Pathologic placental lesions in early and late fetal growth restriction.

INTRODUCTION: The purpose of the study was to evaluate the differences in individual histopathologic placental lesions in pregnancies complicated by early-onset (<32 weeks at diagnosis) and late-onset (≥32 weeks at diagnosis) fetal growth restriction (FGR). MATERIAL AND METHODS: A cohort study of 440 singleton pregnancies complicated by FGR, diagnosed according to standard ultrasonographic criteria, followed up and delivered at the same institution between 2010 and 2016. Placental lesions were classified according to the Amsterdam Placental Workshop Consensus Criteria. Pathologic examination of placentas from 113 healthy singleton term pregnancies served as controls. Binary and multinomial logistic regression models were used to evaluate the independent association of placental lesions with the type of FGR. RESULTS: In our cohort the prevalences of early and late FGR were 37.3% (164/440) and 62.7% (276/440), respectively. The overall rates of preeclampsia (69/164 vs 59/276, P < 0.01) and absent/reversed umbilical artery pulsatility indices (61/164 vs 14/276, P < 0.001) were higher among early FGR than late FGR. Placental characteristics from early and late FGR pregnancies differed mainly in regard to maternal vascular malperfusion scores rather than fetal scores, with preeclampsia found to be a cofactor modulating the rates and severity of associated lesions. In the binary logistic analysis, recent infarcts (OR 2.44, 95% CI 1.2-5), distal villous hypoplasia (OR 1.8, 95% CI 1.0-3.2), atherosis (OR 2.71, 95% CI 1.35-5.47), persistent endovascular trophoblasts (OR 1.67, 95% CI 1.03-2.7), and a reduced fetal/placental weight score (OR 0.27, 95% CI 0.2-0.38) were independently associated with an increased likelihood of early FGR compared with late FGR. The sensitivity, specificity, and area under the curve of the model were 60% (95% CI 51.2-66.2), 89.1% (95% CI 84.9-92.3), and 0.81 (95% CI 0.77-0.85), respectively, suggesting a fair to good predictive value. CONCLUSIONS: Individual placental lesions suggestive of increased rates of ischemia, defective remodeling of spiral arteries, peripheral hypoxia interfering with villus development, and reduced placental efficiency were significantly more common in early FGR than late FGR.

Open Questions on Gestational Diabetes Mellitus in Twin Pregnancies.

BACKGROUND: The concurrent, recent increase in prevalence of Gestational Diabetes Mellitus (GDM) and twin pregnancy, in combination with the shared risk factors, has led to speculation that multiples are a risk factor for GDM and, GDM may contribute to twin complications. Twin pregnancies have different physiology and greater obstetric risks compared to singletons, including prematurity and growth restriction. However, in twins methods of GDM screening, thresholds for diagnosis and treatment, as well as glycaemic control targets, have been predominantly extrapolated from singletons. Studies investigating the impact of GDM on pregnancy outcomes in twin pregnancies are conflicting. OBJECTIVE: To provide a comprehensive, critical overview of evidence on GDM in twin pregnancies with an emphasis on prevalence, methods of screening, thresholds for diagnosis, risk of pregnancy complications and the impact of treatment on perinatal outcomes. METHODS: Review of retrospective and prospective cohort, case-control, and case-series studies on twin pregnancies with GDM published between 1980 and 2021. RESULTS: Glucose tolerance in twin pregnancies is poorly studied. Specific guidance for screening, diagnosis, and treatment of GDM in twins is lacking. Studies evaluating pregnancy outcomes in twins with GDM are few and heterogeneous. The absolute risk of maternal complications is greater in twins with GDM compared to singletons; conversely, differences in risks between twins with and without GDM may be due to maternal confounders rather than to GDM. Most studies agree on a positive effect of GDM on neonatal outcomes in twins, likely mediated by the hyperglycaemia improving fetal growth. The impact of lifestyle-measures versus medical management on pregnancy outcomes in twins with GDM is unknown. CONCLUSION: Larger longitudinal studies evaluating glucose tolerance, pregnancy outcomes and the impact of treatment both in mono and di-chorionic twins with GDM are warranted to gain further insight into the pathophysiology of this condition and guide optimal management.

Human cytomegalovirus non-primary infection during pregnancy: antibody response, risk factors and newborn outcome.

OBJECTIVES: Human cytomegalovirus (HCMV) non-primary infections can occur in pregnant women and may result in congenital infection. Comprehensive studies investigating the frequency, characteristics, risk factors and immune response of non-primary infection in pregnancy are missing, while the rate of vertical transmission is not known. METHODS: HCMV non-primary infection was investigated prospectively in 250 pregnant women. Blood and urine samples as well as saliva and vaginal swabs were collected at 13, 21 and 31 weeks of gestation and at delivery. HCMV-DNA and specific IgG and IgM levels were determined. RESULTS: Overall, 105/250 pregnant women (42.0%) developed non-primary infection. HCMV-DNA was detected more frequently in vaginal secretions (84/250 of the women, 33.6%) than in urine (35/250, 14.0%), saliva (26/250, 10.4%) and blood (7/250, 3.0%). The rate of HCMV non-primary infection increased significantly with the progression of pregnancy (from 12.9% in the first trimesters of gestation to 21.9% at delivery, p < 0.01). IgM was detected in 25/250 of the women (10.0%), with no association with non-primary infection, while anti-gB IgG was significantly higher (p < 0.01) in women with non-primary infection. Age and close contact with children were not associated with non-primary infection. No woman with non-primary infection transmitted the infection to the fetus (95% confidence interval of transmission rate: 0-3.5%). DISCUSSION: Although HCMV non-primary infection is frequent during pregnancy, the rate of congenital infection as a consequence of non-primary infection is likely to be ≤ 3.5%.

The impact of placental massive perivillous fibrin deposition on neonatal outcome in pregnancies complicated by fetal growth restriction.

INTRODUCTION: Massive perivillous fibrin deposition (MPDD) is an uncommon placental lesion which has been associated with an increased risk of adverse pregnancy outcome in retrospective series. The purpose of the study was to evaluate the frequency and consequences of MPFD in pregnancies complicated by fetal growth restriction (FGR). MATERIALS AND METHODS: A cohort study of 355 pregnancies complicated by FGR diagnosed according to standard ultrasonographic criteria, enrolled, followed and delivered at a single obstetric unit. Pathological placental lesions were classified according to the Amsterdam Placental Workshop Consensus. Penalized logistic regression models were used to evaluate the association of MPFD with maternal risk factors, other pathological lesions and neonatal outcome. RESULTS: The rates of moderate (25-50% of villi) and severe (>50% of villi) MPFD were 8.7% (31/355) and 3.1% (11/355), respectively. Compared to other FGR cases, MPFD pregnancies were characterized by higher placental volume (450 ±â€¯144.5 SD as compared to 412.2 ±â€¯151 cm3,p < 0.001) and lower birthweight/placental weight ratio (5.32 ±â€¯1.53 compared to 6.1 ±â€¯1.52,p < 0.001). The rates of abnormal Doppler ultrasound studies of umbilical and middle cerebral artery were similar in MPFD subjects and controls. After correction for gestational age and birthweight, MPFD was associated with an increased risk of neonatal intraventricular hemorrhage (>grade II) (OR = 5.66,95% CI = 1.69-18.97), sepsis (OR = 5.9, 95% CI = 1.27-27.12), proven necrotizing enterocolitis (OR = 9.84,95% CI = 2.49-38.8) and overall severe adverse neonatal outcome (OR = 5.71,95% CI = 2.05-15.87). CONCLUSIONS: Moderate-to-severe MPFD was relatively common among FGR pregnancies and was associated with morphometric modifications of placenta and with an increased risk of severe adverse neonatal outcome.