Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants

AIM—To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants.METHODS—Forty infants were randomly allocated to receive either hydrocortisone (n=21) or dopamine (n=19).RESULTS—All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group.CONCLUSION—Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants.     

Retinopathy of prematurity: age at onset.

The age at which retinopathy of prematurity was first seen was determined in 143 infants. In all, the initial ophthalmological examination was normal. Birth weights varied from 630 to 2700 g and gestational ages from 24.5 to 40.0 weeks. The median postnatal age at which acute retinopathy of prematurity was first seen was 51 and 40 days for those less than 28 and greater than or equal to 28 weeks'' gestational age, respectively, and this difference is highly significant. Similar results were obtained when infants were grouped according to birth weight less than 1000 or greater than or equal to 1000 g. Using postmenstrual age as the variable, the first signs of retinopathy of prematurity were seen over a fairly narrow age range and 86% of infants developed retinopathy between 32.5 and 38.5 weeks of age. These findings suggest that the age (but not the occurrence or severity) at which retinopathy of prematurity is first seen is controlled predominantly by stage of development rather than neonatal events.     

Randomised controlled trial of an aggressive nutritional regimen in sick very low birthweight infants

AIMS—To improve energy intake in sick very low birthweight (VLBW) infants; to decrease growth problems, lessen pulmonary morbidity, shorten hospital stay, and avoid possible feeding related morbidity. Morbidity in VLBW infants thought to be associated with parenteral and enteral feeding includes bronchopulmonary dysplasia, necrotising enterocolitis, septicaemia, cholestasis and osteopenia of prematurity.METHODS—A prospective randomised controlled trial (RCT) comparing two types of nutritional intervention was performed involving 125 sick VLBW infants in the setting of a regional neonatal intensive care unit. Babies were randomly allocated to either an aggressive nutritional regimen (group A) or a control group (group B). Babies in group B received a conservative nutritional regimen while group A received a package of more aggressive parenteral and enteral nutrition. Statistical analysis was done using Student''s t test, the Mann-Whitney U test, the χ² test and logistic regression.RESULTS—There was an excess of sicker babies in group A, as measured by initial disease severity (P <0.01), but mean total energy intakes were significantly higher (P <0.001) in group A at days 3 to 42 while receiving total or partial parenteral nutrition. Survival and the incidences of bronchopulmonary dysplasia, septicaemia, cholestasis, osteopenia and necrotising enterocolitis were similar in both groups. Growth in early life and at discharge from hospital was significantly better in babies in group A. There were no decreases in pulmonary morbidity or hospital stay.CONCLUSION—Nutritional intake in sick VLBW infants can be improved without increasing the risk of adverse clinical or metabolic sequelae. Improved nutritional intake resulted in better growth, both in the early neonatal period and at hospital discharge, but did not decrease pulmonary morbidity or shorten hospital stay.     

Ocular sequelae in extremely premature infants at 5 years of age

Objective To report long-term ophthalmological sequelae in extremely premature infants at 5 years and to determine the relationship between neonatal variables (including retinopathy of prematurity; ROP) and the 5 year ophthalmological outcome of these infants.
Methodology The study cohort comprised 84 surviving infants born with a birthweight <1000 g or gestational age <28 weeks from June 1985 to December 1989. All infants had an ophthalmological assessment between 34 and 40 weeks post conceptional age to document grade of ROP and were assessed at 5 years of age for fundoscopy, visual acuity, refractive error and ocular mobility.
Results Of the 84 long-term survivors 69 (82%) were formally assessed at 5 years. Overall, 30 (43%) had some form of ocular disorder. Nineteen (27%) had reduced visual acuity of <6/6 and three of these were blind. Myopia > −0.5 dioptre was noted in eight (12%), hypermetropia ≥2.0 dioptre in five (8%), astigmatism in seven (11%) and strabismus was present in nine (14%) of the cohort. There was a significant relationship ( P <0.0001) between the incidence of ocular disorders and ROP. However, even those premature children without ROP had a 31% incidence of ocular disorder at 5 years.
Conclusion Long-term ophthalmological follow-up is recommended in all extremely premature infants regardless of the presence of ROP in the neonatal period.     

Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease

BACKGROUND: Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease. AIM: To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants. METHODS: Infants with birth weight < 1000 g were randomised at birth to receive oral vitamin A supplementation (5000 IU/day) or placebo for 28 days. The primary outcome was oxygen dependency at 28 days of age or death. RESULTS: A total of 154 infants were randomised; 77 received vitamin A (median birth weight (interquartile range) 806 (710-890) g), and 77 received placebo (median birth weight (interquartile range) 782 (662-880) g). Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth, 12 hours of age, 7 days, or 28 days of life. There were no significant differences in the proportion of infants who survived, required oxygen at 28 days, required oxygen at 36 weeks postmenstrual age, survived without chronic lung disease at 36 weeks, survived without significant retinopathy, or who survived without significant intraventricular haemorrhage. CONCLUSIONS: Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease. However, this dose may have been inadequate to achieve optimal serum retinol concentrations.     

Use of indomethacin and its relationship to retinopathy of prematurity in very low birthweight infants.

The relationship between the use of indomethacin, a prostaglandin inhibitor, for closure of patent ductus arteriosus (PDA) and the occurrence of retinopathy of prematurity was investigated retrospectively. 63 preterm infants less than or equal to 1500 g who were less than or equal to 32 weeks'' gestational age, appropriate weight for gestational age, with a diagnosis of PDA, and admitted during the first 24 hours of life were studied. Diagnosis of retinopathy was made by retinal examination when each infant was about 4 weeks. Diagnosis of PDA was made by clinical, radiological, and echocardiographic findings. 15 patients were treated with indomethacin because of severe congestive heart failure. There were no differences between gestational ages, birthweights, duration of oxygen therapy, or incidence of retinopathy in treated and untreated patients. We suggest that the use of indomethacin for PDA closure does not increase the incidence of retinopathy in very low birthweight infants.     

Feeding problems in preterm infants of preeclamptic mothers

Aim: Maternal disease can cause prematurity and neonatal complications, notably feeding problems. To determine the relationship between maternal disease and the nature and severity of neonatal feeding problems, we compared feeding profiles, time to demand feeding and length of hospital stay between preterm infants of preeclamptic mothers, mothers with amniotic infection and mothers with other disease causing prematurity. Methods: The retrospective study used labour ward data collected from 2002 to 2005 in a tertiary university centre to analyse three groups of singletons born at <32 completed gestational weeks to mothers with preeclampsia (n = 61), amniotic infection (n = 55) and non‐preeclamptic non‐amniotic infection controls (n = 55). The groups were similar in gestational age, birthweight and sex ratio; all infants received enteral feeding according to departmental guidelines. Feeding profiles and enteral/oral nutrition were compared. Results: Feeding problems occurred in 46% of the preeclamptic group, 11% of the amniotic infection group and 13% of controls. Full oral demand feeding was established at 36 0/7 weeks postmenstrual age, 35 3/7 weeks (P = 0.03) and 35 2/7 weeks (P < 0.0001), respectively. Feeding problems were the main cause of delay (7–10 days) in hospital discharge in the preeclamptic group (P = 0.0002). Conclusions: Feeding problems are greater, and hospital stay longer, in preterm infants of preeclamptic mothers than in other preterm infants.     

Effects of cisapride on QTc interval in neonates

AIM—Prospective survey of the effects of cisapride on QTc interval in neonates given cisapride.METHODS—QTc interval was determined just before and 2.9 (0.9) days after outset of the treatment in 49 neonates treated with cisapride between 1 August 1995 and 29 February 1996.RESULTS—Cisapride significantly increased QTc interval (p = 0.0001), and this was higher when birthweight or gestational age were lower. The prolongation of QTc interval above the arbitrary value of 0.450 (n = 7) was clinically asymptomatic and was significantly more common in the infants born with a gestational age ? 33 weeks (n = 6).CONCLUSION—The findings indicate that cisapride accumulates in less mature neonates. Further pharmacokinetic studies are needed.     

Influence of obstetric management on outcome of extremely preterm growth retarded infants

AIM—To describe the long term outcome of extremely preterm growth retarded infants in relation to obstetric management and various perinatal events.METHODS—A cohort study was undertaken in two tertiary care centres with different obstetric management. All infants with fetal growth retardation due to placental insufficiency and resulting in fetal distress at 26 to 32 weeks of gestation, were included for the years 1984-89. Main outcome measures were impairment, disability, or handicap at 2 years corrected age and at school age (4 1/2 to 10 1/2 years).RESULTS—One hundred and twenty five (98%) were followed up until 2 years corrected age in the outpatient department; 114 (90%) were assessed at school age. Impairments were found in 37% and disabilities or handicaps in 9% of the assessed infants, with no difference between centres. All disabled or handicapped children had already been identified by 2 years corrected age.CONCLUSIONS—Disability or handicap were related to neonatal complications (intracerebral haemorrhage or bronchopulmonary dysplasia) and not to obstetric variables, thus making antenatal prediction impossible. The incidence of disability or handicap in these growth retarded infants was comparable with that of other preterm infants.     

Retinopathy of prematurity and risk factors: a prospective cohort study

Background  

Increased survival of extremely low birth infants due to advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing retinopathy of prematurity (ROP). Therapeutic interventions include the use of antenatal and postnatal steroids however, their effects on the severity of ROP is in dispute. In addition, it has not been investigated whether severe ROP is due to therapeutic interventions or due to the severity of illness. The aim of the present study was to assess the association between the incidence of severe retinopathy of prematurity (greater than stage 2 – International classification of ROP) and mechanical ventilation, oxygen therapy, gestational age, antenatal and postnatal steroids in extremely low birth weight infants.     

Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial

AIM—To investigate the colonisation with Bifidobacterium breve of the bowels of very low birthweight (VLBW) infants.METHODS—The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody.RESULTS—In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B breve significantly decreased aspirated air volume from the stomach and improved weight gain.CONCLUSIONS—B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules.     

High frequency oscillatory ventilation in infants with increased intra-abdominal pressure

AIMS—To describe the short term effect of high frequency oscillatory ventilation on infants with severe abdominal distension who could not be conventionally ventilated.METHODS—Eight infants (25 to 38 gestational weeks, birthweight 600-3200 g, postnatal age 1 to 190 days) with a variety of intra-abdominal pathologies, resulting in severe abdominal distension and failure of conventional ventilation, were studied.RESULTS—The oxygenation status of all infants significantly improved within an hour of changing from conventional to high frequency oscillatory ventilation. Infants who were hypercapneic on conventional ventilation also showed a reduction in PaCO₂. As a group, the mean (SD) PaO₂/FIO₂ improved from 4.99 (0.98) kpa to 11.55 (3.8) kpa (P = 0.002), and the PaCO₂ from 6.48 (2.12) kpa to 4.89 (1.22) kpa (P= 0.028). These improvements were sustained throughout the next 48 hours.CONCLUSION—High frequency oscillatory ventilation seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure.     

Reduced lighting does not improve medical outcomes in very low birth weight infants

OBJECTIVE: To objectively assess the effect of light reduction as an isolated environmental intervention on neonatal morbidity. STUDY DESIGN: Randomized multicenter trial. Neonates < 1251 g birth weight and < 31 weeks gestational age were randomly assigned to receive goggles or to a control group. Goggles that reduced visible light by 97% were placed within 24 hours of birth and remained in use until 31 weeks postmenstrual age or for a minimum of 4 weeks. RESULTS: Four hundred nine infants were enrolled, and outcome data are reported for 359 surviving infants. There were no significant differences between the groups in weight gain, duration of oxygen therapy, mechanical ventilation, or hospital stay either in the unadjusted analyses or in the analyses adjusted for birth weight, gestational age, race, sex, and inborn (born in study hospital) status. There was no difference between the groups in the incidence of intracranial hemorrhage. CONCLUSIONS: This randomized trial of continuous light reduction in the first few weeks of life for very low birth weight infants showed no effect on medical outcomes.     

Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease

AIM—To review systematically the evidence to determine whether dexamethasone treatment of very low birthweight infants begun within 14 days of age prevents chronic lung disease (CLD) without clinically significant side effects.METHODS—Randomised controlled trials of dexamethasone started within this time frame were identified through a search of electronic databases, proceedings of scientific meetings, and personal files. Meta-analyses using event rate ratio (ERR), event rate difference (ERD), and if significant, numbers needed to treat (NNT) for benefits and numbers needed to harm (NNH) for adverse effects were calculated. Weighted mean difference were used for continuous variables. Three prespecified subgroup analyses were performed for; (i) dexamethasone begun within 36 hours (hours) of birth; (ii) dexamethasone initiated between 7-14 days of age; or (iii) if surfactant treatment was used.RESULTS—Ten studies were included in the review; six where dexamethasone was initiated within 36 hours of age, four studies for dexamethasone started between 7 and 14 days and six studies using surfactant. Mortality ERR and NNT with 95% confidence intervals for dexamethasone initiated at 7-14 days of age were 0.35 (0.16, 0.74) and 8 (4,30). ERRs and NNTs for CLD at 28 days and 36 weeks of postmenstrual age were 0.71 (0.61, 0.84), 8 (5, 17), and 0.57 (0.44, 0.76), 10 (6, 23) in the overall analyses. When dexamethasone was started at 7 to 14 days of age ERR and NNT for CLD at 36 weeks were 0.63(0.47, 0.85) and 3 (2, 9). Clinically significant side effects included increased risk of hypertension, hyperglycaemia, and increased time to regain birthweight.CONCLUSIONS—These meta-analyses show a significant reduction in risk of CLD at 28 days and 36 weeks of postmenstrual age. In the subgroup where dexamethasone was started between 7 and 14 days of age mortality was significantly reduced. Caution is warranted in the routine use of dexamethasone because of lack of data on long term neurodevelopmental outcomes.     

Influence of ethnic origin on respiratory distress syndrome in very premature infants

AIM—To determine whether the incidence of respiratory distress syndrome (RDS) is related to ethnic origin in very premature infants (?32 weeks of gestational age and birthweight ?2.0 kg).METHOD—A retrospective cohort study was performed to determine the incidence of respiratory disorders in African, Caribbean, and caucasian infants. An African infant was matched with two infants (one of Caribbean and one of caucasian descent) for gestational age and birth order and, if several eligible matching infants were found, for gender and approximate birth date. Fifty African infants (median gestational age 28 weeks, range 23-32) were matched with an infant of Caribbean and one of caucasian descent.RESULTS—Compared with the incidence of RDS in African infants (40%), that in caucasian infants (75%) was significantly higher (p<0.05), while the incidence in the Caribbean infants (54%) did not differ significantly. Regression analysis showed that ethnic origin was related to the occurrence of RDS independent of gestational age, size for dates, antenatal steroids, hypertension during pregnancy, premature rupture of membranes, maternal smoking, mode of delivery and infant gender.CONCLUSION—The enhanced lung maturation found in certain ethnic groups, even when born prematurely, has implications for clinical management.     

Hepatitis B vaccination in preterm infants

AIM—To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants.METHODS—Recombinant hepatitis B vaccine (H-B-VAX II, 5 µg per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of ?2000 g received three doses at 0, 1, and 6 months of age.RESULTS—After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study.CONCLUSIONS—Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.     

早产儿支气管肺发育不良伴肺动脉高压的临床特征及预后

目的 调查早产儿支气管肺发育不良（BPD）并发肺动脉高压（PH）的临床特征及预后。方法 对191例BPD患儿的临床资料进行回顾性分析。结果 191例BPD患儿中,37例（19.4%）在纠正胎龄36周后并发PH,均发生于中度和重度BPD患儿,中度、重度BPD患儿的PH发生率分别为5.7%（5/87）和47.8%（32/67）。并发PH组患儿的出生胎龄、出生体重明显小于无PH组患儿（P < 0.01）;并发PH组患儿小于胎龄儿（SGA）比例、重度BPD比例、动脉导管未闭（PDA）手术率及新生儿呼吸窘迫综合征、有血流动力学意义的PDA、肺部感染的发生率明显高于无PH组（P < 0.01）;并发PH组患儿的吸氧、气管插管、正压通气时间均明显大于无PH组（P < 0.01）;并发PH组患儿的早产儿视网膜病、宫外生长发育迟缓发生率及病死率均明显高于无PH组,住院时间明显延长（P < 0.01）。37例PH患儿中（6例为轻度PH,14例中度,17例重度）,轻、中度PH患儿均存活,重度PH患儿中15例（88%）死亡。结论 中重度BPD患儿的PH发生率较高,建议定期筛查BPD患儿的肺动脉压力。低出生胎龄和体重、SGA和重度BPD患儿更易并发PH。BPD并发PH患儿的并发症发生率和病死率较高,预后相对不良。     

Effects of early reduced light exposure on central visual development in preterm infants

The aim of this study was to determine, in infants born at < or =29 weeks postmenstrual age until 32 weeks postmenstrual age, whether reduction to light stimulation by occlusion of eyes affected central visual development. The pattern visual-evoked potential responses at 41 and 51 weeks postmenstrual age and 3 y of age did not differ between infants subjected or not to ocular occlusion. Hence, an early marked reduction in light stimulation in preterm infants does not seem deleterious to visual development.     

加拿大新生儿重症监护室院内感染及其变化趋势对胎龄<33周早产儿预后的影响

败血症是新生儿重症监护室(NICU)的危重病症及造成新生儿死亡的重要原因之一,根据其发病时间,可分为早发(生后2 d 内)和晚发(生后2 d 后)。其中晚发的新生儿败血症,一般考虑为院内感染(NI)。胎龄越小,出生体重越低,NI 的发生率越高。NI 的发生率在加拿大各 NICU 之间差别较大,与各中心医护人员的相关诊疗行为密切相关。在国家卫生研究院"基于循证医学的医疗质量改进项目" 的推动下,2003~2009 年间加拿大全国 NICU 总的NI 率明显下降,但不同中心各自感染率的变化趋势仍极为不同。本研究纳入了加拿大全国共24 家 NICU 在2008~2012 年间所有收入院的胎龄<33 周的早产儿共18 961 名,探讨NI 率的变化趋势以及其与早产儿预后的关系。     

Maternal hypertension and neurodevelopmental outcome in very preterm infants

AIM—To determine the outcome of preterm infants born to mothers with hypertension during pregnancy, and preterm controls.
METHODS—107 infants of 24-32 weeks gestation, born to hypertensive mothers, and 107 controls matched for gestational age, sex, and multiple pregnancy, born to normotensive mothers, were prospectively enrolled over 2 years. Information on maternal complications and medication was obtained and neonatal mortality and morbidities recorded. Survivors were followed up to at least 2 years, corrected for prematurity.
RESULTS—One third of the hypertensive mothers were treated with antihypertensive drugs, while 18% received convulsion prophylaxis with phenytoin. Magnesium sulphate was not prescribed. Both groups had a mean gestational age of 29.9 weeks, with the study infants having a significantly lower birthweight than the controls. Four study and three control infants died in the neonatal period. Cerebral palsy was not diagnosed in any infant of a hypertensive mother compared with five of the controls. The mean general quotient for the two groups was very similar and no difference in the incidence of minor neuromotor developmental problems was shown.
CONCLUSIONS—Maternal hypertension seems to protect against cerebral palsy in preterm infants without increasing the risk of cognitive impairment. This was independent of the use of maternally administered magnesium sulphate.