Does Caesarean Section or Preterm Delivery Influence TGF-ß2 Concentrations in Human Colostrum?

Human colostrum (HC) is a rich source of immune mediators that play a role in immune defences of a newly born infant. The mediators include transforming growth factor ß (TGF-ß) which exists in three isoforms that regulate cellular homeostasis and inflammation, can induce or suppress immune responses, limit T helper 1 cells (Th1) reactions and stimulate secretory immunoglobulin A (IgA) production. Human milk TGF-ß also decreases apoptosis of intestinal cells and suppresses macrophage cytokine expression. The aim of the study was to determine the concentration of TGF-ß2 in HC obtained from the mothers who delivered vaginally (VD) or by caesarean section (CS), and to compare the concentrations in HC from mothers who delivered at term (TB) or preterm (PB). In this study, 56% of preterm pregnancies were delivered via CS. The concentrations of TGF-ß2 were measured in HC from 299 women who delivered in the 1st Department of Obstetrics and Gynaecology, Medical University of Warsaw: 192 (VD), 107 (CS), 251 (TB), and 48 (PB). The colostrum samples were collected within 5 days post-partum. TGF-ß2 levels in HC were measured by the enzyme-linked immunosorbent assay (ELISA) test with the Quantikine ELISA Kit-Human TGF-ß2 (cat.no. SB250). Statistical significance between groups was calculated by the Student t-test using StatSoft Statistica 13 software. The mean TGF-ß2 concentration in patients who delivered at term or preterm were comparable. The levels of TGF-ß2 in HC were higher after preterm than term being 4648 vs. 3899 ng/mL (p = 0.1244). The delivery via CS was associated with higher HC concentrations of TGF-ß2. The levels of TGF-ß2 were significantly higher in HC after CS than VD (7429 vs. 5240 ng/mL; p = 0.0017). The data from this study suggest: caesarean section was associated with increased levels of TGF-ß2 in HC. The increased levels of TGF-ß2 in HC of women who delivered prematurely require further research. Early and exclusive breast-feeding by mothers after caesarean section and premature births with colostrum containing high TGF-ß2 levels may prevent the negative impact of pathogens which often colonize the gastrointestinal tract and may reduce the risk of chronic diseases in this group of patients.

Association between maternal omega-3 polyunsaturated fatty acids supplementation and preterm delivery: A proteomic study.

Maternal nutrition during pregnancy influences offspring health. Dietary supplementation of pregnant women with (n-3) long-chain polyunsaturated fatty acids (PUFA) was shown to exert beneficial effects on offspring, through yet unknown mechanisms. Here, we conducted a dietary intervention study on a cohort of 10 women diagnosed with threatened preterm labor with a nutritional integration with eicosapentaenoic and docosahexaenoic acids. Microvesicles (MV) isolated form arterial cord blood of the treated cohort offspring and also of a randomized selection of 10 untreated preterm and 12 term newborns, were characterized by dynamic light scattering and analyzed by proteomic and statistical analysis. Glutathione synthetase was the protein bearing the highest discrimination ability between cohorts. ELISA assay showed that glutathione synthetase was more abundant in cord blood from untreated preterm compared to the other conditions. Assay of free SH-groups showed that serum of preterm subjects was oxidized. Data suggest that preterm suffer from oxidative stress, which was lower in the treated cohort. This study confirms that MV are a representative sample of the individual status and the efficacy of dietary intervention with PUFA in human pregnancy in terms of lowered inflammatory status, increased gestational age and weight at birth.

Relación entre niveles de vitamina D y perfil lipídico en embarazadas de alto riesgo / Relationship between level of vitamin D and lipid profile in high risk pregnant women

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)

In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)

Amniotic Fluid and Maternal Serum Metabolic Signatures in the Second Trimester Associated with Preterm Delivery.

Preterm delivery (PTD) represents a major health problem that occurs in 1 in 10 births. The hypothesis of the present study was that the metabolic profile of different biological fluids, obtained from pregnant women during the second trimester of gestation, could allow useful correlations with pregnancy outcome. Holistic and targeted metabolomics approaches were applied for the complementary assessment of the metabolic content of prospectively collected amniotic fluid (AF) and paired maternal blood serum samples from 35 women who delivered preterm (between 29 weeks + 0 days and 36 weeks +5 days gestation) and 35 women delivered at term. The results revealed trends relating the metabolic content of the analyzed samples with preterm delivery. Untargeted and targeted profiling showed differentiations in certain key metabolites in the biological fluids of the two study groups. In AF, intermediate metabolites involved in energy metabolism (pyruvic acid, glutamic acid, and glutamine) were found to contribute to the classification of the two groups. In maternal serum, increased levels of lipids and alterations of key end-point metabolites were observed in cases of preterm delivery. Overall, the metabolic content of second-trimester AF and maternal blood serum shows potential for the identification of biomarkers related to fetal growth and preterm delivery.

Omega-3 polyunsaturated fatty acids enhance cytokine production and oxidative stress in a mouse model of preterm labor.

OBJECTIVE: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of ω-3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of preterm labor. METHODS: In vivo. Female Swiss Webster mice were fed a normal diet or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On gestational day 15, dams were injected with either saline (n=10 per group) or lipopolysaccharide (LPS, intrauterine) (n=10 per group). Maternal plasma, amniotic fluid, placentas, and uteri were collected 4 h later and assessed for cytokines; maternal plasma and amniotic fluids were analyzed for oxidative stress. In vitro. RAW264.7 mouse macrophage-like cells were treated with either: vehicle, H2O2, docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) (0, 0.1-100 µM) and analyzed for oxidative stress. RESULTS: In vivo. Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (P<0.05-0.01) and increased tumor necrosis factor-α in the uterus (P<0.05) and amniotic fluid (P<0.01) when compared to LPS-treated normal-fed animals. Maternal plasma obtained from FO-fed dams showed higher LPS-induced oxidative stress than control-fed animals (P<0.035). However, no differences in oxidative stress were observed in the amniotic fluid. In vitro. Treatment of macrophage-like cells with ω-3 PUFA significantly and dose-dependently increased oxidative stress (P<0.001-0.0001). CONCLUSIONS: Supplementation with FO for prior to and during pregnancy significantly increased LPS-induced inflammation in the amniotic fluid, uterus, and placenta and significantly increased maternal systemic oxidative stress in vivo. Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in vitro.

Influência da idade gestacional e da paridade sobre a concentração de retinol no colostro humano / Influence of gestational age and parity on the concentration of retinol in human colostrums

A vitamina A é particularmente importante durante os períodos críticos de crescimento, proliferação e desenvolvimento dos tecidos como gestação, período neonatal e infância. Este trabalho tem o objetivo de avaliar a influência das variáveis maternas, como idade gestacional e paridade, sobre os níveis de retinol no colostro e verificar se a concentração de vitamina A no colostro dessas mães fornece a quantidade recomendada deste micronutriente para os recém-nascidos. Foram recrutadas 84 parturientes saudáveis atendidas em uma maternidade pública brasileira. As concentrações de retinol no colostro foram analisadas por cromatografia líquida de alta eficiência. O retinol no colostro de mães a termo (n=49) e pré-termo (n=35) apresentaram valores de 111,3 ± 12,4 µg/dL e 79,2 ± 10,6 µg/dL (p< 0,0001), respectivamente e a concentração de retinol no colostro de primíparas (n= 40) (82,5 ± 8,8 µg/dL) e de multíparas (n= 44) (116,9 ± 10,3 µg/dL) também foi estatisticamente diferente (p< 0,0001). Os níveis de retinol no colostro de mães a termo, bem como os de mães que tiveram um ou mais de um filho neste estudo atendem as necessidades da criança (400 µg de retinol/dia). Entretanto, os níveis de retinol no colostro de mães pré-termo não condizem com as recomendações da DRI para prematuros, que é de 420 µg de retinol/dia. Esses resultados demonstram a necessidade de suplementar com vitamina A as mães pré-termo a fim de garantir um fornecimento adequado dessa vitamina ao recém-nascido.

Vitamin A is particularly important during the critical periods of growth, proliferation and development of tissues such as pregnancy, neonatal period and childhood. This study aims to evaluate the influence of maternal variables such as gestational age and parity, on the levels of retinol in colostrum and verify that the concentration of vitamin A in the colostrum of those mothers provides the recommended amount of this micronutrient for newborns. We recruited 84 healthy pregnant women attended at a Brazilian public hospital. Retinol concentrations in colostrum were analyzed by high performance liquid chromatography. The retinol in colostrum from mothers at term (n = 49) and preterm (n = 35) showed values of 111.3 ± 12.4 µg/dL and 79.2 ± 10.6 µg/dL ( p <0.0001), respectively, and retinol concentration in colostrum from primiparous (n = 40) (82.5 ± 8.8 µg/dL) and multiparous (n = 44) (116.9 ± 10.3 µg/dL) was also statistically different (p <0.0001). Retinol levels in colostrum at term and those whose mothers had one or more than one child in this study meet the needs of the child (400 µg retinol/day). However, levels of retinol in colostrum of preterm infants are not consistent with the recommendations of the DRI for premature infants, which is 420 µg retinol/day. These results demonstrate the need to supplement with vitamin A preterm mothers to ensure an adequate supply of this vitamin to the newborn.

Organochlorine pesticides in colostrums in case of normal and preterm labor (Iasi, Romania).

Assessment of organochlorine pesticides (OCPs) in human body is important for human health because they have weak estrogenic or antiestrogenic effects and are considered endocrine disrupters. We used colostrum of women as indicator for levels of OCPs in human body for mothers with normal and preterm labor from eastern part of Romania. Sixty- three samples of colostrum were extracted by solid-phase extraction. Analyses were carried out using gas chromatography coupled to mass spectrometry (GC-MS). OCPs have been detected in all samples, with p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and gamma-hexachlorocyclohexane (gamma-HCH) being at the highest concentrations. Of the organochlorines measured in clostrum samples from women in preterm labor, median levels of DDTs (470 ng/g) and HCHs (99 ng/g) were higher than for the same compounds from women in normal labor (median of DDTs=268 ng/g and median of HCHs=96 ng/g). Normal labor had higher median concentrations of HCB (19.5 ng/g) versus preterm labor (14 ng/g). Statistical data show high Spearman correlation coefficients between various OCPs. We found a good correlation between alpha-, gamma-, beta- and delta- HCH isomers (p<0.001) for both normal and preterm labor. The most abundant target compound was p,p'-DDE (median value 96 ng/g, and 137 ng/g for mother with normal and preterm labor, respectively) in all colostrum samples. The estimated daily intakes of HCHs by infants exceeded corresponding Health Canada guidelines.

[Influence of gestational age and parity on the concentration of retinol in human colostrums]. / Influência da idade gestacional e da paridade sobre a concentração de retinol no colostro humano.

Vitamin A is particularly important during the critical periods of growth, proliferation and development of tissues such as pregnancy, neonatal period and childhood. This study aims to evaluate the influence of maternal variables such as gestational age and parity, on the levels of retinol in colostrum and verify that the concentration of vitamin A in the colostrum of those mothers provides the recommended amount of this micronutrient for newborns. We recruited 84 healthy pregnant women attended at a Brazilian public hospital. Retinol concentrations in colostrum were analyzed by high performance liquid chromatography. The retinol in colostrum from mothers at term (n=49) and preterm (n=35) showed values of 111.3 +/- 12.4 microg/dL and 79.2 +/- 10.6 microg/dL (p < 0.0001), respectively, and retinol concentration in colostrum from primiparous (n=40) (82.5 +/- 8.8 microg/dL) and multiparous (n=44) (116.9 +/- 10.3 microg/dL) was also statistically different (p < 0.0001). Retinol levels in colostrum at term and those whose mothers had one or more than one child in this study meet the needs of the child (400 microg retinol/day). However, levels of retinol in colostrum of preterm infants are not consistent with the recommendations of the DRI for premature infants, which is 420 microg retinol/day. These results demonstrate the need to supplement with vitamin A preterm mothers to ensure an adequate supply of this vitamin to the newborn.

Effects of oral L-arginine on the pulsatility indices of umbilical artery and middle cerebral artery in preterm labor.

OBJECTIVE: The objective of the study was the estimation of the influence of oral supplementation with low-dose l-arginine on feto-placental circulation in women with threatened preterm labor. STUDY DESIGN: Oral administration of 3g of L-arginine daily or placebo as a supplement to standard tocolytic therapy was tried in 70 women with threatened preterm delivery, randomly assigned to the L-arginine (n=37) or placebo (n=33) groups. Twenty-five and 20 completed the study, respectively. Doppler velocimetry of pulsatility indices (PI) of the umbilical (UA) and middle cerebral (MCA) arteries as well as pregnancy outcome and biochemical markers of nitric oxide synthesis (plasma amino acid and nitrite/nitrate levels, as well as 24 h nitrite/nitrate excretion with urine) were estimated. RESULTS: Starting from the second week of therapy, the UA PI values were significantly lower in the L-arginine group than in the placebo group. Moreover, treatment with L-arginine caused a significant increase in MCA PI and cerebro-placental ratio (CPR) values. The changes in feto-placental circulation in the L-arginine group were not associated with any signs of increased nitric oxide synthesis. CONCLUSION: Oral supplementation with low doses of L-arginine changed feto-placental blood flow distribution in patients with threatened preterm labor. The exact mechanism of L-arginine action on feto-placental circulation requires further investigation.

The regulation of uterine relaxation.

The regulation of uterine relaxation is poorly understood but research in myometrial tissue and other types of smooth muscle has defined a number of receptors, ion channels and regulatory proteins that are likely to be involved. Some of these proteins are substrates for protein kinases, especially cyclic nucleotide dependent kinases. More research is necessary to identify the key molecules involved in the maintenance of uterine quiescence in pregnancy. The use of tocolytics in preterm labour remains controversial; there is a need to identify better pharmacological targets to provoke safe and selective uterine relaxation and improve neonatal outcome.

Characterization of iron, copper and zinc levels in the colostrum of mothers of term and pre-term infants before and after pasteurization.

Pasteurization is a thermal treatment applied to the milk used in human milk banks so as to provoke the thermic inactivation of pathogenic micro-organisms, with the aim of avoiding contamination of milk that will be offered to new-born infants in clinical conditions very often demanding special care. The literature has very little data available relating to the effect of pasteurization on the concentration of oligo-elements in human milk. The objective of this study was to evaluate the effect of pasteurization on the concentrations of iron (Fe), copper (Cu) and zinc (Zn) in the colostrum of mothers of pre-term (PT) and term (T) infants. Samples were collected from the day of birth to the seventh day after birth. The oligo-elements were analyzed using the total reflection X-ray fluorescence technique with synchrotron radiation. The following results of Fe, Cu and Zn (means +/- SD) were obtained for the PT and T colostrum samples, non-pasteurized and pasteurized, respectively: PT: 1.96 +/- 0.73 mg/l Fe/Zn/5.39 +/- 2.73 mg/l Zn; T: 1.71 +/- 1.01 mg/l Fe/1.46 +/- 0.99 mg/l Fe, 0.54 +/- 0.29 mg/l Cu/0.49 +/- 0.19 mg/l Cu, 6.97 +/- 2.82 mg/l Zn/6.75 +/- 2.62 mg/l Zn. There was a significant reduction in the levels of Fe, Cu and Zn in the samples of pasteurized colostrum. These results suggest that, despite the observance of a diminution in the levels of Fe, Cu and Zn in the samples of pasteurized colostrum, the values fell within the acceptable range for the specific nutritional needs of new-born infants during this period of lactation.

Third trimester iron status and pregnancy outcome in non-anaemic women; pregnancy unfavourably affected by maternal iron excess.

A prospective observational study was performed on 488 women with haemoglobin >/=10 g/dl at booking to examine the relationship between serum ferritin concentration quartiles at 28-30 weeks gestation with maternal characteristics, pregnancy complications and infant outcome. While there was no difference in the maternal characteristics or gestational age, the infant size decreased significantly and progressively from the lowest to the highest quartile. Despite a significant difference in the incidence of multiparous women, there was no difference in the incidence of most complications except for prelabour rupture of the membranes and infant admission to the neonatal unit. Compared with the other three quartiles, the highest quartile was associated with increased risk for preterm delivery and neonatal asphyxia, while the lowest quartile was associated with decreased risk of pre-eclampsia, prelabour rupture of the membranes, and infant admission to the neonatal unit. Overall, ferritin quartiles were correlated with other parameters of iron status and red cell indices, and ferritin concentration was inversely correlated with infant birthweight. Our findings suggested that maternal ferritin concentration is primarily a reflection of maternal iron status, and a high level is associated with unfavourable outcome. The rationale of routine iron supplementation in non-anaemic women needs to be re-examined.

[Influences of magnesium sulfate on maternal calcium metabolism in preterm labor].

The effects of intravenous magnesium sulfate tocolysis on calcium metabolism were studied in 10 patients with preterm labor. A loading dose of magnesium sulfate (4g) was administered intravenously maintenance intravenous infusion of magnesium sulfate (1g per hour). All patients simultaneously received 50 micrograms ritodrin per minutes by intravenous infusion. Serum magnesium increased from 1.91 +/- 0.06mg/dl to 4.6 +/- 0.71mg/dl at 30 minutes (p < 0.01) and it remained relatively high. The fall in serum calcium corrected by serum total protein was most rapid during the first 30 minutes, from 9.04 +/- 0.47mg/dl to 8.3 +/- 0.27mg/dl (p < 0.01). Urinary excretion of magnesium, represented as the calcium/creatinine ratio, rose markedly from 0.05 +/- 0.01 to 3.18 +/- 0.8 at an hour (p < 0.01) and thereafter remained higher than the baseline level. Changes in urinary excretion of calcium paralleled those of urinary evcretion of magnesium. Serum parathyroid hormone rose from 118 +/- 42.2pg/ml to 294 +/- 121pg/ml at 6 hours (p < 0.05). Serum 1 alpha,25-(OH)2D3-rose from 89.3 +/- 44.2pg/ml to 126 +/- 38.7pg/ml (p < 0.05). Serum calcitonin showed no significant change. These findings indicate that correction of hypocalcemia mainly depends on secretion of parathyroid hormone in the early stage, and thereafter depends on the cooperative action of parathyroid hormone and 1 alpha,25-(OH)2D3.

Milk macronutrient levels during the first month of term and preterm Nigerian mothers.

The lactose levels of the transition milk of term mothers were significantly higher compared with preterm mothers (5.87 versus 5.32 g/100 ml). The same trends were found in colostrum and mature milk. These differences were not significant. The protein contents of the colostrum in term mothers were significantly lower than in their preterm counterparts (1.80 versus 2.20 g/100 ml). Again the same trend (not significant) was showed in transition and mature milk. A significantly lower level of fat in milk of term mothers than of preterm mothers was found in all 3 types of milk (1.84 versus 2.26; 2.16 versus 2.95; 2.72 versus 3.32 in colostrum, transition milk and mature milk respectively). This study showed differences in the macronutrients measured in the different types of milk, hence term babies in Baby care units should be fed term milk and preterm babies with preterm milk.

Magnesium intake and status and pregnancy outcome in a Danish population.

OBJECTIVE: To investigate the relation between pregnancy outcome and magnesium intake and status. DESIGN: A prospective observational study in which the estimate of nutrient intake and serum samples were obtained before the final outcome of pregnancy was known. A second part of the investigation was a cross-sectional comparison of magnesium status of normal pregnant women and women with certain pathological pregnancies. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics and Gynaecology, University of Aarhus, Denmark. SUBJECTS: 1203 consecutive women in the 30th week gestation were invited to participate in the study, 991 (82.4%) accepted and records for 965 (80.2%) were available for analysis. DATA: Food intake data were collected by a combination of a self administered questionnaire and a structured interview of a dietary history type. Serum samples were obtained from blood withdrawn in the 30th and 37th week gestation. Obstetric data were collected from the midwifery and hospital records. For a second part of the investigation, biopsies from the uterus and the abdominal rectus muscle were obtained from women delivered by caesarean section. RESULTS: In the women with normal pregnancies and in the three groups of pathological pregnancies (pre-eclampsia, SGA-infants and preterm labour) the average magnesium intake was within the range of 200 to 208 mg per 1000 kcal per day (SD 32) and there were no differences between the groups. Neither were differences in serum magnesium observed. Birthweight for gestational age was not influenced by magnesium intake. No differences in magnesium status as assessed by determination of magnesium content in muscle biopsies were found between the normal pregnancies and women with pre-eclampsia, SGA-infants or preterm labour. CONCLUSION: The intake of magnesium seemed adequate, and pre-eclampsia, SGA-infants, or preterm labour did not seem associated with a low dietary intake of magnesium or magnesium deficiency. Routine magnesium supplementation during pregnancy is not recommended for populations of relative good socio-economic status.

Placental transfer of vitamin K1 in preterm pregnancy.

Seventy-eight women at earlier than 35 weeks' gestation with premature rupture of membranes and/or preterm labor were randomly assigned to receive either 10 mg vitamin K1 intramuscularly (IM) or no treatment. If delivery did not occur within 4 days, the dose of vitamin K1 was repeated. Women whose pregnancies continued beyond 8 days received 20 mg of vitamin K1 orally every day until the end of the 34th week or until delivery, whichever occurred earlier. The median maternal plasma vitamin K1 level was significantly higher in treated than in untreated subjects (11.592 versus 0.102 ng/mL; P less than .001). The median cord plasma levels were 0.024 ng/mL in the treated group and 0.010 ng/mL in the controls, a significant difference (P = .046). Median plasma vitamin K1 levels were comparable in mothers receiving the drug by the IM route only and by both the IM and oral routes (10.533 versus 11.928 ng/mL; P = .460). The infants of the latter group, however, had significantly higher median cord plasma levels (0.42 versus 0.017 ng/mL; P less than .001). There was no correlation between cord plasma vitamin K1 levels and gestational age or duration of maternal supplementation with vitamin K1. We conclude that, in preterm pregnancies, vitamin K1 crosses the placenta slowly and to a limited degree.