European reference network for rare inherited congenital anomalies (ERNICA) evidence based guideline on the management of gastroschisis.

BACKGROUND: The European Reference Network for rare Inherited Congenital Anomalies, ERNICA, guidelines for gastroschisis cover perinatal period to help teams to improve care. METHOD: A systematic literature search including 136 publications was conducted. Research findings were assessed following the GRADE methodology. The evidence to decision framework was used to determine the strength and direction of recommendations. RESULTS: The mode or timing of delivery do not impact neonatal mortality, risk of NEC or time on parenteral nutrition (PN). Intra or extra abdominal bowel dilatation predict complex gastroschisis and longer length of hospital stay but not increased perinatal mortality. Outcomes after Bianchi procedure and primary fascia closure under anesthesia are similar. Sutureless closure decreases the rate of surgical site infections and duration of ventilation compared to surgical closure. Silo-staged closure with or without intubation results in similar outcomes. Outcomes of complex gastroschisis (CG) undergoing early or delayed surgical repair are similar. Early enteral feeds starting within 14 days is associated with lower risk of surgical site infection. RECOMMENDATIONS: The panel suggests vaginal birth between 37 and 39 w in cases of uncomplicated gastroschisis. Bianchi's approach is an option in simple gastroschisis. Sutureless closure is suggested when general anesthesia can be avoided, sutured closure. If anesthesia is required. Silo treatment without ventilation and general anesthesia can be considered. In CG with atresia primary intestinal repair can be attempted if the condition of patient and intestine allows. Enteral feeds for simple gastroschisis should start within 14 days.

Next-Generation Sequencing Gene Panels and "Solo" Clinical Exome Sequencing Applied in Structurally Abnormal Fetuses.

OBJECTIVE: The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and "solo" clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation. METHODOLOGY: Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies. RESULTS: During the study period (2015-2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES. CONCLUSIONS: A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES.

Perinatal outcome after selective termination in dichorionic twins discordant for congenital anomalies.

INTRODUCTION: Our objective was to evaluate the perinatal outcome of selective termination of dichorionic twin pregnancies with discordant anomalies, according to gestational age at time of procedure. MATERIAL AND METHODS: Retrospective review of 147 dichorionic twin pregnancies referred to our Fetal Medicine Unit between 2003 and 2018 for selective termination. Gestational age at delivery, fetal loss, and overall and 28-day post-delivery survival rates, were evaluated according to gestational age at time of procedure. Selective termination procedure was defined as early, intermediate, and late when performed before 18 weeks, between 18 and 23 weeks, and after 23 weeks, respectively. Kruskal-Wallis and chi-squared test were used to compare groups. RESULTS: Overall survival at 28 days post-delivery, pregnancy loss, and preterm delivery before 32 weeks of gestation rates were 93.4%, 6.9%, and 15.5%, respectively. When stratified by gestational age at procedure, intermediate selective termination was associated with a lower survival rate than early and late procedures (86% vs. 96.9% and 100%, respectively; p = 0.035), and a nonsignificant trend for higher pregnancy loss (12% vs. 3.1%). Preterm delivery before 32 weeks of gestation occurred in 27% of late procedures, which was significantly higher than in early (9.5%) and intermediate (18.2%) procedures. CONCLUSIONS: Selective termination in dichorionic twin pregnancies with discordant fetal anomaly is associated with low pregnancy loss and preterm delivery rate, primarily when performed before 18 weeks. When legally possible, late procedures can be a good alternative, particularly in those cases diagnosed beyond the 18th week of gestation.

Chromosome microarray analysis should be offered to all invasive prenatal diagnostic testing following a normal rapid aneuploidy test result.

Chromosomal microarray analysis (CMA) has now replaced karyotyping in the analysis of prenatal cases with a fetal structural anomaly, whereas in those pregnancies undergoing invasive prenatal diagnosis with a normal fetal ultrasound, conventional karyotyping is still performed. The aims of this study were to establish the diagnostic yield of CMA in prenatal diagnosis, and to provide new data that might contribute to reconsider current practices. We reviewed 2905 prenatal samples with a normal rapid aneuploidy detection test referred for evaluation by CMA testing. Our study revealed pathogenic and reported susceptibility copy number variants associated with syndromic disorders in 4.8% (n = 138/2905) of cases, being 2.8% (n = 81/2905) the estimated added diagnostic value of CMA over karyotyping. Clinically significant CMA abnormality was detected in 5.4% (107/1975) of the fetuses with ultrasound anomalies and in 1.4% (5/345) of those considered as low-risk pregnancies. Our series shows that in prenatal samples, CMA increases 2-fold the diagnostic yield achieved by conventional karyotyping.

A New Stepwise Molecular Work-Up After Chorionic Villi Sampling in Women With an Early Pregnancy Loss.

Objective: To explore the use of a new molecular work-up based on the stepwise use of Quantitative Fluorescence PCR (QF-PCR) extended to eight chromosomes and single nucleotide polymorphism array (SNP-array) in chorionic villi obtained by chorionic villi sampling (CVS) offered to women experiencing an early pregnancy loss. Methods: During a 3-year period (January 2016-December 2018), CVS was offered to women experiencing an early pregnancy loss before the evacuation of the products of conception (POC) to retrieve chorionic villi, irrespective of the number of previous losses. A new molecular work-up was prospectively assayed encompassing a first QF-PCR round (with the 21, 18, 13, 7, X, and Y chromosomes), a second QF-PCR round (with the 15, 16, and 22 chromosomes), and a high resolution SNP-array in those cases with normal QF-PCR results. A control group in which POC were collected after surgical uterine evacuation was used to be compared with the intervention group. Results: Around 459 women were enrolled in the intervention group (CVS) and 185 in the control group (POC after uterine evacuation). The QF-PCR testing success rates were significantly higher in the intervention group (98.5%: 452/459) as compared to the control group (74%: 109/147; p < 0.001), while the chromosomal anomaly rate at the two QF-PCR rounds was similar between the two groups: 52% (234/452) in the intervention and 42% (46/109) in the control group (p = 0.073). The SNP-array was performed in 202 QF-PCR normal samples of the intervention group and revealed 67 (33%) atypical chromosomal anomalies (>10 Mb), 5 (2.5%) submicroscopic pathogenic copy number variants, and 2 (1%) variant of uncertain significance (VOUS). Conclusion: Eighty-two percent of women experiencing an early pregnancy loss opted for a CVS. The testing success rates were higher in the intervention group (CVS; 98%) as compared to the control group (POC; 74%). The overall yields were 52% by QF-PCR (including three complete hydatiform moles), and 16% by SNP-array, including 15% atypical chromosomal anomalies and 1.1% submicroscopic pathogenic copy number variants.

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

Crown-rump length audit plots with the use of operator-specific PAPP-A and ß-hCG median MoM.

OBJECTIVE: Audit the crown-rump length (CRL) measurements taken at 11 to 13 weeks scan, using operator-specific median multiples of the median (MoM) for pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG) plots, to identify deviations potentially related to a systematic CRL bias. METHODS: Study population included consecutive singleton pregnancies undergoing first trimester combined screening, scanned by sonologists with at least 100 scans, during the 2011 to 2012 period. Previously described plots for PAPP-A and ß-hCG median MoM points, with their 95% confidence intervals circles, in relation with the expected deviation line were used. These plots have been modified to adjust the deviation line to the sonologist-specific expected MoM variation for each CRL millimetre bias according to each sonologist-specific median gestational ages at both blood sampling and ultrasound. RESULTS: Twenty-eight sonologists performing 9472 scans were included, accounting for 36% of the 77 sonologists and 70% of the 13 643 scans initially considered. Mean gestational age was 10 + 2 weeks at blood sampling and 12 + 4 weeks at ultrasound. Fifteen sonologists (53%) did not demonstrate any CRL bias, 10 (36%) present with a significant CRL underestimation, being above 2 mm in 6 (21%), and in 3 (11%) the observed deviation could not be explained by a systematic CRL bias. CONCLUSIONS: In sonologists with more than 100 NT measurements, operator-specific PAPP-A and ß-hCG median MoM plots are able to identify deviations potentially related to a systematic CRL bias. Systematic underestimation above 2 mm was observed in 1/5 of them. © 2016 John Wiley & Sons, Ltd.

Heterotrisomy recurrence risk: a practical maternal age-dependent approach for excess trisomy 21 risk calculation after a previous autosomal trisomy.

A new maternal age-dependent method to estimate absolute excess risks of trisomy 21, either after a previous trisomy 21 (homotrisomy) or after another trisomy (heterotrisomy), is proposed to be added to the estimated risk by conventional screening methods. Excess risk at term for a subsequent trisomy 21 was calculated from midtrimester risks reported by Morris et al., decreasing from 0.49% at 20 years to 0.01% at 46 years at the index pregnancy. Excess risk after a previous uncommon trisomy was derived from data reported by Warburton et al., decreasing from 0.37% at 20 years to 0.01% at 50 years.

Genomic Microarray in Fetuses with Early Growth Restriction: A Multicenter Study.

BACKGROUND: Little information is available about the risk of microdeletion and microduplication syndromes in fetal growth restriction (FGR) with a normal karyotype. OBJECTIVE: To assess the incremental yield of genomic microarray over conventional karyotyping in fetuses with early growth restriction. STUDY DESIGN: Genomic microarray was prospectively performed in fetuses with early growth restriction defined as a fetal weight below the 3rd percentile estimated before 32 weeks of pregnancy, and a normal quantitative fluorescent polymerase chain reaction result. The incremental yield of genomic microarray was defined by the rate of fetuses presenting with a pathogenic copy number variant below 10 Mb. RESULTS: Among 133 fetuses with early FGR, a 6.8% (95% CI: 2.5-11.0) incremental yield of genomic microarray over karyotyping was observed. This incremental yield was 4.8% (95% CI: 0.2-9.3) in isolated FGR, 10% (95% CI: 0-20.7) in FGR with nonstructural anomalies, and 10.5% (95% CI: 0-24.3) in FGR with structural anomalies. CONCLUSION: Our multicenter study reveals that 6.8% of fetuses with early growth restriction present with submicroscopic anomalies after common aneuploidies were excluded. Even when FGR is observed as an isolated finding, genomic microarray analysis should be considered after or instead of karyotyping, due to its 4.8% incremental yield.

Effectiveness of ovarian age as the background risk for aneuploidy screening in an unselected pregnant population.

The aim of this study was to assess the performance of first-trimester combined screening when replacing the chronological maternal age by Anti-Müllerian hormone (AMH) and antral follicle count (AFC)-derived ovarian ages, as the background risk in trisomy risk estimation. A total of 639 pregnant women who completed first-trimester combined screening together with AMH and AFC determination were included. Trisomy risks were estimated based on three distinct 'maternal ages' as a-priori risk (chronological age, AMH- and AFC-derived ovarian age). The screening performance was assessed using three different approaches: received operator curve; detection rate and false positive rates for a fixed 1/250 threshold; and detection rates for a fixed 3% false positive rate. A non-significant trend was shown for AMH-derived age for both an increased area under the curve (0.986 versus 0.979) and an increased detection rate (from 83% to 100%) for a 1/250 risk threshold. For a 3% false-positive rate, a non-significant trend for increased detection with the use of both AMH- and AFC-derived ovarian ages was observed (from 67% to 83%). These results indicate that, although ovarian derived ages seem to potentially reflect a more precise background risk for fetal trisomies, the improvement in screening performance is only residual.

Use of placental growth factor and uterine artery doppler pulsatility index in pregnancies involving intrauterine fetal growth restriction or preeclampsia to predict perinatal outcomes.

AIM: The potential of uterine artery (UA) Doppler pulsatility index (PI) and maternal serum placental growth factor (PlGF) level to predict perinatal outcome was explored in pregnancies complicated by intrauterine fetal growth restriction (IUGR) or preeclampsia (PE). METHODS: This longitudinal, prospective, and case-controlled study was conducted over a period of 24 months. At-risk pregnancies involving small-for-gestational-age (SGA) fetuses, IUGR, gestational hypertension (GH), or PE were investigated, analyzing UA Doppler PI findings and maternal PlGF levels determined at the time of diagnosis (third trimester). RESULTS: UA Doppler PI and maternal serum PlGF values differed significantly in pregnancies complicated by IUGR and/or PE (vs. SGA or GH, p < 0.01). In the context of IUGR or PE, both parameters also differed significantly by perinatal outcome (adverse vs. normal, p < 0.01), although no predictive advantage over UA Doppler PI alone was conferred by adding a PlGF assay. CONCLUSION: UA Doppler PI and maternal serum PlGF determinations in the third trimester help identify pregnancies at the highest risk of adverse perinatal outcomes due to IUGR and/or PE. Although joint testing confers no predictive benefit over UA Doppler PI alone, the two diagnostics are interchangeable for this purpose.

Role of 3-dimensional power Doppler sonography in differentiating pregnant women with threatened preterm labor from those with an asymptomatic short cervix.

OBJECTIVES: To compare cervical volumes and vascularization indices using 3-dimensional power Doppler sonography among singleton pregnancies with threatened preterm labor and an asymptomatic short cervix. METHODS: Three hundred asymptomatic healthy pregnant women between 24 and 34.6 gestational weeks were prospectively scanned for cervical length. If cervical length was short, defined as below the 10th percentile for gestational age, the cervical volume and vascularization indices (vascularization index [VI], vascularization-flow index [VFI], and flow index [FI]) were measured. Women receiving any treatment for preterm delivery prevention were excluded. During this period, the same sonographic parameters were measured among patients with threatened preterm labor admitted to our institution during the first 24 hours after admission. Multiple pregnancies and fetal or maternal pathologic conditions, were exclusion criteria. Data on body mass index, maternal age, smoking, parity, family history of preterm birth, mother who was born preterm, and previous preterm birth among the pregnant women were recorded. Sonographic and medical history parameters were compared between the two groups. RESULTS: Twenty-nine asymptomatic healthy women (9.6%) had a short cervix. Additionally, 71 pregnancies with threatened preterm labor were scanned. There were no statistically significant differences between the groups in medical history parameters or cervical length. The cervical volume was smaller in threatened preterm cases (12.90 versus 17.168 cm(3); P = .005). The VI and VFI were lower in women with an asymptomatic short cervix (VI, 4.369% versus 15.939%; P < .001; VFI, 1.514 versus 4.878; P < .001). The FI was higher in the short cervix group (33.581 versus 30.311; P = .006). CONCLUSIONS: Three-dimensional transvaginal sonography reveals differences in cervical volume and vascularization indices between pregnancies with an asymptomatic short cervix and cases with threatened preterm labor, although cervical length is similar in both groups.

New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia.

To establish gestational phase adapted cutoffs for the use of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio as a diagnostic tool for preeclampsia in the clinical setting, a multicenter case-control study including a total of 1149 patients was performed. We report normal values of sFlt-1, PlGF, and the sFlt-1/PlGF ratio based on the analysis of a total of 877 patients with uneventful pregnancy outcome. A total of 234 patients with preeclampsia and a matched cohort consisting of 468 patients with normal pregnancy outcome were compared, and sFlt-1 and PlGF were measured on an automated platform. Separate cutoffs for the sFlt-1/PlGF ratio were determined for the early (20+0-33+6 weeks) and the late gestational phase (34+0 weeks-delivery). For each of the 2 gestational phases, 2 independent cutoffs framing an equivocal zone were determined: the first cutoff with focus on high sensitivity, and the second focusing on high specificity. Between 20+0 and 33+6 weeks, the cutoffs at ≤33 and ≥85 resulted in a sensitivity/specificity of 95%/94% and 88%/99.5%, respectively. An sFlt-1/PlGF ratio of ≤33 had the lowest likelihood of a negative test (0.05; 95% confidence interval, 0.02-0.13), whereas values ≥85 had the highest likelihood of a positive test (176; 95% confidence interval, 24.88-1245). After 34+0 weeks, the cutoffs at ≤33 and ≥110 yielded a sensitivity/specificity of 89.6%/73.1% and 58.2%/95.5%, respectively. The approach to use multiple cutoffs for the early and late gestational phase enhances the diagnostic accuracy of the sFlt-1/PlGF ratio as a diagnostic tool for preeclampsia.

Cumulative sum plots and retrospective parameters in first-trimester ductus venosus quality assurance.

OBJECTIVE: This study aimed to evaluate the application of two quality assurance methods to the ductus venosus pulsatility index (DVPI), as a first-trimester aneuploidy marker, including retrospective assessment of distribution parameters and cumulative sum (CUSUM) plots. METHODS: The DVPI was measured in 14 444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine centers during a 4-year period. Sonologist-specific quality assurance distribution parameters, previously described for nuchal translucency, were assessed: the median multiples of the median (MoM), the logarithmic standard deviation of DVPI MoMs and the weekly DVPI percent decrease. Quality assurance results were compared between median MoMs and MoM-based CUSUM plots. RESULTS: When sonologist-specific DVPI distribution parameters were retrospectively applied for quality assurance, a 1.0 median MoM, a 0.1 median logarithmic standard deviation and a 3.4 median weekly DVPI drop percentage were observed. CUSUM plots showed good agreement with 0.9-1.1 MoMs range for median MoM, in the assessment of sonologist-specific performances. CONCLUSION: Retrospective and prospective DVPI quality assurance methods appear to be applicable to DVPI at 11+0 to 13+6 weeks. Its use should be encouraged if DVPI is to be added to first-trimester Down syndrome or cardiac defects screening.

Updated reference ranges for the ductus venosus pulsatility index at 11-13 weeks.

OBJECTIVE: To update the reference ranges for the ductus venosus pulsatility index (DVPI) at 11+0 to 13+6 gestational weeks. METHODS: DVPI was calculated in 14,444 singleton fetuses at 11+0 to 13+6 weeks in two Fetal Medicine Centers, during a 4-year period. Using previously described medians, DVPI evolution was assessed both over the study period on a yearly basis and over gestation, grouping fetuses according to 5-mm crown-rump length (CRL) ranges. Weighted DVPI medians, the 5th and 95th percentiles and distribution parameters for unaffected and trisomy 21 fetuses were newly calculated. RESULTS: A significant DVPI multiple of the median decrease was observed over both the study period (p < 0.01) and over gestation (p < 0.01) using previous medians, in the two centers. Newly calculated weighted medians were lower than those previously described, decreasing with CRL. Distribution parameters calculated using the new medians were different from those previously described. CONCLUSION: DVPI reference ranges were lower than those previously reported and decreased with CRL. Updated medians and distribution parameters should be considered to include the DVPI as a Gaussian marker in trisomy 21 screening and for quality control purposes.

Control de calidad en el cribado prenatal de aneuploidías / Quality control in prenatal screening for aneuploidy

Un aspecto esencial e imprescindible de los programas de cribado prenatal es el control de calidad. En este sentido, contrariamente a lo que ocurre en el ámbito del laboratorio clínico, donde las pruebas analíticas están sometidas a estrictos controles de calidad para determinar y confirmar su fiabilidad, en el campo de la medicina fetal y más concretamente en el ámbito de la ecografía prenatal, el concepto de evaluación de la calidad y la certificación solo recientemente ha sido objeto de interés. En todo programa de cribado prenatal, aunque la tasa de detección del síndrome de Down (SD) sigue siendo una prioridad y un indicador de su efectividad, este parámetro no puede ser utilizado como un marcador fiable de la calidad del mismo, fundamentalmente debido a la baja prevalencia de dicha condición. Los esfuerzos en el control de calidad del cribado prenatal de aneuploidías deben incluir indicadores más fiables, realistas y de aplicación individualizada. Este artículo pretende revisar y clarificar los conceptos fundamentales en el ámbito del control de calidad en el cribado prenatal de aneuploidías y propone estrategias para mejorar su fiabilidad (AU)

Quality control is an essential aspect of prenatal screening programs. In this respect, contrary to what happens in the field of the clinical laboratory, where the analytical tests are submitted to strict quality controls to determine and to confirm their reliability in the field of the foetal medicine, and more specifically in the área of prenatal ultrasound, the concept of quality assessment and certification has only recently been a subject of interest. In any prenatal screening program, although the detection rate of Down’s Síndrome (SD) remains being a priority and an indicator of its efficiency, this parameter cannot be used as a reliable marker of its quality, mainly due to the low prevalence of this condition. Efforts in the quality control of prenatal screening for aneuploidy should include more reliable, realistic and individualised applications. This article aims to review and clarify the key concepts in the field of quality control in prenatal screening for aneuploidy and proposes strategies to improve reliability (AU)

Cord blood collection for banking and the risk of maternal hemorrhage.

We determined the effect of cord blood collection before placental expulsion on postpartum maternal blood loss in a retrospective study between a group of cord blood donors and a group of non-donors. The study was conducted in a university hospital blood bank and obstetric services and included Spanish women entered in a European study project (EUPHRATES) and who had consented to donate cord blood for public banking purposes. We measured blood volume lost during delivery by a bag collection method, as well as the need for transfusion and postpartum anemia symptoms. Deliveries at which cord blood was collected presented a significant increase in blood loss (321 ± 273 vs. 255 ± 237 ml, p=0.02). Instrumental deliveries were associated with higher postpartum blood loss than spontaneous deliveries. Cord blood collection can increase intrapartum blood loss, especially at instrumental deliveries. Additional staff who handle the collection are required to allow the leading clinician to focus on maternal care.

Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene.

OBJECTIVE: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. DESIGN: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. RESULTS: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. CONCLUSIONS: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.

The use of biochemical markers in prenatal diagnosis of intrauterine growth retardation: insulin-like growth factor I, Leptin, and alpha-fetoprotein.

OBJECTIVE: To determine the relation between weight deficit at birth and IGF-I, IGFBP-I, Leptin, and AFP levels in amniotic fluid after 14-18 weeks; to assess the diagnostic usefulness of these biochemical markers. STUDY DESIGN: Longitudinal, prospective study. Amniocentesis was performed in pregnant women after 14-18 weeks of gestation. STUDY POPULATION: 86 controls, 18 IUGR <10 percentile, and 17 IUGR <5 percentile. RESULTS: No significant correlation was found between severity of IUGR and IGF-I, IGFBP-I, or Leptin. AFP was inversely correlated with severity of IUGR; results for the IUGR <10 percentile were: S: 65.7%, SP: 56.9%, PPV: 38.3%, NPV: 80.3%, and an overall diagnostic capacity of 65.6%. Results for the IUGR <5 percentile were: S: 76.4%, SP: 54.8%, PPV: 21.6%, NPV: 93.4% were obtained, and an overall capacity of 70.6%. CONCLUSIONS: Elevated values of AFP in amniotic fluid may help early detection of populations at risk of developing IUGR.