Motherisk Int J 2020;1:13
Gideon Koren MD FRCPC FACMT, Liat Korn PhD, Yusuf Kaplan MD
Ariel University (1) and Terafar - Izmir Katip Celebi University, Turkey (2)
We all know that prematurity is associated with adverse effects on cognitive functions and academic achievements. Is late premature can be assumed to be safe or unsafe?”
This question continues to trouble researchers and clinicians. Recent studies, though, suggest that even at 37 wk gestation there are some measurable deficits.
It has long been recognized and documented that prematurity is associated with cognitive delays and suboptimal academic outcome. With the increased survival of preterm infants even at the extreme edge of 24-25 weeks, the burden of prematurity and its long-term effects on society have become a major public health concern. On April 2020 McBryde and colleagues published the largest systematic review and meta- analysis yet on this issue (1). They rigorously selected 33 studies including 4006 preterm and 3317 term babies and followed different academic domains. In general, preterm babies scored significantly lower on reading comprehension, applied mathematic problems, calculations, mathematical knowledge, word identification and mathematical fluency. Because prematurity entails all children born <37 weeks, gestation, the authors stratified the data by gestational age at birth. Compared to extremely preterm infants (<28 wk), very preterm infants born at 28-32 wk gestation did not differ in late reading from term-born children. This could be the result of an outlying study. Importantly for this Motherisk question, late preterm children born at 33-37 wk gestation showed marked reading deficits compared with term-born children. A similar effect in late preterm babies was detected in mathematics impairment.
Other recent publications have similarly attempted to refine the shape of the relationship between gestational age at birth and cognitive development , yet came to different conclusions. Richards and colleagues utilized a large nationally representative US longitudinal birth cohort (n=6150) to try to sharpen differences in scores as a function of weeks of prematurity (2). In general, late preterm (34-36 wk) scored significantly worse than full-term (39-40 wk). Looking at their week-by-week assessments of Bayley Short Form-Research (BSF-R), Richards et al found that even at 37 wk gestation preterm infants- had a small but significant decrement in cognitive scores. This difference was significant when adjusted for corrected age, but became insignificant when fully adjusted for corrected age at assessment, but also for child race/ethnicity, child’s sex, maternal age at birth, maternal educational attainment and household poverty (2).
Similar results from a longitudinal study on late preterm infants (34+0 to 36+6 wk., n=786) were documented by Heinonen et al , showing significantly lower mean of 3.71 points for full scale IQ and 3.11 points on verbal IQ compared with peers born at term (3). In late term babies born small for their gestational age, the differences more than doubled. After adjustment for confounders, many of the differences were rendered non- significant, except for babies who were also small for gestational age (3).
Baron and colleagues discussed an important facet of the late prematurity challenge (4). Often perinatal complications lead to early elective delivery, which is commonly believed by obstetricians to have no long-term effects. The authors document, using a large cohort of late preterm and term babies, that late preterm infants exhibit lower conceptual ability, lower verbal, nonverbal, spatial, visuo-motor and poorer adaptability than term infants. In multivariate analysis, gestational age was the most important contributor to these subtle outcomes, not neonatal medical variables and not being inneonatal intensive care unit.. The authors cautioned that “Gestation is a developmental continuum best not interrupted during its natural course”. Baron et al suggest that “these results have serious implications to obstetric practice and parental decision making regarding elective delivery in the absence of maternal or fetal adverse indications” (4).
Often though, these are very complex decisions. As an example, when women are diagnosed with invasive malignancies in late pregnancy, there is often an urgent need to commence chemotherapy as soon as possible, and many times the concept of early delivery, to spare the chemotherapy from the fetus is considered (5). In contrast, Vandenbroucke and friends had argued, based on large prospective data, that chemotherapy near term is by and large much safer to the fetus than the cognitive risk of prematurity (6).
This example cannot be extrapolated to other perinatal risks, and every case will have to be tested on its own merit, however, the cognitive risks of even late prematurity should not be ignored in the process of decision.
1) McBryde M, Fitzallen GC, Liley HG; et al . Academic Outcomes of School-Aged Children Born PretermA Systematic Review and Meta-analysis. JAMA Network Open. 2020;3(4):e202027. doi:10.1001/jamanetworkopen.2020.2027
2) Richards JL, Drews-Botsch C, Sales JM et al. Describing the shape of the relationship between gestational age at birth and cognitive development in a nationally representative US birth cohort. Paediatr Perinal Epidemiol 2016;30:571-582
3) Heinonen K, Lahti J, Sammallahti S, et al. Neurocognitive outcome in young adults born late-preterm. Dev Med Child Neurol 2018;60:267-274
4) Baron IS, LitmanFR, Ahronovich MD,Baker R. Late Preterm Birth: A Review of Medical and Neuropsychological Childhood Outcomes. Neuropsychol Rev2012 Dec;22(4):438-50.
5) Koren G, Carey N, Gagnon R et al. Cancer chemotherapy and pregnancy. J Obstet Gynaecol Can. 2013;35(3):263-278.
6) Vandenbroucke T, Van Calsteren K, Amant F. Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. N Engl J Med. 2016 Feb 18;374(7):693. doi: 10.1056/NEJMc1515462