Anatomical and functional changes of the fetal adrenal gland in intrauterine growth restriction.

OBJECTIVE: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. STUDY DESIGN: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two-dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. RESULTS: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. CONCLUSIONS: Adrenal sparing correlates with a relative increase in adrenal measurements and function.

Unexpected stillbirth from umbilical cord hematoma.

Background: Umbilical cord hematomas (UCHs) can cause life-threatening outcomes, although extremely uncommon. They can lead to fetal distress and stillbirth. They have been observed in about 1:5500 pregnancies; they are associated with poor outcome in about the 50% of all cases. UCHs commonly occur due to rupture/lesion of umbilical vein's walls, or less frequently of umbilical arteries' ones. Case Report: We present a case of a fetal demise which acutely and unexpectedly occurred in the last phases of labor. In this fetus, the identification of the cause of death was made only after post-mortem examination. The present report depicts the uncommon eventuality of umbilical cord hematomas which can cause unexpected fetal demise. Conclusion: This case points out that in these cases careful examination of umbilical cord's macroscopic/microscopic examination is fundamental to clarify the natural cause of fetal death for statistical purposes; to close parents' mourning process; to ascertain medical malpractice claims.

Antiviral oxysterols are present in human milk at diverse stages of lactation.

Oxysterols are cholesterol oxidation derivatives. Those containing an additional hydroxyl group on the side chain of the cholesterol molecule result from a physiological enzymatic synthesis and include the majority of oxysterols present in the circulation. Among these, 25-hydroxycholesterol (25OHC) and 27-hydroxycholesterol (27OHC) are characterized by a broad antiviral activity and are now considered involved in the innate immune response against viruses. Despite the emerging role of these sterols in the innate antiviral defences, no data are available on their presence in human breast milk (BM) to date. In this study, we investigated the content of oxysterols of enzymatic synthesis in BM of twelve donor mothers at different stages of lactation (i.e. in colostrum, transitional milk, and mature milk) by gas chromatography-mass spectrometry analysis. The side-chain oxysterols 25OHC, 27OHC, and 24S-hydroxycholesterol (24SOHC) were actually present in BM in all stages of lactation, but the concentration of 27OHC showed a remarkable peak in colostrum. Antiviral assays revealed that all the colostrum samples contained 27OHC concentrations that were active in vitro against two relevant pediatric viral pathogens: the human rotavirus and the human rhinovirus. Overall, this study discloses new antiviral components of BM and suggests a passive transfer of these protective factors to the infant via breastfeeding, especially in the first few days of lactation.

Sonographic evaluation of the fetal spine position and success rate of manual rotation of the fetus in occiput posterior position: A randomized controlled trial.

BACKGROUND: To evaluate whether sonographic (US) diagnosis of the fetal spine position could increase the success rate of manual rotation of the fetal occiput (MRFO) in second-stage arrest in persistent occiput posterior position (OPP). METHODS: In this randomized controlled parallel single-center trial, 58 nulliparous in second-stage arrest of labor with fetus in cephalic presentation and OPP diagnosed by US were randomly assigned to group A where the fetal spine position was not known by the operator or to group B where the operator knew it. The main outcome was the success of MRFO in the two groups. Secondary outcomes were perineal injuries, blood loss, duration of expulsive period, and neonatal APGAR at 5 minutes. RESULTS: A priori knowledge of the spine position improves the success of the MRFO (41.4% group A versus 82.8% group B, p value < 0.001), the percentage of spontaneous deliveries (27.6% group A versus 69% group B, p value = 0.01), and maternal outcome (intact perineum and blood loss). No differences were detected on the neonatal side. CONCLUSIONS: MRFO is a safe and useful procedure that should be performed in second-stage arrest in OPP. A better performance was observed when supported by the US knowledge of the spine position. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:472-476, 2017.

Is It Possible to Differentiate Chronic Kidney Disease and Preeclampsia by means of New and Old Biomarkers? A Prospective Study.

OBJECTIVE: Chronic kidney disease (CKD) and preeclampsia (PE) may both present with hypertension and proteinuria in pregnancy. Our objective is to test the possibility of distinguishing CKD from PE by means of uteroplacental flows and maternal circulating sFlt-1/PlGF ratio. DESIGN: Prospective analysis. POPULATION: Seventy-six patients (35 CKD, 24 PE, and 17 other hypertensive disorders), with at least one sFlt-1/PlGF and Doppler evaluation after the 20th gestational week. METHODS: Maternal sFlt-1-PlGF were determined by immunoassays. Abnormal uterine artery Doppler was defined as resistance index ≥ 0.58. Umbilical Doppler was defined with gestational-age-adjusted Pulsatility Index. Clinical diagnosis was considered as reference. Performance of Doppler study was assessed by sensitivity analysis; sFlt-1/PlGF cut-off values were determined by ROC curves. RESULTS: The lowest sFlt-1/PlGF ratio (8.29) was detected in CKD, the highest in PE (317.32) (P < 0.001). Uteroplacental flows were mostly preserved in CKD patients in contrast to PE (P < 0.001). ROC analysis suggested two cut-points: sFlt-1/PlGF ≥ 32.81 (sensitivity 82.93%; specificity 91.43%) and sFlt-1/PlGF ≥ 78.75 (sensitivity 62.89%, specificity 97.14%). Specificity reached 100% at sFlt-1/PlGF ≥ 142.21 (sensitivity: 48.8%). Early-preterm delivery was associated with higher sFlt-1/PlGF ratio and abnormal uteroplacental flows relative to late-preterm and term deliveries. CONCLUSIONS: sFlt-1/PlGF ratio and uteroplacental flows significantly correlated with PE or CKD and preterm delivery.

Risk of Adverse Pregnancy Outcomes in Women with CKD.

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

Ultrasound imaging in prolonged second stage of labor: does it reduce the operative delivery rate?

OBJECTIVE: To reduce the operative delivery rate in the prolonged second stage of labor (PSSL) through intrapartum sonography. METHODS: Sixty-two women - with uncomplicated pregnancies at term, fetus in cephalic presentation and occipitoanterior position, in PSSL - had already undergone epidural anesthesia and oxytocin infusion. Transperineal ultrasound was performed to define fetal head direction (downward, horizontal, and upward) and patients were divided into three groups (D, H, and U). PROPOSED PROTOCOL: Cessation of oxytocin infusion, addition of a dose of anesthesia, invitation to assume a hand-and-knee position, and to relax. After one hour, oxytocin infusion was started again and women were invited to push. Fetal well-being ensured by cardiotocography (CTG). Chi-square test was used to compare the mode of delivery: cesarean section (CS), vacuum extraction (VE), and spontaneous delivery (SD). RESULTS: Group D (n = 20): 4 SD (20%), 4 VE, 12 CS; group H (n = 22): 9 SD (41%), 9 VE, 4 CS; group U (n20): 16 SD (80%), 4 VE. The risk of not having a SD in group D versus U is quadrupled (RR 4; 95% CI 1.6-9.9). CONCLUSIONS: Ultrasound diagnosis of fetal head upward direction is highly predictive of SD in case of PSSL. Further studies are needed to assess this hypothesis.

Pre-eclampsia or chronic kidney disease? The flow hypothesis.

BACKGROUND: Chronic kidney disease (CKD) and pre-eclampsia (PE) occur in 3-5% of pregnancies. They often share hypertension and proteinuria and a differential diagnosis may be impossible. However, in PE, the pathogenesis is related to abnormal placentation, which can be detected by abnormal uterine and umbilical Doppler flow velocities, while in CKD, an intrinsic kidney disease is present. We hypothesize that Doppler studies can help to differentiate PE from CKD, as the flow velocities are altered in PE and normal in CKD. METHODS: We retrospectively selected patients who were followed in our Materno-Foetal Unit (2005-10) and had at least one flow measurement in our setting. CKD patients were included in the presence of proteinuria (≥ 300 mg/day) and hypertension, mimicking PE. The clinical charts were reviewed by the same operators; the clinical diagnoses were taken as reference. Three flow patterns were considered: alteration of both flow velocity waveforms (FVWs) (uterine and umbilical arteries), hypothesized as predictive of PE; normal FVWs at both levels, hypothesized as predictive of CKD; altered FVW in either artery, considered 'mixed'. Uterine FVWs were considered pathological according to the classical cut-point (RI > 0.58). Umbilical flows were evaluated according to standards adjusted for gestational age. Statistical analysis was performed in SPSS. RESULTS: The analysis included 61 cases. The presence of normal FVWs was significantly associated with the diagnosis of CKD (P = 0.0018). Conversely, the presence of both altered flows was significantly associated with PE (P = 0.0233). CONCLUSIONS: In the presence of proteinuria and hypertension, normal flows suggest CKD altered flows PE. Prospective studies are needed to refine this hypothesis based on the first Doppler criteria supporting the differential diagnosis between CKD and PE.

Multiple pregnancies in CKD patients: an explosive mix.

BACKGROUND AND OBJECTIVES: CKD and multiple pregnancies bear important risks for pregnancy outcomes. The aim of the study was to define the risk for adverse pregnancy-related outcomes in multiple pregnancies in CKD patients in comparison with a control group of "low-risk" multiple pregnancies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study was performed in the Maternal Hospital of the University of Turin, Italy. Of 314 pregnancies referred in CKD (2000-2011), 20 were multiple (15 twin deliveries). Control groups consisted of 379 low-risk multiple pregnancies (314 twin deliveries) and 19 (15 twin deliveries) cases with hypertension-collagen diseases. Baseline data and outcomes were compared by univariate and logistic regression analyses. RESULTS: The prevalence of multiple pregnancies was relatively high in the CKD population (6.4%); all referred cases were in early CKD stages (I-II); both creatinine (0.68 to 0.79 mg/dl; P=0.010) and proteinuria (0.81 to 3.42 g/d; P=0.041) significantly increased from referral to delivery. No significant difference in demographic data at baseline was found between cases and low-risk controls. CKD was associated with higher risk of adverse pregnancy outcomes versus low-risk twin pregnancies. Statistical significance was reached for preterm delivery (<34 weeks: 60% vs 26.4%; P=0.005; <32 weeks: 53.3% vs 12.7%; P<0.001), small for gestational age babies (28.6% vs 8.1%; P<0.001), need for Neonatal Intensive Care Unit (60% vs 12.7%; P<0.001), weight discordance between twins (40% vs 17.8%; P=0.032), and neonatal and perinatal mortality (6.6% vs 0.8%; P=0.032). CONCLUSION: This study suggests that maternal-fetal risks are increased in multiple pregnancies in the early CKD stages.

Thymic volume in healthy, small for gestational age and growth restricted fetuses.

OBJECTIVE: The aim of this study was to verify the hypothesis that a difference in thymic size exists between small for gestational age (SGA) fetuses, likely constitutional, and intrauterine growth restricted (IUGR) fetuses because of placental causes. METHODS: We studied 27 SGA and 36 control fetuses. SGA was defined as fetal abdominal circumference (AC) and birthweight <10th percentile for gestational age. We defined as constitutional SGA those with normal uterine and umbilical artery Doppler flow velocity waveforms (FVW), and as IUGR those with abnormal uterine FVW. IUGR were further divided based on normal or abnormal umbilical FVW. Fetal thymic volume (TV) was acquired by three-dimensional ultrasound and reconstructed with virtual organ computer-aided analysis. To correct for the influence of fetal size on thymic dimension, TV/AC ratio was calculated. RESULTS: Controls presented a higher TV/AC compared with each group of SGA (p < 0.001). TV/AC was significantly lower in IUGR with abnormal umbilical FVW compared with both constitutional SGA (p = 0.01) and IUGR with normal umbilical FVW (p = 0.01). CONCLUSIONS: The differences in TV/AC between constitutional SGA and IUGR with abnormal umbilical FVW suggest that, in the latter, a specific 'trigger' might compromise trophoblastic invasion and thymic development; however, some kind of alteration of the immune system might occur in all SGA fetuses.

Vegetarian supplemented low-protein diets. A safe option for pregnant CKD patients: report of 12 pregnancies in 11 patients.

BACKGROUND: Pregnancy in CKD is an increasing challenge, considering also the paucity of therapeutic tools available in pregnant women. While theoretically interesting, the experience with low protein diets in pregnancy is limited. Aim of this feasibility study is to review our experience with supplemented vegetarian low protein diets in pregnancy, as a "rescue treatment" for severe CKD and/or proteinuria. METHODS: Data were gathered prospectively. Diet schema: proteins: 0.6-0.7 g/Kg/day, amino and chetoacid supplementation, 1-3 free meals/week. Compliance, side effects, biochemical data recorded at each visit (at least twice monthly). RESULTS: Between January 2000 and February 2010, out of 168 pregnancies referred, 12 were managed by the diet (11 patients; median age 33, range 20-38). One pregnancy was terminated (patient's choice); the other 10 patients delivered 11 healthy babies. At referral, 2 patients were in stage 4 CKD, 4 in stage 3, 4 had nephrotic proteinuria (3.6-6.3 g/day). One patient doubled serum creatinine; none needed renal replacement therapy within 6 months from delivery. No patient complained of side effects, nor developed hyperkalemia or hypercalcaemia. Two babies from mothers in CKD stage 4 were small for gestational age; 9/11 were delivered by caesarean section (median gestational age 33 weeks: range 28-37; birth weight 935-2620 g) within a policy of delivery in the presence of foetal growth impairment and/or worsening of proteinuria, GFR, hypertension or foetal conditions. All babies are well, 1 month, 7.5 years from delivery. CONCLUSION: Our report suggests considering vegetarian diets as an additional tool in the management of pregnant CKD patients.

Superfetation after ovulation induction and intrauterine insemination performed during an unknown ectopic pregnancy.

This report describes the first case of superfetation after ovarian stimulation with gonadotrophins and intrauterine insemination (IUI) that were performed in the presence of an undiagnosed tubal pregnancy. A 32-year-old woman who underwent repeated attempts of ovarian stimulation and IUI was hospitalized for severe pelvic pain and submitted to laparoscopic salpingectomy because of ruptured salpynx containing a 6-week pregnancy. Transvaginal ultrasound examination showed a simultaneous intrauterine 2-week pregnancy that had been conceived by ovarian stimulation and IUI while the tubal pregnancy was already ongoing and still undiagnosed. The intrauterine pregnancy went on until term and ended with the spontaneous delivery of a healthy baby. This report demonstrates that human superfetation may occur after gonadotrophin treatment and IUI in the presence of an ongoing tubal pregnancy. It is recommended to perform a pregnancy test before starting ovulation induction even when an apparently normal blood discharge appeared.

The significance of fetal ventriculomegaly: etiology, short- and long-term outcomes.

Fetal cerebral ventriculomegaly (VM) is diagnosed when the width of one or both ventricles, measured at the level of the glomus of the choroid plexus (atrium), is > or = 10 mm. VM can result from different processes: abnormal turnover of the cerebrospinal fluid (CSF), neuronal migration disorders, and destructive processes. In a high percentage of cases, it is associated with structural malformations of the central nervous system (CNS), but also of other organs and systems. The rate of associated malformations is higher (> or =60%) in severe VM (>15 mm) and lower (10-50%) in cases of borderline VM (10-15 mm). When malformations are not present, aneuploidies are found in 3-15% of borderline VM; the percentage is lower in severe VM. The neurodevelopmental outcome of isolated VM is normal in > 90% of cases if the measurement of ventricular width is between 10 and 12 mm; it is less favorable when the measurement is > 12 mm.

Doppler indices in the umbilical arteries: influence of vessel curvature induced by bladder filling.

Doppler indices are widely used to assess normal versus pathologic haemodynamics. In obstetrics, the assessment of abnormal values in some critical compartments, such as the umbilical arteries (UA), may be crucial in the clinical management of growth-restricted foetuses. It was recently proposed that the UA should be sampled in their perivesical portion (PVC), i.e., where they surround the foetal urinary bladder. However, measurements at this site could be biased by the degree of curvature of the vessel due to bladder filling. We investigated this possibility in vivo and in vitro, i.e., measurements on rubber tubes at different radii of curvature R(c). There was significant dependence of the Doppler indices A/B and PI on the vessel curvature and insonation angle; in fact, we recorded errors of about 25% when R(c) was 10 times larger than the radius of the vessel and about 100% when R(c) was five times larger than the radius of the vessel. Therefore, measurements of the UA at the PVC site should only be performed when the foetal bladder is empty.