Variable placental thickness affects placental functional efficiency independent of other placental shape abnormalities.

Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases.

Placental surface shape, function, and effects of maternal and fetal vascular pathology.

GOAL: In clinical practice, variability of placental surface shape is common. We measure the average placental shape in a birth cohort and the effect deviations from the average have on placental functional efficiency. We test whether altered placental shape improves the specificity of histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathology for clinical outcomes. MATERIALS AND METHODS: 1225 Placentas from a prospective cohort had chorionic plate digital photographs with perimeters marked at 1-2 cm intervals. After exclusions of pre-term (n = 202) and velamentous cord insertion (n = 44), 979 (95.7%) placentas were analyzed. Median shape and mean perimeter were estimated. The relationship of fetal and placental weight was used as an index of placental efficiency termed "ß". The principal placental histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathologies were coded by review of individual lesion scores. Acute fetal inflammation was scored as a "negative control" pathology not expected to affect shape. ANOVA with Bonferroni tests for subgroup comparisons were used. RESULTS: The mean placental chorionic shape at term was round with a radius estimated at 9.1 cm. Increased variability of the placental shape was associated with lower placental functional efficiency. After stratifying on placental shape, the presence of either maternal uteroplacental or fetoplacental vascular pathology was significantly associated with lower placental efficiency only when shape was abnormal. CONCLUSIONS: Quantifying abnormality of placental shape is a meaningful clinical tool. Abnormal shapes are associated with reduced placental efficiency. We hypothesize that such shapes reflect deformations of placental vascular architecture, and that an abnormal placental shape serves as a marker of maternal uteroplacental and/or fetoplacental vascular pathology of sufficiently long standing to impact placental (and by extension, potentially fetal) development.

Centrality of the umbilical cord insertion in a human placenta influences the placental efficiency.

GOAL: We assess the effect on placental efficiency of the non-centrality of the umbilical cord insertion and on chorionic vascular distribution to determine if cord centrality measurably affects placental function as reflected in birth weight. MATERIALS AND METHODS: 1225 placentas collected from a prospective cohort had digital photographs of the chorionic plate. Of these, 1023 were term, 44 had velamentous cord insertion and 12 had missing clinical data, leaving N=967 (94.5%) cases for analysis. Mathematical tools included a dynamical stochastic growth model of placental vasculature, Fourier analysis of radial parameterization of placental perimeters, and relative chorionic vascular density (a measure of "gaps" in the vascular coverage) derived from manual tracings of the fetal chorionic surface images. Bivariate correlations used Pearson's or Spearman's rank correlation as appropriate, with p<0.05 considered significant. RESULTS: The correlation of the standard deviation of the placental radius (a measure of non-roundness of the placenta) with cord displacement was negligible (r=0.01). Empirical simulations of the vascular growth model with cord displacement showed no deviation from a normal round-to-oval placental shape for cord displacement of 10-50% of placental radius. The correlation of the metabolic scaling exponent beta with cord displacement measured by Fourier analysis is 0.17 (p<0.001). Analysis of the chorionic vascular density in traced images shows a high correlation of the relative vascular distance with cord displacement: 0.59 in one set of 12 images, and 0.20 in the other set of 28 images. CONCLUSION: Non-central cord insertion has little measurable correlation with placental shape in observed or simulated placentas. However, placentas with a displaced cord show a markedly reduced transport efficiency, reflected in a larger value of beta and hence in a smaller birth weight for a given placental weight. Placentas with a non-central cord insertion have a sparser chorionic vascular distribution, as measured by the relative vascular distance. Even if typically a placenta with a non-central insertion is of a normal round shape, its vasculature is less metabolically effective. These findings demonstrate another method by which altered placental structure may affect the fetal environment, influencing birth weight and potentially contributing to later health risks.

Modeling the variability of shapes of a human placenta.

BACKGROUND: Placentas are generally round/oval in shape, but "irregular" shapes are common. In the Collaborative Perinatal Project data, irregular shapes were associated with lower birth weight for placental weight, suggesting variably shaped placentas have altered function. METHODS: (I) Using a 3D one-parameter model of placental vascular growth based on Diffusion Limited Aggregation (an accepted model for generating highly branched fractals), models were run with a branching density growth parameter either fixed or perturbed at either 5-7% or 50% of model growth. (II) In a data set with detailed measures of 1207 placental perimeters, radial standard deviations of placental shapes were calculated from the umbilical cord insertion, and from the centroid of the shape (a biologically arbitrary point). These two were compared to the difference between the observed scaling exponent and the Kleiber scaling exponent (0.75), considered optimal for vascular fractal transport systems. Spearman's rank correlation considered p<0.05 significant. RESULTS: (I) Unperturbed, random values of the growth parameter created round/oval fractal shapes. Perturbation at 5-7% of model growth created multilobate shapes, while perturbation at 50% of model growth created "star-shaped" fractals. (II) The radial standard deviation of the perimeter from the umbilical cord (but not from the centroid) was associated with differences from the Kleiber exponent (p=0.006). CONCLUSIONS: A dynamical DLA model recapitulates multilobate and "star" placental shapes via changing fractal branching density. We suggest that (1) irregular placental outlines reflect deformation of the underlying placental fractal vascular network, (2) such irregularities in placental outline indicate sub-optimal branching structure of the vascular tree, and (3) this accounts for the lower birth weight observed in non-round/oval placentas in the Collaborative Perinatal Project.

Urinary incontinence in pregnancy and the puerperium: a prospective study.

OBJECTIVE: Pregnancy and childbirth are commonly thought to be associated with the development of urinary incontinence and lower urinary tract symptoms. The purpose of this study was to assess the relationship, if any, between pregnancy and the development of lower urinary tract symptoms. STUDY DESIGN: A prospective study of lower urinary tract symptoms was carried out in a cohort of pregnant women who answered a series of symptom questionnaires and kept a 24-hour bladder chart on which frequency of urination and volumes voided were recorded throughout pregnancy and for 8 weeks after birth. RESULTS: A total of 123 women participated in the study. Mean daily urine output (P =.01) and the mean number of voids per day (P =.01) increased with gestational age and declined after delivery. Episodes of urinary incontinence peaked in the third trimester and improved after birth (P =.001). White women had higher mean voided volumes and fewer voiding episodes than did black women. Ingestion of caffeine was associated with smaller voided volumes and greater frequency of urination. CONCLUSION: Pregnancy is associated with an increase in urinary incontinence. This phenomenon decreases in the puerperium. Pregnancy and childbirth trauma are important factors in the development of urinary incontinence among women. These findings warrant further investigation.

Determinants of participation in an epidemiological study of preterm delivery.

We describe the study design and patterns of participation for a cohort study of preterm delivery, focused on genital tract infections, nutrition, tobacco use, illicit drugs and psychosocial stress. Women are recruited at 24-29 weeks' gestation from prenatal clinics at a teaching hospital and a county health department. We recruited 57% of the first 1843 eligible women; 29% refused and 8% could not be contacted. White women were somewhat more likely to participate than African-American women (61% vs. 54% respectively). More notable differences were found comparing teaching hospital and health department clinics (71% vs. 47% participation respectively), with the health department clinic having a greater proportion refuse (24% vs. 33%) and more women who could not be contacted (4% vs. 11%). Participation was affected only minimally by day or timing of recruitment, but inability to contact diminished substantially as the study continued (13-0%). Refusals were largely unrelated to patient attributes. Lower education predicted inability to contact. Risk of preterm delivery was 14% among recruited women, 10% among women who refused, and 15% among women whom we were not able to contact, demonstrating that, overall, risk status was not lower among recruited women.

Predictors of positivity for fetal fibronectin in patients with symptoms of preterm labor.

OBJECTIVE: Identifying patients at risk for preterm delivery continues to be difficult. We analyzed fetal fibronectin immunoassays in 763 subjects with threatened preterm delivery from 10 clinical sites. STUDY DESIGN: Symptomatic women between 24 weeks 0 days and 34 weeks 6 days with intact amniotic membranes and cervical dilatation <3 cm were included. Specimens were obtained from the posterior vaginal fornix and concentrations of fetal fibronectin were measured by enzyme-linked immunosorbent assay. A total of 150 (20%) patients had positive results for the fetal fibronectin immunoassay. The simultaneous effects of multiple variables on predicting positive fetal fibronectin immunoassay results were analyzed with use of logistic regression models. Variables included were patient age (mean 24.2 years), race (40% white), gravidity (29% primigravid), history of previous premature infants (15%), sexual activity within 24 hours of sample collection (66/763 or 9%), cervical examination within 24 hours of sample collection (107/763 or 14%), vaginal bleeding (118/759 or 16%), uterine contractions (192/750 or 26% with three or more in 1 hour), cervical dilatation (94/763 or 12% with dilatation between 1 and 3 cm), estimated gestational age at sampling (mean 30 weeks 2 days). RESULTS: Regardless of the variable selection process (e.g., forward, backward, or stepwise), the reduced model showed five significant variables in predicting positive fetal fibronectin: cervical dilatation (chi2 33.5, p = 0.0006), sexual activity within 24 hours of sample collection (chi2 22.9, p < 0.0001), presence of vaginal bleeding (chi2 17.0, p < 0.0001), cervical examination within 24 hours of sample collection (chi2 11.6, p < 0.0006), and uterine contractions (chi2 6.8, p = 0.01). Deletion of the true positive subset did not change these variables or the magnitude of risk. CONCLUSION: Cervical dilation or manipulation predicts positive fetal fibronectin assays and may serve to explain some of the false-positive results generated by the test.