Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.

Effects of Cooking with Liquefied Petroleum Gas or Biomass on Stunting in Infants.

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Exposure-response relationships for personal exposure to fine particulate matter (PM2·5), carbon monoxide, and black carbon and birthweight: an observational analysis of the multicountry Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure-response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial. METHODS: The HAPIN trial recruited pregnant women (9-<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure-response subanalysis, we measured 24-h personal exposures to PM2·5, carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24-28 weeks and 32-36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata. FINDINGS: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM2·5 (74·5 µg/m3) was associated with a reduction in birthweight and gestational age Z scores (birthweight: -14·8 g [95% CI -28·7 to -0·8]; gestational age Z scores: -0·03 [-0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 µg/m3; -21·9 g [-37·7 to -6·1]; -0·05 [-0·08 to -0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; -3·1 [-12·1 to 5·8]; -0·003 [-0·023 to 0·017]). INTERPRETATION: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries. FUNDING: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279).

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial.

BACKGROUND: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH). METHODS: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records. RESULTS: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode. CONCLUSIONS: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD.

Contributions of Artificial Intelligence Reported in Obstetrics and Gynecology Journals: Systematic Review.

BACKGROUND: The applications of artificial intelligence (AI) processes have grown significantly in all medical disciplines during the last decades. Two main types of AI have been applied in medicine: symbolic AI (eg, knowledge base and ontologies) and nonsymbolic AI (eg, machine learning and artificial neural networks). Consequently, AI has also been applied across most obstetrics and gynecology (OB/GYN) domains, including general obstetrics, gynecology surgery, fetal ultrasound, and assisted reproductive medicine, among others. OBJECTIVE: The aim of this study was to provide a systematic review to establish the actual contributions of AI reported in OB/GYN discipline journals. METHODS: The PubMed database was searched for citations indexed with "artificial intelligence" and at least one of the following medical subject heading (MeSH) terms between January 1, 2000, and April 30, 2020: "obstetrics"; "gynecology"; "reproductive techniques, assisted"; or "pregnancy." All publications in OB/GYN core disciplines journals were considered. The selection of journals was based on disciplines defined in Web of Science. The publications were excluded if no AI process was used in the study. Review, editorial, and commentary articles were also excluded. The study analysis comprised (1) classification of publications into OB/GYN domains, (2) description of AI methods, (3) description of AI algorithms, (4) description of data sets, (5) description of AI contributions, and (6) description of the validation of the AI process. RESULTS: The PubMed search retrieved 579 citations and 66 publications met the selection criteria. All OB/GYN subdomains were covered: obstetrics (41%, 27/66), gynecology (3%, 2/66), assisted reproductive medicine (33%, 22/66), early pregnancy (2%, 1/66), and fetal medicine (21%, 14/66). Both machine learning methods (39/66) and knowledge base methods (25/66) were represented. Machine learning used imaging, numerical, and clinical data sets. Knowledge base methods used mostly omics data sets. The actual contributions of AI were method/algorithm development (53%, 35/66), hypothesis generation (42%, 28/66), or software development (3%, 2/66). Validation was performed on one data set (86%, 57/66) and no external validation was reported. We observed a general rising trend in publications related to AI in OB/GYN over the last two decades. Most of these publications (82%, 54/66) remain out of the scope of the usual OB/GYN journals. CONCLUSIONS: In OB/GYN discipline journals, mostly preliminary work (eg, proof-of-concept algorithm or method) in AI applied to this discipline is reported and clinical validation remains an unmet prerequisite. Improvement driven by new AI research guidelines is expected. However, these guidelines are covering only a part of AI approaches (nonsymbolic) reported in this review; hence, updates need to be considered.

Crown-Rump Length Discordance, Increased Nuchal Translucency, and Detection of Fetal Structural Anomalies in Twin Pregnancies in the First Trimester: 5 Years of Experience in a Tertiary Hospital in China.

OBJECTIVE: To evaluate the efficacy of the first-trimester ultrasound scan in the detection of fetal structural anomalies in twin pregnancies. To examine the association between increased nuchal translucency (NT) thickness, crown-rump length (CRL) or NT discordance, and detection of structural anomalies in a large twin series in China. METHODS: We performed retrospective analysis of twin pregnancies who underwent 11-13+6 -week and second-trimester anomaly scan and booked at Beijing Obstetrics and Gynecology Hospital between January 2012 and December 2016. Measurement of fetal CRL/NT and assessment of fetal anatomic structures were based on standard (not detailed) protocols. Conjoined twins and twin-reversed arterial perfusion sequence (TRAPS) were excluded from structural anomalies. The diagnostic performance of first-trimester ultrasound in detection of fetal structural anomalies in twins was determined and compared with that of second trimester. The accuracy of independent variates associated with structural anomaly detection was calculated. RESULTS: A total of 1442 women with twin pregnancies were included. In 40 women and 45 fetuses, structural anomalies were found. Fetal structural anomalies verified at delivery were detected in 42.5% (17/40) of affected pregnancies in the first trimester and 92.5% (37/40) of affected pregnancies when added second trimester (P = .13). The survival rate of pregnancies detected in second trimester was higher than that of pregnancies detected in first trimester (11.8% vs 65.2%). The mean value of intertwin CRL/NT discordance in cases with fetal structural anomalies was larger in monochorionic twins than dichorionic twins, but monochorionicity was not associated with structural anomalies. CRL discordance ≥10% (OR 3.1, 95%CI 1.5-6.3) and NT ≥95th centile (OR 20.0, 95%CI 9.0-44.2) were associated with fetal structural anomalies. In both dichorionic (DC) and monochorionic (MC) twins, the percentages of CRL discordance ≥10% was larger in twins with structural anomalies than those without structural anomalies (37.5% vs 13.4% in DC twins and 50.0% vs 12.5% in MC twins), and this was also true for NT ≥95th centile (31.3% vs 1.7% in DC twins and 37.5% vs 2.2% in MC twins). In the setting of CRL discordance ≥10%, 40.0% (16/40) of twins with structural anomalies were found, in which the predominant fetal structural anomalies were cardiovascular defects, abdominal wall defects, and central nervous system defects. The AUC for detecting structural anomalies by CRL discordance ≥10% was 0.63. In the setting of NT ≥95th centile, 32.5% (13/40) of twins with structural anomalies were found, in which the predominant fetal structural anomalies were cardiovascular defects, cystic hygroma, and abdominal wall defects. The AUC for detecting structural anomalies by NT ≥95th centile was 0.65. CONCLUSIONS: The detection rate of twins with fetal structural anomalies was 42.5% per pregnancy in the first trimester. CRL discordance ≥10% and NT ≥95th centile may indicate higher risk of fetal structural anomalies in twins, but their efficacy was limited.

Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial.

BACKGROUND: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. OBJECTIVES: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. METHODS: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and ß-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. RESULTS: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 µg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 µg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: ß = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283). CONCLUSIONS: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

Diagnostic accuracy of fetal choroid plexus length to head biometry ratio at 11 to 13 weeks for open spina bifida.

BACKGROUND: Open spina bifida is a major congenital anomaly with an estimated incidence of <1 in 1000. The diagnosis of open spina bifida is usually made during the second trimester, but first-trimester detection rate of spina bifida is increasingly reported. Recently, the mean choroid plexus length to occipitofrontal diameter ratio was reported to be increased in fetuses with open spina bifida. The ratio reflects the so-called dry brain effect caused by cerebrospinal fluid leakage and expansion of the choroid plexus into the lateral ventricles. The mean choroid plexus length to occipitofrontal diameter ratio appears to be a promising tool for early detection of open spina bifida, but its diagnostic accuracy is yet to be determined in a large cohort. OBJECTIVE: This study aimed to assess the predictive accuracy of mean choroid plexus length to occipitofrontal diameter ratio recorded at 11 to 13 weeks' gestation for the detection of open spina bifida. STUDY DESIGN: This was a retrospective cohort of patients treated in a tertiary referral center. Fetuses in which open spina bifida was detected at 16 to 24 weeks' gestation and normal fetuses were included in the cohort. Biparietal diameter and occipitofrontal diameter were measured in an axial view. The length of choroid plexus was measured along its longest diameter in the same plane. Ultrasound images were examined offline, and the operator was blinded to the clinical diagnosis. The predictive accuracy was evaluated using the area under the curve and positive and negative predictive values. RESULTS: We included 3300 pregnant women, of whom 24 (0.73%) had the fetuses affected by open spina bifida. The area under the curve values were 0.921 for mean choroid plexus length to occipitofrontal diameter ratio and 0.933 for its multiple of the median. Mean choroid plexus length to biparietal diameter ratio indicated similar results, with area under the curve values of 0.928 and 0.931 for raw ratio and multiple of the median ratio models, respectively. The optimal cutoffs of the mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratios were 0.662 and 1.263, respectively. The optimal mean choroid plexus to occipitofrontal diameter ratio and multiple of the median ratio cutoffs provided a positive predictive value of 90.9% and a negative predictive value of 99.6%. The number of affected spinal segments was significantly higher in fetuses with a ratio above 0.662 (P=.022). CONCLUSION: The mean choroid plexus length to occipitofrontal diameter ratio at 11 to 13 weeks' gestation is a promising tool for the prenatal detection of open spina bifida.

How often do we incidentally find a fetal abnormality at the routine third-trimester growth scan? A population-based study.

BACKGROUND: Third-trimester scans are increasingly used to try to prevent adverse outcomes associated with abnormalities of fetal growth. Unexpected fetal malformations detected at third-trimester growth scans are rarely reported. OBJECTIVE: To determine the incidence and type of fetal malformations detected in women attending a routine third-trimester growth scan. STUDY DESIGN: This was a population-based study of all women with singleton pregnancy attending antenatal care over a 2-year period in Oxfordshire, UK. Women who had a viable singleton pregnancy at dating scan were included. Women had standard obstetrical care including the offer of a routine dating scan and combined screening for trisomies; a routine anomaly scan at 18 to 22 weeks; and a routine third-trimester growth scan at 36 weeks. The third-trimester scan comprises assessment of fetal presentation, amniotic fluid, biometry, umbilical and middle cerebral artery Dopplers, but no formal anatomic assessment is undertaken. Scans are performed by certified sonographers or clinical fellows (n=54), and any suspected abnormalities are evaluated by a team of fetal medicine specialists. We assessed the frequency and type of incidental congenital malformations identified for the first time at this third-trimester scan. All babies were followed-up after birth for a minimum of 6 months. RESULTS: There were 15,244 women attending routine antenatal care. Anomalies were detected in 474 (3.1%) fetuses as follows: 103 (21.7%) were detected before the anomaly scan, 174 (36.7%) at the anomaly scan, 11 (2.3%) after the anomaly scan and before the third-trimester scan, 43 (9.1%) at the third-trimester scan and 143 (30.2%) after birth. The 43 abnormalities were found in a total of 13,023 women who had a 36 weeks scan, suggesting that in 1 out of 303 (95% confidence interval, 233-432) women attending such a scan, a new malformation was detected. Anomalies detected at the routine third-trimester scan were of the urinary tract (n=30), central nervous system (5), simple ovarian cysts (4), chromosomal (1), splenic cyst (1), skeletal dysplasia (1), and cutaneous lymphangioma (1). Most urinary tract anomalies were renal pelvic dilatation, which showed spontaneous resolution in 57% of the cases. CONCLUSION: When undertaking a program of routine third-trimester growth scans in women who have had previous screening scans, an unexpected congenital malformation is detected in approximately 1 in 300 women.

Safety Indices of Ultrasound: Adherence to Recommendations and Awareness During Routine Obstetric Ultrasound Scanning.

PURPOSE: To analyze bioeffect safety indices and assess how often operators look at these indices during routine obstetric ultrasound. MATERIALS AND METHODS: Automated analysis of prospectively collected data including video recordings of full-length ultrasound scans coupled with operator eye tracking was performed. Using optical recognition, we extracted the Mechanical Index (MI), Thermal Index in soft tissue (TIs), and Thermal Index in bone (TIb) values and ultrasound mode. This allowed us to report the bioeffect safety indices during routine obstetric scans and assess adherence to professional organization recommendations. Eye-tracking analysis allowed us to assess how often operators look at the displayed bioeffect safety indices. RESULTS: A total of 637 ultrasound scans performed by 17 operators were included, of which 178, 216, and 243 scans were first, second, and third-trimester scans, respectively. During live scanning, the mean and range were 0.14 (0.1 to 3.0) for TIb, 0.2 (0.1 to 1.2) for TIs, and 0.9 (0.1 to 1.3) for MI. The mean and standard deviation of TIb were 0.15 ±â€Š0.03, 0.23 ±â€Š0.09, 0.32 ±â€Š0.24 in the first, second, and third trimester, respectively. For B-mode, the highest TIb was 0.8 in all trimesters. The highest TIb was recorded for pulsed-wave Doppler mode in all trimesters. The recommended exposure times were maintained in all scans. Analysis of eye tracking suggested that operators looked at bioeffect safety indices in only 27 (4.2 %) of the scans. CONCLUSION: In this study, recommended bioeffect indices were adhered to in all routine scans. However, eye tracking showed that operators rarely assessed safety indices during scanning.

Randomized Interventional Study on Prediction of Preeclampsia/Eclampsia in Women With Suspected Preeclampsia: INSPIRE.

The ratio of maternal serum sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) has been used retrospectively to rule out the occurrence of preeclampsia, a pregnancy hypertensive disorder, within 7 days in women presenting with clinical suspicion of preeclampsia. A prospective, interventional, parallel-group, randomized clinical trial evaluated the use of sFlt-1/PlGF ratio in women presenting with suspected preeclampsia. Women were assigned to reveal (sFlt-1/PlGF result known to clinicians) or nonreveal (result unknown) arms. A ratio cutoff of 38 was used to define low (≤38) and elevated risk (>38) of developing the condition in the subsequent week. The primary end point was hospitalization within 24 hours of the test. Secondary end points were development of preeclampsia and other adverse maternal-fetal outcomes. We recruited 370 women (186 reveal versus 184 nonreveal). Preeclampsia occurred in 85 women (23%). The number of admissions was not significantly different between groups (n=48 nonreveal versus n=60 reveal; P=0.192). The reveal trial arm admitted 100% of the cases that developed preeclampsia within 7 days, whereas the nonreveal admitted 83% (P=0.038). Use of the test yielded a sensitivity of 100% (95% CI, 85.8-100) and a negative predictive value of 100% (95% CI, 97.1-100) compared with a sensitivity of 83.3 (95% CI, 58.6-96.4) and negative predictive value of 97.8 (95% CI, 93.7-99.5) with clinical practice alone. Use of the sFlt-1/PlGF ratio significantly improved clinical precision without changing the admission rate. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN87470468.

A Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints: the COSGROVE study.

BACKGROUND: Fetal growth restriction refers to a fetus that does not reach its genetically predetermined growth potential. It is well-recognized that growth-restricted fetuses are at increased risk of both short- and long-term adverse outcomes. Systematic evaluation of the evidence from clinical trials of fetal growth restriction is often difficult because of variation in the outcomes that are measured and reported. The development of core outcome sets for fetal growth restriction studies would enable future trials to measure similar meaningful outcomes. OBJECTIVE: The purpose of this study was to develop core outcome sets for trials of prevention or treatment of fetal growth restriction. STUDY DESIGN: This was a Delphi consensus study. A comprehensive literature review was conducted to identify outcomes that were reported in studies of prevention or treatment of fetal growth restriction. All outcomes were presented for prioritization to key stakeholders (135 healthcare providers, 68 researchers/academics, and 35 members of the public) in 3 rounds of online Delphi surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core outcome set at a face-to-face meeting with 5 healthcare providers, 5 researchers/academics, and 6 maternity service users. RESULTS: In total, 22 outcomes were included in the final core outcome set. These outcomes were grouped under 4 domains: maternal (n=4), fetal (n=1), neonatal (n=12), and childhood (n=5). CONCLUSION: The Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints study identified a large number of potentially relevant outcomes and then reached consensus on those factors that, as a minimum, should be measured and reported in all future trials of prevention or treatment of fetal growth restriction. This will enable future trials to measure similar meaningful outcomes and to ensure that findings from different studies can be compared and combined.

Outcome of Fetuses with Supratentorial Extra-Axial Intracranial Cysts: A Systematic Review.

OBJECTIVE: To investigate the incidence of associated anomalies, aneuploidy, cyst progression, need for surgery and neurodevelopmental outcome in fetuses with extra-axial supratentorial intracranial cysts. DATA SOURCES: Medline, Embase and CINAHL databases were searched and the following outcomes analyzed: associated central nervous system (CNS) and extra-CNS anomalies detected at the scan, chromosomal anomalies, additional CNS anomalies detected only at prenatal MRI, additional CNS anomalies detected only after birth, cyst progression in utero, neurological outcome and need for surgery. Two authors reviewed all abstracts independently. Results were reported as proportions, and between-study heterogeneity was explored using the I² statistic; fixed or random effect models were used accordingly. RESULTS: Ten studies involving 47 fetuses were included in the meta-analysis. Arachnoid cysts (n = 24) had associated CNS anomalies and extra-CNS in 73% (95% CI 56-88) and 14% (95% CI 4-29), respectively. The most common associated anomalies were ventriculomegaly and callosal abnormalities. Chromosomal abnormalities were present in 6% (95% CI 0-30), but fetuses with isolated cysts were always euploid (0/7; 95% CI 0-29). Fetal MRI and postnatal examination identified 5 additional cases (21%, 95% CI 1-57). Cavum veli interpositi (CVI) cysts had associated CNS and extra-CNS anomalies in 31% (95% CI 13-52) and 6% (95% CI 0-29), respectively. No chromosomal or callosal anomalies were found in these cases. In isolated CVI cysts, no cases of associated anomalies were detected postnatally. Intrauterine regression occurred in 23% of CVI cysts and in none of the arachnoid cysts. In children with arachnoid cyst, the occurrence of hydrocephaly and mass effect on the adjacent structures were observed in 23.9% (95% CI 8.3-4.4) and 26.8% (95% CI 4.0-60.1), respectively. None of the cases included had abnormal motor outcome or intelligence. The rate of surgery was 34.7% (95% CI 16.0-56.4). None of the children with a prenatal diagnosis of isolated CVI cyst experienced any of the adverse outcomes explored in this review. CONCLUSIONS: Extra-axial supratentorial cysts diagnosed in utero are frequently associated with other neural and extra-neural anomalies. However, this may represent the consequence of a selection bias. Interhemispheric arachnoid cysts were typically associated with callosal anomalies. Abnormal karyotypes were seen only in fetuses with multiple anomalies. Arachnoid, but not CVI, cysts frequently increased in size throughout gestation.