Published by De Gruyter

Volume 40 Issue 4

Issue of Journal of Perinatal Medicine

Contents
Journal Overview

Masthead

Publicly Available June 1, 2012

Masthead

Page range: i-iv

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Review Article

February 13, 2012

Noninvasive prenatal diagnosis of Down syndrome: current knowledge and novel insights

Stavros Sifakis, Nikos Papantoniou, Dimitra Kappou, Aris Antsaklis

Page range: 319-327

Abstract

The noninvasive prenatal diagnosis of trisomy 21 (Down syndrome) is an actively researched area of prenatal medicine, as this is the most common aneuploidy compatible with life and a major cause of mental retardation. The isolation of intact fetal cells, and most importantly, the successful detection of fetal-origin nucleic acids (cell-free fetal DNA and RNA), in maternal plasma even from the early stages of pregnancy has inspired scientists to develop discriminative genetic markers for the prenatal detection of aneuploidy. In the near future, the development of epigenetic fetal-specific markers will possibly allow the universal application of a cell-free fetal DNA-based diagnostic test regardless of the gender of the fetus or its polymorphic status. Other promising approaches rely upon the detection of free placentally derived RNA transcribed from genes located on chromosome 21 and the application of highly sensitive techniques, such as digital polymerase chain reaction and high-throughput shotgun sequencing. However, irrespective of which strategy is selected for isolating or distinguishing fetal genetic material in maternal plasma, the small quantity of fetal origin nucleic acids poses severe technical challenges. In this review article, we present an overview of the current knowledge in the field of noninvasive prenatal assessment of fetuses with Down syndrome and the future perspectives regarding new fetal markers and novel molecular techniques that may eventually be applied in the clinical setting as a valid and safe option for women who opt for noninvasive accurate prenatal diagnosis.

Original Articles – Obstetrics

Open Access June 1, 2012

Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery

Maria-Teresa Gervasi, Roberto Romero, Gabriella Bracalente, Offer Erez, Zhong Dong, Sonia S. Hassan, Lami Yeo, Bo Hyun Yoon, Tinnakorn Chaiworapongsa

Page range: 329-343

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Abstract

Introduction: Intra-amniotic inflammation is traditionally defined as an elevation of amniotic fluid interleukin (IL)-6. Previous case control studies have suggested an association between an elevated midtrimester amniotic fluid IL-6 and preterm delivery, although such an association has been recently challenged. Intra-amniotic inflammation can also be defined by an elevation of the T-cell chemokine, Interferon-gamma-inducible protein (IP)-10. An elevation in amniotic fluid IP-10 has been associated with chronic chorioamnionitis, a lesion frequently found in late spontaneous preterm birth and fetal death. In contrast, an elevation in amniotic fluid IL-6 is typically associated with acute chorioamnionitis and funisitis. This study was conducted to examine the relationship between an elevation in amniotic fluid IL-6 in the midtrimester and preterm delivery at or before 32 weeks of gestation, and the amniotic fluid concentration of IP-10 and preterm delivery after 32 weeks of gestation. Materials and methods: This cohort study included 847 consecutive women undergoing genetic midtrimester amniocentesis; in 796 cases, amniotic fluid and pregnancy outcome was available for study after exclusion of abnormal karyotype and/or fetal congenital anomalies. Spontaneous preterm delivery was defined as early (≤32 weeks) or late (after 32 completed weeks of pregnancy). The amniotic fluid and maternal blood concentrations of IL-6 and IP-10 were measured by specific immunoassays. Results: 1) The prevalence of preterm delivery was 8.3% (66/796), while those of early and late spontaneous preterm delivery were 1.5% (n=12), and 4.5% (n=36), respectively; 2) patients who had a spontaneous preterm delivery after 32 weeks of gestation had a higher median amniotic fluid IP-10 concentration than those who delivered at term [median 713 pg/mL, inter-quartile range (IQR) 509–1427 pg/mL vs. median 589 pg/mL, IQR 402–953 pg/mL; P=0.006] and an elevation of amniotic fluid IP-10 concentration above 502 pg/mL (derived from an ROC curve) was associated with late spontaneous preterm delivery [odds ratio 3.9 (95% CI 1.6–9.9)]; 3) patients who had a spontaneous preterm delivery ≤32 weeks of gestation had a higher median amniotic fluid IL-6 concentration than those who delivered at term [median 2052 pg/mL, IQR 435–3015 pg/mL vs. median 414 pg/mL, IQR 209–930 pg/mL; P=0.006], and an elevated amniotic fluid IL-6 concentration above 1740 pg/mL (derived from an ROC curve) was associated with early spontaneous preterm delivery [odds ratio 9.5 (95% CI 2.9–31.1)]; 4) subclinical intra-amniotic inflammation, defined as an elevation of IL-6 (≥2.9 ng/mL) or IP-10 (≥2.2 ng/mL) concentration above the 95 th percentile of patients who had uncomplicated term delivery (n=652 for IL-6 and n=633 for IP-10), was observed in 6.3% (50/796) and 5.8% (45/770) of cases, respectively. Although each type of inflammation is a risk factor for spontaneous preterm delivery, many patients had a term delivery without complication; 5) the amniotic fluid in the midtrimester did not contain microorganisms detectable with cultivation techniques. Conclusions: Intra-amniotic inflammation is heterogeneous. Some patients have elevated amniotic fluid concentrations of IL-6, and are at risk for spontaneous preterm delivery before 32 weeks of gestation, while others have an elevated IP-10 (a chemotactic T-cell chemokine) and such patients are at risk for spontaneous preterm delivery after 32 weeks of gestation. A fraction of patients have subclinical intra-amniotic inflammation and deliver at term. The clinical significance of this condition remains to be determined.

March 27, 2012

An evolutionary test of the isoform switching hypothesis of functional progesterone withdrawal for parturition: humans have a weaker repressive effect of PR-A than mice

Günter P. Wagner, Yingchun Tong, Deena Emera, Roberto Romero

Page range: 345-351

Abstract

Background: A decrease in maternal serum progesterone (P4) concentrations precedes the onset of labor in most placental mammals. Humans differ by maintaining high levels of P4 throughout birth. Parturition in humans probably includes mechanisms that undercut the pregnancy sustaining function of P4. One attractive hypothesis is the isoform switching hypothesis (ISH). ISH is supported by in vitro evidence that progesterone receptor isoform A (PR-A) inhibits PR-B and that the PR-A/PR-B ratio increases towards term. Materials and methods: Here, we test the hypothesis that isoform switching is an adaptation to high levels of P4 at term, predicting that, in humans, PR-A mediated repression of PR-B is stronger than in mouse. We use reporter assays with human and mouse PRs to detect species differences in the repressive effects of PR-A. Results: We found that human PR-B is less sensitive to repression by human PR-A than mouse PR-B, contrary to our prediction. The difference between human and mouse PR-B sensitivity is most pronounced at PR-A/PR-B ratios typical for the preterm myometrium. Conclusions: Our results are inconsistent with the ISH. We speculate that, instead, the lower sensitivity of human PR-B to PR-A may be relevant for the maintenance of pregnancy at high progesterone levels and increasing PR-A concentrations towards term.

March 22, 2012

Fetomaternal hemorrhage in the second trimester

Waltraut M. Merz, Franziska Patzwaldt, Rolf Fimmers, Birgit Stoffel-Wagner, Ulrich Gembruch

Page range: 353-357

Abstract

Aims: To investigate fetomaternal hemorrhage (FMH) rate and quantity in the second trimester of pregnancies with fetal anomalies and to assess the impact of invasive prenatal and termination procedures. Methods: Blood samples from women before termination of pregnancy were collected and analyzed by dual-color flow cytometry. Various clinical parameters were studied for their association with FMH. Results: In total, 67 women were recruited; pre- and post-termination pairs were collected for 31 women. HbF cells were present in 91.0% of specimens, in 29.9% the transfused blood volume was ≥4.2 mL. FMH ≥30 mL was found in 3.0%, and chronic FMH, defined as FMH ≥40% of fetoplacental blood volume in 7.5%. At the limit of quantification (0.1%) none of the clinical parameters was associated with the presence of HbF cells, nor was there a difference in HbF cell concentrations between pre- and post-termination blood samples. Conclusions: Compared to normal term pregnancy, transfer of fetal red blood cells into the maternal circulation is increased in second-trimester pregnancies with fetal anomalies. FMH is not associated with invasive procedures or surgery performed in the context of termination. We hypothesize that the abnormal pregnancy itself, by means of an abnormal uteroplacental interface, is causing the increased transfer.

February 1, 2012

Contribution of 3D power Doppler ultrasound to the evaluation of placental circulation in normal pregnancies and pregnancies complicated by preeclampsia

Carmen Mihaela Mihu, Tudor Drugan, Dan Mihu

Page range: 359-364

Abstract

Aim: This study assesses the value of intraplacental vascularization indices, determined by three-dimensional (3D) power Doppler ultrasound, in the evaluation of placental circulation. A prospective study has been conducted on two groups of pregnant women. Group I included pregnant women with a normal evolution of the pregnancy, whereas group II consisted of pregnant women with preeclampsia. The subjects were assessed by ultrasound between the 28 th and 38 th week of amenorrhea. Intraplacental vascularization was studied by 3D and Doppler ultrasound. Intraplacental vascularization indices were calculated using the VOCAL program, whereas statistical processing was completed using descriptive and comparative statistical methods. Results: The values of the three intraplacental vascularization indices were lower in the group of pregnancies with preeclampsia compared with the group with normal pregnancies. In normal pregnancies, the evolution of umbilical resistivity index (RI) values was statistically proven to be significantly correlated with the values of intraplacental vascularization indices. In the case of pathological pregnancies, RI values could be maintained within normal limits, whereas vascularization, flow, and vascularization-flow index values decreased significantly compared with the group of normal pregnancies. Conclusions: The determination of intraplacental vascularization indices can play an important role in the monitoring of placental circulation in pregnancies with a normal evolution and those with preeclampsia.

February 16, 2012

Two vs. three or more primary recurrent pregnancy losses – are there any differences in epidemiologic characteristics and index pregnancy outcome?

Asher Bashiri, Ronit Ratzon, Shimon Amar, Ruslan Serjienko, Moshe Mazor, Ilana Shoham-Vardi

Page range: 365-371

Abstract

Objective: To compare obstetric characteristics and pregnancy outcomes of patients following two vs. three or more primary recurrent pregnancy losses (RPL). Study design: A retrospective cohort study including 168 patients with primary RPL followed by subsequent (index) pregnancy, 124 patients with three or more consecutive RPL, and 60 patients with two consecutive RPL was performed. All patients were evaluated and treated in the RPL Clinic in the Soroka University Medical Center. Results: Obstetric characteristics of the study groups were similar. Women with three or more RPL compared to women with two RPL had a higher rate of abnormal thyroid stimulating hormone (TSH) levels (16.3 vs. 2.6%; P=0.033), higher rates of spontaneous pregnancy (91.7 vs. 77.4%; P<0.05), and higher rates of Clexane treatment (40.3% vs. 18.6%; P=0.016). In the index pregnancy, live birth rate was not statistically different between the two groups (81.1% in the two-RPL groups vs. 70.6% in the three-RPL group) nor was neonatal mortality. Conclusions: Patients with two RPL and three RPL had very similar obstetric characteristics and evaluation test results. Differences in index pregnancy outcomes were not statistically significant. Therefore, evaluation in primary RPL is recommended after two RPL.

February 10, 2012

Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo

Ronny P. Etzl, Thomas Vrekoussis, Christina Kuhn, Sandra Schulze, Johannes M. Pöschl, Antonis Makrigiannakis, Udo Jeschke, Daisy E. Rotzoll

Page range: 373-378

Abstract

α-Tocopherol transfer protein (α-TTP) has been identified as the major intracellular transport protein for the antioxidant vitamin E (α-tocopherol). Expression of α-TTP on the reproductive system has been described both in mouse uterus and lately in the human placenta. The aim of this study was to clarify if placental expression of α-TTP can be modified by substances causing oxidative reactions. The human choriocarcinoma cell line BeWo was, therefore, treated with two known pro-oxidants. α-TTP expression was determined with immunocytochemistry and evaluated by applying a semiquantitative score. The presence of pro-oxidants in BeWo cells induced α-TTP expression. We thus hypothesize that stimulation of α-TTP expression by oxidative stress, as this was induced by pro-oxidants, could be part of an antioxidant process occurring in the placenta in the aim of enhancing the supply of α-tocopherol. This process could occur both in normal pregnancies, as well as in pregnancy disorders presented with intensified oxidative stress. In that view, this model is proposed for further oxidative stress studies on trophoblast and placenta, on the grounds of clarifying the role of α-tocopherol in pregnancy physiology and pathophysiology.

February 14, 2012

Risk factors for preeclampsia in twin pregnancies: a population-based matched case-control study

Miha Lučovnik, NataŠa Tul, Ivan Verdenik, Živa Novak, Isaac Blickstein

Page range: 379-382

Abstract

Objective: To evaluate associated factors for preeclampsia in twin gestations and to compare incidences of pregnancy complications among twin pregnancies with vs. without preeclampsia. Patients and methods: We performed a case-control study using a population dataset of twin pregnancies delivered after 24 weeks of gestation, in Slovenia, between 1997 and 2009. Cases were twin gestations complicated by preeclampsia and controls were cases matched by gestational age, parity, and chorionicity. Results: We identified 181 cases (4.7%) of preeclampsia among 3885 twins and 542 matched controls. High pre-pregnancy body mass index (BMI) and gestational diabetes were significantly associated with preeclampsia [odds ratio (OR) 1.8, 95% CI 1.26, 2.77 for overweight (BMI 25.0–29.9); OR 4.72, 95% CI 2.83, 7.89 for obese (BMI≥30), and OR 2.19, 95% CI 1.03, 4.68 for gestational diabetes]. The association was not significant for preexisting hypertension, maternal age, smoking, and pregnancy following assisted reproduction. Placental complications (previa, abruption, or adherent placenta) were more common, and low birth weight less common in the preeclampsia group (P=0.03 and P=0.01, respectively). Conclusions: High pre-pregnancy BMI carries an especially high risk for the development of preeclampsia and its complications in twin gestation.

March 14, 2012

Bishop score and cervical length at 33–35 weeks of gestation and the risk of intrapartum cesarean delivery of twins

Kyo Hoon Park, Sung Youn Lee, Eun Ha Jeong, Aeli Ryu, Kyung Joon Oh, Shi Nae Kim

Page range: 383-388

Abstract

Aim: The aim of this study is to determine the association between Bishop score and cervical length measured at 33–35 weeks of gestation and the intrapartum risk of cesarean delivery of twins. Methods: This prospective observational study recruited women with vertex/vertex twin gestations at 33–35 weeks of gestation. Determination of the Bishop score and ultrasound measurement of the cervical length were performed. A regression model was constructed with control for known intrapartum and postpartum confounders. Results: One hundred and forty-six women were analyzed; 18 women (12.3%) had cesarean deliveries during labor. Based on univariate nalysis, the Bishop score at 33–35 weeks was significantly associated with the risk of intrapartum cesarean delivery of twins, whereas cervical length, maternal age, height, and weight at 33–35 weeks were not associated. Multivariate logistic regression analysis identified induction of labor and birth weight of the first-born twin, but not Bishop score, as independent predictors of intrapartum cesarean delivery of twins. Conclusions: A low Bishop score at 33–35 weeks of gestation was associated with an increased risk of intrapartum cesarean delivery of twin gestations. However, this relationship disappeared after adjusting for relevant intrapartum or postpartum confounders. Only labor induction and high birth weight of the first-born twin were independently associated with an increased risk of cesarean delivery in labor.

February 29, 2012

Primary vs. secondary recurrent pregnancy loss – epidemiological characteristics, etiology, and next pregnancy outcome

Efrat Shapira, Ronit Ratzon, Ilana Shoham-Vardi, Ruslan Serjienko, Moshe Mazor, Asher Bashiri

Page range: 389-396

Abstract

Objective: To compare epidemiological and obstetric characteristics, etiology and next pregnancy outcomes of women with primary vs. secondary recurrent pregnancy loss (RPL). Study design: A retrospective cohort study, including 420 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 162 were primary RPL women and 258 were secondary RPL women. All patients were evaluated and treated in the RPL clinic at the Soroka University Medical Center. Results: Live birth rate in the index pregnancy was not statistically different between primary and secondary RPL women (75.9 and 70.9%, respectively). The only significant difference in the etiology evaluation was in abnormal prolactin levels (14.1% of the primary and 1.4% of the secondary RPL group). Women with primary RPL had, at the index pregnancy, significantly higher rates of preterm delivery, fetal growth restriction, and gestational diabetes mellitus. In a multivariable logistic regression analysis, primary RPL adjusted for maternal age and gravidity, was an independent risk factor for preterm delivery compared with secondary RPL [adjusted OR 2.62, CI (95%) 1.30–5.26]. Conclusions: The prognosis of the two groups was similar regarding live birth rate at the index pregnancy; however, women with primary RPL were more prone to adverse obstetric and neonatal outcomes.

April 2, 2012

Safety and efficacy of high-dose intravenous iron carboxymaltose vs. iron sucrose for treatment of postpartum anemia

Anita Pfenniger, Christine Schuller, Patricia Christoph, Daniel Surbek

Page range: 397-402

Abstract

Objective: The purpose of this study is to compare the safety and efficacy of intravenous (IV) high-dose iron carboxymaltose (ICM) with iron sucrose (IS) for the treatment of postpartum anemia. Study design: We performed a retrospective cohort study with 210 anemic inpatient women in the postpartum period who received IV high-dose ICM (15 mg/kg; maximum, 1000 mg) or IS (2×200 mg), respectively. Safety and tolerability of both groups were compared on the basis of reported systemic and local adverse events. The cohorts were matched for baseline characteristics and their initial hemoglobin (Hb) values. The secondary endpoint included drug efficacy assessment by measurement of Hb level increase up to 8 days after treatment. Results: Rapid administration of high ICM doses was as well tolerated as IS with overall adverse events of 5% (ICM) vs. 6% (IS). The most common complaint was burning and pain at the injection site. ICM was as effective as IS in changing Hb levels from the baseline. There was no difference in the mean daily Hb increase between the groups. Women with severe anemia showed the most effective responsiveness. Conclusions: IV ICM is as safe as IS in the management of postpartum (IDA) iron deficiency anemia despite five times of higher dosage. Both drugs are effective and offer a rapid normalization of Hb after delivery. The single application of ICM shows advantages of lower incidence of side effects at the injection site, a shorter treatment period, and better patient compliance.

June 1, 2012

Knowledge gap of recommendations in ACOG practice bulletins: A survey of members of the Central Association of Obstetricians and Gynecologists

Danish Siddiqui, Khaled Sakhel, David F. Lewis, Suneet P. Chauhan

Page range: 403-412

Abstract

The purpose of this survey was to assess the knowledge gap of recommendations in practice bulletins (PBs). A survey consisting of three questions for 12 selected PBs (six obstetric and six gynecologic) was developed and sent to members of the Central Association. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of the 385 active members, 100 (26%) returned the survey. The overall correct score was 49%. Respondents were significantly more likely to know recommendations in obstetric PBs (60%) than gynecologic PBs (39%; OR 2.45, 95% CI 2.12–2.81). Maternal-fetal medicine sub-specialists (n=27), compared with obstetricians-gynecologists (n=66), did significantly better with obstetric PBs (67% vs. 59%; OR 1.42, 95% CI 1.32–1.77) and substantially worse with gynecologic topics (34% vs. 39%; OR 0.79, 95% CI 0.63–0.98). In conclusion, since members of the Central Association have a substantial knowledge gap, there are ample opportunities to educate and reinforce PB recommendations.

Original Articles – Fetus

Open Access February 1, 2012

Three years’ experience of using a 29-gauge atraumatic needle for amniocentesis

Michael Tchirikov, Carola Arnold, Viktor Oshovskyy, Ulf-Rüdiger Heinrich, Volker Thäle

Page range: 413-417

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Abstract

Aims: To quantify the procedure-related complication rate after using modified technique of amniocentesis with a 29-gauge (29-G) pencil-point needle. Methods: This is a prospective, descriptive study of 316 amniocenteses that were performed by means of atraumatic 29-G pencil-point needle under ultrasound control. Results: A total of 316 amniocenteses were observed through the postprocedural period. The median time needed to retrieve 15 mL of amniotic fluid was 4 min. A total of 19 pregnancies were terminated after genetic testing. No case was regarded as procedure-related fetal loss. No other complications were observed. Seventeen children were born before 37 completed weeks of gestation and five children had a birth weight <2000 g. Conclusions: Amniocentesis with the 29-G atraumatic pencil-point needle seems to be a safe procedure with extremely low risk of complications and is a good alternative to the traditional 22-G Quincke needle.

April 13, 2012

Role of foetal MRI in the evaluation of ischaemic-haemorrhagic lesions of the foetal brain

Lucia Manganaro, Silvia Bernardo, Laura La Barbera, Giuseppe Noia, Lucia Masini, Alessandra Tomei, Francesca Fierro, Valeria Vinci, Paolo Sollazzo, Evelina Silvestri, Antonella Giancotti, Mario Marini

Page range: 419-426

Abstract

Objective: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. Study design: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. Results: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. Conclusions: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.

Original Articles – Newborn

February 29, 2012

Acquisition of full enteral feeds may depend on stooling pattern in very premature infants

Miguel Sáenz de Pipaón Marcos, Ma Teresa Montes Bueno, Belén SanJosé, Esmeralda Torralba, Milagros Gil, Isabel Parada, Pilar Amo

Page range: 427-431

Abstract

Objective: The objective of this study was to determine whether acquisition of normal stooling pattern is associated with full enteral feeding and growth. Study design: This is a prospective observational study of infants with a gestational age of <28 weeks (n=121). All infants admitted to our unit during the study period were managed using the same protocol for rectal stimulation and enemas: we used rectal stimulation if abdominal distension and no defecation occurred in the previous 24 h; enema administration was practiced if abdominal distension persists and no defecation had occurred after rectal stimulation. Age of normal bowel habit (T-NBH) is defined as days when two stools passed each day without enemas or stimulation for three consecutive days. Full enteral feeding is measured by time to receive 120 mL/kg/day (T-120). Multivariable linear regression estimated the contribution of T-NBH on T-120 and the effect of tolerance on growth. Results: T-NBH was 16 days (12, 24 days) and T-120 was 16 days (12, 24 days). T-120 decreased with earlier normal bowel habit (r=0.625, P<0.0001). Change in weight z-score between 36 weeks postmenstrual age and birth was less pronounced with earlier full enteral feeding (r=–0.446, P<0.0001). Conclusion: Normalization of bowel habit is an important determinant of full enteral feeding of very immature infants. Earlier full enteral feeding is associated with less postnatal growth failure.

February 1, 2012

An open-label, randomized efficacy and safety trial of subcutaneous and intramuscular BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of HBV-carrier mothers

Horst Buxmann, Wolfgang Kamin, Gergely Kriván, Pál Siklós, Werner Mendling, Andrea Wartenberg-Demand, Daniele M. Wolf, Rolf L. Schlösser

Page range: 433-438

Abstract

Objective: The objective of the study was to assess the efficacy and safety of subcutaneously (SC) and intramuscularly (IM) administered BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of hepatitis B surface antigen (HBs/HBsAg)-positive mothers in the prevention of hepatitis B infection. Methods: This was an open, prospective, multicenter trial, in which infants were randomized to receive a single SC or IM dose of BT088 (200 IU, 0.4 mL) within 12 h of birth simultaneously with active vaccination against hepatitis B. The primary efficacy variable was the response rate, defined as the proportion of infants whose anti-HBs concentration was negative at predose and ≥100 IU/L 48 to 72 h postdose. Results: The full analysis set included 31 neonates (17 SC and 14 IM). Response was experienced by 30 (96.8%) of 31 infants who received BT088 by either route of administration. The median postdose anti-HBs concentration was 261.2 IU/L. One neonate had a postdose anti-HBs level lower than 100 IU/L (81.0 IU/L). No infant experienced seroconversion during the 7- to 15-month follow-up. BT088 was well tolerated, with no allergic-like, or injection-site reactions observed. Conclusion: SC and IM administration of 200 IU (0.4 mL) BT088 resulted in protective serum anti-HBs titers within 72 h of administration in newborn infants and was well tolerated and effective.

Open Access March 27, 2012

Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis

Horst Buxmann, Otto M.v. Stackelberg, Rolf L. Schlößer, Gisela Enders, Markus Gonser, Matthias Meyer-Wittkopf, Klaus Hamprecht, Martin Enders

Page range: 439-446

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Abstract

Aims: The aim of this study was to investigate the current prenatal “off-label use” of cytomegalovirus hyperimmunoglobulin (CMV-HIG) in the prevention and treatment of congenital CMV (cCMV) infection, including the long-term outcome of the children. Methods: This retrospective observational study comprised mothers and their children, born between January 1, 2006, and October 30, 2010. Prenatal CMV-HIG was administered after diagnosis of primary CMV infection of the mother. Clinical and virological data were collected from maternal and pediatric medical and laboratory reports. Follow-up was 12–36 months after birth. Results: Forty-two women and 43 children met the study criteria. In total, 40 mothers and six unborn infants received 115 doses of CMV-HIG. The treatment group (TG; CMV-DNA polymerase chain reaction-positive amniotic fluid) included four mothers; the multinomial group (MG; CMV-positive mother and unknown CMV status of fetus) included 38 mothers (39 infants). For the four unborn infants in TG, CMV-HIG was administered either intraumbilically or into the amniotic fluid; three of the four mothers received intravenous CMV-HIG. Three children in TG remained CMV-positive and were asymptomatic at birth and during follow-up. One infant in TG had symptomatic cCMV infection in utero , at birth, and during follow-up. In MG, 37 of 38 women received intravenous CMV-HIG and two of 39 infants received CMV-HIG in utero . In total, 9 (23.1%) of 39 children in MG were positive for cCMV (including a terminated pregnancy). All eight instances of cCMV infection at birth in MG were asymptomatic at birth and during follow-up. The fetus from the terminated pregnancy showed no sonographic symptoms of cCMV infection. No severe side effect occurred in 115 CMV-HIG applications. Conclusion: CMV-HIG was well tolerated. Compared with published untreated mother-child pairs, we observed a trend toward a smaller risk for intrauterine CMV transmission following CMV-HIG application. Signs of prenatal cCMV disease were not reversed after CMV-HIG.

March 14, 2012

Therapeutic hypothermia and hypoxic ischemic encephalopathy: opinion and practice of pediatricians in South Africa

Yaseen Joolay, Michael C. Harrison, Alan R. Horn

Page range: 447-453

Abstract

Background: Recent newborn resuscitation guidelines recommend therapeutic hypothermia (TH) as a treatment to reduce long-term neurological deficit in hypoxic ischemic encephalopathy (HIE) survivors. In South Africa, varied resource constraints may present difficulties in the implementation of TH. Objective: To determine the opinions and practice of South African pediatricians, regarding TH and the management of HIE. Methods: We invited 288 South African pediatricians and neonatologists to participate in a web-based survey by e-mail. Practitioners were identified using the Medpages™ database. Results: Responses were received from 37.8% of the e-mails. Seventy-six percent of respondents stated that hypothermia was either effective or very effective while 4% stated TH was ineffective in the management of HIE. Only 42% of respondents offered TH and a further 9% transferred patients to other units for cooling. Twenty-four percent had not implemented TH nor planned to introduce it into practice in the near future. Ninety-eight percent of respondents stated TH should be the standard of care in tertiary neonatal units. Conclusion: Most pediatricians in South Africa who responded to the survey stated that TH is effective to reduce the neurological deficit in HIE, however, less than half offered it as a treatment.

March 22, 2012

Circulating endothelial progenitor cells in premature infants: is there an association with premature birth complications?

Krzysztof Safranow, Maciej Kotowski, Joanna Lewandowska, Anna Machalińska, Violetta Dziedziejko, Ryszard Czajka, Zbigniew Celewicz, Jacek Rudnicki, Bogusław Machaliński

Page range: 455-462

Abstract

Background: The most common morbidities in preterm infants are associated with vascular pathology. Endothelial progenitor cells (EPCs) have been implicated in repair of the vasculature, but their role in the pathogenesis of prematurity complications is not clear. Objectives: We prospectively investigated an association between the number of EPCs circulating in blood during delivery as well as 2 and 6 weeks afterwards, the level of growth factors regulating their migration/homing, and the incidence of premature birth complications. Patients and methods: The study groups consisted of 90 preterm and 52 full-term infants. Early-EPCs (CD133 + CD34 + CD144 + ) and late-EPCs (CD133 – CD34 + CD144 + ) were analysed in cord blood (CB) and peripheral blood (PB). Results: We found higher early- and late-EPC counts in the CB of premature infants compared with full-term babies. The number of circulating early- and late-EPCs was inversely associated with the Apgar score of preterm infants. A positive association between the early-EPC count and the risk of respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, and infections was found. Nevertheless, multivariate analysis revealed that a higher number of EPCs was not an independent predictor of prematurity complications, which were directly related to lower gestational age. The EPC count in full-term infants maintained a constant, relatively low level over the 6-week follow-up, whereas the EPC population in preterm infants gradually decreased during this period. Furthermore, the number of CB late-EPCs in preterm infants positively correlated with VEGF concentration. Conclusions: EPCs may play a considerable role in vascular development in preterm infants.

Short Communication

March 29, 2012

The impact of length of second stage of labor on shoulder dystocia outcomes: a retrospective cohort study

Vasiliki A. Moragianni, Michele R. Hacker, Frank J. Craparo

Page range: 463-465

Abstract

Objective: To compare obstetrical and neonatal outcomes of vaginal deliveries complicated by shoulder dystocia, according to the length of second stage of labor. Methods: We conducted a retrospective cohort study of 177 shoulder dystocia cases that were divided into three categories according to second stage duration (1–20, 21–59, 60–180 min, respectively). The three categories were compared in terms of obstetric characteristics and neonatal outcomes. Statistical analysis utilized the χ 2 -test and analysis of variance where appropriate. The odds ratios of brachial plexus injury and having a 5-min APGAR score <7 across the second stage duration categories were calculated using logistic regression models that adjusted for potential confounders. Results: The incidence of brachial plexus injury was 5.4% (1 st category), 4.4% (2 nd category) and 26.9% (3 rd category); P<0.01. The higher incidence of brachial plexus injury in the group where second stage lasted >1 h was confirmed by logistic regression, with and without adjusting for confounders. Conclusions: The incidence of brachial plexus injury increases with the length of second stage, even after controlling for confounders.

Congress Calender

June 1, 2012

Congress Calendar

Page range: 467-467

Abstract

No Abstract available.

About this journal

Journal of Perinatal Medicine: Happy 50th Anniversary
The Journal of Perinatal Medicine (JPM) is celebrating its 50th anniversary. The first issue was published in January 1973, making it the first scientific journal in the field of perinatal medicine. JPM was founded by Erich Saling of Berlin (Germany), the father of perinatal medicine, and Roberto Caldeyro Barcia of Uruguay, an expert in uterine contractility, Edward Hon from the USA, who pioneered electronic heart rate monitoring of the fetus, and Stanley James, one of the most outstanding neonatologists. Over the past 50 years, JPM has grown with the increasing number of annual submissions and readers, as well as increasing impact within the scientific community.
Enjoy reading the Special Anniversary Issue we published on the occasion of JPM's milestone birthday!

Objective
The Journal of Perinatal Medicine (JPM) is a truly international forum covering the entire field of perinatal medicine. It is an essential news source for all those obstetricians, neonatologists, perinatologists and allied health professionals who wish to keep abreast of progress in perinatal and related research. Ahead-of-print publishing ensures fastest possible knowledge transfer. The Journal provides statements on themes of topical interest as well as information and different views on controversial topics. It also at informs about the academic, organisational and political aims and objectives of the World Association of Perinatal Medicine (WAPM)

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Topics
JPM covers the entire field of perinatal medicine, obstetrics and neonatology. It is published in 9 issues per year.

Article formats
Research Articles, Reviews, Mini Reviews and Opinion Papers, Short Communications, Editorials, Letters to the Editor, WAPM-Newsletters