Biomedical subjects
Publications and source records attributed to S G Gabbe.
Despite improvement in perinatal outcome over the past several decades, controversy still exists regarding both the management and pathophysiology of pregnancy complicated by diabetes mellitus. In this article, potential factors contributing to morbidity observed in the offspring of diabetic women are considered. The clinical management of insulin-dependent and gestational diabetes is also discussed.
With the introduction of silicone indwelling cerebrospinal fluid (CSF) shunts in the 1960s, the prognosis for children with hydrocephalus changed dramatically. These individuals are leading normal and productive lives today. Many women with CSF shunts are not entering the childbearing years. Previously, only 13 cases of pregnancy occurring in patients with CSF shunts have been reported. We present two cases here and review the complications and outcome of the other reported cases. Shunt malfunction appears to be common in pregnancy due to increased intraperitoneal pressure and the enlarging uterus. Rarely is surgical correction or premature delivery necessary. A successful pregnancy ending in the vaginal delivery of a term infant can be expected in the majority of these patients.
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To assess the predictive value of uterine activity as a marker for subsequent preterm labor, 139 black, inner city women were monitored at least three times for 1 hour between 28-32 weeks' gestation using a portable tocodynamometer. All had singleton gestations and gave no previous history of preterm labor or delivery. They were monitored between 8 and 10 AM while sitting in the clinic waiting area. Uterine activity records, numbered randomly, were transmitted by telephone to a site remote from the hospital. No one having any clinical contact with the participants saw or received feedback regarding the contraction data. Tocodynamometry records were then mailed to another center where they were read by one investigator blinded to all clinical information. The mean contraction frequency during the single hour of weekly testing was significantly greater for the 16 women who developed preterm labor than for women who delivered at term at each point between weeks 28-32. Using greater than six contractions per hour on at least one occasion between 28-32 weeks' gestation as a predictor would have identified 12 of 16 women (sensitivity 75%) who subsequently developed preterm labor. This contraction frequency was noted in 26 of 123 women (21%) who labored at term (specificity 79%; P = .0003).
Amniotic fluid cholesteryl palmitate, as measured by thin-layer chromatography, appears to be a very sensitive and specific predictor for the risk of respiratory distress syndrome (RDS) in newborns of normal pregnancies. To assess the effect of diabetes mellitus on fetal pulmonary maturation, we measured cholesteryl palmitate concentration, the lung profile, and total phosphatidylcholine in amniotic fluid obtained from 35 well-controlled diabetic and 39 control pregnancies at term. In women with diabetes, the mean (+/- SD) third-trimester glycosylated hemoglobin level was 6.96 +/- 2.3% (normal 6-8%). Mean cholesteryl palmitate concentration in the diabetic population was 79.12 +/- 13.17 micrograms/mL, versus 153.71 +/- 16.77 micrograms/mL in the control group (P less than .001). The mean cholesteryl palmitate concentration was also significantly different for gestational diabetics and class B-R gravidas (112.75 +/- 26.2 versus 54.45 +/- 7.34 micrograms/mL; P less than .005). Cholesteryl palmitate was decreased despite the presence of a mature lecithin/sphingomyelin ratio and, in most cases, phosphatidylglycerol. These data suggest that even in well-controlled diabetic pregnancies, alterations in maternal metabolism may affect either the biosynthesis or degradation of cholesteryl palmitate.
The pregnancy of a women with diabetes mellitus was complicated by Graves' disease and maternal allergies to propylthiouracil and methimazole. Preparations for surgical removal of the thyroid gland were being made until pregnancy intervened. Several well-documented mechanisms of hyperthyroidism, including increased intestinal absorption of glucose, decreased insulin responsiveness, and increased glucose production may exacerbate glucose intolerance; the daily insulin requirement of this patient rose 80% from her pregestational dosage. When large doses of propranolol failed to control her thyrotoxic symptoms and led to severe, recurrent hypoglycemic episodes, subtotal thyroidectomy was performed. A 42% decrease in insulin requirements was observed postoperatively, with return to the euthyroid state. A propensity for symptomatic postoperative hypoglycemia should be anticipated in diabetic patients undergoing thyroidectomy.
The relationship between glycemic control and perinatal outcome was assessed in a relatively uniform population of 75 White Class B through D pregnant diabetic women. All patients used glucose reflectance meter self-monitoring and performed a minimum of four determinations daily. Mean capillary blood glucose was calculated from a minimum of 16 weeks of determinations. Regression analysis confirmed a correlation between these values and third-trimester hemoglobin A1 (p less than 0.001). The study population was divided into two groups on the basis of mean capillary blood glucose values: group I, mean capillary blood glucose less than 110 mg/dl (43 patients) (mean = 96.8 +/- 7.1); group II, mean capillary blood glucose greater than 110 mg/dl (32 patients) (mean = 126 +/- 9.0). Of the 32 patients in group II, eight had mean capillary blood glucose greater than or equal to 130 mg/dl. The degree of maternal glycemic control appeared to affect perinatal outcome. At least one form of infant morbidity was present in 33% of group I infants compared with 53% of group II. Significant differences were observed for the incidence of hypoglycemia (p less than 0.05), macrosomia (p less than 0.05), and respiratory distress syndrome (p less than 0.01). One of six group I infants delivered at 35 to 36 weeks developed respiratory distress syndrome, compared with four of seven group II patients. The appearance of phosphatidylglycerol in amniotic fluid appeared delayed in group II patients at term. These data suggest that maintaining mean capillary blood glucose values less than 110 mg/dl may serve to reduce several major forms of morbidity in the infant of the diabetic mother. This information is helpful in establishing objectives for glycemic control in pregnant women using self-monitoring techniques.
Plasma glucose determinations were performed 1 hour after a 50 gm oral glucose load in 30 patients receiving long-term terbutaline therapy (20 to 40 mg/day for at least 1 week) and 247 normal control patients. A total of 63% of patients receiving terbutaline had an abnormal 1-hour value (greater than or equal to 140 mg/dl), an incidence much higher than that of control subjects (17.8%) (p less than 0.0001) for a relative risk of 3.54 (95% confidence intervals of 2.29 to 5.42). Mean 1-hour values were 112.1 mg/dl for control subjects and 149.8 mg/dl in the terbutaline group (p less than 0.0001). All abnormal values were followed by a 3-hour 100 gm oral glucose tolerance test. A total of 15.9% of the glucose tolerance tests performed in the control group (2.8% overall) were abnormal as opposed to 52.6% (33.1% overall) in patients receiving terbutaline (p less than 0.01). Nine patients were studied before and after terbutaline therapy. Results obtained during administration of terbutaline were significantly higher (102.2 mg/dl before therapy versus 145.2 mg/dl during therapy). We conclude that treatment with oral terbutaline appears to be associated with impairment of glucose tolerance in pregnancy.
Over a 5-year period we have managed 63 diethylstilbestrol-exposed pregnant patients with a standardized protocol requiring weekly cervical examination and decreased physical activity of the patient. Twenty-six patients (42%) underwent a prophylactic cerclage for a history of second-trimester loss or a hypoplastic cervix on initial clinical examination (group I). Thirty-six patients (58%) were followed expectantly (group II). Sixteen patients (44%) in group II demonstrated cervical change and required an emergency cerclage. Twenty-one patients were managed expectantly with no cerclage. The gestational age at delivery for group I was 37.7 +/- 2.80 versus 34.5 +/- 6.9 weeks for patients without a cerclage (p = 0.04). There were no perinatal deaths if a cerclage was performed, whereas there were five deaths (24%) in the group without cerclage. The five deaths occurred at a mean gestational age of 24.40 +/- 4.0 weeks and a mean birth weight of 614.00 +/- 441.73 gm. Patients with a hypoplastic cervix or prior reproductive loss had a better outcome with early cerclage than patients with a normal cervix followed expectantly. We presently lack a reliable method to detect the diethylstilbestrol-exposed patient at greatest risk for perinatal loss. Based on our experience we believe that placement of a cerclage early in pregnancy should be a strong consideration.
Serum iron was measured in 30 patients with pregnancy-induced hypertension and 24 normal pregnant women. The mean iron concentration was significantly higher in the group with pregnancy-induced hypertension (111 +/- 26 micrograms/ml) than in the controls (69 +/- 17 micrograms/ml) (p less than 0.0001). Readily available laboratory variables were used to determine whether the increased serum iron was the result of (1) hemolysis, (2) hepatocellular injury, or (3) intravascular volume contraction leading to hemoconcentration. It appears that a clinically silent, ongoing hemolytic reaction is responsible for the increase in serum iron seen in patients with pregnancy-induced hypertension.
Risk scoring systems based on traditional demographic, social, and medical factors have limited use, especially in certain populations. Newer approaches, including frequent cervical examinations, periodic outpatient monitoring for contractions, extensive daily monitoring at home for contractions in very high-risk persons, and identification and reduction of modifiable behavioral risks, offer promise.
Cholesteryl palmitate was measured by thin-layer chromatography in 98 amniotic fluid samples obtained from pregnancies ranging from 15 to 40 weeks. Pregnancies complicated by diabetes mellitus or Rh sensitization were excluded. Cholesteryl palmitate concentration increased with gestational age from values less than 5 micrograms/ml at 15 weeks to maximum values of 384 micrograms/ml at term. Seventy-three patients were delivered of their infants within 24 hours of sampling. The mean concentration of cholesteryl palmitate for 55 infants without respiratory distress syndrome was 123.70 +/- 12.21 micrograms/ml (SD). For neonates that developed respiratory distress syndrome (n = 18), the mean concentration was 22.66 +/- 6.16 micrograms/ml (SD). This difference is significant (p less than 0.001). For all patients delivered, respiratory distress syndrome was not seen when the cholesteryl palmitate concentration was greater than 41 micrograms/ml (mean + 3 SD). All infants with a concentration below 38 micrograms/ml developed respiratory distress syndrome. We conclude that measurement of cholesteryl palmitate concentration in amniotic fluid might be another reliable method of assessing fetal lung maturity and may often improve specificity when compared with other tests of fetal lung maturity.
We prospectively studied 40 women with preeclampsia and 26 women with normal pregnancy for the presence of platelet-bound and circulating platelet-bindable immunoglobulin and complement. Although only 12 patients with preeclampsia had a platelet count less than 150,000/mm3, 36 of 40 demonstrated an abnormal direct antiglobulin test, compared with only three of 26 control subjects (p less than 10(-8]. An abnormal indirect test was also detected in 30 of 40 patients with preeclampsia compared with five of 26 healthy pregnant control women (p = 9.3 X 10(-6]. Abnormal antiglobulin tests persisted for 2 to 6 weeks after delivery. Although each neonate had a platelet count greater than 200,000/mm3 at the time of delivery, 10 of 18 had an abnormal direct antiglobulin test compared with one of 14 control subjects (p = 0.0049). The high frequency of abnormal platelet antiglobulin tests in women with preeclampsia and their neonates may indicate an immune cause of certain aspects of the syndrome or may reflect the extent of platelet activation.
An evaluation of 227 consecutive twin gestations was undertaken to assess the role of ultrasound (US) in the diagnosis of major obstetric complications and congenital anomalies. US accurately depicted the growth and development of fetuses in 65 patients with underlying maternal disorders that produced additional risks to the pregnancy. Complications such as malpresentations (104 cases), polyhydramnios (15 cases), oligohydramnios (five cases), and uterine myomas (seven of 11 cases) were demonstrated prenatally with US. Fetal anomalies included anencephaly (two cases), hydrocephalus (two cases), conjoined twins (three cases), twin-twin transfusion syndrome (five cases), and acardiac monsters (two cases). Demise of one twin in 20 gestations and demise of both twins in 18 gestations (overall mortality of 17%) were correctly identified with US. These 38 gestations included intrauterine demise in 12, spontaneous abortion in 13, and neonatal deaths in 13. Therefore, when multiple gestations are suspected clinically, serial real-time US scans should be obtained beginning in the first trimester.
Nine percent of United States births are preterm. The ability to efficiently identify women destined to deliver before term would enable obstetricians to initiate early intervention. The Papiernik-Creasy risk scoring system is being extensively applied for this purpose, without prospective validation in this country. We evaluated prospectively its ability to predict high risk women in a black inner city population, when applied once early in pregnancy. The system, based on social, past medical, and current pregnancy problems, failed to identify at-risk patients. Adjusting the score cutoff and reweighting factors with discriminate analysis did not improve the predictive value. Analysis of an additional 60 social, demographic, and medical factors failed to produce a useful alternative risk assessment tool. We suggest that risk scoring systems such as these may not be helpful in socioeconomically at-risk populations.
Primary sclerosing cholangitis is a chronic, fibrosing, inflammatory disorder of unknown etiology affecting the biliary tree. We describe a case of a pregnancy complicated by this condition. Remarkably, maternal cholestasis improved with advancing gestation. Despite a marked elevation of bile acid levels in cord blood, the patient was delivered of a healthy term infant. The principles of management and potential effects of primary sclerosing cholangitis on pregnancy care are discussed.
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Ultrasound records were examined retrospectively in the cases of 70 fetuses with open spina bifida diagnosed by ultrasonography at 16-23 weeks' gestation. Biparietal diameter was below the 5th centile for gestation in 61% and head circumference measurements in 26%. The anterior horn of the lateral cerebral ventricle to hemisphere ratio was above the 95th centile in 77%, and ventriculomegaly of the posterior horn of the lateral venricle was observed in 86%. In the 54 fetuses for which pictures were taken at the level of the biparietal diameter a scalloping of the frontal bones (the lemon sign) was seen. In 12 of 21 fetuses for which a suboccipital bregmatic view of the cranium had been obtained, the cerebellar hemispheres were curved anteriorly with simultaneous obliteration of the cisterna magna (the banana sign); in a further 8 cases the cerebellum was not displayed. None of these changes was seen in 100 patients presenting consecutively for routine ultrasound examination in the second trimester.