Henry R. Rey

Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

Abstract: We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45,δ of −0.047 mg, p = 0.004; period B, days 45 to 50, δ of −0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, δ of —0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, δ of −0.072 mg, p = 0.001; period E, days 45 to 55, 5 of −0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level). A two-way analysis of variance indicated that the magnitude of the changes was related to both the time of onset and the duration of oligohydramnios. We conclude that even a short period of oligohydramnios interferes with lung development, and that the extent of this interference depends to a large extent on the time of onset and to a lesser extent on the duration of oligohydramnios. Irrespective of duration, the greatest effects were observed during the canalicular stage of lung development.

Patterns of development in fetal breathing activity in the latter third of gestation of the baboon

Patterns of fetal breathing activity were examined in a longitudinal study of the fetal baboon over the latter third of gestation. More than 1400 h of recorded tracheal fluid pressure in 16 or 24 h records from seven fetuses over a range in gestation from 121 to 172 days (term, 175-180 days) were analyzed. In these 81 records, there was a high degree of variability in the percent of time spent breathing by the fetuses (range, 14-83%) with no apparent influence of gestational age (mean +/- S.D., 45.6 +/- 17.6%). Nonetheless, the mean amplitude of fetal breaths increased with gestation from absolute values of about 5-10 mmHg (r = 0.73, P < 0.001) and the mean inspiratory time interval increased from about 0.45-0.55 s (r = 0.40, P < 0.001). During epochs of breathing, the mean rate decreased from about 42-36 breaths per min (r = -0.54, P < 0.001) and the indices of both short term (r = -0.54, P < 0.001) and long term (r = -0.73, P < 0.001) variability in rate decreased. These results demonstrate a clearly defined pattern of development in the breathing activity of the fetal baboon which is comparable to the pattern described for the human fetus in the third trimester of gestation. These similarities suggest that the progressive functional maturation of the mechanisms generating respiratory patterns are comparable among primate species.

Method for processing of fetal breathing epoch analysis: studies in the primate

An automated method for detecting fetal breathing and an analytic technique for providing significant data reduction that take the episodic nature of fetal breathing activity into account are described. The aim of the new technique, called epoch analysis, is to derive parameters of breathing and apnea that both summarize the activity and permit examination of its relationship to changes that occur naturally during day and night and with fetal maturation. The discussion covers: the acquisition of data from pregnant baboons; the breath detection process, for which a program was written; the recognition of breathing; computer recognition of artifacts; epoch characterization; validation of the methods of breath detection and epoch characterization; and application of the method. It is found that the technique has a broad capacity for data reduction and provides summaries of the activity that are amenable to analysis with standard statistical techniques.<<ETX>>

IMPACT OF FETAL HEART RATE MONITORING & BLOOD SAMPLING ON INFANT MORTALITY & MORBIDITY - ONGOING STUDY

Since the introduction of fetal monitoring (heart rate & acid base) 10 years ago, first on a research basis, then as an adjunct to clinical care, the proportion of patients being monitored during labor has increased to 70% (2,000 patients/year). Associated with this there has been a gradual reduction in morbidity as reflected by better Apgar scores and in mortality, for infants weighing 1000 g or more. The proportion of infants with a 1 min. Apgar score of 6 or less prior to monitoring averaged 25%; this has fallen to approximately 12%. There was a comparable improvement in the 5 min. Apgar score. Neonatal death rate has been reduced by almost 40% and perinatal mortality by approximately 10%. Furthermore, of infants requiring intensive care in the neonatal period, those who were monitored during labor were found to require a significantly shorter period in the ICU than those who were not monitored. This difference was even more striking when only infants above 2500 g were considered. Four factors appear to be of major importance in the acceptance and institution of monitoring: an adequate number of monitors maintained in good working order at all times; continuing education of the medical and nursing staff in the use of the equipment and interpretation of records; education of patients; services of a knowledgeable bioengineer and acid-base technician on a regular basis.

Computer Analysis of Ventilatory Parameters for Neonates on Assisted Ventilation

Karl Schulze, M.D. system, on the other hand, is to a quantitative accuracy is preserved Mark Stefanski, B. A. large extent controlled and can be without overwhelming the ability of Thomas Soulos, M.S. reasonably well characterized by exphysicians and nurses to assimilate Th,.omas Soulos, M.S. amining the parameters of the ventilaand analyze the information. In the Julia Masterson, M. S. tor pressure pulse. Optimal ventilafollowing report we describe and illusYoung 1. Kim, B. S. tory assistance requires a balance trate our approach to the acquisition,

497 FETAL CIRCADIAN RHYTHMS: CYCLES OF VASOPRESSIN (VP) LEVELS IN CEREBROSPINAL FLUID (CSF) NOT BLOOD

Besides classical effects on water balance and blood pressure, vasopressin has important functions in brain including modulation of behavioral processes and memory consolidation. In adult animals immunoactive VP in CSF exhibits a circadian pattern of release suggesting that the CSF may be a conduit for the effects of VP on diverse brain areas. To characterize the release of VP by the fetus, CSF was withdrawn continuously (1.0 ml/hr × 3 days) from the prechaismatic fossa of 5 chronically instrumented fetal sheep at 108 to 146 d gestation in 7 studies and plasma sampled intermittently (1.5 ml q 4h ×1 day) in 3 studies. Using a specific VP RIA,daily rhythms of VP in CSF were found for each fetus. Temporal profiles showed low levels of VP (12–25 pg/ml) during daylight alternating with high levels at night (30–45 pg/ml). Cycle length by frequency domain analysis was 22 to 24 hrs<. No similar fluctuations in plasma VP levels (2.1±1.0 pg/ml) were found. The amplitude of the CSF rhythms was increased (125 pg/ml) with chronic hypoxia, acute hemorrhage and in the days immediately preceding term delivery.We conclude that circadian rhythms of VP concentration in CSF but not plasma are present in the fetus during the final 25% of gestation. Changes in the amplitude and/or period of these rhythms may be important in the timing of parturition and the fetal response to suboptimal intrauterine condition.

317 EFFECT OF GLUCOSE ADMINISTRATION ON FETAL BREATHING ACTIVITY (FBA) IN THE BABOON - EPOCH ANALYSIS RESULTS

The relationship of breathing to other fetal activities was studied in 8 chronically catheterized pregnant baboons at 138-155 days of gestation following i.v. infusion of 25g of glucose to the mother. No significant changes in fetal heart rate (FHR), FHR variability and fetal or maternal blood pressure were observed during the infusion period.A computer based epoch analysis method was used to automatically detect fetal breaths from a tracheal fluid pressure signal, distinguish episodes of breathing activity from apnea and generate parameters to characterize FBA. Although the number of epochs of FBA was essentially unchanged and breathing rate and variability increased slightly with glucose infusion, significant decreases in other FBA parameters were observed: mean epoch duration decreased from 13.7 to 12.4 sec; median number of breaths per epoch fell from 12 to 6 while the % of time spent in FBA dropped from 20.6% to 10.8%. Finally, mean breathing amplitude also decreased from −8.3 to −6.7 mmHg.These results were unexpected. In human fetuses increases in plasma glucose have been associated with increased FBA. Our results may reflect variation among primate species. Nonetheless we noted that the direction of change in FBA parameters was consistent among all animals and suggests a need for study of the effect of maternal metabolic state on FBA.

39 BIRTH ASPHYXIA IN THE VERY LOW BIRTH WEIGHT INFANT (VLBW ≤ 1500 GRAMS): IMMEDIATE AND LONGITUDINAL (2 years) OUTCOME

The relationship of birth asphyxia (BA) to neonatal mortality & neurologic & developmental outcome at 2 yrs. of age was investigated in a large prospective study of infants with BW<1500 grams (N=525). BA was defined by an Apgar score of ≤3 at one minute &≤6 at 5 minutes. Multivariate analysis of the data included the following variables: BW, sex, socio-economic status (SES). BA, method of delivery, apnea, RDS & mechanical ventilation (MV). BA was significantly correlated with a higher neonatal mortality, more severe RDS, a greater need for MV, & neurologic & developmental outcome at 2 yrs. Indeed, BA was the only medical variable that was related to the mental development index (MDI) of the Bayley Scales. SES & sex were the most powerful correlates of MDI at 2 yrs. while none of the psycho-social variables were associated with neurologic outcome at 2 yrs. This study indicates the importance of BA on the immediate & long term outcome of the VLBW infant. It also provides evidence that it is inappropriate to assign an outcome index based on combining neuro-logic and developmental outcome. By 2 yrs. it appears that psycho-social & medical factors exert their influence relatively independently on separate systems. Medical factors impact most directly on neurologic outcome, while psycho-social variables influence developmental status. These 2 systems, while interactive, may be more independent than was thought.

303 A NEW METHOD FOR COMPUTER PROCESSING OF FETAL BREATHING ACTIVITY (FBA) BY EPOCH ANALYSIS

Current analytic methods including time and frequency domain approaches are often inadequate to fully characterize FBA. Because of its episodic nature and changing character with gestation, FBA does not lend itself to rigorous statistical analysis. To overcome this problem, we have developed an analytic approach which assumes that the activity occurs quasi-randomly during most of gestation, identifies episodes of activity (breathing) and non-activity (apnea) and characterizes the data within these epochs in a straightforward manner.Using a minicomputer, coded human ultrasonic or baboon tracheal fluid pressure data are digitized, pre-processed for removal of artefacts and breath detection. The distribution of detected breaths is used to identify epochs of FBA and to characterize each epoch with appropriate parameters, including duration, # of breaths, mean fetal breathing rate (FBR), FBR variability and mean breathing amplitude. Tabular and graphical outputs provide epoch by epoch results and summary statistics for a complete study.This approach offers several advantages: 1) data dependence making no assumptions about periodicities or character of breath-activity, 2) focus on the activities of interest while filtering out inherent variability and 3) systematic data reduction and application of standard statistical techniques to multiple recordings from any number of subjects.