Personal care product use patterns in association with phthalate and replacement biomarkers across pregnancy.

BACKGROUND: Humans are exposed to phthalates, a class of non-persistent chemicals, through multiple products, including personal care and cosmetics. Associations between specific phthalates and product use have been inconsistent. However, determining these connections could provide avenues for exposure reduction. OBJECTIVE: Examine the association between patterns of personal care product use and associations with phthalate and replacement biomarkers. METHODS: In the Human Placenta and Phthalates Study, 303 women were enrolled in early pregnancy and followed for up to 8 visits across gestation. At each visit, women completed a questionnaire about product use in the prior 24 hours and contributed urine samples, subsequently analyzed for 18 phthalate and replacement metabolites. At early, mid-, and late pregnancy, questionnaire responses were condensed and repeated metabolite concentrations were averaged. Latent class analysis (LCA) was used to determine groups of women with similar use patterns, and weighted associations between group membership and biomarker concentrations were assessed. RESULTS: LCA sorted women into groups which largely corresponded to: (1) low fragranced product use (16-23% of women); (2) fragranced product and low body wash use (22-26%); 3) fragranced product and low bar soap use (26-51%); and (4) low product use (7-34%). Monoethyl phthalate (MEP) urinary concentrations were 7-10% lower and concentrations of summed di(2-ethylhexyl) terephthalate metabolites were 15-21% lower among women in the "low fragranced product use" group compared to the population mean. Few other consistent associations between group and biomarker concentrations were noted. IMPACT STATEMENT: Personal care products and cosmetics are a known exposure source for phthalates and potentially represent one of the most accessible intervention targets for exposure reduction. However, in this analysis accounting for concurrent use and fragranced status of products, we did not find any use patterns that corresponded to universally lower levels.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction.

BACKGROUND: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration. OBJECTIVE: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction. STUDY DESIGN: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests. RESULTS: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively. CONCLUSION: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity.

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Effects of cohort, genotype, variant, and maternal ß-blocker treatment on foetal heart rate predictors of inherited long QT syndrome.

AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal ß-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal ß-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or ß-adrenergic response) had lower FHR. Maternal ß-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. CONCLUSION: Genotype, LQT1 variant, and maternal ß-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

Variability and Longitudinal Trajectories of Phthalate and Replacement Biomarkers across Pregnancy in the Human Placenta and Phthalates Study.

Human exposure to phthalates is widespread, but assessment of variability across pregnancy has been hampered by short half-lives of phthalate biomarkers and a few repeated measures in prior studies. We aimed to characterize the variability and longitudinal profiles of phthalate and replacement biomarkers across pregnancy. Within the Human Placenta and Phthalates Study, 303 pregnant women provided urine samples at up to 8 visits across gestation. Concentrations of 14 metabolites of phthalates and 4 metabolites of replacements were quantified in each sample, and subject-specific averages within each trimester were calculated. We examined variability in individual biomarker concentrations across the 8 visits, within trimesters, and across trimester-specific averages using intraclass correlation coefficients (ICCs). To explore longitudinal exposure biomarker profiles, we applied group-based trajectory modeling to trimester-specific averages over pregnancy. Pooling multiple visits into trimester-specific averages improved the ICCs for all biomarkers. Most biomarkers generally showed stable concentrations across gestation, i.e., high-, medium-, and low-concentration profiles, with small proportions of participants falling into the "high"-exposure groups. Variability over pregnancy is likely attributable to random fluctuations around a baseline exposure rather than true changes in concentrations over time.

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study.

BACKGROUND: Pregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. OBJECTIVE: Characterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. METHODS: Analyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017-2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. RESULTS: Mono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (ß: -0.36 [95% confidence interval: -0.56, -0.15]) and abdominal circumference (-0.31 [-0.49, -0.12]) z-scores. This association was mainly driven by phthalate biomarkers. CONCLUSIONS: Urine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.

Impact of maternal body mass index on the accuracy of third trimester sonographic estimation of fetal weight.

OBJECTIVES: To Determine whether maternal body mass index (BMI) can affect the accuracy of sonographic estimation of fetal weight (EFW) in the third trimester when compared to neonatal birthweight (BW). METHODS: Secondary analysis from our original prospective cohort of pregnant women beyond 34 weeks, distributed in 4 groups according to their BMI: normal, overweight, obese and morbid obese. Fetal biometry and fluid measurements were obtained by two experienced sonographers, blinded for patient's clinical information and to each other's measurements. Average EFW and neonatal BW were converted into gestational-specific Z-scores. Interobserver correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman (BA) plots were constructed to assess the level of accuracy. RESULTS: 100 women were enrolled (800 measurements obtained by 17 sonographers): 17 had normal BMI (17%), 27 were overweight (27%), 29 were obese (29%) and 27 were morbidly obese (27%). There was no statistical difference for GA at delivery (p = 0.74), EFW (p = 0.05) or BW (p = 0.09) between groups (Table 1). Mean Z-score for EFW was - 0.17 (SD 0.81) and for neonatal BW was - 0.25 (SD 0.74). ICC was 0.69 (95% CI 0.57, 0.78) and CRC was 0.82. Mean Z-score difference was small (Table 2). When stratifying according to BMI categories, the ICC ranged from 0.49 to 0.76. Reliability indices ranged from 0.66 to 0.86. The Z-scores' differences were overall small with no statistical difference (Table 3). BA showed evenly distributed interobserver differences (Fig. 1). CONCLUSIONS: When performed by trained sonographers, fetal weight estimation in the third trimester is accurate when compared to neonatal birthweight at increasing BMI categories.

Genetics of non-isolated hemivertebra: A systematic review of fetal, neonatal, and infant cases.

Hemivertebra is a congenital vertebral malformation caused by unilateral failure of formation during embryogenesis that may be associated with additional abnormalities. A systematic review was conducted to investigate genetic etiologies of non-isolated hemivertebra identified in the fetal, neonatal, and infant periods using PubMed, Cochrane database, Ovid Medline, and ClinicalTrials.gov from inception through May 2022 (PROSPERO ID CRD42021229576). The Human Phenotype Ontology database was accessed May 2022. Studies were deemed eligible for inclusion if they addressed non-isolated hemivertebra or genetic causes of non-isolated hemivertebra identified in the fetal, neonatal, or infant periods. Cases diagnosed clinically without molecular confirmation were included. Systematic review identified 23 cases of non-isolated hemivertebra with karyotypic abnormalities, 2 cases due to microdeletions, 59 cases attributed to single gene disorders, 18 syndromic cases without known genetic etiology, and 14 cases without a known syndromic association. The Human Phenotype Ontology search identified 49 genes associated with hemivertebra. Non-isolated hemivertebra is associated with a diverse spectrum of cytogenetic abnormalities and single gene disorders. Genetic syndromes were notably common. Frequently affected organ systems include musculoskeletal, cardiovascular, central nervous system, genitourinary, gastrointestinal, and facial dysmorphisms. When non-isolated hemivertebra is identified on prenatal ultrasound, the fetus must be assessed for associated anomalies and genetic counseling is recommended.

The aorto-left ventricular tunnel from a fetal perspective: Original case series and literature review.

INTRODUCTION: Aorto-left ventricular tunnel (ALVT) accounts for <0.1% of congenital heart defects. Evidence on the prognosis from a fetal perspective is limited. With this retrospective international case series, we provide information on the outcome of fetuses with ALVT. METHODS: All members of the Association for European Pediatric and Congenital Cardiology's (AEPC) fetal working group and fetal medicine units worldwide were invited for participation. We observed antenatal parameters, neonatal outcome and postnatal follow-up. Additionally, a systematic search of the literature was performed. RESULTS: Twenty fetuses with ALVT were identified in 10 participating centers (2001-2019). Fetal echocardiographic characteristics of ALVT included an increased cardiac-thorax ratio (95%), left ventricular end-diastolic diameter (90%) and a dysplastic aortic valve (90%). Extracardiac malformations were rare (5%). Eight fetuses died at a median gestational age (GA) of 21 + 6 weeks (range, 19-24): all showed signs of hydrops prior to 24 weeks or at autopsy. All others (60%, 12/2) were live-born (median GA 38 + 4, range 37-40), underwent surgery and were alive at last follow up (median 3.2 years, range 0.1-17). The literature reported 22 ALVT fetuses with similar outcome. CONCLUSIONS: In the absence of fetal hydrops, ALVT carries a good prognosis. Fetuses who survive to 24 weeks without hydrops are likely to have a good outcome.

Fetal Myocardial Performance Index in the Third Trimester of Pregnancy: Feasibility and Reproducibility of Conventional Spectral Doppler versus Spectral Tissue Doppler Technique.

OBJECTIVE: This study aims to compare completion rates and reproducibility of myocardial performance index (MPI) using conventional spectral Doppler versus tissue Doppler in an unselected high-risk third trimester population. STUDY DESIGN: This was a prospective cross-sectional study of high-risk pregnancies at ≥28 + 0 weeks' gestation. Conventional spectral and tissue Doppler MPI of the left ventricle (LV) and right ventricle (RV) was attempted on all patients. RESULTS: Seventy-nine pregnancies were evaluated. LV tissue Doppler MPI was completed more frequently than LV conventional spectral Doppler MPI (63/79, 79.7% vs. 45/79, 55.7%), p-value <0.01. RV tissue Doppler MPI was completed more frequently than RV conventional spectral Doppler MPI (68/79, 86% vs. 42/79, 53.2%), p-value <0.01. In obese subjects (n = 50) LV tissue Doppler MPI was completed more frequently than LV conventional spectral Doppler MPI (37/50, 74% vs. 26/50, 52%), p-value <0.01. RV tissue Doppler MPI was completed more frequently than RV conventional spectral Doppler MPI (40/50, 80% vs. 25/50, 50%), p-value <0.01. intraclass correlation coefficient for all modalities ranged between 0.73 and 0.93, except for LV conventional spectral Doppler intraobserver variability which was 0.22. CONCLUSION: Tissue Doppler had statistically higher completion rates than conventional spectral Doppler, including the obese subgroup, with evidence of strong reproducibility in the third trimester.

Can Ultrasound in Early Gestation Improve Visualization of Fetal Cardiac Structures in Obese Pregnant Women?

OBJECTIVES: To determine whether ultrasound (US) imaging of obese pregnant women in early gestation improves fetal cardiac visualization. METHODS: We report a prospective longitudinal trial comparing late first- and early second-trimester US to traditional second-trimester US for fetal cardiac screening in maternal obesity. All study participants received US for fetal cardiac screening at a gestational age of 13 weeks to 15 weeks 6 days using a transvaginal or transabdominal approach (UST1). All patients also underwent a traditional transabdominal examination at 20 to 22 weeks (UST2). If UST2 failed to complete the cardiac visualization, a follow up examination (second UST2) was performed 2 to 4 weeks later. Imaging was considered complete if the visceral situs, 4 chambers, outflow tracts, and 3 vessels were visualized. The completion rates between UST1 and UST2 were the primary outcomes. A power analysis (85%) and sample size calculation (n = 145) were performed. RESULTS: A total of 152 pregnancies met study criteria. Completion rates of cardiac screening were 77% for UST1 and 70% for UST2 (P = .143). This comparison reached statistical significance in patients with a body mass index of greater than 40 kg/m2 (UST1 [69%] versus UST2 [38%]; P = .001). Sixty-two percent of patients with a body mass index of greater than 40 kg/m2 required second UST2. The highest fetal cardiac screening completion rate was achieved when UST1 was combined with UST2 (96.1%). In 1 fetus, congenital heart disease was detected at UST1 and later confirmed. CONCLUSIONS: This study represents the largest prospective trial assessing early-gestation US for fetal cardiac screening in the setting of maternal obesity. In obese pregnancies, the addition of early-gestation US to the 20- to 22-week US substantially improves the visualization of fetal cardiac anatomy.

Prevalence of Sonographic Markers of Placenta Accreta Spectrum in Low-Risk Pregnancies.

OBJECTIVE: This study was aimed to evaluate the prevalence of sonographic markers for placenta accreta spectrum (PAS) in pregnancies at low-risk for PAS. STUDY DESIGN: Pregnant women at low-risk for PAS presenting for routine second trimester ultrasound who enrolled in the study were evaluated prospectively for sonographic markers of PAS during two ultrasounds at 18 to 24 and 28 to 34 weeks. Frequencies of PAS markers were compared between the second and third trimester and between those with and without prior cesarean deliveries (CD). RESULTS: Overall, 174 women were included. Several markers were seen frequently in the second trimester: vascular cervical invasion (57%), lacunae (46%), subplacental hypervascularity (37%), and irregularity of the posterior bladder wall (37%). Other markers were seen infrequently or not at all: loss of the retroplacental clear zone, uterovesical interface < 1 mm, bridging vessels, placental bulge or focal exophytic mass. Frequencies of markers did not differ between women with and without prior CD. Lacunae were larger and more numerous in the third trimester. Two or more PAS markers were observed in 98% of second trimester ultrasounds. CONCLUSION: Several PAS sonographic markers occur commonly in low-risk pregnancies. In the absence of risk factors, the independent predictive value of these markers is questionable.

Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies.

BACKGROUND: Fetal atrioventricular block (AVB) occurs in 2% to 4% of anti-Ro antibody-positive pregnancies and can develop in <24 h. Only rarely has standard fetal heart rate surveillance detected AVB in time for effective treatment. OBJECTIVES: Outcome of anti-Ro pregnancies was surveilled with twice-daily home fetal heart rate and rhythm monitoring (FHRM) and surveillance echocardiography. METHODS: Anti-Ro pregnant women were recruited from 16 international centers in a prospective observational study. Between 18 and 26 weeks' gestation, mothers checked FHRM twice daily with a commercially available Doppler monitor and underwent weekly or biweekly surveillance fetal echocardiograms. If FHRM was abnormal, a diagnostic echocardiogram was performed. Cardiac cycle length and atrioventricular interval were measured, and cardiac function was assessed on all echocardiograms. After 26 weeks, home FHRM and echocardiograms were discontinued, and mothers were monitored during routine obstetrical visits. Postnatal electrocardiograms were performed. RESULTS: Most mothers (273 of 315, 87%) completed the monitoring protocol, generating 1,752 fetal echocardiograms. Abnormal FHRM was detected in 21 mothers (6.7%) who sought medical attention >12 h (n = 7), 3 to 12 h (n = 9), or <3 h (n = 5) after abnormal FHRM. Eighteen fetuses had benign rhythms, and 3 had second- or third-degree AVB. Treatment of second-degree AVB <12 h after abnormal FHRM restored sinus rhythm. Four fetuses had first-degree AVB diagnosed by echocardiography; none progressed to second-degree AVB. No AVB was missed by home FHRM or developed after FHRM. CONCLUSIONS: Home FHRM confirms the rapid progression of normal rhythm to AVB and can define a window of time for successful therapy. (Prospective Maternal Surveillance of SSA [Sjögren Syndrome A] Positive Pregnancies Using a Hand-held Fetal Heart Rate Monitor; NCT02920346).

Relationship Between Cavum Septi Pellucidi Measurements and Fetal Hypoplastic Left Heart Syndrome or Dextro-Transposition of the Great Arteries.

OBJECTIVES: The aim of this study was to compare the size and position of the cavum septi pellucidi (CSP) in fetuses with hypoplastic left heart syndrome (HLHS) or dextro-transposition of the great arteries (d-TGA) with healthy fetuses. METHODS: The CSP length, CSP width, and frontal lobe length were measured in 185 healthy fetuses (404 scans), 11 fetuses with HLHS (16 scans), and 11 fetuses with d-TGA (12 scans) between January 2005 and April 2016. Each measurement was compared between healthy fetuses and those with HLHS or d-TGA, controlling for the biparietal diameter. RESULTS: Positive correlations were noted between biparietal diameter and CSP length, CSP width, and frontal lobe length (adjusted R2 = 0.811, 0.821, and 0.878, respectively). An increased CSP length was found in both fetuses with HLHS and those with d-TGA (P < .0001). The CSP width was only increased in fetuses with d-TGA (P = .0466). No difference in the frontal lobe length was noted. CONCLUSIONS: In fetuses with HLHS, the CSP is increased in length. In fetuses with d-TGA, the CSP is increased in both length and width.

Advances in Fetal Cardiac Imaging.

This review presents a detailed discussion on recent trends in fetal cardiac imaging. Ultrasound technique which are most useful for clinical practice today and will likely change the approach to cardiac evaluation in the future are presented.

The Role of Early Gestation Ultrasound in the Assessment of Fetal Anatomy in Maternal Obesity.

OBJECTIVES: The 2012 Eunice Kennedy Shriver National Institute of Child Health fetal imaging consensus suggested that fetal anatomy ultrasound in obese pregnancies be performed at 20 to 22 weeks, with follow-up in 2 to 4 weeks if anatomy is incomplete. It was postulated that imaging in early gestation may improve visualization, although no prospective trials had been done to date. METHODS: We performed a prospective longitudinal blinded trial comparing an early gestation ultrasound (13 + 0 to 15 + 6 weeks) with the traditional second-trimester ultrasound for completion of the fetal anatomy survey in obese patients. Inclusion criteria included singleton gestation, body mass index (BMI) more than 30, less than 16 + 0 weeks' gestation, and no karyotype abnormality; exclusion criteria included age younger than 18 years, more than 16 weeks' gestation at time of consent, and BMI less than 30. Participants received a transvaginal and/or transabdominal sonogram for fetal anatomic survey at 13 + 0 to 15 + 6 weeks' gestation (US1). Images from US1 were blinded to physicians and sonographers performing subsequent examinations. All participants underwent the traditional transabdominal sonogram at 18 to 24 weeks (US2). If US2 failed to complete the anatomic survey, a repeat transabdominal sonogram (2-US2) was performed 2 to 4 weeks later. RESULTS: A total of 152 pregnancies met the criteria. Anatomy completion rate was 57.2% for US1 and 62.5% for US2, which was not statistically significant, even when stratified by BMI. Excluding the philtrum, the US1 performed better than US2 for class III obesity (65.5% versus 45.5% [P = .035]). Combination of US1 + US2 yielded a higher completion rate than US2 + 2-US2 (94.1% versus 83.6% [P = .0023]). CONCLUSIONS: In the setting of maternal obesity, the addition of an ultrasound in early gestation may be of highest benefit for patients with class III obesity (BMI > 40 kg/m2 ).

Kabuki syndrome as a cause of non-immune fetal hydrops/ascites.

Kabuki syndrome (MIM 147920) is a well-described, multiple congenital anomaly syndrome characterized by growth and developmental delay, cardiac, renal, and vertebral anomalies, as well as persistent fetal finger pads and distinct facial features. Facies are characterized by long palpebral fissures with eversion of lateral third of the lower eyelid, resembling the "Kabuki make-up" theatre genre after which the syndrome is named. Kabuki syndrome is estimated to affect 1/32,000 births, with 55-80% of patients showing nonsense or frameshift mutations in the KMT2D (MLL2) gene, which encodes a histone transferase located on chromosome 12q. Additionally, owing to the heterogeneous nature of Kabuki syndrome, a smaller number of diagnosed patients have been identified with mutations or deletions in KDM6A (a component of the same transcriptional complex as KMT2D) with no mutations in KMT2D, or as those diagnosed with Kabuki syndrome and without alterations in either KMT2D or KDM6A. Diagnosis of the syndrome in newborns and infants is difficult, as the facial features are not as evident as in toddler- or childhood. There are no known "tell-tale" signs of Kabuki syndrome prenatally, and there are no reports of common, specific findings in fetuses that might suggest the diagnosis. We present here two infants who presented with prenatal hydrops/ascites, who were subsequently diagnosed with Kabuki syndrome. Although relatively non-specific, we suggest that Kabuki syndrome be added to the list of genetic syndromes that are suspected in cases of prenatal hydrops, review the molecular etiology of Kabuki syndrome, and broaden the phenotype of this well-described disorder. © 2016 Wiley Periodicals, Inc.

Dilated cavum septi pellucidi in fetuses with microdeletion 22q11.

OBJECTIVES: The cavum septi pellucidi (CSP) is an easily recognizable landmark in the fetal brain. CSP disappears after birth to form the septum pellucidum. Children with microdeletion 22q11 (del. 22q11) were, however, reported to have a persistent dilated CSP. This study was designed to examine whether the CSP is dilated in fetuses with del.22q11. METHODS: This was a case-control study where the CSP width was measured in normal fetuses from 16 to 34 weeks and in fetuses with del. 22q11. CSP width was correlated to the biparietal diameter (BPD). Reference curves were constructed, and z-scores calculated. RESULTS: Cavum septi pellucidi width in 260 normal fetuses showed a linear correlation with BPD. The study group consisted of 37 fetuses with del. 22q11. In 25/37 (67.5%) of fetuses with del. 22q11, the CSP was enlarged with a mean z-score of 2.64 (p < 0.0001). Fetuses with a BPD > 50 mm (>22 weeks of gestation) had a dilated CSP in 85.7% (24/28). CONCLUSIONS: The CSP is a structure routinely evaluated in screening ultrasound. A wide CSP is found in second trimester fetuses with del. 22q11. A dilated CSP may be an important sonographic marker for the presence of del. 22q11 along with conotruncal malformations and thymic hypoplasia. © 2016 John Wiley & Sons, Ltd.

Prenatal and Postnatal Survival of Fetal Tetralogy of Fallot: A Meta-analysis of Perinatal Outcomes and Associated Genetic Disorders.

OBJECTIVES: The aim of this systematic review was to compare the postnatal outcomes, genetic testing results, and sonographic findings in 3 subtypes of tetralogy of Fallot. METHODS: Thirty-six articles from the MEDLINE and EMBASE databases were selected for this review. The postnatal outcomes, karyotyping results, and sonographic findings of fetal tetralogy of Fallot with pulmonary stenosis, tetralogy of Fallot with pulmonary atresia, and tetralogy of Fallot with an absent pulmonary valve were collected and compared. RESULTS: The survival rates (termination of pregnancy was considered fetal death) for prenatally diagnosed tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve at the end of neonatal period were significantly lower than the rate for tetralogy of Fallot with pulmonary stenosis (P < .05). The survival rate for tetralogy of Fallot with pulmonary atresia was also lower at birth (P < .001). Major chromosomal anomalies were more frequently detected in tetralogy of Fallot with pulmonary stenosis (P< .05); conversely, 22q11 deletion was present more often in fetuses with tetralogy of Fallot with pulmonary atresia and tetralogy of Fallot with an absent pulmonary valve (P < .001). Compared to tetralogy of Fallot with pulmonary stenosis, a right aortic arch was more associated with tetralogy of Fallot with pulmonary atresia (32.6%; P < .05), and the ductus arteriosus was almost always absent in tetralogy of Fallot with an absent pulmonary valve (87.5%; P < .001). CONCLUSIONS: The postnatal outcomes, genetic testing results, and sonographic findings are different among subtypes of tetralogy of Fallot. Documenting those details at diagnosis can help specialists better counsel their patients.

Standardized Six-Step Approach to the Performance of the Focused Basic Obstetric Ultrasound Examination.

OBJECTIVES: This study aims to validate the feasibility and accuracy of a new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, and compare the new approach to the regular approach performed in the scheduled obstetric ultrasound examination. STUDY DESIGN: A new standardized six-step approach to the performance of the focused basic obstetric ultrasound examination, to evaluate fetal presentation, fetal cardiac activity, presence of multiple pregnancy, placental localization, amniotic fluid volume evaluation, and biometric measurements, was prospectively performed on 100 pregnant women between 18(+0) and 27(+6) weeks of gestation and another 100 pregnant women between 28(+0) and 36(+6) weeks of gestation. The agreement of findings for each of the six steps of the standardized six-step approach was evaluated against the regular approach. RESULTS: In all ultrasound examinations performed, substantial to perfect agreement (Kappa value between 0.64 and 1.00) was observed between the new standardized six-step approach and the regular approach. CONCLUSION: The new standardized six-step approach to the focused basic obstetric ultrasound examination can be performed successfully and accurately between 18(+0) and 36(+6) weeks of gestation. This standardized approach can be of significant benefit to limited resource settings and in point of care obstetric ultrasound applications.