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Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.~Background~Background~In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.~Methods/design~Methods~Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.~Discussion~Conclusions~Current Controlled Trials ISRCTN16211826.~Trial Registration~Background [ABSTRACT FROM AUTHOR]

Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome., Methods: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death., Results: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g., Conclusions: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome., Trial Registration: Controlled-Trials.com ISRCTN74465643.

The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections. We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides (SC GOS/LC FOS/AOS). We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation. Therefore, we aimed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation, as measured by fecal IL-8 (f-IL-8) and calprotectin (f-calprotectin), in preterm infants. In a randomized controlled trial, infants with a GA <32 wk and/or birth weight <1,500 g received enteral supplementation of prebiotics or placebo (maltodextrin) between d 3 and 30 of life. F-IL-8 and f-calprotectin was assessed at baseline, d 7, 14, and 30 of life. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different in the SC GOS/LC FOS/AOS (n = 55) and the placebo group (n = 58). Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin. F-IL-8 and f-calprotectin were strongly correlated at all time points (p < 0.001). In conclusion, enteral supplementation of prebiotics (SC GOS/LC FOS/AOS) does not affect f-IL-8 and f-calprotectin levels in preterm infants.

Preterm infants have an impaired gut barrier function. We aimed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides (short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides (LCFOS)) and acidic oligosaccharides (AOS) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life. Furthermore, we determined host- and treatment-related factors associated with intestinal permeability. In a randomised controlled trial, preterm infants with a gestational age < 32 weeks and/or birth weight (BW) < 1500 g received enteral supplementation of SCGOS/LCFOS/AOS or placebo (maltodextrin) between days 3 and 30 of life. Intestinal permeability, reflected by the urinary lactulose/mannitol (L/M) ratio after oral ingestion of lactulose and mannitol, was assessed at three time points: before the start of the study (t = 0), at day 4 (t = 1) and at day 7 (t = 2) of life. Data were analysed by generalised estimating equations. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS (n 55) and the placebo groups (n 58). SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2. In both the groups, the L/M ratio decreased from t = 0 to t = 2 (P < 0·001). Low BW increased the L/M ratio (P = 0·002). Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio (P < 0·001 and P < 0·05, respectively). In conclusion, enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life.

Background: Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract., Objective: The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants., Design: In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period., Results: In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively)., Conclusions: Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic heterogeneous autosomal recessive disorder. We report two siblings with FHLH caused by a PRF1 mutation. The first child died in utero with hydrops fetalis and the second presented soon after birth with fatal multiple organ failure. Post-mortem DNA analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in both cases, with their non-consanguineous parents being heterozygous for the same mutation. Review of the literature shows that perinatal presentation of FHLH is rare. Diagnosis is difficult because in most cases histologic examination reveals no hemophagocytosis and the disease is rapidly fatal. The association between hydrops fetalis and FHLH has been reported in four previous reports. We present the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH should be included in the differential diagnosis of non-immune hydrops fetalis and neonatal multiple organ failure.

In contrast with clinical studies in term infants or older children, it is very difficult to investigate possible immunoregulatory effects of a novel infant formula composition in preterm infants. This is mainly because of the multicausal origin of infections in this high-risk population that is usually admitted to the neonatal intensive care unit. Possible effects of nutrition composition on onset and incidence of nosocomial infections in these very small infants have to be compared with infections that may have originated in utero. The development of the gastrointestinal tract may be inhibited after severe intrauterine growth retardation, leading to functional impairment of the gut shortly after birth. This may be related to the onset of necrotizing enterocolitis of the newborn. However, this disease in very small preterm infants is possibly also related to the initiation of oral feeding and/or the amount of feeding. Specific infection risks of neonatal intensive care as a result of invasive techniques such as artificial ventilation or total parenteral nutrition using indwelling umbilical and/or Silastic lines and so-called "all-in-one" mixtures may influence the incidence of infections. Widespread use of intravenous antibiotics in the neonatal intensive care unit may create an even larger infection risk. Investigation of possible immunomodulatory effects of factors such as prebiotics and probiotics added to the nutrition of preterm infants should always be considered along with other nutritional factors known to influence the immature immune system.

Objectives: To examine the characteristics of incident reporting systems in neonatal intensive care units (NICUs) in relation to type, aetiology, outcome and preventability of incidents., Methods: Systematic review., Search Strategy: Medline, Embase, Cochrane Library. Included: relevant systematic reviews, randomised controlled trials, observational studies and qualitative research. Excluded: non-systematic reviews, expert opinions, case reports and letters., Participants: hospital units supplying neonatal intensive care., Intervention: none., Outcome: characteristics of incident reporting systems; type, aetiology, outcome and preventability of incidents., Results: No relevant systematic reviews or randomised controlled trials were found. Eight prospective and two retrospective studies were included. Overall, medication incidents were most frequently reported. Available data in the NICU showed that the total error rate was much higher in studies using voluntary reporting than in a study using mandatory reporting. Multi-institutional reporting identified rare but important errors. A substantial number of incidents were potentially harmful. When a system approach was used, many contributing factors were identified. Information about the impact of system changes on patient safety was scarce., Conclusions: Multi-institutional, voluntary, non-punitive, system based incident reporting is likely to generate valuable information on type, aetiology, outcome and preventability of incidents in the NICU. However, the beneficial effects of incident reporting systems and consecutive system changes on patient safety are difficult to assess from the available evidence and therefore remain to be investigated.

Several studies have described reduced plasma concentrations of arginine, the substrate for nitric oxide synthase (NOS) in infants with necrotizing enterocolitis (NEC). No information on the plasma concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) in patients with NEC is currently available. We investigated whether plasma concentrations of arginine, ADMA, and their ratio differ between premature infants with and without NEC, and between survivors and non-survivors within the NEC group. In a prospective case-control study, arginine and ADMA concentrations were measured in ten premature infants with NEC (median gestational age 193 d, birth weight 968 g), and ten matched control infants (median gestational age 201 d, birth weight 1102 g), who were admitted to the Neonatal Intensive Care Unit. In the premature infants with NEC, median arginine and ADMA concentrations (micromol/l), and the arginine:ADMA ratio were lower compared to the infants without NEC: 21.4 v. 55.9, P= 0.001; 0.59 v. 0.85, P=0.009 and 36.6 v. 72.3, P=0.023 respectively. In the NEC group, median arginine (micromol/l) and the arginine:ADMA ratio were lower in non-surviving infants than in surviving infants: 14.7 v. 33.8, P=0.01 and 32.0 v. 47.5, P=0.038 respectively. In premature infants with NEC not only the NOS substrate arginine, but also the endogenous NOS inhibitor ADMA and the arginine:ADMA ratio were lower than in infants without NEC. In addition, low arginine and arginine:ADMA were associated with mortality in infants with NEC. Overall, these data suggest that a diminished nitric oxide production may be involved in the pathophysiology of NEC, but this needs further investigation.

Background: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life., Objective: The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants., Design: In a double-blind randomized controlled trial, VLBW infants (gestational age <32 wk or birth weight <1500 g) were allocated to receive enteral glutamine supplementation (0.3 g . kg(-1) . d(-1)) or isonitrogenous control supplementation (alanine) between days 3 and 30 of life. The supplementations were added to breast milk or to preterm formula. The primary endpoint for the study was time to full enteral feeding. Secondary endpoints were other variables of feeding tolerance, infectious morbidity, and short-term outcome., Results: Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented (n = 52) and the control (n = 50) groups. The median time to full enteral feeding was 13 d (range: 7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the glutamine-supplemented group, 26 of 52 infants (50%) had >/=1 serious infection compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term outcome were not significantly different between groups., Conclusions: Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants. However, infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition.

Background: Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response., Methods: VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume >/= 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.

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.

Objective: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates., Study Design: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol., Results: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05)., Conclusions: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants.

Our goal for this study was to determine whether the maturation of fat absorption in neonatal life is functionally related to an increased ability to hydrolyze dietary fat, to absorb long-chain fatty acids, or to do both. In 16 preterm and in eight term neonates, the intestinal ability to hydrolyze triacylglycerols and the capacity to absorb long-chain fatty acids were determined at several times between birth and 5 mo after the term age. These processes were compared with the percentage of fat absorption (formula-fed infants) or with fecal fat excretion (breast-fed infants). The functional capacity to digest triacylglycerols and to absorb the lipolytic products was evaluated by measuring serum concentrations of the lipolytic product [1-(13)C]palmitate after the enteral administration of tri-1-(13)C palmitoyl-glycerol. Long-chain fatty acids absorption (i.e. independent of lipolysis) was determined by measuring serum concentrations of [1-(13)C]stearate after its enteral administration. The efficacy of fat absorption increased in preterm infants (formula-fed) from 91.2 +/- 1.1% (mean +/- SEM) at 32.3 wk postconceptional age (PCA) to 97.3 +/- 0.6% at 53.6 wk PCA (p < 0.001), and in term infants from 91.7 +/- 1.8% (40.0 wk PCA) to 97.4 +/- 1.3% (58.9 wk PCA, p = 0.07). Both the serum concentration of [1-(13)C]stearate and that of [1-(13)C]palmitate appeared highly correlated with the efficacy of fat absorption (r = 0.82, p = 0.02; and r = 0.91, p = 0.004; respectively) and with PCA (r = 0.99, p < 0.001; and r = 0.85, p < 0.02; respectively). These results indicate that the functional development of fat absorption in preterm and term infants is related to the capacity to absorb long-chain fatty acids from the intestine.

Minor neurological dysfunction (MND) and quality of movement were studied in relation to neonatal cerebral damage and developmental assessments at 3 1/2 years of age in 66 very low-birthweight children without obvious disability. MND was found in 19 children and was significantly related to the quality of movement. The results demonstrate that MND is associated with neonatal cerebral damage at preschool-age, but that the assessment of quality of movement is associated with more complex sensory motor tasks and simultaneous processing. At preschool-age, quality of movement might therefore be a better marker of later learning problems than traditional signs of minor neurological dysfunction.

During in vitro fertilization, 22 human embryos were exposed to hepatitis B virus (HBV) in contaminated human serum present in the culture medium. All mothers experienced hepatitis B during the first trimester of pregnancy, and two had hepatitis B surface antigen and HBV DNA, as determined by PCR, at the time of delivery. No HBV DNA was found in serum or lymphocytes from the exposed 22 infants. HBV DNA was also absent from one infant at autopsy.

Parent and clinician reports of behaviour problems among very low-birthweight (VLBW) children at 3 1/2 years of age were studied in relation to indicators of neonatal cerebral damage, cognition and social factors. VLBW children had more depressed behaviour and more internalizing problems by parent report, and also scored significantly more often within the clinical range on total problem scores, than children in the comparison group. Neither neonatal cerebral ultrasound nor neurological examinations were directly associated with behavioural outcome. Cerebral damage was related to cognitive development. Cognition directly influenced behaviour problems according to clinician report, while the home environment did so according to parent report. The authors suggest that depressed behaviour of preschool VLBW children might be associated with parental reactions to the birth of a VLBW child, and that their attention problems might be linked indirectly to brain damage via cognitive impairments.

Tumor necrosis factor-alpha, IL-1 beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the study. TNF alpha plasma levels proved to be increased in the newborns with sepsis up to 560 +/- 234 pg/mL (ng/L) versus 36 +/- 4 pg/mL (ng/L) in the control group (p < 0.005), whereas IL-6 plasma levels in newborns with sepsis were 79.700 +/- 37.500 pg/mL (ng/L) versus 55 +/- 28 pg/mL (ng/L) in the control group (p < 0.01). The IL-1 beta plasma levels were only slightly elevated in the group newborns with sepsis [up to 18 +/- 5 pg/mL (ng/L) versus 7 +/- 1 pg/mL (ng/L) in the control group (p < 0.01)]. After the start of therapy with antibiotics, both TNF alpha and IL-6 plasma levels decreased concomitantly with the improvement of the clinical situation within 2 d. These data confirm the abundant presence of TNF alpha and IL-6 during neonatal sepsis, whereas IL-1 beta appeared to be present in small amounts only. Nevertheless, the IL-1 beta but not the TNF alpha plasma level appeared to correlate inversely with the decrease in diastolic tension as standardized according to birth weight (R = 0.66, p = 0.04). TNF alpha, IL-1 beta, and IL-6 were not correlated with any febrile response in the group with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence and type of cerebral lesions in 159 infants born before 30 weeks gestation were studied, using ultrasound. Indomethacin was given as part of tocolytic management to mothers with a high incidence of early rupture of membranes and preterm labour; and 76 fetuses were exposed to the drug as a result. For the remaining 83 pregnancies, in which there was a high incidence of chronic fetal distress and in utero hypoxia, tocolysis was either not started or limited to fenoterol. The neonatal course was similar for both groups of infants, except that patent ductus arteriosus was less commonly diagnosed in the 76 infants exposed to indomethacin. However, the incidence of periventricular leukomalacia was increased among infants exposed to any tocolytic agent; and cystic lesions occurred more commonly in those exposed to indomethacin.

The acuity card procedure was used to assess the visual acuity of 510 neurologically normal and abnormal infants and children. Acuity estimates were obtained for 93 per cent of 842 binocular and 279 monocular tests. The observed development of binocular acuity of normal fullterm and preterm infants agreed well with previous reports using the traditional forced-choice preferential looking technique. Monocular tests seemed to support earlier suggestions that grating acuity may be relatively insensitive to strabismic amblyopia. Infants at risk of later neurological deficits but developing normally had only a slight delay in development of acuity, but there was a high incidence of acuity deficits (54 per cent) among those with severe neurological defects. The great majority of a group of multiply handicapped children had low acuity for age. Repeat tests showed a high degree of test-retest consistency. The acuity card procedure was a successful and useful method for assessing the acuity of infants and children who cannot be tested with standard ophthalmological methods.