Preconception TSH and pregnancy outcomes: a population-based cohort study in 184 611 women.

BACKGROUND: Whether subclinical hypothyroidism adversely impacts pregnancy outcomes is inconclusive, and limited data are available on the optimal TSH range in women planning pregnancy. OBJECTIVE: To investigate the association between maternal preconception TSH levels and pregnancy outcomes. DESIGN: Population-based cohort study. METHODS: From 2010 to 2012, the free National Pre-pregnancy Checkups Project recruited 248 501 pairs of volunteer couples across China, of which 184 611 women, who subsequently became pregnant, were studied. Maternal TSH was measured within 6 months prior to conception. Participants were grouped according to TSH: 0·48-2·49 mIU/l (n = 133 232, 72%), 2·50-4·28 mIU/l (n = 44 239, 24%) and 4·29-10·0 mIU/l (n = 7140, 4%). Multivariable logistic regression models were used to study the association between TSH and pregnancy outcomes. MAIN OUTCOMES: Pregnancy loss, gestational age (GA), delivery modes and birthweight. RESULTS: The overall incidence of adverse pregnancy outcomes was 28·6%. Compared with TSH 0·48-2·50 mIU/l, TSH 2·50-4·29 mIU/l was associated with spontaneous abortion [aOR: 1·10, 95% confidence interval (CI): 1·03-1·18], preterm birth (aOR: 1·09, 95% CI: 1·04-1·15) and operative vaginal delivery (aOR: 1·15, 95% CI: 1·09-1·21), while TSH 4·29-10 mIU/l was correlated with spontaneous abortion (aOR: 1·15, 95% CI: 1·10-1·22), stillbirth (aOR: 1·58, 95% CI: 1·10-2·28), preterm birth (aOR: 1·20, 95% CI: 1·08-1·34), caesarean section (aOR: 1·15, 95% CI: 1·10-1·22) and large for gestational age (LGA) infants (aOR: 1·12, 95% CI: 1·04-1·21). CONCLUSION: Preconception TSH elevation was associated with increased risk of adverse pregnancy outcomes, even within the normal nonpregnant range.

The prevalence and risk factors of preterm small-for-gestational-age infants: a population-based retrospective cohort study in rural Chinese population.

BACKGROUND: Preterm birth and small for gestational age (SGA) are strong indicators of neonatal adverse outcomes. With the growing importance of preterm SGA infants, we aim to evaluate the prevalence and risk factors for preterm SGA in China. METHOD: We analyzed the data of parents and infants from a population-based cohort research of the free National Pre-pregnancy Checkups Project (NPCP) in rural China. Only singleton live births that occurred between 24 weeks +0 days and 36 weeks +6 days of pregnancy were included in this study. SGA was defined as birth weight less than the 10th percentile of the reference birth-weight-for-gestational-age population. A multiple logistic regression model was built using the statistically significant variables from the 371 variables in the questionnaire. RESULTS: A total of 11,474 singleton, preterm, live-birth infants were included. Of the total infants, 317 (2.77%) were preterm SGA infants. A higher risk of preterm SGA infants was observed among mothers who were on oral contraceptives (OR: 8.162, 95% CI: 1.622-41.072), mothers who had syphilis (OR: 12.800, 95% CI: 1.250-131.041), and mothers with a high eosinophil percentage (OR: 13.292, 95% CI: 1.282-135.796). Maternal intake of folic acid at least 3 months before pregnancy (OR: 0.284, 95% CI:0.124-0.654) and paternal intake of egg and meat (OR: 0.097,95% CI:0.030-0.315) were protective factors. Compared with North China, the incidence of preterm SGA infants was higher in South China. CONCLUSION: Preterm SGA infants were associated with both maternal and paternal factors.

Exposure to tobacco smoke and stillbirth: a national prospective cohort study in rural China.

INTRODUCTION: Parental exposure to tobacco smoke has been associated with an increased risk of stillbirth, while only a few studies took the overall parental tobacco exposure status into consideration. We aim to explore the relationship of parental smoking and passive smoking before and during pregnancy with stillbirth in a large Chinese rural cohort. DESIGN: 248 501 couples were enrolled in a national prospective cohort study conducted in rural China. Parental exposure to tobacco smoke before and during pregnancy, along with other risk factors, was ascertained by questionnaires. Pregnancy outcomes were recorded by physicians. RESULTS: The ORs (Odds Ratios) of maternal active smoking, maternal passive smoking, paternal active smoking and paternal passive smoking were 2.07 (95% CI 1.25 to 3.41), 1.22 (95% CI 1.01 to 1.47), 1.36 (95% CI 1.13 to 1.63) and 1.10 (95% CI 0.87 to 1.39), respectively. The rates of stillbirth increased from 0.31% for the maternal non-smoking group to 0.43% for the smoking cessation during pregnancy group, to 0.64% for the decreased smoking group and 1.28% for the continuing smoking group. A similar pattern was found in the change in paternal smoking status and stillbirth. Stratified by maternal passive smoking, the OR of paternal smoking was 1.35 (95% CI 1.13 to 1.61) in the maternal non-smoking group and 1.67 (95% CI 1.09 to 2.56) in the maternal passive smoking group. CONCLUSIONS: Parental exposure to tobacco smoke increased the risk of stillbirth, especially for those continuing smoking during pregnancy. Paternal smoking is an independent risk factor for stillbirth despite maternal passive smoking status.

Risk factors of stillbirth in rural China: A national cohort study.

People living in rural China are more frequently exposed to some specific risk factors which made stillbirth rate higher than urban areas. National Free Preconception Health Examination Project was launched to investigate these risk factors and collected a representative sample of 248501 participants from 31 provinces in China from 2010 to 2013. Parental risk factors were ascertained twice before and during pregnancy respectively by questionnaires. Stillbirth or live birth were recorded by trained physicians. In the analysis, nested case-control study was conducted, and propensity score matching method was used to adjust the confounding. Multi-level logistic regression was used to fit for multi-level sampling. The overall stillbirth rate was 0.35% in rural China, it was higher in North (0.42%) and West (0.64%) areas. Maternal exposure to pesticide (OR (95%CI 1.06, 3.39)), hypertension (OR = 1.58 (95%CI 1.07, 2.34)), lack of appetite for vegetables (OR = 1.99 (95%CI 1.00, 3.93)), stress (compared with no pressure, OR of a little pressure was 1.34(95% CI 1.02, 1.76)); paternal exposure to smoking (OR = 1.22 (95% CI 1.02, 1.46)), organic solvents (OR = 1.64 (95% CI 1.01, 2.69)) were found independent risk factors of stillbirth. Folacin intake 3 months before pregnancy (OR = 0.72 (95%) CI 0.59, 0.89), folacin intake 1-2 months before pregnancy (OR = 0.71 (95% CI 0.55, 0.92)), folacin intake after pregnancy (OR = 0.81 (95% CI 0.65, 1.02) for) were protect factors of stillbirth. Maternal pesticide exposure, lack of vegetables, stress, paternal smoking and exposure to organic solvents were risk factors of stillbirth. Folic acid intake was protective factor of stillbirth, no matter when the intake began.

Decreased insulin sensitivity and abnormal glucose metabolism start in preadolescence in low-birth-weight children-Meta-analysis and systematic review.

AIMS: Our meta-analysis aimed to analyze glucose and insulin abnormalities in small-for-gestational-age (SGA) or low-birth-weight (LBW) young people. METHODS: Our data were collected from several databases, including PubMed, AMED and so on. Cohort studies in English were included. SGA or LBW participants comprised the case group, while non-SGA or non-LBW participants comprised the control group. All subjects were younger than 45 years old. RESULTS: Sixteen studies and 10,060 subjects were included in this meta-analysis. The case group showed higher levels of oral glucose tolerance test (OGTT) 2-h glucose (mean difference (MD) = 0.32 mmol/L, 95% confidence interval (CI) 0.13-0.52 mmol/L, P = 0.0009) and fasting and OGTT 2-h insulin than the control group (respectively, MD = 7.47 pmol/L, 95% CI 1.77-13.17 pmol/L, P = 0.01 and MD = 105.55 pmol/L, 95% CI 65.43-145.66 pmol/L, P < 0.00001). In the preadolescence group (maximum age or 95% CI of age ≤10 years old), the OGTT 2-h glucose in the case group had an upward tendency compared to the control group, while the OGTT 2-h insulin in the case group was significantly higher than that in the control group (MD = 118.51 pmol/L, 95% CI 56.80-180.22 pmol/L, P = 0.0002). In the adolescence group (minimum age >10 years old and maximum age≤20 years old or 10 years old<95% CI of age≤20 years old), subjects in the case group showed significantly higher fasting and OGTT 2-h glucose than did the control group (respectively, MD = 0.14 mmol/L, 95% CI 0.04-0.24 mmol/L, P = 0.005 and MD = 0.40 mmol/L, 95% CI 0.08-0.71 mmol/L, P = 0.01). However, fasting and OGTT 2-h insulin in the case group were not significantly different from those in the control group (respectively, MD = 6.56 pmol/L, 95% CI -4.54-17.65 pmol/L, P = 0.25 and MD = 65.89 pmol/L, 95% CI -50.00-181.78 pmol/L, P = 0.27). CONCLUSIONS: Decreased insulin sensitivity and abnormal glucose metabolism began early in preadolescence. Furthermore, glucose tolerance was worse in adolescence. LBW or SGA status affects glucose metabolism and insulin sensitivity beginning in preadolescence.

The Effects of Genetic Polymorphism on Treatment Response of Recombinant Human Growth Hormone.

BACKGROUND: Recombinant human growth hormone (rhGH) has been widely used in clinical treatment and technology has achieved a great development in different long-acting formulations. Genetic polymorphisms may play a role in the varies of individual responses in treatment process. This article gives an overview of the genetic polymorphisms research of growth hormone in recent years. METHODS: We conducted a scoping literature search of PubMed for all English-language publications to identify studies on recombinant human growth hormone and genetic polymorphism from 2000 to 2016. Included studies were all peer-reviewed primary journal articles. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. RESULTS: In all, 96 studies were included and analyzed. We found that besides some well known factors ,such as races, age, gender, weight, several kinds of gene polymorphism reported ever can also affect the growth hormone response in GHD or non-GHD patients, including GHR-Exon 3, IGF(CA)19, IGFBP-3, APOB, CETP, SOCS2, VDR, LEPR and STAT5B. CONCLUSION: Serum IGF-1 is a good parameter of GH treatment response. But it is influenced by various factors, including races, age, gender, weight, initial IGF-1 level, injection concentration and frequency. Gene polymorphism research has been a research hopspot in recent years, may helping understand the pathogeny and pharmacogenomics of these response varieties during GH treatment.

Height at three months can indicate overweight at two years in catch-up growth of small for gestational age infants.

This study aimed to find an indicator at three months to predict overweight and short stature at two years in small for gestational age (SGA) infants. A total of 468 SGA infants and 4642 appropriate for gestational age (AGA) infants were included. Weight and height were measured at birth, three months and two years. Logistic regression and receiver operating characteristic (ROC) curves were performed for the catch-up growth. As compared to AGA infants, the weight of SGA infants was lower and the length/height was shorter at birth, three months, and two years. The weight of the catch-up group was significantly greater at birth and two years. The length/height of the catch-up group was greater at three months and two years. Trajectories of weight standard deviation score (SDS) and height SDS showed that the overweight group (BMI over the 85th percentile) had a shorter length/height SDS but a higher rate of the change in weight SDS during catch-up growth. The multivariate logistic regression indicated that that height at three months was an independent factor for prediction of catch-up growth at two years. The area under curve (AUC) was 0.801 with the 95% confidence interval (CI) from 0.726 to 0.876. Therefore, height at three months can predict overweight at two years.

Both maternal and paternal risk factors for term singleton low birthweight infants in rural Chinese population: a population-based, retrospective cohort study.

No large population-based study has focused on both maternal paternal risk factors for low birthweight (LBW) in China. We aimed to identify parental risk factors associated with LBW.A population-based, retrospective cohort study was conducted on 202,725 singleton infants at 37-42 weeks. These term singleton newborns were classified as LBW with birthweight ≤2500 g(TLBW) and normal birthweight between 50th to 97th percentile (TNBW 50th-97th) according to Chinese singleton norms. Multiple logistic regression analyses were used to find those parental risk factors of LBW by comparing two groups. TLBW and TNBW(50th-97th) occupied 4.8% and 70.8% of the study population, respectively. Logistic regression showed a significant association with positive maternal hepatitis B surface antigen (RR = 1.979, P = 0.047), irregular folic acid intake (RR = 1.152, P = 0.003), paternal history of varicocele (RR = 2.404, P = 0.003) and female babies (RR = 1.072, P = 0.046). Maternal smoking, hypertension and history of stillbirth were found related to LBW but no statistically significant. Positive maternal hepatitis B surface antigen, irregular folic acid intake, paternal history of varicocele had a negative effect on birth weight. Measures are necessarily taken to avoid them to improve pregnancy outcomes. Further studies should be done to investigate each detailed risk factors on LBW.

Paternal exposure to medical-related radiation associated with low birthweight infants: A large population-based, retrospective cohort study in rural China.

Low birthweight (LBW) is closely associated with fetal and perinatal mortality and morbidity. We identified the risk factors of LBW and geographical differences in LBW incidence in 30 Chinese provinces in the present study.This study was a population-based, retrospective cohort study performed in 30 Chinese provinces. We used data from the free National Pre-pregnancy Checkups Project, which is a countrywide population-based retrospective cohort study. To identify regional differences in LBW incidence, we used the Qinling-Huaihe climate line to divide China into northern and southern sections and the Heihe-Tengchong economic line to divide it into eastern and western sections. Multivariate unconditional logistic regression analysis with SAS 9.4 was used for data analysis. P < .05 was considered statistically significant.LBW incidence was 4.54% in rural China. Southern China had a significantly higher incidence (4.65%) than northern China (4.28%). Our main risk factor for LBW is paternal exposure to radiation (odds ratio = 1.537), which has never been studied before.This study identifies multiple risk factors of couples giving birth to LBW babies including paternal risk factors.

Correlation between preconception maternal non-occupational exposure to interior decoration or oil paint odour and average birth weight of neonates: findings from a nationwide cohort study in China's rural areas.

BACKGROUND: Birth weight is a critical indicator of neonatal health and foretells people's health in adolescence and even adulthood. Some researchers have warned against the adverse effects on babies' birth weight of exposure to pollutants in interior decoration or oil paint by odour intake. This study evaluated the effects of maternal exposure to such factors before conception on the birth weights of neonates. METHODS: Data on 213 461 cases in this study were from the database of the free National Pre-pregnancy Checkups Project. Defined as 'exposed' were those women exposed to oil paint odour or interior decoration at home or in the workplace within 6 months before their pregnancy. The study focused on revealing the correlation between such exposure and the birth weight of the neonates of these women, especially the incidence of macrosomia and low birth weight (LBW). Statistical analysis was conducted using the Kruskal-Wallis H test, the Mann-Whitney U test and logistic regression. RESULTS: The birth weight of babies from mothers non-occupationally exposed to such settings averaged 3465 g (range 3150-3650 g), whereas the birth weight of those from mothers free of such exposure averaged 3300 g (range 3000-3600g). Maternal exposure preconception to interior decoration or oil paint odour reduced the incidence of LBW in their babies (p=0.003, OR 0.749, 95% CI 0.617 to 0.909). Such exposure may also augment the probability of macrosomia (p<0.001, OR 1.297, 95% CI 1.133 to 1.484). CONCLUSION: Maternal exposure to interior decoration or oil paint odour preconception may increase the average birth weight of neonates, as well as the incidence of macrosomia.

Structural isomers and binding sites of guanine-rich quadruplexes investigated by induced circular dichroism of thionin: loops and tails.

Induced circular dichroism has been used to study the binding of thionin molecule to twelve guanine-rich quadruplexes. Substituting the base in the loops and varying the length of the tails could substantial change the induced circular dichroism spectra, which allow us to distinguish structural isomers and to determine the binding sites of quadruplexes. Our results show that external stacking on the end surface of the G-quartet associated with electrostatic interaction with the loops or tails is the major binding mode of thionin with these G-quadruplexes.