OBJECTIVE: High prepregnancy maternal body mass index (BMI) is associated with an increased risk in childhood overweight and obesity. This study sought to expand upon the research of this phenomenon/trend by examining the role of placental weight in inter-generational obesity risk. METHODS: This prospective birth cohort study was conducted at Boston Medical Center in Boston, Massachusetts. Between 1998 and 2016, the study recruited and tracked 1,025 mother-infant pairs who have been followed from birth prospectively up to age 19 and who had data on placental pathology along with pre-, peri-, and post-natal variables, including maternal and child BMI. This study analyzed 6 Groups defined by placental weight tertiles and maternal overweight and obesity (BMI ≥ 25 kg/m2) (binary). Group 0 includes lowest placental tertile and maternal not overweight and obesity. Group 1 includes lowest placental tertile and maternal overweight and obesity. Group 2 includes middle placental tertile and maternal not overweight. Group 3 includes middle placental tertile and maternal overweight and obesity. Group 4 includes highest placental tertile and maternal not overweight. Group 5 includes highest placental tertile and maternal overweight and obesity. MAIN OUTCOMES AND MEASURES: Child BMI z-score was calculated according to United States reference data for specific age and sex. Childhood overweight and obesity was defined as an BMI in the 85th percentile or greater for age and sex. Maternal overweight and obesity was defined as a BMI of 25kg/m2 or greater, and placental weight was classified into tertiles based on sex- and gestational age. RESULTS: The mean (SD) maternal age at delivery was 28.7 (6.6) years and the mean (SD) child age at last visit was 9.5 (4.9) years. Among 1,025 mothers, 54.15% were overweight with an average BMI of 27.0 kg/m2. 68.98% of mothers were black, 76.5% never smoked, and 62.73% had less than a high school education. Among 1,025 children 447 (43.61%) were overweight. As expected, maternal overweight and obesity was associated with the highest risk for childhood overweight and obesity, with an odds ratio of 3.752 (95% CI, 2.137-6.588) as well as the largest increase in child BMI z-score. The strong association remained after adjusting for placental weight and other covariables, including birth weight. When maternal overweight and obesity and placental weight were analyzed in combined groups (0-5), they jointly increased the risk of child overweight or obesity. Using group 0 as reference, the group 5 had the highest risk of child overweight or obese and the largest increase in child BMI z-score. CONCLUSIONS: In this urban low-income prospective birth cohort, we observed a strong inter-generational link of overweight or obesity. Furthermore, there was an additive effect of maternal overweight and obesity and placental weight on child risk of overweight and obesity. Additional studies are warranted to replicate our findings and further investigate the biological pathways underlying the inter-generational obesity risk. / 2021-06-17T00:00:00Z

Abstract Gestational diabetes mellitus (GDM) is defined as disturbed glucose metabolism first recognized during pregnancy. Untreated GDM increases the risk of obstetric and neonatal complications, such as fetal overgrowth (macrosomia). The first-line treatment of GDM includes diet therapy and the self-monitoring of blood glucose concentrations and, if needed, pharmacotherapy, which is most commonly accomplished with insulin. Oral anti-diabetic agents such as metformin have recently been under investigation. GDM increases the risk of developing overt diabetes, metabolic syndrome and cardiovascular diseases. The aim of the present study was to investigate the effect of metformin vs. insulin therapy on pregnancy and neonatal outcome as well as on later growth and development of the infant and to investigate the independent and concomitant effects of GDM and maternal overweight/obesity on pregnancy outcome and maternal long-term risks. In a randomized study of 100 women, metformin therapy was not associated with an increased risk of pregnancy or neonatal complications when compared with insulin treatment. However, 32% of the women treated with metformin needed additional insulin in the achievement of normoglycaemia. The need of additional insulin was associated with maternal obesity, an earlier need of pharmacotherapy and fasting hyperglycaemia in OGTT. Infants exposed to metformin were taller and heavier at the age of 18 months compared with infants exposed to insulin. There was no difference in the motor, social or linguistic development between these children when assessed at the age of 18 months. In an epidemiological study of 24,565 pregnancies, normal-weight women with GDM did not have an increased risk of macrosomia or Caesarean delivery when compared with normal-weight women without GDM. GDM was an independent risk factor of neonatal morbidity, especially hypoglycaemia. Maternal overweight and obesity were independent risk factors of macrosomia and obesity was also an independent risk factor of Caesarean delivery and neonatal morbidity. In a follow-up study (n = 116), women with a history of insulin-treated GDM had an increased risk of metabolic syndrome when compared with women without GDM 19 years after index pregnancy. However, maternal pre-pregnancy overweight as such was a stronger risk factor as regards the development of metabolic syndrome than previous GDM. / Tiivistelmä Raskausdiabetes on ensimmäisen kerran raskauden aikana ilmaantuva glukoosiaineenvaihdunnan häiriö. Hoitamattomana raskausdiabetes lisää raskaana olevan ja vastasyntyneen komplikaatioriskiä, erityisesti sikiön liiallista kasvua (makrosomiaa). Raskausdiabetestä hoidetaan ruokavaliolla, veren glukoosipitoisuuksien omaseurannalla sekä tarvittaessa lääkehoidolla, joka on useimmiten insuliinihoitoa. Muita diabeteslääkkeitä, kuten metformiinia, on tutkittu viime vuosina paljon. Raskausdiabetes lisää myöhemmällä iällä riskiä sairastua diabetekseen, metaboliseen oireyhtymään sekä sydän- ja verisuonisairauksiin. Tämän tutkimuksen tarkoituksena oli selvittää metformiinihoidon tehoa ja turvallisuutta verrattuna insuliiniin raskausdiabeteksen hoidossa. Lisäksi selvitettiin raskausdiabeteksen ja ylipainon itsenäistä vaikutusta raskauskomplikaatioiden esiintyvyyteen sekä naisen myöhempään sairastuvuuteen. Satunnaistetussa tutkimuksessa (n = 100) metformiini ei lisännyt vastasyntyneen makrosomian eikä vastasyntyneen tai raskauskomplikaatioiden riskiä verrattuna insuliiniin. Metformiinilla hoidetuista naisista 32% tarvitsi lisäksi insuliinia normaalin glukoositasapainon saavuttamiseksi. Lisäinsuliinin tarvetta ennustivat äidin lihavuus, varhainen lääkehoidon tarve sekä kohollaan olevat glukoosin paastoarvot sokerirasituksessa. Metformiinille altistuneet lapset olivat sekä pidempiä että painavampia 18 kuukauden iässä kuin insuliinille altistuneet lapset, mutta heidän motorisessa, sosiaalisessa tai kielellisessä kehityksessään ei ollut eroja. Epidemiologisessa tutkimuksessa (n = 24,565) normaalipainoisen naisen raskausdiabetes ei lisännyt keisarileikkauksen tai sikiön makrosomian riskiä verrattuna normaalipainoisiin naisiin, joiden sokeriaineenvaihdunta oli normaali. Raskausdiabetes lisäsi itsenäisesti vastasyntyneen sairastavuuden ja hypoglykemian riskiä. Äidin ylipaino ja lihavuus lisäsivät itsenäisesti makrosomian riskiä ja lihavuus myös keisarileikkauksen ja vastasyntyneen sairastuvuuden riskiä. Seurantatutkimuksessa (n = 116) insuliinihoidettujen raskausdiabeetikoiden riski sairastua 19 vuotta raskauden jälkeen myöhempään metaboliseen oireyhtymään oli lisääntynyt verrattuna terveisiin verrokkeihin. Raskautta edeltävä ylipaino oli vahvempi riskitekijä metabolisen oireyhtymän kehittymiselle kuin aiempi raskausdiabetes.