Outcomes in emergency versus electively scheduled cases of placenta accreta spectrum disorder managed by cesarean-hysterectomy within a multidisciplinary care team.

OBJECTIVE: Compare maternal and perinatal outcomes between emergency and electively scheduled cesarean-hysterectomy for placenta accreta spectrum (PAS) disorders. METHOD: Single-center retrospective cohort study including 125 cases of antenatally suspected and pathologically confirmed PAS disorders. Maternal and perinatal outcomes were analyzed. Multivariate logistic regression was used to test associations. Survival curves exploring risk factors for emergency birth were sought. RESULTS: 25 (20%) and 100 (80%) patients had emergency and electively scheduled birth, respectively. Emergency birth had a higher estimated blood loss (2772 [2256.75] vs. 1561.19 [1152.95], P < 0.001), with a higher rate of coagulopathy (40% vs. 6%; P < 0.001) and bladder injury (44% vs. 13%; P < 0.001); and was associated with increased rates of blood transfusion (aOR 4.9, CI95% 1.3-17.5, P = 0.01), coagulopathy (aOR 16.4, CI95% 2.6-101.4, P = 0.002) and urinary tract injury (aOR 6.96, CI95% 1.5-30.7, P = 0.01). Gestational age at birth was lower in the emergency group (31.55 [4.75] vs. 35.19 [2.77], P = 0.001), no difference in perinatal mortality was found. A sonographically short cervix and/or history of APH had an increased cumulative risk of emergency birth with advancing gestational age. CONCLUSION: Patients with PAS disorders managed in a tertiary center by a multidisciplinary team requiring emergency birth have increased maternal morbidity and poorer perinatal outcomes than those with electively scheduled birth.

Circulating maternal placental growth factor responses to low-molecular-weight heparin in pregnant patients at risk of placental dysfunction.

BACKGROUND: Patients at high risk of severe preeclampsia and fetal growth restriction have low circulating levels of placental growth factor and features of maternal vascular malperfusion placental pathology at delivery. Multimodal screening and commencement of aspirin prophylaxis at 11 to 13 weeks' gestation markedly reduces the risk of preterm delivery with preeclampsia. However, the additional role of low-molecular-weight heparin and mechanisms of action remain uncertain. Because low-molecular-weight heparin augments the production and release of placental growth factor in vitro by both placental villi and vascular endothelium, it may be effective to suppress the risk of severe preeclampsia in a niche group of high-risk patients with low circulating placental growth factor in the early second trimester. OBJECTIVE: This study aimed to define a gestational age-specific reference range for placental growth factor and to test the hypothesis that prophylactic low-molecular-weight heparin administered in the early second trimester may restore deficient circulating placental growth factor levels and thereby prolong pregnancy. STUDY DESIGN: Centile curves for circulating placental growth factor levels from 12 to 36 weeks' gestation were derived using quantile regression of combined data from a published cohort of 4207 unselected nulliparous patients in Cambridge, United Kingdom, at 4 sampling time points (12, 20, 28, and 36 weeks' gestation) and the White majority (n=531) of a healthy nulliparous cohort in Toronto, Canada, at 16 weeks' gestation using the same test platform. Within a specialty high-risk clinic in Toronto, a niche group of 7 patients with a circulating placental growth factor at the <10th centile in the early second trimester received daily prophylactic low-molecular-weight heparin (enoxaparin; 40 mg subcutaneously) and were followed up until delivery (group 1). Their baseline characteristics, delivery details, and placental pathologies were compared with 5 similar patients who did not receive low-molecular-weight heparin during the observation period (group 2) and further with 21 patients who delivered with severe preeclampsia (group 3) in the same institution. RESULTS: A gestational age-specific reference range for placental growth factor levels at weekly intervals between 12 and 36 weeks was established for White women with singleton pregnancies. Within group 1, 5 of 7 patients demonstrated a sustained increase in circulating placental growth factor levels, whereas placental growth factor levels did not increase in group 2 or group 3 patients who did not receive low-molecular-weight heparin. Group 1 patients receiving low-molecular-weight heparin therapy exhibited a later gestation at delivery, relative to groups 2 and 3 (36 weeks [33-37] vs 23 weeks [22-26] and 28 weeks [27-31], respectively), and consequently had higher birthweights (1.93 kg [1.1-2.7] vs 0.32 kg [0.19-0.39] and 0.73 kg [0.52-1.03], respectively). The incidence of stillbirth was lowest in group 1 (14% [1 of 7]), relative to groups 2 and 3 (80% [4 of 5] and 29% [6 of 21], respectively). Maternal vascular malperfusion was the most common placental pathology found in association with abnormal uterine artery Doppler. CONCLUSION: In patients at high risk of a serious adverse pregnancy outcome owing to placental disease, the addition of low-molecular-weight heparin to aspirin prophylaxis in the early second trimester may restore deficient circulating placental growth factor to mediate an improved perinatal outcome. These data support the implementation of a multicenter pilot randomized control trial where patients are recruited primarily based on the assessment of placental function in the early second trimester.

Stillbirth Following Normal Ultrasound Findings and Maternal Placental Growth Factor Levels.

BACKGROUND: Attempts to reduce the current rate of antepartum stillbirth in the late third trimester have largely focused on the accurate identification of fetal growth restriction. Universal ultrasound significantly increases detection, especially when combined with maternal angiogenic growth factors, but this screening strategy is not well suited to identify umbilical cord pathology. While this poses unique challenges to pregnancy care, the recurrence risk of cord obstruction is low in comparison with many intrinsic placental diseases. CASE: A 30-year-old woman with normal uterine artery Doppler waveforms, fetal growth ultrasounds, and circulating placental growth factor experienced an unexpected third-trimester stillbirth. Placental pathology demonstrated fetal vascular malperfusion and cord hyper-coiling. CONCLUSION: Despite normal placental function, the otherwise healthy fetus is at risk of antepartum stillbirth due to cord-related pathology.

Sex differences in uterine artery Doppler during gestation in pregnancies complicated by placental dysfunction.

BACKGROUND: There is growing evidence of sex differences in placental vascular development. The objective of this study was to investigate the effect of fetal sex on uterine artery pulsatility index (PI) throughout gestation in a cohort of normal and complicated pregnancies. METHODS: A prospective longitudinal study was conducted in 240 pregnant women. Pulsed wave Doppler ultrasound of the proximal uterine arteries was performed at a 4-weekly interval between 14 and 40 weeks of gestation. The patients were classified retrospectively as normal or complicated (one or more of maternal preeclampsia, preterm birth, or small for gestational age). To assess if the change in uterine artery PI during gestation differed between normal and complicated pregnancies and between fetal sexes, the uterine artery PI was modeled using a linear function of gestational age and the rate of change was estimated from the slope. RESULTS: While the uterine artery PI did not differ over gestation between females and males for normal pregnancies, the trajectory of this index differed by fetal sex for pregnancies complicated by either preeclampsia, preterm birth, or fetal growth restriction (p < 0.0001). The male fetuses in the complicated pregnancy group had an elevated slope compared to the other groups (p < 0.0001), suggesting a more progressive deterioration in uteroplacental perfusion over gestation. CONCLUSIONS: The uterine artery PI is widely used to assess uteroplacental function in clinical settings. The observation that this metric changes more rapidly in complicated pregnancies where the fetus was male highlights the importance of sex when interpreting hemodynamic markers of placental maturation.

Quantification of Wave Reflection in the Human Umbilical Artery From Asynchronous Doppler Ultrasound Measurements.

Elevated umbilical artery pulsatility is a widely used biomarker for placental pathology leading to intra-uterine growth restriction and, in severe cases, still-birth. It has been hypothesized that placental pathology modifies umbilical artery pulsatility by altering the degree to which the pulse pressure wave, which originates from the fetal heart, is reflected from the placental vasculature to interfere with the incident wave. Here we present a method for estimating the reflected pulse wave in the umbilical artery of human fetuses using asynchronously acquired Doppler ultrasound measurements from the two ends of the umbilical cord. This approach assumes non-dispersive and loss-less propagation of the waves along the artery and models the reflection process as a linear system with a parameterized impulse response. Model parameters are determined from the measured Doppler waveforms by constrained optimization. Velocity waveforms were obtained from 142 pregnant volunteers where 123 met data quality criteria in at least one umbilical artery. The reflection model was consistent with the measured waveforms in 183 of 212 arteries that were analyzed. The analysis method was validated by applying it to simulated datasets and comparing solutions to ground-truth. With measurement noise levels typical of clinical ultrasound, parameters describing the reflected wave were accurately determined.

Wharton's jelly area and its association with placental morphometry and pathology.

INTRODUCTION: Wharton's jelly (WJ) is the mucoid connective tissue that surrounds the vessels in the human umbilical cord and provides protection from compression and torsion in response to fetal movement. WJ is known to be altered in the presence of pregnancy complications such as gestational diabetes mellitus and preeclampsia. The present study examined associations between the cross-sectional area of WJ measured by ultrasound and postpartum placental pathology and morphometry. METHODS: The area of WJ was measured by ultrasound in 156 eligible participants between 23 and 37 weeks' gestation. Morphometric assessment of fixed cord cross sections was conducted, together with assessment of the cord and placenta for specific pathologies using standard criteria. RESULTS: From 156 participants, 123 ultrasound images met the data quality requirements and pathology reporting was completed for 99 placentas. 17 of the participants (14%) delivered a small for gestational age neonate and 32 of the 99 placentas examined (32%) had significant placental pathology findings. Area of WJ was associated with low birth weight (p = 0.002) and was associated with specific placental pathology (p = 0.01). WJ area was positively associated with placental dimensions such as width, length and surface area. DISCUSSION: Decreased WJ area is associated with clinically-significant placental pathology and WJ area scales proportionally with placental size. These findings suggest that WJ area correlates with functional capacity of the placenta and thus merits further evaluation alongside currently-available tests of placental function in clinical practice.