Secular trends of age at menarche and age at menopause in women born since 1951 from a county of Shandong Province, China / 北京大学学报(医学版)

OBJECTIVE@#To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province.@*METHODS@#Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression.@*RESULTS@#The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66).@*CONCLUSION@#The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.

Thyroid function of first-trimester twin pregnant women and its association with preterm delivery / 北京大学学报(医学版)

OBJECTIVE@#To describe the thyroid function abnormality of first-trimester twin pregnant women according to different references, and to explore its association with preterm delivery.@*METHODS@#Participants, first-trimester twin pregnant women, were recruited at Peking University Third Hospital from March 2017 to February 2020. The thyroid hormone reference for ordinary adults identified on the assay kits by Siemens incorporation, thyroid hormone reference specifically for singleton pregnancy established previously, and thyroid hormone reference specifically for twin pregnancy established previously were used in the description of hypothyroidism and hyperthyroidism for first-trimester twin pregnant women. Thyroid autoantibody reference identified on the assay kits by Siemens incorporation was used in the description of positive thyroid autoantibody. Multivariable log-binomial regression was conducted to examine the association between thyroid function and preterm delivery, in which normal pregnant women according to the three references and normal pregnant women according to twin pregnancy reference accompanied with negative thyroid autoantibody were taken as control respectively.@*RESULTS@#A total of 570 twin pregnant women were finally included. Rates of hypothyroidism according to the three references were 1.2%, 1.6% and 3.5%, respectively. Rates of hyperthyroidism according to the three references were 32.6%, 18.1% and 1.1%, respectively. After adjustment for potential confounding factors, risk of preterm delivery significantly increased in pregnant women with hyperthyroidism according to the twin specific pregnancy reference [adjusted relative risk (ARR)=1.41, 95%CI: 1.14-1.75], while no significant increase was found in those with normal thyroid function according to the twin specific pregnancy reference but hyperthyroidism according to the singleton specific pregnancy reference (ARR=1.00, 95%CI: 0.81-1.25) and in those with hyperthyroidism purely according to the ordinary adult reference (ARR=1.06, 95%CI: 0.85-1.32), compared with those normal according to all the references. Risks of preterm delivery almost significantly or significantly increased in pregnant women with hypothyroidism according to the ordinary adult or singleton specific pregnancy reference (ARR=1.40, 95%CI: 0.88-2.22) and those with hypothyroidism according to the twin specific pregnancy reference (ARR=1.53, 95%CI: 1.03-2.28). Overall analysis of thyroid function according to the twin specific pregnancy reference and thyroid autoantibody showed that risks of preterm delivery almost significantly or significantly increased in pregnant women with simple hypothyroidism (ARR=1.46, 95%CI: 0.93-2.27), simple positive thyroid autoantibody (ARR=1.32, 95%CI: 1.15-1.52), and hypothyroidism accompanied with positive thyroid autoantibody (ARR=1.78, 95%CI: 1.30-2.44), compared with those normal according to the twin specific pregnancy reference with negative thyroid autoantibody.@*CONCLUSION@#The ordinary adult reference and that of singleton pregnancy may lead to under-diagnosis of hypothyroidism and over-diagnosis of hyperthyroidism in first-trimester twin pregnant women. Compared with pregnant women with normal thyroid function, those missed in the diagnosis of hypothyroidism were at a higher risk of preterm delivery, while those over-diagnosed as hyperthyroidism had a similar risk of preterm delivery, indicating a need to develop and generalize twin-pregnancy-specific reference on common indicators of thyroid function. Moreover, the thyroid autoantibody should be taken into consideration in the prenatal diagnosis and treatment to twin pregnant women with hypothyroidism.

Relationship of plasma vitamin A levels between neonates and pregnant women in third trimester / 北京大学学报(医学版)

OBJECTIVE@#To study the correlation of plasma vitamin A (VitA) levels between neonates and pregnant women in third trimester.@*METHODS@#A total of 688 pregnant women were recruited in Yuanshi and Laoting counties of Hebei Province, from May to June 2009. Venous blood samples of women before delivery and cord blood samples of newborns were collected and measured for retinol (retinol concentration was used to reflect VitA level) using high performance liquid chromatography assay. According to venous blood plasma retinol concentration, maternal VitA nutritional status was divided into deficiency (<0.70 μmol/L), marginal deficiency (0.70-<1.05 μmol/L), and sufficiency (≥1.05 μmol/L). According to cord blood plasma retinol concentration, neonatal VitA nutritional status was divided into deficiency (<0.35 μmol/L), marginal deficiency (0.35-<0.70 μmol/L), and sufficiency (≥0.70 μmol/L); neonatal VitA relative deficiency was further defined as cord blood plasma retinol concentration lower than the 10th percentile. VitA placental transport ratio was defined as retinol concentration in the neonates divided by that in pregnant women. Multivariable fractional polynomials (MFP) model and Pearson correlation were used to study the dose-response relationship between maternal and neonatal plasma VitA levels, Logistic regression model to estimate the effect of maternal VitA nutritional status on neonatal VitA deficiency, and MFP model and Spearman correlation to describe the relationship between maternal VitA level and VitA placental transport ratio.@*RESULTS@#The average retinol concentration of the pregnant women was (1.15±0.30) μmol/L, and the prevalence of VitA deficiency and marginal deficiency were 4.5% and 37.8%, respectively. Average retinol concentration of the neonates was (0.78±0.13) μmol/L, and no neonates were VitA deficiency, 28.2% of the neonates were marginal deficiency. After multivariable adjustment, the VitA level of the neonates was positively and linearly related to maternal VitA level (pm=1, P<0.05), with the corresponding Pearson correlation coefficient of 0.13 (P<0.01). As compared with the women with sufficient VitA, those with VitA deficiency (crude OR=2.20, 95%CI:1.04-4.66) and marginal deficiency (crude OR=1.43, 95%CI:1.01-2.02) had higher risks to deliver neonates with VitA marginal deficiency; while the risks turned to be non-significant after multivariable adjustment. The pregnant women with VitA deficiency had higher risk to deliver neonates with relative VitA deficiency before and after multivariable adjustment (crude OR=3.02, 95%CI:1.21-7.50; adjusted OR=2.76, 95%CI:1.05-7.22). The maternal VitA level was negatively and non-linearly correlated with placental transport ratio (pm= -0.5, P<0.05), with corresponding adjusted Spearman correlation coefficient of -0.82 (P<0.001).@*CONCLUSION@#There was a positive linear dose-response relationship between VitA levels of newborns and pregnant women in third trimester, indicating that neonatal VitA storing levels at birth was affected by maternal VitA nutritional status.

Mobile terminal-based survey on the birth characteristics for Chinese newborns / 北京大学学报(医学版)

OBJECTIVE@#To describe the birth characteristics for Chinese newborns, to assess the feasibility of collecting basic data on maternal and child health, and to conduct relevant epidemiological studies by using mobile terminals.@*METHODS@#From June 2016 to January 2017, pregnant women who delivered in hospitals were recruited in 166 hospitals scattered across 23 provinces of China. The data on their maternal and child health including delivery mode, gestational age and birth weight, were collected by self-administered questionnaires embedded in a mobile application. The incidences or means of cesarean section, preterm birth, birth weight, length and head circumference were calculated and compared with recognized national data, including 2005 Growth Standards for Chinese Children Under 7 Years of Age, 2006 World Health Organization Child Growth Standards and 2014 Chinese Neonatal Birth Weight Standards by Gestational Age.@*RESULTS@#A total of 9 986 women were investigated, among whom those aged ≥35 years accounted for 11.7% and those received well education (college and above) accounted for 70.2%. The rate of cesarean section, preterm delivery, low birth weight and macrosomia were 38.1%, 4.5%, 2.2%, and 7.8%, respectively. The means were (3.33±0.44) kg [male (3.36±0.44) kg, female (3.29±0.43) kg] for birth weight, (50.97±2.32) cm [male (51.04±2.32) cm, female (50.89±2.32) cm] for birth length, and (33.99±1.56) cm [male (34.01±1.57) cm, female (33.97±1.55) cm] for head circumference, respectively. As compared with the national data, the cesarean section rate and birth weights by gestational age for term-born neonates were similar to the latest national data in 2014, while the means of birth weight and length were obviously higher than those of the 2005 Growth Standards for Chinese Children Under 7 Years of Age and 2006 World Health Organization Child Growth Standards.@*CONCLUSION@#As compared with the national data 10 years ago, the mean birth weights for male and female newborns were increased by 40 g and 80 g respectively and mean lengths by 0.6 cm and 1.3 cm, but changes for mean head circumferences were negligible, indicating that the physical health condition for Chinese newborns improved significantly over past 10 years and emerging information technology likely provided a new approach for epidemiological research.

Melamine Nephrotoxicity is Mediated by Hyperuricemia / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).</p><p><b>METHODS</b>Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.</p><p><b>RESULTS</b>Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.</p><p><b>CONCLUSION</b>Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.</p>

Cesarean delivery on maternal request and childhood intelligence: a cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cesarean section births have been steadily increasing over the past decade and have become an epidemic in China. Cesarean delivery on maternal request is a major contributor to this upward trend, and there has been of much concern about its impact on maternal and child health. Most of mothers believe that cesarean delivery on maternal request can improve the child's intelligence, but direct evidence is sparse. In this cohort study, we aimed to directly assess the impact of cesarean delivery on maternal request on childhood intelligence.</p><p><b>METHODS</b>Intelligence quotient (IQ) of 4144 preschool children from 21 cities/counties of Zhejiang and Jiangsu province whose mothers were registered in a population-based perinatal surveillance program during 1993-1996 was assessed with Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) in 2000. The outcomes were full-scale IQ, verbal IQ, and performance IQ of C-WYCSI. Mode of delivery and covariates were obtained from the surveillance program. We estimated unadjusted and adjusted effects of cesarean delivery on maternal request and assisted vaginal delivery on IQ scores compared with spontaneous vaginal delivery using regression analysis.</p><p><b>RESULTS</b>The mean full-scale, verbal, and performance IQ for all children was 99.3 ± 16.1, 93.6 ± 17.7, and 105.3 ± 14.3. In crude analysis, cesarean delivery on maternal request versus spontaneous vaginal delivery was associated with an increase of 3.9 (95% confidence interval, 0.6 to 7.2) points in full-scale IQ, 4.8 (1.2 to 8.4) points in verbal IQ, and 2.4 (-0.6 to 5.3) points in performance IQ. After adjusting for maternal education, occupation, and IQ, the advantage was reduced to 1.6 (-1.3 to 4.5), 2.3 (-0.8 to 5.5), and 0.6 (-2.0 to 3.3) points for full-scale, verbal, and performance IQ, respectively. Assisted vaginal delivery versus spontaneous vaginal delivery was not associated with IQ scores in any analysis.</p><p><b>CONCLUSION</b>Neither cesarean delivery on maternal request nor assisted vaginal delivery affected children's IQ.</p>

Study on the current status of spontaneous abortion of primigravid women in Jiaxing of Zhejiang province, China / 中华流行病学杂志

Objective To study the current status of spontaneous abortion of primigravid women in Jiaxing areas of Zhejiang province of China. Methods We analyzed the data from both perinatal healthcare surveillance program and spontaneous abortion, collected in Jiaxing areas by the Institute of Reproductive and Child Health, Peking University. The study population consisted of 14 769 primigravid women (excluding induced abortion, ectopic pregnancy and molar pregnancy as outcomes) attempting to become pregnant who registered between 1993 and 1995. Results 1454 spontaneous abortion cases were identified, with the spontaneous abortion rate as 9.8% (95% CI:9.3%-10.3%). The mean gestational weeks at pregnancy diagnosis were 7.6±2.1 weeks, the mean gestational weeks at miscarriage were (10.1±3.1) weeks and the incidence of first-trimester (≤12 weeks) spontaneous abortion was 7.3%(95%CI: 6.8%-7.7%), accounting for 73.7% of all the spontaneous abortion cases. A peak for risk of miscarriage was around 8-13 weeks, accounting for 37.7% of all spontaneous abortion. The observed multiple Cox regression model showed that increased spontaneous abortion rates were observed in women with age at pregnancy ≥30, being peasants and with higher education level. Conclusion The spontaneous abortion rate of primigravid women in Jiaxing areas was higher than in other areas of China. The maximum occurrence of spontaneous abortions was during period of 8-13 gestation weeks.

Prospective cohort study of pregnancy-induced hypertension and risk of preterm delivery and low birth weight / 中华预防医学杂志

<p><b>OBJECTIVE</b>To determine the association between pregnancy-induced hypertension(PIH) and risk of preterm delivery (PD) and low birth weight (LBW).</p><p><b>METHODS</b>A prospective cohort was established based on 131 867 women who delivered a singleton baby in seven cities or counties in Zhejiang province, China, during the period of 1995 - 2000. The exposure group included 14 278 women who were diagnosed as PIH, and the non-exposure group included 117 589 women. The exposure group was divided into mild, moderate, and severe subgroups based on the severity of PIH, and further divided into early, medium and late onset subgroups based on the time of onset of PIH (occurred in second trimester, third trimester, or during delivery). The primary outcome measures were the incidence of PD and LBW. Multiple logistic regression was used to estimate relative risk and 95% confidence intervals after adjustment by maternal age, occupation, education, parity, number of prenatal visits, gestational disease, caesarean delivery, pregnant body mass index, fetal sex, and gestational age (only for LBW).</p><p><b>RESULTS</b>The incidence rates of PD and LBW in exposure group were 4.9% (701/14 278) and 3.6% (507/14 278), and both rates were higher than those of the non-exposure group (3.4% (4031/117 589), 1.8% (2110/117 589)) (chi(2) values were 80.8 and 202.0, P < 0.001). The incidence rates of PD in mild, moderate, and severe subgroups were 3.9% (404/10 358), 5.8% (181/3099), and 14.1% (116/821), and corresponding incidence rates of LBW were 2.5% (258/10 358), 4.9% (151/3099), and 11.9% (98/821). Both rates were increased with the severity of PIH (chi(2) values were 196.4 and 426.1, P-value for trend < 0.001). The incidence rates of PD in early, medium, and late onset subgroup were 8.4% (50/598), 5.7% (278/4867), and 4.2% (373/8813), and corresponding incidence rates of LBW were 5.7% (34/598), 4.2% (206/4867), and 3.0% (267/8813). Both rates were decreased by the time of PIH onset (chi(2) values were 115.4 and 239.8, P-value for trend < 0.001).</p><p><b>CONCLUSION</b>PIH could increase the incidence of PD and LBW.</p>