Cardiac axis in fetuses with abdominal wall defects.

OBJECTIVES: To investigate whether fetal cardiac axis is affected by the presence of an abdominal wall defect (AWD) independent of congenital heart disease (CHD). METHODS: Video ultrasound records from fetuses with AWDs identified from 1991-2004 were reviewed. Still images of the fetal cardiac four-chamber view were digitized and two independent examiners measured the cardiac axis. A cardiac axis of >65 degrees or <25 degrees was considered abnormal. Maternal charts were reviewed for fetal echocardiogram results and neonatal charts were reviewed for confirmation of CHD and type of AWD. RESULTS: Of 17 fetuses with omphalocele and 42 fetuses with gastroschisis, 16 (27%) fetuses had an abnormal cardiac axis, while only seven (12%) had CHD. Fifty-nine percent of fetuses with omphalocele had an abnormal cardiac axis and 35% had CHD. Fourteen percent of fetuses with gastroschisis had an abnormal cardiac axis and 2% had CHD. Of 43 fetuses with a normal cardiac axis, only one had CHD. CONCLUSIONS: Fetal cardiac axis is often affected by the presence of an AWD independent of CHD. A normal cardiac axis in fetuses with AWDs is an accurate predictor of the absence of CHD, the negative predictive value being 97.7%.

Gender-related differences in fetal heart rate during first trimester.

OBJECTIVE: Many expecting parents wish to ascertain fetal gender early in pregnancy. Our goal was to determine whether fetal heart rate (FHR) of males and females during the first trimester is significantly different. MATERIALS AND METHODS: From November 1997 to February 2003 we enrolled pregnant women with singleton gestations who underwent obstetric sonography at less than 14 weeks of gestational age. Indications for the sonographic study included first-trimester bleeding, uncertain gestational dating, poor obstetrical history, and aneuploidy screening by nuchal translucency. The sonographic studies were performed by a single sonographer and reviewed by the first author. The FHR was determined by m-mode. All subjects underwent second-trimester sonography at 18.0-24.0 weeks' gestation by the same team, and fetal gender was recorded. Multiple gestations, miscarriages and pregnancies with uncertain fetal gender were excluded. Sonographically assigned fetal gender was confirmed at delivery. RESULTS: Of the 966 first-trimester studies performed, 477 met the inclusion criteria. Of these, 244 (51%) were female and 233 (49%) were males. There were no statistical differences in mean maternal age, gravidity, parity, and mean gestational age at the time of the first study (9.0 +/- 2.3 weeks for female fetuses and 9.0 +/- 2.3 weeks for males, p = 0.7). The average female FHR was 151.7 +/- 22.7 bpm and male FHR was154.9 +/- 22.8 bpm (p = 0.13). DISCUSSION: Contrary to beliefs commonly held by many pregnant women and their families, there are no significant differences between male and female FHR during the first trimester.

The effect of a single course of antenatal corticosteroids on maternal adrenal function at term.

OBJECTIVE: To determine if one course of antenatal corticosteroids at 32 weeks produces maternal adrenal suppression at term. METHODS: The adrenocorticotropic hormone (ACTH) stimulation test was administered at 38 weeks to 11 pregnant women who had received a single course of antenatal betamethasone prior to 33 weeks and to six control subjects. RESULTS: There was no difference in basal cortisol levels (mean+/-standard deviation) between the two groups: 41.6+/-6.9 microg/dl for controls versus 36.0+/-7.8 microg/dl for the steroid group, p=0.16. Peak cortisol levels at 45 min following ACTH stimulation were not different: 61.6+/-3.5 microg/dl for controls versus 55.0+/-2.6 microg/dl for the steroid group, p=0.16. The power of the study to detect a statistical difference in the observed peak cortisol levels was greater than 95%. None of the study subjects had laboratory criteria or clinical signs of adrenal suppression. CONCLUSIONS: A single course of betamethasone for women at risk for preterm delivery does not produce adrenal insufficiency at term and stress dose steroids are not recommended.

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.

The effects of repeat doses of antenatal corticosteroids on maternal adrenal function.

OBJECTIVE: The purpose of this study was to determine whether repeated doses of maternal corticosteroids suppress the maternal hypothalamic-pituitary-adrenal axis. STUDY DESIGN: The low-dose corticotropin stimulation test (1.0 microg intravenously) was administered a median of 3 days after the last betamethasone dose to 18 pregnant women who had received at least 2 weekly courses of antenatal betamethasone and to 6 control subjects matched for gestational age who had not received antenatal corticosteroids. RESULTS: The mean basal cortisol level was significantly depressed among women who had received betamethasone with respect to control subjects (1.9 +/- 1.5 vs 26.5 +/- 6.2 microg/dL; P <.001). The maternal cortisol level after corticotropin stimulation was significantly lower in all women who had received betamethasone (P <. 001). The mean time to attainment of peak cortisol level was significantly longer among women who had received betamethasone than among control subjects (37 +/- 6.8 vs 27.4 +/- 1.6 minutes; P <.001). CONCLUSIONS: Repeated courses of betamethasone lead to barely detectable maternal basal cortisol levels and secondary adrenal insufficiency.

Effect of digital cervical examination on the expression of fetal fibronectin.

OBJECTIVE: To determine whether oncofetal fibronectin (fFN) assays from symptomatic women are influenced by digital examination of the cervix. STUDY DESIGN: Cervicovaginal fFN specimens were obtained from women at 22-34 weeks' gestational age with symptoms of preterm labor immediately prior to a digital examination of the cervix and two hours after. Fetal fibronectin was assayed by a specific enzyme-linked immunoassay. Results were reported as positive (> or = 50 ng/mL) or negative (< 50 ng/mL). Paired initial and repeat fFN results were compared for statistical difference, and the clinical outcomes were used to assess the accuracy of the initial and repeat results. RESULTS: Fifty symptomatic women at an average gestational age of 29.3 +/- 2.0 weeks were enrolled. Eighty-six percent of the repeat fFN results remained unchanged after a digital examination, (P = .26, beta = .2). The predictive value of a negative fFN obtained after a digital examination was 97% for the absence of spontaneous preterm delivery in < 8 or < 15 days. Two of 16 initially positive results became negative after an examination, and one patient delivered two days later. Five of 34 initially negative fFN results became positive after an examination, and 5/5 delivered more than seven days later. CONCLUSION: Digital examination of the cervix has an effect on fFN results. The routine use of fFN after a digital examination is not recommended.

Prostaglandin E2 cervical ripening without subsequent induction of labor.

OBJECTIVE: To determine whether outpatient administration of intracervical prostaglandin (PG) E2 gel decreases the interval to delivery and duration of labor. METHODS: A randomized, double-blind, placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks' or greater gestation with Bishop scores less than 9. Transvaginal cervical length, fetal fibronectin, and Bishop score were assessed before gel placement. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed. RESULTS: Thirty women were assigned to PGE2 and 31 to placebo. There were no significant demographic differences between the groups and there were no differences in cervical length, fetal fibronectin status, or Bishop scores. Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement (P = .007). The median interval to delivery was significantly shorter in the PGE2 group, at 2.5 days, compared with placebo, at 7 days (P = .02). Nulliparas in the PGE2 group had a median interval to delivery of 2 days, compared with 7 days for nulliparas receiving placebo (P = .03). Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2. CONCLUSION: Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor.

Management of pregnancies complicated by anti-Kell isoimmunization.

OBJECTIVE: To assess the efficacy of managing pregnancies complicated by anti-Kell isoimmunization using the methods developed for evaluating anti-Rh-D isoimmunization. METHODS: We reviewed 156 anti-Kell-positive pregnancies seen from 1959 to 1995, which were managed with serial maternal titers, amniotic fluid deltaOD450 determination, and funipuncture. Data on maternal titers, paternal phenotypes, invasive fetal testing and therapies, and neonatal outcomes were collected and analyzed to determine whether severely affected pregnancies were identified in time for successful fetal and neonatal therapy. RESULTS: Twenty-one fetuses were affected, eight with severe disease, and two fetuses in this group died. All of the severely affected fetuses were associated with maternal serum titers of at least 1:32. A critical titer of 1:32 was found to be 100% sensitive for identifying the affected pregnancies. The affected group had significantly higher amniotic fluid deltaOD450 values over the range of gestational ages than did the unaffected group (P < .001). The upper Liley curve was a specific discriminator for the diagnosis of affected fetuses, and the lower curve was specific for the diagnosis of unaffected or mild cases. CONCLUSION: Fetal anemia due to anti-Kell isoimmunization might be due in part to erythropoietic suppression, but it is still largely a hemolytic process. The methods based on a hemolytic process, including use of a critical maternal serum titer of 1:32, serial amniotic fluid analyses when the titer was exceeded, and liberal use of funipuncture, were successful in identifying severely affected fetuses.

Group B streptococcal infections.

Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible for significant neonatal morbidity and mortality. Group B streptococcus is also the causative agent in 50,000 maternal infections per year. Approximately 30% of women have asymptomatic group B streptococcal colonization at some time during pregnancy, but the neonatal attack rate is only about 2 per 1,000 deliveries. Maternal and neonatal risk factors contribute to the rates of vertical transmission and symptomatic neonatal disease. Options that have been investigated for prevention of neonatal group B streptococcal disease include identification of at-risk pregnancies as well as antenatal, intrapartum, and neonatal treatment. The intrapartum treatment of women at risk for vertical transmission of group B streptococcus to their neonates unequivocally has been shown to decrease the rate of neonatal colonization. Practitioners should implement one of two strategies that incorporate intrapartum prophylaxis for prevention of perinatal group B disease.

Interleukin-1 alpha, epidermal growth factor, and transforming growth factor-beta exhibit differential kinetics on endothelin-1 synthesis in amnion cells.

OBJECTIVE: To investigate the effects of three cytokines, interleukin-1 alpha (IL-1 alpha), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta), on the regulation of endothelin-1 (ET-1) mRNA and protein production in human amnion cells. METHODS: Human amnion cells were harvested from uncomplicated pregnancies undergoing elective cesarean delivery at term and grown in primary monolayer culture. Cells were treated with IL-1 alpha, EGF, and TGF-beta for dose-response and time course experiments. Northern analysis was used to determine ET-1 mRNA expression, and enzyme-linked immunosorbent assay was used for ET-1 peptide determination. RESULTS: Interleukin-1 alpha, EGF, and TGF-beta induced the expression of ET-1 mRNA and protein in a dose- and time-dependent fashion. The kinetics of ET-1 mRNA production did not differ markedly with respect to the inducing cytokine, but the kinetics of ET-1 protein production was quite different. Interleukin-1 alpha and EGF stimulated a rapid increase in ET-1 that peaked by 24 hours, and the levels declined to just above the detection limit by 72 hours. In contrast, TGF-beta-stimulated cells showed modest ET-1 production at early times (4-24 hours) and then gradually increased and peaked at 72 hours. CONCLUSIONS: Cytokines modulate the expression of ET-1 mRNA and its cognate protein in human amnion cells. The differential kinetics of ET-1 peptide expression in amnion cells suggests that ET metabolism as well as synthesis contribute to the net expression of endothelin in amnion.

The potential for ozone depletion in the arctic polar stratosphere.

The nature of the Arctic polar stratosphere is observed to be similar in many respects to that of the Antarctic polar stratosphere, where an ozone hole has been identified. Most of the available chlorine (HCl and ClONO(2)) was converted by reactions on polar stratospheric clouds to reactive ClO and Cl(2)O(2) throughout the Arctic polar vortex before midwinter. Reactive nitrogen was converted to HNO(3), and some, with spatial inhomogeneity, fell out of the stratosphere. These chemical changes ensured characteristic ozone losses of 10 to 15% at altitudes inside the polar vortex where polar stratospheric clouds had occurred. These local losses can translate into 5 to 8% losses in the vertical column abundance of ozone. As the amount of stratospheric chlorine inevitably increases by 50% over the next two decades, ozone losses recognizable as an ozone hole may well appear.

Inhibition of recovery from potentially lethal radiation damage in A549 cells by the K+/H+ ionophore nigericin.

A549 cells held for 4 hr in Hank's balanced salt solution, after 10 Gy irradiation, exhibit potentially lethal damage recovery (PLDR) which is dependent on extracellular pH (pHe). Recovery factors of 2.2 to 3.5 are observed when pHe is 6.40 to 7.30, but recovery factors of less than 1.0 are found when pHe is reduced to 6.20 or 6.00. The K+/H+ ionophore nigericin, when added to cells post-irradiation, inhibits PLDR in a pHe-dependent manner; it is increasingly more effective as pHe is reduced from 6.80 to 6.40. The presence of nigericin thus causes inhibition of PLDR at pHe's that normally promote recovery. The drug does not affect radiation response of A549 cells when present only during irradiation. Effects of low pHe buffer, with and without nigericin, on intracellular pH (pHi) and on ATP levels were examined in an effort to elucidate the mechanisms for inhibition of PLDR and enhancement of radiation response. Incubation of cells in pHe 6.00 buffer results in a slight decrease in pHi and does not induce a drop in ATP levels. In contrast, post-irradiation incubation of cells in pHe 6.40 buffer containing 2 microM nigericin causes an immediate and dramatic decrease in pHi, and a gradual loss of ATP to 30% of control levels by 4 hr. The data obtained so far suggest that a very slight lowering of pHi may influence post-irradiation holding recovery, and that the mechanisms by which pHe 6.00 buffer alone, or pHe 6.40 buffer containing nigericin, affect holding recovery are different.