Cost-benefit analysis of preconception care for women with established diabetes mellitus.

OBJECTIVE: To determine whether the additional costs of preconception care are balanced by the savings from averted complications. Several studies have demonstrated the efficacy of preconception care in reducing congenital anomalies in infants born of mothers with pre-existing diabetes mellitus. RESEARCH DESIGN AND METHODS: This study used literature review, consensus development among an expert panel of physicians, and surveys of medical care personnel to obtain information about the costs and consequences of preconception plus prenatal care compared with prenatal care only for women with established diabetes. Preconception care involves close interaction between the patient and an interdisciplinary health-care team as well as intensified evaluation, follow-up, testing, and monitoring. The outcome measures assessed in this study are the medical costs of preconception care versus prenatal care only and the benefit-cost ratio. RESULTS: The costs of preconception plus prenatal care are $17,519/delivery, whereas the costs of prenatal care only are $13,843/delivery. Taking into account maternal and neonatal adverse outcomes, the net savings of preconception care are $1720/enrollee over prenatal care only and the benefit-cost ratio is 1.86. The preconception care program remained cost saving across a wide range of assumptions regarding incidence of adverse outcomes and program cost components. CONCLUSIONS: Despite significantly higher per delivery costs for participants in a hypothetical preconception care program, intensive medical care before conception resulted in cost savings compared with prenatal care only. Third-party payers can expect to realize cost savings by reimbursing preconception care in this high-risk population.

Financial implications of implementing standards of care for diabetes and pregnancy.

This article examines the financial implications of implementing standards of care for pregnancy among women with diabetes, including both the costs of enhanced treatment and the savings of avoided adverse outcomes. Numerous studies have demonstrated the harmful effects of poor blood glucose control for both mother and fetus. Standards set forth by the American Diabetes Association aim to reduce maternal complications and fetal adverse outcomes, such as congenital malformations. Because the precise configuration of resources required to meet these standards was not outlined in the American Diabetes Association statement, a panel of physicians (all specialists in pregnancy care for women with diabetes) was convened to develop a model program. Implementing such a program during the preconception and prenatal periods will represent an intensification of resource use in the outpatient setting. However, through these preventive measures, medical care costs for maternal and fetal complications can be avoided.

The effect of minor degrees of glucose intolerance on the incidence of neonatal macrosomia.

The incidence of neonatal macrosomia in infants of mothers who have only one abnormal value in a 3-hour glucose tolerance test (GTT) is greater than normal. Often, corrections for gestational age have not been used in the analysis, and in the few studies in which corrections were made, the results conflicted. In this study, the birth weights of infants from 157 patients who had only one abnormal GTT value were compared with the birth weights of infants from normal mothers, with and without correction for gestational age. Analysis using three different GTT criteria revealed that the incidence of birth weight greater than 4000 g was 20% or greater in the infants of mothers who had only one abnormal GTT value and only 12.4% in controls. However, when adjusted for gestational age, there were no differences in the birth weights and percentage of large for gestational age (LGA) infants in the study groups versus controls. The mean and gestational age-adjusted birth weights of the greater-than-4000-g neonates born to women with one abnormal GTT value were no different than those of controls. However, at delivery, the gestational ages of patients with one abnormal GTT value tended to be slightly greater than those of controls by 0.1-0.6 weeks, suggesting that minor degrees of abnormal glucose metabolism may prolong pregnancy in some patients. When compared with the literature, the findings of this study suggest that the National Diabetes Data Group criteria may be too high as a screen for LGA infants.

Failure to obtain follow-up testing for gestational diabetic patients in a rural population.

OBJECTIVE: To determine physician and patient compliance rates for diabetes testing in patients with previous gestational diabetes. METHODS: Questionnaires regarding follow-up testing and personal health history were sent to 66 patients with previous gestational diabetes who did not have diabetes when they participated in a follow-up study conducted 5 years earlier. A 2-hour glucose tolerance test (GTT) was offered to those whose last test was done more than 1 year previously. RESULTS: All 66 individuals returned the questionnaire and 20 (30.3%) reported having received a yearly 2-hour GTT. Of the remaining 46, 19 had been tested at least once in the previous 5 years, but 27 had not been tested. Of the patients who had been tested at least once in the 5-year period, their physicians initiated testing 61.5% of the time and the patients initiated the remainder. There were no significant differences between physician specialty and rate or appropriateness of the testing. Of 39 individuals who had been tested at least once in the 5-year period, eight had diabetes and four were glucose intolerant. Of 12 individuals who had not been tested in the past year and agreed to be tested in 1995, four had diabetes and two had glucose intolerance. CONCLUSION: Although physicians and their gestational diabetic patients knew the risks of diabetes development, compliance with follow-up testing was poor and the risk of developing diabetes high.

A new definition of the nonstress test.

The nonstress portions of 42 abnormal oxytocin challenge tests (OCT) and 50 negative OCT tracings were redefined by 9 criteria in the literature. The results showed that the criteria of Trierweiler et al are the most predictive of fetal outcome but would lead to unnecessary OCTs in 46% of cases. However, the criteria of Trierweiler et al in combination with a new criteria modified from thos of Paul and Miller and Evertson et al are the most predictive and lead to unnecessary OCTs in only 14% of cases.

Ultrastructural changes in preputial neural tissues: effects of maternal drinking.

Peripheral nerves in the prepuces of eight newborns were studied in this investigation. The mothers of four of these newborns were alcohol abusers but did not smoke or take coffee. The other four mothers did not drink alcohol or coffee, nor did they smoke. Using a transmission electron microscope, the peripheral nerves in preputial specimens were studied for pathological changes. In samples taken from the prepuces of those newborns with drinking mothers, the neuropathological changes seen were mainly in the unmyelinated axons. These demonstrated increased vesicular and tubular elements of agranular endoplasmic reticulum and dense bodies not found in the specimens taken from the non-drinking group. Other significant findings in the fetal preputial specimens from the alcohol group were aggregations of mitochondria and collagen entrapment.

Gestational diabetes and neonatal macrosomia in the polycystic ovary syndrome.

Since patients with polycystic ovary syndrome (PCOS) commonly have insulin resistance, albeit with normal glucose tolerance, we evaluated glucose tolerance in PCOS patients exposed to the diabetogenic effect of pregnancy. The clinical material was obtained from two centers, in Springfield, Illinois (22 patients), and New York, New York (31 patients), and the results were compared with a control population with 2,306 consecutive general pregnancies. There were no differences between PCOS patients from the two centers in regard to age or ponderal index (P greater than .1). A review of the medical records showed that the incidence of gestational diabetes in the PCOS patients was 7.5%, similar (P greater than .1) to the 6.6% frequency of gestational diabetes in the controls. The overall incidence of neonatal macrosomia (birth weight greater than 4,000 g) was 7% (4 of 57) among infants born to PCOS women. That was similar to the 12.4% incidence of neonatal macrosomia among infants born to women with normal glucose tolerance and to the 14.5% incidence among infants born to women with gestational diabetes. Preexisting PCOS does not appear to increase the risk of developing gestational diabetes or neonatal macrosomia.

Ultrastructure of human placenta: effects of maternal drinking.

Previous investigations employing both animal models and human subjects have already documented that maternal alcohol consumption during pregnancy has definite deleterious effects upon the developing fetus. In these earlier studies, however, only gross morphological assessments were used to determine the toxicity of alcohol upon placenta and fetus. To date, there is nothing in the literature regarding the effects of alcohol upon the ultrastructure of the placenta. In our laboratory, using both scanning and transmission electron microscopy, placental specimens from mothers who drank heavily during the gestational period revealed ultrastructural abnormalities which suggest that maternal alcohol consumption may indirectly affect the fetus by altering the fine structure of the placenta.

Elevation of a calcium fraction tightly bound to serum proteins in maternal blood at delivery and in cord blood from newborn infants.

The intimate mechanisms for calcium transport and accumulation in bone cells are complex. We have previously observed that calcium tightly bound to serum proteins is taken up by bone cells preferentially over ionized calcium. To explore the significance of this phenomenon as a potential mechanism for calcium transport in vivo, we studied the distribution of calcium in sera from normal individuals, pregnant women, cord blood from newborn infants, and patients with disorders of calcium homeostasis. Tightly bound calcium was defined as the fraction that remained bound to serum proteins after six consecutive ultrafiltration cycles. Cord blood from newborn infants showed striking elevations of total serum calcium, 11.2 +/- 0.3 mg/dl (+/- SEM), and of the fraction tightly bound to serum proteins, 25.1% +/- 1.7%, compared to normal control values of 9.5 +/- 0.1 mg/dl, and 18.9% +/- 1.1%, respectively (p less than 0.01). Maternal blood at delivery also exhibited an increase of the tightly bound calcium fraction, 27.1% +/- 0.7% (p less than 0.01), but normal total serum calcium concentration, 9.4 +/- 0.2 mg/dl. There was no correlation between the simultaneous fractional concentrations of tightly bound calcium in the maternal and fetal blood compartments (r = -0.03; p = 0.92; n = 12 sets of paired samples). The high concentrations of calcium tightly bound to serum proteins in cord blood suggests that this fraction could play a role in the mineralization of fetal bone.

The effect of maternal smoke exposure on the ultrastructure of fetal peripheral blood vessels in the mouse.

Ultrastructural changes have been found in umbilical blood vessels, placental blood vessels, and peripheral blood vessels of human fetuses whose mothers smoked during pregnancy. This study was undertaken to determine if similar changes could be found in peripheral blood vessels of mice fetuses whose mothers were exposed to cigarette smoke during pregnancy. Breeding mice of the C57BL/KsJ strain were placed in a smoking box similar to that described by Younoszai and exposed to cigarette smoke intermittently. This produces carbon monoxide levels in the adult mice similar to that found in human adults smoking one pack of cigarettes per day. Similarly caged mice of the same strain were used as controls. The female mice were not removed from their cage from pre-conception time until after delivery. Upon delivery each pup was sacrificed via neck fracture and the entire pup was immersed in a solution of 2.5% glutaraldehyde in 0.1 M cacodylate buffer at pH 7.3. While still under solution, the rear leg muscles were dissected free, sliced, and immersed in the same preservative for four to five hours. They were then placed in fresh 2.5% glutaraldehyde mixture overnight. The tissues were post-fixed in osmium ferrocyanide and en-block stained with uranyl acetate in a graded series of alcohol. The tissues were infiltrated with and embedded in Spurr. Sections were taken via an ultramicrotome and post-stained with uranyl acetate and lead citrate. The sections were examined in a Philips 201 electron microscope at 60 KV. In the peripheral vessels of the fetuses from smoke-exposed mothers, endothelial blebbing (both surface-type and vacuole-type) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural changes in neonatal liver tissue: effects of maternal drinking.

There is already sufficient evidence in the literature that alcohol abuse during pregnancy has a toxic effect upon the developing fetus; however, previous studies have not revealed any morphological changes in fetal or newborn liver specimens from animals exposed to alcohol in utero. As it is known that alcohol freely crosses the placental barrier, this investigation was an attempt to demonstrate that structural abnormalities can indeed be identified in neonatal mouse liver specimens from pups exposed to alcohol in utero. Chosen as a model for this study was the C57BL/KsJ mouse strain as this particular animal demonstrates an alcohol preference paralleling that of the human alcoholic. Findings appear to indicate the presence of abnormal changes on the morphological level in these study animals.

Ovarian effects upon maternal glucose tolerance.

Ovaries from homozygous diabetic (db/db) female mice were removed and transplanted into the empty left ovarian sacs of normal homozygous (m/m) female mice which had undergone left oophorectomies. To produce controls, the previously removed normal left ovaries were transplanted into the empty left ovarian sacs of other normal (m/m) left oophorectomized females. Glucose tolerance tests were done on the study and control mice before surgery, after surgery, during pregnancy, and after delivery. There were no significant differences in the glucose tolerance test results between study group and controls before or after surgery. However, the study group, when compared to the controls, had a statistically significant glucose intolerance during pregnancy. After delivery, the glucose levels returned to normal. The ovaries from diabetic (db/db) female mice may produce hormones which, by themselves or in concert with the fetal and placental hormones, may produce maternal glucose intolerance during pregnancy.

Ultrastructural changes in neonatal sciatic nerve tissue: effects of passive maternal smoking.

The dangers of cigarette smoking having already been recognized, this study attempts to delineate findings from a passive smoking study at the ultrastructural level. The project utilized a model of mice subjected to cigarette smoke and encompassed the electron microscopic examination of neonatal tissue for morphological abnormalities. Study of sciatic nerve tissue taken from the offspring of passively smoked females revealed definite toxic effects on the neonatal tissue. This investigation, which concentrated on morphological changes, indicates that passive maternal smoke inhalation may result in abnormal changes to the fine structure of fetal tissue although further investigation in this area is necessary to broaden our knowledge and understanding of the mechanisms involved.

A simple and efficient method for obtaining urine samples from rats.

A method for collection of urine from rats was developed that is simple, reliable, and efficient. A 5 ml. polystyrene beaker is placed over the urethra and the base of the tail is stimulated with the fingers of one hand. Depending on the quality and quantity of urine needed the perineal area may be shaved and the beaker may be held by hand or attached with tape.

Inhibin in normal and abnormal pregnancy: maternal serum concentration and partial characterization.

OBJECTIVE: This study evaluated maternal serum inhibin concentration and molecular distribution in normal and abnormal pregnancies. STUDY DESIGN: Serum inhibin levels were measured by radioimmunoassay in 33 abnormal pregnancies (23 singleton and 10 multiple gestations) and 33 matched controls and were compared with pregnancy variables. RESULTS: In the controls serum inhibin concentrations rose with gestational age (correlation coefficient 0.358, p < 0.01) and were higher in mothers with female fetuses (p < 0.05). Inhibin levels were higher in the abnormal singleton pregnancies (2.69 +/- 1.41 ng/ml) than in controls (1.26 +/- 0.32 ng/ml, p < 0.0001) and increased more rapidly with gestational age in multiple pregnancies (p < 0.05). Gel filtration chromatographic analysis of immunoreactive inhibin revealed three peaks with the major form having an apparent molecular weight of 55 to 60 kd. CONCLUSION: Maternal serum inhibin concentrations are affected by gestational age, fetal gender, and complications of pregnancy. Most of the immunoreactive inhibin in maternal circulation is a large-molecular-weight form.

Gestational diabetes diagnostic criteria: long-term maternal follow-up.

OBJECTIVE: The purpose of this study was to determine if the risk of having diabetes later in life was different in those who were gestational diabetic by Coustan criteria and not by National Diabetes Data Group criteria and those who are gestational diabetic only by National Diabetes Data Group criteria. STUDY DESIGN: Between 1988 and 1990, 331 patients from the Springfield area who were diagnosed as gestational diabetic by either criteria since 1975 were examined for the development of diabetes by history or by 2-hour, 75 gm glucose tolerance test. National Diabetes Data Group criteria were used to determine normality or diabetic abnormality. Variables associated with diabetes were obtained. The data were analyzed using three groups: (1) gestational diabetic by National Diabetes Data Group criteria, (2) gestational diabetic by Coustan's criteria only, and (3) both groups 1 and 2. RESULTS: Group 1 had 190 (57.4%) and group 2 had 141 patients (42.6%), of which 25.3% and 25.5% had diabetic abnormality, respectively. Variables predictive for the development of diabetic abnormality were glucose tolerance test fasting value, number of gestational diabetic pregnancies, time to follow-up, and prepregnancy weight index. There were no differences in these variables between the normal patients or those with diabetic abnormality in groups 1 and 2. CONCLUSION: Because Coustan criteria classify an additional 68.9% patients who have the same risk and risk factors for later development of diabetic abnormality and pregnancy complications compared with patients who are gestational diabetic by National Diabetes Data Group criteria, the criteria of Carpenter and Coustan should be adopted as the standard for diagnosing gestational diabetes.

Effect of pregnancy on glucose metabolism in glucose intolerant 'BB' Wistar rats.

Little is known about the effect of pregnancy on the 'BB' Wistar rat, an animal model of insulin-dependent (type I) diabetes. The pathogenesis of diabetes in this animal model seems to result from antibody-mediated natural killer cell destruction of pancreatic beta cells. The glucose metabolism of glucose intolerant female rats (study group) was studied prior to pregnancy, during pregnancy, and postpartum using glucose tolerance tests (GTT). Control rats with normal GTT were studied and bred in a fashion similar to the study animals. Before becoming pregnant, the GTT levels of the chemically diabetic rats were significantly different from those of the controls (p less than 0.05). The GTT values of the study animals decreased during pregnancy to levels seen in pregnant controls. After pregnancy, the GTT values of the study animals returned to prepregnant levels. Based on these observations, it appears that pregnancy may block the autoimmune destruction of beta cells, causing an increase in insulin production and release, thereby improving glucose metabolism.

Diabetic pregnancy. The effect of genetic susceptibility for diabetes on fetal weight.

Since macrosomic infants of diabetic mothers tend to remain obese throughout their lives, and obesity and heredity are factors predisposing to Type II diabetes, it can be hypothesized that infants who are going to develop diabetes later in life are more likely to be macrosomic at birth than those who are not going to develop diabetes as adults. This hypothesis was tested, using the c57/KsJdb+/+m mouse animal model of gestational diabetes. This animal is frankly diabetic in the homozygous diabetic form. In the heterozygous form, it develops gestational diabetes, and in the homozygous normal form, it is normal. The pups of heterozygous males and females that were bred were weighed, classified by sex, and identified. At 4 weeks of age, the genetic makeup of the pups was determined. From 37 litters, 140 pups were born and raised to weaning age. Multiple regression analysis of the data revealed that the homozygous diabetic pups weighed most at birth; the heterozygous gestationally diabetic pups weighed less, and the homozygous normal pups weighed the least. All comparisons of these groups were statistically significant. Sex and interlitter variation also were found to be significant factors determining birthweight. Controlling for sex and interlitter variation did not change the significance of the effect of the genetic tendency for diabetes on birthweight. This study indicates that in Type II diabetes, neonatal macrosomia in part may be determined by the genetic or congenital susceptibility to develop diabetes in the future.

An animal model of gestational diabetes.

Glucose tolerance tests (GTTs), hemoglobin A, levels, and pup weights were studied in both normal (C57BL/KsJ-+m/ + m) and heterozygous (C57BL/KsJ-db+/ + m) mice. There was no difference in GTT or hemoglobin A, levels between heterozygotes and normal animals in the nonpregnant state. However, the pregnant heterozygous mouse had significantly elevated GTTs (p less than 0.001) and hemoglobin A, levels (p less than 0.002) when compared to the normal pregnant mouse. The mean weight of pups from heterozygous parents was significantly greater than that of pups from normal parents (p less than 0.0005). Because the heterozygous mouse (C57BL/KsJ-db+/ + m) exhibits these characteristics of gestational diabetes, it may be possible to use it as an animal model of gestational diabetes.