Visible light-curable methacrylated glycol chitosan hydrogel patches for prenatal closure of fetal myelomeningocele.

In this study, we prepared visible light-curable methacrylated glycol chitosan (MGC) hydrogel patches for the prenatal treatment of fetal myelomeningocele (MMC) and investigated their feasibility using a retinoic acid-induced fetal MMC rat model. 4, 5, and 6 w/v% of MGC were selected as candidate precursor solutions, and photo-cured for 20 s, because the resulting hydrogels were found to possess concentration dependent tunable mechanical properties and structural morphologies. Moreover, these materials exhibited no foreign body reactions with good adhesive properties in animal studies. The inflammation scoring assessment in vivo exhibited the absence of foreign body reactions in MGC hydrogel treated lesion. The complete epithelial coverage of MMC was made with using 6 w/v% MGC hydrogel followed by well-organized granulation along with noticeable decrease of abortion rate and wound size that highlight the therapeutic potential for the prenatal treatment of fetal MMC.

Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms.

BACKGROUND: Mesenchymal stem cells (MSCs) are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties. Although human bone marrow-derived MSCs (BM-MSCs) were the most widely used MSCs in cell therapy until recently, MSCs derived from human umbilical cords (UC-MSCs) have gained popularity as cell therapy material for their ethical and noninvasive collection. AIM: To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs. METHODS: To analyze soluble factors expressed by MSCs, such as indolamine 2,3-dioxygenase, cyclooxygenase-2, prostaglandin E2 and interleukin (IL)-6, inflammatory environments in vitro were reconstituted with combinations of interferon-gamma (IFN-γ), tumor necrosis factor alpha and IL-1ß or with IFN-γ alone. Activated T cells were cocultured with MSCs treated with indomethacin and/or anti-IL-10. To assess the ability of MSCs to inhibit T helper 17 cells and induce regulatory T cells, induced T helper 17 cells were cocultured with MSCs treated with indomethacin or anti-IL-10. Xenogeneic graft-versus-host disease was induced in NOG mice (NOD/Shi-scid/IL-2Rγnull) and UC-MSCs or BM-MSCs were treated as cell therapies. RESULTS: Our data demonstrated that BM-MSCs and UC-MSCs shared similar phenotypic characteristics and immunomodulation abilities. BM-MSCs expressed more indolamine 2,3-dioxygenase after cytokine stimulation with different combinations of IFN-γ, tumor necrosis factor alpha-α and IL-1ß or IFN-γ alone. UC-MSCs expressed more prostaglandin E2, IL-6, programmed death-ligand 1 and 2 in the in vitro inflammatory environment. Cyclooxygenase-2 and IL-10 were key factors in the immunomodulatory mechanisms of both MSCs. In addition, UC-MSCs inhibited more T helper 17 cells and induced more regulatory T cells than BM-MSCs. UC-MSCs and BM-MSCs exhibited similar effects on attenuating graft-versus-host disease. CONCLUSION: UC-MSCs and BM-MSCs exert similar immunosuppressive effects with different mechanisms involved. These findings suggest that UC-MSCs have distinct immunoregulatory functions and may substitute BM-MBSCs in the field of cell therapy.

Application of Tissue Engineering and Regenerative Medicine in Maternal-Fetal Medicine.

A rapid development of ultrasonography has enabled physicians to make earlier prenatal diagnosis of various fetal congenital diseases, in maternal-fetal medicine. Due to the significant mortality and irreversible damage to fetal vital organs during pregnancy, fetal surgeries have been tried in some congenital disease including congenital diaphragmatic hernia, twin-to-twin transfusion syndrome (TTTS), myelomeningocele (MMC), and lower urinary tract obstruction. However, open fetal surgery requires laparotomy followed by hysterotomy, which can cause preterm premature rupture of membrane (pPROM), oligohydramnios, preterm delivery, dehiscence of uterine wall, and other maternal complications during pregnancy. Minimally invasive approach using fetoscopy has been tried, and fetoscopic laser photocoagulation of vascular communications is currently considered as a treatment of choice for TTTS before 26 weeks' gestation. However, more development of surgical instrument and innovative materials using tissue engineering are required to improve outcomes of fetoscopic surgery. Because iatrogenic pPROM is the major challenge after fetoscopic surgery, this review focuses on current development of materials for treatment of spontaneous or iatrogenic pPROM and recent experimental progress of tissue engineering-based technology in prenatal treatment of MMC. Placental tissue is an emerging material for regenerative medicine. This chapter will also review regenerative potential and experiments of placenta and placenta-derived stem cells, as well as prospects of "in utero stem cell therapy."

Effect of maternal age on emergency cesarean section.

Objectives: This study aims to investigate the independent influence of maternal age on the risk of emergency cesarean section (CS) due to nonreassuring fetal heart rate or arrest disorder.Methods: This was a cross-sectional study on women with nulliparous pregnancies, who are attempting vaginal delivery at term and have a cephalic presentation without the indication of elective CS at the onset of labor. The primary outcome was the rate of emergency CS. Independent risk factors were elucidated using multivariate logistic regression analysis.Results: Of 3513 women, 541 (15.4%) delivered by emergency CS during a trial of vaginal delivery, with theses being due to nonreassuring fetal heart rate (N = 150) or arrest disorder (N = 391). In univariate analysis, both individual CS rate due to nonreassuring fetal heart rate or arrest disorder and total emergent CS rate increased with maternal age. The risk of emergency CS was also significantly higher when labor induction was performed (odds ratio (OR) 2.489, 95% confidence interval (CI) 2.043-3.033), while fetal weight was heavier (neonatal weight ≥3.5 kg; OR 2.396, 95% CI 1.956-2.934), and maternal BMI was higher (before pregnancy ≥25 kg/m2; OR 2.751, 95% CI 1.980-3.823, at delivery ≥28 kg/m2; OR 2.375 95% CI 1.915-2.946). Multivariate stepwise regression analysis showed a statistically significant increase in the risk of total emergency CS in mothers over 35 years of age, compared to that in women less than 30 years old (35-39 years group; adjusted OR 1.805 95% CI 1.347-2.418, ≥40 years group; adjusted OR 4.659 95% CI 2.709-8.013). CS due to nonreassuring fetal heart rate increased in mothers over 40 years of age (adjusted OR 5.354, 95% CI 2.386-12.017) and CS due to arrest disorder was also increased in mothers over 30 years of age (30-34 years group; adjusted OR 1.343, 95% CI 1.010-1.785, 35-39 years group; adjusted OR 1.906, 95% CI 1.357-2.679, ≥40 years group; adjusted OR 4.663, 95% CI 2.480-8.768). Similar to the result of univariate analysis, labor induction increased the risk of emergency CS (adjusted OR 2.241, 95% CI 1.828-2.747).Conclusions: Advanced maternal age is an independent risk factor of emergency CS due to nonreassuring fetal heart rate or arrest disorder during the trial of vaginal delivery. The risk of emergency CS was also increased when labor induction was performed. Therefore, the risk of emergency CS needs to be considered, especially when the labor induction is planned, in women aged 40 or more.

The Educational Effects of a Pregnancy Simulation in Medical/Nursing Students and Professionals.

BACKGROUND: The objective of this study was to investigate whether a pregnancy experience program (PREP) simulating physical changes in a mother during the last trimester of pregnancy could increase empathy, understanding, and positive attitude of medical/nursing students and their professional counterparts. METHODS: This was a prospective observational study on medical/nursing students and their professional counterparts. Jefferson Scale of Physician Empathy (JSPE), physical difficulty and positive attitude score, and perceived effectiveness scores prior to PREP were compared to those after PREP. RESULTS: A total of 189 participants completed PREP and questionnaires both prior to and after PREP. Mean JSPE score, physical difficulty score, and positive attitude scores were significantly increased following PREP (p<0.001, all). Perceived effectiveness scores about awareness, empathy, and understanding after PREP were significantly high in the professional group than in the student group (p=0.004, p=0.01, and p=0.017, respectively). Multiple stepwise linear regression analysis revealed that major in medicine (p = 0.014), health care professionals (nurse or physician) (p<0.001), and marriage experience (p < 0.001) were significant predictors of increasing empathy, difficulty feelings and effectiveness scores, respectively. CONCLUSION: PREP is an effective simulation program that can improve empathy, positive attitude, and awareness in medical/nursing students as well as their professional counterparts.

The association between abortion experience and postmenopausal suicidal ideation and mental health: Results from the 5th Korean National Health and Nutrition Examination Survey (KNHANES V).

OBJECTIVE: The association between abortion and postmenopausal mental health has not been clearly established in Asian women. The objective of this study was to evaluate the effect of abortion experiences on suicidal ideation and mental health in Korean postmenopausal women. MATERIALS AND METHODS: This study included 5133 postmenopausal women registered in the Korean National Health and Nutrition Examination Survey between 2010 and 2012. Difference in suicidal ideation according to type and number of abortions was analyzed. We used survey multiple logistic regression analysis to evaluate the effect of abortion experiences on the risk for suicidal ideation expressed as adjusted odd ratios (ORs) with 95% confidence intervals (95%CIs). RESULTS: The risk of suicidal ideation was significantly higher in women who experienced more than three abortions (27.9%). While the incidence of suicidal ideation was not significantly affected by the number of spontaneous abortions (p = 0.718), suicidal ideation was significantly more frequent in women who had undergone ≥ three abortions (p = 0.003). After adjusting for demographic confounding factors, women who underwent ≥ three induced abortions had higher risk for suicidal ideation (OR: 1.510; 95% CI: 1.189-1.919; p = 0.031). This risk remained elevated even after controlling for depression (OR: 1.391; 95% CI: 1.1086-1.871, p = 0.002). Moreover, the risk of experiencing a depressive mood in daily life was also increased with increasing number of induced abortions even after controlling for depression (OR: 1.657; 95% CI: 1.274-2.156, p = 0.002). CONCLUSION: Undergoing three or more induced abortions during reproductive age was associated with postmenopausal suicidal ideation, stress, and depression. However, such association was not noted in those with spontaneous abortion, even in women with more miscarriages. Thus, clinicians should evaluate depression and suicidal ideation in women with multiple induced abortions.

Late-preterm infants, early-term infants, and timing of elective deliveries; current status in a Korean medical center.

OBJECTIVE: The aim of this study was to examine the current perinatal outcomes among infants born late-preterm and early-term compared to those born full-term and evaluate the optimal gestational age for delivery. METHODS: We performed a retrospective cohort study for births occurred at Seoul St. Mary's Hospital over the past 7 years. Statistical comparison was performed using χ2 test and multivariable logistic regression models. RESULTS: A total of 7580 women met the study criteria. Compared to 39 weeks, delivery at late-preterm and early-term had higher risk of composite morbidity, including respiratory morbidities, intracranial hemorrhage (ICH), and admission to neonatal intensive care unit (NICU) (34 weeks adjusted odds ratio [aOR]: 132.54; 95% confidence interval (CI): 74.00-240.10; 37 weeks aOR: 2.14; 95%CI: 1.65-2.77). The risks of sepsis and necrotizing enterocolitis in deliveries before 36 weeks and the risk of feeding difficulty in deliveries before 37 weeks were significantly higher than those of 39 weeks. Neonatal morbidity at deliveries was not significantly different between 38 and 39 weeks. CONCLUSIONS: Neonatal morbidities at late-preterm births are significant and surveillance for them seems increasing. Obstetricians should recognize the risk of respiratory morbidity, ICH, and NICU admission for deliveries before 38 weeks' gestation.

Optimal time of delivery to reduce the risk of infant mortality in small and normally grown fetuses: A national cohort study in Korea.

PURPOSE: To examine the competing risks of stillbirth versus infant death and to evaluate the optimal time of delivery in the population of small for gestational age (SGA) and non-SGA late preterm and term fetuses. METHODS: This was a retrospective national cohort study of all singleton births between 34 0/7 and 42 6/7 weeks of gestation using the Korean vital statistics (n = 2,106,159). We compared the risk of infant mortality with a composite of fetal-infant mortality risk that would occur after expectant management for one additional week and evaluated the optimal time of delivery, in SGA and non-SGA pregnancies. RESULTS: In the total population, the risk of expectant management became significantly higher than the risk of delivery, at 39 weeks and beyond, similar with non-SGA group. In the SGA group, the risk of stillbirth was significantly greater at all GAs than for non-SGA pregnancies, and the risk of infant death was significantly increased until 38 weeks (25.8 per 10,000 live births, 95% CI 20.11-32.47), and the risk of stillbirth was significantly increased at 41 weeks (11.65 per 10,000 ongoing pregnancies, 95% CI 6.95-18.09), compared to 39 weeks (12 per 10,000 live births, 95% CI 8.98-15.64 and 5.12 per 10,000 ongoing pregnancies, 95% CI 3.84-6.66, respectively). CONCLUSION: In Korean women, delivery between 39 and 41 weeks minimizes fetal/infant mortality, in non-SGA pregnancies. In uncomplicated SGA pregnancies, delivery between 39 and 40 weeks can be considered to decrease risk of infant death and stillbirths.

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.

Multiple birth rates of Korea and fetal/neonatal/infant mortality in multiple gestation.

OBJECTIVE: This study was conducted to analyze recent trends of multiple birth rates (MBR) and fetal/neonatal/infant mortalities according to the number of gestations in Korea. METHODS: Data from 2009 to 2015 of live births, infant deaths and stillbirths were obtained from the Korean Vital Statistics. Neonatal mortality rate (NMR), infant mortality rate (IMR), and fetal mortality rate (FMR) in singleton, twin and triplet pregnancies were analyzed according to gestational period (GP; ≤ 23, 24-27, 28-31, and 32-36 weeks). RESULTS: From 2009 to 2015, twin and triplet birth rates increased 34.5% and 154.3%, respectively. In twin births, NMR and FMR have been decreased significantly (from 10.92 to 8.62, p = 0.034 and from 41.00 to 30.55, p< 0.001, respectively), but IMR did not show significant decrease. There was no significant change of NMR, IMR, and FMR, in triplet births. Overall, in singleton, twin, and triplet births, NMR was 1.26 ± 0.09, 10.6 ± 1.12, and 34.32 ± 11.72, respectively, and IMR was 2.38 ± 0.26, 14.52 ± 1.38, and 41.13 ± 12.2, respectively. FMRs were 12 ± 1.73, 35.99 ± 3.55, and 88.85 ± 16.55, respectively, in singleton, twin, and triplet pregnancies. In spite of decreasing trends in overall mortalities, the odds ratios of NMRs and IMRs in 2015 were approximately 9-fold and 6-fold higher, respectively, in twin births, and approximately 37-fold and 20-fold higher, respectively, in triplet births, than those in singleton births. There were no significant differences in odds ratios of NMRs and IMRs at GP 32-36 among single, twin, and triplet births, although the odds ratios of FMR at GP 32-36 in triplet gestation was significantly higher than those in singleton and twin gestation. CONCLUSION: Neonatal/infant mortality in multiple births is still significantly high, which is mainly related with preterm birth. Close fetal monitoring is needed to prevent fetal death in triplet pregnancies, after 32 gestational weeks.

Amnion-Analogous Medical Device for Fetal Membrane Healing: A Preclinical Long-Term Study.

Although recent invasive fetal surgeries have improved fetal outcomes, fetal membrane rupture remains a major complication, leading to premature delivery, thus undermining the complete benefits of such procedures. A biocompatible amnion-analogous medical device (AMED) consisting of polycaprolactone framework and decellularized amniotic membrane (dAM)-derived hydrogel for restoration of amniotic membrane defect is developed using 3D printing technology. Its efficacy on healing iatrogenic fetal membrane defects in vitro is evaluated, showing that the dAM gel contains migratory and proliferative properties. The fetoscope feasibility of the developed AMED is assessed using a pregnant swine model. All animals had successfully recovered from anesthesia and the fetoscopic procedure and maintained a healthy condition until the end of the pregnancy. AMED exhibits superior surgical handling characteristics and is easy to manufacture, nonimmunogenic, biocompatible, and suitable for storage and transport for off-the-shelf use; hence, it can be used in successfully sealing defect sites, thus improving the preservation of the amniotic fluid, which in turn improves fetal survival and development.

Effects of Oncostatin M on Invasion of Primary Trophoblasts under Normoxia and Hypoxia Conditions.

PURPOSE: To investigate the effect of oncostatin M (OSM) on protein expression levels and enzymatic activities of matrix metalloprotainase (MMP)-2 and MMP-9 in primary trophoblasts and the invasiveness thereof under normoxia and hypoxia conditions. MATERIALS AND METHODS: Protein expression levels and enzymatic activities of MMP-2 and MMP-9 in primary trophoblasts under normoxia and hypoxia conditions were examined by Western blot and zymography, respectively. Effects of exogenous OSM on the in vitro invasion activity of trophoblasts according to oxygen concentration were also determined. Signal transducer and activator of transcription 3 (STAT3) siRNA was used to determine whether STAT3 activation in primary trophoblasts was involved in the effect of OSM. RESULTS: OSM enhanced protein expression levels and enzymatic activities of MMP-2 and MMP-9 in term trophoblasts under hypoxia condition, compared to normoxia control (p<0.05). OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly suppressed by STAT3 siRNA silencing under normoxia and hypoxia conditions (p<0.05). Hypoxia alone or OSM alone did not significantly increase the invasiveness of term trophoblasts. However, the invasion activity of term trophoblasts was significantly increased by OSM under hypoxia, compared to that without OSM treatment under normoxia. CONCLUSION: OSM might be involved in the invasiveness of extravillous trophoblasts under hypoxia conditions via increasing MMP-2 and MMP-9 enzymatic activities through STAT3 signaling. Increased MMP-9 activity by OSM seems to be more important in primary trophoblasts.

Fetal Doppler to predict cesarean delivery for non-reassuring fetal status in the severe small-for-gestational-age fetuses of late preterm and term.

OBJECTIVE: To evaluate the significance of fetal Doppler parameters in predicting adverse neonatal outcomes and the risk of cesarean delivery due to non-reassuring fetal status, in severe small for gestational age (SGA) fetuses of late preterm and term gestation. METHODS: Fetal brain and umbilical artery (UmA) Doppler parameters of cerebroplacental ratio (CPR) and UmA pulsatility index (PI) were evaluated in a cohort of 184 SGA fetuses between 34 and 41 weeks gestational age, who were less than the 5th percentile. The risks of neonatal morbidities and cesarean delivery due to non-reassuring fetal status were analyzed. RESULTS: Univariate analysis revealed that abnormal CPR was significantly associated with cesarean delivery due to non-reassuring fetal status (P=0.018), but not with neonatal morbidities. However, abnormal CPR did not increase the risk of cesarean delivery due to non-reassuring fetal status in multivariate logistic regression analysis. Abnormal CPR with abnormal PI of UmA was associated with low Apgar score at 1 minute (P=0.048), mechanical ventilation (P=0.013) and cesarean delivery due to non-reassuring fetal status (P<0.001), in univariate analysis. It increased risk of cesarean delivery for non-reassuring fetal status (adjusted odds ratio, 7.0; 95% confidence interval, 1.2-41.3; P=0.033), but did not increase risk of low Apgar score or mechanical ventilation in multivariate logistic regression analysis. CONCLUSION: Abnormal CPR with abnormal PI of UmA increases the risk of cesarean delivery for non-reassuring fetal status, in severe SGA fetuses of late preterm and term. Monitoring of CPR and PI of UmA can help guide management including maternal hospitalization and fetal monitoring.

Optimal Timing of Delivery Based on the Risk of Stillbirth and Infant Death Associated with Each Additional Week of Expectant Management in Multiple Pregnancies: a National Cohort Study of Koreans.

BACKGROUND: The purpose of this study was to compare the fetal/infant mortality risk associated with each additional week of expectant management to that associated with immediate delivery in women with multiple gestations. METHODS: This was a retrospective national cohort study of 94,170 multiple deliveries, 92,619 (98.4%) twin and 1,352 (1.44%) triplet pregnancies, between 32 0/7 and 42 6/7 weeks of gestation recorded in the Korean vital statistics database. We investigated the risks of stillbirth and infant death after birth in Korea according to the week of gestation in twin and triplet pregnancies. RESULTS: The risk of stillbirth significantly increased between 34 and 35 weeks of gestation and between 37 and 38 weeks of gestation in twin pregnancies and between 34 and 37 weeks of gestation in triplet pregnancies. The risk of infant death following delivery gradually decreased as pregnancies approached full term. Week-by-week differences were statistically significant between 33 and 34 weeks, with decreasing risks of infant death at advancing gestational ages in twin pregnancies. At 37 weeks of gestation, the relative risk of mortality was significantly higher with expectant management compared with immediate delivery (relative risk, 3.00; 95% confidence interval, 1.41-6.38). CONCLUSION: In twin pregnancies, delivery at 37 weeks of gestation can minimize the risks of stillbirth and infant death in uncomplicated cases, although individual maternal and fetal characteristics must be considered when determining the optimal timing of delivery. In multiple pregnancies, close fetal surveillance is needed after 34 weeks of gestation.

Antenatal corticosteroids and outcomes of preterm small-for-gestational-age neonates in a single medical center.

OBJECTIVE: This study investigated the effect of an antenatal corticosteroid (ACS) in preterm small-for-gestational-age (SGA) neonate. METHODS: This study was a retrospective cohort study. We compared women who received ACS with unexposed controls and evaluated neonatal complications among those having a singleton SGA neonate born between 29 and 34 complete gestational weeks. The neonates born after 32 weeks of gestation were divided into subgroups. Multivariable logistic regression analysis was performed. RESULTS: A total 82 of the preterm infants met inclusion criteria; 57 (69.5%) were born after 32 weeks of gestation. There were no significant differences in terms of mechanical ventilation, seizure, intracranial hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, feeding difficulty, and neonatal mortality between infants whose mothers received ACS ant those whose mothers did not (all P>0.05). However, newborns whose mothers received ACS exhibited a significantly increased risk of developing respiratory distress syndrome (RDS) (adjusted odds ratio [aOR], 3.271; 95% confidence interval [CI], 1.038-10.305; P=0.043). In case of neonates born beyond 32 weeks of gestation, the risk of neonatal hypoglycemia was significantly higher in women receiving ACS after controlling for confounding factors (aOR, 5.832; 95% CI, 1.096-31.031; P=0.039). CONCLUSION: ACS did not improve neonatal morbidities, in SGA neonates delivered between 29 and 34 gestational weeks. Rather, ACS could increase the risk of RDS. In cases of SGA neonate delivered between 32 and 34 complete gestational weeks, the risk of hypoglycemia was significantly increased. The use of ACS in women with preterm SGA infants needs to be evaluated further, especially after 32 weeks' gestation.

Maternal serum placental growth factor combined with second trimester aneuploidy screening to predict small-for-gestation neonates without preeclampsia.

OBJECTIVE: To investigate the role of maternal serum placenta growth factor (PlGF) and quadruple test parameters in predicting the risk of small for gestational age (SGA) infants of mothers without preeclampsia. MATERIALS AND METHODS: We prospectively enrolled 300 pregnant patients who underwent blood sampling at 15-18 weeks gestation and followed them until delivery. Cases with SGA neonate delivery (n = 100) were compared with matched AGA neonate controls (n = 200). The plasma PlGF and quadruple markers were measured by enzyme-linked immunosorbent assay. The results were analyzed with Mann-Whitney U tests, and regression analysis was used to develop a model for the prediction of SGA. RESULTS: Women who delivered SGA neonates had decreased levels of PlGF (median 0.71 MoM versus 0.7 MoM; p < 0.01), hCG (median 0.97 MoM versus 1.06 MoM; p = 0.046) and uE3 (median 0.92 MoM versus 1.04 MoM) compared to the AGA group. AFP, hCG and inhibin-A levels did not differ significantly. A PlGF concentration <0.37 MoM had a sensitivity of 28.0% (95% CI: 19.5-37.9) and a specificity of 89.5% (95% CI: 84.4-93.4) for the prediction of SGA neonates without PE. CONCLUSION: SGA neonates in the absence of PE could potentially be identified at 15-18 weeks of pregnancy.

A national cohort study evaluating infant and fetal mortality caused by birth defects in Korea.

OBJECTIVE: To analyse the prevalence of fetal and infant deaths due to birth defects in Korea and those trends according to maternal age. DESIGN: Retrospective national cohort study SETTING: Korean Vital Statistics database of the Korean Statistical Information Service, between 2009 and 2015. PARTICIPANTS: 2176 infant deaths and 4343 fetal deaths caused by birth defects, among 3 181 145 total live births and 43 385 fetal deaths during the study periods. METHODS: Infant and fetal mortality rates (IMRs and FMRs) by birth defects, from deaths caused by birth defects, were analysed. They were compared, according to maternal age groups: (I) '10-19 years'; (II) '20-29 years'; (III) '30-34 years'; (IV) '35-39 years'; and (V) '40-55 years'. MAIN OUTCOME MEASURES: IMRs and FMRs by birth defects and comparison according to maternal age group. RESULTS: IMRs and FMRs by birth defects were 6.84 per 10 000 live births and 13.47 per 10 000 total births. The most common causes of infant deaths and fetal deaths by birth defect were anomaly of the circulatory system (51.1%, IMR 3.5) and chromosomal abnormality (33.1%, FMR 4.46), respectively. Among groups by maternal age, FMRs by birth defects were significantly higher in groups I and V compared with group III (OR 6.59, 95% CI 3.49 to 12.43; and OR 3.46, 95% CI 1.77 to 6.78, respectively). IMR and FMR by nervous system anomaly were significantly higher in group I at 3.63 (OR 2.0, 95% CI 1.97 to 2.03) and 29.84 (OR 15.04, 95% CI 3.59 to 62.96) compared with 0.32 and 1.97 in group III. CONCLUSION: FMRs by birth defects were the highest in the extreme maternal age groups. Severe anomalies, except for chromosomal abnormality, were most prevalent in teenage pregnancies.

Determining optimal gestational weight gain in the Korean population: a retrospective cohort study.

BACKGROUND: The World Health Organization (WHO) international body mass index (BMI) cut-off points defining pre-pregnancy BMI categories in the Institute of Medicine (IOM) guidelines are not directly applicable to Asians. We aimed to define the optimal gestational weight gain (GWG) for the Korean population based on Asia-specific BMI categories. METHODS: Data from 2702 live singleton deliveries in three tertiary centers between 2010 and 2011 were analyzed retrospectively. A multivariable logistic regression analysis was conducted to determine the lowest aggregated risk of composite perinatal outcomes based on Asia-specific BMI categories. The perinatal outcomes included gestational hypertensive disorder, emergency cesarean section, and fetal size for gestational age. In each BMI category, the GWG value corresponding to the lowest aggregated risk was defined as the optimal GWG. RESULTS: Among the study population, 440 (16.3%) were underweight (BMI < 18.5), 1459 (54.0%) were normal weight (18.5 ≤ BMI < 23), 392 (14.5%) were overweight (23 ≤ BMI < 25) and 411 (15.2%) were obese (BMI ≥ 25). The optimal GWG by Asia-specific BMI category was 20.8 kg (range, 16.7 to 24.7) for underweight, 16.6 kg (11.5 to 21.5) for normal weight, 13.1 kg (8.0 to 17.7) for overweight, and 14.4 kg (7.5 to 21.9) for obese. CONCLUSION: Considerably higher and wider optimal GWG ranges than recommended by IOM are found in our study in order to avoid adverse perinatal outcomes. Revised IOM recommendations for GWG could be considered for Korean women according to Asian BMI categories. Further prospective studies are needed in order to determine the optimal GWG for the Korean population.

The associations between parity, other reproductive factors, and osteoarthritis in women aged over 50 years; data from the Korean National Health and Nutrition Examination Survey V (2010-2012).

OBJECTIVE: To evaluate the relationships between sociodemographic factors, reproductive history, and subsequent risk of osteoarthritis (OA) or pain of the hip, knee, and back in Korean women. MATERIALS AND METHODS: This study included data of 5101 women aged over 50 years, taken from the Korean National Health and Nutritional Examination Survey V from 2010 to 2012. Women were stratified according to parity, as well as delivery mode. Multivariate logistic regression analysis was conducted to evaluate relationships between radiographic OA or symptomatically possible OA (back, knee, or hip), and historical factors. RESULTS: Vaginal delivery was associated with an increased risk of symptomatic back OA [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.062, 2.881] but was not associated with symptomatic knee and hip OA in adjusted analysis. Radiographically, vaginal delivery was not associated with risks of back and knee OA, but was negatively associated with hip OA (OR 0.184, 95% CI 0.039, 0.863), compared to cesarean delivery. High parity (over 5) was associated with radiographic knee OA (OR 1.328, 95% CI 1.006, 1.754) in adjusted analysis. High parity (over 3) was associated with symptomatic back OA. CONCLUSION: Parity was associated with higher risk of radiographic knee OA. Vaginal delivery was positively associated with symptomatic back OA, but negatively associated with radiographic knee OA. Further study is required to evaluate the mechanism between delivery mode and subsequent OA.

Placental histologic patterns and neonatal seizure, in preterm premature rupture of membrane.

OBJECTIVE: To investigate the relationship between placenta and perinatal outcomes, in preterm infants born to mothers with preterm premature rupture of fetal membrane (PPROM). METHODS: We report detailed histology of placentas and perinatal outcomes of infants from 79 PPROM pregnancies. Placental histologic pattern and adverse perinatal outcomes were assessed by logistic regression, adjusting for gestational age at birth, birth weight and interval from rupture of membrane to delivery. RESULTS: Mean gestational age at membrane rupture was 29.5 ± 3.4 weeks. The incidence of histologic chorioamnionitis (HCA), fetal inflammatory response (FIR) and vascular thrombotic abnormalities in placental histologic examination were 63.3, 25.3 and 78.5%, respectively. Neonates with FIR showed significantly higher incidence of periventricular leukomalacia (PVL) (85% versus 59.3%, p = 0.0364) at brain ultrasonography, than neonates without FIR, in univariate analysis, but not in logistic regression analysis. In logistic regression analysis, the odds ratio of low Apgar score at 1 min in the neonates with clinical chorioamnionitis was 5.009 (95% CI, 1.242-20.195). The odds ratio of neonatal seizure in the neonates with FIR and vascular thrombotic problem was 7.486 (95% CI, 1.617-34.653). CONCLUSIONS: Our findings support the association between FIR with vascular thrombotic problem in placenta and neonatal seizure, in pregnancies with PPROM.