The effects of caffeine on heart rate variability in newborns with apnea of prematurity.

OBJECTIVE: Apnea of prematurity is a common complication in premature newborns and caffeine is a widespread medication used to treat this complication. Caffeine may have adverse effects on the cardiovascular and central nervous system, yet its effects on the autonomic nervous system modulation of heart rate have not been studied in premature newborns, which was the objective of our study. STUDY DESIGN: We prospectively studied 21 premature newborns who were treated with caffeine. We analyzed heart rate variability by power spectral density and by dynamic nonlinear analyses methods. RESULT: There were no changes in heart rate, blood pressure or the autonomic nervous system tone following administration of caffeine, nor were the nonlinear dynamical properties of the system altered by caffeine. CONCLUSION: Caffeine does not have detrimental effects on heart rate variability, heart rate or blood pressure in conventional doses given to premature newborns.

Isolated hyperechogenic foci in the fetal thalamus in early pregnancy.

OBJECTIVE: To describe the sonographic features and outcome of fetuses with isolated hyperechogenic foci in the thalamic region. METHODS: A detailed sonographic survey was performed in 46,244 consecutive pregnancies. Both low- and high-risk pregnancies were included. Transvaginal examinations were performed at 14-16 weeks' gestation, while transabdominal examinations were performed after 18 weeks' gestation. RESULTS: Isolated hyperechogenic foci in the thalamic region were observed in seven fetuses. All cases were diagnosed at 14-16 weeks' gestation. Six fetuses had one hyperechogenic focus, and one fetus had two foci. The size of these foci ranged from 2-4 mm. A serologic work-up was negative in all these fetuses and their karyotype was normal. The hyperechogenic foci disappeared in mid-pregnancy in all cases, and fetuses were normal at delivery and on follow up to the age of 9 years. CONCLUSIONS: Isolated hyperechogenic foci in the thalamic region in early pregnancy are probably benign in nature.

Importance of insulin content in infant diet: suggestion for a new infant formula.

Oral insulin promotes intestinal maturation and may prevent diabetes in animal models. The aim of this study was to evaluate the concentration of insulin in human milk and in different infant formulas. Our results show that the concentration of insulin in human milk is significantly higher (60.23 +/- 41.05 microU/ml mean +/- SD) compared with cow's milk (16.32 +/- 5.98 microU/ml mean +/- SD) and that insulin is hardly detectable in infant formulas. We propose the addition of human insulin to infant formula to match its composition more closely to human milk.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Persistent intrahepatic right umbilical vein in the fetus: a benign anatomic variant.

OBJECTIVE: To evaluate outcomes of fetuses with antepartum sonographic diagnoses of persistent intrahepatic right umbilical veins. METHODS: A detailed fetal sonographic examination was done in 30,240 consecutive pregnancies at 14-26 weeks' gestation. High- and low-risk pregnancies were included and persistent right umbilical veins specifically were recorded. RESULTS: Sixty-nine fetuses had persistent intrahepatic right umbilical veins, of which 60 had no additional sonographic abnormalities, four had transient nuchal findings, and four had minor anomalies or anatomic variants. Only one of the 69 fetuses had a major anomaly (diaphragmatic hernia), and died after surgery. The remaining 68 fetuses were normal and healthy after birth. CONCLUSION: Persistent intrahepatic right umbilical vein is a fetal anatomic variant that is not rare and usually associated with a favorable outcome.

Natural history of fetal simple renal cysts detected in early pregnancy.

PURPOSE: In this 12-year prospective, longitudinal study we investigated the natural history of fetal simple renal cysts identified by ultrasonography in early pregnancy. MATERIALS AND METHOD: A detailed sonographic examination of the fetus was performed between January 1987 and June 1998 in 29,984 consecutive pregnancies at 14 to 16 weeks of gestation. Amniocenteses and chromosomal investigations were done in all cases in which a simple renal cyst was detected in the fetus. Followup sonography was done in all cases of renal cyst during pregnancy, infancy and, when indicated, childhood. RESULTS: Simple renal cysts were diagnosed at 14 to 16 weeks of gestation in 28 fetuses (1/1,100 pregnancies, 0.09%). In 25 fetuses the cysts resolved during pregnancy. In 2 fetuses the cysts remained benign but persisted postnatally and in 1 a renal cyst that was initially defined as simple was the first sign of unilateral multicystic dysplastic kidney. Except for nonseptated cystic hygroma in 1 fetus, none of the others had associated anomalies of the urinary or other organ systems and no chromosomal anomalies. Postnatal followup in all cases revealed healthy children. CONCLUSIONS: A fetal simple renal cyst can be identified by ultrasonography in early pregnancy. In the absence of associated anatomical or chromosomal abnormalities, the majority of cysts will resolve during pregnancy without any sequelae. Given the transient nature of most fetal simple renal cysts detected in early pregnancy, it is possible that these cysts represent a distinct entity within the spectrum of cystic kidney diseases.

Developmental dysplasia of the hip: a new approach to incidence.

OBJECTIVE: The controversy over the incidence of developmental dysplasia of the hip (DDH) stems mainly from an ambiguity of criteria for defining a genuinely pathologic neonatal hip. In this study, we evaluate an algorithm we devised for the treatment of DDH, for its ability to identify those neonatal hips which, if left untreated, would develop any kind of dysplasia and, therefore, are to be included in the determination of DDH incidence. METHODS: Clinical and ultrasonographic examinations for DDH were performed on 18 060 consecutive neonatal hips at 1 to 3 days of life. Newborns with skeletal deformities, neurologic/muscular disorders, and neural tube defects were excluded. Hips that featured any type of sonographic pathology were reexamined at 2 or 6 weeks, depending on the severity of the findings. Only hips in which the initial pathology was not improved or had deteriorated were treated; all others were examined periodically until the age of 12 months. RESULTS: Sonographic screening of 18 060 hips detected 1001 instances of deviation from normal, indicating a sonographic DDH incidence of 55.1 per 1000. However, only 90 hips remained abnormal and required treatment, indicating a true DDH incidence of 5 per 1000 hips. All the others evolved into normal hips, and no additional instances of DDH were found on follow-up throughout the 12 months. CONCLUSIONS: The implementation of our protocol enables us to distinguish two categories of neonatal hip pathology: one that eventually develops into a normal hip (essentially sonographic DDH); and another that will deteriorate into a hip with some kind of dysplasia, including full dislocation (true DDH). This approach seems to allow for a better-founded definition of DDH, for an appropriate determination of its incidence, for decision-making regarding treatment, and for assessment of the cost-effectiveness of screening programs for the early detection of DDH.

Isolated large fourth ventricle in early pregnancy--a possible benign transient phenomenon.

Twenty-one fetuses with an enlarged fourth ventricle were detected by ultrasound at 14-16 weeks' gestation. No other central nervous system anomalies were observed and a normal size fourth ventricle was noted in all cases on follow-up scans at 22-23 weeks' gestation. Five fetuses had associated structural anomalies: a single umbilical artery in two cases, non-septated cystic hygroma in two cases and ventricular septal defect in one fetus. All fetuses had a normal brain sonogram after delivery. Nineteen newborns who were followed up to the age of one year had no developmental problems. It is concluded that an isolated enlarged fourth ventricle might be a physiological variant in early fetal life.

Fetal mustache in early pregnancy.

OBJECTIVE: The aim of this study was to determine the incidence in an unselected population of a rod-like structure on the fetal upper lip (called a 'mustache') which we had previously observed as an incidental finding. A secondary aim was to determine whether this was associated with any abnormalities or abnormal outcomes. DESIGN: Prospective non-randomized study. SUBJECTS: Three thousand consecutive fetuses from an unselected population were scanned by one sonologist. METHOD: Transvaginal ultrasound examinations were performed at 14-16 weeks' gestation. Repeat sonographic examinations were performed at 20-22 weeks' gestation in cases where a mustache was detected, and these neonates were examined by a pediatrician after delivery. RESULTS: Seven of 3000 fetuses had a mustache-like structure on the upper lip. The 'mustache' disappeared later in gestation. No anomaly of the upper lip was detected after birth in these fetuses. CONCLUSION: A mustache-like structure on the fetal upper lip in early pregnancy probably represents a normal variant of lip development. It is likely to represent a delay in the normal process of lip fusion during embryonic life.

The importance of combined clinical and sonographic examination of instability of the neonatal hip.

A clinically unstable hip in a new-born may be an early sign of congenital dysplasia. Unless followed and treated at a young age, it can progress to a degenerative hip joint disorder with considerable functional disability in adult life. For this reason, the early diagnosis of neonatal hip instability is crucial. We present our experience with 9199 neonates examined independently by clinical and ultrasonographic techniques. Instability was diagnosed in 0.8% of the hips. Only 47% of the unstable hips were diagnosed by the initial clinical examination, in the remainder the dysplasia was recognised only by sonography. Sonographic changes were also detected on re-examination in 6% of the unstable hips following the recognition of clinical instability. It is evident that combined clinical and ultrasonographic examination significantly improves the detection rate of dysplastic hips in new-borns.

Transvaginal sonographic measurement of fetal lingual width in early pregnancy.

Our objective was to construct a nomogram of the fetal lingual size early pregnancy and to assess the size of the tongue in abnormal fetuses. The lingual width was measured by using transvaginal ultrasonography in 80 normal fetuses at 13 and 18 weeks' gestation. In addition the tongue was measured in 22 fetuses at these gestational ages who had an abnormal karyotype or oro-facial malformations. A linear relationship was found between the lingual width and gestational age in normal fetuses. The lingual size was within the normal range in cases of trisomy 13, trisomy 21 and Turner syndrome. A small tongue was observed in fetuses with micrognathia. Correlation between lingual width and gestational age was observed in early pregnancy. The relationship between the size of the tongue and oro-facial malformation needs further evaluation.

Intratracheal pulmonary ventilation in premature infants and children with intractable hypercapnia.

The feasibility of intratracheal pulmonary ventilation (ITPV) was tested in five ventilated moribund neonatal and pediatric patients with uncontrollable hypercapnia: a 2-year-old child, a 52-day-old infant, and three premature infants (29, 29, and 26 weeks gestation; 1300 g, 1100 g and 890 g birth weight, respectively). ITPV was applied for 9.5, 8, 25, 58.5, and 47.5 hr, respectively. An intratracheal catheter (Cook Critical Care, Inc., Bloomington, IN) with a reversed continuous flow of gas at its tip (away from the lungs) allowed flushing of CO2 from the proximal dead space. Marked reductions in Paco2, ranging from 37% to 71% and improvement in pH were achieved within 4-6 hr of applying ITPV. During ITPV, the mean lowest Paco2 was significantly less than the pre-ITPV Paco2 (p < 0.0017), and the mean best pH was significantly higher than the pre-ITPV pH (p < 0.015). In four patients, despite significant reductions in Paco2, there was no substantial improvement in their baseline condition (shock and severe metabolic acidosis or coma) and they were switched back to conventional ventilation. This led to worsening hypercapnia to pre-ITPV values. These four patients subsequently died. It is possible that these patients were already too ill to derive significant benefit from the technique. One premature infant survived, was successfully weaned to conventional ventilation and was eventually discharged home. ITPV can alleviate uncontrollable hypercapnia in ventilated neonatal and pediatric patients.

Ultrasound imaging of fetal neck anomalies: implications for the risk of aneuploidy and structural anomalies.

This study summarizes 24,000 transvaginal ultrasound examinations which were performed in a predominantly low-risk population at 14-16 weeks' gestation. 1254 (5.2 per cent) fetuses had a nuchal fold or a non-septated cystic hygroma. Of these fetuses, 140 (11.1 per cent) had additional structural anomalies. Cardiovascular anomalies were the most commonly detected structural malformations. Forty-three (3.4 per cent) fetuses were aneuploid. Trisomy 21 was the most common chromosomal anomaly (n = 27). Aneuploidy was significantly more common in fetuses who had a nuchal finding and an associated structural anomaly. The prevalence of nuchal fold and non-septated cystic hygroma, as well as the incidence of their associated structural anomalies, was similar. Based on these data, it is concluded that a complete ultrasonic survey of the fetus and karyotyping are advocated in fetuses with a nuchal abnormality, irrespective of maternal age or triple serum screening results.

Prenatal sonographic diagnosis of vermal agenesis.

Agenesis of the vermis as detected during gestation by ultrasonography may indicate the existence of various malformation arrays or syndromes. We report on our observations of five cases of complete vermal agenesis that were detected at 22-31 weeks of gestation. All had a vertex presentation and transvaginal sonography established the diagnosis of vermal agenesis. Two of the vermal agenesis cases had no associated anomalies outside the central nervous system (CNS). In one, the cerebellar cleft was the only abnormality present and the other also had lobar holoprosencephaly. The three remaining fetuses had trisomy 13 and featured various additional extra-CNS anomalies. The association of complete vermal agenesis and trisomy 13 has not been previously reported. Our experience with this series suggests that supplementation with vaginal fetal sonography is a valuable tool for obtaining a more accurate view of the posterior fossa whenever a cyst or a cyst-like abnormality is detected by transabdominal sonography. A finding of isolated vermal agenesis appears to mandate a careful search for additional anomalies and the performance of karyotype analysis.

Single umbilical artery--right or left? does it matter?

Ultrasonographic prenatal diagnosis of single umbilical artery (UA) is well documented, but the exact siding of the single UA and its correlation with the occurrence of other congenital malformations and the outcome of the baby remain unclear. We report our experience with 46 cases of prenatally diagnosed single UA. This is the first prospective study of a large number of consecutive pregnancies in which the side of the existing artery was identified in fetuses with a single UA. Most of the cases were identified by transvaginal sonography at 14-16 weeks' gestation. A right artery was detected in 25 fetuses (54.3 per cent), and a left artery in 21 cases (45.7 per cent). Six fetuses (13 per cent) had associated anomalies, five of them in the urinary system. No correlation was found between the type or severity of the malformations and the side of the missing (or existing) UA. In our experience, the exact location of the single UA can be reliably determined by ultrasonography from the beginning of the second trimester of pregnancy. The selection process of the missing (or existing) vessel is likely to be random, even though a right single artery was seen slightly more often.

The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers.

Microdeletions linked to deletion intervals 5 and 6 of the Y chromosome have been associated with male factor infertility. Members from at least two gene families lie in the region containing azoospermia factor (AZF), namely YRRM and DAZ. With the advent of intracytoplasmic sperm injection (ICSI), it is possible for men with severe male factor infertility to produce a child. The genetic consequences of such a procedure have been questioned. This report describes the first study of a population (32 couples) of infertile fathers and their sons born after ICSI. The objectives were firstly to determine the incidence and map location of Y chromosome microdeletions and to compare the frequencies with other population studies involving severe male factor infertility, and secondly to formulate a working hypothesis concerning developmental aetiology of Y chromosome microdeletions. The incidence of microdeletions in the ICSI population was shown to be 9.4% (within the range 9-18% reported for populations of severe male factor infertility patients). Microdeletions in two out of three affected father/son pairs mapped in the region between AZFb and AZFc and the third involved a large microdeletion in AZFb and AZFc. Of three affected father/son pairs, microdeletions were detected in the blood of one infertile propositus father and three babies. Assuming that the gonomes of the ICSI-derived babies are direct reflections of those of their fathers germ lines, it is possible that two of three infertile fathers were mosaic for intact Y and microdeleted Y chromosomes. In such cases, the developmental aetiology of the microdeletion may be due to a de-novo microdeletion arising as a post-zygotic mitotic error in the infertile propositus father, thus producing a mosaic individual who may or may not transmit the deletion to his ICSI-derived sons depending on the extent of primordial germ cell mosaicism. In one of three affected fathers, the microdeletion detected in his blood was also detected in his ICSI-derived son. In this case the de-novo event giving rise to the microdeletion may have occurred due to a post- (or pre-) meiotic error in the germ line of this father's normally fertile father (i.e. the ICSI-derived baby's grandfather).