17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis.

BACKGROUND: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective. OBJECTIVE: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc). SEARCH STRATEGY: We searched literature databases, trial registries and references in published articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies. DATA COLLECTION AND ANALYSIS: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation. MAIN RESULTS: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes. CONCLUSION: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration. TWEETABLE ABSTRACT: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Optimizing multiphoton fluorescence microscopy light collection from living tissue by noncontact total emission detection (epiTED).

A benefit of multiphoton fluorescence microscopy is the inherent optical sectioning that occurs during excitation at the diffraction-limited spot. The scanned collection of fluorescence emission is incoherent; that is, no real image needs to be formed on the detector plane. The nearly isotropic emission of fluorescence excited at the focal spot allows for new detection schemes that efficiently funnel all attainable photons to detector(s). We previously showed [Combs, C.A., et al. (2007) Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector. J. Microsc. 228, 330-337] that parabolic mirrors and condensers could be combined to collect the totality of solid angle around the excitation spot for tissue blocks, leading to ∼8-fold signal gain. Using a similar approach, we have developed an in vivo total emission detection (epiTED) instrument modified to make noncontact images from outside of living tissue. Simulations suggest that a ∼4-fold enhancement may be possible (much larger with lower NA objectives than the 0.95 NA used here) with this approach, depending on objective characteristics, imaging depth and the characteristics of the sample being imaged. In our initial prototype, 2-fold improvements were demonstrated in the mouse brain and skeletal muscle as well as the rat kidney, using a variety of fluorophores and no compromise of spatial resolution. These results show this epiTED prototype effectively doubles emission signal in vivo; thus, it will maintain the image signal-to-noise ratio at two times the scan rate or enable full scan rate at approximately 30% reduced laser power (to minimize photo-damage).

Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy.

OBJECTIVE: To determine the gestational ages at which maternal hyperglycemia is most closely related to fetal macrosomia; to determine whether macrosomia is related to elevations of fasting glucose, postprandial glucose, or both; and to assess the relationship of macrosomia to maternal insulin dose and caloric intake. RESEARCH DESIGN AND METHODS: One hundred eleven consecutive pregnant women with Class B through RF diabetes were studied longitudinally from 13 to 36 wk gestation. Macrosomia was defined by birthweight greater than 90th percentile for gestational age based on California norms. Women who delivered macrosomic infants were compared with those without macrosomic infants on pre- and postprandial blood glucose, GHb, insulin dose, macronutrient intake, and several other maternal variables. RESULTS: Macrosomia occurred in 32 (29%) cases, although several measures indicated reasonable glycemic control throughout pregnancy. Women delivering macrosomic infants did not differ from those without macrosomic infants in maternal age, prepregnant weight, duration of diabetes, White class, macronutrient intake, GHb, or fasting glucose. Macrosomia was associated with higher postprandial glucose levels up to 32 wk gestation and lower insulin doses from 29 to 36 wk gestation. In multiple logistic regression, macrosomia was significantly associated with postprandial glucose only between 29 and 32 wk gestation. Postprandial glucose values less than 7.3 mM (less than 130 mg/dl) were associated with a higher risk of small-for-gestational-age infants (18%) compared with values above this level (1%). CONCLUSIONS: Because macrosomia was related to postprandial glucose but not fasting glucose, we conclude that postprandial glucose measurement should be a part of routine care for diabetes in pregnancy. A target 1-h postprandial glucose value of 7.3 mM (130 mg/dl) may be the level that optimally reduces the incidence of macrosomia without increasing the incidence of small-for-gestational-age infants.

Lack of effect of pregnancy on renal allograft survival or function.

To determine whether pregnancy had a long-term influence on the survival or function of renal allografts, a case-control study was conducted. Patients were selected from a pool of 915 patients transplanted at the University of Cincinnati from 1967 to 1990. The pregnancy group consisted of 18 women who became pregnant 3 months to 17 years after transplantation and who elected to continue pregnancy. There were 26 nonpregnant female controls, and 23 male control renal transplant recipients. Matching criteria were cause of end-stage renal disease (ESRD), donor source, age at transplantation, calendar year of transplantation, time from transplantation to pregnancy, and serum creatinine concentration at the time corresponding to conception. Matching was performed by one investigator, who had no knowledge of long-term outcome in any of the patients. The three groups were well-matched with regard to these criteria. Male controls had higher baseline creatinine clearances than pregnancy cases or female controls. During pregnancy, serum creatinine levels fell by 20%, and creatinine clearance rose by 53%. Immediately after pregnancy, these values returned to baseline. Graft survival, with a mean posttransplant follow-up of 11-12 years, was 77.8% in the pregnancy cases, 69.2% in the female controls, and 69.6% in the male controls. By life-table analysis, none of these differences was significant. Among surviving grafts, serum creatinine levels and creatinine clearances remained stable throughout the follow-up period. In this study, using well-matched male and nonpregnant female cohorts for comparison, pregnancy did not have an adverse long-term effect on renal allograft function or survival.

Prolonged third stage of labor: morbidity and risk factors.

Although retained placenta is a major cause of postpartum hemorrhage, there is no general agreement regarding when manual placental extraction is indicated to prevent hemorrhage. We sought to determine the following: 1) what duration of the third stage of labor is abnormal, 2) what duration is associated with complications, and 3) what antecedent conditions are associated with prolonged third stage. We studied 12,979 consecutive, singleton vaginal deliveries over an 11-year period. Third-stage duration had a log-normal distribution, with a geometric mean of 6.8 minutes, a median of 6 minutes, and an interquartile range of 4-10 minutes. A third stage of 30 minutes or longer occurred in 3.3% of the deliveries. The incidence of postpartum hemorrhage, transfusion, and D&C remained constant in third stages less than 30 minutes, then rose progressively, reaching a plateau at 75 minutes. The increase in these complications after 30 minutes was observed with both spontaneously delivered and manually extracted placentas. In a logistic regression analysis, factors significantly associated with prolonged third stage included: preterm delivery (odds ratio 3.81), delivery in a labor bed (odds ratio 2.17), preeclampsia (odds ratio 1.76), augmented labor (odds ratio 1.47), and nulliparity (odds ratio 1.45). Because there was no increase in hemorrhage until the third stage exceeded 30 minutes, we suggest that in the absence of bleeding, manual placental extraction is not indicated until 30 minutes have elapsed.

Hepatitis C in obstetrics and gynecology.

Because of the risk of perinatal transmission and possible sexual transmission, it is important for obstetrician-gynecologists to keep abreast of the rapidly expanding literature on hepatitis C. Acute hepatitis C represents about 5% of all reported cases of hepatitis. Approximately 50% of acute infections progress to chronic liver disease. Risk factors for infection include intravenous (IV) drug use (21-42% of cases), previous blood transfusion (6-17%), and multiple sexual partners (6%); 40-50% of cases have no identified risk factors. The seroprevalence of anti-hepatitis C antibody is 70.8% in IV drug users, 11.6% in patients with human immunodeficiency virus, 8.8% in prostitutes, 1.2% in hospital personnel, and 0.5-1.4% in volunteer blood donors. The risk of transmission to the neonate depends on the trimester at exposure. No perinatal transmission has been shown after acute maternal infection in the second trimester. Based on the few reported cases, chronic maternal infection or acute infection in the third trimester may result in neonatal infection rates of 45-87.5%. Universal screening is probably not cost-effective because the prevalence is low and over 70% of screening tests can be falsely positive using the currently approved assay. Selective screening of high-risk patients is recommended.

Pregnancy after mustard repair for transposition of the great arteries.

BACKGROUND: Since the introduction of surgical repair procedures, women with complete transposition of the great arteries are surviving into their reproductive years. Only three successful pregnancies in such women have been described previously. CASES: Three women with transposition of the great arteries repaired in childhood became pregnant in 1991. Two pregnancies were complicated by failure of the systemic ventricle and one by preterm labor. Labor was managed with antibiotic prophylaxis against endocarditis, clinical hemodynamic assessment, epidural anesthesia, avoidance of maternal expulsive efforts in the second stage, and low forceps delivery. Three healthy infants were delivered vaginally between 34-39 weeks' gestation. CONCLUSION: With close cooperation between the cardiologist and obstetrician, successful pregnancy is possible after surgical repair of transposition of the great arteries. However, failure of the systemic ventricle is common and should be diagnosed and treated promptly.

Factors associated with postpartum hemorrhage with vaginal birth.

A case-control study was performed to study risk factors for postpartum hemorrhage. Cases of hemorrhage were defined by a hematocrit decrease of 10 points or more between admission and post-delivery or by the need for red-cell transfusion. Patients with antenatal bleeding were excluded. Among 9598 vaginal deliveries, postpartum hemorrhage occurred in 374 cases (3.9%). Three controls were matched to each case and multiple logistic regression was used to control for covariance among predictor variables. Factors having a significant association with hemorrhage were prolonged third stage of labor (adjusted odds ratio 7.56), preeclampsia (odds ratio 5.02), mediolateral episiotomy (4.67), previous postpartum hemorrhage (3.55), twins (3.31), arrest of descent (2.91), soft-tissue lacerations (2.05), augmented labor (1.66), forceps or vacuum delivery (1.66), Asian (1.73) or Hispanic (1.66) ethnicity, midline episiotomy (1.58), and nulliparity (1.45). These data may help predict postpartum hemorrhage and may be useful in counseling patients about the advisability of home delivery, intravenous access in labor, or autologous blood donation.

Factors associated with hemorrhage in cesarean deliveries.

A case-control study was performed to study risk factors for hemorrhage in cesarean deliveries. Hemorrhage was defined by a pre- to post-delivery hematocrit decrease of 10 points or more or by the need for red-cell transfusion. Patients with antenatal bleeding were excluded. Among 3052 cesarean deliveries, hemorrhage occurred in 196 cases (6.4%). Three controls were matched to each case and multiple logistic regression was used to control for covariance among predictor variables. Factors having a significant association with hemorrhage were: general anesthesia (adjusted odds ratio 2.94), amnionitis (odds ratio 2.69), preeclampsia (2.18), protracted active phase of labor (2.40), second-stage arrest (1.90), and Hispanic ethnicity (1.82). After adjustment for these variables, a classic uterine incision had a small but significant association (odds ratio 1.06) with hemorrhage. Previous cesarean, parity, gestational age, and several other factors had no association with hemorrhage. These data allow one to anticipate hemorrhage in patients at risk and may be useful in planning appropriate use of blood bank resources, including antepartum autologous blood donation.

Cost-benefit analysis of autologous blood donation in obstetrics.

OBJECTIVE: To determine whether there are predictors of peripartum transfusion, other than placenta previa, that identify a population of pregnant women whose risk of transfusion is high enough to justify antepartum autologous blood donation. METHODS: Using an established perinatal data base, we studied 14,267 consecutive term deliveries without placenta previa. Univariate and multivariate analyses were performed to assess ten predictors of peripartum transfusion that might reasonably be detected in the antepartum period. Costs were calculated for a hypothetical autologous blood donation program to prevent transfusion-related infection. RESULTS: Red-cell transfusion was used in 150 deliveries (1.1%). A total of 424 units was transfused (2.9 per 100 deliveries). Four risk factors were significantly (P less than .05) predictive of peripartum red-cell transfusion: preeclampsia (adjusted odds ratio 3.69), multiple gestation (2.82), elective cesarean (1.71), and nulliparity (1.51). Controlling for these, there was no association between transfusion and previous postpartum hemorrhage, previous cesarean with trial of labor, prior abortions, induction of labor, or ethnic group. A hypothetical antepartum blood donation program restricted to patients with three or more risk factors would cost $32,800-130,700 per case to prevent transfusion-related hepatitis and $26,000,000-78,000,000 per case to prevent human immunodeficiency virus infection. CONCLUSION: In obstetric patients without placenta previa, the need for peripartum red-cell transfusion cannot be predicted with sufficient accuracy to justify the costs of antepartum autologous blood donation.

Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle.

A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867-874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo (n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and (31)P-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 microM or decrease the free energy of ATP hydrolysis to -55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 micromol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions (P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control.

Elective induction versus spontaneous labor after sonographic diagnosis of fetal macrosomia.

OBJECTIVE: To test the hypothesis that elective induction of labor, compared to spontaneous labor, reduces the cesarean rate in women with a sonographic diagnosis of fetal macrosomia. METHODS: Sonography results over a period of 27 months were used to select 262 consecutive patients who met the following inclusion criteria: singleton pregnancy at term, estimated fetal weight (EFW) at the 90th percentile or greater, and delivery at our institution. The subjects were divided into four groups based on obstetric management: spontaneous labor (N = 115), elective induction of labor with macrosomia as the sole indication (N = 44), induction of labor for other maternal or fetal indications (N = 48), and elective cesarean delivery (N = 55). The analysis focused on the first two groups. These were compared regarding cesarean rate, indications for cesarean, and shoulder dystocia rate. Multiple logistic regression was used to control for potential confounders. RESULTS: With elective induction, the cesarean rate was 57%, significantly higher than the 31% rate with spontaneous labor (P < .01). The induced group also had a significantly higher EFW and birth weight. When logistic regression was used to control for birth weight, parity, and care provider, elective induction was still associated with a higher risk of cesarean delivery than was spontaneous labor (adjusted odds ratio 2.7, 95% confidence interval 1.2-5.9; P < .02). Shoulder dystocia occurred in one of 19 vaginal deliveries with elective induction (5.3%) and in two of 79 with spontaneous labor (2.5%). CONCLUSION: Because elective induction of labor increased the cesarean rate and did not prevent shoulder dystocia, we conclude that mothers with macrosomic fetuses can safely be managed expectantly unless there is a medical indication for induction.

Early-pregnancy proteinuria in diabetes related to preeclampsia.

OBJECTIVE: To test the hypothesis that the risk of preeclampsia in diabetic mothers is increased with incipient diabetic nephropathy as well as with overt nephropathy. METHODS: Pregnancy outcome was studied in 311 women with class B-RF diabetes from two institutions. Using 104 women without chronic hypertension followed at the University of California, San Francisco, we constructed a receiver-operating characteristic curve relating 24-hour urinary total protein before 20 weeks' gestation to the subsequent development of preeclampsia. From the curve, a predictive cutoff level of proteinuria was selected and tested in two validation groups not used to construct the curve: 158 women without chronic hypertension followed at the University of Cincinnati and 49 women with chronic hypertension from both institutions. RESULTS: The receiver-operating characteristic curve showed an increased risk of preeclampsia with early-pregnancy proteinuria of 190 mg/day or more. In the Cincinnati validation group, the rate of preeclampsia was 7% in women with early-pregnancy proteinuria of less than 190 mg/day, 31% with proteinuria of 190-499 mg/day, and 38% with proteinuria of 500 mg/day or more. In the chronic-hypertension validation group, the rates were 0, 50, and 58%, respectively. By multiple logistic regression, the increased risk of preeclampsia with proteinuria above 190 mg/day persisted after controlling for the effects of parity, chronic hypertension, retinopathy, and glycemic control. CONCLUSIONS: Diabetic gravidas with early-pregnancy proteinuria of 190-499 mg/day are at increased risk for preeclampsia. The risk is comparable to that in women with overt diabetic nephropathy and is independent of chronic hypertension. We speculate that diabetic women with proteinuria in this range have incipient or subclinical diabetic nephropathy.

Sonographic estimation of fetal weight based on a model of fetal volume.

OBJECTIVES: To derive a formula for sonographic estimated fetal weight (EFW) based on a two-compartment model of fetal volume and to test it against two widely used formulas, especially at the extremes of fetal weight for which existing formulas are generally inaccurate. METHODS: We analyzed 865 consecutive sonograms that met the following inclusion criteria: singleton pregnancy, normal anatomy, delivery within 3 days of sonography, and measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The weight of the fetal head was modeled to be proportional to HC3, and the weight of the trunk proportional to AC2 x FL. The proportionality constants were found by multiple linear regression on 380 sonograms performed in 1990 (the "derivation set"). The new formula was tested for accuracy of prediction of actual birth weight against the formulas of Hadlock et al and Shepard et al using 485 sonograms from 1991-1992 (the "validation set"). RESULTS: In the derivation set, the formula EFW = (0.23718 x AC2 x FL) + (0.03312 x HC3) was fit; the correlation with actual birth weight had an r value of 0.996. In the validation set, the new formula produced smaller systematic errors and smaller absolute errors than either the Hadlock or Shepard formula both overall and in fetal weight strata from less than 1000 g to over 4000 g. CONCLUSION: The new formula makes geometric sense and provides accurate estimates of fetal weight across a broad range of weights.

Hemodynamic observations during paroxysmal hypertension in a pregnancy with pheochromocytoma.

A patient with pheochromocytoma diagnosed at 17 weeks' gestation was studied at rest, during an episode of paroxysmal hypertension, and during phenoxybenzamine treatment. Cardiac output was estimated noninvasively by Doppler technique. During paroxysmal hypertension, the mean blood pressure was 102 mmHg, cardiac output fell by 40%, and systemic vascular resistance rose by 250%. Phenoxybenzamine treatment did not change the resting cardiac output or systemic vascular resistance. These observations suggest that serious fetal compromise might occur even with mild episodes of hypertension associated with pheochromocytoma.

Human versus animal insulin in the management of insulin-dependent diabetes: lack of effect on fetal growth.

It is generally accepted that the human placenta is impermeable to free insulin and that insulin present in the fetus is entirely of fetal origin. A recent study suggested that antibody-bound animal insulin crosses the placental barrier and may exert direct effects on fetal growth. We hypothesized that mothers with insulin-dependent diabetes treated with animal insulin would have infants with higher birth weights and ponderal indices compared with mothers treated with human insulin. We studied 209 mothers with insulin-dependent diabetes who were enrolled in our program and who delivered after 28 weeks' gestation: 170 were treated with animal insulin and 39 with human insulin. There were no differences between the groups in the mean birth weight (adjusted by gestational age at delivery) or ponderal index of the infants. The rate of macrosomia (birth weight greater than the 90th percentile for gestational age or ponderal index above 2.85) was similar in both groups. The sample size was adequate to yield a power of 80% to detect a difference between groups of 179 g or more in birth weight and 0.1 g/cm3 in ponderal index. We suggest that the type of insulin (animal versus human) used by the pregnant insulin-dependent diabetic mother has no bearing on fetal weight gain.

Pre-conception management of insulin-dependent diabetes: improvement of pregnancy outcome.

Poor glycemic control in early pregnancy in insulin-dependent diabetes is associated with an increased risk for spontaneous abortions and congenital malformations. Strict glycemic control from the initial stages of embryogenesis is one of the major goals of management in these pregnancies. We hypothesized that insulin-dependent diabetic patients attending a pre-conception program would have improved glycemic control compared with insulin-dependent diabetic patients who enrolled after conception and would have better pregnancy outcome, with fewer spontaneous abortions and fewer major malformations. Ninety-nine pregnant insulin-dependent diabetic patients were recruited before reaching 9 weeks' gestation and were followed prospectively throughout pregnancy. Twenty-eight had attended a pre-conception clinic to optimize glycemic control (study group) and 71 had enrolled after conception (control group). Early glycemic control was significantly better in the study group: Glycohemoglobin values at the first prenatal visit and at 9 and 14 weeks' gestation were significantly lower than in the control group. The rate of spontaneous abortion was significantly lower in the study group (7%) than in the controls (24%). There was one major malformation in the control group and none in the study group. We conclude that patients with insulin-dependent diabetes attending a pre-conception program have a decreased rate of early pregnancy loss compared with those receiving prenatal care early in pregnancy.

Normalized metabolic stress for 31P-MR spectroscopy studies of human skeletal muscle: MVC vs. muscle volume.

A critical requirement of submaximal exercise tests is the comparability of workload and associated metabolic stress between subjects. In this study, 31P-magnetic resonance spectroscopy was used to estimate metabolic strain in the soleus muscle during dynamic, submaximal plantar flexion in which target torque was 10 and 15% of a maximal voluntary contraction (MVC). In 10 healthy, normally active adults, (PCr + Pi)/PCr, where PCr is phosphocreatine, was highly correlated with power output normalized to the volume of muscle in the plantar flexor compartment (r = 0.89, P < 0.001). The same variable was also correlated, although less strongly (r = 0.78, P < 0.001), with power normalized to plantar flexor cross-sectional area. These findings suggest that comparable levels of metabolic strain can be obtained in subjects of different size when the power output, or stress, for dynamic plantar flexion is selected as a function of plantar flexor muscle volume. In contrast, selecting power output as a function of MVC resulted in a positive linear relationship between (PCr + Pi)/PCr and the torque produced, indicating that metabolic strain was increasing rather than achieving constancy as a function of MVC. These findings provide new insight into the design of dynamic muscle contraction protocols aimed at detecting metabolic differences between subjects of different body size but having similar blood flow capacity and mitochondrial volume per unit of muscle.

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.