Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Generalized disruption of inherited genomic imprints leads to wide-ranging placental defects and dysregulated fetal growth.

Monoallelic expression of imprinted genes, including ones solely expressed in the placenta, is essential for normal placental development and fetal growth. To better understand the role of placental imprinting in placental development and fetal growth, we examined conceptuses developing in the absence of maternally derived DNA (cytosine-5-)-methyltransferase 1o (DNMT1o). Absence of DNMT1o results in the partial loss of methylation at imprinted differentially methylated domain (DMD) sequences in the embryo and the placenta. Mid-gestation E9.5 DNMT1o-deficient placentas exhibited structural abnormalities of all tissue layers. At E17.5, all examined placentas had aberrant placental morphology, most notably in the spongiotrophoblast and labyrinth layers. Abnormalities included an expanded volume fraction of spongiotrophoblast tissue with extension of the spongiotrophoblast layer into the labyrinth. Many mutant placentas also demonstrated migration abnormalities of glycogen cells. Additionally, the volume fraction of the labyrinth was reduced, as was the surface area for maternal fetal gas exchange. Despite these placental morphologic abnormalities, approximately one-half of DNMT1o-deficient fetuses survived to late gestation (E17.5). Furthermore, DNMT1o-deficient placentas supported a broad range of fetal growth. The ability of some DNMT1o-deficient and morphologically abnormal placentas to support fetal growth in excess of wild type demonstrates the importance of differential methylation of DMDs and proper imprinting of discrete gene clusters to placental morphogenesis and fetal growth.

Loss of inherited genomic imprints in mice leads to severe disruption in placental lipid metabolism.

INTRODUCTION: Monoallelic expression of imprinted genes is necessary for placental development and normal fetal growth. Differentially methylated domains (DMDs) largely determine the parental-specific monoallelic expression of imprinted genes. Maternally derived DNA (cytosine-5-) -methyltransferase 1o (DNMT1o) maintains DMDs during the eight-cell stage of development. DNMT1o-deficient mouse placentas have a generalized disruption of genomic imprints. Previous studies have demonstrated that DNMT1o deficiency alters placental morphology and broadens the embryonic weight distribution in late gestation. Lipids are critical for fetal growth. Thus, we assessed the impact of disrupted imprinting on placental lipids. METHODS: Lipids were quantified from DNMT1o-deficient mouse placentas and embryos at E17.5 using a modified Folch method. Expression of select genes critical for lipid metabolism was quantified with RT-qPCR. Mitochondrial morphology was assessed by TEM and mitochondrial aconitase and cytoplasmic citrate concentrations quantified. DMD methylation was determined by EpiTYPER. RESULTS: We found that DNMT1o deficiency is associated with increased placental triacylglycerol levels. Neither fetal triacylglycerol concentrations nor expression of select genes that mediate placental lipid transport were different from wild type. Placental triacylglycerol accumulation was associated with impaired beta-oxidation and abnormal citrate metabolism with decreased mitochondrial aconitase activity and increased cytoplasmic citrate concentrations. Loss of methylation at the MEST DMD was strongly associated with placental triacylglycerol accumulation. DISCUSSION: A generalized disruption of genomic imprints leads to triacylglycerol accumulation and abnormal mitochondrial function. This could stem directly from a loss of methylation at a given DMD, such as MEST, or represent a consequence of abnormal placental development.

Gestational weight gain in twin pregnancies and maternal and child health: a systematic review.

Our objective was to systematically review the data interrogating the association between gestational weight gain (GWG) and maternal and child health among women with twin gestations. We identified 15 articles of twin gestations that studied GWG in relation to a maternal, perinatal or child health outcome and controlled for gestational age at delivery and prepregnancy body mass index. A positive association between GWG and fetal size was consistently found. Evidence on preterm birth and pregnancy complications was inconsistent. The existing studies suffer from serious methodological weaknesses, including not properly accounting for the strong correlation between gestational duration and GWG and not controlling for chorionicity. In addition, serious perinatal outcomes were not studied, and no research is available on the association between GWG and outcomes beyond birth. Our systematic review underscores that GWG in twin gestations is a neglected area of research. Rigorous studies are needed to inform future evidence-based guidelines.