An observational study on Ca supplementation and dietary intake during pregnancy on low birth weight and small for gestational age.

OBJECTIVE: To evaluate the effects of dietary Ca intake and Ca supplementation during pregnancy on low birth weight (LBW) and small for gestational age (SGA) infants. DESIGN: A birth cohort study was conducted in 2010-2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. SETTING: A birth cohort study. PARTICIPANTS: Totally, 9595 pregnant women who came to the hospital for delivery at 20 weeks of gestation or more, and who were 18 years of age or older. RESULTS: Compared with non-users, Ca supplement users had a reduced risk of LBW infants (OR = 0·77, 95 % CI: 0·63, 0·95) and a reduced risk of nulliparous women giving birth to LBW infants (OR = 0·75, 95 % CI: 0·58, 0·98) (P < 0·05). More specifically, both the use of Ca supplement before conception and during pregnancy (OR = 0·44, 95 % CI: 0·19, 0·99) and during pregnancy only (OR = 0·80, 95 % CI: 0·65, 0·99) had the main effect of reducing risk of nulliparous women giving birth to LBW infants (P < 0·05). There was no association between Ca supplementation and SGA (OR = 0·87, 95 % CI: 0·75, 1·01) (P > 0·05). However, higher dietary Ca intake during pregnancy decreases the risk of both LBW (quartile 2: OR = 0·72, 95 % CI: 0·55, 0·94; quartile 3: OR = 0·68, 95 % CI: 0·50, 0·62) and SGA infants (quartile 2: OR = 0·77, 95 % CI: 0·63, 0·95; quartile 3: OR = 0·71, 95 % CI: 0·57, 0·88, quartile 4: OR = 0·71, 95 % CI: 0·57, 0·88) (P < 0·05). CONCLUSIONS: Ca supplementation and adequate dietary intake of Ca during pregnancy are associated with a decreased risk of LBW infants born to nulliparous women.

MicroRNA profiling of plasma exosomes from patients with ovarian cancer using high-throughput sequencing.

To the best of our knowledge, the microRNA (miR/miRNA) expression profile of plasma exosomes in ovarian cancer has not been previously studied. The aim of the present study was to investigate the practicality of using plasma exosomal miRNAs as novel serological biomarkers of ovarian cancer. In the study, exosome-like vesicles were purified from the plasma of patients with ovarian cancer and healthy women using differential centrifugation. The purified vesicles, ranging from 50-100 nm in size, were identified as exosomes by transmission electron microscopy and western blotting. High-throughput sequencing demonstrated that 65 known miRNAs, 34 of which were upregulated and 31 downregulated, were differentially expressed between patients with ovarian cancer and healthy women (P<0.05; fold change ≥2). The miRNA expression levels of hsa-miR-106a-5p, hsa-let-7d-5p and hsa-miR-93-5p were significantly increased, whereas hsa-miR-122-5p, hsa-miR-185-5p and hsa-miR-99b-5p expression levels were significantly decreased in the exosomes of patients with ovarian cancer compared with those in the healthy controls. Additionally, the miRNA expression levels of plasma hsa-miR-93-5p were significantly increased in patients with ovarian cancer compared with those in the healthy controls, while the plasma expression levels of hsa-miR-122-5p and hsa-miR-99b-5p were significantly decreased in patients with ovarian cancer compared with those in the healthy controls. Overall, the present study identified plasma and exosomal miRNAs with dysregulated expression in patients with ovarian cancer compared with that in healthy controls, and the differentially expressed miRNAs may have potential as diagnostic and prognostic targets for the treatment of patients with ovarian cancer.

Targeted Next Generation Sequencing Revealed a Novel Homozygous Loss-of-Function Mutation in ILDR1 Gene Causes Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in a Chinese Family.

Hereditary hearing impairment is one of the major and common birth defects in Chinese population. Non-syndromic sensorineural hearing loss (NSHL) is the most common types of hereditary hearing impairment. Genotypically and phenotypically NSHL is extremely heterogenous and follow either autosomal dominant or autosomal recessive or X-linked mode of inheritance. Presently, 127 genes have been identified to be associated with both syndromic and (NSHL). Here, we studied a Chinese family with moderate and profound hearing impairment. The proband is a 30-year old Chinese man. The proband was born with normal hearing and at the age of 5-years, the proband was first noticed with hearing impairment. Gradually and progressively the proband was presented with loss of hearing in his both right and left ears at the age of 30 years. The clinical symptoms, age of onset or progression to loss of hearing was similar in both the proband and his younger brother. The proband's parents are phenotypically normal and non-consanguineous. Clinical diagnosis of the proband and his younger brother has been done by classical pure tone audiogram (PTA). Computed Tomography (CT) found no abnormality in bilateral external ear, middle ear and inner ear. Targeted next generation sequencing was performed with a panel of 127 genes reported to be associated with hereditary hearing impairment. A novel homozygous single nucleotide deletion (c.427delT) in exon 4 of ILDR1 gene has been identified in proband and in his younger brother. Sanger sequencing confirmed that proband's father and mother are carrying this mutation in a heterozygous manner. This mutation has not been identified in 100 normal healthy control individuals. This mutation (c.427delT) causes frameshift (p.Tyr143Ilefs∗19) which leads to the formation of a truncated ILDR1 protein of 162 amino acids instead of the wild type ILDR1 protein of 546 amino acids. ILDR1 associated hereditary hearing impairment is very rare and this is the first report of identifying a loss-of-function mutation in ILDR1 gene associated with hereditary hearing impairment in Chinese population. Our present study also emphasized the significance of rapid, accurate and cost-effective screening for the patient with hereditary hearing impairment by targeted next generation sequencing.

Pre-pregnancy BMI, gestational weight gain and risk of preeclampsia: a birth cohort study in Lanzhou, China.

BACKGROUND: To evaluate the independent and joint effects of maternal pre-pregnancy BMI and gestational weight gain (GWG) on the risk of preeclampsia and its subtypes. METHODS: A birth cohort study was conducted from 2010 to 2012 in Lanzhou, China. Three hundred fourty seven pregnant women with preeclampsia and 9516 normotensive women at Gansu Provincial Maternity and Child Care Hospital were included in the present study. Unconditional logistic regression models were used to evaluate the associations between pre-pregnancy BMI, GWG, and risk of preeclampsia and its subtypes. RESULTS: Compared to women with normal pre-pregnancy BMI, those who were overweight/obese had an increased risk of preeclampsia (OR = 1.81; 95%CI: 1.37-2.39). Women with excessive GWG had an increased risk of preeclampsia (OR = 2.28; 95%CI: 1.70-3.05) compared to women with adequate GWG. The observed increased risk was similar for mild-, severe- and late-onset preeclampsia. No association was found for early-onset preeclampsia. Overweight/obese women with excessive GWG had the highest risk of developing preeclampsia compared to normal weight women with no excessive weight gain (OR = 3.78; 95%CI: 2.65-5.41). CONCLUSIONS: Our results suggested that pre-pregnancy BMI and GWG are independent risk factors for preeclampsia and that the risk might vary by preeclampsia subtypes. Our study also proposed a potential synergistic effect of pre-pregnancy BMI and GWG that warrants further investigation.

Maternal folic acid supplementation and dietary folate intake and congenital heart defects.

BACKGROUND: It has been reported that folic acid supplementation before and/or during pregnancy could reduce the risk of congenital heart defects (CHDs). However, the results from limited epidemiologic studies have been inconclusive. We investigated the associations between maternal folic acid supplementation, dietary folate intake, and the risk of CHDs. METHODS: A birth cohort study was conducted in 2010-2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. After exclusion of stillbirths and multiple births, a total of 94 births were identified with congenital heart defects, and 9,993 births without any birth defects. Unconditional logistic regression was used to estimate the associations. RESULTS: Compared to non-users, folic acid supplement users before pregnancy had a reduced risk of overall CHDs (OR: 0.42, 95% CI: 0.21-0.86, Ptrend = 0.025) after adjusted for potential confounders. A protective effect was observed for certain subtypes of CHDs (OR: 0.37, 95% CI: 0.16-0.85 for malformation of great arteries; 0.26, 0.10-0.68 for malformation of cardiac septa; 0.34, 0.13-0.93 for Atrial septal defect). A similar protective effect was also seen for multiple CHDs (OR: 0.49, 95% CI: 0.26-0.93, Ptrend = 0.004). Compared with the middle quartiles of dietary folate intake, lower dietary folate intake (<149.88 µg/day) during pregnancy were associated with increased risk of overall CHDs (OR: 1.63, 95% CI: 1.01-2.62) and patent ductus arteriosus (OR: 1.85, 95% CI: 1.03-3.32). Women who were non-user folic acid supplement and lower dietary folate intake have almost 2-fold increased CHDs risk in their offspring. CONCLUSIONS: Our study suggested that folic acid supplementation before pregnancy was associated with a reduced risk of CHDs, lower dietary folate intake during pregnancy was associated with increased risk. The observed associations varied by CHD subtypes. A synergistic effect of dietary folate intake and folic acid supplementation was also observed.