The ELGAN study was designed to identify characteristics and exposures that increase the risk of structural and functional neurologic disorders in ELGANs (the acronym for Extremely Low Gestational Age Newborns). During the years 2002–2004, 1249 mothers who gave birth to 1506 infants before the 28th week (1007 singletons, 414 twins, 77 triplets, 2 quadruplets, and 6 septuplets) consented to participate (). The informed consent procedures and documents were approved by everyone of the 14 institutions that enrolled families for this study.
The sample for the brain ultrasound component of this report consists of the 1246 infants (83%) whose placenta was biopsied under sterile conditions for cultures and submitted for histologic evaluation and who had one or more sets of protocol ultrasound scans of the brain read concordantly by two independent sonologists. The sample for the CP component is limited to the 899 children (88% of 1022 survivors) who also had a neurologic examination at 24 months post-term equivalent.
The gestational age estimates were based on a hierarchy of the quality of available information. Most desirable were estimates based on the dates of embryo retrieval or intrauterine insemination or fetal ultrasound before the 14th week (62%). When these were not available, reliance was placed sequentially on a fetal ultrasound at 14 or more weeks (29%), the first day of the last menstrual period (7%), and gestational age recorded in the log of the neonatal intensive care unit (1%).
Ultrasound studies included six standard quasicoronal views and five sagittal views using the anterior fontanel as the sonographic window (26
). The three sets of protocol scans were defined by the postnatal day on which they were obtained (1: days 1–4; 2: days 5–14; 3: day 15- week 40). Details about the procedure and observer variability minimization efforts are presented elsewhere (27
The microbiologic procedures are described in detail elsewhere (28
), as are details about histologic procedures (29
24-month developmental assessment
Procedures to standardize the neurological examination and minimize examiner variability are presented elsewhere (30
). The topographic diagnosis of CP (quadriparesis, diparesis, or hemiparesis) was based on an algorithm using these data (31
We evaluated the following generalized null hypotheses: 1) the risk of an ultrasound lesion of the brain or a CP diagnosis is not associated with the recovery of microorganisms from placenta parenchyma. 2) The risk of an ultrasound lesion of the brain or a CP diagnosis is not associated with any histologic lesion of the placenta. 3) Microorganisms need not elicit histologic inflammation of the placenta to predict an abnormality on an ultrasound scan of the brain, or a CP diagnosis.
In both the ultrasound-assessed sample (N=1246) and in the developmentally assessed sample (N=899), placentas delivered vaginally were more likely than placentas delivered by Cesarean section to harbor a microorganism. Consequently, we evaluated our hypotheses first in the entire sample (), and then in the sub-samples of vaginal and cesarean section deliveries ( for ultrasound lesions and for CP diagnoses).
Sample description. These are the numbers of children who had the characteristics listed at the top of each row and in the left-hand column‡.
Table 2 Odds ratios (and 95% CI) of two ultrasound lesions (ventriculomegaly and an echolucent white matter lesion) and three cerebral palsy diagnoses (quadriparesis, diparesis, and hemiparesis) associated with each placental organism or group of organisms listed (more ...)
Table 3 Odds ratios (and 95% CI) of ventriculomegaly and an echolucent white matter lesion associated with each placental organism or group of organisms listed on the left in the vaginal and Cesarean section delivery subsamples. The only adjustment is for gestational (more ...)
Because ultrasound characteristics tended to occur together, we compared the placentas of infants whose ultrasound scans had a lesion to those of the 975 infants whose scans showed no abnormality.
We created multivariable models to identify the contribution of relevant characteristics and exposures to the outcome of interest. Their contributions are presented as risk ratios with 95% confidence intervals. The only potential cofounders that modified the risk ratios were categories of gestational age (23–24, 25–26, 27 weeks). Therefore, we adjusted for these variables only.
Because the CP diagnoses are mutually exclusive and each is appropriately compared to the same group of children without any CP diagnosis, we used multinomial logistic regression for analyses presented in and . The logistic regression analyses for , however, are not multinomial because the comparison group for each diagnosis consists of children whose placenta neither harbored an organism nor had histologic inflammation.
Table 4 Odds ratios (and 95% CI) of a CP diagnosis of quadriparesis or diparesis associated with each placental organism or group of organisms listed on the left in the vaginal and Cesarean section delivery subsamples. The only adjustment is for gestational age (more ...)
Table 5 Odds ratios (and 95% CI) of two ultrasound lesions (ventriculomegaly and an echolucent white matter lesion) and three cerebral palsy diagnoses (quadriparesis, diparesis, and hemiparesis) associated with each placenta histologic characteristic listed on (more ...)