Additional value of advanced neurosonography and magnetic resonance imaging in fetuses at risk for brain damage.

OBJECTIVE: To assess the additional value of fetal multiplanar (axial, coronal and sagittal) neurosonography and magnetic resonance imaging (MRI) to that of the standard axial ultrasound planes in diagnosing brain damage in fetuses at high risk. METHODS: This was a prospective, multicenter, observational study. Women were eligible for participation if their fetus was at risk for acquired brain anomalies. Risk factors were congenital infection, alloimmune thrombocytopenia, fetal growth restriction, trauma during pregnancy, fetal hydrops, monochorionic twins and prior ultrasound finding suggestive of an acquired brain anomaly. Examinations of the fetal brain before birth comprised axial ultrasound and advanced neurosonography biweekly and MRI once. After birth, neonatal cranial ultrasound was performed at < 24 h and at term-equivalent age. Neonatal brain MRI was performed once at term-equivalent age. An expert panel blinded to medical information, including imaging findings by the other methods, evaluated the presence of periventricular echogenicity (PVE) changes, peri- and intraventricular hemorrhage (IVH) and changes in basal ganglia and/or thalami echogenicity (BGTE) on ultrasound, and the equivalent signal intensity (SI) changes on MRI. Conclusions on imaging findings were generated by consensus. The children were followed up with examinations for psychomotor development at 1 year of age, using the Touwen examination and Alberta Infant Motor Scale, and at 2 years of age using Bayley Scale of Infant Development-III (BSID-III) and behavioral, sensory profile and linguistic questionnaires; scores > 1 SD below the mean were considered suspicious for neurodevelopmental sequelae. RESULTS: Fifty-six fetuses were examined, and in 39/56 fetuses, all fetal-imaging modalities were available. PVE/SI changes were observed in 6/39, 21/39 and 2/39 fetuses on axial ultrasound planes, multiplanar neurosonography and MRI, respectively. IVH was found in 3/39, 11/39 and 1/39 fetuses, and BGTE/SI changes in 0/39, 12/39 and 0/39 fetuses, respectively. Outcome was suspicious for neurodevelopmental sequelae in 13/46 infants at 1 year, and at 2 years, 41/41 children had scores within 1 SD of the mean on BSID-III and 20 had scores > 1 SD below the mean on the behavioral (5/38), sensory profile (17/37) and/or linguistic (6/39) questionnaires. CONCLUSIONS: In this cohort of fetuses at risk for brain damage, the severity of acquired brain anomalies was limited. Nevertheless, multiplanar neurosonography detected more fetal PVE changes, IVH and/or BGTE changes compared to the standard axial ultrasound planes and MRI. Fetal MRI did not demonstrate any anomalies that were not seen on neurosonography. Neurodevelopmental outcome at 2 years of age showed no or mild impairment in most cases. © 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Neurodevelopmental outcome at 2 years of age in preterm infants with late-onset sepsis.

Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. This prospective cohort study aims to establish the effect of sepsis after 72 h of life on cognitive, psychomotor, and language development of preterm infants (below 32 weeks gestational age and/or below 1500 g). At 2 years corrected age, neurodevelopmental outcome was tested using Bayley's Scales of Infant Development-II, Lexilijst (lexical development questionnaire), and behavior checklists. Of 117 patients included, 85 experienced blood culture-proven infection. Coagulase-negative staphylococci were responsible for 55% of the episodes. No significant differences were found in cognitive, motor, and behavioral scores or lexiquotient comparing patients with versus no proven infection. When comparing three groups (coagulase-negative staphylococci, other, and negative blood culture), a significant difference was found in composite cognitive scores (p = 0.016), in favor of the coagulase-negative staphylococci group versus other causal agent group (p = 0.007). No significant differences were found in other subscales.Conclusion: In this cohort, no differences were found in neurodevelopmental outcome at 2 years corrected age between proven and no proven infection groups; confirmation in larger cohorts with a control group is needed. Patients encountering coagulase-negative staphylococci sepsis showed a significant better cognitive outcome compared to other causal agents. What is Known: • Late-onset sepsis is associated with impaired neurodevelopmental outcome in preterm infants. What is New: • Preterm infants encountering late-onset sepsis by coagulase-negative staphylococci show a better cognitive outcome in comparison to other causal infectious agents in this cohort. • No differences were found in neurodevelopment at 2 years of age in preterm infants with suspected lateonset sepsis, between proven and no proven infection groups. Confirmation is needed in larger cohorts with a substantial control group.

Placental Histology After Minor Trauma in Pregnancy: A Pilot Study.

OBJECTIVE: Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. METHODS: A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks' gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. PRINCIPAL RESULTS: Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P = .024. Neurological follow-up was normal. CONCLUSIONS: In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year.

Neurobehavioural outcome in 6-18 year old children after trauma in pregnancy: Case-control study.

BACKGROUND: Maternal trauma complicates pregnancy in approximately 7%. Long-term development of children exposed to maternal trauma is unknown. AIM: To determine neurobehavioural outcome of children (6-18 years) born after maternal trauma in pregnancy compared to a matched control group. STUDY DESIGN: Case-control study performed at a tertiary medical centre. SUBJECTS: All consecutive children born after maternal hospitalization for trauma during pregnancy between 1995 and 2005. Controls were children born at the same hospital and period after an uneventful pregnancy. OUTCOME MEASURES: Trauma type and severity (Injury Severity Score, ≥9: severe); information from medical files at admission (cases). All mothers filled out two questionnaires about the infant; 1. concerning health, motor development and educational level, 2. concerning behavioural development through the validated Dutch version of the Child Behavior Checklist (CBCL). RESULTS: Questionnaires were returned by 34 cases and 28 controls. The traumas concerned mainly motor vehicle accidents and falls, and 3/34 had severe injuries. No differences in health, motor development, educational level and CBCL was found between the cases and controls, except for more hospitalization in the cases (p = 0.009). CONCLUSION: Long-term follow-up of a limited population of children 6-18 years after exposure of mainly non-severe trauma before birth is similar to a control population except for unexplained more hospitalization in the cases.

Trauma in pregnancy, obstetrical outcome in a tertiary centre in the Netherlands.

PURPOSE: To determine obstetrical outcome and predictive value of obstetrical symptoms and diagnostic examinations on adverse outcome after maternal trauma in pregnancy. MATERIALS AND METHODS: Retrospective study in a Dutch tertiary medical center, including women admitted for trauma in pregnancy between 1995 and 2005 and infants born from these pregnancies. Characteristics at trauma (type of trauma, severity) and obstetrical outcome were recorded, as well as prevalence and severity of trauma; prevalence of obstetrical symptoms and abnormal diagnostic examinations. Composite adverse obstetrical outcome was defined as fetal death, placental abruption, birth <37 weeks and/or birth weight <10th percentile. The predictive value of obstetrical symptoms or abnormal diagnostic tests on an adverse pregnancy outcome was analyzed (logistic regression analysis). RESULTS: Trauma admissions occurred in 10 per 1000 deliveries. Injuries were non-severe in 147/159 (92%). Obstetrical symptoms and/or abnormal diagnostic tests were present in 64/159 (40%) and 12/159 (8%) respectively. Adverse pregnancy outcome was encountered in 17/80 cases, mainly preterm births (13/80 (16%)). Severe injuries were predictive for an adverse pregnancy outcome. CONCLUSIONS: We found a considerable rate of trauma during pregnancy. There was an increased risk for preterm birth and severity of injuries was predictive for adverse outcome.

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia.

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.

Cerebral ultrasound abnormalities in preterm infants caused by late-onset sepsis.

INTRODUCTION: This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams. METHODS: The prospective study ("INFANT study") included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities. RESULTS: Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found. CONCLUSION: No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.

Comparison of psychomotor outcome in patients with perinatal asphyxia with versus without therapeutic hypothermia at 4 years using the Ages and Stages Questionnaire screening tool.

INTRODUCTION: Therapeutic hypothermia improves outcome after perinatal asphyxia. The Ages and Stages Questionnaire is a screening tool to detect neurodevelopmental delay. In this study we examined the outcome of patients with perinatal asphyxia (defined as Apgar score <5 at 10 min, or continued need for resuscitation, or pH < 7.00 in umbilical cord or within one hour after birth) with and without therapeutic hypothermia treatment at the age of four years. METHODS: Cohort study of patients with perinatal asphyxia admitted to the Neonatal Intensive Care Units of the VU University Medical Center, Amsterdam and the Wilhelmina Children's Hospital, Utrecht in the year 2008. Parents were asked to fill out the 48 months Ages and Stages Questionnaire (ASQ). In Wilhelmina Children's Hospital treatment with therapeutic hypothermia was implemented in 2008, in the VU University Medical Center in 2009, providing a historical cohort. RESULTS/DISCUSSION: Twenty-three questionnaires were evaluated. Response rate of questionnaires for the VU Medical Center was 63% (n = 10) and Wilhelmina's Childrens Hospital 93% (n = 13). No significant differences were found in the mean scores between both groups. However, the untreated group scored more frequently under the -2 SD threshold. In the fine motor skills domain the difference was statistically significant (p = 0.031). In the treated group no patients developed cerebral palsy and in the untreated group two patients developed cerebral palsy. CONCLUSION: In this study patients treated with hypothermia tend to have a better neurodevelopmental outcome. No significant differences were found between the two groups, apart from the fine motor skills.

[Dumping syndrome in a child with an incorrectly positioned gastrostomy catheter]. / Dumpingsyndroom bij een kind met een verkeerd gelegen gastrostomiekatheter.

A 13-month-old girl experienced an epileptic fit due to hypoglycaemia. She was born with a posterolateral diaphragm defect and at the age of 1.5 months had undergone a Nissen fundoplication with which a gastrostomy was also performed. The tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, the patient made a good recovery. Dumping syndrome is usually the result of a quicker gastric emptying time or a smaller gastric capacity, and in children it is mostly due to a Nissen fundoplication. In patients fed by tube who exhibit symptoms of dumping syndrome, the position of the feeding tube must be checked before other diagnostic or therapeutic steps are undertaken.