Growth patterns and cerebroplacental hemodynamics in fetuses with congenital heart disease.

OBJECTIVES: Congenital heart disease (CHD) has been associated with reduced fetal head circumference (HC), although the underlying pathophysiology remains undetermined. We aimed to define trends in fetal growth and cerebroplacental Doppler flow, and to investigate their relationship, in fetuses with CHD. METHODS: This was a retrospective study in two fetal medicine units in The Netherlands. We included all fetuses with CHD in whom Doppler flow patterns (middle cerebral artery (MCA) pulsatility index (PI), umbilical artery (UA) PI and cerebroplacental ratio (CPR)) and biometry (HC and abdominal circumference (AC)) had been measured serially after 19 weeks' gestation between January 2010 and November 2016. Fetuses were categorized into three groups based on the expected cerebral arterial oxygen saturation of their particular type of CHD: normal; mild to moderately reduced; severely reduced. Trends over time in Z-scores were analyzed using a linear mixed-effects model. RESULTS: A total of 181 fetuses fulfilled the inclusion criteria. Expected cerebral arterial oxygen saturation in CHD was classified as normal in 44 cases, mild to moderately reduced in 84 and severely reduced in 53. In the cohort overall, average trends over time were significant for both HC and AC Z-scores. HC Z-scores showed a tendency to decrease until 23 weeks, then to increase until 33 weeks, followed by another decrease in the late third trimester. AC Z-scores increased progressively with advancing gestation. MCA-PI and UA-PI Z-scores showed significant trends throughout pregnancy, but CPR Z-scores did not. There were no associations between expected cerebral arterial oxygen saturation and fetal growth. Average trends in MCA-PI Z-scores were significantly different between the three subgroups, whereas those in UA-PI Z-scores and in CPR Z-scores were similar between the subgroups. There was no significant association between MCA-PI and HC Z-scores. CONCLUSIONS: Fetal biometry and Doppler flow patterns are within normal range in fetuses with CHD, but show trends over time. Head growth in fetuses with CHD is not associated with cerebral blood flow pattern or placental function and HC is not influenced by the cerebral arterial oxygen saturation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Amplitude-Integrated EEG and Cerebral Near-Infrared Spectroscopy in Cooled, Asphyxiated Infants.

OBJECTIVE: To assess the predictive value of amplitude-integrated electroencephalography EEG (aEEG) and near-infrared spectroscopy (NIRS) during therapeutic hypothermia. PATIENTS AND METHODS: We studied 39 cooled, asphyxiated infants. We assessed aEEG and calculated mean regional cerebral oxygen saturation (rcSO2) during and after treatment. At 30 months, we performed a neurological examination and administered the Bayley Scales of Infant and Toddler Development, 3rd edition. We calculated the odds ratios (ORs) of abnormal aEEG and rcSO2 for severely abnormal outcome. RESULTS: At 6 and 12 hours, severely abnormal aEEGs predicted severely abnormal outcomes (OR, 7.7 [95% confidence interval, CI, 1.39-42.6] and 24.4 [95% CI 4.2-143] respectively), as did epileptic activity (OR 28.9, 4.6-183). During the first 48 hours, rcSO2 was not associated with outcome, but at 72 hours after birth and after rewarming it was, with ORs for severely abnormal outcomes of 12.8 (1.31-124) and 21.6 (1.05-189), respectively. In multivariate analyses, aEEG and rcSO2 remained independently predictive in the model at 48 hours and significantly from 72 hours after birth onward. CONCLUSION: aEEG was a strong predictor of adverse outcome. After 48 hours of cooling, a higher rcSO2 was associated with a severely abnormal outcome, adding to the predictive value of aEEG in cooled, asphyxiated infants.

Correlation between Doppler flow patterns in growth-restricted fetuses and neonatal circulation.

OBJECTIVES: To investigate whether prenatal Doppler parameters in growth-restricted fetuses are correlated with neonatal circulatory changes. METHODS: In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were performed. The last measurement, closest to delivery (< 1 week before birth), was used for analysis. Neonatal circulation was assessed for 2 h/day on Days 1-5, 8 and 15 by near-infrared spectroscopy (NIRS) of the cerebral, renal and splanchnic regions. We calculated fractional tissue oxygen extraction (FTOE) as: (arterial oxygen saturation - NIRS value)/arterial oxygen saturation. The following ratios were calculated: cerebroplacental ratio (CPR; MCA-PI/UA-PI), cerebrorenal ratio (CRR; cerebral/renal FTOE) and cerebrosplanchnic ratio (CSR; cerebral/splanchnic FTOE). Spearman's rank correlation coefficient (ρ) was calculated between prenatal Doppler parameters and neonatal NIRS variables. These analyses were carried out for the entire group, and separately for cases of early FGR (delivered < 34 weeks) and late FGR (≥ 34 weeks). RESULTS: Fetal Doppler parameters correlated with neonatal NIRS variables on Days 1-3: UA-PI correlated with renal FTOE (Day 1: ρ = 0.454, P < 0.01) and CRR (Day 1: ρ = -0.517, P < 0.001). MCA-PI correlated with cerebral FTOE on Day 2 (ρ = 0.469, P < 0.01), approached statistical significance on Day 3 but was not correlated on Day 1. CPR correlated with CRR (Day 1: ρ = 0.474, P < 0.01). Most associations lost their statistical significance when early and late FGR subgroups were considered separately. CONCLUSION: Low MCA-PI and low CPR, indicating brain sparing before birth, are associated with low CRR after birth, indicating relatively greater blood flow to the cerebrum than to the renal region. Based on the results of this study, it could be speculated that if brain sparing is present in the fetal circulation, it persists during the first 3 days after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Relationship between general movements in neonates who were growth restricted in utero and prenatal Doppler flow patterns.

OBJECTIVE: To investigate whether Doppler pulsatility indices (PIs) of the fetal circulation in cases of fetal growth restriction (FGR) are associated with the general movements (GMs) of the neonate after birth. METHODS: This was a prospective observational cohort study including pregnancies with FGR diagnosed between June 2012 and September 2014. A diagnosis of FGR was based on an abdominal circumference or estimated fetal weight < 10th percentile (in conjuction with abnormal Doppler) or declining fetal growth of at least 30 percentiles with respect to previous size measurements. Doppler parameters of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) were measured maximally 1 week prior to delivery. Cerebroplacental ratio (CPR) was calculated as MCA-PI divided by UA-PI. We assessed the quality of neonatal GMs 7 days after birth, around the due date if cases were born preterm, and at 3 months post-term. We performed a detailed analysis of the motor repertoire by calculating a motor optimality score (MOS). RESULTS: Forty-eight FGR cases were included with a median gestational age at delivery of 35 (range, 26-40) weeks. UA-PI, MCA-PI and CPR correlated strongly (ρ, -0.374 to 0.472; P < 0.01) with the MOS on day 7 after birth, but DV-PI did not. Doppler PI measurements did not correlate with MOS at 3 months post-term. CONCLUSION: Fetal arterial Doppler measurements are associated with the quality of neonatal GMs 1 week after birth, but this association is no longer evident at 3 months post-term. Brain sparing in particular is associated strongly with GMs of an abnormal quality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Neurocognitive outcomes in moderately preterm born adolescents.

BACKGROUND: Early preterm (EP) born children are at risk of neurocognitive impairments persisting into adulthood. Less is known about moderately to late (MLP) preterm born children, especially after early childhood. The aim of this study was to assess neurocognitive functioning of MLP adolescents regarding intelligence, executive and attentional functioning, compared with EP and full-term (FT) adolescents. METHODS: This study was part of the Longitudinal Preterm Outcome Project (LOLLIPOP), a large community-based observational cohort study. In total 294 children (81 EP, 130 MLP, and 83 FT) were tested at age 14 to 16 years, regarding intelligence, speed of processing, attention, and executive functions. We used the Dutch version of the Wechsler Intelligence Scale for Children-Third Edition-Dutch Version (WISC-III-NL), the Test of Everyday Attention for Children, and the Behavioural Assessment of the Dysexecutive Syndrome for Children. We assessed differences between preterm-born groups with the FT group as a reference. RESULTS: Compared to the FT group, MLP adolescents scored significantly lower on two subtasks of the WISC-III-NL, i.e. Similarities and Symbol Search. EP adolescents performed significantly lower on all neuropsychological tests than their FT peers, except for the subtask Vocabulary. The MLP adolescents scored in between FT and EP adolescents on all tasks, except for three WISC-III-NL subtasks. CONCLUSIONS: Neurocognitive outcomes of MLP adolescents fell mostly in between outcomes of their EP and FT peers. MLPs generally performed on a low-average to average level, and appeared susceptible to a variety of moderate neurodevelopmental problems at adolescent age, which deserves attention in clinical practice.

The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT.

STUDY QUESTION: Does embryo biopsy inherent to preimplantation genetic screening (PGS) affect neurological, cognitive and behavioural development of 4-year-old children? SUMMARY ANSWER: PGS does not seem to affect neurological, cognitive and behavioural development of 4-year-old singletons; however, our data suggest that it may be associated with altered neurodevelopment in twins. WHAT IS KNOWN ALREADY: Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce. The present study provides information on neurodevelopmental, cognitive and behavioural outcome of 4-year-old PGS offspring. STUDY DESIGN, SIZE, DURATION: A prospective, assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS. PARTICIPANTS/MATERIALS, SETTING, METHODS: At 4 years, 49 children (31 singletons, 9 sets of twins) born following IVF with PGS and 64 children (42 singletons, 11 sets of twins) born following IVF without PGS (controls) were assessed (post-natal attrition 18%). Neurological development was evaluated with the standardized, age-specific and sensitive neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the rate of adverse neurological outcome. Primary outcome was the fluency score, as fluency of movements is easily reduced by subtle dysfunction of the brain. Cognitive development was evaluated with the Kaufman Assessment Battery for Children; behavioural development was evaluated with the Child Behavior Checklist. The effect of PGS was analysed with a mixed effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the intention to treat analysis, neurodevelopmental outcome of PGS children was similar to that of controls. However, additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons. The fluency score of singletons born following PGS was similar to that of control singletons [mean values, 95% confidence intervals (CIs): 12.2 (11.5;12.8) and 12.2 (11.6;12.8)], respectively, P = 0.977) that was also true for the other neurodevelopmental parameters. The fluency score of PGS twins was significantly lower than that of control twins [mean values, 95% CIs: 10.6 (9.8;11.3) and 12.3 (11.5;13.1)], respectively, P = 0.001); the same was true for the NOS. In addition, PGS in twins was associated with a higher sequential intelligence quotient score. On the other hand, other neurodevelopmental parameters were similar for PGS twins and control twins. Post hoc sample size calculation for the primary outcome parameter, the fluency score, indicated that the study groups, including the subgroups of singletons and twins, were adequately powered. LIMITATIONS, REASONS FOR CAUTION: We assessed singletons and twins who contributed to the generalizability of the study. A limitation of our study is the relative small size of our study groups and the selective dropout in both groups (dropouts PGS group: higher gestational age; control group: less well-educated parents). These preclude the conclusion that PGS per se is not associated with neurodevelopmental, cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins. WIDER IMPLICATIONS OF THE FINDINGS: The need for careful long-term monitoring of children born following embryo biopsy remains, as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome.

The impact of IVF/ICSI on parental well-being and anxiety 1 year after childbirth.

BACKGROUND: More couples are delaying childbirth resulting in an increase of age-related subfertility in women. Subfertility and assisted reproductive technology (ART) treatments may affect couples' psychological well-being. The aim of the present study was to investigate whether factors related to IVF/ICSI affect anxiety and mental health in couples 1 year after childbirth. METHOD: In this cohort study, we included couples with a singleton pregnancy following IVF/ICSI treatment (n=113) and subfertile couples who naturally conceived (NC; n=83). Parental trait anxiety (Dutch version of the Spielberger State-Trait Anxiety Inventory) and mental health (Dutch version of General Health Questionnaire) were assessed 1 year after childbirth. The influence of fertility-related factors was analyzed with logistic regression analyses. RESULTS: One hundred and ninety-six couples participated, 93% of those eligible. Trait anxiety and mental health were similar in IVF/ICSI and NC groups. However, NC fathers had more often mental health scores in the clinical range (21%) than fathers in the IVF/ICSI group (9%). The risk of having a trait anxiety or mental health score in the clinical range was reduced by the presence of one of the following factors: for females a higher number of IVF/ICSI treatment cycles, and a maternal cause of subfertility, for males having been treated by IVF/ICSI and a longer time to pregnancy. CONCLUSIONS: The present study indicates (i) that IVF/ICSI treatment is not associated with an increase in clinically relevant Spielberger State-Trait Anxiety Inventory and General Health Questionnaire scores in parents 1 year after childbirth and (ii) a higher number of IVF/ICSI treatment cycles and a longer time to pregnancy were associated with less trait anxiety and better mental health. A limitation of the study is the absence of mental health and trait anxiety data at baseline.

The Groningen ART cohort study: the effects of ovarian hyperstimulation and the IVF laboratory procedures on neurological condition at 2 years.

BACKGROUND: Up to 4% of children are born following assisted reproduction techniques (ART) yet relatively little is known on neurodevelopmental outcome of these children after 18 months of age. Only a limited number of long-term follow-up studies with adequate methodological quality have been reported. Our aim was to evaluate the effects of ovarian hyperstimulation, IVF laboratory procedures and a history of subfertility on neurological condition at 2 years. METHODS: Singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n = 66), modified natural cycle IVF (MNC-IVF, n = 56), natural conception in subfertile couples (Sub-NC, n = 87) and in fertile couples (reference group, n = 101) were assessed (using Hempel approach) by neurological examination at 2 years of age. This resulted in a neurological optimality score (NOS), a fluency score and the prevalence of minor neurological dysfunction (MND). Primary outcome was the fluency score, as fluency of movements is easily affected by subtle dysfunction of the nervous system. RESULTS: Fluency score, NOS and prevalence of MND were similar in COH-IVF, MNC-IVF and Sub-NC children. However, the fluency score (P < 0.01) and NOS (P < 0.001) of the three subfertile groups were higher, and the prevalence of MND was lower (P = 0.045), than those in the reference group. CONCLUSIONS: Neurological condition of 2 year olds born after ART is similar to that of children of subfertile couples conceived naturally. Moreover, subfertility does not seem to be associated with a worse neurological outcome. These findings are reassuring, but we have to keep in mind that subtle neurodevelopmental disorders may emerge as children grow older.

The prognostic value of amplitude integrated EEG in neonatal sepsis and/or meningitis.

AIM: To investigate the longitudinal course and prognostic value of amplitude integrated EEG (aEEG) in infants with neonatal sepsis or meningitis. METHODS: Amplitude integrated EEG recordings of 22 infants with sepsis/meningitis were retrospectively evaluated. Mean gestational age was 38 weeks (range: 34-42 weeks). Thirteen infants had meningitis. Survivors were seen for neurological follow-up. Four infants died, two were severely abnormal at 24 months. Amplitude integrated EEG background pattern, sleep wake cycling (SWC) and electrographic seizure activity (EA) were appraised. RESULTS: All infants with continuous low voltage or flat trace on aEEG (n = 4) had an adverse outcome. Low voltage aEEGs (n = 9) had a positive LR (LR+) for an adverse outcome of 5.3 (95% CI: 1.9-14.8) at 6 h and 8.3 (95% CI: 1.3-55) at 24 h after admission. EA was more frequent in infants with adverse outcome (p < 0.01) and had a LR+ for adverse outcome of 10.6 (95% CI: 1.5-76). SWC appeared more frequent in infants with good outcome (p < 0.05). CONCLUSION: Low voltage background pattern, SWC and EA on aEEG are helpful to predict neurological outcome in infants with neonatal sepsis or meningitis.

Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia.

BACKGROUND: Neonatal therapeutic hypothermia (TH) can ameliorate or prevent the development of dyskinetic cerebral palsy (CP) after hypoxic-ischemic encephalopathy (HIE). The Dyskinesia Impairment Scale (DIS) was recently launched to quantify dyskinetic (dystonic and choreatic) motor features in patients with CP. In TH treated children, who are at risk of developing dyskinetic CP, we aimed to determine DIS-scores at pre-school age. METHOD: In 21 Dutch pre-school children (3-6 years of age) who had received TH according to the Dutch-Flemish treatment protocol, we determined DIS-scores. We associated DIS-scores with 1. age-matched control values (Kuiper et al., 2018) [1], and 2. previously reported DIS-score range in dyskinetic CP (Monbaliu E et al., 2015). RESULTS: The motor phenotype was determined as: normal (n = 18/21), mildly impaired (reduced coordination (n = 2/21)) and abnormal (dyskinetic CP; n = 1/21). In absence of CP (n = 20/21), DIS-scores were lower (more favorable) than in dyskinetic CP, without any overlapping group scores (mean difference: 71 points; p < .05). However, the obtained DIS-scores were still higher than previously reported in healthy age-matched controls (mean difference: 14 points; p < .05). There was an association between DIS-scores and retrospective neonatal MRI (basal ganglia and thalamus injury on diffusion weighted imaging (DWI)) and (a)EEG parameters (p < .05). CONCLUSION: In the vast majority (95%) of Dutch TH-HIE treated pre-school children, the phenotypic motor outcome was favorable. However, DIS-scores were moderately increased compared with healthy age-matched controls. Future studies may elucidate the significance of moderately increased DIS-scores should to further extent.

Time to full enteral feeding after necrotizing enterocolitis in preterm-born children is related to neurodevelopment at 2-3 years of age.

BACKGROUND: Necrotizing enterocolitis (NEC) is associated with poorer neurodevelopment. It is, however, unclear which factors besides surgery affect neurodevelopment in preterm-born children surviving NEC. AIMS: We determined whether time to full enteral feeding (FEFt) and post-NEC complications after NEC were associated with neurodevelopment. STUDY DESIGN: Prospective observational cohort study. SUBJECTS: Two to three year old preterm-born children who survived NEC (Bells stage ≥ 2). We categorized children in two groups, one group shorter and equal and one group longer than the group's median FEFt. Post-NEC complications included recurrent NEC and/or post-NEC stricture. OUTCOME MEASURES: Bayley Scales of Infants and Toddler Development III (Bayley-III) and Child Behavior Checklist (CBCL). Associations between Bayley-III and CBCL scores with FEFt and Post-NEC complications were determined using linear regression analyses, adjusted for severity of illness and potential confounders. RESULTS: We included 44 children, median gestational age of 27.9 [IQR: 26.7-29.3] weeks, birth weight 1148 [IQR: 810-1461] grams. Median FEFt after NEC was 20 [IQR: 16-30] days. Median follow-up age was 25.7 [IQR: 24.8-33.5] months. FEFt > 20 days was associated with lower cognitive and lower motor composite scores of the Bayley-III (B: -8.6, 95% CI -16.7 to -0.4, and B: -9.0, 95% CI, -16.7 to -1.4). FEFt was not associated with CBCL scores. Post-NEC complications (n = 11) were not associated with Bayley-III scores nor with CBCL scores. CONCLUSIONS: Prolonged FEFt after NEC in preterm-born children surviving NEC is associated with lower cognitive and lower motor composite scores at the age of 2-3 years. These results show the importance of limiting the duration of the nil per mouth regimen if and when possible.

The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy.

BACKGROUND: Due to the growing number of children born following assisted reproduction technology, even subtle changes in the children's health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children. METHODS: In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development. RESULTS: The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups. CONCLUSIONS: We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

Necrotizing Enterocolitis Associated with Congenital Heart Disease: a Different Entity?

BACKGROUND: Necrotizing enterocolitis (NEC) predominantly occurs in preterm infants (PT-NEC). In term neonates, NEC occurs more frequently when a congenital heart disease is present (CHDNEC). Our aim was to evaluate differences and similarities in disease characteristics of PT-NEC versus CHD-NEC. METHODS: In this retrospective case-control study we identified all CHD infants who developed NEC Bell's stage ≥2 in our center from 2004 to 2014. We randomly selected (1:2 ratio) PT-NEC infants from the same period. Biochemical and clinical variables were retrieved from patient files. RESULTS: We found 18 CHD-NEC infants and selected 36 PT-NEC infants (gestational age 28.3 [25-35.6] weeks vs. 38.6 [31.7-40.7] weeks). Postnatal age at onset was significantly lower in CHD-NEC patients (4 [2-24] vs. 11 [4-41] days, p < 0.001). Lowest pH levels were lower (7.21 [7.01-7.47] vs. 7.27 [6.68-7.39], p = 0.02), and highest CRP levels were higher (112.5 mg/L [5.0-425.0] vs. 66.0 [5.2-189.0], p = 0.05) in PT-NEC vs. CHD-NEC. Anatomic localisation of the disease differed: the colon was significantly more often involved in CHD-NEC versus PT-NEC (86% vs. 33%, p = 0.03). Mortality caused by NEC was not different (22% vs. 11%, p = 0.47). CONCLUSION: While outcome of NEC in both groups is similar, the predominant NEC localisation differed between CHD-NEC and PT-NEC patients. This suggests that both variants of the disease have a different underlying pathophysiological mechanism that predisposes different intestinal regions to develop NEC. TYPE OF STUDY: Retrospective Case-Control Study. LEVEL OF EVIDENCE: Level III.

General movements in the first fourteen days of life in extremely low birth weight (ELBW) infants.

OBJECTIVE: To assess the quality of general movements (GMs) in the first fourteen days of life in relation to obstetric and postnatal risk factors and neurodevelopmental outcome in extremely low birth weight (ELBW) infants. STUDY DESIGN: The GMs of nineteen infants were assessed on days 2, 4, 6, 10 and 14 with Prechtl's method. Additionally, detailed GM assessment produced optimality scores (OSs). GMs and the OSs were related to obstetric and postnatal data and to neurodevelopmental outcome at 18 months. RESULTS: GMs and OSs fluctuated substantially during the first fourteen days of life. Most infants had abnormal GMs, especially poor repertoire (PR) GMs. No relation was found between GMs and obstetric factors. Regarding postnatal factors, septicaemia correlated to hypokinesia (H) and artificial ventilation correlated to a lower OS. CONCLUSIONS: Due to physiological disturbances the quality of GM in ELBW infants fluctuates substantially during the first fourteen days of life. Abnormal GMs, especially PR GMs, are mostly seen for the same reason. Septicaemia and artificial ventilation are associated with deterioration of the GMs (lower OSs), and in case of septicaemia also with hypokinesia.

Spinal hemorrhages are associated with early neonatal motor function loss in human spina bifida aperta.

BACKGROUND: In spina bifida aperta (SBA), leg movements caudal to the meningomyelocele are present in utero, but they disappear shortly after birth. It is unclear whether leg movements disappear by impact of the neuro-developmental malformation or by superimposed traumatic damage. If superimposed traumatic damage is involved, targeted fetal intervention could improve motor outcome. AIM: To characterize neuromuscular pathology in association with perinatal motor function loss in SBA. PATIENTS/METHODS: In fetal SBA (n=8; 16-40 weeks GA), the median time interval between ultrasound registrations of fetal motor behavior and post-mortem histology was 1 week. Histology was assessed cranial, at and caudal to the meningomyelocele and compared with findings in fetal controls (n=4). RESULTS: Despite fetal movements caudal to the meningomyelocele (5/6), histology indicated muscle fiber alterations (6/6) that concurred with neuro-developmental and traumatic spinal defects [Neuro-developmental defects: spinal ependymal denudation (3/8), reduced amount of (caspase3-negative) lower motor neurons (LMNs; 8/8), aberrant spinal vascularization (8/8). Traumatic defects: gliosis (7/8), acute/fresh spinal hemorrhages near LMNs (8/8)]. CONCLUSION: In all delivered SBA patients, recent spinal hemorrhages were superimposed upon pre-existing defects. If early therapeutic strategies can prevent these superimposed secondary spinal hemorrhages, motor outcome may improve.

Sucking and swallowing in infants and diagnostic tools.

Preterm infants often have difficulties in learning how to suckle from the breast or how to drink from a bottle. As yet, it is unclear whether this is part of their prematurity or whether it is caused by neurological problems. Is it possible to decide on the basis of how an infant learns to suckle or drink whether it needs help and if so, what kind of help? In addition, can any predictions be made regarding the relationship between these difficulties and later neurodevelopmental outcome? We searched the literature for recent insights into the development of sucking and the factors that play a role in acquiring this skill. Our aim was to find a diagnostic tool that focuses on the readiness for feeding or that provides guidelines for interventions. At the same time, we searched for studies on the relationship between early sucking behavior and developmental outcome. It appeared that there is a great need for a reliable, user-friendly and noninvasive diagnostic tool to study sucking in preterm and full-term infants.

Does early intervention in infants at high risk for a developmental motor disorder improve motor and cognitive development?

Infants at high risk for developmental motor disorders are in general referred to early intervention (EI) services. It is a matter of debate to which extent EI may facilitate outcome in various developmental domains. We reviewed the effects of EI programmes aiming at promoting motor and cognitive development. With respect to motor development the data indicated that EI prior to term age probably is most effective when it aims at mimicking the intrauterine environment; after term age general developmental programmes probably are most effective. Some evidence was provided that EI prior to term age has a beneficial effect on cognitive development regardless the type of intervention which is applied. After term age only general developmental programmes seemed to have an effect on cognitive development. The review concludes with preliminary data on the effect a new intervention programme, COPCA, applied between 3 and 6 months corrected age on developmental outcome till 18 months. The results indicated that COPCA was more beneficial for the development of sitting behaviour and cognition than traditional paediatric physiotherapy.

Screening infants with an isolated single umbilical artery for renal anomalies: nonsense?

BACKGROUND: Presently there is no consensus regarding the extent of workup required in newborns who present with an isolated single umbilical artery (SUA). Because of the association with silent renal anomalies, some studies advise to perform renal ultrasonography in infants born with an isolated SUA. AIMS: To decide whether screening (performing a renal ultrasound and in case of abnormalities on the ultrasound performing a micturating cystourethrogram) infants with an isolated SUA is justified by evaluating the prevalence of clinically relevant renal abnormalities. STUDY DESIGN: Retrospective descriptive study. SUBJECTS: Live-born infants with SUA detected by physical examination born between January 1st, 1997 and February 1st, 2005, in a tertiary care university hospital. OUTCOME MEASURES: Renal anomalies detected by renal ultrasonography and a micturating cystourethrogram in infants with abnormalities on renal ultrasound. RESULTS: We included 52 live-born infants with an isolated SUA. Renal ultrasonography was performed in 92.3% of these 52 infants. In this group, abnormalities were found in 5 infants (10.4 %) on renal ultrasound. A relative subpelvine stenosis was detected in 1 infant, the other abnormalities on renal ultrasound were mild hydronephrosis without further consequences. CONCLUSION: Our data suggest that it is not necessary to screen for renal anomalies in infants with a single umbilical artery without other anomalies seen at physical examination.

Pyridoxine induces non-specific EEG alterations in infants with therapy resistant seizures.

PURPOSE: In infants with frequent therapy resistant seizures (TRS-infants), clinical detection of pyridoxine-dependency (PD) or -responsiveness (PR) occurs by empirical intravenous (IV) pyridoxine administration during recording of the EEG. However, in undiagnosed TRS-infants it is still unclear to what extent EEG alterations by pyridoxine-IV are attributable to PD/PR or to non-specific responses. Before EEG alterations by pyridoxine-IV can be ascribed to PD/PR, these non-specific responses should be excluded first. METHODS: In 10 TRS-infants under 1 year of age, we determined the EEG effect by pyridoxine-IV on the EEG-recording. RESULTS: After pyridoxine-IV administration, our data indicate declined (10-15%; p<0.05) EEG-amplitudes and total power (magnitude/frequency-band) at frontal, central and centro-temporal electrodes. CONCLUSION: In TRS-infants, pyridoxine-IV affects EEG-amplitude and -total power in a non-specific way, which does not identify PD/PR.

[Use of SSRIs during pregnancy and possible consequences for the development of the child]. / SSRI-gebruik in de zwangerschap en de mogelijke gevolgen voor de ontwikkeling van het kind.

Infants of depressed mothers are at increased risk for developing cognitive and behavioural problems. Medication is often prescribed for pregnant women suffering from a major depression. Approximately 2% of Dutch pregnant women is using a selective serotonin reuptake inhibitor (SSRI). SSRIs cross the placenta easily. The consequences of prenatal exposure to SSRIs for the developing child remain to be determined. In the postnatal period, increased incidence of respiratory distress, feeding and digestive disturbances, irritability and convulsions, and admission to a neonatal intensive care unit have been described. Long-term effects have not yet been thoroughly examined in humans. Animal studies have shown permanent changes in specific parts of the brain and altered behaviour in adulthood after perinatal exposure to SSRIs. Research into motor and cognitive development at school age and adolescence in children prenatally exposed to SSRIs is urgently needed.