R.M. van Elburg

Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development

We describe the effect on the neonate of administration of rituximab to a woman with idiopathic thrombocytopenic purpura (ITP). Rituximab, an anti-CD20 antibody, was given weekly for 4 weeks to a woman with ITP in her third trimester of pregnancy. One month after the last rituximab administration a healthy girl was born. She had normal growth and development during the first six months. At birth, B-lymphocytes were not detectable. Rituximab levels in mother and neonate were 24000 and 6700 ng/mL, respectively. Only 7 cases of rituximab administration during pregnancy were described. No adverse events are described for fetus and neonate. We demonstrate that rituximab passes the placenta and inhibits neonatal B-lymphocyte development. However, after 6 months B-lymphocyte levels normalized and vaccination titres after 10 months were adequate. No infection-related complications occurred. Rituximab administration during pregnancy appears to be safe for the child but further studies are warranted.

Transplacental transport of IgG antibodies to preterm infants: A review of the literature

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17-22weeks of gestation to 50% at 28-32weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases. The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens. After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.

Implementation of a nation-wide automated auditory brainstem response hearing screening programme in neonatal intensive care units

Aim: As part of a future national neonatal hearing screening programme in the Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate, first stage success rate, pass/referral rates, rescreening compliance, diagnostic referral rates, age of first diagnostic evaluation and prevalence of congenital hearing loss (CHL). Methods: This prospective cohort study collected data on 2513 survivors. NICU graduates with one or more risk factors according to the Joint Committee on Infant Hearing were included in a two‐stage AABR hearing screening programme. Conventional ABR was used to establish a diagnosis of CHL. Results: A total of 2513 newborns enrolled in the programme with a median gestational age of 31.6 (range 24–43) wk and a median birthweight of 1450 (range 510–4820) g. In 25 (1%) cases parents refused screening. Four out of 2513 newborns were initially lost; 2484 newborns have been tested initially. A final 98% participation rate (2465/2513) was obtained for the whole programme. After a median postmenstrual age at the first test of 33.7 (range 27–54) wk, a pass rate of 2284/2484 (92%) resulted at the first stage. The rescreening compliance after the first test was 92% (184/200). A referral rate for diagnostic ABR of 3.1% (77/2484) resulted. Of the 77 referrals 14 (18.2%) had normal screening thresholds, 15 (19.5%) had unilateral CHL and 48 (62.3%) had bilateral CHL. The prevalence of unilateral CHL was 0.6% (15/2484) and of bilateral CHL 1.9% (48/2484).

The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants

Aim:  To determine the effect of neutral oligosaccharides [small‐chain galacto‐oligosaccharides/long‐chain fructo‐oligosaccharides (scGOS/lcFOS)] in combination with acidic oligosaccharides (pAOS) on stool viscosity, stool frequency and stool pH in preterm infants.

Effects of Glutamine on Brain Development in Very Preterm Children at School Age

OBJECTIVES: The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections. METHODS: Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts. RESULTS: Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group. CONCLUSIONS: Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.

Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation

Objective: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants. Design: Randomised controlled trial. Methods: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth. Results: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 − LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p  =  0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance. Conclusions: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

Intestinal microbiota in allergic and nonallergic 1-year-old very low birth weight infants after neonatal glutamine supplementation

Aim:  Previously, glutamine‐enriched enteral nutrition in very low birth weight infants (VLBW) decreased the incidence of atopic dermatitis at age 1 year. The aim of this study was to determine whether this effect is related to changes in intestinal bacterial species that are associated with allergy, such as bifidobacteria, clostridium histolyticum, clostridium lituseburense (Chis/lit group) and Escherichia coli at age 1 year.

The value of the D-xylose test compared with the differential sugar absorption test in recognizing coeliac disease

OBJECTIVE To compare the value of the differential sugar absorption test (SAT) with the blood and urine D-xylose tests (DXTs and DXTu) in diagnosing coeliac disease (CD) the SAT and the standard DXTs and DXTu were performed in 14 coeliacs with abnormal small bowel histology and in 12 patients with aspecific gastrointestinal complaints. METHODS In the SAT a solution of lactulose (L) and mannitol (M) was given to the fasting patient after which the L/M ratio was measured in 5 h urine by gas chromatography. In the DXTs and DXTu a solution of 25 g D-xylose was given to the fasting patient and blood was drawn at 0, 30 and 120 min and urine was collected for 5 h, respectively. RESULTS To measure the power in diagnosing CD of the SAT, DXTs 30 min, DXTs 120 min and DXTu, the test results were plotted in ROC curves and the areas under the curves (AUCs) were calculated. The AUCs were 0.97, 0.77, 0.78 and 0.63, respectively. CONCLUSION In our opinion, the DXTs and DXTu are no longer useful in the investigation of mucosal function of the small bowel.

A randomised trial of enteral glutamine supplementation for very preterm children showed no beneficial or adverse long-term neurodevelopmental outcomes

This study evaluated the long‐term effects of enteral glutamine supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm children at 13 years of age.

O-167 Beneficial Effects Of Short-chain Galacto – And Long-chain Fructo-oligosaccharides, Bifidobacterium Breve And Glutamine On Food Allergy-induced Behavioural Changes In Mice

Background and aims Recent studies reveal an important link between the intestinal immune system, microbiota, brain and behaviour. Previously we have shown that food allergy in male mice caused behavioural and neurochemical changes. This study aimed to investigate the effects of a dietary intervention with immunomodulatory short-chain galacto – and long-chain fructo-oligosaccharides (scGOS/lcFOS), Bifidobacterium breve (Bb) and glutamine (Gln) on behavioural impairments in food allergic mice. Methods Male C3H mice were fed a control, scGOS/lcFOS/Bb, Gln, or scGOS/lcFOS/Bb/Gln (comb) diet shortly after weaning and 2 weeks prior to first sensitisation with whey and cholera toxin (CT), or CT alone. Mice were sensitised for 5 weeks and subsequently orally challenged. Spontaneous alternation was examined in a T maze test 2 days after the last sensitisation and a social interaction test was conducted 1 day after oral challenge. Spontaneous alternation was used to measure exploratory behaviour and spatial memory. Results Supplementation with scGOS/lcFOS/Bb or Gln partially prevented reduced spontaneous alternation, whereas supplementation with scGOS/lcFOS/Bb/Gln completely normalised alternation. Both scGOS/lcFOS/Bb and Gln partially attenuated reduced social behaviour in food allergic mice. No additional effect of the combination was observed on social behaviour. Supplementation with scGOS/lcFOS/Bb and/or Gln did not reduce allergic sensitisation, measured by whey-specific immunoglobulins. Conclusions Supplementation with scGOS/lcFOS/Bb or Gln partially prevented food allergy-induced behavioural impairments and the combination normalised impaired alternation, without changing allergic sensitisation. Therefore, it is of interest to further investigate the effects of dietary supplementation with scGOS/lcFOS/Bb and Gln on immune-induced behavioural impairments in infants. Abstract O-167 Figure 1