Increased mortality of preterm infants transferred between tertiary perinatal centres.

Over 18 months almost one quarter of infants born before 30 weeks'' gestation in a tertiary perinatal centre who required intensive care had to be transferred to other tertiary centres because intensive care facilities were fully occupied. When infants with lethal congenital malformations were excluded half of the 34 infants who were transferred died; this was twice the mortality (24%) in the 111 infants remaining. The difference between the groups was significant (relative odds = 3.1) and remained so after adjustment for any discrepancies in gestational age (relative odds = 4.0). After adjustment for potential confounding variables by logistic function regression the risk of dying for those transferred remained significantly higher than that for infants who remained (relative odds = 4.6, 95% confidence interval 1.8 to 12.1). As the requirement for neonatal intensive care is episodic and unpredictable more flexibility has to be built into the perinatal health care system to enable preterm infants delivered in tertiary perinatal centres to be cared for where they are born.     

Referral of mothers and infants for intensive care.

During 1975-7, 96 mothers were referred to University College Hospital for delivery from 39 other hospitals because their pregnancies were considered to be at very high risk. One hundred of the 111 infants born to the 96 mothers weighed 2500 g or less and 60 weighed 1500 g or less. A high proportion of the infants developed serious illnesses necessitating intensive care. The birth-weight-specific neonatal mortality rates of the infants were much lower than those of infants born in England and Wales as a whole and were also lower than those of the 370 infants transported to this hospital for intensive care after delivery elsewhere. Whenever possible mothers with very high-risk pregnancies should be referred for delivery to centres with full facilities for the intensive care of the mother, fetus, and newborn infant.     

Attitudes to viability of preterm infants and their effect on figures for perinatal mortality.

OBJECTIVE--To examine how local attitudes to management of extreme preterm labour can influence data on perinatal mortality. DESIGN--One year prospective study in a geographically defined population. SETTING--The 17 perinatal units of Trent region. PATIENTS--All preterm infants of less than or equal to 32 weeks'' gestation in the Trent region. INTERVENTIONS--Infants who had been considered viable at birth were referred for intensive care; those who had been considered non-viable received terminal care. MAIN OUTCOME MEASURES--Whether each infant was born alive, dead, or alive but considered non-viable. RESULTS--Large differences were observed among units in the rates of delivery of infants of less than or equal to 27 weeks'' gestation (rates varied from 7.2 to 0 per 1000 births). These differences were not present in the data relating to infants of between 28 and 32 weeks'' gestation. The variation seemed to result from different approaches to the management of extreme preterm labour--that is, whether management took place in a labour ward or a gynaecology ward. CONCLUSIONS--Place of delivery of premature babies (less than or equal to 27 weeks'' gestation) may influence classification and hence figures for perinatal mortality. In addition, the fact that the onus of judgment regarding viability and classification is often placed on relatively junior staff might also affect the figures for perinatal mortality. The introduction of a standard recording system for all infants greater than 500 g would be advantageous.     

Prognosis for infants born at 23 to 28 weeks' gestation.

The survival and neurodevelopmental outcome of 356 extremely preterm infants born at 23 to 28 weeks'' gestation were reported by week of gestation. Their corrected 1 year survival improved from 7% at 23 weeks to 75% at 28 weeks. The overall incidence of impairment was 19% and of major disability 12%. Boys had a significantly lower normal survival than girls. Multiple births had a significantly lower survival and higher incidence of impairment than singleton births. Predictions of outcome were made before delivery, after resuscitation, and at 1 week to aid the development of guidelines on when perinatal intensive care is justified, whether obstetric intervention for fetal reasons is warranted, and what initial and ongoing prognoses to give to parents. Intensive care for progressively smaller and more immature infants, many of whom were previously considered non-viable, needs to be carefully monitored by every perinatal centre.     

Acute Histologic Chorioamnionitis Is a Risk Factor for Adverse Neonatal Outcome in Late Preterm Birth after Preterm Premature Rupture of Membranes

Background

The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.

Methodology/Principal Findings

The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.

Conclusions/Significance

The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.     

Short term outcome in babies refused perinatal intensive care.

OBJECTIVE--To compare the mortality in babies refused admission to a regional perinatal centre with that in babies accepted for intensive care in the centre. DESIGN--Retrospective study with group comparison. SETTING--Based at the Royal Maternity Hospital, Belfast, with follow up of patients in all obstetric units in Northern Ireland. PATIENTS--Requests for transfer of 675 babies to the regional perinatal centre (prenatally and postnatally) were made from hospitals in Northern Ireland between January 1984 and December 1986. In all, 343 babies were refused admission to the centre, and complete data were available for 332 of them. These babies were either admitted to other neonatal intensive care units (261 babies) or remained in hospitals with only special care cots (71 babies). MAIN OUTCOME MEASURE--Short term mortality. RESULTS--Seventy of the 332 babies refused admission to the centre died compared with 51 of the 333 who were admitted. Multivariate analysis based on a logistic model showed a non-significant increase in mortality among babies treated in other intensive care units compared with babies treated in the centre (relative odds 1.2; 95% confidence interval 0.7 to 1.9). The increase in mortality in babies who remained in a special care baby unit, however, was significant (3.5; 1.7 to 7.0). This increase was particularly significant in babies born at less than or equal to 32 weeks'' gestation and who weighed less than 1500 g (8.4; 2.5 to 28.1). CONCLUSIONS--The results of the study confirm the benefits of neonatal intensive care and its particular value in improving survival in babies of low birth weight. As the babies were refused admission to the regional perinatal centre because intensive care cots were not available this deficiency should be corrected.     

Outcome of breech delivery at term.

OBJECTIVE--To compare neonatal mortality and morbidity in term infants presenting by the breech and delivered vaginally or by caesarean section. DESIGN--Population based comparison of outcomes. Data derived from the St Mary''s maternity information system. SETTING--North West Thames Regional Health Authority, 1988-90. SUBJECTS--3447 singleton fetuses presenting by the breech at term. MAIN OUTCOME MEASURES--Intrapartum and neonatal mortality, low Apgar scores, intubation at birth, and admission to special care baby units. RESULTS--After the exclusion of babies with congenital anomalies the incidence of intrapartum and neonatal death associated with vaginal birth was 8/961 (0.83%) compared with 1/2486 (0.03%) in babies born by caesarean section (relative risk 20, 95% confidence interval 2.5 to 163). The numbers of low Apgar scores and neonatal intubation were doubled in babies born vaginally or by emergency caesarean section compared with those delivered by elective operation. CONCLUSIONS--The good neonatal outcome associated with elective caesarean delivery of the term breech fetus may influence the decision of women and their obstetricians about mode of delivery.     

Neonatal intensive care and cost effectiveness.

During the past decade the rate of death among newborns weighing less than 1500 g at birth has decreased by approximately half. This dramatic reduction has resulted from the application of research findings and technologic advances, but it has proved expensive. Perhaps as a consequence of articles demonstrating the costs as well as the recognition that the overall prevalence of disabilities in infants is relatively unchanged, neonatal intensive care has recently been viewed as a possible area for cost containment. We reviewed the literature on the cost of neonatal intensive care and the limited information on other expensive medical programs and found that the cost of neonatal intensive care compared favourably, especially for infants whose birth weight was 1000 to 1500 g. Better information on the outcome of infants of very low birth weight and comparable rigorous studies of the cost effectiveness of other expensive medical programs are required, and other less easily quantified factors must be considered before decisions are made to limit neonatal intensive care on the basis of gestational age or birth weight.     

Survival of extremely premature babies in a geographically defined population: prospective cohort study of 1994-9 compared with 2000-5

Objective To assess changes in survival for infants born before 26 completed weeks of gestation.Design Prospective cohort study in a geographically defined population.Setting Former Trent health region of the United Kingdom.Subjects All infants born at 22+0 to 25+6 weeks’ gestation to mothers living in the region. Terminations were excluded but all other births of babies alive at the onset of labour or the delivery process were included.Main outcome measures Outcome for all infants was categorised as stillbirth, death without admission to neonatal intensivecare, death before discharge from neonatal intensivecare, and survival to discharge home in two time periods: 1994-9 and 2000-5 inclusive.Results The proportion of infants dying in delivery rooms was similar in the two periods, but a significant improvement was seen in the number of infants surviving to discharge (P<0.001). Of 497 infants admitted to neonatal intensive care in 2000-5, 236 (47%) survived to discharge compared with 174/490 (36%) in 1994. These changes were attributable to substantial improvements in the survival of infants born at 24 and 25 weeks. During the 12 years of the study none of the 150 infants born at 22 weeks’ gestation survived. Of the infants born at 23 weeks who were admitted to intensive care, there was no significant improvement in survival to discharge in 2000-5 (12/65 (18%) in 2000-5 v 15/81 (19%) in 1994-9).Conclusions Survival of infants born at 24 and 25 weeks of gestation has significantly increased. Although over half the cohort of infants born at 23 weeks wasadmitted to neonatalintensive care, there was no improvement in survival at this gestation. Care for infants born at 22 weeks remained unsuccessful.     

The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study

Background

Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.

Methods and Findings

There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.

Conclusions

In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing. Please see later in the article for the Editors'' Summary     

Iodine Status of Preterm Infants Born in an Area of Iodine Sufficiency: Are They at Risk of Iodine Deficiency?

ObjectiveTo the assess the iodine status of preterm infants born in an area of iodine sufficiency using the urinary iodine concentration (UIC) and thyroid-stimulating hormone (TSH) levels and compare these values across different feeding practices during the first 7 days of life.MethodsIn this cross-sectional study, 88 preterm infants born at 30 to 34 weeks of gestation and admitted to the neonatal intensive care unit of a referral hospital in Tehran (Iran) were included. The infant UIC and TSH levels and breast milk iodine concentration in mothers who were exclusively breastfeeding were measured.ResultsMedian (interquartile range [IQR]) UIC and TSH levels in the study population were 81 (39-189) μg/L and 1.60 (0.80-2.85) mIU/L, respectively. When preterm infants were stratified by the type of feeding, the median (IQR) UICs were 64 (42-126) μg/L in parenteral nutrition, 125 (41-195) μg/L in exclusively breastfeeding, 57 (28-123) μg/L in formula feeding, and 45 (35-132) μg/L in mixed feeding, with no statistically significant difference between the groups (P = .31). The median (IQR) breast milk iodine concentration was 271 (177-521) μg/L in preterm infants exclusively fed their mothers’ own milk. There was no significant difference in the proportion of the TSH levels of >5 mIU/L between preterm infants who received enteral and parenteral nutrition (P = .27).ConclusionPreterm infants are at risk of iodine deficiency even in an area where the general population has adequate iodine. Only the preterm infants who received exclusively their mothers’ own milk had marginally adequate iodine status. Further studies are warranted to determine the necessity of iodine supplementation for this vulnerable group.     

Neonatal Mortality and Long-Term Outcome of Infants Born between 27 and 32 Weeks of Gestational Age in Breech Presentation: The EPIPAGE Cohort Study

Objective

To determine whether breech presentation is an independent risk factor for neonatal morbidity, mortality, or long-term neurologic morbidity in very preterm infants.

Design

Prospective population-based cohort.

Population

Singletons infants without congenital malformations born from 27 to 32 completed weeks of gestation enrolled in France in 1997 in the EPIPAGE cohort.

Methods

The neonatal and long-term follow-up outcomes of preterm infants were compared between those in breech presentation and those in vertex presentation. The relation of fetal presentation with neonatal mortality and neurodevelopmental outcomes was assessed using multiple logistic regression models.

Results

Among the 1518 infants alive at onset of labor included in this analysis (351 in breech presentation), 1392 were alive at discharge. Among those eligible to follow up and alive at 8 years, follow-up data were available for 1188 children. Neonatal mortality was significantly higher among breech than vertex infants (10.8% vs. 7.5%, P = 0.05). However the differences were not significant after controlling for potential confounders. Neonatal morbidity did not differ significantly according to fetal presentation. Severe cerebral palsy was less frequent in the group born in breech compared to vertex presentation but there was no difference after adjustment. There was no difference according to fetal presentation in cognitive deficiencies/learning disabilities or overall deficiencies.

Conclusion

Our data suggest that breech presentation is not an independent risk factor for neonatal mortality or long-term neurologic deficiencies among very preterm infants.     

Outcome of infants of very low birth weight: a geographically based study.

The outcome of 143 live-born infants of very low birth weight (defined as less than 1500 g) who were born in 1980-81 to women resident in Newfoundland and Labrador is described. Sixty-one infants (43%) died during the first year of life. Of the 82 surviving infants 79 were followed for 18 months to 3 years. Eight (10%) were found to have evidence of severe neurodevelopmental abnormality, and nine (11%) were found to have various minor problems, including seizures, developmental delay and behavioural disorders. There was an inverse association between birth weight and mortality. Neonatal pneumothorax, seizures and clinical evidence of intraventricular hemorrhage were more commonly seen among infants who died; these factors also seemed to be predictive of an adverse long-term outcome. Continuous monitoring of the rates of death and disability among infants of very low birth weight born within a defined region should provide the basis for rational planning and delivery of neonatal intensive care.     

Latent anaphylactic sensitisation of infants of low birth weight to cows' milk proteins.

Latent systemic anaphylactic sensitisation to cows'' milk was assessed in 61 preterm infants who were randomly assigned to receive either a special formula for preterm infants based on cows'' milk or banked breast milk or one or other of these as a supplement to maternal milk. A single sample of venous blood was taken near to the time of discharge from the neonatal intensive care unit, and the histamine release by blood basophils in response to in vitro challenge with cows'' milk and anti-IgE was measured. Compared with the blood from infants fed on human milk, that from infants fed on preterm formula showed a significant increase in histamine release to challenge with cows'' milk, the response being greater in blood from infants of lower birth weight and gestational age. A smaller but significant increase in blood histamine release with anti-IgE challenge was observed in the group fed on preterm formula. Infants of low birth weight fed on preterm formula based on cows'' milk may develop latent systemic sensitisation more rapidly than infants born at term. The clinical importance of this requires further investigation.     

Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study

Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery.Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health.Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided dataParticipants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage).Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics.Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective.Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.     

Reducing Neonatal Mortality in India: Critical Role of Access to Emergency Obstetric Care

Background

Neonatal mortality currently accounts for 41% of all global deaths among children below five years. Despite recording a 33% decline in neonatal deaths between 2000 and 2009, about 900,000 neonates died in India in 2009. The decline in neonatal mortality is slower than in the post-neonatal period, and neonatal mortality rates have increased as a proportion of under-five mortality rates. Neonatal mortality rates are higher among rural dwellers of India, who make up at least two-thirds of India''s population. Identifying the factors influencing neonatal mortality will significantly improve child survival outcomes in India.

Methods

Our analysis is based on household data from the nationally representative 2008 Indian District Level Household Survey (DLHS-3). We use probit regression techniques to analyse the links between neonatal mortality at the household level and households'' access to health facilities. The probability of the child dying in the first month of birth is our dependent variable.

Results

We found that 80% of neonatal deaths occurred within the first week of birth, and that the probability of neonatal mortality is significantly lower when the child''s village is closer to the district hospital (DH), suggesting the critical importance of specialist hospital care in the prevention of newborn deaths. Neonatal deaths were lower in regions where emergency obstetric care was available at the District Hospitals. We also found that parental schooling and household wealth status improved neonatal survival outcomes.

Conclusions

Addressing the main causes of neonatal deaths in India – preterm deliveries, asphyxia, and sepsis – requires adequacy of specialised workforce and facilities for delivery and neonatal intensive care and easy access by mothers and neonates. The slow decline in neonatal death rates reflects a limited attention to factors which contribute to neonatal deaths. The suboptimal quality and coverage of Emergency Obstetric Care facilities in India require urgent attention.     

Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies

Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions.Design Systematic review of controlled studies published 1985-2002.Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls.Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality.Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm (< 32 weeks) and 2.04 (1.80 to 2.32) for preterm (< 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight (< 1500 g), 1.70 (1.50 to 1.92) for low birth weight (< 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends.Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.     

Confidential paediatric inquiry into neonatal deaths in Wessex, 1981 and 1982.

From 1 January 1981 to 31 December 1982, 66 256 births and 386 neonatal deaths were recorded in the Wessex Regional Health Authority, giving a neonatal mortality of 5.8/1000 live births. An experienced consultant paediatrician undertook a confidential inquiry into each death shortly after it had been reported. One hundred and forty four deaths (37%) were found to be due to lethal or severe malformations, an incidence of 2.2/1000 births. Of the 242 normally formed infants, 111 (46%) died within 24 hours of birth. Seventy seven (32%) weighed over 2500 g at birth. Factors operating before delivery accounted for 104 (43%) of the deaths of normally formed infants. The commonest factors were short gestation and low birth weight, and intrauterine hypoxia and birth injury. Factors after delivery accounted for 81 deaths (33%), the commonest being infections and sudden infant deaths. In the remaining 57 deaths (24%) it seemed that a combination of factors before and after birth had led to the death. Factors before birth thus played a part in two thirds of all deaths. Possible adverse factors in medical care were sought in 154 potentially viable babies and were identified in 38--that is, 10% of all neonatal deaths. Better provision and training of district staff in immediate care at birth would achieve more in lowering neonatal mortality in Wessex than the setting up of a regional unit specializing in advanced neonatal intensive care. Moreover, the greatest scope for improving the outcome of childbirth in Wessex would be offered if there were further advances in obstetric rather than neonatal care.