Long-term cognitive benefits of antenatal corticosteroids for prematurely born children with cranial ultrasound abnormalities

OBJECTIVE: Previous studies have examined possible long-term effects of antenatal corticosteroids, but not by the presence of neonatal brain lesions. This study of long-term neurodevelopmental outcomes of antenatal corticosteroid exposure among preterm, very-low-birth-weight infants investigated whether the effects are differential by the presence of neonatal brain injury. STUDY DESIGN: Prospective cohort study of cognition, behavior, and cerebral palsy in 251 children (ages 6-8 years) born at < or = 32 weeks of gestation. This sample included 91 children with abnormal neonatal cranial ultrasound findings and 106 children who had been exposed to antenatal corticosteroids. RESULTS: In children with abnormal cranial ultrasound findings, a complete course of antenatal corticosteroids was associated with an 8.7-point advantage in IQ (95% CI, 1.8, 15.6; P = .016), controlling for confounding factors. Both verbal and nonverbal cognitive scores were increased in a dose-response manner. The advantage was greater for infants born at < or = 28 weeks of gestation and in those with ventriculomegaly. In children with normal cranial ultrasound scans, cognitive function was not related to antenatal corticosteroid exposure. No statistically significant associations were observed between antenatal corticosteroid exposure and either childhood behavioral scores or cerebral palsy. CONCLUSION: Antenatal corticosteroids appear to confer substantial long-term benefits on cognition of very-low-birth-weight infants with cranial ultrasound abnormalities.     

Cerebral palsy in very low birthweight infants surviving to 2 years with modern perinatal intensive care

The rate of cerebral palsy and factors associated with its occurrence were determined in surviving 2-year-old very low birthweight (VLBW) infants born during an era of modern perinatal intensive care. Of the survivors, 12.5% (52/416) of those traced had spastic cerebral palsy. Motor handicaps were mild in 42%, moderate in 25%, and severe in 33% of children with cerebral palsy. The prevalence of cerebral palsy was similar in all birthweight groups up to the upper limit of 1500 gm, and was considerably higher than in survivors born in the same hospital a decade earlier. Although several perinatal variables were associated with the occurrence of cerebral palsy, either singly or in combination, little statistical or clinical confidence would be placed in these associations. Moreover, although 77% of children with cerebral palsy had one or more commonly recognized perinatal risk factors, almost identical rates of risk factors were present in normal children. The advent of cranial ultrasonography during the time of the study was associated with an increase in mortality but no effect on the prevalence of cerebral palsy. Cerebroventricular hemorrhage correlated poorly with the presence of cerebral palsy. The prevalence of cerebral palsy in surviving VLBW infants is unacceptably high; however, no obvious preventable factors in its etiology could be identified.     

Changing diagnosis of cerebral palsy in very low birthweight children

The stability of the diagnosis of cerebral palsy from 2 to 5 years of age was examined in 83 children of birthweight under 1000 gm, and 112 of birthweight 1000 to 1500 gm. In 20 2-year-old children with cerebral palsy, the diagnosis persisted in 11 (55%, 95% confidence intervals 35.1 to 76.9%); 2 of 175 children (1.1%) free of cerebral palsy at 2 years of age subsequently developed the condition. Severe or moderate cerebral palsy at 2 years persisted in all eight children (100%). In 9 of 12 children in whom cerebral palsy at 2 years had disappeared by 5 years, minor neurologic abnormalities and left-hand preference occurred frequently but mean psychologic tests scores were similar to children always free of cerebral palsy. In this cohort, cerebral palsy at 2 years was not a static condition, but overestimated later prevalence.     

Neonatal porencephaly in very low birth weight infants: ultrasound timing of asphyxial injury and neurodevelopmental outcome at two years of age.

OBJECTIVE: To investigate and diagnose the timing of asphyxial injury leading to cerebral cavitation with subsequent developing of neonatal porencephaly in the preterm VLBW infant. All newborns underwent careful neurodevelopmental outcome at 2 years of corrected age. METHODS: 250 consecutive VLBW infants (mean gestational age of 28 weeks and mean birthweight of 1150 g) have been study by means of weekly neonatal transfontanellae ultrasonography. Periventricular white matter necrosis was diagnosed when echolucencies were visible after day 3 from birth. RESULTS: Twelve cases of neonatal porencephaly were diagnosed by ultrasound. The timing of asphyxial insult leading to cerebral cavitation seems to have occurred in 33% of neonates during the antepartum period, in 42% during the peripartum period (antepartum + neonatal period) and 25% in the remaining neonatal period. Periventricular-intraventricular hemorrhage (PVH-IVH) was found in all cases and in 50% a severe IVH (grade III-IV) was diagnosed within 7 days neonatal period. Nine infants had evidence of cerebral palsy at 2 years neurological outcome. CONCLUSIONS: The ultrasound criteria of cerebral cavitation have been priorly selected in order to assure that the damage may have occurred before delivery. A comprehensive prenatal study of fetal brain, integrating ultrasound with high-velocity MRI, is also advocate. This will lead to a more detailed understanding of the underlying cerebral condition that is of critical importance for the clinician in planning the time and mode of delivery and have great deal with further medico-legal consideration.     

Diagnosis, treatment, and prevention of cerebral palsy

Cerebral palsy is the most prevalent cause of persisting motor function impairment with a frequency of about 1/500 births. In developed countries, the prevalence rose after introduction of neonatal intensive care, but in the past decade, this trend has reversed. A recent international workshop defined cerebral palsy as "a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain." In a majority of cases, the predominant motor abnormality is spasticity; other forms of cerebral palsy include dyskinetic (dystonia or choreo-athetosis) and ataxic cerebral palsy. In preterm infants, about one-half of the cases have neuroimaging abnormalities, such as echolucency in the periventricular white matter or ventricular enlargement on cranial ultrasound. Among children born at or near term, about two-thirds have neuroimaging abnormalities, including focal infarction, brain malformations, and periventricular leukomalacia. In addition to the motor impairment, individuals with cerebral palsy may have sensory impairments, cognitive impairment, and epilepsy. Ambulation status, intelligence quotient, quality of speech, and hand function together are predictive of employment status. Mortality risk increases incrementally with increasing number of impairments, including intellectual, limb function, hearing, and vision. The care of individuals with cerebral palsy should include the provision of a primary care medical home for care coordination and support; diagnostic evaluations to identify brain abnormalities, severity of neurologic and functional abnormalities, and associated impairments; management of spasticity; and care for associated problems such as nutritional deficiencies, pain, dental care, bowel and bladder continence, and orthopedic complications. Current strategies to decrease the risk of cerebral palsy include interventions to prolong pregnancy (eg, 17alpha-progesterone), limiting the number of multiple gestations related to assisted reproductive technology, antenatal steroids for mothers expected to deliver prematurely, caffeine for extremely low birth weight neonates, and induced hypothermia for a subgroup of neonates diagnosed with hypoxic-ischemic encephalopathy.     

Perinatal risk factors for adverse neurodevelopmental outcome after spontaneous preterm birth.

OBJECTIVE: The aim of this study was to investigate to what extend perinatal factors contribute to the neurodevelopmental outcome in a group neonates born after spontaneous preterm labour with or without prolonged rupture of the membranes (PROM). METHODS: In a cohort of neonates born after the spontaneous onset of labour with or without PROM before 34 weeks of gestation a stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on adverse outcome. Adverse neurodevelopmental outcome was defined as a Griffith's developmental score <85, cerebral palsy, a major disability or perinatal death associated with severe cerebral damage. RESULTS: The study group consisted of 185 neonates. Seven neonates died with severe cerebral damage. After a forward logistic regression analysis three factors appeared to have an independent influence: gestational age protected against an adverse outcome (odds ratio (OR) per day increase 0.95, 95% confidence interval (CI) 0.90-0.97) while abnormal cranial ultrasound (intraventricular haemorrhage and periventricular leucomalacia) (OR 6.33, 95% CI 2.16-18.52) and the need for a second course of antibiotics (OR 1.85, 95% CI 1.02-3.33) increased the risk for adverse outcome. Comparing the group with a normal neurodevelopmental outcome with those with cerebral palsy, cranial ultrasound abnormalities were independently associated with cerebral palsy (OR 48.75, 95% CI 11.78-201.76). CONCLUSION: The most important way of preventing neurological damage in infants is to increase gestational age at birth and to avoid the development of intraventricular haemorrhage and periventricular leucomalacia.     

Incidence, mechanisms, and patterns of fetal cerebral lesions in twin-to-twin transfusion syndrome.

OBJECTIVE: To determine the incidence of fetal cerebral lesions and their characteristics in twin-to-twin transfusion syndrome (TTTS). DESIGN AND SETTING: This was a retrospective analysis at a single center for the period 1999 to 2004 in which 299 cases of severe TTTS at 15-28 weeks of gestation were reviewed. METHODS: Only cerebral injuries diagnosed during pregnancy or ischemic lesions diagnosed within the first week of life were considered in order to exclude those related to prematurity. We only included cases resulting in at least one survivor at one week after delivery, as well as fetuses that were terminated because of severe cerebral abnormalities. We excluded all fetuses delivered at <24 weeks of gestation that died prior to undergoing postnatal cranial ultrasonography. The main outcome measures were fetal cerebral lesions, intrauterine death, survival, and neonatal death. RESULTS: Two hundred and ninety-nine pregnancies were evaluated. Three hundred and fifteen fetuses were reviewed. Cerebral abnormalities developed antenatally in 26/315 fetuses (8.25%). All lesions but one were diagnosed prenatally. Prenatal diagnosis of these lesions was achieved primarily by ultrasound (US) and magnetic resonance imaging (MRI), in 20/25 (80%) and in 5/25 (20%) fetuses, respectively. Cerebral abnormalities developed following primary laser coagulation in 12/222 (5.40%), following serial amnioreduction in 9/66 (13.63%), and following expectant management in 3/14 (21.4%) fetuses. Abnormalities developed after single intrauterine fetal death (IUFD) in 14 cases. CONCLUSIONS: Cerebral morbidity in TTTS mainly occurs following vascular disruptive lesions. Both donors and recipients are at risk of developing either ischemic or hemorrhagic lesions. The risk of developing cerebral lesions in single survivors is significantly lower following laser treatment. Combined use of a targeted US and fetal MRI could detect most cerebral abnormalities antenatally. Timing of the triggering event is critical for planning serial US and MRI follow-up examinations.     

Risk factors for adverse neurodevelopment in extremely low birth weight infants with normal neonatal cranial ultrasound.

OBJECTIVES: To determine risk factors associated with adverse developmental outcome at 5 years in extremely low birth weight infants or extremely premature infants (<28 weeks) with normal neonatal cranial ultrasounds. DESIGN/METHODS: Data were collected prospectively on 152 infants with gestation <28 weeks or birth-weight <1000 g. Infants were grouped into those with normal development, mild-to-moderate impairment (IQ 70 to 84, or hearing loss 30 to 89 dB, visual acuity 6/18 to 6/60, or mild/moderate cerebral palsy (CP)) and severe impairment (IQ <70, hearing loss > or =90 dB, visual acuity <6/60, or severe CP). RESULTS: Five-year outcomes were available for 144/152 children (95%). In all, 89 (62%) infants had normal development, 39 (27%) had mild-moderate impairment and 16 (11%) had severe impairment. On multivariate logistic regression analysis, factors associated with developmental impairment were serum bilirubin > or =200 micromol/l (odds ratio (OR) - 4.06, p=0.003) and retinopathy of prematurity (ROP) (OR - 1.6, p=0.03). CONCLUSIONS: A serum bilirubin > or =200 micromol/l and presence of ROP are postnatal risk factors associated with an adverse developmental outcome in infants with normal cranial ultrasounds.     

Long-term neurodevelopmental outcome of triplets

OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in triplets and to find out possible connection between the outcome and perinatal events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24-144 months of age correlated with gestational age, birth weight, pregnancy complications, early neonatal period, neonatal cranial ultrasound, period of birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low birth weight and maternal age. In multivariate analysis, both cerebral palsy and minor disabilities correlate significantly with early neonatal complications, neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture of membranes (p=0.047). Children conceived spontaneously do worse than those born after assisted reproduction (p=0.004), those born in the time period 1996-2000 do better than those born before (p=0.021). Seventy-seven percent (77%) of newborns delivered in the time period 1996-2000 and after level 1 antenatal care was introduced, compared with 54% being delivered in the time period before 1996 and with less meticulous types of antenatal care, remain healthy (p=0.015). CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental complications. Stringent perinatal care might appear important determinant of their long-term outcome.     

Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome

OBJECTIVE: The purpose of this study was to determine the long-term neurodevelopmental outcome in children after twin-to-twin transfusion syndrome. STUDY DESIGN: Maternal and neonatal medical records of all twin-to-twin transfusion syndrome patients who were admitted to our center between 1990 and 1998 were reviewed. Neurologic and mental development at school age was assessed during a home visit in all twin-to-twin transfusion syndrome survivors. RESULTS: A total of 33 pregnancies with twin-to-twin transfusion syndrome were identified. Four couples opted for termination of pregnancy. All other pregnancies were treated conservatively, 18 pregnancies (62%) with serial amnioreductions and 11 pregnancies (38%) without intrauterine interventions. Mean gestational age at delivery was 28.6 weeks (range, 20-37 weeks). The perinatal mortality rate was 50% (29/58 infants). The birth weight of the donor twins was less than the recipient twins (P<.001). Systolic blood pressure at birth was lower in donors than in recipients (P=.023), and donors required inotropic support postnatally more frequently than did recipients (P=.008). The incidence of hypertension at birth was higher in recipients than in donors (P=.038). Abnormal cranial ultrasonographic findings were reported in 41% of the neonates (12/29 neonates). All long-term survivors (n=29 neonates) were assessed during a home visit. Mean gestational age at birth of the surviving twin was 31.6 weeks (range, 25-37 weeks). The mean age at follow-up was 6.2 years (range, 4-11 years). The incidence of cerebral palsy was 21% (6/29 infants). Five of 6 children with cerebral palsy had an abnormal mental development. The incidence of cerebral palsy in the group of survivors who were treated with serial amnioreduction was 26% (5/19 infants). Four children were born after the intrauterine fetal demise of their co-twin, 2 of which had cerebral palsy. CONCLUSION: The incidence of adverse neurodevelopmental outcome in twin-to-twin transfusion syndrome survivors is high, especially after the intrauterine fetal demise of a co-twin.     

Neonatal cerebral lesions predict 2-year neurodevelopmental impairment in children treated with laser surgery for twin–twin transfusion syndrome

Objective: The objective of this study is to assess whether postnatally detected cerebral abnormalities are predictive of neurodevelopmental impairment (NDI) in survivors of twin–twin transfusion syndrome (TTTS) that underwent laser surgery.

Materials and methods: Ninety-nine children treated for TTTS had neurodevelopmental assessment at age 2-years (±6 weeks). ‘High-risk survivors’ had cerebral imaging in the neonatal period. ‘High-risk survivors’ were defined as (1) delivered at <32 weeks; or (2) cerebral imaging clinically indicated. NDI was a composite outcome of: Battelle Developmental Inventory 2nd edition (BDI-2) score <70, cerebral palsy, blindness, and/or deafness. Multilevel logistic regression with robust standard errors was used to evaluate associations between cerebral lesions and NDI.

Results: Fifty-six children were ‘high-risk survivors’ and had neonatal cerebral imaging. Ten twins (18%) had at least one cerebral lesion, including grade 1–2 intraventricular hemorrhage (8), cystic periventricular leukomalacia (2), ventriculomegaly (1), and bilateral subependymal cyst (1). The risk of NDI in the ‘high-risk survivors’ was 7% (4/56) compared with 0% (0/43) in the remaining group. Among ‘high-risk survivors’, cerebral lesions were a significant risk factor for NDI (OR?=?19.28, p?Conclusions: Among ‘high-risk survivors’ of TTTS treated with laser surgery, cerebral lesions identified on neonatal imaging were associated with NDI at 2-years.     

Early onset, severe fetal growth restriction with absent or reversed end-diastolic flow velocity waveform in the umbilical artery: Perinatal and long-term outcomes

Objective: To assess perinatal and long-term outcomes for pregnancies complicated by early onset, severe fetal growth restriction with absent or reverse end-diastolic flow velocity waveform (AREDF) in the umbilical artery.
Methods: A retrospective cohort study of 36 singleton pregnancies with AREDF when the estimated fetal weight (EFW) is less than 501 g at presentation.
Results: At presentation, the median gestational age and EFW were 24 (18–29) weeks and 364 (167–496) g, respectively. The median interval between presentation and live birth or diagnosis of intrauterine fetal death (IUFD) was 13 (0–60) days. Delivery was for IUFD in 19 cases (53%), fetal indications in 13 cases (36%) and maternal indications in four cases (11%). Caesarean section (CS) was performed for the 17 live births of which 10 (59%) were by classical CS. Of the total cohort, five infants survived to hospital discharge giving an overall perinatal survival rate of 14%. All survivors had short-term morbidity. The cognitive function in four children was assessed as normal at two years of age. One survivor had developmental delay. None of the surviving children had any evidence of cerebral palsy.
Conclusion: The overall perinatal survival rate for pregnancies complicated by early onset, severe growth restriction with an EFW of < 501 g and AREDF is low. When delivery occurs for fetal indications, the majority of these women require classical CS. Short-term neonatal morbidity is high though none of the survivors had cerebral palsy.     

EPICure: facts and figures: why preterm labour should be treated

The principal objective of the EPICure studies was to determine both short- and long-term outcomes of extremely preterm birth. Data were collected for all births before 26 completed weeks of gestation in the UK and Republic of Ireland for 10 months in 1995. Of 811 infants admitted to neonatal units, 314 (39%) survived. Of these, 283 (92%) were assessed at 2.5 years and 241 (78%) at 6 years, together with a comparator group selected from classmates in normal schools. At 6 years, 32 (13%) of those assessed had disabling cerebral palsy and 31 (13%) had severe sensory impairment. Cognitive impairment was a more frequent adverse outcome: the mean intelligence quotient (IQ) was 82 (SD 19). Fifty children (21%) had IQs > 3 SD less than that of the comparator group, and in 48 children (20%), IQ was 2–3 SD less than that of the comparator group. Infants whose mothers had received antenatal steroids had fewer severely abnormal head scan findings. In this population, abnormal head scan findings are independent predictors of reduced, severe motor disability at 2.5 years. Using step-wise logistic regression analysis, postnatal transfer was associated with severe motor disability; prolonged membrane rupture with reduced Mental Development Index (MDI) and antenatal steroid with increased MDI. It is clear that factors around the time of birth are critical in determining outcome, irrespective of later complications during neonatal intensive care. Since 1995, there is good evidence of improved survival, but it is not clear whether or not the number of survivors with severe adverse outcomes has changed. A new cohort of births <27 completed weeks is currently being collected in English maternity units. Data collection around the time of birth is more detailed than in 1995 in order to better explore the relationship between perinatal factors and later outcomes.     

Perinatal risk factors for cranial ultrasound abnormalities in neonates born after spontaneous labour before 34 weeks

OBJECTIVE: The aim of this study was to identify risk factors for cranial ultrasound abnormalities in neonates born after spontaneous preterm labour with or without prolonged premature rupture of the membranes (PROM). METHODS: The presence of intraventricular haemorrhage and cystic periventricular leucomalacia was investigated in a cohort of neonates born between 24 and 34 weeks using cranial ultrasound. A stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on cranial ultrasound abnormalities. RESULTS: The study group consisted of 205 neonates and cranial ultrasound abnormalities were identified in 27 infants. Early onset neonatal infectious disease (OR 3.09, 95% CI 1.24--7.70, P=0.01) increased the risk for cranial ultrasound abnormalities. Gestational age at birth (OR 0.96, 95% CI 0.93--0.99, P=0.03) and a full course of antenatal steroids (OR 0.33, 95% CI 0.13--0.85, P=0.02) reduced the risk for cranial ultrasound abnormalities. CONCLUSION: Early onset neonatal infectious disease is an independent risk factor for cranial ultrasound abnormalities in the very preterm neonate born after spontaneous labour with or without PROM.     

单绒毛膜双胎选择性生长受限对新生儿脑损伤的影响

目的 探讨单绒毛膜（MC）双胎选择性宫内生长受限（sIUGR）对新生儿脑损伤的影响。方法 选择2011年6月至2014年6月在暨南大学第二临床医学院就诊及分娩的MC双胎并发sIUGR产妇24例和其48个胎儿为sIUGR组,并根据sIUGR儿脐动脉血流多普勒波形将sIUGR组分为Ⅰ型11例、Ⅱ型10例、Ⅲ型3例。同期分娩的无并发症的MC双胎56例及其112个胎儿作为对照组。分娩后对新生儿头颅进行超声检查,如有异常则用超声或磁共振（MRI）复查,随访至新生儿出院。新生儿脑损伤分为轻度：（1）Ⅰ级、Ⅱ级脑室内出血（IVH）。（2）豆状核纹状体血管病变和（或）室管膜下假性囊肿。重度：（1）Ⅲ、Ⅳ级IVH。（2）Ⅱ级以上脑室周围白质软化囊性变（PVL）。（3）脑穿通囊肿和（或）脑室扩张。分析比较两组及3种类型sIUGR之间新生儿结局及脑损伤情况。结果 sIUGR组新生儿重度、轻度脑损伤率分别为（4.2%,1/24）、（10.4%,5/48）;而对照组分别为（0）、（6.2%,7/112）。两组比较差异无统计学意义（P>0.05）。轻度脑损伤12例,均无明显神经系统受损的临床表现,其中11例（11/12,91.7%）复查头颅超声或MRI见影像学明显改善。sIUGR组Ⅰ型有2例（2/22,9.1%）而Ⅱ、Ⅲ型有3例（3/26,11.5%）出现轻度脑损伤,两两比较,差异无统计学意义（P>0.05）。sIUGR组Ⅱ、Ⅲ型各有1例新生儿死亡及1例重度脑损伤,而sIUGRⅠ型无新生儿死亡和重度脑损伤,虽然差异未达统计学意义（P>0.05）,但其预后明显差于Ⅰ型。结论 与正常MC双胎比较, MC双胎并发sIUGR新生儿近期重度、轻度脑损伤发生率无明显差异,且绝大多数轻度脑损伤为暂时性,但sIUGRⅡ、Ⅲ型比Ⅰ型预后差,应加强监测,适时终止妊娠。     

Rates of neonatal death and cerebral palsy associated with fetal growth restriction among very low birthweight infants. A temporal analysis

OBJECTIVE: To assess whether changes over time in neonatal survival and infants' neurodevelopmental outcome among very low birthweight (VLBW) infants was correlated with the obstetric aetiology of VLBW. DESIGN: A cohort study of 773 VLBW infants. SETTING: A University hospital in Northern Italy. POPULATION: All the VLBW infants born over a 20-year period (1983-2002) at a single institution. METHODS: Evaluation of neonatal mortality and neurodevelopmental outcome of the surviving infants at 2 years of corrected age. Logistic regression analysis was used to compare the improvements of neonatal outcome associated with obstetric risk factors over time. MAIN OUTCOME MEASURES: The risk reduction of neonatal death or cerebral palsy associated with each obstetric category responsible for VLBW over time. RESULTS: The overall rates of neonatal mortality and cerebral palsy were 38.7% (43/111) and 17% (9/53) in the period 1983-87 and 13.7% (34/24) and 6.3% (13/205) in the period 1998-2002, respectively. The adjusted decrement per 5-year period was 33.1% (95% CI = 7.9-51.4) for neonatal death and 29.1% (95% CI = 25.3-32.7) for cerebral palsy, respectively. The adjusted rise in the rate of intact survival at 2 years of corrected age was 7.6% (95% CI = 3.1-12.3) per quinquennium. In logistic models with neonatal death or cerebral palsy as a combined outcome variable, and gestational age, corticosteroid use, surfactant use, and time of birth as explanatory variables, fetal growth restriction (P < 0.001) and pre-eclampsia (P= 0.011) interacted significantly with period of birth. The adjusted decrement in the rate of neonatal death or cerebral palsy as a combined variable was 27.5% per 5 years (95% CI = 13-39.6) in the overall population, 54.5% per 5 years (95% CI = 46.8-61.2) (P < 0.001 compared with overall population) among growth-restricted infants and 50.3% per 5 years (95% CI = 42.5-57.1) (P= 0.003 compared with overall population) in infants born to mothers with pre-eclampsia. CONCLUSIONS: Over a period of 20 years, the decrement in the rate of neonatal death or cerebral palsy was higher in growth-restricted fetuses than in other VLBW infants. This reduction was not obtained at the expense of an increased rate of neurodevelopmental impairments in surviving infants.     

Incidence,mechanisms, and patterns of fetal cerebral lesions in twin-to-twin transfusion syndrome

Objective.?To determine the incidence of fetal cerebral lesions and their characteristics in twin-to-twin transfusion syndrome (TTTS).

Design and setting.?This was a retrospective analysis at a single center for the period 1999 to 2004 in which 299 cases of severe TTTS at 15–28 weeks of gestation were reviewed.

Methods.?Only cerebral injuries diagnosed during pregnancy or ischemic lesions diagnosed within the first week of life were considered in order to exclude those related to prematurity. We only included cases resulting in at least one survivor at one week after delivery, as well as fetuses that were terminated because of severe cerebral abnormalities. We excluded all fetuses delivered at <24 weeks of gestation that died prior to undergoing postnatal cranial ultrasonography. The main outcome measures were fetal cerebral lesions, intrauterine death, survival, and neonatal death.

Results.?Two hundred and ninety-nine pregnancies were evaluated. Three hundred and fifteen fetuses were reviewed. Cerebral abnormalities developed antenatally in 26/315 fetuses (8.25%). All lesions but one were diagnosed prenatally. Prenatal diagnosis of these lesions was achieved primarily by ultrasound (US) and magnetic resonance imaging (MRI), in 20/25 (80%) and in 5/25 (20%) fetuses, respectively. Cerebral abnormalities developed following primary laser coagulation in 12/222 (5.40%), following serial amnioreduction in 9/66 (13.63%), and following expectant management in 3/14 (21.4%) fetuses. Abnormalities developed after single intrauterine fetal death (IUFD) in 14 cases.

Conclusions.?Cerebral morbidity in TTTS mainly occurs following vascular disruptive lesions. Both donors and recipients are at risk of developing either ischemic or hemorrhagic lesions. The risk of developing cerebral lesions in single survivors is significantly lower following laser treatment. Combined use of a targeted US and fetal MRI could detect most cerebral abnormalities antenatally. Timing of the triggering event is critical for planning serial US and MRI follow-up examinations.     

The association of coagulase-negative staphylococci isolated from the chorioamnion at delivery and subsequent development of cerebral palsy.

OBJECTIVE: To find out whether there is an association between cultures positive for coagulase negative staphylococci (CONS) taken from babies in the Neonatal Intensive Care Unit (NICU) and a subsequent outcome of cerebral palsy. STUDY DESIGN: At delivery, we obtained cultures from the chorioamnion space and, when medically indicated, we obtained bacterial cultures from children in the NICU. Surviving neonates underwent final examination for cerebral palsy at age 18 months. RESULTS: Of six children in the Magnesium and Neurologic Endpoints Trial who had cerebral palsy, chorioamnion cultures had been obtained for five of six. Four of these five children (80%) had CONS-positive cultures, whereas 26 of 102 (25%) children without cerebral palsy were CONS positive (p = 0.02). In the NICU, of children with cerebral palsy, the prevalence of culture-proven CONS was 80% (4/5); for those without cerebral palsy, the prevalence was 17% (15/86) (p = 0.01). Using multivariable logistic regression to control for confounding, CONS in the chorioamnion remained significant (adjusted odds ratio [OR] 37.7, 95% confidence interval [CI] 3.0 to +infinity; p = 0.003). However, when controlled for extremely low birth weight, nonvertex presentation, and being on a ventilator > or = 20 days, the association between culture-proven CONS in the NICU and cerebral palsy became insignificant (adjusted OR 3.0, 95% CI 0.2 to +infinity; p = 0.42). CONCLUSION: CONS in the chorioamnion space are associated with cerebral palsy, but in these data, CONS in the NICU are not found to be associated with cerebral palsy.     

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.     

Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants

OBJECTIVE: The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy). STUDY DESIGN: In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months. RESULTS: Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03). CONCLUSION: Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion.