极早和超早产儿神经发育结局

极早产(VPT)和超早产(EPT)儿发生脑损伤及神经发育损害的风险高。随着新生儿重症救治水平的提高,VPT和EPT早产儿存活率明显提高,如何降低神经发育损害的发生率以改善远期预后,是目前全球关注的重要问题。了解VPT和EPT早产儿神经发育预后,对指导临床救治及早期干预,改善患儿远期预后具有重要意义。     

Impact of increased neonatal survival on postneonatal mortality in the United States

Summary. Neonatal intensive care has increased neonatal survival, but has also led to postponement of some of the neonatal deaths to the postneonatal period, particularly in very low birthweight (<1.5kg) infants. Our report assesses the impact of the increased neonatal survival and the accompanying delayed deaths on the crude postneonatal mortality rate oi the US, using the national livebirth cohort data of 1960,1980, and 1986. With increased neonatal survival, very low birthweight infants comprised 0.68% of all neonatal survivors in 1986, compared with only 0.31% in 1960. However, postneonatal mortality was increased in infants with birth weights < 1.0 kg from 69 per 1000 neonatal survivors in 1960 to 116 per 1000 in 1986. All other birthweight groups (> 1.0 kg) showed significant reductions in their postneonatal mortality, although the 1.0–1.5 kg group showed the least improvement. Thus, in 1986, 12.1% of all postneonatal deaths were from the very low birthweight neonatal survivors, as compared with 2.7% in 1960. If there had been no improvement in neonatal survival of very low birthweight infants since 1960, the crude postneonatal mortality rate of the US would have been 5.5% and 7.9% less than the actual rates of 3.65 and 3.45 per 1000 neonatal survivors in 1980 and 1986, respectively. However, the impact of these delayed deaths in very low birthweight infants was far less than the increase in their neonatal survival: an additional 416 per 1000 very low birthweight infants survived to 1 year of age in 1986 as compared with 1960. Delayed deaths in the 1.5-2.5 kg birthweight group had a very small effect on postneonatal mortality and there was no such effect of delayed deaths in the > 2.5 kg birthweight group.     

Lower mortality but higher neonatal morbidity over a decade in very preterm infants

Better perinatal care has led to better survival of very preterm children, but may or may not have increased the number of children with cerebral and pulmonary morbidity. We therefore investigated the relationship between changes in perinatal care during one decade, and short-term outcome in very preterm infants. Perinatal risk factors and their effects on 28-day and in-hospital mortality, and on intraventricular haemorrhage and bronchopulmonary dysplasia (BPD) in survivors, were compared in two surveys of very preterm singleton infants in the Netherlands. Between 1983 and 1993, 28-day mortality decreased from 52.1% to 31.8% in infants of 25-27 weeks' gestation and from 15.2% to 11.3% in infants of 28-31 weeks' gestation. The incidence of intraventricular haemorrhage in survivors did not change (44.4% and 43.3% in infants of 25-27 weeks' gestation, and 29.0% and 24.0% in infants of 28-31 weeks' gestation). The incidence of BPD in survivors increased from 40.3% to 60.0% in infants of 25-27 weeks' gestation and remained similar in infants of 28-31 weeks' gestation (8.5% and 9.8% respectively). In multivariable analysis, higher mortality was associated with congenital malformation, low gestational age, low birthweight, no administration of steroids before birth, low Apgar scores and intraventricular haemorrhage, in 1983 as well in 1993, and with male gender in 1993. The effect of maternal age on mortality diminished significantly between 1983 and 1993. Intraventricular haemorrhage in surviving children was associated with low gestational age and artificial ventilation, both in 1983 and in 1993. The effect of artificial ventilation on the incidence of intraventricular haemorrhage diminished significantly between 1983 and 1993. BPD was associated with low gestational age and artificial ventilation, both in 1983 and in 1993, and with low birthweight and caesarean section in 1993. We conclude that the better survival of very preterm infants, especially of those of 25-27 weeks' gestation, has been accompanied by a similar incidence (and thus with an increased absolute number) of children with intraventricular haemorrhage and by an increased incidence of children with BPD.     

早产儿支气管肺发育不良的研究进展

随着新生儿重症监护技术的迅速发展,早产儿,尤其是极低出生体重儿的存活率得到较大提高。早产是导致支气管肺发育不良(BPD)的重要因素之一,加之早产儿可能合并低出生体重、围生期感染和动脉导管未闭等,以及进行机械通气与给氧治疗所致并发症,而使早产儿BPD的发生率呈逐年上升趋势。BPD早产儿的初次住院时间及BPD导致的病死率,均明显高于非BPD早产儿,因此早产儿BPD已成为临床最棘手的问题之一。笔者拟就目前早产儿BPD的研究进展,包括相关危险因素、早期预测生物学标志物及防治等进行综述。     

Nutritional factors influencing infections in preterm infants

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.     

Long-term effects of neonatal glutamine-enriched nutrition in very-low-birth-weight infants

Several studies in very-low-birth-weight (VLBW) infants have investigated the effect of parenteral or enteral glutamine supplementation on morbidity, mortality, and outcome in the neonatal period. No evidence of toxicity of glutamine supplementation was found in these clinical trials, but the results for efficacy on a limited number of outcomes have been mixed. The use of glutamine supplementation in VLBW infants has not become routine. Some authors suggest that further study in this area is no longer warranted. In this review, more recent research in the area of glutamine supplementation is described, which suggests additional studies are warranted.     

Outcome of perinatal care for very preterm infants at 5 years of age: a comparison between 1983 and 1993

Perinatal mortality in very preterm infants has decreased by up to 50% during the last decades. Studies of changes of long-term outcome are inconclusive. We studied the visual, auditory, neuromotor, cognitive and behavioural development of two geographically defined populations of very preterm, singleton infants, born in 1983 and in 1993, and analysed the relationship between perinatal risk factors and outcomes. The incidence of disabling cerebral palsy increased from 6.0% to 11.1% (OR 2.45 [95% CI 1.11, 5.38]). Impaired vision and strabismus decreased significantly, presumably by continuous monitoring of pO(2). Hearing problems, the need for special education and the incidence of behavioural problems did not change over time. The proportion of children who showed optimal performance in every developmental domain increased from 29.5% in 1983 to 43.2% in 1993. Cerebral palsy was associated with male gender in 1983, with low Apgar score and intraventricular haemorrhage in 1993, and with seizures both in 1983 and in 1993. The intensiveness of neonatal treatment has increased, leading to the survival of many more healthy infants, but at the cost of more infants with cerebral damage. Modern perinatal care is no longer limited by the devastating effects of pulmonary problems as it was in the past, but fails to safeguard cerebral integrity in very preterm infants.     

Outcome following extremely preterm birth

Survival and later morbidity after extremely preterm birth are key issues to factor into the care of women and their children at borderline viability. Whereas we have robustly collected information on survival that shows some increases at 24-25 weeks of gestation, few data suggest any change in morbidity. Of babies born before 26 weeks of gestation around one quarter grow up with serious disability. Mild disabilities are common amongst the remainder. Overwhelmingly the major adverse outcome following extremely preterm birth is cognitive impairment, something that may not be apparent until school age, when we make increasing demands on children to perform. Despite these problems, studies of very preterm/very low birthweight children as adults seem to indicate good adaptation and integration into society.     

早产儿神经心理发育及干预研究进展

近年来,我国早产儿的出生率逐年上升。随着围产医学和新生儿重症急救技术的提升,早产儿的死亡率持续下降,但存活下来的早产儿脑损伤和出生后发育异常的发生率居高不下。对比足月儿,早产儿心理及行为发展等方面的问题也较多。本研究对国内外有关早产儿神经心理发育和干预研究进行梳理,总结早产儿神经心理发育特点,分析早产儿的干预研究,为早产儿的养育干预研究提供指导。     

Incidence of Severe Adverse Neonatal Outcomes: Use of a Composite Indicator in a Population Cohort

The aim was to develop a composite outcome indicator to identify infants with severe adverse outcomes in routinely collected population health datasets, and assess the indicator’s association with readmission and infant mortality rates. A comprehensive list of diagnoses and procedures indicative of serious neonatal morbidity was compiled based on literature review, validation studies and expert consultation. Relevant diagnoses and procedures indicative of severe morbidity that are reliably reported were analysed and reviewed, and the neonatal adverse outcome indicator (NAOI) was refined. Data were obtained from linked birth and hospital data for 516,843 liveborn infants ≥24 weeks gestation, in New South Wales, Australia from 2001 to 2006. Face validity of the indicator was examined by calculating the relative risks (and 95% CI) of hospital readmission or death in the first year of life of those infants identified by the NAOI. Overall 4.6% of all infants had one or more conditions included in the NAOI; 35.4% of preterm infants and 2.4% of term infants. Infants identified by the composite indicator were 10 times more likely to die in the first year of life and twice as likely to be readmitted to hospital in the first year of life compared to infants not identified by the NAOI. The NAOI can reliably identify infants with a severe adverse neonatal outcome and can be used to monitor trends, assess obstetric and neonatal interventions and the quality of perinatal care in a uniform and cost-effective way.     

Survival and risk factors for neonatal mortality in a cohort of very low birth weight infants in the southern region of São Paulo city, Brazil

Population studies can help identify the complex set of risk factors for neonatal mortality among very low birth weight infants. A cohort (2000-2001) of 213 live newborns with birth weight < 1,500g in the southern region of S?o Paulo city, Brazil, was studied (112 neonatal deaths and 101 survivors). Data were obtained from home interviews and hospital records. Survival analysis and multiple Cox regression were performed. The high mortality in the delivery room and in the first day of life among neonates < 1,000g and < 28 weeks gestational age and the absence of survival in neonates < 700g suggest that care was actively oriented towards newborns with better prognosis. Increased risk of neonatal mortality was associated with maternal residence in slum areas, history of previous cesarean(s), history of induced abortion(s), adolescent motherhood, vaginal bleeding, and lack of prenatal care. Cesarean section and referral of the newborn to the hospital nursery showed protective effects. Birth weight less than 1,000g and Apgar index < 7 were associated with increased risk. The high mortality was due to poor living conditions and to maternal and neonatal characteristics. Improvement in prenatal and neonatal care could reduce neonatal mortality in these infants.     

Obstetrical volume and early neonatal mortality in preterm infants

Objective Regionalised perinatal care with antenatal transfer of high risk pregnancies to Level III centres is beneficial. However, levels of care are usually not linked to caseload requirements, which remain a point for discussion. We aimed to investigate the impact of annual delivery volume on early neonatal mortality among very preterm births. Methods All neonates with gestational age 24–30 weeks, born 1991–1999 in Lower Saxony were included into this population-based cohort study (n = 5,083). Large units were defined as caring for more than 1,000 deliveries/year, large NICUs as those with at least 36 annual very low birthweight (<1,500 g, VLBW) admissions. Main outcome criterion was mortality until day 7. Adjusted Odds Ratios (adj. OR) and 95% confidence intervals (CI) were calculated based on generalised estimating equation models, accounting for correlation of individuals within units. Results Within the first week of life, 20.6% of all neonates deceased; 10.2% were stillbirths, 3.7% died in the delivery unit, and 6.7% in the NICU. The crude OR for early neonatal mortality after having been delivered in a small delivery unit (excluding stillbirths) was 1.36 (95%CI 1.04–1.78; adj. OR 1.16 (0.82–1.63)). It increased to 1.96 (1.54–2.48; adj. OR 1.21 (0.86–1.70)) after the inclusion of stillbirths. Conclusion This study has shown a slight, but non-significant association between obstetrical volume and early neonatal mortality. In future studies the impact of caseload on outcome may become more evident when referring to high-risk patients instead of to the overall number of deliveries.     

Contribution to the definition of high-risk groups of low birth weight infants

Follow-up studies of low birth weight infants concern usually infants selected on the basis of either the birthweight--inferior or equal to 1500 g--or the gestational age: the upper limit is 31 or 32 weeks. To determine the most pertinent criterium, mortality and neurodevelopmental outcome at two years were compared in 3 groups, selected on the above criteria from a cohort of 369 infants with a birthweight below 2,000 grams admitted in 1983 in the neonatal unit of the University hospital of Lille. Under 1501 grams the rate of small for gestational age infants is high: it could be a part of the explanation for the high rate of minor sequelae. When cohorts are selected on the basis of gestational age, it appears that mortality is low at 32 weeks but the rate of major and moderate sequelae is still high: that fact must be considered when premature induced delivery comes in discussion. Because these criteria select different high risk populations, mortality and neurodevelopmental follow-up studies should include all infants with gestational age inferior or equal to 32 weeks and/or birthweight inferior or equal to 1,500 grams.     

Antenatal administration of glucocorticosteroids in threatened preterm birth]

The administration of glucocorticosteroids to pregnant women results in a striking decrease of neonatal morbidity and mortality in premature infants. A single course of steroids--24 mg of betamethasone or dexamethasone, given in 2 to 4 doses--does not seem to result in long-term adverse effects, although relatively few follow-up studies have been carried out. However, betamethasone causes a temporary--yet considerable--reduction in fetal heart rate variation as well as in fetal breathing and body movements. Familiarity with this phenomenon prevents unnecessary medical intervention (because of presumed fetal distress). Although the use of glucocorticosteroids was for a long time limited due to concerns about negative adverse effects, it has recently become common practice to repeat the courses weekly in the case of a persistent risk of premature birth. However, in contrast to the single course, there is no evidence that repeating a corticosteroid course improves the effectiveness of the treatment. (Long-term) adverse effects are probably dose dependent. The repetition of corticosteroids courses must therefore be advised against for the time being, unless this takes place within the framework of a randomised study.     

早产儿侵袭性真菌病的研究进展（综述）

新生儿重症监护技术的进步使得早产儿存活率得到很大提高。由于早产儿不成熟的免疫系统,生后常因生活力低下或存在并发症/合并症在新生儿重症监护病房救治,较长时间住院,广谱抗生素使用、各种侵入性操作增多,使得早产儿成为侵袭性真菌病的高危人群。IFD缺乏特异性临床表现,造成早期诊治存在困难,已成为威胁早产儿生存质量的重要课题,需在临床中给予更多关注。该文主要对近年来早产儿侵袭性真菌感染防治的研究进展进行综述。     

多学科合作的早产儿系统管理对新生儿重症监护室出院早产儿神经精神发育结局的影响

目的 分析多学科合作系统管理和早期综合干预对新生儿重症监护室(NICU)出院早产儿近期神经发育结局的影响。方法 回顾分析和比较在上海市儿童医院早产儿整合门诊接受随访的早产儿,根据管理模式分为非系统管理且无干预阶段,以及多学科合作开展系统管理阶段,比较两阶段NICU出院早产儿发育迟缓发生率;通过对照研究评价多学科合作的系统管理对NICU早产儿近期神经发育结局的影响。结果 1999年1月-2016年6月累计登记随访NICU出院早产儿997例,两阶段中早产儿随访至校正12月龄段时,系统管理下的早产儿各能区发育迟缓发生率较低(P<0.05)。对照研究表明,NICU出院早产儿接受系统管理后,校正18月龄发育商可达平均水平。结论 多学科合作开展系统的随访管理,能改善NICU出院早产儿近期神经精神发育结局。     

High-risk young mothers: infant mortality and morbidity in four areas in the United States, 1973-1978

An examination of the changes in infant mortality and morbidity in four regions in the United States has revealed high levels of health problems among the infants of two groups of mothers: those less than or equal to 17 years and 18-19 year-old multiparas, many of whom began their childbearing under age 18. Despite decreases over the period of observation, neonatal mortality rates remain over one and a half times as high for infants of these mothers as for other mothers, largely due to the relatively high proportion of low birthweight (LBW) infants born to these mothers. Post-neonatal mortality rates also remain high, and may be increasing; this change cannot be explained solely by differences in proportion of LBW infants between these and older mothers. Both the high post-neonatal mortality rates and the type of morbidity experienced by surviving infants is consistent with the socioeconomic disadvantage of young mothers. The data further indicate the limited resources available to these mothers to cope with their children's health needs, and their potential vulnerability to decreases in public programs supporting child health care.     

Perinatal mortality in the St. Louis metropolitan area

Statistical data in fetal, neonatal, perinatal, and infant mortality were collected from various sources for the St. Louis metropolitan area (St. Louis City and St. Louis County). The overall perinatal mortality rate of 25.8 for the St. Louis metropolitan area in 1973 compares favorably with the national rate of 25.5 in 1973. The prematurity rate at St. Louis City Hospital (SLCH) is almost three times that of St. Mary's Health Center (SMHC), 12.7 in contrast to 4.8. Both the neonatal and perinatal mortality rates at SLCH are about twice the rate of SMHC, neonatal 19.5 versus 7.4 and perinatal 31.7 in contrast to 19.6. Prematurity and its complications still seem to be the leading cause of neonatal mortality. With modern obstetrical and intensive neonatal care, the survival rates for low birth weight infants has improved markedly. The combined survival rates at SLCH and SMHC, 1972 through 1974 for infants weighing 501-1,000 gms 28 percent; 1,001-1,500 gms, 74 percent; 1,501-2,5000 gms, 95.5 percent; and greater than 2,500 gms. 99.7 percent. Recent studies have shown that the long-term prognosis for these low birth weight infants, in terms of neurological or intellectual sequelae is good. Thus, a more aggressive approach to the management of perinatal problems can be expected to yield excellent results.     

极低/超低出生体重儿母乳喂养的研究现状与进展

极低/超低出生体重儿的死亡人数占全部新生儿死亡人数的一半以上,相比低出生体重儿(即≥1 500 g),相关并发症发生率更高,预后相对更差,母乳喂养已被证实可以帮助改善其临床结局。本文对极低/超低出生体重儿母乳喂养的研究现状与进展进行综述。     

Access to intensive neonatal care and neonatal survival in low birthweight infants: A population study in Norway

This study evaluates the impact of regional differences in access to intensive neonatal care on neonatal survival in geographically defined populations of 4,692 low birthweight births in Norway 1979-81. For infants weighting 1,250 to 2,499 g our results are consistent with the existence of a dose-response association between neonatal survival and the level of immediate access to intensive neonatal care. Although not statistically significant, there was a clear gradient in the risk of mortality within 24 hours. A similar pattern of survival could not be consistently demonstrated for infants weighing less than 1,250 g.