Research from JAMA — Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children — A Randomized Controlled Trial

To examine the relationships between clinical or histological chorioamnionitis and cerebral palsy using a meta-analysis approach. A systematic review of the literature appeared in PubMed between 2000 and 2009 was conducted using the search terms "cerebral palsy" and "infection," with broad-scope variations in terminology of "white matter damage," "periventricular leukomalacia," "cystic periventricular leukomalacia," "chorioamnionitis," "intrauterine infection," "intraventricular hemorrhage," "funisitis," "fetal inflammatory response," "early neonatal sepsis," "neurological impairment," "virus," "bacteria," "fungi," and "protozoa," with variations of suffixes (eg, "viral," "bacterial," "fungal," "protozoan," etc), and "urinary tract infection," "bacterial vaginosis," "bacteriuria," and "cytokines." The related key words "gestational age," "small for gestational age," "preterm," and "low birth weight" also were added to the search terms. Only studies published in English were included. Three hundred eight articles were retrieved and systematically reviewed independently by two authors. Application of four inclusion criteria led to 15 studies being considered for data abstraction. An exposure was considered relevant if it met the established criteria for clinical or histological chorioamnionitis. The outcome was a diagnosis of cerebral palsy in accordance with established criteria. The data were abstracted onto standard forms, correlated according to eight characteristics, and tabulated. Twelve of the 15 studies contained information on the association between clinical chorioamnionitis and cerebral palsy, and eight studies included information on the association between histological chorioamnionitis and cerebral palsy. The results indicated that there were significant associations between clinical chorioamnionitis or histological chorioamnionitis and cerebral palsy, for clinical chorioamnionitis (chi1=13.91; P<.001) with a pooled odds ratio of 2.42 (95% confidence interval 1.52-3.84), and for histological chorioamnionitis (chi1=6.86; P=.009) with a pooled odds ratio of 1.83 (95% confidence interval, 1.17-2.89). The data suggested increased risks of 140% and 80% for neonates exposed to clinical chorioamnionitis or histological chorioamnionitis, respectively. The significant association of clinical or histological chorioamnionitis with cerebral palsy suggested that clinical strategies to prevent or reduce chorioamnionitis would lead to a reduction in cerebral palsy. The culture techniques currently used to diagnose the presence of pathogenic microorganisms during pregnancy need to improve, both in their methodology and in the length of time they require.

Infection-related preterm birth is a leading cause of infant mortality and morbidity; knowledge of bacterial populations invading the amniotic cavity and the routes of invasion is required to make progress in the prevention of preterm birth. Significant advances have been made in understanding bacterial communities in the vagina, but much less studied are intra-uterine bacterial populations during pregnancy. A systematic review of data published on the intra-uterine microbiome was performed; molecular information and summaries of species found in healthy individuals and in women with diagnosed infections served to construct a database and to analyse results to date. Thirteen studies fulfilled the review's inclusion criteria. The data of various investigations were collated, organised and re-analysed to achieve a more comprehensive understanding of microbial populations in the intra-amniotic space. The most common intra-amniotic bacterial taxa were species that can colonise the vagina in health and disease; there were others associated with the habitats of the mouth, gastrointestinal tract and respiratory tract. The results suggest a central role for the ascending route of infections during pregnancy, and points to a possible secondary contribution via haematogenous invasion of the intra-amniotic space. The census of the intra-uterine microbiome awaits completion.

To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g; P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g; P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g; P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.