Black father holding newborn baby son to represent the fact that children of all ethnicities can inherit cystic fibrosis
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Cord blood protein levels may be associated with birth weight and growth trajectories early in life, according to a new study. They found seven cord blood proteins overall that showed effects: Two were positively associated with birth weight and/or the birth weight ratio and five were negatively associated.  

“Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics,” the researchers write.

These findings could open a window into predicting, and planning for, lifelong health.

The study was published in JAMA Network Open. The lead author is Thessa Van Pee of the Center for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.

Birth weight reflects in utero health, including the nutritional condition of the mother and development of the fetus. The infant’s sex, maternal diet and smoking during pregnancy, pregnancy complications (eg, diabetes gravidarum, preeclampsia, or gestational hypertension), and socioeconomic status all influence full-term birth weight.

As the researchers note, “Approximately 9% of infants are born with a too-high birth weight (>4000 g) and 15% to 20% are born with too-low birth weight (<2500 g). Both deviations are public health concerns, as they are associated with short- and long-term health consequences, eg, neonatal mortality,childhood hypertension, and type 1 and 2 diabetes.

The cord blood proteome consists of proteins derived from both mother and fetus. It’s thought it might offer valuable insights into the physiological and pathological state of the fetus and even its future health. However, its association with birth weight and growth trajectories early in life have been largely unexplored until now.

This study included 288 newborns from the ongoing prospective Environmental Influence on Early Aging birth cohort study. The researchers aimed to  identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories.

Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages four to six years. Data were analyzed from February 2022 to September 2023.

The outcome measured  was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age four to six years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins.

Among the 288 infants, 125 [43.4%] were male and the mean gestation age was 277.2 days. The mean age of the child at the follow-up examination was 4.6 years old. 

The researchers found significant associations of birth weight and BWR with 7 proteins There were two positive associations, with afamin and secreted frizzled-related protein 4 (SFRP4). They also found five negative associations, cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2), ephrin type-A receptor 4 (EPHA4 SLIT) and NTRK-like protein 1 (SLITRK1), transcobalamin-1 (TCN1), and unc-5 netrin receptor D (UNC5D). 

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