Prospective Study Of Pregnancy Research Articles

Severity of pulmonary hypertension and pregnancy outcomes: newer insights from the M-PAC registry

Abstract Background Pregnancy outcomes in women with pulmonary hypertension remain suboptimal. Pregnant women with pulmonary hypertension (PH) are placed in the modified WHO category IV, regardless of the severity or etiology of PH. Earlier studies have indicated that pregnancy outcomes may differ based on the etiology, with more favourable outcomes observed with PH related to left to right shunts. However, it is possible that the pregnancy outcomes may vary based on the severity of PH also. Purpose To analyse pregnancy outcomes in women with PH and investigate differences based on disease severity. Methods M-PAC Registry, is a single center prospective study of pregnancies in women with heart diseases, conducted between July 2016 and December 2019 in a low-and middle-income country from South Asia, whose methodology and outcomes have been published(1). The current study analysed pregnancies with PH enrolled in the M-PAC registry. The tricuspid regurgitation velocity obtained during transthoracic echocardiography, was used to estimate right ventricular systolic pressure (RVSP). Based on the estimated RVSP, PH was classified into three groups; mild (36-45 mm of Hg), moderate (46-64 mm of Hg) and severe (≥ 65 mm of Hg). The differences in the maternal and foetal outcomes among the groups were analysed. Results Of the 1029 pregnancies complicated by heart disease enrolled in the M-PAC registry, 352(34.2%)had PH. Among these 352 pregnancies, 186(52.8%) had mild, 73 (20.7%) had moderate and 93 (26.5%) had severe PH. Adverse maternal cardiac events occurred in 77 pregnancies (21.8%), with heart failure in 53(15.1%) and mortality in 10(2.8%). The composite adverse foetal event rate was 38.6%, foetal loss at 9.7%, low birth weight at 28.9%, and preterm labour at 7.1%. The mean (±standard deviation) RVSP was higher in pregnancies with adverse maternal outcome (58.81±16.9 vs 51.16±15.9; P < 0.001) or adverse foetal outcome (58.10±17.3 vs 49.52±14.9; P < 0.001)compared to those without. When comparing the three groups, pregnancies with mild PH exhibited significantly lower rates of adverse maternal and fetal events compared to those with severe and moderate PH (Fig-1 and Table-1). Mild PH was associated with outcomes similar to those without PH in the M-PAC registry. Conclusion The severity of PH significantly correlated with the adverse pregnancy outcomes. Women with mild PH tend to experience pregnancy outcomes comparable to those without PH, suggesting that pregnancy should not be deemed contraindicated in this subgroup. Therefore, re-evaluation of the placement of PH within the modified World Health Organization (mWHO) classification is warranted, considering the severity of PH.Figure 1:Pregnancy Outcomes & PH SeverityTable-1 PH Severity & Pregnacny Outcomes

Risk of postpartum hemorrhage according to the planned mode of delivery among twin pregnancies with previous cesarean delivery

IntroductionBoth twin pregnancies and previous cesarean delivery are situations with increased risk of failed vaginal delivery. Cesarean delivery after a trial of labor is associated with an increased risk of postpartum hemorrhage Therefore, in twin pregnancies with a previous cesarean delivery, planned vaginal delivery could lead to an increased risk of postpartum hemorrhage due to an important rate of cesarean delivery after a trial of labor. Our objective was to evaluate the association between the planned mode of delivery and postpartum hemorrhage in women with twin pregnancies and a previous cesarean delivery. MethodsWe conducted a secondary analysis of the JUMODA French population-based prospective cohort study of twin pregnancies (n = 8823). We included women with one previous cesarean and without contraindication to vaginal birth. The primary outcome was postpartum hemorrhage. ResultsAmong the 735 women included, 187 women (25.4%) had planned vaginal delivery and 548 (74.6%) had planned cesarean delivery. Among women with planned vaginal delivery, 125 (66.8%) had a successful vaginal delivery. The incidence of PPH was 8.2% in the planned cesarean group and 9.1% in the planned vaginal delivery group(p = 0.709). After adjustment for confounders, the planned mode of delivery was not associated with the risk of postpartum hemorrhage (adjusted relative risk 0.94, 95% CI 0.56–1.60). There were only 2 uterine ruptures, both in the planned cesarean delivery group. ConclusionIn women with a twin pregnancy and a previous cesarean delivery, there is no overall association between the planned mode of delivery and the risk of postpartum hemorrhage.

Cesarian sections in women with multiple sclerosis: A Canadian prospective pregnancy study.

An increasing number of women with multiple sclerosis (wMS) are considering pregnancy. Prior studies suggest increased rate of elective cesarian sections (C-sections) in wMS. The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on pregnant wMS. This report shows comparisons between (i) CANPREG-MS wMS delivered by C-section and the general population and (ii) C-section and vaginal deliveries in this study cohort. CANPREG-MS has resulted in 170 deliveries with 63 by C-section. The proportion with C-sections in CANPREG-MS (37.1%) was significantly higher than that for the Canadian population (28%) (p = .0085). The majority (66.7%) of C-sections were not planned, and typically were performed for obstetrical indications. C-sections were performed at an earlier gestational age than vaginal deliveries, although birthweight did not differ by mode of delivery in wMS. MS relapses (3.2%) and pseudo-relapses (3.2%) were rare in the first month after C-section deliveries, regardless of disease modifying therapy decisions during gestation and postpartum. C-sections were more common in wMS than the general population, but few were because of maternal MS. CANPREG-MS provides informative data for pregnancies in wMS with well-managed and relatively mild disease. This information is helpful to obstetrical and MS healthcare providers.

Increased risk of severe neonatal opioid withdrawal syndrome in pregnancies with low placental ABCB1 DNA methylation.

Neonatal opioid withdrawal syndrome (NOWS) is unpredictable. We assessed relationships between placental DNA methylation with in-utero opioid exposure and NOWS severity. Secondary analysis of a prospective multicenter cohort study of pregnancies on methadone or buprenorphine, ≥34 weeks, singleton, 18 or greater. Placental biopsies were collected. Placental DNA methylation levels of ABCG1, ABCG2, CYP19A1, and HSD11B2 were quantified via pyrosequencing following bisulfite conversion. CYP19A1 mRNA levels and umbilical cord drug levels were determined by RT-qPCR and LC-MS respectively. Severe NOWS was diagnosed through Finnegan scoring. P value < 0.05 was significant. Thirty-eight dyads were included. Promoter region methylation for placental ABCB1 was lower in severe NOWS compared to non-severe NOWS (p = 0.04). Placental CYP19A1 methylation was inversely related to CYP19A1 mRNA levels and associated with umbilical cord norbuprenorphine levels (p < 0.01), but not umbilical cord methadone levels. Lower placental ABCB1 methylation was associated with severe NOWS. Higher placental CYP19A1 methylation correlated with higher umbilical cord norbuprenorphine levels.

P061 A comparative analysis of Systemic Lupus Erythematosus, Rheumatoid arthritis and Juvenile Idiopathic Arthritis pregnancy outcomes: Results from a three-year prospective, case-controlled, single centre study of 183 patients

Abstract Background/Aims Patients with inflammatory rheumatic diseases (IRD) have an increased risk of adverse pregnancy outcomes (APO), although the comparative risk of APO in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) pregnancies has not been directly compared. Therefore, this study examined pregnancy outcomes (PO) of subjects with RA, JIA, and SLE, who had all received pre-pregnancy counselling to ensure disease control, to identify whether there are any differences in APO between each individual IRD group. Pregnancy outcomes were compared with healthy pregnant subjects lacking IRD, to determine the comparative risk of APO in RA, JIA and SLE pregnancies. Methods A prospective case-controlled study was conducted at University College London Hospital from February 2018 to February 2021. A total of 183 patients were enrolled into the study, consisting of 120 pregnant patients including 60 patients with an IRD (n = 29 RA, n = 12 JIA and n = 19 SLE), 60 pregnant patients without any IRD and 63 non-pregnant patients with IRD (n = 30 RA, n = 12 JIA, n = 21 SLE). Pregnancy outcome data was obtained from all pregnant patients and the individual IRD groups’ outcomes were compared to each other and against outcomes from pregnancies without an IRD. Results Patients were predominantly Caucasian, ranging from 17-45 years of age. Of 111 reported PO, 99.09% (n = 110) resulted in a live birth (n = 27 (100.00%) RA, n = 11 (100.00%) JIA, n = 18 (94.74%) SLE versus n = 54 (100.00%) pregnancies without IRD). Overall, 5.56% (n = 1 SLE pregnancy) resulted in a spontaneous early trimester miscarriage, 6.36% (n = 7) were pre-term births (n = 3 (11.11%) RA, n = 1 (9.09%) JIA, n = 2 (11.11) SLE pregnancies versus n = 1 (1.85%) pregnancy without IRD). No stillbirths/foetal deaths were reported. Only two maternal complications were reported (n = 1 Group B strep infection, n = 1 gestational diabetes in RA pregnancies). In total six foetal complications were observed in four RA (n = 1 each for enlarged kidney, tongue tied, neonatal jaundice and Group B strep infection), n = 1 JIA (tongue tied) and n = 1 SLE (prolapsed cord) pregnancies. In relation to disease activity statuses in pregnancy, the majority of IRD pregnant patients were in remission (n = 42 (73.68%), n = 18 RA, n = 6 JIA and n = 18 SLE), 28 (49.12%) IRD patients had low disease activity (n = 8 RA, n = 2 JIA and n = 18 SLE) and nine (15.79%) had moderate/high disease activity (n = 6 RA, n = 2 JIA and n = 1 SLE). Only two (3.51%) RA patients reported disease flares during pregnancy, whereas no JIA/SLE patients experienced any flares. Conclusion This first prospective case-controlled study of RA, JIA, SLE and healthy pregnancies has identified favourable and comparable PO between IRD pregnancies with good disease control. This study highlights the importance and need for IRD pregnant women to undergo pre-pregnancy counselling and maintenance of disease control during pregnancy to enhance the chances of successful pregnancy outcomes. Disclosure H. Nguyen: None. D.A. Isenberg: Consultancies; AstraZeneca, Merck Serono, Eli Lilly, Servier, Genentech. D.J. Williams: Grants/research support; National Institute for Health Research University College London Hospitals Biomedical Research Centre. I. Giles: Grants/research support; UCB Pharma.

Blood pressure cutoffs at 11–13 weeks of gestation and risk of preeclampsia

A parallel has been drawn between first-trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mm Hg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify the risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. We evaluated the relationship between various blood pressure cutoffs at 11-13 weeks of gestation and the development of preeclampsia, overall and according to key maternal characteristics. This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals, 2006-2020. Blood pressure at 11-13 weeks of gestation was classified according to American College of Cardiology/American Heart Association categories (mm Hg) as (1) normal blood pressure (systolic <120 and diastolic <80), (2) elevated blood pressure (systolic ≥120 and diastolic <80), stage 1 hypertension (systolic ≥130 or diastolic 80-89), and stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen-positive rate, and positive and negative likelihood ratios, with 95% confidence intervals. A P value of <.05 was considered significant. There were 137,458 pregnancies screened at 11-13 weeks of gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with normal blood pressure, stage 2 hypertension was associated with both preterm preeclampsia (0.3% to 4.9%) and term preeclampsia (1.0% to 8.3%). A blood pressure threshold of 140/90 mm Hg was good at identifying women at increased risk of preeclampsia overall (positive likelihood ratio, 5.61 [95% confidence interval, 5.14-6.11]) and across maternal characteristics, compared with elevated blood pressure (positive likelihood ratio, 1.70 [95% confidence interval, 1.63-1.77]) and stage 1 hypertension (positive likelihood ratio, 2.68 [95% confidence interval, 2.58-2.77]). There were 2 exceptions: a blood pressure threshold of 130/80 mm Hg was better for the 2.1% of women with body mass index <18.5 kg/m2 (positive likelihood ratio, 5.13 [95% confidence interval, 3.22-8.16]), and a threshold of 135/85 mm Hg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio, 5.24, [95% confidence interval, 4.77-5.77]). There was no blood pressure threshold below which reassurance could be provided against the development of preeclampsia (all-negative likelihood ratios ≥0.20). The traditional blood pressure threshold of 140/90 mm Hg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however, a randomized trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold is reassured against the development of preeclampsia, regardless of maternal characteristics.

Prediction of preterm birth in women with fetal growth restriction - Is the weekly change in sFlt-1/PlGF ratio or PlGF levels useful?

To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68). Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

Construction of prediction model for fetal growth restriction during first trimester in an Asian population.

To construct a prediction model for fetal growth restriction (FGR) during the first trimester of pregnancy and evaluate its screening performance. This was a prospective cohort study of singleton pregnancies that underwent routine ultrasound screening at 11 to 13 + 6 weeks at the Affiliated Suzhou Hospital of Nanjing Medical University between January 2019 and April 2022. Basic clinical information, ultrasound indicators and serum biomarkers of pregnant women were collected. Fetal weight assessment was based on the fetal growth curve for the Southern Chinese population. FGR was diagnosed according to Delphi consensus criteria. Least absolute shrinkage and selection operator (lasso) regression was used to select variables for inclusion in the model. Discrimination, calibration and clinical effectiveness of the model were evaluated in training and validation cohorts. A total of 1188 pregnant women were included, of whom 108 had FGR. Lasso regression identified seven predictive features, including history of maternal hypertension, maternal smoking or passive smoking, gravidity, uterine artery pulsatility index, ductus venosus pulsatility index and multiples of the median values of placental growth factor and soluble fms-like tyrosine kinase-1. The nomogram prediction model constructed from these seven variables accurately predicted FGR, and the area under the receiver-operating-characteristics curve in the validation cohort was 0.82 (95% CI, 0.74-0.90). The calibration curve and Hosmer-Lemeshow test demonstrated good calibration, and the clinical decision curve and clinical impact curve supported its practical value in a clinical setting. The multi-index prediction model for FGR has good predictive value during the first trimester. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Umbilical–portal–systemic venous shunt and intrauterine growth restriction: an inquiry from a prospective study

BackgroundThe investigation of the fetal umbilical-portal venous system is based on the premise that congenital anomalies of this system may be related to adverse perinatal outcomes. Several retrospective small studies have reported a well-established association between umbilical–portal–systemic venous shunts and fetal growth restriction. However, the prevalence of portosystemic shunts in the fetal growth restricted population is yet to be determined. ObjectivesThe aims of this study were:1. To determine the prevalence of fetal umbilical–portal–systemic venous shunts in pregnancies complicated by fetal growth restriction.2. To compare the perinatal and neonatal outcome of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts. Study DesignA prospective cross-sectional study of pregnancies diagnosed with fetal growth restriction, as defined by the Society for Maternal-Fetal Medicine fetal growth restriction guidelines. All participants underwent a detailed anomaly scan supplemented with a targeted scan of the fetal portal system. Venous shunts were diagnosed using color Doppler mode. The perinatal outcomes of fetal growth restriction pregnancies with and without umbilical–portal–systemic venous shunts were compared. ResultsOne hundred and fifty cases of fetal growth restriction were recruited. The prevalence of umbilical–portal–systemic venous shunts in our cohort was 9.3% (n=14). Compared to the control group (fetal growth restriction without umbilical–portal–systemic venous shunts, n=136), the study group had a significantly lower mean gestational age at time of fetal growth restriction diagnosis [29.7 (±5.6) vs. 32.47 (±4.6) weeks of gestation, p=0.036] as well as an earlier gestational week at delivery [33.50 (±6.0) vs. 36.13 (±2.8), p=0.005]. The study group had a higher rate of fetal death (21.4% vs. 0.7%, p<0.001) and accordingly a lower rate of live births (71.4% vs. 95.6%, p=0.001). Associated additional fetal vascular anomalies were significantly more prevalent in the study group compared to controls (35.7% vs. 4.4%, respectively, p=<0.001). The rate of other associated anomalies was similar. The study group had a significantly lower rate of abnormal uterine artery Doppler indices (0% vs. 40.4% p=0.011) and a higher rate of abnormal ductus venosus Doppler indices (64.3% vs. 23% p=0.001). There were no cases of hypertensive disorders of pregnancy in the study group compared to 12.5% in the control group (p=0.16). Other perinatal and neonatal outcomes were comparable. ConclusionsUmbilical–portal–systemic venous shunt is a relatively common finding in growth restricted fetuses. Compared to fetal growth restriction pregnancies with a normal portal system, these pregnancies complicated by FGR and umbilical–portal–systemic venous shunt are associated with different Doppler flow pattern, increased risk for fetal death, earlier presentation of fetal growth restriction, lower gestational age at delivery, additional congenital vascular anomalies and a lower rate of pregnancy induced hypertensive disorders. Meticulous sonographic evaluation of the portal system should be considered in the prenatal workup of fetal growth restriction, as umbilical–portal–systemic venous shunts may have implications on perinatal outcome.

Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.

Pre-eclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality (i.e. before 60 years of age or in the first year postpartum). PE is associated with adverse left ventricular (LV) remodeling in the peri- and postpartum periods, an independent risk factor for cardiovascular disease. This study aimed to compare LV geometry by LV mass (LVM) and LVM index (LVMI) between participants with a high vs low screening risk for preterm PE in the first trimester. This was a prospective cohort study of singleton pregnancies between 11 + 0 and 13 + 6 weeks' gestation that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, from February 2019 until March 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥ 1 in 50 for preterm PE were classified as high risk and those with a screening risk of ≤ 1 in 500 were classified as low risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low risk and 71 (55.5%) participants as high risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area and body mass index were significantly higher in the high-risk group (all P < 0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous and have a family history of hypertensive disease in pregnancy as well as other cardiovascular disease (all P < 0.05). In addition, mean arterial blood pressure (P < 0.001), mean heart rate (P < 0.001), median LVM (130.06 (interquartile range, 113.62-150.50) g vs 97.44 (81.68-114.16)g; P < 0.001) and mean LVMI (72.87 ± 12.2 g/m2 vs 57.54 ± 12.72 g/m2 ; P < 0.001) were significantly higher in the high-risk group. Consequently, those in the high-risk group were more likely to have abnormal LV geometry (37.1% vs 7.0%; P < 0.001). Early echocardiographic assessment in participants at high risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Afferent venous perfusion of fetal liver: umbilical and portal blood-flow volumes in fetuses born small-for-gestational age.

To quantify the dynamic changes in the afferent venous flow volume of the liver in low-risk pregnancies with fetuses born small-for-gestational age. This was a prospective study of low-risk singleton pregnancies with estimated fetal weight (EFW) and birth weight ≤ 10th centile attending for a routine second- or third-trimester ultrasound examination. Their umbilical and portal blood-flow volumes were compared with those of a control group of fetuses born appropriate-for-gestational age from which normal reference ranges were constructed. Absolute and Z-score differences between the groups were assessed. In total, 133 fetuses were included in the study group and 362 in the control group. The mean umbilical blood-flow volume in the study group, both absolute and normalized per kg of EFW, was below that of the appropriate-for-gestational-age fetuses for most of the period of pregnancy studied (overall mean Z-score, -0.82 and -0.84, respectively). In contrast, the mean portal blood-flow volume, per kg of EFW, showed the opposite trend (overall mean Z-score, +0.86), reaching its maximum level (+1.43) in the late third trimester. This resulted in a steep decrease in the mean placental-to-portal-blood-flow volume ratio, from 14.4 at 24 weeks of gestation (above the 60th centile) to 4.7 at 38 weeks of gestation (15th centile), corresponding to Z-scores of +0.4 and -1.02, respectively. In fetuses born small-for-gestational age, the ratio of blood-flow volume in the umbilical vein to that in the portal vein decreases consistently during pregnancy, and to a greater extent compared with those born appropriate-for-gestational age, reaching a lower nadir in the third trimester. This additional redistribution of liver perfusion affects negatively fetal growth even in low-risk pregnancy, and should be taken into account when planning delivery. We suggest considering liver venous perfusion as an ancillary tool for monitoring small-for-gestational-age pregnancies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal outcomes of a cohort of pregnancies affected by non-immune hydrops fetalis.

To describe the maternal outcomes of a prospective cohort of non-immune hydrops fetalis (NIHF) pregnancies with negative standard-of-care evaluations. This study was a secondary analysis of a prospective cohort study of NIHF pregnancies with negative work-ups (infection, alloimmune anemia, fetomaternal hemorrhage, and chromosomal disorders). Outcomes were obstetric complications, including pre-eclampsia, mirror syndrome, preterm birth, polyhydramnios, postpartum hemorrhage, and maternal mental health. Forty pregnancies were included. Four patients developed pre-eclampsia (4/40, 10.0%); three occurred postpartum. None was diagnosed with mirror syndrome. Of the 31 continued pregnancies, 16 (51.6%) resulted in early fetal death or stillbirth and 15 (48.4%) resulted in live births. Of the 15 live births, 8 (53.3%) were delivered by primary cesarean delivery; 5 (62.5%) were for hydrops fetalis. Eleven live births (73.3%) were delivered preterm; 9 (81.8%) were indicated, most commonly for fetal indications (7/9, 77.8%). Polyhydramnios occurred in 14/40 (35.0%) cases. Where EBL was recorded (n=37), there were 5(13.5%) cases of postpartum hemorrhage and an additional 3(8.1%) had uterine atony without hemorrhage. Eighteen patients (18/40, 45.0%) had new-onset or exacerbated depression or anxiety symptoms. Our study identified several important adverse outcomes of pregnancies complicated by NIHF with negative standard-of-care evaluations, including a high rate of postpartum pre-eclampsia and worsened mental health. We identified a higher rate of cesarean delivery and preterm birth, both primarily for fetal indications. We also observed the known relationship between polyhydramnios, hemorrhage, and atony, but noted that this risk included pregnancies concluding in dilation and evacuation. Counseling after a diagnosis of NIHF should include these adverse outcomes.

Association between adverse pregnancy outcome and placental biomarkers in the first trimester: A prospective cohort study.

To determine the inter-relationships between five first-trimester biomarkers (pregnancy associated plasma protein A [PAPP-A], alpha-fetoprotein [AFP], beta human chorionic gonadotrophin [beta-hCG], placenta growth factor [PlGF] and soluble fms-like tyrosine kinase receptor-1 [sFlt-1]) and a range of adverse pregnancy outcomes (APOs). Prospective cohort study of nulliparous singleton pregnancy. Cambridge, UK. 4056 pregnancy outcome prediction study participants. The biomarker concentrations were measured in maternal serum at ~12 weeks of gestation. Univariable analysis of APOs was performed using logistic regression. Multivariable analysis used best subsets logistic regression with cross-validation. Pre-eclampsia (PE), small for gestational age (SGA), including severe SGA (birthweight <3rd), fetal growth restriction (FGR), preterm birth (PTB, both induced and spontaneous [iPTB and sPTB, respectively]), pre-viable loss and stillbirth, plus combinations of outcomes. Lower values of PAPP-A, PlGF and sFlt-1 and higher values of AFP were associated with FGR (OR for 1 SD higher value 0.59 [95% CI 0.48-0.74], OR 0.56 [95% CI 0.44-0.70], OR 0.68 [95% CI 0.54-0.87] and OR 1.53 [95% CI 1.25-1.88]), severe SGA (OR0.59 [95% CI 0.49-0.72], OR 0.71 [95% CI 0.57-0.87], OR 0.74 [95% CI 0.60-0.91] and OR 1.41 [95% CI 1.17-1.71]), sPTB (OR 0.61 [95% CI 0.50-0.73], OR 0.79 [95% CI 0.66-0.96], OR 0.57 [95% CI 0.47-0.70] and OR 1.41 [95% CI 1.18-1.67]) and iPTB (OR 0.72 [95% CI 0.57-0.91], OR 0.62 [95% CI 0.49-0.78], OR 0.71 [95% CI 0.56-0.90] and OR 1.44 [95% CI 1.16-1.78]), respectively. When combinations of biomarkers were assessed, PAPP-A and AFP were independently associated with severe SGA; PAPP-A alone with PE + PTB; PlGF alone with severe PE; PlGF, beta-hCG, AFP and PAPP-A with the combination of PE and SGA; AFP and sFlt-1 with sPTB; and AFP and PlGF with iPTB. Combinations of first-trimester placental biomarkers are associated with APOs. However, the patterns vary for different types of APO, indicating heterogeneity in the underlying pathophysiological pathways.

Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis

ObjectiveTo estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries.DesignIndividual participant data meta-analysis.SettingProspective pregnancy studies from 24 low and middle...

Prenatal diagnosis of bilobate placenta: incidence, risk factors and impact on pregnancy outcomes.

To investigate the incidence and risk factors of bilobate placenta, as well as to assess its impact on preeclampsia (PE), preterm delivery (PTD) and small-for-gestational age (SGA)neonates. A prospective study of singleton pregnancies, undergoing routine anomaly scan at 20+0-23+6 gestational weeks, was conducted, between 2018 and 2022. The impact of prenatally diagnosed bilobate placenta on PE, PTD and SGA was assessed. Multivariate logistic regression models were employed to assess the independent association between bilobate placenta and the main pregnancy outcomes, using specific confounders. Additionally, a risk factor analysis was performed. The study population included 6,454 pregnancies; the incidence of prenatally diagnosed bilobate placenta was 2.0 % (n=129). Bilobate placenta was associated with PE (aOR: 1.721; 95 % CI: 1.014-2.922), while no statistically significant association was found between this anatomical variation and SGA (aOR: 1.059; 95 % CI: 0.665-1.686) or PTD (aOR: 1.317; 95 % CI: 0.773-2.246). Furthermore, pregnancies with prenatally diagnosed bilobate placenta had an increased prevalence of abnormal cord insertion (marginal or velamentous) (9.8 vs. 27.1 %; p<0.001) and increased mean UtA PI z-score (0.03 vs. 0.23; p=0.039). Conception via ART (aOR: 3.669; 95 % CI: 2.248-5.989), previous history of 1st trimester miscarriage (aOR: 1.814; 95 % CI: 1.218-2.700) and advancing maternal age (aOR: 1.069; 95 % CI: 1.031-1.110) were identified as major risk factors for bilobate placenta. Bilobate placenta, excluding cases of co-existing vasa previa, is associated with higher incidence of PE, increased mean UtA PI z-score and higher probability of abnormal cordinsertion, but not with increased risk for SGA or PTD. It is more common in pregnancies following ART and in women with a previous 1st trimester miscarriage.

Biological Embedding of Social Determinants of Health in Early Life and Across Generations

Population health disparities represent one of the most significant public health challenges. These disparities are evident from the earliest stages of life onwards, persist across the life span, are perpetuated across generations, and are strongly influenced by social and environmental factors. Chronic stress and stress-related biobehavioral processes are discussed as one of the major effectors of the causal pathways linking upstream social determinants with health and health disparities. It is evident that the effects of stress exposure can persist over long periods of time, even across the lifespan, and particularly so if exposure occurs during sensitive developmental windows such as the intrauterine period. In this symposium, presenters will address key questions and knowledge gaps regarding biological embedding of social disadvantage and the role of stress in this context, particularly during pregnancy and early life. Tom O’Connor will present data from the ECHO-UPSIDE cohort, a longitudinal pregnancy cohort study of a socio-economically and racially/ethnically diverse sample at elevated psychosocial risk but normal medical risk status. Results indicate that maternal pre-pregnancy adversity in early childhood is associated with prenatal behavioral and physical health markers, including depressive and anxiety symptoms, stress, body mass index (BMI), sleep disturbance, and diet, as well as maternal-fetal-placental biological markers that predict child health outcomes. Laura Scholaske will present results of a multi-site prospective pregnancy study conducted in Germany that includes people of Turkish origin that are among the biggest migrant groups in Germany. Results of the study suggest that pregnant women of Turkish origin exhibit higher psychological stress levels and alterations in stress-related biological systems (i.e., elevated inflammatory levels, blunted cortisol awakening response and flatter diurnal cortisol slope) compared to non-migrant pregnant women. Shannin N. Moody will address the effects of policing inequities that are one of the most harmful sources of systemic racism perpetuated against Black Americans. In three separate studies, she tested how unjust police encounter biologically “get under the skin” in Black youth from infancy to emerging adulthood. Rates of neighborhood stop-and-frisk were associated with shorter telomeres in infants. Children whose mothers experienced unfair treatment from police showed, during the TSST, blunted cortisol stress reactivity, slower cortisol recovery, and altered cortisol-testosterone coupling. Adolescents who experienced police encounters had higher waking cortisol as emerging adults. Taken together, the studies point so some of the potential pathways through which social determinants of health may propagate and transmit persisting health disparities. Elisabeth Shirtcliff will lead a discussion on the potential implications for early prevention and targeted intervention strategies to prevent or reverse biological embedding of social disadvantage in at risk individuals.

Can prenatal ultrasound predict adverse neonatal outcomes in SARS-CoV-2–affected pregnancies?

On the basis of available data, at least 1 ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. However, reports on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. This study aimed to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound findings with adverse neonatal outcomes. This was an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal ultrasound evaluation was performed at least once after diagnosis of infection, with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was the composite adverse neonatal outcome, defined as ≥1 of the following: preterm birth, neonatal intensive care unit admission, small for gestational age, respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal ultrasound findings were compared with neonatal outcomes, severity of infection, and trimester of infection. A total of 103 SARS-CoV-2-affected mother-infant pairs with prenatal ultrasound evaluation were identified; 3 cases were excluded because of known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had the composite adverse neonatal outcome, and 23 (23%) had at least 1 abnormal prenatal ultrasound finding. The most common abnormalities seen on ultrasound were placentomegaly (11/23; 47.8%) and fetal growth restriction (8/23; 34.8%). The latter was associated with a higher rate of the composite adverse neonatal outcome (25% vs 1.5%; adjusted odds ratio, 22.67; 95% confidence interval, 2.63-194.91; P<.001), even when small for gestational age was removed from this composite outcome. The Cochran Mantel-Haenszel test controlling for possible fetal growth restriction confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; P<.001). Median estimated fetal weight and birthweight were lower in patients with the composite adverse neonatal outcome (P<.001). Infection in the third trimester was associated with lower median percentile of estimated fetal weight (P=.019). An association between placentomegaly and third-trimester SARS-CoV-2 infection was noted (P=.045). In our study of SARS-CoV-2-affected maternal-infant pairs, rates of fetal growth restriction were comparable to those found in the general population. However, composite adverse neonatal outcome rates were high. Pregnancies with fetal growth restriction after SARS-CoV-2 infection were associated with an increased risk for the adverse neonatal outcome and may require close surveillance.

The Fetal Liver Afferent Venous Flow Volumes in Fetuses With Appropriate for Gestational Age Birth Weight.

The present study aimed: 1) to simultaneously investigate the relationship between blood flow volumes of the two fetal liver afferent venous systems of normally appropriate for gestational age newborns. 2) to establish the normal reference range centiles values that will serve as a basis for future investigations. A cross-sectional, prospective study of singleton low obstetric risk pregnancies. Doppler examination included the measurement of the umbilical and the main portal vein vessels' diameters and time-averaged maximum velocity. The absolute and per kilogram of estimated fetal weight flow volumes and the ratio between the placental and portal blood volume flow were calculated from these data. Three hundred and sixty-three pregnant women were included in the study. The umbilical and portal flow volumes' capacity to provide blood flow per kilogram of fetal weight, in the period of maximum fetal growth, was diverse. The placental flow decreased continuously from a mean of 121.2 mL/min/kg at the 20th week of gestation to 64.1 mL/min/kg at the 38th week of gestation. Meanwhile, the portal flow volume per kilogram of fetal weight increased from 9.6 mL/min/kg at 32 weeks of gestation to 10.3 at the 38th week of gestation. This resulted in a decrease in the umbilical to portal flow volume ratio from 13.3 to 9.6 during this period. Our results indicate that in the period of maximum fetal growth, the placental/portal ratio diminishes emphasizing the portal flow's predominance with low oxygen and nutrient supply to the liver.

Prenatal Diagnosis of Isolated Single Umbilical Artery: Incidence, Risk Factors and Impact on Pregnancy Outcomes.

Objectives: To assess the incidence of prenatally diagnosed isolated single umbilical artery (iSUA) and its impact on major pregnancy outcomes, as well as to investigate potential risk factors. Materials and methods: A prospective study of singleton pregnancies, undergoing routine anomaly scans at 20+0-24+0 weeks of gestation, was carried out from 2018 to 2022. The effect of sonographically detected iSUA on small-for-gestational-age neonates (SGA) and preterm delivery (PTD) was evaluated using parameterized Student's t-test, nonparametric Mann-Whitney U test and the chi-square test. Multivariable logistic regression models were implemented to assess the independent association between iSUA and the main outcomes, as well as with potential risk factors, while adjusting for specific confounders. Results: The study population included 6528 singleton pregnancies and the incidence of prenatally diagnosed iSUA was 1.3%. Prenatally diagnosed iSUA had a statistically significant association with both SGA neonates (aOR: 1.909; 95% CI: 1.152-3.163) and PTD (aOR: 1.903; 95% CI: 1.035-3.498), while no association was identified between this sonographic finding and preeclampsia. With regard to risk factors, conception via assisted reproductive technology (ART) was associated with increased risk of iSUA (aOR: 2.234; 95% CI: 1.104-4.523), while no other independent predictor for the development of this anatomical variation was identified. Conclusions: Prenatally diagnosed iSUA seems to be associated with a higher incidence of SGA and PTD and is more common in pregnancies following ART, which constitutes a novel finding.

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features.

Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34week's gestation) severe preeclampsia. 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.