M. Parra-Saavedra

Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies

To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late‐onset small‐for‐gestational‐age (SGA) babies.

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion

OBJECTIVE This study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). METHODS In a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. RESULTS A total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025-0.57]; p = 0.008). DISCUSSION Histologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. CONCLUSIONS Diminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

In-vivo assessment of the biomechanical properties of the uterine cervix in pregnancy

Measuring the stiffness of the cervix might be useful in the prediction of preterm delivery or successful induction of labor. For that purpose, a variety of methods for quantitative determination of physical properties of the pregnant cervix have been developed. Herein, we review studies on the clinical application of these new techniques. They are based on the quantification of mechanical, optical, or electrical properties associated with increased hydration and loss of organization in collagen structure. Quasi‐static elastography determines relative values of stiffness; hence, it can identify differences in deformability. Quasi‐static elastography unfortunately cannot quantify in absolute terms the stiffness of the cervix. Also, the current clinical studies did not demonstrate the ability to predict the time point of delivery. In contrast, measurement of maximum deformability of the cervix (e.g. quantified with the cervical consistency index) provided meaningful results, showing an increase in compliance with gestational age. These findings are consistent with aspiration measurements on the pregnant ectocervix, indicating a progressive decrease of stiffness along gestation. Cervical consistency index and aspiration measurements therefore represent promising techniques for quantitative assessment of the biomechanical properties of the cervix.

Correlation between histological signs of placental underperfusion and perinatal morbidity in late-onset small-for-gestational-age fetuses

To investigate whether signs of placental underperfusion (PUP), defined as any maternal and/or fetal vascular pathology, confer an increased risk of neonatal morbidity in late‐onset small‐for‐gestational‐age (SGA) fetuses with normal umbilical artery (UA) Doppler indices.

Neurodevelopmental outcomes of near-term small-for-gestational-age infants with and without signs of placental underperfusion.

OBJECTIVE To evaluate 2-year neurodevelopmental outcomes of near-term, small-for-gestational-age (SGA) newborns segregated by presence or absence of histopathology reflecting placental underperfusion (PUP). PATIENTS AND METHODS A cohort of consecutive near-term (≥ 34.0 weeks) SGA newborns with normal prenatal umbilical artery Doppler studies was selected. All placentas were inspected for evidence of underperfusion and classified in accordance with established histologic criteria. Neurodevelopmental outcomes at 24 months (age-corrected) were then evaluated, applying the Bayley Scale for Infant and Toddler Development, Third Edition (Bayley-III) to assess cognitive, language, and motor competencies. The impact of PUP on each domain was measured via analysis of covariance, logistic and ordinal regression, with adjustment for smoking, socioeconomic status, gestational age at birth, gender, and breastfeeding. RESULTS A total of 83 near-term SGA deliveries were studied, 46 (55.4%) of which showed signs of PUP. At 2 years, adjusted neurodevelopmental outcomes were significantly poorer in births involving PUP (relative to SGA infants without PUP) for all three domains of the Bayley scale: cognitive (105.5 vs 96.3, adjusted-p = 0.03), language (98.6 vs 87.8, adjusted-p<0.001), and motor (102.7 vs 94.5, adjusted-p = 0.007). Similarly, the adjusted likelihood of abnormal cognitive, language, and motor competencies in instances of underperfusion was 9.3-, 17.5-, and 1.44-fold higher, respectively, differing significantly for the former two domains. CONCLUSIONS In a substantial fraction of near-term SGA babies without Doppler evidence of placental insufficiency, histologic changes compatible with PUP are still identifiable. These infants are at greater risk of abnormal neurodevelopmental outcomes at 2 years.

Contingent versus routine third-trimester screening for late fetal growth restriction.

To evaluate the use of third‐trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population.

Angiogenic Factors and Doppler Evaluation in Normally Growing Fetuses at Routine Third-Trimester Scan: Prediction of Subsequent Low Birth Weight

Objective: To evaluate in normally growing fetuses at routine 32-36 weeks scan the performance of maternal angiogenic factors, Doppler and ultrasound indices in predicting smallness for gestational age (SGA) at birth. Methods: A cohort of 1,000 singleton pregnancies with normal estimated fetal weight (EFW, ≥10th centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples were collected and frozen. Nested in this cohort, maternal circulating placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by enzyme-linked immunosorbent assay in all cases with a birth weight <10th centile by customized standards and in an equivalent number of controls (birth weight ≥10th centile). Results: 160 cases were included (80 SGA and 80 controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65, p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA. The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not predictive of SGA. Conclusions: In normally growing fetuses, maternal angiogenic factors add to ultrasound parameters in predicting subsequent SGA at birth. This supports further research to investigate composite scores in order to improve the definition and identification of fetal growth restriction.

Added value of umbilical vein flow as a predictor of perinatal outcome in term small-for-gestational-age fetuses

To compare umbilical vein (UV) flow with standard Doppler parameters in prediction of adverse perinatal outcome in late‐onset small‐for‐gestational age (SGA) fetuses.

Serial Head and Brain Imaging of 17 Fetuses With Confirmed Zika Virus Infection in Colombia, South America

OBJECTIVE To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection. METHODS We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibagué, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated. RESULTS We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications. CONCLUSION Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.

How to perform an amniocentesis

Amniocentesis is a technique for withdrawing amniotic fluid from the uterine cavity using a needle, via a transabdominal approach and under continuous ultrasound guidance, in order to obtain a sample of fetal exfoliated cells, transudates, urine or secretions. It can be performed from 16 weeks of pregnancy onwards, with various chromosomal, biochemical, molecular and microbial studies being performed on the amniotic fluid sample. The most common reasons for the procedure are to enable prenatal diagnosis of chromosomal abnormalities, single gene disorders, fetal infection and intra-amniotic inflammation, as well as to assess fetal lung maturity and blood or platelet type. The procedure has a risk of fetal loss of approximately 0.5% (range, 0.06–1%)1 when performed in the second trimester, after the amniotic membrane has fused with the chorion; there is also a risk of amniotic fluid leakage (approximately 0.3% of cases) and other rare complications, such as placental hemorrhage, intra-amniotic infection, abdominal wall hematoma and fetal lesion. There is an important lack of good-quality evidence to support most recommendations for the procedure, and a recent review suggested that operators should use those methods and technique modifications with which they are most familiar when performing an amniocentesis2. The aim of this summary article and the full version, included as supplementary material online, is to describe the amniocentesis technique, presenting a practical guideline for its performance. We also describe the use of a Vacutainer® (BD Vacutainer Systems, Plymouth, UK) aspiration system in order to produce a continuous vacuum for amniotic fluid aspiration as an alternative to using manually operated syringes.