Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia: diagnosis and management

OBJECTIVE: We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia. METHODS: A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. RESULTS AND RECOMMENDATIONS: We recommend the following: (1) middle cerebral artery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluid delta OD450 not be used to diagnosis fetal anemia; (3) MCA-PSV assessment be reserved for those patients who are at risk of having an anemic fetus (proper technique for MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus is deemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing the second procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.(AU)

Choice of antenatal testing significantly effects a patient's work obligations.

OBJECTIVE: We sought to compare two approaches to antenatal testing for their impact on the workforce. STUDY DESIGN: This is a prospective observational study of women who presented for antenatal testing. All women were given a survey upon presentation. As per hospital protocol, nonstress testing (NST) was performed semiweekly and biophysical profile (BPP) was performed weekly. The choice of testing was determined by the attending physician. chi2- and Student's t-tests were performed where appropriate. A P-value of <0.05 was considered significant. RESULT: A total of 195 women were surveyed. Among them, 94 women had an NST and 101 had a BPP. Overall, 59.2% were multiparous, 33.1% had to arrange for child care and 97.2% felt reassured by the testing. There were no differences in demographic characteristics, education, type of insurance or employment status between the groups. Women who had NSTs were more likely to lose time from work than those who had BPPs (218.4 versus 68.9 min; P<0.001). Of the women who had semiweekly NSTs, 80.6% would have preferred weekly testing. If the 94 women who received semiweekly testing had weekly testing, a total of 534.4 h would have been available for the workforce. CONCLUSION: Twice-weekly NST results in a significant increase in time lost from the workforce compared with weekly BPP.

Neonatal hearing assessment in very low birth weight infants exposed to antenatal steroids.

OBJECTIVE: We sought to evaluate neonatal hearing assessment by the otoacoustic emission (OAE) test in very low birth weight (VLBW) infants exposed to antenatal steroids. STUDY DESIGN: This is a retrospective cohort study of infants <1500 g delivered between July 1998 and July 2004 who completed hearing screens on discharge. All screens were performed by the OAE. Only infants who failed or passed the exam were included in the analysis. Infants with a partial or an inadequate exam were excluded. Neonates exposed to antenatal steroids were then compared to unexposed infants for the results of their OAE. RESULT: A total of 68,000 deliveries were performed during the study period. There were 703 VLBW infants who had hearing exams, of which 548 (78%) passed the screen, 95 (14%) failed and 59 (8%) were indeterminate. Gestational age, birth weight, score for neonatal acute physiology and severe intraventricular hemorrhage were associated with a failed screen (P<0.01). Antenatal steroid exposure was not associated with a failed screen (odds ratio: 0.83 (95% confidence interval 0.5-1.4), P=0.43). CONCLUSION: In our population, antenatal steroids were not associated with a positive or negative effect on hearing assessment of VLBW infants.

Transcervical Foley catheter for preinduction cervical ripening in an outpatient versus inpatient setting.

OBJECTIVE: To compare use of the Foley catheter for preinduction cervical ripening in an inpatient versus outpatient setting. METHODS: A randomized trial was conducted from May 1998 to December 1999. Women with a term gestation in the vertex presentation, a reactive nonstress test, an amniotic fluid index above the fifth percentile, and a Bishop score of no more than 5 were included. The primary outcome variable was a change in Bishop score. A Foley catheter with a 30-mL balloon was placed through the cervix on gentle traction in each group. The outpatient group was then discharged home with written instructions and returned in the morning for induction. The inpatient group was admitted to labor and delivery, with induction started upon extrusion of the Foley. RESULTS: Sixty-one women were randomized into the outpatient group, and 50 women into the inpatient group. Maternal age, gravidity, previous cesarean delivery, and gestational age did not differ between the groups. The median Bishop score at entry was 3.0 for each group (P =.97). The mean change in Bishop scores after catheter placement was not different between the inpatient and outpatient groups (3.0 versus 3.0; P =.74). The maximum dose of oxytocin, time of oxytocin, epidural rate, induction time, 1-minute and 5-minute Apgar scores, and cord pH were not significantly different. The outpatient group on average avoided 9.6 hours of hospitalization. There were no adverse events or maternal morbidity in either group. CONCLUSIONS: The Foley bulb is as effective in the outpatient as the inpatient setting for preinduction cervical ripening.

In vitro sealing of punctured fetal membranes: potential treatment for midtrimester premature rupture of membranes.

OBJECTIVE: Midtrimester premature rupture of membranes causes significant perinatal morbidity and death. No effective treatment exists. We investigated (1) whether a needle puncture in the fetal membranes could be sealed in vitro and (2) the optimal composition of the sealant to be used. STUDY DESIGN: Membranes from second trimester pregnancies (16-24 weeks of gestation) were stretched over a modified syringe with a 2.5-cm open diameter. The syringe was filled with 20 mL of second trimester amniotic fluid, and the membrane was punctured with a 20-gauge needle. Sealants were injected into the amniotic fluid. The primary outcome variable was time for leakage of amniotic fluid. Median times for leakage for the formulations were compared by Wilcoxon exact rank sum test. RESULTS: Platelets alone failed to seal the puncture site. All other formulations stopped leakage temporarily. Tisseel (Baxter Corp, Glendale, Calif) and cryoprecipitate/thrombin preparations led to more prolonged sealing of punctured amniotic membranes than platelets (P <.01) and were not significantly different from each other. CONCLUSION: Of the sealants tested in vitro, amniotic membranes are best sealed by a fibrin/thrombin-based sealant.

A new device for measuring intrauterine temperature.

OBJECTIVE: We evaluated a new device that uses the intrauterine pressure catheter to measure the maternal temperature in patients who are in labor. STUDY DESIGN: The study was conducted at two medical centers, Christiana Hospital in Newark, Delaware, and Saint Louis University/St Mary's Health Center in St Louis, Missouri, from September 1, 1997, to May 2, 1998. An intrauterine pressure catheter with a thermistor sensor in the tip was placed into the uterus after spontaneous rupture of membranes. The intrauterine, oral, and tympanic temperatures were simultaneously obtained immediately after insertion of the intrauterine pressure catheter and then hourly until delivery or the initiation of amnioinfusion. RESULTS: The study comprised 97 patients and 404 temperature readings with a temperature range of 34.7 degrees C to 40.7 degrees C. The normal mean +/- SD for the oral, tympanic, and intrauterine temperatures was 36.7 degrees C +/- 0.5 degrees C, 36.8 degrees C +/- 0.5 degrees C, and 37.3 degrees C +/- 0.4 degrees C, respectively. There was a linear relationship among the oral, tympanic, and intrauterine temperatures. All three methods showed a significant increase in mean body temperature after epidural anesthesia. CONCLUSION: The new device, the intrauterine pressure-temperature catheter, provides a convenient and accurate means of continuously measuring uterine temperature in patients who are in labor and require intrauterine monitoring.

Intracervical fibrin sealants: a potential treatment for early preterm premature rupture of the membranes.

OBJECTIVE: We report our experience with a transvaginally applied intracervical fibrin sealant at <24 weeks' gestation. STUDY DESIGN: This is an observational study of a referred patient population, with preterm premature rupture of the membranes at <24 weeks' gestation. RESULTS: Twelve women consented to our protocol. The mean gestational age at preterm premature rupture of membranes was 19 weeks 4 days (range, 13-23 weeks); the mean gestational age at treatment was 20 weeks 5 days (range, 17-23 weeks). All women had a diminution in the amount of amniotic fluid leakage with an increase in amniotic fluid index. Among the 12 pregnancies (13 fetuses), there were 7 surviving neonates. Two women had apparent "resealing" of the membranes. CONCLUSION: Fibrin sealants in midtrimester rupture of the membranes may lead to improved outcomes and now warrant formal evaluation.

A randomized comparison of transcervical Foley catheter to intravaginal misoprostol for preinduction cervical ripening.

OBJECTIVE: To compare the efficacy of intravaginal misoprostol tablets with transcervical Foley catheter for preinduction cervical ripening. METHODS: Pregnant women who presented for induction of labor with unfavorable cervices (Bishop score less than 6) were assigned randomly to intravaginal misoprostol (50 microg tablet every 4 hours for a maximum of six doses) or 30-mL Foley catheter placed transcervically with maintenance of traction. RESULTS: Among 111 women, 53 were allocated to misoprostol and 58 to Foley bulb. Contractile abnormalities were more frequent in the misoprostol group (20.4%) than the Foley group (0%) (P <.001). No statistically significant differences were noted between groups in change in Bishop score, preinduction cervical ripening times, and total induction times. There were no statistically significant differences in mode of delivery or adverse neonatal outcomes. Uterine rupture occurred in one woman with two previous cesarean deliveries in the misoprostol group. CONCLUSION: Intravaginal misoprostol and transcervical Foley catheter are equivalent for cervical ripening. Uterine contractile abnormalities and meconium passage are more common with misoprostol.

A prospective, randomized comparison of Foley catheter insertion versus intracervical prostaglandin E2 gel for preinduction cervical ripening.

OBJECTIVE: The objective of this study was to compare intracervical prostaglandin E2 gel with insertion of a Foley bulb for efficacy in preinduction cervical ripening. STUDY DESIGN: Women who came to the hospital for induction of labor with a Bishop score

Factors affecting fellowship satisfaction, thesis completion, and career direction among maternal-fetal medicine fellows.

OBJECTIVE: To determine fellowship satisfaction through a survey of maternal-fetal medicine fellows. METHODS: We constructed a survey using multiple choice, Likert scale, ordinal, and categorical scale questions. The questions focused on faculty involvement, mentorship, research time and productivity, education, fellowship selection, ultimate goals of fellows, and satisfaction. We sent the survey in two mailings to all maternal-fetal medicine fellows during April and May 1996. RESULTS: One hundred thirty-eight surveys were mailed, and 136 were returned (98.5% return rate). Twenty-seven percent of fellows did not believe they would complete their thesis by the end of their fellowship. No statistically significant relationship was noted between the fellows' predicted thesis completion and the availability of funding, support for statistical analysis, the presence of animal research facilities, age, number of dependents, or year of fellowship. The presence of a mentor on the maternal-fetal medicine faculty increased the likelihood of thesis completion from 52.3% to 83.5% (P < .001). Similarly, the presence of a faculty advisor increased the likelihood of thesis completion from 58.9% to 83.5% (P = .001). Thirty-two percent of the respondents did not have a mentor on the faculty, and 41% did not have a faculty advisor. Forty percent indicated that they were too involved in clinical pursuits to perform research. This group was significantly more likely to believe that their theses would not be completed (63% versus 80%, P = .029). Overall, 22% of the fellows would not recommend their fellowships. Fellows with a mentor (88.2% versus 55.8%; P < .001) or faculty advisor (87.3% versus 64.9%; P = .002) were more likely than those without to recommend their fellowship. CONCLUSION: A mentor or faculty advisor plays a significant role in the training of maternal-fetal medicine fellows and is associated with a higher incidence of satisfaction with the fellowship program, thesis completion, and entrance into academic practice.

Tocolysis of preterm contractions does not improve preterm delivery rate or perinatal outcomes.

To determine whether hospital admission and parenteral tocolysis of patients with threatened preterm labor results in a decreased preterm delivery rate and improved perinatal outcome, we performed a prospective cohort study comparing tocolytic treatment versus no tocolytic treatment. Women between 20 and 37 weeks' gestation who presented with at least eight uterine contractions per hour and a cervical examination <2 cm dilated, <80% effaced, and no cervical change over a 2-hr period were entered into the study. Exclusion criteria included cervical change, multiple gestation, chorioamnionitis, rupture of membranes, placenta previa or abruption, undiagnosed vaginal bleeding, and prior tocolytic therapy in the current pregnancy. Seventy-five patients were admitted to the hospital for tocolysis (tocolysis cohort) and 81 were observed and discharged to home (observation cohort). There was no significant difference in mean gestational age at delivery, mean birth weight, or in preterm delivery rate between the two cohorts. Four of the eight women in the observation cohort who delivered preterm had a history of preterm delivery. We conclude that discharging women with preterm contractions without objective evidence of labor does not result in an increase in preterm births. More importantly, tocolysis did not decrease the preterm delivery rate in this cohort.

Uterine rupture during preinduction cervical ripening with misoprostol in a patient with a previous Caesarean delivery.

We report a case of uterine rupture in a patient with a previous low transverse Caesarean delivery, in which transvaginal misoprostol was used for preinduction cervical ripening.

An analysis of neonatal morbidity and mortality in maternal (in utero) and neonatal transports at 24-34 weeks' gestation.

Sophisticated neonatal transport has improved the safety of transporting preterm infants, but may not substitute for the benefits of in utero transport. To describe gestational age trends and assess differences in complications between maternal (in utero) and neonatal transports, we analyzed maternal and neonatal transports, over 3 years, to the only tertiary center in the region. Those who delivered between 24 and 34 weeks' gestation were included in the analysis. Gestational age trends for each complication are described, showing, in general, decreasing morbidity with gestational age in both groups. These trends were usually parallel, but not equal. A significantly greater mean neonatal intensive care unit (p = 0.003) and total length of stay (p = 0.006) as well as longer ventilator time (p = 0.01) and oxygen therapy exposure (p = 0.018) were noted in those transported neonatally. The incidence of respiratory distress syndrome (p < 0.001), bronchopulmonary dysplasia (p = 0.027), intraventricular hemorrhage (p = 0.041), intraventricular hemorrhage grades III and IV (p = 0.008), patent ductus arteriosus (p = 0.032), and mortality (p = 0.001) were all significantly greater among the neonatal transports. The differences were not significant for retinopathy of prematurity, hyperbilirubinemia, necrotizing enterocolitis, periventricular leukomalacia, and culture proven sepsis. Specialized neonatal transport and advanced neonatology techniques have not removed the significant advantage of decreased morbidity, mortality, and length of hospital intervention resulting from maternal (in utero) transport.

Indicators of platelet turnover in thrombocytopenic infants.

Glycocalicin has been found to be a marker of increased platelet turnover, while interleukin-6 may be increased in response to thrombocytopenia. We used these markers to study the pathophysiology of thrombocytopenia in newborn infants. Cord blood platelet counts were obtained from 499 infants. Thrombocytopenic infants (< 100,000/mm3) and a control group had ELISA assays for interleukin-6 and glycocalicin performed. The mean levels of glycocalicin and interleukin-6 were elevated in cord blood of thrombocytopaenic infants. Infants with intrauterine growth restriction and thrombocytopaenia had no detectable glycocalicin in their plasma, despite elevated levels of interleukin-6. This probably reflects impaired thrombopoiesis in these infants.

Increase in ambient temperature may explain decrease in amniotic fluid index.

In the third trimester, the amniotic fluid index (AFI) may be affected by maternal fluid status. As the ambient temperature increases, there is an increase in insensible fluid loss and the potential for dehydration. We hypothesize that as temperature increases there would be a concomitant decrease in AFI. From June 11 to August 16, 1993, during a period of unusual high heat, 42 women with singleton pregnancies between 27 and 40 weeks' gestation undergoing serial antenatal testing had AFI determinations recorded at least weekly. The daily high ambient temperature in our urban area was subsequently obtained. A 2-, 3-, and 4-day mean temperature prior to the test date was compared to AFI using a Spearman-rank Correlation. The daily high temperature ranged from 71 to 104 degrees F and AFI values ranged from 1.7 to 24.7 cm during the study period. There was a significant correlation between the 2-, 3-, and 4-day mean temperature and AFI, with the 4-day mean being the most significant (r = 0.31, p < 0.001). Fluctuations in ambient temperature are inversely correlated to changes in AFI. This relationship should be taken into account when interpreting the AFI as a measure of fetal well-being.

Adjustment of birth weight standards for maternal and infant characteristics improves the prediction of outcome in the small-for-gestational-age infant.

OBJECTIVE: Birth weight is a function of gestational age. Various maternal and infant characteristics also affect birth weight. This study sought to adjust for these factors to better define abnormal growth. STUDY DESIGN: Maternal and infant characteristics from normal pregnancies were correlated with birth weight. A formula was developed and applied to a second group in which we compared perinatal outcomes in normally grown infants with those who were small for gestational age. We compared outcomes between small-for-gestational-age infants defined by the formula with those defined by conventional tables. RESULTS: Infants defined by the formula as small-for-gestational-age were more likely to have morbidity and mortality than those who were normally grown (p < 0.001). Small-for-gestational-age infants defined by the formula had more deaths and adverse outcomes than those defined by gestational age. CONCLUSION: Adjusting birth weight standards for maternal and infant characteristics may improve the prediction of adverse outcomes.

Surgery for pancreatic tumors during pregnancy: a case report and review of the literature.

Seven cases of surgery of pancreatic tumors during pregnancy have been reported in the literature. Six of the cases resulted in live term births. The patient discussed herein, a 37-year-old para 2-0-0-2 white female, had surgery for the removal of a pancreatic mass at 20 2/7 weeks' gestation. No intraoperative complications occurred, and both mother and fetus appeared to have done well. The postoperative course was complicated by pseudomembranous enterocolitis caused by C. difficile, which was treated with antibiotics. Despite treatment, diarrhea continued, and the patient was readmitted to the hospital for hydration and further antibiotics at 27 weeks. Three days after admission, the fetus was noted to have poor biophysical testing and a caesarean delivery was performed. The infant was found to have a large intracerebral hemorrhage, which most likely occurred antenatally, and life support was discontinued shortly after birth. We conclude from this that surgery for a pancreatic mass in pregnancy should be approached cautiously, and the risk to both the mother and fetus should be considered.

Molecular genotyping of fetal platelet antigens with uncultured amniocytes.

OBJECTIVE: Amino acid substitutions in platelet membrane glycoproteins result in alloantigens implicated in neonatal alloimmune thrombocytopenia. We report the use of the reverse dot blot technique to genotype the five major fetal platelet alloantigens from amniotic fluid cells. STUDY DESIGN: We evaluated a patient with Bakb platelet antibodies who had a previous pregnancy complicated by fetal intracranial hemorrhage. The father was heterozygous Baka/Bakb, giving the pregnancy a 50% risk for platelet incompatibility between mother and fetus. Amniotic fluid was obtained at 16 weeks. Deoxyribonuleic acid was extracted from uncultured amniocytes and amplified with polymerase chain reaction. These products were hybridized to filters containing oligonucleotides specific for each of the 10 different platelet antigen alleles. Reactivity was detected with a chromogenic substrate. RESULTS: The reverse dot blot genotyping of uncultured amniocytes revealed the fetus to be Baka/Baka, thus not at risk for neonatal alloimmune thrombocytopenia. CONCLUSION: Precise knowledge of fetal platelet type by amniocentesis could obviate the need for fetal blood sampling and significantly alter prenatal management of neonatal alloimmune thrombocytopenia.

The use of polymerase chain reaction to determine fetal RhD status.

OBJECTIVE: Our purpose was (1) to establish the accuracy of a deoxyribonucleic acid amplification method in determination of RhD status in adult blood samples, including weak D variants (previously referred to as Du) and a D mosaic, and (2) to apply the method to determine fetal RhD status in alloimmunized pregnancies. STUDY DESIGN: Twenty-five adult blood samples, including five weak D variants and one D mosaic, were analyzed with a polymerase chain reaction to determine RhD type. The method was then applied to amniotic fluid samples obtained by amniocentesis from three RhD-negative women with known RhD sensitization. RESULTS: RhD type determined by polymerase chain reaction for all adult blood samples agreed with serologic typing results. All weak D variants and the D mosaic gave results consistent with RhD positivity. Fetal RhD status was determined in each of the three alloimmunized pregnancies, and obstetric management decisions were made on the basis of these results. CONCLUSIONS: This polymerase chain reaction method allows rapid and accurate determinations of fetal RhD status by amniocentesis. Fetal blood sampling or serial amniocenteses may be avoided when the fetus is RhD negative, and plans for surveillance and intervention can be confidently made if the fetus is RhD positive. However, before the widespread use of this assay, its sensitivity and specificity must be established. Because weak D variants and a D mosaic demonstrated RhD-positive status by polymerase chain reaction, the method described is applicable to these RhD variants.