Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFß suppression.

ETS transcription factors ETV2, FLI1, and ERG1 specify pluripotent stem cells into induced vascular endothelial cells (iVECs). However, iVECs are unstable and drift toward nonvascular cells. We show that human midgestation c-Kit(-) lineage-committed amniotic cells (ACs) can be reprogrammed into vascular endothelial cells (rAC-VECs) without transitioning through a pluripotent state. Transient ETV2 expression in ACs generates immature rAC-VECs, whereas coexpression with FLI1/ERG1 endows rAC-VECs with a vascular repertoire and morphology matching mature endothelial cells (ECs). Brief TGFß-inhibition functionalizes VEGFR2 signaling, augmenting specification of ACs into rAC-VECs. Genome-wide transcriptional analyses showed that rAC-VECs are similar to adult ECs in which vascular-specific genes are expressed and nonvascular genes are silenced. Functionally, rAC-VECs form stable vasculature in Matrigel plugs and regenerating livers. Therefore, short-term ETV2 expression and TGFß inhibition with constitutive ERG1/FLI1 coexpression reprogram mature ACs into durable rAC-VECs with clinical-scale expansion potential. Banking of HLA-typed rAC-VECs establishes a vascular inventory for treatment of diverse disorders.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

First-Trimester Cell-Free DNA Fetal Fraction and Birth Weight in Twin Pregnancies.

OBJECTIVE: The relationship between fetal fraction and birth weight in twin gestations is poorly understood. This study aimed to investigate the relationship between first-trimester cell-free DNA (cfDNA) fetal fraction and birth weight <10th percentile in twin gestations. STUDY DESIGN: This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from December 2011 to February 2022, excluding those with positive screen results for chromosomal aneuploidy. cfDNA testing was performed by a single laboratory using massively parallel sequencing. Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared with those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. RESULTS: A total of 1,041 twin pregnancies were included. Chronic hypertension, elevated body mass index, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [interquartile range (IQR)] fetal fraction: 12.2% [9.8, 14.8] vs. those with normal birth weight (≥10th percentile) in both twins (median [IQR] fetal fraction: 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p = 0.45) or both (p = 0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p = 0.44) or both (p = 0.74) twins. The results were unchanged after adjustment for potential confounders. CONCLUSION: In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birth weight <10th percentile, suggesting that first-trimester fetal fraction may not predict impaired fetal growth in twin gestations. KEY POINTS: · No association between fetal fraction and small for gestational age birth weight in twins.. · Results suggest that fetal fraction does not predict birth weight in twin gestations.. · These results differ from the relationship between fetal fraction and birth weight in singletons..

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Is Amniocentesis after CVS Risky?

OBJECTIVE: Approximately, 2% of women who undergo chorionic villi sampling (CVS) will subsequently undergo amniocentesis due to placental mosaicism or sampling/laboratory issues. Our objective was to compare obstetric outcomes in women who underwent both procedures with those who had CVS alone. STUDY DESIGN: Retrospective case-control study of patients with singleton pregnancies undergoing invasive testing from 2010 to 2020 was performed. All women who underwent CVS followed by amniocentesis were compared with a control group who underwent CVS alone matched (2:1) for age and year of pregnancy. Women with pregnancy loss at <16 weeks were excluded from the control group. Pregnancies terminated for genetic abnormalities were excluded. Obstetric outcomes were compared between cases and controls. Student t-test and Fisher's exact test were used for statistical comparison. RESULTS: During the study period 2,539 women underwent CVS, and 66 (2.6%) subsequently underwent amniocentesis. The 66 cases were compared with 132 age-matched controls who underwent CVS alone. Mean maternal age was 36.8 ± 3.4 years, and 43% of women were nulliparous. Amniocentesis was performed due to sampling or laboratory issues in 33% of cases, placental mosaicism in 44%, and further diagnostic testing in 23%. There were no pregnancy losses or stillbirths in either group. Those who had two invasive procedures delivered at similar gestational ages and birthweights and did not have higher rates of adverse outcomes compared with those who underwent CVS alone. CONCLUSION: Patients considering CVS who are concerned about the possibility that a second invasive procedure could be required should be reassured that this does not appear to be associated with higher rates of adverse outcomes. Due to study size, we cannot exclude the possibility of small differences in uncommon outcomes, such as pregnancy loss or stillbirth. KEY POINTS: · Amniocentesis may be recommended after CVS due to mosaicism, sampling issues, or further testing.. · Amniocentesis after CVS is not associated with pregnancy loss or other adverse outcomes compared.. · Patients who have both CVS and amniocentesis deliver at similar gestational ages and birthweights..

Potentially Preventable Primary Cesarean Sections in Future Placenta Accreta Spectrum.

OBJECTIVE: Prior cesarean delivery is a well-known risk factor for placenta accreta spectrum disorders. While primary cesarean section is unavoidable in some patients, in others it may not be clearly indicated. The aim of the study is to determine the proportion of patients with placenta accreta spectrum who had a potentially preventable primary cesarean section and to identify factors associated with preventable placenta accreta spectrum. STUDY DESIGN: This was a single-center retrospective cohort study of women with pathology-confirmed placenta accreta spectrum from 2007 to 2019. Primary cesarean sections were categorized as potentially preventable or unpreventable based on practice consistent with the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine "Safe Prevention of the Primary Cesarean Delivery" recommendations. Fisher's exact test and Mann-Whitney U-test were used for comparison with p <0.05 considered statistically significant. RESULTS: Seventy-two patients had pathology-confirmed placenta accreta spectrum over the course of the study period, 15 (20.8%) of whom required a cesarean hysterectomy at the time of primary cesarean section. Fifty-seven patients had placenta accreta spectrum in a pregnancy following their primary cesarean section. Of these, 29 (50.9%) were considered potentially preventable. Most were performed without clear medical indication (37.9%) or for fetal malpresentation without attempted external cephalic version (37.9%). The remainder were due to arrest of labor not meeting criteria (17.2%) and abnormal or indeterminate fetal heart patterns with documented recovery (6.9%). Of the 11 patients without clear medical indication for primary cesarean section, eight (72.7%) were patient-choice cesarean sections and three (27.3%) were for suspected fetal macrosomia with estimated fetal weights not meeting criteria for cesarean delivery. There was no difference in the incidence of potentially preventable primary cesarean sections before and after the ACOG-SMFM "Safe Prevention of the Primary Cesarean Delivery" publication (48.8 vs. 57.1%, p = 0.59). Privately insured patients were more likely to have a potentially preventable primary cesarean section than those with Medicaid (62.5 vs. 23.5%, p = 0.008) and were more likely to have a primary cesarean section without clear medical indication (81.8 vs. 18.2%, p = 0.004). CONCLUSION: Many patients with placenta accreta spectrum had a potentially preventable primary cesarean section. Most were performed without clear medical indication or for malpresentation without attempted external cephalic version, suggesting that at least a subset of placenta accreta spectrum cases may be preventable. This was particularly true for privately insured patients. These findings call for continued investigation of potentially preventable primary cesarean sections with initiatives to address concerns at the patient, provider, and hospital level. KEY POINTS: · Many patients with placenta accreta spectrum have potentially preventable primary cesarean sections.. · Privately insured patients are more likely to have potentially preventable primary cesarean sections.. · Our findings suggest that at least a subset of placenta accreta spectrum cases may be preventable..

Suspected Placenta Accreta: Using Imaging to Stratify Risk of Morbidity.

OBJECTIVE: This study was aimed to compare clinical outcomes and use of interventions in women with suspected accreta based on the degree of antenatal suspicion. STUDY DESIGN: This was a retrospective cohort study of women with suspected accreta from 2007 to 2019. Included patients had one or more imaging studies suggestive of accreta. Cases were classified as "lower risk" if imaging showed possible signs of accreta including mild or superficial myometrial infiltration, an abnormal uterine contour, an abnormal uteroplacental interface, or loss of the retroplacental hypoechoic zone and "higher risk" if there was clear evidence of more than superficial myometrial infiltration, placental tissue extruding beyond the uterine serosa, bridging vessel(s), or placental lacunae with high velocity and/or turbulent flow. The primary study outcome was a composite maternal morbidity including cesarean hysterectomy, transfusion of blood or blood products, unintentional cystotomy, or intensive care unit (ICU) admission. Chi-square, Fisher's exact test, and Mann-Whitney U-test were used for analysis. RESULTS: A total of 78 women had a suspected accreta on imaging, 36 with "lower risk" features and 42 with "higher risk" features. There were no differences in baseline maternal demographics. Women in the "higher risk" group were more likely to have a placenta previa (p < 0.01) and preoperative consultation with gynecologic oncology (p = 0.04). There was a significant difference in composite maternal morbidity between patients with "lower risk" and "higher risk" features of accreta on imaging (50 vs. 92.9%, p < 0.01). Median gestational age at planned and actual delivery were earlier in the "higher risk" group (36.6 vs. 34.9 weeks, p < 0.01; 36.0 vs. 34.7 weeks, p < 0.01). CONCLUSION: Stratification of women with suspected accreta based on imaging corresponded to rates of maternal morbidity and operative complications, and appears to have been used clinically in selecting timing of delivery and interventions. KEY POINTS: · Increased morbidity with high risk accreta imaging.. · Interventions correlate with accreta imaging risk.. · Imaging can be used to stratify accreta cases..

Obstetrical Complications and Long-Term Cardiovascular Outcomes.

PURPOSE OF REVIEW: Obstetrical complications including indicated preterm birth (PTB), hypertension (HTN), IUGR, and GDM are risk factors for future cardiovascular disease. To identify patients at risk, the American Heart Association recommends obtaining a detailed obstetric history. Our objective was to determine if non-OB-GYN physicians-in-training obtain an obstetric history when assessing a risk profile for cardiovascular disease and to identify differences based on level of training. In 2019, an anonymous survey was distributed to trainees in internal medicine, cardiology, endocrinology, nephrology, and neurology. Subjects were queried about frequency of asking a history of PTB, IUGR, GDM, and HTN in pregnancy. Survey options were always/frequently/sometimes/rarely/never and were categorized into two groups: "ask" (always/frequently/sometimes) vs. "do not ask" (rarely/never). Comparisons between specialties and levels of training were made using chi-square and Fisher's exact test. Comparisons within subjects were made using McNemar's test. RECENT FINDINGS: The response rate was 64% (210 total possible participants), including 98 internal medicine residents and 37 fellows in cardiology (21), endocrinology (3), nephrology (8), and neurology (5). Asking about medical complications (HTN + GDM) was significantly more common than asking about OB complications (PTB + IUGR) (p < 0.001). Internal medicine residents were less likely than subspecialty fellows to ask about HTN (31% vs. 70%; p < 0.001). There were no differences in likelihood of eliciting OB history based on PGY level. An OB history can identify risk factors for cardiovascular morbidity. Our data demonstrates that physicians caring for women lack awareness on the association between complications in pregnancy and cardiovascular health.

Pregnancy Outcomes in Women with Incidentally Detected Unicornuate Uteri.

OBJECTIVE: To estimate the incidence of adverse pregnancy outcomes in women with incidentally detected unicornuate uteri. STUDY DESIGN: This is a descriptive study. Database review identified patients with unicornuate uteri and singleton pregnancies at ≥12 weeks' gestation. Patients were excluded if the diagnosis of unicornuate uterus was made after a midtrimester loss or preterm delivery. Records were reviewed to obtain clinical outcomes. Chi-square test, Fisher's exact test, and Mann-Whitney U-test were used for statistical analysis. RESULTS: Forty patients with 67 pregnancies were included. Most diagnoses were made during infertility work-up (76.2%). There was one midtrimester loss (1.5%). In the remaining 66 pregnancies, median gestational age at delivery was 38 weeks. There were 20 (30.3%) preterm births, 9 (13.6%) spontaneous preterm births, and 11 (16.7%) indicated preterm births. Women with indicated preterm births were more likely to have placental abnormalities. Of the available placental pathology, 45.2% had histological lesions of malperfusion. Cesarean delivery was performed in 77.3% of cases. CONCLUSION: Most women with incidentally detected unicornuate uteri gave birth at term. More than half the preterm births were indicated, with relatively high rates of placental abnormalities. In patients without a poor obstetrical history, rates of midtrimester loss and spontaneous preterm birth were lower than previously described.

Diagnostic accuracy of isolated clubfoot in twin compared to singleton gestations.

Background Our objective was to determine the predictive value of the prenatal diagnosis of isolated clubfoot in twin gestations compared to singleton gestations. Methods A prospectively entered ultrasound database was reviewed for all pregnancies scanned at our institution from 2002 to 2014. Cases of suspected clubfoot were identified. Neonates with associated anomalies or aneuploidy, and patients who delivered at other institutions were excluded. Neonatal charts were reviewed for the confirmation of clubfoot. The chi-squared (χ2) test, Fisher's exact test and the Mann-Whitney U test were used in the analysis, with p < 0.05 considered significant. Results Of those women who had prenatal ultrasound and subsequently delivered at our hospital, 84 pregnancies had isolated clubfoot suspected in the antenatal period. Of these pregnancies, 20 were twin gestations and 64 were singleton gestations. Overall, 51/84 (60.7%) pregnancies had clubfoot confirmed during the neonatal period. Of the twin pregnancies, only 35% (7/20) had a confirmed diagnosis of clubfoot at birth compared to 68.8% (44/64) of the singleton pregnancies (P = 0.008). Gestational age at diagnosis, breech presentation, neonatal gender, unilateral vs. bilateral clubfoot and suspicion of clubfoot in the presenting twin (Twin A) vs. the non-presenting twin (Twin B) did not correlate with an accurate diagnosis of clubfoot in twins. Conclusion False-positive prenatal diagnosis of isolated clubfoot is more common in twin gestations compared to singletons. This may be due to transient malpositioning or a result of diminished space. Obstetric providers should consider the possibility of a false-positive diagnosis and use caution when counseling patients about a prenatal suspicion for clubfoot, especially in twin gestations.

Testing for Noonan syndrome after increased nuchal translucency.

OBJECTIVE: The aim of this study was to report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. METHODS: This is a retrospective chart review. INCLUSION CRITERIA: (1) first trimester NT measurement ≥3 mm, (2) normal karyotype by either a CVS or an amniocentesis procedure, and (3) prenatal molecular genetic testing for NS completed. Results with known pathogenic variants were considered positive, while those with variants of unknown clinical significance, or with no variants, were considered negative. RESULTS: A total of 804 fetuses had an NT measurement of ≥3 mm, with a median NT thickness of 3.6 mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0 mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3 mm were not tested for NS (p = 0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. CONCLUSION: In euploid fetuses, increased NT is associated with a 10% risk of NS. © 2017 John Wiley & Sons, Ltd.

Hyponatremia associated with preeclampsia.

OBJECTIVE: The objective of our study was to evaluate the prevalence and clinical factors associated with hyponatremia in patients with preeclampsia. STUDY DESIGN: This is a descriptive study of all patients who delivered at our institution from 2013 to 2014. Patients with preeclampsia were identified from electronic medical records. Preeclampsia with and without severe features was defined using the criteria outlined in the American Congress of Obstetricians and Gynecologists Hypertension in Pregnancy guidelines. As sodium levels have been shown to be approximately 5 mEq/L lower in pregnancy, hyponatremia was defined as a sodium level <130 mEq/L. RESULTS: We identified 332 pregnancies complicated by preeclampsia, including 277 singletons and 55 twins. Hyponatremia was noted in 32 (9.7%) patients. Preeclampsia with severe features was present in the majority of patients with hyponatremia, and hyponatremia was more common in those with preeclampsia with severe features compared to those without (P<0.001). Hyponatremia also occurred more frequently in twins (P=0.001) and in older women (P=0.017). Only one patient without hyponatremia had an eclamptic seizure. CONCLUSION: Hyponatremia is not uncommon in preeclampsia, and is even more common in those with preeclampsia with severe features and twin gestations. As women with preeclampsia are at risk for hyponatremia, serum sodium should be monitored, especially in women with preeclampsia with severe features or twin gestations.

Placental malperfusion as a possible mechanism of preterm birth in patients with Müllerian anomalies.

OBJECTIVE: Müllerian anomalies are associated with increased risk of miscarriage, intrauterine growth restriction (IUGR) and preterm birth. While a commonly implicated cause is restricted expansion of endometrial cavity, alternatively it could be due to abnormal placentation. We sought to examine clinical and histopathologic factors associated with preterm delivery in women with Müllerian anomalies. STUDY DESIGN: One hundred and eleven singleton pregnancies in 85 women were analyzed retrospectively. There were 42 pregnancies with bicornaute, 24 with unicornuate, 24 with septate, 19 with didelphys and one each with arcuate and T-shaped uterus. Primary outcomes included gestational age at delivery, placental histopathology, placenta previa and accreta. RESULTS: Twenty-eight (25.2%) of pregnancies were delivered prior to term. Of those, only 14 (50%) were due to preterm labor or preterm premature rupture of membranes (PPROM). Histological evidence of placental malperfusion was present in 22% of all pregnancies and those delivered at an earlier median gestational age [34 (IQR 31-37) vs. 37 weeks (IQR 34-39); P=0.001]. Malperfusion was more common in preterm than in full term births (46% vs. 14%; P=0.04). Conversely, inflammation was not more common in preterm compared to term deliveries (17.9% vs. 16.9%; P=0.89). Five pregnancies had placenta previa, three of which were complicated by accreta. CONCLUSION: Placental malperfusion, rather than inflammation, was more commonly associated with preterm births in women with uterine anomalies.

Planned home birth and the association with neonatal hypoxic ischemic encephalopathy.

OBJECTIVE: To evaluate the association between planned home birth and neonatal hypoxic ischemic encephalopathy (HIE). METHODS: This is a case-control study in which a database of neonates who underwent head cooling for HIE at our institution from 2007 to 2011 was linked to New York City (NYC) vital records. Four normal controls per case were then randomly selected from the birth certificate data after matching for year of birth, geographic location, and gestational age. Demographic and obstetric information was obtained from the vital records for both the cases and controls. Location of birth was analyzed as hospital or out of hospital birth. Details from the out of hospital deliveries were reviewed to determine if the delivery was a planned home birth. Maternal and pregnancy characteristics were examined as covariates and potential confounders. Logistic regression was used to determine the odds of HIE by intended location of delivery. RESULTS: Sixty-nine neonates who underwent head cooling for HIE had available vital record data on their births. The 69 cases were matched to 276 normal controls. After adjusting for pregnancy characteristics and mode of delivery, neonates with HIE had a 44.0-fold [95% confidence interval (CI) 1.7-256.4] odds of having delivered out of hospital, whether unplanned or planned. Infants with HIE had a 21.0-fold (95% CI 1.7-256.4) increase in adjusted odds of having had a planned home birth compared to infants without HIE. CONCLUSION: Out of hospital birth, whether planned home birth or unplanned out of hospital birth, is associated with an increase in the odds of neonatal HIE.

First trimester cystic hygroma: does early detection matter?

OBJECTIVE: To describe the association of abnormal outcomes with fetal cystic hygroma detected when crown-rump length measures less than 45 mm, and to compare them to outcomes among fetuses with cystic hygroma detected when crown-rump length measures 45-84 mm. METHODS: We performed a retrospective cohort study of fetuses with first trimester nuchal cystic hygroma from 2005 to 2015. RESULTS: A total of 212 fetuses were included. Abnormal karyotype was found in 20 of 46 (43.4%) fetuses with cystic hygroma detected when crown-rump length measured below 45 mm, compared to 108 of 148 (73%) fetuses with cystic hygroma detected at crown-rump lengths of 45-84 mm (p = 0.001). There were no differences in rates of major structural anomaly (27% vs 36%; p = 0.53) or pregnancy loss (23% vs 7%; p = 0.22) among fetuses with normal karyotype. Those with cystic hygroma diagnosed at crown-rump lengths below 45 mm were more likely to have a normal neonatal outcome compared to cases diagnosed with crown-rump lengths of 45-84 mm (25% vs 11%; p = 0.02). CONCLUSION: Cystic hygroma detected when crown-rump length measures below 45 mm have lower rates of chromosomal abnormalities and a higher proportion of normal birth outcomes when compared to those detected later in the first trimester. © 2016 John Wiley & Sons, Ltd.

Low PAPP-A: the impact of ultrasound to evaluate fetal growth.

OBJECTIVE: Our objective was to describe utilization and impact of sonographic growth assessment in pregnancies with low pregnancy-associated plasma protein-A (PAPP-A). METHODS: Singleton pregnancies with PAPP-A ≤5th percentile and no other risk factors for fetal growth restriction from January 2011-June 2013 were included. Antepartum and delivery data were obtained by reviewing medical records. Outcomes of pregnancies referred for sonographic growth assessment were compared with those not referred for ultrasound. Fisher's exact test, chi-square analysis, and Mann-Whitney U were used for statistical comparison. RESULTS: Two hundred ninety-five patients were included. Of 285 pregnancies reaching the third trimester, 77.5% were referred for ultrasound, with the initial scan at a median gestational age of 28 weeks [26-29]. Referral for growth scans was associated with earlier gestational age at delivery and higher rates of delivery for fetal indications. Those who did not undergo growth scans were more likely to deliver a small for gestational age infant at term, 20.7% versus 35.0% (p = 0.04). There was one third-trimester fetal demise, occurring in a patient who had been undergoing growth scans. CONCLUSION: Growth scans in those with low PAPP-A were associated with delivery at earlier gestational age, with higher rates of delivery for fetal indications and lower rates of small for gestational age newborns at term. No significant differences in neonatal outcomes were observed.

Unilateral Fetal Renal Abnormalities: Are They Really Isolated?

OBJECTIVES: Our objective was to describe the association between unilateral fetal renal abnormalities and other major anomalies that were not apparent in the second trimester. METHODS: A review of the ultrasound database identified fetuses with suspected unilateral renal agenesis, unilateral multicystic dysplastic kidney, and renal ectopia from 2005 to 2014. Neonatal records were reviewed to identify anomalies not suspected in the second trimester, and postnatal imaging studies were reviewed. Categorical data were compared by &x003C7;(2) analysis and the Fisher exact test. RESULTS: We identified 102 cases, including 36 with suspected renal agenesis, 28 with suspected multicystic dysplastic kidney, and 38 with suspected renal ectopia. There were 8 cases (7.8%) with major anomalies not suspected in the second trimester. In 5 cases (4.9%), there were no associated findings in the second trimester. There were no significant differences in the rates of unsuspected abnormalities between the 3 groups. There was a trend toward a higher rate of unsuspected anomalies in the cases with a single umbilical artery compared to those with a 3-vessel cord (28.6% vs 6.3%; P= .09). CONCLUSIONS: In fetuses with unilateral renal abnormalities, major anomalies that were not suspected in the second trimester were uncommon. However, patients should be aware of the possibility that other major anomalies could subsequently be identified, and the outcome may depend on more than postnatal renal function.

Trends in timing of prenatal diagnosis and abortion for fetal chromosomal abnormalities.

OBJECTIVE: Our objective was to evaluate changes in the timing of prenatal diagnosis and abortion for chromosomal abnormalities over the past 10 years. STUDY DESIGN: This retrospective review identified singleton pregnancies with fetal chromosomal abnormalities that were diagnosed from 2005-2014 and included Down syndrome, Trisomy 18, and Trisomy 13. The study period was divided into 3 intervals: 2005-2006; 2007-2011; and 2012-2014. Gestational ages at prenatal diagnosis and abortion were compared over these intervals. RESULTS: The 213 cases included 142 cases of Down syndrome (66.7%), 47 cases of Trisomy 18 (22.1%), and 24 cases of Trisomy 13 (11.3%). Two hundred one women (94.4%) chose to undergo abortion. The median gestational ages at prenatal diagnosis and abortion for Trisomy 18 or 13 were 12 weeks (interquartile range, 12-13 weeks) and 13 weeks (interquartile range, 12-15.5 weeks) and did not change over the study period. In contrast, in pregnancies with Down syndrome, the median gestational age at prenatal diagnosis (16, 13, and 12 weeks; P < .001) and abortion (17, 14, and 13 weeks; P < .001) both decreased significantly over the study intervals. In Down syndrome pregnancies, the proportion of women who underwent chorionic villus sampling significantly increased over the 3 study intervals (36%, 63%, and 86%; P < .001). CONCLUSION: Since 2005, the gestational ages at prenatal diagnosis and abortion for Down syndrome have declined significantly. These changes are likely attributable to improvements in early screening that leads to higher rates of chorionic villus sampling.

Maternal serum analyte screening for fetal aneuploidy.

In the first and second trimesters, chemicals produced by the fetoplacental unit are measured to assess risks of fetal abnormalities. Consistent associations between levels of these proteins in such pregnancies enable these biomarkers to be used to calculate risk for Down syndrome and other chromosomal abnormalities in individual pregnancies. Special consideration may be required when assessing risk in multiple pregnancies and pregnancies achieved with infertility therapy.

Echogenic intracardiac foci: disclosure and the rate of amniocentesis in low-risk patients.

OBJECTIVE: Our objective was to determine the impact of disclosure of echogenic intracardiac focus (EIF) on the rate of amniocentesis in women who have undergone sequential testing. STUDY DESIGN: This was a retrospective study of women who had sequential testing for Down syndrome from 2009 through 2011. The Down syndrome risk was doubled in pregnancies with EIF, consistent with counseling provided to patients. In the control group Down syndrome risk was based on sequential testing. Within risk categories (1 in <250, 251-1000, 1001-5000, >5000) rates of amniocentesis with and without documented EIF were compared using Fisher exact test. RESULTS: In all, 4429 women at a median maternal age were included, including 229 with EIF (5.2%). In those at highest Down syndrome risk (1 in <250), rates of amniocentesis were similar between the 2 groups. In those at lower levels of risk, the rate of amniocentesis was significantly higher following disclosure of EIF compared to pregnancies without EIF at similar levels of risk. CONCLUSION: Except for those at highest risk, rates of invasive testing were significantly higher in pregnancies with isolated EIF vs those at comparable risk.