New approaches in predicting and diagnosing preeclampsia: Congo Red Dot Paper Test (Review).

Preeclampsia (PE), a complication of pregnancy that is characterized by de novo hypertension and proteinuria, remains a leading cause of morbidity and mortality during pregnancy, influencing 2.5-7% of singleton and 7-21% of twin pregnancies. At present, diagnosis is based on traditional but unreliable and nonspecific clinical markers, and treatment of PE is suboptimal, with minimal effect on maternal and fetal mortality and morbidity. With the hope of developing an affordable and simple procedure for PE prediction for developing countries, a previous study examined the use of Congo red staining of misfolded and damaged proteins in the urine of women with PE. This feature has diagnostic and prognostic potential since it precedes the onset of clinical manifestations and correlates with disease severity. The test is inexpensive, popular within the medical staff, easy to use, and identifies women with PE in only 3 min. Obstetrical providers benefit from the Congo Red Dot Paper Test analysis, since a negative result promotes lesser waiting times in triage, prevents unneeded admissions, and diminishes the health costs associated per case.

Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks.

OBJECTIVE: To develop models for prediction of pre-eclampsia (PE) based on maternal factors and biophysical and biochemical markers at 11-13 weeks' gestation. METHODS: Screening study of singleton pregnancies at 11-13 weeks including 752 (2.2%) that subsequently developed PE and 32,850 that were unaffected by PE. Models were developed for the prediction of early PE, requiring delivery before 34 weeks, intermediate PE with delivery at 34-37 weeks and late PE delivering after 37 weeks. The data used for the models were firstly, maternal characteristics and history, uterine artery pulsatility index, mean arterial pressure and serum pregnancy-associated plasma protein-A obtained from the screening study and secondly, maternal serum or plasma concentration of placental growth factor, placental protein-13, inhibin-A, activin-A, soluble endoglin, pentraxin-3 and P-selectin obtained from case-control studies. RESULTS: In screening for PE by maternal factors only at a fixed false positive rate of 5%, the estimated detection rates were 33.0% for early PE, 27.8% for intermediate PE and 24.5% for late PE. The respective detection rates in screening by a combination of maternal factors, biophysical and biochemical markers were 91.0, 79.4 and 60.9%. CONCLUSIONS: Effective prediction of PE can be achieved at 11-13 weeks' gestation.

Liver volume in trisomy 21 and euploid fetuses at 11 to 13 weeks.

OBJECTIVES: To compare liver volume between trisomy 21 and euploid fetuses at 11 to 13 weeks' gestation. METHODS: Fetal liver volume was measured by 3D ultrasound in fetuses at low risk of aneuploidies (n = 200) and another group at high risk, including 148 euploid and 37 with trisomy 21. The association of liver volume with fetal nuchal translucency (NT) thickness, tricuspid regurgitation and reversed a-wave in the ductus venosus was investigated. RESULTS: In the low-risk group, fetal liver volume increased exponentially with fetal crown-rump length (CRL) from a median of 0.5 cm(3) at CRL of 45 mm to about 2.5 cm(3) at CRL of 84 mm. In 27 (73.0%) of the trisomy 21 fetuses liver volume was above the 95th percentile of the low-risk group, whereas in the euploid fetuses liver volume was not significantly altered (P = 0.521). There were no significant contributions to liver volume from fetal NT (P = 0.508), tricuspid regurgitation (P = 0.958) or reversed a-wave in the ductus venosus (P = 0.872). CONCLUSION: In trisomy 21 fetuses at 11 to 13 weeks liver volume is increased.

Hepatic artery Doppler in trisomy 21 and euploid fetuses at 11-13 weeks.

OBJECTIVE: To determine possible differences in hepatic artery flow between trisomy 21 and euploid fetuses at 11-13 weeks' gestation. METHODS: Hepatic artery pulsatility index (PI) and peak systolic velocity (PSV) were measured in fetuses at low risk of aneuploidies (n = 350) and another group at high risk, including 283 euploid and 47 with trisomy 21. The association of hepatic artery PI and PSV with trisomy 21, fetal nuchal translucency (NT) thickness, tricuspid regurgitation, and reversed a-wave in the ductus venosus was investigated. RESULTS: In the low-risk group, the median hepatic artery PSV was 10.0 cm/s and the 95th centile was 14.3 cm/s. The distribution of hepatic artery PI was skewed, but for PI of 2 or more the distribution was Gaussian. In 325 (92.9%) cases, the PI was 2 or more (high PI) and in 25 (7.1%) it was below 2 (low PI). In 33 (70.2%) of the trisomy 21 pregnancies, the PSV was above the 95th centile and the PI was below 2. Multiple regression analysis showed that in the prediction of hepatic artery PSV there were significant contributions from fetal karyotype, tricuspid regurgitation, and reversed a-wave in the ductus venosus, but not delta NT, pregnancy-associated plasma protein-A, or free ß-human chorionic gonadotrophin. CONCLUSION: Trisomy 21 at 11-13 weeks is associated with increased flow in the hepatic artery.

Adrenal gland length in euploid and trisomy 18 fetuses at 11-13 weeks.

OBJECTIVES: To establish a normal range for fetal adrenal gland length at 11-13 weeks' gestation and to investigate whether the length is altered in fetal trisomy 18. METHODS: Fetal adrenal gland length was measured by three-dimensional ultrasound in fetuses at low risk of aneuploidies (n = 400) and another group at high risk, including 380 euploid fetuses and 41 with trisomy 18. The data of the low-risk group were used to establish a reference range of adrenal gland length with crown-rump length (CRL). In the high-risk group, adrenal gland length in the euploid and trisomy 18 groups was compared. RESULTS: In the low-risk group, fetal adrenal gland size increased exponentially with fetal CRL from a median of 2.3 mm at CRL of 45 mm to about 4.4 cm at CRL of 84 mm. In trisomy 18, the median adrenal gland length for CRL was significantly lower than the median in the low-risk group (-1.37 mm; interquartile range: - 1.67 to - 0.99 mm, p < 0.0001). In euploid fetuses, the adrenal gland size was not significantly from the low-risk group (p = 0.100). CONCLUSION: Trisomy 18 is associated with adrenal gland hypoplasia which is apparent at 11-13 weeks' gestation.

Benefits of α-lipoic acid in high-risk pregnancies (Review).

α-Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti-inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8 and IL-17), while increasing the secretion of anti-inflammatory cytokines (IL-10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.

Posterior fossa assessment in the axial view of the head at 11-14 weeks of gestation in normal and aneuploid fetuses.

Posterior fossa ultrasound appearance may offer clues for brain anomalies as early as the first trimester. The purpose of the study was to find an easy, reproducible method to examine the posterior fossa. From January 2017 to March 2018, 132 consecutive pregnancies presenting for first-trimester screening, were selected at 11-14 weeks' gestation. An oblique axial view of the fetal head was routinely achieved with visualization of the posterior fossa, wherein the cisterna magna (CM) and the fourth ventricle (V4) anteroposterior diameter was measured. Moreover, 81 patients had a follow-up scan at 19-24 weeks, and the CM and transverse cerebellar diameter (TCD) were measured. Normal ranges were established at 11-14 weeks for CM and V4 according to crown-rump length (CRL). The 50th centile for CM ranges from 1.2 mm to 2.3 mm at a CRL between 45 and 85 mm. The V4 50th centile ranges from 1.8 to 2.4 mm. A positive correlation was found between the first-trimester and second-trimester CM diameter and between the first-trimester V4 and second-trimester TCD. There is an inverse correlation between the first-trimester CM and second-trimester TCD. The measurements of different components of the posterior fossa in the first trimester cannot predict the size of CM and TCD in the second trimester. The presence of the three hypoechoic structures (cerebral peduncles, V4, and CM) separated by two hyperechoic lines is easy to see and measure.

Reference ranges for the fetal mesencephalon to occiput measurement at 11 to 13+6 weeks of gestation.

The objective was to have a quantitative description of the normal position of the fetal midbrain in the first trimester, through defining the reference ranges for the mesencephalon to the occipital bone distance, in the axial plane. This was a prospective study that included normal fetuses screened between 11 and 13 weeks of gestation. The distance was measured between the posterior limit of the mesencephalon to the occipital bone in the same axial view as the one required for the biparietal diameter (BPD) assessment, at this gestational age (GA). The reference ranges using quantile regression, according to the crown-rump length (CRL), BPD, and GA were fitted. Data analysis included 428 ultrasound measurements. A good, linear correlation was observed between mesencephalon to occiput (MO) distance and CRL, BPD, or GA. It increased linearly with advancing gestation (log10MO = -0.1834 + 0.0092 x CRL, R2=0.48, P<0.0001) and was independent of maternal demographic characteristics and intracranial translucency (IT). In our study, the 1st percentile of the normal MO distance varies from 1.31 mm at a CRL of 45 mm to 2.08 mm at a CRL of 84 mm. The intraclass correlation coefficient (ICC) was 0.89 for intraobserver variability. A significant increase in the MO distance was found in the patients who did not receive folic acid in the first trimester of pregnancy [1.056 vs. 1.008 multiple of median (MoM), P=0.014]. A simple measurement is described between the midbrain and the occipital bone, obtained in the same axial view. It increases linearly with advancing gestation. Integration of this measurement into the routine ultrasound screening in association with the 'crash sign' and recognizing the lower extreme values could lead to an early diagnosis of open spina bifida (OSB).

Non-sexual HPV transmission and role of vaccination for a better future (Review).

Human papilloma viruses (HPVs) belong to the Papillomaviridae family and are epitheliotropic infecting squamous epithelia (skin and mucosae). HPV is estimated to be the cause of 99% of cervical cancers (there is no evidence of significant genetic predisposition for cervical cancer), 90% of anal cancer, 65% vaginal cancers, 50% vulvar cancers, and 45-90% oropharyngeal cancers. The route of HPV transmission is primarily through skin-to-skin or skin-to-mucosa contact. Sexual transmission is the most documented, but there have been studies suggesting non-sexual courses. The horizontal transfer of HPV includes fomites, fingers, and mouth, skin contact (other than sexual). Self-inoculation is described in studies as a potential HPV transmission route, as it was certified in female virgins, and in children with genital warts (low-risk HPV) without a personal history of sexual abuse. Vertical transmission from mother to child is another HPV transfer course. Several studies have emphasized the possibility of infection through the amniotic fluid, or the placenta, or via contact with maternal genital mucosa during natural birth. Waterborne transmission of HPV has never been demonstrated; however, HPV DNA has been detected in water environments. Routine hygiene measures are proven to be inefficient in preventing HPV transmission, as the studies which have evaluated samples of HPV on contaminated medical equipment (after standard disinfection) have found them to be still positive. Annual costs associated with the morbidity and mortality of HPV-related diseases are estimated at approximately $4 billion. Once the HPV vaccine program in Australia was launched, many studies reported the initial effects: A decrease in the incidence of high-grade cervical abnormalities, no new genital warts cases in females under 21 years. Promoting greater understanding in the general public about the evident benefits of vaccination can create positive vaccine attitudes and scatter the myths of spurious side effects.

Impact of early supplementation with low-dose aspirin on functional first trimester parameters in low-risk pregnancies.

INTRODUCTION: There is recent evidence that prophylaxis with 150 mg of aspirin given before 14-16 weeks significantly reduces preeclampsia rates and may improve pregnancy outcome. We conducted an observational study that investigates the effect of low-dose aspirin initiated early in pregnancy or in preconception on functional parameters assessed at 11-14 weeks. MATERIALS AND METHODS: We have retrospectively selected 128 pregnant women that presented for the first trimester screening for aneuploidies between 11+0 and 13+6 weeks of gestation and received low-dose aspirin before 14 weeks. We excluded cases with an estimated high risk for early preeclampsia (cut-off > 1:100). This group was matched to 1044 cases that did not receive aspirin in early pregnancy. We have selected for statistical analysis maternal parameters, ultrasound parameters (crown-rump length, nuchal translucency thickness, pulsatility index in uterine arteries - left, right, average and average uterine PI expressed in multiple of median (MoM)), first trimester maternal biochemical markers (free ß hCG and PAPP-A expressed in MoM), and the calculated risk for early onset and late onset preeclampsia. RESULTS: The most common dosages of aspirin were 75 mg (77 cases) and 100 mg (32 cases). The most significant results are within the aspirin group. In the subgroup that received aspirin before 11 weeks (110 cases), irrespective of the dosage, the uterine blood flow is significantly improved (average uterine PI 1.7 compared with 2.22, p < .05, (0.24-0.7) 95% CI) and the PAPP-A levels are higher (1.2 compared with 0.82, p > .05, [(-0.65) - 0.02] 95% CI). The estimated risk for both early and late onset preeclampsia in this group is reduced (1:2141 compared with 1:333 for early preeclampsia, p < .05, (1216-2398) 95% CI; 1:361 compared with 1:99 for late onset preeclampsia, p < .05, (173-351) 95% CI). CONCLUSION: Even though the results are not always statistically significant, they demonstrate that placentation parameters improve with higher doses of aspirin started before 11 weeks.

Magnetic resonance imaging in obstetrics.

UNLABELLED: Ultrasonography is the primary screening modality for obstetrics imaging. When additional information is needed to care for pregnant patients, computed tomography and magnetic resonance imaging (MRI) can be used. Because MRI provides superior contrast resolution compared with CT, uses no ionizing radiation, and permits imaging in more than one plane, it has been used in feto-maternal imaging. This article presents principles, practical aspects and indications of MRI in obstetrics: diagnosis of fetal anomalies, prenatal counseling and management, placental position and placenta praevia, pregnant patient with associated pathology (e.g. acute abdomen, hydronephrosis, adnexal masses) and pelvimetry. The article presents, also, fetal central nervous system malformations (one of the most frequent indication of MRI in obstetrics) and other fetal anomalies like diaphragmatic hernia or gastroschisis. CONCLUSIONS: Ultrasound continues to be the screening modality of choice in the evaluation of the fetus. Proper use and interpretation of ultrasound limits the cases in which magnetic resonance is necessitated. However, there are many cases in which MRI alternative imaging is useful, complementary to ultrasounds.