The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes

Background@#The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. @*Methods@#This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. @*Results@#The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. @*Conclusion@#Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Obesity Is Associated With Higher Risk of Adverse Maternal and Neonatal Outcomes Than Supervised Gestational Diabetes

Background@#Unlike gestational diabetic mellitus (GDM), which is strictly managed by most patients and physicians, obesity does not have proper management guidelines, and the importance of its management during pregnancy is often ignored. The aim of this study was to compare maternal and neonatal outcomes according to obesity and GDM, alone or in combination. @*Methods@#This was a retrospective cohort study of 3,078 consecutive pregnant women who experienced prenatal care and delivery of a live singleton neonate between January 2016 and December 2020 at our institution. Study participants were categorized into 4 mutually exclusive groups, as follows: group 1, no GDM without obesity; group 2, GDM without obesity; group 3, no GDM with obesity; and group 4, GDM with obesity. @*Results@#Compared to group 2, group 3 had higher rates of pre-eclampsia, cesarean section including emergent cesarean section rate. Also, neonates in group 3 were heavier and had lower glucose levels compared to those in group 2. Of note, there was no significant difference in maternal or neonatal outcomes except the rate of large-for-gestational-age (LGA) between group 1 and group 2. Among the GDM groups, group 4 had higher risks for pre-eclampsia, cesarean section, and LGA infant status than group 2. @*Conclusion@#Our data showed that obese women without GDM face higher risk of adverse pregnancy outcomes than women with supervised GDM and non-obese women. We also confirmed that adverse pregnancy outcomes associated with GDM were mainly attributable to obesity among women receiving GDM education.

Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants

Background@#Though antenatal magnesium sulfate (MgSO4 ) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. @*Methods@#We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks. @*Results@#Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4 ). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. @*Conclusion@#Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.

Influence of Pre-Pregnancy Underweight Body Mass Index on Fetal Abdominal Circumference, Estimated Weight, and Pregnancy Outcomes in Gestational Diabetes Mellitus

This study aimed to determine the influence of pre-pregnancy body mass index on pregnancy outcomes in gestational diabetes mellitus (GDM), comparing underweight patients with GDM with normal weight patients with GDM. Maternal baseline characteristics, ultrasonographic results, and pregnancy and neonatal outcomes were reviewed in 946 women with GDM with singleton pregnancies. Underweight patients with GDM showed a benign course in most aspects during pregnancy, except for developing a higher risk of giving birth to small for gestational age neonates. Underweight women with GDM required less insulin treatment, had a higher rate of vaginal delivery, and had a lower rate of cesarean delivery. In addition, their neonates were more likely to have fetal abdominal circumference and estimated fetal weight below the 10th percentile both at the time of GDM diagnosis and before delivery. Notably, their risk for preeclampsia and macrosomia were lower. Collectively, our data suggest that underweight women with GDM may require a different approach in terms of diagnosis and management throughout their pregnancy.

Summary of clinically diagnosed amniotic fluid embolism cases in Korea and disagreement with 4 criteria proposed for research purpose

Objective@#This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion. @*Methods@#This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality. @*Results@#The median maternal age was 33 years (range, 28–40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion. @*Conclusion@#Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.

Validation of a Strict Obesity Definition Proposed for Asians to Predict Adverse Pregnancy Outcomes in Korean Pregnant Women

Background@#People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m 2 and 30.0 kg/m 2 , respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2 : overweight, ≥ 25 kg/m2 : obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. @*Methods@#We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to followup were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2 , respectively. @*Results@#Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. @*Conclusion@#Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Prenatal ultrasonographic findings of esophageal atresia: potential diagnostic role of the stomach shape

Objective@#We investigated prenatal sonographic characteristics of esophageal atresia (EA) with advancing gestation. We focused on the degree of polyhydramnios and the stomach shape. @*Methods@#This study included 27 EA cases (EA group) and 81 idiopathic polyhydramnios cases (non-EA group). The non-EA group consisted of cases without any fetal structural anomaly, musculoskeletal disorder, chromosomal abnormality, or maternal diabetes. Both groups included only singleton pregnancies. Amniotic fluid index (AFI) and width/length (W/L) ratio as well as the product of width and length (W×L) of stomach were serially assessed during gestation and compared between the 2 groups. To predict EA using W/L ratio and W×L, receiver operating characteristic curve analysis was performed. @*Results@#Polyhydramnios was evident in 77.8% of EA cases. We observed 25.9% and 22.2% EA cases with an absent stomach and a small visible stomach, respectively. After 28 weeks, the EA group manifested significantly higher AFI than the non-EA group. After 32 weeks, W/L ratio in the EA group tended to be lower than that in the non-EA group (32–36 weeks: 1.36 vs. 1.72, P=0.092; >36 weeks: 1.43 vs. 1.63, P=0.024). To predict EA, the calculated area under the curve for W/L ratio was 0.651 after 32 weeks. The diagnosis of EA using a cut-off value of W/L ratio <1.376 showed sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio to be 84.6%, 52.9%, 1.796, and 0.081, respectively. @*Conclusion@#A low W/L ratio of stomach after 32 weeks with progressive idiopathic polyhydramnios may be used to predict EA.

The effects of maternal body mass index and plurality on maternal and umbilical cord serum magnesium levels in preterm birth at less than 32 weeks of gestation

Objective@#To evaluate the effects of maternal body mass index (BMI) and plurality on maternal and umbilical cord serum magnesium levels after antenatal magnesium sulfate treatment. @*Methods@#This was a retrospective cohort analysis of 135 women treated with antenatal magnesium sulfate at less than 32 weeks of gestation between January 2012 and June 2018. Subjects were stratified into groups according to maternal BMI (group I [18.5–22.9 kg/m²], group II [23.0–24.9 kg/m²], and group III [≥25.0 kg/m²]) and plurality (singleton and twin). Univariable and multivariable analyses were performed to compare the umbilical cord serum magnesium levels between the groups. @*Results@#Maternal serum magnesium levels were not significantly different between the maternal BMI groups and singleton and twin pregnancies. Umbilical cord serum magnesium levels were significantly different among the maternal BMI groups (3.3±1.2 mg/dL in group I, 3.3±1.2 mg/dL in group II, and 4.0±1.4 mg/dL in group III, P=0.003). The trend of increase in magnesium levels was statistically significant (P=0.001, Jonckheere-Terpstra test). Umbilical cord serum magnesium levels were not significantly different according to plurality. However, in the multivariable analysis, maternal BMI and plurality were not significantly associated with umbilical cord serum magnesium levels after adjusting for indication and total dose of magnesium sulfate treatment, gestational age at delivery, mode of delivery, neonatal sex, and birth weight. @*Conclusion@#Maternal BMI and plurality were not significantly associated with maternal or umbilical cord serum magnesium levels after exposure to antenatal magnesium sulfate treatment.

Summary of clinically diagnosed amniotic fluid embolism cases in Korea and disagreement with 4 criteria proposed for research purpose

Objective@#This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion. @*Methods@#This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality. @*Results@#The median maternal age was 33 years (range, 28–40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion. @*Conclusion@#Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.

17β-Estradiol Inhibits Lysophosphatidylcholine-Induced Apoptosis in Cultured Vascular Smooth Muscle Cells

Objectives@#Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17β-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. @*Methods@#VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. @*Results@#After pre-treatment for 24 hours, 17β-E2 suppressed lysoPC-induced (15 mM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17β-E2 (10−6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17β-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF- κB-mediated transcriptional activity were reduced with 17β-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. @*Conclusions@#In cultured VSMCs treated with lysoPC, 17β-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.

Perinatal outcome of twin pregnancies according to maternal age

OBJECTIVE: To investigate the perinatal outcomes of twin pregnancies according to maternal age. METHODS: This is a retrospective cohort study of twin pregnancies delivered ≥24 weeks' gestation at a tertiary academic hospital from 1995 to 2016. Subjects were categorized into 5 groups according to maternal age: < 25, 25–29, 30–34, 35–39, and ≥40 years. Maternal and neonatal outcomes of each maternal age group were analyzed using the Jonckheere-Terpstra test and the linear-by-linear association test. RESULTS: A total of 1,936 twin pregnant women were included, of which 47 (2.4%), 470 (24.3%), 948 (49.0%), 417 (21.5%), and 54 (2.7%) women were aged < 25, 25–29, 30–34, 35–39, and ≥40 years, respectively. Higher maternal age was significantly associated with a higher rate of dichorionic twins and a higher risk of gestational diabetes and placenta previa. However, rates of preterm labor, preterm premature rupture of membranes, cervical incompetence, preterm delivery, preeclampsia, placenta abruption, and cesarean section were not associated with maternal age. Birth weight increased and the rate of admission to the neonatal intensive care unit (NICU) decreased with older maternal age, but other neonatal outcomes did not change with age. Maternal age was significantly associated with a lower rate of NICU admission after controlling for potential confounding factors in multivariable analysis. CONCLUSION: Advanced maternal age in twin pregnancies was associated with increased risk of gestational diabetes, placenta previa, and higher birth weight but a lower rate of NICU admission. However, other outcomes were not significantly associated with maternal age.

Sirolimus therapy for fetal cardiac rhabdomyoma in a pregnant woman with tuberous sclerosis

Rhabdomyoma is the most common fetal cardiac tumor, and its development is related to tuberous sclerosis. Fetal cardiac rhabdomyomas often spontaneously regress in utero or after birth, but large tumors can cause hemodynamic obstruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used as an immunosuppressant after organ transplantation. The mTOR inhibitors are well-known to have anti-tumor activity, and they have been used for the treatment of patients with tuberous sclerosis. In the current case, fetal cardiac rhabdomyoma was completely resolved in utero during oral sirolimus treatment in the mother with tuberous sclerosis. This case shows that oral sirolimus therapy in pregnancy may be a treatment for multiple or large fetal cardiac rhabdomyomas.

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.

The Effect of Multidisciplinary Approach on the Birth Rate of Fetuses with Prenatally Diagnosed Congenital Heart Disease

BACKGROUND: This study aimed to determine the effect of a multidisciplinary approach on the birth rate of fetuses with prenatally diagnosed congenital heart diseases (CHDs). METHODS: Among the fetuses of 724 gravidas who underwent fetal echocardiography in Samsung Medical Center from January 2013 to June 2017, 463 fetuses with normal cardiac structure, arrhythmia or simple left-to-right shunt were excluded, and the remaining 261 were included in the study. The subjects were subdivided into groups based on whether they were consulted multidisciplinarily, that is, consulted simultaneously by pediatric cardiologists, obstetricians and pediatric cardiac surgeons or not. They were also categorized based on the initial fetal echocardiogram results. RESULTS: Among the fetuses in the multidisciplinary group, 64.5% of the fetuses were given birth to, and the proportion was not different from that in the non-multidisciplinary group (68.6%, P = 0.48). The delivery rate in the multidisciplinary consultation group were 69.2% in the transposition of the great arteries group, 63.6% in the tetralogy of Fallot group, 68.8% in the pulmonary atresia or interrupted aortic arch group, 62.5% in the coarctation of aorta group, 60.0% in the atrioventricular septal defect group, 70.0% in the functional single ventricle group, and 55.6% in the hypoplastic left heart syndrome group; there were no significant differences between the 10 echocardiogram groups. However, when the subjects were categorized into Fontan repair group and biventricular repair group, the Fontan repair group showed a significant increase in the likelihood of delivery when a multidisciplinary approach was taken (P = 0.035). CONCLUSION: When a fetus was diagnosed with a CHD where Fontan repair should be considered, a multidisciplinary approach resulted in increased possibility of delivery.

Prevalence of vaginal microorganisms among pregnant women according to trimester and association with preterm birth

OBJECTIVE: The aim of this study was to investigate the prevalence of abnormal vaginal microorganisms in pregnant women according to trimester, and to determine whether the presence of abnormal vaginal colonization is associated with higher risk of miscarriage or preterm delivery. Furthermore, we analyzed delivery outcomes according to individual microorganism species. METHODS: We included pregnant women who underwent vaginal culture during routine prenatal check-up between January 2011 and June 2016. We compared delivery outcomes according to the presence or absence of abnormal vaginal flora grouped by trimester. RESULTS: This study included 593 singleton pregnancies. We classified participants into 3 groups, according to the trimester in which vaginal culture was performed; 1st trimester (n=221), 2nd trimester (n=138), and 3rd trimester (n=234). Abnormal vaginal colonization rate significantly decreased with advancing trimester of pregnancy (21.7% for 1st, 21.0% for 2nd, 14.5% for 3rd; P=0.048). Abnormal vaginal colonization detected in the 2nd trimester but not in 1st trimester was associated with a significant increase in preterm delivery before 28 weeks of gestation (6.9% vs. 0%; P=0.006). Among abnormal vaginal flora isolated in the 2nd trimester, the presence of Klebsiella pneumonia was identified as significant microorganism associated with preterm delivery before 28 weeks of gestation (50% vs. 0.7% for K. pneumonia; P=0.029). CONCLUSION: There is an association between abnormal vaginal colonization detected in the 2nd trimester and preterm delivery before 28 weeks. K. pneumonia has been identified as the likely causative microorganisms.

Indications and characteristics of obstetric patients admitted to the intensive care unit: a 22-year review in a tertiary care center

OBJECTIVE: Reviewing indications and characteristics of obstetric patients admitted to the intensive care unit (ICU) of a tertiary care center, comparing those patients by time period and place of delivery, and to verify clinical utility of acute physiology and chronic health evaluation (APACHE) II score in ICU-admitted women. METHODS: Retrospective analyses were carried out for parturients admitted to the ICU of our institution from 1994 to 2015. Clinical characteristics were compared between time period (period 1: 1994–2004; period 2: 2005–2015) and place of delivery (our institution and local hospitals). Receiver operating characteristic (ROC) curve analysis was used to evaluate the usefulness of APACHE II score to predict maternal mortality. RESULTS: During 22-year period, 176 women required ICU admission, showing the incidence of 2.2 per 1,000 deliveries. The most common reason for ICU admission was postpartum hemorrhage (56.3%), followed by hypertensive disorders (19.3%), sepsis (3.4%), and pulmonary and amniotic fluid embolism (2.3%). Period 2 showed older maternal age (32.7±4.8 vs. 30.8±4.4 years, P=0.006, higher embolization rate (26.4% vs.1.2%, P < 0.001), and lower hysterectomy rate (30.8% vs. 49.4%, P=0.012). Cases from local hospitals showed significantly higher proportion of postpartum hemorrhage (84.5% vs. 42.2%, P < 0.001). Overall maternal death occurred in 5.1% (9/176) including 6 direct maternal deaths. The APACHE II score showed area under the ROC curve of 0.813 (confidence interval [CI], 0.607–1.000) for prediction of maternal mortality. CONCLUSION: The incidence of obstetric ICU admission was 2.2 per 1,000 deliveries and the most common reason was postpartum hemorrhage followed by hypertensive disorders. APACHE II score could be used to predict mortality in obstetric ICU admission.

Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

An extremely rare case of hand prolapse with preterm premature rupture in the membrane of one twin

The latency in preterm premature rupture of membranes (PPROM) can last for weeks. We describe an extremely rare case of hand prolapse with PPROM that was exposed for 23 days before delivery. The patient had spontaneous PPROM of twin A at 21.4 weeks of gestation with shoulder presentation. The right arm of the fetus eventually protruded out the vagina and the hand was exposed for extended period of time of 23 days until delivery. Daily dressing by applying collagen to dry skin and silicone to keep moisture was done to the protruding hand to prevent dehydration and desquamation of the skin. Prophylactic antibiotics were used and the patient underwent emergent cesarean section due to uncontrolled preterm labor at 25.2 weeks. To the best of our knowledge, this is the first case of hand prolapse of one twin with extended period of latency before delivery.

The trends and risk factors to predict adverse outcomes in gestational diabetes mellitus: a 10-year experience from 2006 to 2015 in a single tertiary center

OBJECTIVE: To investigate the change of maternal characteristics, delivery and neonatal outcomes in gestational diabetes mellitus (GDM) over recent 10 years and to identify the risk factors associated with adverse outcome. METHODS: Consecutive GDM patients (n=947) delivered in our institution were included. Research period was arbitrarily divided into 2 periods (period 1: from 2006 to 2010, period 2: from 2011 to 2015). Multiple pregnancies or preexisting diabetes were excluded. Maternal baseline characteristics, delivery and neonatal outcomes were reviewed. Fetal biometric findings by prenatal ultrasonography were collected. Adverse pregnancy outcome (APO) was defined by the presence of one of the followings; shoulder dystocia, neonatal macrosomia (>4 kg), neonatal hypoglycemia (< 35 mg/dL), respiratory distress syndrome (RDS), and admission to the neonatal intensive care unit (NICU) in term pregnancy. RESULTS: Period 2 was associated with older maternal age (34 vs. 33, P < 0.001) and higher proportion of GDM A2 compared to period 1 (30.9% vs. 23.0%, P=0.009). By univariate analysis, APO was associated with increased body mass index (BMI) at pre-pregnancy (23.4 kg/m² vs. 21.8 kg/m², P=0.001) or delivery (27.9 kg/m² vs. 25.8 kg/m², P < 0.001), higher HbA1c at diagnosis (5.6% vs. 5.3%, P < 0.001) or delivery (5.8% vs. 5.5%, P=0.044), and larger fetal biometric findings (abdominal circumference [AC] and estimated fetal weight, P=0.029 and P=0.007, respectively). Multivariate analysis showed pre-pregnancy BMI (odds ratio [OR], 1.101; 90% confidence interval [CI], 1.028–1.180) and fetal AC (OR, 1.218; 90% CI, 1.012–1.466) were independently associated with adverse outcomes. CONCLUSION: Our study demonstrated the trends and relevant factors associated with the adverse outcomes.

Predicting factors for success of vaginal delivery in preterm induction with prostaglandin E₂

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E₂ for preterm labor induction and to investigate the predictive factors for the success of vaginal delivery. METHODS: A retrospective cohort study was performed in women (n=155) at 24+0 to 36+6 weeks of gestation who underwent induction of labor using a PGE₂ vaginal pessary (10 mg, Propess) from January 2009 to December 2015. Success rates of vaginal delivery according to gestational age at induction and incidence of intrapartum complications such as tachysystole and nonreassuring fetal heart rate were investigated. Multivariable logistic regression analysis was performed to evaluate the predictive factors for success of labor induction. RESULTS: The vaginal delivery rate was 57% (n=89) and the rate of cesarean delivery after induction was 43% (n=66). According to gestational age, labor induction was successful in 16.7%, 50.0%, and 62.8% of patients at 24 to 31, 32 to 33, and 34 to 36 weeks, showing a stepwise increase (P=0.006). There were 18 cases (11%) of fetal distress, 9 cases (5.8%) of tachysystole, and 6 cases (3.8%) of massive postpartum bleeding (>1,000 mL). After adjusting for confounding factors, multiparity (odds ratio [OR], 8.47; 95% confidence interval [CI], 3.10 to 23.14), younger maternal age (OR, 0.84; 95% CI, 0.75 to 0.94), advanced gestational age at induction (OR, 1.06; 95% CI, 1.02 to 1.09), rupture of membranes (OR, 11.83; 95% CI, 3.55 to 39.40), and the Bishop score change after removal of PGE₂ (OR, 2.19; 95% CI, 1.0 to 4.8) were significant predictors of successful preterm vaginal delivery. CONCLUSION: An understanding of the principal predictive factors of successful preterm labor induction, as well as the safety of PGE₂, will provide useful information when clinicians consult with preterm pregnant women requiring premature delivery.