Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Unveiling sex bias and adverse neonatal outcomes in ultrasound estimation of gestational age: A population-based cohort study.

BACKGROUND: Gestational age estimation by second-trimester ultrasound biometry introduces systematic errors due to sex differences in early foetal growth, consequently increasing the risk of adverse neonatal outcomes. Ultrasound estimation earlier in pregnancy may reduce this bias. OBJECTIVES: To investigate the distribution of sex ratio by gestational age and estimate the risk of adverse outcomes in male foetuses born early-term and female foetuses born post-term by first- and second-trimester ultrasound estimations. METHODS: This population-based study compared two cohorts of births with gestational age based on first- and second-trimester ultrasound in the Medical Birth Registry of Norway between 2016 and 2020. We used a log-binomial regression model to estimate adjusted relative risk (RR) with 95% confidence interval (CI) for Apgar score <7 at 5 min, umbilical artery pH <7.05, neonatal intensive care unit (NICU) admission and respiratory morbidity in relation to foetal sex. RESULTS: The sex ratio at birth in gestational weeks 36-43 showed less male predominance in pregnancies estimated in first compared to second trimester. Any adverse outcome was registered in 627 of 4470 male infants born in gestational weeks 37-38 and 618 of 6406 females born ≥41 weeks. Male infants born in weeks 37-38 had lower risk of NICU admission (RR 0.76, 95% CI 0.58, 0.99), Apgar score <7 at 5 min (RR 0.63, 95% CI 0.28, 1.41) and respiratory morbidity (RR 0.68, 95% CI 0.37, 1.25) in first- compared to second-trimester estimations. Female infants estimated in first trimester born ≥41 weeks had lower risk of umbilical artery pH <7.05, NICU admissions and respiratory morbidity; however, CIs were wide. CONCLUSIONS: Early ultrasound estimation of gestational age may reduce the excess risk of adverse neonatal outcomes and highlight the role of foetal sex and the timing of ultrasound assessment in the clinical evaluation of preterm and post-term pregnancies.

The impact of late pregnancy dating on the detection of fetal growth restriction at term.

INTRODUCTION: The inaccuracy of late pregnancy dating is often discussed, and the impact on diagnosis of fetal growth restriction is a concern. However, the magnitude and direction of this effect has not previously been demonstrated. In this study, we aimed to investigate the effect of late pregnancy dating by head circumference on the detection of late onset growth restriction, compared to first trimester crown-rump length dating. MATERIAL AND METHODS: This was a cohort study of 14 013 pregnancies receiving obstetric care at a tertiary center over a three-year period. Universal scans were performed at 12 weeks, including crown-rump length; at 20 weeks including fetal biometry; and at 36 weeks, where biometry, umbilical artery doppler and cerebroplacental ratio were used to determine the incidence of fetal growth restriction according to the Delphi consensus. For the entire cohort, the gestational age was first calculated using T1 dating; and was then recalculated using head circumference at 20 weeks (T2 dating); and at 36 weeks (T3 dating). The incidence of fetal growth restriction following T2 and T3 dating was compared to T1 dating using four-by-four sensitivity tables. RESULTS: When the cohort was redated from T1 to T2, the median gestation at delivery changed from 40 + 0 to 40 + 2 weeks (p < 0.001). When the cohort was redated from T1 to T3, the median gestation at delivery changed from 40 + 0 to 40 + 3 weeks (p < 0.001). T2 dating resulted in fetal growth restriction sensitivity of 80.2% with positive predictive value of 78.8% compared to T1 dating. T3 dating resulted in sensitivity of 8.6% and positive predictive value of 27.7%, respectively. The sensitivity of abnormal CPR remained high despite T2 and T3 redating; 98.0% and 89.4%, respectively. CONCLUSIONS: Although dating at 11-14 weeks is recommended, late pregnancy dating is sometimes inevitable, and this can prolong the estimated due date by an average of two to three days. One in five pregnancies which would be classified as growth restricted if the pregnancy was dated in the first trimester, will be reclassified as nongrowth restricted following dating at 20 weeks, whereas nine out of 10 pregnancies will be reclassified as non-growth restricted with 36-week dating.

Association between first-trimester uterine artery Doppler and crown-rump length with growth discordance: does it make a difference.

OBJECTIVES: The purpose of this study was to investigate the association between first-trimester uterine artery pulsatility index (UtA-PI) and crown-rump length discordance (CRLD) with growth discordance (GD) in twins and analyze the influence of chorionicity in these parameters. METHODS: This retrospective analysis integrated data from the twin pregnancy database of Centro Hospitalar São João (2019-2023), including 184 fetuses, with 19 monochorionic and 73 dichorionic gestations. To determine the association between UtA-PI and CRLD with GD, correlation analyses were computed and linear regression models were carried out. Separate analyses were conducted for each type of placentation. Logistic regression analysis was carried out to determine the association of mean UtA-PI and CRLD with severe GD, defined as discordance ≥25 %. RESULTS: GD≥25 % was detected in 9.80 % of pregnancies. A statistically significant difference between monochorionic and dichorionic gestations was found in crown-rump length (p=0.009), CRLD (p<0.001) and birth weight (p=0.025), but not in mean UtA-PI (p=0.853) or GD (p=0.556). Mean UtA-PI was significantly higher in discordant than in concordant pairs (p<0.001), but that association was not seen in CRLD (p=0.931). Mean UtA-PI and GD were correlated by the regression line "GD=3.844 × UtA-PI + 6.638", with R2 0.027. CRLD and GD were correlated by the regression line "GD=0.280 × CRLD + 10.79", with R2 0.010. Mean UtA-PI, but not CRLD, was significantly associated with severe GD (odds ratio, 22.753; p=0.002). CONCLUSIONS: Mean UtA-PI, but not CRLD, is associated with GD. The prevalence of severe GD increases significantly with increasing mean UtA-PI.

The prognostic role of CRL discordance in first trimester ultrasound.

OBJECTIVES: In the first trimester, intertwin crown-rump length (CRL) discordance has emerged as a notable factor linked to adverse perinatal health effects. It is frequently employed as a basis for counseling parents regarding potential adverse pregnancy outcomes. Despite its established association with adverse outcomes, the significance of CRL discordance in substantially predicting pregnancy problems and its efficacy in pregnancy screening remain subjects of ongoing discussion. The aim of this manuscript is to present current knowledge on CRL discordance. METHODS: PubMed was searched for related articles with terms "Crown-Rump length", "Prenatal Screening", "Twin pregnancy", "Discordance". RESULTS: Twenty-two studies were included in our study with six reporting data on monochorionic and 16 assessing the correlation between CRL discordance and adverse pregnancy outcomes. Fetal loss at the 20th and 24th week of the pregnancy, SGA neonates, pre-term delivery (32 weeks), perinatal death (24 weeks) are all reported adverse outcomes associated with CRL discordance. The reported cut-off for increased risk of adverse perinatal outcomes is a discordance of at least 10% or more. CONCLUSIONS: Increased CRL (>10 %) discordance is linked to a higher risk of sFGR in both monochorionic and dichorionic pregnancies, fetal loss, and preterm delivery.

First trimester identification of fetal sex by ultrasound.

PURPOSE: The hypothesis was fetal sex determination by ultrasound at 11-14 weeks' gestation has sufficient accuracy to be clinically relevant. METHODS: Fetal sex assessment by transabdominal ultrasound was performed in 567 fetuses at 11-14 weeks' gestation (CRL: 45-84 mm). A mid-sagittal view of the genital region was obtained. The angle of the genital tubercle to a horizontal line through the lumbosacral skin surface was measured. The fetus was assigned male sex if the angle was > 30°, and female sex if the genital tubercle was parallel or convergent (< 10°). At an intermediate angle of 10-30°, the sex was not assigned. The results were divided into three categories based on gestational age: 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation. To establish its accuracy, the first trimester fetal sex determination was compared to fetal sex determined on a mid-second trimester ultrasound. RESULTS: Sex assignment was successful in 534/683 (78%) of the cases. The overall accuracy of fetal sex assignment across all gestational ages studied was 94.4%. It was 88.3%, 94.7%, and 98.6% at 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation, respectively. CONCLUSION: Prenatal sex assignment at the time of first trimester ultrasound screening has a high accuracy rate. The accuracy improved with increasing gestational age, which suggests that if clinically important decisions, such as chorionic villus sampling, are to be made based on fetal sex, they should be delayed until the latter part of the first trimester.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients.

BACKGROUND: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. OBJECTIVE: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. STUDY DESIGN: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. RESULTS: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. CONCLUSION: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

High sensitivity and specificity in fetal gender identification in the first trimester, using ultrasound and Noninvasive Prenatal Screening (NIPS) in twin pregnancies, a prospective study.

INTRODUCTION: Determination of the fetal gender in the first trimester is important in twin pregnancy cases of familial X-linked genetic syndromes and helps determine chorionicity. We assessed and compared the accuracy of first-trimester ultrasound scans, and cell-free fetal DNA (CfDNA) in determining fetal gender in the first trimester of twin pregnancies. METHODS: Women with twin pregnancies were recruited prospectively during the first trimester. Fetal gender was determined using both ultrasound scans and CfDNA screening. Both results were compared to the newborn gender after delivery. RESULTS: A total of 113 women with twin pregnancies were enrolled. There was 100% sensitivity and specificity in Y chromosome detection using CfDNA. Gender assignment using ultrasound in any first-trimester scans was 79.7%. Accuracy level increased from 54.2% in CRL 45-54 mm to 87.7% in CRL 55-67 mm and 91.5% in CRL 67-87 mm. Male fetuses had significantly higher chances of a gender assignment error compared to female fetuses, odds ratio = 23.574 (CI 7.346 - 75.656). CONCLUSIONS: CfDNA is highly sensitive and specific in determining the presence of the Y chromosome in twin pregnancies in the first trimester. Between CRL 55-87 mm, ultrasound scanning offers a highly accurate determination of fetal gender in twin pregnancies.

Can Early First Trimester Ultrasounds Correctly Determine Gestational Age Compared to Ultrasounds Performed Between 7 to 14 Weeks Gestational Age?

OBJECTIVES: The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends the use of an ultrasound performed between 7 and 14 weeks gestation to accurately predict gestational age (GA). This study aimed to assess the accuracy of earlier ultrasounds (5 to 66 weeks gestation) by comparing the estimated delivery dates (EDD) in participants that had undergone both an earlier ultrasound and ultrasound completed during the standard of care timeframe. METHODS: EDD based on crown-rump length were retrospectively reviewed for patients that had undergone an ultrasound between 5-66 weeks GA versus the recommended 7-14 weeks GA at the Montfort Hospital during 2018 and 2019. The charts of 981 patients that had an ultrasound prior to 7 weeks GA and at 7-14 weeks GA were reviewed; 54 were included. RESULTS: There was no significant difference (P = 0.307) between the EDD of the early (5-66 weeks GA) and the second ultrasound (7-14 weeks GA). The first ultrasounds were then separated into very early (5-56 weeks GA) and early (6-66 weeks GA) and compared. No significant differences (P = 0.579) were found. Similarly, no difference was found between the EDD of the early (6-66 weeks GA) and standard of care timing (P = 0.324). CONCLUSION: These results show no significant difference in accurately determining the EDD between ultrasounds completed at the early and standard of care time points. This could result in cost-saving benefits by foregoing a repeat ultrasound; however, further research is required prior to applying these findings in clinical settings.

Validation of Ultrasound Dating Protocols Using Data From Twins Conceived Through In Vitro Fertilization in Nova Scotia: A Retrospective Cohort Study.

OBJECTIVES: Clinical practice guidelines recommend determining gestational age (GA) for twin pregnancies using the fetal crown rump length (CRL) of the larger fetus. This study investigated whether the CRL of the larger or smaller fetus at 11-14 weeks best predicted in vitro fertilization (IVF) assigned GA. METHODS: A retrospective cohort study of twin pregnancies conceived by IVF ± intracytoplasmic sperm injection, 2004-2022, generated GA estimations for each co-twin CRL at the 11-14 week ultrasound, to determine which fetus (smaller or larger) more consistently predicted IVF-assigned GA. Monoamniotic twins and twins with known structural or vascular abnormalities were excluded. Paired t tests evaluated the ability of CRL to predict GA, and logistic regression evaluated the predictive ability of each of the co-twin groups with increasing size differences. Statistical significance was set at P < 0.05. RESULTS: Viewpoint 6 identified 359 eligible twin pairs. CRL was closest with the smaller fetus (0.38 days); CRL for both the smaller (95% CI 0.16-0.61) and the larger (2.25 days, 95% CI 2.04-2.46) fetus showed deviation from IVF-assigned GA. As the absolute difference between the small and large fetus increased, the ultrasound-estimated GA of the smaller fetus was still consistently closer to IVF-assigned GA. CONCLUSIONS: In this selected population of twins with known GA, the CRL of the smaller fetus more accurately predicted IVF-assigned GA even with increasing differences in fetal size. These findings provide important information for appropriately dating pregnancies to facilitate adherence to national guidelines to monitor for pregnancy complications, and plan frequency and type of fetal surveillance, as well as timing of delivery.