George A. Macones

The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: Update on definitions, interpretation, and research guidelines

In April 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine partnered to sponsor a 2-day workshop to revisit nomenclature, interpretation, and research recommendations for intrapartum electronic fetal heart rate monitoring. Participants included obstetric experts and representatives from relevant stakeholder groups and organizations. This article provides a summary of the discussions at the workshop. This includes a discussion of terminology and nomenclature for the description of fetal heart tracings and uterine contractions for use in clinical practice and research. A three-tier system for fetal heart rate tracing interpretation is also described. Lastly, prioritized topics for future research are provided.

Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations

OBJECTIVE Bacteria have been identified in different regions of the placenta. Here, we tested the hypothesis that the maternal basal plate of the placenta harbors microbes that may be associated with adverse pregnancy outcomes. STUDY DESIGN We performed a cross-sectional study of pregnancies from a single tertiary care hospital. Maternal medical and obstetric characteristics were obtained and pregnancies followed up prospectively for outcomes and placental collection. After delivery, systematic random sampling of the placental basal plate was performed. Paraffin sections of basal plates were stained with 4 histologic stains and scored for morphological evidence of bacteria. RESULTS Of 195 total patients in the study, Gram-positive and -negative intracellular bacteria of diverse morphologies were documented in the basal plates of 27% of all placentas. Of the patients, 35% delivered preterm. No difference was noted between placental basal plates from preterm or term gestations. Intracellular bacteria were found in the placental basal plates of 54% spontaneous preterm deliveries <28 weeks, and in 26% of term spontaneous deliveries (P = .02). Intracellular bacteria were also documented in placentas without clinical or pathologic chorioamnionitis. CONCLUSION A total of 27% of placentas demonstrated intracellular bacteria in the placental basal plate using morphological techniques. Thus, the maternal basal plate is a possible source of intrauterine colonization and placental pathological examination could include examination for bacteria in this important maternal-fetal interface.

Sleep deprivation during pregnancy and maternal and fetal outcomes: Is there a relationship?

Sleep duration in the population has been declining. Women occupy an increasingly prominent place in the work force without reducing most of their responsibilities at home. Consequently, sleep needs are often pushed to the bottom of womens daily priority list. Prior research has indicated that sleep deprivation is associated with higher levels of pro-inflammatory serum cytokines. This is important because higher plasma concentrations of pro-inflammatory serum cytokine levels are associated with postpartum depression and adverse birth outcomes such as preterm delivery. However, little research has directly examined how sleep deprivation may affect maternal and fetal outcomes. This review summarizes the existing data on the effect of sleep deprivation during pregnancy on maternal and fetal outcomes. We review supporting evidence for the hypotheses that sleep deprivation during pregnancy increases the risk of preterm delivery and postpartum depression, and that systemic inflammation is the causal mechanism in the association. Prior research on sleep in pregnancy has been limited by varying data collection methods, subjective self-reported sleep measures, small and non-representative samples, cross-sectional designs; descriptive or non-hypothesis driven studies. Future research with longitudinal study designs is needed to allow examination of the effect of sleep deprivation on adverse maternal and fetal outcomes.

The 2008 national institute of child health and human development workshop report on electronic fetal monitoring: Update on definitions, interpretation, and research guidelines

In April 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine partnered to sponsor a 2-day workshop to revisit nomenclature, interpretation, and research recommendations for intrapartum electronic fetal heart rate monitoring. Participants included obstetric experts and representatives from relevant stakeholder groups and organizations. This article provides a summary of the discussions at the workshop. This includes a discussion of terminology and nomenclature for the description of fetal heart tracings and uterine contractions for use in clinical practice and research. A three-tier system for fetal heart rate tracing interpretation is also described. Lastly, prioritized topics for future research are provided.

Revisiting the Fetal Loss Rate After Second-Trimester Genetic Amniocentesis : A Single Center's 16-Year Experience

OBJECTIVE: To estimate an institution’s specific fetal loss rate after a second-trimester genetic amniocentesis. METHODS: This is a retrospective cohort study using our prenatal diagnosis database for all pregnant women presenting for care between 1990 and 2006. We compared the fetal loss rate in women who underwent amniocentesis between 15 and 22 weeks of gestation with those women who did not have any invasive procedure and had a live fetus documented on ultrasound examination between 15 and 22 weeks. Only singleton gestations were included. Logistic regression analysis was used to adjust for potential confounders between the groups. RESULTS: Among 58,436 women meeting the inclusion criteria, complete outcome data were available for 51,557 (88%), 11,746 (91%) in the amniocentesis group and 39,811 (87%) in the group that did not have amniocentesis. The fetal loss (miscarriages and intrauterine fetal death) rate in the amniocentesis group was 0.4% compared with 0.26% in those without amniocentesis (relative risk 1.6, 95% confidence interval [CI] 1.1–2.2). Fetal loss less than 24 weeks (including induction for ruptured membranes and oligohydramnios) occurred in 0.97% of the amniocentesis group and 0.84% of the group with no procedure (P=.33). The fetal loss rate less than 24 weeks attributable to amniocentesis was 0.13% (95% CI –0.07 to 0.20%) or 1 in 769. The only subgroup that had a significantly higher amniocentesis attributable fetal loss rate was women with a normal serum screen (0.17%, P=.03). CONCLUSION: The institutional fetal loss rate attributable to amniocentesis is 0.13%, or 1 in 769 at Washington University School of Medicine. The total fetal loss rate was not significantly different from that observed in patients who had no procedure. LEVEL OF EVIDENCE: II

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization

OBJECTIVE To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. DESIGN Prospective cohort study. SETTING University in vitro fertilization (IVF) practice. PATIENT(S) A total of 102 women undergoing IVF. INTERVENTION(S) Measurement of FFAs in serum and ovarian follicular fluid. MAIN OUTCOME MEASURE(S) Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. RESULT(S) Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). CONCLUSION(S) Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility.

Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.

Treatment of localized periodontal disease in pregnancy does not reduce the occurrence of preterm birth: results from the Periodontal Infections and Prematurity Study (PIPS)

OBJECTIVE The purpose of this study was to test whether treating periodontal disease (PD) in pregnancy will reduce the incidence of spontaneous preterm delivery (SPTD) at < or = 35 weeks of gestation. STUDY DESIGN A multicenter, randomized clinical trial was performed. Subjects with PD were randomized to scaling and root planing (active) or tooth polishing (control). The primary outcome was the occurrence of SPTD at <35 weeks of gestation. RESULTS We screened 3563 subjects for PD; the prevalence of PD was 50%. Seven hundred fifty-seven subjects were assigned randomly; 378 subjects were assigned to the active group, and 379 subjects were assigned to the placebo group. Active treatment did not reduce the risk of SPTD at <35 weeks of gestation (relative risk, 1.19; 95% confidence interval [CI], 0.62-2.28) or composite neonatal morbidity (relative risk, 1.30; 95% CI, 0.83-2.04). There was a suggestion of an increase in the risk of indicated SPTD at <35 weeks of gestation in those subjects who received active treatment (relative risk, 3.01; 95% CI, 0.95-4.24). CONCLUSION Treating periodontal disease does not reduce the incidence of SPTD.

Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00

OBJECTIVE Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. STUDY DESIGN In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. RESULTS We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively. CONCLUSION Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

Congenital uterine anomalies and adverse pregnancy outcomes

OBJECTIVE We sought to estimate whether the presence of a maternal uterine anomaly is associated with adverse pregnancy outcomes. STUDY DESIGN This retrospective cohort study included singleton pregnancies undergoing routine anatomic survey from 1990 through 2008 at a major tertiary care medical center. Pregnancies with a diagnosis of uterine anomaly (uterine septum, unicornuate uterus, bicornuate uterus, uterine didelphys) were compared to those with normal anatomy. Primary outcomes of interest were spontaneous preterm birth (PTB), breech presentation, and cesarean delivery. RESULTS The presence of an anomaly was associated with PTB <34 weeks (adjusted odds ratio [aOR], 7.4; 95% confidence interval [CI], 4.8-11.4; P < .01), PTB <37 weeks (aOR, 5.9, 95% CI, 4.3-8.1; P < .01), primary nonbreech cesarean delivery (aOR, 2.6; 95% CI, 1.7-4.0; P < .01), preterm premature rupture of membranes (aOR, 3.2; 95% CI, 1.8-5.6; P < .01), and breech presentation (aOR, 8.6; 95% CI, 6.2-12.0; P < .01). CONCLUSION Women with a uterine anomaly are at risk for PTB, highlighting an at-risk population that needs additional study for possible interventions for PTB prevention.