Biomedical subjects
Publications and source records attributed to H McNamara.
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Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.
OBJECTIVE: The purpose of this study was to analyze cervical dilatation patterns among women with uterine rupture by means of a mathematic model and to use the results to determine optimal intervention criteria. STUDY DESIGN: This was a case-control review that compared a case patient group of 19 women with uterine rupture during labor with control groups with either no previous cesarean deliveries, vaginal birth after cesarean delivery, or failure of attempted vaginal birth after cesarean delivery. The mathematic model quantified dilatation and adjusted for conditions specific to each patient. Case patients were compared with matched control subjects by means of paired t tests, analysis of variance, odds ratios, and conditional logistic regression. RESULTS: Dystocia was present in 31.6% to 47.4% of patients with uterine rupture, versus 2.6% to 13.2% of the control group with no previous cesarean deliveries (P< or =.001). The incidence of an arrest disorder among patients with uterine rupture was similar to that seen in the control group with failure of attempted vaginal birth after cesarean delivery. However, the interval from diagnosis to rupture or cesarean delivery was 5.5 +/- 3.3 hours among case patients with uterine rupture and 1.5 +/- 1.3 hours in the control group with failure of attempted vaginal birth after cesarean delivery. CONCLUSION: When cervical dilatation was lower than the 10th percentile and was arrested for > or =2 hours, cesarean delivery would have prevented 42.1% of the cases of uterine rupture and resulted in excess 2.6% and 7.9% cesarean delivery rates among women with no previous cesarean deliveries and women with vaginal birth after cesarean delivery, respectively.
OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.
BACKGROUND: Previous etiologic studies have defined intrauterine growth restriction (IUGR) based on a single cutoff. OBJECTIVE: To assess the relative importance of known etiologic determinants for different degrees (mild versus severe) and timing (preterm versus term) of fetal growth restriction. DESIGN: Hospital-based cohort study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Sixty-five thousand two hundred eighty inborn singleton infants without major congenital anomalies delivered between January 1, 1978 and March 31, 1996. MEASUREMENTS: Comparison of adjusted odds ratios (ORs) and 95% confidence intervals for mild IUGR (defined as birth weight 75% to <85% of the mean for gestational age, the latter cutoff equivalent to the 9.9th percentile for this cohort) and severe IUGR (<75% of mean, or 2.3rd percentile), after controlling for maternal age, education, marital status, and other potential determinants by means of multiple logistic regression. RESULTS: Maternal prepregnancy overweight (body mass index [BMI] >26.0-29.0 kg/m2) and obesity (BMI >29.0 kg/m2) had stronger protective effects against mild IUGR than against severe IUGR, but most of the determinants showed the opposite pattern. This was especially true for pathologic determinants; ORs (and 95% confidence intervals) for severe versus mild IUGR were 18.5 (14.5-23.8) vs 4.6 (3.6-5.8) for severe pregnancy-induced hypertension (PIH), 3.5 (2.2-5.5) vs 2.3 (1. 5-3.4) for prepregnancy hypertension, and 3.4 (2.9-3.9) vs 2.2 (2. 0-2.4) for smoking >/=11 cigarettes/day. Primiparity, short stature, prepregnancy BMI, maternal weight gain, and cigarette smoking had significantly larger effects on term IUGR, whereas the effect of severe PIH was more than twice as large for preterm IUGR (OR = 9.7 [7.3-13.0]) as for term IUGR (OR = 4.0 [3.0-5.3]). CONCLUSION: Pathologic determinants of IUGR such as prepregnancy and PIH and cigarette smoking predispose to more severe fetal growth retardation, and PIH in particular seems to do so before 37 weeks. Growth-restricted newborns are not, therefore, all created equal(ly).
OBJECTIVE: To observe fetal arteriolar oxygen saturation during maternal epidural analgesia. DESIGN: An observation study of 27 epidural top-ups. SETTING: Labour ward, St James's University Hospital and Leeds General Infirmary, Leeds University, UK. SAMPLE: Seventeen fetuses in uncomplicated labour monitored with a N400 fetal pulse oximeter. OUTCOME MEASURE: A change in fetal pulse oximetry reading following epidural analgesia. RESULTS: There is no change in fetal oxygen saturation following an uncomplicated epidural top-up (F = 0.93; df 35 and 784). CONCLUSION: An uneventful maternal epidural has no measurable effect on fetal oxygen saturation measured with a N400 pulse oximeter.
OBJECTIVE: To find out what happens to fetal arteriolar oxygen saturation during a uterine contraction. DESIGN: Prospective observational study. SETTING: Labour ward, St James's University Hospital, Leeds. SUBJECTS: Eighteen women in normal labour monitored with a fetal scalp surface pulse oximetry sensor, an intrauterine pressure catheter, and a head to cervix force transducer. METHODS: The effect of intrauterine pressure and head to cervix force on fetal arteriolar oxygen saturation was examined using time series analysis and a regression model of 159 contractions. OUTCOME MEASURE: Fetal oxygen saturation during a contraction. RESULTS: The average oxygen saturation drops after a contraction. The greatest drop in oxygen saturation is reached 92 s after the peak of a contraction and takes approximately 1 min 30 s to recover (P = 0.036). CONCLUSION: Uterine contractions during normal labour affect fetal oxygen saturation.
OBJECTIVE: To determine whether pulse oximetry has the potential to replace scalp blood pH sampling in infants with abnormal cardiotocographs. STUDY DESIGN: The average scalp oximetry reading in labor recorded with an experimental N400 system was compared with fetal scalp blood pH. RESULTS: The average oximetry readings were unrelated to the pH of aerobically sampled fetal scalp blood. There was no subgroup of acidemic infants with a low oximetry reading. CONCLUSION: Pulse oximetry readings with present technology do not reflect scalp pH. The equipment is improving, but at this time pulse oximetry is not a simple alternative for scalp capillary blood sampling.
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Experimental pulse oximetry devices, similar to the existing systems used in adult and neonatal monitoring, can be used on the fetus to provide safe, and rapid information about oxygenation. They have been calibrated using fetal lambs and validated in human cross-sectional studies. Experiments have shown that fetal oxygen saturation decreases during normal labour, and drops after a uterine contraction especially with oxytocin-induced tachysystole. When the mother is given oxygen the fetal oxygen saturation increases. Readings are effected by caput and movement, and trends seem to be more meaningful than absolute values. Pulse oximetry can predict fetal outcome and a normal oxygen saturation result is specific for a good outcome perhaps even if the CTG is abnormal. However the technique is still experimental and there is insufficient data to support its use as a replacement for fetal blood sampling or a discriminator for an abnormal fetal heart trace.
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OBJECTIVE: To determine if pulse oximetry could detect any changes in fetal arteriolar oxygen saturation resulting from maternal administration of oxygen. DESIGN: A prospective study comparing study comparing the fetal pulse oximetry reading before and after giving 27% and 100% oxygen to the mother. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: Labour ward, St. Jame's University Hospital, Leeds University, UK. SUBJECTS: Twelve fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURES: The change in fetal arteriolar oxygen saturation recorded by the pulse oximeter in response to oxygen administration to the mother. RESULTS: Twenty-seven percent oxygen increased the average fetal arteriolar oxygen saturation by 7.5%, the effect being reversed when the oxygen was withdrawn. One hundred percent oxygen increased fetal arteriolar oxygen saturation by 11% and when the oxygen was withdrawn oxygen saturation dropped by 10%. One hundred percent inspired maternal oxygen was more effective than 27%. The gradient of the fetal oxygen regression slope is steeper with 100% oxygen than 27% and it is steeper when oxygen is given compared to when it is withdrawn. This suggests that the fetus responds to the new placental oxygen gradient by accepting oxygen more rapidly than it gives it up. Using a quadratic regression model, it took 9 min for fetal oxygen saturation to reach its maximum value after giving the mother oxygen. CONCLUSION: This study confirms that a pulse oximeter is able to measure an increase in fetal arteriolar oxygen saturation when oxygen is administered to the mother.
OBJECTIVE: To assess the accuracy of a pulse oximeter in the fetus. DESIGN: A prospective descriptive study, comparing oxygenation and acidaemia of cord blood with oxygen saturation in the arteries of the fetal scalp measured by a pulse oximeter just before delivery. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: The labour ward in a teaching hospital. SUBJECTS: Thirty seven Caucasian fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURE: Fetal pulse oximetry reading shortly before birth, umbilical cord oxygenation and pH, and Apgar scores. RESULTS: Data of sufficient quality were obtained from 28 fetuses. There was a highly significant correlation between pulse oximetry reading and umbilical vein oxygen saturation r = 0.59, P = < 0.001). There was also a significant correlation between the pulse oximeter reading and cord blood pH (vein: r = 0.57, P = 0.002, artery: r = 0.63, P = 0.001). Apgar scores were not related to the oximetry results. CONCLUSION: Pulse oximetry readings reflect fetal oxygenation at birth.
Reflectance probes are being developed for neonatal use and obstetricians are beginning to use reflectance pulse oximetry to monitor the fetus. When a reflectance probe was used to monitor the arterial oxygen saturation of a baby whose skin was stained with meconium an artificially low result was obtained. This is because meconium absorbs more red than infra-red light and acts as a red light filter between the vascular bed and the probe. This effect may be reproduced by interposing a red filter between a reflectance pulse oximetry probe and the skin. Obstetricians who use a pulse oximeter to assess the fetus through intact membranes will record an erroneously low result if they are stained with meconium. Similarly neonatologists should avoid placing a reflectance pulse oximetry probe on babies skin which is stained with meconium.
Infants undergoing phototherapy may develop loose stools. Acquired lactase deficiency secondary to this treatment modality was suggested as a cause for the diarrhea. The effects of light energy directly on intestinal enzymes and indirectly through bilirubin photooxidation products were studied. Adult homozygote and heterozygote Gunn rats were treated with light for varying periods while littermate controls were kept in the dark. Intestinal lactase, sucrase and GGTP activities and serum bilirubin concentrations were determined. Jaundiced and non-jaundiced 1-week-old suckling Gunn rats were treated with light for 96 h, and intestinal lactase activity determined. No decreases in lactase, sucrase or GGTP activities were observed suggesting the reported diarrheal states following phototherapy are not related to light energy or photooxidation products.
Seven-day-old rats were fed 1% lead acetate tetrahydrate solution for 2, 4, or 7 days. Adult rats were fed the same lead solution for 6--8 wk. In the newborn rats, hepatic UDP-bilirubin glucuronyl transferase (GT) and gamma glutamyl transpeptidase (GGTP) activities were markedly increased. GT activity was increased after 4 days as compared to the controls (6.3 +/- 0.3 vs. 4.3 +/- 0.3, P less than 0.001), and was maximal after 7 days of treatment (7.5 +/- 0.4 vs. 4.6 +/- 0.4, P less than 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 +/- 0.2 vs. 0.4 +/- 0.1, P less than 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 +/- 0.3 vs. 5.1 +/- 0.1, P less than 0.001, and 0.7 +/- 0.1 vs. 0.4 +/- 0.1, P less than 0.005, respectively). In vitro studies adding lead citrate to liver homogenates did not produce any direct effect on GT and GGTP activities.
The course, incidence, and severity of neonatal jaundice was studied in 95 Alaskan Eskimo infants. Breast-fed infants had higher bilirubin concentrations than bottle-fed babies. Both groups experienced high bilirubin levels, similar to those previously reported in Navajo and Oriental infants but greater than those observed in whites and blacks. A marked capacity to inhibit hepatic glucuronyl transferase was observed in breast-milk specimens but only partly accounted for the bilirubin differences between breast-fed and bottle-fed Eskimo infants. These data suggest that in some racial groups predisposed to neonatal jaundice, feeding practices significantly alter the course and severity of hyperbilirubinemia.
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