G. C. Di Renzo

Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference

Abstract Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

Counseling for non-invasive prenatal testing (NIPT): what pregnant women may want to know

Sequencing of cell-free fetal and maternal DNA fragments (cfDNA) in maternal plasma can be used to test for fetal chromosomal abnormalities. In particular, prediction of the presence or absence of fetal trisomy 21, the most common fetal chromosomal abnormality, has been proved to be highly accurate. The first studies, showing > 99% accuracy, were done in selected high-risk groups1,2. More recent studies in average-risk populations of pregnant women confirm, as was expected biologically, that the test works equally well in the general population3–7. Not surprisingly, this safe and accurate test, commonly referred to as non-invasive prenatal testing (NIPT), increasingly is being offered by clinicians and requested by pregnant women who want to be informed about the possibility of trisomy 21 in their unborn child. With the first studies suggesting very high accuracy of trisomy 21 detection, there was hope that after decades of searching for this ‘Holy Grail’, a safe blood test could replace chorionic villus sampling and amniocentesis, eliminating (fear of) procedure-related miscarriages. From larger follow-up studies, we now know that while an NIPT result positive for trisomy 21 often means that the fetus is affected, this is not always the case, and therefore confirmation using an invasive test remains necessary, at least when the woman is considering an irreversible decision. Furthermore, sensitivity for detection of trisomy 21 is > 99% in practically all studies, but some missed cases have been reported. Thus, although highly accurate, NIPT is not perfect. In the not-so-distant past, the use of maternal age alone to select women to undergo invasive testing was replaced by various forms of measuring maternal serum markers with or without nuchal translucency (NT) measurement. In countries in which this was implemented well, unnecessary invasive tests (and related miscarriages) significantly decreased, with concomitant improved detection, thus improving women’s reproductive choices8. Still, the vast majority of invasive tests following screening for trisomy reveal a normal result, while the screening test is falsely reassuring in at least one in 10 pregnancies with a trisomy 21 fetus. The use of NIPT enables us to further improve the quality of prenatal testing for fetal abnormalities. The aim of counseling a pregnant woman before she chooses to undergo any test which can have major consequences is to provide sufficient understanding of the test characteristics, limitations and risks for her to make what we call an ‘informed choice’ regarding whether she wants to undergo this test, another one or no test at all. The introduction of NIPT does not change this general principle. We have been counseling women of advanced maternal age on invasive testing for decades, and we are used to discussing serumand NT-based screening, which, when all aspects of the various tests are to be explained, is quite a complex task. Following the first publications on NIPT for trisomy 21, clinicians for a while were under the impression that pretest counseling would become an easier, if not almost superfluous, task. A simple message (‘If you want to know about trisomy 21, we take a tube of blood and let you know in a week or so whether your baby is affected.’) was thought, at least by some, to be capable of replacing the complex explanation involving serum markers, the meaning of this rim of fluid in the baby’s neck, an algorithm including the age of the mother and not so easy-to-understand reasons behind the cut-off between high and low risk. However, with the increasing use of NIPT in clinical practice, there is a rising awareness among professionals and policy makers that adequate pre-test counseling is still important, even for NIPT, in order to prevent misconceptions, disappointments and, in some cases, inappropriate selection of this test by women or doctors. In this Opinion paper, we describe what pregnant women may want to know about NIPT before consenting to undergo this test, and summarize useful aspects, which could be included in various forms of patient information (websites, guidelines, booklets or by personal contact in the clinic).

Occiput posterior position diagnosis: vaginal examination or intrapartum sonography? A clinical review.

Abstract The occiput posterior (OP) position is one of the most frequent malposition during labor. During the first stage of labor, the fetal head may stay in the OP position in 30% of the cases, but of these only 5–7% remains as such at time of delivery. The diagnosis of OP position in the second stage of labor is made difficult by the presence of the caput succedaneum or scalp hair, both of which may give some problem in the identification of fetal head sutures and fontanels and their location in relationship to maternal pelvic landmarks. The capability of diagnosing a fetus in OP position by digital examination has been extremely inaccurate, whereas an ultrasound approach, transabdominal, transperineal and transvaginal, has clearly shown its superior diagnostic accuracy. This is true not only for diagnosis of malpositions, detected in both first and second stage of labor, but also in cases of marked asynclitism.

Deficiency of human placental lactogen in an otherwise normal pregnancy

SummaryWE report a further case of human placental lactogen (HPL) deficiency associated with a normal pregnancy. To our knowledge, this is the first case reported from Italy and the fifth in the literature (Gaede et al., 1978; Nielsen et al., 1979; Moshirpur et al., 1981; Borody and Carlton, 1981).

Is twisted head position lateral asynclitism in the first stage of labor

Figure 1 (a) Transabdominal ultrasound image of fetus with left-sided asynclitism in first stage of labor, showing asymmetrical fetal profile. (b) Diagrammatic representation of corresponding presentation. Circle denotes fetal orbit. Arrow denotes axis of scan. malpositions during labor1. It is defined as anterior when the anterior parietal bone is presenting and posterior when the posterior parietal bone is presenting. Similar to cases complicated by persistent occiput posterior position, asynclitism may be associated with lateral deviation of the fetal cervical spine2, as reported by Ghi et al.3, who observed five cases of lateral flexion of the fetal head, not aligned with the cervical portion of the spine. In fact, different terminology should be used when the occiput and entire fetal spine are exactly anterior or posterior1–3. In these conditions, the suboccipitobregmatic diameter is parallel to the anteroposterior diameter, and asynclitism can no longer be defined as either anterior or posterior, but rather as lateral – left or right lateral asynclitism3. Diagnosis of asynclitism by digital vaginal examination is not an easy task, although even if head molding and caput succedaneum make the task more difficult, the presenting part is always the parietal bone, anteriorly or posteriorly. In cases of lateral asynclitism, the clinician may palpate the anterior fontanel and sagittal suture, deviated to the left or right. The use of ultrasound in labor has allowed the identification of both fetal orbits as a landmark for a correct diagnosis. In the presence of asynclitism, only one orbit can be visualized, the so-called ‘squint sign’4. In cases of left occiput posterior position, identification of the right anterior orbit may suggest a diagnosis of anterior asynclitism, whereas identification of the left posterior orbit is compatible with posterior asynclitism5. Location of the fetal head and spine can be determined by transabdominal ultrasound (Figure 1), whereas determination of the side of the squint sign can be achieved using either a transabdominal or transperineal/translabial approach (Figure 2). This seems to be related specifically to the presence of some disproportion between the fetal biparietal diameter and the maternal interspinous diameter, the latter being smaller than the former. On transabdominal ultrasound, the squint sign is seen on a transverse section, whereas the asymmetric fetal profile is seen on a longitudinal section (Figure 1). Clear identification of the fetal spine and specific fetal landmarks by ultrasound during labor enables a correct diagnosis of anterior, posterior or lateral (right or left) asynclitism1–3. The obstetric implication of lateral asynclitism associated with occiput posterior position and posterior spine is severe dystocia, which is an indication for operative delivery. Only when a correct diagnosis has been made can an appropriate clinical decision be taken. New data clearly show that, in many cases, the use of ultrasound seems able to fill the gap created by inaccurate digital vaginal examination during labor complicated by dystocia.

Umbilical cord haematoma with altered fetal heart rate

British Thoracic Society. 1998. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Joint Tuberculosis Committee of the British Thoracic Society. Thorax 53:536–548. Frieden TR, Sterling TR, Munsiff SS et al. 2003. Tuberculosis. Lancet 362:887–899. Gasparetto EL, Tazoniero P, de Carvalho Neto A. 2003. Disseminated tuberculosis in a pregnant woman presenting with numerous brain tuberculomas: case report. Arquivos de Neuro-psiquiatria 61:855–858. Khilnani GC. 2004. Tuberculosis and pregnancy. Indian Journal of Chest Diseases and Allied Sciences 46:105– 111. Knight M, on behalf of UKOSS. 2007. Tuberculosis in pregnancy in the UK: A national study to describe disease incidence, prognostic factors, management and outcomes, London: The UK Obstetric Surveillance System (UKOSS). Kothari A, Mahadevan N, Girling J. 2006. Tuberculosis and pregnancy. Results of a study in a high prevalence area in London. European Journal of Obstetrics, Gynaecology and Reproductive Biology 126:48–55.

Inflammation and Neurotransmission of the Vescico-Uterine Space in Cesarean Sections

Collagen IV and laminin play a key role in regulating stiffness, elasticity and flexibility of the vescico-uterine space (VUS) tissue. The neurotensin (NT), the neuropeptide tyrosine (NPY) and the protein gene product 9.5 (PGP 9.5) possessing vasorelaxation and tissue vascularization activities, play key roles in cervical ripening, scar innervations and pain control. We propose that the integrity of these substances in VUS tissue is compromised after Cesarean section (CS), since wound healing disturbances and pelvic pain, as well as pregnancy and delivery complications, are related with lower uterine segment dysfunctions after CS. Therefore, the contents of collagen IV, laminin, NT, NPY and PGP 9.5 nerve fibres from the VUS tissue samples obtained during the first CS and the repeated CS were comparatively studied. VUS specimens were collected from 104 patients during CS and evaluated by immunohistochemistry. Collagen IV and laminin were mostly found in the vascular membrane bounds and their images were quantitatively evaluated by Quantimet Leica analyzer software. Differences of collagen IV, laminin, NT, NPY and PGP 9.5 values in VUS tissue between the first CS and the repeat CS samples were calculated by Students Mest. Reduced laminin and increased collagen IV values were observed in the VUS scar tissue after the repeated CS in comparison with those of VUS intact tissue obtained during the first CS. Significantly higher values of nerve fibres, containing NT, NPY and PGP 9.5 were registered in intact VUS tissue samples, respectively 5±0.7, 7±0.6 and 5±0.9 CU, than those of VUS scar tissue samples obtained during the repeated CS, respectively 3±0.6,2±0.4 and 3±0.7 CU (p<0.05). The authors observed increased collagen IV and reduced laminin values after the repeated CS which might be the key signs of inflammatory damage of VUS scar tissue by CS. These findings were strengthened by the registration of decreased NT, NPY and PGP 9.5 values in the same samples, which are important neurotransmitters and are responsible for optimal wound healing, pain control and lower uterine segment functions.

Clinical significance of fetal hyperechogenicities

Case report A 36-year-old primigravida was referred to our centre at 22 weeks ’ gestation for routine morphological ultrasound examination. During this scan, focal hyperechogenic findings were detected in the bowel, heart and liver surface (Figure 1). The patient was then closely monitored with serial ultrasound examinations that showed dilated ileal bowel loops with peristalsis present. Maternal virus investigations were negative; she was negative for cystic fibrosis (CFTR gene investigated by oligonucleotide ligation assay for most frequent mutations in our population) and the amniocentesis showed a normal fetal karyotype. The induction of lung maturity was performed, with betamethasone (12 mg/day for 2 days), at 33 weeks, for increasing enlargement of the intestinal loops. Lung maturity was then checked by amniocentesis for L/S ratio and phosphatidylglycerol presence and delivery by caesarean section occurred at 35 weeks. At birth, the infant showed a good adaptation to extrauterine life (weight: 3.160 kg; Apgar scores: 9 at 1 min and 10 at 5 min). In the first hours of life, progressive further abdominal distension was shown. After radiological evaluation, the child was subjected to exploratory laparotomy on the 2nd day of life, which showed a jejunal atresia type IV and double ileal atresia type I (Shorter et al. 2006) and the atresia was recanalised. The baby was discharged on the 31st day with a follow-up programme in place. The child is 3 years old at the time of writing and is in good health.

Compound fetal presentation, uterine rupture and dreadful outcome: just a historical tale?

Compound presentation is defined as presentation of a fetal extremity alongside the presenting part. It may involve one or more extremities (hand, arm and foot) with the vertex or the breech. The majority of compound presentations is represented by the fetal hand or arm presenting with the vertex [1]. Compound presentation complicates from 1 in 700 to 1 in 1000 deliveries [2]. It is more likely to occur when the pelvis is not fully occupied by the fetus because of low birth weight, multiple gestation, polyhydramnios or a large pelvis [2]. Rupture of membranes when the presenting part is still high also increases the risk of compound presentation, cord prolapse or both. During the process of external version, a fetal limb (hand, arm or sometimes the foot) can be “trapped” below the fetal head, becoming the presenting part when labor ensues. Management of these individual events differs according to the finding and the circumstances. The literature on this subject is surprisingly scarce, although a number of case records have been published. One dreadful complication of compound presentation is represented by the uterine rupture, especially in case of obstructed labor. This rare but often catastrophic complication has a high incidence of fetal and maternal morbidity, due to hemorrhage, fetal anoxia or both. Among the most common risk factors, besides malpresentation, direct uterine trauma and multiparity play a very important role, as the uterus may be weakened by thinning and stretching of muscle fibers during labor, especially with aging and repeated pregnancies [3]. Even nowadays, the premonitory signs and the short time for instituting definitive therapeutic action make uterine rupture a fearful event: epidemiological data on uterine rupture confirm the necessity that obstetricians take careful note of the classic signs and symptoms of uterine rupture, above all where prenatal diagnostic means are not available. The tragic consequences of uterine rupture were obviously more common in the past, causing the unavoidable death of the woman. In the developed countries, the diagnosis of compound presentation will prompt, in most cases, the performance of a caesarean section avoiding any further complication. However, in poor resource countries, this is not the case and many women today may experience the same destiny that Giovanna of Austria had a few centuries ago. Giovanna was the unfortunate wife of Francesco de’ Medici, the second Grand Duke of Tuscany. In this editorial, we reconstruct her death, in the light of the archive documents and of the paleopathological evidence, showing similarities with many maternal deaths still occurring in many countries around the world.

The role of serial amnioinfusions in the management of previable pre-term premature rupture of membranes

predict a higher risk of malformations in subsequent pregnancies (Persson et al. 2009). Unfortunately, this malformation is not thoroughly characterised by conventional two-dimensional obstetric ultrasound. The role of 3D ultrasound in this case is to assess the type and extent of the cleft and for the parents’ reassurance, so they can understand the cosmetic appearance of the defect before birth. Prenatal counselling is based on the extent of the lesion and associated malformations. Treatment consists of multidisciplinary surgical correction, usually in several stages. Three-dimensional ultrasound imaging reduces parental anxiety, helps decide about pregnancy termination and allows discussion about the technical details of surgical treatment and the postnatal aspect of the newborn.