Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.).

OBJECTIVE: To assess whether sonographic diagnosis of fetal head position before instrumental vaginal delivery can reduce the risk of failed vacuum extraction and improve delivery outcome. METHODS: Randomised Italian Sonography for occiput POSition Trial Ante vacuum (R.I.S.POS.T.A.) is a randomized controlled trial of term (37 + 0 to 41 + 6 weeks' gestation) singleton pregnancies with cephalic presentation requiring instrumental delivery by vacuum extraction, which was conducted between April 2014 and June 2017 and involved 13 Italian maternity hospitals. Patients were randomized to assessment of fetal head position before attempted instrumental delivery by either vaginal examination (VE) alone or VE plus transabdominal sonography (TAS). Primary outcome was incidence of emergency Cesarean section due to failed vacuum extraction. A sample size of 653 women per group was planned to compare the primary outcome between the two groups. The sample size estimation was based on the hypothesis that the risk of failed vacuum delivery in the VE group would be 5% and that ultrasound assessment of fetal position prior to vacuum extraction would decrease this risk to 2%. RESULTS: On interim analysis, the trial was stopped for futility. During this period, 222 women were randomized and 221 were included in the final data analysis, of whom 132 (59.7%) were randomized to evaluation of fetal head position by VE only and 89 (40.3%) to assessment by VE plus TAS prior to vacuum extraction. No significant differences were observed between the two groups with respect to incidence of emergency Cesarean section due to failed instrumental delivery and other maternal and fetal outcomes. Women randomized to assessment by VE plus TAS showed higher incidence of non-occiput anterior position of the fetal head at randomization and lower incidence of incorrect diagnosis of occiput position compared with women undergoing assessment by VE alone. A higher rate of episiotomy was noted in the women undergoing both VE and TAS compared with those in the VE-only group. CONCLUSIONS: Our prematurely discontinued randomized controlled trial did not demonstrate any benefit in terms of reduced risk of failed instrumental delivery or maternal and fetal morbidity in women undergoing sonographic assessment of fetal head position prior to vacuum extraction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study.

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results: Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P < 0.001). Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelines showed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribing physicians might prefer either drug in some particular situations where the different impacts of treatment on lipid profile and bilirubin may have clinical relevance.

Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood.

OBJECTIVE: To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV). DESIGN: Retrospective observational study. SETTING: Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy. POPULATION: HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995-2009. METHODS: Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection. MAIN OUTCOME MEASURES: A statistical analysis was performed to determine the value of each parameter in predicting outcome. RESULTS: Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were ß(2) -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. ß(2) -Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy. CONCLUSIONS: The determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.

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.

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.

Serum beta 2-microglobulin in fetuses with urinary tract anomalies.

OBJECTIVE: Our purpose was to establish a reference range of fetal serum beta 2-microglobulin, an index of glomerular filtration rate, and to compare the values obtained in fetuses with urinary tract anomalies with this range. STUDY DESIGN: Serum beta 2-microglobulin was measured in 53 control fetuses at 18 to 39 weeks' gestation and in 14 fetuses with urinary tract anomalies, 9 of which had simultaneous urine sampling. RESULTS: In controls fetal serum beta 2-microglobulin had a mean value of 3.4 mg/L (95% data intervals 2.0 to 4.9) and did not correlate with gestational age. In the 14 fetuses with urinary tract anomalies beta 2-microglobulin levels were increased overall compared with controls (median Z score 1.7, range -0.1 to 9.2), and this was also the case in the five fetuses with unilateral renal disorders (median Z score 1.7, range -0.1 to 3.8) and in a fetus who underwent vesicoamniotic shunting and had normal renal function at birth. Serum beta 2-microglobulin was normal in 4 fetuses with bilateral urinary tract obstruction and normal function at postnatal follow-up and also in 1 of 5 fetuses with renal failure. In fetuses with bilateral uropathy urinary sodium correlated with serum beta 2-microglobulin levels. CONCLUSIONS: Increased values of serum beta 2-microglobulin in fetuses with urinary tract anomalies indicate an impaired glomerular filtration rate. The finding of raised concentrations in fetuses with unilateral damage suggests that the compensatory role of the normal kidney is not complete during intrauterine life. Larger series are required to ascertain whether fetal blood sampling is warranted in the antenatal investigation of renal function, especially in view of the close correlation between urinary sodium and serum beta 2-microglobulin levels in fetuses with bilateral obstruction.

Patterns of evoked behaviour in twin pregnancies during the first 22 weeks of gestation.

The objective of this work was to investigate the emergence of intrapair stimulation between twin fetuses and the presence of possible changes in types and percentage of evoked patterns with advancing gestational age. The existence of intrapair stimulation would indicate the functioning of fetal tactile and proprioceptive sensibility. This was studied from video recordings of 30 min ultrasonographic observations of 8 twin pregnancies at 8, 9 and 10 weeks gestational age, of 20 twin pregnancies at 11, 12 and 13 weeks and of 20 twin pregnancies studied with 60 min observations at 15-16, 18-19 and 21-22 weeks. All age groups were subdivided in Monochorionic (Mc) and Dichorionic (Dc) pregnancies. Intrapair stimulation before 11 weeks gestational age is an exceptional event. Due to greater spatial contiguity and thinness of the membrane dividing the two amniotic sacs in Mc pregnancies, it was noted only in these. From 12 weeks onwards, evoked movements began to be observed in Dc pregnancies as well. After the 15th week, intrapair stimulation is a constant and increasing feature of all twin gestations. Movements vary from generalized bodily activity to being progressively localized. No specific evoked movement patterns were observed.

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.

Resolution of hyperthyroidism in a pregnant woman with toxic thyroid nodule by percutaneous ethanol injection.

Overt hyperthyroidism was found in a 35-year-old pregnant woman at the 13th week of gestation who was referred to us for tachycardia, tremors, and weight loss. Clinical signs, symptoms, and laboratory findings led to the diagnosis of toxic thyroid nodule. She was treated with ultrasound guided percutaneous ethanol injection (PEI) and, after 2 weeks of treatment, the woman was completely euthyroid. These findings suggest that during pregnancy PEI appears to be a rapid and safe therapy for toxic nodular goiter and an effective alternative to the administration of antithyroid drugs.

Changes in blood flow velocity waveforms following fetal blood sampling.

The umbilical artery, aorta, and middle cerebral artery pulsatility indices were investigated by pulsed Doppler ultrasound in 73 fetuses at 18-37 weeks of gestation, before and after fetal blood sampling performed either at the placental cord insertion (n = 46) or at the intrahepatic vein (n = 27). At the end of the procedure, after randomization, 35 fetuses were infused amounts of normal saline equal to the blood volume withdrawn, and 38 fetuses served as controls. Following blood sampling, the umbilical artery pulsatility indices decreased both in controls (p = 0.004) and in the saline group (p = 0.006). The middle cerebral artery velocity waveforms exhibited similar changes only in controls (p = 0.01), and no changes in fetal heart rate and aortic pulsatility indices were recorded in either group. The changes in blood flow velocity waveforms did not correlate with gestational age and the blood volume sampled, and were similar whether the site of sampling was the placental cord insertion or the intrahepatic vein. In 10 acidemic and/or hypoxemic fetuses, pulsatility indices in the umbilical and middle cerebral arteries were not modified by the blood sampling procedure. The release of vasoactive substances is most likely the cause of diminished vascular resistances following fetal blood sampling. Hypoxemic/acidemic fetuses may fail to mount a normal vasodilative response to needle puncture.

Prenatal diagnosis of congenital human cytomegalovirus infection.

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16-30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases and > or = 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.

Prenatal testing in a fetus at risk for autosomal dominant polycystic kidney disease and autosomal recessive junctional epidermolysis bullosa with pyloric atresia.

Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in a fetus at risk for autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia. A previous son of the couple under investigation had died at 3 months of EBJ. The mother of the propositus has ADPKD. Genetic linkage studies were carried out in 11 relatives (4 with ADPKD), and on fetal DNA obtained from cultured amniocytes, using 8 flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and a DNA marker linked to another putative ADPKD locus on chromosome 2p. The linkage results indicated that the fetus had not inherited the ADPKD chromosome from the affected mother, with a diagnostic accuracy of > 99%. Ultrastructural and immunohistochemical analyses of multiple fetal skin biopsies showed no EBJ-associated abnormalities. Thus, combining recent morphological and molecular diagnostic methods, we could show that the fetus was free from both diseases. After 40 weeks of gestation, a normal male infant was delivered.