Are Extremely Low Gestational Age Newborns Born to Obese Women at Increased Risk of Cerebral Palsy at 2 Years?

The authors hypothesized that the risk of cerebral palsy at 2 years in children born extremely preterm to overweight and obese women is increased relative to the risk among children born to neither overweight nor obese women. In a multicenter prospective cohort study, the authors created multinomial logistic regression models of the risk of diparetic, quadriparetic, and hemiparetic cerebral palsy that included the prepregnancy body mass index of mothers of 1014 children born extremely preterm, cerebral palsy diagnoses of children at 2 years, as well as information about potential confounders. Overweight and obese women were not at increased risk of giving birth to a child who had cerebral palsy. The risk ratios associated with overweight varied between 1.1 for quadriparesis (95% CI = 0.5, 2.1) to 2.0 for hemiparesis (95% CI = 0.4, 9.8). The risk ratios associated with obesity varied between 0.7 for diparesis (95% CI = 0.2, 2.5) to 2.5 for hemiparesis (95% CI = 0.4, 13).

Elevations of inflammatory proteins in neonatal blood are associated with obesity and overweight among 2-year-old children born extremely premature.

BackgroundChildhood obesity is associated with elevated blood concentrations of inflammation markers. It is not known to what extent inflammation precedes the development of obesity.MethodsIn a cohort of 882 infants born before 28 weeks of gestation, we examined relationships between concentrations of 25 inflammation-related proteins in blood obtained during the first two postnatal weeks and body mass index at 2 years of age.ResultsAmong children delivered for spontaneous indications (n=734), obesity was associated with elevated concentrations of four proteins (IL-1ß, IL-6, TNF-R1, and MCP-1) on the first postnatal day; one protein (IL-6) on postnatal day 7; and two proteins (ICAM-3 and VEGF-R1) on postnatal day 14. Among children delivered for maternal or fetal indications (n=148), obesity was associated with elevated concentrations of seven proteins on the 14th postnatal day. In multivariable models in the spontaneous indications subsample, elevated IL-6 on day 1 predicted obesity (odds ratio: 2.9; 95% confidence limits: 1.2, 6.8), whereas elevated VCAM-1 on day 14 predicted overweight at 2 years of age (odds ratio: 2.3; 95% confidence limits: 1.2, 4.3).ConclusionsIn this cohort, neonatal systemic inflammation preceded the onset of obesity, suggesting that inflammation might contribute to the development of obesity.

Maternal obesity and attention-related symptoms in the preterm offspring.

BACKGROUND: Maternal pre-pregnancy obesity, in term-born children, is associated with an increased risk of attention problems, however this relationship has not been explored among children born extremely preterm. AIM: To estimate the risk of attention problems at age 10years in children born very preterm to overweight (i.e., body mass index (BMI) 25-29kg/m2) and obese (i.e., BMI≥30kg/m2) women relative to the risk among children born to women who were neither overweight nor obese (i.e. BMI<25kg/m2). STUDY DESIGN: Multi-center prospective cohort study. METHODS: A total of 764 children born before the 28th week of gestation and whose mother's pre-pregnancy height and pre-pregnancy weight were obtained at birth had an IQ≥70 at age 10years when parents and teachers completed Child Symptom Inventory-4 questionnaires that included items about the presence of ADHD. RESULTS: Compared to children whose mother's pre-pregnancy weight was in the normal range (BMI<25kg/m2), children were at increased risk of parent-identified ADHD behaviors if their mother was overweight (odds ratio (OR)=1.9; 95% confidence interval (CI): 1.1, 3.3), or obese (OR=2.3; 95% CI: 1.4, 3.9). They were not at increased risk of teacher-identified ADHD characteristics if their mother was overweight before her pregnancy (OR=1.0; 95% CI: 0.6, 1.8), or obese (OR=1.0; 95% CI: 0.6, 1.6). CONCLUSION: Maternal overweight and obesity are associated with increased risk of parent-identified ADHD characteristics at 10years of age in children born extremely preterm.

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.

The role of systemic inflammation linking maternal BMI to neurodevelopment in children.

Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.

Maternal obesity and development of the preterm newborn at 2 years.

AIM: To evaluate to what extent extremely preterm children (<28 weeks' gestational age) of overweight (BMI 25-29) or obese (BMI ≥30) women are at increased risk of adverse development at 2 years measured with the Bayley Scales of Infant Development II in a multicenter prospective cohort study. METHODS: Heights and prepregnancy weights of the mothers of 852 preterm born children were collected and included in multinomial logistic regression models. RESULTS: Compared to newborns born to mothers with normal BMIs, newborns of obese mothers, but not those of overweight mothers, were more likely to have Bayley Scales indices more than 3 standard deviations below the reference mean (mental: OR = 2.1; 95% CI: 1.3, 3.5) (motor: OR = 1.7; 95% CI: 1.1, 2.7). These associations were even more prominent in children who did not have the intermittent or sustained systemic inflammation profile previously shown to be associated with severely impaired development (mental: OR = 4.6; 95% CI: 1.6, 14) (motor: OR = 3.7; 95% CI: 1.5, 8.9). CONCLUSION: Maternal obesity is associated with an increased risk of impaired offspring development. Some of this impaired development cannot be attributed to confounding due to immaturity, socio-economic correlates or neonatal systemic inflammation.

Is maternal obesity associated with sustained inflammation in extremely low gestational age newborns?

BACKGROUND: The offspring of obese women are at increased risk for systemic inflammation. Blood concentrations of inflammatory proteins in preterm newborns of obese women have not been reported. AIM: To compare blood concentrations in the highest quartile for gestational age of inflammatory proteins and day of blood specimen collection on two days at least one week apart of newborns of overweight (i.e., BMI 25-29) and obese women (i.e., BMI ≥ 30) with newborns of women with lower BMIs. Because deliveries for spontaneous indications are more likely than those for other indications to be associated with inflammation, we evaluated spontaneous indication deliveries separately from maternal or fetal indications. STUDY DESIGN: Prospective cohort study. SUBJECTS AND OUTCOME MEASURES: We measured from 939 children born before the 28th week of gestation 25 inflammation-related proteins in blood obtained on postnatal day 1 (range 1-3), day 7 (range 5-8) and day 14 (range 12-15). RESULTS: Among infants delivered for spontaneous indications, maternal BMI was not related to elevated concentrations of any protein. Among infants delivered for maternal (i.e., preeclampsia) or fetal indications, those whose mother was overweight or obese were more likely than others to have elevated concentrations of inflammation proteins. CONCLUSIONS: Maternal pre-pregnancy overweight and obesity appear to contribute to a pro-inflammatory state in very preterm newborns delivered for maternal or fetal indications. Our failure to see a similar pattern among newborns delivered for spontaneous indications, which often have inflammatory characteristics, might reflect competing risks.