The influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida: a Korean National Cohort Study over 15 years.

Objective: To assess the influence of advanced maternal age on congenital malformations, and short- and long-term outcomes in offspring of nulligravida. Methods: A retrospective study was conducted using the Korean National Health Insurance Service database spanning from January 2005 to December 2019. All live-born offspring of nulligravida (n=3,685,817) were included. The maternal age was subdivided into the following subgroups: <25 years (n=153,818), 25-29 years (n=845,355), 30-34 years (n=1,738,299), 35-39 years (n=787,530), 40-44 years (n=151,519), and >44 years (n=9,296). Outcomes were assessed based on ICD-10 codes. Adjusted odds ratios (aORs) were calculated with the group of 25-29 years as a reference using logistic regression and Cox proportional hazards model analysis. Results: Most congenital malformations showed an age-dependent increase, but cleft lip and abdominal wall defect exhibited a U-shape curve, indicating an increase even in those <25 years old. Similarly, various disorders included in the neonatal composite outcomes from short-term outcomes showed an age-dependent escalation. However, preterm birth from the short-term outcomes and most of the long-term developmental outcomes, except for motor developmental delays and Tics, showed a U-shaped pattern. The aOR of autism and cerebral palsy, showing the most obvious U-shaped curved in the long-term outcomes, was 1.50 (95% CI 1.24-1.82) and 1.54 (95% CI 1.17-2.03), respectively in the >44 years old group and 1.18 (95% confidence interval [CI], 1.11-1.25) and 1.19 (95% CI, 1.09-1.30) in the <25 years old group. Conclusion: Overall, an advanced maternal age shows an age-dependent correlation with most congenital malformations, as well as short- and long-term outcomes of neonates.

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.

Effect of delayed cord clamping on maternal and neonatal outcome in twin pregnancies: a retrospective cohort study.

The objective of this study was to compare the maternal and neonatal outcomes following delayed cord clamping (DCC) versus immediate cord clamping (ICC) in twin pregnancies. This was a retrospective cohort study of 705 twin pregnancies who delivered at ≥ 24 weeks of gestation. Maternal and neonatal hemoglobin levels, blood transfusion, and neonatal outcomes were compared between DCC (n = 225) and ICC (n = 480) groups. Mean maternal predelivery and postpartum hemoglobin levels and the rate of postpartum hemoglobin drop ≥ 20% or maternal blood transfusion were comparable between the two groups. The DCC group had a significantly higher mean neonatal hemoglobin level (DCC vs. ICC: 17.4 ± 3.5 vs. 16.6 ± 2.7 g/dl, P = 0.010) but significantly lower rates of neonatal blood transfusion (DCC vs. ICC: 3.3% vs. 8.8%, P < 0.001) and respiratory distress syndrome (DCC vs. ICC: 6.7% vs. 15.2%, P < 0.001) than the ICC group. In conclusion, DCC compared with ICC in twin pregnancy was not associated with an increase of maternal postpartum bleeding complications, but it was associated with higher neonatal hemoglobin level and lower risks of neonatal blood transfusion and respiratory distress syndrome.

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.

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.

Effect of chewing gum on anxiety in women undergoing elective cesarean section: a randomized controlled study.

BACKGROUND: Preoperative anxiety is a common problem in pregnant women undergoing elective cesarean section. We aimed to determine the anxiolytic effects of chewing gum in pregnant women undergoing elective cesarean section under regional anesthesia. METHODS: This was a single-center, prospective, randomized controlled trial. Sixty-six women were randomly assigned to either the control group (n=33) or gum group (n=33) in a 1:1 ratio. In the gum group, the participants chewed xylitol gum for at least 10 min/h, regardless of fasting. Gum chewing was started at 5 pm a day before surgery and continued till the participant entered the operation room. In the control group, participants were requested to follow fasting guidelines without further instruction. The primary outcome was preoperative anxiety measured using the Amsterdam Preoperative Anxiety and Information Scale (APAIS) immediately before surgery. RESULTS: The APAIS score immediately before surgery showed no significant difference between the control and the gum group (19.2±5.8 vs. 19.1±4.1, P>0.99). There were no statistically significant differences in the eight items related to anxiety: unfitness, concentration difficulty, hunger, thirst, dry mouth, fatigue, headache, and nausea. However, the pain score during the procedure of combined spinal epidural anesthesia was significantly lower in the chewing gum group [4 (IQR, 3-5.5)] than in the control group [5 (IQR, 3-7), P=0.045]. CONCLUSIONS: Preoperative gum chewing did not reduce anxiety levels measured immediately before entering the operating room in the participants undergoing elective cesarean section. TRIAL REGISTRATION: Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0006602; date of registration: September 27, 2021; principal investigator's name: RyungA Kang.

Abnormal Vaginal Flora in Cervical Incompetence Patients - the Impact of Escherichia coli.

The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056-14.055) and NEC (OR: 12.410, 95% CI: 1.290-119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess.

A randomized clinical trial of antibiotic treatment duration in preterm pre-labor rupture of membranes: 7 days vs until delivery.

BACKGROUND: Antibiotic treatment in preterm pre-labor rupture of membranes can prolong the interval from membrane rupture to delivery and improve neonatal outcomes. However, the duration of antibiotic treatment for preterm pre-labor rupture of membranes has been rarely compared in prospective studies. OBJECTIVE: This study aimed to investigate the optimal duration of antibiotic treatment for pre-labor rupture of membranes. We performed a randomized controlled trial comparing neonatal morbidity and infantile neurologic outcomes between 2 groups of patients with preterm pre-labor rupture of membranes who received antibiotic treatment for 7 days or until delivery, respectively. STUDY DESIGN: This prospective randomized study included patients who were diagnosed with preterm pre-labor rupture of membranes between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dosage every 12 hours) and oral clarithromycin (500 mg dosage every 12 hours) either for 7 days or until delivery. The study protocol was registered at ClinicalTrials.gov under identifier NCT01503606. The primary outcome was a neonatal composite morbidity, and the secondary outcome was neurologic outcomes at 12 months of corrected age. We enrolled 151 patients and allocated 75 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. RESULTS: After excluding cases lost to follow-up and those with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) patients with preterm pre-labor rupture of membranes and their babies were compared. There was no significant difference in the pregnancy outcomes, including gestational age at delivery and the interval from rupture of membranes to delivery, between the 2 groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rates of respiratory distress syndrome (32.8% vs 50.8%; P=.039) and composite neonatal morbidities (34.4% vs 53.9%; P=.026) were lower in the until-delivery group than in the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, antenatal corticosteroids treatment, gestational age at delivery, interval from rupture of membranes to delivery, and clinical chorioamnionitis. Infantile neurologic outcomes were evaluated in 71.4% of the babies discharged alive and did not differ between the groups. CONCLUSION: Overall, the until-delivery regimen of cefazolin and clarithromycin in preterm pre-labor rupture of membranes led to a lower incidence of composite neonatal morbidity and respiratory distress syndrome than the 7-day regimen, and both regimens otherwise showed similar individual neonatal morbidities and infantile neurologic outcomes.

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial.

BACKGROUND: Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. METHODS: In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. DISCUSSION: This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021.

Growing threat of extended-spectrum ß-lactamase-producing Enterobacteriaceae colonisation in high-risk pregnancies: A cross-sectional study.

OBJECTIVE: To investigate the epidemiological changes in extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) vaginal colonisation in pregnant women deemed at high risk, and to identify independent risk factors. Further, the differences in perinatal outcomes according to maternal ESBL-E vaginal colonisation were analysed. DESIGN: Cross-sectional study. SETTING: Republic of Korea. POPULATION: A cohort of 1460 women admitted to our high-risk pregnancy unit between 14+0 and 36+6  weeks of gestation. METHODS: The trend of changes in the association of ESBL-E vaginal colonisation from January 2010 to December 2020 was analysed. The main outcomes were analysed over the study period and ESBL-E vaginal colonisation. MAIN OUTCOME MEASURES: Rate of ESBL-E vaginal colonisation, risk factors for ESBL-E vaginal colonisation and perinatal outcomes. RESULTS: The ESBL-E vaginal colonisation rate has tended to increase over the past 11 years, which was attributed to a significantly higher proportion of ESBL-producing Escherichia coli. Cerclage (RR 3.7, 95% CI 2.19-6.40) and prior antibiotic treatment (RR 4.0, 95% CI 2.44-6.54) were found as independent risk factors for ESBL-E vaginal colonisation. Earlier gestational age at delivery and higher proven early-onset neonatal sepsis (EONS) rate were observed in the ESBL-E-positive group. CONCLUSIONS: The ESBL-E vaginal colonisation rate in pregnant patients at high risk has increased over the past decade, and the independent risk factors for colonisation are cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E vaginal colonisation is associated with higher rates of proven EONS.

Hydroxychloroquine reduces hypertension and soluble fms-like kinase-1 in a Nω-nitro-l-arginine methyl ester-induced preeclampsia rat model.

OBJECTIVE: Hydroxychloroquine, a drug used for malaria and autoimmune diseases reportedly has beneficial effects against preeclampsia in pregnant women with lupus. However, its mechanism against preeclampsia remains unclear. We investigated the effect of hydroxychloroquine on an Nω-nitro-l-arginine methyl ester-induced preeclampsia rat model. METHODS: Pregnant Sprague-Dawley rats were divided into four groups based on treatment (administered on gestational days 7-18): control, Nω-nitro-l-arginine methyl ester, hydroxychloroquine, and Nω-nitro-l-arginine methyl ester plus hydroxychloroquine. All animals were sacrificed on gestational day 19. We assayed tube formation and determined reactive oxygen species levels using human umbilical vein endothelial cells. RESULTS: Results showed that hydroxychloroquine significantly lowered mean systolic blood pressure (P  < 0.05) in Nω-nitro-l-arginine methyl ester-treated rats. Hydroxychloroquine did not affect their fetal and placental weights. Hydroxychloroquine mitigated Nω-nitro-l-arginine methyl ester-associated changes in proteinuria (P  < 0.05). It normalized plasma soluble fms-like kinase-1 (P  < 0.05) and endothelin-1 (P  < 0.01) levels. In the tube formation assay, hydroxychloroquine increased the total meshes area (P  < 0.05) and mitigated Nω-nitro-l-arginine methyl ester-induced reactive oxygen species formation (P  < 0.05) in human umbilical vein endothelial cells. CONCLUSION: We conclude that hydroxychloroquine alleviated hypertension, proteinuria, and normalized soluble fms-like kinase-1 and endothelin-1 levels in our preeclampsia model and that these changes may involve the restoration of endothelial dysfunction; thus, hydroxychloroquine could potentially be used for preventing preeclampsia, even in the absence of lupus.

Effect of hydroxychloroquine and chloroquine on syncytial differentiation and autophagy in primary human trophoblasts.

During placentation, cytotrophoblasts differentiate and fuse to form multinucleated cells (syncytiotrophoblasts) in a process that involves autophagy. Appropriate syncytial differentiation is essential for establishing a healthy pregnancy. In this study, we evaluated the effect of two chloroquine compounds, hydroxychloroquine (HCQ) and chloroquine (CQ), on syncytial differentiation and autophagy in cultured primary human trophoblasts (PHTs). PHT cells were isolated from the human term placenta. Bafilomycin, a well-known autophagy inhibitor, was used as a positive control. Biochemical and morphological differentiation was assessed in syncytiotrophoblasts, and autophagy-related proteins and genes were evaluated. Affymetrix Human Gene 2.0 ST Array profiling was used to identify genes affected by HCQ during syncytial differentiation. Chloroquine compounds lowered the production of beta-human chorionic gonadotropin (ß-hCG) and the fusion index in PHTs. Syncytial differentiation in PHT was associated with the increased expression of ATG4C mRNA (autophagy-related gene), and this expression was affected by CQ but not by HCQ. Microarray analysis revealed that HCQ or CQ affected several genes (MMP15, GPC3, CXCL10, TET-1, and S100A7) during syncytial differentiation, which were different from that of the syncytial differentiation suppression (Ham's/Waymouth media) or autophagy inhibition (bafilomycin treatment). Using Kyoto Encyclopedia of Genes and Genomes analysis we identified that HCQ might affect JAK2 signaling in the syncytial differentiation of PHT. In conclusion, chloroquine compounds could mitigate biochemical and morphological syncytial trophoblast differentiation in cultured PHT cells through the JAK signaling pathway rather than the inhibition of autophagic activity.

Do the Causes of Spontaneous Preterm Delivery Affect Placental Inflammatory Pathology and Neonatal Outcomes?

Objective: To investigate the severity of histologic chorioamnionitis /funisitis according to the indication for preterm delivery and their corresponding neonatal outcomes. Method: This study included 411 singleton women who delivered between 21+0 and 31+6 week of gestation due to preterm labor (PTL, n = 165), preterm premature rupture of membranes (PPROM, n = 202), or incompetent internal os of the cervix (IIOC, n = 44). The primary outcome measure was the rate of severe histological chorioamnionitis/funisitis. Secondary outcome measure was neonatal outcomes including neonatal and infant death, and neonatal composite morbidity. Results: The PPROM group demonstrated a higher rate of severe histological chorioamnionitis/funisitis compared to the PTL group (severe histological chorioamnionitis; PPROM, 66.3% vs. PTL, 49.1%, p = 0.001, severe funisitis; PPROM, 44.1% vs. PTL, 23.6%, p < 0.001) and this remained significant after multivariable analysis (severe histologic chorioamnionitis, OR 2.367, 95% CI 1.517−3.693; severe funisitis, OR 2.668, 95% CI 1.684−4.226). For neonatal outcomes only, a higher rate of patent ductus arteriosus was observed in the IIOC group compared to the PTL and PPROM groups (IIOC, 77.3% vs. PTL, 54.0% vs. PPROM, 54.0%, p = 0.043) and this remained significant after multivariable analysis. Conclusion: Indication of spontaneous preterm delivery might affect the placental inflammatory pathology and neonatal morbidity.

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.

Obstetric and neonatal outcomes of gestational diabetes mellitus in twin pregnancies according to changes in its diagnostic criteria from National Diabetes Data Group criteria to Carpenter and Coustan criteria: a retrospective cohort study.

BACKGROUND: To compare obstetric and neonatal outcomes in twin pregnancies with or without gestational diabetes mellitus (GDM) before and after changes in GDM diagnostic criteria. METHODS: This was a retrospective cohort study of 1,764 twin pregnancies including 130 women with GDM (GDM group) and 1,634 women without GDM (non-GDM group). Patients with pregestational diabetes, unknown GDM status, and fetal death at < 24 gestational weeks were excluded. Obstetric and neonatal outcomes were compared between the two groups by two periods: period 1 (1995-2005) and period 2 (2005-2018) when National Diabetes Data Group criteria and Carpenter and Coustan criteria were used for diagnosis of GDM, respectively. RESULTS: The incidence of GDM in twin pregnancies increased from 4.0% in period 1 to 9.3% in period 2. Composite obstetric complications rate was significantly higher in the GDM group than that in the non-GDM group during period 1 (72.0% vs. 45.5%, P = 0.009). However, it became comparable during period 2 (60.0% vs. 57.4%, P = 0.601). Interaction between GDM and period indicated a significant differential effect of GDM by period on the rate of composite obstetric complications. The rate of composite neonatal complications was similar between the two groups during both periods. The interaction between GDM and period was not significant. CONCLUSION: After changes of GDM diagnostic criteria, the incidence of GDM increased more than twice, and the rate of composite obstetric complications decreased, but the rate of composite neonatal complications did not change significantly.

Increased Risk of Meconium-Related Ileus in Extremely Premature Infants Exposed to Antenatal Magnesium Sulfate.

INTRODUCTION: We experienced an increased incidence of meconium-related ileus (MRI) in extremely premature infants (EPIs) while adopting the antenatal magnesium sulfate (MgSO4) protocol for fetal neuroprotection in our neonatal intensive care unit. This study aimed to test whether antenatal MgSO4 use was associated with increased risk of MRI in EPIs. METHODS: The incidences of complicated MRI requiring aggressive enema or surgical intervention and other intestinal complications were compared among period 1 (January 2012-December 2013, n = 79), before adoption of the antenatal MgSO4 protocol for fetal neuroprotection; period 2 (January 2014-March 2016, n = 72), when the protocol was adopted; and period 3 (April 2016-September 2018, n = 75), when the protocol was temporarily withdrawn due to concern regarding intestinal complications in EPIs. RESULTS: Despite similar baseline clinical characteristics among infants across the study periods, the MRI and MRI with surgical treatment incidences were higher in period 2 than those in periods 1 and 3 (13% vs. 8% and 6%, p = 0.391, and 11% vs. 0% and 1%, p = 0.001, respectively). In multivariable analysis, exposure to antenatal MgSO4 independently increased the risk of MRI (adjusted odds ratio, 3.8; 95% confidence interval, 1.4, 10.6). CONCLUSION: Antenatal MgSO4 may increase the risk of MRI, frequently requiring surgical intervention, in EPIs with a gestational age of 25 weeks or less.

Differential impact of abnormal vaginal colonization on perinatal outcome and association with early-onset neonatal sepsis: preterm labor vs. preterm premature rupture of membrane.

OBJECTIVE: The purpose of this study was to check whether the impact of abnormal vaginal colonization on perinatal outcomes would be different in patients with preterm labor (PTL) and premature membrane rupture (PPROM). We also sought to determine the concordance rate of microorganisms isolated from the maternal vagina and neonatal blood in cases of early-onset neonatal sepsis (EONS) in PTL and PPROM. METHODS: This retrospective study included 996 singleton pregnancies who were admitted to the high risk care unit of our institution due to PTL (n = 519) or PPROM (n = 477) and underwent vaginal culture examination at admission between January 2005 and April 2019. Abnormal vaginal colonization was defined upon isolation of aerobic microorganisms. The maternal baseline characteristics, delivery, and neonatal outcomes were compared according to the presence or absence of abnormal vaginal flora, both in PTL and PPROM. RESULTS: The rate of abnormal vaginal colonization in PTL and PPROM was 17.0 and 21.4%, respectively. Both in PTL and PPROM, the gestational age at admission was lower in the abnormal vaginal colonization group (PTL, 27.2 ± 3.5 vs. 28.2 ± 3.5 weeks, p = .024; PPROM, 26.1 ± 5.3 vs. 27.5 ± 4.5 weeks, p = .007). Multivariable analysis demonstrated that the group with abnormal bacteria in PPROM but not in PTL had a significantly higher rate of EONS than the group without abnormal bacteria after adjustment for confounders including gestational age at admission (PPROM, odds ratio, OR [95% confidence interval, CI]: 4.172 [1.426-12.206]; PTL, OR [95% CI]: 0.661 [0.079-5.505]). Concordance analysis showed that the maternal vaginal bacteria colonization by Escherichia coli (5.9 vs. 0.5%, p = .033) and Staphylococcus aureus (14.3 vs. 0.2%, p = .032) in PPROM was significantly correlated with the microorganisms from the neonatal blood culture EONS cases. In PTL, no specific microorganisms showed concordance between maternal vaginal bacteria and microorganisms causing EONS. CONCLUSION: Our data showed that maternal vaginal colonization in PPROM, but not in PTL, is an independent risk factor for EONS.

Maternal Baseline Risk Factors for Abnormal Vaginal Colonisation among High-Risk Pregnant Women and the Association with Adverse Pregnancy Outcomes: A Retrospective Cohort Study.

Abnormal vaginal colonisation can lead to adverse pregnancy outcomes such as preterm birth through intra-amniotic inflammation. Despite the concern, little is known about its risk factors and impact in pregnant women at high-risk for spontaneous preterm birth. Thus, we conducted this single-centre retrospective cohort study including 1381 consecutive women who were admitted to the high-risk pregnancy unit. The results of vaginal culture at admission were categorised according to the colonising organism: bacteria (Gram-negative or -positive) and genital mycoplasmas. Maternal baseline socioeconomic, and clinical characteristics, as well as pregnancy, delivery, and neonatal outcomes were compared according to the category. Maternal risk factors for Gram-negative colonisation included advanced maternal age, increased pre-pregnancy BMI, a greater number of past spontaneous abortions, earlier gestational age at admission, and IVF. Gram-positive colonisation was likewise associated with earlier gestational age at admission. Genital mycoplasmal colonisation was associated with a greater number of past induced abortions, a lower level of education completed, and a lower rate of multifetal pregnancy and IVF. The neonates from mothers with Gram-negative colonisation had a greater risk of NICU admission, proven early onset neonatal sepsis, and mortality. However, not Gram-positive bacteria or genital mycoplasma was directly associated with adverse pregnancy outcomes.

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/m² and 30.0 kg/m², 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 follow-up 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.

Maternal pre-pregnancy body mass index and the risk for gestational diabetes mellitus in women with twin pregnancy in South Korea.

OBJECTIVE: To investigate the association between maternal pre-pregnancy body mass index (BMI) and the risk for gestational diabetes mellitus (GDM) in women with twin pregnancy in South Korea. MATERIALS AND METHODS: We performed a single-center, retrospective cohort study involving 1028 women with twin pregnancy from January 2006 to December 2018 in South Korea. Pregnancies with monoamnionic twins, twin-twin transfusion syndrome, fetal death in utero before 24 weeks, pre-gestational diabetes mellitus, and unknown BMI or GDM status were excluded. Subjects were grouped into four groups based on pre-pregnancy BMI: underweight (<18.5 kg/m2), normal (18.5-22.9 kg/m2), overweight (23.0-24.9 kg/m2), and obese (≥25.0 kg/m2). RESULTS: Among 1028 women who were included in the analysis, 169 (16.4%), 655 (63.7%), 111 (10.8%), and 93 (9.0%) women were underweight, normal, overweight, and obese, respectively, before pregnancy. The incidence of GDM was 8.9% in the total study population: 4.7%, 8.2%, 11.7%, and 17.2% in the underweight, normal, overweight, and obese group, respectively (p = 0.005). The incidence of GDM significantly increased according to the increase in pre-pregnancy BMI (p < 0.001). Women in the obese group were more likely to be affected by GDM compared to the normal group (adjusted odds ratio = 2.20, 95% confidence interval = 1.19-4.08) after controlling for maternal age, parity, type of conception, and chorionicity. CONCLUSION: In twin pregnancies in South Korea, the risk of GDM increased as maternal pre-pregnancy BMI increased and obese women before pregnancy were more likely to be affected by GDM.