Umbilical cord diameter percentile curves and their correlation to birth weight and placental pathology.

OBJECTIVE: The aims of this study were to develop a nomogram of umbilical cord diameter (UCD) for pathologic examination of the placenta, to identify the umbilical cord components responsible for variations in UCD, and to examine the relationship between UCD and other placental pathologic features and perinatal outcome. STUDY DESIGN: We prospectively collected 497 umbilical cords between 18 and 41 weeks' gestation over a 1-year period. Fresh-tissue UCD were grouped according to gestational age and compared to sonographic and histological measurements. Associations between UCD percentile and placental pathologic findings or obstetrical outcomes were examined. RESULTS: Mean UCD increased with gestational age until a plateau at 1.0 cm in the third trimester, a value that was 0.56 cm less than sonographic measurements prior to delivery and 0.17 cm greater than UCD measured histologically. Umbilical cord components varied with UCD percentile, with umbilical vessel area increased in thick cords (p < 0.001) and Wharton's jelly area reduced in thin cords (p = 0.002). Thin umbilical cords were associated with at least one pathologic histological placental finding (p = 0.02), low placental weight (p < 0.001), single umbilical artery (p = 0.02), marginal cord insertion (p = 0.01), and low infant birth weight (p < 0.001). CONCLUSIONS: This study provides reference curves for post-delivery UCD from 18 to 41 weeks' gestation for use by perinatal pathologists. We show that increased UCD is a function of increased umbilical blood vessel volume and decreased UCD is a function of decreased Wharton's jelly volume. UCD shows a strong association with placental and infant birth weight.

Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial.

OBJECTIVE: To conduct a pilot randomized controlled trial of unfractionated heparin (UFH) in women considered at high risk of placental insufficiency in the second trimester. METHODS: Women with either false-positive first trimester (pregnancy-associated placental protein-A [PAPP-A] < 0.35 MoM) or second trimester (alpha-fetoprotein [AFP] > 2.0 MoM, inhibin > 3.0 MoM, human chorionic gonadotropin > 4.0 MoM) serum screening tests or medical/obstetric risk factors were screened for placental insufficiency by sonographic evaluation of the placenta and uterine artery Doppler between 18 and 22 weeks. Thrombophilia screen-negative women with two or three abnormal test categories were randomized by 23+6 weeks to self-administration of subcutaneous unfractionated heparin (UFH) 7500 IU twice daily until birth or 34 weeks, or to standard care. Maternal anxiety and other maternal-infant outcomes were determined. RESULTS: Thirty-two out of 41 eligible women consented, with 16 women randomized to UFH and 16 to standard care. There was no statistically significant difference identified between the two treatment groups (standard care vs. UFH) for the following: maternal anxiety score (mean [standard deviation]), 14.2 [± 1.6] vs. 14.0 [± 1.8]; birth weight (median [range]), 1795 [470-3295]g vs. 1860 [730-3050]g; perinatal death, 3 vs. 0; severe preeclampsia, 2 vs. 6; placental weight < 10th percentile, 7 vs. 4; or placental infarction, 4 vs. 3. CONCLUSION: Our study design identified women at high risk of adverse maternal-infant outcomes attributable to placental insufficiency. Women with evidence of placental insufficiency were willing to undergo randomization and self-administration of UFH without increased maternal anxiety.

Pathologic basis of echogenic cystic lesions in the human placenta: role of ultrasound-guided wire localization.

OBJECTIVE: The sonographic appearance of the placenta is normally homogenous throughout the second trimester. A variety of abnormalities in placental texture have been described, some of which may be pathologic and associated with adverse clinical outcomes. We characterized the pathologic basis of one lesion termed echogenic cystic lesions (ECLs) that may be a prognostic marker in intrauterine growth restriction (IUGR). STUDY DESIGN: We retrospectively correlated placental pathology in 50 pregnancies that had a total of 84 ECLs documented by ultrasound prior to delivery. Six additional women with placental ECLs prospectively underwent immediate post-delivery ultrasound-guided wire localization of 9 lesions followed by placental pathology. Obstetric outcome data were recorded. RESULTS: Severe pre-eclampsia (20%) and extreme IUGR (18%) were common outcomes. Of 93 ECLs identified, 46 (49%) gross lesions were found by placental pathology. Inter-villous thrombosis was the most significant lesion found (30/46, 65%) compared to all other lesions (35%; Z-Test, p = 0.007). Ultrasound guidance identified 8/9 (89%) lesions of which 6/8 (67%) were inter-villous thrombosis. Associated lesions (infarction, 36%; advanced villous maturation, 27%) and small placental weight (<10th centile, 38%) were present in 50%, but did not increase the risk of adverse perinatal outcome. CONCLUSIONS: ECLs are most commonly due to inter-villous thrombosis. The adverse clinical outcomes may be mediated by associated lesions not readily detectable by ultrasound. Ultrasound-guided wire localization is a promising research tool for future large-scale cohort studies needed to define the clinical utility of placental ultrasound findings.

Incorporation of femur length leads to underestimation of fetal weight in asymmetric preterm growth restriction.

OBJECTIVE: To review the performance of a variety of biometry formulae for estimated fetal weight (EFW) in the management of severely growth restricted fetuses with abnormal umbilical artery Doppler at a single perinatal institution. METHODS: Forty-three pregnancies were retrospectively reviewed. Inclusion criteria were: chromosomally/ structurally normal fetus; complete ultrasound biometry at < or = 7 days from delivery; EFW < 10(th) centile; absent/reversed end-diastolic flow in the umbilical arteries; and delivery at < 32 + 6 weeks. EFW accuracy and precision were compared among nine formulae utilizing combinations of head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) measurements. RESULTS: Twenty-six (60.5%) fetuses showed asymmetric growth (HC/AC ratio > 95(th) centile). Analysis of the systematic and random errors associated with each formula showed that the birth weight of asymmetrically-grown fetuses was most closely approximated by the Hadlock equation that utilized BPD and AC measurements only. The birth weight of symmetrically-grown fetuses was most closely approximated by EFW derived from Hadlock equations that utilized > or = three biometry measurements, including FL. Incorporation of FL into Hadlock formulae led to significant underestimation of birth weight in the fetuses with asymmetric growth (mean percentage error +/- SD: EFW(FL-AC), -13.3 +/- 9.8%; EFW(BPD-FL-AC), -10.8 +/- 9.8%; EFW(HC-FL-AC), -11.8 +/- 9.3%; EFW(BPD-HC-FL-AC), -11.7 +/- 9.5%; P < 0.001). The same equations were accurate in fetuses with symmetric growth (EFW(FL-AC), 3.1 +/- 10.0%; EFW(BPD-FL-AC), 1.0 +/- 8.9%; EFW(HC-FL-AC), 0.3 +/- 8.7%; EFW(BPD-HC-FL-AC), 0.4 +/- 15.5%). Use of the best performing equation (Hadlock 3), which does not include FL, to estimate weight in asymmetrically-grown fetuses over 28 weeks' gestation, would have reduced the proportion of those with an underestimation of fetal weight of > 100 g from nine (50.0%) to three (16.7%). CONCLUSIONS: Biometry methods that exclude FL should be considered in asymmetric intrauterine growth restriction associated with abnormal umbilical artery Doppler waveforms.

Placental size and the prediction of severe early-onset intrauterine growth restriction in women with low pregnancy-associated plasma protein-A.

OBJECTIVES: Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A. METHODS: We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A

Early gene expression and morphogenesis of the murine chorioallantoic placenta in vivo and in vitro.

BACKGROUND: In mice the exchange of oxygen and nutrients between mother and fetus occurs in the chorioallantoic placenta where fetal capillaries come in close proximity with maternal blood perfusing trophoblast-lined sinusoids. Despite its critical importance, quantitative in vivo gene expression over the initial stages of chorioallantoic placental development has not been described, nor are there in vitro systems recapitulating the critical syncytiotrophoblast differentiation step in its formation. Here we describe molecular events that occur during the onset of chorioallantoic morphogenesis in mice in vivo, and in placental explant and whole conceptus cultures in vitro. RESULTS: Chorioallantoic morphogenesis began immediately following allantoic fusion with the chorion in vivo, and was associated with significant upregulation of syncytiotrophoblast associated mRNA (Gcm1 and Syncytin A). However mouse placentas with chorioallantoic point attachment cultured with the allantois or as whole conceptuses did not upregulate Gcm1 and/or Syncytin A, suggesting that syncytiotrophoblast differentiation did not occur in vitro. Failure of morphogenesis appeared to be due to failure to sustain in vitro the chorionic trophoblast cells from which the syncytiotrophoblast cells are derived. In vitro culture conditions did support the upregulation of ectoplacental cone marker Tpbpalpha, maintenance of giant cell marker Pl1, and maintenance of Fgfr2 expression; all of which mimicked in vivo events observed over this developmental interval. CONCLUSIONS: We conclude that chorionic trophoblast maintenance and the early events that occur in vivo between chorioallantoic point attachment and primary villous formation are dependent on undefined intrauterine factors that were not present in the in vitro culture system. Nevertheless, in vitro culture conditions were appropriate to reproduce in vivo expression levels of Fgfr2, Pl1, and Tpbpalpha in placental explants.