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.

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.

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.

Prenatal iron containing supplements provided to Chinese women with no or mild anemia had no effect on hemoglobin concentration in post-partum women or their infants at 6 and 12 months of age.

BACKGROUND: Although prenatal iron-containing supplements have been associated with lower anemia prevalence in later pregnancy, few trials have examined the effect of supplements on the anemia status of post-partum women and their infants. OBJECTIVE: We compared the effects of folic acid alone (FA), iron-folic acid (IFA) and multiple micronutrients (MMN) when provided to pregnant women with no or mild anemia on the hemoglobin levels of post-partum women and their infants at 6 and 12 months of age. We also examined the potential modifying effect of maternal hemoglobin concentration at enrollment. METHODS: A double-blind randomized controlled trial was conducted in China; 18,775 nulliparous women with a hemoglobin concentration > 100 g/L were randomly assigned to receive daily FA (400 µg); IFA (FA, Fe 30 mg), or MMN (FA, Fe and 13 micronutrients) from before 20 gestational weeks until delivery. RESULTS: Compared with daily prenatal FA, supplementation with IFA or MMN did not affect the prevalence of anemia at 4-6 weeks post-partum (27.2%, 26.8%, and 26.3%, respectively). At 6 months of age, the anemia prevalence in infants was 6.9%, 6.7%, and 6.7%, respectively. Findings were similar at 12 months of age. Among both post-partum women and infants, findings were similar across all levels of hemoglobin at enrollment. CONCLUSIONS: Compared to FA alone, prenatal IFA and MMN provided to women with no or mild anemia did not affect anemia in women post-partum or their infants regardless of baseline maternal hemoglobin concentration at enrollment.

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.

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.

DHA in Pregnant and Lactating Women from Coastland, Lakeland, and Inland Areas of China: Results of a DHA Evaluation in Women (DEW) Study.

Few studies have examined docosahexaenoic acid (DHA) in pregnant and lactating women in developing countries like China, where DHA-enriched supplements are increasingly popular. We aimed to assess the DHA status among Chinese pregnant and lactating women residing areas differing in the availability of aquatic products. In total, 1211 women in mid-pregnancy (17 ± 2 weeks), late pregnancy (39 ± 2 weeks), or lactation (42 ± 7 days) were enrolled from Weihai (coastland), Yueyang (lakeland), and Baotou (inland) city, with approximately 135 women in each participant group by region. DHA concentrations were measured using capillary gas chromatography, and are reported as weight percent of total fatty acids. Mean plasma DHA concentrations were higher in coastland (mid-pregnancy 3.19%, late pregnancy 2.54%, lactation 2.24%) and lakeland women (2.45%, 1.95%, 2.26%) than inland women (2.25%, 1.67%, 1.68%) (p values < 0.001). Similar differences were observed for erythrocyte DHA. We conclude that DHA concentrations of Chinese pregnant and lactating women are higher in coastland and lakeland regions than in inland areas. DHA status in the study population appears to be stronger than populations from other countries studied to date.

Association of cesarean delivery with anemia in infants and children in 2 large longitudinal Chinese birth cohorts.

BACKGROUND: Cesarean delivery may reduce placental-fetal transfusion and thus increase the risk of early childhood anemia compared with vaginal delivery, but this notion has not been carefully studied in longitudinal cohorts. OBJECTIVE: The aim was to assess the association of cesarean delivery with anemia in infants and children in 2 longitudinal Chinese birth cohorts from different socioeconomic settings. DESIGN: Cohort 1 was recruited from 5 counties in northeastern China and cohort 2 from 21 counties or cities in southeastern China. Cohort 1 involved 17,423 infants born during 2006-2009 to mothers with early pregnancy baseline hemoglobin concentrations ranging from 100 to 177 g/L, whereas cohort 2 involved 122,777 children born during 1993-1996 to mothers with baseline hemoglobin concentrations ranging from 60 to 190 g/L. The main outcomes were anemia at 6 and 12 mo in cohort 1 and at 58 mo in cohort 2. Multiple logistic regressions were used to estimate adjusted ORs of anemia for cesarean compared with vaginal delivery. Stratified analyses were performed by pre- and postlabor cesarean delivery and according to maternal baseline hemoglobin concentration (≤109, 110-119, 120-129, and ≥130 g/L). RESULTS: Cesarean delivery was not associated with anemia at 6 mo in cohort 1 (adjusted OR: 1.05; 95% CI: 0.93, 1.19); however, cesarean delivery was associated with increased anemia at 12 mo in cohort 1 (adjusted OR: 1.19; 95% CI: 1.04, 1.37) and at 58 mo in cohort 2 (adjusted OR: 1.11; 95% CI: 1.08, 1.15). The positive associations for anemia at 12 and 58 mo were consistent across maternal hemoglobin subgroups and persisted for cesarean delivery subtypes. CONCLUSION: Cesarean delivery is likely associated with anemia in children, which suggests a possible need for exploring changes in obstetric care that might prevent anemia in cesarean-delivered children.

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.

Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China.

BACKGROUND: Beyond perinatal folic acid supplementation, the need for additional prenatal prophylaxis of iron with or without other micronutrients remains unclear. We aim to investigate the maternal and infant health effects of iron plus folic acid and multiple micronutrient supplements vs folic acid alone when provided to pregnant women with no or mild anemia. METHODS: In this randomized double-blind controlled trial, 18,775 nulliparous pregnant women with mild or no anemia were enrolled from 5 counties of northern China from May 2006 through April 2009. Women were randomly assigned to daily folic acid (400 µg) (control), folic acid-iron (30 mg), or folic acid, iron, and 13 additional vitamins and minerals provided before 20 weeks gestation to delivery. Primary outcome was perinatal mortality. Secondary outcomes included neonatal and infant mortality, preterm delivery, birth weight, birth length, gestational duration, and maternal hemoglobin concentration and anemia. RESULTS: A total of 92.7% of women consumed 80% to 100% of supplements as instructed. On average, women consumed 177 supplements. Compared with daily prenatal folic acid, supplementation with iron-folic acid with or without other micronutrients did not affect the rate of perinatal mortality (8.8, 8.7, and 8.3, respectively) per 1000 births, and relative risks (RRs) were 1.00 (95% CI, 0.68-1.46; P = .99) and 0.94 (95% CI, 0.64-1.39; P = .76), respectively. Risk of other adverse maternal and infant outcomes also did not differ, except that RRs for third-trimester maternal anemia were 0.72 (95% CI, 0.63-0.83; P < .001) and 0.71 (95% CI, 0.62-0.82; P < .001), respectively. CONCLUSION: Prenatal iron-folic acid and other micronutrient supplements provided to Chinese women with no or mild anemia prevented later pregnancy anemia beyond any benefit conferred by folic acid alone but did not affect perinatal mortality or other infant outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00133744.

Body iron stores and their determinants in healthy postmenopausal US women.

BACKGROUND: Data on the determinants of body iron stores in middle-aged women are sparse. OBJECTIVE: We prospectively evaluated nondietary and dietary determinants of iron stores. DESIGN: Using blood samples collected in 1989-1990, we measured plasma ferritin concentrations in 620 healthy postmenopausal women aged 44-69 y who participated in the Nurses' Health Study. Food-frequency questionnaires completed in 1980, 1984, and 1986 were used to calculate average dietary intakes. Generalized linear regression and multiple logistic regression models were used to assess the association between plasma ferritin and its determinants. RESULTS: Among these postmenopausal women, the median plasma ferritin concentration was 73.8 ng/mL (interquartile range: 41.6-125.8 ng/mL), 2.7% were iron depleted (ferritin concentration < 12 ng/mL), and 9.8% had an elevated ferritin concentration (> 200 ng/mL). Age, time since menopause, time since the last postmenopausal hormone (PMH) use, body mass index, iron supplement use, and alcohol and heme-iron intakes were positively associated with ferritin concentrations, whereas PMH use, physical activity, aspirin use, and gastrointestinal ulcer were inversely related. The association between heme-iron intake and ferritin was most apparent among the women who consumed > 30 g alcohol/d. CONCLUSIONS: Our prospective data confirm that in postmenopausal women, intakes of heme iron, supplemental iron, and alcohol are dietary determinants of plasma ferritin, and age, PMH use, body mass index, physical activity, aspirin use, and gastrointestinal ulcer are nondietary determinants.