Hemoglobin distributions and prevalence of anemia in a multiethnic United States pregnant population.

BACKGROUND: Few normative longitudinal hemoglobin data are available to estimate the prevalence and risk factors for anemia among a multiethnic United States pregnant population. OBJECTIVES: The aim of this study was to characterize hemoglobin distributions and prevalence of anemia in a pregnant population receiving care at a large urban medical center. METHODS: A retrospective medical chart review was undertaken in 41,226 uncomplicated pregnancies of 30,603 pregnant individuals who received prenatal care between 2011 and 2020. Mean hemoglobin concentrations and anemia prevalence in each trimester and incidence of anemia during pregnancy in a subset of 4821 women with data in each trimester were evaluated in relation to self-reported race and ethnicity and other possible risk factors. Risk ratios (RRs) of anemia were determined using generalized linear mixed-effects models. Smoothed curves describing changes in hemoglobin across pregnancy were created using generalized additive models. RESULTS: The overall prevalence of anemia was 26.7%. The observed fifth percentiles of the hemoglobin distributions were significantly lower than the United States CDC anemia cutoffs in the second and third trimesters (T3). The RR (95% CI) of anemia were 3.23 (3.03, 3.45), 6.18 (5.09, 7.52), and 2.59 (2.48, 2.70) times higher in Black women than that in White women in each trimester, respectively. Asian women recorded the lowest risk of anemia compared with other racial groups in T3 (compared with White womenRR: 0.84; 95% CI: 0.74, 0.96). Hispanic women presented a higher risk of anemia in T3 than non-Hispanic women (RR: 1.36; 95% CI: 1.28, 1.45). In addition, adolescents, individuals with higher parity, and those carrying multiple fetuses experienced a higher risk of developing anemia in late gestation. CONCLUSIONS: Anemia was evident in more than one-quarter of a multiethnic United States pregnant population despite current universal prenatal iron supplementation recommendations. Prevalence of anemia was higher among Black women and lowest among Asian and White women.

Vitamin B12 Status in Pregnant Adolescents and Their Infants.

Vitamin B12 deficiency has been associated with increased risk of adverse pregnancy outcomes. Few prospective studies have investigated the burden or determinants of vitamin B12 deficiency early in life, particularly among pregnant adolescents and their children. The objectives of this study were to determine the prevalence of vitamin B12 deficiency and to examine associations between maternal and neonatal vitamin B12 status in a cohort study of healthy pregnant adolescents. Serum vitamin B12 and folate concentrations were measured in adolescents at mid-gestation (n = 124; 26.4 ± 3.5 weeks) and delivery (n = 131; 40.0 ± 1.3 weeks), and in neonates at birth using cord blood. Linear regression was used to examine associations between maternal and neonatal vitamin B12 status. Although the prevalence of vitamin B12 deficiency (<148.0 pmol/L; 1.6%) in adolescents was low during pregnancy, 22.6% of adolescents were vitamin B12 insufficient (<221.0 pmol/L; 22.6%) at mid-gestation. Maternal vitamin B12 concentrations significantly decreased from mid-gestation to delivery (p < 0.0001), and 53.4% had insufficient vitamin B12 status at delivery. Maternal vitamin B12 concentrations (p < 0.001) and vitamin B12 deficiency (p = 0.002) at delivery were significantly associated with infant vitamin B12 concentrations in multivariate analyses, adjusting for gestational age, maternal age, parity, smoking status, relationship status, prenatal supplement use, pre-pregnancy body mass index, race, and intake of vitamin B12 and folate. Maternal vitamin B12 concentrations significantly decreased during pregnancy and predicted neonatal vitamin B12 status in a cohort of healthy pregnant adolescents.

Longitudinal changes in serum vitamin D binding protein and free 25-hydroxyvitamin D in a multiracial cohort of pregnant adolescents.

Serum free 25-hydroxyvitamin D (25(OH)D) rather than total 25(OH)D may better indicate vitamin D status during pregnancy given the pregnancy-associated increase in serum vitamin D binding protein (DBP) concentration. Our aims were to assess changes in DBP and free 25(OH)D across gestation and to determine whether free compared with total 25(OH)D more strongly correlates with markers of vitamin D and calcium metabolism during pregnancy. This ancillary study included 58 pregnant adolescents (53% African American, 47% White) who completed a vitamin D3 supplementation study in Rochester, NY. Blood was collected at entry, mid-study, and delivery (median 17, 29, and 40 weeks' gestation). Mixed-effects regression was used to test for differences in DBP, directly measured free 25(OH)D, and other serum markers by study visit and race. Free and total 25(OH)D were evaluated in relation to serum PTH, 1,25(OH)2D, 24,25(OH)2D, and calcium. The mean DBP concentration was above nonpregnant reference values at entry and increased across gestation (P < 0.0001). Total 25(OH)D explained most of the variance in free 25(OH)D (r ≥ 0.67; P < 0.0001). Holding total 25(OH)D constant, each 100 mg/L increase in DBP was associated with a 0.4 pg/mL decrease in free 25(OH)D (P < 0.01). The percent free 25(OH)D was inversely related to both DBP and total 25(OH)D at each visit. Regardless of race or visit, total 25(OH)D was a stronger correlate of PTH, 1,25(OH)2D, and 24,25(OH)2D, and neither total nor free 25(OH)D was related to serum calcium. African Americans had lower total 25(OH)D (P < 0.0001), but free 25(OH)D did not significantly differ by race (P = 0.2). In pregnant adolescents, DBP concentration was elevated and inversely associated with percent free 25(OH)D, but measured free 25(OH)D provided no advantage over total 25(OH)D as a predictor of PTH, 1,25(OH)2D, 24,25(OH)2D, or calcium. The clinical relevance of the small racial difference in percent free 25(OH)D requires further investigation.

Gestational Age and Maternal Serum 25-hydroxyvitamin D Concentration Interact to Affect the 24,25-dihydroxyvitamin D Concentration in Pregnant Adolescents.

Background: Interpretation of serum vitamin D biomarkers across pregnancy is complex due to limited understanding of pregnancy adaptations in vitamin D metabolism. During pregnancy, both gestational age and serum 25-hydroxyvitamin D [25(OH)D] concentrations may influence the concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D], and parathyroid hormone (PTH). Objective: We aimed to identify predictors of change in serum 25(OH)D across gestation in pregnant adolescents and to assess the contribution made by cholecalciferol (vitamin D3) supplementation. We sought to determine whether gestational age and 25(OH)D concentration interacted to affect serum 1,25(OH)2D, 24,25(OH)2D, or PTH. Methods: Pregnant adolescents (n = 78, 59% African American, mean ± SD age: 17 ± 1 y) living in Rochester, NY (latitude 43°N) were supplemented with 200 IU or 2000 IU vitamin D3/d and allowed to continue their daily prenatal supplement that contained 400 IU vitamin D3. Serum was collected at study entry (18 ± 5 wk of gestation), halfway through study participation, and at delivery (40 ± 2 wk). Serum concentrations of the biochemical markers were modeled with linear mixed-effects regression models. Results: Vitamin D3 supplement intake and season of delivery determined change in 25(OH)D across pregnancy. Fall-winter delivery was associated with a decline in 25(OH)D unless vitamin D3 supplement intake was >872 IU/d. The interaction of gestational age and 25(OH)D affected 24,25(OH)2D concentrations. For a given 25(OH)D concentration, model-predicted serum 24,25(OH)2D increased across gestation except when 25(OH)D was <13 ng/mL. Below this threshold, 24,25(OH)2D was predicted to decline over time. Mean serum 1,25(OH)2D was elevated (>100 pg/mL) throughout the study. Conclusion: Our results suggest that when maternal serum 25(OH)D was low, its catabolism into 24,25(OH)2D decreased or remained stable as pregnancy progressed in order to maintain persistently elevated serum 1,25(OH)2D. Furthermore, in adolescents living at latitude 43°N, standard prenatal supplementation did not prevent a seasonal decline in 25(OH)D during pregnancy. This study was registered at clinicaltrials.gov as NCT01815047.

Iron deficiency and anemia are prevalent in women with multiple gestations.

BACKGROUND: Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births. OBJECTIVE: We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia. DESIGN: A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6. RESULTS: The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 µg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery. CONCLUSIONS: ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802.

Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy.

BACKGROUND: Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations. OBJECTIVE: We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status. DESIGN: The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum. RESULTS: Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin. CONCLUSIONS: In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens.

Gestational iron deficiency is associated with pica behaviors in adolescents.

A relation between pica (the craving and purposive consumption of nonfood items) during pregnancy and anemia is observed frequently. However, few studies related pica behaviors to biomarkers of iron status, and little is known about pica prevalence in U.S. pregnant adolescents. To address this, we undertook a longitudinal study examining iron status and pica behaviors among a group of 158 pregnant adolescents (aged ≤18 y). Approximately two-thirds of the participants were African American and 25% were Hispanic. Maternal iron status indicators [hemoglobin, soluble transferrin receptor, serum ferritin (SF), total body iron (TBI), and serum hepcidin] were assessed during pregnancy (18.5-37.3 wk) and at delivery. Pica behavior was assessed up to 3 times across gestation. Among the 158 adolescents, 46% reported engaging in pica behavior. Substances ingested included ice (37%), starches (8%), powders (4%), and soap (3%). During pregnancy, mean SF [geometric mean: 13.6 µg/L (95% CI: 11.0, 17.0 µg/L)], TBI (mean ± SD: 2.5 ± 4.2 mg/kg), and hepcidin [geometric mean: 19.1 µg/L (95% CI: 16.3, 22.2 µg/L)] concentrations were significantly lower (P < 0.05) in the pica group (n = 72) than values observed among the non-pica group [SF, geometric mean: 21.1 µg/L (95% CI: 18.0, 25.0 µg/L); TBI, mean ± SD: 4.3 ± 3.5 mg/kg; hepcidin, geometric mean: 27.1 µg/L (95%: 23.1, 32.1 µg/L); n = 86]. Although additional studies must address the etiology of these relations, this practice should be screened for, given its association with low iron status and because many of the substances ingested may be harmful. This trial was registered at clinicaltrials.gov as NCT01019902.

Maternal inflammation at delivery affects assessment of maternal iron status.

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.

A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1).

This study investigated the influence of maternal choline intake on the human placental transcriptome, with a special interest in its role in modulating placental vascular function. Healthy pregnant women (n=26, wk 26-29 gestation) were randomized to 480 mg choline/d, an intake level approximating the adequate intake of 450 mg/d, or 930 mg/d for 12 wk. Maternal blood and placental samples were retrieved at delivery. Whole genome expression microarrays were used to identify placental genes and biological processes impacted by maternal choline intake. Maternal choline intake influenced a wide array of genes (n=166) and biological processes (n=197), including those related to vascular function. Of special interest was the 30% down-regulation (P=0.05) of the antiangiogenic factor and preeclampsia risk marker fms-like tyrosine kinase-1 (sFLT1) in the placenta tissues obtained from the 930 vs. 480 mg/d choline intake group. Similar decreases (P=0.04) were detected in maternal blood sFLT1 protein concentrations. The down-regulation of sFLT1 by choline treatment was confirmed in a human trophoblast cell culture model and may be related to enhanced acetylcholine signaling. These findings indicate that supplementing the maternal diet with extra choline may improve placental angiogenesis and mitigate some of the pathological antecedents of preeclampsia.

Effects of maternal antioxidant supplementation on maternal and fetal antioxidant levels: a randomized, double-blind study.

OBJECTIVE: We sought to determine whether vitamins C and E could be delivered to the fetal-placental unit through maternal oral supplementation. STUDY DESIGN: In a randomized, double-blind study, 20 women received a daily prenatal vitamin with or without 400 IU of vitamin E and 500 mg of vitamin C, starting at 35 weeks' gestation. At randomization, a nutritional questionnaire, plasma vitamin C and E and red blood cell (RBC) vitamin E levels were determined. At delivery, concentrations of maternal and fetal plasma vitamin C and E, maternal and fetal RBC vitamin E, amniotic fluid vitamin C, and chorioamnion vitamin E and tensile strength were determined. RESULTS: Maternal plasma vitamin E levels increased in the supplemented women but not in the control subjects. No changes in maternal vitamin C levels were noted. Maternal plasma vitamin C concentrations at delivery correlated closely with amniotic fluid vitamin C levels. Similarly, maternal plasma vitamin E levels at delivery correlated with the chorioamnion concentration of vitamin E. CONCLUSIONS: Maternal plasma vitamin E levels are increased by oral supplementation. Maternal plasma vitamin C and E concentrations correlate with the concentration of vitamin C in the amniotic fluid and vitamin E in the chorioamnion, respectively.

Preterm premature rupture of the membranes and antioxidants: the free radical connection.

AIM: To discuss the role of oxidant stress in preterm, premature rupture of the membranes (PPROM). RESULTS: There is evidence to suggest that preterm, premature rupture of the membranes occurs secondary to focal collagen damage in the fetal membranes. CONCLUSION: Oxidant stress caused by increased ROS formation and/or antioxidant depletion may disrupt collagen and cause premature membrane rupture. We propose that supplementation with vitamins C and E may synergistically protect the fetal membranes, and decrease the risks of PPROM.