Background Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce. Methods In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography. Results In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5–101.8, versus 104.4, 95% CI: 100.4–108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6–4.3, versus 4.5, 95% CI: 4.1–4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02). Conclusions Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years. Clinical trial registration The study is registered at ClinicalTrials.gov, NCT00330447 .
Although chorioamnionitis (CA) is a well-known risk factor for white matter disease of prematurity, the association with intraventricular hemorrhage (IVH) is controversial and has not been yet systematically reviewed. We performed a systematic review and meta-analysis of studies exploring the association between CA and IVH. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 July 2017. Studies were included if they examined preterm infants and reported primary data that could be used to measure the association between exposure to CA and the presence of IVH. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). We found 1,284 potentially relevant studies, of which 85 met the inclusion criteria (46,244 infants, 13,432 CA cases). Meta-analysis showed that CA exposure was significantly associated with all grades IVH (OR 1.88, 95% CI 1.61–2.19), with grades 1–2 IVH (OR 1.69, 95% CI 1.22–2.34), and with grades 3–4 IVH (OR 1.62, 95% CI 1.42–1.85). Both clinical and histological CA were associated with an increased risk for developing IVH in very preterm infants. In contrast, the presence of funisitis did not increase IVH risk when compared to CA in the absence of funisitis (OR 1.22, 95% CI 0.89–1.67). Further meta-analyses confirmed earlier findings that CA-exposed infants have significantly lower gestational age (GA; mean difference [MD] −1.20 weeks) and lower birth weight (BW; MD −55 g) than the infants not exposed to CA. However, meta-regression and subgroup analysis could not demonstrate an association between the lower GA and BW and the risk of IVH in the CA-exposed infants. In conclusion, our data show that CA is a risk factor for IVH, but also a risk factor for greater prematurity and more clinical instability. In contrast to other complications of prematurity, such as patent ductus arteriosus, retinopathy of prematurity, or bronchopulmonary dysplasia, the effect of CA on IVH appears to be independent of CA as causative factor for very preterm birth.
Early interventions promoting mother self-efficacy and involvement in multisensory stimulation have beneficial effects on human milk feeding in preterm infants.
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