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OBJECTIVE: Previous studies have established the association between fetal hypoxia and elevated nucleated red blood cells (NRBCs). Animal studies have demonstrated that a rise in plasma erythropoietin (EPO) is not detectable until 4 to 6 hours after the initiation of hypoxia. In contrast, interleukin-6 (IL-6) has the capacity to directly induce erythroid maturation. Therefore, we set forth to evaluate the role of EPO and IL-6 as potential mediators of elevated fetal NRBCs in response to acute hypoxia. STUDY DESIGN: Low-risk pregnancies with a normal fetal heart rate at admission to labor and delivery were eligible for participation. Deliveries for 'nonreassuring fetal status' comprised the study group. All other deliveries served as controls. Umbilical cord blood was prospectively collected for blood gas analysis, NRBC counts, EPO, and IL-6. RESULTS: One hundred women participated in the study. Nonparametric univariate analysis demonstrated a significant association between elevated NRBC counts and Apgar scores, arterial cord blood pH, base excess, EPO, and IL-6 levels (all P values <.01). Stepwise regression analysis identified only pH, IL-6, and EPO as independent variables associated with elevated NRBC counts at birth (all P values <.0001 with R2 of 0.27, 0.42, and 0.46, respectively). A significant increase in NRBC counts was noted in study patients. IL-6 was significantly increased in study patients, whereas there was no difference in EPO between groups. CONCLUSION: The fact that NRBC counts were elevated in fetuses who were delivered for 'nonreassuring fetal status' with EPO being normal and IL-6 being elevated implies that IL-6 may have a unique, short-term role in elevating fetal NRBC counts. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the association between timing and indication for previous cesarean section (C-section) and its association with postpartum risks for adverse maternal outcomes, primarily postpartum hemorrhage (PPH) in vaginal birth after cesarean (VBAC)., Methods: This retrospective case-control study examined women following term vaginal delivery in a university-affiliated medical center between 2008 and 2018. Postpartum complications were compared between women who had their first VBAC and a control group comprised of women who had vaginal delivery without prior C-section. Additional analysis was performed to evaluate the association between the timing of previous C-section and the severity of postpartum adverse outcomes., Results: Of the women meeting the inclusion criteria (n = 2879), 1,455 had VBAC and 1,424 were in the control group. Overall, significant postpartum complications, primarily PPH, were observed in the VBAC group compared to controls. Women who underwent C-section during second-stage of labor experienced higher PPH rates and increased drop in hemoglobin levels compared to women who underwent C-section during the first stage of labor or an elective C-Sect. (4.3 ± 0.9 g/dL vs. 2.8 ± 1.1 g/dL vs. 2.4 ± 0.8, p = 0.033). Concomitant increased need for blood transfusion (8.1% vs. 3.5% vs. 2.9%, respectively, p < 0.0001) and uterine atony (12.6% vs. 6.2% vs. 4.4%, respectively, p = 0.009) were also observed. No significant differences were demonstrated in other postpartum adverse effects evaluated., Conclusion: VBAC is associated with higher rates of postpartum complications, primarily PPH. The risk is significantly increased in VBAC following a second stage cesarean section. This data should be taken into consideration in the management of laboring women after C-section., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In recent years, cell-free DNA screening has significantly reduced the number of invasive prenatal diagnostic testing in pregnancy. Preimplantation genetic testing for aneuploidies (PGT-A) is a commonly performed screening test in in vitro fertilization (IVF) pregnancies. Therefore, we aimed to determine the impact of PGT-A on subsequent utilization of prenatal diagnostic testing in IVF pregnancies., Methods: Retrospective cohort of singleton and twin IVF pregnancies at a single center from January 2014 to December 2017. The rate of invasive diagnostic genetic testing (chorionic villus sampling (CVS) and/or amniocentesis) was compared between patients with pregnancies achieved after transfer of a euploid embryo by PGT-A ( n  = 71) and those with pregnancies achieved after transfer of an untested embryo ( n  = 38). Wilcoxon rank sum and Fisher's exact tests were used for statistical analysis., Results: There was no statistically significant difference in the number of prenatal diagnostic procedures (25.4% PGT-A euploid embryo versus 31.6% untested embryo, p  = .51 and p  = .32 for one-sided and two-sided analyses, respectively) between the two groups. Maternal age, nuchal translucency measurements and the rate of abnormal sonographic findings were similar between the two groups. Patients without PGT-A pregnancies had a higher BMI (mean 29.6, p  = .01) and were ethnically different ( p  = .013) compared to those with PGT-A., Conclusion: The implementation of PGT-A in IVF patients did not reduce the number of invasive diagnostic tests performed at our institution.

Maternal natural vaginal progesterone (nVP) administration has been shown to reduce the risk of preterm birth (PTB). The largest randomized trial of nVP for PTB (OPPTIMUM) noted a sonographic reduction in neonatal brain injury following nVP treatment. We investigated the neuroinflammatory protective effect of maternal nVP in a mouse model for maternal inflammation. Pregnant mice (n = 24) were randomized to nVP (1 mg/day) or vehicle from days 13-16 of gestation. At days 15 and 16, lipopolysaccharide (30 μg) or saline were administered. Mice were sacrificed 4 h following the last injection. Fetal brains and placentas were collected. Levels of NF-κB, nNOS, IL-6, and TNFα were determined by Western blot. Maternal lipopolysaccharide significantly increased fetal brain levels of IL-6 (0.33 ± 0.02 vs. 0.11 ± 0.01 u), TNFα (0.3 ± 0.02 vs. 0.10 ± 0.01 u), NF-κB (0.32 ± 0.01 vs. 0.17 ± 0.01 u), and nNOS (0.24 ± 0.04 vs. 0.08 ± 0.01 u), and reduced the total glutathione levels (0.014 ± 0.001 vs. 0.026 ± 0.001 pmol/μl; p < 0.01) compared with control. Maternal nVP significantly reduced fetal brain levels of IL-6 (0.14 ± 0.01 vs. 0.33 ± 0.02 u), TNFα (0.2 ± 0.06 vs. 0.3 ± 0.02 u), NF-κB (0.16 ± 0.01 vs 0.32 ± 0.01 u), and nNOS (0.14 ± 0.01 vs 0.24 ± 0.04 u), and prevented the reduction of fetal brain total glutathione levels (0.022 ± 0.001 vs. 0.014 ± 0.001 pmol/μl; p < 0.01) to levels similar to controls. A similar pattern was demonstrated in the placenta. Maternal nVP for PTB may protect the fetal brain from inflammation-induced brain injury by inhibiting specific inflammatory and oxidative pathways in both brain and placenta.

Background: Asymptomatic short cervical length is an independent risk factor for spontaneous preterm birth. However, most studies have focused on the associated risk of a short cervical length when encountered between 16 and 23 weeks' gestation. The relationship between cervical length and risk of spontaneous preterm birth after 23 weeks is not well known., Objective: To evaluate the risk of spontaneous preterm birth in asymptomatic women with a short cervix (≤25 mm) at 23-28 weeks' gestation., Materials and Methods: A retrospective cohort study of women with asymptomatic short cervix (cervical length ≤25 mm) at extreme prematurity, defined as 23-28 weeks' gestation, was performed at a single center from January 2015 to March 2018. Women with symptoms of preterm labor, multiple gestations, fetal or uterine anomalies, cervical cerclage, or those with incomplete data were excluded from the study. Demographic information as well as data on risk factors for spontaneous preterm birth were collected. Patients were divided into 4 groups based on the cervical length measurement (≤10 mm, 11-15 mm, 16-20 mm, and 21-25 mm). The primary outcome was time interval from enrollment to delivery. Secondary outcomes included delivery within 1 and 2 weeks of enrollment, gestational age at delivery, and delivery prior to 32, 34, and 37 weeks, respectively. Continuous variables were compared using Kruskal-Wallis test, whereas categorical variables were compared using the χ 2 or Fisher exact test as appropriate. The Wilcoxon test for difference in survival time was used to compare gestational age at delivery among the 4 cervical length groups, with data stratified based on gestational age at enrollment., Results: Of the 126 pregnancies that met inclusion criteria, 22 (17.4%) had a cervical length of ≤10 mm, 23 (18.3%) had a cervical length of 11-15 mm, 37 (29.4%) had a cervical length of 16-20 mm, and 44 (34.9%) had a cervical length of 21-25 mm. Baseline characteristics were similar among all 4 groups. The shorter cervical length group was associated with a shorter time interval from enrollment to delivery (cervical length ≤10 mm, 10 weeks; cervical length 11-15 mm, 12.7 weeks; cervical length of 16-20 mm, 13 weeks; cervical length of 21-25 mm, 13.2 weeks; P = .006). Regardless of the cervical length measurement, delivery within 2 weeks was extremely uncommon (1 patient; 0.8%). The prevalence of spontaneous preterm birth at <32 weeks or <34 weeks was higher in women with a cervical length of ≤10 mm compared to those with a longer cervical length (P < .001)., Conclusions: The risk of spontaneous preterm birth in asymptomatic women with a sonographic short cervix increases as cervical length decreases. The risk is substantially higher in women with a cervical length of ≤10 mm. Women with a cervical length of ≤10 mm also had the shortest time interval to delivery. Nevertheless, delivery within 1 or 2 weeks is highly unlikely, regardless of the cervical length at the time of enrollment. Therefore, based on our data, we suggest that management decisions such as timing of administration of antenatal corticosteroids in asymptomatic patients with a cervical length of ≤25 mm at 23-28 weeks' gestation may be delayed until additional indications are present., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether abnormal levels of first-trimester maternal serum free β-hCG and PAPP-A are associated with significant copy number variants (CNVs) on chromosomal microarray analysis (CMA)., Methods: Retrospective cohort of singleton prenatal CMA studies (n = 2880). Cases with an abnormal karyotype, benign familial or de novo variants, and absence of heterozygosity were excluded. The prevalence of abnormal serum analytes was compared between patients with significant CNVs (n = 56) and those with normal CMA (n = 884). Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using Fisher's exact test. Mantel-Haenszel method was utilized to adjust ORs for prenatal diagnostic procedure type and indications for testing. Statistical significance was determined as P value < 0.05., Results: Abnormally low serum free β-hCG (≤0.45 MoM) was associated with an increased risk of significant CNVs (OR 3.53, 95% CI, 1.25-8.66, P < 0.01). This association remained significant after adjusting for abnormal nuchal translucency and advanced maternal age (AMA) (adjusted OR 3.04, 95% CI, 1.05-7.48, P < 0.05) or procedure type and AMA (adjusted OR 3.21, 95% CI 1.13-8.16, P < 0.05). The associations of abnormally high serum free β-hCG, low PAPP-A, and high PAPP-A with significant CNVs were not statistically significant., Conclusion: Low first-trimester serum β-hCG is associated with an increased risk of significant CNVs on CMA., (© 2018 John Wiley & Sons, Ltd.)

Objective: To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth., Methods: Pregnant rats were exposed to a severe hypoxia (9.5%-10% O 2 ) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O 2 ) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student's t test and simple regression were used for statistical analysis., Results: As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count., Conclusion: In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.

Objective  To assess the additive value of prenatal chromosomal microarray analysis (CMA) for all indications and the likelihood of detecting pathologic copy number variations (CNVs) based on specific indications. Methods  A retrospective analysis was performed on amniocentesis and chorionic villi sampling results obtained between 2010 and 2014 in a single institution. A total of 3,314 consecutive patients undergoing invasive genetic testing for different indications were offered CMA in addition to standard karyotype. The prevalence of pathologic CNVs was compared between patients with low-risk indications and those with high-risk indications. Likewise, the prevalence of pathologic CNVs among patients with different sonographic abnormalities was calculated and compared with the low-risk group. Chi-square and Fisher exact tests were used for statistical analysis. Results  The prevalence of pathologic CNVs was significantly higher in patients with high-risk indications and specifically those with sonographic abnormalities, compared with the low-risk group (2.8 and 5.9% vs. 0.4%, respectively; all p  < 0.05). Conclusion  Prenatal CMA detected clinically relevant CNVs in fetuses with a normal karyotype. Major structural malformations and nuchal translucency (NT) ≥ 3.0 mm are associated with the highest risk for a CMA abnormality. Nevertheless, the prevalence of pathologic CNVs in the low-risk population was high enough (1:250) to consider genetic counseling in this group., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Maternal chorioamnionitis is associated with newborn neurologic injury. Recent evidence suggests that maternal administration of magnesium sulphate (MG) may protect fetuses from white matter injury. Previously we demonstrated evidence by magnetic resonance imaging that MG may prevent maternal inflammation-induced gray matter injury of offspring. Thus, we sought to determine the potential of maternal inflammation to induce fetal neurological/behavioral deficits and assess whether maternal MG attenuates these effects., Study Design: Pregnant rats at day 18 received injections of intraperitoneal lipopolysaccharide (LPS) or saline. Dams were treated with subcutaneous saline/MG (270 mg/kg followed by 27 mg/kg every 20 minutes) for 2 hours before and following LPS/saline injections. Pups were delivered spontaneously. At 1 and 3 months of age, 11-12 offspring of each group (saline, LPS, MG, LPS-MG) underwent a 2-way shuttle box avoidance testing. The shuttle box is divided in half and the animal moves between compartments to avoid an electric shock in response to an auditory stimulus., Results: Control offspring demonstrated significantly improved learning and memory abilities from age 1 to 3 months. At 1 month, LPS-treated dams' offspring were similar to controls with no improvement in learning abilities at 3 months. MG treatment of LPS dams significantly improved offspring learning at 3 months, to equal or better than that of controls., Conclusion: LPS-stimulated inflammation during pregnancy impairs offspring learning ability and memory, which is ameliorated by maternal MG treatment. These results suggest that maternal MG therapy may prevent white and gray matter injuries associated with maternal infection/inflammation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report 2 cases in which first-trimester measurements of the intracranial translucency and the brain stem-to-occipital bone diameter were markedly enlarged. This finding was thought to represent an abnormal fourth ventricle-cisterna magna complex. Subsequently, the diagnoses of a Dandy-Walker malformation with partial vermian agenesis in 1 case and inferior vermian hypoplasia in the other were established and confirmed by either postmortem autopsy or postnatal magnetic resonance imaging. These cases suggest that evaluation of the fourth ventricle-cisterna magna complex, by measuring the intracranial translucency or brain stem-to-occipital bone diameter may identify some cases with structural malformations of the cerebellum as early as the first trimester.

We delineated and analyzed directly oriented paralogous low-copy repeats (DP-LCRs) in the most recent version of the human haploid reference genome. The computationally defined DP-LCRs were cross-referenced with our chromosomal microarray analysis (CMA) database of 25,144 patients subjected to genome-wide assays. This computationally guided approach to the empirically derived large data set allowed us to investigate genomic rearrangement relative frequencies and identify new loci for recurrent nonallelic homologous recombination (NAHR)-mediated copy-number variants (CNVs). The most commonly observed recurrent CNVs were NPHP1 duplications (233), CHRNA7 duplications (175), and 22q11.21 deletions (DiGeorge/velocardiofacial syndrome, 166). In the ∼25% of CMA cases for which parental studies were available, we identified 190 de novo recurrent CNVs. In this group, the most frequently observed events were deletions of 22q11.21 (48), 16p11.2 (autism, 34), and 7q11.23 (Williams-Beuren syndrome, 11). Several features of DP-LCRs, including length, distance between NAHR substrate elements, DNA sequence identity (fraction matching), GC content, and concentration of the homologous recombination (HR) hot spot motif 5'-CCNCCNTNNCCNC-3', correlate with the frequencies of the recurrent CNVs events. Four novel adjacent DP-LCR-flanked and NAHR-prone regions, involving 2q12.2q13, were elucidated in association with novel genomic disorders. Our study quantitates genome architectural features responsible for NAHR-mediated genomic instability and further elucidates the role of NAHR in human disease.

Purpose: To evaluate whether patients with isolated elevation of umbilical artery (UA) systolic/diastolic (S/D) ratio are at increased risk for adverse perinatal outcome., Methods: This is a retrospective cohort study of 330 patients who underwent routine evaluation at our maternal fetal medicine center. We regularly perform UA S/D ratio analysis with every third trimester sonogram. All identified patients were included and divided into four groups based on estimated fetal weight (EFW) and UA S/D ratio. Perinatal outcome was compared between the groups., Results: Regardless of the EFW, fetuses with persistent elevated UA S/D ratio showed significantly more preterm deliveries (p < .001), neonatal intensive care unit (NICU) admissions (p < .001), longer stay in the NICU (p < .001) and lower birth weight (p < .001) relative to controls. Stepwise logistic regression analysis demonstrated that being a member in any study group significantly and independently predicted birth weight less than the 10th percentile and preterm delivery. Patients with persistently elevated S/D ratio were significantly and independently from other factors, more likely to have a newborn admitted to the NICU., Conclusion: Our results indicate a suboptimal perinatal outcome in all pregnancies with an elevated UA S/D ratio. These fetuses may benefit from intensive monitoring.

Objective: To compare the indications for invasive prenatal testing resulting in the detection of translocation Down syndrome and complete trisomy 21., Study Design: This case control study was based on a large amniocentesis and chorionic villi samples database (n = 534,795). All specimens with translocation Down syndrome (n = 203) comprised the translocation group and were compared with a maternal age-matched group (4 to 1, n = 812) in which complete trisomy 21 was detected. Women with a normal karyotype were randomly selected (n = 812) and served as controls. Indications for invasive testing were compared among the 3 paired groups using χ(2) analysis., Results: There were no differences in the incidence of abnormal first- and second-trimester screening tests between the translocation Down syndrome and the complete trisomy 21 groups. History of prior aneuploidy was significantly more frequent in the translocation Down syndrome group, as compared with either complete trisomy 21 fetuses or normal controls., Conclusion: Fetuses with translocation Down syndrome present with the same screening abnormalities as fetuses with complete trisomy 21., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objectives: To evaluate the impact of maternal body mass index (BMI) as well as maternal ethnicity on the detection of either echogenic intra-cardiac focus (EIF) or echogenic bowel (EB)., Methods: This prospective study identified 74 uncomplicated singleton fetuses in which EIF and/or EB were detected between 18 and 21 weeks of gestation (i.e. study group). Seventy four consecutively scanned fetuses without EIF or EB, at the same gestational age, were selected as controls. The differences in maternal BMI and maternal ethnicity were compared between the two groups using the chi(2) test, Fisher's exact test, and the Student t-test. A multivariable logistic regression model was constructed to control for confounders. Odds ratios (OR) and their 95% confidence interval (CI) were computed., Results: The mean maternal BMI was significantly lower in the study group as compared to controls (22.9 +/- 3.1 vs. 28.0 +/- 7.5 kg/m(2), respectively; p < 0.0001). Patients with fetal EIF and/or EB were significantly more likely to be Asians (20.3% vs. 5.4%, OR = 4.5; 95% CI 1.3-16.9). Using a multivariable analysis, controlling for ethnicity, the association between maternal BMI and fetal EIF or EB remained significant (OR = 0.83; 95% CI 0.76-0.91). However, based on this model Asian ethnicity was not an independent risk factor for the detection of EIF and/or EB (OR = 2.6; 95% CI 0.8-8.9)., Conclusions: Our data suggests an inverse relationship between the maternal BMI and the detection of fetal EIF and/or EB. Moreover, it appears that low maternal BMI, and not Asian ethnicity, is an independent risk factor for the detection of these echogenic fetal findings.

The surgical approach in a patient with a ventriculoperitoneal shunt in need of abdominal surgery remains controversial. The risk of increased intracranial pressure with pneumoperitoneum in laparoscopy is still unresolved. We used the LapDisc (Ethicon, Inc., Somerville, New Jersey) to access the shunt and temporarily seal it, which enabled us to perform laparoscopic resection of endometriosis without subjecting the shunt to high intraabdominal pressure. The benefits of this approach are the ability to perform laparoscopy, less skin-to-shunt contact minimizing infection, and elimination of possible increased intracranial pressure secondary to pneumoperitoneum. With the progress made in the management of hydrocephalus, patients with ventriculoperitoneal (VP) shunts enjoy a longer lifespan. Therefore, the gynecologic laparoscopic surgeon can expect to treat a patient with a VP shunt in place., (Copyright (c) 2010 AAGL. Published by Elsevier Inc. All rights reserved.)

Traditionally, monochorionicity in multiple pregnancies is associated with monozygocity. We present a case of a spontaneous, monochorionic dizygotic, sex-discordant twin pregnancy. The diagnosis of monochorionicity was initially done during first-trimester ultrasound evaluation and then confirmed by postnatal placental pathology. Furthermore, both twins were found to have blood chimerism. We also review the literature on dizygotic-monochorionic twins and blood-chimerism. We suggest that further prospective postnatal genetic studies are needed to define the reliability of prenatal diagnosis of identical twins in cases of monochorionicity.

Objective: We sought to compare the indications for amniocentesis leading to the detection of either mosaicism of trisomy 21 (mosaic-T21) or complete trisomy 21 (T21)., Study Design: A retrospective review of a large amniocentesis database (n = 494,163) was conducted. All specimens with mosaic-T21 (n = 124) were compared with a maternal age-matched group of T21 fetuses (n = 496). Samples with normal karyotypes were matched for maternal age and served as normal controls (n = 496). The chi(2) testing was used for statistical analysis., Results: The presence of an abnormal first-trimester screen, abnormal sonographic findings, and specifically the single sonographic abnormalities of either a cystic hygroma or a cardiac anomaly were significantly less common in the mosaic-T21 as compared with the T21 group. There were no such differences between the mosaic-T21 and the normal control group., Conclusion: Fetuses with mosaic-T21, similar to those with normal karyotype, do not present with the same abnormal screening tests as fetuses with T21.

Aims: To measure the amniotic fluid index (AFI) in cases of preterm premature rupture of membranes (PPROM)., Methods: A retrospective study of pregnancies complicated with PPROM was performed. Data collected included maternal age, parity, gestational age at PPROM and at birth, and AFI on admission. Gestational age matched AFIs were obtained from a low-risk control group in a 3:1 ratio., Results: One hundred and two singleton pregnancies with PPROM formed the study population. The mean gestational age at PPROM was 29+/-5.3 weeks (range: 14-36.6 weeks). The mean AFI in the PPROM and the control groups was 5.8+/-3.6 cm (0-18.5 cm) and 13.7+/-3.2 cm (7.3-24.4 cm), respectively (P<0.001). The area under the ROC curve of AFI in the prediction of PPROM was 0.95 (P<0.001). An AFI of < or =10 cm had sensitivity, specificity, positive and negative predictive values of 89.2%, 88.5%, 72.2% and 96%, respectively, in supporting the diagnosis of PPROM., Conclusions: The presence of low AFI supports the diagnosis of PPROM. ROC curve analysis revealed that an AFI < or =10 cm is the optimal cut-off value in the suspicion of PPROM.

Aims: Recent advances in prenatal screening, including first and second trimester genetic screening as well as targeted sonography, have significantly improved the detection of trisomy 21. Therefore, several investigators have questioned the validity of recommending genetic amniocentesis to all women who are 35 years or older at delivery. Thus, we sought to investigate the risks and benefits associated with performing genetic amniocentesis in women whose sole indication for testing was advanced maternal age (AMA)., Methods: A retrospective review of a Genzyme Genetics amniocentesis database (January 2006-December 2006) was performed. All specimens obtained from women of AMA as the sole indication were eligible for analysis. The amniocentesis-related potential fetal loss was calculated based on the traditional fetal loss rate of 1/200 as well as the recently published loss rate of 1/1600 procedures. Risk-benefit analysis was performed by comparing the number of trisomy 21 fetuses identified within the AMA group to the potential number of amniocentesis-related fetal losses within this group., Results: A total of 87,241 amniocentesis specimens were processed during the study period. AMA was the sole indication for genetic amniocentesis in 43,303 cases which formed the study group. In 399 (0.92%) of these cases, a trisomy 21 was identified. Assuming an amniocentesis related fetal loss rates of 1/200 or 1/1600; 217 or 27 fetal losses would have been expected, respectively., Conclusions: Our analysis suggests that the benefit of genetic amniocentesis for the sole indication of AMA far outweighs the potential amniocentesis-related fetal loss rate, regardless of the actual rate one considers.

Objective: To determine the association between fetal biometry in the first or early second trimester and severe macrosomia at delivery., Methods: This case-control study included 30 term severely macrosomic neonates; 90 appropriate-for-gestational age (AGA) neonates served as controls. All pregnancies underwent nuchal translucency (NT) screening at 11-14 weeks' gestation. Pregnancies were dated by accurate last menstrual period consistent with crown-rump length (CRL) measurements at the time of screening, early pregnancy CRL or date of fertilization. The association between birth weight and the difference between the measured and the expected CRL at the time of NT screening was analyzed., Results: The difference between measured and expected CRL, expressed both in mm and in days of gestation, was statistically greater in the severely macrosomic neonates compared with controls (mean, 6.66 +/- 4.78 mm vs. 1.17 +/- 4.6 mm, P < 0.0001 and 3 +/- 2.2 days vs. 0.5 +/- 2.3 days, P < 0.0001, respectively). Furthermore, there were significant correlations between the extent of macrosomia and the discrepancy between expected and measured fetal size at the time of NT screening (r = 0.47, P < 0.01 and r = 0.48, P < 0.01, respectively)., Conclusion: Severe macrosomia apparently manifests as early as 11-14 weeks' gestation., ((c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)

The standard definition of a prolonged pregnancy is 42 completed weeks of gestation. The incidence of prolonged pregnancy varies depending on the criteria used to define gestational age at birth. It is estimated that 4 to 19% of pregnancies reach or exceed 42 weeks gestation. Several studies that have used very large computerized databases of well-dated pregnancies provided insights into the incidence and nature of adverse perinatal outcome such as an increased fetal and neonatal mortality as well as increased fetal and maternal morbidity in prolonged pregnancy. Fetal surveillance may be used in an attempt to observe the prolonged pregnancy while awaiting the onset of spontaneous labor. This article reviews the different methodologies and protocols for fetal surveillance in prolonged pregnancies. On the one hand, false-positive tests commonly lead to unnecessary interventions that are potentially hazardous to the gravida. On the other hand, to date, no program of fetal testing has been shown to completely eliminate the risk of stillbirth.

Objective: This study was undertaken to evaluate the contribution of either an abnormal second-trimester maternal serum screen or the presence of additional sonographic markers of aneuploidy to the risk of a major trisomy (13, 18, and 21) in fetuses with pyelectasis., Study Design: A retrospective review of a large amniocentesis database was performed. Specimens obtained after the sonographic detection of fetal pyelectasis were eligible for analysis. Age-matched women who underwent amniocentesis solely for maternal anxiety or advanced maternal age served as controls., Results: 760,495 amniocentesis specimens were analyzed. Fetal pyelectasis was detected in 671 cases. Pyelectasis, with either a single or multiple additional sonographic markers, was associated with an 8-fold and 62-fold increase in the prevalence of major trisomies (odds ratio = 7.7, 95% CI = 1.2-32.6, P = 0.02) and (odds ratio = 61.9, 95% CI = 13.2-144.6, P < .001), respectively. Pyelectasis with an abnormal maternal serum screen, with or without additional sonographic markers, was associated with a 32-fold and a 205-fold increase in major trisomies (odds ratio = 32.2, 95% CI = 5.3-94.8, P < .001) and (odds ratio = 205.8, 95% CI = 37.9-427.6, P < .001), respectively., Conclusion: In fetuses with pyelectasis, the presence of additional sonographic markers or an abnormal maternal serum screen significantly increases the risk of trisomy 13, 18, and 21.

Objective: To evaluate combined analysis with amniotic fluid index (AFI) and estimated fetal weight (EFW) for prediction of severe macrosomia at birth., Study Design: In this retrospective case-control study, 50 term severe macrosomic newborns (birthweight [BW] > or = 97th percentile) were included in the study group and 100 appropriate for gestational age newborns served as controls. All pregnancies underwent a third-trimester sonographic evaluation in which AFI and EFW were measured. The association between BW and AFI and EFW percentiles was examined. The statistical analysis included Student t test, simple regression and receiver-operating curve analyses, and 2x2 tables., Results: The mean mid-third-trimester AFI percentile and EFW percentile in severe macrosomic infants were 72.4 +/- 22.5 and 83 +/- 12, respectively, which was significantly higher than in controls (P < .0001). Significant correlations were detected between BW and AFI and EFW percentiles (r = 0.44 and r = 0.72, respectively; P < .0001). Receiver-operating characteristic analysis identified AFI > or = 60th percentile and EFW > or = 71st percentile as best predictors of severe macrosomia. The combined analysis with AFI > or = 60th percentile and EFW > or = 71st percentile resulted in a positive predictive value of 85%., Conclusion: There is a significant correlation between mid-third-trimester AFI and BW. AFI > or = 60th percentile and EFW > or = 71st percentile during the mid third trimester are useful predictors of severe macrosomia at birth.

Objective: Elevated counts of nucleated red blood cells (NRBCs), as well as prolongation of pregnancy, have been suggested as predictors of adverse perinatal outcome. However, the association between these 2 variables has received only minimal attention. We sought to evaluate fetal NRBCs in prolonged pregnancies., Methods: Umbilical cord blood was prospectively collected at delivery from 75 prolonged (at or beyond 287 days) pregnancies. One hundred and fifty term deliveries (260-286 days) served as controls. All pregnancies were accurately dated with the use of first-trimester sonography. Fetal biophysical profile testing was initiated at 40 weeks of gestation. Patients were delivered if they were in spontaneous labor or the biophysical profile was nonreassuring or by 42 weeks of gestation. Nucleated red blood cell counts were expressed per 100 white blood cells (WBC). Umbilical artery pH studies, as well as other demographic and clinical variables, were obtained., Results: Prolonged pregnancy was associated with a significantly increased incidence of induction of labor and a greater birth weight. There were no other differences between the study group and controls. The median NRBCs per 100 WBCs in prolonged pregnancy was not significantly elevated over the term values (median 3, range 0-35 versus median 3, range 0-34, respectively; P =.25). Neonatal outcome was also comparable between groups. The univariate regression analysis demonstrated a significant association between elevated NRBC counts and low arterial cord blood pH (P <.008, R = 0.175), elevated base excess (P =.02, R = 0.149), low platelet counts (P =.046, R = 0.134), and male gender (P =.028). Stepwise regression analysis revealed that low arterial cord blood pH and male gender were the only independent variables predicting elevated NRBC counts at birth., Conclusion: The findings of this study suggest that elevated NRBC counts are associated with specific pregnancy complications rather than uncomplicated prolonged pregnancies in general.

Objective: Animal and human studies demonstrated elevated erythropoietin (EPO) levels in response to intrauterine hypoxic events. Other studies documented an association between fetal hypoxia and elevated nucleated red blood cell (NRBC) counts and have speculated that it is the elevation of EPO that results in an increase in NRBC counts. Thus, the purpose of our study was to determine the correlation between EPO levels and NRBC counts in the human fetus., Study Design: Data were collected prospectively between April and July of 2003. Term singleton pregnancies were eligible to participate in the study. Umbilical cord blood was collected immediately after birth for determination of fetal EPO levels and NRBC counts., Results: Forty pregnancies formed the study population. The mean gestational age at delivery was 39.5 +/- 1.2 weeks (+/-SD) and the mean birth weight was 3500 +/- 372 g. The median EPO (mU/mL) was 34 (range 13-427). The median NRBC/100 white blood cells was 10 (range 0-150). A simple regression analysis indicated that NRBC counts are significantly and positively correlated with EPO (P=.0004, R(2)=0.287)., Conclusion: Our results suggest a significant association between EPO and NRBC counts in term singleton fetuses. These results support the hypothesis that fetal NRBC and EPO are interrelated. However, the relatively low R(2) indicates that there are other (yet to be determined) hypoxia-derived mediators that result in an elevation of fetal NRBC counts.

Objective: To determine whether measuring maternal glycosylated hemoglobin (HbA1c) can improve the accuracy of sonographic estimation of fetal macrosomia., Methods: Sonographic estimation of fetal weight (EFW) and maternal HbA1c were obtained in term, non-diabetic patients within 1 week before delivery. Neonatal birth weights were recorded at delivery and compared with both sonographic estimations and HbA1c. Macrosomia was defined as birth weight of >or=4000 g. The absolute error of the sonographic EFW was calculated. Receiver-operating characteristics (ROC) curve analysis was used to evaluate sonographic EFW and HbA1c as predictors of birth weight >or=4000 g. Variables were tested using regression analysis and student's t-test., Results: One hundred and sixty two patients were evaluated between July and December 2002. Twenty-eight patients (17.3%) delivered macrosomic infants. Sonographic EFW >or=4000 g predicted macrosomia with sensitivity, specificity and positive and negative predictive values of 66.6%, 88.8%, 54.5% and 93.0%, respectively. Its overall accuracy was 85.5%. The area under the ROC curve of sonographic EFW in the prediction of macrosomia was 0.9 (P < 0.001). HbA1c levels in women delivering macrosomic and non-macrosomic neonates were 5.3 +/- 0.7% and 5.2 +/- 0.5%, respectively (P = 0.27). The area under the ROC curve of HbA1c in the prediction of macrosomia was 0.53 (P = 0.27)., Conclusions: Maternal HbA1c is not a useful test in the prediction of birth weight. It therefore cannot be used to improve the accuracy of sonographic EFW., (Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd.)