Win Tin

Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation

AIM To determine whether differing policies with regard to the control of oxygen saturation have any impact on the number of babies who develop retinopathy of prematurity and the number surviving with or without signs of cerebral palsy at one year. METHODS An examination of the case notes of all the 295 babies who survived infancy after delivery before 28 weeks gestation in the north of England in 1990–1994. RESULTS Babies given enough supplemental oxygen to maintain an oxygen saturation of 88–98%, as measured by pulse oximetry, for at least the first 8 weeks of life developed retinopathy of prematurity severe enough to be treated with cryotherapy four times as often as babies only given enough oxygen to maintain an oxygen saturation of 70–90% (27.2%v 6.2%). Surviving babies were also ventilated longer (31.4 v 13.9 days), more likely to be in oxygen at a postmenstrual age of 36 weeks (46%v 18 %), and more likely to have a weight below the third centile at discharge (45% v17%). There was no difference in the proportion who survived infancy (53% v 52%) or who later developed cerebral palsy (17% v 15%). The lowest incidence of retinopathy in the study was associated with a policy that made little use of arterial lines. CONCLUSIONS Attempts to keep oxygen saturation at a normal “physiological” level may do more harm than good in babies of less than 28 weeks gestation.

Survival Without Disability to Age 5 Years After Neonatal Caffeine Therapy for Apnea of Prematurity

CONTEXT Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. OBJECTIVE To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. DESIGN, SETTING, AND PARTICIPANTS Five-year follow-up from 2005 to 2011 in 31 of 35 academic hospitals in Canada, Australia, Europe, and Israel, where 1932 of 2006 participants (96.3%) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004. A total of 1640 children (84.9%) with birth weights of 500 to 1250 g had adequate data for the main outcome at 5 years. MAIN OUTCOME MEASURES Combined outcome of death or survival to 5 years with 1 or more of motor impairment (defined as a Gross Motor Function Classification System level of 3 to 5), cognitive impairment (defined as a Full Scale IQ<70), behavior problems, poor general health, deafness, and blindness. RESULTS The combined outcome of death or disability was not significantly different for the 833 children assigned to caffeine from that for the 807 children assigned to placebo (21.1% vs 24.8%; odds ratio adjusted for center, 0.82; 95% CI, 0.65-1.03; P = .09). The rates of death, motor impairment, behavior problems, poor general health, deafness, and blindness did not differ significantly between the 2 groups. The incidence of cognitive impairment was lower at 5 years than at 18 months and similar in the 2 groups (4.9% vs 5.1%; odds ratio adjusted for center, 0.97; 95% CI, 0.61-1.55; P = .89). CONCLUSION Neonatal caffeine therapy was no longer associated with a significantly improved rate of survival without disability in children with very low birth weights who were assessed at 5 years.

Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty

AIM To determine whether those most easily reviewed in a population prevalence study differ from those followed up only with difficulty. METHODS All babies born before 32 weeks of gestation in the North of England in 1983, 1990, and 1991 were traced, and all the survivors assessed at two years by one of two independent clinicians. RESULTS 818 of the 1138 live born babies survived to discharge. There was some non-significant, excess disability in the 5% of long term survivors who were difficult to trace because of social mobility, but eight times as much severe disability in the 1% (9/796) in care and in the 5% (38/796) whose parents initially failed to keep a series of home or hospital appointments for interview, and five times as much emergent disability in the 2.7% (22/818) who died after discharge but before their second birthday. Had the babies who were seen without difficulty been considered representative of all the babies surviving to discharge, the reported disability rate would have been two thirds what it really was (6.9% instead of 11.0%). CONCLUSIONS Population prevalence studies that ignore those who seem reluctant to cooperate risk serious ascertainment bias. Key messages Children seen for review without difficulty in any study of community prevalence are seldom representative of those who are not assessed Failure to review those who prove difficult to trace introduces less bias than failure to review those who prove difficult to review once traced Studies where it is not possible to see some children for assessment might usefully include a calculation of what the total prevalence would be if there was a fivefold difference in the proportion with the condition in question among the children who were not seen Parental support for any such study can nearly always be obtained if an effort is made to make the family feel, from the outset, that they are partners in a collaborative exercise of genuine worth

Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups

OBJECTIVE To determine whether the benefits of caffeine vary in three subgroups of 2006 participants in the Caffeine for Apnea of Prematurity (CAP) trial. STUDY DESIGN Post-hoc subgroup analyses were performed on the basis of: (1) indication for commencement of study drug: treat apnea, prevent apnea, or facilitate extubation; (2) positive pressure ventilation (PPV) at randomization: endotracheal tube (ETT), noninvasive ventilation, or none; and (3) timing of commencement of study drug: early or late (< or =3 versus >3 days). Outcomes assessed were those showing treatment effects in the original analyses. We investigated the consistency of caffeine effects by using regression models that incorporated treatment/subgroup factor interactions. RESULTS There was little evidence of a differential treatment effect of caffeine in subgroups defined by the clinical indication for starting study drug. The size and direction of the caffeine effect on death or disability differed depending on PPV at randomization (P = .03). Odds ratios (95% CI) were: no support, 1.32 (0.81-2.14); noninvasive support, 0.73 (0.52-1.03); and ETT, 0.73 (0.57-0.94). Adjustment for baseline factors strengthened this effect (P = .02). Starting caffeine early resulted in larger reductions in days of respiratory support. Postmenstrual age at time of discontinuing PPV was shorter with earlier treatment (P = .01). Mean differences (95% CI) were: early, 1.35 weeks (0.90-1.81); and late 0.55 weeks (-0.11-0.99). Adjustment for baseline factors weakened this effect (P = .03). CONCLUSIONS There is evidence of variable beneficial effects of caffeine. Infants receiving respiratory support appeared to derive more neurodevelopmental benefits from caffeine than infants not receiving support. Earlier initiation of caffeine may be associated with a greater reduction in time on ventilation.

Risk factors for strabismus in children born before 32 weeks’ gestation

AIM To investigate risk factors associated with strabismus in children born prematurely. METHODS Prospective study of all children born before 32 weeks’ gestation between 1 January 1990 and 31 December 1991 in a geographically defined population of approximately 3 million in the Northern Region of the United Kingdom. All children were examined aged 2 years by the same ophthalmologist and paediatrician. RESULTS 558 children (98.6% of study group) were examined. Logistic regression showed an increased risk of strabismus in children with cicatricial retinopathy of prematurity (p=0.02), refractive error (p=0.003), family history of strabismus (p<0.0001), and poor neurodevelopmental outcome (p<0.0001), in particular impaired locomotor skills (p=0.008) and hand-eye coordination (p=0.001). Gestational age and regressed acute ROP were not independent risk factors for strabismus (p=0.92 and 0.85 respectively). CONCLUSIONS This study has identified factors which are independently related to strabismus (although not necessarily causative) and others which are related only indirectly. This may contribute both to the management of children born prematurely and to future studies of the aetiology of strabismus.

Ocular abnormalities associated with cerebral palsy after preterm birth

Purpose To document the ocular abnormalities in children with cerebral palsy (CP) after premature birth.Methods All the children born before 32 weeks gestation between 1 January 1990 and 31 December 1991 in a geographically defined population of approximately 3 million, were examined by an ophthalmologist and a paediatrician at 2 years old.Results Five hundred and fifty-eight children (98.8% of the study group) were examined, of whom 41 had disabling CP and 13 had nondisabling CP. Children with CP had a higher incidence of abnormalities compared with children without CP: cicatricial retinopathy of prematurity occurred in 8 children with CP (14.8%) compared with 8 without CP (1.6%, p 0.0001), cortical visual impairment occurred in 6 with CP (11.1%) compared with 1 child without CP (0.2%, p 0.0001) and concomitant strabismus in 28 with CP (51.9%) compared with 42 without CP (8.4%, p 0.0001). The prevalence of refractive error without other ocular abnormalities was similar for children with CP (4/54, 7.4%) and those without CP (54/504, 10.7%, p = 0.90). Significant ocular abnormalities had been previously unrecognised in 8 children with CP (14.8%).Conclusion There are some differences between these results and previous series. These differences probably reflect the fact that previous work has studied severe CP of more diverse aetiology. The high frequency of abnormalities highlights the importance of ocular assessment of these children.

Optimal Oxygen Saturation for Preterm Babies

Oxygen is the most commonly used ‘drug’ in neonatal units as an integral part of respiratory support. It has also been known for half of the century that it is easy to damage the eyes of preterm infants by giving too much oxygen especially in the first few weeks of life. Despite this knowledge there is still a wide variation in approaches to oxygen monitoring within neonatal units. A randomized controlled trial conducted more than 50 years ago first made clinicians aware of ‘oxygen toxicity’ in preterm infants, but no other controlled trial has ever been conducted since to clarify how much oxygen infants really need, or what oxygen saturation level is optimal in caring these preterm babies. Perhaps time has come for clinicians to resolve this ‘uncertainty’ by well-designed randomized trials.

15-year follow-up of recurrent "hypoglycemia" in preterm infants.

BACKGROUND: Observational study of 543 infants who weighed <1850 g, published in 1988 reported seriously impaired motor and cognitive development at 18 months in those with recurrent, asymptomatic hypoglycemia (plasma glucose level ≤2.5 mmol/L on ≥3 days). No study has yet replicated this observation. AIM: To quantify disability in a similar cohort of children followed up throughout childhood. POPULATION: All children born at <32 weeks’ gestation in the north of England in 1990–1991 and had laboratory blood glucose levels measured daily for the first 10 days of life. RESULTS: Forty-seven index children of the 566 who survived to 2 years had a blood glucose level of ≤2.5 mmol/L on ≥3 days. All of these children and hypoglycemia-free controls, matched for hospital of care, gestation, and birth weight, were assessed at age 2. No differences in developmental progress or physical disability were detected. The families were seen again when the children were 15 years old, and 38 of the index children (81%) and matched controls agreed to detailed psychometric assessment. Findings in the 2 groups were nearly identical (mean full-scale IQ: 80.7 vs 81.2). Findings in the 21 children with a level of ≤2.5 mmol/L on ≥4 days, 7 children with a level this low on 5 days, and 11 children with a level of <2.0 mmol/L on 3 different days did not alter these conclusions. CONCLUSIONS: This study found no evidence to support the belief that recurrent low blood glucose levels (≤2.5 mmol/L) in the first 10 days of life usually pose a hazard to preterm infants.

Gestational assessment assessed

AIMS To review the accuracy with which obstetric information on gestation is recorded in the neonatal records; and the reliability of the methods used for assessing gestational age after birth. METHODS Service information on all babies born in 1989, and research information on all babies of <32 weeks gestation born in the Northern Region in 1990–91, were reviewed to determine the accuracy with which antenatally collected information had been recorded in the neonatal records after birth. A prospective study was also mounted to assess how reliably paediatric staff could assess the gestational age of babies born to mothers with certain obstetric dates under service conditions. Paediatric residents looked at 347 babies of > 32 weeks gestation, and senior staff looked at 105 babies of < 30 weeks gestation. RESULTS The best techniques for estimating gestation immediately after birth were only half as accurate (95% CI ± 17 days) as estimates based on antenatal ultrasound at 15–19 weeks gestation. Assessments that relied on the tone, posture, and appearance of the baby at birth in those of < 32 weeks gestation were less reliable than assessments based on a retrospective review of when various reflex responses first appeared. They also tended to overestimate true gestation. Antenatal information of high quality was ignored, and arithmetic and transcription errors were introduced during the transfer of antenatal information into over 10% of postnatal records. CONCLUSIONS Current ultrasound techniques for “dating” pregnancy antenatally are better than any of the methods of postnatal assessment. Given the reliability of the antenatal information now available, it is regrettable that so many inaccuracies have been allowed to creep into the routine computation and recording of gestation at birth. Key messages The best techniques for estimating gestation immediately after birth are only half as accurate (95% CI ± 17 days) as estimates based on antenatal ultrasound Such estimates are even less accurate than this in babies of less than 30 weeks gestation Documenting when various reflexes appear can provide a better retrospective estimate of gestation in the preterm baby than methods based on posture, tone and physical appearance The transfer of obstetric information relating to gestation into the neonatal record is frequently faulty; such records were in error by > one week in 15% of preterm babies entered into one recent multi-centre research study, and 92% of the errors involved an under recording of gestation More care should be taken over collecting obstetric information relating to gestation at birth, given its potential value

Six years' experience of prophylactic oral vitamin K

AIMS The ability of oral vitamin K to eliminate all risk of vitamin K deficiency bleeding during the first three months of life was studied. METHODS Babies (n=182 000) in the north of England judged well enough to be offered milk within 12 hours of birth were given 1 mg of phytomenadione (vitamin K1) suspended in a medium chain triglyceride oil by mouth at delivery between 1993 and 1998. The parents of those who were breastfed were given a further three doses to give to the baby once every two weeks after discharge. RESULTS Four breastfed babies developed late vitamin K deficiency bleeding. In two, staff failed to follow policy guidelines, and in two there was undiagnosed α1 antitrypsin deficiency. Audit suggested that 93% of breastfed babies had all four doses, as advised. CONCLUSIONS An oral product that parents can administer themselves would be popular if licensed, but the total dose offered may need to be more than in this study if babies with undiagnosed liver disease are to be protected.