Marianna Pina Rambaldi

Stillbirth and fetal growth restriction

Objective: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. Methods: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. Results: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). Conclusions: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.

Inherited and Acquired Thrombophilias

Thrombophilias represent an evolving story that continues to stir controversy for care providers and obstetrical patients. The predominant thrombophilic mutations include the factor V Leiden mutation, prothrombin gene mutation G20210A, methylene tetrahydrafolate reductase C667T, and deficiencies of the natural anticoagulants proteins C and S, and antithrombin. Prospective cohort studies have provided an accurate assessment of the risk of placenta-mediated complications posed by common inherited thrombophilic conditions. Acquired thrombophilic conditions consist of the antiphospholipid antibody syndrome (APAS) and hyperhomocysteinemia. Well-conducted, placebo-controlled, randomized trials have demonstrated no benefit of anticoagulation in women with recurrent pregnancy loss and inherited thrombophilia. The routine use of anticoagulation to prevent other placenta-mediated complications in the setting of inherited thrombophilia should be considered experimental until the results of adequate clinical trials are available. Heparin anticoagulation and antiplatelet therapies are the cornerstone of treatment of APAS in pregnancy.

Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology.

Objective To investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births. Methods A retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions. Results There was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR. Conclusion The assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes

Abstract Introduction: Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. Materials and methods: Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ2-test (significant values when p < .05). Results: The prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine >1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine <1.2 mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73 m2 resulted in a 18.73 times greater risk of preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery. Discussion: A multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

Human leukocyte antigen DQ2/DQ8 positivity in women with history of stillbirth

The aim of this study was to investigate the prevalence of human leukocyte antigens (HLA) DQ2 and DQ8 haplotypes, two common polymorphisms associate with celiac disease (CD), in women with previous stillbirth, but not affected by CD.

Doppler velocimetry and adverse outcome in labor induction for late IUGR.

Abstract Background: Late onset intrauterine growth restriction (IUGR) represents one of the main causes of perinatal morbidity/mortality. No guidelines are available on labor induction in IUGRs, even if delivery at 37/38 weeks is suggested. This study aims to assess maternal–fetal variables related to adverse outcome in labor induction for late IUGR. Methods: One hundred cases of induction for late IUGR were retrospectively revised on fetal weight, MCA, UA, CPR and uterine artery (utA) Doppler, oligohydramnios, Bishop score, start of induction, augmentation. The variables were matched with the following adverse outcomes: CS or vacuum extractor delivery (IVD); NICU admission; low Apgar score; UA pH < 7.10. Results: Regular vaginal delivery occurred in 65% of cases; the rate of CS and IVD was 32% and 5%. UA, MCA and CPR abnormalities were all significantly related to a higher risk of CS. Bishop score < 3 and start of induction by oxitocin resulted statistically associated to CS, while prostaglandins were related to vaginal delivery. No augmentation and oxitocin in labor were positively related to vaginal delivery. Maternal morbidity and Bishop score < 3 showed a significant association with NICU admission. Discussion: Doppler velocimetry of UA, MCA and CPR are useful tools for the identification and management of the late term IUGRs.

D4. MCA/UtA ratio at first observation is associated with birthweight in late onset IUGR.

Abstract Introduction: MCA and uterine artery Doppler PI are commonly used in the evaluation of IUGR. Targets: This retrospective pilot study aims to investigate whether MCA/UtA ratio may identify adverse outcome in late onset IUGRs. A cohort of 69 pregnancies affected with late IUGR which underwent labor induction according to local protocols was retrospectively revised on the relationship between MCA/UtA ratio at first observation and the following adverse outcomes: cesarean section for nonreassuring fetal status, birthweight (expressed as percentile and continuous values, umbilical artery pH, NICU admission and Apgar score < 7 after 1 and 5 min. Results: The study population included 75.4% nulliparous women. Mean gestational age was 36.7 and 38.7 weeks’ gestation for diagnosis and induction, respectively. MCA/UtA ratio resulted significantly associated with a lower trend in birthweight, with a variation of 109.72 g for each unit considered (p = 0.040). The other outcomes considered showed no association. Conclusions: MCA/UtA ratio at first observation may be associated with lower birthweight in late onset IUGRs. Further prospective studies are expected.

PP109. Risk of preeclampsia in homologous and oocyte donation IVF pregnancies.

INTRODUCTION Women who conceived by donor oocyte in vitro fertilization (IVF) are at high risk for placenta-related complications, because of advanced maternal age, nulliparity and maybe for an altered immune response. OBJECTIVES The aim of this case-control study is to compare the incidence and the characteristics of preeclampsia in women who conceived by oocyte donor or by homologous IVF. METHODS Data were collected from 65 consecutive women who conceived through oocyte donor IVF and 71 consecutive pregnancies from homologous IVF in women older than 35years (control group), who attended our institution between 2009 and 2011. Data are expressed as percentage, average and standard deviation (SD). Statistical analysis was performed by chi-square test for unpaired data and the results were considered significant with p<0.05. RESULTS Thirteen women from the donor oocyte group were excluded because of first trimester miscarriage, ectopic pregnancy and lack of data. After the exclusion, 52 pregnancies from oocyte donation were compared to the control group. Baseline characteristics, such as maternal age, BMI, parity and prevalence of twin pregnancies were similar in the two groups. Preexisting hypertension was present only in the oocyte donor IVF group (n=6 cases). The risk of preeclampsia was significantly related to oocyte donor IVF (27% vs 5.6%, p=0.0024 OR=6.17), even when only singleton pregnancies were considered (16.7 vs 1.9%; p=0.02, OR=9). When women with preexisting hypertension were excluded, the incidence of severe preeclampsia remained significant (p=0.02). This result was not confirmed when both preexisting hypertension and twin pregnancies were excluded (p=0.09), even if the percentage of cases was higher in the oocyte donor IVF group (10.7% vs 1.85%). Three cases of life threatening severe preeclampsia occurred before the 24th week, two of which required interruption of pregnancy; one case was complicated by eclampsia. The two groups did not show significant differences in terms of prevalence of IUGR, both in multiple and singleton pregnancies, even if percentage values were higher in the donor IVF group (multiple: 21.2% vs 11.3%, p=0.21/ singleton 10% vs 5.6%, p=0.48). CONCLUSION IVF with oocyte donation stands as an independent risk factor for preeclampsia. The risk of developing a severe and early preeclampsia may be increased when chronic hypertension occurs.

PP120. Hydatidiform mole as a cause of eclampsia in the first trimester: A case report

INTRODUCTION The occurrence of preeclampsia before the 20th week of gestation is rare and it has been associated with hydatidiform molar pregnancy. OBJECTIVES We describe a case of first trimester eclampsia which occurred in a patient with hydatidiform mole. METHODS Case report. RESULTS A 16-year-old woman came to emergency service for abdominal pain and vaginal bleeding. She had been suffering of vomiting after meals and complaining for abdominal mass for 2months, without consulting her physician. The last reported period was 1month before; the patient told her periods were regular and the only disease she reported was chronic HBV hepatitis. Vital parameters were all normal. Urine pregnancy test resulted always negative. The gynecological exam reported an increased uterus and a little bleeding, so serum bhCG was performed because of the exam findings and resulted 110,5317UI/L. The transvaginal ultrasound showed images consistent with gestational trophoblastic disease. Computed tomography (CT) scan revealed the presence of an uterine mass and three lung nodules, reported as possibly metastatic. A few days later, the patient underwent dilation and curettage (D&C). Second grade hydatiform mole was diagnosed by histology. After D&C, the serum bhCG was 202,511UI/L. The day after, the patient presented bilateral acute blindness, followed by incoming general seizures, concurrent hypertension and tachycardia. Intravenous diazepam, levetiracetam and mannitol controlled the seizures, but the conscious state of the patient remained critical. Temperature reached 40°C, with concurrent leukocytosis. Then, a lumbar puncture was performed but it resulted negative for inflammatory/infective processes. A head CT was performed the same day and showed a posterior reversible encephalopathy syndrome (PRES). Intravenous methylprednisolone was started. Long term therapy with methylprednisolone and levetiracetam was effective and the patients status improved and stabilized. A subsequent chemotherapy with EMA/CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine/oncovine) was performed for six cycles, until serum bhCG resulted negative and the abdomen/pelvis ultrasound, head NMR and chest X-ray resulted normal. CONCLUSION Preeclampsia and eclampsia are regarded as common causes of PRES, which is considered to be the result of vasogenic brain edema. Clinical and imaging findings are usually reversible. Early diagnosis and elimination of possible causes are important in order to avoid permanent visual or brain injury. Imaging (especially MRI) should be carried out in eclamptic patients with visual disturbance in order to exclude other causes of blindness. Molar pregnancy is a rare but important cause of eclampsia, and it has always to be considered in case of early manifestations.

L16. The role of glycemic control in the development of preeclampsia in type 1 diabetic women.

the release of the IPG P-type has been described at placental level with acquired alterations in the activation of proteins involved in insulin signalling in preeclamptic specimens: this was proposed to explain the glycogen accumulation found in these placentas. This confirms that in preeclampsia the placenta is insulin resistant and this is known to extend to the mother with IPG-P as a unifying mediator. In fact, a very high concentration of IPG P-type was reported in the amniotic fluid under physiological conditions (suggesting a role in the maintenance of the carbohydrate metabolism in the fetal-placental unit) and a significant increase of its concentrations in maternal fluids during preeclampsia suggesting a leakage of IPG-P into the maternal blood that probably contributes to the disease syndrome of preeclampsia. The study of the relationship between the nutrients provided by endometrial glands during early pregnancy and how this matches the metabolic requirements of the fetus in its low oxygen environment may explain the bases of the pathophysiology of preeclampsia. In fact, if a disconnect occurs between the placental/fetal metabolism and oxygen tension this could lead to a preeclamptic type of syndrome via leakage of Wharburg/IPG mediators into the maternal circulation.