Does the combined antenatal use of corticosteroids and antibiotics increase late-onset neonatal sepsis in the very low birth weight infant?

OBJECTIVE: The purpose of this study was to determine whether the combined use of maternal antenatal corticosteroids and antibiotic therapy is associated with an increased risk of late-onset neonatal sepsis among very low birth weight infants. STUDY DESIGN: The outcomes of infants admitted to the 3 Cincinnati neonatal intensive care units between May 1991 and May 2000 were retrospectively evaluated. Late-onset neonatal sepsis was defined either as the occurrence of a positive blood culture obtained after 72 hours of life with clinical signs of sepsis or as the need for >5 consecutive days of antibiotic therapy for presumed sepsis that initiated after 72 hours of life. Wilcoxon rank sum, chi-square test, and multiple logistic regression were used for analysis. RESULTS: Among the parturients delivering the study infants, 434 women (24%) received corticosteroids only, 175 women (9%) received antibiotics only, 819 women (46%) received both corticosteroids and antibiotics, and 370 women (20%) received neither corticosteroids nor antibiotics. Among 1978 study infants, there were 732 infants (41%) with late-onset neonatal sepsis. By univariate analysis, the odds ratio for late-onset neonatal sepsis caused by combined corticosteroid and antibiotic use was 0.96 (95% CI, 0.89%, 1.04%). Multiple logistic regression analysis was used to evaluate the risk of combined corticosteroids and antibiotic use after controlling for potential covariates and confounders. After controlling for outborn birth (odds ratio, 1.3; 95% CI, 1.0%-1.8%), increasing gestational age at delivery (odds ratio, 0.63; 95% CI, 0.60%-0.66%), interaction between white race and male gender (P =.01) and interaction between antibiotics and prolonged rupture of membranes (P =.02), the use of corticosteroids and antibiotics was not associated with an increased risk of late-onset neonatal sepsis (P =.9). CONCLUSION: The combined use of maternal corticosteroids and antibiotic therapy is not associated with an increased risk for late-onset neonatal sepsis.

A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor.

OBJECTIVE: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor. STUDY DESIGN: Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis. RESULTS: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05). CONCLUSION: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.

Is human myometrial sampling at the time of cesarean delivery safe?

OBJECTIVE: The mechanism for the initiation of human labor remains unknown and is under extensive investigation. Myometrium from patients in labor and not in labor is the ideal tissue to study structural, cellular, and molecular changes that occur during parturition. This study was designed to determine whether myometrial sampling at the time of cesarean delivery increases maternal morbidity. STUDY DESIGN: This is a prospective cohort study including 118 study and 236 control patients. A full-thickness myometrial sample was obtained from the superior edge of a transverse uterine incision at the time of cesarean delivery. Demographics and standard surgical morbidity data were collected. Statistical methods used included univariate and multivariate analysis. RESULTS: The study and control groups did not differ significantly with respect to age, gravidity, parity, birth weight, and Apgar scores. The estimated intraoperative blood loss was greater in the control group (P <.02); however, the change in hematocrit level (preoperative vs postoperative values) was not different. There were no significant differences in the rates of endometritis, wound infection, and venous thrombosis up to 6 weeks post partum. When study and control patients were stratified into term in labor, term not in labor, preterm in labor, and preterm not in labor categories and compared for maternal morbidity, there were still no significant differences for any of the outcome measures evaluated. CONCLUSION: On the basis of our data, human myometrial sampling at cesarean delivery does not increase overall maternal morbidity, irrespective of gestational age and the presence or absence of labor.

Is insulin lispro associated with the development or progression of diabetic retinopathy during pregnancy?

OBJECTIVE: This study was designed to determine whether there is an association between the use of insulin lispro during pregnancy and the development or progression of diabetic retinopathy. STUDY DESIGN: This observational cohort study included women with type 1 diabetes mellitus (n = 12) who were enrolled in our diabetes mellitus in pregnancy program and were treated with insulin lispro during pregnancy. We compared these women with a historical cohort (n = 42) who were treated with regular insulin during pregnancy. All patients underwent ophthalmologic examinations before 24 weeks' gestation and post partum, and retinopathy was graded according to a previously defined scale. RESULTS: Whereas none of the patients in the insulin lispro group showed any change in retinopathy status, 6 patients in the regular insulin group (14%) demonstrated changes in retinopathy status. Mild background retinopathy (change from grade 0 to 1) developed in 3 of these patients, and extensive proliferative retinopathy developed in 1 patient after normal results of the baseline examination (change from grade 0 to 6). Two patients had progression of retinopathy--1 had progression from background retinopathy to mild proliferative retinopathy (change from grade 2 to 4) and 1 had progression from mild proliferative retinopathy to extensive proliferative retinopathy (change from grade 4 to 6). CONCLUSIONS: These preliminary findings provide no evidence that insulin lispro treatment during pregnancy is associated with the development or progression of diabetic retinopathy.

Is vaginal delivery preferable to elective cesarean delivery in fetuses with a known ventral wall defect?

OBJECTIVE: We sought to test the hypothesis that vaginal delivery compared with elective cesarean delivery results in improved neonatal outcome in fetuses with a known isolated ventral wall defect. STUDY DESIGN: We performed a retrospective chart review. RESULTS: Between 1989 and 1999, we identified 102 infants with a confirmed antenatal diagnosis of an isolated ventral wall defect with either the diagnosis of an omphalocele or gastroschisis. Sixty-six infants were delivered by cesarean and 36 were delivered vaginally. There were no significant demographic differences between the study groups or between the two sites except that one center (Cincinnati) usually delivered these fetuses by cesarean whereas the other (Louisville) usually delivered such fetuses vaginally. Overall, there were a greater number of infants with gastroschisis than omphalocele (gastroschisis, n = 71; omphalocele, n = 31). After we controlled for primary versus staged closure of ventral wall defect and gestational age at delivery; the medians and interquartile ranges for cesarean and vaginal delivery were 39 (25, 63) days versus 42 (26, 75) days, respectively (P =.32), for neonatal length of stay and 13 (9, 18) days versus 13 (9, 26) days, respectively (P =.16), for days to enteral feeding. After we controlled for the size of the defect and the amount of bowel resected, the odds of primary closure given a vaginal delivery was about half that given a cesarean delivery (odds ratio, 0.56; 95% confidence interval, 0.18-1. 69), but this was not statistically significant. There was no statistically significant difference in the rates of neonatal death (2 [3%] vs 2 [6%]; P =.61) and neonatal sepsis (2 [3%] vs 4 [11%]; P =.18) for cesarean versus vaginal delivery. Maternal length of stay after delivery was found to be 1 day less after vaginal delivery [vaginal, 2 (2, 2) days; cesarean, 3 (2, 3) days; P =.0001]. There were 5 instances of maternal complications, and all 5 pregnancies were delivered by cesarean (P =.16). CONCLUSION: Fetuses with an antenatal diagnosis of an isolated ventral wall defect may safely be delivered vaginally, and cesarean delivery should be performed for obstetric indications only.

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.

In vivo ultrasonographic exposimetry: human tissue-specific attenuation coefficients in the gynecologic examination.

OBJECTIVE: The purpose of the current study was to determine in vivo, tissue-specific ultrasonic attenuation coefficients for each of the tissue layers comprising the anterior abdominal wall, uterus, and vagina with use of a quantitative multilayer tissue model. We wanted to validate the "homogeneous" tissue model-based Food and Drug Administration derating factor of 0.3 dB/cm-MHz applied to obstetric-use ultrasonography systems. STUDY DESIGN: With use of a 3. 0-MHz mechanical sector scanner and our previously tested exposimetry equipment, we obtained a set of at least 5 separate acoustic pressure waveforms from each test subject by placing a calibrated 7-element linear-array hydrophone in the anterior vaginal fornix while she was undergoing transabdominal ultrasonography. Corresponding sets of reference in vitro acoustic pressure waveforms were also recorded for each test subject in a 37 degrees C water bath. All linear measurements of individual layer thicknesses and total distances were made on-line with use of electronic calipers. A set of multiple and independent insertion loss values, denoted ILn, was calculated for path n between the abdominal surface and the hydrophone from n sonograms for each test subject. Each tissue layer type was identified and its thickness along each path n was measured. The thickness of tissue type m along path n was denoted by dnm. The only unknown quantities left were the attenuation coefficients Am of each of the m tissue layers for that test subject. The overestimated set of equations dnm Am = ILn was solved for Am with use of a nonnegative least-squares solution technique. RESULTS: With use of data from 162 independent insertion loss estimate paths, the overall tissue-specific attenuation coefficients for each of the tissue layer types, expressed as mean value +/- SD, were 2.3 +/- 1.5 dB/cm-MHz for the skin and subcutaneous layer, 3.1 +/- 2.5 dB/cm-MHz for skeletal muscle, 0.6 +/- 0.5 dB/cm-MHz for myometrium, and 3.6 +/- 2.7 dB/cm-MHz for the vaginal wall. The overall insertion loss assuming the "homogeneous" tissue model was 0.7 +/- 0.3 dB/cm-MHz. CONCLUSIONS: We have determined the specific ultrasonic attenuation coefficients for each of the tissue layers comprising the anterior abdominal wall, uterus, and vagina and validated the Food and Drug Administration derating factor of 0.3 dB/cm-MHz applied to obstetric use ultrasonography systems. Of all the models proposed, the "homogeneous" tissue model appears to be the best model for determining ultrasonic exposure risk during reproductive ultrasonographic examinations.

Changes in activity of cytosolic phospholipase A2 in human amnion at parturition.

OBJECTIVE: The purpose of this study was to determine whether increased cytosolic phospholipase A2 activity mediated arachidonic acid mobilization for prostaglandin synthesis in amnion at parturition. STUDY DESIGN: Amnion was collected immediately after delivery from four groups of patients: preterm (<37 weeks) with no labor or labor and term (>37 weeks) with no labor or labor and stored at -70 degrees C. Tissues were homogenized and centrifuged for 1 hour at 100,000 g, and cytosol was assayed for cytosolic phospholipase A2 activity with use of carbon 14-labeled 1-stearoyl-2 arachidonyl phosphatidylcholine plus 10 micromol/L unlabeled substrate and 5 mmol/L calcium in 10 mmol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, pH 7.4. Incubations were performed in duplicate +/- 10 micromol/L arachidonyl trifluoromethyl ketone, a specific inhibitor of cytosolic phospholipase A2 activity, at 30 degrees C for 45 minutes. RESULTS: Total cytosolic phospholipase A2 activity (in picomoles of arachidonic acid per minute per milligram of protein) calculated as the difference between the activity in the presence and absence of arachidonyl trifluoromethyl ketone was (mean +/- SE) as follows: preterm no labor (n = 7) 8.94 +/- 3.08, preterm with labor (n = 6) 6.79 +/- 2.31, term no labor (n = 7) 14.85 +/- 1.66, and term with labor (n = 5) 5.51 +/- 1.52. Enzyme activity increased with gestational age and was highest in the term no labor group. A significant decrease in cytosolic phospholipase A2 activity occurred with labor (p < 0.05). The greatest decrease in activity was in the term group (p < 0.05). CONCLUSION: Total cellular cytosolic phospholipase A2 activity in amnion is highest in anticipation of labor but during labor total activity is depleted, resulting in the low activity measured after delivery of the placenta. The substrate specificity and changes in amnion total cytosolic phospholipase A2 activity with labor strongly suggests a role in mediation of arachidonic acid mobilization and prostaglandin synthesis at labor.

The effect of early discharge after vaginal delivery on neonatal readmission rates.

OBJECTIVE: To determine the effect of a structured program for early neonatal discharge from a tertiary medical center on the risk of neonatal readmission. METHODS: An early-discharge program was instituted at our tertiary medical center in July 1993, with the objective of discharging mothers and infants within 24 hours after vaginal birth. The readmission rate of vaginally delivered infants during the early-discharge period (July 1, 1993, through March 31, 1995) was compared with the rate during a conventional-discharge period (January 1, 1992, through June 30, 1993). Analyses were performed to examine two groups within the early-discharge group: those discharged within 24 hours of vaginal delivery; and those discharged within 1 hospital day of vaginal delivery. RESULTS: During the early-discharge period, 1.24% of neonates were readmitted within 10 days of birth, compared with 1.35% during the conventional-discharge period. In the early-discharge period group, infants born vaginally and discharged within 24 hours of birth had a readmission rate of 1.46% compared with 1.14% for those who stayed longer than 24 hours after delivery. Similarly, the readmission rate was no different for infants who were discharged within 1 hospital day. The primary indications for readmission in both periods were infections and jaundice. CONCLUSION: Implementation of a structured program for early neonatal discharge does not have an association with increased risk of neonatal readmission to the hospital.

Deficient counterregulation: a possible risk factor for excessive fetal growth in IDDM pregnancies.

OBJECTIVE: The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS: Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 and at 32-34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS: All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS: Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.

Immunohistochemical localization of phospholipase A2 isoforms in human myometrium during pregnancy and parturition.

OBJECTIVE: The purpose of this study was to localize secretory phospholipase A2 and cytosolic phospholipase A2 isoforms in pregnant human myometrium and to determine changes in expression with gestational age or parturition. STUDY DESIGN: Myometrium was collected at cesarean section at term (>37 weeks) or preterm (<37 weeks) from patients who were or were not in labor (n = 5 each group). Frozen sections were incubated with specific monoclonal antibodies against secretory phospholipase A2 or cytosolic phospholipase A2 and immunostaining visualized with the Vectastain ABC method. The intensity of immunostaining in different cellular localizations was scored by an investigator blinded to tissue identity and compared among tissues with use of the Mantel-Haenszel chi2 test. RESULTS: Secretory phospholipase A2 immunostaining was dispersed in the perinuclear region throughout the myometrial smooth muscle fibers and in vascular smooth muscle. Cytosolic phospholipase A2 immunostaining was predominantly localized to endothelial cells of myometrial blood vessels and weakly throughout myometrial fibers. There was no apparent change in intensity of immunostaining for either isoform with gestational age or with the absence or presence of labor. CONCLUSION: The differential localization of the two phospholipase A2 isoforms suggests different functions. The apparent lack of change in expression during late gestation or with labor possibly suggests changes in myometrial phospholipase A2 activity and hence local myometrial arachidonic acid mobilization and presumably prostaglandin synthesis may not be associated with the onset of or maintenance of parturition.

Does pregnancy increase the risk for development and progression of diabetic nephropathy?

OBJECTIVE: This study was designed to determine whether pregnancy and increasing parity in women with insulin-dependent diabetes mellitus (1) increases the risk for diabetic nephropathy and (2) accelerates the progression of diabetic nephropathy. STUDY DESIGN: The study included women with insulin-dependent diabetes mellitus who enrolled in our diabetes-in-pregnancy trial with a pregnancy that continued beyond 20 weeks' gestation and who were delivered between 1978 and December 31, 1991, to allow for a minimum of 3 years' follow-up. Pregnancy and follow-up information was obtained from the medical records and from our computerized database. For patients followed up elsewhere, information was obtained from their current physicians. Life-table analysis was used to determine (1) the risk for nephropathy developing de novo as a function of duration of disease and the association of this risk with parity and (2) the risk of renal failure developing in women with preexisting nephropathy and its association with parity. RESULTS: The study population included 182 pregnant women with insulin-dependent diabetes mellitus: 46 with overt nephropathy (group F) and 136 without nephropathy (group NF). Pregnancy and increasing parity did not increase the overall risk for nephropathy (44% after 27 years of diabetes). In group NF 10% had nephropathy within 10.1 +/- 4.2 years of the pregnancy. Proteinuria appearing during pregnancy and glycemic control during pregnancy were significantly associated with the subsequent development of nephropathy. In group F 26% had end-stage renal disease after a median period of 6 years from the pregnancy. Pregnancy or increasing parity did not increase the risk for renal failure in women with nephropathy. CONCLUSIONS: Our data support the premise that pregnancy in women with insulin-dependent diabetes mellitus does not increase the risk of subsequent nephropathy and does not accelerate progression of renal disease in women with preexisting nephropathy.

Counterregulatory hormonal responses to hypoglycemia during pregnancy.

OBJECTIVE: To evaluate the counterregulatory responses to insulin-induced hypoglycemia in healthy women and in women with insulin-dependent diabetes during pregnancy and in the nonpregnant state. METHODS: Hypoglycemia was induced using the hypoglycemic clamp technique in 17 women with insulin-dependent diabetes and in ten healthy controls, both in the nonpregnant state (study 1), at 24-28 weeks' gestation (study 2), and at 32-34 weeks' gestation (study 3). Plasma glucose concentrations were decreased to 60 mg/dL and maintained at this level for 1 hour. Blood samples were drawn every 15 minutes to measure epinephrine, glucagon, growth hormone, and cortisol concentrations. Statistical analyses compared counterregulatory responses between women with and without diabetes, and between the pregnant and nonpregnant state. RESULTS: Women with diabetes had significantly diminished peak epinephrine responses to hypoglycemia compared with controls (mean +/- standard error of the mean [SEM]): 52 +/- 11 versus 191 +/- 42 pg/mL in study 1, 30 +/- 9 versus 102 +/- 47 pg/mL in study 2, and 38 +/- 10 versus 148 +/- 38 pg/mL in study 3 (P < .05). Their responses during pregnancy were also diminished compared with their own nonpregnant epinephrine responses. Women with diabetes also had no recognizable cortisol or glucagon responses to hypoglycemia, and in healthy controls the glucagon responses were significantly diminished during pregnancy compared with their own nonpregnant responses. In both groups, growth hormone responses (mean +/- SEM) diminished progressively during pregnancy from study 1 (14.6 +/- 2.5 and 12.5 +/- 5.2 ng/mL) to study 2 (4.4 +/- 1.1 and 7.3 +/- 2.7 ng/mL) to study 3 (2.5 +/- 0.9 and 4.4 +/- 2.3 ng/mL) in women with diabetes and in controls, respectively. CONCLUSION: Counterregulatory epinephrine and growth hormone responses to hypoglycemia are diminished in women with insulin-dependent diabetes during pregnancy. This may be due, in part, to an independent effect of pregnancy, contributing to the increased incidence of hypoglycemia in these patients during pregnancy.

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.

Hypoglycemia: the price of intensive insulin therapy for pregnant women with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the risk of hypoglycemia associated with intensive insulin therapy of type I diabetes during pregnancy. METHODS: Eighty-four women with type I diabetes were recruited before 9 weeks' gestation and received intensive insulin therapy throughout pregnancy. Patients monitored glucose concentrations with memory glucometers, and insulin dosages were adjusted weekly accordingly. A detailed history of clinical hypoglycemic events was obtained at each weekly clinic visit. RESULTS: Clinically significant hypoglycemia requiring assistance from another person occurred in 71% of pregnant patients, with a peak incidence between 10-15 weeks. Severe hypoglycemia during the early weeks of embryogenesis was not associated with an increase in embryopathy. Glycemic control was similar in women with or without recurrent hypoglycemia, but glucose fluctuations were significantly greater in hypoglycemic women. CONCLUSION: Severe hypoglycemia is a significant maternal risk associated with intensive insulin therapy of pregnant women with type I diabetes. In women with recurrent episodes of hypoglycemia, the clear benefits of strict glycemic control must be weighed against the hazards of hypoglycemia.

Normalization of blood glucose in insulin-dependent diabetic pregnancies and the risks of hypoglycemia: a therapeutic dilemma.

Intensive insulin therapy delays the onset and progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Such therapy, however, is associated with an increased risk of potentially life-threatening hypoglycemia due to the loss of normal counterregulatory hormonal responses to hypoglycemia and to the syndrome of hypoglycemia unawareness. Current standards for glycemic control during pregnancy in IDDM women require intensive insulin therapy to optimize pregnancy outcome. Therefore, obstetricians and gynecologists providing prenatal care for women with IDDM should be aware that intensive insulin therapy predisposes these patients to the significant risks of severe hypoglycemia. It often becomes necessary to individualize the optimal balance between glycemic control during pregnancy and the risks of hypoglycemia.

In situ human obstetrical ultrasound exposimetry: estimates of derating factors for each of three different tissue models.

A specialized in vivo exposimetry system was developed to acquire transabdominal in situ ultrasound exposure quantities in obstetric patients. Under surgical conditions, the sterilized 7-element calibrated linear array hydrophone was introduced into the uterus under direct ultrasound guidance and placed in direct contact with the products of conception, usually in the saggital midplane of the uterine cavity. Twenty-five patients with empty bladders and 10 patients with full bladders were studied at gestational ages between 7 and 20 weeks. In the empty bladder condition, the sound beam traversed the anterior abdominal wall, uterus, amniotic fluid and fetal parts and in the full bladder condition, the sound beam also traversed the fluid-filled bladder. Each study was conducted with a 3 MHz, mechanical sector transducer in combination with an ATL Ultramark 4 diagnostic ultrasound imaging system. Calibration data were recorded after completion of each in vivo patient study. The acquired exposimetry data from the 35 obstetric patients were used to evaluate the appropriateness of three tissue attenuation models, viz., fixed path, homogeneous and overlying. All three tissue models yield a mean attenuation coefficient value of about a factor of 3 to 4 greater than their respective minimum values. In the case of the overlying and homogeneous tissue models, there was a statistically significant correlation between their calculated attenuation coefficients and total distance for the combined data set whereas there was no such dependency for the calculated fixed-path tissue model. In summary, any one of the three tissue models may be used to estimate in utero acoustic quantities during the first and second trimesters of human pregnancy based on this study.

Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus.

OBJECTIVE: To test the hypothesis that women with insulin-dependent (type I) diabetes have a threshold of glycemic control in early pregnancy for increased risks of spontaneous abortion and congenital malformations. METHODS: Receiver-operating characteristic (ROC) curves were formed for the occurrence of abortion and malformations as a function of the median first-trimester preprandial blood glucose concentration and the first measured glycohemoglobin concentration in pregnant women with type I diabetes. RESULTS: Fifty-two of the 215 women (24%) who enrolled before 9 weeks' gestation had spontaneous abortions. Six percent of the women enrolled before 14 weeks had infants with major congenital malformations. Thresholds for an increased risk of abortion and malformations were a median first-trimester blood glucose concentration of 120-130 mg/dL or an initial glycohemoglobin concentration of 12-13% (6.2-7.5 standard deviations above the normal mean). CONCLUSIONS: Type I diabetic women with initial glycohemoglobin concentrations in pregnancy above 12% or median first-trimester preprandial glucose concentrations above 120 mg/dL have an increased risk of abortion and malformations. Below these glycemic thresholds, the risks are comparable to those in nondiabetic women.

Nitric oxide metabolites and preterm pregnancy complications.

OBJECTIVE: Intraamniotic infection may play a significant role in preterm labor and premature rupture of membranes. Synthesis of nitric oxide and its metabolites nitrite and nitrate purportedly are increased in infection. This project was designed to evaluate whether plasma or urine nitrate concentrations are increased in patients with either preterm labor or premature rupture of membranes in comparison with pregnant controls. STUDY DESIGN: A total of 42 patients between 24 and 35 weeks' gestation (20 with preterm labor; 14 with premature rupture of membranes, and 8 with premature rupture of membranes and contractions) and 35 additional patients without preterm labor or premature rupture of membranes (controls) had blood and urine collected for nitrate determination. Nitrate was reduced to nitrite and quantitated with the Griess reagent. RESULTS: The urine nitrate concentrations were significantly higher only in the preterm labor group compared with the control group (1.23 +/- 0.22 vs 0.67 +/- 0.05 mumol/mg creatinine, p < 0.05). The plasma nitrate level, however, was significantly higher in both the preterm labor and the premature rupture of membranes groups compared with the control group (52.47 +/- 10.11 and 40.05 +/- 5.38 mumol/L vs 16.29 +/- 2.89 mumol/L, p < 0.05). However, the concentrations of nitrate in the urine or plasma did not correlate with time from admission to delivery (p > 0.2). Finally, the presence of positive cervical or urine cultures, a clinical examination consistent with chorioamnionitis, or a maternal temperature > 100.4 degrees F was not associated with higher levels of nitrates in this small series of patients. CONCLUSION: Patients with preterm labor or premature rupture of membranes do have increased nitrate concentrations; however, this increased concentration is not predictive of impending delivery but may indicate that a subclinical infectious process is occurring.