Magnesium. An update on physiological, clinical and analytical aspects.

Purpose. Describing the epidemiology of cerebral palsy (CP), its impairments and risk factors.Method. Literature review 1965 – 2004. Search terms: Cerebral palsy, incidence, prevalence, impairments...

The epidemiology of cerebral palsy: Incidence, impairments and risk factors

ContextChorioamnionitis has been implicated in the pathogenesis of cerebral
palsy, but most studies have not reported a significant association. Cystic
periventricular leukomalacia (cPVL) is believed to be a precursor of cerebral
palsy in preterm infants.ObjectivesTo determine whether chorioamnionitis is associated with cerebral palsy
or cPVL and to examine factors that may explain differences in study results.Data SourcesSearches of MEDLINE (1966-1999), Index Medicus (1960-1965), Doctoral
Dissertation Abstracts On-Line (1861-1999), bibliographies, and online conference
proceedings (1999) were performed for English-language studies with titles
or abstracts that discussed prenatal risk factors for cerebral palsy or cPVL.Study SelectionOf 229 initially identified publications, meta-analyses were performed
on studies that addressed the association between clinical (n = 19) or histologic
(n = 7) chorioamnionitis and cerebral palsy or cPVL in both preterm and full-term
infants. Inclusion criteria were: presence of appropriate exposure and outcome
measures, case-control or cohort study design, and provision of sufficient
data to calculate relative risks (RRs) or odds ratios with 95% confidence
intervals (CIs). Studies evaluating risk of cerebral palsy following maternal
fever, urinary tract infection, or other maternal infection were collected,
but not included in the meta-analysis.Data ExtractionInformation from individual studies was abstracted using standardized
forms by 2 independent observers blinded to authors' names, journal titles,
and funding sources.Data SynthesisUsing a random effects model, clinical chorioamnionitis was significantly
associated with both cerebral palsy (RR, 1.9; 95% CI, 1.4-2.5) and cPVL (RR,
3.0; 95% CI, 2.2-4.0) in preterm infants. The RR of histologic chorioamnionitis
and cerebral palsy was 1.6 (95% CI, 0.9-2.7) in preterm infants, and histologic
chorioamnionitis was significantly associated with cPVL (RR, 2.1; 95% CI,
1.5-2.9). Among full-term infants, a positive association was found between
clinical chorioamnionitis and cerebral palsy (RR, 4.7; 95% CI, 1.3-16.2).
Factors explaining differences in study results included varying definitions
of clinical chorioamnionitis, extent of blinding in determining exposure status,
and whether individual studies adjusted for potential confounders.ConclusionOur meta-analysis indicates that chorioamnionitis is a risk factor for
both cerebral palsy and cPVL.

https://jamanetwork.com/journals/jama/articlepdf/193084/JMA00019.pdf

Chorioamnionitis as a risk factor for cerebral palsy: A meta-analysis.

Objective: To identify intrapartum predictors of newborn encephalopathy in term infants. Design: Population based, unmatched case-control study. Setting: Metropolitan area of Western Australia, June 1993 to September 1995. Subjects: All 164 term infants with moderate or severe newborn encephalopathy; 400 randomly selected controls. Main outcome measures: Adjusted odds ratio estimates. Results: The birth prevalence of moderate or severe newborn encephalopathy was 3.8/1000 term live births. The neonatal fatality was 9.1%. Maternal pyrexia (odds ratio 3.82), a persistent occipitoposterior position (4.29), and an acute intrapartum event (4.44) were all risk factors for newborn encephalopathy. More case infants than control infants were induced (41.5% and 30.5%, respectively) and fewer case infants were delivered by caesarean section without labour (3.7% and 14.5%, respectively). Operative vaginal delivery (2.34) and emergency caesarean section (2.17) were both associated with an increased risk. There was an inverse relation between elective caesarean section (0.17) and newborn encephalopathy. After application of a set of consensus criteria for elective caesarean section only three (7%) eligible case mothers compared with 33 (65%) eligible control mothers were sectioned electively. Of all the case infants, 113 (69%) had only antepartum risk factors for newborn encephalopathy identified; 39 (24%) had antepartum and intrapartum factors; eight (5%) had only intrapartum factors; and four (2%) had no recognised antepartum or intrapartum factors. Conclusions: The causes of newborn encephalopathy are heterogeneous and many relate to the antepartum period. Elective caesarean section has an inverse association with newborn encephalopathy. Intrapartum hypoxia alone accounts for only a small proportion of newborn encephalopathy. These results question the view that most risk factors for newborn encephalopathy lie in the intrapartum period.

https://www.bmj.com/content/bmj/317/7172/1554.full.pdf

Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study

We examined prenatal and perinatal factors predicting cerebral palsy, using multivariate analysis to investigate which factors were most important and the proportion of cases for which they accounted. Maternal mental retardation, birth weight below 2001 g, and fetal malformation were among the leading predictors. Breech presentation was also a predictor, but breech delivery was not. A third of the children with cerebral palsy who had breech presentations had a major noncerebral malformation. Among 189 children with cerebral palsy, 40 (21 percent) had at least one of three clinical markers suggestive of asphyxia; only 17 of these 40 children (9 percent of all cases) lacked major congenital malformation or other intrinsic defects that might have contributed to an unfavorable outcome. When all the principal risk factors present by the time labor began were considered, the 5 percent of the population at highest estimated risk was seen to have contributed 34 percent of the cases. When all the risk factors present during the period beginning before pregnancy and extending through the nursery stay were included, the 5 percent at highest risk was seen to have contributed 37 percent of the cases. Thus, the inclusion of information about the events of birth and the neonatal period accounted for a proportion of cerebral palsy only slightly higher than that accounted for when consideration was limited to characteristics identified before labor began.

Antecedents of cerebral palsy. Multivariate analysis of risk.

Objectives. To investigate whether in utero exposure to magnesium sulfate (MgSO4) was associated with a lower prevalence of cerebral palsy (CP) in infants born weighing Design. Singleton infants weighing Results. During the admission for delivery, 7.1% of the 42 VLBW infants with later CP and 36% of the 75 VLBW controls were exposed to MgSO4 (odds ratio (OR) .14, 95% confidence interval (CI) .05, .51). The overall association of MgSO4 with reduced risk of CP was also observed in the subgroup of infants born to women who were not preeclamptic (OR .25, CI .08, .97). Infants with CP were less often exposed antenatally to MgSO4 whether or not there was cotreatment with non-MgSO4 tocolytics (other tocolytics administered, OR for MgSO4 exposure .23, CI .06, 1.2; other tocolytics not administered, OR for MgSO4 .08, CI .02, .68), or antenatal corticosteroids (steroids given, OR for MgSO4 exposure .24, CI .06, 1.3; steroids not given, OR for MgSO4, .08, CI .02, .72). Apparent benefit of magnesium was observed in the presence or absence of a variety of characteristics of pregnancies, births, and infants. Conclusion. In this observational study, in utero exposure to MgSO4 was more frequent in controls than in children with CP, suggesting a protective effect of MgSO4 against CP in these VLBW infants.

Can Magnesium Sulfate Reduce the Risk of Cerebral Palsy in Very Low Birthweight Infants

In a prospective study, late obstetric complications were common, one or more occurring in 62% of 51,285 pregnancies. We examined these complications as risk factors for cerebral palsy (CP) or nonfebrile seizure disorders. Certain complications were associated with an increased rate of CP, but in babies over 2,500 g, the observed rate of CP did not exceed 2% following any condition evaluated. For most conditions, the CP rate was highest in the small subgroup of children who had five-minute Apgar scores of 3 or less. Most babies over 2,500 g born after each complication achieved five-minute Apgar scores of 7 or higher, and for them the risk of CP was not significantly greater than in children whose births were uncomplicated. Neither the complications considered nor Apgar scores were important antecedents of nonfebrile seizure disorders in children free of CP. (JAMA1984;251:1843-1848)

Obstetric complications as risk factors for cerebral palsy or seizure disorders.

Fifty children with marked neurological abnormality manifested by moderate or severe motor disability and severe mental retardation were compared with a large control population with respect to prospectively ascertained perinatal characteristics. None of 60 prenatal factors distinguished the affected group from controls. In labor and delivery, lowest fetal heart rate in the second stage of labor, arrested progress of labor, and use of midforceps discriminated between the two groups. Neonatal characteristics of children who were later severely handicapped differed from controls, particularly with respect to difficulty in initiating and maintaining respiration, intracranial hemorrhage, neonatal seizures, low birth weight and small head circumference, lowest hemoglobin or hematocrit, and overall neurological status.



Multivariate analysis, including factors from all epochs, indicated that intracranial hemorrhage and neonatal seizures were the strongest independent discriminators between the neurologically impaired children and controls.

Perinatal risk factors in children with serious motor and mental handicaps.

Aim The aim of this study was to investigate whether current literature provides a useful body of evidence reflecting the proportion of cerebral palsy (CP) that is attributable to birth asphyxia.

Method  We identified 23 studies conducted between 1986 and 2010 that provided data on intrapartum risks of CP.

Results  The proportion of CP with birth asphyxia as a precursor (case exposure rate) varied from less than 3% to over 50% in the 23 studies reviewed. The studies were heterogeneous in many regards, including the definitions for birth asphyxia and the outcome of CP.

Interpretations  Current data do not support the belief, widely held in the medical and legal communities, that birth asphyxia can be recognized reliably and specifically, or that much of CP is due to birth asphyxia. The very high case exposure rates linking birth asphyxia to CP can probably be attributed to several factors: the fact that the clinical picture at birth cannot specifically identify birth asphyxia; the definition of CP employed; and confusion of proximal effects – results – with causes. Further research is needed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/dmcn.12016

Karin B. Nelson

Papers

Can Magnesium Sulfate Reduce the Risk of Cerebral Palsy in Very Low Birthweight Infants

Can Magnesium Sulfate Reduce the Risk of Cerebral Palsy in Very Low Birthweight Infants

Obstetric complications as risk factors for cerebral palsy or seizure disorders.

Perinatal risk factors in children with serious motor and mental handicaps.

The association of cerebral palsy with birth asphyxia: a definitional quagmire.