In vitro fertilisation and use of ovulation enhancers may both influence childhood height in very low birthweight infants.

CONTEXT: Term-born children conceived by in vitro fertilisation (IVF) are reportedly taller than naturally conceived (NC) children. High levels of growth promoting hormones and epigenetic imprinting have been suggested as pathogenetic mechanisms. HYPOTHESIS: Tall stature in prematurely born IVF-conceived (IVF-C) children suggests pre- or early implantation imprinting rather than a postnatal effect. METHODS: We studied 334 very low birthweight (VLBW: birth weight <1500 g) children born prematurely during 1995-1999 and obtained their anthropometric measures at 6-10 years of age. Perinatal and neonatal data were obtained from the Israeli VLBW database. We compared IVF-C, ovulating agents conceived (OA-C) and naturally conceived (NC) groups of children with respect to their and their parents' anthropometry and their perinatal/neonatal variables. RESULTS: Childhood height standard deviation scores (SDSs) were greatest in IVF-C (-0.12 (SD 1.25); p<0.022) and insignificantly greater in OA-C (-0.37 (SD 1.02)) as compared to NC (-0.58 (SD 1.36)) children. The IVF-C and NC groups were significantly different regarding 17 parental and perinatal variables; however, multiple regression analysis including these variables showed that, as compared with NC, IVF-C children had significantly older mothers at birth with earlier follow-up during pregnancy and more multi-fetal pregnancies. CONCLUSIONS: IVF-C and to a lesser extent OA-C prematurely born children are taller than otherwise NC children. After ruling out postnatal and parental causes, we speculate that pre- or early implantation factors might have contributed to the taller stature of IVF-C children.

Neonatal lenticulostriate vasculopathy: further characterisation.

BACKGROUND: Lenticulostriate vasculopathy (LSV) is sometimes detected on routine brain ultrasonography in neonates, and is often associated with various perinatal and neonatal abnormalities. However, most reports on LSV are retrospective with no controls. OBJECTIVES: To compare the perinatal and neonatal clinical characteristics of neonates with LSV with matched controls and to summarise all published reports of LSV. DESIGN: A prospective study that summarises the clinical, laboratory, and neurosonographic data of neonates with LSV. METHODS: Of 1184 neonates admitted to the neonatal intensive care unit (NICU) during a three year period, 857 had a routine head ultrasound examination. Twenty one had LSV, and were compared with 42 matched controls with regard to gestational, perinatal, neonatal, laboratory, and neurosonographic characteristics. RESULTS: LSV was detected in 21 of the 857 (2.45%) neonates. It was bilateral in 10 of the 21 cases and located in the thalamus (n = 14) and basal ganglia (n = 7). Infants with LSV were not significantly different from matched controls in most tested variables. However, compared with the control group, the LSV group included significantly more multiple births and more disturbances in amniotic fluid volume, but less meconial amniotic fluid. In addition, the patients with LSV required fewer blood transfusions and less phototherapy. CONCLUSIONS: Except for more multiple births, neonates with LSV did not display more adverse findings than their matched controls.

Insulin in human milk: postpartum changes and effect of gestational age.

OBJECTIVE: To determine if human milk insulin (HMI) concentrations are affected by gestational age and postnatal age. DESIGN AND SETTING: An observational study carried out in a level III neonatal intensive care unit. Insulin concentrations were determined in human milk of 90 parturient mothers who delivered between 30 and 41 weeks gestation. Samples were collected on days 3 and 10 after delivery. RESULTS: HMI concentrations for mothers of preterm infants were not significantly different from those of full term infants, on either day 3 or 10 post partum. When results for all 90 mothers were pooled, regardless of gestational age, HMI concentration fell significantly from day 3 to day 10 (50.1 (34.6) v 41.1 (28.5) microU/ml; p = 0.01; mean (SD)). However, this decrease was only significant for mothers delivering at term (37-41 weeks). CONCLUSIONS: HMI concentrations were not influenced by gestational age at delivery. They decreased post partum, mainly in mothers of term infants. The postnatal changes in HMI concentrations and the effects of oral insulin on the immature intestinal mucosa warrant further investigation.

Staphylococcal scalded-skin syndrome in a very low birth weight premature infant.

Exfoliative skin diseases are rare in neonates. When caused by coagulase-positive Staphylococcus aureus, scalded-skin diseases such as staphylococcal scalded-skin syndrome (SSSS), bullous impetigo, and staphylococcal scarlet fever may develop. These diseases might cause significant complications and mortality. SSSS is caused by staphylococcal exfoliative toxins A or B, which split the granular layer of the skin, induce proteolysis, and might exhibit superantigen activities, such as epidermolysis and lymphocyte mitogenicity. We describe a 1378-g premature male infant who was born at 29 weeks' gestation and developed SSSS on day 3 of life, with no clinical signs of neonatal sepsis. After cultures from the lesion and bloodstream were obtained, intravenous cloxacillin therapy was started. Infection control measures were implemented instantly and included isolation of the infected infant, personnel handwashing with hexachlorophene, and placement of exposed neonates into a cohort. The initial lesion expanded and additional lesions appeared, but 12 hours after initiation of antibacterial therapy, the lesions ceased to proliferate. Cultures from scalded-skin lesions grew coagulase-positive Staphylococcus aureus, whereas the bloodstream culture was sterile. The lesions resolved completely within 6 days, and the infant's subsequent course was uneventful. No similar skin lesions were noticed in other infants in the neonatal intensive care unit. We discuss recent advances in understanding the pathogenesis of neonatal SSSS, highlight the importance of early diagnosis and treatment, and stress the need for new adjunctive therapies for this disease.

Transient mega-esophagus in a neonate with congenital diaphragmatic hernia.

Esophageal dilatation (ED) in neonates is rare. In the present case, ED was detected in a chest radiograph following repair of congenital diaphragmatic hernia (CDH) in a term neonate. A roentgenographic swallow study on the seventh day of life demonstrated ED and a sub-diaphragmatic stomach. The infant thrived adequately on enteral feeding. A swallow study on the twentieth day of life showed a normal-width esophagus with gastroesophageal reflux and small hiatus hernia. The longstanding herniated stomach in the fetus apparently caused kinking, edema, and obstruction of the gastroesophageal junction. This led to a significant ED and concealment of gastroesophageal reflux. We aim to arouse awareness about the occurrence of ED with CDH, and about its benign course under conservative management.

Congenital subependymal pseudocysts: own data and meta-analysis of the literature.

BACKGROUND: Congenital subependymal pseudocysts are incidental findings that are found in 0.5-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC. OBJECTIVE: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC. METHODS: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases. RESULTS: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC; 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infections, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handicap. CONCLUSIONS: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.

Caudal dysplasia sequence with penile enlargement: case report and a potential pathogenic hypothesis.

The clinical spectrum of caudal dysplasia sequence (CDS) is noted for its diversity. The origin of CDS remains unknown, though poorly controlled gestational diabetes has been implicated in some cases. Here we describe the case of a newborn with CDS associated with penile enlargement (PE). The main anomalies included anal atresia, agenesis of the kidneys and of the sacrococcygeal vertebrae, dysgenesis of lumbar vertebrae, and bilateral cryptorchidism. Penile enlargement (7 cm), a rather unusual finding, has so far not been reported in association with CDS. Chromosomal analysis failed, and the neonate died 30 min after birth. Comparative genomic hybridization analysis using stored DNA showed a balanced normal male DNA content, which negates chromosomal losses or gains as a cause of CDS and/or PE. PE due to virilizing-type adrenal hyperplasia, caused by common mutations in the genes encoding for the adrenal enzymes 21-hydroxylase and 11-hydroxylase, was ruled out. We report on a previously unpublished case of the coexistence of PE and severe CDS and propose a possible pathogenetic hypothesis of this association.

Review of 49 neonates with acquired fungal sepsis: further characterization.

BACKGROUND: Neonatal acquired fungal sepsis (AFS) is a risky condition that warrants every effort for early diagnosis and management. METHODS: We retrospectively reviewed the medical charts of all 4445 neonatal intensive care unit (NICU) admissions in the past 10 years and detected 49 neonates with AFS. We then compared their data with those of 49 matched control neonates who did not have AFS. The following details were collected: gestational, perinatal and neonatal courses; bacterial sepsis; antibacterial therapy; laboratory and imaging investigations; and antifungal therapy and its complications. RESULTS: The incidence of AFS was.4 to 2 cases per 1000 live-births and 3.8% to 12.9% of very low birth weight (VLBW) infants. Compared with 1989 through 1992, between 1993 and 1995 the rate of AFS in VLBW neonates significantly increased (3. 8%-5.6% --> 9.6%-12.9%), along with a significant increase of NICU admission rate (369-410 --> 496-510 admissions/year). Compared with controls, AFS neonates had significantly longer hospitalizations, higher rates of mechanical ventilation, umbilical vein catheterization, and previous treatment with broad-spectrum antibacterial agents (amikacin, vancomycin, ceftazidime, or imipenem). At the onset of AFS, 42.8% of patients had hyperthermia and 40.9% had normal white blood cell count. Causative fungi were as follows: Candida albicans-42.8% of cases, Candida parapsilosis-26.5%, and Candida tropicalis-20.4%. Fungal dissemination was rare, complications of antifungal therapy were infrequent, and no deaths occurred. CONCLUSIONS: First, non-albicans Candida have become more frequent in neonatal AFS. Second, mechanical ventilation and antibacterial agents are significant risk factors for AFS. Third, hyperthermia is a frequent presenting sign of AFS. Fourth, a normal white blood cell count does not rule out AFS. Fifth, meningeal involvement in neonatal AFS should be ruled out before initiation of antifungal therapy. Sixth, the policy of empiric antifungal therapy for AFS should be considered on an individual NICU basis.newborn infant, fungal sepsis, clinical signs, risk factors.

Neonatal transverse cerebellar diameter in normal and growth-restricted infants.

OBJECTIVE: To assess the transverse cerebellar diameter (TCD) in preterm and term neonates with normal growth or growth restriction. METHODS: TCD was sonographically measured after birth in 404 neonates born between 23 and 42 weeks of gestation. The study included two groups: Group 1: 334 appropriately grown for gestational age (AGA) neonates (both birthweight (BW) and head circumference (HC) were between the 3rd and 97th centiles), which were subdivided into two subgroups according to the HC measurements. Group 2: 70 small for gestational age (SGA) neonates (BW <3rd centile), were further divided into three subgroups according to HC measurements. RESULTS: In Group 1 of AGA neonates, a linear growth function was observed between the TCD and GA (R = 0.914, P < 0.00001, TCD = 0.279 + 0.142 X GA), and between TCD and HC (R = 0.886, P < 0.00001, TCD = -0.333 + 1.777 X HC). The percentage of neonates with normal TCD (> or =10th centile) was more than 85% of the AGA and asymmetric SGA subgroups, and 60.7% of the microcephalic SGA subgroup (P < 0.02). CONCLUSIONS: This study provides normative data of neonatal TCD across gestational age. TCD measurement via sonography is a new adjunctive criterion for objectively assessing gestational age in infants when a precise determination of gestational age is necessary. This is very important since utility of the TCD is effective for both AGA and asymmetric SGA infants.

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.

Congenital hypothyroidism and nonimmune hydrops fetalis: associated?

Hydrops fetalis (HF) consists of an abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Almost all observed cases of HF are of the nonimmune type, the causes of which remain undetermined in 15% of patients. We report a newborn infant with nonimmune hydrops fetalis (NIHF) and congenital hypothyroidism. The infant's mother was healthy and there were no malformations of the placenta or umbilical cord. The infant did not show any structural abnormalities of his central nervous, cardiovascular, gastrointestinal, or urinary tract systems, and there was no evidence of anemia, infectious disease, or inborn error of metabolism. An immune-based process was unlikely, because the blood group of the mother and infant was A-positive and results of an indirect Coombs test in the mother and a direct Coombs test in the infant were negative. The patient's condition gradually improved with mechanical ventilation, repeated thoracocentesis, and total parenteral nutrition. By day 5 of age the skin edema, pericardial effusion, and ascites disappeared, but accumulation of significant amounts of chylous pleural fluid persisted. Because of lethargy, FT4 and thyroid-stimulating hormone levels were obtained and showed hypothyroidism. Thyroid hormone supplementation was then started, and within 4 days the infant became more vigorous and was weaned from mechanical ventilation. After 7 days, the chylothorax resolved completely as the serum thyroxine level normalized. No reaccumulation of pleural effusion was noticed. The infant started to gain weight and was discharged from the hospital at 35 days of age. A possible pathophysiologic association between congenital hypothyroidism and NIHF is discussed. NIHF may be caused by lymphatic congestion attributable to an impairment of lymphatic flow and a delayed return of lymph to the vascular compartment. There could be a possibility that because of thyroid hormone deficiency in this patient, there was reduced adrenergic stimulation of the lymphatic system. This could result in a sluggish flow of the lymph with engorgement of the lymphatic system, leakage of lymph into the pleura and the interstitial spaces, and the production of chylothorax with NIHF. Animal studies demonstrate a direct relationship between lymph flow rate or lung liquid clearance and adrenergic receptor activity in the lymphatic system. These observations support our hypothesis that deficient adrenergic activity in congenital hypothyroidism might lead to chylothorax with NIHF in the fetus. We speculate that thyroid hormone may play a role in the regulation of adrenergic receptors in the lymphatic system and lungs, thus modulating both the lymphatic flow rate and lung liquid clearance, and facilitating the resolution of chylothorax. Examination of thyroid functions should be included in the investigation of fetuses and neonates with NIHF of an obscure origin.

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.

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.

Urgent delivery, the treatment of choice in term pregnant women with extended burn injury.

Two pregnant patients at term, suffering from major burn wounds, were treated in our burn unit during the year 1995, both were delivered immediately after admission by caesarean section. One of them had smoke inhalation injury which needed mechanical ventilation, both mothers and newborns survived. In spite of low maternal carboxyhaemoglobin the fetal cord blood carboxyhaemaglobin was high, supporting an objective physiological basis for the previous empirical conclusion of early delivery in pregnant patients at term with extensive burn injury (50 per cent TBSA and more). This obvious favourable outcome highlights the importance of urgent delivery in term pregnant women suffering a major burn injury.

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.