Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting.

OBJECTIVE: Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting. METHODS: The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay-predicted fetal risk. RESULTS: Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub-group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%-99.90%), specificity of 95.2% (95% CI: 92.98%-96.92%), average PPV of 50.0% (95% CI: 35.23%-64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%-99.99%). The end-to-end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real-life setting. CONCLUSION: This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first-line approach.

First-trimester biochemistry and outcomes in twin pregnancy.

OBJECTIVE: To examine the relationship between levels of first-trimester serum analytes used in aneuploidy risk assessment and obstetric outcomes in twin pregnancy. STUDY DESIGN: Twin pregnancies undergoing first-trimester risk assessment from 2003 to 2005 were identified. Pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) were measured at 9-14 weeks. The association between extreme biochemical values (< 5th and > 95th percentile) and adverse outcomes was examined. Fisher's exact test and Mann-Whitney U were used for comparison. RESULTS: A total of 326 pregnancies were included. Median maternal age was 35 years. Median gestational age at delivery was 36 weeks. There were no significant associations between extreme free beta-hCG or high PAPP-A values and the rates of any adverse outcomes. Low PAPP-A (< 0.52 multiples of the median) was associated with higher rates of discordant growth (50% vs. 13%; p = 0.001) and hypertensive disorders of pregnancy (41.2% vs. 15.5%, p = 0.01). CONCLUSION: In twin pregnancies, low PAPP-A is associated with discordant growth and hypertensive disorders.

First-trimester risk assessment for trisomies 21 and 18 in twin pregnancy.

OBJECTIVE: Our objective was to describe performance of first-trimester combined risk assessment in twin pregnancies. STUDY DESIGN: Twin pregnancies that underwent risk assessment in our ultrasound unit from 2003-2006 were included. Adjusted risks for trisomies 21 and 18 that were based on age, nuchal translucency (NT), and biochemistry were provided for each twin. Detection rates for Down syndrome and trisomy 18 were calculated for age/NT, and age/NT/biochemistry at a screen-positive rate of 5% of pregnancies. RESULTS: Five hundred thirty-five pregnancies were included. Median maternal age was 34 years, with 47% of women > or = 35 years old. There were 7 fetuses in 6 dichorionic pregnancies with Down syndrome and 3 fetuses in 3 pregnancies with trisomy 18. For a 5% false-positive rate, age/NT identified 83.3% of Down syndrome and 66.7% of Trisomy 18 pregnancies. Adding biochemistry resulted in 100% detection rates for both conditions. CONCLUSION: The addition of biochemistry may enhance first-trimester risk assessment in twin pregnancies. Further studies with larger numbers of affected pregnancies are needed.

Antenatal assessment of discordant umbilical arteries in singleton pregnancies.

AIM: To assess the relationship between discordant umbilical arterial size and resultant blood flow parameters and determine the impact of discordance on fetal outcome. METHODS: This is a descriptive, cross-sectional study of 200 patients with a singleton gestation, who underwent a fetal anatomy survey between 18 to 23 weeks of gestation, with documented umbilical cord morphological patterns and blood flow characteristics. Umbilical vessel diameters and Doppler parameters (umbilical vein blood flow volume, mean resistance index, and peak-systolic velocity) were analyzed for discordance. Discordances encountered were examined for their possible association with perinatal outcome. RESULTS: We had adequate ultrasound umbilical cord images, Doppler flow parameters, and all necessary demographic data for 154 patients. Umbilical artery discordance averaged 13.1% and was significantly correlated with both the expected and the true percent of difference in resistance index values (RI, P<0.001). In 12 patients (7.8%), a significant discordance of more than 29.5%, or 95th percentile, was observed between the two umbilical artery diameters. However, in these cases no associated adverse perinatal outcome or significant placental pathology was noted. There was no significant difference between patients discordant or concordant umbilical artery in terms of maternal, labor, and neonatal data. CONCLUSION: The magnitude of umbilical arteries' luminal discordance directly influences the corresponding blood flow parameters. In our sample of patients, the presence of discordant-in-size umbilical arteries was not associated with umbilical cord or placental abnormalities.

Are in vitro fertilization pregnancies with early spontaneous reduction high risk?

OBJECTIVE: The objective of the study was to determine whether spontaneous reduction in in vitro fertilization pregnancies results in outcomes comparable with in vitro fertilization singleton pregnancies or ongoing twin pregnancies. STUDY DESIGN: Women with in vitro fertilization pregnancies from 2003 to 2005 who had first-trimester ultrasound and delivered in our hospital were identified. Those with documented reduction from dichorionic twins to a single viable fetus at 14 weeks or less were categorized as spontaneous reduction pregnancies and were compared with dichorionic twin and singleton pregnancies without reduction. RESULTS: One hundred sixty-eight singleton, 55 spontaneous reduction, and 86 twin pregnancies were included. Gestational age at delivery was similar in the singleton and spontaneous reduction groups; twins delivered significantly earlier. Spontaneous reduction was associated with lower birth weight than other singleton pregnancies (median 3062 g versus 3425 g; P = .005). The rate of pre-eclampsia was higher in pregnancies with spontaneous reduction, compared with other singleton pregnancies 9.3% versus 2.4%; P = .04). CONCLUSION: Spontaneous reduction of a twin to a singleton pregnancy is associated with prolonged gestation and higher birth weight for the remaining fetus.

Does a "vanishing twin" affect first-trimester biochemistry in Down syndrome risk assessment?

OBJECTIVE: The purpose of this study was to evaluate the impact of spontaneous reduction in multifetal pregnancy on first-trimester maternal serum biochemistry. STUDY DESIGN: We evaluated first-trimester pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin levels in singleton euploid pregnancies. Biochemical values in pregnancies with evidence of spontaneous reduction were compared to other singleton pregnancies. Mann-Whitney U, Student t test, Fisher exact test, and logistic regression analysis were used for statistical comparison. RESULTS: There were 41 cases (0.9%) of spontaneous reduction. Though spontaneous reduction was not associated with different levels of either analyte, reduction within 4 weeks was associated with higher levels of both PAPP-A (1.79 vs 1.18; P = .002) and free beta-hCG (1.28 vs 0.96; P = .03) compared with other pregnancies. Spontaneous reduction was associated with a higher frequency of PAPP-A >95th %ile (17.1 vs 4.7%; P = .003) and free beta-hCG >95th %ile (17.1% vs 5.0%; P = .004). Logistic regression identified independent associations between spontaneous reduction and both high PAPP-A and high free beta-hCG. CONCLUSION: Recent spontaneous reduction is associated with higher values of PAPP-A and free beta-hCG. These differences have the potential to affect risk assessment for fetal aneuploidy.

Extracellular 70-kd heat shock protein in mid-trimester amniotic fluid and its effect on cytokine production by ex vivo-cultured amniotic fluid cells.

OBJECTIVE: The 70-kd heat shock protein is released from cells in response to stress and functions as a regulator of innate immunity. We hypothesized that 70-kd heat shock protein in mid-trimester amniotic fluid might regulate local immune system activation. STUDY DESIGN: Amniotic fluid that was obtained from 200 women who underwent amniocentesis at 15 to 19 weeks of gestation was tested by enzyme-linked immunosorbent assay for 70-kd heat shock protein, tumor necrosis factor-alpha, and interleukin-1beta and -6. The amniotic fluid cellular fraction also was evaluated for Mycoplasma hominis by gene amplification. Whole amniotic fluids were incubated ex vivo in medium alone or medium that contained peptidoglycan, a TLR2 ligand, or lipopolysaccharide, a TLR4 ligand. After 24 hours, the supernatants were collected and assayed for 70-kd heat shock protein. The influence of exogenous 70-kd heat shock protein on tumor necrosis factor-alpha and interleukin-1beta and -6 production by whole amniotic fluid was assessed similarly. RESULTS: The 70-kd heat shock protein was detected in all amniotic fluids with a median (range) of 11.5 ng/mL (1.2-76.7). The intra-amniotic 70-kd heat shock protein concentration was correlated positively only with amniotic fluid tumor necrosis factor-alpha levels (P = .0002). Detection of M hominis was associated with an increased 70-kd heat shock protein concentration (median, 17.2 ng/mL; P = .01). The addition of peptidoglycan resulted in a stimulation of 70-kd heat shock protein production, and exogenous 70-kd heat shock protein stimulated the release of tumor necrosis factor-alpha by amniotic fluid cells. CONCLUSION: The 70-kd heat shock protein is released from cells in mid-trimester amniotic fluid as a consequence of TLR2 stimulation and potentiates tumor necrosis factor-alpha production.

Clinical use of first-trimester aneuploidy screening in a United States population can replicate data from clinical trials.

OBJECTIVE: The clinical application of first-trimester aneuploidy screening remains controversial in the United States. The aim of our study was to evaluate the performance of maternal age, fetal nuchal translucency measurements, pregnancy-associated plasma protein A, and free beta-human chorionic gonadotrophin used in aneuploidy screening in a single institution outside of a clinical trial. STUDY DESIGN: Four thousand eight hundred eighty three patients underwent first-trimester aneuploidy screening at 11 to 13 6/7 weeks of gestation (fetal crown-rump length 45 mm to 84 mm) at our institution between January 2003 and September 2004. Measurement of nuchal translucency was performed according to the Fetal Medicine Foundation standards and was included in the overall risk assessment performed by NTD Laboratories. Measurement of pregnancy-associated plasma protein A and free beta-human chorionic gonadotrophin on maternal dried whole blood samples was conducted by NTD Laboratories and was reported as gestational-specific multiples of the median adjusted for ethnicity. Risk adjustment for trisomy 21 and trisomy 18 was done with a standard algorithm using maternal age, serum biochemistry, and nuchal translucency. Only singleton gestations (N = 4615) were included in the analysis. RESULTS: The median maternal age was 33.0 years (interquartile range 31.0 to 36.0) and the median crown-rump length was 61.2 mm (interquartile range 55.7 to 67.2) at the time of screening. There were a total of 22 fetuses diagnosed with trisomy 21 and 8 with trisomy 18. The detection rates for trisomy 21 for a 5% false-positive rate and 1% false-positive rate were 90.9% (20 of 22) and 77.3% (17 of 22), respectively. Similarly, the detection rates for trisomy 18 at a 5% false-positive rate and a 1% false-positive rate were 100% (8 of 8) and 100% (8 of 8), respectively. CONCLUSION: Non-investigational use of first-trimester aneuploidy screening for trisomy 21 and trisomy 18 can replicate results from investigational trials.

Absence of a relationship between umbilical cord thickness and coiling patterns.

OBJECTIVE: The purpose of this study was to evaluate a relationship between the umbilical cord thickness and cord coiling patterns during the fetal sonographic anatomic survey in the second trimester of pregnancy. METHODS: This was a prospective study of 470 patients with singleton pregnancies who had a fetal anatomic survey with recorded umbilical coiling patterns between 18 and 23 weeks' gestation. The umbilical cord thickness was assessed as an umbilical diameter at the level of the fetal abdominal cord insertion and compared with the antenatal umbilical coiling index (aUCI), calculated as a reciprocal value of the distance between a pair of umbilical cord coils. RESULTS: Three hundred twenty-one patients had adequate sonographic umbilical cord images and maternal demographic, antenatal, and labor data to meet inclusion criteria. The mean aUCI was 0.41 with 10th and 90th percentiles of 0.21 and 0.60, respectively. A total of 10.6% (34/321) and 9.3% (30/321) of patients were categorized as having hypocoiled and hypercoiled umbilical cords, respectively. The mean cord diameter +/- SD was 9.48 +/- 0.97 mm (range 7.0-12.5 mm). There was no statistically significant correlation between aUCI and umbilical cord thickness (P = .1164). CONCLUSIONS: An aUCI, or umbilical coiling pattern, does not correlate with umbilical cord thickness. It appears that a lesser amount of the umbilical supportive tissue, mainly Wharton jelly, is not related to an increased umbilical cord coiling pattern.

Clara cell protein 16 concentration in mid-trimester amniotic fluid: association with fetal gender, fetal G>A +38 CC16 gene polymorphism and pregnancy outcome.

Clara cell protein 16 (CC16) is a major immunomodulatory protein produced in the fetal lung. We hypothesized that the mid-trimester amniotic fluid concentration of CC16 would vary according to a +38 CC16 polymorphism in the fetal genome and that increased levels would be an early indicator of subsequent adverse pregnancy outcome. Mid-trimester singleton amniotic fluids from 244 women were assayed for CC16 by ELISA. DNA from fetal cells in 179 amniotic fluids were tested for the A>G polymorphism at position +38 in exon 1 by PCR. Outcome data were obtained from 233 women after completion of laboratory testing. Median CC16 levels were higher in amniotic fluids containing male fetuses than in those with females (p=0.0005). Median amniotic fluid CC16 levels were higher in Hispanics than in Whites and Asians (p<0.05). CC16*G homozygosity was associated with elevated amniotic fluid CC16 concentrations compared to CC16*A homozygotes (p=0.02). Intraamniotic CC16 levels were highest in pregnancies that subsequently resulted in preterm premature rupture of membranes (PPROM) (p=0.01). We conclude that mid-trimester intraamniotic CC16 concentrations vary by gender, ethnicity and fetal CC16 gene polymorphism. Elevated CC16 levels are predictive of subsequent development of PPROM.

Isolated fetal ascites caused by bowel perforation due to colonic atresia.

An isolated fetal ascites is a rare ultrasonographic finding. It is commonly diagnosed in association with fetal genitourinary or gastrointestinal conditions, mainly bowel obstruction. We present the sonographic features and neonatal outcome of a fetus with a large bowel obstruction, perforation and subsequent development of meconium peritonitis, prenatally diagnosed as isolated fetal ascites. A colonic atresia should be also included in the differential diagnosis of isolated fetal ascites.

Differential expression of immune system-related components in midtrimester amniotic fluid from singleton and twin pregnancies.

OBJECTIVE: We investigated differences between singleton and twin gestations in immune mediators in midtrimester amniotic fluid. STUDY DESIGN: Amniotic fluid from 252 singleton and 46 twin gestations were tested by enzyme-linked immunosorbent assay for interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, tumor necrosis factor-alpha, nitric oxide, Clara cell protein 16, leptin, and the 70-kDa heat shock protein. A subset of amniotic fluid was also tested for leukemia inhibitory factor, angiogenin, and migration inhibitory factor-related protein 8 and migration inhibitory factor-related protein 14. Data were analyzed by the Mann-Whitney U test and Spearman rank correlation. RESULTS: Median concentrations of interleukin-1beta, tumor necrosis factor-alpha, interleukin-4, Clara cell protein 16, leptin, and angiogenin were increased in amniotic fluid from twins; median levels of the 70-kDa heat shock protein, leukemia inhibitory factor, migration inhibitory factor-related protein 8, and migration inhibitory factor-related protein 14 were highest in amniotic fluid from singletons (P < .001). CONCLUSION: Elevated levels of immune activators may contribute to the increased rate of preterm premature rupture of membranes and spontaneous preterm birth in twin populations.

The umbilical cord thickness measured at 18-23 weeks of gestational age.

OBJECTIVE: To establish an umbilical cord thickness nomogram from anatomy ultrasound scans performed between 18 and 23 weeks of gestational age in singleton pregnancies, and compare it to two previously published nomograms. MATERIAL AND METHODS: In this retrospective cohort study of 1107 patients, a total of 650 singleton pregnancies were included. The umbilical cord diameter measurements were performed at the level of fetal abdominal wall insertion, and were correlated with gestational age (GA) and estimated fetal weight (EFW). Statistical analysis with non-parametric polynomial least squares regression analysis was performed. RESULTS: A statistically significant correlation between umbilical cord diameter and GA (P<0001, r=0.399, 95% CI 0.331 to 0.464), and EFW (P<0001, r=0.420, 95% CI 0.353-0.483) was observed. A nomogram of umbilical cord thickness according to GA (y), and EFW (y'), was generated from the following equations:y=-51.30+5.367*x-0.1165*x(2) and y'=6.917+0.007233*x, respectively. CONCLUSION: Our nomogram is in agreement with one of the previously published nomograms that also measured umbilical cord diameter at the level of the fetal abdominal umbilical cord insertion. Therefore, we recommend umbilical cord thickness to be measured in close proximity to the fetal abdominal wall, but no further than 0.5 cm away from the wall insertion.

Ultrasound evaluation of abnormal umbilical cord coiling in second trimester of gestation in association with adverse pregnancy outcome.

OBJECTIVE: The purpose of this study was to evaluate the antenatal umbilical cord coiling index obtained during the fetal anatomic survey in the second trimester as a predictor of adverse pregnancy outcome. STUDY DESIGN: Four hundred twenty-five consecutive women who had a fetal anatomic survey between 18 to 23 weeks of gestation were evaluated for umbilical cord coiling. The antenatal umbilical cord coiling index was calculated as a reciprocal value of the distance between a pair of coils (antenatal umbilical cord coiling index = 1/distance in cm) and was correlated with the following adverse pregnancy outcomes: (1) small for gestational age, (2) mode of delivery, (3) presence of meconium-stained amniotic fluid, (4) presence of nonreassuring fetal status in labor, and (5) Apgar scores at 1 and 5 minutes. RESULTS: A total of 294 patients had adequate ultrasound images and all antenatal and labor data to meet the study inclusion criteria. Abnormal coiling was associated significantly with small for gestational age neonates at birth (P = .043) and non-reassuring fetal status in labor (P = .007). Nine of 58 neonates (15.5%) with abnormal umbilical coiling were small for gestational age infants compared with 15 of 236 small for gestational age neonates (6.4%) who had normal cord coiling. A non-reassuring fetal status in labor was observed in 25.7% of fetuses (15/58 fetuses) with abnormal umbilical coiling compared with 11.0% of fetuses (26/236 fetuses) with normal cord coiling. In contrast, no statistical difference for Apgar scores at 1 and 5 minutes or higher prevalence of interventional deliveries and meconium-stained amniotic fluid in labor between the groups with normal and abnormal umbilical cord coiling was observed. CONCLUSION: Abnormal umbilical cord coiling that is detected at the fetal ultrasound anatomic survey in the second trimester is associated with a higher prevalence of small for gestational age neonates and non-reassuring fetal status in labor. This observation can be used potentially as a predictor of adverse antenatal or perinatal events in future studies.

Fetal growth assessment and neonatal birth weight in fetuses with an isolated single umbilical artery.

OBJECTIVE: To evaluate interval fetal growth and compare the incidence of small-for-gestational age (SGA) newborns between fetuses with an isolated single umbilical artery and those with a 3-vessel umbilical cord. METHODS: A retrospective, case-controlled study in which 84 singleton pregnancies with an isolated single umbilical artery were compared with 3-vessel umbilical cord fetuses as the control group. RESULTS: There was no statistical difference between the groups in maternal demographic data, except for ethnicity and neonatal outcomes, respectively. The mean newborn birth weight was similar between the isolated single umbilical artery and the control groups, 3,268 +/- 596 g and 3,274 +/- 627 g, respectively. The prevalence of SGA newborns was 7.1% (6 of 84) in the isolated single umbilical artery group and 4.8% (4 of 84) in the control group. An ultrasound examination demonstrated fetal growth restriction in 50% of cases (3 of 6) in the isolated single umbilical artery group and in 25% of subjects (1 of 4) in the control group, respectively. CONCLUSION: Fetuses with an isolated single umbilical artery are at similar risk for SGA compared with fetuses with 3-vessel umbilical cords. It appears that antepartum serial ultrasound examination does not provide more information for interval fetal growth assessment in fetuses with an isolated single umbilical artery.

Human immunodeficiency virus, pregnancy, and Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening dermatologic disorders that are more common in the setting of a compromised immune system. We present the case of a pregnant patient with known human immunodeficiency virus (HIV) infection who presented with Stevens-Johnson syndrome after treatment with antibiotics for a urinary tract infection. CASE: A young woman at 33 4/7 weeks of gestation with known HIV infection presented to the emergency room with a chief complaint of rash, fever, blisters, and lower abdominal pain. Her symptoms were present for 2 days after ingestion of nitrofurantoin, prescribed for a urinary tract infection. She was diagnosed with preterm labor and possibly Stevens-Johnson syndrome. Due to active labor, HIV, and vaginal stenosis, a primary cesarean was performed. A skin biopsy performed at the time of admission confirmed the diagnosis of a drug-induced dermatosis (erythema multiforme), evidenced by subepidermal bullae, hemorrhage, and acantolated, dyskeratotic eosinophilic cells. CONCLUSION: Stevens-Johnson syndrome and toxic epidermal necrolysis represent a spectrum of disease that has been long associated with multiple drugs, recently including many antiretroviral medications. It also seems that the incidence of these conditions is increased in immunocompromised patients. We speculate that the combination of HIV and pregnancy in addition to antibiotic treatment, such as with nitrofurantoin, may induce Stevens-Johnson syndrome in patients with severely altered immune systems.

A sonographic assessment of different patterns of placenta previa "migration" in the third trimester of pregnancy.

OBJECTIVE: The purpose of this study was to compare the rates and patterns of placental "migration" with the mode of fetal and placental delivery and the incidence of peripartum complications. METHODS: This was a retrospective study of 163 cases of placenta previa diagnosed by transvaginal sonography at 28 weeks' gestation that were followed serially by sonography. The patients were stratified into 3 groups depending on the placenta-to-internal cervical os distance: (1) an overlap of 0.0 cm or greater over the cervical os, (2) 0.1 to 2.9 cm, and (3) 3.0 cm or greater. The mean rate of placental migration (millimeters per week) was obtained at 28 to 32 and 32 to 36 weeks' gestation. A pattern of placental migration was classified as one with acceleration or deceleration of the placental migration in the late third trimester based on a comparison between the migration rates at 28 to 32 and 32 to 36 weeks' gestation. RESULTS: At the time of delivery, 22, 29, and 112 patients were included in groups 1, 2, and 3, respectively. The rates of placental migration correlated with the final placental distance from the internal cervical os (0.1 to 4.1 mm/wk for groups 1 and 3, respectively). Significantly higher rates of interventional cesarean delivery (CD) (P=.0002), elective CD (P=.0254), manual placenta removal (P=.0419), and placenta accreta (P=.0039), but not CD for indications other than placenta previa (P=.0752), were associated with a placental distance of less than 2.0 cm away from the cervix and a deceleration pattern of placental migration. In contrast, vaginal delivery was significantly associated with a placental distance of 2.0 cm or greater away from the cervix and an acceleration pattern of placental migration (P=.0034). CONCLUSIONS: A final placental distance of less than 2.0 cm from the internal cervical os and a deceleration pattern of placental migration were significantly associated with an interventional CD and a higher rate of peripartum complications.

Placental pathology and pregnancy outcomes in donor and non-donor oocyte in vitro fertilization pregnancies.

OBJECTIVE: Intrinsically poor maternal adaptation to pregnancy and dysregulated processes have been postulated to occur as a consequence of an immune response to the feto-placental unit as "foreign" material. The aim of our study was to compare placental pathology and pregnancy outcomes of in vitro fertilization (IVF) pregnancies conceived by donor oocytes with those conceived by non-donor oocytes. STUDY DESIGN: We conducted a retrospective, case-control study on 91 placentas from IVF pregnancies (36 from donor oocytes and 55 from non-donor cycles). All placentas were examined by a single pathologist for signs indicative of an immune response, including chronic villitis, chronic deciduitis, increased perivillous fibrin, ischemic change/infarction, decidual vasculopathy, increased syncytial knots, intervillous thrombi, and retroplacental hematomas. RESULTS: Placentas from donor cycles were significantly more likely to demonstrate certain pathologic findings: chronic villitis (P<0.001), chronic deciduitis (P=0.034), increased perivillous fibrin (P=0.001), ischemic change/ infarction (P=0.001), and intervillous thrombi (P =0.008). There was no statistical significance with respect to decidual vasculopathy, increased syncytial knots, or retroplacental hematomas. CONCLUSION: Pathologic evidence of an immune-mediated process is much more pronounced in donor oocyte IVF pregnancies compared to non-donor cycles. Clinical implications of these findings have yet to be determined.

Assessment of umbilical cord coiling during the routine fetal sonographic anatomic survey in the second trimester.

OBJECTIVE: The purpose of this study was to evaluate the sonographic accuracy to determine the umbilical coiling index (UCI) during the routine fetal anatomic survey in the second trimester. METHODS: In 300 consecutive women with singleton pregnancies and absence of gross fetal anomalies who had a routine second-trimester fetal anatomic survey, a distance between 2 pairs of coils was measured from the longitudinal images of the umbilical cord, and the antenatal UCI (aUCI) was calculated. The aUCI was compared with true UCI results obtained after birth. RESULTS: Two hundred thirty-six patients had adequate sonographic umbilical cord images, and all required demographic, antenatal, and labor data collection to meet the inclusion criteria. A statistically significant correlation between aUCI and true UCI was found (P < .0001; r = 0.643). The mean aUCI was 0.402 (80% confidence interval, 0.382), and the true UCI at birth was 0.203 (80% confidence interval, 0.176). The sonographic evaluation showed 12.3% and 8.9% of hypocoiled and hypercoiled cords, whereas evaluation at birth found 10.6% and 8.1% hypocoiled and hypercoiled umbilical cords, respectively. The sensitivity values of sonography to predict hypocoiling and hypercoiling at birth were 78.9% and 25.4%, respectively. CONCLUSIONS: A sonographic evaluation of umbilical cord coiling in the second trimester correlates with the true UCI at birth, although the sensitivity in predicting coiling patterns as hypocoiled and hypercoiled cords is less accurate. A difference between the aUCI and matched UCI at birth could be explained by a sonographic error in the sampling of different umbilical cord segments with discordant coiling patterns or the possibility of a dynamically evolving UCI with advancing gestational age.