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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.06.046 Byline: Robin Roberson (a), Jade E. Woodard (a), Laura Toso (a), Daniel Abebe (a), Sarah H. Poggi (a)(b), Catherine Y. Spong (a) Abstract: In humans, cerebral palsy (CP) may originate from inflammation during the second and third trimesters of gestation when preoligodendrocytes (Pre-OL) are most vulnerable to an inflammatory insult. We studied a postnatal CP model to evaluate injury that would correlate with presence of Pre-OL in human pregnancy. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (b) Department of Obstetrics and Gynecology, INOVA Hospital, Alexandria, VA Article History: Received 8 March 2006; Revised 5 May 2006; Accepted 9 June 2006 Article Note: (footnote) Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development and NIAAA. Presented at the 26th Annual Meeting of the Society for Maternal Fetal Medicine, January 30-February 4, 2006, Miami, FL. Reprints not available from the authors.

A study is conducted to determine whether unscheduled cesarean deliveries have complication rates that vary by shift of occurrence, and morbidities are evaluated by delivery shift hypothesizing that such complications would be more frequent during the night shift (11 PM-7 AM) due to sleep deprivation of staff. Results indicate that though neonatal intensive care unit admissions increase at night, maternal and neonatal complications of cesarean delivery do not increase with delivery during the night shift.

The rate of successful trial of labor after previous cesarean delivery for dystocia is assessed in a large cohort based on the relative birth weights of the two pregnancies. It is likely that increased fetal size relative to previous birth weight plays a significant role in the outcome of a subsequent trial of labor for patients with previous cesarean delivery for dystocia, reducing chances of vaginal delivery.

The success rates of vaginal birth after cesarean (VBAC) delivery, uterine rupture and major maternal/perinatal outcomes are compared between women, with previous cesarean deliveries undergoing trial of labor (TOL) with preterm and term pregnancies, and also maternal and neonatal morbidities in women with preterm pregnancies undergoing a TOL versus repeat cesarean delivery without labor (RCD). The likelihood of VBAC success after TOL in preterm pregnancies is comparable to term gestations, with a lower risk of uterine rupture, and perinatal outcomes are similar with preterm TOL and RCD.

A postnatal inflammatory rat model for cerebral palsy (CP) is studied to evaluate white matter damage (WMD) in the brain induced by a chronic stimulus that would correlate with the presence of Pre-OL (preoligodendrocytes) in human pregnancy. It is found that targeting Pre-OL maturation does not result in a discernable CP phenotype in the rat model.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.01.098 Byline: Laura Toso (a)(b), Robin Roberson (a), Jade Woodard (a), Daniel Abebe (a), Catherine Y. Spong (a) Abstract: In a model for fetal alcohol syndrome (FAS), we have previously found an alteration in NMDA receptors suggesting mediation, at least in part, of alcohol-related learning deficit. NMDA and GABA receptors interact in a multisynaptic circuit for the regulation of the inhibitory tone through the CNS. The GABA receptor subunit GABA.sub.A[alpha].sub.5 is involved in learning and is developmentally regulated, as it is excitatory in the perinatal brain and inhibitory in the adult. We were interested to evaluate alcohol's effect on GABA.sub.A[alpha].sub.5 expression to further understand alcohol-induced learning dysfunction. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development (b) National Institue of Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD Article History: Received 7 December 2005; Revised 20 January 2006; Accepted 24 January 2006 Article Note: (footnote) Supported by the Division of Intramural Research of National Institute of Child Health and Human Development.

The alcohol's effect on [gamma]- aminobutyric-acid type A [[alpha].sub.5] (GAB[A.sub.A][[alpha].sub.5]) is evaluated in order to understand alcohol-induced learning dysfunction. Prenatal alcohol exposure alters developmental GAB[A.sub.A][[alpha].sub.5] expression, suggesting that alcohol-induced learning impairment is likely the result of alterations of both N-Methyl-D-A-Asparate and GABA expression and function.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.12.023 Byline: Laura Toso (a)(b), Melanie Endres (a), Joy Vink (a), Daniel T. Abebe (a), Douglas E. Brenneman (a), Catherine Y. Spong (a) Abstract: Previous work has demonstrated that two synthetic peptides can prevent prenatal alcohol-induced damage as assessed by prevention of learning abnormalities in adult offspring as well as improve outcome from traumatic brain damage. The current studies were undertaken to evaluate whether these peptides could enhance performance in a learning and memory paradigm when administered either prenatally or to aged mice. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Development (b) National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD Article History: Received 14 November 2005; Accepted 15 December 2005 Article Note: (footnote) Presented at the Twenty-Fourth Annual Meeting of the American Gynecological and Obstetrical Society, September 29 to October 1, 2005, Victoria, British Columbia, Canada. Reprints not available from the authors.

A study was undertaken to determine whether women with recurrent spontaneous preterm births (rSPBs) having different clinical characteristics or systemic markers than those with isolated preterm (iSPBs) or recurrent term births (rTBs), when assessed remote from delivery. Women with rSPBs are leaner, contract more, have shorter cervixes, and have more advanced Bishop scores than women with iSPBs or rTBs.

A study is conducted to evaluate whether two synthetic peptides could enhance performance in a learning and memory paradigm when administered either prenatally or to aged mice. Findings suggest potential therapeutic interventions during critical developmental period and in aged animals.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.01.003 Byline: Laura Toso (a)(b), Sarah H. Poggi (a)(c), Robin Roberson (a), Jade Woodard (a), Jane Park (a), Daniel Abebe (a), Catherine Y. Spong (a) Abstract: Vasoactive intestinal peptide (VIP)-related peptides prevented the learning deficit in the offspring in a model for fetal alcohol syndrome. We evaluated whether the mechanism of the peptide protection included NR2B, NR2A, and GABA.sub.A[alpha].sub.5. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child and Human Development (b) National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD (c) Department of Obstetrics and Gynecology, INOVA Hospital, Alexandria, VA Article History: Received 7 December 2005; Revised 5 January 2006; Accepted 7 January 2006 Article Note: (footnote) Presented at the 26th Annual Meeting of the Society for Maternal Fetal Medicine, Miami, FL, January 30-February 4, 2006. This work was supported by the Division of Intramural Research of National Institute of Child and Human Development.

A study was conducted to evaluate whether the mechanism of the peptide protection included NR2B, NR2A, and GABA(sub A)alpha(sub 5). The result showed that vasoactive intestinal peptide (VIP)-related peptides prevented alcohol-induced changes in NR2B, NR2A, and GABA(sub A)alpha(sub 5), which explains, at least in part, the peptides' prevention of alcohol-induced learning deficits.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.02.105 Byline: Laura Toso (a)(b), Sarah H. Poggi (a)(c), Daniel Abebe (a), Robin Roberson (a), Veronica Dunlap (a), Jane Park (a), Catherine Y. Spong (a)(c) Abstract: Alcohol-related neurodevelopmental disorders are contributors to long-term learning disabilities. By using a model for fetal alcohol syndrome, we have shown that prenatal alcohol exposure results in adult learning deficits of unknown mechanisms. In the developing hippocampus, the N-methyl-D-aspartate (NMDA) receptor subunit NR2B triggers long-term potentiation, fundamental to learning and memory; this is supplemented by the less plastic NR2A subunit in the adult. To understand the mechanism of learning deficits in FAS, we evaluated NR2B and NR2A expression in embryonic and adult mice. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, NICHD (b) National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD (c) Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC Article History: Received 16 November 2004; Accepted 18 February 2005 Article Note: (footnote) Supported by the DIR of National Institutes of Child Health and Human Development.

A study evaluates whether the expression of N-methyl-D-aspartate receptors (NMDARs), NR2A and NR2B subunits is affected by prenatal alcohol exposure during development and whether the alcohol-induced learning deficits are due to a change in these subunits in the composition of the NMDAR. Results suggest that prenatal alcohol exposure during development induces NR2B expression deregulation in the embryos that persists until adulthood, when a relative increase in the less modifiable subunit NR2A occurs.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2005.02.101 Byline: Joy Vink, Jonathan Auth, Daniel T. Abebe, Douglas E. Brenneman, Catherine Y. Spong Abstract: Previously, the novel peptides NAPVSIPQ and SALLRSIPA were shown to prevent alcohol-induced fetal death and growth abnormalities in a mouse model of fetal alcohol syndrome. This study evaluated whether these peptides could prevent long-term alcohol-induced learning abnormalities. In addition, because specific cytokines are known to effect long-term potentiation, a model of learning at the molecular level, we studied the effect of these novel peptides on tumor necrosis factor-[alpha], interleukin-6, and interferon-[gamma] levels. Author Affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD Article History: Received 11 October 2004; Revised 2 January 2005; Accepted 17 February 2005

A study is conducted to evaluate whether novel peptides like NAPVSIPQ and SALLRSIPA could prevent long-term alcohol-induced learning abnormalities and also examine the effect of these novel peptides on tumor necrosis factor-alpha, interleukin-6 and interferon-gamma levels. Results show that alcohol treatment increased tumor necrosis factor-alpha levels versus control levels while NAPVSIPQ and SALLRSIPA pretreatment prevented this increase, with levels similar to control.

The success rates and risks in women with a twin pregnancy who attempt a trial of labor after cesarean delivery are identified. A trial of labor with twins after previous cesarean delivery does not appear to increase maternal morbidity.

The developmental, behavioral and motor outcomes in a lipopolysaccharide (LPS) model for periventicular leukomalacia (PVL) are evaluated for examining the association between histologic end point and cerebral palsy (CP) phenotype. No significant phenotypic differences consistent with the motor and cognitive damage sequelae of CP were demonstrated.

The developmental, behavioral and motor outcomes in a lipopolysaccharide (LPS) model for periventicular leukomalacia (PVL) are evaluated for examining the association between histologic end point and cerebral palsy (CP) phenotype. No significant phenotypic differences consistent with the motor and cognitive damage sequelae of CP were demonstrated.

Evaluating this concept in a prospective manner by using a force-sensing system that quantitatively assesses clinical-applied force applied to multiparous patients during delivery. In this study population, epidural anaesthesia is associated with increased clinician force used to effect delivery, but this force is not associated with an increase in perineal trauma.

The objective of this study is to evaluate whether the delivery force in multiparous patients is reduced with the prophylactic McRoberts maneuver as compared with the lithotomy position under actual delivery conditions with the use of a force-measuring glove. In general the McRoberts' maneuver is considered safe, but there are anecdotal reports of maternal injuries that are associated with its extended use, so it may be wise to reserve the maneuver for clinical diagnosis of shoulder dystocia only.

The relationship between chorioamnionitis and its duration to adverse maternal, fetal and neonatal outcomes is examined. Chorioamnionitis is reported to increasingly cause maternal and neonatal morbidity after cesarean at term.

The level of activity-dependent neuroprotective protein (ADNP) in fetal tissues is greatest early in the pregnancy and decreases thereafter until birth, according to a study of mice. This protein protects the developing nervous system and part of the protein has been shown to protect the fetus from fetal alcohol syndrome.

Severe meconium aspiration syndrome may not be caused by aspiration of meconium. Instead, it may have some other cause such as asphyxia or infection and the finding of meconium in the lungs is purely coincidental.

Fetuses whose mothers have more than one antibody against a fetal antigen are more likely to require one or more blood transfusions. Antibodies against the Rh(sub O)D antigen are most common, but other fetal antigens include the C, c, E, e, Kell, Duffy, and Kidd antigens.

Cytokines in amniotic fluid samples may be destroyed if the samples are stored too long. This would make frozen amniotic fluid samples useless for research purposes unless some way is found to preserve the cytokines. Cytokines are immune system proteins.

Magnesium sulfate could affect a pregnant woman's mental processes, which could make it difficult to obtain informed consent for invasive procedures such as fetal blood sampling. Magnesium sulfate is often given to pregnant women in premature labor. It does not seem to affect long-term memory, however.

Some components of amniotic fluid may not be stable for long periods of time when the fluid is frozen. Samples of amniotic fluid are often frozen for use in later research. Researchers measured interleukin-6 and angiogenin in the same amniotic fluid sample from 30 pregnant women on two occasions one year apart. Interleukin-6 and angiogenin are both natural components of amniotic fluid. The level of both was significantly lower in 1996 than it had been in 1995. Storage time must be taken into account when these types of samples are thawed and analyzed.

Byline: Catherine Y. Spong, Alessandro Ghidini, Miguel Ossandon, Charles N. Walker, John C. Pezzullo Keywords: Cytokines; prolonged freezing; stability Abstract: OBJECTIVE: To determine the stability of cytokines in frozen stored amniotic fluid samples, we measured angiogenin, a potent inducer of neovascularization and interleukin-6, an inflammatory cytokine, in the same sample of midtrimester amniotic fluid 1 year apart. STUDY DESIGN: In this study paired aliquots of amniotic fluid kept at -70[degrees] C were immunoassayed for angiogenin and interleukin-6 at two different time periods 1 year apart. Inclusion criteria were (1) samples with clearly identifiable numbers, (2) no evidence of breaks in sealing of samples, and (3) singleton gestation. Amniotic fluid was immunoassayed for angiogenin and interleukin-6 in July 1995 and 1996. Angiogenin sensitivities were 0.078 and 0.026 ng/ml, interassay coefficients of variation were 3.8% and 4.6%, and intraassay coefficients of variation were 2.7% and 2.9%, respectively, in 1995 and 1996. Interleukin-6 sensitivities were 1.74 and 2.37 pg/ml, interassay coefficients of variation were 8.9% and 2.6%, and intraassay coefficients of variation were 3.5% and 1.9%, respectively, in 1995 and 1996. Statistical analysis included paired t test, Wilcoxon signed-rank test, and regression with p < 0.05 significant. Angiogenin and interleukin-6 values were normalized with natural log transformation for statistical analysis. RESULTS: Paired amniotic fluid samples from 30 patients were immunoassayed from 1993 to 1995. The values of angiogenin were significantly lower in the 1996 assay compared with the 1995 assay (median 12.4 [range 5.6 to 61.3] vs 26.7 [range 13.6 to 159.2] ng/ml, p < 0.001). A significant correlation was found between the change in angiogenin levels and the year of the sample, with older samples having the greatest change in values (r = 0.5, p = 0.008). The values of interleukin-6 were significantly lower in the 1996 assay compared with the 1995 assay (median 230.8 [range 40.9 to 3711.3] vs 289.2 [range 53.7 to 19100.0] pg/ml, p < 0.001). CONCLUSIONS: Angiogenin and interleukin-6 values in amniotic fluid appear to decrease with time despite optimal freezing conditions. The year of sampling and length of storage should be taken into consideration when evaluating amniotic fluid cytokine levels from stored samples. (Am J Obstet Gynecol 1998;178:783-6.) Author Affiliation: Bethesda, Maryland, and Washington, D.C Article History: Received 18 September 1997; Revised 14 November 1997; Accepted 11 December 1997 Article Note: (footnote) [star] From the Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health,a Departments of Obstetrics and Gynecology,b and Biomathematics and Biostatistics,c Georgetown University Medical Center., [star][star] The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government., a Reprint requests: Catherine Y. Spong, MD, Laboratory of Developmental Neurobiology, NICHD, NIH, Building 49, Room 5A-38, 9000 Rockville Pike, Bethesda, MD 20892., aa 6/6/88219

Byline: Catherine Y. Spong, Alessandro Ghidini, David M. Sherer, John C. Pezzullo, Miguel Ossandon, Gary S. Eglinton Keywords: preterm delivery; angiogenin; amniotic fluid Abstract: OBJECTIVE: Neovascularization is a response of tissue to ischemic damage. Placental ischemia is thought to underlie a significant portion of preterm deliveries. Our objective was to evaluate whether angiogenin, a potent inducer of neovascularization, is increased in midtrimester amniotic fluid of patients destined to be delivered preterm. STUDY DESIGN: We designed a case-control study of singleton gestations undergoing midtrimester amniocentesis for standard genetic indications. Inclusion criteria were (1) pregnancy outcome information available, (2) gestational age at amniocentesis 15 to 20 weeks, (3) no evidence of fetal structural or chromosomal anomalies, and (4) absence of conditions associated with preterm delivery. Amniotic fluid angiogenin levels were measured by immunoassay and normalized by natural log transformation for statistical analysis. RESULTS: Eleven patients with preterm deliveries were matched with 33 controls. Amniotic fluid angiogenin levels were significantly higher in patients with preterm deliveries compared with controls (median 30.1 ng/ml [range 13.6 to 71.0 ng/ml] vs 17.8 ng/ml [7.8 to 43.3 ng/ml], p = 0.002). Demographic data were not significantly different. The association between angiogenin levels and preterm delivery persisted after small-for-gestational-age neonates were excluded (p = 0.02). Receiver-operator characteristic curve analysis showed that an angiogenin level of 31.0 ng/ml was the optimal cutoff point for prediction of preterm delivery (sensitivity 45.5%, specificity 91.0%, p = 0.03, odds ratio 6.0). CONCLUSIONS: Midtrimester amniotic fluid angiogenin levels are elevated in patients with preterm delivery. This supports the theory that preexisting intrauterine ischemia and inflammation are important risk factors for preterm delivery and may be already present in the early midtrimester. (Am J Obstet Gynecol 1997;176:415-8.) Author Affiliation: Washington, D.C Article History: Received 15 July 1996; Revised 3 September 1996; Accepted 10 October 1996 Article Note: (footnote) [star] From the Perinatal Research Branch, National Institute of Child Health and Human Development,a and the Perinatal Research Facility, Department of Obstetrics and Gynecology, Georgetown University Medical Center.b , [star][star] Supported in part with federal funds from the National Institute of Child Health and Human Development, Perinatology Research Branch, National Institutes of Health, under contract No. NO1-HD-3-3198., a The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government., aa Reprints not available from the authors., acents 6/1/78529

A marker for preterm delivery may be evident in midtrimester amniotic fluid. Researchers evaluated amniotic fluid obtained through midtrimester amniocentesis for levels of angiogenin, a substance that promotes development of new blood vessels. Angiogenin levels were much higher among the 11 women with spontaneous preterm deliveries compared to the levels of 33 women with term deliveries. The presence of angiogenin may indicate that the placenta supplies an insufficient amount of blood, since the body's response to lack of blood is to create new blood vessels.

The amount of amniotic fluid present prior to amnioinfusion during labor may predict the success of amnioinfusion at relieving fetal distress. During amnioinfusion, saline is infused into the uterus via a vaginal catheter. The intent is to restore amniotic fluid volume, thus relieving umbilical cord compression. Of 85 women having amnioinfusion for abnormal fetal heart rate, the probability of success rose as the amount of amniotic fluid prior to infusion fell. More women with adequate amniotic fluid had an umbilical cord wrapped around the neck or a true knot, which are other causes of compression-related fetal distress.

Byline: Catherine Y. Spong, Frances McKindsey, Michael G. Ross Abstract: Objective: Our purpose was to determine whether intrapartum amniotic fluid index before amnioinfusion can be used to predict response to therapeutic amnioinfusion. Study Design: Intrapartum patients (n=85) with repetitive variable decelerations in fetal heart rate that necessitated amnioinfusion (10 ml/min for 60 minutes) underwent determination of amniotic fluid index before and after bolus amnioinfusion. The fetal heart tracing was scored (scorer blinded to amniotic fluid index values) for number and characteristics of variable decelerations before and 1 hour after initiation of amnioinfusion. The amnioinfusion was considered successful if it resulted in a decrease of [greater than or equal to]50% in total number of variable decelerations or a decrease of [greater than or equal to]50% in the rate of atypical or severe variable decelerations after administration of the bolus. Spontaneous vaginal births before completion of administration of the bolus (n=18) were excluded from analysis. The probability of success of amnioinfusion in relation to amniotic fluid index was analyzed with the I.sup.2 test for progressive sequence. Results: The mean amniotic fluid index before amnioinfusion was 6.2[+ or -]3.3 cm. An amniotic fluid index of [less than or equal to]5 cm was present in 40% of patients (27/67), and an amniotic fluid index of [less than or equal to]8 cm was present in 72% of patients (48/67). The probability of success of amnioinfusion decreased with increasing amniotic fluid index before amnioinfusion (76% [16/21] when initial amniotic fluid index was 0 to 4 cm, 63% [17/27] when initial amniotic fluid index was 4 to 8 cm, 44% [7/16] when initial amniotic fluid index was 8 to 12 cm, and 33% [1/3] when initial amniotic fluid index was >12 cm, p=0.03). The incidence of nuchal cords or true umbilical cord knots increased in relation to amniotic fluid index before amnioinfusion. Conclusions: Amniotic fluid index before amnioinfusion can be used to predict the success of amnioinfusion for relief of variable decelerations in fetal heart rate. Failure of amnioinfusion at a high amniotic fluid index before amnioinfusion may be explained by the increased prevalence of nuchal cords or true knots in the umbilical cord. Author Affiliation: Division of Maternal-Fetal-Medicine, Department of Obstetrics and Gynecology, Harbor-University of California, Los Angeles Medical Center Torrance, California USA Article Note: (footnote) * Technical support of the perinatal clinical research nurses was funded in part by GCRC grant MO1-RR00425, National Center for Research Resources, National Institutes of Health., ** Presented at the Sixteenth Annual Meeting of the Society of Perinatal Obstetricians, Kamuela, Hawaii, February 4-10, 1996.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.07.004 Byline: Joy Y. Vink (a), Sarah H. Poggi (b), Alessandro Ghidini (b), Catherine Y. Spong (b) Abstract: This study was undertaken to evaluate if the previously demonstrated relationship between macrosomia (>4000 g) and polyhydramnios (>25 cm) is linear across birth weights (BW) in diabetic patients with poor glycemic control. Author Affiliation: (a) Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC (b) Perinatal Diagnostic Center, Inova Alexandria Hospital, Alexandria, VA Article History: Received 8 March 2006; Revised 4 July 2006; Accepted 10 July 2006 Article Note: (footnote) Presented at the Twenty-Sixth Annual Meeting of the Society for Maternal Fetal Medicine, Miami, FL, January 30-February 4, 2006.

Patients undergoing amniocentesis is analyzed to evaluate if the previously demonstrated relationship between macrosomia and polyhydramnios is linear across birth weights in diabetic patients with poor glycemic control. The results have shown that the previously noted relationship between elevated amniotic fluid index (AFI) and birth weights (BW) centiles in the general patient population is linear in diabetic patients with poor glycemic control.

Elevated alpha-fetoprotein (AFP) levels in maternal blood may be reflected by elevated levels of angiogenin in the amniotic fluid, and could be associated with insufficient circulation in the placenta. Angiogenin promotes growth of blood vessels. Angiogenin was significantly elevated in nine patients with high AFP levels, compared to 18 patients with normal AFP values. Poor pregnancy outcomes and preterm delivery were strongly associated with these elevated levels. Excess angiogenin may reflect an attempt to repair placental circulatory damage resulting in fetal oxygen deprivation.

Byline: Catherine Y. Spong, Alessandro Ghidini, Charles N. Walker, Miguel Ossandon, John C. Pezzullo Keywords: Elevated maternal serum [alpha]-fetoprotein; angiogenin; fetoplacental ischemia Abstract: Objective: Elevation of maternal serum [alpha]-fetoprotein in the second trimester is associated with poor pregnancy outcome, including fetal death, preterm delivery, and fetal growth restriction. We hypothesized that placental ischemia may be the common underlying pathogenesis of these outcomes. Thus we tested angiogenin, a potent inducer of neovascularization, in midtrimester amniotic fluid of patients with elevated maternal serum [alpha]-fetoprotein values to determine whether [alpha]-fetoprotein elevation is due to ischemia with subsequent stimulation of angiogenesis. Study Design: In this case-control study, patients with elevated maternal serum [alpha]-fetoprotein levels ([greater than or equal to]2.0 multiples of the median, n = 9) at triple screen were matched with two controls (n = 18) on the basis of year of amniocentesis and maternal age, race, and parity. The median elevation of maternal serum [alpha]-fetoprotein in the study population was 4.01 multiples of the median (range 2.65 to 7.24 multiples of the median). Inclusion criteria were (1) singleton gestation, (2) no evidence of fetal structural or chromosomal anomalies, and (3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin (Quantikine, R&D Systems; sensitivity 0.026 ng/ml, interassay and intraassay coefficients of variation 4.6% and 2.9%, respectively). Statistical analysis included one-way analysis of variance and regression with p < 0.05 significant. Angiogenin and maternal serum [alpha]-fetoprotein values were normalized with use of natural log transformation for statistical analysis. Results: Angiogenin values were significantly elevated in patients with high maternal serum [alpha]-fetoprotein levels (median 31.1 [range 9.2 to 54.6] vs 17.1 [range 9.0 to 29.2] ng/ml, p = 0.02). Mean gestational age at sampling, maternal age, and year of amniocentesis were not significantly different between the study and control groups (each p > 0.05). As anticipated, there was a significant increase in preterm deliveries and small-for-gestational-age neonates in the patients with elevated maternal serum [alpha]-fetoprotein levels (each p < 0.01). Conclusions: Midtrimester amniotic fluid angiogenin levels are significantly elevated in patients with elevated midtrimester maternal serum [alpha]-fetoprotein levels. Because angiogenin is a known marker of tissue ischemia, resulting in neovascularization, we hypothesize that elevation of maternal serum [alpha]-fetoprotein levels at triple screen is due to placental ischemia. Author Affiliation: Bethesda, Maryland, and Washington, D.C Article Note: (footnote) [star] From the Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health,a and the Departments of Obstetrics and Gynecology and Biomathematics and Biostatistics, Georgetown University Medical Center.b , [star][star] Supported in part with funds from the Dougherty Foundation., a The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government., aa Reprints not available from the authors., acents 6/6/84381

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2010.03.050 Byline: Maddalena Incerti (a), Joy Vink (a)(b), Robin Roberson (a), Ines Benassou (a), Daniel Abebe (a), Catherine Y. Spong (a) Keywords: brain-derived neurotrophic factor; fetal alcohol syndrome; mouse; NAPVSIPQ; SALLRSIPA Abstract: Our objective was to evaluate whether brain-derived neurotrophic factor (BDNF) expression is affected by prenatal alcohol exposure and whether the neuroprotective effects of the vasoactive intestinal peptide (VIP)-related peptides, NAPVSIPQ (NAP) and SALLRSIPA (SAL), are mediated through BDNF. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD (b) Division of Maternal-Fetal Medicine, Columbia University Medical Center, New York, NY Article Note: (footnote) Cite this article as: Incerti M, Vink J, Roberson R, et al. Prevention of the alcohol-induced changes in brain-derived neurotrophic factor expression using neuroprotective peptides in a model of fetal alcohol syndrome. Am J Obstet Gynecol 2010;202:457.e1-4. , The racing flag logo above indicates that this article was rushed to press for the benefit of the scientific community., Reprints not available from the authors., This study was supported in part by the Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health., C.Y.S. is named on patent applications for the peptides NAP and SAL.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2009.01.052 Byline: Joy Vink (a)(c), Maddelena Incerti (a), Laura Toso (b), Robin Roberson (a), Daniel Abebe (a), Catherine Y. Spong (a) Keywords: Down syndrome; [gamma]-aminobutyric acid; learning; N-methyl-D-aspartic acid; NAPVSIPQ; SALLRSIPA; Ts65Dn Abstract: Down syndrome (DS) affects 1/800 infants. Prenatal NAPVSIPQ (NAP) and SALLRSIPA (SAL) (NAP+SAL) prevent developmental delay in Ts65Dn mice, a mouse model of DS. We investigated whether this finding involves N-methyl-D-aspartic acid and [gamma]-aminobutyric acid (GABA) receptor subunits. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (b) Department of Obstetrics and Gynecology, George Washington University, Washington, DC (c) Department of Obstetrics and Gynecology, Georgetown University Hospital, Washington, DC Article History: Received 24 November 2008; Revised 20 January 2009; Accepted 29 January 2009 Article Note: (footnote) This research was supported by the Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health., Cite this article as: Vink J, Incerti M, Toso L, et al. Prenatal NAP+SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and [gamma]-aminobutyric acid receptors. Am J Obstet Gynecol 2009;200:524.e1-524.e4.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2008.08.054 Byline: Robin Roberson (a), Irene Cameroni (b), Laura Toso (a), Daniel Abebe (a), Stephanie Bissel (a), Catherine Y. Spong (a) Keywords: apoptosis; fetal alcohol syndrome; hippocampus; mouse; phosphorylated cyclic adenosine monophosphate response element of binding protein Abstract: Fetal alcohol syndrome (FAS) is the leading cause of a spectrum of preventable nongenetic learning and behavioral disorders. In adult (FAS) mice, we measured phosphorylated cyclic adenosine monophosphate response element of binding protein (pCREB) staining in hippocampal subregions to evaluate a possible mechanism underlying FAS learning deficits. Author Affiliation: (a) Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (b) Department of Obstetrics and Gynecology, University of Milano-Bicocca, Monza, Milan, Italy Article History: Received 18 April 2008; Revised 18 July 2008; Accepted 30 August 2008 Article Note: (footnote) Cite this article as: Roberson R, Cameroni I, Toso L, et al. Alterations in phosphorylated cyclic adenosine monophosphate response element of binding protein activity: a pathway for fetal alcohol syndrome-related neurotoxicity. Am J Obstet Gynecol 2009;200:193.e1-193.e5. , This study was supported in part by the Division of Intramural Research, National Institute of Child Health and Human Development, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2008.01.033 Byline: Robin Roberson, Laura Toso, Daniel Abebe, Catherine Y. Spong Keywords: Down syndrome; KIF17; NR2B; synaptic plasticity; Ts65Dn Abstract: Down syndrome (DS), a major cause of mental retardation, affects 1 of 800 newborns. Mouse models for Down syndrome have been studied and found to have developmental and learning deficits, including the Ts65Dn (DS) mouse model. N-methyl-d-aspartate receptor NR2B subunit enhances synaptic plasticity. The up-regulation of KIF17, a motor protein that transports NR2B to the synaptic region parallels up-regulation of synaptic NR2B. Down regulation of KIF17 reflects up-regulation of less plastic NR2A subunit. We evaluated NR2B, NR2A, and KIF17 in Ts65Dn and control mice. Author Affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD. Article History: Received 30 November 2007; Revised 3 January 2008; Accepted 19 January 2008 Article Note: (footnote) Cite this article as: Roberson R, Toso L, Abebe D, et al. Altered expression of KIF17, a kinesin motor protein associated with NR2B trafficking, may mediate learning deficits in a Down syndrome mouse model. Am J Obstet Gynecol 2008;198:313.e1-313.e4. This study was sponsored by the Division of Intramural Research, National Institute of Child Health and Human Development, National Institutes of Health.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.05.049 Byline: Laura Toso, Andrea Johnson, Stephanie Bissell, Robin Roberson, Daniel Abebe, Catherine Y. Spong Keywords: activity-dependent neurotrophic factor (ADNF); activity-dependent neuroprotective protein (ADNP); gamma-aminobutyric acid (GABA); learning; N-methyl-d-aspartate (NMDA) Abstract: The administration of neurotrophic peptides NAPVSIPQ (NAP) + SALLRSIPA (SAL) to aged mice resulted in significant learning enhancement. N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) receptors are fundamental for learning because they are the major modulators of the long-term potentiation, the electrophysiologic mechanism for learning. Also, these receptors have been shown to be involved in NAP + SAL prevention of learning deficit in a mouse model for fetal alcohol syndrome, when administered prenatally during development. Our objective was to test whether NMDA and GABA receptors contribute to the learning enhancement that is induced by the peptides after adult administration. Author Affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD Article History: Received 13 March 2007; Revised 24 April 2007; Accepted 31 May 2007 Article Note: (footnote) Supported by the Intramural Research Program of the National Institute of Child Health and Human Development and the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD., Cite this article as: Toso L, Johnson A, Bissell S, Roberson R, Abebe D, Spong CY. Understanding the mechanism of learning enhancement: NMDA and GABA receptor expression. Am J Obstet Gynecol 2007;197:267.e1-267.e4.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.01.015 Byline: Laura Toso, Robin Roberson, Daniel Abebe, Catherine Y. Spong Keywords: fetal alcohol syndrome; [gamma]-aminobutyric acid A (GABA); N-methyl-D-aspartate (NMDA); mouse; learning Abstract: Prenatal alcohol exposure affects 1 in 100 births in the United States and results in craniofacial dysmorphologic condition and learning disabilities. In a model for fetal alcohol syndrome, neuroprotective peptides prevented fetal death and learning deficits. The [gamma]-aminobutyric acid A (GABA) receptor subunit GABA[beta]3 plays a critical role for nervous system and palate development. Our objective was to determine whether the neuropeptides prevented alcohol-induced damage through GABA[beta]3. Author Affiliation: Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Article Note: (footnote) Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development and National Institute of Alcohol Abuse and Alcoholism., Cite this article as: Toso L, Roberson R, Abebe D, Spong CY. Neuroprotective peptides prevent some alcohol-induced alteration in GABA[beta]3, which plays a role in cleft lip and palate and learning in fetal alcohol syndrome. Am J Obstet Gynecol 2007;196:259.e1-259.e5.