affected by hypertensive disorders and/or preterm labour, at risk for preterm birth (26–34weeks gestational age).Outcome measures: Prevalence of abnormal GMs, GM parameters (amplitude, speed and complexity), and moderate echogenicity changes in the fetal brain (periventricular ≥IB, intraventricular grade II/III, and basal ganglia/thalamus locally increased). Predictive values of GMs for clinical parameters and moderate echogenicity changes.Results: GMs were abnormal in 58%, with amplitude affected in 96%, and speed and complexity in 59%. Abnormal GMs correlated with oligohydramnios (p=0.002) and hypertensive disorders (p=0.015). Echogenicity changes of the brain were absent, mild and moderate in 27%, 39% and 31%, respectively. The sensitivity of GMs for moderate echogenicity changes in the three areas combined was 0.65, and the periventricular area 0.85, specificity both 0.44, negative predictive values 0.73 and 0.96 respectively.Conclusions: Qualitative abnormal GMs are frequent in fetuses of compromised pregnancies, and correlate with hypertensive disorders and oligohydramnios. The amplitude of GMs was most frequently affected. Abnormal GMs relate to moderate echogenicity changes especially in the periventricular area of the fetal brain, while normal GMs predict absence of moderate echogenicity changes.

IL-6 and TNFα across the umbilical circulation in term pregnancies: Relationship with labour events

2010-02-01

Abstract: Objective: We have determined venous and arterial cord blood levels for IL-6 and TNFα at the time of delivery to assess gestational tissue versus fetal sources in labouring and non-labouring patients at term, and the relationship to labour events.Methods: Fifty-five patients were studied (elective cesarean section n=24, and labouring n=31) with blood sampling from a clamped segment of cord after delivery of the fetus and from the cord at its insertion into the placenta after delivery of the placenta, with subsequent measurement of blood gases, pH, IL-6 and TNFα.Results: Umbilical cord levels for IL-6 were increased by 4 fold in low risk labouring patients, and a further 6 fold when showing histologic chorioamnionitis, but with no evident effect of nuchal cord with ‘variable’ fetal heart rate decelerations, fetal acidemia, nor of labour duration. IL-6 levels from the cord at its insertion into the placenta were generally higher than those from the respective umbilical levels indicating that placental release of IL-6 into cord blood must be occurring. However, a consistent venoarterial difference for IL-6 and thereby a net flux from the placenta could not be demonstrated. TNFα levels for both patient groups were uniformly low for all of the cord measurements with no significant differences noted.Conclusion: Umbilical cord levels for IL-6 are increased in low risk labouring patients at term in the absence of evident infection which likely involves both gestational tissue and fetal contributions. Cord levels for IL-6 are further increased in low risk labouring patients showing histologic chorioamnionitis which might then contribute to newborn morbidity in these pregnancies.

A longitudinal study of differences in electroencephalographic activity among breastfed, milk formula-fed, and soy formula-fed infants during the first year of life

Hongkui Jing, Janet M. Gilchrist, Thomas M. Badger, R.T. Pivik — 2010-02-01

Abstract: Background: The extent to which adequate nutrition from infant diets differentially influence developmental outcomes in healthy infants has not been determined.Aim: To compare the effects of the major infant diets on the development of brain electrical activity during infancy.Study design: Scalp EEG signals (124 sites) recorded from the same infants during quiet wakefulness at 3, 6, 9, and 12months.Subjects: Healthy, full-term infants (40/group; gender matched) either breastfed (BF) or fed milk formula (MF) or soy formula (SF) through the first 6months.Outcome measures: Power spectral values for frequencies in the 0.1–30Hz range.Results: Significant diet-related differences were present across frequency bands and included effects that were time- [peaks in 0.1–3Hz at 6 (MF,SF) and 9months (BF); 3–6Hz at 6months (MF, SF>BF); increases in 6–9Hz from 3 to 6months (MF>BF) and from 6 to 9months (MF>SF)] and gender-related (9–12Hz and 12–30Hz: at 9months BF>MF, SF boys, and MF>SF girls).Conclusions: The development of brain electrical activity during infancy differs between those who are breastfed compared with those fed either milk or soy formula, but is generally similar for formula-fed groups. These variations in EEG activity reflect diet-related influences on the development of brain structure and function that could put infants on different neurodevelopmental trajectories along which cognitive and brain function development will proceed.

The relationship between cortisol concentrations in pregnancy and systemic vascular resistance in childhood

2010-02-01

Abstract: Objective: To assess the relationship between cortisol concentrations in the last trimester of pregnancy and systemic vascular resistance — SVR in childhood.Materials and methods: This study is part of a cohort involving 130 Brazilian pregnant women and their children, ages 5 to 7years. Maternal cortisol was determined in saliva by an enzyme immunoassay utilizing the mean concentration of 9 samples of saliva (3 in each different day), collected at the same time, early in the morning. SVR was assessed by the HDI/PulseWave CR-2000 Cardiovascular Profiling System®. Socioeconomic and demographic characteristics and life style factors were determined by a questionnaire. The nutritional status of the women and children was assessed by the body mass index — BMI. The association between maternal cortisol and SVR in childhood was calculated by multivariate linear regression analysis.Results: There were statistically significant associations between maternal cortisol and SVR (p=0.043) and BMI-z score of the children (p=0.027), controlling for maternal BMI, birth weight, age, and gender of the children.Conclusion: As far as we know this is the first study in the literature assessing the association between cortisol concentrations in pregnancy and SVR in childhood. Overall, the data suggest that exposure to excess glucocorticoid in the prenatal period is associated to vascular complications in childhood, predisposing to cardiovascular diseases in later life.

Vitamin D supplementation of mother and infant could reduce risk of sepsis in premature infants

William B. Grant — 2010-02-01

The recent paper on risk factors and prevention of late-onset sepsis in premature infants was useful but overlooked an important risk factor for sepsis — low serum 25-hydroxyvitamin D [25(OH)D] levels. An ecological study reviewed the epidemiology of adult septicemia in the United States and concluded that there was a strong correlation with indices for solar ultraviolet-B doses and vitamin D production . A subsequent case–control study found that those with septicemia had low serum levels . Vitamin D is very important for the innate immune system, leading to production of cathelicidin and defensins that have antimicrobial and antiendotoxin activities .