Impact of maternal obesity on the risk of preterm delivery: insights into pathogenic mechanisms.

PURPOSE: Preterm delivery (PTD) represents the leading cause of neonatal death and disability. Among risk factors for PTD, maternal obesity (MO) is becoming an ever more relevant condition in developed countries, although the mechanisms relating this condition to higher risk of PTD is not clear. Aim of this narrative review is to summarize evidences from clinical and translational research showing how MO might negatively impact on pregnancy and neonatal outcomes, particularly, by increasing the risk of PTD. METHODS: We performed comprehensive review of the literature in PubMed and Google Scholar databases for studies from 1998 to 2018 linking MO to PTD and inflammation. RESULTS: Chronic inflammatory status associated to increased synthesis of adipokines and cytokines from fat tissue has been shown in obesity. Obese women have a higher risk of both spontaneous and medically induced PTD. In about 50% of cases of spontaneous PTD, an infection-induced chorion amnionitis can be detected while in the remaining 50% a sterile inflammatory response has been described. Activation of uterine innate immunity system in intra-amniotic cavity and in chorioamniotic membranes might represent the missing link between MO and the pathogenesis of PTD. CONCLUSION: Tissue inflammation might represent the pathogenic link between MO and increased occurrence of PTD. The achievement of pre-pregnancy normal maternal weight and body mass index is a fundamental aim of public health to reduce the incidence of PTD and get optimal reproductive outcomes.

Perinatal outcome in gestational hypertension: Which role for developing preeclampsia. A population-based cohort study.

OBJECTIVE: To analyze perinatal outcome in singleton pregnancies complicated by gestational hypertension (GH), to investigate the rate of women developing preeclampsia (PE) and to describe maternal features associated with progression to PE. STUDY DESIGN: This is a population-based retrospective cohort-study involving 514 singleton pregnancies with a diagnosis of GH at admission. RESULTS: In pregnancies with GH, a poorer pregnancy outcome in comparison to healthy controls was observed in terms of gestational age at delivery, birthweight and birthweight percentile. The observed overall rate of developing PE was 11.7 %. Of all pregnancies with GH at admission, two different groups were identified based on the diagnosis at delivery: GHPE, i.e. women who developed PE (60/514; 11.7 %), and GHnoPE, i.e. women who did not develop PE (454/514; 88.3 %). In the GHPE group it was observed that the 62 % of the women with diagnosis of GH earlier than 28 weeks developed PE while only 2% developed PE if the diagnosis of GH was performed later than 36 weeks. The observed rate of developing PE was 14.7 % in pharmacologically treated hypertensive women, whereas the diagnosis of PE has been made in only 3% of non-treated women. CONCLUSION: Pregnant women with raised blood pressure are at risk of having a less favourable perinatal outcome. The risk is mainly associated with the progression to PE. Major determinants of the risk of developing PE are the earlier gestational age at diagnosis of GH, the necessity of treatment and the number of anti-hypertensive drugs needed for controlling blood pressure.

Fetal Doppler Parameters at Term in Pregnancies Affected by Gestational Diabetes: Role in the Prediction of Perinatal Outcomes.

OBJECTIVE: The timing of delivery for women affected by gestational diabetes (GDM) is still controversial. Good clinical practice often suggests offering induction of labor at term in order to reduce the complications associated with this condition, while recent evidence supports expectant management. Fetal Doppler parameters represent a validated tool for testing fetal well-being at term and can select pregnancies that need increased surveillance. The aim of the present study was to evaluate the role of fetal Doppler parameters at term for the prediction of pregnancy outcomes in patients affected by GDM. METHODS: Prospective cohort study in a single center. Evaluation of umbilical artery (UA) PI, middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR) and umbilical-to-cerebral ratio (UCR) at > 37 weeks of gestation in singleton, morphologically normal pregnancies affected by GDM, was performed in order to estimate the association between ultrasound measurements at term and perinatal outcome. Regression linear analysis was used to estimate the association between fetal Doppler parameters and neonatal pH, neonatal Apgar score, neonatal weight and a composite adverse outcome. The receiver operating characteristic (ROC) curve was used to estimate the possible predictive value of the above association. RESULTS: Our results on 130 women showed MCA PI to be the best predictor of perinatal outcomes in terms of low Apgar score at the 1st minute (p = 0.00), pH (p = 0.02) and composite adverse outcome (p = 0.05). UCR showed a significant correlation with neonatal pH (p = 0.02). No significant correlations for UA PI and CPR MoMs have been demonstrated in our population. However, the small sample size is a limitation of the study. CONCLUSION: Evaluation of MCA Doppler and eventually UCR at term can be a useful tool to discriminate pregnancies affected by GDM that can benefit from IOL before 41 weeks in order to reduce complications related to this condition.

The pathogenic role of autoantibodies in recurrent pregnancy loss.

In the present manuscript, we review the recent research investigating the pathogenic association between most studied autoantibodies and recurrent pregnancy loss. Pregnancy loss represents a common obstetric complication occurring in about 15%-25% of all clinically recognized pregnancies. The recurrence of pregnancy loss identifies a distinct clinical entity, that is recurrent pregnancy loss (RPL), affecting about 2%-4% of couples. Several factors, including age, chromosomal abnormalities, uterine anomalies, thrombophilic disorders, endocrinopathies, hormonal and metabolic disorders, infections, sperm quality, and lifestyle issues, are involved in RPL. The role of autoantibodies in RPL is only partially determined. In some cases (antiphospholipid antibodies [aPL]), their involvement is well established. In other cases (anti-thyroid autoantibodies, antinuclear, anti-transglutaminase, and anti-endomysial antibodies), it is still debated, despite multiple, although not fully conclusive, evidences strongly suggest a possible involvement in RPL. Further extensive research is needed to definitively confirm or exclude their actual role.

Ultrasound features and clinical outcome of patients with malignant ovarian masses diagnosed during pregnancy: experience of a gynecological oncology ultrasound center.

OBJECTIVE: The number of women diagnosed with ovarian masses during pregnancy has increased in recent years and the management of these women can be controversial. We aim to describe ultrasound characteristics and clinical outcomes of patients with malignant ovarian masses diagnosed during pregnancy. METHODS: Patients with a histological diagnosis of malignant ovarian mass detected during pregnancy who underwent pre-operative ultrasound by experienced ultrasound examiners between December 2000 and November 2017 were included in this retrospective observational study. Ultrasound characteristics of the masses were described using International Ovarian Tumor Analysis terminology. Patients with ovarian masses but without histopathological reports were excluded. Results are presented as absolute frequency (percentage) for nominal variables and as median (range) for continuous variables. Results A total of 22 patients were included in the analysis. The median age was 32.5 (range 23-42) years and median gestational age at diagnosis was 13.5 (range 4-30) weeks. Eight (36.4%) patients had a serous/endocervical-type borderline tumor, seven (31.8%) patients had a primary epithelial ovarian carcinoma, five (22.8%) patients had a metastatic tumor to the ovary, and two (9%) patients had a mucinous borderline tumor. At ultrasound, mucinous borderline tumors were multilocular (1/2, 50%) or multilocular-solid (1/2, 50%) lesions. Serous/endocervical-type borderline tumors were unilocular-solid (3/8, 37.5%) or multilocular-solid (5/8, 62.5%) masses and all had papillary projections. Most invasive epithelial ovarian cancers were multilocular-solid masses (5/7, 71.4%). All metastatic tumors appeared as solid masses. No patients with borderline tumors had a cesarean section due to disease, whereas most patients with epithelial ovarian carcinomas (4/7, 57.2%) and with ovarian metastases (3/5, 60%) had a cesarean section due to disease. No neonatal complication was reported for patients with borderline tumors or epithelial ovarian carcinomas, whereas two of three newborns of patients with metastatic tumor died of the disease. CONCLUSION: At ultrasound, morphological features of malignant ovarian masses detected during pregnancy are similar to those described in non-pregnant patients. The likelihood of undergoing cesarean section increases with malignant disease in the ovary.

The impact of primary Sjogren's syndrome on pregnancy outcome: our series and review of the literature.

OBJECTIVE: Firstly, to investigate the pregnancy outcome of women with primary Sjogren's Syndrome (pSS) in a case-control study; secondly, to perform a review of the literature in order to clarify if the pregnancy outcome is affected by pSS and influenced by the disease clinical onset. METHOD OF STUDY: Thirty-four pregnancies with pSS and 136 controls were retrospectively collected. RESULTS: Six pregnancies occurred before the pSS diagnosis and 28 after the pSS diagnosis. Two cases were complicated by intrauterine atrio-ventricular block. A statistically significant increase of the rate of spontaneous abortions, preterm deliveries and cesarean section was found in pSS pregnancies. The mean neonatal birth weight and the mean neonatal birth weight percentile were significantly lower in the offspring of women with pSS in comparison to controls. Similar pregnancy outcome was observed in women with pSS diagnosis before and after the index pregnancy. CONCLUSIONS: Women with pSS experienced complicated pregnancies more frequently than controls, regardless of the onset of the symptoms, showing that the immunological disturbance is present throughout the reproductive life.

Neonatal outcome in hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders in pregnancy account for increased perinatal morbidity and mortality when compared to uneventful gestations. AIMS: To analyze perinatal outcome of pregnancies complicated by different kinds of hypertension to uncomplicated pregnancies in a series of Italian women and to compare our data with series from other countries. STUDY DESIGN: The sample was divided into four groups of hypertensive women: chronic hypertension (CH), gestational hypertension (GH), preeclampsia (PE), and chronic hypertension complicated by preeclampsia (CHPE). One thousand normal pregnancies served as controls. SUBJECTS: Neonatal features of the offspring of 965 Italian women with hypertension in pregnancy were evaluated. MEASURES: Gestational age, birthweight and the rate of small for gestational age were the outcomes. Perinatal asphyxia and mortality were also assessed. RESULTS: Gestational age, the mean of birth weight and birth percentile were significantly lower in all groups with hypertensive complications when compared with controls. The rate of very early preterm delivery (<32 weeks) was 7.8% in CH, 5.9% in GH, 21.2% in PE and 37.2% in CHPE while it was to 1.2% in the control group. The rate of SGA was globally 16.2% in CH, 22.8% in GH, 50.7% in PE, 37.2% in CHPE and 5% in controls. The rate of SGA in PE was much higher than reported in series from other countries. CONCLUSION: Comparing our data with those reported from other countries, it is evident that the rate of fetal growth restriction in PE we found in our center, is significantly higher even in the presence of a global lower incidence of PE.

Predictors of pregnancy outcome in antiphospholipid syndrome: a review.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.

Uterine artery velocity waveforms as predictors of pregnancy outcome in patients with antiphospholipid syndrome: a review.

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low-resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.

Cancer in pregnancy: results of a series of 32 patients.

BACKGROUND: Cancer complicates approximately 1 in 1000 pregnancies. In pregnancy management, whether the benefits outweigh the risks derived from therapy must be carefully considered. MATERIALS AND METHODS: Thirty-two pregnant patients with the diagnosis of malignancy were followed. The indications and timing for surgery, chemotherapy, radiotherapy or delayed treatment were decided according to the malignancy characteristics and gestational age. The patient's consent was obtained before every decision. RESULTS: The rate of live births, premature deliveries, foetal abnormalities and neonatal deaths was 97%, 82%, 9% and 3%, respectively. Three women (9%) died during puerperium because of disease progression. CONCLUSION: The cancer treatment took into full consideration the specific condition of each pregnant patient. A good rate of live births was observed, even if a high rate of preterm delivery occurred. The management of malignancy required a team of experts in order to optimise every available choice for maternal health and neonatal well-being.

Inherited thrombophilia: treatment during pregnancy.

OBJECTIVE: Inherited thrombophilia is associated with thromboembolic events and/or poor obstetric outcome. We evaluated the pregnancy outcome in women with inherited thrombophilia treated with low-molecular-weight heparin (LMWH). METHODS: 38 thrombophilic women with a history of thromboembolic events and/or poor obstetric outcome were treated during their 39 consecutive pregnancies with LMWH from pregnancy verification until 4-6 weeks in puerperium. A fixed dose of enoxaparin 4,000 IU/day (except 1 case who required nadroparin 0.3 ml/day) was administered in most cases, adopting a higher dose (6,000 IU/day to 6,000 IU twice a day) in those with previous thromboembolic events. RESULTS: In the treated women, all had a good obstetric outcome, whereas in the previous untreated pregnancies (n = 78), the rate of fetal loss (early and late) was 76.9%, only 12 live infants survived (66.6%). Moreover, birth weight resulted significantly higher in live infants born to treated pregnancies in comparison to that of previous untreated pregnancies (p = 0.009). No maternal thrombosis or major bleeding complications were recorded. CONCLUSIONS: The treatment with LMWH improved pregnancy outcome resulting effective and safe in thrombophilic women with a history of thromboembolic events and/or poor obstetric outcome.