Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia.

Adverse placental effect of formic acid on hCG secretion is mitigated by folic acid.

AIMS: Formic acid has recently been detected in maternal blood and umbilical cord blood of infants born to alcohol abusing mothers. This toxic metabolite of methanol requires folate for detoxification. We hypothesized that formic acid produced in the maternal circulation will transfer across the placenta and will be toxic to the placenta. Our objectives were, first, to determine whether formic acid transfers across the human placenta and whether it is toxic to the placenta and second, to determine whether folate can decrease transplacental transfer of formic acid and mitigate toxicity. METHODS: Dual perfusion of a single placental lobule ex vivo was used to characterize the transfer of formic acid across the placenta. After a 1-h control period, formic acid (2 mM) was introduced into the maternal circulation with (n = 4) or without folate (1 µM) (n = 4) and was allowed to equilibrate for 3 h. RESULTS: Formic acid transferred rapidly from the maternal to the fetal circulation, and transfer was not altered with the addition of folate. Compared with the control period, there was a significant decrease in hCG secretion (P = 0.03) after addition of formic acid. The addition of folic acid to the perfusate mitigated the decrease in hCG. CONCLUSIONS: Formic acid rapidly transfers across the placenta and thus has the potential to be toxic to the developing fetus. Formic acid decreases hCG secretion in the placenta, which may alter steroidogenesis and differentiation of the cytotrophoblasts, and this adverse effect can be mitigated by folate.

Is severe macrosomia manifested at 11-14 weeks of gestation?

OBJECTIVE: To determine the association between fetal biometry in the first or early second trimester and severe macrosomia at delivery. METHODS: This case-control study included 30 term severely macrosomic neonates; 90 appropriate-for-gestational age (AGA) neonates served as controls. All pregnancies underwent nuchal translucency (NT) screening at 11-14 weeks' gestation. Pregnancies were dated by accurate last menstrual period consistent with crown-rump length (CRL) measurements at the time of screening, early pregnancy CRL or date of fertilization. The association between birth weight and the difference between the measured and the expected CRL at the time of NT screening was analyzed. RESULTS: The difference between measured and expected CRL, expressed both in mm and in days of gestation, was statistically greater in the severely macrosomic neonates compared with controls (mean, 6.66 +/- 4.78 mm vs. 1.17 +/- 4.6 mm, P < 0.0001 and 3 +/- 2.2 days vs. 0.5 +/- 2.3 days, P < 0.0001, respectively). Furthermore, there were significant correlations between the extent of macrosomia and the discrepancy between expected and measured fetal size at the time of NT screening (r = 0.47, P < 0.01 and r = 0.48, P < 0.01, respectively). CONCLUSION: Severe macrosomia apparently manifests as early as 11-14 weeks' gestation.

A comparison between acoustic output indices in 2D and 3D/4D ultrasound in obstetrics.

OBJECTIVE: Three-dimensional (3D) ultrasound is gaining popularity in prenatal diagnosis. While there are no studies regarding the safety of 3D ultrasound, it is now widely performed in non-medical facilities, for non-diagnostic purposes. The present study was aimed at comparing the acoustic output, as expressed by thermal index (TI) and mechanical index (MI), of conventional two-dimensional (2D) and 3D/4D ultrasound during pregnancy. METHODS: A prospective, observational study was conducted, using three different commercially available machines (iU22, Philips Medical Systems; Prosound Alfa-10, Aloka; and Voluson 730 Expert, General Electric). Patients undergoing additional 3D/4D ultrasound examinations were recruited from those scheduled for fetal anatomy and follow-up exams. Fetuses with anomalies were excluded from the analysis. Data were collected regarding duration of the exam, and each MI and TI during 2D and 3D/4D ultrasound exams. RESULTS: A total of 40 ultrasound examinations were evaluated. Mean gestational age was 31.1 +/- 5.8 weeks, and mean duration of the exam was 20.1 +/- 9.9 min. Mean TIs during the 3D (0.27 +/- 0.1) and 4D examinations (0.24 +/- 0.1) were comparable with the TI during B-mode scanning (0.28 +/- 0.1, P = 0.343). The MIs during the 3D volume acquisitions were significantly lower than those in the 2D B-mode ultrasound studies (0.89 +/- 0.2 vs. 1.12 +/- 0.1, P = 0.018). The 3D volume acquisitions added 2.0 +/- 1.8 min of actual ultrasound scanning time (i.e. not including data processing and manipulation, or 3D displays, which are all post-processing steps). The 4D added 2.2 +/- 1.2 min. CONCLUSIONS: Acoustic exposure levels during 3D/4D ultrasound examination, as expressed by TI, are comparable with those of 2D B-mode ultrasound. However, it is very difficult to evaluate the additional scanning time needed to choose an adequate scanning plane and to acquire a diagnostic 3D volume.

The hazards to practitioners of obstetric and gynecological ultrasound.

OBJECTIVES: To investigate the specific complaints of physicians and technicians performing obstetric and gynecological ultrasound. METHODS: This was a cross-sectional retrospective survey. Questionnaires were distributed to members of the Israeli Society of Gynecological Ultrasound, including questions on gender and profession, number and type of scans performed, pain related to profession and any therapy undergone. Statistical analysis included chi-square or Fisher's exact test, Student's t-test, Pearson's correlation coefficient and logistic regression. RESULTS: Joint pain was reported by 51.7% (30/58) of the technicians compared with 25.3% (19/75) of the physicians (P = 0.002). It was more common in females than in males (P = 0.05) and it was more common among those who performed transabdominal sonography more frequently than they did transvaginal sonography (P = 0.004). There was a significant association between performing transabdominal ultrasound and back pain (P = 0.05). Although females reported pain more frequently, the rate of surgical procedures was higher among males (P < 0.05). CONCLUSIONS: A technician is 3.5 times more likely to report joint pain than is a physician. Transabdominal sonography is a risk for both joint and back pain. There may be gender differences in pain perception.

Incidence, obstetric risk factors and pregnancy outcome of preterm placental abruption: a retrospective analysis.

OBJECTIVE: To determine obstetric risk factors for the occurrence of preterm placental abruption and to investigate its subsequent perinatal outcome. STUDY DESIGN: A retrospective comparison of all singleton preterm deliveries complicated with placental abruption, between the years 1990-1998, to all singleton preterm deliveries without placental abruption, in the Soroka University Medical Center. RESULTS: Placental abruption complicated 300 (5.1%) of all preterm deliveries (n = 5934). A backstep multivariable analysis found the following factors to be independently correlated with the occurrence of preterm placental abruption: grandmultiparity (more than five deliveries), early gestational age, severe pregnancy-induced hypertension, previous second-trimester bleeding and non-vertex presentation. These pregnancies had a significantly lower rate of preterm premature rupture of membranes than preterm pregnancies without placental abruption. Pregnancies complicated with preterm placental abruption had significantly higher rates of cord prolapse, non-reassuring fetal heart rate patterns, congenital malformations, Cesarean deliveries, perinatal mortality, Apgar scores lower than 7 at 5 min, postpartum anemia and delayed discharge from the hospital than did preterm deliveries without placental abruption. In order to assess whether the increased risk for perinatal mortality was due to the placental abruption, or due to its significant association with other risk factors, a multivariable analysis was constructed with perinatal mortality as the outcome variable. Placental abruption (OR 3.0, 95% CI 2.1-4.1) as well as cord prolapse, previous perinatal death, low birth weight and congenital malformations were found to be independent risk factors for perinatal mortality. CONCLUSION: Preterm placental abruption is an unpredictable severe complication associated with significant perinatal morbidity and mortality. Factors found to be independently associated with placental abruption were grandmultiparity, severe pregnancy-induced hypertension, malpresentation, earlier gestational age and a history of second-trimester vaginal bleeding.

[Hormone replacement therapy and the risk of breast cancer].

There is a growing use of hormone replacement therapy during menopause in the western world. Although most of epidemiologic studies have not found a cause-effect relation between this therapy and breast cancer, the fear of breast cancer related to this therapy limits its vast use. Controversy continues to surround the issue of the relationship between postmenopausal hormone therapy and the risk of breast cancer. Physicians, willing to prescribe this treatment, have often been asked by their patients if these hormones can cause breast cancer. Sufficient evidence exists to indicate the possibility of a slightly increased risk of breast cancer with long duration of hormone replacement therapy. However, the epidemiologic data on this cause and effect relation are inconsistent. Therefore, they cannot provide a definitive conclusion on this issue. Furthermore, evidence has shown that women treated with hormone replacement therapy have only localized disease with less metastasis than non-users. This might be due to detection/surveillance bias, but it might also be due to acceleration/deceleration of preexisting disease that reflects our misunderstanding of the breast cancer pathogenesis. Hormone replacement therapy has a cardinal role in the treatment and prevention of immediate and late sequela of menopause such as osteoporosis, cardiovascular diseases, urinary incontinence, etc. A large group of doctors such as family doctors, orthopedics, cardiologist, gynecologists and others recommend this therapy. Patients must also consider all the risks and advantages in their informed decision-making. Therefore we believe that it is important to review this treatment in connection with breast carcinoma.

Multiple pregnancies in women after renal transplantation. Case report that rises a management dilemma.

OBJECTIVES: To report the pregnancy outcome in women with multiple pregnancies after renal transplantation. MATERIALS AND METHODS: We report two cases of multiple pregnancies (triplets and twins) in renal allograft recipients and evaluate the pregnancy courses and maternal and fetal outcome of these patients. RESULTS: After fetal reduction from triplet to twin pregnancy the first patient delivered healthy twin babies at 36 weeks gestation. Six months after delivery the woman is well with no signs of renal function impairment. Although the second patient did not meet the optimal criteria for consideration of pregnancy in renal transplant recipients, she delivered normal twin babies at 33 weeks' gestation. Maternal complications during pregnancy included preeclampsia, mild deterioration of renal function tests, and secondary complications due to drug therapy that was resolved after delivery. No graft rejection episodes were noted in either case during pregnancy. CONCLUSIONS: Multifetal gestation in renal allograft recipients represents a high-risk pregnancy that should be managed at a tertiary care institution. The overall outcome in properly consulted patients can be considered favorable. Based on our limited experience with two cases, we suggest reduction of triplets to a twin pregnancy which is consistent with the current literature data.

Elevated concentrations of interleukin-6 in intra-amniotic infection with Ureaplasma urealyticum in asymptomatic women during genetic amniocentesis.

BACKGROUND: Intra-amniotic infection is an important cause of preterm delivery and interleukin-6 (IL-6) determination was recently applied for identification of microbial invasion of the amniotic cavity. Our aim was to determine the levels of IL-6 in culture-positive amniotic fluids at genetic amniocentesis and to evaluate their significance in relation to pregnancy outcome. METHODS: Seven culture-positive and 23 culture-negative amniotic fluids, obtained at 17-19 weeks of gestation, were analyzed for IL-6 levels by an immunoassay (ELISA). Pregnancy outcomes of all 30 women were obtained from the medical charts. RESULTS: The mean level of IL-6 in the culture-negative amniotic fluids was 78+/-206 pg/ml. Among the seven culture-positive, high levels of IL-6 were found only in three amniotic fluids that were culture-positive for Ureaplasma urealyticum (1834, 1342 and 2832 pg/ml). Low levels of IL-6, ranging from zero to 60 pg/ml, were found in four AFs that were culture-positive for Staphylococcus epidermidis (n=3) and Bacillus Gram-positive (n= 1). Adverse pregnancy outcome occurred in the three women who had intra-amniotic infection with U. urealyticum accompanied by high levels of IL-6 (two fetal loss and one preterm delivery at 28 weeks of gestation). The four women with culture-positive but IL-6 negative amniotic fluids, had normal pregnancy outcome and term delivery. Two of the 23 women with culture-negative had preterm delivery, one with high (1000 pg/ml) and one with low (80 pg/ml) levels of IL-6. CONCLUSION: High levels of IL-6 are suggestive of a genuine intra-amniotic infection with urea-plasmas resulting in adverse pregnancy outcome, while culture-positive amniotic fluids with normal IL-6 levels, may suggest a state of contamination.

[Brucellosis in pregnancy].

Brucellosis is rare in pregnancy. Recently, an increase in the incidence of this disease has been observed in our area. We present 7 cases of brucellosis in pregnancy and review the literature on the effects of brucellosis on the outcome of pregnancy. Brucellosis is rare in the Middle East and Africa and the most common source of infection is unpasteurized milk products. Brucella is a coccobacillus, gram-negative bacterium, whose hosts are mostly animals. There is controversy about the relationship between brucellosis and the outcome of pregnancy. There is some evidence that there is a higher rate of complications such as abortion, premature rupture of membranes and preterm delivery in infected animals. Reasons for this difference in the impact of brucella in animals and man include the absence of the carbohydrate erythritol in the human placenta, which appears to be a preferential medium and growth factor for brucella in the placentas of animals. There is uncertainty regarding effects of brucella in early pregnancy and no evidence of its transplacental passage in later pregnancy, causing adverse obstetrical outcome, although recently there has been a single report of Brucella abortus (biotype 2). We present 7 cases of brucellosis in pregnant women found between 1977-1988. Its incidence among the women who delivered here is 0.007% (7/92, 768 deliveries). Our first case was complicated by preterm premature rupture of membranes and preterm delivery in the 20th week of gestation. In 2 other cases there was preterm delivery with 1 developing clinical chorioamnionitis. The 4 remaining women delivered at term, although 1 had preterm premature rupture of membranes and intra-uterine growth retardation, and 2 had postpartum endometritis.