Volume 38, Issue 2

This template was produced by the Working Group on Multiple Pregnancy and was endorsed by the International Board of the World Association of Perinatal Medicine. The purpose of this document is to expand the 2007 Istanbul international consensus statement on the perinatal care of multiple pregnancy and to focus on the care of monochorionic (MC) twins. The document represents the view and opinion of individuals who composed this ad hoc committee and discusses various aspects that are specific and relevant to the care of MC twin gestations.

A pregnancy reaching 42 completed weeks (294 days) is defined as postterm (PT). The use of ultrasound in early pregnancy for precise dating significantly reduces the number of PT pregnancies compared to dating based on the last menstrual period. Although the fetal, maternal and neonatal risks increase beyond 41 weeks, there is no conclusive evidence that prolongation of pregnancy, per se , is the major risk factor. Other specific risk factors for adverse outcomes have been identified, the most important of which are restricted fetal growth and fetal malformations. In order to prevent PT and associated complications routine induction before 42 weeks has been proposed. There is no conclusive evidence that this policy improves fetal, maternal and neonatal outcomes as compared to expectant management. It is also unclear if the rate of cesarean sections is different between the two management strategies. After careful identification and exclusion of specific risks, it would seem appropriate to let women make an informed decision about which management they wish to undertake. There is consensus that the number of inductions necessary to possibly avoid one stillbirth is very high. If induction is preferred, procedures for cervical ripening should be used, especially in nulliparous women. Close intrapartum fetal surveillance should be offered, irrespective of whether labor was induced or not.

Twin-twin transfusion is the major cause of mortality and morbidity in monochorionic twins. Its pathogenesis has been gradually elucidated over the last three centuries. Among obstetricians, there was a long-lasting controversy on the existence of placental anastomoses and whether or not to tie the placental end of the firstborn infant's cord. However, a twin pregnancy practically never could be excluded. Stalpart van der Wiel described a twin-twin vessel connection in 1687. Studies on interfetal anastomoses using injection of placental vessels were published by Smellie in 1752, Osiander in 1781, and Brachet in 1821. Different types of anastomoses, and their associated fetal disorders were classified by Schatz in a series of papers at the end of the 19 th century. With the advent of ultrasound and laser techniques, prenatal diagnosis and treatment became available in the last decade of the 20 th century.

Objective: Dysregulation of maternal circulating adipokines has been implicated in several “great obstetrical syndromes” including preeclampsia (PE), small-for-gestational age (SGA) neonate and fetal death (FD). It has been suggested that adipokines provide a molecular link between metabolic derangements and inflammatory response in complicated pregnancies. Retinol binding protein 4 (RBP4), a novel adipokine, plays a role in obesity-related disorders, as well as in the regulation of the immune response. The aim of this study was to determine whether there are changes in maternal plasma concentrations of RBP4 in patients with PE and in those with an SGA neonate or FD. Study design: This cross-sectional study included patients in the following groups: 1) normal pregnancy (n=134); 2) PE (n=104); 3) SGA neonate (n=28); and 4) FD (n=37). Maternal plasma RBP4 concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) The median maternal plasma RBP4 concentration was higher among patients with PE than in those with a normal pregnancy (P=0.03); 2) The median maternal plasma RBP4 concentrations of patients with preterm PE (<37 weeks) was higher than that of those with term PE (P=0.017) and than that of those with a normal pregnancy (P=0.002); 3) The median maternal plasma RBP4 concentration did not differ significantly between patients with a normal pregnancy and those with an SGA neonate or with an FD; 4) Among normal pregnant women, the maternal plasma RBP4 concentrations did not correlate with pre-pregnancy body mass index, gestational age at blood sampling and neonatal birthweight. Conclusions: 1) Preeclampsia, but not pregnancy with an SGA neonate or an FD, is associated with a higher median maternal plasma concentration of RBP4 than normal pregnancy; 2) Preterm PE, and specifically early-onset PE, is associated with higher median RBP4 concentrations in maternal plasma compared to term PE. These findings suggest a role for RBP4 in the pathogenesis of preterm PE, but not in SGA and FD.

Aims: To investigate metabolic characteristics and perinatal outcomes of gestational diabetes mellitus (GDM) in women with polycystic ovary syndrome (PCOS). Methods: We evaluated 34 GDM in women with PCOS and 70 GDM in women without PCOS in this prospective study. All GDM women were treated with medical nutrition therapy (MNT). Pre-pregnancy clinical data, fasting glucose, fasting insulin (FINS), blood lipid, homeostasis model assessment index of insulin resistance (HOMA-IR) and perinatal outcomes were investigated. Results: GDM in women with PCOS had higher pre-pregnancy body mass index (BMI), higher incidence of overweight than in the non-PCOS group (each P<0.001). Incidence of history of infertility was also significantly higher in the PCOS group than in the non-PCOS group (20.6% vs. 2.9%, P<0.01). A higher incidence of early pregnancy loss (EPL) was found in the PCOS group than in the non-PCOS group (20.6% vs. 7.1%, P<0.05). Significantly higher in vitro fertilization and embryo transfer (IVF-ET) rate and insulin administration was also observed in the PCOS group than in the controls. No significant difference was found in the prevalence of preeclampsia, premature delivery, macrosomia, fetal death and neonatal congenital anomaly between GDM in women with and without PCOS (all P<0.05). Conclusions: Compared with the controls, no significant increase in the incidence of adverse perinatal outcomes was detected in GDM in women with PCOS by appropriate management.

Objective: Adipokines (cytokines produced by adipose tissue) play a major role in the control of body weight and energy distribution. Retinol-binding protein 4 (RBP4), only recently recognized as an adipokine, has been proposed to modulate systemic insulin sensitivity. The goal of this study was to determine whether there is an association between maternal plasma RBP4 concentration and the birth of a large-for-gestational-age (LGA) newborn in women with and without gestational diabetes mellitus (GDM). Study design: This cross-sectional study included pregnant women at term in the following groups: 1) normal pregnancy with an appropriate-for-gestational-age (AGA) neonate (n=64); 2) normal pregnancy with an LGA neonate (n=44); 3) GDM with an AGA neonate (n=55); and 4) GDM with an LGA neonate (n=42). Maternal plasma RBP4 concentration was determined by ELISA. Parametric and non-parametric statistics were used for analyses. Results: 1) Patients with GDM, either with AGA or LGA neonates, had a higher median plasma concentration of RBP4 than normal pregnant women who delivered an AGA neonate (P=0.01 and P=0.008, respectively); 2) mothers without GDM but with LGA neonates had a higher median plasma concentration of RBP4 than those with normal pregnancy and AGA newborns (P=0.001); 3) these findings remained significant after adjusting for maternal age, body mass index and gestational age at blood sampling. Conclusion: GDM is characterized by alterations in maternal circulating RBP4 concentrations akin to those of Type 2 diabetes mellitus. RBP4 concentrations in maternal plasma may play a role in accelerated fetal growth in the absence of overt carbohydrate intolerance.

Aim: To assess the preferences of pregnant women regarding the type of assistance desired to alleviate the consequences of nausea and vomiting of pregnancy (NVP). Methods: Women with NVP were asked to complete an online survey of 12 questions assessing the extent of NVP and the perspective on the importance of different healthcare professionals for their improvement. Results: A total of 121 pregnant women completed the survey. The median maternal age was 29 years and the average gestational age was 12.4±7.6 weeks. Sixty-four of the women (52.9%) had NVP in their previous pregnancy, which resulted in an average of 14.6±21.1 lost days of paid work. NVP necessitated admission to the emergency room in 36 (29.7%). When asked to rate (max 4 points) which healthcare professional would provide the best assistance for NVP, the physician was rated as the most important (average score of 3.56/4), followed by dietician (3.40/4), nurse (3.05/4) and social worker/psychologist as least important (1.77/4). Conclusion: Our findings illustrate women's perspective on NVP. According to our online survey, women perceive medically- and nutritionally-based care as most useful, whereas psychosocial factors are perceived to be less useful despite playing a central role in NVP.

Objective: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR) that has an important role in immunoregulation and vascular integrity. The aim of this study was to determine if PTX3 is present in amniotic fluid (AF) and whether its concentration changes with gestational age (GA), in the presence of preterm or term labor, and in cases of intra-amniotic infection/inflammation (IAI) associated with spontaneous preterm labor (PTL) or preterm prelabor rupture of membranes (PROM). Study design: This cross-sectional study included the following groups: 1) mid-trimester (n=45); 2) uncomplicated pregnancies at term with (n=48) and without (n=40) spontaneous labor; 3) women with PTL and intact membranes who: a) delivered at term (n=44); b) delivered preterm without IAI (n=40); or c) delivered preterm with IAI (n=62); 4) women with preterm PROM with (n=63) and without (n=36) IAI. PTX3 concentration in AF was determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) Among women with PTL and intact membranes, the median AF PTX3 concentration was significantly higher in women with IAI than in those without IAI (7.95 ng/mL vs. 0.38 ng/mL; P<0.001) and than in those who delivered at term (0.55 ng/mL; P<0.001); 2) women with preterm PROM and IAI had a higher median AF PTX3 concentration than those without IAI (9.12 ng/mL vs. 0.76 ng/mL; P<0.001); 3) the median AF PTX3 concentration did not change with GA (mid-trimester: 0.79 ng/mL vs. term not in labor: 0.58 ng/mL; P=0.09); and 4) labor at term was not associated with a significant change of AF PTX 3 concentration (in labor: 0.54 ng/mL vs. not in labor: 0.58 ng/mL, P=0.9). Conclusions: PTX3 is a physiologic constituent of the AF, and its median concentration is elevated in the presence of IAI, suggesting that PTX3 may play a role in the innate immune response against IAI.

Aim: To measure puerperal symphysis fundus distance (SFD) by two manual methods and to calculate individual normal values. Study design: Prospective cohort study including women after single pregnancy without special problems in uterine involution. Methods: SFD was daily measured on the 1 st –5 th postpartum days by counting the number of midwife's fingers put horizontally on the mother's abdomen and by a paper tape, respectively. Linear mixed model analysis was performed to determine SFD normal values. Results: Independent variables determining the SFD on different days after delivery were the gestational age and the delivery mode (finger method) and the maternal age, body mass index (BMI), delivery mode and birth weight (tape method). Individual normal values were calculated by regression equation including the coefficients for the independent variables. Conclusion: Puerperal SFD values measured by tape have more independent variables than those measured by fingers and reflect better the actual situation of the patient. It should be verified whether values deviating from normal values of tape measurements may prevent postpartum complications.

Objective: We compared a non-invasive fetal electrocardiogram (fECG) to Doppler cardiotocogram (CTG) during the 1 st stage of labor. Study design: This was a prospective observational study of non-invasive fECG using five abdominal electrodes and one Doppler ultrasound probe in 27 patients. Data were analyzed for reliability, clinical and statistical equivalence. Results: The fECG was similar to the traditional Doppler method. The fECG characterizes a fetal heart rate (FHR) trace in a similar way with regards to acceleration count, decelerations count and coincidence, variability and baseline. The FHR was overall correlated (Pearson's r=0.91). Conclusion: This non-invasive fECG presents an alternative, reliable and accurate assessment for fetal well-being during the 1 st stage of labor.

Aims: To assess staff acceptability of STAN ® monitoring system. Methods: This was a prospective study of health care professionals involved in the first 18 months of STAN ® use at a high risk maternity unit. Results: During the study period 75% of midwives and 80% of doctors questioned felt confident when interpreting STAN ® cases. A total of 88% of midwives and 90% of doctors felt adequately supported in their actual clinical use of the system. Of all the obstetricians who used the STAN ® , 95% felt it was an acceptable alternative to fetal blood sampling. One of the main complaints was poor signal quality which occurred in 16% of cases. As many as 97% of doctors and 96% of midwives considered STAN ® to be an acceptable way of monitoring high risk women after its introduction. Conclusions : Introduction of a new monitoring system to a high risk labor ward is possible, and acceptable to its staff. Constant practical and theoretical support and adherence to strict, easily understood guidelines is required.

Aims: To compare between computer analysis of intrapartum cardiotocography (CTG) features by the Omniview-SisPorto ® 3.5 and a consensus of clinicians. Methods: Agreement study using 50 consecutively acquired tracings (206 h of signals) with >60 min duration, <10% signal loss and recorded in labor at term by internal fetal heart rate (FHR) monitoring. Tracings were divided into 10-min segments and independently analyzed by three experienced clinicians, in order to estimate the FHR baseline and identify periodic events. A consensus was reached using a three round Delphi procedure. Results were compared with the analysis provided by the Omniview-SisPorto ® 3.5 system. Results: For baseline estimation, agreement between the computer and the consensus was high [intraclass correlation coefficient (ICC)=0.85; 95% confidence interval (CI) 0.46–0.93], with a mean difference of 3.7 bpm (limits of agreement –4.4–11.9 bpm), and 99% of differences under 15 bpm. A concordant identification was observed in 71% of accelerations (95% CI: 69%–73%), 68% of decelerations (95% CI: 66%–70%), and 87% of uterine contractions (95% CI: 85%–89%). Conclusions: A high agreement was observed between the Omniview-SisPorto ® 3.5 and a consensus of clinicians in evaluation of intrapartum CTG baseline, accelerations, decelerations and uterine contractions.

Aims: To determine the loss of fetal heart rate (FHR) baseline variability by frequency analysis. Methods: The FHR tracings of 12 normal fetuses and others with various conditions, as well as flat FHR tracings of a late deceleration (LD) and anencephaly recorded with Doppler fetal monitors, were scanned and processed using fast Fourier transform (FFT) analysis. The ratio of the area under the low frequency spectrum divided by the area under the whole spectrum (La/Ta) and the peak power spectrum density (PPSD) were determined. Results: Long-term variability (LTV) measures >10 bpm revealed significantly more La/Ta and PPSD than LTV <10 bpm in normal FHR tracings. The La/Ta and PPSD were >15% and 60 bpm 2 /Hz, respectively, in representative values of normal FHR cases and in those of fetal respiration, hiccupps and non-reactive FHR, whereas those of the flat baseline of LD and anencephaly were <15% and 60 bpm 2 /Hz. Conclusion: Loss of baseline variability is diagnosed when the La/Ta ratio and PPSD are <15% and 60 bpm 2 /Hz, respectively, based on the FFT frequency analysis of the FHR baseline.

Aims: To evaluate the arteriovenous (AV) pH difference in cord blood as a possible indicator of fetal O 2 -utilization at delivery. Furthermore to examine which maternal, fetal and obstetrical factors lead to elevated O 2 -utilization. Methods: In this retrospective study all singleton live births, delivered within a four-month period at the University Hospital in Innsbruck, Austria, were analyzed. In total 491 deliveries were evaluated. Arterial and venous cord blood samples were collected at birth and analyzed by using a Radiometer ABL 510. Results: Spontaneous deliveries showed a highly significant elevation in AV-difference (pH 0.10) as compared to cesarean sections (pH 0.05). In spontaneous births, the AV-difference was high in the case of low arterial cord blood pH (P<0.01), as well as in nuchal cord (P<0.01), high parity (P<0.01), very short labor (P<0.05) and elevated birth size and weight (P<0.05). Conclusions: As a result of increased fetal stress at birth, spontaneous delivery leads to higher O 2 -utilization than cesarean section, which is detectable in an elevated AV-difference. The AV-difference in combination with absolute pH-values can be used for the objective evaluation of fetal O 2 -utilization and consecutively the fetal stress at birth.

Aims: There is a rapid rise in the male-to-female sex ratio at birth in Hong Kong, which coincides with the influx of Mainland Chinese mothers crossing the border to give birth in Hong Kong. Our objective is to explore the sex ratio patterns among Hong Kong Chinese and Mainland Chinese. Methods: Analysis of the statistics from Hong Kong public hospitals from 2003 to 2007. Results: For the 194,602 babies studied, 140,962 (72.4%) were eligible (Hong Kong Chinese) and 52,741 (27.1%) were non-eligible (Mainland Chinese). The overall sex ratio at birth (defined as males per 1000 females) was 1088; 1078 for eligible and 1116 for non-eligible. For eligible persons, the sex ratios were 1060 for parity 0, 1073 for parity 1 and 1184 for parity 2 or above. For non-eligible persons, the sex ratios were 1047 for parity 0, 1149 for parity 1 and 1745 for parity 2 or above. Non-eligible persons of parity 1 or above were more likely to have sons than eligible persons of same parity (P<0.000). Conclusion: We believe that the rapid rise of sex ratio in Hong Kong can be partly explained by the influx of Mainland Chinese who may have practiced sex selection more than Hong Kong Chinese.

Aims: Fetal hypoxic-ischemic brain injury (HIBI) is a severe condition for which no effective therapy exists. In this study mesenchymal stem cells (MSCs) from human umbilical cord blood (UCB) of full-term newborns were isolated and intracerebrally transplanted into rat neonates after HIBI induction. Nerve function was assessed by the modified neurological severity scores (mNSS) to establish if MSCs could alleviate nerve injury. Results: Immunostaining showed the transplanted MSCs migrated to the hippocampus. Rats receiving MSCs treatment showed significant improvement in the mNSS when compared with controls. Also, histochemical study showed alleviation of brain tissue injury after MSCs treatment. Differentiation of MSCs to astrocytes, but not neurons, was observed. Conclusions: The results indicate a beneficial effect of intracerebral transplantation of MSCs on the functional recovery of rat neonates with HIBI.

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