Jenn-Jeih Hsu

Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus

The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother‐to‐infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)– and hepatitis B e antigen–positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30‐32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF‐group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375–386

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.

Tumor vascular pattern and blood flow impedance in the differential diagnosis of leiomyoma and adenomyosis by color Doppler sonography.

Purpose:Our objective was to evaluate the differences between leiomyoma and adenomyosis by color Doppler sonography with new criteria.Methods:A total of 78 patients with symptomatic uterine nodularities who were sonographically suspected to have leiomyoma or adenomyosis without other coexisting pathologic conditions was enrolled in the study. All patients underwent transvaginal color Doppler sonography (7.0-MHz vaginal probe) or transabdominal color Doppler sonography (5.0 MHz) during the early follicular phase. The morphology, tumor vascular pattern, and blood flow impedance of the uterine tumors were measured. All of the patients underwent surgery and the pathologic reports were used as references.Results:The mean age was not statistically significant in patients with adenomyosis versus leiomyoma (P > 0.05). The morphologic criteria for adenomyosis and leiomyoma by sonography detected 79% of adenomyosis and 84% of leiomyoma. Adenomyosis had 87% randomly scattered vessels or intratumoral signals and 88% of leiomyomas showed peripheral scattered vessels or outer feeding vessels. Eighty-two percent of adenomyoses had a pulsitility index (PI) of arteries within or around uterine tumors >1.17 and 84% of leiomyomas had a PI ≤ 1.17. The reliability test of tumor vascular pattern and blood flow impedance were better than that of using morphological criteria alone.Conclusions:With the aid of color Doppler sonography, tumor vascular pattern and blood flow impedance of the arteries within or around uterine tumors could more accurately diagnose adenomyosis and leiomyoma in addition to the morphologic criteria on transvaginal sonography.

Fetal gender screening by ultrasound at 11 to 13+6 weeks

Background. To survey the accuracy of fetal gender determination during first trimester screening and scan for congenital anomalies. Methods. A prospective observational study was performed on 496 singleton pregnancies at the first trimester ultrasound screening. The doctor was a certified sonographer of first trimester screening by the Fetal Medicine Foundation (FMF). Ultrasound examination was performed on a GE Voluson 730 Pro, transabdominally, between 11 and 13+6 weeks. Both transverse and mid‐sagittal planes of a section of the fetal genital tubercle were performed to identify the gender. The subsequent gender at birth was obtained from karyotyping reports or hospital birth records. Results. During the study, 496 patients requested gender information at the time of first trimester screening. Of the patients it was possible to determine gender (441 out of 496), the scan achieved an overall success rate of 91.8% in correctly identifying gender. The success rate for correctly identifying fetal gender (where identification was possible) increased with gestational age, from 71.9% at 11 weeks, 92% at 12 weeks, and 98.3% at 13 weeks, respectively, where gestational age was calculated from the crown‐rump length in conjunction with menstrual or ovulation dating (p<0.001). Of the 55 cases where no identification of gender was possible, 39 were in the 11‐week gestational age group, representing 40.6% of this category. The overall fetal gender accuracy rate for male fetus was slightly better than female (92.5 versus 91.2%), but was not statistically significant. Conclusions. This study demonstrated that the gestational age of the fetus has a material effect on the accuracy rate of gender determination. At 12 weeks and over, the average success rate for correctly identifying gender, where gender identification was possible, was 94.8%, with the accuracy at 13 weeks of 98.3% approaching that achieved by invasive testing. Fetal gender identification at 11 weeks (where crown‐rump length is <57 mm) is difficult and liable to high rates of inaccuracy when a determination is made.

Management of primary abdominal pregnancy: twelve years of experience in a medical centre

Background. The aim of this study was to evaluate our institutions 12‐year experience in managing primary abdominal pregnancy by laparotomy or laparoscopy. Methods. We identified 11 cases of primary abdominal pregnancy treated at our institution between January 1994 and December 2005, and separated the cases into 2 groups based on type of surgical management. The outcome measures we evaluated were operative time, blood loss and duration of hospital stay. In addition, the incidence rates for all types of ectopic pregnancy were recorded. Analysis excluded secondary abdominal pregnancy. Results. Of the 11 primary abdominal pregnancies, 6 were treated with laparotomy and 5 with laparoscopy. The laparoscopy group had significantly better results in operative time, blood loss and hospital stay (p<0.05). The difference in gestational age was not significant (p = 0.141), even after excluding the patient whose abdominal pregnancy was only identified after cesarean delivery. Conclusion. Our experience shows a trend toward better management of primary abdominal pregnancy with laparoscopy. These patients had shorter operative time, reduced blood loss, and fewer days in hospital then patients treated with laparotomy. Choice of management should depend on the patients condition, gestational age of the pregnancy, and the physicians clinical experience.

Growth discordancy, birth weight, and neonatal adverse events in third trimester twin gestations

In order to understand the effects of intrauterine growth discordancy (15% or more birth weight difference), birth weight, and gestational age on the neonatal adverse events (including 1- or 5-min Apgar scores < 7, neonatal death, ICU admission, respiratory distress, hypoglycemia, hypocalcemia, perinatal infection, blood transfusion, and hyperbilirubinemia) in third trimester twin gestations, 279 consecutive twin pairs delivered from January 1986 to December 1991 were studied. Univariate analyses showed discordant twins were smaller than concordant twins in gestational age by 1.4 weeks (35.74 and 37.14 weeks respectively). When birth weight was compared, that of smaller (one with lower birth weight in a pair) discordant twins (1,951 g) was significantly lower than that of smaller concordant twins (2,423 g), while larger (one with higher birth weight in a pair) discordant twins (2,556 g) and concordant twins (2,594 g) showed no significant difference. Univariate analysis indicated there was a tendency for adverse events to occur in discordant twins, especially in the smaller twin. Through logistic regression analysis, it was found that birth weight and gestational age, but not discordancy, are the predictors of the occurrence of adverse events. A smaller twin weighing no more than 2,000 g has a 10 times greater risk to develop an adverse event as compared to a twin with a birth weight over 2,000 g and a similar gestational age; while a twin with a gestational age of less than 34 weeks has a 5 times greater risk than one 34 weeks or over with a similar birth weight.

The impact of interpregnancy interval and previous preterm birth on the subsequent risk of preterm birth

Objective: To examine the impact of the interpregnancy interval and a previous preterm birth on the subsequent risk of a preterm birth. Methods: A retrospective analysis was conducted on a group of 4072 women who had at least two consecutive births, excluding multiple gestation, fetal anomalies, cervical incompetence, and stillbirth. Multivariate logistic regression was used to investigate the association between interpregnancy interval, preterm birth of the first child in the pair (index pregnancy), and the risk of a preterm birth of the second child in the pair (outcome pregnancy). Results: Women with interpregnancy intervals of less than 12 months (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.01. 1.7) were at increased risks of preterm birth with the outcome pregnancy. Furthermore, there was an increased risk for a subsequent preterm birth in women who had a preterm birth in the index pregnancy (OR 4.2; 95% CI 3.0-6.0). The risk decreased as the interpregnancy interval increased, with a relatively low risk at 18 to 48 months; subsequently, it increased sharply. In contrast, women who had delivered their previous infants at term carried an increased risk of preterm birth with the outcome pregnancy only if the interval was less than 6 months. Conclusion: A difference was found in the impact of the interpregnancy interval on the subsequent risk of preterm birth between women with a prior preterm birth and those who previously delivered an infant at term.

Risk factors for recurrence of group B streptococcus colonization in a subsequent pregnancy.

OBJECTIVE: To document rates of recurrent group B streptococci (GBS) colonization in women with previous GBS colonization in an initial pregnancy and to assess maternal risk factors associated with recurrence. METHODS: A retrospective, longitudinal study was performed in a teaching hospital on women with GBS colonization who were pregnant between 2002 and 2006 and had at least one subsequent pregnancy during the same time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 251 women. The rate of recurrence was estimated for GBS colonization in the pregnancy after the index pregnancy for GBS colonization. Multivariable regression models were constructed to model recurrence of GBS colonization in a subsequent pregnancy as functions of potential predictors to estimate relative risks and confidence intervals. RESULTS: The rate of recurrence of GBS colonization in the pregnancy subsequent to the index pregnancy was 38.2% (95% confidence interval 33.5–42.9%). Multivariable regression models showed that the time interval between the two pregnancies and the intensity of GBS colonization from the index pregnancy were predictive of recurrent GBS colonization. CONCLUSION: More than one third of women had recurrent GBS colonization in a subsequent pregnancy. These findings should assist clinicians in counseling women with GBS colonization about their risk for recurrence, the importance of appropriate prenatal GBS screening in a subsequent pregnancy, and intrapartum antibiotic prophylaxis for unknown GBS status. LEVEL OF EVIDENCE: II

Comparison of Down's syndrome screening strategies in Asians combining serum free beta-hCG and alpha-fetoprotein with maternal age.

High free beta human chorionic gonadotropin (β‐hCG) and low alpha‐fetoprotein (AFP) levels were found in 47 Asian Downs syndrome pregnancies (median values 2·79 and 0·77 MOM, respectively). At a 5 per cent false‐positive rate, free β‐hCG alone would identify 46·8 per cent of Downs syndrome pregnancies, age alone detected 34·5 per cent of affected cases, whilst AFP alone detected 17 per cent and free β‐hCG/AFP MOM ratios detected 48·9 per cent of Downs syndrome cases. When combined with maternal age‐specific risk, free β‐hCG could achieve a 59·6 per cent detection rate, with AFP achieving 42·6 per cent, free β‐hCG/AFP MOM ratios 61·7 per cent, and combined free β‐hCG and AFP a detection rate of 63·8 per cent for a 5 per cent false‐positive rate. Downs syndrome screening at an early gestational age (before 18 weeks) could achieve a 68 per cent detection rate with a 5 per cent false‐positive rate, compared with a 59·1 per cent detection rate for a 5·2 per cent false‐positive rate when screening at a late gestational age. The use of free β‐hCG in Downs syndrome screening programmes can yield an improved efficacy in the detection of Downs syndrome in an Asian population.

First- and Second-trimester Down Syndrome Screening: Current Strategies and Clinical Guidelines

Down syndrome (DS) is the most common human disease caused by a structural chromosome defect. The original screening test for DS was maternal age or a history of a previously affected infant. Maternal serum screening has been incorporated into routine prenatal checkup in Taiwan since 1994. We used free beta-human chorionic gonadotropin and alpha-fetoprotein (double test) as the serum markers, and this was carried out between the 15th to 20th week of gestation. The overall detection rate was 56% and was compatible with studies of Caucasian populations. The impact of double tests in Taiwan has shown itself by a dramatic lowering of the rate of DS live birth from 0.63 before screening to 0.16 per 1,000 live births at present. However, because of its relatively low detection rate and poor cost-effectiveness, the double test is not justified as a routine screening tool currently. First-trimester combined test is now becoming more widely available and provides increased sensitivity when detecting DS; it has a detection rate of approximately 85% with a false-positive rate of 5%. Nuchal translucency measurement requires ongoing quality control and sufficient certified obstetricians; therefore, first-trimester ultrasound is limited only in designated centers. The quadruple test, having comparable detection rate, should be considered for incorporation into second-trimester screening in Taiwan in the near future. Other screening approaches and combinations have also been utilized in the Western countries. In this review, we outline the various options with respect to DS screening and hope that this will provide practical information for physicians offering such screenings.