Band 39, Heft 2

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies, characterized by the development of unbalanced chronic blood transfer from one twin, defined as donor twin, to the other, defined as recipient, through placental anastomoses. If left untreated, TTTS is associated with very high perinatal mortality and morbidity rates, due to a combination of fetal and/or obstetric complications. The reported prevalence is 10–15% of all MC twins, or about 1 in 2000 pregnancies. This consensus document reviews available evidence and offers practical guidance to clinicians by providing recommendations on various aspects concerning diagnosis and management of TTTS.

Anemia during pregnancy and the postpartum period is commonly caused by iron deficiency and is a significant worldwide issue with severe consequences for both mother and developing fetus. From a worldwide perspective, iron-deficiency anemia (IDA) during pregnancy is highest in the Asia-Pacific region; however, there has been little guidance in this region for safe and effective treatment. An expert panel was convened to develop a concise and informative set of recommendations for the treatment of IDA in pregnant and postpartum women in the Asia-Pacific region. This manuscript provides these recommendations and aims to reduce the morbidity and mortality associated with IDA in pregnant and postpartum women in the Asia-Pacific region. The consensus recommendations define anemia as a hemoglobin (Hb) level <10.5 g/dL during pregnancy and <10 g/dL during the postpartum period, and provide cut-off Hb levels to initiate therapy with oral iron, intravenous iron or red blood cell transfusion.

Background: Gestational weight gain (GWG) above the recently recommended ranges is likely to be related to adverse pregnancy outcomes and therefore a challenge in industrialized countries. Aims: We conducted a systematic review on observational studies in order to gain more evidence on whether diets with lower caloric/protein content or other diets might be associated with lower GWG. Methods: We searched in MEDLINE and EMBASE for observational studies written in English or German reporting associations between diet and GWG in singleton pregnancies of healthy women in industrialized countries. Results: We identified 12 studies which met the inclusion criteria. Five studies suggested significant positive associations between energy intake and GWG, whereas three found no significant association. Further significant positive associations of GWG were reported with respect to protein intake, animal lipids, energy density and a number of different food servings per day, whereas intake of carbohydrates and vegetarian diet were associated with less GWG. Conclusions: We suggest that GWG might be reduced by lower energy intake in pregnancy.

Objective: To determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes. Study design: An amniotic fluid index (AFI) was determined before amniocentesis (<24 h) in 272 patients with preterm labor and intact membranes (<35 weeks of gestation). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8 (MMP-8). Non-parametric statistical techniques and survival analysis were used. Results: 1) The overall prevalence of oligohydramnios (AFI of ≤5 cm) in patients with preterm labor and intact membranes was 2.6% (7/272); 2) patients with oligohydramnios had a higher frequency of AF infection and/or inflammation than those without oligohydramnios [85.7% (6/7) vs. 32.8% (87/265); P<0.01]; 3) patients with oligohydramnios had a higher median AF MMP-8 concentration than those without oligohydramnios [median 664.2 (range 16.6–3424.7) ng/mL vs. median 2.3 (range <0.3–6142.6) ng/mL; P<0.01]; 4) women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios [median 18 h (range 0–74 h) vs. median 311 h (range 0–3228 h); P<0.01], and this difference remained significant after adjusting for gestational age and the presence or absence of AF infection/inflammation. Conclusion: Patients with preterm labor and oligohydramnios are at increased risk for impending preterm delivery and intra-amniotic inflammation and, therefore, may benefit from careful surveillance.

Aims: The purpose of this study was to investigate correlations between first trimester placental volume (PV) and blood flow indexes (FIs), bilateral uterine artery pulsatility indexes, notching, and biochemical parameters: pregnancy-associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotropin (f-β-hCG), and insulin-like growth factor-1 (IGF-1) to predict the high-risk pregnancies in the first trimester. Methods: We prospectively examined 310 patients at 11–14 weeks of pregnancy using transabdominal 3D gray scale and power Doppler ultrasound for assessing PV, vascularization index, FI, and vascularization FI (VFI). The acquired volumes were analyzed using VOCAL™ imaging software. The results were correlated with biochemical parameters. Results: We found significant correlations between PV and biochemical parameters, and between placental blood flow studies and other parameters. Finally, PV/crown-rump length so called the placental quotient is also related to both PAPP-A and VFI. Conclusions: Placental volumetry, uterine artery Doppler studies, blood flow calculations and biochemical parameters, such as f-β-hCG, PAPP-A, and IGF-1 could be important in the early and rapid diagnosis of high-risk pregnancies. Thus, they may be useful in first trimester prediction of fetal growth restriction presenting with alterations in PV and vascularity.

Aims: To evaluate the impact of umbilical and uterine artery Doppler in the second and third trimester on antenatal course, labor and delivery in a low-risk primigravid population. Methods: Prospective recruitment of 1011 low-risk primigravidas with uterine and umbilical artery Doppler assessment at 22–24 weeks and 36 weeks. All mothers and infants were reviewed postnatally with a retrospective analysis of ultrasound and clinical outcome data. Results: Elevated uterine artery indices were associated with increased rates of threatened miscarriage, higher rates of pre-eclampsia (PET) and a higher incidence of fetal birth weight <2 nd and 9 th centile for gestation. Uterine artery pulsatility index (PI) >95 th centile for gestation was associated with statistically higher rates of small-for-gestational age (SGA) infants. Elevated umbilical artery indices were associated with higher rates of induction of labor and a higher incidence of fetal birth weight infants <2 nd and 9 th centile for gestation. Umbilical artery PI >95 th centile for gestation was associated with statistically higher rates of SGA infants. Conclusion: Elevated uterine and umbilical artery indices are associated with higher rates of maternal and fetal disease.

Aims: To investigate the relation between serum levels of C-reactive protein (CRP) at pre-/post-cerclage points and preterm birth at <33 weeks of gestation in women with indicated cervical cerclage (CC). Methods: Fifty-eight women with CC indicated for a short or soft cervix, but no visible or protruding fetal membranes into the vagina, between 17 and 26 weeks of gestation, were reviewed. Serum CRP levels were examined three times: just before cerclage, and on day 1 and day 2 post-cerclage. Results: Serum CRP levels on day 1 and day 2, but not just before cerclage, predicted the occurrence of very preterm birth. In women with cervical dilatation of <3.0 cm, serum CRP levels on post-cerclage day 1 were associated with the increase of very preterm birth [CRP ≥1.5 mg/dL vs. <1.5 mg/dL: 4/5 (80%) vs. 8/31 (26%), P=0.033]. In women with cervical dilatation of <3.0 cm, serum CRP ≥3.0 mg/dL on post-cerclage day 2 was also associated with the increase of very preterm birth. Conclusion: In women with indicated CC between 17 and 26 weeks of gestation, increased levels of serum CRP on post-cerclage day 1 or 2 might be ominous signs for very preterm birth.

Objective: To elucidate the possible etiological role of the vascular endothelial growth factor (VEGF) in the inverse correlation between nuchal translucency (NT) thickness and fetomaternal transfusion (FMT). Methods: The level of FMT was determined prospectively in 80 viable, singleton pregnancies in which 10–14-week ultrasonographic scanning, NT thickness measurement; chorionic villus sampling (CVS) for fetal karyotyping and VEGF concentration determination were performed. The grouping procedures were based either on NT thickness (<2 MoM in Group I, and ≥2 MoM in Group II), or on karyotype (euploid in Group A, and aneuploid in Group B). The level of FMT was determined via maternal serum α-fetoprotein levels before and after CVS. The FMT and the VEGF concentration of the chorionic tissue were analysed in comparisons between Groups I and II, and between Groups “A” and “B”. Results: The mean level of FMT after CVS was 72.5±21.3 μL and 19.28±5.4 μL in Groups I (n=44) and II (n=36), respectively (P<0.02). The VEGF concentration of the chorionic tissue in Groups I and II was 40.6±16.7 pg/mg protein and 21.1±6.3 pg/mg protein, respectively (P=0.28). The mean level of FMT was 57.9±15.0 μL and 8.1±3.9 μL in Groups A and B, respectively (P<0.003). The VEGF concentration of the chorionic tissue in Groups A and B was 25.9±10.7 pg/mg protein and 21.3±11.3 pg/mg protein, respectively (P=0.77). Conclusion: No difference exists in the VEGF concentration in the aspirated chorionic tissue between Groups I and II and between Groups A and B. A higher level of FMT was observed among the aneuploid pregnancies after CVS than among the euploid cases. Chorionic VEGF does not influence the inverse relationship between the pre-CVS NT thickness and FMT.

Objective: To determine rate of and risk factors for birth defects in infants born to HIV-infected women receiving nucleoside and protease inhibitor antiretroviral (ARV) therapy. Methods: Birth defects were evaluated among infants on the Pediatric AIDS Clinical Trials Group 316 trial that studied addition of peripartum nevirapine to established ARV regimen for prevention of mother-to-child transmission. Maternal therapy was categorized by trimester of earliest exposure. Birth defects were coded using conventions of the Antiretroviral Pregnancy Registry. Results: Birth defects were detected in 60/1414 (4.2%; 95% CI 3.3–5.4%) infants including 30/636 (4.7%; 95% CI 3.2–6.7%) with first trimester ARV exposure and 30/778 (3.9%; 95% CI 2.6–5.5%) with exposure only after the first trimester (P=0.51). Rates of classes of defects were similar between first trimester compared to later exposure groups except heart defects which occurred in 16 (2.5%; 95% CI 1.4–4.1%) with first trimester ARV exposure and in six (0.8%; 95% CI 0.3–1.7%) infants with later exposure (P=0.02). Exposure to ARV was not associated with specific types of heart defects. Two cases of cardiomyopathy were noted. Conclusion: ARV use in early pregnancy was not associated with an increased risk of birth defects overall. The possible association of ARV exposure with heart defects requires further surveillance.

Neurobehavior represents development of the central nervous system (CNS). Fetuses and newborns exhibit a large number of endogenously generated motor patterns, among which general movements are often investigated pre- and post-natally. Spontaneous activity is probably a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli while testing reflexes. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects particularly on brain growth and function. Unfavorable intrauterine environment can affect adversely brain growth. All endogenously generated movement patterns from un-stimulated CNS might be observed as early as from the seven to eight weeks' gestation, with a rich repertoire of movements within the next two or three weeks, continuing for five to six months postnatally. It is still uncertain whether a new scoring system for prenatal neurological assessment will be adequate for the distinction between normal and abnormal fetuses in low-risk pregnancies. The continuity of behavioral patterns from prenatal to postnatal life might answer these intriguing questions.

Objective: Our objective was to determine the obstetrical risk for spontaneous focal intestinal perforation (FIP) in very low birth weight (VLBW) infants. Methods: Eight mothers delivered infants who underwent laparotomy for FIP between 2001 and 2006 in our hospital. A retrospective case-control study of the eight case mothers and 32 control mothers was conducted. Clinical findings were retrospectively analyzed. Results: There were significant differences in the frequency of oligohydramnios (P<0.01) and velamentous cord insertion (P<0.05) between cases and controls. The 1-min Apgar score was significantly lower in the FIP group than in the control group (P<0.05). Moreover, primigravidity was significantly associated with a risk of FIP. Conclusions: The etiology of FIP may be related to changes in the blood circulation, such as fetal hypoxic-ischemic episodes or disturbance in the umbilical blood flow, during the antepartum and/or intrapartum periods.

Aim: To evaluate the use of three-dimensional ultrasonography (3D) as an alternative for examining fetal anatomy and nuchal translucency (NT) in the 1 st trimester of pregnancy. Method: Prospective study of 199 low risk pregnant women undergoing 1 st trimester ultrasound scan for fetal anomalies. The NT and fetal anatomy were evaluated by three-dimensional (3D) ultrasonography after the standard two-dimensional (2D) examination. The gold standard in this study was the 2D ultrasonography. Results: In some of the evaluated parameters the 3D method approaches the conventional 2D results. These parameters are the crown-rump length (CRL), the skull – brain anatomy (93.5%), the spine (85.4%), the upper (88.4%) and lower limbs (87.9%) and the examination of the fetal abdomen (98.5%). Some of the anatomic parameters under evaluation revealed a statistically significant difference in favor of the 2D examination. During the 3D examination the nasal bone was identified in 62.1% of the cases, the stomach in 85.9%, and the urinary bladder in 57.3% of the cases. The NT was assessed accurately in half of the cases compared to 2D examination. Conclusion: The 3D ultrasound is insufficient for the detailed fetal anatomy examination during the 1 st trimester of pregnancy. Nevertheless, the method might be improved in order to be considered as a screening method.

Although popularly designated as “identical”, monozygotic (MZ) twins are rarely identical. Much has been speculated on the origin of MZ twins and several theories have been proposed. Post-fertilization events, such as chromosomal mosaicism, skewed X-inactivation and imprinting mechanisms, as well as other epigenetic mechanisms are responsible for the differences between MZ twins. Numerous discordant MZ twins have been reported including discordance for lateral asymmetry, major malformation, growth and intrauterine death of the co-twin. This discrepancy may have long-term implications on complex diseases and their predisposition, organ transplantation and interpretation of twin-based studies. We reviewed the genotypic and phenotypic differences between MZ twins and discuss their main causes.

Aims: To assess the relationship between clinically maternal chorioamnionitis and outcome in preterm very-low-birth weight (VLBW) infants. Methods: An observational case-control study was conducted in the neonatology departments of 12 acute care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (≤1500 g) infants who were born to a mother with clinical chorioamnionitis were enrolled. The controls included infants who were born to mothers without chorioamnionitis, matched by gestational age, and immediately born after each index case. At a corrected age of 24 months, a neurological examination and a psychological assessment of the surviving children were performed. Results: Sixty-six of the newborn infants died; therefore, 262 infants from the original sample were available for the study. Follow-up data were obtained at a corrected age of 24 months from a total of 209 children (106 cases and 103 controls, 80% of the original sample size). Seventy children (33.5%) were diagnosed with some type of sequelae. The following conditions were all more prevalent in infants born to mothers with chorioamnionitis in comparison to controls: low development quotient (98.3±12.15 vs. 95.9±15.64; P=0.497), cerebral palsy (4.9% vs. 10.4%; P=0.138), seizures (1.0% vs. 3.8%; P=0.369), and other neurological or sensorial sequelae (32.0% vs. 34.9%; P=0.611). Conclusions: After controlling for gestational age, the study population demonstrated that the neurological outcomes in infants at a corrected age of 24 months was not worsened by chorioamnionitis.

Objective: Recently, the International Association of Diabetes and Pregnancy Study Groups have suggested new criteria for the diagnosis of gestational diabetes including a fasting glucose level of ≥92 mg/dL. We determined reference levels for normal fasting plasma glucose levels throughout pregnancy and evaluated the new normal cut-off for fasting glucose level. Methods: Charts of patients who delivered in our hospital between June 2001 and June 2006 were reviewed. Women with pregestational diabetes, fasting glucose level >105mg/dL or delivery at <24 weeks were excluded. Fasting glucose levels were assessed in 11 time categories between three months prior and four months postpartum in 7946 women. Results: Compared to preconception levels, fasting glucose levels decreased by a median of 3 mg/dL in the first trimester (81–78 mg/dL). During the third trimester a slight further glucose reduction was observed (median 76 mg/dL). After delivery fasting glucose levels increased sharply (84 mg/dL in the puerperium and 81 mg/dL by three months postpartum). Throughout pregnancy 5.2–9.0% of pregnant women had a fasting glucose level of ≥92 mg/dL ;ibcompared to 8.2% in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study]. Conclusion: Fasting glucose levels decrease early in pregnancy with only slight further decrease later on. It seems that the same fasting glucose cut-off can be used throughout pregnancy for the diagnosis of gestational diabetes mellitus.

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