Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study.

BACKGROUND: Newborns exhibit substantial variation in fat mass accretion over gestation. These individual differences in newborn adiposity extend into infancy and childhood and relate to subsequent risk of obesity and metabolic dysregulation. Maternal glucose homeostasis in pregnancy has been proposed as an underlying mechanism; however, the timing in gestation when maternal glucose regulation influences the progression of fetal fat deposition remain unclear. OBJECTIVE: This study aimed to investigate the cross-sectional and longitudinal association of maternal insulin resistance in early, mid, and late pregnancy with fetal fat deposition in uncomplicated pregnancies. We hypothesized that maternal insulin resistance at early, mid, and late gestation is positively associated with fetal fat deposition, and that the magnitude of the association is greater for the mid and late gestation measures than for the early gestation measure. STUDY DESIGN: In a longitudinal study of 137 low-risk pregnancies, a fasting maternal blood sample was obtained and fetal ultrasonography was performed at ≈ 12, 20, and 30 weeks' gestation. Maternal insulin resistance was quantified using the homeostasis model assessment of insulin resistance (fasting insulin×fasting glucose/405). Estimated fetal adiposity was calculated by integrating measurements of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness. The associations between maternal homeostasis model assessment of insulin resistance and estimated fetal adiposity and estimated fetal weight were determined by multiple linear regression adjusted for potential confounding factors including maternal age, parity, race and ethnicity, prepregnancy body mass index, gestational weight gain per week, fetal sex, and gestational age at assessments. RESULTS: Maternal homeostasis model assessment of insulin resistance at ≈ 12, 20, and 30 weeks was 2.79±1.79 (±standard deviation), 2.78±1.54, and 3.76±2.30, respectively. Homeostasis model assessment of insulin resistance at 20 weeks was positively associated with estimated fetal adiposity at 20 weeks (r=0.261; P=.005). Homeostasis model assessment of insulin resistance at 20 weeks (r=0.215; P=.011) and 30 weeks (r=0.285; P=.001) were also positively associated with estimated fetal adiposity at 30 weeks. These relationships remained significant after adjustment for confounding factors. There was no significant correlation between homeostasis model assessment of insulin resistance and estimated fetal weight at 20 and 30 weeks' gestation. CONCLUSION: In low-risk pregnancies, maternal insulin resistance at mid and late but not early pregnancy is significantly associated with fetal adiposity but not with fetal weight. Maternal insulin resistance in mid-gestation could provide a basis for risk identification and interventions that target child adiposity.

Delayed rhythm formation of normal-structured, growth-restricted fetuses using fetal heart rate monitoring patterns.

AIMS: Growth-restricted fetuses have delayed rhythm formation in utero. The awake-sleep cycle of fetal heart rate pattern is thought to represent fetal rhythm. We aimed to study if the emergence of rhythm formation on fetal heart rate pattern delays in fetal growth restriction compared to appropriate-for-date fetuses. METHODS: This was a retrospective cohort study including 75, normal-structured, singleton fetuses. Of them, 21 were fetal growth restriction and the remaining 54 were appropriate-for-date infants. We examined timing of emergence of rhythm formation on fetal heart rate pattern comparing between fetal growth restriction and appropriate-for-date fetuses after adjusting possible confounding factors as outcome measures. RESULTS: Rhythm formation was significantly delayed in fetal growth restriction (<10th percentile) compared to the appropriate-for-date subgroups (10-30, 30-50, 50-70 and 70-90th percentile) by 1-2 weeks. After adjusting confounding factors, growth restriction was the only independent variable to delay fetal rhythm formation. One infant for each group had neurodevelopmental disorder and the incidence did not reach statistically significant. CONCLUSION: Based on fetal heart rate pattern analysis, growth-restricted fetuses show 1-2 weeks delay in rhythm formation compared to appropriate-for-date fetuses.

Prenatal diagnosis of premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome.

Premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome is a rare genetic disorder. In this case report, we describe the prenatal diagnosis of PCS/MVA syndrome in a 24-year-old, gravida 1, para 1, woman who was referred to us in her second trimester due to fetal growth restriction and extreme microcephaly (-5.0 standard deviations). Amniocentesis and chromosomal analysis confirmed PCS in 80% of cultured fetal cells. PCS findings were positive in 9% of paternal cells and 11% of maternal cells, indicative that both were PCS carriers. Genetic analysis confirmed that the fetus carried a combined heterozygote of maternal G > A point mutation of the promoter area of the BUB1B gene and a paternal Alu sequence insertion between intron 8 and exon 9 of the BUB1B gene. As PCS/MVA syndrome is associated with the development of various malignancies in early life, prenatal diagnosis is important for effective planning of post-natal care.

Prospective association of fetal liver blood flow at 30 weeks gestation with newborn adiposity.

BACKGROUND: The production of variation in adipose tissue accretion represents a key fetal adaptation to energy substrate availability during gestation. Because umbilical venous blood transports nutrient substrate from the maternal to the fetal compartment and because the fetal liver is the primary organ in which nutrient interconversion occurs, it has been proposed that variations in the relative distribution of umbilical venous blood flow shunting either through ductus venosus or perfusing the fetal liver represents a mechanism underlying this adaptation. OBJECTIVE: The objective of the present study was to determine whether fetal liver blood flow assessed before the period of maximal fetal fat deposition (ie, the third trimester of gestation) is prospectively associated with newborn adiposity. STUDY DESIGN: A prospective study was conducted in a cohort of 62 uncomplicated singleton pregnancies. Fetal ultrasonography was performed at 30 weeks gestation for conventional fetal biometry and characterization of fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Newborn body fat percentage was quantified by dual energy X-ray absorptiometry imaging at 25.8 ± 3.3 (mean ± standard error of the mean) postnatal days. Multiple regression analysis was used to determine the proportion of variation in newborn body fat percentage explained by fetal liver blood flow. Potential confounding factors included maternal age, parity, prepregnancy body mass index, gestational weight gain, gestational age at birth, infant sex, postnatal age at dual energy X-ray absorptiometry scan, and mode of infant feeding. RESULTS: Newborn body fat percentage was 13.5% ± 2.4% (mean ± standard error of the mean). Fetal liver blood flow at 30 weeks gestation was significantly and positively associated with newborn total fat mass (r=0.397; P<.001) and body fat percentage (r=0.369; P=.004), but not with lean mass (r=0.100; P=.441). After accounting for the effects of covariates, fetal liver blood flow explained 13.5% of the variance in newborn fat mass. The magnitude of this association was pronounced particularly in nonoverweight/nonobese mothers (prepregnancy body mass index, <25 kg/m2; n=36) in whom fetal liver blood flow explained 24.4% of the variation in newborn body fat percentage. CONCLUSION: Fetal liver blood flow at the beginning of the third trimester of gestation is associated positively with newborn adiposity, particularly among nonoverweight/nonobese mothers. This finding supports the role of fetal liver blood flow as a putative fetal adaptation underlying variation in adipose tissue accretion.

Preterm labor and neonatal sepsis caused by intrauterine Helicobacter cinaedi infection.

Helicobacter cinaedi is a rare pathogen but known to cause bacteremia, cellulitis and enterocolitis. Recently, cases of involving various organs are increasingly reported such as endocarditis, meningitis, and kidney cyst infection. We report a case of intrauterine H. cinaedi infection leading preterm birth and neonatal sepsis. A 29-year-old pregnant women who was no underlying disease hospitalized due to threatened preterm labor at 22 weeks of gestation. Clinical findings showed uterine tenderness, fever, leukocytosis and elevated C-reactive protein. H. cinaedi was isolated from amniotic fluid obtained by transabdominal amniocentesis. We diagnosed as intrauterine H. cinaedi infection and administered intravenous ampicillin followed by oxytocin to terminate pregnancy. A live 446 g male infant was delivered. The patient was no signs of infection throughout postpartum course and discharged on post-delivery day 5. The neonate was admitted in neonatal intensive care unit and administered ampicillin and amikacin. H. cinaedi was isolated from umbilical cord blood culture. He has no signs of infection on day 5 but died from uncontrollable hyperglycemia and ketoacidosis on 15 days of age. H. cinaedi can cause intrauterine infection during pregnancy and lead preterm labor and neonatal sepsis.

Developmental changes in catecholamine requirement, volume load and corticosteroid supplementation in premature infants born at 22 to 28 weeks of gestation.

BACKGROUND: Due to circulatory instability, premature infants require volume loads, catecholamines and steroid supplementation to improve mortality and neurodevelopmental outcome. However, a complete quantitative analysis concerning the relationship between supplementation and gestational age, especially in infants born at 22 to 24 weeks of gestation, is lacking. AIM: To investigate whether less mature infants need higher doses of catecholamine, volume loads and steroid, and whether those who require higher doses have poorer outcome. STUDY DESIGN: A retrospective, observational study was performed at a tertiary center in a university setting. Among the consecutive 221 premature infants born at 22 to 28 weeks of gestation, we selected 108 infants who had no apparent pathological conditions other than prematurity. Catecholamines, volume loads and steroid, given to attain sufficient blood pressure and urinary output, were quantitatively analyzed during the first 24 hours. OUTCOME MEASURES: Quantity of catecholamines, volume expanders and steroid supplementation as a function of gestational age and childhood outcome at 2 years. RESULTS: Catecholamines and volume loads were increased in a step-wise manner with decreasing gestational age. Intact survival rate was significantly lower in infants born before 25 weeks of gestation compared with the more mature infants. Among infants born at 22 to 24 weeks' gestation, catecholamine and volume load increased significantly in poor outcome infants compared with good outcome infants. CONCLUSIONS: From a developmental viewpoint, progressively larger doses of catecholamine, volume expanders and corticosteroid are required to stabilize circulatory adaptation to neonatal life in infants between 22 to 28 weeks of gestation.