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Biomedical subjects

R O Davis

Publications and source records attributed to R O Davis.

At least 19 recordsLinked to original sources

Laboratory methods for assessing human semen in epidemiologic studies: a consensus report.

It is clear that additional methodologic work needs to be performed. Some data gaps described above are being actively investigated. Other standards were not addressed at this meeting; statistical handling of the data, differences among CASA machines, and factors to consider as potential confounders in analysis are just a few. These may be the subject of future workshops, which will also review progress made in the existing knowledge base. For now, this effort represents a first attempt to share information and to use it to encourage investigators in different laboratories to employ similar methods. In this way more direct comparisons among studies can be made, and our collective data base can be strengthened.

Computers

Elevated levels of midtrimester maternal serum alpha-fetoprotein are associated with preterm delivery but not with fetal growth retardation.

OBJECTIVE: Our objective was to determine if the low birth weight associated with unexplained elevations of midtrimester maternal serum alpha-fetoprotein levels is due to prematurity or to fetal growth retardation. STUDY DESIGN: Rates of preterm delivery and fetal growth retardation were analyzed according to incremental maternal serum alpha-fetoprotein levels in 5555 women, predominantly white, who were screened for neural tube defects (group 1) and 843 women, predominantly black, with risk factors for low birth weight (group 2). Statistical methods included chi 2, t tests, analysis of variance, and regression analysis. RESULTS: In both groups increasing levels of maternal serum alpha-fetoprotein are significantly associated with preterm delivery but not with fetal growth retardation. The preterm delivery rate increased in each group from 8% at levels less than 0.5 multiples of the median to 18.1% (p less than 0.001) at levels greater than or equal to 2.5 multiples of the median in group 1 and 28.1% (p = 0.01) in group 2. CONCLUSIONS: Women with unexplained elevations of maternal serum alpha-fetoprotein are at increased risk for preterm delivery but not fetal growth retardation. Because of the wide availability of maternal serum alpha-fetoprotein screening, women at increased risk for preterm delivery can be identified in the midtrimester of pregnancy.

Black People

Neonatal periventricular-intraventricular hemorrhage after maternal beta-sympathomimetic tocolysis. The March of Dimes Multicenter Study Group.

OBJECTIVE: Our objective was to determine if the rate of periventricular-intraventricular hemorrhage is increased in the offspring of women who received a beta-sympathomimetic agent as part of the management of preterm labor. STUDY DESIGN: This retrospective study consists of 2827 women who were delivered of a singleton, live infant free of congenital neurologic anomalies between 25 and 36 completed weeks of gestation during a multicenter preterm birth prevention trial. The data were analyzed, adjusting for type of tocolytic agent, race, infant sex, gestational age, birth weight, health care center, route of delivery, indication for delivery, intrapartum fetal distress, respiratory distress syndrome, and neonatal sepsis. RESULTS: The overall incidence of periventricular-intraventricular hemorrhage in this population was 5.6%. In a univariate analysis in which no adjustment was made for potentially confounding variables, beta-sympathomimetic tocolysis was found to be associated with nearly a fourfold increase in the incidence of periventricular-intraventricular hemorrhage when compared with the use of either magnesium sulfate or no tocolytic agent. The results of a multivariate regression analysis revealed that beta-sympathomimetic agents were associated with a statistically significant increase in the overall incidence of periventricular-intraventricular hemorrhage (odds ratio 2.47, 95% confidence interval 1.34 to 4.56, p = 0.004) and a similar, but not significant, increase in the incidence of grades 3 and 4 periventricular-intraventricular hemorrhage (odds ratio 2.50, 95% confidence interval 0.96 to 6.48, p = 0.06). CONCLUSION: beta-Sympathomimetic tocolytic therapy may be associated with a more than twofold increase in the incidence of neonatal periventricular-intraventricular hemorrhage.

Birth Weight

Transverse uterine incision closure: one versus two layers.

OBJECTIVE: Closure of a low transverse cesarean incision with one layer of suture results in less operating time, better hemostasis, and less infectious morbidity than a two-layer closure. STUDY DESIGN: At our institution 906 women were randomized to closure of a low transverse cesarean incision with either one continuous layer of a locking No. 1 chromic suture and a CTX needle (n = 457) or two continuous layers of No. 1 chromic suture with the first layer locked (n = 449). The Student t test, chi 2 test of proportion, and Wilcoxon rank sum test were used to compare groups of patients. RESULTS: A one-layer closure required less operative time, 43.8 versus 47.5 minutes (p = 0.0003). Fewer additional uterine hemostatic sutures were required in 369 women in whom either the one- (n = 179) or the two-layer (n = 190) closure did not achieve hemostasis (p = 0.046). Endometritis was similar in both groups, 83 (22%) in the one-layer group versus 65 (18%) in the two-layer group (p = 0.17). In no outcome assessment was the two-layer closure superior to the one-layer closure. CONCLUSION: We recommend a one-layer closure when its use is anatomically feasible.

Adult

Blood pressure, growth retardation, and preterm delivery.

The effect of various levels of both diastolic and systolic blood pressure at various times during pregnancy on the rates of intrauterine growth retardation (IUGR) and preterm delivery (PTD) were determined. Low systolic and diastolic pressures were associated with both IUGR and PTD, as were high pressures. Low pressures tended to be associated with spontaneous preterm deliveries, whereas high pressures were associated with more indicated preterm deliveries.

Blood Pressure Determination

Nutrient levels in amniotic fluid from women with normal and neural tube defect pregnancies.

We analyzed nutrient levels in amniotic fluid obtained during the second trimester of normal, uncomplicated pregnancies from 221 women who delivered apparently healthy infants and from 8 with neural tube defect (NTD) pregnancies. Folate was measured by microbiological assay, vitamin B12 by a radiobinding method, and zinc, copper and iron by atomic absorption spectrophotometry. We found that the mean amniotic fluid nutrient levels of normal pregnancies were 24.7 nmol/l for folate, 600 pmol/l for vitamin B12, and 1.7, 1.9, and 9.0 mumol/l for zinc, copper and iron, respectively. Amniotic fluid folate, zinc, copper and iron levels of NTD pregnancies were similar to those found during normal pregnancy, however, vitamin B12 levels were markedly lower than those of normal pregnancies.

Adolescent

Prenatal differentiation of ventral abdominal wall defects. Are amniotic fluid markers useful adjuncts?

We retrospectively reviewed 29 cases of ventral abdominal wall defects to evaluate the usefulness of amniotic fluid markers in the prenatal assessment of those disorders. Amniotic fluid alpha-fetoprotein (AF-AFP) values were available in 17 cases diagnosed prior to 22 weeks' gestation and acetylcholinesterase (AF-ACE) values, in 21 cases. All 7 fetuses with a gastroschisis had an elevated AF-AFP, while only 2 of the 10 fetuses with an omphalocele had elevated values (P = .002). ACE was present in 80% of the cases of gastroschisis versus 27.3% of the cases of omphalocele (P = .03). With equivocal sonographic findings, a normal AF-AFP and negative AF-ACE may be more compatible with an omphalocele.

Acetylcholinesterase

Accuracy and precision of the CellForm-Human automated sperm morphometry instrument.

OBJECTIVE: To evaluate the accuracy and precision of the CellForm-Human (CFH) automated sperm morphometry instrument (Motion Analysis Corp., Santa Rosa, CA). SETTING: Clinical and research andrology and in vitro fertilization laboratories. PATIENTS: Individuals undergoing semen evaluation and infertility work-up. RESULTS: Coefficients of variation for repeated measures of the same sperm were 1%. Coefficients of variation of normal sperm measurements were 7.4% to 12.8%, depending on the measure. Of the objects recognized as sperm by the instrument, 6.8% were debris; hence, the sperm recognition algorithms need improvement. Mean values for all CFH measures of normal sperm from specimens clinically classified as having predominantly normal, tapered, or amorphous sperm were not different; hence, the morphometry of normal sperm from normal specimens was similar to normal sperm from specimens with two different abnormalities. The instrument classified sperm as abnormal if their length or width fell outside a critical range of values recommended by the World Health Organization. Using this method, manual and CFH classification agreed unambiguously 60% of the time. When disagreement occurred, length or width marginally exceeded the range by no more than 0.1 microns. In these cases, the technician classified sperm as normal 25% of the time and classified them as abnormal 6% of the time. Because this disagreement between methods is well below the resolution of manual methods, the overall accuracy of CFH was 91% for cell type classification. CONCLUSION: At its present stage of development, the CFH instrument exceeds the accuracy and precision of most manual approaches. With improvements in sperm recognition and type classification algorithms, it could significantly improve the reliability of morphology assays in clinical and research laboratories.

Equipment Design

The role of digital image analysis in reproductive biology and medicine.

The use of high-speed computers, direct digitization of video images, and new methods to probe soft tissues has revolutionized our view of biology. Many of these new techniques are now commonly used in several areas of medicine, but their use in reproductive biology has just begun. At present, digital image processing is limited to a few applications in reproductive medicine, including digital colposcopy and the laboratory analysis of spermatozoon motility and cellular morphology. Early implementations of digital image processing experienced problems typical of any newly introduced high technology. Today, however, with careful attention to operational details, digital image processing instruments can be productively used in the clinical diagnosis of cervical cancer, in the laboratory diagnosis of male infertility, and in more basic cell biological research. Such instruments also promise to play a significant role in laboratory quality assurance and control and in technologist training and education. In the near future, digital image processing instruments will also be applied to other areas of reproductive laboratory medicine, such as oocyte evaluation and embryo monitoring in the in vitro fertilization laboratory.

Embryo, Mammalian

The relationships among psychosocial profile, maternal size, and smoking in predicting fetal growth retardation.

OBJECTIVE: We explored the relationships among measures of psychosocial well-being, maternal size, and smoking in predicting infant size at birth. METHODS: Participants in this population-based cohort study were drawn from public health prenatal clinics in Jefferson County, Alabama during 1985-1988. Para 1 and 2 women were screened for 11 risk factors for low birth weight, including small stature, a previous low birth weight infant, and smoking. RESULTS: Poor scores on five of six psychosocial scales, as well as on a combined profile, were associated with a significantly higher relative risk of fetal growth retardation (FGR) only in thinner women, defined as having a body mass index less than the median (relative risk [RR] 2.11, 95% confidence interval [CI] 1.47, 3.04). A significant association between the psychosocial profile and birth weight was demonstrated for thin women in a multivariate analysis adjusting for gestational age, race, infant sex, and smoking (P = .0003). The relationship remained significant when hypertension, alcohol and drug use, and weight gain were added to the model (P = .003). In women with a body mass index above the median, a poor psychosocial profile showed little association with FGR (RR 1.20, 95% CI 0.73, 1.98) and did not have a significant association with birth weight. A poor profile had a greater association with FGR in non-smokers (RR 2.04, 95% CI 1.29, 3.22) than in smokers (RR 1.4, 95% CI 0.95, 2.06). CONCLUSIONS: Greater pre-pregnancy weight for height appears to protect against the adverse effects of a poor psychosocial profile in a population of poor, primarily black women. In thinner women, both smoking and a poor psychosocial profile were associated with a substantially increased rate of FGR, indicating a subgroup of women who may receive greater benefits from intervention programs.

Body Mass Index

Accuracy and precision of computer-aided sperm analysis in multicenter studies.

STUDY OBJECTIVES: To develop methods of instrument calibration and standardization that enable the use of computer-aided sperm analysis (CASA) technology in multicenter studies of sperm motility. SETTING: Clinical semen evaluation for the andrology laboratory and in vitro fertilization programs. PATIENTS: Semen specimens were selected from the videotape archives of the University of California at Davis Andrology Laboratory and used to produce a videotape reference standard for CASA instrument testing and calibration. Four identical CASA instruments, two each at two sites, were used to analyze the videotape. Machine accuracy was verified by manual analysis of the videotape. RESULTS: The coefficient of variation (CV) for repeated measures was between 1% and 8% for each variable on all CASA instruments. Mean values for CASA parameters varied as a function of the digitization threshold. A minimum CV was obtained at a particular threshold setting, suggesting an optimum for each machine. Because of high within-machine precision, slight differences in mean values between machines were statistically significant for some variables and some specimens; such differences are probably not biologically significant. CONCLUSION: Multicenter standardization of CASA instrumentation is possible, but threshold settings are one source of variation that must be controlled using CVs or another means of objective calibration. One method is to adjust the threshold of each instrument until the count obtained by CASA equals the count obtained by the manual method used to determine the dilution requirements for neat semen.

Computers

Movement characteristics of human epididymal sperm used for fertilization of human oocytes in vitro.

STUDY OBJECTIVE: To develop mathematical models using kinematic parameters from Computer-Aided Sperm Analysis (CASA) that predict the fertilization rate of sperm recovered from the caput epididymidis and to test the hypothesis that fertilization was enhanced by the presence of specific sperm subpopulations in the inseminate. SETTING: In vitro fertilization (IVF) program. PATIENTS: Thirteen patients with congenital absence of the vas deferens provided epididymal sperm for IVF as well as for CASA. RESULTS: The mathematical model that was most predictive of fertilization rates included kinematic parameters of the epididymal aspirate (percent motility), the inseminate used for IVF (curvilinear velocity [VCL]), and the change in sperm movement after in vitro processing by the mini-Percoll technique (difference in amplitude of lateral head displacement [ALH]). Multivariate cluster analysis revealed that inseminates that resulted in higher fertilization rates had subpopulations of sperm that were characterized by high VCL and high mean angular displacement, as well as a greater change in ALH after processing. CONCLUSION: In vitro fertilization with epididymal sperm was more likely to succeed when the sperm population that was initially aspirated had a higher proportion of motile cells and when these sperm were capable of capacitation in vitro as indicated by the appearance of sperm subpopulations with motility that resembled hyperactivation.

Diagnosis, Computer-Assisted

Management of prenatally detected nonlethal fetal anomalies: is a karyotype of benefit?

The pregnancy outcomes of 155 women who underwent an amniocentesis for a prenatal karyotype after being diagnosed by ultrasound as having one or more nonlethal structural anomalies are presented. Thirty-three (21%) patients were found to have an abnormal karyotype. Knowledge of the prenatal karyotype was useful in the subsequent management of these pregnancies. A pregnancy with a fetal anomaly diagnosed prior to 24 weeks was more likely to be terminated if an abnormal karyotype was also present. In women who were diagnosed as having a fetal anomaly with an abnormal karyotype at 24 weeks or later, only 3 of 13 (23%) infants survived the neonatal period. Knowledge of the karyotype results influenced decisions regarding the place, timing, and route of delivery in these fetuses. In 32 women, (21%) a karyotype was beneficial by avoiding maternal transport, cesarean delivery, and neonatal expenses at a Level III perinatal center.

Abortion, Induced

Maternal serum alpha 2-macroglobulin and fetal growth retardation.

Maternal serum alpha 2-macroglobulin levels were measured twice, at approximately 18 and 30 weeks' gestation, in 289 pregnant women who later delivered at or after 37 weeks. Levels were elevated as early as 18 weeks' gestation in women destined to have a growth-retarded infant, and this elevation persisted through 30 weeks' gestational age. Furthermore, levels were higher in white women than black, in smokers than in non-smokers, and in thin than in heavier women. When the effect of alpha 2-macroglobulin on birth weight was evaluated in a multiple regression analysis adjusting for gestational age, race, body size, smoking, fetal sex, and a history of a low birth weight infant, high alpha 2-macroglobulin levels were associated with a statistically significant decrease in birth weight. The effect was greater in women who smoked. This relationship did not appear to be associated with differences in serum zinc or hematocrit levels.

Adult

Fetal obstructive uropathies. Importance of chromosomal abnormalities and associated anomalies to perinatal outcome.

The ultrasound records of 30 fetuses suspected of having an obstructive uropathy were reviewed retrospectively. A prenatal karyotype was obtained with amniocentesis on each patient. After delivery, neonatal urologic records, renal ultrasound reports and autopsy information were reviewed and compared to the ultrasound records and fetal karyotype results. Chromosomal defects were found in 23% of fetuses with a suspected obstructive fetal uropathy. In five patients the chromosomal abnormality was lethal and caused 45% of the perinatal deaths in this series. If a fetus with an obstructive uropathy was female, there was a significant likelihood of an extrarenal anomaly or a complex genitourinary tract malformation. Seventeen percent of patients with an obstructive uropathy had a coexistent extrarenal defect. A prenatal karyotype should be obtained if a fetal obstructive uropathy is suspected antenatally since lethal chromosomal defects are an important cause of perinatal death. A female karyotype may indicate a fetus at higher risk of extrarenal anomalies or complex genitourinary malformations.

Adult

Black-white differences in newborn anthropometric measurements.

The mean birth weight of black infants is consistently less than that of white infants. In 1518 low-income multiparous women, the mean difference in singleton births was 171 g, of which 38 g was partitioned to preterm births and another 35 g reflected lower gestational ages in term births. A series of regression analyses were used to determine the effect of black race on various newborn measurements in 1205 term newborns, adjusting for other known risk factors. In this model, black race accounted for a mean decrease of 148 g in weight and 0.52 cm in length. There were also significant decreases in mean head (0.44 cm), chest (0.66 cm), and abdominal (0.56 cm) circumferences. Arm and leg lengths were not different, but black arm circumferences (0.14 cm) were significantly larger. Triceps and thigh skin fold measurements were not statistically different, but black subscapular skin fold values were significantly smaller (0.17 mm). The ponderal index in blacks was significantly less than in whites. These data suggest that in this population, intrinsic and/or extrinsic factors associated with race account for most smaller black newborn measurements and for much of the racial difference in birth weight.

Alabama

Etiologies of preterm birth in an indigent population: is prevention a logical expectation?

To assess the expectations of preterm birth prevention, we determined the causes of preterm birth in a population of indigent women. We studied 13,119 singleton births in a predominantly black, indigent population occurring between November 1982 and April 1986 to identify the proportion of preterm births that may have been prevented using current treatment modalities. Forty-four percent of the preterm births occurred at 35 to 36 weeks' gestational age, a time when most practitioners do not attempt tocolysis. Of the remainder, 17% occurred before 35 weeks but were indicated for maternal medical or obstetric complications, and another 17% occurred before 35 weeks but followed spontaneous premature rupture of the membranes. Therefore, of the 1445 preterm births, we calculated that only 336 (23.2%) were theoretically preventable. A fourth of these presented at less than 3 cm cervical dilatation and were treated appropriately with tocolytics, but delivered anyway. Therefore, most of the potentially preventable births occurred in the group that presented with cervical dilatation of more than 3 cm. We conclude that improving the preterm birth rate significantly below current levels may be difficult to achieve.

Black People

Smoking, maternal age, fetal growth, and gestational age at delivery.

The relationship between smoking and maternal age and their combined effects on birth weight, intrauterine growth retardation, and preterm delivery were studied. Smoking lowers birth weight both by decreasing fetal growth and by lowering gestational age at delivery. However, the effect of smoking on both fetal growth and gestational age is significantly greater as maternal age advances. In a multiple logistic regression model adjusting for race, parity, marital status, maternal weight, weight gain, and alcohol use, smoking was associated with a fivefold increased risk of growth retardation in women older than 35 but less than a twofold increased risk in women younger than 17. Smoking reduced birth weight by 134 gm in young women but 301 gm in women older than 35. Smoking in older women also was associated with more instances of preterm delivery and a lower mean gestational age when compared to women 25 or younger.

Birth Weight