Bi-allelic Mutations in NADSYN1 Cause Multiple Organ Defects and Expand the Genotypic Spectrum of Congenital NAD Deficiency Disorders.

Birth defects occur in up to 3% of all live births and are the leading cause of infant death. Here we present five individuals from four unrelated families, individuals who share similar phenotypes with disease-causal bi-allelic variants in NADSYN1, encoding NAD synthetase 1, the final enzyme of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway. Defects range from the isolated absence of both kidneys to multiple malformations of the vertebrae, heart, limbs, and kidney, and no affected individual survived for more than three months postnatally.

Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments.

Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation.

First trimester combined screening for Trisomy 21 in Hong Kong: outcome of the first 10,000 cases.

Objective: To examine the effectiveness of first trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency, maternal serum levels of free beta-hCG and PAPP-A in a predominantly Chinese population in Hong Kong.

Methods: Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation between 2003 and 2007 were recruited. Risk of T21 was calculated using Fetal Medicine Foundation algorithm and karyotyping was advised when the risk was 1:300 or above.

Impact of first childbirth on changes in women's preference for mode of delivery: follow-up of a longitudinal observational study.

Background: A woman's childbirth experience has an influence on her future preferred mode of delivery. This study aimed to identify determinants for women who changed from preferring a planned vaginal birth to an elective cesarean section after their first childbirth.

Methods: This prospective longitudinal observational study involved two units that provide obstetric care in Hong Kong.

Fetal parvovirus B19 infection in a twin pregnancy with 1 twin presenting with hydrops fetalis and the other asymptomatic: a case report.

Background: Parvovirus B19 infection during pregnancy is a known cause of nonimmune hydrops, while about one third of maternal infection is asymptomatic. Spontaneous abortion, hydrops fetalis, intrauterine growth retardation and meconium peritonitis are possible manifestations of fetal infection, but the infection can also be asymptomatic.

Case: Both fetuses in a dichorionic, diamniotic twin pregnancy were infected with parvovirus B19 infection, but only 1 fetus presented with hydrops fetalis.

Maternal fear associated with pregnancy and childbirth in Hong Kong Chinese women.

Background: Women's fear toward pregnancy and childbirth is a common and important health concern. This study examined the objects, causes, and manifestations of maternal fears and their associated demographic factors in a sample of Hong Kong Chinese pregnant women.

Methods: Three hundred Chinese pregnant women were recruited in an obstetric unit in Hong Kong in 2003.

Hypermethylation of RASSF1A in human and rhesus placentas.

The pseudomalignant nature of the placenta prompted us to search for tumor suppressor gene hypermethylation, a phenomenon widely reported in cancer, in the human placenta. Nine tumor suppressor genes were studied. Hypermethylation of the Ras association domain family 1 A (RASSF1A) gene was found in human placentas from all three trimesters of pregnancy but was absent in other fetal tissues.

Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection.

Current methods for prenatal diagnosis of chromosomal aneuploidies involve the invasive sampling of fetal materials using procedures such as amniocentesis or chorionic villus sampling and constitute a finite risk to the fetus. Here, we outline a strategy for fetal chromosome dosage assessment that can be performed noninvasively through analysis of placental expressed mRNA in maternal plasma. We achieved noninvasive prenatal diagnosis of fetal trisomy 21 by determining the ratio between alleles of a single-nucleotide polymorphism (SNP) in PLAC4 mRNA, which is transcribed from chromosome 21 and expressed by the placenta, in maternal plasma.

Innate immune response by ficolin binding in apoptotic placenta is associated with the clinical syndrome of preeclampsia.

Background: Unidentified circulating factors derived from placenta are thought to be responsible for the exaggerated systemic inflammation leading to preeclampsia. Our aim was to identify the circulating factors present in preeclampsia and to investigate their relationship to the underlying systemic immune response responsible for the associated clinical manifestations.

Methods: We obtained blood samples from pregnant women with and without preeclampsia and performed comparative proteomic analyses to identify the abnormal circulating factors by 2-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time of flight for protein separation and identification.

Psychological responses of pregnant women to an infectious outbreak: a case-control study of the 2003 SARS outbreak in Hong Kong.

Objective: The aim of the present study was to examine the behavioral and psychological responses of pregnant women during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong.

Methods: Ethnographic interviews were first conducted to identify the common psychological and behavioral responses to the outbreak. This was followed by a case-control study of 235 consecutive pregnant women recruited during the SARS epidemic, and a historical cohort of 939 pregnant women recruited a year before the outbreak.

Hypermethylated RASSF1A in maternal plasma: A universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis.

Background: We recently demonstrated that the promoter of the RASSF1A gene is hypermethylated in the placenta and hypomethylated in maternal blood cells. This methylation pattern allows the use of methylation-sensitive restriction enzyme digestion for detecting the placental-derived hypermethylated RASSF1A sequences in maternal plasma.

Methods: We performed real-time PCR after methylation-sensitive restriction enzyme digestion to detect placental-derived RASSF1A sequences in the plasma of 28 1st-trimester and 43 3rd-trimester pregnant women.

Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: Theoretical and empirical considerations.

Background: The discovery of cell-free fetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. However, the use of maternal plasma fetal DNA for the direct detection of fetal chromosomal aneuploidies has not been reported. We postulate that the aneuploidy status of a fetus could be revealed by an epigenetic allelic ratio approach, i.

Dextrocardia in pregnancy: 20 years' experience.

Objective: To identify all pregnancies complicated by maternal dextrocardia and report the obstetric performance in these patients.

Study Design: A retrospective review of all deliveries between May 1984 and December 2004 at Prince of Wales Hospital, Chinese University of Hong Kong. Maternal demographic data as well as information on the antenatal course and delivery outcome were abstracted from the maternal records.

Risk factors for procedure-related fetal losses after mid-trimester genetic amniocentesis.

Background: The objective of this study was to determine the institutional pregnancy loss rate following second-trimester genetic amniocentesis and to ascertain whether factors exist which would identify pregnancies at increased risk of having a procedure-related fetal loss.

Setting: University Teaching Hospital

Methods: Details of the procedure and pregnancy outcome of all patients who had amniocentesis planned or performed between 15-22 gestational weeks between January 1997 and June 2004 were extracted from our clinical audit database. The procedure-related fetal loss rate, defined as all unintended abortions, stillbirths and neonatal deaths without major fetal abnormalities or obvious obstetric causes, was determined and compared to a presumed background fetal loss rate of 0.

The utility assessment of Chinese pregnant women towards the birth of a baby with Down syndrome compared to a procedure-related miscarriage.

Objective: This study was performed to investigate the preferences of Chinese pregnant women for Down syndrome-affected birth compared to invasive test-related miscarriage, using the standard gamble approach, and to investigate whether there is a difference in Utility Score between general obstetric patients and those who request prenatal screening.

Methods: An interviewer-administered survey was conducted on 67 women who presented to the General Obstetric Clinic for booking visits and 69 women who presented to the first-trimester Combined Screening Clinic for fetal Down syndrome in a University Obstetric Unit. Preferences for Down syndrome-affected birth compared to invasive test-related miscarriage were assessed using the standard gamble approach.

Effect of prostaglandin E2 for cervical priming on fetal hemodynamics.

Objective: To assess the effect of the prostaglandin E2 (PGE2) on fetal vascular blood flow during cervical priming.

Study Design: In a prospective, observational study, 32 pregnant women > or =37 weeks of gestation requiring PGE2 for induction of labor were recruited. The resistance indices (RIs) of umbilical artery, middle cerebral artery, renal artery and ductus venosum were measured before, 2 and 4 hours after insertion of a PGE2 vaginal pessary.

Higher median levels of free beta-hCG and PAPP-A in the first trimester of pregnancy in a Chinese ethnic group. Implication for first trimester combined screening for Down's syndrome in the Chinese population.

Objective: To study the effect of ethnic Chinese on the medians of free beta-hCG and PAPP-A in the first trimester of pregnancy.

Methods: The data of 943 women undergoing first trimester combined screening for fetal Down syndrome were analysed to derive the Chinese-specific medians. The calculated risk of Down syndrome based on these Chinese-specific medians was compared with that based on the original algorithm of the Fetal Medicine Foundation (FMF).

Expectation and knowledge of women undergoing first-trimester combined screening for Down syndrome in a Chinese population.

Objectives: To study the preference of pregnant women regarding the time taken to report the results of first-trimester combined screening for Down syndrome and their knowledge about it.

Methods: A questionnaire survey was conducted on a cohort of 325 pregnant participants who attended our first-trimester combined nuchal translucency and biochemical screening programme for fetal Down syndrome. This service was operated in a one-stop setting and the result of the screening test was available within 1 to 2 h after the collection of blood sample.

Sleep disturbances in Chinese pregnant women.

In a prospective study of 247 pregnant Chinese women, the prevalence of sleep disturbances across pregnancy has been assessed using a set of validated questionnaires including the Sleep and Health Questionnaire (SHQ) and the Epworth Sleepiness Scale (ESS). The frequency of self-reported snoring increased from 29.7% in the first trimester to 40.

Reference charts of gestation-specific tissue Doppler imaging indices of systolic and diastolic functions in the normal fetal heart.

Background: Assessment of fetal cardiac function is difficult because of limited accessibility. Tissue Doppler imaging (TDI) is a promising technique in assessing diastolic function in adults. There has been sparseness concerning the use of TDI in assessing fetal cardiac function.