Preterm Babies: Higher Insulin at Birth, in Early Childhood

February 11, 2014

Children born prematurely have higher insulin levels at birth and in early childhood than those delivered full term, new research indicates. And the more prematurely they are born, the higher their insulin levels are, the study shows.

Given that premature births are increasing, especially among certain ethnic minorities, this finding has important clinical implications, said lead author Guoying Wang MD, PhD, from Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. She and her colleagues report their results today in the February 12 issue of the Journal of the American Medical Association.

Prematurity is "now a major public-health threat, affecting everyone, not just the poor, and it is growing," with 12% of all babies in the United States born preterm, a figure that rises to almost 20% among African Americans, Dr. Wang told Medscape Medical News.

Although prematurity has previously been linked with type 2 diabetes in later life — in children, adolescents, and adults — this new work "is the first to demonstrate that this linkage starts in utero," noted Dr. Wang. She and her colleagues show that the disturbance in insulin regulation "is evident even at birth, which means that it happens in the womb. This is the missing piece," she observed. Further strengthening the observation is the "dose-response" relationship seen (ie, the more premature the baby, the higher the insulin levels), she noted.

There are several clinical implications, said Dr. Wang. First, the results reinforce recent guidelines from the American College of Obstetricians and Gynecologists (ACOG), which is trying to curb early delivery wherever possible — for example, by advising delaying C-sections "if not clinically indicated." Included in these recommendations is a new definition of "full term," which is now 39 weeks' gestation or greater, she noted. "Preterm" is defined as any birth occurring before 37 weeks' gestation.

Second, there is an important message here for pediatricians, she said, observing that the "link between being born preterm and metabolic disorders is not well recognized" in this community. Such babies are historically given high calorific feeds to help them grow, she noted, and while this is indicated, it is vital that preterm babies simply catch up rather than end up with excess weight gain, she stressed. "Preterm babies should be given optimal nutrition, but their growth trajectory should be carefully monitored. Also, at some point, their blood glucose and insulin should be measured."

And there is an important role here for family practitioners and GPs, too, Dr. Wang added. "If we promote healthy adults, we will reduce premature births [both underweight and overweight/obese women are at higher risk of giving birth prematurely]. If people do have preterm babies, we can help minimize the consequences; we shouldn't always regard preventing chronic disease as adult business."

Writing in an accompanying editorial, Mark Hanson, DPhil, FRCOG, from University Hospital, Southampton, United Kingdom, says the report by Dr. Wang and colleagues "adds a new chapter" to the story of the "thrifty phenotype." "The data support earlier findings from prepubertal children that preterm birth is associated with elevated plasma insulin but now provide data at earlier time points," he notes.

Insulin Levels up to 2-Fold Higher for Early Premature

To investigate whether altered insulin homeostasis is detectable at birth and through childhood, Dr. Wang and colleagues prospectively tracked a predominantly urban minority cohort of 1358 children recruited at birth from 1998 to 2010 and followed up from 2005 to 2012 at Boston Medical Center, Massachusetts.

Random plasma insulin levels were measured at 2 time points: at birth (cord blood) and in early childhood (venous blood). The median age for the second measurement was 1.4 years (range, 0.5 – 6.5 years) among 4 gestational age groups: full term (>39 weeks), early term (37 – 38 weeks), late preterm (34 – 36 weeks), and early preterm (<34 weeks).

The geometric mean of insulin levels at birth were 9.2 µIU/mL for full term, 10.3 µIU/mL for early term, 13.2 µIU/mL for late preterm, and 18.9 µIU/mL for early preterm.

Insulin levels at birth were higher by 1.13-fold for early term, 1.45-fold for late preterm, and 2.05-fold for early preterm than for those born full term.

In early childhood, mean insulin levels were 11.2 µIU/mL for full term, 12.4 µIU/mL for early term, 13.3 µIU/mL for late preterm, and 14.6 µIU/mL for early preterm.

At the same stage, random plasma insulin levels were higher by 1.12-fold for early term, 1.19-fold for late preterm, and 1.31-fold for early preterm than those born full term.

Infants ranked in the top insulin tertile at birth were more likely to remain in the top tertile (41.2%) compared with children ranked in the lowest tertile (28.6%) in early childhood.

"We found that plasma insulin levels at birth were inversely associated with gestational age in a dose-response fashion, even after adjustment for birth weight for gestational age and other measured prenatal and perinatal variables. This association was also observed in early childhood," Dr. Wang and colleagues observe.

Trajectory of Risk Commencing Early in Life

"This study fills a gap in the knowledge base regarding insulin levels during early developmental periods in children born preterm," they add. "Our findings suggest that insulin resistance exhibited by adolescents and adults born preterm may originate in utero and that the developmental programming that occurs in small-for-gestational-age births may also occur in preterm births, irrespective of whether they are small or appropriate for gestational age.

"These findings provide additional evidence that preterm birth (and perhaps early-term birth as well) may be a risk factor for the future development of insulin resistance and type 2 diabetes," they state.

Dr. Hanson says in his editorial that the fact that the higher levels of plasma insulin at birth track into early childhood strengthens "the argument for a trajectory of risk commencing very early in life." The findings also persisted after correction for infant's sex, Apgar score and leptin level at birth, maternal race, cigarette smoking, parity, mother's prepregnancy body mass index, gestational or pregestational diabetes, and antenatal steroid administration for preterm delivery, he stresses.

Hence, this study and others reveal "just how early the first steps toward prevention of diabetes may be possible and raise the prospect that rigorous studies of early-life interventions could form an important aspect of helping to reduce noncommunicable-disease risk," he concludes.

Dr. Wang agrees: "Preterm babies are recognized as a high-risk population for infant mortality and childhood morbidity and have issues with neurodevelopment, such as chronic hearing problems, as well as a higher risk of other conditions like chronic lung disease. But I don't think the link between being born preterm and metabolic disorders is well recognized.

"Ten years ago, blood pressure was added to the list of things that pediatricians monitor, and cholesterol levels are taken from age 9 now, but insulin and glucose levels are at the discretion of the pediatrician. Particularly for preterm babies, they should be monitored routinely," she concluded.

Dr. Wang reports no relevant financial relationships. Disclosures for the coauthors are listed in the article. Dr. Hanson reports consulting for National Children's Research Centre, Dublin; grant funding or grants pending from the British Heart Foundation, Biotechnology and Biological Sciences Research Council, the European Union Seventh Framework Program, National Institute for Health Research, and the Bupa Foundation; receiving payment for lectures from Nestec, Danone, and Abbott; and receiving travel accommodations from Novo Nordisk.

JAMA. 2014;311:575-576, 587-596. Abstract Editorial


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