Clinical Implementation of Next-generation Sequencing in the Field of Prenatal Diagnostics

The possibility to receive genetic information of the fetus from maternal blood during the course of pregnancy has been one of the main goals of research in prenatal medicine for decades. First, the detection of cell-free fetal DNA in maternal blood and finally, the development of the powerful technique of “next-generation sequencing” (NGS) were required to finally transfer this analysis into clinical practice. Since its introduction in 2011, the clinical demand for the technique of non-invasive prenatal testing (NIPT) has been enormous. NIPT initially was available for the most common aneuploidies (trisomy 21, 13, and 18), but the varieties of diseases that can be detected prenatally by NIPT are increasing rapidly

Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy

Introduction: In the western world, cannabis is the most widely used drug of abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical reaction in individuals with a particular predisposition, is characterized by cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms are unresponsive to antiemetic drugs, compulsive hot baths result in a considerable symptom relief. Methods: We report the first case of cannabinoid hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our clinic in the 10th week of gestation. Conclusion: Before undertaking time-consuming and expensive medical examinations to rule out other medical reasons for therapy-resistant hyperemesis in pregnancy, obstetricians should determine whether compulsive bathing or showering provides symptomatic relief and ask specific questions regarding possible/suspected cannabis consumptio

Role of omega 3-fatty acids and multivitamins in gestation

There is a rising interest in a balanced and varied women's diet not only preconceptionally but also during pregnancy and in the breastfeeding period in order to reduce fetal, neonatal, and maternal risks. A decreased intake of omega 3-fatty acids (FA) or deficiencies of micronutrients are a global health problem, not only in developing countries, where micronutrient-rich food and fortified aliments are often not available, and also in the industrialized world. In contrast to data about the daily periconceptionally intake of folate acid that has been shown to reduce substantially the occurrence and recurrence of neural tube defects (NTD), the benefit of other micronutrients is less determinant. Deficiencies of omega 3-FA may be a contributing factor for severe complications in pregnancy and postpartum. A meta-analysis for the role of omega 3-FA in preeclampsia and maternal postpartum depression is less consistent, some meta-view's results differ substantially or are even contradictory to large observational studies. Further well-designed studies are warranted. A personal interview and counseling concerning the daily diet should be integrated in the preconceptional and in the antenatal care and an individual supplementation should be offered, if indicate

Determination of fetal chromosome aberrations from fetal DNA in maternal blood: has the challenge finally been met?

The analysis of cell-free fetal nucleic acids in maternal blood for prenatal diagnosis has been transformed by several recent profound technology developments. The most noteworthy of these are ‘digital PCR' and ‘next-generation sequencing' (NGS), which might finally deliver the long-sought goal of noninvasive detection of fetal aneuploidy. Recent data, however, indicate that NGS might even be able to offer a much more detailed appraisal of the fetal genome, including paternal and maternal inheritance of point mutations for mendelian disorders such as β-thalassaemia. Although these developments are very exciting, in their current form they are still too complex and costly, and will need to be simplified considerably for their optimal translation to the clinic. In this regard, targeted NGS does appear to be a step in the right direction, although this should be seen in the context of ongoing progress with the isolation of fetal cells and with proteomic screening marker

Two- versus three-dimensional ultrasound in the second and third trimester of pregnancy: impact on recognition and maternal-fetal bonding. A prospective pilot study

Objective: To assess the impact of three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) on maternal-fetal bonding. Study design: Prospective randomized pilot study among low risk women with singleton fetuses in the second and third trimester. Dependent on the randomization pattern, US was commenced either with 2D US or 3D US and the effects were recorded with standardized questionnaires. Results: Sixty patients were included. Although the quality of 2D US, assessed by the examinator, was superior to 3D US, maternal recognition was higher with 3-D US (P=0.004). With 2D US, nulliparous patients had significantly more difficulties visualizing the fetus, than multiparous (P=0.03). However, the maternal preference of 3D US had no significant impact on maternal-fetal bonding. Conclusion: Ultrasound had no significant effect on maternal-fetal bonding. Three-dimensional images may facilitate recognition of the fetus, but 3D US did not have higher impact on maternal-fetal bonding. This finding may be a reason not to consider 3D ultrasound for routine scannin

Water birth, more than a trendy alternative: a prospective, observational study

Objective: To prospectively assess the effect of water birth on maternal and fetal outcomes in a selected low-risk collective of a tertiary obstetrical unit. Method: In this prospective observational study, 513 patients of a low-risk collective, who requested a water birth, were studied during the years 1998-2002. Primary outcome measurements included the maternal and fetal parameters. Secondary outcome measurements comprised data on the incidence of water births in an interested, low-risk population in an academic hospital. Result: All groups were similar in terms of demographic and obstetric data. Significant differences were observed in maternal outcome parameters, which included the use of analgesia/anesthesia during labor, the duration of first and second stages of labor, perineal tears and episiotomy rate. No differences were seen in all observed fetal outcome parameters including APGAR scores, arterial and venous pH, admission rate to neonatal intensive care unit and infection rate. Conclusion: Water birth is a valuable and promising alternative to traditional delivery methods. The maternal and fetal outcomes were similar to traditional land births. However, currently there still exist some deficits in the scientific evaluation of its safety. Therefore, the selection of a low-risk collective is essential to minimize the risks with the addition of strictly maintained guidelines and continuous intrapartum observation and fetal monitoring. Based on our results and the literature, water births are justifiable when certain criteria are met and risk factors are exclude

Placental α-microglobulin-1 to detect uncertain rupture of membranes in a European cohort of pregnancies

Purpose: We evaluated the performance of the placental alpha-microglobulin-1 immunoassay (AmniSure®, AT) in cervicovaginal secretions in patients with uncertain rupture of membranes (ROM) and investigated the influence of the examiners experience. Methods: This prospective cohort study was performed in pregnant women (17-42weeks of gestation) with signs of possible ROM. Evaluation included clinical assessment, examination for cervical leakage, Nitrazine test and measurement of the amniotic fluid index by ultrasound and AT. ROM occurrence was based on review of the medical records after delivery. Results: 199 women were included. AT had a sensitivity of 94.4%; specificity of 98.6%; positive predictive value, 96.2%; negative predictive value, 98.0%. Clinical assessment showed a sensitivity of 72.2%; specificity of 97.8%; positive predictive value, 92.9%; negative predictive value, 90.6%. AT was more sensitive for diagnosing ROM (p=0.00596) compared to clinical assessment, independent of the examiners experience. Furthermore, the sole use of AT reduced costs by 58.4% compared to clinical assessment. Conclusions: AT was more sensitive compared to clinical assessment, independent of the examiners experience and gestational age. Our data extend its use in patients with uncertain ROM. Moreover, AT seems to be a cost-effective approach in the assessment of these patient

Quantitative Proteomic (iTRAQ) Analysis of 1st Trimester Maternal Plasma Samples in Pregnancies at Risk for Preeclampsia

A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for the detection of new preeclampsia screening markers

Impact of hormone replacement therapy on the histologic subtype of breast cancer

Objective: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer. Patients and methods: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for ≥6 months. Results: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). Conclusions: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cance

Increased peri- and post-elective cesarean section morbidity in women infected with human immunodeficiency virus-1: a case-controlled multicenter study

Objective: Although elective cesarean section (ECS) is the currently recommended modality for delivering women infected with the human immunodeficiency virus (HIV), historical evidence suggests that they are at higher risk of postoperative complications than noninfected women. Those risks have to be carefully balanced against the presumed minimal benefit of ECS, especially in the case of low viral load and high CD4 counts. We therefore compared the incidence and type of post-ECS complications in HIV-infected women, most with low viral loads and high CD4 cell counts, with those in matched noninfected women treated by the same surgical teams. Study design: A Swiss 8-center, prospective, matched case-control study compared minor and major post-ECS complication prevalence, hospital stay and confounding factors (surgeon experience) between HIV-infected and noninfected women. Results: Minor complications in the 53 matched pairs were eightfold more frequent overall in infected women. More frequent specific minor complications were anemia, blood loss and urinary tract infection. Yet the surgeons performing ECS in infected women were more experienced. Complications prolonged hospital stay in infected women. Major complication rates did not significantly differ between the groups. Conclusion: HIV-positive women have a higher risk of post-ECS morbidity, even with high CD4 counts and low viral load. Therefore, the blanket recommendation of ECS in HIV-infected women requires a revie