Allan Chang

Quantitative Analysis of Fetal DNA in Maternal Plasma and Serum: Implications for Noninvasive Prenatal Diagnosis

We have developed a real-time quantitative PCR assay to measure the concentration of fetal DNA in maternal plasma and serum. Our results show that fetal DNA is present in high concentrations in maternal plasma, reaching a mean of 25.4 genome equivalents/ml (range 3.3-69. 4) in early pregnancy and 292.2 genome equivalents/ml (range 76. 9-769) in late pregnancy. These concentrations correspond to 3.4% (range 0.39%-11.9%) and 6.2% (range 2.33%-11.4%) of the total plasma DNA in early and late pregnancy, respectively. Sequential follow-up study of women who conceived by in vitro fertilization shows that fetal DNA can be detected in maternal serum as early as the 7th wk of gestation and that it then increases in concentration as pregnancy progresses. These data suggest that fetal DNA can be readily detected in maternal plasma and serum and may be a valuable source of material for noninvasive prenatal diagnosis.

Rapid Clearance of Fetal DNA from Maternal Plasma

Fetal DNA has been detected in maternal plasma during pregnancy. We investigated the clearance of circulating fetal DNA after delivery, using quantitative PCR analysis of the sex-determining region Y gene as a marker for male fetuses. We analyzed plasma samples from 12 women 1-42 d after delivery of male babies and found that circulating fetal DNA was undetectable by day 1 after delivery. To obtain a higher time-resolution picture of fetal DNA clearance, we performed serial sampling of eight women, which indicated that most women (seven) had undetectable levels of circulating fetal DNA by 2 h postpartum. The mean half-life for circulating fetal DNA was 16.3 min (range 4-30 min). Plasma nucleases were found to account for only part of the clearance of plasma fetal DNA. The rapid turnover of circulating DNA suggests that plasma DNA analysis may be less susceptible to false-positive results, which result from carryover from previous pregnancies, than is the detection of fetal cells in maternal blood; also, rapid turnover may be useful for the monitoring of feto-maternal events with rapid dynamics. These results also may have implications for the study of other types of nonhost DNA in plasma, such as circulating tumor-derived and graft-derived DNA in oncology and transplant patients, respectively.

A randomized prospective study of laparoscopy and laparotomy in the management of benign ovarian masses.

OBJECTIVE Our purpose was to compare the results of laparoscopy with laparotomy in the management of ovarian masses not suspected to be malignant. STUDY DESIGN In a prospective randomized study 102 patients requiring surgical management of ovarian masses were randomly assigned to laparoscopy (52) or laparotomy (50) in a teaching hospital from July 1994 to September 1995. Inclusion criteria was tumor not suspected to be malignant with a diameter of < or = 10 cm as measured by ultrasonography. All operations were performed by trainees under the supervision of an experienced surgeon. Statistical analysis included t tests and chi2 tests. RESULTS There were no differences in demographic characteristics between the two groups nor any difference in the size of ovarian masses, adnexal adhesion score, or frequency of bilateral disease. All the ovarian masses were benign. Endometriotic cysts and dermoid cysts were the most common disorder in the two groups. Cystectomy was performed in > 70% of cases in each group. Operating time was not increased with the laparoscopic approach, and the frequency of inadvertent rupture of the ovarian masses was just as high as in laparotomy. The laparoscopic approach was associated with a significant reduction in operative morbidity (odds ratio 0.34, 95% confidence interval 0.13 to 0.88), postoperative pain and analgesic requirement, hospital stay, and recovery period. Patients in general were satisfied with the operation, but significantly more patients were satisfied with the laparoscopy scar. CONCLUSION Operative laparoscopy should replace laparotomy in the management of benign ovarian masses.

Controlled trial of fetal intensive care

A fetal intensive care unit was formed at the Queen Victoria Memorial Hospital in 1972. Because of some doubt concerning the value of fetal intensive care, a controlled clinical trial including all high-risk patients was performed. The trial clearly showed that intensive care is associated with improved neurologic and biochemical status of the neonate; however, it is possible that this improvement results from the use of fetal diagnostic tests or some other factor associated with intensive care. Sufficient evidence was gathered to warrant the continuation of fetal intensive care in this hospital, but in other contries, where funding is difficult to obtain, a controlled trial would appear justified.

Methylation of p16INK4A in primary gynecologic malignancy

The p16INK4A gene mapped on band p21 of chromosome 9 can be inactivated via multiple mechanisms including homozygous deletion, point mutation and promoter hypermethylation in various human tumors. A polymerase chain reaction (PCR) based analysis was performed to examine methylation of the p16INK4A gene promoter in 196 primary gynecologic malignancies including 98 cervical, 49 endometrial and 49 ovarian carcinomas. Methylation of p16INK4A was detected in 31% of cervical, 20% of endometrial, and 4% of ovarian carcinomas, respectively. The incidence of p16INK4A methylation in patients with cervical and endometrial carcinomas at advanced stages (stages III-IV) was statistically higher than those at early stages (stages I-II). There were also significant differences in the incidence of p16INK4A methylation in both cancers between the patients who had died of their disease or were alive with evidence of disease, and those without evidence of disease. The results indicate that methylation of the p16INK4A gene is present in a proportion of primary gynecologic malignancies and this alteration may be associated with poor outcome in cervical and endometrial carcinomas.

Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice.

BACKGROUND: Ex vivo expansion of cord blood (CB) hematopoietic stem and progenitor cells increases cell dose and may reduce the severity and duration of neutropenia and thrombocytopenia after transplantation. This studys purpose was to establish a clinically applicable culture system by investigating the use of cytokines, serum‐free media, and autologous plasma for the expansion of CB cells and the engraftment of expanded product in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.

Updated gestational age specific birth weight, crown-heel length, and head circumference of Chinese newborns

Objective: To construct gestation specific standards of birth weight, crown-heel length, and head circumference of Chinese infants. Design: A prospective cross sectional population study. Methods: The birth weight, crown-heel length, and head circumference were prospectively measured using standard equipment in newborns delivered at 24–42 weeks gestation in the maternity units of 10 public hospitals and two private hospitals in Hong Kong. The findings were used to construct gestation specific standards of these variables. The LMS method using maximum penalised likelihood was used to perform model fitting. The results were compared with those obtained from a cohort of infants born in the same locality between 1982 and 1986. Results: From October 1998 to September 2000, a total of 10 032 infants were measured, representing 9.6% of the total deliveries in Hong Kong during that period. An extra 307 infants with gestation ≤ 35 weeks were recruited from October 2000 to June 2001. Each of the three variables showed a normal distribution at each gestational week. Gestation specific reference standards for each variable were constructed for male and female infants separately. Comparison with the 1982–1986 cohort showed a significant secular trend to increased birth weight. The trend was small, but significant, for crown-heel length and head circumference. Conclusion: These growth standards will provide useful references for the care of newborns of ethnic Chinese origin. These standards, especially that for birth weight, should be updated regularly.

The effects of parity on birthweight using successive pregnancies

Objective. Accurate assessment of the difference in birthweight between first and second live‐births to the same woman having excluded the effects of physiological factors known to affect birthweight.

Information control and the exercise of power in the obstetrical encounter

Interactions between doctor and patient involve participants with unequal power and possibly different interests. While a number of studies have focused upon the doctor/patient relationship, few have examined the utility of the concept of power and its capacity to help us understand the outcome of these interactions. The information sought by pregnant women from their obstetricians is used to provide a case study of one conceptualization and test of the utility of the concept of power. Pregnant women and their obstetricians are found to have different perceptions of the information that should be exchanged during their interactions. Women generally fail to obtain the information they want. Lower social class patients desire more and obtain less information than their higher status counterparts.

Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks.

Objective To test whether maternal corticotrophin‐releasing hormone levels are elevated in the mid–trimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery.