Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

DHA turnover in pregnant women using the natural abundance variation of 13C: a pilot study.

The importance of DHA intake to support fetal development and maternal health is well established. In this pilot study we applied the natural abundance approach to determine the contribution of 200 mg/day of DHA supplement to the plasma DHA pool in 19 healthy pregnant women on a free diet.Women received DHA, from pregnancy week 20 until delivery, from an algal source (N=13, Algae group) or from fish oil (N=6, Fish group) with slightly different content of 13C.We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3).The δ13C of DHA in algae and fish supplements were -15.8±0.2 mUr and -25.3±0.2 mUr (p<0.001).DHA δ13C in the Algae group increased from -27.7±1.6 mUr (T0) to -21.9±2.2 mUr (T3) (p<0.001), whereas there were not significant changes in the Fish group (-27.8±0.9 mUr at T0 and -27.3±1.1 mUr at T3, p=0.09).In the Algae group 200 mg/day of DHA contributed to the plasma phospholipid pool by a median value of 53% (31-75% minimum and maximum). This estimation was not possible in the fish group.Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk.

OBJECTIVE: Our aim was to assess diagnostic accuracy in the prediction of small for gestational age (SGA <10th centile) and fetal growth restricted (FGR) (SGA <3rd centile) fetuses using three different sonographic methods in pregnancies at increased risk of fetal growth restriction: 1) fetal abdominal circumference (AC) z-scores, 2) estimated fetal weight (EFW) z-scores according to postnatal reference standard; 3) EFW z-scores according to a prenatal reference standard. METHODS: Singleton pregnancies at increased risk of fetal growth restriction seen in two university hospitals between 2014 and 2015 were studied retrospectively. EFW was calculated using formulas proposed by the INTERGROWTH-21st project and Hadlock; data derived from publications by the INTEGROWTH-twenty-first century project and Hadlock were used to calculate z-scores (AC and EFW). The accuracy of different methods was calculated and compared. RESULTS: The study group included 406 patients. Prenatal standard EFW z-scores derived from INTERGROWTH-21st project and Hadlock and co-workers performed similarly and were more accurate in identifying SGA infants than using AC z-scores or a postnatal reference standard. The subgroups analysis demonstrated that EFW prenatal standard was more or similarly accurate compared to other methods across all subgroups, defined by gestational age and birth weight. CONCLUSIONS: Prenatal standard EFW z-scores derived from either INTERGROWTH-21 st project or Hadlock and co-workers publications demonstrated a statistically significant advantage over other biometric methods in the diagnosis of SGA fetuses.

Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study.

OBJECTIVES: Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn's immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were (1) to examine the effects of pPROM on the newborn's and mother's immune system and (2) to assess the predictive value of immune system changes in neonatal morbidity. METHODS: Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. RESULTS: pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns' lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). CONCLUSIONS: pPROM prompts maturation of the newborn's T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Inositol (ISL) embraces a family of simple carbohydrates with insulin-sensitizing properties, whose most common isoforms are Myo-inositol (MYO) and D-chiro inositol (DCI). The aim of the present study was to assess the efficacy and safety of ISL supplementation during pregnancy for the prevention of gestational diabetes (GDM). METHODS: We conducted a systematic literature search in electronic databases until October 2017. We included all randomized controlled trials (RCTs) comparing pregnant women with GDM who were randomized to either ISL (i.e., intervention group) or either placebo or no treatment (i.e., control group). The primary outcome was the preventive effect on GDM, defined as the rate of GDM in women without a prior diagnosis of GDM. Pooled results were expressed as odds ratio (OR) with a 95% confidence interval (95% CI). RESULTS: Five RCTs were included (including 965 participants). ISL supplementation was associated with lower rate of GDM (OR 0.49, 95% CI 0.24-1.03, p = 0.01) and lower preterm delivery rate (OR 0.35, 95% CI 0.17-0.74, p = 0.006). No adverse effects were reported. Adjusting for the type of intervention (MYO 2 g twice daily vs MYO 1100 mg plus DCI 27.6 mg daily), a significant effect was found only in patients receiving 2 g MYO twice daily. CONCLUSIONS: ISLs administration during pregnancy appears to be safe and may represent a novel strategy for GDM prevention. In particular, the double administration of MYO 2 g per day may improve the glycemic homeostasis and may reduce GDM rate and preterm delivery rate.

Fetal Abdominal Aorta: Doppler and Structural Evaluation of Endothelial Function in Intrauterine Growth Restriction and Controls.

PURPOSE: The human aorta stores strain energy in the distended wall during systole through the extracellular matrix of the tunica media that could be influenced by blood pressure, flow, or increased peripheral resistance. In intrauterine growth restriction (IUGR) fetuses, the increased aorta intima media thickness (aIMT) could reflect a different extracellular matrix composition and, therefore, functionality. The aim of this study was to analyze the resistance to flow in the fetal descending aorta and its relation to aIMT and systolic and diastolic fetal abdominal aorta diameters in IUGR fetuses and controls. MATERIALS AND METHODS: This is a prospective case control study of single pregnancies collected at a tertiary center for feto-maternal medicine in Northeast Italy. An IUGR group as cases and a group of fetuses appropriate for gestational age (AGA) as controls were included. RESULTS: We found a greater PI of the fetal abdominal aorta in the IUGR group (1.82) than in the AGA group (1.21) (p < 0.05). The change between the systolic and diastolic fetal abdominal aorta diameters was significantly greater in IUGR fetuses (0.10 mm (IQR 0.07 - 0.28)) than in the AGA group (0.04 mm (0.03 - 0.05)) (p < 0.05). In the IUGR group aIMT was significantly correlated with peak systolic velocity (PSV) and systolic-diastolic aorta diameter change, while these two correlations were not found in the control group. CONCLUSION: The change between the systolic and diastolic fetal abdominal aorta diameters in IUGR cases during the early third trimester of pregnancy was significantly increased and aIMT in the IUGR group was significantly correlated to systolic-diastolic diameter change and PSV, probably reflecting aortic wall adaptation to blood flow changes in IUGR fetuses.

Clinical Validation of the INTERGROWTH-21st Standards of Fetal Abdominal Circumference for the Prediction of Small-for-Gestational-Age Neonates in Italy.

OBJECTIVES: To compare the accuracy of the INTERGROWTH-21st (IG-21) with the Italian Society of Ultrasound in Obstetrics and Gynecology (SIEOG) abdominal circumference (AC) standards in the detection of small-for-gestational-age (SGA) fetuses in a high-risk population. MATERIAL AND METHODS: Our study included all pregnant patients with an increased risk of placental insufficiency that were seen in two Italian university hospitals between 2014 and 2015. The accuracy of IG-21 and SIEOG AC standards in the detection of SGA neonates was analyzed by means of the area under the receiver operating characteristic curve (ROC-AUC) at 4 gestational age intervals (24-27, 28-31, 32-35, >35 weeks). RESULTS: We enrolled 428 patients (278 Italians). There was no significant difference between the ROC-AUC of AC according to IG-21 and SIEOG standards for all birthweight thresholds and gestational intervals that were considered. The diagnostic performance was similar in Italian and non-Italian patients. The accuracy was, however, limited, with values of ROC-AUC ranging between 0.80 and 0.89. CONCLUSIONS: The IG-21 and SIEOG AC standards are interchangeable for the diagnosis of SGA fetuses. The diagnostic accuracy is, however, limited. We provide figures that can be used to stratify the probability that an infant will be SGA in an obstetric population at increased risk of growth restriction.

Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale.

One of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome.

Origin and levels of circulating microparticles in normal pregnancy: A longitudinal observation in healthy women.

OBJECTIVE: Microparticles (MP) are actively involved in the hypercoagulable state reported both in normal pregnancies and in pregnancy diagnosed with placenta-mediated complications. In this study the origin and the levels of plasma MP as well as MP activity were evaluated in a group of healthy women during the three trimesters of a normal pregnancy. MATERIALS AND METHODS: Seventy-five healthy normotensive pregnant women were enrolled and blood samples were prospectively collected at three different time points corresponding to 1st trimester, 2nd trimester, 3rd trimester of pregnancy. A group of age- matched healthy non-pregnant women acted as controls. Both standard clotting parameters and MP of different origin were measured. MP were identified by size and annexin V- FITC labelling using flow-cytometer. MP subtypes were identified using specific monoclonal antibodies. Procoagulant activity of MP was assessed using the STA® Procoag PPL assay. RESULTS: The levels of total, platelet-, endothelial-, leukocyte-derived and tissue factor-bearing MP, as well as the MP procoagulant activity, in non-complicated pregnancy were higher in the 1st trimester as compared to non-pregnant age-matched women. Regardless of the origin, MP levels gradually increase during pregnancy, with the highest values reached in the 3rd trimester. CONCLUSIONS: MP levels gradually increase during normotensive pregnancy. All types of MP including TF+ present with the highest levels in the 3rd trimester. MP convey prothrombotic and proinflammatory antigens already from the first trimester of normal pregnancy. This may contribute to the global hypercoagulable state observed, particularly in the last months of pregnancy, also in healthy women.

Uncertainties about laparoscopic myomectomy during pregnancy: A lack of evidence or an inherited misconception? A critical literature review starting from a peculiar case.

OBJECTIVE: The aim of this report was to perform a critical review of the literature about feasibility, safety, limitations and contraindications of laparoscopic myomectomy during pregnancy starting from a peculiar case of a 15-weeks pregnant woman affected by a symptomatic large myoma. CASE REPORT: A 35 year-old Caucasian-nulliparous-woman was referred to our unit at nine weeks of gestation for abdominal heaviness and constipation. The ultrasound examination revealed the presence of a 24 cm pedunculated myoma. The initial management was conservative until the achievement of 15 gestational weeks, when the worsening of abdominal pain led to the need of a laparoscopic myomectomy. Intraoperative blood-loss was 600 ml and operating-time was 150 minutes (70 minutes were required for the morcellement); the postoperative course was normal. The pregnancy evolved regularly and, at 41 weeks, the patient delivered by urgent caesarean section (because intrapartum fetal heart rate abnormalities) a healthy male baby weighing 4460 gr. Both post-partum and puerperium period had a regular course. CONCLUSION: Laparoscopic myomectomy is feasible and safe during pregnancy for both mother and fetus and vaginal delivery should not be contraindicated. Evidence from our and other reported cases suggests that, during pregnancy, laparoscopic myomectomy should be considered the best surgical choice when subserous peduncolated myomas are symptomatic.

Timing of delivery and neonatal outcomes for small-for-gestational-age fetuses.

OBJECTIVES: To investigate whether antenatal recognition of small-for-gestational-age (SGA) fetuses with normal maternal and fetal Doppler values delivered after 34 weeks' gestation is associated with changes in the risk of adverse maternal and neonatal outcomes. METHODS: In this retrospective study, we included 313 singleton SGA fetuses and 313 appropriate-for-gestational-age control fetuses born between 34 and 42 weeks' gestation from 2009 to 2012. Small-for-gestational-age fetuses identified before delivery (n = 124), for whom antenatal surveillance was performed until delivery (estimated fetal weight twice weekly and Doppler evaluation of the fetal compartment once weekly), were compared to those not identified at delivery (n = 189). The latter group did not undergo antenatal surveillance for several reasons (women for whom a sonographic evaluation or gynecologic consultation was not performed in the third trimester and incorrect sonographic biometric evaluation in the third trimester). Main outcome measures were mode of delivery, perinatal complications, and neonatal intensive care unit admission. The risk of serious fetal complications was assessed by cross-tabulation analysis adjusted for gestational age and degree of SGA. RESULTS: Prenatally recognized SGA fetuses were smaller and delivered earlier than unrecognized SGA fetuses (P< .05). Fetal acidemia (pH <7.10) was significantly more common in unrecognized SGA fetuses (3.7% versus 0%). Small-for-gestational-age fetuses at or below the 3rd percentile were more commonly recognized prenatally and hospitalized in the neonatal intensive care unit. Unrecognized SGA fetuses also had worse fetal outcomes compared to controls (P< .05). Recognized and unrecognized SGA fetuses were born significantly more frequently by cesarean delivery (P < .05). No significant differences in perinatal outcomes were found between recognized SGA deliveries with or without medical induction. CONCLUSIONS: Antenatal recognition of SGA fetuses delivered after 34 weeks' gestation might improve perinatal outcomes. Medical induction of labor did not modify neonatal outcomes among prenatally recognized SGA fetuses.

Efficacy and 9 years' follow-up of posterior intravaginal slingplasty for genital prolapse.

AIM: The aim of this study was to assess the long-term efficacy and complication rates of posterior intravaginal slingplasty (IVS) in women suffering from genital prolapse. MATERIAL AND METHODS: Posterior IVS or infracoccygeal sacropexy is a minimally invasive procedure for suspension of the vagina with the goal of creating new uterosacral ligaments through the insertion of a polypropylene tape. Forty-four patients were enrolled: 25 patients, affected by uterovaginal prolapse, were subjected to vaginal hysterectomy and posterior IVS; and 19 patients, diagnosed with vaginal vault prolapse, were subjected to posterior IVS alone. The primary outcome for posterior IVS was 12-month, 24-month and annual 9-year postoperative efficacy that is based on a Pelvic Organ Prolapse Quantitative score of -5 at point C, which describes the vaginal apex. RESULTS: Of the 44 patients who underwent posterior IVS, none required blood transfusions with an average reduction of perioperative hemoglobin of 1.2 ± 0.4 g/dl, and the average time of hospitalization was 4.3 ± 0.6 days. The rate of success was 93.18% (41/44) at 9 years' follow-up. We had only one case of extrusion (2.27%) and three cases of recurrence (6.82%), such as two cases of cystocele and of rectocele. CONCLUSIONS: Most patients interviewed confirmed that their quality of life improved after surgery, 86.36% of the operated patients reported that their sexual performance improved and that they would recommend this surgery for their friends. Posterior IVS was a minimally invasive surgical procedure with a high success rate for genital prolapse.

Does the contraceptive pill influence peak nasal inspiratory flow values?

BACKGROUND: Early oral contraceptive pills (OCP) had higher estrogen levels and have been thought to cause nasal obstruction in about 40% of women users. A recent small study conducted on women taking OCP showed no significant effects on nasal patency. The aim of the present study was to analyse in a large number of volunteers if Peak Nasal Inspiratory Flow (PNIF) values could be influenced by modern OCP. METHODOLOGY: PNIF was measured in 257 women (from 14 to 51 years old), divided into two groups: the study group composed of 109 healthy women taking modern OCP; the control group composed of 148 healthy women who did not take OCP. 9 women in the study group were excluded because of allergic disease, 248 females were finally considered. Data were statistically analysed and figures/tables were produced to see the effect of OCP on PNIF. RESULTS: The present study could not show any effect of OCP on nasal function. Moreover, while height influenced PNIF in both groups, age was not statistically significant. CONCLUSION: From the present study, it seems that OCP could have no effects on nasal airflow, confirming that modern OCP with lower estrogen doses should not affect nasal mucosa or nasal patency.

Burden of Congenital CMV Infection: A Narrative Review and Implications for Public Health Interventions.

Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate.

Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. OBJECTIVE: To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. STUDY DESIGN: This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. RESULTS: A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. CONCLUSION: The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

Aortic wall thickness and amniotic fluid albuminuria in growth-restricted twin fetuses.

BACKGROUND AND OBJECTIVE: Intrauterine growth restriction (IUGR) may be associated with significantly higher aortic intima-media thickening (aIMT) values. It is unknown if fetal aIMT is associated with glomerulosclerosis and amniotic albuminuria in utero. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Fetal abdominal aIMT and amniotic albumin/creatinine ratio (ACR) were measured in 126 individual twin fetuses, recruited by the Obstetrics and Gynaecology Clinics of the University of Padua (Italy) Medical Center. The IUGR twin fetuses were classified into two groups: Group A were those fetuses whose estimated fetal weight (EFW) was <10th percentile with pulsatility index >2 SD and Group B were those fetuses whose EFW was <10th percentile and had no velocimetry abnormalities. RESULTS: The median fetal aIMT was significantly different in the three groups (Group A = 0.9 mm; Group B = 0.7 mm; and appropriate for gestational age (AGA) = 0.5 mm; p < .0001). It was significantly higher in Group A than in the AGA group (p < .0001) and than in the Group B fetuses (p = .003), respectively. In addition, ACR was different in the three groups (Group A = 183,500 mg/g; Group B = 6,4720 mg/g; and AGA = 8,2750 mg/g; p = .0002). It was significantly higher in Group A than in the AGA group (p = .03) and than in Group B (p = .02), respectively. CONCLUSIONS: Growth-restricted twin fetuses with velocimetry abnormalities present are associated with aIMT and higher ACR levels in amniotic fluid, which could be possible markers in utero of preclinical atherosclerosis, and early glomerulosclerosis.

Selective intrauterine growth restriction in monochorionic twin pregnancies: markers of endothelial damage and metabolomic profile.

The aim of this study was to assess the aorta-intima thickness (aIT) and serum metabolomic profile in selective intrauterine growth-restricted (sIUGR) monochorionic diamniotic (MCDA) twin fetuses presenting Doppler velocimetry alterations. Fetal abdominal aIT was measured by ultrasound at 32 weeks of gestation, enrolling 24 MCDA twin fetuses (8 sIUGR and 16 controls). sIUGR twin fetuses were classified into two groups: Group 1 consisted of sIUGR with abnormal umbilical artery (UA) Doppler waveforms and Group 2 included sIUGR with normal UA Doppler. Group 3 were control fetuses appropriate for gestational age (AGA). Fetal blood samples were obtained from the umbilical vein immediately after fetal extraction. A non-targeted metabolomic profiling investigated fetal metabolism alterations by using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Median fetal aIT was significantly larger in Group 1 (median value = 0.9 mm; range = 0.8-1.0 mm; p < .002) and Group 2 (median value = 0.8 mm; range = 0.7-0.8 mm; p < .002) than in AGA Group 3 (median value = 0.5 mm; range = 0.4-0.6 mm; p < .002). Metabolomic analyses, performed on four sIUGR cases (Group 1) compared with four AGA co-twins, showed an upregulation of phenylalanine, sphingosine, glycerophosphocholine, and choline, and a downregulation of valine, tryptophan, isoleucine, and proline sIUGR Group 1 compared with AGA. Although for metabolomics data only a statistical tendency (and not a statistical significance) was reached due to the small sample size, we believe that our results represent a valid starting point for further in-depth metabolomic and proteomic investigations of sIUGR in MCDA fetuses.

Developmental programming of cardiovascular risk in intrauterine growth-restricted twin fetuses according to aortic intima thickness.

OBJECTIVES: We aimed to test the hypothesis that aortic intima thickness is greater in intrauterine growth-restricted (IUGR) twin fetuses compared to normally developing twins, thus defining an increased cardiovascular risk that reflects genetic factors in fetuses sharing the same womb. METHODS: We conducted a prospective study performed on twins from January 2009 to July 2011. Twins were classified into 3 groups: IUGR fetuses with an estimated fetal weight below the 10th percentile and an umbilical artery pulsatility index of greater than 2 SDs (group A), fetuses with an estimated fetal weight below the 10th percentile and normal Doppler findings (group B), and fetuses with an estimated fetal weight appropriate for gestational age (group C). Aortic intima thickness was measured at a median gestational age of 32 weeks. Values were compared among groups and between each twin and cotwin, also considering sex and chorionicity. RESULTS: Twenty-five fetuses were classified as group A, 36 as group B, and 95 as group C. The median aortic intima thickness values were 0.9 mm in group A, 0.7 mm in group B, and 0.6 mm in group C (P < .0001). There was a statistically significant difference between the aortic intima thickness of the twins and cotwins in groups A and B (P < .0001). Sex and chorionicity did not correlate with aortic intima thickness. CONCLUSIONS: In this study, IUGR fetuses with Doppler abnormalities had greater aortic intima thickness, and IUGR twins with normal Doppler findings had intermediate thickness, supporting a genetic predisposition to cardiovascular risk independent of sex and chorionicity.

Expectant management in type II selective intrauterine growth restriction and abnormal cord insertion in monochorionic twins.

OBJECTIVE: To assess perinatal outcome in type II monochorionic (MC) diamniotic twin pregnancies (DA) affected by selective intrauterine growth restriction (sIUGR) and abnormal cord insertion managed expectantly. METHODS: A prospective longitudinal study from June 2008 and July 2011 on 24 MCDA sIUGR twins. sIUGR was defined as estimated fetal weight below the 10th percentile in one twin and was classified into three groups based on umbilical artery (UA) Doppler diastolic flow (I: presence; II: constantly absent/reverse (AEDF/ARED); III: intermittently absent or reverse). Marginal cord insertion was defined as insertion within 2 cm of the placental disc edge, and velamentous insertion as a cord insertion into the fetal membranes. Expectant management was chosen in these twins, and absent or reverse A wave in the ductus venosus (DV) was a criterion for delivery. Neonatal outcome was available for all twins delivered. Pathological examination and vascular cast of placentas were performed in all cases. RESULTS: Fourteen twin pregnancies were type II sIUGR, and ten presented an abnormal umbilical cord insertion. Median gestational age (GA) at diagnosis of sIUGR was 18 weeks' gestation (range 16-20 weeks), and all sIUGR co-twins showed AEDF of UA at a median gestational age of 20 weeks (range 18-22 weeks). Median gestational age at delivery was 30 weeks (range 28-34 weeks) with a median birth weight of 1285 g (range 307-1725 g). pH at birth and base excess (BE) were normal in all IUGR co-twin (pH>7.10, median BE 5.5); Apgar score at 5 min was >7. Perinatal outcome was favorable in all cases. Placental pathological examination confirmed the marginal insertion of the umbilical cord and the absence of anastomosis between the two portions of umbilical insertion. CONCLUSIONS: This study highlights that expectant management for sIUGR type II twins with or without an abnormal cord insertion should be a valid option to time delivery for these fetuses as shown by the favorable neonatal outcome.