Associations between genetically predicted iron status and cardiovascular disease risk: A Mendelian randomization study.

Background: Mendelian randomization (MR) studies suggest a causal effect of iron (Fe) status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables (IV) on CVD risk factors. We aimed to investigate the effect of Fe status on CVD risk controlling for CVD risk factors. Methods: Fe biomarker IVs (total Fe binding capacity (TIBC, n=208,422), transferrin saturation (TSAT, n=198,516), serum Fe (SI, n=236,612), ferritin (n=257,953)) were selected from a European GWAS meta-analysis. We performed two-sample univariate (UV) MR of each Fe trait on CVD outcomes (all-cause ischemic stroke (IS), cardioembolic IS (CES), large artery IS (LAS), small vessel IS (SVS), and coronary heart disease (CHD)) from MEGASTROKE (n=440,328) and CARDIoGRAMplusC4D (n=183,305). We then implemented multivariate (MV) MR conditioning on six CVD risk factors from independent European samples to evaluate their potential confounding and/or mediating effects on the observed Fe-CVD associations. Results: With UVMR analyses, we found higher genetically predicted Fe status to be associated with a greater risk of CES (TSAT: OR 1.17 [95%CI 1.03, 1.33], SI: OR 1.21 [ 95%CI 1.02, 1.44]; TIBC: OR 0.81 [95%CI 0.69, 0.94]). The detrimental effects of Fe status on CES risk remained unaffected when adjusting for CVD risk factors (all P<0.05). Additionally, we found diastolic blood pressure (DBP) to mediate between 7.1-8.8% of the total effect of Fe status on CES incidence. While UVMR initially suggested a protective effect of Fe status on LAS and CHD, MVMR analyses factoring CVD risk factors revealed a complete annulment of this perceived protective effect (all P>0.05). Discussion: Higher Fe status was associated with a greater risk of CES independent of CVD risk factors, and this effect was partly mediated by DBP. These findings support a role of Fe status as a modifiable risk factor for CES.

Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia.

BACKGROUND: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. OBJECTIVES: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. METHODS: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). RESULTS: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: ß: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: ß: 0.20; 95% CI: 0.03, 0.18; hepcidin: ß: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (ß-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (ß: -0.02; 95% CI: -0.03, -0.003), EPO (ß: 0.07; 95% CI: 0.01, 0.14), and sTfR (ß: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (ß: 0.08, 95% CI: 0.02, 0.14), TBI (ß: 0.02; 95% CI: 0.009, 0.04), EPO (ß: -0.10; 95% CI: -0.19, -0.01), sTfR (ß: -0.16: 95% CI: -0.27, -0.06), and hepcidin (ß: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). CONCLUSIONS: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples.

BACKGROUND: The iron regulatory hormones erythroferrone (ERFE), erythropoietin (EPO), and hepcidin, and the cargo receptor nuclear receptor coactivator 4 (NCOA4) are expressed in the placenta. However, determinants of placental expression of these proteins and their associations with maternal or neonatal iron status are unknown. OBJECTIVES: To characterize expression of placental ERFE, EPO, and NCOA4 mRNA in placentae from newborns at increased risk of iron deficiency and to evaluate these in relation to maternal and neonatal iron status and regulatory hormones. METHODS: Placentae were collected from 114 neonates born to adolescents carrying singletons (14-18 y) and 110 neonates born to 54 adults (20-46 y) carrying multiples. Placental EPO, ERFE, and NCOA4 mRNA expression were measured by RT-qPCR and compared with maternal and neonatal iron status indicators (SF, sTfR, total body iron, serum iron) and hormones. RESULTS: Placental ERFE, EPO, and NCOA4 mRNA were detected in all placentae delivered between 25 and 42 wk of gestation. Relationships between placental ERFE and EPO differed by cohort. In the multiples cohort, placental EPO and ERFE were positively correlated (P = 0.004), but only a positive trend (P = 0.08) was evident in the adolescents. Placental EPO and ERFE were not associated with maternal or neonatal iron status markers or hormones in either cohort. Placental NCOA4 was not associated with placental EPO or ERFE in either cohort but was negatively associated with maternal SF (P = 0.03) in the multiples cohort and positively associated with neonatal sTfR (P = 0.009) in the adolescents. CONCLUSIONS: The human placenta expresses ERFE, EPO, and NCOA4 mRNA as early as 25 wk of gestation. Placental expression of ERFE and EPO transcripts was not associated with maternal or neonatal iron status. Greater placental NCOA4 transcript expression was evident in women and newborns with poor iron status (lower SF and higher sTfR, respectively). Further research is needed to characterize the roles of these proteins in the human placenta. TRIAL REGISTRATION NUMBER: These clinical trials were registered at clinicaltrials.gov as NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902) and NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802).

Mid-trimester uterine electromyography in patients with a short cervix.

BACKGROUND: Preterm birth is the largest single cause of infant death in the United States. A cervical length of <2.5 cm, measured in the mid-trimester, has been shown to identify individuals at increased risk. Uterine electromyography is an emerging technology for noninvasively assessing uterine bioelectrical activity. With its ability to characterize nuanced differences in myometrial signals, uterine electromyography assessments during the mid-trimester may provide insight into the mechanisms of cervical shortening. OBJECTIVE: This study aimed to characterize uterine bioelectrical activity in pregnant individuals with short cervices in the mid-trimester compared with that of pregnant individuals of the same gestational age with normal cervical lengths. STUDY DESIGN: This is a prospective cohort study of subjects with singleton, nonanomalous pregnancies between 16 weeks and 0 days and 22 weeks and 6 days of gestational age. Subjects with normal cervical length (≥3.0 cm) were compared with subjects with short cervical length (<2.5 cm). The short-cervical-length cohort was further stratified by history of preterm birth. Multichannel uterine electromyography recordings were obtained for ∼60 minutes using proprietary, directional electromyography sensors on the abdomen. Uterine electromyography signals were observed and classified in groups as spikes, short bursts, and bursts. Primary outcomes were relative expression of spike, short-burst, and burst uterine electromyography signals. Subgroup analyses assessed each signal percentage by cervical length, history of preterm birth, and gestational age at delivery. Differences in percentage of uterine electromyography signals according to cervical length were analyzed using nonparametric tests of significance. RESULTS: Of the 28 included subjects, 10 had normal and 18 had short cervical length. There were 9 subjects with short cervical length and a history of preterm birth. Spikes were the most commonly recorded signals and were higher in the normal-cervical-length cohort (96.3% [interquartile range, 93.1%-100.0%]) than the short-cervical-length cohort (75.2% [interquartile range, 66.7%-92.0%], P=.001). In contrast, median percentages of short-bursts and bursts were significantly higher in subjects with a short cervical length (17.3% [interquartile range, 13.6%-23.9%] vs 2.5% for normal cervical length [interquartile range, 0%-5.5%], P=.001 and 6.6% [interquartile range, 0%-13.4%] vs 0% for normal cervical length [interquartile range, 0%-2.8%], P=.014, respectively). Within subgroup analyses, cervical length was inversely proportional to percentage of observed short-bursts (P=.013) and bursts (P=.014). Subjects with short cervical length and history of preterm birth had higher burst percentages (12.8% [interquartile range, 9.0%-15.7%]) than those with short cervical length and no history of preterm birth (3.3% [interquartile range, 0%-5.0%], P=.003). CONCLUSION: Short-burst and burst uterine electromyography signals are observed more frequently in mid-trimester patients with short cervical lengths. This relationship provides insight into abnormal myometrial activation in the mid-trimester and offers a plausible biophysiological link to cervical shortening.

Fetal iron uptake from recent maternal diet and the maternal RBC iron pool.

BACKGROUND: During pregnancy iron can be obtained from the diet, body iron stores, or iron released from RBC catabolism. Little is known about the relative use of these sources to support fetal iron acquisition. OBJECTIVES: To describe longitudinal change in iron absorption and enrichment across gestation and partitioning of RBC iron to the fetus. METHODS: Fifteen pregnant women ingested an oral stable iron isotope (57Fe) in the second trimester (T2) of pregnancy (weeks 14-16) to label the RBC pool, and a second oral stable isotope (58Fe) in the third trimester (T3) (weeks 32-35). Absorption was measured at T2 and T3. Change in RBC 57Fe enrichment was monitored (18.8-26.6 wk) to quantify net iron loss from this pool. Iron transfer to the fetus was determined based on RBC 57Fe and 58Fe enrichment in umbilical cord blood at delivery. RESULTS: Iron absorption averaged 9% at T2 and increased significantly to 20% (P = 0.01) by T3. The net increase in iron absorption from T2 to T3 was strongly associated with net loss in maternal total body iron (TBI) from T2 to T3 (P = 0.01). Mean time for the labeled RBC 57Fe turnover based on change in RBC enrichment was 94.9 d (95% CI: 43.5, 207.1 d), and a greater decrease in RBC 57Fe enrichment was associated with higher iron absorption in T2 (P = 0.001). Women with a greater decrease in RBC 57Fe enrichment transferred more RBC-derived iron to their fetus (P < 0.05). CONCLUSIONS: Iron absorption doubled from T2 to T3 as maternal TBI declined. Women with low TBI had a greater decrease in RBC iron enrichment and transferred more RBC-derived iron to their neonate. These findings suggest maternal RBC iron serves as a significant source of iron for the fetus, particularly in women with depleted body iron stores.

Complications of Pregnancy in Adolescents.

Teenage pregnancy is a complex issue that can have negative socioeconomic and health outcomes. About 11% of births worldwide are by adolescents aged between 15 and 19 years and middle- and low-income countries account for more than 90% of these births. Despite the downward trend in international adolescent pregnancy rates, 10 million unplanned adolescent pregnancies occur annually. Adolescents are also at increase risks of poor obstetric outcomes including preterm delivery, low birth weight, eclampsia, postpartum hemorrhage, anemia, and infant, as well as maternal morbidity. Important additional considerations include increased risk of depression, poor social support, and the need for a multidisciplinary approach to their obstetric care. We look to highlight both the unique socioeconomic and medical factors to consider when caring for these patients and demonstrate that these factors are intertwined.

Placental Iron Content Is Lower than Previously Estimated and Is Associated with Maternal Iron Status in Women at Greater Risk of Gestational Iron Deficiency and Anemia.

BACKGROUND: Based on limited data, it is estimated that the placenta retains 90 mg of iron. Little is known about determinants of placental iron content. Animal data indicate that the placenta prioritizes iron for its own needs, but this hypothesis has not been evaluated in humans. OBJECTIVES: To characterize placental iron content and placental iron concentration (p[Fe]) in pregnant women at risk of iron insufficiency and identify determinants of p[Fe]. METHODS: Placentas were collected from 132 neonates born to teens carrying singletons (≤18 y) and 101 neonates born to 48 women carrying multiples (20-46 y). Maternal and neonatal iron status indicators [hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), serum iron, total body iron (TBI)] and hormones (erythropoietin, hepcidin) were measured. p[Fe] was measured using inductively coupled plasma-mass spectrometry. Correlation analyses and mixed-effects models were constructed to identify determinants of p[Fe]. RESULTS: Mean placental iron content was 23 mg per placenta (95% CI: 15, 33 mg) in the multiples and 40 mg (95% CI: 31, 51 mg) in the teens (P = 0.03). Mean p[Fe] did not differ between the cohorts. p[Fe] was higher in anemic (175 µg/g; 95% CI: 120, 254 µg/g) compared with nonanemic (46 µg/g; 95% CI: 26, 82 µg/g) women carrying multiples (P = 0.009), but did not differ between anemic (62 µg/g; 95% CI: 40, 102 µg/g) and nonanemic (73 µg/g; 95% CI: 56, 97 µg/g) teens. In women carrying multiples, low maternal iron status [lower SF (P = 0.002) and lower TBI (P = 0.01)] was associated with higher p[Fe], whereas in teens, improved iron status [lower sTfR (P = 0.03) and higher TBI (P = 0.03)] was associated with higher p[Fe]. CONCLUSIONS: Placental iron content was ∼50% lower than previously estimated. p[Fe] is significantly associated with maternal iron status. In women carrying multiples, poor maternal iron status was associated with higher p[Fe], whereas in teens, improved iron status was associated with higher p[Fe]. More data are needed to understand determinants of p[Fe] and the variable iron partitioning in teens compared with mature women.

Vitamin D kinetics in nonpregnant and pregnant women after a single oral dose of trideuterated vitamin D3.

The plasma pool of the hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) is increased throughout most of human pregnancy. Mechanisms behind this adaptation are unclear, in part due to limited data on vitamin D kinetics during pregnancy. Stable isotopes make it possible to study vitamin D kinetics in vulnerable study populations like pregnant women. We conducted a pilot study of vitamin D kinetics in nonpregnant and pregnant women. We evaluated a clinical protocol and developed analytical methods to assess the serum appearance and disappearance of trideuterated vitamin D3 (d3-vitamin D3) and trideuterated 25-hydroxyvitamin D3 (d3-25(OH)D3) after a single oral dose of 25 µg of [6,19,19-2H]-vitamin D3 (d3-vitamin D3). Blood was collected at baseline and 2, 4, 6, 24, 168, 264, and 456 hours post-dosing. We then described the serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 in nonpregnant and pregnant women. Serum kinetic profiles of d3-vitamin D3 and d3-25(OH)D3 followed a time course in line with previous pharmacokinetic studies. There was marked variability between participants in the area under the concentration-time curve (AUC) of d3-25(OH)D3 over the 20-day study period. This AUC of d3-25(OH)D3 was positively correlated with the serum vitamin D binding protein (DBP) concentration, which was higher in pregnant compared with nonpregnant women. The mean serum half-life of 25(OH)D3 was longer but not significantly different in pregnant women (18.8 days) compared with nonpregnant women (13.6 days). Our pilot study demonstrated that a single oral dose of 25 µg of d3-vitamin D3 can be used to study vitamin D kinetics. Serum DBP concentration is an important predictor of vitamin D kinetics, and more research is needed to fully understand the significance of elevated DBP concentration during pregnancy.

Umbilical Cord Erythroferrone Is Inversely Associated with Hepcidin, but Does Not Capture the Most Variability in Iron Status of Neonates Born to Teens Carrying Singletons and Women Carrying Multiples.

BACKGROUND: The developing fetus requires adequate iron and produces its own hormones to regulate this process. Erythroferrone (ERFE) is a recently identified iron regulatory hormone, and normative data on ERFE concentrations and relations between iron status and other iron regulatory hormones at birth are needed. OBJECTIVES: The objective of this study was to characterize cord ERFE concentrations at birth and assess interrelations between ERFE, iron regulatory hormones, and iron status biomarkers in 2 cohorts of newborns at higher risk of neonatal anemia. METHODS: Umbilical cord ERFE concentrations were measured in extant serum samples collected from neonates born to women carrying multiples (age: 21-43 y; n = 127) or teens (age: 14-19 y; n = 164). Relations between cord blood ERFE and other markers of iron status or erythropoiesis in cord blood were assessed by linear regression and mediation analysis. RESULTS: Cord ERFE was detectable in all newborns delivered between 30 and 42 weeks of gestation, and mean concentration at birth was 0.73 ng/mL (95% CI: 0.63, 0.85 ng/mL). Cord ERFE was on average 0.25 ng/mL lower in newborns of black as opposed to white ancestry (P = 0.04). Cord ERFE was significantly associated with transferrin receptor (ß: 1.17, P < 0.001), ferritin (ß: -0.27, P < 0.01), and hemoglobin (Hb) (ß: 0.04, P < 0.05). However, cord hepcidin and the hepcidin:erythropoietin (EPO) ratio captured the most variance in newborn iron and hematologic status (>25% of variance explained). CONCLUSIONS: Neonates born to teens and women carrying multiples were able to produce ERFE in response to neonatal cord iron status and erythropoietic demand. ERFE, however, did not capture significant variance in newborn iron or Hb concentrations. In these newborns, cord hepcidin and the hepcidin:EPO ratio explained the most variance in iron status indicators at birth.

Serum Erythroferrone During Pregnancy Is Related to Erythropoietin but Does Not Predict the Risk of Anemia.

BACKGROUND: Maintaining adequate iron status during pregnancy is important for the mother and her developing fetus. Iron homeostasis is influenced by 3 regulatory hormones: erythropoietin (EPO), hepcidin, and erythroferrone (ERFE). To date, normative data on ERFE across pregnancy and its relations to other hormones and iron status indicators are limited. OBJECTIVES: The objective of this study was to characterize maternal ERFE across pregnancy and at delivery and evaluate the utility of hepcidin, ERFE, and EPO in identifying women with increased iron needs. METHODS: ERFE was measured in extant serum samples collected from 2 longitudinal cohorts composed of women carrying multiple fetuses (n = 79) and pregnant adolescents (n = 218) at midgestation (∼26 wk) and delivery (∼39 wk). Receiver operating characteristic curves were generated to characterize the predictive ability of serum ERFE, hepcidin, and EPO and their ratios to identify women at increased risk of iron deficiency and anemia. RESULTS: In these pregnant women, mean ERFE was 0.48 ng/mL at both ∼25 wk of gestation and at delivery. ERFE was positively associated with EPO at midgestation (ß = 0.14, P = 0.002, n = 202) and delivery (ß = 0.12, P < 0.001, n = 225) but was not significantly associated with maternal hepcidin at any time point surveyed. Of all hormones measured at midgestation and delivery, EPO was best able to identify women with anemia (AUC: 0.86 and 0.75, respectively) and depleted iron stores (AUC: 0.77 and 0.84), whereas the hepcidin-to-EPO ratio was best able to identify women with iron deficiency anemia (AUC: 0.85 and 0.84). CONCLUSIONS: Maternal ERFE was significantly associated with EPO but was not able to identify women with gestational iron deficiency. At term, the hepcidin-to-EPO ratio, an index that accounts for both iron status and erythropoietic demand, and EPO were the strongest indicators of maternal iron deficiency and anemia. This trial was registered at clinicaltrials.gov as NCT04517734 (https://clinicaltrials.gov/ct2/show/NCT04517734).

Improved Recognition of Maternal Deaths Using Modern Data Analytics.

OBJECTIVE: To use a data-fusion approach to improve ascertainment of maternal deaths not detected with standard surveillance strategies. METHODS: We conducted a retrospective cohort study from the electronic health records of a tertiary medical center from 2011 to 2018. Cases of maternal death were identified in two ways: 1) using a standard medical informatics service query of hospital data and 2) using the TriNetX discovery tool as patients with a vital status of "deceased" and evidence of antecedent pregnancy exposure based on such factors as obstetric diagnostic codes or obstetric-related procedures. Potential cases of maternal death identified by the latter method underwent chart review to confirm timing of death compared with timing of last appreciable pregnancy, and to characterize the details of these deaths. The primary outcome was pregnancy-associated mortality during pregnancy or within the first postpartum year in the discovery cohort compared with the hospital-identified cohort. Secondary outcomes included causes of death and comorbidities. RESULTS: During the study period, the standard service query identified 23 maternal deaths. The discovery tool identified 18 additional patients confirmed on subsequent chart review to represent pregnancy-associated deaths, a 78% increase in ascertainment of which a greater proportion represented postpartum deaths. The majority (61%) of newly ascertained mortalities were related to cardiac causes or other medical comorbidities. Although many hospital-ascertained cases were associated with deaths after delivery of a living newborn, more deaths after early pregnancy loss or termination were identified through the discovery tool. CONCLUSION: Improved recognition of pregnancy-associated deaths can be achieved with modern data analytics.

Does transvaginal ultrasound at 13-15 weeks improve anatomic survey completion rates in obese gravidas?

Objective: Obesity increases the difficulty of completing the fetal anatomic survey. This is of added concern in obese gravidas who are at higher risk of congenital fetal anomalies. We hypothesized that incorporation of an early transvaginal assessment could improve the completion rate of the fetal anatomic survey in obese women.Methods: We performed a prospective, longitudinal, blinded study of obese gravidas (BMI ≥ 35 kg/m2) comparing the use of a single early second trimester transvaginal ultrasound in addition to midtrimester transabdominal ultrasound versus traditional serial midtrimester ultrasound alone for completion of the anatomic survey. Transvaginal ultrasound for anatomy was performed between 13 0/7 and 15 6/7 week followed by midtrimester anatomic ultrasound, with each patient serving as her own control. Structures were marked as optimally or suboptimally viewed after each ultrasound. Sonographers and reviewers were blinded to images from the transvaginal ultrasound. Completion rates and gestational age at completion were compared between groups.Results: Fifty subjects were included. Fetal anatomic survey was completed in 62% using standard midtrimester assessment versus 78% with the addition of early transvaginal assessment (p = .04). The survey was completed at an earlier gestational age utilizing the transvaginal approach (22 0/7 ± 6 3/7) compared to traditional midtrimester transabdominal ultrasound approach (25 2/7 ± 5 3/7) p < .0005.Conclusions: Incorporation of an early transvaginal assessment of anatomy in obese women improved the rate of completion and led to earlier gestational age at completion of the fetal anatomic survey. Consideration should be given to including an early transvaginal sonogram as part of routine assessment of women with a BMI ≥ 35.

Iron absorption during pregnancy is underestimated when iron utilization by the placenta and fetus is ignored.

BACKGROUND: Maternal iron absorption during pregnancy can be evaluated using RBC incorporation of orally administered stable iron isotope. This approach underestimates true maternal absorption of iron as it does not account for absorbed iron that is transferred to the fetus or retained within the placenta. OBJECTIVE: Our objective was to re-evaluate maternal iron absorption after factoring in these losses and identify factors associated with iron partitioning between the maternal, neonatal, and placental compartments. METHODS: This study utilized data from stable iron isotope studies carried out in 68 women during the third trimester of pregnancy. Iron status indicators and stable iron isotopic enrichment were measured in maternal blood, umbilical cord blood, and placental tissue when available. Factors associated with iron isotope partitioning between the maternal, neonatal, and placental compartments were identified. RESULTS: On average, true maternal absorption of iron increased by 10% (from 19% to 21%) after accounting for absorbed iron present in the newborn (P < 0.001), and further increased by 7%, (from 39% to 42%, P < 0.001) after accounting for iron retained within the placenta. On average, 2% of recovered tracer was present in the placenta and 6% was found in the newborn. Net transfer of iron to the neonate was higher in women with lower total body iron (standardized ß = -0.48, P < 0.01) and lower maternal hepcidin (standardized ß = -0.66, P < 0.01). In women carrying multiple fetuses, neonatal hepcidin explained a significant amount of observed variance in net placental transfer of absorbed iron (R = 0.95, P = 0.03). CONCLUSIONS: Maternal RBC iron incorporation of an orally ingested tracer underestimated true maternal iron absorption. The degree of underestimation was greatest in women with low body iron. Maternal hepcidin was inversely associated with maternal RBC iron utilization, whereas neonatal hepcidin explained variance in net transfer of iron to the neonatal compartment.These trials were registered at clinicaltrials.gov as NCT01019096 and NCT01582802.

A social media intervention to improve nutrition knowledge and behaviors of low income, pregnant adolescents and adult women.

Pregnant adolescents are at increased risk of adverse pregnancy outcomes compared to adult women, necessitating a need for early and comprehensive health care. This study aimed to evaluate the effectiveness of a social media intervention (i.e. weekly prenatal health messages) on improving diet quality, and health beliefs and knowledge. Participants (10 adolescents and 12 adults) completed pre-post intervention interviews, nutrition knowledge and health belief questionnaires, and 24-hour diet recalls. Participants entering pregnancy as overweight or obese were more likely to experience excessive GWG during the intervention. The adults had greater participation during the study despite high levels of social media access among both groups. Participants were able to identify sugar-sweetened foods and acknowledged the benefits of whole grains; however, overall knowledge of MyPlate Guidelines was limited. Social media-based education was well received by participants but did not result in large changes in dietary intake and knowledge. Although larger studies are needed, social media appears to have the potential to reach high-risk women.

Umbilical Cord Serum Ferritin Concentration is Inversely Associated with Umbilical Cord Hemoglobin in Neonates Born to Adolescents Carrying Singletons and Women Carrying Multiples.

BACKGROUND: It has been proposed that the fetus prioritizes iron for hemoglobin production over delivery to tissues. However, few studies have evaluated the interrelations between hemoglobin and multiple iron status biomarkers in umbilical cord blood. A full understanding is needed of how these parameters influence each other within cord blood to fully interpret iron and hematologic status at birth. OBJECTIVES: We evaluated the determinants of neonatal hemoglobin and assessed the interrelations between hemoglobin, serum iron status indicators, and serum iron regulatory hormones in healthy neonates. METHODS: This was an observational study that assessed umbilical cord hemoglobin (Hb), serum ferritin (SF), erythropoietin (EPO), soluble transferrin receptor (sTfR), serum iron, hepcidin, vitamin B-12, folate, IL-6, and CRP measured in 234 neonates born to adolescents or to women carrying multiples. Correlations between these indicators were evaluated and mediation models consistent with the observed significant determinants of cord Hb concentrations were developed. RESULTS: A highly significant inverse association was found between cord SF and Hb concentrations that was not attributable to neonatal or maternal inflammation (as measured by IL-6 and CRP). The inverse association was present in the combined cohort, as well as in the adolescent and multiples cohorts independently. Mediation analyses found that EPO and hepcidin had significant indirect effects on cord Hb, associations that are explicable by mediation through SF and sTfR. CONCLUSION: In contrast to observations made in older infants, a highly significant inverse association between Hb and SF, as well positive associations between Hb and both sTfR and EPO, were observed in umbilical cord blood from neonates born to adolescents or women carrying multiples. These findings, combined with review of the published literature, indicate a need for analysis of the relations between multiple parameters to assess iron and hematologic status at birth. These clinical trials were registered at clinicaltrials.gov as NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802) and NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902).

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.

Patterns and Correlates of Self-Reported Physical Activity in a Cohort of Racially Diverse Pregnant Adolescents.

STUDY OBJECTIVE: Regular physical activity (PA) during pregnancy decreases the risk of gestational hypertension and preeclampsia. Currently, little is known about the PA of pregnant adolescents. Our intent was to characterize the PA behaviors of a group of racially diverse, low-income pregnant teens and to identify potential determinants of PA. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A cohort of 157 racially diverse pregnant adolescents (13-18 years of age) completed up to 3 previous day PA recalls as part of a larger prospective longitudinal study on determinants of maternal and fetal bone health. Subjects self-reported activities from 7 AM to 11:30 PM, choosing from a list of 37 activities including a category for "other." Subjects recorded activities in 30-minute intervals. MAIN OUTCOME MEASURES: Estimated metabolic equivalent task (MET) values were assigned to each activity and summed for a measure of total daily PA in MET min/d. Determinants of PA were evaluated using a stepwise linear mixed effect model. RESULTS: The average calculated MET min/d was 1478 ± 130. Significant determinants of MET min/d included race (P = .007), maternal age at conception (P = .042), gestational age (P = .002), and attending school (P < .001). Black teens were less physically active than white teens, and older teens were more active than younger teens; activity decreased throughout gestation, and teens currently attending school were more active. CONCLUSION: PA is low across gestation and pregnant teens spent more than half of their monitored time in sedentary activities. Targeted interventions are needed to achieve current PA goals in this pediatric obstetric population.

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.