Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome.

OBJECTIVE: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. METHODS: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. RESULTS: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57-100.00%) and 99.92% (95% CI 99.83-99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14-76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. DISCUSSION/CONCLUSION: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

Changes in anti-müllerian hormone after ultrasound guided aspiration and ethanol sclerotic therapy of ovarian cyst.

OBJECTIVE: To evaluate the effect of transvaginal ultrasound-guided aspiration and ethanol sclerotherapy on anti-müllerian hormone (AMH) in patients with ovarian endometriomas. SETTING: Teaching hospital affiliated with Chang Gung University, Taipei. MATERIAL AND METHODS: We retrospectively reviewed 124 patients, with ovarian endometriomas who underwent transvaginal aspiration and sclerotherapy of endometrioma(s) at a tertiary medical center, Chang Gung Memorial Hospital, Taipei, Taiwan. Preoperative evaluation included AMH, midcycle serum CA-125 level, and ultrasonography to exclude possibility of malignancies. Patients underwent ultrasonographic guided transvaginal aspiration and sclerotherapy with 95% ethanol irrigation of the cystic cavity. Patients were grouped into group 1, n = 44, retention of ethanol, and group 2, n = 80, no retention. Serum AMH level was checked at 6 months after aspiration. Those who were infertile prior to therapy were followed up for subsequent pregnancies (either by assisted reproductive technologies, or by natural conception). RESULTS: The mean pre-operative AMH levels for the group without retention of ethanol and with ethanol retention were 3.80 and 3.06 respectively (p > 0.05). The change in AMH at 6-month follow up for retained group patients was significantly more than for non-retained group patients, with mean decrease of 0.72 (23.6%) and 0.10 (2.7%) respectively (p < 0.05). 54.5% (retained) and 47.2% (non-retained) of patients failed to achieve pregnancy during the observation period. CONCLUSIONS: Transvaginal aspiration of endometriomas followed by sclerotherapy with ethanol can be effective in preserving ovarian reserve, provided that no ethanol is left in situ.

Prenatal transplantation of human amniotic fluid stem cell could improve clinical outcome of type III spinal muscular atrophy in mice.

Spinal muscular atrophy (SMA) is a single gene disorder affecting motor function in uterus. Amniotic fluid is an alternative source of stem cell to ameliorate SMA. Therefore, this study aims to examine the therapeutic potential of Human amniotic fluid stem cell (hAFSC) for SMA. Our SMA model mice were generated by deletion of exon 7 of Smn gene and knock-in of human SMN2. A total of 16 SMA model mice were injected with 1 × 105 hAFSC in uterus, and the other 16 mice served as the negative control. Motor function was analyzed by three behavioral tests. Engraftment of hAFSC in organs were assessed by flow cytometry and RNA scope. Frequency of myocytes, neurons and innervated receptors were estimated by staining. With hAFSC transplantation, 15 fetuses survived (93.75% survival) and showed better performance in all motor function tests. Higher engraftment frequency were observed in muscle and liver. Besides, the muscle with hAFSC transplantation expressed much laminin α and PAX-7. Significantly higher frequency of myocytes, neurons and innervated receptors were observed. In our study, hAFSC engrafted on neuromuscular organs and improved cellular and behavioral outcomes of SMA model mice. This fetal therapy could preserve the time window and treat in the uterus.

A novel de novo mutation in COL2A1 gene associated with fetal skeletal dysplasia.

OBJECTIVE: Skeletal dysplasias, caused by genetic mutations, are a heterogenous group of heritable disorders affecting bone development during fetal life. Stickler syndrome, one of the skeletal dysplasias, is an autosomal dominant connective tissue disorder caused by abnormal collagen synthesis owing to a genetic mutation in COL2A1. CASE REPORT: We present the case of a 38-year-old multipara woman whose first trimester screening showed a normal karyotype. However, the bilateral femur and humerus length symmetrically shortened after 20 weeks. Next-generation sequencing for mutations in potential genes leading to skeletal dysplasia detected a novel de novo mutation (c.1438G > A, p.Gly480Arg) in COL2A1, causing Stickler syndrome type 1. This pathogenic mutation might impair or destabilize the collagen structure, leading to collagen type II, IX, and XI dysfunction. CONCLUSION: We identified a novel de novo mutation in COL2A1 related to the STL1 syndrome and delineated the extent of the skeletal dysplasia disease spectrum.

Risk factors for abnormal postpartum glycemic states in women diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria.

AIMS/INTRODUCTION: To evaluate the rate of postpartum glycemic screening tests (PGST) in women with gestational diabetes mellitus (GDM), and to investigate risk factors for abnormal PGST results. MATERIALS AND METHODS: We retrospectively analyzed the obstetric data of 1,648 women with GDM who gave birth after 28 completed weeks of gestation between 1 July 2011 and 31 December 2019 at Taipei Chang Gung Memorial Hospital, Taiwan. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. PGST was carried out at 6-12 weeks postpartum with a 75-g, 2-h oral glucose tolerance test, and the results were classified into normal, prediabetes and diabetes mellitus. Multiple logistic regression was used to assess the associations between various risk factors and abnormal PGST results. RESULTS: In total, 493 (29.9%) women underwent PGST and 162 (32.9%) had abnormal results, including 135 (27.4%) with prediabetes and 27 (5.5%) with diabetes mellitus. Significant risk factors for postpartum diabetes mellitus included insulin therapy during pregnancy (adjusted odds ratio [OR] 10.79, 95% confidence interval [CI] 4.07-28.58), birthweight >4,000 g (adjusted OR 10.22, 95% CI 1.74-59.89) and preterm birth <37 weeks' gestation (adjusted OR 3.33, 95% CI 1.09-10.22); whereas prepregnancy body mass index >24.9 kg/m2 (adjusted OR 1.99, 95% CI 1.24-3.21) was the major risk factor for postpartum prediabetes. CONCLUSIONS: Less than one-third of women with GDM underwent PGST, and nearly one-third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.

Risk factors and adverse maternal and perinatal outcomes for women with dichorionic twin pregnancies complicated by gestational diabetes mellitus: A retrospective cross-sectional study.

AIMS/INTRODUCTION: The association between gestational diabetes mellitus (GDM) and adverse maternal and perinatal outcomes in twin pregnancies remains unclear. This study was undertaken to highlight risk factors for GDM in women with dichorionic (DC) twins, and to determine the association between GDM DC twins and adverse maternal and perinatal outcomes in a large homogeneous Taiwanese population. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out on 645 women with DC twins, excluding pregnancies complicated by one or both fetuses with demise (n = 22) or congenital anomalies (n = 9), who gave birth after 28 complete gestational weeks between 1 January 2001 and 31 December 2018. Univariable and multiple logistic regression analyses were carried out. RESULTS: Maternal age >34 years (adjusted odds ratio 2.52; 95% confidence interval 1.25-5.07) and pre-pregnancy body mass index >24.9 kg/m2 (adjusted odds ratio 2.83, 95% confidence interval 1.47-5.46) were independent risk factors for GDM in women with DC twins. Newborns from women with GDM DC twins were more likely to be admitted to the neonatal intensive care unit (adjusted odds ratio 1.70, 95% confidence interval 1.06-2.72) than newborns from women with non-GDM DC twins. Other pregnancy and neonatal outcomes were similar between the two groups. CONCLUSIONS: Advanced maternal age and pre-pregnancy overweight or obesity are risk factors for GDM in women with DC twins. Except for a nearly twofold increased risk of neonatal intensive care unit admission of newborns, the pregnancy and neonatal outcomes for women with GDM DC twins are similar to those for women with non-GDM DC twins.

Association between maternal anemia at admission for delivery and adverse perinatal outcomes.

BACKGROUND: Maternal anemia is a risk factor for poor pregnancy outcomes and threatens maternal or fetal life. Anemia increases the risk of low birth weight and preterm birth. We aimed to determine the cutoff level of hemoglobin and risk factors for maternal anemia at admission for delivery and investigate the association between maternal anemia and adverse perinatal outcomes in contemporary Taiwanese women. METHODS: About 32,234 women admitted to the Taipei Chang Gung Memorial Hospital from 2001 to 2016 were enrolled in this retrospective observational cohort study. The prevalence of pre-delivery maternal anemia in Taiwan and the maternal demographic and perinatal outcomes associated with maternal anemia was assessed. RESULTS: The 10th and 5th percentile hemoglobin levels of the test cohort (2001-2008, n = 15,602) were 10.8 g/dL and 9.9 g/dL, respectively. In the study cohort (2009-2016, n = 13,026), women who were multiparous, who were aged >34 years, with history of cesarean delivery, and with history of uterine fibroids had higher prevalence of anemia. Anemic women were at increased risk of cesarean delivery, primary cesarean delivery, premature rupture of membranes, early preterm birth <34 weeks, having very low birth weight infants (<1,500 g), having large for gestational age infants, and neonatal intensive care center transfer, but at lower risk of having small for gestational age infants. CONCLUSION: Maternal anemia at delivery is a risk factor for primary cesarean delivery and adverse maternal and neonatal outcomes. Furthermore, we hypothesize that maternal anemia might increase fetoplacental vasculogenesis and angiogenesis as an adaptive response.

Decreased placental apoptosis and autophagy in pregnancies complicated by gestational diabetes with large-for-gestational age fetuses.

INTRODUCTION: Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. METHODS: Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. RESULTS: Compared to placentas from normal pregnant women, those from GDM women with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. DISCUSSION: There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDM women with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes.

Soluble epoxide hydrolase in the human placenta throughout gestation.

OBJECTIVE: To investigate the spatial and temporal changes of soluble epoxide hydrolase (sEH) in the human placenta throughout gestation and to study the effects of hypoxia-reoxygenation (HR) on the expression of sEH in villous explants in vitro. MATERIALS AND METHODS: Placental samples were obtained from women of different gestation and grouped as early (8-12 weeks, n = 10), mid- (16-28 weeks, n = 6), and late gestation (38-39 weeks, n = 10) according to gestational age. Immunohistochemistry, western blot, and real-time quantitative PCR were used to assess the cellular distribution and temporal changes of sEH. Villous explant cultures were used to study the effect of HR (8 h at 2% oxygen, followed by 16 h at 8% oxygen, two cycles) on the expression of sEH. RESULTS: Using a mouse monoclonal antibody against human sEH, immunoreactivity of sEH was observed mainly localized in the cytotrophoblasts and, to a lesser extent, the syncytiotrophoblast in the villous tissues throughout gestation. Compared to villous tissues of early gestation, the levels of sEH mRNA and protein were significantly increased in villous samples of mid- and late gestation. Furthermore, villous explants subjected to HR had significantly higher levels of sEH mRNA and protein compared to villous tissues kept at 8% oxygen throughout the experiment. CONCLUSION: Our results indicate that sEH is likely to play an essential role in the development of human placenta and HR is a possible factor regulating the expression of sEH in the placenta.

Risk factors for gestational diabetes mellitus among women screened with the two-step and one-step methods: A before-and-after study.

OBJECTIVE: To compare the risk profiles for gestational diabetes mellitus (GDM) using a one-step and two-step screening method and diagnostic criteria. MATERIALS AND METHODS: A retrospective cohort study was conducted among women screened using Carpenter and Coustan's (C&C) criteria (two-step method) and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (one-step method). All deliveries after 28 weeks of gestation, except for pregnancies complicated by pre-pregnancy diabetes mellitus, were analyzed. Multiple logistic regression was used to assess the associations between GDM and various potential risk factors. RESULTS: Risk factors for C&C-defined GDM were pre-pregnancy body mass index >24.2 kg/m2 (adjusted odds ratio [OR] 2.49, 95% confidence interval [CI] 1.92-3.23), maternal age at delivery >34 years (adjusted OR 2.46, 95% CI 1.96-3.09), history of fetal death (adjusted OR 2.56, 95% CI 1.37-4.78), and chronic hypertension (adjusted OR 3.66, 95% CI 1.50-8.91). In addition to these factors, conception assisted by reproductive technology (adjusted OR 1.64, 95% CI 1.19-2.25) and genetic amniocentesis (adjusted OR 1.19, 95% CI 1.03-1.38) were IADPSG-defined GDM risk factors. CONCLUSION: Risk factors for GDM differ with the diagnostic criteria used. This information is important when changing GDM screening strategies from the two-step approach to the one-step approach.

A comparison of the efficacy of carbetocin and oxytocin on hemorrhage-related changes in women with cesarean deliveries for different indications.

OBJECTIVE: To compare the efficacy of carbetocin and oxytocin on hemorrhage-related changes in women with cesarean deliveries (CS) for different indications. MATERIALS AND METHODS: A retrospective cohort study was conducted on 1568 women with CS before labor onset (elective CS, n = 1153) or during labor (intrapartum CS, n = 415) after 24 weeks' gestation. We compared the fall in hemoglobin (Hb) and hematocrit (Hct) levels after CS, estimated blood loss, the need for additional uterotonic agents, blood transfusion, and the rate of postpartum hemorrhage between women with carbetocin and women with oxytocin treatment, stratified by indications for CS. RESULTS: For women with elective CS, decreased Hb and Hct falls were noted with carbetocin treatment compared to oxytocin treatment in women with indications for prior CS, fetal malpresentation, and multiple gestation. The need for additional uterotonics was less in CS for prior CS, fetal malpresentation, and cephalopelvic disproportion and fewer transfusions in CS for multiple gestation in women with carbetocin compared to women with oxytocin treatment. For women with intrapartum CS, carbetocin was associated with decreased use of additional uterotonic agents and transfusion in CS for dysfunctional labor. CONCLUSION: Carbetocin and oxytocin had differential effects on hemorrhage-related changes in women with CS for different indications.

Risk of abnormal fetal growth in women with early- and late-onset preeclampsia.

OBJECTIVES: To investigate the risks of delivering small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants in women with early- (delivered before 34weeks of gestation) and late-onset (delivered at or after 34weeks of gestation) preeclampsia. STUDY DESIGN: We conducted a retrospective cohort study of 29,494 singleton deliveries after 24weeks' gestation, excluding pregnancies complicated by fetal anomalies, stillbirths, and prepregnancy diabetes mellitus. Univariate and multivariate logistic analyses adjusted for potential confounding factors, including prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM), were performed. RESULTS: Among women who delivered before 34weeks, significantly more women with preeclampsia delivered SGA infants than women without preeclampsia (50.6% vs. 7.0%; adjusted odds ratio [OR] 16.3; 95% confidence interval [CI] 8.1-32.9). Among women who delivered at or after 34weeks, women with preeclampsia had higher rates of delivering SGA (25.5% vs. 7.0%) and LGA (13.7% vs. 9.9%) infants than women without preeclampsia. After adjustment for confounding factors, preeclampsia remained a significant risk factor for delivering SGA infants (adjusted OR 5.7; 95% CI 4.6-7.1), but the association between preeclampsia and the delivery of LGA infants was diminished (adjusted OR 0.8; 95% CI 0.6-1.1). CONCLUSIONS: Our results confirm that preeclampsia is associated with SGA and that the association is stronger with early-onset disease. Although women with late-onset preeclampsia had a higher rate of delivering LGA infants, the association between late-onset preeclampsia and LGA is due to confounding factors, such as high prepregnancy BMI, excessive GWG, and GDM, related to maternal metabolic abnormalities.

Human amniotic fluid stem cells have better potential in early second trimester of pregnancy and can be reprogramed to iPS.

OBJECTIVE: To study the difference of amniotic fluid stem cell potential at different gestational age. MATERIALS AND METHODS: Second trimester amniocentesis was performed during 15 to 22nd week of gestational age in a single medical center from 2015 to 2016. Early second trimester amniotic fluid stem cells (E-AFS) and later one (L-AFS) were defined 15-18th week, and 19-22nd week, respectively. Cell characteristics, surface markers and ability to form induced pluripotent stem cells (iPS) were studied. RESULTS: All the amniotic fluid stem cells samples could be isolated and cultured from second trimester amniocentesis. E-AFS showed more Ckit + cell, shorted doubling time, smaller cell size and higher cell density compared to L-AFS. Both groups had the same stem cell surface markers with highly expression of CD44, CD73, CD90, and CD105, negative for CD45. They can easily be reprogramed into amniotic fluid stem cell derived iPS via standard induction. CONCLUSION: Human amniotic fluid stem cells could be isolated from early or late second trimester amniocentesis with the similar stem cell surface markers presentation, especially in mesenchymal stem cells markers. However, the cells from early second trimester amniocentesis have more Ckit + number and more potential characteristics compared to late second trimester amniocentesis. Both E-AFS and L-AFS could form the iPS easily which lead to the future disease modeling study.

Mammalian target of rapamycin signaling is a mechanistic link between increased endoplasmic reticulum stress and autophagy in the placentas of pregnancies complicated by growth restriction.

INTRODUCTION: Increased endoplasmic reticulum (ER) stress and autophagy have been noted in the placentas of pregnancies complicated by idiopathic intrauterine growth restriction (IUGR); however, the cause of these phenomena remains unclear. We surmised that oxygen-glucose deprivation (OGD) may increase ER stress and autophagy and that mammalian target of rapamycin (mTOR) signaling is involved in regulating placental ER stress and autophagy in pregnancies complicated by IUGR. METHODS: We obtained placentas from women with normal term pregnancies and pregnancies complicated by IUGR to compare ER stress, mTOR signaling, and levels of autophagy-related proteins between the two groups and used primary cytotrophoblast cells treated with or without salubrinal (an ER stress inhibitor), MHY1485 (an mTOR activator), or rapamycin (an mTOR inhibitor) to investigate the effects of OGD on ER stress, mTOR activity, and autophagy levels in vitro. RESULTS: Women with pregnancies complicated by IUGR displayed higher placental ER stress and autophagy levels but lower mTOR activity than women with normal pregnancies. Furthermore, OGD increased ER stress, regulated in development and DNA damage responses-1 (REDD1), phosphorylated tuberous sclerosis complex 2 (TSC2), and autophagy levels and decreased mTOR activity compared to the standard culture condition; however, the salubrinal treatment attenuated these changes. Moreover, the administration of MHY1485 or rapamycin to OGD-treated cells decreased or increased autophagy levels, respectively. DISCUSSION: Based on our results, mTOR is a mechanistic link between OGD-induced ER stress and autophagy in cytotrophoblast cells; thus, mTOR plays an essential role in the pathogenesis of pregnancies complicated by IUGR.

Micronized progesterone pretreatment affects the inflammatory response of human gestational tissues and the cervix to lipopolysaccharide stimulation.

INTRODUCTION: Vaginal administration of micronized progesterone (utrogestan capsule, UG) reduces the risk of preterm birth (PTB) in asymptomatic women with a sonographic short cervix at mid-trimester or with a prior history of spontaneous PTB; however, its exact mechanisms remain unclear. We hypothesized that UG limits the inflammatory processes within the gestational tissues and the cervix. METHODS: Fetal membranes and villous tissues were obtained from normal term placentas from women with cesarean delivery before labor onset. Ectocervical tissues were obtained from premenopausal women undergoing hysterectomies for uterine fibroids. Explant tissue cultures were pretreated with UG for 24 h and then exposed to UG with or without lipopolysaccharide (LPS) for 48 h. Tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-γ, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 levels in tissue homogenates and culture medium were measured by enzyme-linked immunosorbent assays. Real-time quantitative PCR, Western blot, and gelatine zymography were used to measure matrix metalloproteinase (MMP)-9 and MMP-2 mRNA, protein, and activity levels, respectively. RESULTS: UG pretreatment did not cause a significant change in basal levels or in LPS-induced production and secretion of cytokines, chemokines, and TIMPs in the three tissues. However, UG pretreatment significantly reduced MMP-9 and MMP-2 expression and activity in fetal membranes stimulated with LPS but not in villous or cervical tissues. DISCUSSION: UG pretreatment significantly reduced MMP-9 and MMP-2 expression and activity in fetal membranes stimulated with LPS, suggesting a possible protective mechanism of micronized progesterone in preventing infection-associated PTB.

Ex utero intrapartum treatment for extremely low birth-weight neonates requiring resuscitation at birth.

OBJECTIVE: Difficulties often encountered during intubation in extremely low birth-weight (ELBW) neonates requiring resuscitation at birth because of the smaller airway and the pressure from the limited number of attempts before hemodynamic instability occurs. CASE REPORT: We evaluated two pregnant women at 26 weeks of gestation with premature rupture of membranes and evidence of chorioamnionitis and applied the concept of ex utero intrapartum treatment, which involved delaying cord clamping (DCC) after establishing a secured airway with adequate ventilation during cesarean delivery. The resuscitative procedure was smooth and all three neonates had favorable outcomes at one month of age. CONCLUSION: When cesarean delivery is indicated in ELBW infants and intubation after birth is anticipated, DCC after establishing a secured airway may help maintain neonatal cardiovascular stability and allow physicians to resolve the technical difficulties of intubation.

Pregestational body mass index, gestational weight gain, and risks for adverse pregnancy outcomes among Taiwanese women: A retrospective cohort study.

OBJECTIVE: To investigate the associations between maternal pregestational body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes among Taiwanese women. MATERIALS AND METHODS: A retrospective cohort study was conducted among all singletons without fetal anomalies delivered to women at Taipei Chang Gung Memorial Hospital between 2009 and 2015. Two study cohorts were selected for analysis: all deliveries after 24 0/7 weeks of gestation (Cohort 1, n=12,064) and all live births after 37 0/7 weeks of gestation excluding maternal overt diabetes mellitus and chronic hypertension (Cohort 2, n=10,973). The associations between pregestational BMI, GWG outside the 2009 Institute of Medicine (IOM) guidelines, and adverse pregnancy outcomes were assessed using multivariable logistic regression analysis. RESULTS: In Cohort 1, the prevalence of pregestational underweight, normal weight, overweight, and obesity was 14.0%, 74.8%, 9.0%, and 2.2%, respectively. Compared with the women with normal weight, maternal underweight was associated with increased risk for placental abruption, small-for-gestational age, and low birth weight (<2500 g). In contrast, overweight and obese women were at risk for gestational diabetes mellitus, preeclampsia, dysfunctional labor, cephalopelvic disproportion, large-for-gestational age, and macrosomia (>4000 g). In Cohort 2, GWG below the IOM guidelines were associated with higher rates of gestational diabetes mellitus, small-for-gestational age, and low birth weight, while GWG above the IOM guidelines were with higher rates of primary cesarean delivery, large-for-gestational age, and macrosomia in women with pregestational underweight or normal weight. Normal weight women were more likely to have placental abruption with GWG below the guidelines and to have preeclampsia with GWG above the guidelines. For overweight and obese women, GWG below the guidelines was associated with a higher rate of gestational diabetes mellitus, but GWG above the guidelines was associated with a higher rate of macrosomia. CONCLUSIONS: Women with abnormal pregestational BMI are at risk for adverse maternal and neonatal outcomes. Moreover, GWG has a differential effect on the rates of adverse pregnancy outcomes between women of different pregestational BMI categories.

Proteomic profiling reveals α1-antitrypsin, α1-microglobulin, and clusterin as preeclampsia-related serum proteins in pregnant women.

OBJECTIVE: Preeclampsia is a major cause of mortality in pregnant women but the underlying mechanism remains unclear to date. In this study, we attempted to identify candidate proteins that might be associated with preeclampsia in pregnant women by means of proteomics tools. MATERIALS AND METHODS: Differentially expressed proteins in serum samples obtained from pregnant women with severe preeclampsia (n = 8) and control participants (n = 8) were identified using two-dimensional gel electrophoresis (2-DE) followed by peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Additional serum samples from 50 normal and 41 pregnant women with severe preeclampsia were analyzed by immunoassay for validation. RESULTS: Ten protein spots were found to be upregulated significantly in women with severe preeclampsia. These protein spots had the peptide mass fingerprints matched to α1-antitrypsin, α1-microglobulin, clusterin, and haptoglobin. Immunoassays in an independent series of serum samples showed that serum α1-antitrypsin, α1-microglobulin, and clusterin levels of severe preeclampsia patients (n = 41) were significantly higher than those in the normal participants (n = 50; α1-antitrypsin 295.95 ± 50.94 mg/dL vs. 259.31 ± 33.90 mg/dL, p = 0.02; α1-microglobulin 0.029 ± 0.004 mg/mL vs. 0.020 ± 0.004 mg/mL, p < 0.0001; clusterin 77.6 ± 16.15 µg/dL vs. 67.6 ± 15.87 µg/dL, p < 0.05). CONCLUSION: Identification of these proteins by proteomics analysis enables further understanding of the pathophysiology of preeclampsia. Further studies are warranted to investigate the role of these biomarkers in prediction of this disease.

Contemporary second stage labor patterns in Taiwanese women with normal neonatal outcomes.

OBJECTIVE: To compare the duration of second stage labor among modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes and women who delivered during the early 1990 s. MATERIALS AND METHODS: Data were collected from women who underwent spontaneous labor and vaginally delivered cephalic singleton fetuses with normal neonatal outcomes at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan from 1991-1995 (Cohort 1, n = 10,721) and 2010-2014 (Cohort 2, n = 3734). We calculated the median duration and 95th percentiles of second stage labor. The women were stratified according to analgesia and parity. Multiple linear regression analysis was used to determine the association between the maternal/pregnancy characteristics and second stage labor duration. RESULTS: The median second stage labor duration was significantly longer for Cohort 2 than for Cohort 1. For nulliparous women, the 95th percentile second stage labor thresholds were 255 minutes and 152 minutes (Cohort 2) and 165 minutes and 107 minutes (Cohort 1) for women with and without epidural analgesia, respectively. For multiparous women, the 95th percentile second stage labor thresholds were 136 minutes and 43 minutes (Cohort 2) and 125 minutes and 39 minutes (Cohort 1) for women with and without epidural analgesia, respectively. Birth weight, maternal age at delivery, and time period (2010-2014 vs. 1991-1995) were significant factors associated with the duration of second stage labor. CONCLUSION: Modern Taiwanese women who achieved vaginal delivery without adverse neonatal outcomes experienced longer second stage labors than women 25 years ago. The 95th percentile thresholds differed between nulliparous and multiparous women with and without epidural analgesia.

Gestational weight gain and risks for adverse perinatal outcomes: A retrospective cohort study based on the 2009 Institute of Medicine guidelines.

OBJECTIVE: To investigate perinatal outcomes according to the 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines. MATERIALS AND METHODS: A retrospective cohort study was conducted among all term, singleton, live births to women who delivered at the Taipei Chang Gung Memorial Hospital, Taipei, Taiwan between 2009 and 2014. Women were categorized into three groups based on prepregnancy body mass index and GWG relative to the IOM guidelines. Multivariable logistic regression analysis was used to assess the associations between GWG outside the IOM guidelines and adverse perinatal outcomes. Women with GWG within the guidelines served as the reference group. RESULTS: Of 9301 pregnancies, 2574 (27.7%), 4189 (45.0%), and 2538 (27.3%) women had GWG below, within, and above the IOM guidelines. Women with GWG above the IOM guidelines were at risk for preeclampsia [adjusted odds ratio (OR) 3.0, 95% confidence interval (CI) 1.9-4.7], primary cesarean delivery (adjusted OR 1.4, 95% CI 1.2-1.6) due to dysfunctional labor and cephalopelvic disproportion, large-for-gestational age (adjusted OR 1.8, 95% CI 1.5-2.1), and macrosomic neonates (adjusted OR 2.2, 95% CI 1.6-3.1). Women with GWG below the IOM guidelines were more likely to be diagnosed with gestational diabetes mellitus (adjusted OR 1.5, 95% CI 1.3-1.8) and were at higher risk for placental abruption (adjusted OR 1.7, 95% CI 1.1-2.5), small-for-gestational age (adjusted OR 1.6, 95% CI 1.4-1.9), and low birth weight neonates (adjusted OR 1.9, 95% CI 1.4-2.4). CONCLUSION: Women with GWG outside the 2009 IOM guidelines were at risk for adverse maternal and neonatal outcomes.