D N DiSalvo

Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 ×g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; feto-placental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n= 537), or after a longer interval (n= 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born ≥1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8;p= 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9;p= 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Fluctuating Pressure-Passivity Is Common in the Cerebral Circulation of Sick Premature Infants

Cerebral blood flow pressure-passivity results when pressure autoregulation is impaired, or overwhelmed, and is thought to underlie cerebrovascular injury in the premature infant. Earlier bedside observations suggested that transient periods of cerebral pressure-passivity occurred in premature infants. However, these transient events cannot be detected reliably by intermittent static measurements of pressure autoregulation. We therefore used continuous bedside recordings of mean arterial pressure (MAP; from an indwelling arterial catheter) and cerebral perfusion [using the near-infrared spectroscopy (NIRS) Hb difference (HbD) signal) to detect cerebral pressure-passivity in the first 5 d after birth in infants with birth weight <1500 g. Because the Hb difference (HbD) signal [HbD = oxyhemoglobin (HbO2) − Hb] correlates with cerebral blood flow (CBF), we used coherence between MAP and HbD to define pressure-passivity. We measured the prevalence of pressure-passivity using a pressure-passive index (PPI), defined as the percentage of 10-min epochs with significant low-frequency coherence between the MAP and HbD signals. Pressure-passivity occurred in 87 of 90 premature infants, with a mean PPI of 20.3%. Cerebral pressure-passivity was significantly associated with low gestational age and birth weight, systemic hypotension, and maternal hemodynamic factors, but not with markers of maternal infection. Future studies using consistent serial brain imaging are needed to define the relationship between PPI and cerebrovascular injury in the sick premature infant.

Cerebellar Hemorrhage in the Preterm Infant: Ultrasonographic Findings and Risk Factors

Cerebellar hemorrhage (CBH) in premature infants is increasingly diagnosed secondary to improved neuroimaging techniques and survival of very small preterm infants. Information is limited, however, on the incidence, topography, and risk factors for CBH in the preterm infant. Objectives. To define the incidence of CBH in preterm infants diagnosed by neonatal cranial ultrasound (US), describe the sonographic features of CBH, and identify maternal and perinatal risk factors associated with this lesion. Methods. A systematic electronic database search identified preterm infants born 1998–2002 with US diagnosis of CBH. For 35 cases of CBH we double-matched (according to gestational age, gender, and year of birth) 70 preterm controls with normal cranial USs and performed detailed medical-record reviews for both patients and controls. Results. Unilateral CBH was seen in 25 patients (71%), vermian hemorrhage was seen in 7 (20%), and combined bihemispheric and vermian hemorrhage was seen in 3 (9%). Isolated CBH occurred in 8 patients (23%); the remaining infants had associated supratentorial lesions. The incidence of CBH in preterm infants weighing <750 g at birth showed significant increase over the study period. Univariate analyses identified maternal, intrapartum, and early postnatal hemodynamic risk factors; multivariate regressions indicated that emergent caesarian section, patent ductus arteriosus, and lower 5-day minimum pH independently increased the odds of CBH. Neonatal mortality and morbidity were significantly higher among patients with CBH compared with preterm controls. Conclusions. CBH is an important complication of extreme preterm birth and has been underrecognized in surviving preterm infants. Predictors of CBH seem to be multifactorial and include combined maternal, intrapartum, and early postnatal factors.

White matter disorders of prematurity: Association with intraventricular hemorrhage and ventriculomegaly

OBJECTIVES Because intraventricular hemorrhage (IVH) often precedes the development of sonographically defined white matter damage (WMD) in very preterm infants, we sought to identify the IVH characteristics that predict WMD. HYPOTHESES We evaluated variations on the null hypothesis that infants with IVH are no more likely than infants without IVH to have WMD. These variations dealt with characteristics of the IVH (presence or absence of ventriculomegaly) or characteristics of the WMD (size, localization, and laterality). METHODS A total of 1605 infants weighing 500 to 1500 g at birth between January 1991 and December 1993 underwent standardized cranial ultrasound studies with 6 standard coronal and 5 sagittal views at postnatal days 1 to 3, 7 to 10, and at 3 to 8 weeks. RESULTS A total of 129 (8%) infants had WMD, either an echodensity alone (n = 59), an echolucency alone (n = 18), or both (n = 52). In analyses that controlled for gestational age, IVH was associated with a fivefold to ninefold increased risk of WMD regardless of size, laterality, or extent of lesions (P </=.0005). Compared with infants with neither IVH nor ventriculomegaly, infants with both were at 18- to 29-fold greater risk of WMD (P </=.0005). CONCLUSIONS In this study IVH and ventriculomegaly were powerful predictors of WMD occurrence, whether small or large, unilateral or bilateral, localized or diffuse.

Ultrasonographic features and severity scoring of periventricular hemorrhagic infarction in relation to risk factors and outcome

OBJECTIVE. Early diagnosis of periventricular hemorrhagic infarction in premature infants is based on bedside neonatal cranial ultrasonography. Currently, evaluation of its morphology and evolution by cranial ultrasound relies largely on data predating major advances in perinatal care and lacks a consistent classification system for determining severity of injury. The objective of this study was to examine the ultrasonographic morphology and evolution of periventricular hemorrhagic infarction in the modern NICU and to determine the value of a cranial ultrasonography-based severity score for predicting outcome. METHODS. We retrospectively evaluated all cranial ultrasounds and medical records of 58 premature infants with periventricular hemorrhagic infarction. We assigned each subject a severity score based on extent of echodensity, unilateral versus bilateral, and presence or absence of midline shift. A neurologic examination was performed after 12 months adjusted age. RESULTS. The parenchymal echodensity of periventricular hemorrhagic infarction most often involved parietal and frontal territories and evolved into single and/or multiple cysts. One quarter of cases were bilateral, and nearly 70% were extensive. Higher severity scores were significantly associated with pulmonary hemorrhage and low bicarbonate levels and with outcomes of fatality, early neonatal seizures, and motor disability. CONCLUSIONS. Despite advances in perinatal medicine, periventricular hemorrhagic infarction remains an important complication of prematurity. Periventricular hemorrhagic infarction can be graded using a scoring system based on sonographic characteristics. Higher severity scores predict worse outcome. Such severity scoring could improve the clinicians ability to counsel parents regarding management decisions and early intervention strategies.

Current Definitions of Hypotension Do Not Predict Abnormal Cranial Ultrasound Findings in Preterm Infants

OBJECTIVE. Hypotension is a commonly treated complication of prematurity, although definitions and management guidelines vary widely. Our goal was to examine the relationship between current definitions of hypotension and early abnormal cranial ultrasound findings. METHODS. We prospectively measured mean arterial pressure in 84 infants who were ≤30 weeks’ gestational age and had umbilical arterial catheters in the first 3 days of life. Sequential 5-minute epochs of continuous mean arterial pressure recordings were assigned a mean value and a coefficient of variation. We applied to our data 3 definitions of hypotension in current clinical use and derived a hypotensive index for each definition. We examined the association between these definitions of hypotension and abnormal cranial ultrasound findings between days 5 and 10. In addition, we evaluated the effect of illness severity (Score for Neonatal Acute Physiology II) on cranial ultrasound findings. RESULTS. Acquired lesions as shown on cranial ultrasound, present in 34 (40%) infants, were not predicted by any of the standard definitions of hypotension or by mean arterial pressure variability. With hypotension defined as mean arterial pressure < 10th percentile (<33 mmHg) for our overall cohort, mean value for mean arterial pressure and hypotensive index predicted abnormal ultrasound findings but only in infants who were ≥27 weeks’ gestational age and those with lower illness severity scores. CONCLUSIONS. Hypotension as diagnosed by currently applied thresholds for preterm infants is not associated with brain injury on early cranial ultrasounds. Blood pressure management directed at these population-based thresholds alone may not prevent brain injury in this vulnerable population.

Placental Surface Cysts Detected on Sonography Histologic and Clinical Correlation

Objective. To evaluate the clinical outcome and histologic findings of pregnancies in which placental surface cysts were detected on prenatal sonography. Methods. A computerized search of our obstetric sonographic database from 1988 through 2000 identified 34 cases. Results of pathologic examinations, when performed, were obtained. Sonographic features were correlated with histologic findings and clinical parameters. Results. On review of available microscopic slides, in all cases in which the cyst was seen at pathologic examination, there was subchorionic fibrin with central cyst formation. All pregnancies resulted in live births, although intrauterine growth restriction occurred in 4 (12%) of 34. Three (11%) of 28 cases with placental pathologic findings had maternal floor infarction. Only 2 significant associations between sonographic features and postnatal findings were found. In all cases of intrauterine growth restriction, average cyst size was larger than 4.5 cm. Of 12 cysts larger than 4.5 cm, 4 (33%) had intrauterine growth restriction. Of 22 cysts smaller than 4.5 cm, there were no instances of intrauterine growth restriction (P = .01). Of 32 cases with 3 or fewer cysts, only 2 had intrauterine growth restriction, whereas in 2 cases with more than 3 cysts, both had intrauterine growth restriction (P = .01). Conclusions. Most placental surface cysts are associated with a normal pregnancy outcome. Most such cysts are related to cystic change in an area of subchorionic fibrin. Cysts larger than 4.5 cm or more than 3 in number are more frequently associated with intrauterine growth restriction.

Pilot Point-of-Care Ultrasound Curriculum at Harvard Medical School: Early Experience

Introduction Point-of-care ultrasound (POCUS) is expanding across all medical specialties. As the benefits of US technology are becoming apparent, efforts to integrate US into pre-clinical medical education are growing. Our objective was to describe our process of integrating POCUS as an educational tool into the medical school curriculum and how such efforts are perceived by students. Methods This was a pilot study to introduce ultrasonography into the Harvard Medical School curriculum to first- and second-year medical students. Didactic and hands-on sessions were introduced to first-year students during gross anatomy and to second-year students in the physical exam course. Student-perceived attitudes, understanding, and knowledge of US, and its applications to learning the physical exam, were measured by a post-assessment survey. Results All first-year anatomy students (n=176) participated in small group hands-on US sessions. In the second-year physical diagnosis course, 38 students participated in four sessions. All students (91%) agreed or strongly agreed that additional US teaching should be incorporated throughout the four-year medical school curriculum. Conclusion POCUS can effectively be integrated into the existing medical school curriculum by using didactic and small group hands-on sessions. Medical students perceived US training as valuable in understanding human anatomy and in learning physical exam skills. This innovative program demonstrates US as an additional learning modality. Future goals include expanding on this work to incorporate US education into all four years of medical school.

Role of Doppler ultrasonography in the prediction of pregnancy outcome in women with recurrent spontaneous abortion.

We prospectively studied 96 patients with a history of recurrent spontaneous abortion to determine whether the resistive index of the main uterine artery or subchorionic vessels can allow prediction of pregnancy outcome. The subchorionic RI declined progressively for a mean of 0.54 at 6 weeks to 0.42 at 13 weeks (P < 10(‐8), F‐test). No significant difference was found in subchorionic RI values between outcomes for liveborn infants versus loss. Uterine artery RI values also declined significantly through the first trimester (P < 10(‐8), F‐test). Uterine artery RI values tended to be lower in pregnancies ending in loss than in successful gestations; however, there was too much overlap for this index to be clinically useful. In conclusion, first trimester RI does not allow prediction of pregnancy outcome in patients with recurrent abortion.

Sonographically detected subarachnoid hemorrhage: an independent predictor of neonatal posthemorrhagic hydrocephalus?

Blood from an intraventricular hemorrhage (IVH) can collect in the basilar cisterns and cause ventriculomegaly and eventual need for ventriculoperitoneal (VP) shunt. We looked for sonographic evidence of subarachnoid hemorrhage (SAH) in three basal cisterns and in the Sylvian fissure of 82 infants with IVH, 30 of whom had ventriculomegaly. We found that ultrasonographically diagnosed SAH and measurement of ventricular blood volume predict ventriculomegaly and need for VP shunt.