Early antenatal risk factors for births before arrival: An unmatched case-control study.

INTRODUCTION: Birth before arrival is associated with maternal morbidity and neonatal morbidity and mortality. Yet, timely risk stratification remains challenging. Our objective was to identify risk factors for birth before arrival which may be determined at the first antenatal appointment. MATERIAL AND METHODS: This was an unmatched case-control study involving 37 348 persons who gave birth at a minimum of 22+0 weeks' gestation over a 5-year period from January 2014 to October 2019 (IRAS project ID 222260; REC reference: 17/SC/0374). The setting was a large UK university hospital. Data obtained on maternal characteristics at booking was examined for association with birth before arrival using a stepwise multivariable logistic regression analysis. Data are presented as adjusted odds ratios with 95% confidence intervals. Area under the receiver-operator characteristic curves (C-statistic) were employed to enable discriminant analysis assessing the risk prediction of the booking data on the outcome. RESULTS: Multivariable analysis identified significant independent predictors of birth before arrival that were detectable at booking: parity, ethnicity, multiple deprivation, employment status, timing of booking, distance from home to the nearest maternity unit, and safeguarding concerns raised at booking by clinical staff. Our model demonstrated good discrimination for birth before arrival; together, the predictors accounted for 77% of the data variance (95% confidence interval 0.74-0.80). CONCLUSIONS: Information gathered routinely at booking may discriminate individuals at risk for birth before arrival. Better recognition of early factors may enable maternity staff to direct higher-risk women towards specialized care services at an early point in their pregnancy, enabling time for clinical and social interventions.

Ultrasound predictors of adverse outcome in pregnancy complicated by pre-existing and gestational diabetes.

INTRODUCTION: Ultrasound assessment of fetuses subjected to hyperglycemia is recommended but, apart from increased size, little is known about its interpretation, and the identification of which large fetuses of diabetic pregnancy are at risk is unclear. Newer markers of adverse outcomes, abdominal circumference growth velocity and cerebro-placental ratio, help to predict risk in non-diabetic pregnancy. Our study aims to assess their role in pregnancies complicated by diabetes. MATERIAL AND METHODS: This is a retrospective analysis of a cohort of singleton, non-anomalous fetuses of women with pre-existing or gestational diabetes mellitus, and estimated fetal weight at the 10th centile or above. Gestational diabetes was diagnosed by selective screening of at risk groups. A universal ultrasound scan was offered at 20 and 36 weeks of gestation. Estimated fetal weight, abdominal circumference growth velocity, presence of polyhydramnios, and cerebro-placental ratio were evaluated at the 36-week scan. A composite adverse outcome was defined as the presence of one or more of perinatal death, arterial cord pH less than 7.1, admission to Neonatal Unit, 5-minute Apgar less than 7, severe hypoglycemia, or cesarean section for fetal compromise. A chi-squared test was used to test the association of estimated fetal weight at the 90th centile or above, polyhydramnios, abdominal circumference growth velocity at the 90th centile or above, and cerebro-placental ratio at the 5th centile or below with the composite outcome. Logistic regression was used to assess which ultrasound markers were independent risk factors. Odds ratios of composite adverse outcome with combinations of independent ultrasound markers were calculated. RESULTS: A total of 1044 pregnancies were included, comprising 87 women with pre-existing diabetes mellitus and 957 with gestational diabetes. Estimated fetal weight at the 90th centile or above, abdominal circumference growth velocity at the 90th centile or above, cerebro-placental ratio at the 5th centile or below, but not polyhydramnios, were significantly associated with adverse outcomes: odds ratios (95% confidence intervals) 1.85 (1.21-2.84), 1.54 (1.02-2.31), 1.92 (1.21-3.30), and 1.53 (0.79-2.99), respectively. Only estimated fetal weight at the 90th centile or above and cerebro-placental ratio at the 5th centile or below were independent risk factors. The greatest risk (odds ratio 6.85, 95% confidence interval 2.06-22.78) was found where both the estimated fetal weight is at the 90th centile or above and the cerebro-placental ratio is at the 5th centile or below. CONCLUSIONS: In diabetic pregnancies, a low cerebro-placental ratio, particularly in a macrosomic fetus, confers additional risk.

Ebola virus disease in pregnancy: a systematic review and meta-analysis.

This review synthesises and appraises evidence on the effects of Ebola virus disease (EVD) in pregnancy. We searched bibliographic databases from dates of inception to November 2020, yielding 28 included studies. The absolute risk of maternal death associated with EVD was estimated at 67.8% (95% confidence interval [CI] 49.8 to 83.7, I2=85%, p<0.01) and the relative risk of death in pregnant women compared with non-pregnant women was estimated at 1.18 (95% CI 0.59 to 2.35, I2=31.0%, p=0.230). The absolute risk for foetal losses was estimated at 76.9% (95% CI 45.0 to 98.3, I2=96%, p<0.01) and neonatal death was 98.5% (95% CI 84.9 to 100, I2=0.0%, p=0.40). The gap analysis suggests limited or no data on the clinical course, non-fatal perinatal outcomes and EVD management in pregnant women. The review suggests that EVD has a high maternal and perinatal mortality, underscoring the urgent need for preventative and therapeutic solutions and improved screening and follow-up of pregnant women and newborns during outbreaks. There is not enough evidence to conclusively rule out pregnancy as a risk factor for mortality and there is limited evidence on the disease course, outcomes and management of EVD in pregnancy, and this supports the need for robust clinical trials and prospective studies that include pregnant women.

The Immediate and Long-Term Impact of Preeclampsia on Offspring Vascular and Cardiac Physiology in the Preterm Infant.

Hypertensive disorders of pregnancy, including preeclampsia, affect nearly 10% of all pregnancies and are associated with significant long-term detrimental effects on both maternal and offspring cardiovascular health. Current management of preeclampsia involves timely delivery with the more severe form of disease requiring iatrogenic preterm birth. The effects on the maternal cardiovascular system have been studied extensively; however, less is known about the short- and long-term impacts on offspring cardiovascular health. There is a growing body of evidence suggesting that the offspring of pre-eclamptic pregnancies have an altered cardiac structure and function, along with a unique vascular physiology driven by lower endothelial function. Many of these changes can also be seen in those born preterm even in the absence of pregnancy hypertension. It is difficult to determine the relative contribution of pre-maturity and preeclampsia to the cardiovascular phenotype of those exposed to these pregnancy complications as they are, in many cases, inextricably linked. This review, therefore, focuses specifically on the evidence from clinical studies showing a negative cardiovascular impact of preeclampsia in preterm-born offspring, investigating phenotypic similarities and differences between offspring born preterm to normotensive vs. pre-eclamptic pregnancies. We explore the unique cardiac and vascular alterations in pre-eclamptic offspring born preterm, highlighting knowledge gaps, and potential areas of further research in the field.

Fertility issues and pregnancy outcomes in Turner syndrome.

OBJECTIVE: To study fertility issues and pregnancy outcomes in Turner syndrome (TS). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): One hundred fifty-six TS patients, median age 32 years, 23 mosaic 45,X/46,XX, 45,X/47,XXX, 45,X/46,XX/47,XXX. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertility choices, spontaneous pregnancy, and oocyte donation (OD) outcomes. Conditions associated with aortic dissection and poor pregnancy outcomes at preconception were considered. Pregnancy-related aortic dimension changes and the long-term impact of pregnancy on TS-related comorbidities were assessed. RESULTS(S): In all, 13.5% had spontaneous pregnancies, resulting in a pregnancy with live birth in 18 patients (37 newborns); 16% considered OD, one adopted, and one underwent fertility preservation. Spontaneous pregnancy predictive factors were a karyotype with a second or third cell line with more than one X and spontaneous menarche. In all, 47.6% had miscarriages, two experienced preeclampsia, and two had gestational diabetes. One daughter was diagnosed with TS in adulthood. Seven of 14 who attempted OD had a pregnancy with live birth; two of seven had gestational diabetes; 64.3% attempting OD had risk factors associated with poor pregnancy outcomes, including four who had double embryo transfer. Cardiac status at preconception was evaluated in 12 of 25 women who had a pregnancy. The aortic diameters during pregnancy increased. The aortic growth at sinuses was 0.51 ± 0.71 mm/year and at ascending aorta 0.67 ± 0.67 mm/year, reaching a significant difference at sinuses compared with the growth in nulliparous TS. Among women who had a pregnancy, none experienced aortic dissection during and in the years after pregnancy. CONCLUSION(S): This study highlights the importance of a TS-dedicated multidisciplinary management of pregnancy, before and during pregnancy and in the postpartum period.

Prenatal and Postnatal Cardiac Development in Offspring of Hypertensive Pregnancies.

Background Pregnancy complications such as preterm birth and fetal growth restriction are associated with altered prenatal and postnatal cardiac development. We studied whether there were changes related specifically to pregnancy hypertension. Methods and Results Left and right ventricular volumes, mass, and function were assessed at birth and 3 months of age by echocardiography in 134 term-born infants. Fifty-four had been born to mothers who had normotensive pregnancy and 80 had a diagnosis of preeclampsia or pregnancy-induced hypertension. Differences between groups were interpreted, taking into account severity of pregnancy disorder, sex, body size, and blood pressure. Left and right ventricular mass indexed to body surface area (LVMI and RVMI) were similar in both groups at birth (LVMI 20.9±3.7 versus 20.6±4.0 g/m2, P=0.64, RVMI 17.5±3.7 versus 18.1±4.7 g/m2, P=0.57). However, right ventricular end diastolic volume index was significantly smaller in those born to hypertensive pregnancy (16.8±5.3 versus 12.7±4.7 mL/m2, P=0.001), persisting at 3 months of age (16.4±3.2 versus 14.4±4.8 mL/m2, P=0.04). By 3 months of age these infants also had significantly greater LVMI and RVMI (LVMI 24.9±4.6 versus 26.8±4.9 g/m2, P=0.04; RVMI 17.1±4.2 versus 21.1±3.9 g/m2, P<0.001). Differences in RVMI and right ventricular end diastolic volume index at 3 months, but not left ventricular measures, correlated with severity of the hypertensive disorder. No differences in systolic or diastolic function were evident. Conclusions Infants born at term to a hypertensive pregnancy have evidence of both prenatal and postnatal differences in cardiac development, with right ventricular changes proportional to the severity of the pregnancy disorder. Whether differences persist long term as well as their underlying cause and relationship to increased cardiovascular risk requires further study.

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m2; P=0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; P=0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; P=0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m2; P=0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; P=0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; P=0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm2; P=0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (P<0.01, P=0.01, and P=0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.

Lassa fever in pregnancy: a systematic review and meta-analysis.

Lassa fever is a zoonotic infection endemic to West Africa and is known to have adverse effects in pregnancy. We sought to synthesize and critically appraise currently available evidence on the effects of Lassa fever in pregnancy. An exhaustive bibliographic search from dates of inception to 30 September 2019 yielded 13 studies, from which individual patient data were extracted. The absolute risk of maternal death associated with Lassa fever was estimated at 33.73% (95% CI 22.05 to 46.42%, I2=72.40%, p=0.0014). The relative risk of death in pregnant women compared with non-pregnant women was estimated at 2·86 (95% CI 1.77 to 4.63, I2=27.27%, p=0.239). The formal gap analysis shows imprecise data on the risk of Lassa-related maternal and perinatal mortality and insufficient data for other pregnancy outcomes. The currently available evidence for the use of ribavirin in pregnant patients is not conclusive. With a threefold increased risk of mortality, there is a need to prioritize pregnant women as a special subgroup of interest for Lassa research. Robust prospective studies estimating the true incidence of adverse maternal and perinatal outcomes and randomized controlled trials to evaluate the efficacy of therapeutics for maternal Lassa virus infection are urgently needed.

Does self-reported pregnancy loss identify women at risk of an adverse cardiovascular phenotype in later life? Insights from UK Biobank.

INTRODUCTION: Cardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk. METHODS: Pregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40-69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors. RESULTS: Data were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1). CONCLUSION: Women who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk.

Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring.

Hypertensive disorders of pregnancy affect up to 10% of pregnancies worldwide, which includes the 3%-5% of all pregnancies complicated by preeclampsia. Preeclampsia is defined as new onset hypertension after 20 weeks' gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. Despite its prevalence, the risk factors that have been identified lack accuracy in predicting its onset and preventative therapies only moderately reduce a woman's risk of preeclampsia. Preeclampsia is a major cause of maternal morbidity and is associated with adverse foetal outcomes including intra-uterine growth restriction, preterm birth, placental abruption, foetal distress, and foetal death in utero. At present, national guidelines for foetal surveillance in preeclamptic pregnancies are inconsistent, due to a lack of evidence detailing the most appropriate assessment modalities as well as the timing and frequency at which assessments should be conducted. Current management of the foetus in preeclampsia involves timely delivery and prevention of adverse effects of prematurity with antenatal corticosteroids and/or magnesium sulphate depending on gestation. Alongside the risks to the foetus during pregnancy, there is also growing evidence that preeclampsia has long-term adverse effects on the offspring. In particular, preeclampsia has been associated with cardiovascular sequelae in the offspring including hypertension and altered vascular function.

Neonatal Micro-RNA Profile Determines Endothelial Function in Offspring of Hypertensive Pregnancies.

Offspring of hypertensive pregnancies are at increased risk of developing hypertension in adulthood. In the neonatal period they display endothelial cell dysfunction and altered microvascular development. MicroRNAs, as important endothelial cellular regulators, may play a role in this early endothelial dysfunction. Therefore we identified differential microRNA patterns in endothelial cells from offspring of hypertensive pregnancies and determined their role in postnatal vascular cell function. Studies were performed on human umbilical vein endothelial cell (HUVECs) samples from 57 pregnancies. Unbiased RNA-sequencing identified 30 endothelial-related microRNAs differentially expressed in HUVECs from hypertensive compared to normotensive pregnancies. Quantitative reverse transcription PCR (RT-qPCR) confirmed a significant higher expression level of the top candidate, miR-146a. Combined miR-146a targeted gene expression and pathway analysis revealed significant alterations in genes involved in inflammation, angiogenesis and immune response in the same HUVECs. Elevated miR-146a expression level at birth identified cells with reduced ability for in vitro vascular tube formation, which was rescued by miR-146a inhibition. In contrast, miR-146a overexpression significantly reduced vascular tube formation in HUVECs from normotensive pregnancies. Finally, we confirmed that mir146a levels at birth predicted in vivo microvascular development during the first three postnatal months. Offspring of hypertensive pregnancy have a distinct endothelial regulatory microRNA profile at birth, which is related to altered endothelial cell behaviour, and predicts patterns of microvascular development during the first three months of life. Modification of this microRNA profile in vitro can restore impaired vascular cell function.

Neonatal autonomic function after pregnancy complications and early cardiovascular development.

BACKGROUND: Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. METHODS: Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. RESULTS: Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p < 0.001, p = 0.009 and p = 0.007, respectively). We also demonstrated a relative imbalance between sympathetic and parasympathetic tone, compared to the term infants. However, differences in autonomic function did not predict cardiovascular measures at either time point. CONCLUSIONS: Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Two-Dimensional Echocardiography Estimates of Fetal Ventricular Mass throughout Gestation.

BACKGROUND: Two-dimensional (2D) ultrasound quality has improved in recent years. Quantification of cardiac dimensions is important to screen and monitor certain fetal conditions. We assessed the feasibility and reproducibility of fetal ventricular measures using 2D echocardiography, reported normal ranges in our cohort, and compared estimates to other modalities. METHODS: Mass and end-diastolic volume were estimated by manual contouring in the four-chamber view using TomTec Image Arena 4.6 in end diastole. Nomograms were created from smoothed centiles of measures, constructed using fractional polynomials after log transformation. The results were compared to those of previous studies using other modalities. RESULTS: A total of 294 scans from 146 fetuses from 15+0 to 41+6 weeks of gestation were included. Seven percent of scans were unanalysable and intraobserver variability was good (intraclass correlation coefficients for left and right ventricular mass 0.97 [0.87-0.99] and 0.99 [0.95-1.0], respectively). Mass and volume increased exponentially, showing good agreement with 3D mass estimates up to 28 weeks of gestation, after which our measurements were in better agreement with neonatal cardiac magnetic resonance imaging. There was good agreement with 4D volume estimates for the left ventricle. CONCLUSION: Current state-of-the-art 2D echocardiography platforms provide accurate, feasible, and reproducible fetal ventricular measures across gestation, and in certain circumstances may be the modality of choice.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Aortic stiffness and blood pressure variability in young people: a multimodality investigation of central and peripheral vasculature.

INTRODUCTION: Increased blood pressure (BP) variability is a cardiovascular risk marker for young individuals and may relate to the ability of their aorta to buffer cardiac output. We used a multimodality approach to determine relations between central and peripheral arterial stiffness and BP variability. METHODS: We studied 152 adults (mean age of 31 years) who had BP variability measures based on SD of awake ambulatory BPs, 24-h weighted SD and average real variability (ARV). Global and regional aortic distensibility was measured by cardiovascular magnetic resonance, arterial stiffness by cardio-ankle vascular index (CAVI) and pulse wave velocity (PWV) by SphygmoCor (carotid-femoral) and Vicorder (brachial-femoral). RESULTS: In young people, free from overt cardiovascular disease, all indices of SBP and DBP variability correlated with aortic distensibility (global aortic distensibility versus awake SBP SD: r = -0.39, P < 0.001; SBP ARV: r = -0.34, P < 0.001; weighted 24-h SBP SD: r = -0.42, P < 0.001). CAVI, which closely associated with aortic distensibility, also related to DBP variability, as well as awake SBP SD (r = 0.19, P < 0.05) and weighted 24-h SBP SD (r = 0.24, P < 0.01), with a trend for SBP ARV (r = 0.17, P = 0.06). In contrast, associations with PWV were only between carotid-femoral PWV and weighted SD of SBP (r = 0.20, P = 0.03) as well as weighted and ARV of DBP. CONCLUSION: Greater BP variability in young people relates to increases in central aortic stiffness, strategies to measure and protect aortic function from a young age may be important to reduce cardiovascular risk.

Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth.

Comparison of 2-D and 3-D estimates of placental volume in early pregnancy.

Ultrasound estimation of placental volume (PlaV) between 11 and 13 wk has been proposed as part of a screening test for small-for-gestational-age babies. A semi-automated 3-D technique, validated against the gold standard of manual delineation, has been found at this stage of gestation to predict small-for-gestational-age at term. Recently, when used in the third trimester, an estimate obtained using a 2-D technique was found to correlate with placental weight at delivery. Given its greater simplicity, the 2-D technique might be more useful as part of an early screening test. We investigated if the two techniques produced similar results when used in the first trimester. The correlation between PlaV values calculated by the two different techniques was assessed in 139 first-trimester placentas. The agreement on PlaV and derived "standardized placental volume," a dimensionless index correcting for gestational age, was explored with the Mann-Whitney test and Bland-Altman plots. Placentas were categorized into five different shape subtypes, and a subgroup analysis was performed. Agreement was poor for both PlaV and standardized PlaV (p < 0.001 and p < 0.001), with the 2-D technique yielding larger estimates for both indices compared with the 3-D method. The mean difference in standardized PlaV values between the two methods was 0.007 (95% confidence interval: 0.006-0.009). The best agreement was found for regular rectangle-shaped placentas (p = 0.438 and p = 0.408). The poor correlation between the 2-D and 3-D techniques may result from the heterogeneity of placental morphology at this stage of gestation. In early gestation, the simpler 2-D estimates of PlaV do not correlate strongly with those obtained with the validated 3-D technique.