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.

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.

An extremely rare case of prenatally diagnosed absent both aortic and pulmonary valves.

We describe a case of absent aortic and pulmonary valves, diagnosed at 16.4 weeks of gestation. Fetal echocardiography showed cardiomegaly with dilated both ventricles. No valve leaflets were observed in the aorta and pulmonary artery, and a typical to-and-fro flow pattern was noted in both great arteries on color Doppler imaging. Fetal hydrops was also detected. Follow-up ultrasonographic evaluation at 19 weeks demonstrated intrauterine fetal death. Postmortem autopsy revealed the absence of both aortic and pulmonary valve leaflets. To the best of our knowledge, this is the earliest diagnosed case of absent both aortic and pulmonary valves and only the second case to be diagnosed prenatally.

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.

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.

Impaction of an intrathoracic kidney acted as a shield against herniation of the abdominal viscera in a case of right congenital diaphragmatic hernia.

We describe a case of an intrathoracic kidney combined with right congenital diaphragmatic hernia (CDH) that was diagnosed at 32 weeks of gestation. Although it has been well established that a right CDH shows a poorer outcome than a left CDH, our present case showed a good outcome because there was no herniation of other abdominal viscera, except for the right kidney. Our findings in this case indicate that impaction of the intrathoracic kidney may act as a 'shield' against further herniation of other abdominal viscera into the thoracic cavity.

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.

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.

Prenatal diagnosis of atrial isomerism in the Korean population.

OBJECTIVE: To report our experiences in the prenatal diagnosis of atrial isomerism and postnatal outcomes. METHODS: A total of 80 fetuses prenatally diagnosed with atrial isomerism were retrospectively analyzed between 1999 and 2011 at a single institution. RESULTS: Of 43 fetuses with prenatally diagnosed right atrial isomerism (RAI), 40 cases were analyzed. The diagnostic accuracy was 93%. The main intracardiac anomalies in RAI were atrioventricular septal defect (AVSD), abnormal pulmonary venous connection, bilateral superior vena cava (BSVC), and pulmonary atresia. Among 28 live births, three infants were lost to follow up, and the overall survival rate was 60%. Of 37 fetuses with prenatally diagnosed left atrial isomerism (LAI), 35 were evaluated. The diagnostic accuracy was 97%. The main intracardiac anomalies in LAI were ventricular septal defect, BSVC, AVSD, double outlet right ventricle, and bradyarrhythmia. Among seven patients with bradyarrhythmia, only one showed a complete atrioventricular block. All fetuses had an interrupted inferior vena cava with azygous continuation. The overall survival rate was 90%. CONCLUSION: Our study confirms the previous findings of fetal atrial isomerism. We also demonstrates a much lower prevalence of AVSD and complete heart block in LAI and a better survival rate in RAI. Although the postnatal outcomes for RAI were worse than those for LAI, successful postnatal surgery with active management improved the survival rate.

Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome.

OBJECTIVE: To analyze the spectrum of prenatally diagnosed congenital heart disease in a Korean population with 22q11.2 deletion syndrome, and to provide guidelines for screening 22q11.2 deletion prenatally. METHODS: This retrospective study evaluated 1,137 consecutive fetuses that had prenatal genetic testing for 22q11.2 deletion because of suspected congenital heart disease between September 2002 and December 2012, at Asan Medical Center, Seoul, Korea. RESULTS: Main cardiovascular diseases in the 53 fetuses with confirmed 22q11.2 deletions were tetralogy of Fallot (n = 24, 45%), interrupted aortic arch (n = 10, 19%), ventricular septal defect (n = 5, 9%), double outlet right ventricle (n = 4, 8%), and coarctation of the aorta (n = 4, 8%). Other cardiac defects were rarely associated with 22q11.2 deletion. One fetus had persistent truncus arteriosus, one had aortic stenosis, and one had hypoplastic right heart syndrome. Two fetuses had normal intracardiac anatomy with an isolated right aortic arch, and one had an isolated bilateral superior vena cava. CONCLUSION: A variety of congenital heart diseases were seen during the prenatal period. Conotruncal cardiac defects except transposition of great arteries were strongly associated with 22q11.2 deletion. When such anomalies are diagnosed by fetal echocardiography, genetic testing for 22q11.2 deletion should be offered. Even if less frequent deletion-related cardiac defects are detected, other related anomalies, such as thymic hypoplasia or aplasia, should be evaluated to rule out a 22q11.2 deletion.

Intrauterine therapy for macrocystic congenital cystic adenomatoid malformation of the lung.

OBJECTIVE: To report on our experiences with thoracoamniotic shunting and/or the injection of a sclerosing agent (OK-432) to treat fetuses diagnosed with macrocystic congenital cystic adenomatoid malformation (CCAM) of the lung. METHODS: A retrospective study was undertaken in six fetuses with macrocystic CCAM at our institute that had been confirmed by postnatal surgery between August 1999 and January 2012. RESULTS: Six fetuses that had been diagnosed with macrocystic CCAM were analyzed. The median gestational age at diagnosis was 23.5 weeks (range, 19.5-31.0 weeks), and at the time of primary treatment was 24.0 weeks (range, 20.5-31.0 weeks). The mean size of the largest cyst at the initial assessment was 42.5±15 mm. Four fetuses were associated with mediastinal shifting, and one also showed fetal hydrops. All fetuses underwent a shunting procedure within the cysts, one case among them was also treated with OK-432. After the completion of all procedures, the mean size of the largest cyst was all decreased (14.2±12 mm). The median gestational age at delivery was 38.0 weeks (range, 32.4-40.3 weeks). All of the newborns underwent the surgical resection at a median age of 6 days (range, 1-136 days) and are currently doing well without any complications. CONCLUSION: We suggest that intrauterine decompression therapy to manage fetal macrocystic CCAM is recommendable treatment for good perinatal outcome.

Thanatophoric dysplasia in a dichorionic twin confirmed by genetic analysis at the early second trimester: A case report and literature review.

Thanatophoric dysplasia (TD) is caused by mutation of the gene that encodes fibroblast growth factor 3 (FGFR3). Owing to the poor prognosis for TD, prenatal diagnosis is critical to optimal perinatal management. We report here a case of TD in twin pregnancy, which was prenatally diagnosed by DNA analysis following amniocentesis at 15 weeks, and was managed by selective fetal termination. Prenatal ultrasonography and molecular analysis to detect TD-specific mutations enable accurate diagnosis of FGFR3-related TD in utero and appropriate obstetrical management at early gestation during twin pregnancy.

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.

A case report of prenatally diagnosed tetrasomy 18p.

Tetrasomy 18p, one of the most commonly observed isochromosomes, consists of two copies of the p arms on chromosome 18[i(18p)]. It is known as a de novo occurrence of non-disjunction or centromeric mis-division during meiosis II in the vast majority of cases. It has a prevalence of 1/140,000-180,000 live births and affects both genders equally. A 28-year-old woman was referred at 33+2 weeks gestation to rule out fetal congenital heart disease. Her prenatal ultrasonography showed intrauterine growth retardation, cardiomegaly, and imperforate anus. Doppler ultrasonographic finding showed fetal anemia. Tetrasomy 18p was confirmed by conventional karyotyping and fluorescence in situ hybridization. Because of its very low prevalence rate, only several cases of tetrasomy 18p has been reported worldwide and it has not yet been reported in Korea before. Therefore, we report a case of prenatally diagnosed tetrasomy 18p.

Conservative multidisciplinary management of placenta percreta following in vitro fertilization.

Placenta percreta is an extremely rare and the most severe form of placental invasion, that is associated with severe maternal morbidity and mortality. We report a case of nulliparous woman who underwent 10 cycles of in vitro fertilization (IVF) without any known risk factors. We conserved her uterus by spontaneous vaginal delivery, leaving the placenta in situ, pelvic arterial embolization, and primary resection of the remaining placental tissues. This case demonstrates that repetitive IVF is a possible risk factor for placental invasion, and that conservation of the uterus can be achieved in such cases using a multidisciplinary approach.

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.