The role of fetal inflammatory response syndrome and fetal anemia in nonpreventable term neonatal encephalopathy.

OBJECTIVE: To evaluate asphyxial patterns in term encephalopathic newborns caused by chorioamnionitis or intrapartum blood loss that resulted in cerebral palsy and allegations of obstetrical professional liability. STUDY DESIGN: As an expert witness, JKM identified term newborns with profound neurologic impairment: 18 born in the presence of chorioamnionitis and 14 with significant anemia. RESULT: In both study groups, profound depression with low 10-min Apgars was associated with early-onset seizures (88%), multiorgan failure (94%) and a partial prolonged injury to the cortex and subcortical white matter (94%). A cord arterial pH>7.00 was noted in 68% and deep gray matter injury involving the basal ganglia and thalamus occurred in only 19% of the newborns studied. CONCLUSION: The cord arterial pH and pCO2 values, early-onset seizures and paucity of isolated deep gray matter injury support that significant injury occurred postnatally despite appropriate resuscitation. This unique pattern may refute allegations of obstetrical mismanagement in the intrapartum period.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Fetal macrocrania: diagnosis, delivery and outcomes.

OBJECTIVE: To describe fetal macrocrania including prenatal diagnosis, delivery considerations and clinical outcomes. STUDY DESIGN: A retrospective case series was developed by reviewing 26 885 ultrasounds performed between 1 March 2003 and 30 June 2007 for the prenatal diagnosis of macrocrania. Medical records of each mother/infant pair were reviewed for demographic information, ultrasound findings, obstetric management and outcomes. RESULT: Twenty-three fetuses were diagnosed with macrocrania. Median gestational age at diagnosis was 31.1 weeks (range 18.3-38.1) and at delivery was 36.9 weeks (range 30.7-39.9). Fifteen patients (65%) underwent amniocentesis for karyotype; none were aneuploid but one had a duplication on chromosome 7. All the 23 infants were liveborn. Twenty-one deliveries were by Cesarean (91%), with thirteen of these by classical incision (62%). Of the infants, 5 (22%) died shortly after birth, 16 (70%) were stabilized in the neonatal intensive care unit and were discharged alive and 2 (8%) were transferred to another center and subsequently died. Eighteen babies required ventriculoperitoneal shunting (78%). CONCLUSION: Macrocrania is a diagnosis usually made in children but can also be made prenatally. Fetal macrocrania is usually a result of ventriculomegaly due to an obstructive process to cerebrospinal fluid flow. Abdominal delivery is usually required, often necessitating a classical uterine incision. Targeted ultrasonography, extensive counseling of parents and delivery at a tertiary care center with availability of neurosurgery is recommended.

Association between small for gestational age and paternally inherited 5' insulin haplotypes.

OBJECTIVE: To test the association between small for gestational age and polymorphisms in the insulin gene in newborns and their mothers, as well as the effect of the parental transmission of haplotypes. SUBJECTS: Pairs of healthy African-American full-term newborns (N=207) and mothers were recruited from Memphis TN and Jackson MS with birth weights ranging from 2210 to 4735 g. METHODS: Six single nucleotide polymorphisms (SNPs) located in the insulin (INS) and insulin-like growth factor 2 (IGF2) genes were genotyped in mothers and newborns. Haplotypes composed of three SNPs in the 5' region of the INS-IGF2 locus were computationally inferred. Odds ratios for risk of small for gestational age (SGA) birth were calculated for individual SNPs and inferred haplotypes in the newborns and in the mothers using logistic regression. For 162 mother--newborn pairs the parental transmission of the haplotypes could be inferred, and the risks for SGA birth were calculated for the three common haplotypes in this sample. RESULTS: Three INS SNPs exhibited significant association with risk for SGA birth. The SNP alleles associated with increased risk for SGA were opposite in the maternal and newborn genomes, implying opposing influences on the rate of fetal growth. Consistent with these results, haplotypes composed of complementary nucleotide sequences (CAC at rs3842738, rs689 and rs3842748, respectively, in the newborn versus GTG in the mother) were significantly associated with risk for SGA birth. In analyses of haplotypes according to parental transmission, the same trend in risk for SGA was observed for both maternally and paternally transmitted haplotypes, although a significant difference in risk was observed only for paternally transmitted haplotypes. CONCLUSION: Polymorphisms near the 5' end of the INS-IGF2 locus are significantly associated with risk for SGA birth with a major effect due to the paternally transmitted haplotype, which is preferentially expressed due to imprinting.

Changing patterns of fetal lung maturity testing.

OBJECTIVE: In our laboratory, a decrease in fetal lung maturity (FLM) testing on amniotic fluid occurred over a 10-year period, and we desired to determine if this was a national phenomenon and, if present, ascertain possible etiologies. STUDY DESIGN: Society of Maternal-Fetal Medicine fellows, both in academic centers and private practice, were surveyed with regard to current usage of FLM testing. RESULT: Of 680 surveys, 417 (61%) responses were returned and 60% noted a decrease in FLM testing (range of reduction--foam stability index 65%, fluorescence polarization 35%, phosphatidyl glycerol 71%, lecithin/sphingomyelin ratio 70%). The most common reason suggested for the decline is that the tests were not needed for patient management. CONCLUSION: Obstetric patterns of FLM testing have declined, principally in near-term pregnancies, and this could adversely affect neonatal outcome.

Second trimester placental location as a predictor of an adverse pregnancy outcome.

OBJECTIVE: To determine if the second trimester placental location is associated with perinatal outcomes. MATERIALS AND METHODS: Observational study of placental location and the subsequent risk of an adverse pregnancy outcome. Placental location was divided into three categories, low, high lateral and high fundal. RESULTS: There were 3336 pregnancies analyzed in this study. Low implantation sites had a greater risk of preterm labor (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.38 to 2.90, P<0.001), preterm delivery (OR 1.86, 95% CI 1.36 to 2.54, P<0.001), fewer fetuses with macrosomia (OR 0.56, 95% CI 0.38 to 0.83, P=0.010) and reduced risk of postpartum hemorrhage (OR 0.56, 95% CI 0.46 to 0.95, P=0.026). High lateral implantations had a greater risk of low 1-min (OR 1.80, 95% CI 1.11 to 2.93, P=0.017) and 5-min (OR 3.49, 95% CI 1.46 to 8.36, P=0.005) Apgar scores. CONCLUSIONS: Low placental implantation was associated with an increased risk of preterm labor, preterm delivery and a reduced risk of postpartum hemorrhage, and of a macrosomic fetus. High lateral implantation was associated with low Apgar scores.

Pre-pregnancy body mass index and pregnancy outcomes.

OBJECTIVE: To determine the effect of maternal pre-pregnancy BMI on pregnancy outcomes. METHODS: Pregnancy cohort recruited pregnancies between 16 and 18 weeks. BMI evaluated underweight, BMI<18.5, normal, BMI 18.5-25, overweight BMI 25-30, and obese BMI>30 women. RESULTS: Pre-pregnancy BMI classified 331 women as underweight (11.7%), 1982 normal (69.9%), 326 overweight (11.5%), and 188 as obese (6.6%). Obese women were more likely to develop gestational diabetes (p<0.001), hypertension (p<0.001), preeclampsia (p<0.001), need labor induction (p<0.001), cesarean delivery for fetal distress (p<0.001), postpartum hemorrhage (p=0.003), need neonatal resuscitation (p=0.001) and deliver hypoglycemic infants (p=0.007). Being underweight is correlated with fetal growth restriction (p=0.001). CONCLUSION: Pre-pregnancy obesity is a risk factor for gestational diabetes, preeclampsia, labor induction, cesarean for fetal distress, postpartum hemorrhage and neonatal hypoglycemic and need for resuscitation. Being underweight is risk factor for fetal growth restriction.

Frequency of nursing, physician and hospital interventions in women at risk for preterm delivery.

OBJECTIVE: To determine the frequency of nursing intervention, physician treatment and hospital evaluation for women receiving outpatient management services for preterm labor. METHODS: Outpatient services included: patient education; daily and as-needed nursing assessment of monitored uterine activity (MUA) and patient symptoms; treatment compliance; and physician notification for values exceeding established limits. We analyzed service data from women with singleton gestations at 20.0-34.9 weeks. RESULTS: Overall, 307 249 days of data from 10 660 women were reviewed, and 634 983 hours of MUA was assessed. On 53 665 (17.5%) of monitored days, patients exhibited increased MUA and/or symptoms of preterm labor with nursing intervention and reassessment. Physician notification/intervention was required 7316 (13.6%) times, and hospital admission was needed for 3163 (43.2%) of these patients. In the hospital 1400 (44.3%) patients received tocolysis. The mean ( +/- standard deviation) length of hospital stay was 3.2 +/- 7.2 days, and 428 (13.5%) of women remained hospitalized until delivery, with 324 (10.2%) delivering within 48 h. CONCLUSION: In this population of women receiving outpatient preterm-labor management services, 95.1% of excessive MUA or patient-reported symptoms of preterm labor were managed on an outpatient basis. Outpatient management allowed for appropriate identification and triage of women requiring hospital admission.

Application of learning theory to obstetric maloccurrence.

The average fellow of the American College of Obstetricians and Gynecologists performs approximately 140 deliveries per year. Based on this estimation and the established prevalence of three commonly litigated maloccurrences, we calculated the number of years of clinical experience required to encounter one case. Permanent brachial plexus palsy complicates only 1 per 4553 deliveries so a clinician would encounter such a case in 33 years of practice. For every 6667 deliveries, there is a case of cerebral palsy attributable to intrapartum hypoxia, so a practioner would see only one case every 48 years. Since the rate of asphyxia with uterine rupture is 1 per 2819 vaginal births after Cesarean section and the average provider performs seven vaginal births after Cesarean deliveries per year, a clinician would have a case in 403 years of practice. Adverse outcomes expressed as an absolute percentage or as the number of cases per number of deliveries are statistically accurate. Expression of these maloccurrences in terms of the number of years of clinical experience permits the generation of a clinically relevant data point and also allows insight into why their prevalence has not decreased.

Ultrasound estimation of amniotic fluid volume using the largest vertical pocket containing umbilical cord: measure to or through the cord?

OBJECTIVES: The purpose of this investigation was to determine the preferable method, either measuring to the umbilical cord or through the umbilical cord to the base of the pocket, of ultrasonically estimating amniotic fluid volume. SUBJECT AND METHODS: This was a prospective study carried out in singleton pregnancies undergoing a third-trimester amniocentesis. The amniotic fluid index (AFI) and single deepest pocket (SDP) were measured prior to amniocentesis. If measured spaces contained umbilical cord, measurements were made to and through the cord. Actual amniotic fluid volume was determined by the dye-dilution technique. RESULTS: One-hundred pregnancies were evaluated. Low dye-determined volume was identified in a significantly greater number of pregnancies using the AFI to the cord (7/28, 25%) compared to through the cord (2/28, 7%) (P = 0.025). The SDP technique to the cord was superior in low volumes (2/28, 7%) vs. (0/28, 0%) through the cord (although statistical significance could not be determined because there were no low through-the-cord measurements). CONCLUSIONS: For the detection of low amniotic fluid volumes, the AFI to the cord is better than through the cord. Measurement to the cord and through the cord had similar accuracy for both the AFI and SDP techniques in normal and high dye-determined amniotic fluid volumes.

Dye-dilution techniques using aminohippurate sodium: do they accurately reflect amniotic fluid volume?

OBJECTIVE: To determine whether the dye-dilution technique using aminohippurate sodium accurately measures amniotic fluid volume. METHODS: Singleton pregnancies with intact membranes undergoing a Cesarean delivery had their amniotic fluid volume assessed by the dye-dilution technique and direct measurement. RESULTS: Fifteen women were prospectively assessed. Six patients had their amniocentesis on the delivery table and nine patients at 4-24 h prior to the Cesarean delivery. The six women undergoing an amniocentesis just before delivery had good concordance between the dye-determined and direct measurement of amniotic fluid volume (r = 0.99, p = < 0.001). Among the nine women with varying times from amniocentesis to direct measurement, the correlation was not significant (r = 0.36, p = 0.08). The percentage difference between the dye-determined and directly measured amniotic fluid volume was significantly smaller in the women undergoing amniocentesis just prior to delivery (7%) than in the women with varying times from amniocentesis to delivery (37%, P < 0.001). CONCLUSION: Dye-determined amniotic fluid volume accurately reflects actual amniotic fluid volume but the dye-determined concentrations, in vivo, may undergo rapid changes.

Outpatient cervical ripening with prostaglandin E2 and estradiol.

OBJECTIVE: To determine whether weekly outpatient administration of prostaglandin gel or estrogen cream initiated labor in women with an unfavorable cervix. METHODS: All uncomplicated pregnancies at term gestation who were candidates for a vaginal delivery with a Bishop score of < or = 6 were randomly assigned to receive on a weekly basis: prostaglandin E2 gel (n = 41); estrogen cream (n = 44); or inert lubricant jelly (n = 43). RESULTS: In the three groups no differences were observed among 128 subjects in the weekly Bishop scores, cervical dilatation or gestational age upon admission to the labor and delivery suite, the percentage of patients presenting with spontaneous labor or ruptured membranes, the number of post-date inductions or neonatal outcome. CONCLUSIONS: Weekly out-patient cervical ripening using either prostaglandin gel or estrogen in women with an unfavorable cervix at 37 weeks' gestation was no more effective than a placebo in Bishop score improvement or in preventing post-date inductions.

Does uterine wiping influence the rate of post-Cesarean endometritis?

OBJECTIVE: To compare two methods of uterine cleansing to remove residual amnion-chorion at the time of Cesarean delivery. METHODS: All consenting uninfected parturients undergoing a non-emergency Cesarean delivery at the university were enrolled. All patients received antibiotic prophylaxis of a 1-g intravenous bolus of a first-generation cephalosporin immediately after cord clamping. Postpartum endometritis was defined as a temperature of > or = 100.4 degrees F (38 degrees C) on two occasions 6 h apart after the first 24 h with uterine tenderness and/or foul-smelling lochia. RESULTS: Between January 1998 and February 2000 there were 1400 patients enrolled in this investigation. A total of 153 women were determined to have chorioamnionitis present at surgery and 17 women refused participation, leaving 614 women in the uterine wipe group and 616 in the no wipe group. Maternal demographics were similar between patient groups (NS). Intrapartum factors including gestational age at time of Cesarean section, type of anesthesia used for the operative delivery, hours of amnion rupture prior to delivery, use of internal monitoring devices, type of skin incision, method of placental removal, total operative time and estimated blood loss were similar between patient groups (NS). An almost identical number of patients in each arm of the study developed post-Cesarean endometritis (65 out of 614, 10.5%, in the uterine wipe group vs. 66 out of 616, 10.7%, in the no wipe group; p = 1). CONCLUSIONS: Both methods of removing residual amnion-chorion membrane tissue and associated debris at surgery were comparably effective, but neither produced a dramatic reduction in the incidence of postoperative endometritis.

A Canadian faculty of medicine and dentistry's survey of career development needs.

INTRODUCTION: Career development efforts for adult learners are more likely to succeed if they are responsive to the learners' needs, offered at convenient times, and provided in a variety of forms. METHODS: The Faculty of Medicine and Dentistry at the University of Alberta conducted a self-administered career development needs survey of full-time academic faculty. Faculty members were asked to identify how useful each of 35 career development skills would be to them and at which stage in an academic career it would be most useful. Preferred educational modes and times of delivery were also assessed. The mean rankings of skill needs were examined overall as well as by gender, academic rank, departmental category (clinician versus basic scientist), marital status, and the presence of school-aged children at home. RESULTS: 185 of 446 (41%) mailings were returned, of which 181 were evaluated. The number one perceived career development need across all subgroups was 'Effective writing of grants and publications'. Six of the top 10 needs were identified as useful at all career stages. Significant differences in rankings of needs were noted between subgroups. Half days were preferred to full days for career development efforts and short courses to other educational modes. DISCUSSION: Several career development skills were identified as priorities independently of gender, academic rank, and clinical versus basic science career tracks. Differences suggest that within a basic global programme, a variety of career development modules may need to be developed for subgroups.

Changes in Thy1 gene expression associated with damaged retinal ganglion cells.

PURPOSE: The temporal series of molecular events that occur in dying retinal ganglion cells is poorly understood. We have examined the change in expression of a normally-expressed ganglion cell marker gene, Thy1, relative to the kinetics of cell loss caused by acute and chronic damaging stimuli. METHODS: For acute experiments, mice were subjected to optic nerve crush or intravitreal injections of N-methyl-D-aspartate (NMDA) to induce ganglion cell death. RNase protection analysis was used to quantify Thy1 mRNA levels from total retina RNA and in situ hybridization was used to monitor the pattern of Thy1 positive cells. Changes in Thy1 expression were compared to the time course of cell loss induced by each treatment. To induce elevated intraocular pressure (IOP), the episcleral veins of rats were injected with hypertonic saline, which scleroses Schlemm's Canal and the trabecular meshwork. Elevated IOP was monitored every day for 35 days after which the animals were sacrificed and the retinas harvested for quantitative RT-PCR or fixed for in situ hybridization studies. Evaluation of glaucomatous damage caused by elevated IOP was determined from histological sections of the optic nerves of all rat eyes. RESULTS: After optic nerve crush, Thy1 mRNA levels decreased within 24 h, although the number of expressing cells did not decline until 7 days. Both measures showed a loss of Thy1 well in advance of cell loss, which was detected by 2 weeks after surgery. This change in expression was not dependent on execution of the cell death program since a similar decrease was detected in Bax-/- ganglion cells, which are resistant to cell death induced by optic nerve crush. Thy1 mRNA levels and the number of expressing cells also decreased within 6 h after NMDA injection, in advance of cell loss, which was detected by 24 h. Similarly, elevated intraocular pressure was associated with a decrease in mRNA and expressing cells in a pressure-dependent manner. In moderately hypertensive rat eyes, the number of cells expressing Thy1 decreased before significant cell loss in the retina. Virtually no Thy1-expressing cells were detected in eyes with severe disease. CONCLUSIONS: Thy1 mRNA abundance and expressing cells, decreased in advance of detectable ganglion cell loss caused by three different modalities of damage. This change is independent of the committed step of cell death.

Labor and membrane rupture in twin gestation. Can they affect the ability to estimate fetal weight?

OBJECTIVE: To determine whether labor or fetal membrane rupture adversely affects the ability of ultrasound to accurately estimate fetal weight (EFW) in a twin gestation. STUDY DESIGN: A medical record audit was performed of the two-year experience of women delivering live born twins and undergoing a complete ultrasound examination within 72 hours of delivery. Those patients experiencing labor or membrane rupture at the time of the previous ultrasound examination were compared to those without these factors to determine if there was any detrimental impact on the accuracy of ultrasound to EFW. RESULTS: The overall ability of ultrasound to accurately EFW was in the range of 64-76%. This was not significantly different from the accuracy in women experiencing labor (62-80%) or in women with membrane rupture (63-81%). The ability of ultrasound to detect fetal discordance is this series ranged from 78% to 100%, with specificity that ranged from 84% to 89%. CONCLUSION: The ability of sonography to accurately EFW as well as detect discordant twin gestation is not altered by the presence of labor or membrane rupture.

Maternal morbidity and mortality associated with intrauterine fetal demise: five-year experience in a tertiary referral hospital.

BACKGROUND: Risk factors for and management of intrauterine fetal demise (IUFD) have been investigated, but the maternal morbidity has not been evaluated. METHODS: Over a 60-month interval, all cases of IUFD after 20 weeks' gestation were reviewed for maternal trauma and maternal postpartum complications. RESULTS: In this retrospective analysis, 498 singleton and 24 twin pregnancies with an IUFD were identified. A cervical or perineal laceration requiring surgical repair complicated 9.4% of pregnancies. One uterine dehiscence and one uterine rupture occurred. Endometritis, the most common postpartum complication, occurred in 63 of 522 patients (12%). One maternal death occurred. Total mean hospital stay was 4.9 +/- 5.7 days. CONCLUSION: Maternal morbidity and rarely mortality can follow IUFD, but this morbidity is similar to that observed without IUFD.

Pregnancy outcome in women with preterm labor symptoms without cervical change.

OBJECTIVE: This study was undertaken to determine pregnancy outcome in women who have preterm labor symptoms without cervical change according to fetal fibronectin status. STUDY DESIGN: Patients who were examined at the obstetric emergency department with symptoms of preterm labor but without cervical change underwent fetal fibronectin collection. Pregnancy outcome and fetal fibronectin results were analyzed after delivery. RESULTS: Of the 235 patients sampled, 20% (n = 48) had positive fetal fibronectin results. The mean +/- SD gestational age at delivery was lower in women with positive fetal fibronectin results (34.2 +/- 4.1 vs 37.7 +/- 2.3 weeks; P <.001); these women were more likely to deliver preterm as a result of preterm labor than women with other obstetric indications (46% vs 19%; P <.001). Infants born to these women demonstrated lower birth weight (2317 +/- 895 g vs 2877 +/- 557 g; P =.003), were more likely to be admitted to the neonatal intensive care unit (42% vs 14%; P <.001), and were more likely to die in the neonatal period (11% vs 0%; P <.001). CONCLUSION: Patients with symptoms of preterm labor but without cervical change who have negative fetal fibronectin results are less likely to deliver preterm. Therefore in women with symptoms but without cervical change fetal fibronectin should be considered for risk assessment.

Subjective versus objective evaluation of amniotic fluid volume of pregnancies of less than 24 weeks' gestation: how can we be accurate?

This study was undertaken to compare subjective versus objective ultrasonic evaluation of amniotic fluid volume in pregnancies of less than 24 weeks' gestation. Amniotic fluid volume was subjectively (visualization without ultrasonic measurements) and objectively (visual interpretation with ultrasonic measurements) evaluated in 42 singleton pregnancies undergoing termination. The actual amniotic fluid volume was then determined using a dye-dilution technique. The women evaluated were in their mid-20s, primarily African American, and between 15 and 23 weeks' gestation. There was no significant difference in the total number of correct estimates of amniotic fluid volume when the data were stratified by level of operator experience (P = .34), ultrasonic technique (P = .33), or the combined correct subjective versus combined correct objective estimates (P = .68). We have concluded that the accuracy of amniotic fluid volume assessment in pregnancies of less than 24 weeks is not influenced by the level of operator experience or the type of ultrasonic measurement.