Zika virus infection in pregnancy and adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study.

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016-23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2-22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0-52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.

Urinary catecholamines during stress and ambulatory blood pressure in children born full term but small for gestational age: a pilot study.

OBJECTIVES: Increased sympathetic activity is proposed to be a mechanism of high blood pressure in children born small for gestational age. Ambulatory blood pressure monitoring is a form of blood pressure measurement that can detect high blood pressure outside the hospital in patients with normal office blood pressure. This condition is called masked hypertension. There are limited data on association between ambulatory blood pressure and urinary catecholamines during exposure to stress in children born small for gestational age. METHODS: Nineteen children born small for gestational age and 17 healthy controls ages 6-14 years old were included. Demographic data and office blood pressure were collected. Urinary catecholamines were collected before and after exposure to stress including mathematical test and venipuncture. Afterwards, ambulatory blood pressure monitoring was performed to obtain 24-hour blood pressure profiles. RESULTS: All children had normal office blood pressure but ambulatory blood pressure monitoring revealed masked hypertension in six children born small for gestational age (32%) and two controls (11.7%). After stress, median percentage of increase in urine norepinephrine levels was greater in children born small for gestational age with masked hypertension than that of children born small for gestational age without masked hypertension (9.2 vs. -13.2 µg/g creatinine, P = 0.05). There was no increase in urine norepinephrine levels in controls with masked hypertension. Among children born small for gestational age, awake SBP z-scores had significant positive correlations with pre- and post-stress urinary dopamine levels (r = 0.530, P = 0.02 and r = 0.597, P = 0.007, respectively). CONCLUSION: Masked hypertension is not uncommon in children born small for gestational age. After stress, urinary norepinephrine levels were increased in children born small for gestational age with masked hypertension.

Effects of Sustained Inflation or Positive Pressure Ventilation on the Release of Adrenomedullin in Preterm Infants with Respiratory Failure at Birth.

OBJECTIVE: Delivery room (DR) management may play an important role in the development and prevention of lung injury. Therefore, in a cohort of low birth weight infants (LBW), we investigated the effects of two different lung recruitment maneuvers, such as positive pressure ventilation (PPV) and sustained inflation (SI) on adrenomedullin (AM), a well-established lung-specific vasoactive agent. STUDY DESIGN: This is a prospective case-control randomized study in 44 LBW infants spontaneously breathing with respiratory failure at birth requiring respiratory support. LBW were randomized to receive PPV (n = 22) or SI (n = 22) support. AM was measured from blood in samples collected at birth from arterial artery (BLT0) and at 1-hour (BLT1) and at 24-hour (BLT2) from peripheral venous site. AM assessment in urine samples was performed at 1-hour (URT1) and at 24-hour (URT2). RESULTS: No significant differences in AM (p > 0.05) blood (T0-T2) and urine (T1, T2) levels were observed between groups. CONCLUSION: The present data, showing the absence of any differences in AM blood and urine levels, suggest that PPV and SI are both feasible and equally effective DR maneuvers. The findings open the way to further studies evaluating the effects of PPV and SI on short-/long-term respiratory outcome through biomarkers assessment.

Does Pasteurized Donor Human Milk Efficiently Protect Preterm Infants Against Oxidative Stress?

Pasteurized donor human milk (DHM) is the preferred alternative for infant nutrition when own mother's milk (OMM) is unavailable. Whether DHM is an efficient means for protecting preterm infants from oxidative stress remains unknown. We quantified a panel of oxidative stress biomarkers in urine samples from preterm infants (≤32 weeks of gestation and a birth weight ≤1500 g) receiving ≥80% of feeding volume as either DHM or OMM. The noninvasive in vivo assessment of oxidative stress showed no statistically significant difference between both groups at the time when full enteral nutrition (150 mL/kg body weight) was achieved and until hospital discharge. In addition, the changes of urinary biomarker levels with time were assessed. This is the first longitudinal study on oxidative stress levels in preterm infants fed with DHM in comparison with OMM. There is no statistically significant difference in urinary oxidative stress levels of preterm infants from both groups indicating that despite the effects of pasteurization, DHM is a valid alternative when OMM is not available. Based on the results, we raise the hypothesis that pasteurized DHM protects preterm infants from oxidative stress as good as OMM, and consequently, its use could prevent oxidative stress-related diseases. Antioxid. Redox Signal. 31, 791-799.

Birth weight [corrected] and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study.

Low birth weight (BWT) may contribute to kidney disease and could explain some of the variance in the development of early diabetic kidney disease. This hypothesis was tested in the multicenter SEARCH study (3,714 youth with diabetes <20 years of age). A morning spot urine sample, laboratory and anthropometric data, and a medical history were obtained. Elevated albumin to creatinine ratio (ACR) was defined as > or =30 mcg albumin/mg creatinine, and BWT was categorized as low (<2,500 g), reference (2,500-4,000 g), or high (>4,000 g). The relationship of BWT to elevated ACR was analyzed using multiple logistic regression. In youth with diabetes, the prevalence of elevated ACR was 12.6% in those with low BWT, 9.7% in those with reference BWT, and 8.9% in those with high BWT. BWT category was not significantly associated with elevated ACR (p = 0.23). Those with diabetes duration >18 months (2,032) had the following association of BWT category with elevated ACR [odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.00-2.69, p = 0.0503] for low BWT compared with reference BWT. Whereas low BWT may be a factor in kidney disease, little evidence was found of a relationship between low BWT and elevated ACR in this study population of youth with diabetes.

Increased catecholamines and heart rate in children with low birth weight: perinatal contributions to sympathoadrenal overactivity.

BACKGROUND: Low birth weight is associated with cardiovascular disease. The underlying mechanisms are unknown. We hypothesized that perinatal stress alters autonomic regulation of the cardiovascular system. In this study, catecholamines, heart rate (HR) and blood pressure (BP) were measured in healthy children with low birth weight. METHODS: This clinical study included 105 children (mean age 9.6 years) in three groups; born at term with normal birth weight (controls, n=37), born at term but small for gestational age (SGA, n=29) and born preterm (Preterm, n=39). Dopamine, adrenaline and noradrenaline were determined in urine. HR and BP were measured at rest, during an orthostatic test and after a mathematical mental stress test. RESULTS: Children in the Preterm and SGA groups excreted higher levels of catecholamines when compared with controls. HR (mean [SD] values) were higher at rest and after mental stress in Preterm (at rest 76 [9] and after mental stress 82 [12] min(-1)) and in SGA (79 [8] and 82 [10]) when compared with controls (70 [9] and 75 [9]). HR correlated with urinary catecholamines (r=0.24-0.27, P<0.05). Blood pressures measured at rest, during orthostatic testing and after mental stress did not differ between the groups. CONCLUSIONS: Preterm birth and fetal growth restriction are associated with increased sympathoadrenal activity in childhood, as indicated by stress-induced increases in HR and urinary catecholamines. These findings suggest that the cardiovascular control is differently programmed in these children with possibly higher risk of developing hypertension in adulthood.

Oxidative stress in pregnant women and birth weight reduction.

The purpose of this study is to evaluate the role of maternal oxidative stress in lowering neonatal birth weight. Women (N=261) with singleton pregnancy were analyzed for biomarker levels of oxidative stress after recruitment at the time of hospitalization for delivery in Korea between 2000 and 2001. Among the neonates, 247 births were full-term infants and 14 births were pre-term infants. Biomarkers measured for oxidative stress were maternal urinary 8-hydroxydeoxyguanosine (8-OH-dG) and malondialdehyde (MDA). The women with pre-term infants had higher concentrations of urinary 8-OH-dG and MDA than those with full-term babies. The concentrations of maternal urinary 8-OH-dG and MDA were inversely associated with birth weight of full-term deliveries after adjusting for potential confounders including maternal age, body mass index, dietary intake, alcohol consumption, smoking exposure, occupational status, and neonatal sex (P<0.05). This study demonstrates that increase of 8-OH-dG and MDA concentrations in urine of pregnant women were associated with reduced birth weight in full-term deliveries.

Oxidative stress in very low birth weight infants as measured by urinary 8-OHdG.

Very low birth weight (VLBW) infants can be subjected to oxidative stress in the course of intensive care. We measured 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative stress, and estimated the degree of oxidative stress in such infants. We also examined if the administered oxygen was related to oxidative stress. Urine samples of 50 Japanese VLBW infants [birth weights: 956.3+/-277.6g, and gestational ages: 28.0+/-2.6 weeks (mean +/- SD)] were collected on various postnatal days and 8-OHdG levels were determined using an ELISA kit. Sixteen term infants served as normal controls. As body weights at sampling increased, the average levels of urinary 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants under 1000g, 29.5+/-16.4 micromol/mol creatinine (n = 24); 1000-1500g, 23.8+/-14.9 (n = 12); over 1500g, 16.1+/-8.5 (n = 14); and control, 10.9+/-7.2 (n = 16). Significant differences were found between <1000g group and > or = 1500g group (p = 0.0030), <1000g group and control (p < 0.0001), and 1000-1500g group and control (p = 0.0108). Also as postconceptional age at sampling increased, the average levels of 8-OHdG decreased. 8-Hydroxydeoxyguanosine levels were: infants before 252 days (36 weeks) of postconception: 27.4+/-15.5 micromol/mol creatinine (n = 34); after 252 days, 18.2+/-12.5 (n = 16). Differences between <252 days group and control (p < 0.0001), and <252 days group and > or = 252 days groups (p = 0.0253) were statistically significant. Among the three groups based on ambient oxygen concentration (21%, 22-29%, and > or = 30%) there was no significant difference (p = 0.417). The more premature the infants were, the more intense was the oxidative stress, hence, it is the prematurity rather than the administered oxygen which causes oxidative stress in VLBW infants. Drury et al. ["Urinary 8-hydroxydeoxyguanosine in infants and children" Free Radic. Res. 28 (1998) 423-4281 measured urinary 8-OHdG of 28 infants (24-40 weeks gestation) and found no gestation or birthweight related differences. This discrepancy seemed to be because of difference in birth weights and sampling period of the subjects.

Urinary nitrite excretion in low birth weight neonates with systemic inflammatory response syndrome.

Increased nitric oxide (NO) levels are thought to play an important role in the pathophysiology of the systemic inflammatory response syndrome (SIRS) which is caused by disseminated vascular endothelial damage. Clinical studies have shown that urinary nitrite (NO2-) and nitrate (NO3-) excretions can be utilized as indexes of NO formation. The SIRS and NO relationship was investigated in 15 neonates with SIRS, gestational age 32.5 +/- 4.4 weeks and weight 1,737 +/- 753 g. The control group comprised 18 neonates with a gestational age of 32.8 +/- 3.5 weeks and a weight of 1,778 +/- 538 g. There was no significant difference in birth weights and gestational ages between the two groups (p > 0.05 and p > 0.05). The urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. The mean urinary nitrite levels in the control group neonates were found to be 4.22 +/- 1.8 micromol/mmol creatinine on the 1st day, 4.09 +/- 2.28 on the 2nd, 3.62 +/- 1.6 on the 3rd, and 4.01 +/- 1.12 micromol/mmol creatinine on the 7th day. There were no statistically significant differences between these levels (p > 0.05). We determined urinary levels of nitrite in neonates in the study group within the first 24 h of SIRS symptoms and found these levels (18.35 +/- 11.16 micromol nitrite/mmol creatinine) to be elevated as compared with those of the control subjects on the 7th day of life (p < 0.0005). In conclusion, urinary nitrite excretion is significantly elevated in neonates with SIRS due to septic events, and these results suggest that NO might play a part in SIRS.

La fracción excretada de potasio en neonatos pretérmino. ¿Es de utilidad en la práctica clínica? / The excreted fraction of potassium in neonates preterm . She is fof utility in the clinical practice?

Se estudiaron 110 recién nacidos (RN) de pretérmino para: 1 determinar el valor normal de la fracción excretada de potacio (FeK), 2. establecer si había correlación con la fracción excretada de sodio (FeNa) y 3. determinar su probable utilidad en el RN prematuro. Ninguno de ellos tenían datos clínicos de insuficiencia renal y su creatinina sérica era normal. La FeK varió de 0.29 a 81.12 por ciento con un promedio de 11.5 ñ 10.5 y con una moda de 10 por ciento. La edad gestacional osciló de 28 a 36, con un promedio de 34 ñ 1.8 demanas, el peso fue desde 725 a 2,475, con un promedio de 1,834 ñ 370 gramos. El valor de la FeNa varió de 0.01 a 4 (sólo en un caso pasó de 2.98 por ciento) con un promedio de 0.5 ñ 0.62 por ciento. Existió correlación entre Fek y FeNa con una r de 0.51 y p < 0.001. Se concluye que la FeK puede ser de utilidad en el RN prematuro de 28 a 36 semanas para evaluar su función renal. Aunque se registró un valor de 82 por ciento es conveniente hacer estudios en RN prematuros con y sin alteraciones renales para definir los límites de normalidad

Elevated urinary leukotriene E4 in chronic lung disease of extreme prematurity.

We determined if pulmonary peptidoleukotrienes contribute to the pathogenesis of chronic lung disease of extreme prematurity (CLD) by measuring urinary leukotriene E4 (uLTE4). Study patients had a birth weight < 1000 g and were about 28 d old when they were classified as normal control subjects (n = 8) or as having CLD (n = 26, abnormal chest X-ray, supplemental O2 requirement +/- ventilator). Urinary LTE4 levels were significantly elevated in CLD compared with the control group (288 +/- 92 versus 35 +/- 10 pg/mg creatinine, mean +/- SE, p < 0.05). Ventilator-dependent CLD patients, who required dexamethasone and had demonstrated uLTE4 levels above the normal range, needed significantly higher peak inspiratory pressures (20 +/- 1 cm H2O versus 15 +/- 1 cm H2O) than similar patients with uLTE4 in the normal range, and the former group had a significant reduction in uLTE4 in the first 5 d of dexamethasone therapy (626 +/- 198 to 451 +/- 176 pg/mg Cr) as ventilatory support was reduced. We conclude that peptidoleukotriene production is activated in patients with CLD (and no other detectable organ dysfunction) to pathophysiologic levels described in adults with acute asthma. Prospective studies focused on infants dependent on high levels of ventilatory support may provide insights into the role of leukotriene synthesis inhibitors or receptor antagonists in the treatment of CLD.

Fracción excretada de sodio en el recién nacido de pretérmino con creatinina sérica normal / Fractional sodium excretion in preterm neonates with normal plasma creatinine

El propósito de este trabajo prospectivo fue determinar el valor normal de la fracción excretada de sodio (FENa) en el recién nacido (RN) de pretérmino, debido a que en la literatura existen controversias en sus resultados, lo que la ha hecho poco útil en este tipo de pacientes. Por ello se estudiaron 110 RN de pretérmino de enero a noviembre de 1993; 70 fueron masculinos y 40 femeninos, sin datos clínicos de insuficiencia renal y con creatinina sérica normal. La FENa varió de 0.01 a 4 por ciento (este último dato se dio únicamente en un sólo paciente, en los restantes no pasó de 2.98 por ciento), con un promedio de 0.5ñ0.62 por ciento, una mediana de 0.28 por ciento y una moda de 0.12 por ciento. La edad gestacional varió de 28 a 36 semanas con un promedio de 34ñ1.8 semanas. El peso varió de 725 a 2,475 g con un promedio de 1,834ñ370 g, con una moda de 1,750 g. No hubo diferencia estadísticamente significativa de la FENa, sodio urinario, sodio sérico, creatinina urinaria, cratinina sérica entre los pacientes con edades comprendidas entre la primera, segunda, tercera y cuarta semanas de vida extrauterina. Tampoco hubo diferencia significativa entre la FENa de pacientes de 30 semanas o menos y la FENa de los mayores de esa edad gestacional. Se concluye que la FENa es un parámetro útil para evaluar la función renal en el RN de pretérmino de 28 a 36 semanas de edad gestacional pudiéndose tomar como valores hasta 3 por ciento

Calciuria and aminoaciduria in very low birth weight infants fed a high-mineral premature formula with varying levels of protein.

To assess the influence of protein intake on renal excretion of calcium and amino acids and on bone mineralization in preterm infants, we randomly selected within weight group strata 27 infants who weighed < 1500 gm at birth (nine per group) to be fed a high-mineral (calcium, 940 mg/L; phosphorus, 470 mg/L) premature formula with one of the following protein contents: formula A, 3.0 gm/100 kcal; formula B, 2.7 gm/100 kcal; and formula C, 2.2 gm/100 kcal. Mean (+/- SD) daily weight gain was greater in infants receiving the higher protein intakes for the first 30 days (formula A, 24.8 +/- 5.1 gm; formula B, 20.5 +/- 3.8 gm; formula C, 16.2 +/- 5.9 gm (analysis of variance: p < 0.01; C < A, p < 0.05)). Bone mineral content did not differ at any time point, and all groups had a high prevalence of generalized aminoaciduria (4 weeks: formula A, 56%; formula B, 71%; formula C, 75%). Urinary calcium corrected for creatinine (in milligrams per milligram) increased as protein content decreased (2 weeks: formula A, 0.16 +/- 0.10; formula B, 0.20 +/- 013; formula C, 0.44 +/- 0.33 (C > A, C > B, p < 0.05); 4 weeks: formula A, 0.23 +/- 0.15; formula B,0.34 +/- 0.47; formula C, 0.49 +/- 0.22 (C > A, p < 0.01). We conclude that the high mineral content and other components of premature formulas result in a higher growth rate and may increase protein requirements. Failure to meet protein requirements may result in underutilization of absorbed calcium and increased renal excretion of calcium. In preterm infants, higher protein intake probably supports rather than jeopardizes bone mineral accretion, and reduces rather then increases calciuria.

Maternal lactoferrin in the urine of preterm infants. Evidence for retention of structure and function.

Intact (i.e., 78-kDa) lactoferrin has been purified from the urine of preterm infants fed human milk. The maternal origin of this lactoferrin, and the integrity of its primary structure have been documented. Computer analyses of the circular dichroism spectra revealed a composite secondary structure for the urinary lactoferrin that was indistinguishable from that of purified human milk lactoferrin and similar to that observed in the crystal structure. Intact function was suggested by iron binding; an approximate 2:1 molar ratio of iron to lactoferrin was confirmed. Thus, maternal lactoferrin is absorbed intact by the preterm infant and appears to remain structurally and functionally intact within the circulatory system and during urinary excretion. It is possible, therefore, that maternal lactoferrin has an immunoregulatory influence in newborn infants fed human milk.

Decreased growth rate of low-birth-weight infants with prolonged maximum renal acid stimulation.

In a prospective randomized study, the urine pH of 170 premature and small-for-gestational-age (SGA) newborns was routinely screened to detect patients with spontaneously developing maximum renal acid stimulation, an obligatory early stage in the development of late metabolic acidosis. Nitrogen assimilation was evaluated from the ratio of urinary nitrogen excretion and intake. Forty-two premature infants and 10 SGA prematures and newborns after intensive care therapy with body weights greater than 1.5 kg and 25 prematures (including 7 SGA infants) with body weights less than 1.5 kg, spontaneously showed urine pH values below 5.4 on two consecutive days, suggesting maximum renal acid stimulation. These patients were randomly given either oral alkali therapy with sodium bicarbonate 2 mmol/kg/day or no therapy for a period of seven days. In both groups, urine pH was controlled daily. Patients in the control group without alkali therapy and with urine pH values less than 5.4 for seven days showed a significant decrease in weight gain and a tendency to decreased nitrogen assimilation. We assume that a regular check of urine pH in low-birth-weight infants is a useful non-invasive method of detecting patients in the early stages of development of late metabolic acidosis, i.e. in the stage of "incipient late metabolic acidosis". This would provide the possibility of starting early effective therapy and thereby reduce the mean duration of admission to neonatal wards.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of parenteral calcium and phosphorus therapy on mineral retention and bone mineral content in very low birth weight infants.

HYPOTHESIS: If calcium and phosphorus are administered to very low birth weight infants in amounts larger than those currently used in standard parenteral nutrition solutions, apparent retention of calcium and phosphorus (intake minus urinary excretion) will increase and bone mineralization will improve. DESIGN: Randomized, controlled, double-blind trial. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-four very low birth weight infants (< 1.2 kg) expected to receive parenteral nutrition exclusively for approximately 3 weeks beginning 3 days after birth. INTERVENTIONS: Infants received parenteral nutrition solutions, either the standard mixture containing 1.25 mmol calcium and 1.5 mmol phosphorus per deciliter (group STAND: n = 12, birth weight 921 +/- 171 gm, gestational age 27 +/- 2 weeks (mean +/- SD)) or 1.7 mmol calcium and 2.0 mmol phosphorus per deciliter (group HIGH: n = 12, 857 +/- 180 gm, 27 +/- 2 weeks). MAIN OUTCOME MEASURES: Intake, urinary excretion, and apparent retention of calcium, phosphorus, and magnesium every 3 days during parenteral nutrition therapy. Serum indexes of mineral status twice during therapy. Bone mineral content of the distal segment of the left radius at 1, 4, 8, and 26 weeks. RESULTS: Apparent calcium retention (1.2 +/- 0.2 vs 1.6 +/- 0.2 mmol.kg-1.d-1) and phosphorus retention (1.4 +/- 0.2 vs 1.8 +/- 0.4 mmol.kg-1.d-1) differed significantly (p < 0.01) between groups STAND and HIGH, respectively; neither changed with the duration of parenteral nutrition therapy. Serum calcium, magnesium, parathyroid hormone, 25-hydroxyvitamin D, and osteocalcin concentrations were similar in both groups. Serum phosphorus concentration was significantly higher in group HIGH than in group STAND (p = 0.025). The absolute bone mineral content and the rate of increase in bone mineral content between 1 and 4, 1 and 8, and 1 and 26 weeks were significantly greater in group HIGH than in group STAND. CONCLUSIONS: Increased parenteral intakes of calcium and phosphorus resulted in greater retention of these minerals during parenteral nutrition therapy and in greater bone mineral content after therapy.

Urinary nitrite excretion in premature infants: effects of transfusion or indomethacin.

Urinary nitrite excretion, an index of L-arginine-dependent nitric oxide formation, was quantified daily for two weeks, in very low-birth-weight (< 1500 g) premature infants. A transient 52% reduction in nitrite excretion was noted on the day of transfusions (54 +/- 10 versus 26 +/- 6 mumol/mmol creatinine, before and during transfusion, respectively, n = 24, p < 0.02). Indomethacin administration in six infants was associated with a dramatic increase in nitrite excretion from a basal median value of 3 to 76 mumol/mmol creatinine (p < 0.05). Nitrite excretion returned to baseline on day 3 after indomethacin administration. In two infants who received indomethacin and transfusions on the same day, the stimulatory effect on nitrite excretion by indomethacin overwhelmed any depressive effect of transfusions. These results suggest that L-arginine utilization is influenced by common therapeutic strategies in these high-risk infants.

Risk of intracranial hemorrhage and other adverse outcomes after cocaine exposure in a cohort of 323 very low birth weight infants.

We conducted a prospective cohort study of 323 consecutively born very low birth weight infants (< or = 1499 gm) to determine any association between prenatal cocaine exposure and (1) intracranial ultrasonographic abnormalities and (2) other adverse perinatal outcomes. The infants were assigned to either a cocaine-exposed group (n = 86) or a cocaine-nonexposed group (n = 146) on the basis of combined detection methods for prenatal maternal cocaine abuse including maternal history, maternal and infant urine immunoassay (Emit), and meconium analysis (high-performance liquid chromatography and gas chromatography-mass spectrometry). Ninety-one infants were not assigned because of early death before complete testing (n = 80) or missed tests (n = 11). The detected incidence of cocaine exposure in the assigned population was 37% (86/232). Meconium testing with high-performance liquid chromatography and gas chromatography-mass spectrometry was the sole means of detection in 30% (26/86) of cases. The cocaine-nonexposed infants did not differ from the cocaine-exposed infants in the incidence of intraventricular hemorrhage (36% vs 35%), grades III and IV intraventricular hemorrhage (14% vs 14%), or periventricular leukomalacia (4% vs 2%). Adverse outcomes increased by cocaine exposure were abruptio placentae (8% vs 18%; p = 0.046), surgical ligation of a patent ductus arteriosus (1% vs 7%; p = 0.02), and seizures (5% vs 17%; p = 0.004). We conclude that prenatal cocaine exposure does not increase the incidence or severity of intracranial hemorrhage or periventricular leukomalacia but does increase the risk of abruptio placentae, surgical ligation of a patent ductus arteriosus and seizures in very low birth weight infants.