Impact of cesarean section on metabolic syndrome components in offspring rats.

INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

Association of caesarean delivery with offspring health outcomes in full-cohort versus sibling-comparison studies: a comparative meta-analysis and simulation study.

BACKGROUND: Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery. METHODS: A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis. RESULTS: Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study. CONCLUSIONS: Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.

Geographic variations and determinants of EPA plus DHA and EPA alone in pregnant and lactating women from China.

EPA and DHA are essential for maternal and fetal health, but epidemiological data are sparse in China. We examined the trends of EPA alone and a combination of EPA plus DHA in pregnant and lactating women in three distinct geographic regions in China and explored their potential influencing factors. A total of 1015 healthy women during mid-pregnancy, late pregnancy or lactation were recruited from Weihai (coastland), Yueyang (lakeland) and Baotou (inland) cities of China between May and July of 2014. Maternal EPA and DHA concentrations (percentage of total fatty acids) in plasma and erythrocytes were measured by capillary GC. Adjusted EPA plus DHA concentrations in both plasma and erythrocytes significantly declined from mid-pregnancy (2·92 %, 6·95 %) to late pregnancy (2·20 %, 6·42 %) and lactation (2·40 %, 6·29 %) (Ptrend < 0·001); and both concentrations were highest in coastland, followed by lakeland, and lowest in inland (P < 0·001). Regarding EPA alone, the concentrations were higher in women during lactation or late pregnancy and in women in coastland and inland areas. Moreover, concentrations of EPA or EPA plus DHA were higher in women with older age, higher education, higher annual family income per capita and higher dietary intake of marine aquatic product and mutton. In lactating women, erythrocyte EPA concentration was higher in those having breast-feeding partially v. exclusively. In conclusion, maternal plasma and erythrocyte concentrations of EPA plus DHA or EPA alone differed with geographic regions, physiological periods and maternal characteristics, indicating a need of population-specific health strategies to improve fatty acids status in pregnant and lactating women.

Trends and influencing factors of plasma folate levels in Chinese women at mid-pregnancy, late pregnancy and lactation periods.

Folate status for women during early pregnancy has been investigated, but data for women during mid-pregnancy, late pregnancy or lactation are sparse or lacking. Between May and July 2014, we conducted a cross-sectional study in 1211 pregnant and lactating women from three representative regions in China. Approximately 135 women were enrolled in each stratum by physiological periods (mid-pregnancy, late pregnancy or lactation) and regions (south, central or north). Plasma folate concentrations were measured by microbiological assay. The adjusted medians of folate concentration decreased from 28·8 (interquartile range (IQR) 19·9, 38·2) nmol/l in mid-pregnancy to 18·6 (IQR 13·2, 26·4) nmol/l in late pregnancy, and to 17·0 (IQR 12·3, 22·5) nmol/l in lactation (Pfor trend < 0·001). Overall, lower folate concentrations were more likely to be observed in women residing in the northern region, with younger age, higher pre-pregnancy BMI, lower education or multiparity, and in lactating women who had undergone a Caesarean delivery or who were breastfeeding exclusively. In total, 380 (31·4 %) women had a suboptimal folate status (folate concentration <13·5 nmol/l). Women in late pregnancy and lactating, residing in the northern region, having multiparity and low education level had a higher risk of suboptimal folate status, while those with older age had a lower risk. In conclusion, maternal plasma folate concentrations decreased as pregnancy progressed, and were influenced by geographic region and maternal socio-demographic characteristics. Future studies are warranted to assess the necessity of folic acid supplementation during later pregnancy and lactation especially for women at a higher risk of folate depletion.

Effects of prenatal micronutrients supplementation timing on pregnancy-induced hypertension: Secondary analysis of a double-blind randomized controlled trial.

In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

Effects of Prenatal Micronutrient Supplementation on Spontaneous Preterm Birth: A Double-Blind Randomized Controlled Trial in China.

In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks' gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group.

Geographic Variations and Temporal Trends in Cesarean Delivery Rates in China, 2008-2014.

Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100 873 051 live births, of which 32 947 229 (32.7%) were by cesarean delivery. In 2008, there were 13 160 634 live births, of which 3 788 029 (28.8%) were by cesarean delivery and in 2014 there were 15 123 276 live births, of which 5 280 124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.

Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: This study examined the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. STUDY DESIGN: This analysis included 17 193 women who entered the trial when they were ≥20 years of age, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. RESULTS: Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the 2 post-partum periods. The risk of infant anemia at 5-7 months of age increased when maternal Hb concentration was ≤109 g/L during 24-28 weeks of gestation (aOR, 1.95; 95% CI, 1.59-2.40) and 11-13 months of age (aOR, 1.72; 95% CI, 1.36-2.18), whereas the risk of anemia during 5-7 months of age as well as 11-13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (aOR for 5-7 months, 0.74 [95% CI, 0.64-0.85]; aOR for 11-13 months, 0.72 [95% CI, 0.61-0.85]), or ≥130 g/L (aOR for 5-7 months, 0.75 [95% CI, 0.63-0.90]; aOR for 11-13 months, 0.89 [95% CI, 0.73-1.08]). CONCLUSIONS: Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00133744.

C-reactive protein increases with gestational age during pregnancy among Chinese women.

OBJECTIVE: To examine the concentration of C-reactive protein (CRP) in relation to gestational weeks during pregnancy among Chinese women. METHODS: From a randomized control trial of prenatal supplementation with folic acid, iron-folic acid, and multiple micronutrients in China, we examined 834 pregnant women with CRP measured initially between 5 and 20 weeks and at follow-up between 28 and 32 weeks gestation. We calculated and plotted CRP geometric means by gestational weeks. The same analysis was repeated for women who had normal pregnancies (624 women) by excluding women with stillbirth, preterm, small for gestational age, body mass index <18.5 kg/m(2) or >30 kg/m(2) at enrollment, and hypertension or anemia during pregnancy. RESULTS: We observed a significant positive trend between log-transformed CRP and gestational age from 5 to 20 weeks and from 28 to 32 weeks both in the full sample and in the subset of women who had normal pregnancies. CRP geometric mean was 0.81 mg/l at 5-7 weeks of gestation, 2.85 mg/l at 19-20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation. A similar increasing trend in the CRP median or percentage of elevated CRP were also observed. CONCLUSION: We concluded that CRP increased with gestational age among healthy Chinese women who delivered healthy infants. Am. J. Hum. Biol. 28:574-579, 2016. © 2016 Wiley Periodicals, Inc.

Melamine Nephrotoxicity is Mediated by Hyperuricemia.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Secular trends of premarital medical examination in China during 1996 and 2013].

OBJECTIVE: To describe the secular trends of premarital medical examination (PME) in China during 1996 and 2013 and to assess the impacts of national health policies on the PME rate. METHODS: The information on marriage and PME for districts and counties in 31 provinces of China was annually collected by the Office for National Maternal & Child Health Statistics of China, and the information on the health policies was from official governmental websites. According to the main health policies, the calendar years were categorized into 3 periods: 1996 to 2003 was mandatory PME period; 2004 to 2008 was encouraged voluntary PME period; and 2009 to 2013 was free-paid voluntary PME period. RESULTS: During the 18-year period, 284 242 719 people were registered for a marriage in which 107 198 795 were examined, giving the PME rate of 37.7%. During the mandatory PME period, the rate ranged 52.7%-67.7% with an average of 60.9% (urban 71.5%, and rural 51.7%). In 2004, the first year when the PME became voluntary, the rate was abruptly dropped to 2.6%, and thereafter gradually increased to 11.5% in 2008. As the policies of the free-paid voluntary PME were subsequently issued, the rate was quickly increased to 52.3% (urban 49.8%, and rural 54.6%) in 2013. The increasing trend was consistently observed both in urban and rural areas, and across East, Middle, West, and Northeast economical regions. However, the rates differed greatly among provinces. In 2013, 5 provinces had rates of >90% (Guangxi 97.5%, Fujian 96.0%, Ningxia 95.4%, Zhejiang 93.4% and Anhui 90.1%), whereas some provinces were stuck at a low rate, including developed and underdeveloped provinces/cities. The PME rate in 2013 was 27.4% for Shanghai, 25.5% for Guangdong, 12.4% for Chongqing, 5.8% for Beijing and 4.6% for Tianjin. Underdeveloped provinces were Guizhou (6.4%) and Qinghai (1.8%). CONCLUSION: As various national policies to promote voluntary PME were issued, the PME rate was significantly increased after a sharp decline, though it varied greatly by provinces. For provinces with high PME rate, PME-related health benefits need to be evaluated; for provinces with low rate, it is of important practical significance to explore a cost-effective health service model that is likely incorporated with pre-pregnancy examination.

Iron-containing micronutrient supplementation of Chinese women with no or mild anemia during pregnancy improved iron status but did not affect perinatal anemia.

Universal prenatal daily iron-folic acid (IFA) and multiple micronutrient (MM) supplements are recommended to reduce the risk of low birth weight, maternal anemia, and iron deficiency (ID) during pregnancy, but the evidence of their effect on iron status among women with mild or no anemia is limited. The aim of this study was to describe the iron status [serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI)] before and after micronutrient supplementation during pregnancy. We examined 834 pregnant women with hemoglobin > 100 g/L at enrollment before 20 wk of gestation and with iron measurement data from a subset of a randomized, double-blind trial in China. Women were randomly assigned to take daily 400 µg of folic acid (FA) (control), FA plus 30 mg of iron, or FA, iron, plus 13 additional MMs provided before 20 wk of gestation to delivery. Venous blood was collected in this subset during study enrollment (before 20 wk of gestation) and 28-32 wk of gestation. We found that, at 28-32 wk of gestation, compared with the FA group, both the IFA and MM groups had significantly lower prevalence of ID regardless of which indicator (SF, sTfR, or BI) was used for defining ID. The prevalence of ID at 28-32 wk of gestation for IFA, MM, and FA were 35.3%, 42.7%, and 59.6% by using low SF, 53.6%, 59.9%, and 69.9% by using high sTfR, and 34.5%, 41.2%, and 59.6% by using low BI, respectively. However, there was no difference in anemia prevalence (hemoglobin < 110 g/L) between FA and IFA or MM groups. We concluded that, compared with FA alone, prenatal IFA and MM supplements provided to women with no or mild anemia improved iron status later during pregnancy but did not affect perinatal anemia. This trial was registered at clinicaltrials.gov as NCT00137744.

[Secular trends in cesarean delivery and cesarean delivery on maternal request among multiparous women who delivered a full-term singleton in Southern China during 1993-2005].

OBJECTIVE: To explore the secular trends of cesarean delivery and cesarean delivery on maternal request(CDMR) among multiparous women who delivered a full-term singleton in Southern China during 1993-2005. METHODS: The Perinatal Healthcare Surveillance System was established in 21 cities/ counties of 2 Chinese Southern provinces since 1993. A total of 191 058 multiparous women were monitored during 1993-2005. Chi-square tests were performed to assess the linear trends in the prevalence of cesarean delivery and CDMR. RESULTS: During the 13-years period, 56 968 cesarean deliveries and 10 134 CDMRs were identified. The prevalence rates of cesarean delivery during 1993-1995, 1996-2000 and 2001-2005 were 13.1%, 28.3% and 50.4%( χ(2)trend=17 829.0,P<0.001 ); the prevalence rates of CDMR were 0.6%, 3.8%, and 12.9%(χ(2)trend=7 729.0,P<0.001). The cesarean delivery rate during 2001-2005 were 97.5% for women with previous cesarean section and 40.3% for women without previous cesarean section; the CDMR rate of women without previous cesarean section was 14.4%, accounting for 35.9% of the primary cesarean deliveries. CONCLUSION: The prevalence rates of cesarean delivery and CDMR among multiparous women in Southern China increased dramatically during 1993-2005; CDMR was a non-negligible component of the primary cesarean deliveries for multiparous women.

[A cohort study of longer-term impact of melamine contaminated formula on infant health].

OBJECTIVE: To prospectively evaluate the health status of infants with exposure to melamine-contaminated milk formula prior to September 2008. METHODS: The cohort study was conducted in an area close to the manufacturer of Sanlu dairy products. There were three groups (n = 47 each). In September 2008, the exposure group I included infants with exposure to melamine and a diagnosis of renal abnormalities, the exposure group IIhad exposure to melamine but there was no diagnosis of renal abnormalities and the non-exposure group had no exposure to melamine. The exposure II and non-exposure groups were matched with those of exposure group I by birthplaces, gender and date of birth ( ± 3 months). Kidney function tests (urea nitrogen, serum creatinine, uric acid, serum albumin, ß2-microglobulin and cystatin C), liver function tests (alanine aminotransferase and aspartate aminotransferase), growth and development assessment and urinary system ultrasonography were implemented between November 2011 and June 2012. The analysis of covariance (least significant difference method) was performed to compare the differences of relevant variables among three groups. RESULTS: The urinary system ultrasonography showed that all abnormalities disappeared in exposure group I and all infants of another two groups had normal ultrasonography. There were statistically significant differences in serum uric acid and albumin of kidney function in exposure group I, exposure group II and non-exposure group ((344 ± 75) and (338 ± 98) and (282 ± 69) µmol/L , (47 ± 5) and (47 ± 6) and (43 ± 5) g/L, all P < 0.05) among three groups. However the differences in the remaining markers of kidney function, markers of liver function and Z scores of weight-for-age and height-for age were all statistically insignificant (all P > 0.05). Further pair-wise comparisons showed that the levels of serum uric acid and albumin in exposure group I were higher than those in non-exposure group (P = 0.001 and 0.010). And the levels of serum uric acid and albumin in exposure group II were also higher than those in non-exposure group (P = 0.003 and 0.005). CONCLUSIONS: All affected infants have recovered from kidney abnormalities. Early infant exposure to melamine-contaminated milk formula appears to have no obvious impact on liver function and growth. But its potential impact on kidney function should be further assessed.

Effects of vaginal seeding on gut microbiota, body mass index, and allergy risks in infants born through cesarean delivery: a randomized clinical trial.

BACKGROUND: Vaginal seeding-exposure of neonates to maternal vaginal fluids-has been proposed to improve the microbiota of infants born through cesarean delivery, but its impacts on the infants' subsequent health outcomes remain unclear. OBJECTIVE: This study aimed to examine the impacts of vaginal seeding on gut microbiota, growth, and allergy risks in infants born through cesarean delivery. STUDY DESIGN: This randomized controlled trial was conducted at Liuyang Maternal and Child Health Care Hospital in Hunan, China. We estimated that a minimum sample size of 106 was needed by assuming a standardized effect size of 0.6 for the primary outcomes, with a statistical power of 80%, a 2-sided type I error of 0.05, and an expected loss to follow-up rate of 15%. Finally, 120 singleton term pregnant women scheduled for cesarean delivery were enrolled from November 2018 to September 2019. Infant follow-up was completed in September 2021. The participants were randomized in a 1:1 ratio to the vaginal seeding group (n=60; infants were swabbed immediately after birth using gauze preincubated in maternal vagina) or the control group (n=60; routine standard care). The first set of primary outcomes was infant body mass index and body mass index z-scores at 6, 12, 18, and 24 months of age. The other primary outcome was the total allergy risk score at 18 months for 20 common allergens (each scored from 0-6 points). Characteristics of gut microbiota, overweight/obesity, and allergic diseases and symptoms were included as secondary outcomes. The main analyses were performed according to the modified intention-to-treat principle. RESULTS: Of 120 infants, 117 were included in the analyses. Infant body mass index and body mass index z-scores did not significantly differ between the 2 groups at any of the 4 time points, with the largest difference in point estimates occurring at 6 months: the mean (standard deviation) body mass index was 17.5 (1.4) kg/m2 and 17.8 (1.8) kg/m2 in the vaginal seeding and control groups, respectively (mean difference, -0.31 kg/m2 [95% confidence interval, -0.91 to 0.28]; P=.30), and body mass index z-score was 0.2 (1.0) and 0.4 (1.1), respectively (mean difference, -0.20 [95% confidence interval, -0.58 to 0.18]; P=.31). The median total allergy risk score was 1.5 (interquartile range, 0.0-4.0) in the vaginal seeding group and 2.0 (interquartile range, 1.0-3.0) in the control group (median difference, 0.00 [95% confidence interval, -1.00 to 1.00]; P=.48). For infants from the vaginal seeding group, the relative abundance of genera Lactobacillus and Bacteroides in the gut microbiota was slightly yet nonsignificantly elevated at birth and 6 months, and the risk of overweight/obesity was lower at 6 months (0/57 vs 6/59; relative risk, 0.03 [95% confidence interval, 0.00-0.57]; P=.03) though not at subsequent time points. Other secondary outcomes did not differ between groups. No adverse events related to the intervention were reported. CONCLUSION: For infants born through cesarean delivery, vaginal seeding has no significant impacts on the gut microbiota, growth, or allergy risks during the first 2 years of life.

[Secular trends of cesarean delivery and cesarean delivery on maternal request among primiparous women with singleton pregnancy in Southern and Northern China during 1993-2010].

OBJECTIVE: To explore the secular trends of cesarean delivery and cesarean delivery on maternal request (CDMR) among primiparous women with singleton pregnancy in Southern and Northern China. METHODS: The Perinatal Healthcare Surveillance System was established in 26 counties/cities of 3 Chinese provinces since 1993. A total of 1 317 774 primiparous women with singleton pregnancy were monitored through the system during the 1993 - 2010 period. Chi-square tests were performed to assess the linear trends in the prevalence of cesarean delivery and CDMR. RESULTS: During the 18-year period, 496 054 cesarean deliveries and 129 219 CDMRs were identified. The prevalence rates of cesarean delivery and CDMR were 37.6% and 10.0% respectively. CDMR accounted for 26.0% of all cesarean births. The prevalence of cesarean delivery increased from 29.4% during the 1993 - 1995 period to 58.7% during the 2006 - 2010 in Southern urban area, from 18.2% to 58.3% in Southern rural area and from 4.3% to 49.5% in Northern rural area. The prevalence of CDMR increased by 34 folds from 0.6% during the 1993 - 1995 period to 21.3% during the 2006 - 2010 period in Southern urban area, by 40 folds from 0.6% to 24.4% in Southern rural area and by 44 folds from 0.6% to 27.3% in Northern rural area. The proportions of CDMR in all cesarean deliveries significantly increased in all three regions. Women aged over 30 years, overweight and well-educated were more likely to experience a cesarean delivery including CDMR. CONCLUSION: The Chinese prevalence rates of cesarean delivery and CDMR increased dramatically during the 1993 - 2010 period and ranked the highest in the world by 2010. And CDMR became a non-negligible component in all cesarean sections.

Gestational Diabetes Mellitus as an Effect Modifier of the Association of Gestational Weight Gain with Perinatal Outcomes: A Prospective Cohort Study in China.

The association of gestational weight gain (GWG) with perinatal outcomes seems to differ between women with and without gestational diabetes mellitus (GDM). Whether GDM is an effect-modifier of the association has not been verified. This study aimed to assess the modifying effect of GDM on the association of GWG with perinatal outcomes. Data on 12,128 pregnant women (3013 with GDM and 9115 without GDM) were extracted from a prospective, multicenter, cohort study in China. The associations of total and trimester-specific GWG rates (GWGR) with perinatal outcomes, including small size for gestational age, large size for gestational age (LGA), preterm birth, cesarean delivery, and gestational hypertension disorders, were assessed. The modifying effect of GDM on the association was assessed on both multiplicative and additive scales, as estimated by mixed-effects logistic regression. As a result, total GWGR was associated with all of the perinatal outcomes. GDM modified the association of total GWGR with LGA and cesarean delivery on both scales (all p < 0.05) but did not modify the association with other outcomes. The modifying effect was observed in the third trimester but not in the first or the second trimester. Therefore, maternal GWG is associated with perinatal outcomes, and GDM modifies the association with LGA and cesarean delivery in the third trimester.

Cesarean delivery on maternal request and common child health outcomes: A prospective cohort study in China.

Background: Cesarean delivery vs vaginal delivery was reported to increase the risks of childhood obesity, pneumonia, anemia, and neurobehavioral disorders, but few studies were able to deal with the confounding biases associated with medical conditions indicating cesareans. This prospective cohort study aims to investigate the associations of non-medically indicated cesarean delivery on maternal request (CDMR) with these child health outcomes. Methods: Among 17 748 liveborn infants whose mothers (primiparas) participated in a randomized controlled trial on micronutrient supplementation and pregnancy outcomes during 2006-2009 in 5 rural counties in Hebei Province, China, 6972 singletons born by full-term spontaneous vaginal delivery (SVD) and 3626 by CDMR were extracted for the assessments of obesity (weight-for-height z-score >3) and pneumonia (self-reported) at 1.5-5 years in 2011. Some children were further randomly selected from these two groups for the assessments of anemia (hemoglobin <110 g/L, 2341 SVD and 2417 CDMR) and neurobehavioral disorders (raw score of Child Behavior Checklist larger than the 90th percentile of the normative sample, 1257 SVD and 1060 CDMR). Results: Compared with SVD, CDMR was associated with increased risks of obesity (adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) = 1.14-1.75, P = 0.002) and anemia (aOR = 1.65, 95% CI = 1.28-2.12, P < 0.001), but not with the risk of pneumonia (aOR = 1.16, 95% CI = 0.94-1.45, P = 0.17) or neurobehavioral disorders (aORs varied from 0.82 to 0.91, P > 0.05) in childhood. Conclusions: Cesarean delivery, independent of cesarean indications, is likely associated with childhood obesity and anemia, indicating a need to keep pregnant women informed, especially those seeking CDMR, a need to explore possible improvement on obstetric service, and even a need for main stakeholders to reach a compromise in making a cesarean decision. Trial registration: ClinicalTrials.gov: NCT00133744 and NCT01404416.

Urinary tract abnormalities in Chinese rural children who consumed melamine-contaminated dairy products: a population-based screening and follow-up study.

BACKGROUND: Kidney damage related to consumption of melamine-contaminated dairy products by young children in China has been described. However, no studies have reported on the population-based prevalence of kidney damage among exposed children or on the condition of affected children after follow-up. METHODS: We conducted an ultrasound-based screening in September 2008 of 7933 children younger than 36 months of age who lived in a rural area in China where the dairy products most highly contaminated with melamine were sold. We monitored children who had evidence of nephrolithiasis or hydronephrosis at screening using renal ultrasonography after one, three and six months. We also collected information from the mothers of affected children about consumption of melamine-contaminated products between June and August 2008. RESULTS: The overall prevalence of urinary tract abnormalities among screened children was 0.61% (95% confidence interval [CI] 0.45%-0.80%). The mean exposure dose of melamine was estimated to be 116 (range 36-220) mg per day. Of the 48 affected children, 43 (89.6%) were asymptomatic, 2 had symptoms and were hospitalized, and 3 had symptoms but treatment had been not sought for them. Of the 46 children for whom six-month follow-up information was available, renal abnormalities persisted in 5 children and resolved in the remaining 41. INTERPRETATION: Among children who underwent screening, 0.61% showed ultrasonographic evidence of nephrolithiasis or hydronephrosis. Most of the affected children were asymptomatic. The majority of the affected children recovered from the toxic effects of melamine over time without specific treatment. Renal abnormalities remained in 12% of the affected children.