Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women.

BACKGROUND: We performed a post-hoc subgroup analysis in Korean women who participated in the Phase III FER-ASAP (FERric carboxymaltose-Assessment of SAfety and efficacy in Pregnancy) study to compare the efficacy and safety of ferric carboxymaltose (FCM) with oral ferrous sulfate (FS). METHODS: Pregnant Korean women (gestational weeks 16-33) with iron-deficiency anemia (IDA) were randomized 1:1 to FCM (n = 46; 1000-1500 mg iron) or FS (n = 44; 200 mg iron/day) group for 12 weeks. The primary objective was to compare the mean hemoglobin (Hb) increase at week 3; secondary objectives included change in iron parameters, quality of life (QoL), and safety. RESULTS: Baseline characteristics of the Korean subgroup were consistent with those of non-Korean FER-ASAP population except for lower body-mass index and higher maternal age. Hb level increases were comparable between the two treatment groups in Korean women at week 3 (FCM 1.23 ± 0.89 g/dL vs FS 1.14 ± 1.72 g/dL). Iron parameters improved over time as secondary endpoints were significantly in favor of FCM. In terms of QoL, FCM treatment significantly improved the mental and physical components as well as vitality prior to delivery. Both treatments were well tolerated. CONCLUSIONS: FCM provided significantly greater improvements in iron parameters and QoL compared to FS in the Korean subgroup. FCM may be a preferable alternative to currently available treatments for IDA during pregnancy.

Novel Technique for Measurement of Fetal Right Myocardial Performance Index Using Dual Gate Pulsed-Wave Doppler.

OBJECTIVES: To evaluate the reproducibility of the fetal right myocardial performance index determined by simultaneous recording of inflow and outflow using a dual gate pulsed-wave Doppler (DD). METHODS: This was a prospective study of 39 normal singleton fetuses. Two experienced operators each measured the right myocardial performance index in three ways, twice: (1) separate recording of the inflow and outflow using single-gate pulsed-wave Doppler (PD), (2) simultaneous recordings of the inflow and outflow using tissue Doppler (TD), and (3) simultaneous recordings of the inflow and outflow using DD. Intra- and interoperator reproducibility were assessed with intraclass correlation coefficients. The measurements from all three methods taken by the more experienced operator were compared using Bland-Altman plots and mean differences. RESULTS: For both operators, intra-operator reproducibility was the highest when using DD, followed by PD, and TD. Interoperator agreement was the highest for PD measurements, followed by DD, and TD. The smallest mean difference was between the PD and DD measurements by the more experienced operator. There was a positive correlation between PD and DD values (r = 0.369, P < .001). CONCLUSIONS: Dual gate pulsed-wave Doppler may be an effective alternative to the PD or TD methods, and can separately evaluate systolic and diastolic myocardial function.

Fetal left modified myocardial performance index measured by the Auto Mod-MPI system: development of reference values and application to recipients of twin-to-twin transfusion syndrome.

OBJECTIVES: To establish normal reference ranges for the fetal left modified myocardial performance index (Mod-MPI) measured by the Auto Mod-MPI system and evaluate Mod-MPI changes in recipients of twin-to-twin transfusion syndrome (TTTS) before and after fetoscopic laser coagulation. METHODS: This was a prospective longitudinal study of normal singleton fetuses from 12.0 to 40.0 weeks of gestation. TTTS cases treated by laser coagulation were reviewed for Mod-MPI measurements of recipients. All measurements were performed using the Auto Mod-MPI system by a single experienced operator. RESULTS: Among a total 447 examinations from 222 fetuses, we were unable to measure the Mod-MPI in two cases, and therefore, 445 examinations were analyzed. The median Mod-MPI consistently increased from 0.44 to 0.56 throughout gestation. The median isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) also increased with advancing gestational age. The ejection time (ET) increased until 27 weeks of gestation and decreased thereafter. In the 30 recipients, Mod-MPI, ICT, and IRT increased before laser coagulation and significantly decreased after laser coagulation. CONCLUSION: Normal reference values for left Mod-MPI were established using the Auto Mod-MPI system, and these might be useful for assessing cardiac function in TTTS. © 2016 John Wiley & Sons, Ltd.

Sonographic Determination of Type in a Fetal Imperforate Anus.

OBJECTIVES: The purpose of this study was to determine the type of an imperforate anus by using sonography in the prenatal period. METHODS: This retrospective study evaluated the fetal anus in all pregnant women, including low- and high-risk populations, between February 2010 and November 2013. High-type imperforate anuses were diagnosed by prenatal sonography when the anal sphincter muscles and anal canal mucosa were not visible. Low-type imperforate anuses were prenatally suspected when at least 1 of the following was present: (1) a small anus; (2) no visible anal mucosa; or (3) close location of the genitalia by the anus without a visible perineal body, particularly in a female fetus. RESULTS: Among the 9499 fetuses, 41 were prenatally suspected of having an imperforate anus, and 32 were confirmed to have this disorder. During the same study period, there were 11 false-negative cases, for a diagnostic sensitivity rate of 74%. All 9 fetuses who were confirmed to have a normal anus were prenatally suspected of having a low-type imperforate anus. Among the 32 fetuses with a confirmed imperforate anus, 19 were confirmed to have a high or intermediate type and 13 to have a low type. The type in 3 fetuses was incorrectly determined prenatally. CONCLUSIONS: Although an imperforate anus is not always diagnosed prenatally, its type can be determined by prenatal sonography.

Unusual prenatal sonographic findings without an elevated maternal serum alpha-fetoprotein level in a fetus with epidermolysis bullosa.

A 31-year-old pregnant woman was referred to us at 34.6 weeks' menstrual age for sonographic evaluation of a fetal left lower limb abnormality. Sonographic findings revealed shortening of the left tibia and dorsal hyperflexion of the left foot. There was no family history of genetic disease, and the maternal serum alpha-fetoprotein concentration was normal. A male infant was born with extensive skin peeling, mainly on his left leg, associated with muscular dystrophy. Epidermolysis bullosa was confirmed on a skin biopsy; the neonate died 53 days after birth as a result of severe sepsis. Although cutaneous epidermolysis bullosa is difficult to diagnose prenatally, shortening and deformity of extremities may provide a clue to the diagnosis, even when the maternal alpha-fetoprotein concentration is normal. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:319-321, 2016.

Perinatal outcomes of fetal pleural effusion following thoracoamniotic shunting.

OBJECTIVE: The aim is to evaluate perinatal outcomes of fetal pleural effusion after thoracoamniotic shunting. METHODS: This was a retrospective study of 68 singleton pregnancies with massive fetal pleural effusion that underwent thoracoamniotic shunting between 1999 and 2012 at Asan Medical Center, Seoul, Korea. Through a review of medical records, we investigated perinatal outcomes according to the presence of fetal hydrops and identified prognostic factors by stepwise multivariate logistic regression analysis. RESULTS: Of the 68 pregnancies, three were lost to follow-up and two fetuses died in utero. The median gestational age at shunting was 28.3 weeks (range, 18.5-34.1 weeks). Of the 65 fetuses, 50 (76.9%) were hydropic, of which hydrops resolved following shunting in 29 fetuses (58.0%). Among the 63 live births, the median gestational age at delivery was 33.6 weeks (range, 26.2-40.0 weeks), with 36 fetuses (57.1%) delivered preterm. The overall survival rate was 75.4% (49/65), and in a subgroup analysis, the survival rate was highest for non-hydropic fetuses (14/15, 93.3%), followed by fetuses whose hydrops resolved (25/29, 86.2%) and remained after shunting (10/21, 47.6%). CONCLUSION: Thoracoamniotic shunting can be helpful for fetuses with massive pleural effusion. While fetal hydrops can occur in such cases, perinatal outcomes can be improved by successful shunting.

Clinical features of 10 fetuses with prenatally diagnosed parvovirus b19 infection and fetal hydrops.

OBJECTIVES: To evaluate the clinical features of fetuses with prenatally diagnosed parvovirus B19 infection and fetal hydrops. METHODS: Parvovirus infection was diagnosed by PCR analysis of amniotic fluid or fetal blood. Fetal anemia was assessed by Doppler measurements of the middle cerebral artery peak systolic velocity (MCA-PSV) and confirmed by fetal blood. Intrauterine transfusions (IUT) were performed only if the MCA-PSV was > 1.5°MoM. RESULTS: In our study population 10 cases of parvovirus infection which were associated with fetal hydrops were reviewed. The median gestational age at diagnosis was 21 (16.3-24.2) weeks. Five of our cases received IUT and four fetuses survived. The remaining five cases were managed conservatively and two fetuses survived. CONCLUSIONS: The survival rate for parvovirus infection associated with fetal hydrops was 60%. MCA-PSV and IUT are useful for the management and treatment of fetal anemia due to parvovirus infection.

Changes in the cesarean section rate in Korea (1982-2012) and a review of the associated factors.

Although Cesarean section (CS) itself has contributed to the reduction in maternal and perinatal mortality, an undue rise in the CS rate (CSR) has been issued in Korea as well as globally. The CSR in Korea increased over the past two decades, but has remained at approximately 36% since 2006. Contributing factors associated with the CSR in Korea were an improvement in socio-economic status, a higher maternal age, a rise in multiple pregnancies, and maternal obesity. We found that countries with a no-fault compensation system maintained a lower CSR compared to that in countries with civil action, indicating the close relationship between the CSR and the medico-legal system within a country. The Korean government has implemented strategies including an incentive system relating to the CSR or encouraging vaginal birth after Cesarean to decrease CSR, but such strategies have proved ineffective. To optimize the CSR in Korea, efforts on lowering the maternal childbearing age or reducing maternal obesity are needed at individual level. And from a national view point, reforming health care system, which could encourage the experienced obstetricians to be trained properly and be relieved from legal pressure with deliveries is necessary.

Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy.

The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics.

Clinical outcomes of prenatally diagnosed cases of isolated and nonisolated pericardial effusion.

OBJECTIVE: The purpose of this study was to investigate the clinical outcome of fetal pericardial effusion (PE). METHODS: This study involved a retrospective review of prenatally diagnosed PE cases. The criterion for inclusion was pericardial fluid in an area greater than 2 mm in diameter. RESULTS: A total of 276 cases of PE and 252 cases diagnosed with other anomalies were initially reviewed. PE is associated with cardiac malformation, hydrops fetalis, extracardiac abnormalities, infections, anemias, intrauterine growth restriction, and aneuploidy markers in fetuses. Of these reviewed cases, 24 cases of isolated fetal PE were studied. In all cases, pericardial fluid filled an area ranging from 2 to 17 mm in diameter. Four cases of isolated PE had an abnormal postnatal condition, and 3 cases were excluded due to lack of follow-up. The size of the PE was not related to the regression of pericardial fluid, adverse outcomes or mortality rate associated with the isolated PE. All newborns were healthy, and there were no chromosomal abnormalities in the study population. CONCLUSIONS: There were no adverse clinical outcomes or chromosomal abnormalities in the fetuses diagnosed with isolated PE. Most cases of isolated PE resolved spontaneously and were associated with a good prognosis.

Measurement of intracranial translucency using three-dimensional ultrasound and Volume IT™.

OBJECTIVES: To establish the reference range of intracranial translucency (IT) in the Korean population, and to evaluate whether Volume IT™ is a reliable technique for measuring IT. METHODS: We retrospectively analyzed the IT of 93 singleton fetuses at 10.5 to 12.6 weeks of gestation using previously obtained three-dimensional volume data. The IT was measured manually and automatically using Volume IT™ in each fetus by one experienced and one beginner operator. We measured the IT values according to the crown-rump length and evaluated whether Volume IT™ can successfully measure the IT. Inter-observer agreement and intra-observer reproducibility were analyzed using the intraclass correlation coefficients (ICC), and the IT measurements obtained by the experienced operator using the manual and automated methods were then compared using the Bland-Altman plot and ICC. RESULTS: Among 93 cases, 2 were lost to follow-up after the first trimester scan and were excluded from further evaluation. Both operators identified the fourth ventricle in all 91 cases using Volume IT™. The experienced and beginner operators were able to measure the IT in 89 (98%) fetuses, with 4 and 13, respectively, requiring adjustments. The IT values increased with gestational age (correlation coefficient, r=0.491, P <0.0001). Inter-operator agreement was moderate (ICC=0.580 for automated and 0.546 for manual measurements), and intra-operator reproducibility was highest for automated measurements by the experienced operator (ICC=0.944). Agreement of the IT values between the manual and automated methods was high (ICC=0.950). CONCLUSIONS: Our results provide the reference range of IT in the Korean population. The Volume IT™ may be a reliable technique for measuring IT.

Perinatal outcome of sacrococcygeal teratoma.

OBJECTIVE: To evaluate the outcome in a cohort of fetuses with isolated sacrococcygeal teratoma (SCT) in relation to the need for in utero intervention. METHODS: We retrospectively analyzed a cohort of fetuses prenatally diagnosed with SCT between September 2000 and December 2010. Postnatal outcomes were evaluated in relation to the need for intervention in utero by reviewing medical records. RESULTS: Of the 35 fetuses diagnosed with SCT during the study period, ten were lost to follow up and three had been misdiagnosed as SCT. Among the remaining 22 cases, in utero interventions were performed in eight, including radiofrequency ablation (RFA) in four, shunt operations in two, RFA plus cyst aspiration in one, and RFA with subsequent shunt operation in one. Tumors of cases undergoing in utero intervention were larger with rapidly growing, more frequently vascular, and with associated polyhydramnios or cardiomegaly. The rate of preterm births was higher in the cases that underwent interventions compared with those that did not (7/8 vs 2/14). Only one tumor showed regression after RFA while the other seven increased in size. Median tumor size at birth was significantly larger in the intervention group than in the nonintervention group (136 mm vs 80 mm). The neonatal survival rate was 6/8 for the prenatal intervention group and 14/14 for the nonintervention group. Resection of SCT was required in all neonates. The most common complication after postnatal surgery was fecal incontinence. CONCLUSION: Fetuses with SCT undergoing in utero intervention have worse prognostic features, yet their neonatal outcome is similar to those of fetuses not requiring intervention.

"Hugging sisters": thoracoomphalopagus with anencephaly confirmed by three-dimensional ultrasonography at 9 weeks of gestation.

We describe a rare conjoined twinning at 9 weeks of gestation. We compared the results of two- and three-dimensional sonography with autopsy findings after the termination of pregnancy. These results showed a thoracoomphalopagus with a shared heart and visceral organs. Three-dimensional sonography showed anencephaly in one of the embryos. Early and accurate prenatal diagnosis of this type of conjoined twins using three-dimensional sonography is critical for both parental counseling and minimizing maternal morbidity.

The frequency and clinical significance of twin gestations according to zygosity and chorionicity.

BACKGROUND: Although the clinical importance of chorionicity in twin pregnancies has been studied widely, the significance of perinatal determination of zygosity using molecular genetic analyses remains controversial. The purpose of this study was to determine the frequency and clinical significance of twin gestations according to zygosity and chorionicity in a Korean population. METHODS: We enrolled 569 women who delivered twin newborns (> 24 weeks) at Seoul National University Hospital between 1999 and 2008. Chorionicity was established by histologic examination of placentae. Zygosity was determined with sex of neonates, chorionicity, and DNA analysis of umbilical cord blood. RESULTS: The frequency of dizygotic (DZ) twins was 71.0% (404/569 pairs) based on the opposite sex (238/404 [58.9%]) and DNA analyses (166/404 [41.1%]); that of monozygotic (MZ) twins was 29.0% (165/569), including monochorionic (MC) (72.1% [119/165]) and dichorionic (DC) twins (27.9% [46/165]), which was confirmed by DNA analyses. Among spontaneously conceived twins, the frequency of MZ twins was more than twice that of DZ twins. The risk of low birth weight was 1.8-fold higher among MZDC twins and 1.9-fold higher among MZMC twins than among DZDC twins (p < .05). Bronchopulmonary dysplasia occurred more frequently among MZMC twins than among DZDC twins (adjusted OR 8.42, 95% CI 1.82-39.08, p < .01). However, the frequencies of other neonatal morbidities were not significantly higher in the MZMC group than in the MZDC and DZDC groups. The perinatal mortality rate was 15 per 1000 total births in the DZDC twins, 20 per 1000 total births in the MZDC and 56 per 1000 total births in the MZMC (p < .01). CONCLUSIONS: Although monozygosity was shown to be a risk factor for perinatal death and accurate determination of zygosity plays a great role in the future consideration of organ transplantation and twin studies, the value of zygosity determination along with chorionicity in relation to overall neonatal morbidity was not definite.

Quantitative risk estimation for large for gestational age using the area under the 100-g oral glucose tolerance test curve.

We devised a complementary quantitative method for gestational diabetes (GDM) that uses the area under the curve (AUC) of the results of the oral glucose tolerance test (OGTT), and evaluated its efficacy in predicting neonates that would be large for gestational age (LGA). The study subjects were 648 pregnant women. The AUC-OGTT (concentration x time) was calculated from the 100-g OGTT results. The incidence of LGA according to each range of the AUC-OGTT was estimated and odds ratios were analyzed using multiple logistic regression analysis.The incidence of LGA increased with the AUC-OGTT value and was 0% for AUC<300, 7.8% for 300-400, 14.9% for 400-500, 20.8% for 500-600, and 45.5% for > or = 600. The odds ratio of LGA increased by approximately two-fold with an increase of 100 in the AUC-OGTT. The results indicated that the AUC-OGTT can be used to quantify the risk of LGA in GDM. The AUC-OGTT could complement a diagnosis of GDM using conventional diagnostic criteria.

How much have the perinatal outcomes of triplet pregnancies improved over the last two decades?

OBJECTIVE: This study was conducted to demonstrate the temporal trends in perinatal outcomes of triplet pregnancies over the last two decades. METHODS: The medical records of patients with triplet pregnancies at two Korean tertiary-care hospitals from 1992 to 2012 were retrospectively reviewed in regard to maternal and neonatal outcomes. The study was divided into two periods for analysis: period I (1992-2001) and period II (2003-2012). RESULTS: Over a 21-year period, 65 women with triplet pregnancies and 185 neonates were analyzed. Period II, when compared with period I, was associated with improved maternal outcomes, characterized by a decreased incidence of preeclampsia (31.8% vs. 2.3%, P=0.002) and anemia (68.2% vs. 30.2%, P=0.003) during pregnancy. Regarding neonatal aspects, the composite morbidity of period II was significantly decreased compared with that of period I, as assessed with a generalized estimating equation for logistic regression (26.2% vs. 8.1%, P=0.03). Multivariable analysis revealed that the gestational age at delivery and the period were significantly associated with the composite neonatal morbidity (P<0.001 and 0.007, respectively). CONCLUSION: Improved neonatal morbidity was associated with a higher gestational age at delivery and with the more recent decade.

Changes in intestinal waste products during the antenatal management of gastroschisis by serial amniotic fluid exchange and infusion.

Despite the good survival rate of fetuses with gastroschisis, the length and cost of hospitalization for surgically repaired gastroschisis are high. In gastroschisis, prolonged exposure of the intestine to amniotic fluid (AF) containing intestinal waste products results in intestinal damage, including intestinal wall thickening and fibrous peel formation. The deleterious effects of AF on gastroschisis can be prevented by lowering the concentration of intestinal waste products. We describe the treatment of a case of fetal gastroschisis by repeated AF exchange and infusion. Following repeated, successful transabdominal AF exchange and infusion, the concentrations of various intestinal waste products were decreased. AF exchange and infusion may prevent intestinal damage and improve postnatal outcome in gastroschisis by diluting the AF, probably by lowering the concentrations of intestinal waste products.

Vascular endothelial growth factor gene +936 C/T polymorphism is associated with preeclampsia in Korean women.

OBJECTIVE: The purpose of this study was to evaluate potential associations between vascular endothelial growth factor (VEGF) gene polymorphisms and preeclampsia. STUDY DESIGN: One hundred ten patients with preeclampsia and 209 healthy pregnant control subjects were enrolled in the study. After peripheral blood was obtained from all women and the genomic DNA was isolated, we genotyped +936C/T polymorphisms in the 3'-untranslated region of the VEGF gene, using polymerase chain reaction and restriction fragment length polymorphism techniques. RESULTS: The distribution of genotypes of the +936C/T polymorphism was significantly different between women with preeclampsia and the control group (P < .001). Carriage of the +936T allele was significantly more frequent in preeclamptic patients than in control subjects (odds ratio, 2.06; 95% CI,1.38-3.08). Logistic regression analysis on VEGF genotype and clinical parameters such as age, educational status, body mass index, and neonatal gender showed carriage of the 936T allele to be significantly more frequent in preeclamptic patients than in control subjects (adjusted odds ratio, 2.23; 95% CI, 1.46-3.42). CONCLUSION: Carriage of the +936T allele of the VEGF gene may be associated with increased susceptibility to the development of preeclampsia and may be an independent risk factor for preeclampsia.

Antenatal diagnosis of meconium peritonitis in dichorionic twins: a case report.

BACKGROUND: Meconium peritonitis (MP) is a chemical peritonitis, and little is known about its natural history. Below we report MP in both fetuses from a twin pregnancy, with identical clinical ultrasonographic findings but a delay in presentation. CASE: A 31-year-old woman with a twin pregnancy was referred to our institution due to fetal bowel dilatation and ascites. Serial ultrasonography demonstrated gradual but dynamic changes. Both infants were delivered at 29 weeks'gestation. The larger infant had type II MP and experienced more postoperative complications and longer ventilatory care, parenteral nutrition and hospital stay than the smaller one, who had type III MP. CONCLUSION: The type of MP at birth may be more important than birth weight in terms of neonatal morbidity. This case increases our understanding of the natural history and prognosis of MP.