High Maternal Pre-pregnancy Body Mass Research Articles

Associations of polymetabolic risk of high maternal pre-pregnancy body mass index with pregnancy complications, birth outcomes, and early childhood neurodevelopment: findings from two pregnancy cohorts

BackgroundA substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(< 30 kg/m2) or normal weight(18.5–24.99 kg/m2) and their children may suffer from adversities. Evidence suggests that BMI-related metabolic changes during pregnancy may predict adverse mother–child outcomes better than maternal anthropometric BMI.MethodsIn a cohort of 425 mother–child dyads, we identified maternal BMI-defined metabolome based on associations of 95 metabolic measures measured three times during pregnancy with maternal pre-pregnancy BMI. We then examined whether maternal BMI-defined metabolome performed better than anthropometric BMI in predicting gestational diabetes, hypertensive disorders, gestational weight gain (GWG), Caesarian section delivery, child gestational age and weight at birth, preterm birth, admission to neonatal intensive care unit (NICU), and childhood neurodevelopment. Based on metabolic measures with the highest contributions to BMI-defined metabolome, including inflammatory and glycolysis-related measures, fatty acids, fluid balance, ketone bodies, lipids and amino acids, we created a set of maternal high BMI-related polymetabolic risk scores (PMRSs), and in an independent replication cohort of 489 mother–child dyads tested their performance in predicting the same set of mother–child outcomes in comparison to anthropometric BMI.ResultsBMI-defined metabolome predicted all of the studied mother–child outcomes and improved their prediction over anthropometric BMI, except for gestational hypertension and GWG. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarian section delivery, admission to NICU, lower gestational age at birth, lower cognitive development score of the child, and improved their prediction over anthropometric BMI. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarean section delivery, NICU admission and child’s lower gestational age at birth even at the levels of maternal non-obesity and normal weight.ConclusionsMaternal BMI-defined metabolome improves the prediction of pregnancy complications, birth outcomes, and neurodevelopment in children over anthropometric BMI. The novel, BMI-related PMRSs generated based on the BMI-defined metabolome have the potential to become biomarkers identifying at-risk mothers and their children for timely targeted interventions even at the level of maternal non-obesity and normal weight.

Non-linear associations of maternal pre-pregnancy body mass index with risk of stillbirth, infant, and neonatal mortality in over 28 million births in the USA: a retrospective cohort study

Higher maternal pre-pregnancy body mass index (BMI) has been associated with higher risk of stillbirth, infant and neonatal mortality. Studies exploring underweight have varied in their conclusions. Our aim was to examine the risk of stillbirth, infant and neonatal mortality across the BMI distribution and establish a likely healthy BMI range. In this retrospective cohort study, we used publicly available datasets (covering 1st January 2014 to 31st December 2021) from the US National Center for Health Statistics National Vital Statistics System. All births were eligible; analyses included those with non-missing data. Fractional polynomial multivariable logistic regression was used to examine the associations of maternal pre-pregnant BMI with stillbirth (birth with no signs of life at ≥24 weeks), infant mortality (death of a live born baby aged <365 days) and neonatal mortality (death of a live born baby aged <28 days). There were 77,896/28,310,154 (2.8 per 1000 births) stillbirths, 143,620/28,231,807 (5.1 per 1000 live births) infant deaths and 94,246/28,231,807 (3.3 per 1000 live births) neonatal deaths among complete cases. Mean (SD) BMI was 27.1kg/m2 (6.7kg/m2). We found non-linear associations between BMI and all three outcomes; risk was elevated at both low and high BMIs although, for stillbirth, the increased risk at low BMI was less marked than for infant/neonatal mortality. The lowest risk was at a BMI of 21kg/m2 for infant and neonatal mortality and 19kg/m2 for stillbirth. Public health messaging for preconception and postnatal care should focus on healthy weight to maximise maternal and child health, and not focus solely on maternal overweight or obesity. European Research Council, US National Institute of Health, UK Medical Research Council and National Institute for Health and Care Research.

Maternal pre-pregnancy obesity affects the uncinate fasciculus white matter tract in preterm infants.

A growing body of evidence suggests an association between a higher maternal pre-pregnancy body mass index (BMI) and adverse long-term neurodevelopmental outcomes for their offspring. Despite recent attention to the effects of maternal obesity on fetal and neonatal brain development, changes in the brain microstructure of preterm infants born to mothers with pre-pregnancy obesity are still not well understood. This study aimed to detect the changes in the brain microstructure of obese mothers in pre-pregnancy and their offspring born as preterm infants using diffusion tensor imaging (DTI). A total of 32 preterm infants (born to 16 mothers with normal BMI and 16 mothers with a high BMI) at <32 weeks of gestation without brain injury underwent brain magnetic resonance imaging at term-equivalent age (TEA). The BMI of all pregnant women was measured within approximately 12 weeks before pregnancy or the first 2 weeks of gestation. We analyzed the brain volume using a morphologically adaptive neonatal tissue segmentation toolbox and calculated the major white matter (WM) tracts using probabilistic maps of the Johns Hopkins University neonatal atlas. We investigated the differences in brain volume and WM microstructure between preterm infants of mothers with normal and high BMI. The DTI parameters were compared among groups using analysis of covariance adjusted for postmenstrual age at scan and multiple comparisons. Preterm infants born to mothers with a high BMI showed significantly increased cortical gray matter volume (p = 0.001) and decreased WM volume (p = 0.003) after controlling for postmenstrual age and multiple comparisons. We found a significantly lower axial diffusivity in the uncinate fasciculus (UNC) in mothers with high BMI than that in mothers with normal BMI (1.690 ± 0.066 vs. 1.762 ± 0.101, respectively; p = 0.005). Our study is the first to demonstrate that maternal obesity impacts perinatal brain development patterns in preterm infants at TEA, even in the absence of apparent brain injury. These findings provide evidence for the detrimental effects of maternal obesity on brain developmental trajectories in offspring and suggest potential neurodevelopmental outcomes based on an altered UNC WM microstructure, which is known to be critical for language and social-emotional functions.

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Impact of prepregnancy body mass index on adverse pregnancy outcomes: analysis from the Longitudinal Indian Family hEalth cohort study

BACKGROUNDBoth high and low maternal prepregnancy body mass index can lead to suboptimal fetal growth and risk of pregnancy complications. In developed countries, nearly half of all women of childbearing age are either overweight or obese, and most data linking maternal body mass index and adverse pregnancy complications are limited to these populations. OBJECTIVEThis study aimed to prospectively evaluate the relationships between prepregnancy body mass index and adverse pregnancy outcomes using the Longitudinal Indian Family hEalth (LIFE) study. STUDY DESIGNWe modeled the relationships between prepregnancy body mass index and adverse pregnancy outcomes such as low birthweight, preterm birth, cesarean delivery, intrauterine growth restriction, miscarriage, and fetal death among 675 women aged 15 to 35 years with singleton pregnancies in the Longitudinal Indian Family hEalth study, a population-based prospective pregnancy cohort study conducted in Telangana, India. Prepregnancy body mass index was calculated as weight in kilograms divided by height in meters squared and was classified into 4 categories using the World Health Organization recommendations for Asian adults. Prepregnancy body mass index was assessed at a mean of 12.3 months before pregnancy. Odds ratios and 95% confidence intervals of adverse pregnancy outcomes were modeled and adjusted for confounders. RESULTSObese women had a 3-fold increased risk of cesarean delivery (odds ratio, 3.13; 95% confidence interval, 1.56–6.29) compared with normal-weight women. Those who were overweight also had a marginally increased risk of cesarean delivery, albeit not statistically significant (odds ratio, 1.17; 95% confidence interval, 0.61–2.24). Underweight women had a modestly increased risk of low birthweight, compared with normal-weight women (odds ratio, 1.12; 95% confidence interval, 0.71–1.77), although results were not significant. Conversely, obese (odds ratio, 0.71; 95% confidence interval, 0.28–1.77) and overweight (odds ratio, 0.61; 95% confidence interval, 0.24–1.51) women had a marginally decreased risk of low birthweight. CONCLUSIONOur data suggest that women with elevated prepregnancy body mass index may have a higher risk of adverse pregnancy outcomes, especially cesarean delivery. Although this study has limited generalizability, our findings are generalizable to rural to periurban regions of India. Further studies exploring the translatability of these findings to other populations are needed. In addition, targeted prepregnancy intervention studies and programs that include counseling on optimization of preconception health and lifestyle modification for improvement of subsequent pregnancy outcomes among overweight and obese women are needed.

Maternal Lipid Metabolism Is Associated With Neonatal Adiposity: A Longitudinal Study.

Pregnancy is characterized by progressive decreases in glucose insulin sensitivity. Low insulin sensitivity resulting in hyperglycemia is associated with higher neonatal adiposity. However, less is known regarding lipid metabolism, particularly lipid insulin sensitivity in pregnancy and neonatal adiposity. Because higher maternal prepregnancy body mass index is strongly associated with both hyperlipidemia and neonatal adiposity, we aimed to examine the longitudinal changes in basal and clamp maternal lipid metabolism as contributors to neonatal adiposity. Twelve women planning a pregnancy were evaluated before pregnancy, in early (12-14 weeks), and late (34-36 weeks) gestation. Body composition was estimated using hydrodensitometry. Basal and hyperinsulinemic-euglycemic clamp glucose and glycerol turnover (GLYTO) were measured using 2H2-glucose and 2H5-glycerol and substrate oxidative/nonoxidative metabolism with indirect calorimetry. Total body electrical conductivity was used to estimate neonatal body composition. Basal free-fatty acids decreased with advancing gestation (P = 0.0210); however, basal GLYTO and nonoxidative lipid metabolism increased over time (P = 0.0046 and P = 0.0052, respectively). Further, clamp GLYTO and lipid oxidation increased longitudinally over time (P = 0.0004 and P = 0.0238, respectively). There was a median 50% increase and significant positive correlation during both basal and clamp GLYTO from prepregnancy through late gestation. Neonatal adiposity correlated with late pregnancy basal and clamp GLYTO (r = 0.6515, P = 0.0217; and r = 0.6051, P = 0.0371). Maternal prepregnancy and late pregnancy measures of basal and clamp lipid metabolism are highly correlated. Late pregnancy basal and clamp GLYTO are significantly associated with neonatal adiposity and account for ~40% of the variance in neonatal adiposity. These data emphasize the importance of maternal lipid metabolism relating to fetal fat accrual.

Effects of the healthy start randomized intervention on psychological stress and sleep habits among obesity-susceptible healthy weight children and their parents.

Poor sleep and psychological stress are obesity determinants that are rarely included in obesity prevention programs. The aim was to report the effects of the Healthy Start randomized intervention on the secondary outcomes psychological stress and sleep duration and onset latency. Data was obtained from the Healthy Start randomized intervention conducted in 2009-2012 among Danish healthy weight children aged 2-6 years, who had either a high birth weight (>4,000 g), high maternal pre-pregnancy body mass index (>28 kg/m2), or low maternal educational level (≤10 years of schooling) and their parents. The intervention was designed to deliver improvements in diet and physical activity habits, optimization of sleep habits, and reduction of psychological family stress. The average intervention period was 15 months. Children with information on a 7-day sleep record, sleep onset latency, Strengths and Difficulties Questionnaire (SDQ), and a modified version of Parenting Stress Index (PSI) were included. The effects of the intervention on sleep habits, PSI scores, SDQ Total Difficulties (SDQ-TD) and Pro-social Behavior scores, and 95% Confidence Intervals (95% CI) were analyzed using linear regression intention-to-treat (n = 543 (intervention group n = 271, control group n = 272)) analyses. No statistically significant effects on sleep duration, sleep onset latency, PSI score, or SDQ Pro-social Behavior score were observed. Values both before and after the intervention were within the normal range both for children in the intervention and children in the control group. Mean change in SDQ-TD was 0.09 points (95% CI -0.57;0.59) in the intervention group, and -0.69 points (95% CI -1.16; -0.23) in the control group (p = 0.06). In conclusion, there were no intervention effects in relation to sleep duration, sleep onset latency, PSI score, or SDQ Pro-social behavior. There was an indication that children in the intervention group had slightly more behavioral problems than the control group after the intervention, but values were within normal range both before and after the intervention, and the difference is not considered to be clinically meaningful.

Association of Maternal Prepregnancy Body Mass Index With Fetal Growth and Neonatal Thalamic Brain Connectivity Among Adolescent and Young Women

Higher maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with adverse long-term outcomes for offspring, including obesity, poorer cognitive and social abilities, and increased risk of psychiatric disorders. Less clear is whether higher maternal BMI disrupts fetal growth and brain development. To investigate the association of maternal prepregnancy BMI with fetal growth and neonatal functional connectivity. This prospective longitudinal cohort study was conducted from 2012 to 2017. Participants included nulliparous pregnant adolescent and young adult women, aged 14 to 19 years who were recruited in the second trimester through Columbia University Irving Medical Center and Weill Cornell Medical College. Women received routine prenatal care and had no major health problems at the time of recruitment. Data were analyzed from January 2018 to March 2020. Maternal prepregnancy BMI. The main outcomes were fetal growth, measured as estimated fetal weight, and neonatal functional connectivity, measured using magnetic resonance imaging. Prepregnancy BMI and fetal ultrasonographic measurements were obtained from electronic health record review. Resting-state brain imaging data were acquired in infants within the first month of postnatal life. Functional connectivity was measured using intrinsic functional distribution and seed-based methods. Among 129 women recruited, 105 had ultrasonographic data from at least 2 points and were included in analyses. The mean (SD) age at delivery was 17.82 (1.31) years. Maternal prepregnancy BMI was positively associated with the slope of estimated fetal weight (β = 0.668; 95% CI, 0.163 to 1.175; P = .01) but not with fetal head circumference (β = -0.004; 95% CI, -0.024 to 0.016; P = .70). In a subsample of 45 infants with magnetic resonance imaging data, maternal prepregnancy BMI was positively correlated with global connectivity in the left thalamus. Using this thalamic region as a seed, higher maternal BMI was associated with greater local thalamic (both hemispheres) and lower frontothalamic connectivity. These results suggest that maternal prepregnancy BMI was associated with the development of regulation of body weight and thalamic functional brain connectivity in offspring even during fetal development.

Abstract P290: The Association of Maternal Pre-pregnancy Weight With Childhood and Adolescent Blood Pressure and the Modifying Role of Vitamin D

Introduction: High blood pressure (BP) is the leading modifiable risk factor of cardiovascular diseases. High maternal pre-pregnancy body mass index (BMI) may be one of earliest risk factors for high child BP, but evidence supporting this hypothesis is limited. Vitamin D was recently found to protect against elevated BP in childhood, yet no studies to our knowledge have examined if Vitamin D could be a modifiable target for mitigating the association of pre-pregnancy BMI and child BP. Methods: We analyzed longitudinal data of 719 mother-child pairs in the Boston Birth Cohort enrolled from 1998-2012 at the Boston Medical Center. We calculated child systolic BP (SBP) percentile according to a US reference and defined low Vitamin D as cord blood 25(OH)D concentration &lt;11 ng/mL. We examined the change in child SBP percentile per 5-kg/m 2 increment in pre-pregnancy BMI using linear regression models with GEE estimates. We adjusted for confounders (see Figure footnote) and assessed mediation by further adjusting for child BMI-z score. Results: Our analytic sample included 451 (63%) African American/Haitian mothers, 361 (50%) girls, and 304 (42%) children with low cord blood Vitamin D. A 5-kg/m 2 increment in maternal pre-pregnancy BMI was associated with a 1.99 (95% CI: 1.08, 2.90) percentile increase in child SBP (during childhood [3-12 years]: 1.85, 95% CI: 0.97, 2.73; during adolescence [13-18 years]: 4.22, 95% CI: 1.19, 7.25). Cord blood Vitamin D status modified the associations (P-interaction = 0.023) (Figure, Panel A). Results were attenuated in the mediation analysis, but the interaction remained significant (Figure, Panel B). Conclusion: Higher maternal pre-pregnancy BMI is associated with higher offspring BP in childhood and adolescence, and this association is partially mediated by child weight. The inter-generational association disappeared if mother-newborn cord blood had high Vitamin D. Optimizing maternal Vitamin D status during pregnancy may help prevent the inter-generational cycle of cardiovascular risk.

Pre-pregnancy parental BMI and offspring blood pressure in infancy.

AimsA growing body of evidence suggests that a higher maternal pre-pregnancy body mass index results in higher offspring’s blood pressure, but there is inconsistency about the impact of father’s body mass index. Furthermore, evidence is limited with regard to low and middle income countries. We aimed to determine the association between parental pre-pregnancy body mass index and offspring’s blood pressure during the first year of life.MethodsIn 587 infants of the BReastfeeding Attitude and Volume Optimization (BRAVO) trial systolic and diastolic blood pressure were measured twice at the right leg in a supine position, using an automatic oscillometric device at day 7, month 1, 2, 4, 6, 9 and 12. Parental pre-pregnancy body mass index was based on self-reported weight and height. Linear mixed models were performed to investigate the associations between parental pre-pregnancy body mass index and offspring blood pressure patterns.ResultsEach unit increase in maternal body mass index was associated with 0.24 mmHg (95% confidence interval 0.05; 0.44) and 0.13 mmHg (0.01; 0.25) higher offspring’s mean systolic and diastolic blood pressure, respectively, during the first year of life. A higher offspring blood pressure with increased maternal pre-pregnancy body mass index was seen at birth and remained higher during the first year of life. The association with systolic blood pressure remained similar after including birth size and offspring’s weight and height over time. The association with diastolic blood pressure attenuated slightly to a non-significant result after including these variables. Paternal body mass index was not associated with offspring’s blood pressure.ConclusionHigher maternal pre-pregnancy body mass index, but not paternal pre-pregnancy body mass index, is associated with higher offspring blood pressure already from birth onwards.

Are observed associations between a high maternal prepregnancy body mass index and offspring IQ likely to be causal?

BackgroundA high maternal prepregnancy body mass index has been associated with lower offspring IQ, but it is unclear if the relationship is causal. To explore this, our objectives were to...

Early life risk factors for childhood obesity-Does physical activity modify the associations? The MoBa cohort study.

ObjectivesHigh maternal pre‐pregnancy body mass index (BMI), high birth weight, and rapid infant weight gain are associated with increased risk of childhood obesity. We examined whether moderate‐to‐vigorous physical activity (MVPA) or vigorous physical activity (VPA) in 9‐ to 12‐year‐olds modified the associations between these early life risk factors and subsequent body composition and BMI.MethodsWe used data from a sub‐cohort of the Norwegian Mother and Child Cohort Study (MoBa), including 445 children with available data on accelerometer assessed physical activity (PA). All participants had data on BMI, 186 of them provided data on body composition (dual energy X‐ray absorptiometry (DXA)). We used multiple regression analyses to examine the modifying effect of PA by including interaction terms.ResultsMaternal pre‐pregnancy BMI and infant weight gain were more strongly related to childhood body composition in boys than in girls. Higher VPA attenuated the association between maternal pre‐pregnancy BMI and BMI in boys (low VPA: B = 0.32, 95% CI = 0.22, 0.41; high VPA B = 0.22, 95% CI = 0.12, 0.31). Birth weight was unrelated to childhood body composition, and there was no effect modification by PA. PA attenuated the associations between infant weight gain and childhood fat mass (low MVPA: B = 2.32, 95% CI = 0.48, 4.17; high MVPA: B = 1.00, 95% CI = 0.10, 1.90) and percent fat (low MVPA: B = 3.35, 95% CI = 0.56, 6.14; high MVPA: B = 1.41, 95% CI = −0.06, 2.87) in boys, but not girls.ConclusionFindings from this study suggest that MVPA and VPA may attenuate the increased risk of an unfavorable body composition and BMI due to high maternal pre‐pregnancy BMI and rapid infant weight gain in boys, but not in girls.

The relationship between maternal weight gain in pregnancy and newborn weight

AimThis study investigated the impacts of different pre-pregnancy body mass indexes and gestational weight gain on the risk of delivering a high birth weight infant in China. MethodsA retrospective cohort study was conducted from 2013 to 2014 in the Maternal and Child Health Care Hospital of Jinan City, Shandong Province and 2415 women who had a singleton birth were included in the study. A logistic regression model and restricted cubic spline regression were used to analyse the association. FindingsThe risk of delivering a high birth weight infant increases when the mother’s pre-pregnancy body mass index exceeds 24kg/m2. Compared with women whose pre-pregnancy body mass index was 21kg/m2, the adjusted risk of delivering a high birth weight infant doubled when the mother’s pre-pregnancy body mass index was 29kg/m2, and nearly tripled when the mother’s pre-pregnancy body mass index was 31kg/m2. Compared with women who had a gestational weight gain of 12.0kg, women having a gestational weight gain of 20.0kg, 22.0kg, and 26.0kg had a 1.7-, 2.2-, and 3.5-fold increased risk of delivering a high birth weight infant. When the mother experiences a gestational weight gain greater than 27kg, the risk of delivering a high birth weight infant is at least 4-fold greater than that for a mother who has a gestational weight gain of 12.0kg. ConclusionsProposed strategies to raise public awareness of the risks to infants posed by high maternal pre-pregnancy body mass index and gestational weight gain are required. All clinical recommendations and measures are for all pregnant women, not just overweight and obese pregnant women.

Higher prepregnancy body mass index is a risk factor for developing preeclampsia in Maya-Mestizo women: a cohort study

ABSTRACTAim: Preeclampsia and obesity are two closely related syndromes. The high maternal prepregnancy body mass index (BMI) is a risk factor for present preeclampsia, independently of the ethnic background of the studied population. The aim of this study was to analyse in a prospective cohort study the relation between prepregnancy BMI and development of preeclampsia in Maya-Mestizo women.Design: This is a prospective cohort study of 642 pregnant women that were included in the first trimester of the pregnancy (gestational age ≤12 weeks at the first antenatal visit) and all of them were of Maya-Mestizo ethnic origin from the state of Yucatán, México. We assessed the potential risk factors for preeclampsia and documented the prepregnancy BMI (kg/m2) that was based on measured height and maternal self-report of prepregnancy weight at the initial visit. Besides, in the antenatal visit we documented if the pregnant women developed preeclampsia.Results: Of the 642 pregnant Maya-Mestizo women, 49 developed preeclampsia, with an incidence of 7.6% (44.9% had severe and 55% mild). The prepregnancy BMI was higher in women with developed preeclampsia than in those with normal pregnancies. Women with overweight or obesity in comparison with normal weight presented a RR = 2.82 (95% CI: 1.32–6.03; P = 0.008) and RR= 4.22 (95% CI: 2.07–8.61; P = 0.001), respectively.Conclusions: Our findings expand the previous studies to show that the higher prepregnancy BMI is a strong, independent risk factor for preeclampsia.

High Maternal Age and Low Pre-Pregnancy Body Mass Index Correlate with Lower Birth Weight of Male Infants.

In Japan, the percentage of leanness has been increasing in young women, and the percentage of low birth weight infants (< 2,500 g) has increased. Moreover, the average age of primiparas rose 3.5 years during the last 30 years. The purpose of this study was to clarify the relationship between maternal age and the influence of maternal pre-pregnancy physique on the neonatal physique of infants. Questionnaires were issued to the participants and collected when they submitted their gestational notifications at their local ward office in Kyoto Prefecture. After delivery, we obtained information on the course of the pregnancy and the neonatal physique of the infants from the participant's maternal passbooks. A total of 454 mothers (age 20 ≥) were analyzed: 161 young mothers (aged 20 to 29 years), 185 mothers (aged 30 to 34 years), and 108 older mothers (age ≥ 35). Overall, the mean rate of leanness (pre-pregnancy BMI < 18.5) was 23.8%. We found that birth weight was significantly lower in female infants, born to lean young mothers, compared to non-lean young mothers, whereas no significant difference was detected in other mothers (age ≥ 30), irrespective of pre-pregnancy BMI. By contrast, male infants, born to older lean mothers (age ≥ 35), showed significantly lower birth weight. Thus, maternal pre-pregnancy BMI exerts differential effects on the fetal growth (neonatal physique), depending on the maternal age and the sex of infants. We need to improve BMI in pre-pregnancy women, especially those in the twenties and 35 years old or over.

Maternal prepregnancy body mass index and offspring attention-deficit/hyperactivity disorder: aquasi-experimental sibling-comparison, population-based design.

High maternal prepregnancy body mass index (BMI) has been associated with increased risk of offspring attention-deficit/hyperactivity disorder (ADHD). However, whether this effect is attributable to maternal or familial level confounds has been little examined. The present study sought to examine these associations, utilizing data from the medical records of a health care system which treats 350,000 patients annually and a sibling-comparison design in a sample of 4,682 children born to 3,645 mothers. When examining the overall maternal effect, a linear association was observed between maternal prepregnancy BMI and child ADHD [b=0.04, 95% confidence interval (95% CI)=0.02-0.06, p=.0003], such that a one-unit (i.e. 1kg/m2 ) increase in prepregnancy BMI was associated with a 4% increase in the odds of ADHD (exp b=1.04). However, when the model was reparameterized to take full advantage of the sibling design to allow for the examination of both maternal and child-specific effects, the child-specific prepregnancy BMI effect was not reliably different from zero (b=-0.08, 95% CI=-0.23 to 0.06, p=.24). In contrast, at the maternal-level, average prepregnancy BMI was a reliably non-zero predictor of child ADHD (b=0.04, 95% CI=0.02-0.06, p<.0001) with each one-unit increase in maternal prepregnancy BMI associated with a 4.2% increase in the odds of ADHD (exp b=1.04, 95% CI=1.02-1.06). The association between maternal prepregnancy BMI and offspring ADHD may be better accounted for by familial or maternal confounds rather than a direct causal effect of BMI.

Maternal obesity, gestational weight gain and childhood cardiac outcomes: role of childhood body mass index.

Maternal obesity may affect cardiovascular outcomes in the offspring. We examined the associations of maternal prepregnancy body mass index and gestational weight gain with childhood cardiac outcomes and explored whether these associations were explained by parental characteristics, infant characteristics or childhood body mass index. In a population-based prospective cohort study among 4852 parents and their children, we obtained maternal weight before pregnancy and in early, mid- and late pregnancy. At age 6 years, we measured aortic root diameter (cm) and left ventricular dimensions. We calculated left ventricular mass (g), left ventricular mass index (g m(-2.7)), relative wall thickness ((2 × left ventricular posterior wall thickness)/left ventricular diameter), fractional shorting (%), eccentric left ventricular hypertrophy and concentric remodeling. A one standard deviation score (SDS) higher maternal prepregnancy body mass index was associated with higher left ventricular mass (0.10 SDS (95% confidence interval (CI) 0.08, 0.13)), left ventricular mass index (0.06 SDS (95% CI 0.03, 0.09)) and aortic root diameter (0.09 SDS (95% CI 0.06, 0.12)), but not with relative wall thickness or fractional shortening. A one SDS higher maternal prepregnancy body mass index was associated with an increased risk of eccentric left ventricular hypertrophy (odds ratio 1.21 (95% CI 1.03, 1.41)), but not of concentric remodeling. When analyzing the effects of maternal weight in different periods simultaneously, only maternal prepregnancy weight and early pregnancy weight were associated with left ventricular mass, left ventricular mass index and aortic root diameter (P-values<0.05), independent of weight in other pregnancy periods. All observed associations were independent of parental and infant characteristics, but attenuated to non-significance after adjustment for childhood body mass index. Maternal prepregnancy body mass index and weight gain in early pregnancy are both associated with offspring cardiac structure in childhood, but these associations seem to be fully explained by childhood body mass index.

Hypospadias: One Defect, Multiple Causes, Acting Through Shared Pathways

Hypospadias is one of the most common birth defects among males. Although the birth prevalence of hypospadias has been reported as increasing in some geographic regions, inconsistencies in ascertainment of mild cases and variability in reporting standards are likely contributing to these apparent trends. While hypospadias is highly heritable, there is limited knowledge about the specific genetic and epigenetic factors that play a role in its etiology. Risk factors for hypospadias include family history, older maternal age, nulliparity, high maternal prepregnancy body mass index, hypertension or preeclampsia, multiple gestations, reduced birth weight, and small for gestational age. Of the various prenatal exposures to medications that have been studied, the strongest evidence supports valproic acid as a contributor to hypospadias. Studies evaluating the impact of assisted reproductive technologies (ART) on hypospadias are inconclusive because of potential confounding by subfertility. Many causes of hypospadias may act through a few shared pathways, such as placental dysfunction.

Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design.

High maternal pre-pregnancy body mass index (BMI) is associated with increased risk of offspring attention deficit hyperactivity disorder (ADHD). However, the role of unmeasured familial confounding for this association remains unclear. We conducted a population-based cohort study via linkage of Swedish national and regional registers to investigate maternal pre-pregnancy BMI (underweight: BMI <18.5; overweight: 25≤ BMI <30; obesity: BMI ≥30) in relation to offspring ADHD. We followed 673 632 individuals born in Sweden between 1992 and 2000, with prospectively collected information on maternal pre-pregnancy BMI, until they received an ADHD diagnosis or ADHD medication, death, emigration or 31 December 2009. Hazard ratios (HRs) were estimated by Cox proportional hazards models. Stratified Cox proportional hazards models were applied to data on full siblings to control for unmeasured familial confounding. At the population level, pre-pregnancy overweight/obesity was associated with increased risk of offspring ADHD (HR(overweight) = 1.23, 95% CI = 1.18-1.27, P = 0.01; HR(obesity) = 1.64, 95% CI = 1.57-1.73, P = 0.01), after adjustment for measured covariates. In full sibling comparisons, however, previously observed associations no longer remained (HR(overweight) = 0.98, 95% CI = 0.83-1.16, P = 0.82; HR(obesity) = 1.15, 95% CI = 0.85-1.56, P = 0.38). The results suggested that the association between maternal pre-pregnancy overweight/obesity and offspring ADHD could be ascribed to unmeasured familial confounding.

Prediction of early and late pre‐eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy

To develop a predictive model for pre-eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy. This was a nested case-control study within a pre-eclampsia screening project that involved 5367 asymptomatic pregnant women undergoing routine transvaginal uterine artery (UtA) Doppler at 11 + 0 to 13 + 6 weeks. Following exclusions, there were 70 pregnant women who later developed pre-eclampsia and 289 control patients enrolled during the first trimester who had serum or plasma samples taken at enrolment available for the purposes of this study. Of these, 17 pregnancies were diagnosed with early-onset (delivery < 34 weeks) pre-eclampsia and 53 with late-onset (delivery ≥ 34 weeks) pre-eclampsia. The lowest, highest and mean of left and right UtA pulsatility indices (PI) were calculated. Blood samples were stored at -84 °C until biochemical analysis for markers of vasculogenesis was performed. The distributions of the lowest UtA-PI and the biochemical markers were adjusted for maternal characteristics, expressed as multiples of the median (MoM), and compared between groups. Logistic regression analysis was used to evaluate if any variable was significantly associated with pre-eclampsia. Pregnancies that later developed pre-eclampsia were associated with higher maternal prepregnancy body mass index. An increased lowest UtA-PI was significantly associated with both early- and late-onset disease. Placental growth factor (PlGF) MoM was significantly reduced in women who later developed early- or late-onset pre-eclampsia compared with controls (median (interquartile range), 0.69 (0.33-1.46) and 1.10 (0.39-1.56), respectively, vs 1.19 (0.65-1.84), P < 0.05). Different combined models were generated by logistic regression analysis, and the detection rate with a fixed 10% false-positive rate was 47% and 29% for early- and late-onset pre-eclampsia, respectively. Pregnancies that later developed early or late pre-eclampsia were characterized by impaired placentation and an anti-angiogenic state during the first trimester of pregnancy. Regression models which include maternal characteristics, UtA Doppler and PlGF can apparently predict approximately half of pregnancies that will be complicated by early-onset pre-eclampsia. We believe more research in several areas is needed to aid in the creation of a better and more population-specific screening test for pre-eclampsia during the first trimester of pregnancy.