Prediction of spontaneous preterm birth using fetal fibronectin in women with a low-lying placenta

Objective: To determine the effect of a low-lying placenta on the concentration of quantitative fetal fibronectin (qfFN) in the cervicovaginal fluid (CVF), and predictive accuracy for spontaneous preterm birth in asymptomatic high-risk women (18?⁺?⁰–24?⁺?⁰ weeks gestation). Methods: Median concentrations of qfFN were compared in women who had a low-lying placenta, covering the cervical os (n?=?61) to matched controls (n=?61) without a low-lying placenta. Proportions of women with raised qfFN concentrations (>10?ng/ml), and false positive and negative rates (FPR and FNR) for spontaneous preterm delivery were also compared. Results: The median concentration of qfFN in women with low-lying placenta was 5.0?ng/mL, compared with 6.0?ng/mL in controls. Proportion of women with raised levels (>10?ng/mL), positive levels (>50?ng/mL) and very high levels (>200?ng/mL) were similar in both groups (62.3% versus 59.0%, 16.3% versus 22.0% and 6.5% versus 4.9%, p?>?0.05 for all thresholds). The FPR and FNR rate for delivery before 34 and 37 weeks were also comparable (FPR 90.0% versus 85.7% and 80.0% versus 78.6%; FNR 5.8% versus 4.3% and 9.8% versus 8.5%).

Conclusions: CVF qfFN concentrations in asymptomatic high-risk women are not affected by the presence of a low-lying placenta.     

Maternal GRB10 microdeletion is a novel cause of cystic placenta: Spectrum of genomic changes in the etiology of enlarged cystic placenta

IntroductionThe genetics and pathology of diploid complete and triploid partial hydatidiform moles have been well established. Enlarged cystic placenta often indicates an underlying etiology and is frequently associated with adverse pregnancy outcome. Several imprinted genes are strongly expressed in placental tissues and essential for normal placental growth and development. Disruption of these imprinted genes can lead to abnormal placental pathology and placental stunting or overgrowth. We present the genetic etiologies of five unusual mosaic cases of enlarged cystic placentas and report a novel etiology, mosaicism for deletion of the maternal GRB10 gene.MethodsFive mosaic placental mesenchymal dysplasia cases with discrete populations of “cystic” and “normal” villi and/or atypical p57^KIP2 immunostaining were evaluated by genetic analysis; including G-banded karyotyping, fluorescence in situ hybridization (FISH), whole genome CGH + SNP microarray, conventional Sanger sequencing, and STR microsatellite analysis.ResultsGenetic etiologies ranged from genome-wide changes, including mosaic androgenetic isodisomy and mosaic diandric triploidy, to a novel microdeletion of the maternally-expressed GRB10 gene. An abnormal mosaic population of cells was also detected in the fetus in two cases.DiscussionFour cases were mosaic for either diandric triploidy or an androgenetic cell population, and the enlarged cystic placentas were likely due to an excess of paternally-expressed growth promoting genes and also the absence of maternally-expressed growth restricting genes. Also we identified mosaicism for a novel microdeletion of the maternal GRB10 allele, a potent growth inhibitor, which resulted in placental overgrowth in the cystic area of one placenta. We advocate the use of ancillary techniques to investigate complex mosaic cases of enlarged cystic placentas to discover atypical genetic etiologies and to increase our understanding of the placental genome.     

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.

Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2?g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.

Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p?Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p?p?p?Igf2-P0, Vegf, and Flt-1, respectively).

Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.     

Recovery of uterine and ovarian function in patients with complete placenta previa after caesarean delivery: A retrospective study

This retrospective study was designed to explore the recovery of uterine and ovarian function in patients with complete placenta previa (PP) after caesarean delivery (CD). 136 complete placenta previa patients (group completed placenta previa) and 140 patients without complete PP (group non-PP, control group) were included in this study from Jan 2016 to Dec 2018. Subgroup analysis of patients with complete PP was made to determine the impact of different hemostatic methods used during CD on the recovery of uterine function. There were no statistically significant differences between the 2 groups in postpartum menstrual cycle changes, ovarian hormone, and uterine vascular supply as measured by pulsatility index and systolic/diastolic ratio (P > .05). However, the group with complete PP had a reduced endometrial thickness (0.47 ± 0.11 vs 0.50 ± 0.12, P < .001), a lower uterine resistance index at 42nd days (0.84 ± 0.03 vs 0.90 ± 0.03, P < .001), and a delayed resumption menstruation (7.07 ± 2.61 vs 5.31 ± 2.16, P < .001) when compared with control group. Subgroup analysis showed that RI index of all subgroups in completed PP group was lower, endometrial thickness was thinner and the time to menstrual recovery was longer than that of non-PP group. In conclusion, the endometrial thickness and blood supply at 42nd days, not ovarian function, maybe affected after CD in patients with complete PP.     

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients

Aims/hypothesis: We have previously shown that placentae from patients with gestational diabetes mellitus who did not receive insulin had lower glucose transport and utilisation than non-diabetic control subjects. To assess the placental glucose handling characteristics of women with gestational diabetes mellitus receiving insulin, we examined glucose transport and utilisation in placentae from three groups of women after term delivery: those with gestational diabetes mellitus and receiving insulin (n = 9, insulin group); those with gestational diabetes mellitus and not receiving insulin (n = 10, no insulin group); and those with normal, non-diabetic pregnancies (n = 9, control group). Methods: Dual perfusion of an isolated placental lobule was done using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l. Glucose and l-lactate concentrations in the maternal and fetal effluents were measured. Direct glucose transfer from the maternal to the fetal effluent was measured using ¹⁴C-d-glucose. Mean rates in μmol ming^–1 (wet tissue) at maternal glucose concentration of 8 mmol/l are shown. Results: Glucose uptake from the maternal perfusate (insulin group 0.57, no insulin group 0.30) and net glucose transfer to the fetal effluent (insulin group 0.41, no insulin group 0.20) both increased in the placentae of women receiving insulin compared with the diabetic group not receiving insulin. Both groups of patients had lower placental glucose utilisation than the control group (insulin group 0.16, no insulin group 0.10, control group 0.25). Conclusion/interpretation: These results suggest that materno-fetal glucose transport increases in the placentae of women with gestational diabetes mellitus who receive insulin compared with those women who do not receive insulin. [Diabetologia (2001) 44: 1133–1139] Received: 19 February 2001 and in revised form: 17 April 2001     

Increased human leukocyte antigen-G expression at the maternal–fetal interface is associated with preterm birth

Objective: The maternal–fetal interface must modulate immune function to allow tolerance of fetal cells while still reacting to pathogens to suppress infection. Human leukocyte antigen-G (HLA-G) is a class Ib major histocompatibility complex protein involved in maternal–fetal tolerance. We posited that alterations in placental HLA-G expression predispose women to preterm birth. The aim of this study was to compare HLA-G expression in the maternal–fetal interface of term versus preterm human placentas.

Methods: We performed a cross-sectional study of specimens from the basal plate of the human placenta from women enrolled in a tissue specimen and clinical data consortium. Immunohistochemistry with digital microscopic analysis was used to quantify HLA-G protein expression in the basal plate from preterm and term placentas.

Results: Preterm birth <37 weeks occurred in 29.5% of 149 singleton pregnancies. HLA-G-positive cells occupied one-third of the basal plates, and the HLA-G-positive area was increased by 14% in placentas from preterm births than in those from term births (32.1% in term placentas versus 36.6% in preterm placentas).

Conclusion: Although HLA-G is required for maternal tolerance of the semi-allogeneic fetus, higher levels of HLA-G expression at the maternal–fetal interface is associated with preterm birth.