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Biomedical subjects

M F Greene

Publications and source records attributed to M F Greene.

At least 37 records · Page 2Linked to original sources

Maternal metabolic control and risk of microcephaly among infants of diabetic mothers.

OBJECTIVE: To measure the incidence of microcephaly among infants of diabetic mothers (IDM) and assess its relationship to metabolic control during pregnancy. RESEARCH DESIGN AND METHODS: Head circumference data for 556 consecutive live-born singleton infants of women with insulin-requiring diabetes antedating pregnancy delivered between 28 and 40 weeks of gestation and the results of 3,242 HbA1 determinations collected during their pregnancies were examined. RESULTS: There were fewer head circumferences at or below the 3rd percentile and more at or above the 97th percentile than expected. Head circumference was not related to maternal metabolic control as documented by the HbA1 values. CONCLUSIONS: The less-than-expected incidence of microcephaly observed in this patient population probably reflects the well-known tendency of IDM toward macrosomia.

Adult↗

The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence.

BACKGROUND: Although the medical complications associated with multiple-gestation pregnancies have been well documented, little is known about the effects of such pregnancies on the use of health care resources and the associated costs. This is an important issue because of the increasing use of assisted-reproduction techniques, which commonly result in multiple-gestation pregnancies. METHODS: We determined hospital charges and the use of assisted-reproduction techniques (such as induction of ovulation, in vitro fertilization, and gamete intrafallopian transfer) for 13,206 pregnant women (11,986 with singleton pregnancies, 1135 with twin pregnancies, and 85 with more than two fetuses) who were admitted for delivery to Brigham and Women's Hospital, Boston, in 1986 through 1991 and their 14,033 neonates (11,671 singletons, 2144 twins, and 218 resulting from higher-order multiple gestations). RESULTS: After we controlled for variables known to affect hospital charges, the predicted total charges to the family in 1991 for a singleton delivery were $9,845, as compared with $37,947 for twins ($18,974 per baby) and $109,765 for triplets ($36,588 per baby). Assisted-reproduction techniques were used in 2 percent of singleton, 35 percent of twin, and 77 percent of higher-order multiple-gestation pregnancies; such procedures were approximately equally divided between induction of ovulation alone and in vitro fertilization or gamete intrafallopian transfer. CONCLUSIONS: Multiple-gestation pregnancies, a high proportion of which result from the use of assisted-reproduction techniques, dramatically increase hospital charges. If all the multiple gestations resulting from assisted-reproduction techniques, dramatically increase hospital charges. If all the multiple gestations resulting from assisted-reproduction techniques had been singleton pregnancies, the predicted savings to the health care delivery system in the study hospital alone would have been over $3 million per year. Although assisted reproduction provides tremendous benefits to families with infertility, the increased medical risks entailed by multiple-gestation pregnancies and the associated costs cannot be ignored. We suggest that more attention be paid to approaches to infertility that reduce the likelihood of multiple gestation.

Adolescent↗

A predictive model for fetal lung maturity employing gestational age and test results.

Most laboratory tests for fetal lung maturity (FLM) are optimized to exclude false-negative predictions of absence of respiratory distress syndrome (RDS), with a reciprocal low predictive value for maturity. The authors employed FLM Surfactant/Albumin Ratio (FLM S/A) test results to construct a predictive model for FLM that included the obstetric estimates of gestational age. The charts of 388 newborns were abstracted and reviewed. The clinical outcome was the gold standard of the multivariate logistic analysis. Both the obstetric estimates of gestational age and the test result were significant predictors of the clinical outcome (P values of < .0002 and .001, respectively). The prediction rule for RDS as a function of both of these variables allows for adjustment of the test cutoffs, so that there is a consistent probability of RDS at the cutoff FLM S/A result for different gestational ages. Fetal lung maturity probability reporting may facilitate clinical decision-making.

Albumins↗

Glucose intolerance as a predictor of hypertension in pregnancy.

Insulin resistance is associated with and may be causal in essential hypertension, but the relation between insulin resistance and hypertension arising de novo in pregnancy is unclear. Transient hypertension of pregnancy (new-onset nonproteinuric hypertension of late pregnancy) is associated with a high risk of later essential hypertension and thus may have similar pathophysiology. To assess the association between glucose intolerance and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension or overt glucose intolerance, we performed a retrospective case-control study comparing glucose levels on routine screening for gestational diabetes mellitus among women subsequently developing hypertension. Women who developed hypertension in pregnancy (n = 97) had significantly higher glucose levels on 50-g oral glucose loading test (P < .01) and a significantly higher frequency of abnormal glucose loading tests (> or = 7.8 mmol/L) (P < .01) than women who remained normotensive (n = 77). Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. Women who developed hypertension also had greater prepregnancy body mass index (P < or = .0001) and baseline systolic and diastolic blood pressures (P < or = .0001 for both), although all subjects were normotensive at baseline by study design. However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (P < .05) and, specifically, nonproteinuric hypertension in pregnancy (P < .01). Among a subgroup of women in whom insulin levels were also measured (n = 80), there was a nonsignificant trend toward higher insulin levels in women developing hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Animal models for perinatal transmission of pathogenic viruses.

In earlier work, mouse models have been used to demonstrate the efficacy and lack of toxicity of transplacental and perinatal AZT therapy. These practical small animal models can be useful for evaluating antiviral drugs aimed at common retroviral functions only, since Type C MuLVs are used. A primate model for fetal infection with an immunosuppressive lentivirus, SIV, has been established using ultrasound-guided inoculation of the amniotic fluid. The infection rate was 86% overall and 100% if the fetal SIV exposure occurred at least 19 days before delivery. The suspected major route of vertical HIV-1 transmission, that is, virus entry through fetal mucous membranes or skin, is replicated by our approach. The high fetal infection rate will allow studies of SIV pathogenesis during various stages of fetal development. This model should be well suited to development and evaluation of therapeutic strategies for preventing fetal infection.

Animals↗

Renal dysplasia, megalocystis, and sirenomelia in four siblings.

First degree relatives of infants with bilateral renal agenesis or dysplasia have an increased risk of renal abnormalities including renal agenesis. We report a family in which four successive offspring exhibited a previously undescribed combination of congenital lethal renal disorders: bilateral renal dysplasia, megalocystis secondary to urethral obstruction and, sirenomelia with associated renal agenesis.

Abnormalities, Multiple↗

Prevention and diagnosis of congenital anomalies in diabetic pregnancies.

The high rate of major congenital malformations among infants of diabetic women represents the largest and most refractory problem in the perinatal care of these women. The prenatal diagnosis of these malformations will always be easier than their prevention. They are clearly not, however, entirely "beyond our therapeutic control."

Abortion, Spontaneous↗

Simian immunodeficiency virus infection via amniotic fluid: a model to study fetal immunopathogenesis and prophylaxis.

The rising prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in young women will increase the number of infected children worldwide. Because HIV-1 seems to be transmitted mostly intrapartum, fetal infection probably occurs mainly via skin or mucous membrane exposure. A model for this route of fetal infection has been established in primates. After injecting the simian immunodeficiency virus (SIV) into amniotic fluid during late gestation, six of seven rhesus monkeys were born infected. All infected neonates were viable and showed signs of disease, such as low birth weights, lymphadenopathy, and rashes. Cytotoxic T-cell responses to SIV were absent in neonates, but present in mothers. The high fetal infection rate allows studies of lentiviral immunopathogenesis during ontogeny and the development of strategies to prevent maternal HIV-1 transmission.

Amniotic Fluid↗

Estimating the time of death in stillborn fetuses: I. Histologic evaluation of fetal organs; an autopsy study of 150 stillborns.

OBJECTIVE: To determine whether the autopsy histology of fetal tissues can determine the time of death of stillborn fetuses. METHODS: Hematoxylin and eosin slides from autopsies of 150 stillborn fetuses with well-timed deaths were evaluated retrospectively. Fetuses were divided into a learning set (100 fetuses) and a test set (50 fetuses). RESULTS: From assessment of the 100 fetuses in the learning set, 23 histologic features were identified with possible temporal associations with fetal death. When those histologic features were randomly and blindly assessed in the 50 test fetuses, ten features performed well as diagnostic tests (sensitivity, specificity, and positive predictive values at or above 0.875), correctly classifying 43 of 50 fetuses (86%) with respect to the time of death. The ten histologic features and their predicted death-to-delivery intervals were: loss of nuclear basophilia in individual cells in renal cortical tubules (4 hours), liver (24 hours), inner half of the myocardium (24 hours), outer half of the myocardium (48 hours), bronchial epithelium (96 hours), and tracheal cartilage (1 week); and loss of nuclear basophilia of all cells in the liver (96 hours), gastrointestinal tract (1 week), adrenal (1 week), and kidney (4 weeks). The development of these histologic changes appeared to be accelerated by fetal hydrops and a delivery-to-autopsy interval exceeding 24 hours and decelerated by fetal gestational age under 25 weeks. CONCLUSION: Histologic changes identifiable in hematoxylin and eosin-stained fetal tissue may be useful for estimating the time of death in many stillborn fetuses.

Autopsy↗

Fetal abdominal wall defect: a new complication of vesicoamniotic shunting.

Vesicoamniotic shunting for fetal obstructive uropathy is beneficial in selected cases. We report a new complication, fetal abdominal wall defect secondary to vesicoamniotic shunting. Placement of the shunt should be as low and as close to the fetal midline as possible in order to reduce the risk of this complication.

Abdominal Muscles↗

Prenatal diagnosis in diabetic gravidas: utility of ultrasound and maternal serum alpha-fetoprotein screening.

The differences in both the biology of pregnancy and the content of routine care between gravidas with and without diabetes mellitus lead to important differences in the potential utility of both ultrasound examination and maternal serum alpha-fetoprotein (MSAFP) screening. However, both diagnostic methods have become standards of care for these patients, without critical evaluation. This study examines the utility of both ultrasound and MSAFP in diabetic women. Four hundred thirty-two women with diabetes mellitus antedating pregnancy were examined sonographically between 12-23 weeks' gestation. Of these, 393 were also screened with MSAFP determinations. At delivery, 32 of these fetuses were found to have 38 major congenital malformations. All fatal or potentially life-threatening defects had been diagnosed in utero by sonography before 24 weeks' gestation. Ultrasound had a positive predictive value of 90% and a negative predictive value of 97% for identification of major birth defects before 24 weeks' gestation. There were 14 MSAFP values greater than 2.0 multiples of the median, and nine of these patients elected to undergo amniocentesis. Maternal serum alpha-fetoprotein screening had a positive predictive value of 17% and a negative predictive value of 94%. No malformations were detected through MSAFP screening that had not been diagnosed by sonography. No malformations missed sonographically were detected by MSAFP screening, and none of the amniocenteses were helpful diagnostically. We conclude that MSAFP screening is of minimal utility for diagnosing major congenital malformations in a high-risk population examined universally by an experienced sonographer.

Congenital Abnormalities↗

First-trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy.

The relationship between the level of hemoglobin A1 (Hb A1) in the first trimester and major malformations and spontaneous abortions was examined in 303 insulin-requiring diabetic gravidas. During the study period, all patients with insulin-requiring diabetes mellitus antedating pregnancy who registered for prenatal care prior to 12 weeks' gestation and who had a known outcome were included. Thirty-five percent of the patients entered with a first-trimester Hb A1 of greater than 11.0% of total hemoglobin (9 standard deviations above the mean for a nondiabetic population). A broad spectrum of glycemic control was therefore represented. The risk of spontaneous abortion was 12.4% with first-trimester Hb A1 less than or equal to 9.3% and 37.5% with Hb A1 greater than 14.4% (risk ratio 3.0; 95% confidence interval 1.3-7.0). The risk for major malformation was 3.0% with Hb A1 less than or equal to 9.3% and 40% with Hb A1 greater than 14.4% (risk ratio 13.2; 95% confidence interval 4.3-40.4). Although the risks for both adverse outcomes were markedly elevated following a first trimester in very poor metabolic control, there was a broad range of control over which the risks were not substantially elevated. To keep malformations and spontaneous abortions to a minimum among diabetic women does not require "excellent" control; there seems to be a fairly broad range of "acceptable" control.

Abortion, Spontaneous↗

Prematurity among insulin-requiring diabetic gravid women.

From Jan. 1, 1983, through Dec. 31, 1987, 420 gravidas with insulin-requiring diabetes antedating pregnancy delivered on the Joslin Clinic service. Among them, 110 pregnancies (26.2% of the total) delivered before 37 completed weeks of gestation compared with a 9.7% incidence (906/9368) for the general population at the Brigham and Women's Hospital during calendar year 1985. Thirty-three percent of all premature deliveries were the result of the development of preeclampsia. The relative risk of prematurity for diabetic patients with any hypertensive complication was 2.0 (95% confidence interval, 1.40 to 2.87) compared with normotensive diabetic subjects. Compared with the general population, most of the excess risk of prematurity was confined to hypertensive diabetics and normotensive patients of more advanced White class. A history of having had a previous premature delivery, increasing duration of diabetes antedating pregnancy, and carrying a male fetus in the index pregnancy were significantly associated with premature delivery. Future efforts to reduce the incidence of prematurity among diabetic gravidas should be directed toward reducing the incidence of preeclampsia.

Diabetes Mellitus, Type 1↗

Fetal surgery and general anesthesia: a case report and review.

Fetal surgery, in utero, is now a viable option for some congenital conditions due to recent advances in ultrasound and microsurgical technology. Previous reports of anesthesia for such procedures have focused on spinal or epidural conduction techniques. General endotracheal anesthesia may have several advantages in this setting. In addition to maternal anesthesia, general anesthesia can provide fetal neuromuscular block (without direct fetal injection of blocking agents) and uterine relaxation. It may also blunt fetal response to surgical stimulation.

Adult↗

Pregnancy outcome after premature rupture of the membranes at or before 26 weeks' gestation.

Pregnancy outcome was examined in 59 clinically stable patients with rupture of the membranes at or before 26 weeks' gestation. The mean gestational age at rupture of the membranes was 23.2 weeks, and the mean latent period was 21.5 days. Delivery occurred within 7 days in 29 patients (49.2%), chorioamnionitis developed in 27 patients (45.8%), and operative delivery was required in 24 patients (40.7%). Sixty-three infants were delivered, with a perinatal mortality rate of 49.1%. Among survivors, 84% required newborn intensive care during the initial hospitalization, 77% were discharged with minor to moderate reversible sequelae, and 16% were discharged with sequelae that were likely to be of long-term duration. Obstetric factors present at rupture of the membranes were evaluated for their ability to predict maternal and neonatal morbid outcomes; obstetric interventions were evaluated for their ability to modify outcomes. These data suggest that outcomes in this subset of patients may not be uniformly dismal, and support clinical decision-making on an individualized basis.

Adult↗