Accuracy and clinical utility of standard postmortem radiological imaging after early second trimester termination of pregnancy.

OBJECTIVE: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at <23 weeks' gestation for congenital fetal malformations in comparison to autopsy. STUDY DESIGN: This a prospective single-center study on fetuses underwent termination of pregnancy for fetal defects. Overall concordance between any radiological exam and autopsy was evaluated. For postmortem MRI only, the following subgroups were analyzed: 1) total agreement; 2) agreement for main findings; 3) agreement for main findings but major relevant additional findings at autopsy; 4) total disagreement. RESULTS: 174 cases were collected. The overall concordance with autopsy for main findings was 71% (115/163) for postmortem MRI and 99% (173/174) for prenatal ultrasound (US). Postmortem MRI detection rate was high for central nervous system (CNS) defects (98%), gastrointestinal, genitourinary and respiratory defects (100%), while it was poor for cardiovascular and musculoskeletal defects (25% and 42%, respectively). For musculoskeletal abnormalities, the performance of postmortem XR and postmortem CT exams improved the detection rate from 42% for postmortem MRI alone to 92%. CONCLUSIONS: Postmortem MRI has a good overall concordance for fetal defects after termination of pregnancy performed at <23 weeks. Along with autopsy, postmortem MRI may be offered for all cases of CNS defects in order to prevent inconclusive exams due to autolysis of the brain tissue, while postmortem CT and postmortem XR are indicated for musculoskeletal defects. In the presence of multiple abnormalities or cardiac defects the couple should be counseled on the poor performance of radiological investigations.

Intrauterine versus post-mortem magnetic resonance in second trimester termination of pregnancy for central nervous system abnormalities.

OBJECTIVE: To evaluate if limiting factors of intrauterine magnetic resonance imaging (iuMRI) performed in the early second trimester of pregnancy (19-23 weeks) affect its accuracy in comparison to post-mortem MRI (pmMRI) in fetuses that underwent termination of pregnancy (TOP) for central nervous system (CNS) defects. STUDY DESIGN: This is a secondary analysis of a 10 years prospective observational study. Cases of TOP < 23 weeks for CNS malformation that had undergone neurosonography (NSG), iuMRI, pmMRI and autopsy were included. The agreement between iuMRI and pmMRI was calculated. The autopsy represented the gold-standard. RESULTS: Overall, 143 TOPs for fetal congenital anomaly underwent the post-mortem diagnostic protocol. Of these, 31 cases underwent iuMRI and pmMRI for CNS abnormality. Three cases were excluded due to brain autolysis at autopsy. Corpus callosum defects were the most represented (16/28; 57 %). In only one case of posterior fossa defect, pmMRI identified the presence of vermian hypoplasia not diagnosed at iuMRI. In 2 cases (7%), iuMRI added clinically relevant additional findings to NSG, that were posteriorly confirmed by pmMRI. CONCLUSIONS: The study shows that, at 19-23 weeks and for CNS defects, limiting factors that might influence the performance of iuMRI have little influence on iuMRI accuracy. This finding is particularly important for professionals who work in countries with legal bound for TOP in the early second trimester.

The association of first trimester uterine arteries Doppler velocimetry with different clinical phenotypes of hypertensive disorders of pregnancy: a longitudinal study.

Introduction: Current classification of hypertensive disorders of pregnancy (HDP) is mostly based on temporal classification differentiating HDP according to early and late onset of the disease. However, epidemiological and clinical data suggest that there are two different clinical phenotypes of HDP that coexist at any gestational age: HDP associated to intrauterine growth restriction (HDP-IUGR) and HDP associated to appropriate for gestational age fetal growth (HDP-AGAf). The aim of the study was to evaluate the association of first trimester uterine arteries (UtA) by Doppler velocimetry, and maternal risk factors with HDP according to two different classifications: one based on gestational age at delivery (early- and late-HDP), and one based on longitudinal ultrasound evaluation of fetal growth (HDP-IUGR and HDP-AGAf), independently of the gestational age. Methods: Maternal characteristics and mean pulsatility index (PI) of UtA were collected at 11-13 gestational weeks. A longitudinal ultrasound follow-up of fetal growth in each trimester and clinical outcome were obtained in 4290 singleton pregnancies. Results: UtA-PI was significantly higher in women who developed HDP-IUGR (n = 22) and the odds ratio (OR) to develop HDP-IUGR from 25 to 39 weeks was 8.6 (p < .0001). HDP-AGAf (n = 112) was significantly associated with a higher BMI, multiparity, and maternal age, but not with UtA-PI (OR 1.3; p = .2). In women with an abnormal UtA-PI, the odds of developing early (n = 15) and late-HDP (n = 119) were 3.0 (p = .03) and 1.7 (p = .002), respectively. The AUCs for HDP-IUGR and early-HDP were 0.84 and 0.71, respectively. Discussion: UtA Doppler velocimetry in the first trimester was strongly associated with HDP-IUGR all along gestation, as a proxy of placental insufficiency, and showed no association with HDP-AGAf. Our findings suggest an efficacy of first trimester UtA Doppler velocimetry to identify HDP-IUGR independently of the gestational age, and a limited value for HDP not associated with intrauterine growth restriction (IUGR).

Pregnancy and postpartum following a prenatal diagnosis of fetal thoracoabdominal malformation: the parental perspective.

PURPOSE: The study's aim was to evaluate how information related to a prenatal diagnosis of fetal malformation could modify parenthood experience descriptions during pregnancy and after the child's birth. METHODS: A longitudinal case-control clinical study was conducted. Data on parenthood experience descriptions collected using a validated semantic differential technique during pregnancy and after the child's birth were compared between seven couples of parents receiving a prenatal diagnosis of fetal malformation and seven couples without any fetal diagnosis. RESULTS: Our results show that during pregnancy parents in the clinical group describe themselves as more fragile, passive, and timid [p=0.007] than those in the control group. On the other hand, after the child's birth, there are no significant differences between groups. CONCLUSIONS: Data are discussed with reference to better knowledge of the psychological dynamics involved in becoming a parent and to rational planning of support for parents receiving a diagnosis of fetal malformation.

The development of upper limb movements: from fetal to post-natal life.

BACKGROUND: The aim of this longitudinal study was to investigate how the kinematic organization of upper limb movements changes from fetal to post-natal life. By means of off-line kinematical techniques we compared the kinematics of hand-to-mouth and hand-to-eye movements, in the same individuals, during prenatal life and early postnatal life, as well as the kinematics of hand-to-mouth and reaching-toward-object movements in the later age periods. METHODOLOGY/PRINCIPAL FINDINGS: Movements recorded at the 14(th), 18(th) and 22(nd) week of gestation were compared with similar movements recorded in an ecological context at 1, 2, 3, 4, 8, and 12 months after birth. The results indicate a similar kinematic organization depending on movement type (i.e., eye, mouth) for the infants at one month and for the fetuses at 22 weeks of gestation. At two and three months such differential motor planning depending on target is lost and no statistical differences emerge. Hand to eye movements were no longer observed after the fourth month of life, therefore we compared kinematics for hand to mouth with hand to object movements. Results of these analyses revealed differences in the performance of hand to mouth and reaching to object movements in the length of the deceleration phase of the movement, depending on target. CONCLUSION/SIGNIFICANCE: Data are discussed in terms of how the passage from intrauterine to extra-uterine environments modifies motor planning. These results provide novel evidence of how different types of upper extremity movements, those directed towards one's own face and those directed to external objects, develop.

Prenatal anteroposterior pelvic diameter cutoffs for postnatal referral for isolated pyelectasis and hydronephrosis: more is not always better.

PURPOSE: Congenital hydronephrosis and isolated pyelectasis are frequently diagnosed by prenatal ultrasound. About 80% of cases resolve spontaneously in early childhood. Currently there is no agreed on protocol for prenatal followup. Most clinicians use a renal pelvis anteroposterior diameter of greater than 4 mm as a threshold for identifying isolated pyelectasis and hydronephrosis at 33 weeks of gestation or anteroposterior diameter greater than 7 mm at 40 weeks of gestation. We sought to determine a fetal renal pelvis diameter cutoff at 20 and 30 weeks of gestation that would be able to predict significant nephron uropathy requiring surgery. MATERIALS AND METHODS: Our protocol included 2 prenatal ultrasounds at 20 and 30 weeks of gestation and 3 postnatal ultrasounds at ages 1, 6 and 12 months. Between January 2009 and December 2011 we evaluated 149 prenatal cases (130 males, 19 females) of isolated pyelectasis and 41 cases (28 males, 13 females) of hydronephrosis with a renal pelvis anteroposterior diameter of greater than 4 mm at 20 weeks of gestation. RESULTS: For isolated pyelectasis we identified cutoffs of 6 mm at 20 weeks of gestation (100% sensitivity, 84.3% specificity) and 10 mm at 30 weeks of gestation (100% sensitivity, 91.9% specificity). For hydronephrosis we identified cutoffs of 10 mm at 20 weeks of gestation (100% sensitivity, 86.1% specificity) and 12 mm at 30 weeks of gestation (100% sensitivity, 66.7% specificity). CONCLUSIONS: Using these thresholds, we could avoid a significant number of followup ultrasounds in the prenatal and postnatal periods, as well as invasive postnatal tests (ie voiding cystourethrography and mercaptoacetyltriglycine scintigraphy) without missing even a single case of obstructive nephropathy requiring surgery.

Third trimester abdominal circumference, estimated fetal weight and uterine artery doppler for the identification of newborns small and large for gestational age.

OBJECTIVE: To understand if ultrasound biometric evaluation at 30-32 weeks of gestation is a valuable screening tool for the detection of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants at birth in a low risk population. STUDY DESIGN: We enrolled 1848 pregnant women with singleton pregnancy undergoing routine fetal biometry. We divided the infants into four groups: moderate SGA, severe SGA, moderate LGA and severe LGA. We considered third-trimester estimated fetal weight (EFW), abdominal circumference (AC), EFW centile (EFWc), AC centile (ACc) and compared their prediction toward SGA and LGA to determine which of these parameters was the best estimator for fetal size. Then we took the strongest predictive value and added all history-related and ultrasound factors to run a stepdown multivariate logistic regression. All the variables were then dichotomized and sensitivity models only for statistically significant parameters were calculated. RESULTS: We identified the following predictive factors for each outcome: for severe SGA: EFWc with p<0.001, uterine artery pulsatility index (UtA PI) with p<0.002. For moderate SGA: EFWc with p<0.001, UtA PI with p<0.004, maternal preeclampsia p<0.002. For moderate and severe LGA: EFWc with p<0.001. CONCLUSION: We can detect in a low-risk population a group at risk of growth deviations. Adding Doppler velocimetry to 30-32 weeks EFWc improves the specificity (84%) regarding SGA newborns, maintaining a good sensitivity (71%), and reducing the population to be re-screened from 27 to 17%. An ultrasound examination at 34-36 weeks or the clinical assessment of maternal risk factors remain the best tools for LGA newborns.

Circulating TRAIL shows a significant post-partum decline associated to stressful conditions.

BACKGROUND: Since circulating levels of TNF-related apoptosis inducing ligand (TRAIL) may be important in the physiopathology of pregnancy, we tested the hypothesis that TRAIL levels change at delivery in response to stressful conditions. METHODS/PRINCIPAL FINDINGS: We conducted a longitudinal study in a cohort of 73 women examined at week 12, week 16, delivery and in the corresponding cord blood (CB). Serum TRAIL was assessed in relationship with maternal characteristics and to biochemical parameters. TRAIL did not vary between 12 (67.6±27.6 pg/ml, means±SD) and 16 (64.0±16.2 pg/ml) weeks' gestation, while displaying a significant decline after partum (49.3±26.4 pg/ml). Using a cut-off decline >20 pg/ml between week 12 and delivery, the subset of women with the higher decline of circulating TRAIL (41.7%) showed the following characteristics: i) nullipara, ii) higher age, iii) operational vaginal delivery or urgent CS, iv) did not receive analgesia during labor, v) induced labor. CB TRAIL was significantly higher (131.6±52 pg/ml) with respect to the corresponding maternal TRAIL, and the variables significantly associated with the first quartile of CB TRAIL (<90 pg/ml) were higher pre-pregnancy BMI, induction of labor and fetal distress. With respect to the biochemical parameters, maternal TRAIL at delivery showed an inverse correlation with C-reactive protein (CRP), total cortisol, glycemia and insulin at bivariate analysis, but only with CRP at multivariate analysis. CONCLUSIONS: Stressful partum conditions and elevated CRP levels are associated with a decrease of circulating TRAIL.

Wired to be social: the ontogeny of human interaction.

BACKGROUND: Newborns come into the world wired to socially interact. Is a propensity to socially oriented action already present before birth? Twin pregnancies provide a unique opportunity to investigate the social pre-wiring hypothesis. Although various types of inter-twins contact have been demonstrated starting from the 11(th) week of gestation, no study has so far investigated the critical question whether intra-pair contact is the result of motor planning rather then the accidental outcome of spatial proximity. METHODOLOGY/PRINCIPAL FINDINGS: Kinematic profiles of movements in five pairs of twin foetuses were studied by using four-dimensional ultrasonography during two separate recording sessions carried out at the 14(th) and 18(th) week of gestation. We demonstrate that by the 14th week of gestation twin foetuses do not only display movements directed towards the uterine wall and self-directed movements, but also movements specifically aimed at the co-twin, the proportion of which increases between the 14(th) and 18(th) gestational week. Kinematic analysis revealed that movement duration was longer and deceleration time was prolonged for other-directed movements compared to movements directed towards the uterine wall. Similar kinematic profiles were observed for movements directed towards the co-twin and self-directed movements aimed at the eye-region, i.e. the most delicate region of the body. CONCLUSIONS/SIGNIFICANCE: We conclude that performance of movements towards the co-twin is not accidental: already starting from the 14th week of gestation twin foetuses execute movements specifically aimed at the co-twin.

Prenatal detection of the cystic form of meconium peritonitis: no issues for delayed postnatal surgery.

Prenatal ultrasound (US) diagnosis and postnatal outcome are reviewed in three babies with the complex form of meconium peritonitis (MP), the cystic type. Perinatal management is discussed. Large intra-abdominal cysts with signs of calcifications were detected during the second mid-trimester. Meconium ascites and polyhydramnios appeared between 32 and 35 weeks of gestation. Signs of anaemia were assessed on median cerebral artery peak systolic velocity. Sudden appearance of hydrops and anaemia required preterm delivery, neonatal resuscitation and urgent abdominal drainage. Postnatal US imaging confirmed prenatal sonographic evidence. Abdominal X-ray showed calcifications and no free abdominal air. Intestinal diversion was performed in two patients on their first day of life and evolution was uneventful. Hospital death occurred in one baby, who was submitted to delayed surgery due to unstable hemodynamic conditions. Distal ileal perforation walled off by pseudocysts was detected in all cases. One baby was found to be affected by cystic fibrosis. Ileal intussusception was described in the non-surviving infant. The cystic type of MP may have a potentially rapid lethal course and the onset of foetal anaemia and polyhydramnios is a bad prognostic factor. Severe evolution in hydrops and foetal distress may occur at any moment suggesting the persistence of a leakage or re-rupture of the cysts with new meconium spillage into the abdomen. Prenatal detection of ascites, polyhydramnios and pseudocysts requires a strict follow-up, and timing of delivery has to be planned in a tertiary centre. Postnatal radiological imaging does not offer further information over prenatal imaging and surgical decision should not be influenced by the absence of abdominal free air. Urgent abdominal drainage at birth, followed by intestinal diversion of persistent intestinal perforation on the first day of life, may prevent bacterial colonisation and improve prognosis.

Evidence of early development of action planning in the human foetus: a kinematic study.

The aim of the present study was to investigate whether foetal hand movements are planned and how they are executed. We performed a kinematic analysis of hand movements directed towards the mouth and the eyes in the foetuses of eight women with normally evolving pregnancies. At 14, 18 and 22 weeks of gestation, eight foetuses underwent a 20-min four-dimensional-ultrasound session. The video recordings for these movements were then imported into in-house software developed to perform kinematic analysis. We found that spatial and temporal characteristics of foetal movements are by no means uncoordinated or unpatterned. By 22 weeks of gestation the movements seem to show the recognizable form of intentional actions, with kinematic patterns that depend on the goal of the action, suggesting a surprisingly advanced level of motor planning.

First-trimester intrauterine hematoma and outcome of pregnancy.

OBJECTIVE: To evaluate the outcome of pregnancies complicated by first-trimester intrauterine hematoma. METHODS: An analysis was performed on 248 cases. The pregnancy outcome was correlated with hematoma volume, gestational age (weeks), and maternal age (years). RESULTS: One hundred eighty-two cases were eligible for the study. Clinical complications occurred in 38.5% of the cases (adverse outcome group). Spontaneous abortion (14.3%), fetal growth restriction (7.7%), and preterm delivery (6.6%) were the most frequent clinical conditions observed. Considering the hematoma variables in adverse and favorable outcome groups, we found a significant difference only for gestational age at diagnosis. The median gestational age was significantly lower (P < .02) in the adverse outcome group (7.27, I and III quartiles 6.22-8.78) than in the favorable outcome cases (8.62, I and III quartiles 6.70-9.98). Among clinical conditions, the median gestational age was significantly lower (P = .02) in pregnancies complicated by spontaneous abortion (6.60, I and III quartiles 5.95-8.36) than in cases not ending in a miscarriage (8.50, I and III quartiles 6.70-9.91). The overall risk of adverse outcome was 2.4 times higher when the hematoma was diagnosed before 9 weeks (odds ratio 2.37, 95% confidence interval 1.20-4.70). In particular, intrauterine hematoma observed before 9 weeks significantly increases the risk of spontaneous abortion (odds ratio 14.79, 95% confidence interval 1.95-112.09) CONCLUSION: Intrauterine hematoma can affect the outcome of pregnancy. The risk of spontaneous abortion is related to gestational age and is significantly increased if diagnosed before 9 weeks. LEVEL OF EVIDENCE: III.