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OBJECTIVE: To compare perinatal outcomes between elective induction of labour (eIOL) and expectant management in obese women. DESIGN: Retrospective cohort study. SETTING: Deliveries in California in 2007. POPULATION: Term, singleton, vertex, nonanomalous deliveries among obese women (n = 74 725). METHODS: Women who underwent eIOL at 37 weeks were compared with women who were expectantly managed at that gestational age. Similar comparisons were made at 38, 39, and 40 weeks. Results were stratified by parity. Chi-square tests and multivariable logistic regression were used for statistical comparison. MAIN OUTCOME MEASURES: Method of delivery, severe perineal lacerations, postpartum haemorrhage, chorioamnionitis, macrosomia, shoulder dystocia, brachial plexus injury, respiratory distress syndrome. RESULTS: The odds of caesarean delivery were lower among nulliparous women with eIOL at 37 weeks [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.34-0.90] and 39 weeks (OR 0.77, 95% CI 0.63-0.95) compared to expectant management. Among multiparous women with a prior vaginal delivery, eIOL at 37 (OR 0.39, 95% CI 0.24-0.64), 38 (OR 0.65, 95% CI 0.51-0.82), and 39 weeks (OR 0.67, 95% CI 0.56-0.81) was associated with lower odds of caesarean. Additionally, eIOL at 38, 39, and 40 weeks was associated with lower odds of macrosomia. There were no differences in the odds of operative vaginal delivery, lacerations, brachial plexus injury or respiratory distress syndrome. CONCLUSIONS: In obese women, term eIOL may decrease the risk of caesarean delivery, particularly in multiparas, without increasing the risks of other adverse outcomes when compared with expectant management.

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OBJECTIVE: To examine the impact of change in body mass index (BMI) during pregnancy on the incidence of gestational hypertension/preeclampsia. STUDY DESIGN: This is a retrospective cohort study using linked California birth certificate and discharge diagnosis data from the year 2007. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for the outcome of gestational hypertension/preeclampsia, as a function of a categorical change in pregnancy BMI: BMI loss (<-0.5), no change (-0.5 to 0.5), minimal (0.6 to 5), moderate (5.1 to 10) and excessive (>10). The impact of change in pregnancy BMI was evaluated for the entire cohort and then as a function of prepregnancy BMI category. Women with no change in pregnancy BMI served as the reference group. RESULT: The study population consisted of 436 414 women with singleton gestations. Overall, women with excessive BMI change had a nearly twofold increased odds of gestational hypertension/preeclampsia (aOR=1.94; 95% CI=1.72 to 2.20). By prepregnancy BMI class, overweight and obese women who had a moderate change in pregnancy BMI also had increased odds of developing gestational hypertension/preeclampsia with aOR ranging from 1.73 to 1.97. CONCLUSION: Regardless of prepregnancy BMI category, women with excessive BMI change have a higher chance of developing gestational hypertension/preeclampsia. Overweight and obese women with moderate BMI change may also be at increased risk.

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OBJECTIVE: In a selected low-risk population with spontaneous term labor we sought to determine whether there was a continuous effect of maternal age on uterine function. STUDY DESIGN: With our comprehensive computerized database and medical record system, we identified 8496 patients who were nulliparous and in spontaneous labor at term (> or =37 weeks' gestation) with singleton fetuses in vertex presentation. This group was then analyzed according to maternal age for measures of labor dysfunction and rates of operative delivery. Analysis of variance and chi(2) statistics were used. RESULTS: Use of oxytocin, duration of second stage of labor, cesarean delivery, cesarean delivery for failure to progress, and operative vaginal delivery rates were significantly increased with advancing maternal age (P <.0001). These increases appeared to be continuous functions beginning during the early 20s rather than new phenomena beginning after age 35 years. CONCLUSION: Among nulliparous patients with uncomplicated labor there is a continuously increasing risk of uterine dysfunction related to maternal age.

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OBJECTIVE: In a large private tertiary care hospital we compared the two different approaches to group B streptococcal screening and intrapartum chemoprophylaxis suggested by The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention: risk factor-based protocol and culture-based protocol. STUDY DESIGN: A 2-year baseline period was followed by sequential prospective observational studies of the impacts of two different group B streptococcal management protocols, 3 years with the risk-based approach and 2 years with the culture-based approach of universal screening at 35 to 37 weeks' gestation. RESULTS: During the baseline period the rate of early-onset group B streptococcal infection was 1. 1 cases per 1000 births (n = 8 cases per 6829 births). With the risk-based strategy the rate was also 1.1 cases per 1000 births (15 cases/13,270 births). After we switched to the culture-based protocol for 2 years, there were no cases of early-onset group B streptococcal infections among 9304 births (P =.001; chi(2) = 10.9). There were no increases in other early-onset infections or in antibiotic resistance. CONCLUSIONS: In our setting, which included good prenatal care and good communication between laboratories and the hospital, the approach based on maternal culture at 35 to 37 weeks' gestation and treatment during labor of all patients with positive results significantly reduced early-onset group B streptococcal infections without increasing infections from resistant organisms.

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Reduction of cesarean section rates has been a difficult process that has not been easily accomplished by the institution of guidelines. It is more a process of changing physician behavior rather than of medical education. This article analyzed the role of intensive feedback of outcomes to bring about such changes. Two large private obstetric services in San Francisco, CA, were studied. Intensive outcomes feedback using a computerized information system, The Perinatal Data Center, regarding cesarean birth rates and a variety of obstetric outcomes was provided to the medical and nursing staff at one hospital. The other center served as a control. After the first observation period, the outcomes system was introduced to the second hospital. Finally, "open label" feedback, intradepartmental release of everyone's key statistics with names attached, was performed. Active management of labor was not practiced at either hospital. Results. Cesarean birth rates were stable in the baseline period from 1980 through 1988 at 24% to 25%. Introduction of the Perinatal Data Center outcomes system was associated with a reduction to 21% at the first hospital with no change in the control hospital. Subsequent introduction of the system 3 years later in the control hospital resulted in a decline from 25% to 20.5%. After merger of the two obstetric units and the institution of "open label" feedback, an additional decline to 18.5% was observed. Conclusion. Physician practice patterns and cesarean birth rates can be altered with the intensive use of comparative outcome data and strong physician leadership. Nonblinded, intradepartmental distribution of outcomes is an even more effective tool.

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PROBLEM: Several studies have evaluated the effect of intravenous gammaglobulin (IVIG) in women with unexplained recurrent spontaneous abortions (RSA). Data regarding the underlying immunologic abnormalities in these patients is scant. This study reports the pregnancy outcome and immunologic changes observed in a large group of women with RSA associated with well-defined alloimmune and autoimmune abnormalities treated with IVIG. METHODS: Thirty-five patients with three or more recurrent miscarriages were studied. None of the patients had identifiable alloimmune response to paternal lymphocytes. Twenty-four patients had anti-thyroid antibodies, ten patients had high levels of circulating immune complexes, and six patients had anti-cardiolipin antibodies. Five patients had Hashimoto's disease, one had immune thrombocytopenic purpura, and one had Crohn's disease. Twenty-three patients had more than one autoimmune abnormality. All patients received IVIG infusions (200-250 mg/kg) every 3 weeks during the first 8 months of pregnancy. RESULTS: Twenty-eight patients (80%) had a successful pregnancy. Decrease of the level of autoantibodies and circulating immune complexes was observed in all patients who had a successful pregnancy. Only three of these patients developed measurable alloimmune response to paternal antigens. CONCLUSIONS: This preliminary study suggests that IVIG may be of benefit to patients with recurrent pregnancy associated with combined alloimmune and autoimmune abnormalities. This benefit was seen in spite of lack of detectable correction of the alloimmune abnormality in the majority of patients.

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PROBLEM: Human trophoblast expression of class I human leukocyte antigen (HLA) genes is unique in that there is no classical gene expression, but nonclassical HLA-G is expressed and only by cytotrophoblast cells. This differential expression of classical versus nonclassical class I genes suggests tissue specific regulation. Recently, a negative regulatory element (NRE), 180 bp 5' to transcription initiation was identified in a murine embryonal carcinoma cell line that markedly inhibited class I gene expression (Flanagan et al., Proc Natl Acad Sci USA 1991; 83:3145-3149). METHOD: Here we analyzed the human HLA-A2 gene for a putative NRE sequence and determined whether such a sequence is capable of binding to factors present in a variety of class I-null cell lines. RESULTS: Sequence analysis revealed that the NRE for human HLA-A2 is identical to that for mouse H-2Ld. Using gel shift assays with nuclear extracts (NE) from a variety of cell types, we demonstrated specific binding to the HLA-A2 NRE sequence. The choriocarcinoma cell lines JEG and BeWo and the F9 cells (all negative for classical gene expression) contained this DNA binding factor(s). This binding factor was not present in NE from lymphocytes or a variety of other cell lines that were positive for classical gene expression. CONCLUSION: Human trophoblasts appear to have a tissue specific nuclear binding factor that may down regulate classical class I expression upon binding to the NRE sequence. The HLA-G gene does not have this NRE region thus enabling its expression by these cells.

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OBJECTIVE: Expression of the histocompatibility antigen HLA-G may be required for appropriate invasion and remodeling of uterine spiral arteries. Inappropriate expression of this antigen may result in failure of invasion, leading to partial placental ischemia and gestational disease. STUDY DESIGN: To test the hypothesis that the level of expression of HLA-G is reduced in trophoblasts from patients with gestational complications (preeclampsia, intrauterine growth retardation, or gestational hypertension) compared with patients with normal pregnancy, total ribonucleic acid was isolated from the fetal membrane or decidual interface of term placenta from several patient groups. Ribonuclease protection assay was used to determine levels of HLA-G expression, which was normalized for total ribonucleic acid input with beta-actin and for trophoblast content in the tissue by cytokeratin 8. RESULTS: When normalized for total ribonucleic acid input (beta-actin), term placental expression of HLA-G was reduced for all forms of preeclampsia but not for intrauterine growth retardation or gestational hypertension. When tissue expression of cytokeratin, an indicator of trophoblast input, was normalized for trophoblast input, was normalized for total ribonucleic acid input, primary preeclampsia and intrauterine growth retardation had reduced numbers of trophoblast per unit tissue. When controlled for trophoblast input HLA-G expression was similar to normal for all clinical groups, except for intrauterine growth retardation, which was slightly increased. CONCLUSION: Level of expression of HLA-G in placental tissue was reduced in preeclampsia. This decrease in expression appears to be related to reduced numbers of trophoblasts in placental tissue examined at term from patients with primary preeclampsia.

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OBJECTIVE: To determine by reverse transcription-polymerase chain reaction (PCR) whether human leukocyte antigen (HLA) class I messenger RNA (mRNA) is present in mature human spermatozoa. DESIGN: Mature human spermatozoa was isolated from donor semen using a swim-up technique. Total RNA was extracted via guanidinium isothiocyanate-cesium chloride ultracentrifugation. By the method previously validated in our laboratory, reverse transcription-PCR was performed using primers specific for HLA class I transcripts. Positive control cells included a choriocarcinoma cell line (JEG) and human fetal tissue. Transformed peripheral blood lymphocytes (PBL) were used as a negative control for somatic cellular contamination. RESULTS: Human spermatozoa were positive for HLA class I (-G and -B) mRNA by reverse transcription-PCR, consistent with the positive controls. We did not detect any mRNA for beta-actin, retinoblastoma (RB), CD4, or kappa light chain genes in the sperm complementary DNA samples, verifying that the class I mRNA detected was not due to somatic cellular contamination of the purified sperm samples. CONCLUSION: These experiments provide the first evidence that mRNA for HLA class I molecules are present in mature human spermatozoa. The physiological role of these transcripts is unknown at present. Further experiments characterizing the expression of HLA class I (-G and -B) mRNA in oocytes and preimplantation embryos are in progress.

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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.

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OBJECTIVE: The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics. STUDY DESIGN: Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data. RESULTS: Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine. CONCLUSIONS: Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.

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In their severest forms, pre-eclampsia and eclampsia may be life-threatening complications of pregnancy. We describe a patient with severe post-partum eclampsia characterized by seizures, deep coma, hypertension, renal insufficiency, coagulopathy, and microangiopathic hemolysis. The patient responded to treatment that included intensive plasma exchange, and she achieved full recovery. Our case supports the use of plasma exchange in patients with severe pre-eclampsia and eclampsia.

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To test the value of intensive management of diabetes before and during early pregnancy, 84 women recruited prior to conception were compared with 110 women who were already pregnant referred at 6 to 30 weeks' gestation. All underwent daily measurement of fasting and postprandial capillary blood glucose levels. Mean blood glucose levels during embryogenesis and organogenesis were within 3.3 to 7.8 mmol/L in 50% of preconception subjects and exceeded 10 mmol/L in 6.5%. One major congenital anomaly occurred in 84 infants (1.2%) of women treated before conception compared with 12 anomalies in 110 infants (10.9%) of mothers in the postconception group. Transient symptomatic hypoglycemia occurred during embryogenesis in 60% of women in the preconception group, with a median frequency of 2.7 episodes per week, but was not associated with excess malformations. We conclude that education and intensive management for glycemic control of diabetic women before and during early pregnancy will prevent excess rates of congenital anomalies in their infants.

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The role of the placental tissue in the perinatal transmission of HIV is still far from being understood. Significant data regarding transplacental infection have been collected, but differences in technique have led to controversy. It appears clear that many Hofbauer cells are CD4+ and can become infected with HIV. Less certain but probable is infection of trophoblasts themselves. Whether infection is CD4 mediated or via cell-cell fusion is not established. Transplacental traffic of virus and cells remains a little-studied possibility. Further data are needed regarding the fascinating concept of the placenta as a modulator of infection.

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The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts.

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Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.

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A case of fetal bradycardia associated with severe maternal hypothermia (92.9F) is reported. Until maternal temperature was corrected, the baseline fetal heart rate (FHR) remained between 90-110 beats per minute without other evidence of fetal distress and despite normal maternal blood pressure and pulse. With rewarming, the FHR gradually returned to normal. Upon return of maternal hypothermia, fetal bradycardia recurred, again responding only to rewarming. This evidence suggests that low maternal temperature alone may lead to alterations of FHR.

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The expression and regulation of HLA antigens were examined in isolated human trophoblasts. Immunocytochemical studies that used monoclonal antibodies against class I (HLA-A, B, and C) antigens revealed that both cytotrophoblasts and syncytiotrophoblasts can express HLA heavy chains and beta 2-microglobulin. Expression of these antigens increased with time in culture. The addition of recombinant gamma-interferon (1000 U/ml) to the cultures significantly increased cellular staining for these antigens over controls throughout the 72-hour time course studied. In addition, we noted that gene expression for HLA class I heavy chain was also markedly augmented by the addition of gamma-interferon. Expression of class II (HLA-DR) antigens was not detected in any of the experiments. These results suggest that during in vitro differentiation, cytotrophoblasts can express class I HLA antigens and the genes controlling their production can be regulated. Alterations in the expression or suppression of these antigens during pregnancy could be responsible for some pregnancy complications.

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