-
[show abstract]
[hide abstract]
ABSTRACT: Background:This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model where placental underdevelopment induces fetal hypoxemia and hypoglycemia.Methods:Umbilical uptakes of AA, oxygen, glucose and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C).Results:The FGR group demonstrated significantly reducted umbilical uptakes per Kg fetus of oxygen, glucose, lactate, and eleven AAs. The combined uptake of glucose, lactate and AA, expressed as nutrient/oxygen quotients was reduced almost to 1.00 (FGR: 1.05 vs C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AA which were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essentials were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels.Conclusion:We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate which combine to reduce fetal AA demand.Pediatric Research (2013); doi:10.1038/pr.2013.30.
Pediatric Research 02/2013; · 2.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to determine relative contributions of transplacental flux vs. fetal production for inositol and mannose in normal term pregnancies.
Seven term uncomplicated pregnancies undergoing cesarean section were infused with (13)C- and (2)H-labeled isotopes of glucose, inositol, and mannose until a steady state was achieved. Maternal and fetal concentrations of labeled and unlabeled glucose, mannose, and inositol were measured using gas chromatography/mass spectroscopy. The fetomaternal molar percentage excess ratio was calculated for each glucose, mannose, and inositol.
The fetomaternal molar percentage excess ratio of mannose in the fetal artery (F(artery)/M) was 0.99 [97.5% confidence interval (CI), 0.91-1.07] and in the fetal vein (F(vein)/M), 1.02 (97.5% CI, 0.95-1.10). Both were not significantly different from 1.0, consistent with transplacental supply. The fetomaternal ratios for glucose were similar to mannose (fetal artery, 0.95; 97.5% CI, 0.84-1.15; and fetal vein, 0.96; 97.5% CI, 0.85-1.07). The fetomaternal ratio for inositol was significantly less than 1.0 (fetal artery, 0.08; 97.5% CI, 0.05-0.12; fetal vein, 0.12; 97.5% CI, 0.06-0.18), indicating little transplacental flux and significant fetal production.
In normal term pregnancies, fetal mannose and glucose concentrations are dependent upon maternal transplacental supply. Fetal inositol is not dependent upon transplacental supply.
The Journal of clinical endocrinology and metabolism 04/2012; 97(7):2497-502. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective: The time course over which hypertension develops in children with a history of growth restriction has not been fully elucidated. The purpose of this study was to determine whether commonly obtained hemodynamic parameters were different between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates. Methods: This was a retrospective case-control study matching 24 SGA neonates in a 1:2 fashion with 48 AGA neonates delivered during the same gestational week. Hemodynamic parameters were evaluated during the first week of life and the week prior to discharge. Results: There were no differences in blood pressure (BP) parameters during the first week of life. Compared to AGA controls, SGA neonates had a significantly lower heart rate (HR) at birth (148.2 ± 19.2 vs. 159.2 ± 17.1, p < 0.001), and a greater need for vasopressor support (OR 5.66; 95% CI 2.28, 14.04). The SGA neonates had a lower systolic BP during the week prior to discharge (68.3 ± 1.2 vs. 73.5 ± 1.2 mmHg, p < 0.001). Conclusions: SGA newborns had a lower HR at birth and greater need for vasopressor support during the first week of life despite similar BP parameters. SGA newborns had a lower systolic BP prior to discharge. Further studies are needed to understand the progression to adult hypertension.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2012; 25(10):2093-7. · 1.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: TonEBP/NFAT5 (the tonicity-responsive enhancer binding protein/nuclear factor of activated T cells) modulates cellular response to osmotic changes by accumulating inositol and sorbitol inside the cells. Our objective was to assess placental osmolytes, TonEBP/NFAT5 RNA and protein expression, and signaling molecules across gestation between control and intrauterine growth restriction (IUGR) ovine pregnancies. Pregnant sheep were placed in hyperthermic conditions to induce IUGR. Placental tissues were collected at 55, 95, and 130 days gestational age (dGA) to measure inositol, sorbitol, TonEBP/NFAT5 (NFAT5), sodium-dependent myo-inositol transporter (SMIT; official symbol SLC5A3), aldose reductase (AR), and NADPH (official symbol DE-CR1). Placental weight was reduced in IUGR compared to controls at 95 and 130 dGA. Osmolyte concentrations were similar between control and IUGR placentas, but both groups demonstrated a significant decrease in inositol concentration and an increase in sorbitol concentration with advancing gestation. Cytosolic NFAT5 protein decreased significantly from 55 to 95 dGA in both groups, and nuclear NFAT5 protein increased only at 130 dGA in the IUGR group, but no differences were seen between groups for either cytosolic or nuclear NFAT5 protein concentrations. DE-CR1 concentrations were similar between groups and increased significantly with advancing gestational age. AR was lowest at 55dGA, and SLC5A3 increased with advancing gestational age. We conclude that both placental osmolytes inositol and sorbitol (and their corresponding proteins SLC5A3 and AR) change with gestational age and are regulated, at least in part, by NFAT5 and DE-CR1 (NADPH). The inverse relationship between each osmolyte across gestation (e.g., inositol higher in early gestation and sorbitol higher in late gestation) may reflect nutritional needs that change across gestation.
Biology of Reproduction 12/2011; 86(3):94. · 4.01 Impact Factor
-
John C Hobbins,
Gianluigi Pilu,
Alfred Abuhumad,
Zarko Alfirevic,
Ray O Bahado-Singh,
Beryl R Benacerraf,
Richard L Berkowitz,
Irene Cetin,
Joshua A Copel,
Sturla Eik-Nes, [......],
Pasquale Martinelli,
Thomas R Moore,
Aris T Papageorghiou,
Lawrence D Platt,
Nicola Rizzo,
Ann Tabor,
Baskaran Thilaganathan,
Ilan E Timor-Tritsch,
Tullia Todros,
Simcha Yagel
Prenatal Diagnosis 12/2011; 31(12):1213-4; author reply 1215. · 2.11 Impact Factor
-
Henry L Galan
[show abstract]
[hide abstract]
ABSTRACT: Intrauterine growth restriction (IUGR) is commonly defined as an estimated fetal weight of less than the 10th percentile. While 70% of these are small for normal reasons and not at risk, 30% are pathologically small at risk for numerous complications including fetal death. In the late preterm IUGR fetus (>34 weeks), prematurity risks less and the risk of fetal demise becomes the primary concern. Pulsed-wave Doppler interrogation of the umbilical and middle cerebral artery is useful in reducing perinatal mortality, however, Doppler changes in these vessels of the IUGR fetus may not occur after 34 weeks gestation. There are no randomized trials addressing the timing of delivery of the IUGR fetus in the late preterm or early-term period. However, retrospective reports show an increase risk of fetal demise. While timing the delivery of the late preterm/early-term IUGR fetus requires consideration of multiple factors (e.g. degree of growth restriction, etiology, amniotic fluid volume, and biophysical and Doppler testing), available data suggests that delivery should occur by 37 to 38 weeks for singleton IUGR fetuses. In twin pregnancies with a co-twin IUGR fetus, chorionicity also impacts timing of delivery, but delivery should occur by 34-36 weeks.
Seminars in perinatology 10/2011; 35(5):262-9. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To explore the relationship between signal-stimulated increases in intracellular calcium ([Ca(2+)](i)) and depletion and refilling of the endoplasmic reticulum (ER) Ca(2+) stores ([Ca(2+)](L)) in human myometrial cells, we measured simultaneous changes in [Ca(2+)](i) and [Ca(2+)](L) using Fura-2 and Mag-fluo-4, respectively, in PHM1-41 immortalized and primary cells derived from pregnant myometrium and in primary cells derived from nonpregnant tissue. Signal- and extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and ER refilling stimulated by oxytocin and cyclopiazonic acid were not inhibited by voltage-operated channel blocker nifedipine or mibefradil, inhibition of Na(+)/Ca(2+) exchange with KB-R7943, or zero extracellular Na(+) in PHM1-41 cells. Gadolinium-inhibited oxytocin- and cyclopiazonic acid-induced SRCE and slowed ER store refilling. TRPC1 mRNA knockdown specifically inhibited oxytocin-stimulated SRCE but had no statistically significant effect on ER store refilling and no effect on either parameter following cyclopiazonic acid treatment. Dominant negative STIMΔERM expression attenuated oxytocin- and thapsigargin-stimulated SRCE. Both STIM1 and ORAI1-ORAI3 mRNA knockdowns significantly attenuated oxytocin- and cyclopiazonic acid-stimulated SRCE. The data also suggest that reduction in STIM1 or ORAI1-ORAI3 mRNA can impede the rate of ER store refilling following removal of SERCA inhibition. These data provide evidence for both distinct and overlapping influences of TRPC1, STIM1, and ORAI1-ORAI3 on SRCE and ER store refilling in human myometrial cells that may contribute to the regulation of myometrial Ca(2+) dynamics. These findings have important implications for understanding the control of myometrial Ca(2+) dynamics in relation to myometrial contractile function.
Biology of Reproduction 05/2011; 85(2):315-26. · 4.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypoxia is commonly associated with complicated pregnancies such as intrauterine growth restriction. We evaluated the effects of hypoxia on phospho (p)-eNOS, p-ERK, p-AKT and apoptosis in human trophoblast.
Isolated trophoblast were cultured in 21% oxygen or 2% oxygen for 24, 48 and 72 hr. p-eNOS, p-ERK and p-AKT protein were assessed by Western blot and apoptosis by TUNEL assay. NOx was determined in the culture media.
Compared to controls, hypoxia-exposed CT showed the following: (1) decreased eNOS at 48 and 72 hr, (2) increased p-eNOS at 48 hr, (3) no differences in total NOx production, (4) increased p-ERK at 24, 48 and 72 hr, (5) increased p-AKT at 24 hr (P < 0.05) and (6) increased apoptosis at 48 hr.
Hypoxia increases activation of p-ERK and induces apoptosis of cultured trophoblast. Hypoxia decreases overall total eNOS but increases p-eNOS, which may allow for NO production to be maintained in trophoblast cells.
American Journal Of Reproductive Immunology 04/2011; 65(4):407-14. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our objective was to determine signaling molecules and apoptosis rate in the term placenta of a baboon model of maternal nutrient reduction (MNR).
Female baboons were fed ad libitum for controls (n = 7) or 70% of control baboon diet (MNR; n = 6) from 30-165 days of gestation with necropsy at 165 days of gestation. Placental tissues were collected and fixed for immunohistochemistry or snap frozen to measure extracellular signal-regulated kinases, protein kinase B, JUN NH(2)-terminal kinase, X-linked inhibitor of apoptosis protein, and caspase 3. Placental villous apoptosis was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling and cytokeratin 18 cleavage.
Compared with the control placentas, MNR placentas demonstrated reduced placental weight (P < .02), decreased phospho (p)-ERK (P < .04), increased placental villous apoptosis (P < .001), increased villous cytokeratin 18 cleavage, increased X-linked inhibitor of apoptosis protein (P < .007), and increased active caspase 3 (P < .02).
We conclude that placental apoptosis is increased in this baboon model of MNR at term and that the increase in X-linked inhibitor of apoptosis protein may be a protective mechanism against this apoptosis.
American journal of obstetrics and gynecology 10/2010; 203(4):364.e13-8. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of glucose and mannose were greater in the PI-IUGR fetus; glucose: C (n = 7), 2.68 +/- 0.14 mmol/L versus PI-IUGR (n = 9), 3.18 +/- 0.16 mmol/L (P < 0.02) and mannose: C, 42.9 +/- 8.1 micromol/L versus PI-IUGR, 68.5 +/- 19.1 micromol/L (P < 0.001). For PI-IUGR fetuses, fetal arterial plasma myo-inositol concentrations were significantly increased (P < 0.001). The concentrations of sorbitol, glucose and fructose were significantly reduced (P < 0.03, 0.01, 0.02, respectively). The cotyledons of IUGR placentas had a significantly increased concentration of myo-inositol (P < 0.003) and decreased concentrations of sorbitol, fructose and glycerol (P < 0.01, 0.02, 0.01, respectively). Fetal hepatic concentrations of sorbitol (P < 0.001) and fructose (P < 0.03) were also significantly reduced. These profound changes in both placental and fetal concentrations of polyols and sugars in sheep PI-IUGR pregnancies support the conclusion that within the PI-IUGR placenta there is an increased flux through the glucose 6-P:inositol 1-P cyclase system and decreased flux through the polyol dehydrogenase system, leading to increased placental myo-inositol production and decreased sorbitol production. The decreased placental supply of sorbitol to the fetal liver may lead to decreased fetal hepatic fructose production. These observations highlight that, in association with hypoxic and hypoglycemic PI-IUGR fetuses, there are major placental and fetal alterations in polyol production. The manner in which these alterations in fetoplacental carbohydrate metabolism contribute to the pathophysiology of PI-IUGR is currently unknown.
Experimental Biology and Medicine 08/2010; 235(8):999-1006. · 2.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intrauterine growth restriction (IUGR) is a disease responsible for neonatal morbidity and mortality and perinatal death affecting 8% of all pregnancies. In sheep, IUGR that mimics the human IUGR disease closely can be brought on by environmental hyperthermia. Endothelial nitric oxidase synthase (eNOS) and nitric oxide (NO) are important in the regulation of blood flow in the fetal-placental circulation and are modulated by several factors including hypoxia. eNOS activity is also regulated by the phosphorylation of ERK1/2 and AKT proteins in various tissues. In a hyperthermic (HT) ovine model of IUGR with systemic hypertension and increased blood flow resistance, our objective was to determine the relationship between p-ERK, p-AKT, eNOS, and NO concentrations in the placenta, uterine, and umbilical vessels at mid-gestation and near-term. Eight pregnant ewes were exposed to hyperthermic conditions for either 55 or 80 days to induce IUGR. Sheep necropsies were performed at mid-gestation and near-term for collection of placentomes, umbilical vessels, and the uterine artery. Tissues were assessed for eNOS mRNA and protein, and p-ERK and p-AKT protein. Blood was collected for NO determination at the time of necropsy. Placental insufficiency and IUGR (PI-IUGR) pregnancies demonstrated: 1) reduced placental weight at mid-gestation and reduced placental and fetal weight near-term, 2) no changes in eNOS protein concentration in the uterine artery and umbilical vessels, but an increase in NO in umbilical vein blood at both time points, 3) no significant changes in signal transduction makers (ERK/AKT) in placental tissue at mid-gestation but a significant increase near-term in cotyledon tissues, and 4) an increase in p-AKT in the uterine vessels at term. The near-term findings of increased placental p-ERK and p-AKT proteins and umbilical vein NO concentration suggest one mechanism responsible for the increase in placental eNOS previously described in this PI-IUGR model characterized by fetal systemic hypertension and abnormal umbilical artery Doppler velocimetry.
Systems biology in reproductive medicine 02/2010; 56(1):62-73. · 0.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An increase in intracellular Ca(2+) ([Ca(2+)](i)) as a result of release of Ca(2+) from intracellular stores or influx of extracellular Ca(2+) contributes to the regulation of smooth muscle contractile activity. Human uterine smooth muscle cells exhibit receptor-, store-, and diacylglycerol (OAG)-mediated extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and express canonical transient receptor potential-like channels (TRPC) mRNAs (predominantly TRPC1, -4, and -6) that have been implicated in SRCE. To determine the role of TRPC6 in human myometrial SRCE, short hairpin RNA constructs were designed that effectively targeted a TRPC6 mRNA reporter for degradation. One sequence was used to produce an adenovirus construct (TC6sh1). TC6sh1 reduced TRPC6 mRNA but not TRPC1, -3, -4, -5, or -7 mRNAs in PHM1-41 myometrial cells. Compared with uninfected cells or cells infected with empty vector, the increase in [Ca(2+)](i) in response to OAG was specifically inhibited by TC6sh1, whereas SRCE responses elicited by either oxytocin or thapsigargin were not changed. Similar findings were observed in primary pregnant human myometrial cells. When PHM1-41 cells were activated by OAG in the absence of extracellular Na(+), the increase in [Ca(2+)](i) was partially reduced. Furthermore, pretreatment with nifedipine, an L-type calcium channel blocker, also partially reduced the OAG-induced [Ca(2+)](i) increase. Similar effects were observed in primary human myometrial cells. These findings suggest that OAG activates channels containing TRPC6 in myometrial cells and that these channels act via both enhanced Na(+) entry coupled to activation of voltage-dependent Ca(2+) entry channels and a nifedipine-independent Ca(2+) entry mechanism to promote elevation of intracellular Ca(2+).
Endocrinology 11/2009; 151(1):406-16. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Both phosphorylated (p) mammalian target of rapamycin (mTOR) and protein S6 kinase 1 (p70S6K) are known to regulate protein synthesis and are affected during intrauterine growth restriction (IUGR). We studied the mTOR pathway during hyperthermia (HT)-induced IUGR in sheep.
Beginning at 40 days gestational age, 4 ewes were exposed to HT for 55 days and 4 were exposed for 80 days to induce IUGR. Western blot analyses were performed for mTOR, p70S6K, 4E-binding protein 1, extracellularly regulated kinase (ERK), and AKT.
HT animals showed: smaller fetuses and placentas near term; reduced placental weight at midgestation; increased p-mTOR, p-ERK, and p-AKT; decreased p70S6K in the near-term cotyledons; decreased p- p70S6K; and increased p-ERK in the caruncles (maternal) near term.
Near-term IUGR ovine cotyledons showed up-regulation of p-mTOR, whereas p70S6K was decreased. This suggests that the changes in placental mTOR signaling proteins could be driven by the fetal stress observed near term in this model of IUGR.
American journal of obstetrics and gynecology 10/2009; 201(6):616.e1-7. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Osmotic stress results in the accumulation of osmolytes in tissues. Synthesis of these osmolytes is mediated by the transcription factor NFAT5/TonEBP in the human kidney. We tested for the presence of NFAT5 mRNA and protein in the human and ovine placenta and confirmed sorbitol and inositol osmolyte concentrations in these tissues. To determine NFAT5 protein, human and ovine placenta were tested for inositol, sorbitol and glucose using high performance liquid chromatography (HPLC). Additionally, RNA was extracted and cDNA was made from these tissues. PCR was performed and products were sequenced. Western blotting was used to assess the expression of the NFAT5 protein. Human and ovine placenta demonstrated: 1) high concentrations of sorbitol and inositol, 2) presence of NFAT5 mRNA, 3) confirmation by NFAT5 sequence identity, and 4) presence of NFAT5 protein. NFAT5 is present in the ovine and human placenta at the RNA and protein levels that suggest a role for this protein in the induction of these osmolytes. Further trophoblast studies of osmotic stress effects on osmolytes are planned.
Systems biology in reproductive medicine 08/2009; 55(4):164-70. · 0.80 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Doppler ultrasound has become an indispensable tool in evaluating pregnancies at risk for conditions such as preeclampsia, intrauterine growth restriction, fetal anemia, and umbilical cord abnormalities. Use of umbilical artery, middle cerebral artery, and uterine artery Doppler has been the mainstay of assessment.
Recent findings promote the use of ductus venosus Doppler to aid in timing delivery of severely growth-restricted fetuses. Whereas initially it appeared that abnormalities in ductus venosus waveform were the endpoint for pregnancies afflicted with intrauterine growth restriction, newer data suggest that these abnormalities may plateau prior to further fetal deterioration as witnessed by changes in the biophysical profile.
In this review, we will discuss current ultrasound Doppler literature and the recommendations of the experts. We observe that the best algorithm for incorporation of the ductus venosus into intrauterine growth restriction management is yet to be determined. This remains a subject of intense research aimed at optimizing pregnancy outcomes and will be important to follow to provide up-to-date care of our patients.
Current opinion in obstetrics & gynecology 04/2009; 21(2):161-6. · 2.49 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To study changes in umbilical vein (UV) blood flow velocity, diameter and blood flow volume in intrauterine growth retardation (IUGR) fetuses who die in utero (IUD-IUGR).
Twelve singleton IUGR fetuses who died in utero below 600 g were included. All cases had abnormal uterine and umbilical arteries PI. UV diameter and velocity were measured at the time of diagnosis, and at the last exam, within 24 hours prior to intrauterine death. UV flow was calculated per unit weight (mL/min/kg) and abdominal circumference (AC) (mL/min/cm). UV diameter and velocity were normalized per unit AC. Findings were compared to 14 severe viable-IUGR and 22 normal gestational age-matched fetuses.
UV flow (mL/min/kg) was significantly lower in IUD-IUGR compared to viable-IUGR (87 +/- 30 mL/min/kg) and control fetuses (131 +/- 33 mL/min/kg) both at the first (79 +/- 40 mL/min/kg) (P < 0.0001), and at the last exam (54 +/- 29 mL/min/kg) (P < 0.0001). No significant longitudinal flow changes were observed. UV velocity/AC was significantly reduced both in IUD-IUGR and viable-IUGR compared to normal fetuses. UV diameter/AC, was significantly reduced only in IUD-IUGR and not in viable-IUGR compared to normal fetuses.
UV flow (mL/min/kg) was significantly lower in IUD-IUGR fetuses both versus viable-IUGR and normal fetuses. A low flow was due to a decreased UV flow velocity, but also due to a reduced vessel size. This significantly smaller UV size observed in IUGR fetuses with the worst outcome could be considered a severe prognostic sign because of the diagnosis of severe growth restriction.
Prenatal Diagnosis 11/2008; 28(10):908-13. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to assess the placental transport of the essential amino acids (EAAs) in normal pregnancies.
Nine ((13)C or (2)H) EAAs were infused simultaneously as a bolus into the maternal circulation of 12 patients with uncomplicated pregnancy before cesarean delivery. Maternal samples were collected before and after the bolus; umbilical blood was collected at delivery. The fetal/maternal molar percent enrichment for each EAA was calculated for both the umbilical vein and artery. Plasma amino acids enrichments were analyzed by gas chromatography mass spectrometry and concentrations by high performance liquid chromatography. Data were analyzed with paired and unpaired t-test.
The umbilical arterial enrichments were significantly lower than the venous. Fetal/maternal ratios for leucine, isoleucine, methionine, and phenylalanine were > 0.80, with no significant differences among their molar percent enrichment ratios, whereas fetal/maternal ratios of the other 5 EAAs were significantly lower (< 0.60).
The EAAs showed significant umbilical uptake and striking differences in their transport rates in vivo.
American journal of obstetrics and gynecology 11/2008; 200(1):91.e1-7. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Accurate gestational dating is one of the most important assessments obstetrical providers make in pregnancy, given that all of the various management strategies are dependent on knowing where the patient is in gestation. In addition to traditional biometry, ancillary biometric and nonbiometric measurements can help narrow the biologic variability between fetuses. Moreover, one can employ these nontraditional measurements both in late gestation to assist in determining appropriate gestational age and fetal lung maturity, and in other specific clinical situations-such as oligohydramnios, in which compression of the fetal head and abdomen can lead to difficulty in obtaining an accurate biparietal diameter and abdominal circumference. This chapter focuses on nontraditional fetal ultrasound measurements, including the transverse cerebellar diameter, fetal foot length, ratios of biometric and nonbiometric measurements, epiphyseal ossification centers, amniotic fluid volume, placental grading, and other miscellaneous markers in the context of evaluating a fetus with possible intrauterine growth restriction.
Seminars in Perinatology 07/2008; 32(3):154-60. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of the study was to assess placental apoptosis at both midgestation and near term in an ovine model of placental insufficiency (PI) and intrauterine growth restriction (IUGR).
At 40 days' gestational age (dGA), 2 groups of 4 ewes were exposed to hyperthermic conditions for either 55 days or 80 days to induce IUGR with necropsies at 95 (midgestation) and 130 dGA (term = 140 dGA), respectively. Blood gases were assessed and placental tissues obtained for apoptosis analyses.
PI-IUGR pregnancies showed: (1) a decrease in fetal O(2) saturation and pO(2) (P < .04), (2) an increase in placental villi apoptosis (P < .05) at midgestation and near term, and (3) a decrease of cotyledon X-linked inhibitor of apoptosis protein (XIAP) at both gestational periods (P < .04) with no differences in caruncle XIAP protein.
Placental villous apoptosis is increased at midgestation and near term in our ovine model of IUGR, and this increase is associated with a significant decrease in XIAP protein in the cotyledon of IUGR animals.
American journal of obstetrics and gynecology 07/2008; 199(1):80.e1-8. · 3.28 Impact Factor
-
Anita C Manogura,
Ozhan Turan,
Michelle L Kush,
Christoph Berg,
Amarnath Bhide,
Sifa Turan,
Dolores Moyano,
Sarah Bower,
Kypros H Nicolaides, Henry L Galan,
Thomas Müller,
Baskaran Thilaganathan,
Ulrich Gembruch,
Christopher R Harman,
Ahmet A Baschat
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to test the hypothesis that multivessel fetal Doppler imaging provides enhanced prediction of necrotizing enterocolitis (NEC) in preterm placental insufficiency.
Placental-based growth-restricted fetuses (abdominal circumference <5%, abnormal umbilical artery [UA] Doppler imaging) were examined. UA, middle cerebral artery, ductus venosus, and umbilical vein (UV) were evaluated prenatally and were assessed for their ability to predict NEC in neonates who were delivered at <37 weeks of gestation.
Thirty-nine of 404 neonates (9.7%) experienced NEC. Among these, the mortality rate was 15.4% (6/39 neonates; odds ratio, 2.7; 95% CI, 1.03-7.11). NEC cases had higher UA Doppler indices prenatally (P = .023), lower gestational ages and birthweight at delivery (P < .0001, respectively), 5-minute Apgar scores of <7, and higher umbilical cord artery base deficit (P < .01, respectively). NEC was more likely after prenatal UV pulsations (odds ratio, 2.4; 95% CI, 1.13-5.14; P = .028) and severe cardiovascular abnormality (composite variable incorporating UA- absent or reversed end diastolic velocity, absent or reversed ductus venosus a-wave, or UV pulsations; odds ratio, 2.1; 95% CI, 1.06-4.05; P = .029) Logistic regression revealed birthweight and base deficit as the main contributors of NEC (r(2) = 0.20; P < .0001). Receiver operating characteristic analyses revealed birthweight of <790 g (sensitivity, 74.4%; specificity, 72.9%; P < .0001) and gestational age of < or =32.2 weeks (sensitivity, 94.9%; specificity, 45.8%; P < .0001) as optimal cut-offs that provide an odds ratio for NEC of 8.2 (95% CI, 3.9-17.6; P < .0001).
Placental disease predisposes the severely growth-restricted neonate to necrotizing enterocolitis. Even when arterial and venous Doppler variables are taken into consideration, birthweight remains the predominant risk factor for NEC. Further research should focus on the critical transition to neonatal life to identify relevant triggers in predisposed neonates.
American journal of obstetrics and gynecology 06/2008; 198(6):638.e1-5. · 3.28 Impact Factor
