Adenosine diphosphate-induced platelet activation inhibited by magnesium in a dose-dependent manner.

OBJECTIVE: To examine the hypothesis that magnesium inhibits platelet activation at concentrations equivalent to therapeutic levels. METHODS: Fifteen subjects were enrolled: five healthy, female donors with regular, spontaneous menstrual cycles; five women with uncomplicated third-trimester pregnancies; and five preeclamptic subjects before magnesium therapy. Anticoagulated whole blood was added to tubes containing 0.5 micromol/L adenosine diphosphate (to activate platelets), HP1-1D (activation-independent platelet antibody), CD62 antibody and CD63 antibody (activation-dependent platelet antibodies), and magnesium sulfate in increasing concentrations (2-100 mg/dL). The percentage of activated platelets (CD62 or CD63 positive) was determined using three-color flow cytometric analysis. Data were analyzed using the Student t test, repeated measures analysis of variance, two-way analysis of variance, and Student-Newman-Keuls for pairwise comparison in appropriate cases. P < .05 was considered significant. RESULTS: Adenosine diphosphate-induced platelet activation was inhibited with increasing magnesium concentration in all subjects (P < .001). Significant inhibition of CD62 and CD63 expression first occurred at a magnesium concentration of 4 mg/dL in the normal pregnant group (P < .05), at 6 mg/dL in the preeclamptic group (P < .05), and at 8 mg/dL in the nonpregnant group (P < .05). CONCLUSION: Magnesium inhibits adenosine diphosphate-induced platelet activation in a dose-dependent manner. This effect initially attains statistical significance at concentrations equivalent to therapeutic levels.

Cesarean deliveries at a university hospital: analysis of rates and indications.

The objective of this paper is to evaluate the influence of patient risk status on the incidence of and indications for cesarean delivery. All live births > or = 23 weeks at the University of Vermont in 1995 (n = 2395) were retrospectively analyzed for delivery route, indication for cesarean, gestational age, parity, and practice group (to reflect risk status). The total cesarean rate was 14.4% (344 of 2395), and the primary rate was 11.4% (244 of 2144). Abnormal presentation was the most common indication (25.6%, 88 of 344). The "corrected" cesarean rate (maternal-fetal medicine and transported patients excluded) was 12.4% (273 of 2194), and the "corrected" primary rate was 9.6% (190 of 1975). Furthermore, when all deliveries were analyzed, regardless of risk status but limited to gestational age > or = 36 weeks, the rates did not change (12.6%, 280 of 2214; primary 9.2%, 183 of 1994). Arrest of dilation was the most common indication in both "corrected" subgroups (23.4 and 24.6%, respectively). Cesarean rates at tertiary care hospitals should be compared with rates at community hospitals only after correcting for dissimilar patient groups or gestational age.

Labor induction with a prenatal diagnosis of fetal macrosomia.

Since our institution has a low cesarean rate (14%), it was our hypothesis that the rate of cesarean delivery in patients who underwent induction for macrosomia would be similar to the cesarean rate in patients with similar birth weights who entered labor spontaneously. A retrospective analysis of cases seen from December 1993 to July 1995 revealed 53 nondiabetic patients who underwent induction for fetal macrosomia. These study patients were matched to the next nondiabetic patient delivering a child of equal or greater birth weight who entered labor spontaneously. Maternal demographics, labor characteristics, and neonatal outcome data were reviewed. There were no differences between the induction and spontaneous labor groups in maternal age, gestational age, rate of nulliparity, incidence of shoulder dystocia, Apgar scores, or vaginal birth after prior cesarean delivery. The cesarean delivery rate was higher in the induction group when compared to the spontaneous labor group (36% vs. 17%, P < 0.05) despite a lower birth weight in the induction group (4,102 +/- 374 g vs. 349 g, P < 0.05). Regional analgesia was administered more frequently in the induction group (38% vs. 53%, P < 0.05). An increased risk of cesarean delivery was observed in subjects undergoing induction for the indication of fetal macrosomia. These data support a plan of expectant management when fetal macrosomia is suspected.

Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy.

Female carriers of Duchenne muscular dystrophy (DMD) may demonstrate elevated serum creatine kinase (CK) and reduction of muscle dystrophin in all muscle types. We hypothesized that decreased dystrophin in uterine or pelvic girdle musculature might affect the obstetrical performance of females heterozygous for a dystrophin mutation. We reviewed the outcome of 34 deliveries resulting in 35 children from 13 women who were mothers of males attending a muscular dystrophy clinic. Obstetrical performance was examined retrospectively by chart review and patient contact. Of 35 children, 6 (17%) were delivered in the breech position, which is a fivefold increase above the national standards for term pregnancies. Of the six infants with breech presentation, two were males affected with DMD, one was a female heterozygote, one was a male who died perinatally, and the carrier status of the other two females is unknown. Most DMD affected males (12/14) were delivered in the vertex position. Thus, it is likely that maternal, rather than fetal, muscle weakness was the significant factor in determination of fetal position at term. We speculate that subtle changes in uterine or pelvic girdle muscle tone may contribute to a higher rate of fetal breech position in carriers of the DMD gene.

Hysterotomy to effect vaginal delivery with mentum anterior head entrapment.

BACKGROUND: Entrapment of the aftercoming head after mentum anterior rotation is a life-threatening complication of vaginal breech delivery. Few options exist when rotation and flexion from this position cannot be performed successfully either transabdominally or with vaginal maneuvers. CASE: A term primigravida presented with a singleton breech in advanced labor. The fetal torso and arms delivered vaginally, but the aftercoming head became extended and was entrapped in a mentum anterior position. The fetal head could not be rotated and flexed, either vaginally or transabdominally with suprapubic pressure. Laparotomy and hysterotomy were performed, and vaginal delivery of a live fetus was accomplished after rotation and flexion of the fetal head through this incision. CONCLUSION: Hysterotomy is a safe and effective maneuver for delivery of the entrapped fetal head with mentum anterior rotation after standard procedures have failed.

Uterine artery Doppler velocimetry in the detection of adverse obstetric outcomes in women with unexplained elevated maternal serum alpha-fetoprotein levels.

OBJECTIVE: We hypothesized that in pregnancies complicated by unexplained elevations of maternal serum alpha-fetoprotein, second-trimester uterine artery Doppler findings would detect adverse obstetric outcomes. STUDY DESIGN: One hundred three subjects with unexplained elevations of maternal serum alpha-fetoprotein had uterine artery Doppler velocimetry studies performed at the time of targeted ultrasonographic examination (17 to 22 weeks). A resistance index > 95th percentile or the presence of a uterine notch was considered abnormal. Adverse outcomes included preeclampsia, preterm birth, low birth weight, intrauterine growth restriction, abruptio placentae, and fetal death. Statistical analysis was performed by Student t test, chi 2 analysis, and stepwise logistic regression analysis. RESULTS: An elevated uterine resistance index was associated with an increased relative risk for both preeclampsia (relative risk 41.82, 95% confidence interval 5.36 to 326.13) and low birth weight (relative risk 4.65, 95% confidence interval 1.90 to 11.39). A uterine artery notch was associated with an increased risk of preeclampsia (relative risk 52.22, 95% confidence interval 6.82 to 399.70), preterm birth (relative risk 3.21, 95% confidence interval 1.32 to 7.81), and low birth weight (relative risk 4.18, 95% confidence interval 1.64 to 10.66). When the presence of a uterine notch, vaginal bleeding, and level of maternal serum AFP were analyzed by stepwise logistic regression, the presence of a notch was found to be the only significant factor (odds ratio 6.95, 95% confidence interval 1.24 to 39.10) for the development of an adverse outcome. CONCLUSIONS: Abnormal uterine artery Doppler findings are associated with an increased frequency of adverse obstetric outcomes in women with unexplained elevated maternal serum AFP levels. Abnormal Doppler findings demonstrated high sensitivity for the development of preeclampsia but were less sensitive in predicting other outcomes. The presence of a uterine artery notch is a better independent predictor of adverse outcome than are early vaginal bleeding or maternal serum AFP level.

Detection of fetal HLA-DQa sequences in maternal blood: a gender-independent technique of fetal cell identification.

The objective of this study was to detect fetal HLA-DQa gene sequences in maternal blood. HLA-DQa genotypes of 70 pregnant women and their partners were determined for type A1. We specifically sought couples where the father, but not the mother, had genotype A1. In 12 women, maternal blood samples were flow-sorted. Candidate fetal cells were isolated and amplified by using PCR primers specific for a paternal HLA-DQa A1 allele. Fetal HLA-DQa A1 genotype was predicted from sorted cells; amniocytes or cheek swabs were used for confirmation. Six of twelve sorted samples had amplification products indicating the presence of the HLA-DQa A1 allele; 6/12 did not. Prediction of the fetal genotype was 100 per cent correct, as determined by subsequent amplification of amniocytes or cheek swabs. We conclude that paternally inherited uniquely fetal HLA-DQa gene sequences can be identified in maternal blood. This system permits the identification of fetal cells independent of fetal gender, and has the potential for non-invasive prenatal diagnosis of paternally inherited conditions.

The effect of sustained exercise on follicular phase levels of 17 beta-estradiol in recreational athletes.

OBJECTIVE: Our purpose was to test the hypothesis that sustained exercise elevates circulating levels of 17 beta-estradiol in an intensity-dependent manner. STUDY DESIGN: Blood samples were obtained in the follicular phase of the menstrual cycle from 75 female recreational athletes before and immediately after 20 minutes of aerobics or running at their usual exercise intensity. RESULTS: The levels of 17 beta-estradiol rose after exercise 97% of the time. At exercise intensities between 50% and 88% of maximum capacity there was a direct linear relationship (r = 0.57) between exercise intensity and magnitude of increase in estradiol levels. A similar relationship was not present for cortisol. CONCLUSION: Sustained exercise produces an intensity-dependent increase in the levels of 17 beta-estradiol that probably reflects decreased hepatic clearance caused by the fall in splanchnic blood flow. Thus the magnitude of the increase in the level of 17 beta-estradiol can be used as a rough index of the exercise-induced decrease in splanchnic blood flow.

Fetal heart rate response to sustained recreational exercise.

OBJECTIVE: We aimed to test the hypotheses that fetal heart rate increases during and after sustained exercise and that the magnitude of the increases is related to gestational age and the duration, intensity, and type of exercise. STUDY DESIGN: Maternal oxygen uptake and fetal heart rate were monitored in 120 regularly exercising women in association with routine 20-minute workouts between 16 and 39 weeks' gestation. RESULTS: In 97% of the studies fetal heart rate increased during and after exercise. This was significant at all gestational ages and with all forms of exercise with an overall increase of 15 +/- 11 beats.min-1 at 60% +/- 12% of maximal aerobic capacity (mean +/- SD). The magnitude increased with gestational age (10 +/- 8 to 20 +/- 11 beats.min-1), exercise intensity (8 +/- 7 to 21 +/- 13 beats.min-1), and exercise duration (8 +/- 4 to 16 +/- 7 beats.min-1). CONCLUSION: We concluded that the hypothesis is correct and speculate that these changes represent a maturing fetal response to a reduction in Po2.

Hepatitis B surface antigen screening in a nonindigent population.

The recommendation for universal screening of all pregnant women for hepatitis B surface antigen (HBsAg) is based on data from publicly funded hospitals. We retrospectively reviewed screening results of 2,696 mothers who delivered between May 1989 and April 1990. Our population was 85% privately funded. Screening for HBsAg was positive in 0.07%, negative in 80.4% and not done in 19.6%. All positive screens would have been identified by screening only patients with recognized risk factors. We conclude that the sensitivity of identifiable risk factors to detect HBsAg carriers may be high in some populations. We speculate that universal screening in these populations is not cost efficient.

Pregnancy loss and thrombosis with protein C deficiency.

OBJECTIVES: Protein C inhibits coagulation and promotes fibrinolysis. This study investigates the association between protein C deficiency and pregnancy loss, thrombosis in pregnancy, and thrombosis with oral contraception. STUDY DESIGN: Fifteen protein C--deficient patients and 37 controls from a single kindred were studied. An obstetric history was obtained by telephone. Data were analyzed by logistic regression, Fisher's exact test, and Student t test. RESULTS: Protein C--deficient women experienced a 33% pregnancy loss versus 19% in the controls (not significant). Thromboembolism during pregnancy in protein C--deficient women was 33% (45% in those not receiving prophylactic anticoagulation) versus 5% in controls (odds ratio 7.37, p = 0.026). Five of 12 protein C--deficient women using oral contraception developed thrombosis versus 0 of 33 controls. The risk of thrombosis for protein C--deficient women using oral contraception is increased (p < 0.001). CONCLUSIONS: Perinatal outcome is not statistically different with protein C deficiency. Protein C deficiency increases the risk of thrombosis during pregnancy and with oral contraception. Prophylactic heparin is suggested during pregnancy for protein C--deficient women with personal or family histories of thrombosis. Oral contraception is not advised.

PIP: Protein C inhibits coagulation and promotes fibrinolysis. This New England study investigated the association between protein C deficiency and pregnancy loss, thrombosis in pregnancy, and thrombosis with oral contraceptives (OCs). 15 protein C-deficient patients and 37 controls from a single kindred were studied. An obstetric history was obtained by telephone. Data were analyzed by logistic regression, Fisher's exact test, and Student t test. The protein C-deficient women experienced a 33% pregnancy loss vs 19% among the controls (not significant). Thromboembolism during pregnancy in protein C-deficient women was 33% (45% in those not receiving prophylactic anticoagulation) vs 5% in the controls (odds ration 7.37, p=0.026). 5 of 12 protein C-deficient women using OCs developed thrombosis vs. none of the 33 controls. The risk of thrombosis for protein C-deficient women using OCs is increased (p0.001). Perinatal outcome is not statistically different with protein C deficiency. Protein C deficiency increases the risk of thrombosis during pregnancy and while taking OCs. Prophylactic heparin is suggested during pregnancy for protein C-deficient women with personal or family histories of thrombosis. Oral contraception is not advised.

Elevated maternal serum alpha-fetoprotein levels and maternal risk factors. Their association with pregnancy complications.

Maternal serum alpha-fetoprotein (MS-AFP) screening programs identify a population of pregnant women with elevated MS-AFP values. When the levels are unassociated with a fetal anomaly, those women have a high incidence of pregnancy complications. Such patients were compared to a population with normal MS-AFP values to determine the incidence of historical risk factors and to ascertain if their presence affected the rate of pregnancy complications. A total of 358 patients were followed prospectively, 23 with elevated MS-AFP levels and 335 with normal levels (control group). Historical risk factors were more frequent in the patients with elevated MS-AFP levels. There was a fourfold increase in the rate of pregnancy complications when a patient had both risk factors and elevated MS-AFP levels as compared with elevated MS-AFP levels alone. In the control group, patients with known risk factors experienced twice the incidence of pregnancy complications as did patients with no risk factors. Using multiple logistic regression analysis, elevated MS-AFP levels were shown to be an independent variable in the risk assessment. The results of this study have wide application in the counseling and follow-up of patients identified by MS-AFP screening programs.

Prenatal diagnosis of autosomal recessive polycystic kidney disease: variable outcome within one family.

Autosomal recessive polycystic kidney disease is frequently diagnosed in utero by obstetric ultrasonography. We report a case in which there were varying outcomes of this disorder in three affected fetuses in a family. Recognition of variable expression within one family is important when parents are considering termination of a pregnancy with an affected fetus.

Elevated maternal serum alpha-fetoprotein: association with placental sonolucencies, fetomaternal hemorrhage, vaginal bleeding, and pregnancy outcome in the absence of fetal anomalies.

Elevated maternal serum alpha-fetoprotein (MSAFP) levels have been associated with an increased incidence of both placental sonolucencies and pregnancy complications. We designed a prospective study to test the hypothesis that the presence of these sonolucencies or a positive maternal Kleihauer-Betke stain would be associated with an elevated risk of obstetric complications. We enrolled 95 women with singleton pregnancies, elevated MSAFP, and no evidence of fetal anomalies on second-trimester ultrasound evaluation. Placental sonolucencies were documented at the time of ultrasound examination, and a maternal Kleihauer-Betke stain for fetal cells was obtained on the same day. Complications of pregnancy included fetal growth retardation, preterm delivery, late vaginal bleeding (at or after the 20th week of gestation), and fetal death. Women with elevated MSAFP had an increased incidence of placental sonolucencies, positive maternal Kleihauer-Betke stains, first-trimester vaginal bleeding, late vaginal bleeding, preterm delivery, fetal growth retardation, and fetal death compared with controls. Thirty-nine of 95 women with elevated MSAFP (41.1%) had at least one complication. In women with elevated levels, neither the presence of placental sonolucencies nor a positive Kleihauer-Betke stain correlated with first-trimester vaginal bleeding, the MSAFP level, or an increased risk of pregnancy complications. First-trimester vaginal bleeding was associated with an increased risk of preterm delivery in subjects with elevated MSAFP.

The changing glycemic response to exercise during pregnancy.

This study was designed to test the hypothesis that pregnancy reverses the nonpregnant hyperglycemic response to sustained exercise. Serial data were obtained from 75 exercising women. Before pregnancy, exercise produced an intensity-dependent increase in blood glucose that averaged 1.5 mmol/L at high intensities. By the eighth week this response was blunted and blood glucose increased only when exercise intensity exceeded 80% of maximum. At 15 weeks this progressed and was not associated with a change in either the insulin or catecholamine response. By the twenty-third week exercise produced a decrease in blood glucose that was no longer related to exercise intensity. We conclude that the hypothesis is correct and speculate that the early change in the response is related to decreased hepatic glucose release coupled with increased glucose oxidation. In late pregnancy this is probably accentuated by fetoplacental demands.

When do cardiovascular parameters return to their preconception values?

To determine if the postpartum period is reflective of a woman's cardiovascular status before pregnancy, we performed serial studies of 13 women before conception and at 6 and 12 weeks post partum. All pregnancies were singleton without hypertensive complications. Cardiac output, stroke volume, and end-diastolic volume were calculated with M-mode echocardiography from the left ventricular dimensions with subjects in the left lateral position. Systemic vascular resistance was calculated from cardiac output and simultaneous measurements of blood pressure. Stroke volume and end-diastolic volume remained consistently elevated over preconception values at 6 and 12 weeks. Systemic vascular resistance remained decreased, compared with baseline, at 12 weeks. Thus cardiovascular parameters had not returned to the preconception baseline, and previous studies that have used this time period for comparison have underestimated the contribution of stroke volume to the total change in cardiac output during pregnancy.

Neonatal morphometrics after endurance exercise during pregnancy.

This study was designed to test the hypothesis that continuation of a regular running and/or aerobics program during late pregnancy at or above 50% of preconceptional levels limits fetal growth. Accordingly, detailed neonatal morphometric data were gathered in the offspring of two groups: 77 well-conditioned recreational runners and aerobic dancers who were delivered at term after continuing their exercise regimen at or above 50% of the preconceptional level throughout pregnancy and 55 matched controls. Daily exercise performance was quantitated before conception and throughout pregnancy. Significant reductions in birth weight (-310 gm), birth weight percentile (-20), ponderal index (-0.24), its percentile (-30), and the fetoplacental weight ratio (-0.7) were seen in the offspring of the exercise group whereas crown-heel length (51.4 cm) and head circumference (35.0) were similar in the two groups. Reductions in two-site skin-fold thickness (-1.5 mm), skin-fold percentile (-30), calculated percent body fat (-5.0%), and fat mass (-220 gm) in the offspring of the exercise group confirmed the asymmetric pattern of growth restriction and indicated that approximately 70% of the difference in birth weight could be explained by the difference in neonatal fat mass. In runners, the relative level of exercise performance in the last 5 months of pregnancy explained 40% of the variability in birth weight over an 1100 gm birth weight range. We conclude that continuation of a regular aerobic or running program at or above a minimal training level during late pregnancy results in an asymmetric pattern of growth restriction that primarily impacts on neonatal fat mass.

Fetomaternal bleeding as a cause of recurrent fetal morbidity and mortality.

A woman had fetomaternal bleeding of unknown cause during at least three of five pregnancies. Each event was associated with significant fetal morbidity or mortality. Although fetomaternal bleeding has been reported as a cause of unexplained fetal death, its occurrence in subsequent pregnancies has not been described previously.

Successful pregnancy outcome in association with lipoatrophic diabetes mellitus.

Lipoatrophic diabetes mellitus is a rare syndrome characterized by lipoatrophy and insulin-resistant diabetes mellitus. Partial lipodystrophy without clinical diabetes mellitus has been associated with intrauterine growth retardation and fetal death. We report successful pregnancy outcomes in two women with lipoatrophic diabetes mellitus.