Phosphorylated insulin-like growth factor binding protein-1 in cervical secretions and sonographic cervical length in the prediction of spontaneous preterm delivery.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the test for the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 (phIGFBP-1) in endocervical secretions in predicting preterm delivery in women with uterine contractions. METHODS: The study included 210 women with a singleton pregnancy with documented uterine contractions and intact membranes at between 24 and 34 weeks' gestation who underwent the cervicovaginal phIGFBP-1 test and transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point for cervical length. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for preterm delivery following univariate analysis. RESULTS: ROC curves indicated that 26 mm was the optimal cut-off value for cervical length in predicting preterm delivery. A cervical length of < 26 mm and the presence of phIGFBP-1 were statistically significant in univariate logistic regression analyses (P < 0.0001) with odds ratios of 16.18 and 9.29 for preterm delivery, respectively. Multivariate analysis of cervical length and phIGFBP-1 showed that they were independent and therefore useful in combination for predicting preterm delivery. CONCLUSIONS: Cervical length and the phIGFBP-1 test are independent variables that can be used together to predict preterm delivery in women with uterine contractions. A sonographically measured cervical length of > 26 mm with a negative phIGFBP-1 test in a patient with regular uterine contractions before 37 weeks' gestation seems to indicate a low risk of preterm delivery and may therefore allow avoidance of unnecessary therapies.

A randomized study to assess two different techniques of aspiration while performing transabdominal chorionic villus sampling.

OBJECTIVE: The technique used to perform transabdominal chorionic villus sampling (CVS) is not standardized, but aspiration of villi is generally obtained by discontinuous vacuum created in a syringe, manually or by a hand-grip device. We evaluated the feasibility of a new method of performing CVS which employs a 4-mL Vacutainer connected to the needle, producing a continuous negative pressure. METHODS: Two hundred pregnant women, whose gestational age ranged from 10 + 2 to 16 + 2 (mean, 12 + 1) weeks, entered the randomized study, which was powered to detect with 90% probability the absence of any difference in the size of chorionic samples obtained by using a 20-mL syringe with the vacuum obtained by a hand-grip device (Group 1) or by a vacutainer (Group 2). Four operators with different levels of experience performed all the procedures, which were done transabdominally using a freehand technique with a 20-gauge needle under ultrasound guidance. RESULTS: Maternal age, body mass index, gestational age and the way the needle was inserted within the chorion were similar in the two groups. The median amount of villi sampled was 20 mg, with no differences between the two groups. The rate of fetal loss was 1.7%. All losses occurred in women of Group 1 who had only one needle insertion. A second needle insertion was required more frequently while using the vacutainer. CONCLUSION: This new technique for performing transabdominal CVS uses a readily available device and is as effective as traditional sampling systems to aspirate villi. It has the advantage of being a one-operator procedure.

Circadian rhythm of maternal blood pressure and fetal growth.

This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 +/- 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1-2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0-1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5-1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier.

[Vaginal swab in pediatric age]. / II tampone vaginale in età pediatrica.

Vaginal secretion sampling in young patients. The aim of the study was to evaluate whether different instrumental tools (the classical cotton swab, the urethral cotton swab, the balloon shape cotton swab and cyto-brush) yield different sampling success in young patients presenting with suspected vulvovaginitis. The study was conducted in a randomised prospective way on 100 children with symptoms of vulvovaginal infection (age range: 4 months -8 years ) seen at the Clinic of Paediatric Gynaecology of the Department of Obstetric and Gynaecology, "V.Buzzi" Children's Hospital, Milano (Italy). Children's compliance and the number of samples which had to be discontinued, because of children's intolerance have allowed the evaluation of each tools. Each of these tools was tested on 25 young patients. The vaginal secretion sampling was not possible on 8 patients out of 25 with cyto-brush (32%), on 7 out of 25 with the balloon shape cotton swab (28%), on 4 out of 25 with the classical cotton swab (16%) and only 1 out of 25 with the urethral cotton swab (4%). In conclusion all the instruments tested allow sampling of vaginal secretion in young children, but the reaction and compliance of the patients has been best with the otologic cotton swab.

Biochemical markers for the prediction of spontaneous pre-term birth.

OBJECTIVES: The aim of this study was to identify predictive biochemical markers for preterm labor. METHODS: In this prospective study we included 225 asymptomatic Caucasian women consecutively enrolled at 24 weeks of gestation. The following data were collected only once at 24 weeks of gestation: vaginal pH, vaginal fFN, cervical and serum concentration of IL-6, IL-8 and TNFalpha, maternal blood serum, ferritin. Student's t-test, the chi(2)-test and multiple linear regression were used as statistical methods. RESULTS: There were no differences between the age of patients, parity and gestational age at sampling between women who delivered at term and those who delivered pre-term (<37 weeks' gestation). There was a significant increase of cervical IL-6 (pre-term 608+/-1595 pg/l vs. at term 58.9+/-112 pg/l) and serum ferritin (pre-term microg/l 74.4+/-1.1 vs. at term 26.3+/-56.5 microg/l) in pregnant women who delivered pre-term (P<0.05). No differences in cervical IL-8 and cervical TNFalpha between pre-term and term deliveries were found. Multiple linear regression confirmed that the vaginal pH value and cervical fFN test were the best predictive biochemical markers of pre-term birth (standardized coefficient Beta=0.33 and 0.22, respectively). CONCLUSIONS: In order to evaluate pregnancies for pre-term labor, the presence of pH>4.5 and a positive fFN test seems to be predictive of subsequent pre-term delivery.

Invasive assessment of fetal renal abnormalities: urinalysis, fetal blood sampling and biopsy.

There are a number of potential biochemical markers that may have some role in predicting renal function postnatally. These include urinary sodium, calcium and beta2-microglobulin. The latter may also be measured in fetal serum. However, the accuracy of these parameters at a point in time is far from perfect as urinary tract obstruction is a progressive disease which may be best defined by repeated observations throughout pregnancy.

A new approach to prenatal treatment of extralobar pulmonary sequestration.

Fetal hydrothorax and hydrops is a frequent complication of extralobar pulmonary sequestration which is associated with a high perinatal mortality and severe respiratory insufficiency in the newborn. In a 27-week-old fetus with this condition, injection of 1 ml of pure alcohol and pleuro-amniotic shunting achieved resolution of hydrops. The pregnancy progressed to term and a healthy neonate was delivered who did not require postnatal surgery.

Prenatal diagnosis of genetic syndromes may be facilitated by serendipitous findings at fetal blood sampling.

Two women without a specific risk had fetuses with multiple malformations diagnosed by ultrasound; extensive biochemical investigations on fetal blood revealed clues which would have allowed the correct diagnosis of a genetic condition: Pallister-Killian syndrome in one with increased fetal LDH, and Smith-Lemli-Opitz type II syndrome in the other with low fetal cholesterolaemia. When compared with chorionic villus sampling and amniocentesis, rapid karyotyping in women with multiple fetal malformations by fetal blood sampling allows the collection of additional data which may lead to the diagnosis of specific genetic syndromes.

Varying clinical course of large placental chorioangiomas. Report of 3 cases.

Three cases of placental chorioangiomas, from 6.5 to 10 cm in diameter, were diagnosed prenatally by ultrasound and color Doppler imaging at 21-34 weeks of gestation. In 1 case, due to fetal hydrops and maternal 'mirror syndrome', immediate delivery of a neonate, who was severely anemic, thrombocytopenic and had consumption coagulopathy, was required. In the other 2 pregnancies, conservative management was possible, once fetal cardiac failure and anemia were ruled out by the combination of fetal blood sampling and serial echographic and Doppler investigations.

In fetuses with isolated hydronephrosis, urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) have a limited role in the prediction of postnatal renal function.

Seventy-one fetal urine samples were taken from the bladder or renal pelvis of 33 fetuses at 13-36 weeks' gestation with a diagnosis of urinary tract anomaly. Severe isolated hydronephrosis in the absence of an enlarged bladder was the indication for sampling in 12/33 fetuses (26 samples), who were retrospectively classified into three groups: normal, intermediate, and dysplastic, based on the evaluation of postnatal renal function or histology. For all samples, urinary sodium (Na+), calcium (Ca2+), creatinine, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) were measured. Among the 71 fetal urine samples, both beta 2-microglobulin and NAG correlated inversely with gestational age, Na+, and Ca2+, but not with creatinine concentrations. However, the correlation of urinary beta 2-microglobulin with gestational age was dependent on the Na+ and Ca2+ concentrations, whereas urinary NAG correlated significantly with urinary Na+ and Ca2+, and also with gestational age. In fetuses with isolated hydronephrosis, only Na+, and not Ca2+, was significantly related to both beta 2-microglobulin and NAG. Only Na+ and beta 2-microglobulin were significantly, and similarly, higher in both dysplastic and intermediate kidneys when compared with fetuses with normal postnatal function. If only the last urine sampled was considered, there was overlapping of all parameters in the three groups. In isolated hydronephrosis, only the most extreme forms of renal failure might be suggested by elevated levels of Na+, Ca2+, beta 2-microglobulin, and NAG, without an obvious superiority of any of these parameters.

Shortcomings in predicting postnatal renal function using prenatal urine biochemistry in fetuses with congenital hydronephrosis.

Ten fetuses with hydronephrosis underwent one to seven urine sampling procedures at 23 to 36 weeks' gestation to evaluate renal function. Postnatally, the infants' renal function was assessed by a combination of serum creatinine measurement, ultrasonography and renal scintigraphy. Six infants had pyelo-ureteric junction obstruction, two had megabladder with megaureter, and two had vesico-ureteric reflux. All infants had normal serum creatinine levels at the time of postnatal follow-up, but five of the seven with unilateral involvement had moderate or severe renal damage. Abnormal urinary electrolyte concentrations were found antenatally in only two of them. For the three infants with bilateral hydronephrosis, postnatal evaluation showed moderately or severely damaged kidneys despite prenatal evidence of normal biochemical indexes. Fetal urine electrolyte measurement may be accurate in the diagnosis of renal dysplasia, but its sensitivity is poor in predicting moderate renal dysfunction.

Prenatal diagnosis of congenital varicella infection.

Fourteen fetuses at risk of Varicella-Zoster virus (VZV) infection underwent prenatal diagnosis at 10-24 weeks' gestation by a combination of chorionic villus sampling, amniocentesis, and fetal blood sampling. Polymerase chain reaction (PCR) was done on fetal and placental tissues, using primers which define a 221 bp region of the gene coding for the 44 kD protein of VZV. Positive cases were further analysed by dot blot hybridization, using radiolabelled DNA probes corresponding to the Hind III fragment VZV genome. The rate of placental/fetal infection was 36 per cent (5/14 fetuses: 2/11 in the first and 3/3 in the second trimester). At post-mortem examination, two aborted fetuses had hydrocephaly and VZV DNA was found in most of the examined tissues. The nine women who tested negative at prenatal investigation delivered healthy neonates whose VZV-specific IgM antibody titres were negative and none of them developed herpes zoster infection. In view of the high frequency of fetal VZV infection and the reported low rate of malformations, the role of invasive prenatal diagnosis in women who acquire the infection in the first half of gestation is mainly that of reassurance when the test is negative.

Expression pattern of c-sis, c-fos and c-jun in human placenta and embryofetal organs.

The expression pattern of c-sis, c-fos and c-jun was investigated in placenta and embryofetal organ specimens from the first trimester. Northern analysis of the placentae showed c-sis transcripts and c-fos expression. Northern analysis of the same genes in embryofetal organs pointed to the brain as the only organ where consistent transcriptional activity could be observed. RT-PCR analysis of c-fos and c-jun in placentae, staged at four different time periods in pregnancy, allowed to detect the expected fragments in all cases. The same was true when c-fos and c-jun were analyzed at the 13th week of gestation in all the embryofetal organs.

Maternal and fetal platelet activation in normal pregnancy.

OBJECTIVE: To study the platelet activation phase in normal pregnant women and their fetuses, both in vivo under basal conditions and in vitro after stimulation by adenosine diphosphate (ADP), a weak agonist, and U46619, a strong one. METHODS: Platelet function was investigated in 39 normal pregnant women and their fetuses undergoing fetal blood sampling at 18-37 weeks' gestation, using flow cytometry and the anti-GMP140 monoclonal antibody. This combined technique allows platelets to be investigated in small aliquots of whole blood, and it detects platelet secretion regardless of aggregation. In all cases, the percentage of activated platelets was determined under basal conditions and after addition of platelet agonists: ADP at concentrations of 10 and 50 mumol/L, and U46619, a stable analogue of thromboxane A2, at 1 mumol/L. RESULTS: Compared to nonpregnant controls, pregnant women had a significantly lower percentage of activated platelets after addition of U46619 (P = .02). Compared to their mothers, fetuses had significantly inferior platelet activation after addition of both platelet-activating factors at all concentrations used (ADP 10 mumol/L, P < .0001 and ADP 50 mumol/L, P < .0001; U46619, P < .0001). Maternal and fetal platelet activation did not change with duration of gestation. In the fetus, the percentage of activated platelets did not correlate with hematocrit, pH, or oxygen pressure, but it correlated significantly with platelet count after addition of U46619 (r = 0.45, P = .006). CONCLUSIONS: Decreased platelet activation in both pregnant women and fetuses suggests the action of a plasma factor that selectively inhibits prostaglandin-dependent activation. Prostacyclin, which is known to decrease platelet aggregation and release reactions caused by agonists, might have a greater inhibitory effect in the fetus than in the mother, or be present in larger amounts in the fetus.

Prenatal confirmation of trisomy 12 mosaicism by fetal skin biopsy.

Trisomy 12 mosaicism diagnosed at 16 weeks' amniocentesis in a 42-year-old woman was not confirmed at 18 weeks' gestational age in amniotic fluid or fetal blood. Fetal skin biopsy performed at the same time did, however, allow the detection of trisomy 12 in 1 of 14 fibroblasts analysed. Fetal skin biopsy can be included within the diagnostic procedures to be performed when a level III mosaicism is found in the amniotic fluid.

Prenatal diagnosis of anatomical connections in conjoined twins by use of contrast magnetic resonance imaging.

Omphalopagus conjoined twins were diagnosed by ultrasonography in a pregnant woman at 21 weeks' gestation. In order to clarify the anatomical connections, magnetic resonance imaging (MRI) was performed, having achieved fetal paralysis by intravascular injection of 100 mg of pancuronium into each twin. Prior to MRI, 2 ml of a 0.0001 mmol/ml solution of gadolinium DTPA was also injected into the stomach of one twin. The contrast agent opacified the bowel loops of both twins, indicating bowel to bowel anastomosis. Following pregnancy termination, autopsy confirmed the prenatal diagnosis.

46,XY/47,XY, + 17p + mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype.

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy-Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post-axial polydactyly and neuroblastoma-in-situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.

Prenatal diagnosis and fetal therapy.

The protective effect of folic acid supplementation has been demonstrated in patients at risk of neural tube defects by a large, randomized double-blind study. The feasibility of second-trimester screening for Down syndrome, based on the combination of maternal and biochemical markers on maternal blood, has also been verified in two large series from both the United Kingdom and the United States. These results represent major advances in the field of prenatal diagnosis, which, in the future, is likely to rely more and more on better selection by noninvasive testing of high-risk patients. The emphasis has moved away from very early invasive testing due to concerns related to the safety of both early chorionic villus sampling and amniocentesis. Evaluation of renal damage in fetuses with obstructive uropathy by analysis of urinary biochemistry may constitute the basis for more efficient selection of cases amenable to antenatal treatment. Twin-to-twin transfusion syndrome remains a challenge for the future.