Sean Blackwell

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization

Background Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. Methods We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. Results Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; an...

The impact of maternal obesity on midtrimester sonographic visualization of fetal cardiac and craniospinal structures

OBJECTIVE: To examine the impact of maternal obesity on the rate of suboptimal ultrasound visualization (SUV) of fetal anatomy and determine the optimal timing of prenatal ultrasound examination for the obese gravida.METHODS: A computerized ultrasound database was used to identify ultrasound examinations for singleton gestations performed between 140/7 and 236/7 weeks at a tertiary care, university-based hospital. Patients were divided into four groups and categorized based on body mass index (BMI): nonobese (BMI <30 kg/m2), class I obesity (30≤BMI<35 kg/m2), class II obesity (35≤BMI<40 kg/m2), and extreme obesity (BMI ≥40 kg/m2). The rates of SUV for fetal cardiac and craniospinal structures were calculated for each group and compared.RESULTS: A total of 11 019 pregnancies were studied, of which 38.6% of the patients were obese. Overall, the rate of SUV of the fetal structures was higher for obese compared to nonobese women for both cardiac (37.3 [1723/4200] vs 18.7% [1275/6819]; P<0.0001) and craniospinal structures (42.8 [1798/4200] vs 29.5% [2012/6819]; P<0.0001). Increased severity of maternal obesity was associated with SUV rate for both the cardiac (nonobese 18.7% [1275/6819], class I 29.6% [599/2022], class II 39.0% [472/1123], and extreme obesity 49.3% [580/1055]; P<0.0001) and for the craniospinal structures: (nonobese 29.5% [2012/6819], class I 36.8% [744/2022], class II 43.3% [486/1123], and extreme obesity 53.4% [563/1055]; P<0.0001). With increasing gestational age at examination, the rate of SUV decreased for both obese and nonobese women. However, for obese women there was minimal improvement in visualization after 18–20 weeks. Even after adjustment for gestational age and the type of ultrasound machine, obese women (class I, class II, and extreme obesity) were still associated with increased odds for SUV of the fetal cardiac and craniospinal structures compared to nonobese women.CONCLUSION: Maternal obesity increases the rate of SUV for the fetal cardiac structures by 49.8% and for the craniospinal structures by 31%. The optimal gestational age for visualization of fetal cardiac and craniospinal anatomy in obese patients may be after 18–20 weeks.

Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes

Objective: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. Study design: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI and calprotectin in amniotic fluid were determined by specific and sensitive immunoassays. Placentae of patients in both preterm labor with intact membranes and preterm PROM groups who delivered within 72 h of amniocentesis were examined. Non-parametric statistics, receiver-operating characteristic (ROC) curves and Cox regression models were used for analysis. A p value of < 0.05 was considered statistically significant. Results: Intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin in both women with preterm labor and intact membranes, and women with preterm PROM. Preterm PROM was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Preterm parturition was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin, while parturition at term was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3. Among patients with preterm labor and intact membranes, elevation of amniotic fluid HNP 1-3, BPI and calprotectin concentrations was associated with intra-amniotic inflammation, histological chorioamnionitis and a shorter interval to delivery. Conclusion: MIAC, preterm parturition and preterm PROM are associated with increased amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Moreover, elevated amniotic fluid concentrations of BPI, immunoreactive HNP 1-3 and calprotectin are associated with intra-amniotic inflammation, histological chorioamnionitis and shorter amniocentesis-to-delivery interval in patients presenting with preterm labor with intact membranes.

Suboptimal second-trimester ultrasonographic visualization of the fetal heart in obese women: should we repeat the examination?

The purpose of this study was to determine whether a repeated antenatal ultrasound examination improves fetal cardiac visualization for the obese and nonobese population.

What factors are associated with neonatal injury following shoulder dystocia

Objective:To identify factors associated with the development of neonatal injury in the setting of shoulder dystocia.Study design:Medical record ICD-9 codes and a computerized perinatal database were reviewed to identify cases of shoulder dystocia from January 1996 to January 2001 in a tertiary care center. For confirmation of the diagnosis and collection of data, both maternal and neonatal charts were then reviewed and neonatal injuries categorized as either neurological (brachial plexus injury) or skeletal (clavicular fracture, humeral fracture). Shoulder dystocia cases were divided into groups based on the presence of neonatal injury at delivery or at discharge (with or without Erbs palsy). The group with neonatal injury was compared for demographic and obstetrical factors to the group without injury (control). χ 2 test, Mann–Whitney test and logistic regression were used as appropriate.Results:During this 5-year period, there were 25 995 deliveries and 206 (0.8%) confirmed cases of shoulder dystocia. Of these cases, 36 (17.5%) had neonatal injury diagnosed at delivery and 25 (12%) remained with significant residual injury at discharge. Of these there were 19 cases of Erbs palsy and six cases of clavicular fracture. No association was found between neonatal injury and maternal age, ethnicity, diabetes, operative vaginal delivery or number of obstetrical maneuvers. However, maternal body mass index >30 kg/m2, a second stage of labor >20 min and a birth weight >4500 g were all associated with an increased risk of neonatal injury at delivery and at discharge, including Erbs palsy. After logistic regression analysis, only a second stage of delivery >20 min remained significantly associated with neonatal injury at discharge.Conclusion:In our population, maternal obesity was associated with an increased risk of neonatal injury after shoulder dystocia. In addition, a short second stage of labor (<20 min) was associated with a lower rate of neonatal injury.

Maternal and fetal inflammatory responses in unexplained fetal death.

Objective: The role of intra-amniotic infection in the etiology of fetal death has been proposed. This study was conducted to determine the prevalence of microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal and/or fetal inflammation in patients presenting with a fetal death. Methods: A prospective study was conducted in patients with a fetal death. Amniocenteses were performed for clinical indications (karyotype), as well as to assess the microbiological and cytological state of the amniotic cavity. Fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. An amniotic fluid white blood cell count and glucose determinations were also performed. Histological examination of the placenta was conducted to identify a maternal inflammatory response (acute chorioamnionitis) or a fetal inflammatory response (funisitis). Results: This study included 44 patients with intrauterine fetal death. The median gestational age at diagnosis was 30.1 weeks (range 16.3-40.4 weeks). One patient had documented MIAC (1/44). Acute histological chorioamnionitis was found in 20.9% (9/43), but a fetal inflammatory response was observed in only 2.3% (1/43) of cases. One patient had a positive amniotic fluid culture for Streptococcus agalactiae (group B streptococcus). Conclusion: Histological chorioamnionitis was present in 20.9% of cases, but MIAC could be demonstrated with conventional microbiological techniques in only one case. A fetal inflammatory response was nine times less frequent than a maternal inflammatory response (maternal 20.9% vs. fetal 2.3%, p = 0.008) in cases of fetal death.

Congenital diaphragmatic hernia: associated anomalies and antenatal diagnosis. Outcome-related variables at two Detroit hospitals.

This retrospective study reviews the medical records of 77 fetuses and babies with congenital diaphragmatic hernia (CDH) referred to two hospitals in Detroit from 1986 through 2000. The aims were to examine the effects on outcome of multiple variables, especially the type of CDH, associated anomalies, and ultrasound prognostic parameters. Ultrasound measurements of head (HC), chest (CC), and abdominal circumferences (AC) were obtained from videotapes. ANOVA and chi-square analysis were used to determine statistical significance between groups and proportions. Eighty-nine percent (65/73) of pregnancies resulted in live births, and 54% (35/65) of patients survived past 30 days. Liveborn patients with low APGAR scores were less likely to survive. Forty-three percent (30/70) had major associated anomalies, with cardiac anomalies constituting about 52% (33/64) of the major associated anomalies. Seventy percent of patients with isolated CDH survived versus 36% of patients with both CDH and cardiac anomalies. Sixty-seven percent (8/12) of fetuses antenatally diagnosed before 25 weeks of gestation survived past 30 days of birth. The survival rate of right-sided CDH with liver herniation was 80% (8/10), compared with 29% (4/14) for left-sided CDH with liver herniation ( p =0.088). There was a significant linear relationship ( r =0.603, p =0.029) between CC/AC and CC/HC among patients with CDH; survivors had higher CC/AC and CC/HC values than nonsurvivors. These results support the utility of CC/AC and CC/HC measurements and the presence of liver herniation as important prognostic factors that can be used in antenatal counseling and in planning clinical trials.

Subclinical myocardial injury in small-for-gestational-age neonates

Objective: Small-for-gestational-age (SGA) infants are at risk for premature death from cardiovascular disease (myocardial infarction and stroke), hypertension, and diabetes in adult life. Severe intrauterine growth restriction is often associated with subclinical cardiovascular abnormalities detectable during fetal echocardiography. The objective of this study was to determine whether SGA newborns have evidence of myocardial injury at birth. Study design: Cardiac troponin I, a specific marker of myocardial injury widely used for the diagnosis of myocardial infarction in adults, was determined in umbilical cord blood. Umbilical cord venous blood was obtained at the time of birth from 72 SGA newborns (birth weight below the 10th centile for gestational age) and 309 newborns whose birth weights were appropriate for gestational age (AGA). Cardiac troponin I was determined with a commercially available immunoassay (sensitivity 0.2 ng/ml) employed in clinical laboratories (Immulite 2000, Diagnostic Products Corp., Los Angeles, CA). Results: Cardiac troponin I was not detectable in any of the blood samples from AGA infants. In contrast, 4.2% (3/72) of SGA infants had detectable cardiac troponin I in umbilical cord blood (Fishers exact test, p = 0.007). Conclusion: A subgroup of SGA newborns undergoes myocardial injury before birth. This insult may predispose to the development of adult premature cardiovascular disease and death.

Role of amniocentesis for the diagnosis of subclinical intra-amniotic infection in preterm premature rupture of the membranes

The clinical role of amniocentesis in the management of pregnancies that are complicated by preterm premature rupture of the membranes remains unclear. The indiscriminant use of expectant management, corticosteroids, and empiric antibiotic therapy without knowledge of the presence or absence of intra-amniotic infection poses underappreciated risks to the fetus. This clinical opinion presents the argument that amniocentesis should be an integral part of the management of patients with preterm premature rupture of the membranes. The technical aspects of amniocentesis, the associations between subclinical infection and neonatal morbidity, and the limitations of current interventions are reviewed, and suggestions for future studies that are sorely needed are offered.

Timing of Fetal Nucleated Red Blood Cell Count Elevation in Response to Acute Hypoxia

We determined the effect of an acute episode of severe hypoxia on peripheral nucleated red blood cell (RBC) counts in the fetal rat. Timed pregnant rats were randomized to a 2-hour exposure to hypoxia (placement in a chamber containing a gas mixture with 9% O2 +3% CO2 + balanced N2) or to a 2-hour exposure to a sham chamber containing room air. Two maternal animals per group underwent cesarean section immediately after the 2-hour period and then 4, 12, 24, 36, 48, and 60 h after exposure. Fetal nucleated RBC counts were compared between groups at each time interval. The nucleated RBC counts were not significantly different in the hypoxia group until 12 h (mean ± SEM 158.0 ± 22.4 RBC/10 high-power fields vs. 90.6 ± 11.0; p = 0.03) and 24 h (133.2 ± 16.0 vs. 84.1 ± 9.0; p = 0.04) after exposure. There were no differences between groups 36, 48, and 60 h after exposure. In the near-term rat fetus, acute hypoxia was associated with a delayed but transient increase in peripheral nucleated RBC counts.