Biomedical subjects

M Miodovnik

Publications and source records attributed to M Miodovnik.

151 records · Page 9Linked to original sources

PubMedDate not supplied

A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels.

OBJECTIVE: To evaluate the impact of a focused preconceptional and early pregnancy program specializing in the care of women with Type 1 diabetes on perinatal mortality and congenital malformations. METHODS: This clinical study included women with Type 1 diabetes in an interdisciplinary Diabetes in Pregnancy Program Project Grant (PPG) funded by the NIH (1978-1993); these women were enrolled preconceptionally or during the first trimester (up to 14 weeks) and had pregnancies continuing beyond 20 weeks gestation. Strict glucose control was implemented and adherence assessed. Antepartum fetal surveillance was started at 32 weeks gestation. All live-born infants and stillbirths were examined. A retrospective comparison analysis of the period before PPG I (1973-1978) and after cessation of funding (1993-1999) was performed, specifically evaluating perinatal mortality and congenital malformation rates. Data were analyzed using analysis of variance, chi2, and Fisher's exact test. RESULTS: Three hundred and six women were enrolled in three 5-year periods: PPG I (1978-1983) n = 111, PPG II (1983-1988) n = 103, and PPG III (1988-1993) n = 92. Entry and interval glycohemoglobin A1 concentrations obtained decreased with each consecutive PPG. An emphasis on preconception care began in 1984, with preconception enrollment reaching 23% for PPG II and increasing in PPG III to 37%. As preconception enrollment increased, perinatal mortality rate decreased from 3% for PPG I and 2% for PPG II, to 0% in PPG III, and the congenital malformation rate decreased to a low 2.2% by PPG III. Comparison data collected for the period before PPG 1 (1973-1978) n = 79 revealed a perinatal mortality rate of 7% and a congenital malformation rate of 14%. Also, a postprogram retrospective analysis of the period 1993-1999 (n = 82) revealed an increase in perinatal mortality, with one death compared to none in PPG III, and a congenital malformation rate of 3.65% compared to 2.2% during PPG III. The preconception enrollment for this period decreased (19.5%). CONCLUSIONS: A program emphasizing preconceptional care, strict glycemic control preconceptionally and throughout gestation, and the use of antepartum fetal surveillance was associated with a significant decrease in the rate of perinatal mortality and congenital malformations in infants of women with Type 1 diabetes. However, ongoing improved outcome appears to depend on the availability of funding for a specialized preconception program.

Adult↗

PubMedDate not supplied

Glycemic control in the diabetic pregnancy: is tighter always better?

Glucose is the principal nutrient that the mother supplies to the fetus through the placenta by way of concentration-dependent mechanisms. In the presence of maternal hypoglycemia, with limited glucose supply, fetal hypoglycemia and hypoinsulinism ensue. This may be viewed as an adaptive mechanism to increase the chances of fetal survival in the face of limited maternal supply, albeit of a growth-restricted fetus. Fetal nutrient deprivation and the resulting hypoinsulinism may have both short- and long-term consequences. Intrauterine growth failure is associated with higher rates of gestational age-specific neonatal mortality and with long-term cognitive deficits. Furthermore, epidemiologic data suggest that diabetes, coronary artery disease, and hypertension are more common among adults who were small for gestational age at birth. Thus, pancreatic failure in adulthood may be either a response to excessive exposure to glucose as a result of maternal hyperglycemia, or as a result of hypoglycemia where nutrient deprivation leads to fetal growth restriction and reduced islet cell proliferation. Because low mean concentrations of maternal glucose in gestational diabetes are associated with an increased risk of fetal growth restriction, overzealous glycemic control during pregnancy may raise concerns regarding the possible effects on the infant. In the mother with Type 1 diabetes, strict glycemic control is often associated with an increased incidence of severe hypoglycemia. Up to 40% of women report at least one episode of severe hypoglycemia during pregnancy, requiring assistance by another person or professional intervention. It is quite possible that in some patients striving to optimize pregnancy outcome by maintaining the best possible glycemic control jeopardizes the well-being of the mother and the fetus. Thus, with respect to tight glycemic control of pregnant women with diabetes, the question arises: How tight is too tight? Is there a threshold below which the trade-off in terms of maternal morbidity as well as fetal growth restriction and its consequences outweighs the benefits of preventing the effects of maternal hyperglycemia?

Adult↗

PubMedDate not supplied

Sonographic EFW and macrosomia: is there an optimum formula to predict diabetic fetal macrosomia?

OBJECTIVE: To compare the accuracy of 31 published formulas for estimated fetal weight (EFW) in predicting macrosomia (birthweight 4,000 gm or more) in infants of diabetic mothers. METHODS: The study population comprised 165 women with gestational or pregestational diabetes who had sonograms to estimate fetal weight after 36 weeks of gestation and within 2 weeks of delivery. Three measures of accuracy were compared: 1) area under the receiver operating characteristic (ROC) curve relating EFW to macrosomia, 2) systematic error, and 3) absolute error. For each measure, the 31 formulas were rank-ordered from 1 (best) to 31 (worst). For each formula, the three rank scores were summed to give a total score. The formula with the lowest total score was considered the "best" formula. RESULTS: Macrosomia occurred in 49 cases (30%). Areas under the ROC curves ranged from 0.8361-0.8978. Differences in areas were not significantly different between the 31 formulas. The 1986 formula of Ott et al. had the lowest total score. Using this "best" formula, an EFW of 4,000 gm or more had a sensitivity of 45% to predict macrosomia and a positive predictive value of 81%. To achieve 90% sensitivity with this formula would have required diagnosis of macrosomia with an EFW of 3,535 gm or more, but this would have comprised 46% of the population with a 42% false-positive rate. All 31 formulas were better at predicting macrosomia than predictions based on gestational age alone, and 28 were better than predictions based on abdominal circumference alone. CONCLUSIONS: All 31 formulas for EFW had comparably poor accuracy for prediction of macrosomia. Delivery decisions based on EFW will often be in error. Future studies should determine whether specific sonographic measurements, ratios, or differences are better than EFW or birthweight as predictors of birth trauma.

Birth Injuries↗

PubMedDate not supplied

Fetal membrane histology in preterm premature rupture of membranes: comparison to controls, and between antibiotic and placebo treatment. The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network, Bethesda, MD, USA.

The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.

Adult↗

PubMedDate not supplied

Perinatal pathology of interhemispheric cyst with thinned posterior corpus callosum: four cases.

This paper presents four posterior, interhemispheric cerebral cysts found at perinatal autopsy. All cysts appeared to attenuate the overlying posterior corpus callosum. All had a base over the roof of the third ventricle and midbrain with a lining that resembled tela choroidea with the choroid plexus tufts projecting into the lumen of the cyst. Three cases had enlargement of the lateral ventricles. One case had complete communication between the cyst and the posterior lateral ventricles reminiscent of a holoprosencephaly confined to the posterior telencephalon. One case demonstrated a complete VATER association and two others had some features of the VATER association. We hypothesize that this latter relationship suggests an origin for the cysts during blastogenesis.

Abortion, Induced↗

PubMedDate not supplied

Histologic features of chorioamnion membrane rupture: development of methodology.

This study developed a set of histologic features that will allow subclassification of placentas with preterm premature rupture of membranes. Placentas were obtained from patients participating in a multi-institutional NICHD Maternal-Fetal Medicine Unit Network study of antimicrobial therapy after preterm premature rupture of membranes. The rupture site was sampled by inking the open sac margin and rolling a membrane strip in four quadrants from the ink to the placental margin. Independently, four pathologists used a provisional feature list to score the slides from 15 placentas. A concordance analysis was performed on those results. With those results, the slides were reviewed concurrently to discover the source of disagreements and to revise the feature list. The sampling method frequently demonstrated a rupture site with histology distinct from that of the remainder of the membranes. After review of the preliminary scoring results, 29 features of membrane histology present in preterm premature rupture could be objectively described with agreement among four pathologists. The feature list allows both novel and commonly recognized histologic features of fetal membranes to be recorded with objectivity. This list, with the described sampling technique, is presented as a tool for clinical correlation in studies of membrane rupture, especially in preterm, premature rupture.

Amnion↗

PubMedDate not supplied

Selective vasodilator effects of atrial natriuretic peptide in the human placental vasculature.

OBJECTIVE: To determine whether atrial natriuretic peptide (ANP) attenuates the vasoconstrictor effects of angiotensin II (AII), a thromboxane mimetic (U46619), and endothelin-1 in the human fetal-placental vasculature and to determine whether nitric oxide (NO) has a role in the vasodilator activity of ANP. METHODS: Isolated placental cotyledons were dually perfused, with fetal perfusion pressure used as an index of vascular response. The effects of AII (10(-10)-10(-6) mol/L bolus injection), endothelin-1 (10(-7) mol/L bolus), and U46619 (10(-9)-10(-6) mol/L bolus or 10(-8) mol/L infusion) were established in the absence or presence of ANP (10(-8) mol/L). The role of NO as a mediator of ANP action was investigated by perfusion with n-nitro-L-arginine (NNLA, 10(-3) mol/L), an inhibitor of NO synthase. Statistical significance was determined by analysis of variance. RESULTS: Atrial natriuretic peptide caused significant attenuation of vasoconstrictor responses to AII, but weak attenuation of endothelin-1 and no attenuation of U46619. Use of NNLA did not affect the attenuation of AII-induced vasoconstriction by ANP. CONCLUSIONS: Atrial natriuretic peptide is a vasodilator of the fetal-placental vasculature constricted with AII and endothelin-1, but not with U46619. Nitric oxide does not mediate the action of ANP.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗