S100B protein cord blood levels and development of fetal behavioral states: a study in normal and small-for-dates fetuses.

OBJECTIVE: We aimed to determine whether S100B protein levels in cord blood and the development of fetal behavioral states were altered and interrelated in small-for-dates (SFD) fetuses. METHODS: Umbilical cord blood samples were collected from 12 SFD fetuses with normal umbilical artery (UA) Doppler findings, from six SFD fetuses with abnormal Doppler waveform patterns and from 36 controls matched for gestational age. S100B protein levels were measured by means of a specific radioimmunoassay. Fetal behavioral state recordings were made before delivery by Cesarean section and data were expressed as percentage of quiet sleep coincidence (C1F), of activity state coincidence (C2-4F) and of no coincidence (NOC). Flow velocimetry waveforms were recorded from the uterine artery, UA and fetal middle cerebral artery (MCA). RESULTS: Mean S100B protein levels in umbilical plasma were significantly higher in the six SFD infants with abnormal prenatal Doppler findings (3.31 +/- 0.65 microg/l) than in SFD infants with normal Doppler findings (1.56 +/- 0.35 microg/l) and in controls (1.23 +/- 0.43 microg/l). Similarly in these fetuses NOC was higher and C2F significantly lower (p < 0.05), but there was no significant difference in C1F. S100B concentrations were correlated with the UA pulsatility index (PI) (r = 0.78, p < 0.01), with the MCA PI (r = -0.78, p < 0.01) and with the UA PI/MCA PI ratio (r = 0.80, p < 0.01). Also, NOC and C2F percentages were correlated with the UA PI (r = 0.61, p < 0.01 and r = -0.61, p < 0.01, respectively), with the MCAPI (r = -0.72, p < 0.001 and r = 0.66, p < 0.01, respectively), and with the UA PI/MCA PI ratio (r = 0.60, p < 0.01 and r = -0.54, p < 0.05, respectively). NOC was also correlated with S100B protein (r = 0.48, p < 0.05); the correlation of S100B protein and C2F almost reached significance (r = -0.47, p < 0.05). CONCLUSIONS: This study provides evidence of a relationship between a biochemical marker of brain development and/or integrity and the development of fetal behavioral states, offering additional information on brain maturation in normal and high-risk pregnancies.

Effect of L-arginine load on platelet aggregation: a comparison between normotensive and preeclamptic pregnant women.

BACKGROUND: In the present study we hypothesized that a derangement of the L-arginine-nitric oxide system could be involved in the development of the hypercoagulative status found during preeclampsia. In order to verify such hypothesis we have compared the effects of nitric oxide substrate, L-arginine on platelet aggregation. Moreover, we have also measured the L-citrulline plasma levels as a stochiometric metabolite resulting from the conversion L-arginine to nitric oxide. METHODS: Nine preeclamptic women and 11 normotensive pregnant women were enrolled for the study. Subjects were infused with saline and with 30gr of L-arginine. Blood samples were drawn during the saline infusion (30 min), during L-arginine administration (30 min) and 30 min thereafter. ADP and collagen-induced platelet aggregation was studied as per Born with a dual-channel aggregometer (Chrono-Log, Mascia Brunelli, Italy) and L-citrulline was measured by HPLC. RESULTS: In normotensive women the infusion significantly decreased ADP and collagen-induced aggregation after 15 minutes of L-arginine load; whereas no effects were observed in preeclamptic women. Similarly in normotensive but not in preeclamptic women L-arginine load was able to increase L-citrulline plasma levels. CONCLUSIONS: In normotensive women the in vivo L-arginine administration decreases platelet aggregation with an increase of L-citrulline plasma levels. On the contrary, no effects were observed in preeclamptic women. These findings confirm that a hypercoagulative status characterizes preeclampsia and that such phenomenon could be explained by a derangement of the platelet L-arginine-nitric oxide pathway.

Dietary nucleotide supplementation raises erythrocyte 2, 3-diphosphoglycerate concentration in neonatal rats.

The present study was designed to test if dietary intake of nucleotides increases erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in neonatal rats. To this end, rat pups were fed a nucleotide-supplemented formula (S, n = 14) from d 9 until d 16 after birth. The results were compared with those obtained from a group of breast-fed pups (C, n = 14) and a group of pups artificially fed with nucleotide-free formula (NS, n = 14). Neonatal weight, 2,3-DPG concentration, hematocrit (Hct) and hemoglobin concentration (Hb) were determined before the experiment (d 9) and after 7 d of treatment (d 16). In all groups, 2,3-DPG concentration was greater at d 16 than d 9, and the increase was greater in the S group than in the NS group. Alterations in neonatal weight, Hct and Hb concentration did not differ among the groups. On d 16 the 2, 3-DPG/Hb ratio, reflecting the affinity of hemoglobin for oxygen, was significantly higher in the C and S groups than in the NS group. We conclude that in neonatal rats, dietary nucleotides increase erythrocyte 2,3-DPG concentration. Studies need to be conducted in humans to assess the effect of this increase on both neonatal peripheral hemodynamics and metabolism in this species.

Pregnancy-induced hypertension, antihypertensive drugs and the development of fetal behavioural states.

In 21 pregnancies complicated by pregnancy-induced hypertension (PIH) which was treated by antihypertensive drugs (labetalol, nifedipine), fetal behavioural recordings (quiet state, C1F; active state, C2F; no coincidence, NOC) and Doppler measurements of blood flow velocity in the umbilical artery (UA) (resistance index, RI) were made on two occasions (27-32 and 33-36 weeks of gestation). Data were compared to those of a control group of normally grown fetuses (n = 96); in 15 cases we were able to match fetuses from the study group for age (+/- 1 week) and weight (+/- 150 g) at birth with fetales from a control group. It was the aim of this study to investigate if there are disturbances in the development of fetal behavioural states and if possible disturbances are due to poor fetal growth or to antihypertensive therapy. Our results show that in PIH treated by antihypertensive drugs, there are disturbances in the development of fetal behavioural states with higher percentages of NOC and C1F, lower percentages of C2F, and higher UA RI values. These disturbances are mainly due to coexisting placental impairment and poor fetal growth rather than to nifedipine or labetalol therapy, although these drugs may cause some redistribution of states.

Behavioural development and Doppler velocimetry in relation to perinatal outcome in small for dates fetuses.

Twenty-two small for dates (SFD) fetuses and 96 fetuses from uncomplicated pregnancies were monitored on two occasions between 27 and 32 weeks and the second time between 33 and 36 weeks of gestation by studying the development of behavioural states (coincidence 1F and 2F; no coincidence) and umbilical artery Doppler waveform patterns (UA; Resistance Index, RI). Data were related to neurological outcome at 8 months after birth. The purpose of this study was to investigate if the development of behavioural state is disturbed in SFD fetuses and if SFD fetuses who needed to be delivered early and/or had abnormal neurological outcome showed different state development and RI than SFD fetuses delivered later in pregnancy or with normal neurological outcome. Finally, we studied if there was a relationship between state development and RI. At 27-32 weeks of gestation the percentage of coincidence 2F (C2F%) was lower and the percentage of coincidence 1F (C1F%) and no coincidence (NOC%) were higher in the SFD fetuses than in the control group. At 33-36 weeks C2F% was lower and NOC% was higher but not statistically different (P = 0.2 and P = 0.07, respectively). SFD fetuses who needed to be delivered early had poorer state development than SFD fetuses at lower risk and infants who were abnormal at 8 months of life showed a higher C1F% and lower C2F% at 27-32 weeks. There were significant correlations between RI on the one hand and NOC% (r = 0.62) and C2F% (r = -0.48) on the other hand at 27-32 weeks in the subgroup with abnormal neurological outcome. In conclusion, in SFD fetuses there are disturbances in the development of behavioural states as well in the distribution of the periods of coincidence (with a decrease in C2F% and an increase in C1F%). Poorest state development is present in SFD fetuses at highest risk and in this group there appears to be a significant relationship between the degree of utero-placental insufficiency (RI) and disturbances in behavioural development.

Doppler velocimetry and behavioural state development in relation to perinatal outcome in pregnancies complicated by gestational diabetes.

Seventy-one pregnancies complicated by gestational diabetes and 100 healthy pregnancies were monitored on two occasions (between 27th-32nd and 33rd-36th week of gestation) by behavioural state analysis (1F coincidence; 2F coincidence) and umbilical artery Doppler velocimetry (UA) (Resistance Index, RI). The purpose of our study was to determine if the development of behavioural states and Doppler velocimetry: (1) differ between normal and gestational diabetic cases; (2) in gestational diabetic cases, are they related to the degree of abnormality of the maternal oral glucose tolerance test (OGTT)?; and (3) are they predictors of perinatal outcome? (i.e. emergency caesarean section; low Apgar scores; respiratory distress syndrome; neonatal hypoglycaemia and neurological abnormality in the neonate and/or at 4 months of age). Our findings suggest that: (1) results on behavioral state development and Doppler velocimetry were significantly different in gestational diabetic cases; (2) infants of women with gestational diabetes who are neurologically abnormal during the newborn period, had a poor development of coincidence 2F during fetal life and had neonatal hypoglycaemia more often than infants with a normal neurological outcome; (3) in cases with abnormal neurological outcome, the maternal diabetes was more severe than in those cases with normal outcome.

[Osteopetrosis and renal acidosis: a new case of this rare syndrome]. / Osteopetrosi ed acidosi renale: un nuovo caso di questa rara sindrome.

The association between osteopetrosis and renal acidosis is not accidental, but represents a well-known syndrome with autosomal recessive transmission, due to carbonic anhydrase II(CA II) deficiency. The disease is extremely rare (only few reports in the literature). The diagnosis is confirmed by CA II erythrocyte assay. However, this finding is not essential when the clinical picture is complete, as in the case reported in this paper, which presents a patient with osteopetrosis, proximal tubular acidosis, intracranial calcifications, psychomotor retardation and short stature. Prenatal diagnosis will rely on the genetic study of DNA by molecular probes, since it is already well-known that the coding gene for CA II is on the long arm of chromosome 8 (8q22).

Predictors of perinatal outcome in intrauterine growth retardation: a long term study.

UNLABELLED: Fifty-three intrauterine retarded fetuses (IUGR) and seventy-five healthy pregnancies were monitored by neurobehavioural profile (quiet state or S1F and activity state or S2F percentages) and umbilical artery Doppler velocimetry (UA RI) on two occasions between the 27th-32nd and the 33rd-36th week of gestation. The aims of the present study were the following 1) to relate S1F, S2F and RI to mild and severe IUGR 2) to relate behavioural state analysis and UA Doppler velocimetry to the following perinatal outcomes: Cesarean section (CS); Preterm delivery (PD); small for gestational age (SGA); Apgar score at 1st and 5th min < 7; Respiratory Distress Syndrome (RDS); Neurological Injury (NI) (evaluated at the birth, the 4th, the 8th and the 12th month of life). 3) to establish the best predictors of perinatal outcome with these monitoring parameters by a stepwise computerized processing. Our results suggest: 1) mild IUGR, characterized by a progressive increase in peripheral vascular resistances, positive diastolic peak flow (RI: 0.72 +/- 0.01; mean +/- SD), is associated with gradual increase in S1F (12.51 +/- 2.84; mean +/- SD) and a decrease in S2F (27.51 +/- 2.81; mean +/- SD) percentages; 2) severe IUGR, characterized by zero or negative diastolic peak flow (UA RI-->1), is associated with a significant increase in S1F (21.32 +/- 12.11; mean +/- SD) and a decrease in S2F percentages (30.93 +/- 20.35; mean +/- SD). IN CONCLUSION: S1F is the best predictor of severe IUGR and significant for all the perinatal outcomes selected; S2F is the best predictor of mild IUGR and significant for SGA; UA RI is the best parameter for recognizing mild IUGR and evolution to severe IUGR.