Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish tertiary care centres. Part 2: infant survival.

AIM: To determine neonatal survival rates based on both foetal (stillborn) and neonatal deaths among infants delivered at 23-25 wk, and to identify maternal and neonatal factors associated with survival. METHODS: The medical records of 224 infants who were delivered in two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Data were analysed by gestational age groups and considered in three time periods. Logistic regression models were used to identify factors associated with survival. RESULTS: The rate of foetal death was 5%. Of infants born alive, 63% survived to discharge. Survival rates including foetal deaths in the denominator at 23, 24 and 25 wk were 37%, 61% and 74%, respectively, and survival rates excluding foetal deaths were 43%, 63% and 77%, respectively. Of infants born with 1-min Apgar scores of 0-1, 43% survived. In the total cohort, survival rates including foetal deaths in the denominator increased from 52% in time period 1 to 61% in time period 2 and 74% in time period 3 (p < 0.02). On multivariate logistic regression analysis, higher birthweight (OR: 1.91 per 100 g increment; 95% CI: 1.45-2.52), female gender (OR: 3.33; 95% CI: 1.65-6.75), administration of antenatal steroids (OR: 2.95; 95% CI: 1.46-5.98) and intrauterine referral from a peripheral hospital (OR: 2.35; 95% CI: 1.18-4.68) were associated with survival. Apgar score < or = 3 at 1 min (OR: 0.46; 95% CI: 0.22-0.95) was associated with decreased survival. The use of antenatal steroids was protective at 23-24 wk (OR: 5.2; 95% CI: 2.0-13.7), but not at 25 wk. CONCLUSIONS: Active perinatal management that included universal initiation of neonatal intensive care virtually eliminated intrapartum stillbirths and delivery room deaths, and resulted in survival rates that compare favourably with those of recent studies. However, the policies of active care postponed death in non-survivors. Individual variations in outcome in relation to the infant's condition at birth as reflected by the Apgar scores preclude the making of treatment decisions in the delivery room.

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish perinatal centres. Part 3: neonatal morbidity.

AIM: To determine major neonatal morbidity in surviving infants born at 23-25 weeks, and to identify maternal and infant factors associated with major morbidity. METHODS: The medical records of 224 infants who were delivered at two tertiary care centres in 1992-1998 were reviewed retrospectively. At these centres, policies of active perinatal and neonatal management were universally applied. Of the 213 liveborn infants, 140 (66%) survived to discharge. Data were analysed by gestational age and considered in three time periods. Logistic regression models were used to identify factors associated with morbidity. RESULTS: Of the survivors, 6% had intraventricular haemorrhage grade > or = 3 (severe IVH) or periventricular leukomalacia (PVL), 15% retinopathy of prematurity > or = stage 3 (severe ROP) and 36% bronchopulmonary dysplasia (BPD). On logistic regression analysis, severe IVH or PVL was associated with duration of mechanical ventilation (odds ratio, OR: 1.53 per 1-wk increment in duration; 95% confidence interval, CI: 1.01-2.33). Severe ROP was associated with the presence of a patent ductus arteriosus (PDA) (OR: 3.31; 95% CI: 1.11-9.90) and birth in time period 3 versus time periods 1 and 2 combined (OR: 6.28; 95% CI: 2.10-18.74). BPD was associated with duration of mechanical ventilation (OR: 2.71 per 1-wk increment in duration; 95% CI: 1.76-4.18) and with the presence of any obstetric complication (OR: 2.67; 95% CI: 1.07-6.65). Gestational age and birthweight were not associated with major morbidity. Of all survivors, 81% were discharged home without severe IVH, PVL or severe ROP. CONCLUSIONS: Increased survival as a result of active perinatal and neonatal management was associated with favourable morbidity rates compared with those in recent studies. Among survivors born at 23-25 weeks, neither gestational age nor birthweight was a significant determinant of major morbidity.

Short-term outcome after active perinatal management at 23-25 weeks of gestation. A study from two Swedish tertiary care centres. Part 1: maternal and obstetric factors.

AIMS: To provide descriptive data on women who delivered at 23-25 wk of gestation, and to relate foetal and neonatal outcomes to maternal factors, obstetric management and the principal reasons for preterm birth. METHODS: Medical records of all women who had delivered in two tertiary care centres in 1992-1998 were reviewed. At the two centres, policies of active perinatal and neonatal management were universally applied. Logistic regression models were used to identify prenatal factors associated with survival. RESULTS: Of 197 women who delivered at 23-25 wk, 65% had experienced a previous miscarriage, 15% a previous stillbirth and 12% a neonatal death. The current pregnancy was the result of artificial reproduction in 13% of the women. In 71%, the pregnancy was complicated either by pre-eclampsia, chorioamnionitis, placental abruption or premature rupture of membranes. Antenatal steroids were given in 63%. Delivery was by caesarean section in 47%. The reasons for preterm birth were idiopathic preterm labour in 36%, premature rupture of membranes in 41% and physician-indicated deliveries in 23% of the mothers. Demographic details, use of antenatal steroids, caesarean section delivery and birthweight differed between mothers depending on the reason for preterm delivery. Of 224 infants, 5% were stillbirths and 63% survived to discharge. On multivariate logistic regression analysis comprising prenatally known variables, reasons for preterm birth were not associated with survival. Advanced gestational duration (OR: 2.43 per wk; 95% CI: 1.59-3.74), administration of any antenatal steroids (OR: 2.21; 95% Cl: 1.14-4.28) and intrauterine referral from a peripheral hospital (OR: 2.93; 95% CI: 1.5-5.73) were associated with survival. CONCLUSIONS: Women who deliver at 23-25 wk comprise a risk group characterized by a high risk of reproductive failure and pregnancy complications. Survival rates were similar regardless of the reason for preterm birth. Policies of active perinatal management virtually eliminated intrapartum stillbirths.

Cognitive function at 10 years of age in children who have required neonatal intensive care.

AIM: To study cognitive function at 10y of age in a cohort of children who required neonatal intensive care within the Uppsala Neonatal Follow-up Study. METHODS: 226 children, who were born in 1986-1989 and had required neonatal intensive care (NIC) and 72 full-term, healthy control children were enrolled in the study. NIC children were grouped according to gestational age (group I, 23-31 wk; subgroup IA, 23-27 wk; IB 28-31 wk; group II, 32-36 wk; group III, > 36 wk), with infants with congenital malformation (IWCM) included and excluded from the main groups. The Kaufman Assessment Battery for Children (K-ABC) was administered and results were analysed in relation to the K-ABC global scales: sequential, simultaneous, mental processing composite and achievement. RESULTS: The great majority of children had well-developed cognitive function, reaching scores at an average level or above. When groups were compared, full-term children that required NIC (group III) showed lower scores than controls on all scales measured by the K-ABC. Preterm children from all the studied groups (groups IA, IB, II) showed poorer performance than controls in the simultaneous processing scale, and group IA scored lower than controls in the achievement scale. The incidence of major cognitive impairment (IQ < 70) was low in NIC children (< 5%), but children from group IA showed significant higher frequency of impairment in the simultaneous, mental processing composite and achievement scales. Children from group IA presented a high frequency of discrepancy between the K-ABC scales, with lower simultaneous and higher sequential scores. Analysis with IWCM excluded from the main groups revealed identical results. CONCLUSION: Most children who needed neonatal intensive care had developed well their cognitive function at 10 y of age. The long-term effect of neonatal intensive care on cognitive function was more evident in extremely preterm infants (group IA), especially in tasks involving simultaneous ways of processing information.

Gender differences in outcome after neonatal intensive care: speech and language skills are less influenced in boys than in girls at 6.5 years.

AIM: To study language development at age 6.5 y in 230 children who had required neonatal intensive care (NIC) and 71 full-term neonatally healthy control children, all born in 1986-1989, with a focus on comparison between genders. METHODS: Eight aspects of spontaneous speech, 3 fine motor functions, 10 linguistic areas, Peabody Picture Vocabulary Test, and digit recall (ITPA) were assessed. RESULTS: Achievements for gender and gestational age groups were analysed (group I, 23-31 wk; subgroup IA, 23-27 wk; IB, 28-31 wk; group II, 32-36 wk; group III, >36 wk), with children with congenital malformations as a separate group. As a group, at 6.5 y NIC girls had more developed spontaneous speech than NIC boys, and performed better than NIC boys in some linguistic areas. NIC girls of group I had lower results than control girls in spontaneous speech aspects such as speech motor function, interaction and motivation, and in many areas of linguistic skills. In contrast, NIC boys of group I had higher results than control boys in auditory memory, and only regarding information and speech motor function in spontaneous speech were their results lower. Analysis of results of matched pairs of group I NIC girls versus control girls and group I NIC boys versus control boys revealed even more marked differences between NIC girls and their matched controls than between NIC boys and their matched controls. CONCLUSION: Language development in extremely or very preterm NIC boys seems to be less influenced than that in NIC girls by the need for and administration of NIC. The neonatal factors associated with low scores in girls are different from those in boys.

Antenatal terbutaline administration decreases the lung hyaluronan concentration in preterm rabbit pups.

OBJECTIVE: To determine whether antenatal exposure to terbutaline alters the lung hyaluronan concentration or lung water content at birth in preterm rabbit pups. STUDY DESIGN: Rabbit dams (n = 18) with timed pregnancies were injected with 30 microg terbutaline or saline (controls) one day before delivery at 27-29 days of gestation. Pups were killed immediately after delivery. Lung water content and hyaluronan concentrations were determined. RESULTS: Pups exposed antenatally to terbutaline had lower mean lung hyaluronan concentrations than control pups. Lung hyaluronan/dry lung weight was significantly lower in pups delivered at 28 (p = 0.034) or 29 days (p < 0.001), while lung hyaluronan/wet lung weight was significantly lower at all three gestational ages. CONCLUSION: Antenatal exposure to terbutaline lowers the lung hyaluronan concentration at birth in preterm (27-29 days) rabbit pups without altering the lung water content.

Effects of the inspiratory pressure waveform during patient-triggered ventilation on pulmonary stretch receptor and phrenic nerve activity in cats.

OBJECTIVE: To examine the effects of square wave, sinusoidal, and linear inspiratory pressure waveforms during pressure-controlled assist/control ventilation on the firing pattern of pulmonary stretch receptors and phrenic nerve activity. DESIGN: Experimental, comparative study. SETTING: Research laboratory at a university biomedical center. SUBJECTS: Nine anesthetized, endotracheally intubated young cats (2.5-3.4 kg). INTERVENTION: With interposed periods of continuous positive airway pressure (0.2 kPa), each cat was exposed to periods of assist/control ventilation with three different pressure waveforms, where the peak inspiratory pressure (0.74 +/- 0.13 kPa), end-expiratory pressure (0.2 +/- 0.02 kPa), and tidal volume (14.9 +/- 5.22 mL/kg) were kept constant. Preset controlled ventilator rate was set below the rate of spontaneous breathing, and the mechanical inflation time equaled the inspiratory time during spontaneous breathing on continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS: Respiratory rate and arterial blood gases did not change between the three pressure waveforms during assist/control ventilation. Peak pulmonary stretch receptor activity was lower and mean phrenic nerve activity higher during continuous positive airway pressure than during assist/control ventilation (p <.05). Peak inspiratory pulmonary stretch receptor activity was the same with all three pressure waveforms (82 +/- 17 impulses.sec-1) but occurred earlier with square wave than with sinusoidal or linear pressure waveforms (p <.05). The total number of impulses in the phrenic nerve activity burst was smaller with square wave than with the other two pressure waveforms (0.21 +/- 0.17 vs. 0.33 +/- 0.27 and 0.42 +/- 0.30 arbitrary units; p <.05), and the phrenic nerve activity burst duration was shorter with square wave (1.10 +/- 0.45 vs. 1.54 +/- 0.36 and 1.64 +/- 0.25 secs; p <.05). CONCLUSION: Square wave pressure waveform during pressure-controlled assist/control ventilation strongly inhibits spontaneous inspiratory activity in cats. One mechanism for this inhibition is earlier and sustained peak pulmonary stretch receptor activity during inspiration. These findings show that differences in inspiratory pressure waveforms influence the spontaneous breathing effort during assist/control ventilation in cats.

Antenatal betamethasone administration decreases the lung hyaluronan concentration in preterm rabbit pups.

Maternal treatment with corticosteroids before preterm delivery is effective in reducing the incidence of respiratory distress syndrome and neonatal mortality. We hypothesized that corticosteroids might lower the lung hyaluronan concentration. Twenty-five rabbit dams (term = 31 d) with timed pregnancies were injected s.c. with 0.75 mg of betamethasone or saline (controls) 1 d before delivery. In addition, two dams delivered at 25 d of gestation were injected with 0.75 mg of betamethasone on two consecutive days before delivery. A total of 238 live pups were delivered by preterm cesarean section at 25, 27, 28, or 29 d of gestation and killed immediately. Their lung hyaluronan concentrations were measured with a radiometric assay, and wet/dry lung weight ratios were determined. Lungs of rabbit pups exposed antenatally to betamethasone and delivered at 25 or 27 d of gestation, but not at 28 or 29 d, displayed significantly (p = 0.001 and p = 0.008, respectively) lower hyaluronan concentrations than control pups, accompanied by less intense subepithelial staining for hyaluronan in alveolar walls. There was no significant difference in wet/dry lung weight ratio between pups exposed to one dose of betamethasone and controls. Antenatal corticosteroid exposure lowers the lung hyaluronan concentration in preterm rabbit pups delivered at 25 or 27 d of gestation, but not in those delivered at 28 or 29 d.

Spontaneous speech at 6 1/2 years of age in children who required neonatal intensive care in 1986-1989.

UNLABELLED: Spontaneous speech at 6 1/2 y of age was studied in a follow-up of 230 children born in 1986-89 who had required neonatal intensive care (NIC) and 71 fullterm neonatally healthy control children. Eight aspects of spontaneous speech were examined: Information, speech motor function, sound pattern, word finding, word selection, grammar, interaction and motivation. The results were analysed in relation to gestational age groups (group I, 23-31 wk; subgroup IA, 23-27 wk; IB, 28-31 wk; group II, 32-36 wk; group III, >36 wk) and a separate group of children with congenital malformations (IWCM). Between 66.7% (group IA) and 55.7% (group III) had no obvious deviations in any aspect of spontaneous speech compared with 80.3% of controls. Children born at <32 wk of gestation (group I) had few pronounced deviations in speech motor function or formal aspects of spontaneous speech. No ability, or hardly any ability, in an aspect of spontaneous speech was only found in children born at >32 wk. Deviations in prosody and poor facial expressions accompanying spontaneous speech were more common in group I than in controls. CONCLUSION: Most children who needed intensive care neonatally had well-developed spontaneous speech.

Linguistic skills at 6 1/2 years of age in children who required neonatal intensive care in 1986-1989.

UNLABELLED: Linguistic skills at 6 1/2 y of age, corrected for gestational age at birth, were examined in a cohort of 230 children who had required neonatal intensive care (NIC) in 1986-89, and in 71 fullterm neonatally healthy control children (C) matched to the NIC children born at < 32 gestational weeks. Ten linguistic areas were assessed. The 10th percentile score of the controls was identified in each linguistic area and used for comparisons. In 77.5% of the controls and 63.5% of the NIC children, no score was lower than the 10th percentile score of the controls. Scores lower than the 10th percentile score were more common in NIC children born at term or at 23-31 wk, and within this group of children those born at 23-27 wk, than in controls. CONCLUSION: In preterm children of < 32 wk the results in the linguistic areas of imitation of articulatory positions, comprehension of logical grammatical constructions, phonemes and word fluency differed from those of the matched controls, and in NIC children born at > or = 32 weeks the results for imitation of articulatory positions, articulatory patterns and sentences, auditory discrimination and word fluency were poorer than those of the controls.

Brain water and proton magnetic resonance relaxation in preterm and term rabbit pups: their relation to tissue hyaluronan.

The present study was performed to investigate simultaneously total brain water, T1 and T2 relaxation times, and hyaluronan (HA) in fetal and neonatal rabbits. Attempts were also made to establish the relationship of HA to total brain water and to T2-derived motionally distinct water fractions, since HA is known to bind water and to limit tissue water mobility. Experiments were carried out in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 days and at a postnatal age of 4 days. The brain tissue water content (desiccation method), T1 and T2 relaxation times (H1-NMR method), and HA concentration (radioassay HA 50) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T2 relaxation curves. Compared with values in newborn pups, water and HA contents were found to be highly elevated in the preterm brain and decreased markedly during early postnatal life. The trends and time courses of T1 and T2 relaxation times proved to be similar, but the postnatal decrease in T2 was preceded by a significant decline in late gestation. Maturity-related changes occurred in the T2 relaxation derived bound water fraction which amounted to 4-19% of brain water. The bound water fraction appeared to be independent of total brain water and HA concentration, and HA is, therefore, unlikely to be the only factor controlling brain water mobility. The clear dissociation of bound water fraction from total water suggests restructuring of brain water during the perinatal period.

Lung water and proton magnetic resonance relaxation in preterm and term rabbit pups: their relation to tissue hyaluronan.

The present study was performed to investigate simultaneously total lung water, T(1) and T(2) relaxation times, and hyaluronan (HA) in preterm and term rabbits. Attempts were also made to establish the relationship of HA to total lung water and to T(2)-derived motionally distinct water fractions. Experiments were performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation method), T(1) and T(2) relaxation times (H(1)-NMR method), and HA concentration (radioassay) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T(2) relaxation curves. Lung water content and T(1) and T(2) relaxation times were highest at a gestational age of 27 d and then declined steadily during the whole study period. Similar trends and time courses were seen for the fast and slow components of the T(2) relaxation curve. The T(2)-derived free water fraction remained unchanged at a gestational age of 25-29 d ( approximately 67%), but increased progressively to a value of 78.5 +/- 7.9% at 31 d (p < 0. 001) and to 83.4 +/- 9.4% at the postnatal age of 4 d (p < 0.01). Opposite changes occurred in the bound water fraction. Lung HA concentration decreased with advancing gestation from 870.8 +/- 205.2 microg/g dry weight at 25 d to 162.6 +/- 32.4 microg/g dry weight at 31 d (p < 0.001), but it was increased 2-fold postnatally. HA correlated positively with total lung water (r = 0.39; p < 0.001) but not with the bound water fraction. It is suggested that the physiologic lung dehydration is associated with macromolecule-related reorganization of lung water and that the role of HA in this process needs to be further investigated.

Photoplethysmography for simultaneous recording of heart and respiratory rates in newborn infants.

Ten newborn infants, born at 25-41 wk of gestation and nursed in a neonatal intensive care unit or in a neonatal intermediate care unit, underwent monitoring of heart and respiratory rates with a new technique using an optical sensor, 0-60 d postnatally. The aim of this study was to compare the heart and respiratory rates recorded in infants by photoplethysmography with a probe positioned on three monitoring sites, namely the leg, buttock and interscapular region, with the rates recorded by ECG and transthoracic impedance, respectively. The recordings were compared in order to determine which individual heart beats and respiratory cycles were recorded with one or both relevant techniques. A high degree of association (r =0.99) was found between the respiratory rates recorded by photoplethysmography and by transthoracic impedance. Recordings of heart rates by ECG were also highly associated with the photoplethysmographic rates as measured at two (r = 0.99) of the three monitoring sites. It is concluded that heart and respiratory rates in infants can be monitored satisfactorily by the new method based on photoplethysmography. This method offers the advantage of recording several physiological parameters non-invasively with a single probe during the neonatal period.

Speech and language skills in children who required neonatal intensive care: evaluation at 6.5 y of age based on interviews with parents.

Speech and language skills at 6.5 y of age were studied in a follow-up of a cohort of children who had required neonatal intensive care (NIC) at Uppsala University Children's Hospital. An interview with the parents indicated that preterm and full-term NIC children were older than control children when they reached certain stages in language development (short sentences, intelligible speech). Absence of babbling was more common in NIC children born at 23-27 wk than in other preterm NIC children, and occurrence of stuttering was more commonly noticed in preterm NIC children born at 23-27 wk than in those born at >32 wk and controls.

Assisted mechanical ventilation using combined elastic and resistive unloading in cats with severe respiratory failure: effects on gas exchange and phrenic nerve activity.

This study tests the efficacy of respiratory mechanical unloading as a mode of assisted mechanical ventilation in cats with an intact breathing-control system but severe pulmonary parenchymal injury. Twelve anaesthetized, intubated cats received multiple saline lung lavages so that their total respiratory system compliance decreased from 56.1+/-10.4 to 26.8+/-6.8 ml/kPa (p < 0.001) and their PaO2 fell to 12.38+/-4.71 kPa when 100% O2 was used as inspired gas. They were then exposed to three consecutive 15-min periods of CPAP of 0.5 kPa, respiratory unloading and again CPAP of 0.5 kPa. Unloading was applied with end-expiratory pressure of 0.5 kPa, elastic assistance of 0.03 kPa/ml and resistance compensation of 2.0 kPa/l/s. Arterial blood gases for the CPAP baselines did not differ significantly before and after unloading: pH 7.14+/-0.04 vs. 7.16+/-0.06; PaCO2 8.99+/-2.07 vs. 8.33+/-2.01 kPa; PaO2 12.4+/-4.7 vs. 13.3+/-7.6 kPa. Nor did the baselines differ in terms of tidal volume, respiratory rate and phrenic nerve activity. Unloading increased tidal volume substantially by about 50% and increased respiratory rate slightly, while inspiratory time remained unchanged. PaCO2 fell to 6.63+/-1.57 kPa and pH rose to 7.25+/-0.06. Phrenic nerve activity was significantly down-regulated in terms of total number of impulses and mean impulse frequency in the phrenic nerve burst. These results suggest that combined elastic and resistive unloading may be an effective means of assisted mechanical ventilation in severe respiratory failure of pulmonary parenchymal origin.

Short-term outcome of perinatal care in a Swedish county. Mortality, neonatal intensive care and overall evaluation of neuromotor function at 0-10 months of corrected age in preterm and term infants.

Improvements in obstetrical and neonatal care during the last decades have led to a marked increase in survival rate of preterm and term infants. In order to study the short- and long-term outcome in infants who survived neonatal intensive care (NIC) and were born in the county of Uppsala between January 1st 1986 and April 30th 1989, a prospective long-term follow-up study was conducted. Epidemiological data on all infants born in the county during the study period and the short-term outcome, measured as overall neuromotor function at term and at 2, 4, 6 and 10 months of corrected age in 245 infants surviving NIC and 72 healthy control infants are presented. The infants' neuromotor function was evaluated with different clinical neurological methods. In the study population of NIC infants 85.9% survived the neonatal period. The early infant mortality was high in this group 11.6% compared to that of all infants born in the county of Uppsala (0.30%). Only a minority of the infants showed abnormal neuromotor function. A comparison of the results of the overall evaluation of neuromotor function at 10 months of age with those of the examinations made at an earlier age showed poor correspondence in individual infants, especially in preterm and very preterm infants.