What Are The Limits of (Preterm) Viability?

A retrospective recent study (PL Watkins et al. J Pediatr 2020; 217: 52-8) provides data that suggests that preterm infants at 22-23 weeks gestation can have good outcomes.

Cohort:

  • n=70 for 22-23 weeks (22 weeks, n=20, 23 weeks, n=50)
  • n=178 for 24-25 weeks (24 weeks, n=79, 25 weeks, n=99)

Key findings:

  • Survival to hospital discharge: 78% for 22-23 week cohort, 89% for 24-25 week cohort
  • No or mild neurodevelopmental impairment 64% or 22-23 week cohort, 76% for 24-25 week cohort. This was based on prospectively collected data at 18-22 months with Bayley Scales (BSID-III) (≥85) and being free from vision and hearing impairment

These survival and neurodevelopmental outcomes far exceed previous reports.  The study and the associated editorial (pg 9) identify several treatment characteristics that could have helped optimize outcomes: antenatal steroids, high-frequency ventilation, and a specialized environment.  Also, the authors did not include infants who were outborn, stillborn or died in the delivery room.

My take: This article’s data needs to be replicated elsewhere; in the meanwhile, it is going to challenge the notion of nihilism for infants born at 22-23 weeks gestation.

Related article: AH Jobe. J Pediatr 2020; 217: 184-8.  This commentary discusses the potential lifetime consequences of antenatal steroids, which may affect neurodevelopment and cardiovascular outcomes. “Antenatal corticosteroids are frequently used to disrupt normal development in rodent models”

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St Thomas Harbor

Preterm Infants with Increased Infections Following Acid Suppression Therapy

A recent study (P Manzoni et al. J Pediatr 2018; 193: 62-7) provide more data on the detrimental effects of gastric acid inhibitors (eg. proton pump inhibitors, histamine-2 receptor antagonists).  This study was a secondary analysis using prospectively collected data from 235 preterm very low birth weight infants. Key findings:

  • “After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS [late-onset sepsis] (OR 1.03); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS.”
  • Acid suppression therapy was associated with gram-negative (P<.001) and fungal pathogens (P=.001)
  • The study showed an association between acid blockers and with necrotizing enterocolitis, which was mitigated in those who received bovine lactoferrin

My take (borrowed, in part, from authors): This data “confirm, strengthen, and expand on previous reports describing an association between inhibitors of gastric acidity and infections.”  Thus, the risks of these medications is likely greater than the benefits in the majority of preterm infants.

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Bright Angel Trail

Preterm Neonatal Microbiota and Effect of Perinatal Antibiotics

A recent study (Arboleya, S et al. J Pediatr 2015; 166: 538-44) provide sequential data regarding the intestinal microbiome in preterm infants in comparison to full-term infants; in addition, this study offers some insight into the changes that occur with perinatal antibiotics.

The researchers examined fecal samples at approximately 2 days of life, and then days 10, 30, and 90 in 27 preterm infants and 13 full-term babies. The study figures show the progression and changes of the microbiota over the first 90 days. In Figures 1, the profiles are the most similar between the full-term and preterm infants but there remains significant differences.

Key findings:

  • Preterm infants had higher initial percentage of Lactobacillaceae and reduced Bacteroidacease.
  • Perinatal antibiotics (including intrapartum antimicrobial prophylaxis) were noted to affect gut microbiota with increased Enterobacteriaceae organisms in these infants.

There were many confounding variables noted, including different diets, which make interpretation of the data difficult.  The full-term infants received exclusive breast milk whereas the preterm infants received mixed feedings.

A recent review (Houghteling, PD, Walker, WA.”Why Is Initial Bacterial Colonization of the Intestine Important to Infants’ and Children’s Health?” JPGN 2015; 60: 294-307) had a relevant figure:

From NASPGHAN Twitter Feed

From NASPGHAN Twitter Feed

Bottomline: Overall, Arboleya et al provide some additional baseline data but much more is needed to ascertain what factors will make children healthier –starting from before birth. The understanding of the microbiome is truly in its infancy.

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Better growth charts for preterm children

A community-based cohort study from the Netherlands involving 1690 preterm infants (25-36 weeks) and a random sample of 634 full term infants provides a more precise tool for monitoring growth over the first four years of life (J Pediatr 2012; 161: 460-5).

Key findings:

  • The lower the gestational age, the lower the median value for both weight and height.  A quick glance at their tables indicate that infants born at 25 weeks gestation remained on average about 2 kg and 4 cm smaller than full term infants.  Infants born at 32 weeks gestation were on average about 1 kg and 2 cm smaller through the study period.
  • The absolute differences in weight and height were nearly constant, indicating that there was a lack of ‘catch-up’ growth.  At the same time, a child ‘following his own curve’ parallel to growth curve is likely a normal pattern
  • Head circumference at the end of the first year was similar between preterm and term infants
  • Greater variability was noted in boys

While this study did not adjust for maternal height, it is known that short maternal height does correlate with increased likelihood of short offspring.  This is partly mediated by having a small for gestational age birth.  Other limitations of the study included that the cohort was >90% Caucasian, and there was no adjustment for multiple births.

Useful links/references:

  • Growth Charts – Homepage -CDC growth charts
  • Pediatrics 2011; 128: e1187-94.  Growth and predictors of growth restraint in moderately preterm-born children.
  • Pediatrics 2003; 112: e30-8.  Growth of preterm infants during 1st 20 years.