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To examine obstetrician-gynecologists' knowledge, opinions, and practice patterns related to cesarean delivery on maternal request.Questionnaires were mailed to 1,031 American College of Obstetricians and Gynecologists Fellows in February 2006, with a response rate of 68%. The questionnaire queried respondents' demographic characteristics, practices and attitudes surrounding vaginal and cesarean deliveries, knowledge and beliefs regarding the risks and benefits of elective and nonelective cesarean delivery, and counseling practices and department policies for cesarean delivery on maternal request.About half of respondents believe women have the right to cesarean delivery on maternal request, and a similar percentage acknowledge having performed at least one cesarean delivery on maternal request. Fifty-eight percent of respondents note an increase in patient inquiries regarding cesarean delivery over the past year, yet most of their practices do not have a policy regarding this procedure. Respondents attribute the increase in inquiries to the increase of information from the media and to convenience. Respondents cited more risks than benefits of cesarean delivery on maternal request, and nearly all discuss these risks with patients who are considering one. Females were more negative toward cesarean delivery on maternal request than males and endorsed more risks and fewer benefits. There were no relationships between assessment of risks and benefits or practice with clinician age or patient characteristics.Most obstetrician-gynecologists in this study recognized an increased demand for cesarean delivery on maternal request within their practices, while believing that the risks of this procedure outweigh the benefits. Clinicians would benefit from strong evidence regarding risks and benefits, evidence that is crucial to guiding policy making with regard to cesarean delivery on maternal request.III.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.

Objective We sought to describe the prevalence of serious maternal complications following early preterm birth by gestational age (GA), delivery route, and type of cesarean incision. Study Design Trained personnel abstracted data from maternal and neonatal charts for all deliveries on randomly selected days representing one third of deliveries across 25 US hospitals over 3 years (n = 115,502). All women delivering nonanomalous singletons between 23-33 weeks' gestation were included. Women were excluded for antepartum stillbirth and highly morbid conditions for which route of delivery would not likely impact morbidity including nonreassuring fetal status, cord prolapse, placenta previa, placenta accreta, placental abruption, and severe and unstable maternal conditions (cardiopulmonary collapse, acute respiratory distress syndrome, seizures). Serious maternal complications were defined as: hemorrhage (blood loss ≥1500 mL, blood transfusion, or hysterectomy for hemorrhage), infection (endometritis, wound dehiscence, or wound infection requiring antibiotics, reopening, or unexpected procedure), intensive care unit admission, or death. Delivery route was categorized as classic cesarean delivery (CCD), low transverse cesarean delivery (LTCD), low vertical cesarean delivery (LVCD), and vaginal delivery. Association of delivery route with complications was estimated using multivariable regression models yielding adjusted relative risks (aRR) controlling for maternal age, race, body mass index, hypertension, diabetes, preterm premature rupture of membranes, preterm labor, GA, and hospital of delivery. Results Of 2659 women who met criteria for inclusion in this analysis, 8.6% of women experienced serious maternal complications. Complications were associated with GA and were highest between 23-27 weeks of gestation. The frequency of complications was associated with delivery route; compared with 3.5% of vaginal delivery, 23.0% of CCD (aRR, 3.54; 95% confidence interval (CI), 2.29–5.48), 12.1% of LTCD (aRR, 2.59; 95% CI, 1.77–3.77), and 10.3% of LVCD (aRR, 2.27; 95% CI, 0.68–7.55) experienced complications. There was no significant difference in complication rates between CCD and LTCD (aRR, 1.37; 95% CI, 0.95–1.97) or between CCD and LVCD (aRR, 1.56; 95% CI, 0.48–5.07). Conclusion The risk of maternal complications after early preterm delivery is substantial, particularly in women who undergo cesarean delivery. Obstetricians need to be prepared to manage potential hemorrhage, infection, and intensive care unit admission for early preterm births requiring cesarean delivery.

We sought to evaluate the frequency of, and factors associated with, the use of 3 evidence-based interventions: antenatal corticosteroids for fetal lung maturity, progesterone for prevention of recurrent preterm birth, and magnesium sulfate for fetal neuroprotection.A self-administered survey was conducted from January through May 2011 among obstetricians from 21 hospitals that included 30 questions regarding their knowledge, attitudes, and practice of the 3 evidence-based interventions and the 14-item short version of the Team Climate for Innovation survey. Frequency of use of each intervention was ascertained from an obstetrical cohort of women between January 2010 and February 2011.A total of 329 obstetricians (74% response rate) who managed 16,946 deliveries within the obstetrical cohort participated in the survey. More than 90% of obstetricians reported that they incorporated each intervention into routine practice. Actual frequency of administration in women eligible for the treatments was 93% for corticosteroids, 39% for progesterone, and 71% for magnesium sulfate. Provider satisfaction with quality of treatment evidence was 97% for corticosteroids, 82% for progesterone, and 57% for magnesium sulfate. Obstetricians perceived that barriers to treatment were most frequent for progesterone (76%), 30% for magnesium sulfate, and 17% for corticosteroids. Progesterone use was more frequent among patients whose provider reported the quality of the evidence was above average to excellent compared with poor to average (42% vs 25%, respectively; P.001), and they were satisfied with their knowledge of the intervention (41% vs 28%; P = .02), and was less common among patients whose provider reported barriers to hospital or pharmacy drug delivery (31% vs 42%; P = .01). Corticosteroid administration was more common among patients who delivered at hospitals with 24 hours a day-7 days a week maternal-fetal medicine specialist coverage (93% vs 84%; P = .046), CONCLUSION: Obstetricians in Maternal-Fetal Medicine Units Network hospitals frequently use these evidence-based interventions; however, progesterone use was found to be related to their assessment of evidence quality. Neither progesterone nor the other interventions were associated with overall climate of innovation within a hospital as measured by the Team Climate for Innovation. National Institutes of Health Consensus Conference Statements may also have an impact on use; there is such a statement for antenatal corticosteroids but not for progesterone for preterm prevention or magnesium sulfate for fetal neuroprotection.

To evaluate whether women who agree to future use of their biologic specimens for genetic studies reflect the larger study population from which they are derived.Women were questioned as to the future disposition of their maternal and fetal DNA samples upon enrollment in a multicenter, observational study originally designed to identify factor V Leiden mutation carriers and prospectively ascertain the estimated rate of pregnancy-related venous thromboembolism and adverse pregnancy outcome. Univariate and multivariate analyses was carried out on the 5,003 of 5,188 enrolled women who indicated their desire regarding future disposition of their DNA samples.Among these 5,003 women, 20.1% desired that their samples be discarded and not available for future genetic studies. Multivariate analysis demonstrated that women who agreed to subsequent use of samples were less likely African-American (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.7) or Hispanic (OR 0.4, 95% CI 0.3-0.5), and more likely to use tobacco (OR 1.2, 95% CI 1.0-1.6) than those who desired that their samples be discarded.Genetic samples from women agreeing to their use in a sample repository may not be representative of the index study cohort. This should be considered in their subsequent interpretation and generalizability.III.

To describe the incidence and type of fetal injury identified in women undergoing cesarean delivery.Between January 1, 1999, and December 31, 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 university centers. Information regarding maternal and infant outcomes was abstracted directly from hospital charts.A total of 37,110 cesarean deliveries were included in the registry, and 418 (1.1%) had an identified fetal injury. The most common injury was skin laceration (n = 272, 0.7%). Other injuries included cephalohematoma (n = 88), clavicular fracture (n = 11), brachial plexus (n = 9), skull fracture (n = 6), and facial nerve palsy (n = 11). Among primary cesarean deliveries, deliveries with a failed forceps or vacuum attempt had the highest rate of injuries (6.9%). In women with a prior cesarean delivery, the highest rate of injury also occurred in the unsuccessful trial of forceps or vacuum (1.7%), and the lowest rate occurred in the elective repeat cesarean group (0.5%). The type of uterine incision was associated with fetal injury, 3.4% "T" or "J" incision, 1.4% for vertical incision, and 1.1% for a low transverse (P = .003), as was a skin incision-to-delivery time of 3 minutes or less. Fetal injury did not vary in frequency with the type of skin incision, preterm delivery, maternal body mass index, or infant birth weight greater than 4,000 g.Fetal injuries complicate 1.1% of cesarean deliveries. The frequency of fetal injury at cesarean delivery varies with the indication for surgery as well as with the duration of the skin incision-to-delivery interval and the type of uterine incision.II-3.

The purpose of this study was to determine the influence of change in infant birth weight between pregnancies on the outcome of a trial of labor for women whose first cesarean delivery was performed for dystocia.Secondary analysis of 7081 patients with 1 previous cesarean delivery and no other deliveries after 20 weeks' gestation, undergoing a trial of labor with a singleton gestation. Cases were classified as dystocia if the listed indication for the cesarean delivery in the first pregnancy was failed induction, cephalo-pelvic disproportion, failure to progress, or failed forceps or vacuum. Outcomes of the trial of labor were correlated with fetal size relative to birth weight in the initial pregnancy for those women whose initial cesarean delivery was for dystocia and those with other indications.For the cohort being studied (n = 7081), dystocia was the indication for the first cesarean delivery for 3182 (44.9%). Trial of labor resulted in vaginal delivery for 54% of patients whose first cesarean delivery was performed for dystocia, compared with 67% for those with other indications (P.01). For those whose first cesarean delivery was for dystocia, trial of labor success was correlated with birth weight differences between the pregnancies, with only 38% delivering vaginally if the trial of labor birth weight exceeded the initial pregnancy birth weight by more than 500 g. Using logistic regression and adjusting for other potential confounding factors, the odds of success decreased by 3.8% for each increase of 100 g in birth weight in the trial of labor relative to the first birth weight.For women with previous cesarean delivery for dystocia, increasing birth weight in the subsequent trial of labor relative to the first birth weight diminishes the chances of successful vaginal delivery.

Objective This study was undertaken to compare success rates of vaginal birth after cesarean (VBAC) delivery, and uterine rupture as well as maternal/perinatal outcomes between women with preterm and term pregnancies undergoing trial of labor (TOL), and to compare maternal and neonatal morbidities in those women with preterm pregnancies undergoing a TOL versus repeat cesarean delivery without labor (RCD). Study design Prospective 4-year observational study of women with a singleton gestation and a prior cesarean delivery at 19 academic centers. Clinical characteristics, maternal complications and VBAC delivery success for those with a preterm (24 0 -36 6 weeks) TOL, preterm RCD and term TOL (≥37 weeks) were analyzed. Results Among 3119 preterm pregnancies with prior cesarean delivery, 2338 (75%) underwent a TOL. 15,331 women undergoing TOL at term were also analyzed as a control group. TOL success rates for preterm and term pregnancies were similar (72.8% vs 73.3%, P = .64). Rates of uterine rupture (0.34% vs 0.74%, P = .03) and dehiscence (0.26% vs 0.67%, P = .02) were lower in preterm compared with term TOL. Thromboembolic disease, coagulopathy and transfusion were more common in women undergoing a preterm TOL than those at term. Among women undergoing a preterm TOL, rates of uterine dehiscence, coagulopathy, transfusion, and endometritis were similar to those having a preterm RCD. After controlling for gestational age at delivery and race, neonatal outcomes such as Neonatal Intensive Care Unit (NICU) admission, intraventricular hemorrhage, sepsis, and ventilatory support were similar in both groups except for a higher rate of respiratory distress syndrome in those delivered after a TOL. Conclusion The likelihood of VBAC success after TOL in preterm pregnancies is comparable to term gestations, with a lower risk of uterine rupture. Perinatal outcomes are similar with preterm TOL and RCD. TOL should be considered as an option for women undergoing preterm delivery with a history of prior cesarean delivery.

The mechanism through which VIP prevents neurotoxicity associated with HIV envelope protein has been shown to involve the release of a beta-chemokine, MIP-1 alpha. Astrocytes stimulated with subnanomolar concentrations of VIP caused the release of MIP-1 alpha and RANTES, both of which have been shown to prevent neuronal cell death associated with gp120. It is further proposed that gp120 causes neuronal cell death, in part, by competing with endogenous chemokines at various chemokines receptors in the brain that are necessary for neuronal survival. Although the chemokines are known to be mediators of inflammation, our studies suggest that these compounds have additional roles as neuroprotective agents that depend on the concentration of chemokine, cellular microenvironment, and stage of development of target neurons. Our studies further imply that in a developing system, stimulation with a MIP-1 alpha like substance is necessary for neuronal survival and interference with this action results in neuronal cell death.

Electrodeposited nanocrystalline Co offers a relatively unique opportunity to study the interaction of two fundamentally different elementary solid state reactions: grain growth and e (HCP) to α (FCC) allotropic phase transformation. Samples were isothermally annealed at temperatures above and below the equilibrium transformation temperature (Teα = 695 K) and quenched to ambient for subsequent characterization by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Isothermal annealing above 695 K resulted in concurrent grain growth and e to α transformation. Unexpectedly, however, simultaneous grain growth and e to α transformation also occurred during isothermal annealing at temperatures as low as 573 K, i.e. 122 K below the expected equilibrium Teα. It was observed that non-equilibrium α-Co formed within a matrix of nanocrystalline e-Co via abnormal grain growth, and is therefore fundamentally different from the e to α transformation typically observed in conventional polycrystalline Co.

Objective The purpose of this study was to define independent risk factors for uterine atony after primary cesarean delivery, and to assess their overall association with atony in the study cohort. Study design This was a 13–university center prospective observational study. All women who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Trained and certified research nurses performed systematic data abstraction. The definition of atony required both the clinical diagnosis and the use of methergine or a prostaglandin preparation. Risk factors for uterine atony were assessed in univariable and multivariable logistic regression analyses, and these analyses then used to inform an assessment of the association of the various risk factors with the occurrence of uterine atony in the overall cohort. Results Twenty-three thousand, three hundred and ninety pregnancies were analyzed. Uterine atony occurred in 1416 women (6%). Several variables were independently associated with atony in a multivariable model, including multiple gestation (odds ratio [OR] 2.40, 95% CI 1.95-2.93), maternal Hispanic race (2.21, 1.90-2.57), induced or augmented labor for >18 hours (2.23, 1.92-2.60), infant birth weight >4500 g (2.05, 1.53-2.69), and clinically diagnosed chorioamnionitis (1.80, 1.55-2.09). However, because the various risk factors were not very powerful, approximately half of the cases of atony were associated with the 2/3 of women lacking a given risk factor or combination of risk factors. Conclusion Although certain risk factors and uterine atony were clearly associated, the associations are of limited practical clinical use.

To quantify anesthesia-related complications associated with cesarean delivery in a well-described, prospectively ascertained cohort from multiple university-based hospitals in the United States and to evaluate whether certain factors would identify women at increased risk for a failed regional anesthetic.A prospective observational study was conducted of women (n = 37,142) with singleton gestations undergoing cesarean delivery in the centers forming the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Detailed information was collected regarding choice of anesthesia and procedure-related complications, including failed regional anesthetic and maternal death. Potential risk factors for a failed regional anesthetic were analyzed.Of the women studied, 34,615 (93%) received a regional anesthetic. Few (3.0%) regional procedures failed, and related maternal morbidity was rare. Increased maternal size, higher preoperative risk, rapid decision-to-incision interval, and placement later in labor were all significantly related to an increased risk of a failed regional procedure. Of the general anesthetics, 38% were administered when the decision-to-incision interval was less than 15 minutes. Women deemed at the greatest preoperative risk (American Society of Anesthesiologists scoreor = 4) were approximately 7-fold more likely to receive a general anesthetic (odds ratio 6.9, 95% confidence interval 5.83-8.07). There was one maternal death, due to a failed intubation, in which the anesthetic procedure was directly implicated.Regional techniques have become the preferred method of anesthesia for cesarean delivery. Procedure-related complications are rare and attest to the safety of modern obstetric anesthesia for cesarean delivery in the United States.

Objective Cerebral palsy (CP) is associated with childhood spasticity, seizures, and paralysis. Oligodendrocyte damage resulting in periventicular leukomalacia (PVL) in the developing brain has been implicated. Animal models of CP have used prenatal hypoxia and infection with histopathology of PVL as the end point. To evaluate whether this histologic end point is associated with a CP phenotype, we reproduced a lipopolysaccharide (LPS) model for PVL, 1 and evaluated developmental, behavioral, and motor outcomes. Study design On gestational day 15, Fischer 344 rats were intracervically injected with .1 mg/kg LPS (n=5) or saline (n=4). After delivery, evaluation for developmental milestones was performed on days 1 to 21 (LPS=45; control=30 pups). Males were also tested at 2.5 months using open-field, rotarod, and anxiety tests. On day 21, 2 pups/litter were perfused for immunohistochemistry, and stained with 2 oligodendrocyte antibodies: 2′, d'-cyclic nucleotide phosphodiesterase (CNP), and myelin proteolipid protein (PLP) with relative densities of staining assessed using NIH Image software. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA). Results LPS pups demonstrated decreased CNP ( P =.04) and PLP ( P =.06) staining, replicating the model. There was no difference seen in neonatal weight, righting, negative geotaxis, cliff aversion, rooting, forelimb grasp, audio startle, air righting, eye opening, and activity. Surprisingly, LPS-exposed neonatal rats mastered forelimb placement ( P P =.02) earlier than control rats. There were no differences between adult groups in open field distance traveled ( P =.8), open-field locomotion time ( P =.6), rotarod ( P =.6), or anxiety ( P =.7). Conclusion Histologic evidence of white matter damage can be replicated using an LPS model for intrauterine inflammation. Significant phenotypic differences consistent with the motor and cognitive damage sequelae of such lesions (ie, CP) were not demonstrated. When evaluating animal models, it is important to assess not only biochemical markers for human disease, but also clinically relevant phenotypes.

Objective. To determine if antepartum administration of magnesium sulfate affects the Score for Neonatal Acute Physiology (SNAP).Methods. We reviewed a database of consecutive preterm admissions to our neonatal intensive care unit over a 12-month period. Information on delivery indication, magnesium sulfate use, betamethasone administration, neonatal SNAP scores, neonatal serum magnesium levels, and other data was collected. Data was analyzed by Chi-square, Student t-test, and multiple linear regression with P

Fewer women today are attempting vaginal delivery after a previous cesarean delivery, mostly because of concern about its safety. This prospective cohort study, carried out at 19 academic medical centers, compared outcomes in 17,898 women with a history of cesarean section who attempted vaginal delivery and 15,801 others who had elective repeat cesarean section without labor. Women having a trial of labor were more likely than those having elective repeat cesarean delivery to be less than 30 years of age, black, unmarried, and nonobese. They also were likelier to have both preterm and delayed delivery. Vaginal delivery succeeded in 73.4% of women. The rate of symptomatic uterine rupture in women having a trial of labor was 0.7%. It was the same for those having a previous low transverse incision and 2.0% in those with a previous low vertical incision. Uterine rupture was associated with augmentation of labor using oxytocin and also with induction of labor by any method. Both endometritis and maternal blood transfusion were significantly more frequent with a trial of labor. Hysterectomy was performed in 88 women, in 41 after a trial of labor. The odds ratio for maternal adverse events in women having a trial of labor was 1.96 (95% confidence interval, 1.73-2.22) after adjusting for demographic differences and maternal diseases. Hypoxic-ischemic encephalopathy was significantly more frequent when women had a trial of labor at term than in the infants of women having elective repeat cesarean delivery. Both stillbirths and neonatal deaths were more frequent in the trial of labor group. There were no intrapartum fetal deaths. Adverse perinatal outcomes are more frequent when women with a history of cesarean delivery who undergo a trial of labor. Maternal adverse events also are increased. Although the degree of risk is small, it is important that both pregnant women and the healthcare providers who advise them be aware of the possible consequences.

Objective In an effort to reduce shoulder dystocia incidence and morbidity, some obstetricians use prophylactic maternal hip hyperflexion (McRoberts maneuver), with the hope of facilitating delivery and decreasing the traction needed for delivery. The objective of this study was to evaluate whether the delivery force is reduced with the prophylactic McRoberts maneuver in a prospective, objective manner. Study design Between April 2002 and July 2003, we randomly assigned multiparous women with term, cephalic singleton gestations to delivery in the lithotomy or McRoberts position. A single physician used a force-measuring system that consisted of a custom glove with force sensors to record the amount of force that was exerted on the fetal head. The primary outcomes of the study were peak force (pounds; highest force needed to accomplish entire delivery), peak force for delivery of anterior shoulder (pounds), and peak force rate (pounds per second; the duration required to reach the peak force). Results The peak force was not different between the patients in the lithotomy position (n=13) versus the McRoberts position (n=14; 7.2 ± 0.8 lbs vs 8.0 ± 0.7 lbs; P =.5). The peak force for delivery of the anterior shoulder (6.7 ± 0.8 lbs vs 7.1 ± 0.7 lbs; P =.7) and peak force rate (32.3 ± 7.0 lbs/sec vs 29.1 ± 3.5 lbs/sec; P =.7) were not different between the patients in the lithotomy position versus the McRoberts position, respectively. There was no difference between the groups for gestational age, birth weight, incidence of diabetes mellitus, or operative vaginal delivery. The subjective degree of difficulty of the delivery correlated with the peak force ( R 2 =0.53; P =.001). Conclusion The use of the McRoberts maneuver before clinical diagnosis of shoulder dystocia provides no reduction in the force that is used in traction on the fetal head during vaginal delivery in multiparous patients. The acceptance of this maneuver to be used prophylactically requires re-evaluation.

The purpose of this study was to evaluate the relationship between chorioamnionitis and its duration to adverse maternal, fetal, and neonatal outcomes.This was a 13-university center, prospective observational study. All women at term carrying a singleton gestation who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Data abstraction was systematic and performed by trained research nurses. Selected adverse outcomes were compared between pregnancies with, and without, clinically diagnosed chorioamnionitis using relative risks (RRs) and 95% CIs. The duration of chorioamnionitis was stratified into 5 intervals (or=3 h,3-6 h,6-9 h,9-12 h, and12 h), and respective outcomes compared by Mantel-Haenszel test for trend. Additionally, regression analysis was used to compute odds ratios (ORs) and 95% CIs for chorioamnionitis duration length as a continuous explanatory variable.16,650 pregnancies were analyzed, 1965 (12%) with chorioamnionitis, which was associated with significantly increased risks of maternal blood transfusion, uterine atony, septic pelvic thrombophlebitis, and pelvic abscess (RR 2.3-3.7), as well as 5-minute Apgaror=3, neonatal sepsis, and seizures (RR 2.1-2.8). By test of trend, only uterine atony (P.01), maternal blood transfusion (P=.03), maternal admission to intensive care unit (P=.02), and 5-minute Apgaror=3 (P.01) were associated with duration of chorioamnionitis. By logistic analysis, only uterine atony (OR for each hour of chorioamnionitis 1.03, 95% CI 1.00-1.06), 5-minute Apgaror=3 (OR 1.09, 95% CI 1.00-1.16), and neonatal mechanical ventilation within 24 hours of birth (OR 1.07, 95% CI 1.01-1.12) were significantly associated with chorioamnionitis duration.Chorioamnionitis was associated with increased rates of morbidity after cesarean at term. The duration of chorioamnionitis, however, was not related to most measures of adverse maternal or fetal-neonatal outcome.

Placental trophoblast invasion and amniotic fluid cytokine receptor levels have been reported to vary with fetal gender. We investigated whether fetal gender affects amniotic fluid levels of the inflammatory cytokines interleukin (IL)-6 and IL-10 and the pro-angiogenesis cytokine angiogenin.Specimens from singleton gestations undergoing mid-trimester amniocentesis for genetic indications were used. Inclusion criteria were (1) outcome information available, (2) no structural or chromosomal anomaly and (3) no conditions associated with preterm delivery. Amniotic fluid IL-6, IL-10 and angiogenin levels were measured by immunoassay. Statistical analysis included the Mann-Whitney U test and Fisher's exact test with p0.05 indicating significance.A total of 74 samples were analyzed. Angiogenin levels were significantly lower in amniotic fluid samples from pregnancies with a male than with a female fetus (median (range): 22.2 (5.9-66.4) vs. 32.0 (11.4-159.2) ng/ml, p=0.007), in contrast to no differences in amniotic fluid IL-6 and IL-10 levels (p=0.4 and p=0.1, respectively). In pregnancies with male fetuses delivering preterm (37 weeks), angiogenin was also detected at lower levels (p=0.02). There were no gender differences with respect to race, nulliparity or maternal age.Angiogenin levels, but not IL-6 or IL-10 levels, are significantly lower in second-trimester amniotic fluid of women with male compared with female fetuses, including those women delivering preterm.

Previous reports identified two peptides that mimic the action of neuroprotective proteins derived from astrocytes. These peptides, NAPVSIPQ and SALLRSIPA, prevent neuronal cell death produced by electrical blockade, N-methyl-d-aspartate, and beta-amyloid peptide (25-35). In the present study, all d-amino acid peptides of NAPVSIPQ and SALLRSIPA were synthesized and compared respectively to the corresponding all l-amino acid peptides. In rat cerebral cortical test cultures cotreated with 1 microM tetrodotoxin, the d-amino acid peptides produced similar potency and efficacy for neuroprotection as that observed for their respective l-amino acid peptides. Since all these peptides tested individually exhibited attenuation of efficacy at concentrations of10 pM, combinations of these peptides were tested for possible synergies. Equimolar d-NAPVSIPQ and d-SALLRSIPA combination treatment produced potent neuroprotection (EC(50), 0.03 fM) that did not attenuate with increasing concentrations. Similarly, the combination of l-NAPVSIPQ and d-SALLRSIPA also had high potency (EC(50), 0.07 fM) without attenuation of efficacy. Combined administration of peptides was tested in a model of fetal alcohol syndrome and in a model of learning impairment: apolipoprotein E knockout mice. Intraperitoneal administration of d-NAPVSIPQ plus d-SALLRSIPA to pregnant mice (embryonic day 8) attenuated fetal demise after treatment with an acute high dose of alcohol. Furthermore, oral administration of d-NAPVSIPQ plus d-SALLRSIPA significantly increased fetal survival after maternal alcohol treatment. Apolipoprotein E knockout mice injected with d-NAPVSIPQ plus d-SALLRSIPA showed improved performance in the Morris water maze. These studies suggest therapeutic potential for the combined administration of neuroprotective peptides that can act through a mechanism independent of chiral recognition.

We evaluated a 9-amino-acid peptide, SALLRSIPA (SAL), an agonist of activity-dependent neurotrophic factor (ADNF), for its protective properties against fetal alcohol-related brain growth retardation, using an established liquid diet model of alcohol-related neurodevelopmental disorder (ARND) in C57BL/6 mice. Alcohol exposure during neurulation reduced body weight, head size, and specifically brain weight and volume. Major gross brain deficits include underdevelopment of brain areas, cortical thinning, ventricle enlargement, and restricted midline neural tissue growth leading to openings at the roof/floor plate. SALLRSIPA (SAL) treatment increased fetal body weight and restored brain weight, brain volume, and regional brain size. Furthermore, SAL restored cortical thickness, reduced the size and frequency of neural tube openings, and attenuated ventricular enlargement. The ability of SAL to antagonize alcohol-retarded brain growth and development of forebrain and midline neural tube at midgestation suggests its potential use as an antagonist against fetal alcohol- rendered microencephaly early in development.

Objective Fetal alcohol syndrome (FAS) results in stillbirth, fetal growth restriction, and mental retardation with injury attributed to oxidative stress. Our objective was to identify signal transduction pathways expressed in a model of FAS and to quantify expression of c- fos , a gene in the stress signal pathway. Study design Timed, pregnant C57Bl6/J mice were injected on E8 with saline solution or alcohol. RNA was extracted from decidua and embryo 6 and 24 hours later. Microarray analysis was used to screen gene pathways. Differential gene expression was confirmed using real-time polymerase chain reaction with results presented as the ratio of c- fos concentration to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results Differential gene expression between alcohol and control was noted for stress signal pathway genes including c- fos . Real-time polymerase chain reaction demonstrated that c- fos messenger RNA expression was greater in the alcohol than control decidua at 6 hours after injection ( P P fos expression in embryos whose mothers received alcohol versus control after 6 hours ( P = .12) or 24 hours ( P = .89). Conclusion Alcohol administration during pregnancy results in differential gene expression in the stress signal pathway, particularly in c- fos . C- fos expression in the decidua increases from 6 to 24 hours after alcohol injection, but does not change in the embryo, which may contribute to alcohol-induced damage in FAS.

Background Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. Methods We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Results Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 1...

This literature review examines whether smoking or alcohol use during pregnancy increases maternal micronutrient requirements and whether smoking or alcohol use interacts with micronutrient deficiencies to affect pregnancy outcomes. Studies suggest that vitamin C requirements increase for pregnant smokers. Studies also indicate that beta-carotene, vitamin B-12, vitamin B-6 and folate concentrations appear lower in pregnant smokers than in pregnant nonsmokers, although it is unclear whether lower serum concentrations are due to increased requirements, lower dietary or supplement intakes or other factors. Experimental animal studies suggest that iron supplementation partially ameliorates impaired fetal growth caused by cadmium, a heavy metal inhaled from cigarette smoke, but studies in humans have not substantiated cadmium's effect on fetal growth. Animal studies also suggest chronic alcohol consumption at levels of 20-50% of energy intake during pregnancy may mobilize fetal vitamin A concentration from the liver and result in increases in vitamin A in fetal organs and subsequent defects. Evidence is lacking, however, on whether zinc metabolism is altered by alcohol intake during pregnancy. Health care practitioners should consider increasing nutrient levels in pregnant women who do not meet the Recommended Dietary Allowances through their diet. Future studies that examine the nutrient levels of women exposed to cigarette smoke and alcohol should control for dietary intake. In addition, randomized controlled studies of the health impact of micronutrient supplementation in pregnant women should consider stratification by exposure to cigarette smoke and alcohol use.

This month, we focus on current research in maternal-fetal medicine. Dr. Spong discusses six recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts.

The envelope protein (gp120) of the human immunodeficiency virus produces neuronal cell death in cultures that can be prevented by co-treatment with pituitary adenylate activating peptide-38 (PACAP-38) or chemokines. To investigate the hypothesis that a functional relationship exists between these two protectants, the release of chemokines was measured in rat astrocyte cultures after PACAP-38 treatment. Chemokine analyses were performed by immunoaffinity capillary electrophoresis. Bell-shaped dose-responses for PACAP-mediated release of chemokines into the culture medium were observed with EC(50)'s of 3 x 10(15) M (RANTES: regulated upon activation normal T cell expressed and secreted), 3 x 10(-11) M (MIP-1 beta) and 10(-7)M (MIP-1 alpha). In addition, PACAP-mediated depletion of chemokines from cultured astrocytes exhibited inverted bell-shaped curves, with similar EC(50)'s to those observed for chemokine measurements of the medium. Comparative studies with structurally related peptides (vasoactive intestinal peptide [VIP] and secretin) revealed that PACAP was the most potent secretagogue for RANTES on astrocyte cultures. Gp120-mediated neuronal cell death was prevented by co-treatment with PACAP-38, although the efficacy of protection varied significantly among the gp120 isolates. A bi-model dose-response was observed with EC(50)'s of 3 x 10(-15) and 3 x 10(-11) M. Co-treatment with neutralizing antiserum to RANTES attenuated PACAP-mediated protection from toxicity associated with gp120. In contrast to previous studies with VIP and gp120 toxicity, co-treatment with anti-MIP-1 alpha did not affect PACAP-induced protection. These studies support the hypothesis that PACAP produces neuroprotection from gp120 toxicity, in part, through the release of RANTES and this mechanism is distinct from that observed with VIP.

Objective: A planned study is described which will determine whether a benefit exists for the treatment of mild carbohydrate intolerance during pregnancy. Methods: A randomized clinical trial of women with mild gestational diabetes will compare perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. Results: The primary outcome of this study will be a composite of neonatal morbidity in the treatment and control groups. Conclusions: A randomized treatment trial of mild gestational diabetes mellitus will clarify whether identification and treatment of mild gestational diabetes mellitus reduces perinatal morbidity. This information will aid in selecting appropriate thresholds for the treatment of gestational diabetes mellitus.

To assess the optimal thresholds of the lecithin/sphingomyelin (L/S) ratio and lamellar body count for the prediction of the presence of phosphatidyl glycerol (PG) in diabetic pregnant women.We accessed a database of clear amniotic fluid specimens obtained by transabdominal amniocentesis in diabetic women with singleton non-malformed fetuses. PG results were classified as 'absent' or 'present'. Receiver operating characteristic (ROC) curve analysis was constructed of different L/S ratios and lamellar body counts to identify the optimal threshold for prediction of the presence of PG. Sensitivity was defined as the rate of L/S ratio and lamellar body count above specific thresholds among cases with present PG. The false-positive rate was that of L/S ratios or lamellar body counts above specific thresholds among cases with absent PG. Statistical analysis included one-way analysis of variance with post-hoc analysis, with p0.05 considered significant.A total of 76 consecutive women were included in the analysis, 74% (n = 56) using insulin and the remainder treated by diet alone. L/S and PG results were both available in 72 women. PG was reported as 'present' in 70% (51/73) of specimens. As expected, there was a significant relationship between L/S ratios and presence of PG (area under the curve = 0.932, p0.001). An L/S ratio ofor = 3.0 represented the optimal trade-off between sensitivity (68%) and false-positive rate (6%) in the prediction of present PG. Similarly, there was a significant relationship between lamellar body count values and presence of PG (area under the curve = 0.976, p0.001). A lamellar body count ofor = 50 000 represented the optimal trade-off between sensitivity (92%) and false-positive rate (0%) in the prediction of present PG.In diabetic pregnant patients, the presence of PG in the amniotic fluid more closely corresponded to an L/S ratio ofor = 3.0 or to a lamellar body count ofor = 50,000.

This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks' gestation.This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks' gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death.A total of 1,259 women were included. The rate of delivery48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups.Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.

OBJECTIVE The objective of the article is to describe latency for patients with preterm premature membrane rupture (PPROM) between 24(0/7) and 31(6/7) weeks' gestation. STUDY DESIGN Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than six contractions per hour at enrollment who were candidates for expectant management (n = 1,377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture. RESULTS At each week of gestation, median latency between 24 and 28 weeks was similar at approximately 9 days, but it was significantly shorter with PPROM at 29, 30, and 31 weeks (p

Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time.

Objective: To describe the pregnancy course and outcome, and use of anakinra, a recombinant selective IL-1 receptor blocker, during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal onset multi-system inflammatory disease (NOMID). Methods: Women currently enrolled in natural history protocols (NCT00059748, and/or NCT00069329 under IND) who have been pregnant were included. Subjects underwent a structured, standardized interview with regards to maternal health, pregnancy and fetal outcomes. Medical records were reviewed. Results: Nine women (four with FCAS, one with MWS and four with NOMID) reported one to four pregnancies, each resulting in a total of fifteen FCAS, three MWS, and six NOMID pregnancies. Six births from FCAS mothers and three births from NOMID mothers occurred while patients were receiving anakinra. If a woman became pregnant while taking anakinra, the pre-pregnancy anakinra dose was continued. Anakinra dose was increased during one twin pregnancy. No preterm births or serious complications of pregnancy were observed. One fetus of the twin pregnancy had renal agenesis and suffered fetal demise. Genetic testing showed the deceased twin carried the same NLRP3 c.785TC, p.V262A mutation as the mother. The other twin is healthy and mutation negative. Conclusions: Anakinra was continued during pregnancy in women with CAPS and provided significant, persistent CAPS symptom relief while continuing to prevent the long-term sequelae of CAPS. Anakinra was well tolerated. Although a causal relation between anakinra and renal agenesis seems unlikely, further safety data are needed.

Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child.

Objective: Evaluation and management of patients with multiple maternal antibody isoimmunization is unclear. The presence of ≥ 1 maternal antibody may suggest a worse scenario. The objective of this study was 2-fold: first, to determine whether the presence of multiple antibodies predicts a more severe course than single antibodies and second, to determine the utility of the Queenan curves/protocol in evaluating multiple-antibody isoimmunization. Study Design: Amniotic fluid ΔOD 450 measurements were obtained from the antenatal testing logbook and confirmed by chart review. Cases were categorized by antibody type and clinical outcomes obtained by chart review. Results: Twenty-four pregnancies with isoimmunization and multiple maternal antibodies were identified; of these, 17 had 2 antibodies (anti-D and -C in 13; anti-D and -E in 1; anti-D and -Jka in 1; anti-c and -E in 1; and anti-c and -Jka in 1), and 7 had > 2 antibodies (anti-D, -C, and -E in 4; anti-D, -C, and -N in 1; anti-c, -E, and -FYA in 1; and anti-E, -K, -Fya, -S, and -C in 1). Eleven patients (46%) required at least 1 intrauterine fetal transfusion (mean initial fetal hematocrit, 15%; range, 4.9%-24%). In those not transfused, no ΔOD 450 measurements occurred in the Queenan "fetal death risk" zone. Poorest outcomes (multiple transfusions/hydrops/fetal demise) were in patients with anti-D and anti-C, with or without anti-E. The absence of anti-D was associated with no need for fetal transfusions. The overall transfusion rate was significantly higher compared with a group of 57 isoimmunization patients with only anti-D (46% vs 25%, P ≤.05). Conclusions: The presence of anti-D appears to be the most significant factor guiding the course of isoimmunization with multiple antibodies. The presence of another antibody with anti-D appears to significantly increase the need for intrauterine fetal transfusions. The Queenan protocol can successfully treat patients with multiple maternal red blood cell antibodies. (Am J Obstet Gynecol 2001;185:481-4.)

Objective: Many studies use stored amniotic fluid samples to assay cytokines and other proteins for outcome-based research; however, there is little information on the optimal methods of storage. The objective of our study was to evaluate cytokine stability in amniotic fluid stored at different temperatures both with and without a proteolytic enzyme inhibitor. Study Design: Patients undergoing midtrimester genetic amniocentesis for routine indications gave consent for the study. After the sample was centrifuged, the acellular portion of the sample was mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at 4°C, –20°C, and –80°C with and without the protease inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6, and vascular endothelial growth factor were performed simultaneously on each aliquot. Results: Thirty samples were assayed for each storage condition. Results were calculated as the percentage of its own sister aliquot stored at -80°C without aprotinin. In all samples, there was a significant relation between storage temperature and cytokine levels, with the lowest levels found at 4°C and the highest at –80°C (angiogenin, P =.004; interleukin-6, P

Background. The objective of this study is to assess whether antenatal exposure to magnesium sulfate may decrease the risk of necrotizing enterocolitis in preterm infants.Methods. We have compared the rate of magnesium sulfate exposure before birth among 23 consecutive infants diagnosed with necrotizing enterocolitis with that of 46 controls matched by gestational age at delivery and gender. Relevant obstetric and neonatal variables were compared between the two groups using chi-square and Fisher’s exact test for categorical data, and one-way analysis of variance for continuous variables, with a two-tailed p-value.Results. No significant differences were present between the two groups in mode of delivery (p=0.9), rate of Apgar score at five minutes below seven (p=0.4), prenatal exposure to indocin (p=0.5) or steroids (p=0.6), or neonatal administration of surfactant (p=0.1). Similar proportions of babies with necrotizing enterocolitis and controls were diagnosed with respiratory distress syndrome (p=0.5), i...

PROBLEM Although estrogen receptor (ER)-alpha has been well characterized, the recently identified novel ER-beta has not. In some tissues, there is overlap of the ERs, which allows for rescue in cases of deficiency; in other tissues, the ERs appear to have opposite effects. The objective of this study was to evaluate the expression of ER-beta during pregnancy. METHOD OF STUDY Pregnant mouse uteri (embryonic days 6-14, 16, 18) were studied. ER-alpha and ER-beta oligonucleotide probes were end-labeled and in situ hybridization histochemistry was performed. RESULTS ER-beta was strongly expressed in maternal ovaries; there was no other evidence of strong expression during gestation. ER-alpha was expressed in the uterus throughout gestation, with decreasing intensity as gestation progressed, and in maternal ovarian tissue. CONCLUSIONS Differential expression of the two ERs was apparent during pregnancy, with ER-alpha playing a dominant role. This may have implications for selective drug treatment targeting estrogen receptors.

Objective: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. Study Design: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery, sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. Results: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 ± 8 vs 7 ± 7; P P = .7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P > .1). Conclusions: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy. (Am J Obstet Gynecol 2000;183:940-4.)

Objective: To assess the performance of the biophysical profile (BPP) and its components within 24 hours of delivery in predicting histopathologic evidence of severe acute placental inflammation in women with premature rupture of membranes (PROM) before 32 weeks’ gestation. Methods: We examined placentas from a series of consecutive, nonanomalous, live-born, singleton infants delivered before 32 weeks’ gestation after PROM. In 166 cases, biophysical profiles (BPP) were done within 24 hours of birth. Histologic evidence of acute inflammation was assessed in the maternal (amnion) and fetal (chorionic and umbilical cord vessels) compartments, and scored on a severity scale of 0–4 by a single pathologist masked to clinical data. The presence and severity of acute inflammation was related to BPP results and its individual components. Results: The overall prevalence of severe acute inflammation, ie, a score of 3 or 4, was 59% (98 of 166). In 30 (18%) cases it was present in the amnion, in 49 (30%) cases in chorionic or umbilical cord vessels, and in 19 (11%) cases in maternal and fetal compartments. There was no association between abnormal BPP score and presence or absence of severe acute placental inflammation (48% versus 46%, P = .7). Our study had a 90% power to detect a 0.26 difference between them. When rates of abnormal BPP scores were compared in cases with different degrees of acute inflammation in the maternal, fetal, or both compartments, no association was found. When the individual components of the BPP were analyzed in relation to site and severity of acute inflammation, no association was detected. Conclusion: We did not find evidence of a dose-response relationship between acute placental inflammation and BPP score or its individual components in cases of PROM with infants delivered before 32 weeks. Mediators other than infection might affect BPP in preterm PROM.

The risk of neonatal adverse respiratory outcomes is higher among infants delivered before 39 weeks' gestation than after 39 weeks', and among infants delivered by prelabor cesarean compared to those delivered vaginally. Thus, elective cesarean section before 39 weeks is discouraged in the absence of fetal lung maturity. This prospective study compared neonatal outcomes among infants delivered by elective cesarean delivery at 37, 38, and 39 weeks' gestation. The study cohort was pregnant women with viable singleton pregnancies undergoing repeat cesarean delivery at 19 academic medical centers. The women were delivered before onset of labor and had no medical or obstetrical indications for delivery before 39 weeks. The primary study outcome was a composite of any adverse neonatal outcome or death. Adverse outcomes included respiratory complications, admission to the neonatal intensive care unit (ICU), newborn sepsis, treated hypoglycemia, and hospitalization for 5 days or longer. Logistic regression models were used to calculate adjusted odds ratios for the association between neonatal outcomes and gestational age at birth relative to 39 completed weeks. Among the study cohort, 13,258 women underwent elective repeat cesarean section at term. Of these, 49.1% had the procedure at 39 weeks', and 35.8% had the procedure before 39 completed weeks' gestation (6.3% at 37 weeks and 29.5% at 38 weeks). With increasing gestational age at birth, the risk of the primary outcome decreased. Unadjusted analysis showed that the incidence of the primary outcome was 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks (P for trend

Vasoactive intestinal peptide (VIP) is an important growth regulator of the embryonic day (E)9-E11 mouse. In comparably aged rat embryos, VIP messenger RNA (mRNA) is not detectable; however, peak concentrations of VIP in maternal rat serum indicate a nonembryonic source. In the current study, mouse maternal and embryonic tissues were examined from E6-E12. Although RT-PCR revealed VIP mRNA in E6-E7 conceptuses, by E8 (when extraembryonic tissues could be separated from the embryo), VIP mRNA was detected only in the decidua/trophoblast. Decidual/trophoblastic VIP mRNA decreased until E10, after which it was not detectable. VIP mRNA was not apparent in the embryo until E11-E12. At E9, VIP immunoreactivity was localized to abundant, diffuse cells in the decidua basalis, which were also immunoreactive for T cell markers. VIP binding sites were dense in the decidua/trophoblast at E6, but gradually decreased until E10, after which they were not apparent. VIP binding sites were detected in embryonic neuroepithelium by E9. The transient presence of VIP binding sites and mRNA in the decidua/trophoblast correlate with the critical period of VIP growth regulation, when VIP mRNA is absent in the embryo. These findings suggest that maternal lymphocytes are the source of VIP's regulating early postimplantation embryonic growth.

In insulin dependent diabetic (IDDM) gestations, fetal pulmonary maturity is delayed in the presence of suboptimal glycemic control. Serum glycosylated hemoglobin (HbA1c) provides a means of assessing glycemic control. We evaluated maternal HbA1 c in IDDM pregnancies at term undergoing amniocentesis for lung maturity to establish if euglycemia is associated with improved fetal lung maturity. Between July 1995 and June 1996, IDDM patients undergoing amniocentesis at term for lung maturity studies had a maternal serum sample analyzed for HbA1c. Fetal lung maturity was established by the presence of phosphatidylglycerol (PG) in amniotic fluid. HbA1c was considered elevated if >6.2%. Mean HbA1 c level was 6.8% (range 4.4 to 9.9%). PG was present in 54% of patients with elevated HbA1c (7/13) versus 80% of those with normal HbA1 c (8/10) (p = 0.4). Although birth weight was higher in the elevated than in the normal HbA1c group (3770 ± 514 vs. 3215 ± 610 g), no association was present between birth weight and HbA1 c level (r = 0.22, p = 0.4). The rate of a mature pulmonic profile at term is not significantly different between IDDM women with good or poor glycemic control. HbA1 c values should not be used to predict the presence or absence of amniotic fluid PG.

Objective: To measure angiogenin, a potent inducer of neovascularization and interleukin-6, as an indicator of acute inflammation, in second-trimester amniotic fluid of patients with elevated maternal serum hCG. Methods: In this case-control study, 20 patients with elevated maternal serum hCG (at least 2.0 multiples of median) at triple screen were matched 2:1 with controls on the basis of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation 4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%, and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6 values were normalized by using natural log transformation for statistical analysis. Statistical analysis included analysis of variance and stepwise regression, with P Results: After correcting (by multivariate regression) for gestational age at sampling and nulliparity, amniotic fluid angiogenin levels were significantly lower in the study subjects than in controls (26% ± 11% lower, P = .004), whereas the interleukin-6 levels did not change significantly (34% ± 40% lower, P = .3). Conclusion: Amniotic fluid angiogenin levels are significantly lower in patients with elevated maternal serum hCG at triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do not differ significantly.