Noninvasive single-cell-based prenatal genetic testing: A proof of concept clinical study.

OBJECTIVE: To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood. METHODS: Blood was obtained from 401 (243 + 158) individuals (8-22 weeks) and shipped overnight. Red cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 and enriched for positive CK staining. Automated scanning was used to identify and pick single CK+ /CD45- trophoblasts which were subjected to next-generation sequencing. RESULTS: Blood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin with Williams syndrome deletion). The deletion was confirmed in both fetuses. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results in 133 cases. Seven had aneuploidy results, and there were three likely pathogenic deletions/duplications, including one15q11-q13 deletion. CONCLUSION: Although the sample size is modest and statistically accurate measures of test performance are not possible, the Luna test detected aneuploidy and deletions/duplications based on concordance with CVS/amniocentesis.

Collaboration between maternal-fetal medicine and family planning: a survey of Northeast US academic medical centers.

OBJECTIVES: To explore how complex family planning (CFP) and maternal-fetal medicine (MFM) in Northeast academic medical centers work together to provide abortion care. METHODS: We distributed an exploratory cross-sectional online survey to CFP and MFM faculty and fellows at academic medical centers in the Northeast between July and September of 2020. The survey included demographic information, assessment of practice patterns, hospital/administration support and assessment of collaboration. Likert scale questions examined opinions about collaboration and an open-ended question solicited ideas for improvement. We performed bivariate analysis to examine the association between subspecialty and practice location regarding provision of abortion care and perceived barriers to care. RESULTS: The response rate was 31 % and was similar by specialty. Of the 69 respondents, 83 % were MFMs, 75 % were faculty, and 54 % practiced in New York. More than 85 % reported personal participation in some portion of abortion care. The two most common perceived barriers to care were "lack or reluctance of physicians/staff" and state laws prohibiting termination. Nearly all (95 %) stated there was a good working relationship between CFP and MFM divisions; however, almost one-third agreed with or were neutral to the statements "MFM and CFP are siloed in terms of work/patient care." CONCLUSIONS: Academic MFM and CFP providers in the Northeast collaborate well in providing abortion care, though our findings highlight areas that would benefit from improvement. Optimizing collaboration in the Northeast is important given its regional role for ensuring abortion access in the current national landscape. Improved education of all members of the patient care team on the importance of abortion access may also help provide optimal patient care where abortion services still legally exist.

Low-Dose Aspirin during Pregnancy and Postpartum Bleeding.

OBJECTIVE: This study aimed to investigate whether aspirin 81 mg daily for preeclampsia prevention is associated with increased risk of postpartum blood loss at the time of delivery. STUDY DESIGN: This is a retrospective cohort study performed at a tertiary hospital from January 2018 to April 2021. Data were extracted from the electronic medical record. Patients prescribed low-dose aspirin (LDA) were compared with patients who were not. The primary outcome was a composite of postpartum blood loss, defined as: estimated blood loss (EBL) >1,000 mL, documentation of International Classification of Diseases-9/-10 codes for postpartum hemorrhage (PPH), or red blood cell (RBC) transfusion. Bivariate analysis, and unadjusted and adjusted logistic regression modeling were performed. RESULTS: Among 16,980 deliveries, 1,922 (11.3%) were prescribed LDA. Patients prescribed LDA were more likely to be >35 years old, nulliparous, obese, taking other anticoagulants, or have diagnoses of diabetes, systemic lupus erythematosus, fibroids, or hypertensive disease of pregnancy. After adjusting for potential confounders, the significant association between LDA use and the composite did not persist (adjusted odds ratio [aOR]: 1.1, 95% confidence interval [CI]: 1.0-1.3) nor did the association between EBL > 1,000 mL (aOR: 1.0, 95% CI: 0.9-1.3) and RBC transfusion (aOR: 1.3, 95% CI: 0.9-1.7). The association between LDA and PPH remained significant (aOR: 1.3, 95% CI: 1.1-1.6). Patients who discontinued LDA <7 days prior to delivery had an increased risk of the postpartum blood loss composite compared discontinuation ≥7 days (15.0 vs. 9.3%; p = 0.03). CONCLUSION: There may be an association between LDA use and increased risk of postpartum bleeding. This suggests that use of LDA outside the recommended guidelines should be cautioned and further investigation is needed to determine its ideal dosing and timing of discontinuation. KEY POINTS: · There may be an association with LDA and an increased risk of postpartum bleeding.. · Patients who discontinued LDA less than 7 days prior to delivery had an increased rate of postpartum bleeding.. · Additional research is need to determine optimal LDA dose and timing of discontinuation..

Maternal Morbidity Risk Factors in Nulliparas.

OBJECTIVE: For every incidence of maternal mortality, maternal morbidity is thought to occur in another 50 to 100 individuals in the United States. Multiple risk factors for severe maternal morbidity have been identified, but counseling about specific risk in pregnancy remains difficult, particularly nulliparous individuals as prior obstetric history is one of the factors influencing risk for severe maternal morbidity. The objective of this study is to examine the association between sociodemographic and laboratory assessments in the first trimester and maternal morbidity in nulliparas. STUDY DESIGN: This was a secondary analysis of a large, multicenter prospective observational cohort of nulliparas. The primary maternal outcome was a composite of hypertensive disorders of pregnancy (HDP), hemorrhage (transfusion, hemorrhage, hysterectomy, other surgery, readmission for bleeding), infection (endometritis, wound infection or dehiscence, pneumonia, sepsis, infection during labor and delivery, readmission for infection through day 14), venous thromboembolic events (VTE) (deep venous thrombosis, or pulmonary embolus), or maternal death within 14 days of delivery. Sociodemographic and clinical factors were compared between people with and without maternal morbidity. Relative risk and 95% confidence interval for maternal morbidity was calculated using log-binomial regression, adjusted for baseline characteristics that had a significant independent relationship with maternal morbidity with a p-value <0.05. RESULTS: Of 9,445 pregnant people in the analysis, 18.2% (n = 1,716) experienced the composite maternal morbidity; the most common component was HDP (13.1%, n = 1,244) followed by infection (4.43%, n = 420), hemorrhage (2.27%, n = 215), VTE (0.12%, n = 11), and death (0.01%, n = 1). In a multivariable model, self-identified Black race, first trimester obesity, pregestational diabetes, chronic hypertension, and chronic kidney disease were significantly associated with the primary maternal outcome. CONCLUSION: More than one in six nulliparas experienced the composite maternal morbidities. Maternal morbidity was associated with self-identified Black race, obesity, and multiple preexisting medical comorbidities. KEY POINTS: · One in six nulliparas experience maternal morbidity in their first pregnancy related to hypertensive disorders of pregnancy, infection, hemorrhage, and venous thromboembolism.. · Risk factors for maternal morbidity in nulliparas include Black race, prepregnancy body mass index, and preexisting medical conditions.. · The preexisting medical conditions with the strongest association with maternal morbidity included pregestational diabetes, chronic hypertension, and chronic kidney disease..

Does Antenatal Progesterone Administration Modify the Risk of Neonatal Intraventricular Hemorrhage?

OBJECTIVE: Progesterone administration has been associated with improved neurological outcomes following traumatic brain injury in adults. However, studies examining the effect of progesterone on the risk of neonatal intraventricular hemorrhage (IVH) are inconsistent. We sought to determine if maternal administration of intramuscular 17-α-hydroxyprogesterone caproate (17-OHPC) is associated with decreased rates of IVH in infants born before 32-weeks gestation. STUDY DESIGN: This is a retrospective study of liveborn singleton deliveries between 20- and 32-weeks gestation at two large academic medical centers from January 1, 2012 to August 30, 2020. Data were extracted from hospital electronic medical record data warehouses using standardized definitions and billing and diagnosis codes. We evaluated receipt of 17-OHPC in the antepartum period and diagnosis of IVH (grade I-IV, per Volpe classification) during the neonatal delivery hospitalization encounter. Bivariate and multivariate analyses were performed to examine the association between 17-OHPC and neonatal IVH adjusting for potential confounders. Odds ratio (ORs) and 95% confidence intervals (CIs) were presented. RESULTS: Among 749 neonates born between 20- and 32-week gestation, 140 (18.7%) of their mothers had received antenatal 17-OHPC and 148 (19.8%) were diagnosed with IVH after birth. No significant association was observed between maternal 17-OHPC and neonatal IVH in unadjusted (OR 1.14, 95% CI 0.72-1.78) or adjusted analyses (adjusted odds ratio 1.14, 95% CI 0.71-1.84). Independent of exposure to 17-OHPC, as expected, infants born <28-weeks gestation or those with very low birthweight (<1,500 g) were at an increased risk of IVH (OR 2.32, 95% CI 1.55-3.48 and OR 2.19, 95% CI 1.09-4.38, respectively). CONCLUSION: Antenatal maternal 17-OHPC administration was not associated with the risk of neonatal IVH. Further research may be warranted to determine whether timing, route of delivery, and duration of progesterone therapy impact rates of neonatal IVH. KEY POINTS: · This study aimed to compare the frequency of intraventricular hemorrhage in preterm neonates exposed to antenatal 17-α-hydroxyprogesterone caproate to those not exposed.. · In neonates born at <32-weeks gestation, maternal use of progesterone is not associated with the risk of intraventricular hemorrhage.. · In contrast to preclinical and adult data, this study suggests that progesterone exposure is not associated with the prevention of neonatal brain injury..

Perinatal Outcomes in Obese Women with One Abnormal Value on 3-Hour Oral Glucose Tolerance Test.

OBJECTIVE: This study aimed to determine if one abnormal value of four on the diagnostic 3-hour oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes in obese women. STUDY DESIGN: This is a secondary analysis of a prospective study of nulliparous women in eight geographic regions. Women with body mass index <30 kg/m2 and pregestational diabetes mellitus (GDM) were excluded. Four groups were compared: (1) normal 50-g 1-hour glucose screen, (2) elevated 1-hour glucose screen with normal 100-g 3-hour diagnostic OGTT, (3) elevated 1-hour glucose screen and one of four abnormal values on 3-hour OGTT, and (4) GDM. Using multivariable logistic regression adjusting for covariates, the women in the groups with dysglycemia were compared with those in the normal screen group for maternal and neonatal outcomes. RESULTS: Among 1,713 obese women, 1,418 (82.8%) had a normal 1-hour glucose screen, 125 (7.3%) had a normal 3-hour diagnostic OGTT, 72 (4.2%) had one abnormal value on their diagnostic OGTT, and 98 (5.7%) were diagnosed with GDM. The one abnormal value group had increased risk of large for gestational age (LGA) neonates (adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.31-3.82), cesarean delivery (aOR = 2.19, 95% CI: 1.34-3.58), and hypertensive disorders of pregnancy (aOR = 2.19, 95% CI: 1.32-3.63) compared with normal screens. The one abnormal value group also had an increased risk of preterm birth <37 weeks (aOR = 2.63, 95% CI: 1.43-4.84), neonatal respiratory support (aOR = 2.38, 95% CI: 1.23-4.60), and neonatal hyperbilirubinemia (aOR = 2.00, 95% CI: 1.08-3.71). There was no association between one abnormal value with shoulder dystocia and neonatal hypoglycemia. CONCLUSION: For obese women, one abnormal value on the 3-hour OGTT confers increased perinatal adverse outcomes. These women should be studied further to determine if nutrition counseling and closer fetal monitoring improve outcomes even in the absence of a diagnosis of GDM. KEY POINTS: · Study of obese women with one abnormal value on OGTT.. · Adverse maternal and neonatal outcomes were found, including more LGA neonates.. · Neonates were not at increased risk of hypoglycemia..

Implications for preeclampsia: hypoxia-induced Notch promotes trophoblast migration.

In the first trimester of human pregnancy, low oxygen tension or hypoxia is essential for proper placentation and placenta function. Low oxygen levels and activation of signaling pathways have been implicated as critical mediators in the promotion of trophoblast differentiation, migration, and invasion with inappropriate changes in oxygen tension and aberrant Notch signaling both individually reported as causative to abnormal placentation. Despite crosstalk between hypoxia and Notch signaling in multiple cell types, the relationship between hypoxia and Notch in first trimester trophoblast function is not understood. To determine how a low oxygen environment impacts Notch signaling and cellular motility, we utilized the human first trimester trophoblast cell line, HTR-8/SVneo. Gene set enrichment and ontology analyses identified pathways involved in angiogenesis, Notch and cellular migration as upregulated in HTR-8/SVneo cells exposed to hypoxic conditions. DAPT, a γ-secretase inhibitor that inhibits Notch activation, was used to interrogate the crosstalk between Notch and hypoxia pathways in HTR-8/SVneo cells. We found that hypoxia requires Notch activation to mediate HTR-8/SVneo cell migration, but not invasion. To determine if our in vitro findings were associated with preeclampsia, we analyzed the second trimester chorionic villous sampling (CVS) samples and third trimester placentas. We found a significant decrease in expression of migration and invasion genes in CVS from preeclamptic pregnancies and significantly lower levels of JAG1 in placentas from pregnancies with early-onset preeclampsia with severe features. Our data support a role for Notch in mediating hypoxia-induced trophoblast migration, which may contribute to preeclampsia development.

Factors associated with appropriate treatment of acute-onset severe obstetrical hypertension.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends that pregnant patients receive expeditious treatment with first-line antihypertensive agents within 1 hour of confirmed severe hypertension to reduce the risk for maternal stroke. However, it is unknown how often this guideline is followed and what factors influence a patient's likelihood of receiving guideline-concordant care. OBJECTIVE: We aimed to identify factors associated with receiving guideline-concordant treatment for an obstetrical hypertensive emergency. STUDY DESIGN: We present a case-control study of all pregnant and postpartum patients who had persistent severe hypertension (≥2 systolic blood pressures ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, or both within 1 hour of each other) during their delivery hospitalization at a tertiary hospital from October 1, 2013, to August 31, 2020. Data were extracted from the hospital electronic medical records using standard definitions and billing and diagnosis codes. We defined receipt of the recommended treatment as administration of a first-line antihypertensive agent (intravenous labetalol, intravenous hydralazine, or immediate-release oral nifedipine) within 60 minutes of the first or second severe-range blood pressure measurement during their delivery hospitalization. Delayed treatment was defined as the administration of a first-line agent >60 minutes after the second elevated blood pressure measurement. Patients were considered untreated if a first-line agent was never administered. Maternal sociodemographic, clinical and pregnancy factors, and time and day of the week of the hypertensive emergency were compared among patients who received the recommended treatment, those who received delayed treatment, and those who were untreated. Bivariate analyses were performed, and multinomial and multivariable logistic regression models were used to adjust for potential confounders. RESULTS: Of the 39,918 deliveries in the cohort, 1987 (5.0%) were complicated by severe, persistent obstetrical hypertension. Of these patients, 532 (26.8%) received the recommended treatment, 356 (17.9%) received delayed treatment, and 1099 (55.3%) did not receive any first-line antihypertensive therapy. The multinomial regression models that were used to compare these 3 groups indicated that patients who received the recommended treatment were more likely to be Black (adjusted odds ratio, 1.85; 95% confidence interval, 1.36-2.51), Hispanic (adjusted odds ratio, 1.77; 95% confidence interval, 1.28-2.52), or pregnant and at <37 weeks of gestation (adjusted odds ratio, 6.65; 95% confidence interval, 5.08-8.72). Treatment was less likely if the severe obstetrical hypertension emergency occurred overnight (7:00 PM to 6:59 AM) (adjusted odds ratio, 0.79; 95% confidence interval, 0.64-0.97) or during the postpartum period (adjusted odds ratio, 0.66; 95% confidence interval, 0.51-0.86). CONCLUSION: Approximately half of obstetrical patients with at least 2 documented severely elevated blood pressure measurements did not receive the recommended antihypertensive treatment. Of those who did receive treatment, about 40% had delayed treatment. Black and Hispanic race and preterm gestation were associated with an increased likelihood of receiving the recommended treatment when compared with White race and term pregnancies. Patients whose severe obstetrical hypertension emergency occurred overnight and those who were postpartum were less likely to receive any first-line antihypertensive treatment. Overall, patients without sociodemographic and clinical risk factors for severe obstetrical hypertension or other pregnancy complications were less likely to be treated. However, treatment improved significantly over time with the implementation of targeted quality measures and specific institutional policies based on the American College of Obstetricians and Gynecologists' latest severe obstetrical hypertension management guidelines.

A Single-Center Experience with a Pregnant Immigrant Population and Zika Virus Serologic Screening in New York City.

OBJECTIVE: Our institution is in an area of New York City with a large population of immigrants from Zika virus endemic areas. With the recent Zika virus outbreak, we sought to examine our center's experience with screening for Zika virus and outcomes among patients who tested positive for the disease during pregnancy. STUDY DESIGN: We performed a chart review of all pregnant patients who tested positive (positive serum or urine polymerase chain reaction [PCR]) or presumed positive (immunoglobulin M [IgM] enzyme-linked immunosorbent assay [ELISA] positive or IgM ELISA equivocal with positive plaque reduction neutralization test) for Zika virus. All tests were performed by the Department of Health (DOH) and followed Centers for Disease Control and Prevention guidelines in effect at the time of specimen collection. Testing of cord blood, placenta, and/or neonatal blood were/was performed by the DOH for New York County. Prenatal ultrasounds for fetal head size and surveillance for calcifications were performed by maternal-fetal medicine specialists. Infant head ultrasound results were included when available. RESULTS: Between March 2016 and April 2017, 70 pregnant patients were positive or presumed positive for Zika infection during pregnancy. Of those, 16 women had positive urine or serum PCR and the remaining 54 were presumed positive. Among positive cases, five women tested positive via urine PCR only, nine women tested positive via serum PCR only, and two women had both positive urine and serum PCR. Fifteen of 67 infants (22%) born during the study period were born to mothers with positive urine or serum PCR testing. Sixty-five newborns were clinically normal with normal head measurements. Of the intracranial ultrasound performed, one infant had a grade 1 intraventricular hemorrhage, four had incidental choroid plexus cysts, and one had severe ventriculomegaly that was also noted antenatally. There were 2 positive and 15 equivocal infant serum IgM samples and 1 positive placental PCR from these pregnancies. There were four pregnancy terminations and two cases with fetal anomalies in this population that were split evenly between patients who tested positive and those who tested presumed positive for Zika virus during pregnancy. CONCLUSION: We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic.

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF164 expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection.

BACKGROUND: Zika virus is a mosquito-transmitted flavivirus, which can induce fetal brain injury and growth restriction following maternal infection during pregnancy. Prenatal diagnosis of Zika virus-associated fetal injury in the absence of microcephaly is challenging due to an incomplete understanding of how maternal Zika virus infection affects fetal growth and the use of different sonographic reference standards around the world. We hypothesized that skeletal growth is unaffected by Zika virus infection and that the femur length can represent an internal standard to detect growth deceleration of the fetal head and/or abdomen by ultrasound. OBJECTIVE: We sought to determine if maternal Zika virus infection is associated with a femur-sparing pattern of intrauterine growth restriction through analysis of fetal biometric measures and/or body ratios using the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic references. STUDY DESIGN: Pregnant women diagnosed with a possible recent Zika virus infection at Columbia University Medical Center after traveling to an endemic area were retrospectively identified and included if a fetal ultrasound was performed. Data were collected regarding Zika virus testing, fetal biometry, pregnancy, and neonatal outcomes. The 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic standards were applied to obtain Z-scores and/or percentiles for fetal head circumference, abdominal circumference, and femur length specific for each gestational week. A novel 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project standard was also developed to generate Z-scores for fetal body ratios with respect to femur length (head circumference:femur length, abdominal circumference:femur length). Data were then grouped within clinically relevant gestational age strata (<24, 24-27 6/7, 28-33 6/7, >34 weeks) to analyze time-dependent effects of Zika virus infection on fetal size. Statistical analysis was performed using Wilcoxon signed-rank test on paired data, comparing either abdominal circumference or head circumference to femur length. RESULTS: A total of 56 pregnant women were included in the study with laboratory evidence of a confirmed or possible recent Zika virus infection. Based on the Centers for Disease Control and Prevention definition for microcephaly after congenital Zika virus exposure, microcephaly was diagnosed in 5% (3/56) by both the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart standards (head circumference Z-score ≤-2 or ≤2.3%). Using 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, intrauterine fetal growth restriction was diagnosed in 18% of pregnancies (10/56; abdominal circumference Z-score ≤-1.3, <10%). Analysis of fetal size using the last ultrasound scan for all subjects revealed a significantly abnormal skewing of fetal biometrics with a smaller abdominal circumference vs femur length by either 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project or World Health Organization Fetal Growth Chart (P < .001 for both). A difference in distribution of fetal abdominal circumference compared to femur length was first apparent in the 24-27 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P = .002; World Health Organization Fetal Growth Chart, P = .001). A significantly smaller head circumference compared to femur length was also observed by 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project as early as the 28-33 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P = .007). Overall, a femur-sparing pattern of growth restriction was detected in 52% of pregnancies with either head circumference:femur length or abdominal circumference:femur length fetal body ratio <10th percentile (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project Z-score ≤-1.3). CONCLUSION: An unusual femur-sparing pattern of fetal growth restriction was detected in the majority of fetuses with congenital Zika virus exposure. Fetal body ratios may represent a more sensitive ultrasound biomarker to detect viral injury in nonmicrocephalic fetuses that could impart long-term risk for complications of congenital Zika virus infection.

A survey of the knowledge, attitudes and practices on Zika virus in new York City.

BACKGROUND: Over 900 travel-associated Zika virus cases have been identified in New York City (NYC), New York. A survey was administered in NYC adapted from the Knowledge, Attitudes, and Practices (KAP) survey on Zika virus developed by the World Health Organization (WHO). METHODS: A standardized, self-administered, anonymous questionnaire was administered to a convenience sample in Manhattan and the Bronx from June 30th, 2016 to October 21st, 2016. Responses were grouped into six domains based on the content and structure of the questions and were summarized using descriptive statistics or converted into a continuous knowledge score and assessed for associations with pregnancy status and travel history using linear regression. RESULTS: There were 224 respondents with a mean age of 33 (SD ± 11.6) with 77% (170/224) female and 24% (51/224) pregnant. The majority (98% (213/217)) were unable to identify all of the symptoms associated with acute Zika virus infection and all modes of transmission (97% (213/219)). Most participants (85% (187/219)) identified mosquitoes as a mode of transmission. 95% (116/122) reported an association between Zika virus and microcephaly. The most concerning aspect of Zika virus in 46% (91/200) was the risk of disabilities to babies, and risk of sexual transmission (25% (49/200)). When asked what precautions pregnant persons should to reduce the risk of transmission when traveling to a Zika endemic region, only 27% (50/185) identified using condoms during intercourse or refraining from intercourse while pregnant. Knowledge of Zika transmission is significantly positively associated with pregnancy status, but not with travel history. CONCLUSION: Our results indicate an overall poor understanding of Zika virus symptoms and possible complications, transmission modes, and current recommended prevention guidelines. Pregnancy is positively associated with Knowledge of Zika Transmission, but not other knowledge scores. Reported travel history to Zika endemic regions is not significantly associated with Zika knowledge. There is a need for implementing future public health interventions that particularly focus on protection against Zika transmission, that Zika is sexually transmitted, and risks that the Guillain-Barré Syndrome poses a risk to adults.

Effect of Maternal Age and Fetal Number on the Risk of Hypertensive Disorders of Pregnancy.

OBJECTIVE: Our primary objective was to compare the differential contribution of fetal number and maternal age to the risk of hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a secondary analysis of a large study of primary cesarean delivery. Women with singleton, twin, or triplet gestations were included. Women were divided into groups based on fetal number and maternal age. The primary outcome was HDP. A logistic regression model was fit to adjust for confounders. The incidence of HDP was compared with the reference group and within exposure groups. RESULTS: Of the 70,417 women included, HDP occurred in 8,079 (12%) women. The frequency of HDP among the comparison groups ranged from 11 to 38%. Nearly all groups had significantly increased risk of HDP compared with young maternal age singletons. Twin and triplet gestations increased the risk of HDP over singletons irrespective of maternal age after adjusting for baseline disease and race. The risk of HDP did not significantly increase with maternal age when fetal number was similar. CONCLUSION: Fetal number significantly increased the risk of HDP and contributed more to that risk than maternal age. Maternal age became significant in groups with age greater than 40 years.

Postpartum Thromboembolism Prophylaxis during Delivery Hospitalizations.

OBJECTIVE: This article evaluates trends in venous thromboembolism (VTE) prophylaxis during delivery hospitalizations in the United States. METHODS: We utilized an administrative database to determine if women hospitalized for vaginal or cesarean delivery received pharmacologic VTE prophylaxis, mechanical VTE prophylaxis, or both from January 2011 through March 2015. Mechanical prophylaxis included sequential compression devices, graduated compression stockings, and other pneumatic devices. Pharmacologic prophylaxis included unfractionated heparin, low molecular weight heparin, or fondaparinux. Probability of use of thromboprophylaxis for individual hospitals was estimated in an adjusted model. RESULTS: A total of 956,428 women who underwent cesarean and 1,914,142 women who underwent vaginal delivery were included in the analysis. Cesarean VTE prophylaxis declined between 2011 (50.3%) and 2015 (47.7%; p < 0.01). Of women undergoing vaginal delivery, 2.9% received prophylaxis. Delivery hospital was an important determinant of cesarean prophylaxis: in the adjusted model, one-third of hospitals used prophylaxis for less than 20% of deliveries, one-third of hospitals used prophylaxis for 20 to 80% of deliveries, and the final third of hospitals used prophylaxis in greater than 80% of deliveries. CONCLUSION: While many hospitals appear to be following best clinical practices, some do not provide routine cesarean VTE prophylaxis. Minimizing care quality variation may improve maternal safety.

Do Doppler studies enhance surveillance of uncomplicated monochorionic diamniotic twins?

OBJECTIVES: To determine whether isolated abnormal Doppler indices before 28 weeks predict adverse pregnancy outcomes in uncomplicated monochorionic diamniotic (MCDA) twins. METHODS: A retrospective cohort study of MCDA twin pregnancies receiving antenatal testing at a single center between 2007 and 2013 was conducted. Sonographic surveillance, including Doppler velocimetric studies of the umbilical artery, ductus venosus, and middle cerebral artery of each twin, was initiated by 28 weeks and repeated at least every 2 weeks. All pregnancies were deemed "uncomplicated" at initial sonography, without evidence of polyhydramnios, oligohydramnios, intrauterine growth restriction, twin growth discordance of at least 20%, structural or chromosomal anomalies, or unclear chorionicity. Pregnancies were divided into 2 groups: those with isolated Doppler abnormalities before 28 weeks and those with normal Doppler indices. The primary outcome was a composite including twin-twin transfusion syndrome, intrauterine growth restriction of more than 1 twin, growth discordance of at least 20%, preterm delivery before 34 weeks for fetal indications, or demise of more than 1 fetus. RESULTS: Ninety-six patients were included, with 22 (22.9%) having isolated Doppler abnormalities before 28 weeks. The incidence of the primary outcome did not differ between groups (36.4% versus 28.4%; P = .47). The abnormal Doppler group underwent a greater number of sonographic examinations (15 versus 10; P= .001) and more antenatal admissions for fetal concerns (50.0% versus 12.2%; P < .001). CONCLUSIONS: Isolated Doppler abnormalities are commonly encountered in uncomplicated MCDA pregnancies before 28 weeks yet are not clearly predictive of twin-specific complications. Doppler abnormalities were associated with increased sonographic surveillance and antenatal hospitalizations, suggesting an influence on physician practice patterns. Data may not support Doppler studies before 28 weeks for routine MCDA twin monitoring.

Fetal outcomes of elective delivery.

Retrospective observational studies have suggested that delivery at or beyond 39 weeks has numerous neonatal benefits including less need for respiratory support, fewer neurodevelopmental delays and lower health care costs. This has lead governmental agencies, and professional organizations to endorse a policy of limiting elective delivery prior to 39 weeks. Nonetheless, studies which have examined the implications of instituting such policies, have demonstrated mixed benefits and signaled some concerns about unintended outcomes, such as stillbirth. This chapter will detail the evidence that these policies have on certain neonatal outcomes and examine why the promise of such policies may remain unfilled.