Cognitive assessment of very low birth weight infants using the Dutch version of the PARCA-R parent questionnaire.

OBJECTIVE: Very low birth weight (VLBW) infants are at an increased risk of long-term cognitive impairment. Early identification and timely interventions are important. We aimed to validate the Dutch version of the revised Parent Report of Children's Abilities (PARCA-R) questionnaire. METHODS: The subjects were survivors from the Belgian participating centers to the NIRTURE trial. As part of a study-related follow-up, PARCA-R was sent out at the age of 2 years. As part of a normal hospital follow-up, these infants were assessed by the Bayley Scales of Infant Development - second edition (BSID-II) at the age of 9, 18 and 36 months. MRI was performed at term in the group of VLBW infants of ZOL Genk as standard care. RESULTS: PARCA-R was sent out to 193 surviving infants. BSID-II was performed in 36% (n=70) at 9 months, in 30% (n=58) at 18 months and in 12% (n=23) at 36 months. MRI was available for 32 infants. We received 86 responses to the PARCA-R. Parent report composite (PRC) scores were significantly correlated with the Mental Development Index (MDI) (p<0.0001 (9 months); p=0.003 (18 months); p=0.01 (36 months)). PRC scores were significantly lower in those with an abnormal MRI (92 vs.124; p=0.04). CONCLUSION: We support the use of the PARCA-R as a time and cost efficient alternative for identifying cognitive delay. PRACTICE IMPLICATIONS: We suggest that the combination of BSID-II, MRI at term and PARCA-R would be the ideal testing method for identifying VLBW infants at risk for cognitive developmental delay by two years of age.

Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves' disease.

BACKGROUND: Fetal/neonatal hyperthyroidism is a well-known complication of maternal Graves' disease with high concentrations of TSH-receptor antibodies (TRAb). Few data are available on the management of fetal hyperthyroidism in surgically treated Graves' disease. METHODS: Clinical, ultrasound and biochemical data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10 years before and whose sibling was thin and hyperthyroid at birth. RESULTS: Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was treated through maternal antithyroid drug (ATD) administration; the dose was reduced gradually once fetal tachycardia and valve dysfunction disappeared and normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was maintained. The neonate showed normal growth for GA and T4 concentration at birth but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained strongly suppressed throughout the pre- and postnatal course. CONCLUSIONS: Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the severity or duration of the neonatal hyperthyroid flare.

Validation of the continuous glucose monitoring sensor in preterm infants.

OBJECTIVE: Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. DESIGN: Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. SETTING: An international multicentre randomised controlled trial. PATIENTS: One hundred and eighty-eight very low birth weight control infants. OUTCOME MEASURES: Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. RESULTS: The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. CONCLUSIONS: CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.

Maternal bariatric surgery: adverse outcomes in neonates.

BACKGROUND: The obesity epidemic in developed countries has led to an increased prevalence of obese women of reproductive age. As maternal obesity has far-reaching consequences for both mother and child, the consensus is that weight loss before pregnancy will reduce obesity-related morbidity and mortality. Therefore, an increasing number of women become pregnant after undergoing obesity surgery. RESULTS AND DISCUSSION: From the literature, data shows that perinatal outcome after bariatric surgery is generally considered as favourable for both mother and child. Only a few case reports highlight the possibility of side effects on the foetus and neonate. We report on five cases with severe intracranial bleeding, all possibly related to vitamin K deficiency following maternal bariatric surgery. CONCLUSION: These reports indicate that careful nutritional follow-up during pregnancy after obesity surgery is mandatory, because nutritional deficiencies such as vitamin K deficiency can lead to life-threatening bleeding.

High-resolution perineal ultrasound of a paraurethral cyst in a neonate (2008: 8b).

We present high-resolution ultrasonography of a paraurethral cyst, a rare cause of an interlabial mass in a newborn. Although not always performed in these cases, ultrasonographic evaluation is an easily performed examination in assessment of the final diagnosis and therapeutic decisions.

Both postnatal and postmenstrual age contribute to the interindividual variability in tramadol glucuronidation in neonates.

INTRODUCTION: Although of pharmacokinetic and -dynamic relevance, data on ontogeny of UDP-glucuronosyltransferase (UGT) activity in neonates are scant. We therefore wanted to assess the impact of both postnatal and postmenstrual age (PNA/PMA) on the interindividual variability of glucuronidation to overall tramadol urinary elimination in neonates. METHODS: O-demethyl tramadol (M1) and M1-glucuronide (M1G) were determined in 24 hour urine collections during continuous intravenous tramadol administration in neonates. Glucuronidation fraction (%) was calculated by the ratio of M1G to the sum of M1G and M1 free (M1total). Fractions (%) in early (

O-demethylation of tramadol in the first months of life.

OBJECTIVE: Assess in vivo O-demethylation activity in the first months of life. METHODS: Time-concentration profiles of tramadol (M) and O-demethyl tramadol (M1) in plasma and urine were simultaneously collected in the first 24 h of continuous intravenous tramadol administration in neonates and young infants. M and M1 were determined by high performance liquid chromatography. Correlations between perinatal characteristics [postnatal age (PNA), postmenstrual age (PMA)] and the contribution of metabolites (M, M1) to overall tramadol elimination and to the plasma and urine log M/M1 were calculated. RESULTS: Plasma samples were available in 20/29 and complete 24-h urine collections were available in 25/29 neonates (25-53 weeks PMA). Mean plasma log M/M1 value (>4 h, n=86) was 0.8 (SD 0.4). A significant correlation between plasma log M/M1 and PMA (r=-0.73, P<0.0001) and PNA (r=-0.58, P<0.005) was observed. In a multiple regression model, only PMA remained an independent variable. Mean urine log M/M1 was 0.94 (SD 0.7). Significant correlations of the urine log M/M1 ratio with PMA (r=-0.73, P<0.0001) and PNA (r=-0.56, P=0.0035) were observed. In a multiple regression model with the urine log M/M1 ratio as dependent variable, only PMA remained an independent variable. The maturational half-life of the log M/M1 ratio in early neonatal life in the age range evaluated is about 12-16 weeks without plateau. CONCLUSIONS: O-demethylation activity was already observed in early neonatal life. A significant correlation with PMA was documented, but PMA can only partially explain the observed variability in O-demethylation activity. Polymorphism therefore likely already contributes to the interindividual variability observed in neonates.

Ibuprofen and cerebral oxygenation and circulation.

The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.

Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin in preterm infants during the first days of life.

The aim of this study was to assess the effects of intravenous co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of life in preterm infants. The pharmacokinetics of amikacin were retrospectively calculated in a cohort of 73 neonates (gestational age <31 weeks) who received either ibuprofen-lysine or placebo following inclusion in the multicentre ibuprofen prophylaxis study. Assuming a one-compartment model with instantaneous input and first-order output, there was no significant difference in the median distribution volume (0.63 vs. 0.59 liters/kg), but the median serum half-life (16.4 vs. 12.4 h) of amikacin was significantly longer (p <0.02), and the clearance (0.36 vs. 0.6 ml/kg/min; p <0.005) of amikacin was significantly lower in infants who received ibuprofen-lysine. We conclude that the time interval between consecutive amikacin administrations should be prolonged, if ibuprofen-lysine is co-administered.

Continuous infusion of medications in very low birth weight infants.

OBJECTIVE: To develop a safe and accurate method for the administration in the neonatal intensive care unit of several potent medications as a continuous infusion without overloading the infant, especially the very low birth weight (VLBW) infant by diluents. METHOD: The method designed is based on a weight-adapted solution limiting the diluent administration and allowing for a versatile modulation of dose administration. As this method was initially designed for VLBW infants, the point of departure of this method is a standard maximal fluid load of 0.3 ml/h for each medication, delivered in a low compliant circuit with a high-precision syringe driver. Solutions are made for 24 h, which is a compromise between drug stability and repeated pressure drops in the circuit when changing the syringe and administration set. To translate a prescription into a solution a conversion factor is calculated. In addition to the calculation principle, this conversion factor is given for a number of commonly used drugs in neonatal care. CONCLUSIONS: In our experience, the method described adds to the safety and accuracy of continuous drug administration in neonatal care.

The use of methohexital during chest tube removal in neonates.

BACKGROUND: The aim of the study was the evaluation of the effect of methohexital during chest tube removal (CTR) in neonates. METHODS: Evaluation was based on the degree of sedation (grades 1-4) and relaxation (grades 1-4) and trends in vital signs heart rate, mean arterial blood pressure (MAP), oxygen saturation at time points (-10, -5, -3, -1, 0, 1, 3, 5, and 10 min) before and after administration of methohexital. A multidimensional pain scale [Leuven Neonatal Pain Scale (LNPS)] was used to evaluate pain expression. Effective sedation and relaxation (grade >2) would enable the physician to perform CTR without difficulties. Paired Wilcoxon was used to compare vital signs and pain expression before and after the procedure. RESULTS: Twenty-two procedures in 22 infants were recorded. Eleven infants were ventilated and 21 infants were having intravenous analgesics during CTR. Birth weight was 2645 g (range 1235-4500 g). Postnatal age was 6 days (range 1-80 days). Methohexital had no effect on ventilatory weaning, MAP or oxygen saturation. Heart rate increased from 144 (49) to 162 (43) (P = 0.012) b.min(-1). Sedation and relaxation were effective (>grade 2) and lasted for <5 min. No major side effects were documented. Adequate analgesia by LNPS was more difficult to evaluate as clinical pain evaluation was not feasible during full muscular relaxation. CONCLUSIONS: Administration of methohexital for CTR resulted in adequate sedation and relaxation without major side effects in neonates. This approach should be compared with other strategies.

Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age.

AIM: To investigate the pharmacokinetics and pharmacodynamics of single dose propacetamol in preterm and term infants on the first day of life. METHODS: Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41 weeks) infants received a single dose of propacetamol in the first 24 hours of life when they had minor, painful procedures or as additional treatment in infants receiving opioids. Blood samples were taken from an arterial line, and pain was evaluated by a multidimensional pain scale. Results were reported as mean (SD). Student's t and Wilcoxon tests were used to compare the groups. RESULTS: Thirty neonates were included, 10 of which were term infants. Serum half life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational age correlated with serum half life (r = -0.46). No effect of sex or administration of prenatal steroids was found on the pharmacokinetics of paracetamol. In neonates who only received propacetamol (n = 15), the level of analgesia seemed to be associated with the therapeutic (> 5 mg/l) level. CONCLUSIONS: A correlation was found between gestational age and the serum half life of propacetamol. The maturational trend of clearance and half life in preterm and term neonates is in line with data on the pharmacokinetics of propacetamol beyond the newborn period.

Methemoglobinemia and hemolysis after enteral administration of methylene blue in a preterm infant: relevance for pediatric surgeons.

A preterm infant had methaemoglobulinemia and hemolytic anemia after enteral administration of methylene blue. The dye was administered to exclude a tracheoesophageal fistula. Methylene blue is a noxious product, especially in neonates. It should be considered a potential cause of acquired methemoglobulinemia, even after enteral administration.

Cryotherapy for threshold retinopathy: perioperative management in a single center.

Perioperative management and complications during and after surgery were reviewed in a population of premature infants who received cryotherapy because of threshold retinopathy by retrospective analysis of medical, anaesthetic, and ophthalmologic files. Infants (n=31) who received cryotherapy between January 1, 1996 and January 1, 2001 and were treated during the neonatal period in the unit were included in the study. Cryotherapy was performed under general anesthesia on the neonatal ward. Neonatal and preoperative characteristics of this cohort point to a vulnerable group of infants with a preoperative weight of 1622 g (1519 to 1862 g), bronchopulmonary dysplasia criteria applying in 29 of 31 patients and methylxanthins prescribed in 26 of 31 patients. No single cryotherapy session had to be interrupted because of systemic complications. Still marked cardiorespiratory instability was documented until 36 hours postoperative in 8 patients. Performing surgical procedures on the neonatal ward is a feasible option. Perioperative management in infants who received cryotherapy is used as an illustration of this approach.

Incidence, perinatal risk factors, visual outcome and management of threshold retinopathy.

The incidence of threshold retinopathy, clinical characteristics and risk factors to develop threshold retinopathy are described in a group of preterm infants admitted between 1996 and 2000 in a single tertiary neonatal intensive care unit. A subset of these infants (n = 31) developed threshold retinopathy (ROP). Incidence of threshold ROP in survivors with a birth weight below 1500 g is 6.4%. Pre-, peri- and postnatal characteristics of these infants are described and compared with matched controls of the same gestational age (GA) and admitted in the same unit in an attempt to focus on relevant risk factors of threshold ROP. We also report on visual outcome data in infants who developed threshold retinopathy. Finally, we describe our experience with perioperative management in this cohort.

The value of fast MR imaging as an adjunct to ultrasound in prenatal diagnosis.

The aim of this study was to evaluate the role of MR imaging of the fetus to improve sonographic prenatal diagnosis of congenital anomalies. In 40 fetuses (not consecutive cases) with an abnormality diagnosed with ultrasound, additional MR imaging was performed. The basic sequence was a T2-weighted single-shot half Fourier (HASTE) technique. Head, neck, spinal, thoracic, urogenital, and abdominal fetal pathologies were found. This retrospective, observational study compared MR imaging findings with ultrasonographic findings regarding detection, topography, and etiology of the pathology. The MR findings were evaluated as superior, equal to, or inferior compared with US, in consent with the referring gynecologists. The role of these findings in relation to pregnancy management was studied and compared with postnatal follow-up in 30 of 40 babies. Fetal MRI technique was successful in 36 of 39 examinations and provided additional information in 21 of 40 fetuses (one twin pregnancy with two members to evaluate). More precise anatomy and location of fetal pathology (20 of 40 cases) and additional etiologic information (8 of 40 cases) were substantial advantages in cerebrospinal abnormalities [ventriculomegaly, encephalocele, vein of Galen malformation, callosal malformations, meningo(myelo)cele], in retroperitoneal abnormalities (lymphangioma, renal agenesis, multicystic renal dysplasia), and in neck/thoracic pathology [cervical cystic teratoma, congenital hernia diaphragmatica, congenital cystic adenomatoid lung malformation (CCAM)]. This improved parental counseling and pregnancy management in 15 pregnancies. In 3 cases, prenatal MRI findings did not correlate with prenatal ultrasonographic findings or neonatal diagnosis. The MRI provided a more detailed description and insight into fetal anatomy, pathology, and etiology in the vast majority of these selected cases. This improved prenatal parental counseling and postnatal therapeutic planning.