Early Human Development

Editorial Board

2009-12-01

Fatty acid composition of the brain of intrauterine growth retardation rats and the effect of maternal docosahexaenoic acid enriched diet

2009-12-01

Abstract: Aim: To determine whether the intrauterine environment affects lipid metabolism, we measured the fatty acid composition of the brain in rats with intrauterine growth retardation (IUGR) induced by synthetic thromboxane A2 (STA2). Additionally, we evaluated the effect of maternal docosahexaenoic acid (DHA)-enriched diet.Methods: Two experimental diets were provided: soy bean oil and DHA-enriched diets. Maternal rats were divided randomly into three groups, STA2−/Soy (Sham), STA2+/Soy (IUGR), and STA2+/DHA (DHA) groups. The Sham and IUGR groups were fed the soy diet, and the DHA group received the DHA-enriched diet from embryonic day 7 until delivery. On postnatal days 1 and 7, the pups were weighed and their brains were removed for lipid analysis.Results: The body weight of the IUGR and DHA groups was significantly less than that of the Sham group both on the postnatal days 1 and 7, whereas it was not significantly different between the IUGR and DHA groups either on postnatal day 1 or day 7. There was no significant difference in the percentage of DHA between the Sham and IUGR groups either on postnatal day 1 or 7. On the other hand, the percentage of DHA was higher in the DHA group than in the IUGR group both on the postnatal days 1 and 7.Conclusions: The fatty acid composition in the brain was not altered in the STA2-induced IUGR rat model. Increased DHA percentage was observed in the maternal DHA-enriched diet group, although no beneficial effect on body weight gain was observed.

New Dutch reference curves for birthweight by gestational age

2009-12-01

Abstract: Objective: To construct new Dutch reference curves for birthweight by parity, sex and ethnic background.Design: Retrospective nationwide study.Material and methods: Reference curves for birthweight were constructed using the LMS model and were based on 176,000 singleton births in the Netherlands in the year 2001 (approximately 95% of all births in that year).Results: Separate birthweight curves were constructed for male and female babies born from primiparous and multiparous women from 25 to 43weeks gestational age. The reference curves are similar to the Swedish references. Birthweight at early gestation was lower than in the previous Dutch reference curves and higher from term onwards. Infants of Hindustani women had a significantly lower birthweight, so that a separate reference curve was constructed.Conclusion: The new Dutch reference curves show a different pattern than the Dutch reference curves collected more than 50years ago, reflecting changes in prenatal conditions and care.

Infertility, infertility treatment, and mixed-handedness in children

2009-12-01

Abstract: Background: Mixed-handedness, which may reflect atypical brain laterality, has been linked to a number of medical conditions as well as prenatal stress.Aims: The aim of the study was to examine whether infertility or infertility treatment was associated with an increased risk of mixed-handedness in children.Study design, subjects and outcome measures: We used data from three population-based birth cohorts in Denmark: the Aalborg-Odense Birth Cohort (1984–1987), the Aarhus Birth Cohort (1990–1992) and the Danish National Birth Cohort (1996–2002) (N=7728, 5720 and 29486, respectively). Data on time to pregnancy and infertility treatment were collected during pregnancy. Handedness was reported in a follow-up questionnaire when the children were at least 7years old. Children were categorized as mixed-handed if their mothers reported that they used both hands equally.Results: Children born after infertility treatment, particularly intrauterine insemination, had a higher risk of being mixed-handed compared to children of fertile couples with a time to pregnancy ≤12months (odds ratio 1.41, 95% confidence interval 1.09–1.82). Children of couples with unplanned pregnancies, particularly after an oral contraceptives failure, were also more likely to be mixed-handed. There was no association between a long waiting time to pregnancy and mixed-handedness in children.Conclusions: Children born after infertility treatment, particularly intrauterine insemination, and children exposed to oral contraceptives during early gestation may have a higher risk of being mixed-handed.

Visuospatial and verbal fluency relative deficits in ‘complicated’ late-preterm preschool children

2009-12-01

Abstract: Background: Late-preterm children constitute a majority of all preterm deliveries (75%). Their immature brain development at birth has been associated with an increased risk for morbidities. Data have been sparse regarding neuropsychological outcomes in the preschool years.Aim: To examine general cognition, attention/working memory, language, manual coordination/motor dexterity, visuomotor, visuospatial, and executive functions in preschoolers born late-preterm (LPT; 34–36 gestational weeks) who required NICU admission compared to term-born participants.Design: Single-center retrospective cohort study of 95 three-year-old children; 60 born LPT in 2004–2005 and admitted to the NICU compared to 35 healthy term-born participants born ≥37 gestational weeks and ≥2500g.Results: LPT birth was associated with visuospatial (p=.005), visuomotor (p=.012), and executive function (noun [p=.018] and action-verb [p=.026] fluency) relative deficits, but not attention/working memory, receptive or expressive language, nonverbal reasoning, or manual coordination/dexterity deficit.Conclusions: Late-preterm birth is likely to be associated with negative neuropsychological sequelae, although subtle and selective compared to effects reported for children born at an earlier gestational age. Visuospatial function appears to be especially vulnerable to disruption even at preschool age, and verbal fluency may be useful as an early predictor of executive dysfunction in childhood. Routine preschool neuropsychological evaluation is recommended to identify delay or deficit in LPT children preparing for school entry, and may highlight underlying vulnerable neural networks in LPT children.

Growth and health outcome of 102 2-year-old children conceived after preimplantation genetic diagnosis or screening

2009-12-01

Abstract: Objective: The major objective of this study was to determine whether the embryo biopsy procedure might cause growth restriction or affect health outcome of children.Study design: Auxological data and physical findings were compared at birth and age 2 for 102 children (70 singletons and 32 twins) born after PGD/PGS and 102 matched children born after intracytoplasmic sperm injection (ICSI) in a prospective study.Results: No statistically significant differences regarding weight, height and head circumference standard deviation scores (SDS) at birth and at age two years were observed. At two years of age the mean BMI SDS tended to be lower in PGD/PGS children (p=0.058). PGD/PGS babies had been more often breastfed (p=0.013), but mostly during a shorter time.The prevalence of major as well as minor congenital anomalies, hospital admissions and surgical interventions was similar.Conclusion: Children born after embryo biopsy applied in PGD/PGS present similar prenatal and postnatal growth and health outcome in the first two years of life compared to ICSI children. Up till now, PGD and PGS appear not to be associated with a higher risk for health problems.

The influence of extrauterine life on the aEEG maturation in normal preterm infants

2009-12-01

Abstract: Objective: To study, the maturational changes of the amplitude-integrated electroencephalogram (aEEG) in preterm infants without neurological disorders and especially the influence of the duration of extrauterine life, over this process.Methods: 96 preterm infants, 25–34weeks' gestational age (GA) at birth, clinically stable and without ultrasonographic evidence of neurological abnormalities, were studied. The aEEG recordings were obtained within 72h of life and then weekly until discharge. Four aspects of each tracing (continuity, sleep–wake cycling, bandwidth, and lower border), were evaluated by visual analysis, applying pre-established criteria.Results: We analysed 624 aEEG recordings at postmenstrual age (PMA) of 25–42weeks. With advanced GA the aEEG becomes more continuous (p: 0.022), it displays definite sleep–wake cycles (p: 0.011), and its bandwidth acquires the mature pattern (p: 0.012). A positive significant interaction of GA and PMA in the evolution of aEEG was found regarding continuity (p: 0.002), sleep–wake cycling (p: 0.002), and bandwidth (p: 0.02).Conclusion: The evolution of the aEEG tracing depends on both GA and PMA. The older the infants at birth the more mature the aEEG pattern. At the same PMA, preterm infants of lower GA display an advanced maturation of the aEEG comparing with others of higher GA.

Oxidative stress after antenatal betamethasone: Acute downregulation of glutathione peroxidase-3

Johan Verhaeghe, Rita van Bree, Erik Van Herck — 2009-12-01

Abstract: Background: Human and experimental data show that antenatal exposure to glucocorticoids (GC) temporarily reduces fetal well-being and impairs the fetal response to hypoxemia.Aims: We tested the hypothesis that antenatal betamethasone provokes transient oxidative stress, which may be triggered directly by the GC or indirectly by metabolic signals such as increased glucose and free fatty acid (FFA) concentrations.Study design: Prospective (single center, 18months) cohort study in newborns <34weeks gestational age at birth.Methods: We studied 105 newborns and measured oxidative damage to lipids [malondialdehyde (MDA)] and proteins (protein carbonyls), as well as glutathione peroxidase-3 (GPx3), an important antioxidant enzyme, in umbilical vein (UV) plasma. In addition, we measured umbilical artery and UV blood gases, and metabolic indices (plasma glucose, FFA and insulin) in UV.Results: MDA but not protein carbonyl concentrations was inversely related to time elapsed since the first or last betamethasone administration (p=0.006); MDA remained elevated by 69–96% for at least 72h after the last betamethasone. By contrast, GPx3 concentrations were repressed in newborns who received betamethasone ≤24h before birth. GPx3 and MDA concentrations were correlated (r=−0.38, p<0.001). Labor, GA, sex, size at birth, blood gases or metabolic indices did not explain the effects of betamethasone on MDA and GPx3.Conclusions: Antenatal GC elicit a rapid suppression of the GPx3 antioxidant defense system which may contribute to a longer-lasting but also transient rise in lipid oxidative damage.

Patterns in sleep–wakefulness in three-month old infants exposed to methadone or buprenorphine

Monica Sarfi, Harald Martinsen, Brittelise Bakstad, Jo Røislien, Helge Waal — 2009-12-01

Abstract: Background: Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation.Aim: This study examines sleep–wakefulness–distress patterns as indicators of regulatory mechanisms at 3months of age.Participants: A national infant cohort (N=35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N=36) of low-risk infants born in the same period.Outcome measures: Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups.Results: Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics.Conclusions: Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep–wakefulness patterns.

A patient care system for early 3.0Tesla magnetic resonance imaging of very low birth weight infants

2009-12-01

Abstract: Background: Very low birth weight (VLBW) infants (weight <1500g) are increasingly cared for without prolonged periods of positive pressure ventilation (PPV).Aims: To develop a system for 3.0T magnetic resonance (MR) image acquisition from VLBW infants who are not receiving PPV, and to test the clinical stability of a consecutive cohort of such infants.Design: Seventy VLBW infants whose median weight at image acquisition was 940g (590–1490) underwent brain MR imaging with the developed care system as participants in research. Twenty infants (29%) received nasal continuous positive airway pressure (nCPAP), 28 (40%) received supplemental oxygen by nasal cannulae, and 22 (31%) breathed spontaneously in air during the MR examination.Results: There were no significant adverse events. Seventy-six percent had none or transient self-correcting oxygen desaturations. Desaturations that required interruption of the scan for assessment were less common among infants receiving nCPAP (2/20) or breathing spontaneously in air (2/22), compared with those receiving nasal cannulae oxygen (13/28), p=0.003. Sixty-four (91%) infants had an axillary temperature ≥36°C at completion of the scan (lowest 35.7°C), There was no relationship between weight (p=0.167) or use of nCPAP (p=0.453) and axillary temperature <36°C. No infant became hyperthermic.Conclusion: VLBW infants who do not require ventilation by endotracheal tube can be imaged successfully and safely at 3.0T, including those receiving nCPAP from a customised system.

Serial postural and motor assessment of Fetal Akinesia Deformation Sequence (FADS)

2009-12-01

Abstract: Background: Fetal Akinesia Deformation Sequence (FADS) is a rare, in most cases autosomal recessive, disorder. Its heterogeneous origin results in variable onset and expression of motor and postural anomalies. DNA-diagnostic possibilities are limited, thus prenatal diagnosis is chiefly dependent on sonographic examinations.Aim: To explore postural and motor development from a systematic sonographic protocol for fetuses at high risk for FADS. Specific questions are: which motor (i.e., specific movement patterns, quality and quantity of general movements) and postural aspects are most informative about emerging FADS and is the gestational age of onset range of FADS more limited for siblings?Methods: Ten families underwent 45, 15-minute sonographic assessments for motility and posture for ten index fetuses with FADS and nine subsequent pregnancies from five families.Results: FADS was diagnosed between 18 and 33weeks gestation in ten index pregnancies and between 11 and 18weeks gestation in 4/9 subsequent pregnancies, 1–12weeks earlier than their index pregnancies. From the four assessment aspects, posture and movement quality were always abnormal, movement quantity in 7/14 and differentiation into specific movement patterns were reduced in comparison with healthy siblings (p<0.01). Deterioration occurred in a 2week period.Conclusions: Serial postural and qualitative assessments were most informative diagnosing FADS. Quantity and differentiation into specific movement patterns contributed substantially. Onset range of FADS within siblings was suggested to be more limited than between families.

Maternal psychological impact of medical information in the neonatal period after premature birth

2009-12-01

Abstract: The mothers of premature infant born 7years ago were interviewed regarding memory of neonatal hospitalization during a 40-minute phone interview using a questionnaire exploring emotional feeling and satisfaction. The memory of a high emotional feeling was significantly associated with cranial ultrasound abnormalities in neonatal period, but not outcome. Dissatisfaction was reduced by antenatal maternal hospitalization. We speculate that medical information gathered during perinatal hospitalization explains these relationships.

Power spectrum analysis of fetal heart rate variability at near term and post term gestation during active sleep and quiet sleep

J.O.E.H. van Laar, C.H.L. Peters, R. Vullings, S. Houterman, S.G. Oei — 2009-12-01

Abstract: Background: Spectral analysis of fetal heart rate variability is promising for assessing fetal condition. Before using spectral analysis for fetal monitoring it has to be determined whether there should be a correction for gestational age or behavioural state.Aims: Compare spectral values of heart rate variability between near term and post term fetuses during active and quiet sleep.Study design: Case–control. Cases had a gestational age of ≥42weeks; controls were 36 to 37weeks. Fetuses were matched for birth weight percentile.Subjects: STAN® registrations from healthy fetuses. For each fetus one 5-minute segment was selected during active and one during quiet sleep.Outcome measures: Absolute and normalized low (0.04–0.15Hz) and high frequency power (0.4–1.5Hz) of heart rate variability.Results: Twenty fetuses were included. No significant differences were found between cases and controls in absolute (481 and 429 respectively, P=0.88) or normalized low (0.78 and 0.80 respectively, P=0.50) or absolute (41 and 21 respectively, P=0.23) or normalized high frequency power (0.08 and 0.07 respectively, P=0.20) during active state. During rest, normalized low frequency power was lower (0.58 and 0.69 respectively, P=0.03) and absolute (16 and 10 respectively, P=0.04) and normalized high frequency power were higher (0.21 and 0.14 respectively, P=0.01) in cases compared to controls. Absolute and normalized low frequency power were higher during active state compared to rest in both groups (all P values <0.05).Conclusions: We found sympathetic predominance during active state in fetuses around term. Post term parasympathetic modulation during rest was increased compared to near term.