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.     

Assessment of Fetal Lung Maturity by Estimation of Amniotic Fluid Palmitic Acid

The measurement of palmitic acid in amniotic fluid has been shown to be a rapid means of assessing the lecithin concentration. The level of palmitic acid increases quickly when the fetal lung matures at about 35 weeks'' gestation, and the level in amniotic fluid obtained 24 hours or less before delivery clearly distinguishes which infants are likely to develop respiratory distress syndrome and which are mature.     

Changing prognosis for babies of less than 28 weeks' gestation in the north of England between 1983 and 1994. Northern Neonatal Network.

OBJECTIVE: To investigate the changing prognosis for babies of less than 28 weeks'' gestation. DESIGN: A prospective, collaborative, population based survey. SETTING: The former Northern Regional Health Authority. SUBJECTS: All the births between 1983 and 1994 at 22 to 27 completed weeks'' gestation to women normally resident in the region. MAIN OUTCOME MEASURES: Miscarriage, stillbirth, death in the first year of life, and disability in survivors. RESULTS: There were 479070 registered births in the study period. No baby of 22 weeks'' gestation survived; only eight (4%) of the 197 babies of 23 weeks who were alive at the onset of labour survived for a year-a proportion that did not change during the study period. Survival among other babies of less than 28 weeks improved progressively between 1983-6 and 1991-4, but administration of artificial surfactant to babies requiring ventilation from mid-1990 was associated with further improvement in survival only in those over 25 weeks'' gestation. Babies of 24 weeks required three times as much high dependency care per survivor as babies of 27 weeks (76 v 26 days). The rate of severe disability in the one year survivors of less than 26 weeks'' gestation (30/123; 24%) was similar to that seen in the sampled survivors of 26 and 27 weeks (29/108; 27%); the proportion disabled did not change significantly during the study period. All the children born in 1983, 1987, and 1991 were later reassessed in greater detail: 10% (13/136) seemed destined for a continuing life of total dependency. CONCLUSIONS: Gestation, if accurately assessed, can give a woman facing very preterm delivery a clear indication of the prognosis for her baby and help her judge the appropriateness of accepting obstetric intervention and sustained perinatal support.     

Continuous-flow plasmapheresis in management of severe rhesus disease.

Eight patients with severe rhesus disease and expected fetal loss were treated by intensive plasmapheresis using a continuous-flow cell separator. Plasmapheresis was started at 16-27 weeks'' gestation, and continued until planned intrauterine transfusion or until the infant was delivered or the rhesus disease became uncontrolled again. Altogether 24 to 2371 of plasma was exchanged over periods ranging from seven to 16 weeks. In seven of the eight patients the anti-D concentration fell during the period of plasmapheresis. Amniotic fluid spectrophotometry values remained below those recorded in the preceding pregnancy in six out of seven women. In five patients an attempt was made to control the rhesus disease by plasmapheresis alone, and two of these women delivered infants who survived. In the other three cases the infants died, one from the idiopathic respiratory distress syndrome and the other two in utero. These preliminary findings suggest that intensive plasmapheresis with a cell separator may reduce fetal haemolysis is delivered. Nevertheless, plasmapheresis may best be used to reduce haemolysis until intrauterine transfusions may be given more safely after 30 weeks'' gestation.     

Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies.

Forty four babies, of less than 32 weeks'' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks'' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles.     

Elective delivery and the neonatal respiratory distress syndrome.

A prospective study was carried out to determine how often moderate or severe respiratory distress syndrome in infants delivered electively after 32 weeks'' gestation or more is avoidable. During a 9-month period 64 such newborns were evaluated. The disease was considered avoidable in 14 (22%) since the indication for elective delivery was questionable. The mean birth weight and gestational age of these 14 infants were 2550 +/- 430 g and 36.3 +/- 1.7 weeks, and the mortality was 14%. This study demonstrated that elective delivery can produce severe neonatal complications, that despite their availability diagnostic tests of fetal age and maturity of the fetal lungs are not being used universally, and that the indications for elective delivery in cases of premature rupture of the membranes must be re-evaluated.     

Neonatal risk factors for cerebral palsy in very preterm babies: case-control study.

OBJECTIVE: To identify neonatal risk factors for cerebral palsy among very preterm babies and in particular the associations independent of the coexistence of antenatal and intrapartum factors. DESIGN: Case-control study. SETTING: Oxford health region. SUBJECTS: Singleton babies born between 1984 and 1990 at less than 32 weeks'' gestation who survived to discharge from hospital: 59 with cerebral palsy and 234 randomly selected controls without cerebral palsy. MAIN OUTCOME MEASURES: Adverse neonatal factors expressed as odds ratios and 95% confidence intervals. RESULTS: Factors associated with an increased risk of cerebral palsy after adjustment for gestational age and the presence of previously identified antenatal and intrapartum risk factors were patent ductus arteriosus (odds ratio 2.3; 95% confidence interval 1.2 to 4.5), hypotension (2.3; 1.3 to 4.7), blood transfusion (4.8; 2.5 to 9.3), prolonged ventilation (4.8; 2.5 to 9.0), pneumothorax (3.5; 1.6 to 7.6), sepsis (3.6; 1.8 to 7.4), hyponatraemia (7.9; 2.1 to 29.6) and total parenteral nutrition (5.5; 2.8 to 10.5). Seizures were associated with an increased risk of cerebral palsy (10.0; 4.1 to 24.7), as were parenchymal damage (32; 12.4 to 84.4) and appreciable ventricular dilatation (5.4; 3.0 to 9.8) detected by cerebral ultrasound. CONCLUSION: A reduction in the rate of cerebral palsy in very preterm babies requires an integrated approach to management throughout the antenatal, intrapartum, and neonatal periods.     

Changing overall workload in neonatal units.

An epidemiological study was carried out in the current Nottingham health district to determine changes in both neonatal unit workload and in the infants requiring neonatal care during two study periods. All admissions for 1977 and again for the 12 months 1 April 1983 to 31 March 1984 were reviewed. Total numbers of admissions have shown roughly a 50% reduction because of a more rigorous admission policy locally. The admissions of infants of 33 weeks'' gestation or less have shown a significant increase, while the overall survival of infants less than 33 weeks'' gestation has improved.     

Incidence and duration of lactation and lactational performance among mothers of low-birth-weight and term infants.

The lactation experience of 55 mothers of 62 infants of low birth weight (2500 g or less) was prospectively compared with that of 55 mothers of 55 control infants (38 weeks'' gestation or more, birth weight more than 2500 g) born at the same institution. The incidence rates of lactation at delivery were 73% for the control group and 58% for the low-birth-weight group; 11% of the infants of low birth weight fed breast milk were never put to the breast. The mean age at first suckling was 277.3 hours in the low-birth-weight group, compared with 3.3 hours in the control group (p less than 0.0005). At first suckling 81% of the low-birth-weight infants and 25% of the control infants sucked poorly or refused the breast (p less than 0.001). At discharge 65% of the breast-milk-fed control infants were exclusively breast-fed, compared with 3% of the low-birth-weight infants fed breast milk (p less than 0.001). The incidence rates of lactation over time were similar in the control and low-birth-weight groups (51% v. 44% at 1 month, 29% v. 13% at 3 months, 13% v. 4% at 6 months and 4% v. 2% at 12 months). The mean duration of lactation was 3.2 months for the control group and 2.5 months for the low-birth-weight group. In the long term 37% of the low-birth-weight infants fed breast milk failed to breast-feed, compared with 2% of the control infants, and only 31% were exclusively breast-fed, compared with 85% of the control infants (p less than 0.001). However, the degree of satisfaction with the lactation experience was similar in the two groups. We conclude that mothers of low-birth-weight infants have good potential for lactation.     

Postnatal thyroxine administration for idiopathic respiratory distress syndrome in preterm infants

Thirty-six preterm infants of less than 34 weeks of gestation with idiopathic respiratory distress syndrome (IRDS) were studied. Eighteen of them were treated with intravenous thyroxine (T4) and compared with 18 control prematures to evaluate the effect of postnatal T4 administration on the course of IRDS. After treatment, serum T4 levels were similar to those of healthy term infants. No statistically significant effect on mortality rate, duration of mechanical ventilation (p greater than 0.3), need of high oxygen environment (p greater than 0.05) and development of bronchopulmonary dysplasia (p greater than 0.2) was observed between the two groups. These observations show that postnatal use of T4 does not carry any benefit for preterm infants with IRDS.     

Maternal and fetal nutrition in south India.

The relation between the nutrition of the mother and that of her baby was assessed in a south Indian community where malnutrition is common and women do not smoke. Unselected mothers and their infants of over 37 weeks'' gestation were studied in two groups: those who paid for their care (150) and a poorer group who did not (172). There were significnat differences between the paying and non-paying groups in maternal triceps skinfold thickness, infant weight, and infant length. Overall there was a significant positive correlation between maternal triceps thickness and infant weight, length, and triceps and subscapular skinfold thickness. The correlation with the infant head circumference was less significant. These findings are further evidence that the nutrition of the mother has an important effect on the nutrition of her baby and that malnutrition is an important reason why Indian babies are lighter than European ones.     

Spontaneous preterm labour and delivery at under 34 weeks' gestation.

The management and outcome of 242 infants delivered between 26 and 34 weeks'' gestation in an obstetrical and neonatal regional referral centre as a result of spontaneous preterm labour were recorded prospectively. Results of the survey show that the decision to intervene and delay delivery will depend on the availability of neonatal intensive care facilities. Infants likely to require intensive neonatal care should be transferred in utero to a centre with these facilities. The use of steroids reduces the mortality of preterm infants. The maximum effect occurs between 30 and 32 weeks'' gestation, and there is no benefit after 34 weeks. If the weight is over 1500 g the mode of delivery of the preterm infant presenting by the breech does not influence outcome; if under 1500 g a caesarean section improves survival over those infants born by vaginal breech delivery.     

Formation of prostacyclin (PGI2) by the ductus arteriosus of fetal lambs at different stages of gestation

Prostaglandins appear to play a role in maintaining patency of the ductus arteriosus during gestation. Prostacyclin (PGI₂) is the major product of prostaglandin biosynthesis in the lamb ductus arteriosus. This factor is both a vasodilator and a potent inhibitor of human platelet aggregation. We used inhibition of platelet aggregation as a sensitive bioassay to measure PGI₂ generation in rings of ductus arteriosus from fetal lambs. Mechanical manipulation accelerated the rate of PGI₂ released from the tissue 10 to 50 times. Tranylcypromine, an antagonist of prostacyclin synthetase, suppressed production of PGI₂ by rings of ductus arteriosus. Rings from immature animals (98–103 days gestation, term is 150 days) released significantly more PGI₂ (190 ± 28 ng/g wet weight/ 20 min, n=9) than did those from near term animals (136–146 days; 106 ± 23 ng/g wet weight/20 min, n=10). The capacity of the ductus arteriosus to generate more PGI₂ earlier in gestation is consistent with the observation that vessels from animals less than 110 days gestation have a significantly larger indomethacin induced contraction than do vessels near term.     

Contribution of twin pregnancy to perinatal mortality and fetal growth retardation; reversal of growth retardation after birth.

A survey of factors associated with perinatal mortality in 511 twins and fetal growth retardation and its reversal in 262 twins is presented. The incidence of stillbirth was almost 50% higher in twins than in singletons and the neonatal mortality was six times as high. Eighty percent of the neonatal deaths occurred in infants born prior to or at 30 weeks of gestation; 93% of the deaths were in infants weighing less than 1500 g and 75% occurred within 48 hours of birth. Fetal malnutrition was the main cause of stillbirth, and respiratory distress syndrome and asphyxia neonatorum were the main causes of neonatal death. One quarter of the twins had fetal growth retardation, a prevalence 10 times that in singletons. In almost all, the growth retardation was reversed by high-energy feedings. Although twins represented only 1% of all pregnancies and 2% of live births, they composed 12% of infants with early neonatal death and 17% of growth-retarded infants. A program is suggested for reduction of twin mortality and morbidity.     

A matched cohort comparison of the outcome of twin versus singleton pregnancies in Flanders, Belgium.

To compare perinatal outcome of singleton versus twin pregnancies a matched cohort study was performed in Flanders, Belgium. All twins delivered in the region of Flanders during 1998-1999 were compared to singletons, matched for gestational age, fetal sex and maternal parity, resulting in 4384 infants in each group. Above 32 weeks of gestation, birthweight was significantly lower in twins (2095 +/- 364 g versus 2315 +/- 523 g; p < 0.001, 95% confidence interval 193 to 246 g). Perinatal mortality was also significantly lower in twins (1.98% versus 1.26%; odds ratio for twins 0.63; 95% confidence interval 0.53-0.75; p < 0.001 ), this was mostly due to fetal and not to early neonatal mortality. Congenital malformations occurred less frequently in twins (2.5% versus 3.7%; odds ratio for twins 0.80, 95% confidence interval 0.69-0.92; p = 0.001). From gestational age of 32 weeks on, respiratory distress syndrome was less frequent in twins (6.7% versus 8.0%; odds ratio for twins 0.81; 95% confidence interval 0.68-0.97; p = 0.011 ). No significant differences were noted with regard to intraventricular haemorrhage, neonatal infections and retinopathy of prematurity. Although twins have a lower birthweight, their outcome is more favorable compared to singletons, when matched for gestational age.     

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.     

Maternal fatness and viability of preterm infants

To investigate the effect of maternal fatness on the mortality of infants born preterm up to the corrected age of 18 months 795 mother-infant pairs were studied. Maternal fatness was defined by Quetelet''s index (weight/(height²)) and all infants weighed less than 1850 g at birth. In 771 mother-infant pairs maternal age, complications of pregnancy, mode of delivery, parity, social class, and the baby''s sex and gestation were analysed by a logistic regression model for associations with infant mortality (but deaths from severe congenital abnormalities and those occurring during the first 48 hours after birth were excluded). In a subgroup of 284 mother-infant pairs all infant deaths except those from severe congenital abnormalities were analysed in association with the infant''s birth weight and gestation and the mother''s height and weight; this second analysis included another 24 infants who had died within 48 hours after birth. In the first analysis mortality overall was 7% (55/771), rising from 4% (71/173) in thin mothers (Quetelet''s index <20) to 15% (6/40) in mothers with grades II and III obesity (Quetelet''s index >30). After adjusting for major demographic and antenatal factors, including serious complications of pregnancy, maternal fatness was second in importance only to length of gestation in predicting death of infants born preterm. In the second analysis mortality overall was 15% (44/284), rising from 9% (5/53) in thin mothers to 47% (8/17) in mothers with grades II and III obesity. In both analyses the relative risk of death by 18 months post-term was nearly four times greater in infants born to obese mothers than in those born to thin mothers. In addition, maternal fatness was associated with reduced birth weight, whereas it is associated with macrosomia in term infants.These data differ fundamentally from those reported in full term babies of obese mothers. It is speculated that the altered metabolic milieu in obesity may reduce the ability of the fetus to adapt to extrauterine life if it is born preterm.     

Umbilical cord clamping and preterm infants: a randomised trial.

OBJECTIVE--To investigate the clinical effects of regulating umbilical cord clamping in preterm infants. DESIGN--A prospective randomised study. SETTING--The Queen Mother''s Hospital, Glasgow. SUBJECTS--36 vaginally delivered infants over 27 and under 33 weeks'' gestation. INTERVENTION--Holding the infant 20 cm below the introitus for 30 seconds before clamping the umbilical cord ("regulated" group, 17 patients), or conventional management ("random" group, 19 patients). MAIN OUTCOME MEASURES--Initial packed cell volume, peak serum bilirubin concentrations, red cell transfusion requirements, and respiratory impairment (assessed by ventilatory requirements, arterial-alveolar oxygen tension ratio over the first day in ventilated infants, and duration of dependence on supplemental oxygen). RESULTS--There were statistically significant differences between the two groups in mean initial packed cell volume (regulated group 0.564, random group 0.509) and median red cell transfusion requirements (regulated group zero, random group 23 ml/kg). 13 infants from each group underwent mechanical ventilation and showed significant differences in mean minimum arterial-alveolar oxygen tension ratio on the first day (regulated group 0.42, random group 0.22) and in median duration of dependence on supplemental oxygen (regulated group three days, random group 10 days). Differences in final outcome measures such as duration of supplemental oxygen dependence and red cell transfusion requirements were mediated primarily through arterial-alveolar oxygen tension ratio and also packed cell volume. CONCLUSIONS--This intervention at preterm deliveries produces clinical and economic benefits.     

Association between birth weight in preterm neonates and the BclI polymorphism of the glucocorticoid receptor gene

Endogenous and exogenous glucocorticoids influence fetal growth and development, and maternal administration of synthetic glucocorticoids may decrease the risk of perinatal morbidity including lung disease in preterm neonates. Because polymorphisms of the glucocorticoid receptor gene are known to influence the sensitivity to glucocorticoids, in the present study we examined whether any associations could exist among the BclI, N363S and ER22/23EK polymorphisms of the glucocorticoid receptor gene and gestational age, birth weight and/or perinatal morbidity of 125 preterm neonates born at 28-35 weeks' gestation with (n=57) or without maternal dexamethasone treatment (n=68). The prevalence of the three polymorphisms in the whole group of preterm infants was similar to that reported in healthy adult Hungarian population. However, we found that the BclI polymorphism significantly associated with higher birth weight adjusted for the gestational age (p=0.004, ANOVA analysis). None of the three polymorphisms showed an association with perinatal morbidities, including necrotizing enterocolitis, intraventricular hemorrhagia, patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia and sepsis in the two groups of preterm neonates with and without maternal dexamethasone treatment. These results suggest that the BclI polymorphism of the glucocorticoid receptor gene may have an impact on gestational age-adjusted birth weight, but it does not influence perinatal morbidities of preterm neonates.