Obesity, Twin Pregnancy, and the Role of Assisted Reproductive Technology.

Importance: The prevalence of overweight and obesity (body mass index [BMI] ≥25) has increased globally, and high BMI has been linked to higher rates of twin birth. However, evidence from large population-based studies is lacking; the issue needs careful study, as women with obesity are also more likely to use assisted reproductive technology (ART), which frequently results in twin pregnancy. Objective: To examine the association between BMI and twin birth and the role of ART as a potential mediator in this association. Design, Setting, and Participants: This retrospective cohort study included all live births and stillbirths with gestational age of 20 weeks or longer in British Columbia, Canada, from 2008 to 2020, using data from the British Columbia Perinatal Database Registry. Data analysis was conducted from November 2022 to June 2023. Exposures: Prepregnancy BMI, calculated as weight in kilograms divided by height in meters squared, and use of ART. Main Outcomes and Measures: The study assessed whether prepregnancy BMI is associated with the rate of twin vs singleton delivery and whether this association is explained by the differential use of ART in women with obesity. Results: A total of 524 845 deliveries at 20 weeks' or longer gestation occurred in British Columbia during the study period, and 392 046 women had complete data on prepregnancy BMI. The median (IQR) age was 31.4 (27.7-35.0) years, approximately half were nulliparous (243 443 [46.4%]) and less than 10% smoked during pregnancy (36 894 [7.1%]). Overall, 8295 women had a twin delivery (15.8 per 1000 deliveries), and rates per 1000 deliveries by prepregnancy BMI categories were 11.9 (underweight), 15.1 (normal), 16.0 (overweight), 16.0 (obesity class I), 16.7 (obesity class II), and 18.9 (obesity class III). After adjustment for other covariates, women with underweight had relatively 16% fewer twins compared with women with normal BMI (adjusted risk ratio [aRR], 0.84; 95% CI, 0.74-0.95), while women with overweight, class I obesity, class II obesity, and class III obesity had 14% (aRR, 1.14; 95% CI, 1.07-1.21), 16% (aRR, 1.16; 95% CI, 1.06-1.27), 17% (aRR, 1.17; 95% CI, 1.02-1.34), and 41% higher rates (aRR, 1.41; 95% CI, 1.19-1.66), respectively. The proportion of women who conceived by ART increased with increasing BMI, and ART was associated with nearly a 12-fold higher rate of twin delivery (aRR, 11.80; 95% CI 11.10-12.54). ART explained about a quarter of the association between obesity class I and II and twin delivery (eg, obesity class I, 23% mediated; 95% CI, 7%-39% mediated), but none of this association was mediated by ART in women with class III obesity. Conclusions and relevance: In this cohort study of 524 845 births, the rate of twin birth increased with increasing prepregnancy BMI. In women with a BMI between 30 and 40, approximately one-quarter of this association was explained by higher use of ART; however, there was no evidence of such mediation in women with BMI of 40 or greater.

Predictive ability of fetal growth charts in identifying kindergarten-age developmental challenges: a cohort study.

BACKGROUND: The Society for Maternal-Fetal Medicine recommends defining fetal growth restriction as an estimated fetal weight or abdominal circumference <10th percentile of a population-based reference. However, because multiple references are available, an understanding of their ability to identify infants at increased risk due to fetal growth restriction is critical. Previous studies have focused on the ability of different population references to identify short-term outcomes, but fetal growth restriction also has longer-term consequences for child development. OBJECTIVE: This study aimed to estimate the association between estimated fetal weight percentiles on the INTERGROWTH-21st and World Health Organization fetal growth charts and kindergarten-age childhood development, and establish the charts' discriminatory ability in predicting kindergarten-age developmental challenges. STUDY DESIGN: We conducted a retrospective cohort study linking obstetrical ultrasound scans conducted at BC Women's Hospital, Vancouver, Canada, with population-based standardized kindergarten test results. The cohort was limited to nonanomalous, singleton fetuses scanned at ≥28 weeks' gestation from 2000 to 2011, with follow-up until 2017. We classified estimated fetal weight into percentiles using the INTERGROWTH-21st and World Health Organization charts. We used generalized additive modeling to link estimated fetal weight percentile with routine province-wide kindergarten readiness test results. We calculated the area under the receiver-operating characteristic curve and other measures of diagnostic accuracy with 95% confidence intervals at select percentile cut-points of the charts. We repeated analyses using the Hadlock chart to help contextualize findings. The main outcome measure was the total Early Development Instrument score (/50). Secondary outcomes were Early Development Instrument subdomain scores for language and cognitive development, and for communication skills and general knowledge, as well as designation of "developmentally vulnerable" or "special needs". RESULTS: Among 3418 eligible fetuses, those with lower estimated fetal weight percentiles had systematically lower Early Development Instrument scores and increased risks of developmental vulnerability. However, the clinical significance of differences was modest in magnitude (eg, total Early Development Instrument score -2.8 [95% confidence interval, -5.1 to -0.5] in children with an estimated fetal weight in 3rd-9th percentile of INTERGROWTH-21st chart [vs reference of 31st-90th]). The charts' predictive abilities for adverse child development were limited (eg, area under the receiver-operating characteristic curve <0.53 for all 3 charts). CONCLUSION: Lower estimated fetal weight percentiles on the INTERGROWTH-21st and World Health Organization charts indicate increased risks of adverse kindergarten-age child development at the population level, but are not accurate individual-level predictors of adverse child development.

Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada.

Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8-21 weeks' gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.

Pre-pregnancy body mass index and adverse maternal and perinatal outcomes in twins: A population retrospective cohort study.

OBJECTIVE: To examine the association between pre-pregnancy BMI and severe maternal morbidity (SMM), perinatal death and severe neonatal morbidity in twin pregnancies. METHODS: All twin births at ≥ 20 weeks gestation in British Columbia, Canada, from 2000 to 2017 were included. We estimated rates of SMM, a perinatal composite of death and severe morbidity, and its components per 10,000 pregnancies. Confounder-adjusted rate ratios (aRR) between pre-pregnancy BMI and outcomes were estimated using robust Poisson regression. RESULTS: Overall, 7770 (368 underweight, 1704 overweight, and 1016 obese) women with twin pregnancy were included. The rates of SMM were: 271.1, 320.4, 270.0, and 225.9 in underweight, normal BMI, overweight and obese women, respectively. There was little association between obesity and any of the primary outcomes (e.g., aRR = 1.09, 95% CI = 0.85, 1.38 for composite perinatal outcome). Underweight women had higher rates of the composite perinatal adverse outcome (aRR = 1.79, 95% CI = 1.32-2.43), driven by increased rates of severe respiratory distress syndrome, and neonatal death. CONCLUSIONS: There was no evidence of elevated risk of adverse outcomes among twin pregnancies of women who were overweight or obese. Risk was higher in underweight women, who may require specific care when carrying twins.

Prepregnancy body mass index and adverse perinatal outcomes in the presence of other maternal risk factors.

BACKGROUND: High prepregnancy body mass index is one of the most common risk factors for adverse perinatal events. OBJECTIVE: This study aimed to assess whether the association between maternal body mass index and adverse perinatal outcome is modified by other concomitant maternal risk factors. STUDY DESIGN: This was a retrospective cohort study of all singleton live births and stillbirths in the United States from 2016 to 2017, using data from the National Center for Health Statistics. Logistic regression was used to estimate the adjusted odds ratios and 95% confidence intervals between prepregnancy body mass index and a composite outcome of stillbirth, neonatal death, and severe neonatal morbidity. Modification of this association by maternal age, nulliparity, chronic hypertension, and prepregnancy diabetes mellitus was assessed on both multiplicative and additive scales. RESULTS: The study population included 7,576,417 women with singleton pregnancy; 254,225 (3.5%) were underweight, 3,220,432 (43.9%) had normal body mass index, 1,918,480 (26.1%) were overweight, and 1,062,177 (14.4%), 516,693 (7.0%), and 365,357 (5.0%) had class I, II, and III obesity, respectively. Rates of the composite outcome increased with increasing body mass index above normal values, compared with women with normal body mass index. Nulliparity (289,776; 38.6%), chronic hypertension (135,328; 1.8%), and prepregnancy diabetes mellitus (67,744; 0.89%) modified the association between body mass index and the composite perinatal outcome on both the additive and multiplicative scales. Nulliparous (vs parous) women had a higher rate of increase in adverse outcomes with increasing body mass index. For example, in nulliparous women, class III obesity was associated with 1.8-fold higher odds compared with normal body mass index (adjusted odds ratio, 1.77; 95% confidence interval, 1.73-1.83), whereas in parous women, the adjusted odds ratio was 1.35 (95% confidence interval, 1.32-1.39). Women with chronic hypertension or prepregnancy diabetes mellitus had higher outcome rates overall; however, the dose-response relationship with increasing body mass index was absent. Although the composite outcome rates increased with maternal age, the risk curves were relatively similar across obesity classes in all maternal age groups. Overall, underweight women had 7% higher odds of the composite outcome, and this increased to 21% in parous women. CONCLUSION: Women with elevated prepregnancy body mass index are at increased risk of adverse perinatal outcomes, and the magnitude of these risks differs by concomitant risk factors, including prepregnancy diabetes mellitus, chronic hypertension, and nulliparity. In particular, in woman with chronic hypertension or prepregnancy diabetes mellitus, there is no impact of increasing body mass index on adverse perinatal outcomes. However, overall rates remain high, and prepregnancy prevention of hypertension and diabetes mellitus should be emphasized among all women irrespective of body mass index.

SWAVE 2.0 Imaging of Placental Elasticity and Viscosity: Potential Biomarkers for Placenta-Mediated Disease Detection.

Pregnancy complications such as pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with structural and functional changes in the placenta. Different elastography techniques with an ability to assess the mechanical properties of tissue can identify and monitor the pathological state of the placenta. Currently available elastography techniques have been used with promising results to detect placenta abnormalities; however, limitations include inadequate measurement depth and safety concerns from high negative pressure pulses. Previously, we described a shear wave absolute vibro-elastography (SWAVE) method by applying external low-frequency mechanical vibrations to generate shear waves and studied 61 post-delivery clinically normal placentas to explore the feasibility of SWAVE for placental assessment and establish a measurement baseline. This next phase of the study, namely, SWAVE 2.0, improves the previous system and elasticity reconstruction by incorporating a multi-frequency acquisition system and using a 3-D local frequency estimation (LFE) method. Compared with its 2-D counterpart, the proposed system using 3-D LFE was found to reduce the bias and variance in elasticity measurements in tissue-mimicking phantoms. In the aim of investigating the potential of improved SWAVE 2.0 measurements to identify placental abnormalities, we studied 46 post-delivery placentas, including 26 diseased (16 IUGR and 10 PE) and 20 normal control placentas. By use of a 3.33-MHz motorized curved-array transducer, multi-frequency (80,100 and 120 Hz) elasticity measures were obtained with 3-D LFE, and both IUGR (15.30 ± 2.96 kPa, p = 3.35e-5) and PE (12.33 ± 4.88 kPa, p = 0.017) placentas were found to be significantly stiffer compared with the control placentas (8.32 ± 3.67 kPa). A linear discriminant analysis (LDA) classifier was able to classify between healthy and diseased placentas with a sensitivity, specificity and accuracy of 87%, 78% and 83% and an area under the receiver operating curve of 0.90 (95% confidence interval: 0.8-0.99). Further, the pregnancy outcome in terms of neonatal intensive care unit admission was predicted with a sensitivity, specificity and accuracy of 70%, 71%, 71%, respectively, and area under the receiver operating curve of 0.78 (confidence interval: 0.62-0.93). A viscoelastic characterization of placentas using a fractional rheological model revealed that the viscosity measures in terms of viscosity parameter n were significantly higher in IUGR (2.3 ± 0.21) and PE (2.11 ± 0.52) placentas than in normal placentas (1.45 ± 0.65). This work illustrates the potential relevance of elasticity and viscosity imaging using SWAVE 2.0 as a non-invasive technology for detection of placental abnormalities and the prediction of pregnancy outcomes.

Project SWAVE 2.0: An overview of the study design for multimodal placental image acquisition and alignment.

Development of non-invasive and in utero placenta imaging techniques can potentially identify biomarkers of placental health. Correlative imaging using multiple multiscale modalities is particularly important to advance the understanding of placenta structure, function and their relationship. The objective of the project SWAVE 2.0 was to understand human placental structure and function and thereby identify quantifiable measures of placental health using a multimodal correlative approach. In this paper, we present a multimodal image acquisition protocol designed to acquire and align data from ex vivo placenta specimens derived from both healthy and complicated pregnancies. Qualitative and quantitative validation of the alignment method were performed. The qualitative analysis showed good correlation between findings in the MRI, ultrasound and histopathology images. The proposed protocol would enable future studies on comprehensive analysis of placental anatomy, function and their relationship. ● An overview of a novel multimodal placental image acquisition protocol is presented. ● A co-registration method using surface markers and external fiducials is described. ● A preliminary correlative imaging analysis for a placenta specimen is presented.

The association between pre-pregnancy body mass index and perinatal death and the role of gestational age at delivery.

INTRODUCTION: The pathophysiology behind the association between obesity and perinatal death is not fully understood but may be in part due to higher rates of pregnancy complications at earlier gestation amongst obese women. We aimed to quantify the proportion of perinatal deaths amongst obese and overweight women mediated by gestational age at stillbirth or live birth. METHODS: The study included all singleton births at ≥20 weeks' gestation in British Columbia, 2004-2017, and excluded pregnancy terminations. The proportion of the association between BMI and perinatal death mediated by gestational age at delivery (in weeks) was estimated using natural effect models, with adjustment for potential confounders. Sensitivity analyses for unmeasured confounding and women missing BMI were conducted. RESULTS: Of 392,820 included women, 20.6% were overweight and 12.8% obese. Women with higher BMI had a lower gestational age at delivery. Perinatal mortality was 0.5% (1834 pregnancies); and was elevated in overweight (adjusted odds ratio [AOR] = 1.22, 95% confidence interval [CI] 1.08-1.37) and obese women (AOR = 1.55, 95% CI 1.36-1.77). Mediation analysis showed that 63.1% of the association between obesity and perinatal death was mediated by gestational age at delivery (natural indirect effect AOR = 1.32, 95% CI 1.23-1.42, natural direct effect AOR = 1.18, 95% CI 1.05-1.32). Similar, but smaller effects were seen when comparing overweight women vs. women with a normal BMI. Estimated effects were not affected by adjustment for additional risk factors for perinatal death or sensitivity analyses for missing data. CONCLUSION: Obese pregnancies have a higher risk of perinatal death in part mediated by a lower gestational age at delivery.

Which chart and which cut-point: deciding on the INTERGROWTH, World Health Organization, or Hadlock fetal growth chart.

OBJECTIVE: To determine how various centile cut points on the INTERGROWTH-21st (INTERGROWTH), World Health Organization (WHO), and Hadlock fetal growth charts predict perinatal morbidity/mortality, and how this relates to choosing a fetal growth chart for clinical use. METHODS: We linked antenatal ultrasound measurements for fetuses > 28 weeks' gestation from the British Columbia Women's hospital ultrasound unit with the provincial perinatal database. We estimated the risk of perinatal morbidity/mortality (decreased cord pH, neonatal seizures, hypoglycemia, and perinatal death) associated with select centiles on each fetal growth chart (the 3rd, 10th, the centile identifying 10% of the population, and the optimal cut-point by Youden's Index), and determined how well each centile predicted perinatal morbidity/mortality. RESULTS: Among 10,366 pregnancies, the 10th centile cut-point had a sensitivity of 11% (95% CI 8, 14), 13% (95% CI 10, 16), and 12% (95% CI 10, 16), to detect fetuses with perinatal morbidity/mortality on the INTERGROWTH, WHO, and Hadlock charts, respectively. All charts performed similarly in predicting perinatal morbidity/mortality (area under the curve [AUC] =0.54 for all three charts). The statistically optimal cut-points were the 39th, 31st, and 32nd centiles on the INTERGROWTH, WHO, and Hadlock charts respectively. CONCLUSION: The INTERGROWTH, WHO, and Hadlock fetal growth charts performed similarly in predicting perinatal morbidity/mortality, even when evaluating multiple cut points. Deciding which cut-point and chart to use may be guided by other considerations such as impact on workflow and how the chart was derived.

Incidence and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm and term gestation: a population-based study.

BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study.

BACKGROUND: North American health authorities recommend 0.4 mg/day folic acid before conception and throughout pregnancy to reduce the risk of neural tube defects. Folic acid is a synthetic form of folate that must be reduced by dihydrofolate reductase and then further metabolized. Recent evidence suggests that the maximal capacity for this process is limited and unmetabolized folic acid has been detected in the circulation. The biological effects of unmetabolized folic acid are unknown. A natural form of folate, (6S)-5-methyltetrahydrofolic acid (Metafolin®), may be a superior alternative because it does not need to be reduced in the small intestine. Metafolin® is currently used in some prenatal multivitamins; however, it has yet to be evaluated during pregnancy. METHODS/DESIGN: This double-blind, randomized trial will recruit 60 pregnant women aged 19-42 years. The women will receive either 0.6 mg/day folic acid or an equimolar dose (0.625 mg/day) of (6S)-5-methyltetrahydrofolic acid for 16 weeks. The trial will be initiated at 8-21 weeks' gestation (after neural tube closure) to reduce the risk of harm should (6S)-5-methyltetrahydrofolic acid prove less effective. All women will also receive a prenatal multivitamin (not containing folate) to ensure adequacy of other nutrients. Baseline and endline blood samples will be collected to assess primary outcome measures, including serum folate, red blood cell folate and unmetabolized folic acid. The extent to which the change in primary outcomes from baseline to endline differs between treatment groups, controlling for baseline level, will be estimated using linear regression. Participants will have the option to continue supplementing until 1 week postpartum to provide a breastmilk and blood sample. Exploratory analyses will be completed to evaluate breastmilk and postpartum blood folate concentrations. DISCUSSION: This proof-of-concept trial is needed to obtain estimates of the effect of (6S)-5-methyltetrahydrofolic acid compared to folic acid on circulating biomarkers of folate status during pregnancy. These estimates will inform the design of a definitive trial which will be powered to assess whether (6S)-5-methyltetrahydrofolic acid is as effective as folic acid in raising blood folate concentrations during pregnancy. Ultimately, these findings will inform folate supplementation policies for pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04022135. Registered on 14 July 2019.

Attenuation Coefficient Estimation of Normal Placentas.

Attenuation coefficient estimation has the potential to be a useful tool for placental tissue characterization. A current challenge is the presence of inhomogeneities in biological tissue that result in a large variance in the attenuation coefficient estimate (ACE), restricting its clinical utility. In this work, we propose a new Attenuation Estimation Region Of Interest (AEROI) selection method for computing the ACE based on the (i) envelope signal-to-noise ratio deviation and (ii) coefficient of variation of the transmit pulse bandwidth. The method was first validated on a tissue-mimicking phantom, for which an 18%-21% reduction in the standard deviation of ACE and a 14%-24% reduction in the ACE error, expressed as a percentage of reported ACE, were obtained. A study on 59 post-delivery clinically normal placentas was then performed. The proposed AEROI selection method reduced the intra-subject standard deviation of ACE from 0.72 to 0.39 dB/cm/MHz. The measured ACE of 59 placentas was 0.77 ± 0.37 dB/cm/MHz, which establishes a baseline for future studies on placental tissue characterization.

Automated Placenta Segmentation with a Convolutional Neural Network Weighted by Acoustic Shadow Detection.

Placental assessment through routine obstetrical ultrasound is often limited to documenting its location and ruling out placenta previa. However, many obstetrical complications originate from abnormal focal or global placental development. Technical difficulties in assessing the placenta as well as a lack of established objective criteria to classify echotexture are barriers to diagnosis of pathology by ultrasound imaging. As a first step towards the development of a computer aided placental assessment tool, we developed a fully automated method for placental segmentation using a convolutional neural network. The network contains a novel layer weighted by automated acoustic shadow detection to recognize artifacts specific to ultrasound. In order to develop a detection algorithm usable in different imaging scenarios, we acquired a dataset containing 1364 fetal ultrasound images from 247 patients acquired over 47 months was taken with different machines, operators, and at a range of gestational ages. Mean Dice coefficients for automated segmentation on the full dataset with and without the acoustic shadow detection layer were 0.92±0.04 and 0.91±0.03 when comparing to manual segmentation. Mean Dice coefficients on the subset of images containing acoustic shadows with and without acoustic shadow detection were 0.87±0.04 and 0.75±0.05. The method requires no user input to tune the detection. The automated placenta segmentation method can serve as a preprocessing step for further image analysis in artificial intelligence methods requiring large scale data processing of placental images.

Multiparametric QUS Analysis for Placental Tissue Characterization.

Multiparametric Quantitative Ultrasound (QUS) holds promise for characterizing placental tissue and detecting placental disorders. In this study, we simultaneously extract two qualitatively different QUS parameters, namely attenuation coefficient estimate (ACE) and shear wave speed from ultrasound radio frequency data acquired using a shear wave vibro elastography (SWAVE) method. The study comprised data from 59 post-delivery clinically normal placentas. The shear wave speed was found to be equal to 1.74 ± 0.13 m/s whereas the attenuation coefficient estimate was 0.57 ± 0.48 dB/cm-MHz. This provides a baseline for future studies of placental disorders.

SWAVE Imaging of Placental Elasticity and Viscosity: Proof of Concept.

The placenta is the interface between the fetus and the mother and is vital for fetal development. Ultrasound elastography provides a non-invasive way to examine in vivo the stiffness of the placenta; increased stiffness has previously been linked to fetal growth restriction. This study used a previously developed dynamic elastography method, called shear wave absolute vibro-elastography, to study 61 post-delivery clinically normal placentas. The shear wave speeds in the placenta were recorded under five different low-frequency mechanical excitations. The elasticity and viscosity were estimated through rheological modeling. The shear wave speeds at excitation frequencies of 60, 80, 90, 100 and 120 Hz were measured to be 1.23 ± 0.44, 1.67 ± 0.76, 1.74 ± 0.72, 1.80 ± 0.78 and 2.25 ± 0.80 m/s. The shear wave speed values we obtained are consistent with previous studies. In addition, our multi-frequency acquisition approach enables us to provide viscosity estimates that have not been previously reported.

Maternal morbidity associated with early-onset and late-onset preeclampsia.

OBJECTIVE: To examine temporal trends in early-onset compared with late-onset preeclampsia and associated severe maternal morbidity. METHODS: The study included all singleton deliveries in Washington State between 2000 and 2008 (N=670,120). Preeclampsia onset was determined using hospital records linked to birth certificates. Severe maternal morbidity was defined as any potentially life-threatening condition. Logistic regression was used to obtain adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: The preeclampsia rate was 3.0 per 100 singleton births, and increased slightly from 2.9 to 3.1 between 2000 and 2008. Rates of early-onset and late-onset disease were 0.3% and 2.7%, respectively. The temporal increase was significant only for early-onset disease (4.5%/year; 95% CI 2.3-5.8%) after adjustment for changes in maternal characteristics. Maternal death rates were higher among women with early-onset (42.1/100,000 deliveries) and late-onset preeclampsia (11.2/100,000) compared with women without preeclampsia (4.2/100,000). The rate of severe maternal morbidity (excluding obstetric trauma) was 12.2 per 100 deliveries in the early-onset group (aOR 3.7, 95% CI 3.2-4.3), 5.5 per 100 deliveries in the late-onset group (aOR 1.7, 95% CI 1.6-1.9), and approximately 3 per 100 in women without preeclampsia. Early-onset preeclampsia conferred a substantially higher risk of cardiovascular, respiratory, central nervous system, renal, hepatic, and other morbidity. However, rates of obstetric trauma were significantly lower among women with preeclampsia. CONCLUSION: Women with early-onset and late-onset preeclampsia have significantly higher rates of specific maternal morbidity compared with women without early-onset and late-onset disease. LEVEL OF EVIDENCE: : II.

Can we select fetuses with intra-abdominal calcification for delivery in neonatal surgical centres?

BACKGROUND: Prenatal ultrasound (US) diagnosis of fetal intra-abdominal calcification (iAC) is frequently caused by an in utero perforation causing meconium peritonitis. Our ability to predict which fetuses will require postnatal surgery is limited. The aim of our study is to correlate iAC and associated US findings with postnatal outcome. METHODS: A single centre retrospective review of all cases of fetal iAC diagnosed between 2004 and 2010 was performed. Maternal demographics, fetal US findings, and outcomes (need for surgery and mortality) were collected. Descriptive and comparative statistical analyses were performed. RESULTS: Twenty-three cases of iAC were identified. There were no cases of fetal demise or postnatal deaths. Three liveborns (13%) required abdominal surgery at a median of 2 days (0-3) for intestinal atresia. US findings of iAC and dilated bowel with (p=0.008) or without (p=0.005) polyhydramnios predicted a need for postnatal surgery as did the combination of iAC, polyhydramnios, and ascites (p=0.008). Conversely, iAC alone or associated with oligohydramnios, polyhydramnios, ascites, or growth restriction did not predict need for postnatal surgery. CONCLUSION: The majority of fetuses with iAC on prenatal US do not require surgery. Associated US findings (bowel dilation) can be used to select fetuses for delivery in neonatal surgical centres.

Adaptation of the HINT (hearing in noise test) for adult Canadian Francophone populations.

The HINT provides an efficient and reliable method of assessing speech intelligibility in quiet and in noise by using an adaptive strategy to measure speech reception thresholds for sentences, thus avoiding ceiling and floor effects that plague traditional measures performed at fixed presentation levels A strong need for such a test within the Canadian Francophone population, led us to develop a French version of the HINT. Here we describe the development of this test. The Canadian French version is composed of 240-recorded sentences, equated for intelligibility, and cast into 12 phonemically balanced 20-sentence lists. Average headphone SRTs, measured with 36 adult Canadian Francophone native speakers with normal hearing, were 16.4 dBA in quiet, -3.0 dBA SNR in a 65 dBA noise front condition and -11.4 dBA SNR in a 65 dBA noise side condition. Reliability was established by means of within-subjects standard deviation of repeated SRT measurements over different lists and yielded values of 2.2 and 1.1 dB for the quiet and noise conditions, respectively.