Comparative analysis of ultrasonographic fetal lung texture in twin and singleton fetuses.

OBJECTIVES: Increased fetal lung heterogeneity has been associated with term fetal lungs in singleton gestations. The objective of this study was to determine if fetal lung heterogeneity index (HI) differs between twin and singleton fetuses in the late second and third trimesters. METHODS: Prospective cohort study of women with singleton and twin gestations with medically-indicated ultrasound examinations at 24 weeks of gestation onward. Grayscale transverse fetal lung images were obtained at the level of the four-chamber heart. A region of interest was selected in each fetal lung image. Fetal lung HI was determined with MATLAB software using a dithering technique with ultrasound image pixels transformed into a binary map form from which a dynamic range value was determined. HI averages and standard deviations were generated for twin and singleton fetuses from 24 weeks gestation onward. Two sample t-tests were used to compare the mean HI at each gestational week between singleton and twin fetuses. RESULTS: In total, 388 singleton and 478 twin images were analyzed. From 35 through 38 weeks of gestation a statistically significant divergence in mean HI was observed with higher means in singleton compared to twin fetuses. At 24 weeks of gestation there was a significantly higher HI in twin fetuses compared to singletons. No differences in fetal lung HI were observed between 25 and 34 weeks gestational age. CONCLUSIONS: Differences in fetal lung HI were observed when comparing twin and singleton fetuses. Further investigation is required to determine the potential clinical significance of these findings.

Presence and Size of Placental Lakes on 20-Week Fetal Anatomy Ultrasound and Obstetrical Outcomes.

Our objective was to determine if placental lake presence or size is associated with adverse pregnancy outcomes. This was a retrospective cohort of patients who had fetal anatomy ultrasounds at 18-22 weeks and delivered between 2018 and 2022. Placental lakes were classified as small (>2.0 to 3.9 cm) or large (≥4 cm). Multiple gestations, placenta previas, and placenta accretas were excluded. Outcomes included low birthweight, cesarean delivery, primary cesarean for non-reassuring fetal heart tracing, fetal growth restriction, preterm birth, and severe preeclampsia. A total of 1052 patients were included; 294 had placental lakes (204 small, 90 large). No differences in pregnancy outcomes were observed.

Novel characterization of CASK variant c.1963 A>G (p.Asn655Asp) through whole-exome sequencing in a monochorionic diamniotic twin fetus with significant brain anomalies: A case report.

Whole-exome sequencing is an evolving technology in perinatal diagnosis which allows identification of genetic etiologies that would otherwise go undetermined. In this case report, a 38-year-old Hispanic woman, G5P3013, with a monochorionic diamniotic twin gestation with one fetus displaying significant cranial abnormalities on prenatal ultrasound and magnetic resonance imaging (MRI) of the brain is presented. Fetal anomalies included bilateral ventriculomegaly, absent cavum septum pellucidum, and absent corpus callosum. Diagnostic amniocentesis with chromosome analysis, chromosomal microarray, alpha-fetoprotein, cytomegalovirus, toxoplasmosis, and parvovirus had normal results. Whole-exome sequencing for the anomalous fetus detected a de novo mosaic variant of uncertain significance (VUS) in the calcium/calmodulin dependent serine protein kinase (CASK) gene: c.1963 A > G (p.Asn655Asp). This variant was absent in the normal twin fetus, the mother, and the father. Pathogenic CASK gene mutations are associated with three syndromes: FG syndrome 4, intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH), and intellectual developmental disorder with or without nystagmus. Whole-exome sequencing identified a potential etiology for the anomalies detected. The variant likely arose de novo and was the potential cause of the identified cranial abnormalities in one fetus of this monochorionic diamniotic twin gestation. Whole-exome sequencing may provide additional diagnostic utility when standard diagnostic testing is noncontributory.

Socioeconomic and clinical factors associated with excessive gestational weight gain.

PURPOSE: Excessive gestational weight gain (EGWG) is associated with adverse maternal and offspring outcomes but efforts to identify women at high risk for EGWG have been limited. The objective of this study is to identify socioeconomic and clinical factors associated with EGWG. METHODS: This retrospective cohort included pregnant patients who delivered live, term, singleton newborns between January 2018 and February 2020 at seven hospitals within a large health system in New York. Patients were stratified by pre-pregnancy body mass index and then classified based on whether they exceeded the Institute of Medicine guidelines for gestational weight gain (GWG) and whether they gained more than 50 pounds in pregnancy. RESULTS: A total of 44,872 subjects were included for analysis: 48% had EGWG and 17% had GWG exceeding 50 pounds. Patients with EGWG were more likely to be Black race, English speakers, overweight or obese pre-pregnancy, and have a mood disorder diagnosis. Patients who were underweight, multiparous, and those with gestational diabetes were less likely to have EGWG. CONCLUSION: Sociodemographic and clinical findings associated with GWG > 50 pounds were similar but only overweight and not obese patients were at increased risk. Patients at risk for EGWG may benefit from early nutrition counseling and education on lifestyle changes.

Severity of excessive gestational weight gain and risk of severe maternal morbidity.

BACKGROUND: Both obesity and excessive gestational weight gain are associated with severe maternal morbidity, but there is limited literature evaluating whether the risk of severe maternal morbidity is further increased by the degree or severity of excessive gestational weight gain. OBJECTIVE: This study aimed to determine whether pregnant patients with excessive gestational weight gain who gained more than 50 lb were at increased risk of severe maternal morbidity compared with those who only moderately exceeded recommended gestational weight gain guidelines. A secondary objective was to determine whether patients who gained 10 lb more than the recommended upper limit of total weight gain for a given prepregnancy body mass index group were at increased risk of severe maternal morbidity compared with those who exceeded that upper limit by a lesser amount. STUDY DESIGN: This was a retrospective cohort study of all patients with live, term, singleton deliveries with excessive gestational weight gain from 7 hospitals within a large health system in New York between January 2019 and February 2020. Excessive gestational weight gain was defined as exceeding the recommended upper limit of total weight gain for a given prepregnancy body mass index category using the National Academy of Medicine gestational weight gain guidelines: >40 lb for a body mass index of <18.5 kg/m2, >35 lb for a body mass index of 18.5 to 24.9 kg/m2, >25 lb for a body mass index of 25.0 to 29.9 kg/m2, and >20 lb for a body mass index of ³30.0 kg/m2. Patient height and weight data were self-reported at the time of delivery hospitalization and retrieved from the electronic medical record system. Patients were classified into 2 excessive gestational weight gain groups: moderate (≤50 lb) or severe (>50 lb). Patients with missing body mass index or gestational weight gain were excluded. The primary exposure was severe excessive gestational weight gain. The primary outcome was severe maternal morbidity, defined using the Centers for Disease Control and Prevention criteria. Logistic regression was used to model the likelihood of severe maternal morbidity, adjusting for race and ethnicity, nulliparity, advanced maternal age, gestational diabetes mellitus, and maternal mood disorder. For the secondary analysis, severe maternal morbidity rates were compared between patients who exceeded their body mass index-specific upper limit of total weight gain by ≥10 lb and those who exceeded it by <10 lb. RESULTS: A total of 11,506 patients were included for analysis, and 1965 patients (17.1%) had severe excessive gestational weight gain. The overall rate of severe maternal morbidity was 3.3%. Severe maternal morbidity occurred in 85 of 1965 patients (4.3%) with severe excessive gestational weight gain and 292 of 9541 patients (3.1%) with moderate excessive gestational weight gain. On regression analysis, after adjustment for covariate factors, patients with a severe excessive gestational weight gain were 39% more likely to experience severe maternal morbidity than those with moderate excessive gestational weight gain (adjusted odds ratio, 1.39; 95% confidence interval, 1.08-1.79). Patients with excessive gestational weight gain of ≥10 lb above the recommended body mass index-specific upper limit for gestational weight gain were 32% more likely (adjusted odds ratio, 1.32; 95% confidence interval, 1.07-1.62) to experience severe maternal morbidity than patients who exceeded that upper limit by <10 lb. CONCLUSION: Patients with live, term, singleton pregnancies who gain more than 50 lb are at increased risk of severe maternal morbidity compared with those who only moderately exceed gestational weight gain guidelines. Similarly, patients who gain ≥10 lb above the recommended body mass index-specific upper limit for gestational weight gain are at increased risk. Further study is warranted to determine the most effective interventions to manage gestational weight gain and mitigate maternal risk.

Fetal hypertrophic cardiomyopathy with elevated middle cerebral artery peak systolic velocity (MCA PSV): A potentially grim association.

An elevated middle cerebral artery peak systolic velocity (MCA PSV) in the setting of nondiabetic hypertrophic cardiomyopathy may portend an especially poor prognosis.

The effect of colorization on the fetal lung heterogeneity index.

No previous studies have quantitatively assessed the effect of color tones on ultrasound texture analysis techniques. Our objective was to compare heterogeneity index (HI) between fetal lung images captured in grayscale and those same images after conversion to Ice and Sepia. Fetal lung images were obtained during medically indicated ultrasound examinations. We observed that HI is affected by the application of color tones to ultrasound images of the fetal lung. Therefore, for each type of biological tissue and color tone, determination of distinct HI nomograms and cut off points is recommended.

Predicting perinatal outcomes with an obstructive sleep apnea screening tool.

The objective was to determine if a screening tool for obstructive sleep apnea could be used to predict adverse perinatal outcomes. This was a prospective observational study of patients receiving prenatal care and universally screened for obstructive sleep apnea with the STOP Questionnaire (four questions related to Snoring, Tiredness during daytime, Observed apnea, and high blood Pressure). Confounding variables were included in a backwards logistic regression model to predict adverse perinatal outcomes. The study population of 442 women had positive STOP screens (64; 14.5%) associated with preterm delivery and neonatal intensive care unit admissions. For preterm delivery, history of preterm delivery was the strongest predictor with odds ratios of 4.2 (95% confidence interval 2.0-8.8; p < 0.001), followed by STOP, odds ratios 2.8 (95% confidence interval 1.4-5.8; p = 0.004) and nulliparity, odds ratios 2.3 (95% confidence interval 1.2-4.4; p = 0.013). A positive STOP was the only significant predictor for neonatal intensive care unit admissions, odds ratios 2.5 (95% confidence interval 1.1-5.7; p = 0.036). STOP screening test performance indicated low sensitivity but high specificity: preterm delivery (28.3%, 87.4%), neonatal intensive care unit admissions (27.3%, 86.6%), low birth weight (25.0%, 86.9%), and preeclampsia (16.7%, 85.6%). As a stand-alone tool, the STOP Questionnaire has limited performance, but could be explored in combination with other factors that might increase sensitivity to predict preterm delivery and neonatal intensive care unit admission.

Fetal Lung Echo Texture in Pregnancies at Risk for Pulmonary Hypoplasia.

Pulmonary hypoplasia is associated with severe respiratory distress immediately after birth and frequently leads to neonatal death. In this study, we compared the fetal lung echo texture in pregnancies at high and low risk for pulmonary hypoplasia. Ultrasonic tissue heterogeneity was determined by a dynamic range calculation. This quantification uses a dithering technique based on the Floyd-Steinberg algorithm, in which the pixels are transformed into a binary map. Pregnancies at high risk for pulmonary hypoplasia showed decreased fetal lung heterogeneity on ultrasound imaging. This image-processing technique may allow improved risk stratification, patient counseling, and treatment approaches for pulmonary hypoplasia.

A Vulvar Venous Malformation in a 14-Year-Old Adolescent.

A vulvar venous malformation is a rare condition that can be misdiagnosed as vulvar varicose veins, but they are not the same entity. We describe the case of a 14-year-old nulliparous girl who presented with pelvic discomfort and limited ambulation secondary to a small, purple vulvar mass. The diagnosis was confirmed with the use of invasive imaging techniques after initial conservative management. Clinicians should consider venous malformations in the differential diagnosis of vulvar swelling in adolescents, and an earlier use of phlebography in patients with discordance between workup and symptoms to ensure a prompt diagnosis and decreased patient morbidity.

Effect of Chorionicity on Umbilical Cord Blood Acid-Base Analysis of the Second Twin.

Our objective was to determine whether chorionicity affects umbilical cord blood acid-base parameters of the second twin. This was a retrospective cohort of twin pregnancies delivered at ≥23 weeks of gestation at a tertiary hospital from 2010 to 2016. Patients were included if arterial and venous umbilical cord gas results were available for both newborns and chorionicity was confirmed histologically. Exclusion criteria included intrauterine fetal demise of either twin prior to labor, major fetal anomalies, monoamnionicity, uncertain chronicity and twin-to-twin transfusion syndrome. The primary outcome evaluated was the umbilical artery (UA) pH of the second twin. A total of 593 dichorionic (DC) and 86 monochorionic (MC) twin pregnancies were included. No difference in UA pH was observed between MC and DC twins. Among vaginal deliveries (n = 97), the UA pH of the first twin was higher than the second twin (7.26 vs. 7.24; p = .01). Twin-to-twin delivery interval (TTDI) ≥20 min was associated with a higher UA pH in the first twin compared to the second twin (7.25 vs. 7.16, respectively; p = .006). Multivariable logistic regression was used to predict arterial pH < 7.20 for the second twin; the most predictive factors were arterial pH < 7.20 for the first twin, chronic hypertension and prolonged TTDI. Chorionicity was not associated with any acid-base parameter of umbilical cord blood in either the first or second twin. No differences in neonatal outcomes were observed based on chorionicity or birth order. Populations with a lower cesarean delivery rate may yield different findings.

Congenital pulmonary airway malformation associated with mosaic Klinefelter syndrome.

A 26-year-old female, G4 P2012 presented for an anatomy scan at 18 weeks. Multiple macrocysts were seen in the left fetal lung, which lead to a diagnosis of congenital pulmonary airway malformation (CPAM) type II. A fetal MRI examination performed at 24 weeks of gestation confirmed the diagnosis of CPAM type II. A genetic amniocentesis was done to rule out a fetal chromosomal abnormality and the fetus was found to have mosaic Klinefelter syndrome. Fetal CPAM is not usually associated with chromosomal abnormalities unless there are other fetal malformations present. This is the first known case where a fetus with CPAM and no other malformation was found to have mosaic Klinefelter syndrome. Therefore, we believe it is prudent to offer prenatal diagnostic testing whenever a fetus with CPAM is identified with ultrasound.

Screening for prenatal alcohol exposure and corresponding short-term neonatal outcomes.

Detection of prenatal alcohol exposure (PAE) is important for early intervention and treatment. The main purpose of this study was to compare 1.) PAE rates using the biomarker, phosphatidylethanol (PEth), in umbilical cord (UC) blood vs. ethyl glucuronide (EtG) in UC tissue, the standard of care, and 2.) Pregnancy characteristics and neonatal outcomes in newborns positive vs. negative for PAE biomarkers. We examined records of neonates born over a two-year span receiving UC-PEth dried blood spots testing at the time of delivery in addition to standard of care PAE screening (n = 146). UC-PEth testing had a higher PAE detection rate (26%) vs. UC tissue EtG (0%, p < 0.01). PAE was not associated with any neonatal dysmorphic features or short-term adverse outcomes. The absence of significant clinical findings for identifying PAE in neonates reinforces alcohol biomarker necessity. We conclude that UC-PEth may be a valuable test for assessing PAE at birth and in identifying infants at risk for developing fetal alcohol spectrum disorder.

Outcomes in an obstetrical population with hereditary thrombophilia and high tobacco use.

OBJECTIVE: The purpose of this study was to examine birth outcomes in women treated or untreated for thrombophilia during pregnancies affected or not by tobacco exposure. METHODS: This was a retrospective cohort study of consecutive women from a single maternal fetal medicine clinic who delivered between January 2009 and December 2013. We compared birth outcomes by four groups of thrombophilia and smoking combinations and then by treated or untreated groups. RESULTS: Of the 8889 pregnant women in this study, 113 had thrombophilia and 97 received treatment. Thromboprophylaxis included: low molecular weight heparin, aspirin, unfractionated heparin, folic acid, and combinations of these. Smokers with thrombophilia had significantly higher rates of preeclampsia, intrauterine growth restriction, preterm birth (<37 weeks gestation) and low birth weight (all p ≤ .001). Conversely, this group had significantly lower rates of hemolysis, elevated liver enzymes, low platelet count (HELLP syndrome) and placental abruption. Women with thrombophilia who received thromboprophylaxis had lower rates of adverse birth outcomes, reaching significance for preterm birth <32 weeks gestation (4.3% versus 21.1%, p = .026). CONCLUSION: Pregnant women who smoke and have thrombophilia may be more likely to experience adverse birth outcomes and receive more benefit from thromboprophylaxis than their nonsmoking counterparts.

Improving screening for alcohol consumption during pregnancy with phosphatidylethanol.

OBJECTIVE: The study objective was to compare rates of alcohol use between urine ethanol testing and self- reporting (Method: 1) and Phosphatidylethanol (PEth) dried blood spot testing and self-reporting (Method: 2). METHODS: This was a prospective observational study in an obstetric clinic with universal alcohol screening. RESULTS: Method: 1 identified 11 patients with alcohol use (5 urine and 6 self-reported); Method: 2 identified 28 (22 PEth and 6 self-reported) out of 315 patients (one patient positive for both urine and PEth). The six patients with self-reported use had negative urine and PEth testing. We had fair agreement between the two methods (282 negative and 7 positive; 289/314=92.0%; Kappa 0.32, p<0.001); method 2 identified significantly more women (McNemar, p<0.001). Combining methods: resulted in an alcohol detection rate of 10.2% (32/314). CONCLUSION: Method: 2 identified more alcohol users than Method: 1. Combining both methods: identified the most alcohol consumption.

Quantitative Ultrasound Texture Analysis for Differentiating Preterm From Term Fetal Lungs.

OBJECTIVES: To differentiate preterm (<37 weeks' gestation) from term (≥37 weeks' gestation) fetal lungs by using quantitative texture analysis of ultrasound images. METHODS: This study retrospectively evaluated singleton gestations with valid dating at 20 weeks' gestational age (GA) or later between January 2015 and December 2015. Images were obtained from Voluson E8 ultrasound systems (GE Healthcare, Milwaukee, WI). A region of interest was selected in each fetal lung image at the level of the 4 heart chambers from an area that appeared most representative of the overall lung tissue and had the least shadow. Ultrasonic tissue heterogeneity (heterogeneity index) based on dynamic range calculation was determined for all lung images. This quantification was performed with a custom-made software program that used a dithering technique based on the Floyd-Steinberg algorithm, in which the pixels are transformed into a binary map. Regression analysis was used to determine the correlation and functional association between the heterogeneity index and GA. A receiver operating characteristic curve was used to identify the optimal heterogeneity index cutoff point for differentiating preterm from term fetal lungs. RESULTS: A total of 425 fetal lung ultrasound images (313 preterm and 112 term) were analyzed. Quantitative texture analysis predicted GA with sensitivity and specificity of 87.9% and 92.0%, respectively, based on the optimal receiver operating characteristic cutoff point. CONCLUSIONS: Quantitative ultrasound texture analysis of fetal lung tissue can differentiate preterm fetal lungs from term fetal lungs. Our data suggest that decreased fetal lung heterogeneity on ultrasound imaging is associated with preterm fetuses.

Relationship Between Methadone, Selective Serotonin Reuptake Inhibitors, and Neonatal Abstinence Syndrome.

OBJECTIVE: To compare incidence and severity of neo- natal abstinence syndrome (NAS) in neonates exposed to methadone and selective serotonin reuptake inhibitors (SSRIs) with neonates ex- posed to methadone alone. STUDY DESIGN: Retro- spective cohort study of women on methadone main- tenance with live births be- tween January 1, 2003, and December 31, 2009, at a tertiary care hospital. Data were abstracted from electronic medical records, exclud- ing cases of multiple gestations and lack of neonatal abstinence score documentation. Data analysis included Mann-Whitney U, Fisher's exact test, a receiver operat- ing characteristic curve, and a scatter diagram. RESULTS: A total of 91 cases comprised our study population, with 85 (93.4%) assigned to the methadone- only group and 6 (6.6%) assigned to the methadone and SSRIs group. NAS incidence was not significantly different between the methadone/SSRI group and the methadone group (5/6 [83.3%] vs. 43/85 [50.6%], p=0.21). However, severity of NAS (median 14.0 vs. 10.0, p=0.04) and neonatal intensive care unit stay were significantly higher and longer in the methadone/ SSRI group. CONCLUSION: While currently neonates exposed to SSRIs are not screened for NAS, health care providers may need to pay closer attention to the effects of SSRIs on neonates.

Cannabinoid Hyperemesis Syndrome During Pregnancy: A Case Report.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a syndrome characterized by chronic marijuana use, cyclic vomiting, and compulsive bathing. Given the similarities this syndrome shares with hyperemesis gravidarum, it is likely that this is a highly underdiagnosed syndrome. We present a case of severe nausea and vomiting during pregnancy that met the criteria for CHS. CASE: This case outlines the course of recurrent nausea and vomiting due to cannabinoid hyperemesis in a pregnant patient and illustrates the similarities between hyperemesis gravidarum and CHS and the value of obtaining a complete history that includes the use of marijuana. CONCLUSION: Recognition of this syndrome will aid in patient care, lessen the economic burden of an extensive workup, and hopefully lessen provider frustration with diagnosis and treatment of a common and underdiagnosed entity.

Sociocultural characteristics, obesity and inflammatory biomarkers in Puerto Rican toddlers born in New York City.

BACKGROUND: In the USA, Puerto Rican children have a higher prevalence of asthma than other Latino ethnicities, and acculturation is one of hypothesized reasons for this difference. We examined associations between sociocultural characteristics and serum leptin, high-sensitivity C-reactive protein (hsCRP), and body mass index (BMI), and further, among hsCRP, leptin levels, BMI percentiles, and allergic sensitization in 2-year-old children. METHODS: IgE antibodies, leptin, and hsCRP concentrations were measured in serum from Puerto Rican toddlers (n = 143) born in New York City with a maternal history of allergy and/or asthma. Demographic and home characteristics questionnaires were administered to the mother, postpartum and two years later. Children's weight and height were measured to determine BMI percentiles. RESULTS: More girls (60%) had leptin levels above the median compared with boys (37%) (p = 0.0063). Leptin was positively correlated with BMI (r = 0.25; p = 0.0042). Children in daycare were more likely to be obese (40% vs. 24% p < 0.06). Maternal birthplace was significantly associated with children's leptin but not with hsCRP. Leptin levels were lower for children whose mothers were born on the US mainland (GM = 2.5 ng/ml, 95% CI [2.2-2.7]) compared with those whose mothers were born in Puerto Rico or another country (GM = 3.2 ng/ml, 95% CI [2.2-3.9], t-test p = 0.01). Mothers born in another country were more likely than those born in the US mainland or Puerto Rico to have obese children (60% vs. 26% p < 0.02). Leptin, hsCRP, and BMI percentile were not associated with sensitization to any of the measured inhalant allergens or total IgE. CONCLUSION: Even at a very young age, some acculturation factors were associated with biomarkers and anthropometric measures of obesity among this Puerto Rican pediatric population. To our knowledge, this is the first study demonstrating the association of mother's birth place with child BMI and leptin as early as 24 months.