Liang-Ming Lo

Risk factors for pre-eclampsia in an Asian population.

Objective: To identify the risk factors for pre‐eclampsia in an Asian population. Method: We conducted a retrospective cohort study involving 29 375 Taiwanese women who delivered between July 1990 and September 1998, excluding pregnancies complicated by chronic hypertension or fetal malformations. Result: Four hundred and fifteen women had pre‐eclampsia (1.4%). Women who had a history of pre‐eclampsia (OR 6.3, 95% CI 4.4, 9.2), multiple gestation (OR 3.6, 95% CI 2.4, 5.5), a prepregnancy BMI>24.2 kg/m2 (OR 2.4, 95% CI 1.8, 3.1), were>34 years of age (OR 1.8, 95% CI 1.4, 2.4), nulliparous (OR 1.3, 95% CI 1.2, 1.5), had urinary tract infection (OR 4.8, 95% CI 1.5, 15.8), or worked during pregnancy (OR 1.9, 95% CI 1.4, 2.4) were at increased risk of pre‐eclampsia. Conclusion: Some of the risk factors for pre‐eclampsia among Asian women are the same as those of other ethnic groups, whereas some of the risk factors are different.

Advanced maternal age and adverse perinatal outcomes in an Asian population

OBJECTIVE To investigate (1) whether there is an increasing trend in the mean maternal age at the birth of the first child and in the group of women giving birth at age 35 or older, and (2) the association between advanced maternal age and adverse perinatal outcomes in an Asian population. STUDY DESIGN We conducted a retrospective cohort study involving 39,763 Taiwanese women who delivered after 24 weeks of gestation between July 1990 and December 2003. Multivariable logistic regression was used to adjust for potential confounding variables. RESULTS During the study period, the mean maternal age at the birth of the first child increased from 28.0 to 29.7 years, and the proportion of women giving birth at age 35 or older increased from 11.4% to 19.1%. Compared to women aged 20-34 years, women giving birth at age 35 or older carried a nearly 1.5-fold increased risk for pregnancy complications and a 1.6-2.6-fold increased risk for adverse perinatal outcomes. After adjusting for the confounding effects of maternal characteristics and coexisting pregnancy complications, women aged 35-39 years were at increased risk for operative vaginal delivery (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-1.7) and cesarean delivery (adjusted OR 1.6, 95% CI 1.5-1.7), while women aged 40 years and older were at increased risk for preterm delivery (before 37 weeks of gestation) (adjusted OR 1.7, 95% CI 1.3-2.2), operative vaginal delivery (adjusted OR 3.1, 95% CI 2.0-4.6), and cesarean delivery (adjusted OR 2.6, 95% CI 2.2-3.1). In those women who had a completely uncomplicated pregnancy and a normal vaginal delivery, advanced maternal age was still significantly associated with early preterm delivery (before 34 weeks of gestation), a birth weight <1500 g, low Apgar scores, fetal demise, and neonatal death. CONCLUSION In this population of Taiwanese women, there is an increasing trend in the mean maternal age at the birth of the first child. Furthermore, advanced maternal age is independently associated with specific adverse perinatal outcomes.

Increased Autophagy in Placentas of Intrauterine Growth-Restricted Pregnancies

Background Unexplained intrauterine growth restriction (IUGR) may be a consequence of placental insufficiency; however, its etiology is not fully understood. We surmised that defective placentation in IUGR dysregulates cellular bioenergic homeostasis, leading to increased autophagy in the villous trophoblast. The aims of this work were (1) to compare the differences in autophagy, p53 expression, and apoptosis between placentas of women with normal or IUGR pregnancies; (2) to study the effects of hypoxia and the role of p53 in regulating trophoblast autophagy; and (3) to investigate the relationship between autophagy and apoptosis in hypoxic trophoblasts. Methodology/Principal Findings Compared with normal pregnant women, women with IUGR had higher placental levels of autophagy-related proteins LC3B-II, beclin-1, and damage-regulated autophagy modulator (DRAM), with increased p53 and caspase-cleaved cytokeratin 18 (M30). Furthermore, cytotrophoblasts cultured under hypoxia (2% oxygen) in the presence or absence of nutlin-3 (a p53 activity stimulator) had higher levels of LC3B-II, DRAM, and M30 proteins and increased Bax mRNA expression compared with controls cultured under standard conditions. In contrast, administration of pifithrin-α (a p53 activity inhibitor) during hypoxia resulted in protein levels that were similar to those of the control groups. Moreover, cytotrophoblasts transfected with LC3B, beclin-1, or DRAM siRNA had higher levels of M30 compared with the controls under hypoxia. However, transfection with Bcl-2 or Bax siRNA did not cause any significant change in the levels of LC3B-II in hypoxic cytotrophoblasts. Conclusions/Significance Together, these results suggest that there is a crosstalk between autophagy and apoptosis in IUGR and that p53 plays a pivotal and complex role in regulating trophoblast cell turnover in response to hypoxic stress.

The associations between labor and delivery mode and maternal and placental oxidative stress

To study oxidative stress differences between women with normal vaginal deliveries (VD) and those with elective cesarean sections without labor (CS), total antioxidant capacity (TAC), erythrocyte glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity, 8-isoprostane, nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in blood, urine, and placental samples were assessed. The VD group had significantly higher placental 8-isoprostane and 8-OHdG levels as well as greater plasma TAC and 8-OHdG levels and lower erythrocyte SOD activity in umbilical venous blood. Women with VD exhibited differential changes in maternal oxidative stress before and after delivery compared with women with CS. Furthermore, we found that repetitive hypoxia-reoxygenation increased the 8-isoprostane and 8-OHdG levels in villous explants compared with the normoxic controls. Together, these results indicate that labor is associated with increased placental oxidative stress and has an influence on maternal oxidative stress. Therefore, women with VD exhibit different oxidative stress indicators than do those with CS.

Perinatal Outcome of Oligohydramnios without Associated Premature Rupture of Membranes and Fetal Anomalies

To investigate the perinatal outcome of patients with oligohydramnios (amniotic fluid index ≤5 cm), but without premature rupture of membranes and fetal congenital anomalies, data from 245 singleton pregnancies were analyzed and compared to those with normal amniotic fluid volumes (5 < amniotic fluid index < 24 cm, n = 27,261). Significantly higher incidences of primiparity, pregnancy-induced hypertension, premature separation of placenta, past history of intrauterine fetal death, past history of preterm delivery, postterm pregnancy, and advanced maternal age were noted to be associated with the occurrence of oligohydramnios. Pregnancies complicated by a markedly diminished amniotic fluid volume assessed antenatally by ultrasound were significantly more frequently associated with adverse perinatal outcomes such as preterm delivery, low or very low birth weight, low Apgar scores, intrauterine fetal death, small-for-gestational-age newborns, meconium staining, cesarean delivery, neonatal intensive care, and neonatal death.

Twenty-one years of experience with ovarian ectopic pregnancy at one institution in Taiwan.

To review the experience with patients with ovarian ectopic pregnancy (OEP) at Chang Gung Memorial Hospital, Lin‐Kou Medical Center, Tao‐Yuan, Taiwan, between 1989 and 2009.

Prenatal diagnostic rates and postnatal outcomes of fetal orofacial clefts in a Taiwanese population.

To report the incidence, prenatal diagnostic rate, and postnatal outcomes of fetal orofacial cleft at a tertiary referral center in Taiwan.

Risk factors and perinatal outcomes associated with idiopathic small for gestational age Taiwanese newborns

To determine risk factors and perinatal outcomes associated with small for gestational age (SGA) neonates among healthy pregnant women.

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.

Ovarian pregnancy following intrauterine insemination.

Primary ovarian pregnancy, which was first reported by Saint Maurice in 1692 [1], represents 1e3% of all ectopic pregnancies [2,3]. Its incidence after natural conception ranges from 1 in 7000 to 1 in 60,000 [2,4,5], and it remains a rare phenomenon despite the increased incidence of ectopic pregnancies following assisted conception [6]. Ovarian pregnancy occurs in the corpus luteum and often results in ovarian rupture and massive hemoperitoneum. Clinical diagnosis is tricky, and intraoperative detection requires a high index of suspicion. Several theories have been suggested to explain the ovarian implantation of the conceptus following natural conception [3,7] and in vitro fertilization [6e8]. Here, we report a case of ruptured intrafollicular primary ovarian pregnancy with hemoperitoneum that followed superovulation and intrauterine insemination. A nulliparous 24-year-old woman presented to the emergency room with bilateral lower abdominal pain. She had a 2year history of primary infertility and had been diagnosed with polycystic ovarian syndrome. She underwent two controlled, ovarian stimulation cycles induced by clomiphene citrate (Clomid; Merrel-Dow, France S.A., Neuilly-sur-Seine, France). The insufficient ovarian response prompted a third cycle with 100 mg clomiphene citrate for 5 consecutive days beginning on days 3e7 of the cycle, and two ampoules of human menopausal gonadotropin (Pergonal; I.F. Serono S.P.A., Rome, Italy) per day on days 5e9. Baseline transvaginal ultrasound (US) scan was performed at the beginning of the first treatment cycle to exclude residual ovarian cysts. US scans were repeated between days 10 and 12 of the cycle to confirm the follicular development. The scan on the night of cycle day 12 revealed three large follicles on the left ovary (mean diameter: 17 2.1 mm) and two large follicles on the right ovary