Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Body mass index z-scores in the first 2 years of life were associated with adverse metabolic and anthropometric outcomes at 3 years of age.

AIM: We investigated associations between body mass index (BMI) z-scores for children aged 0-2 years and the BMI z-scores, body fat percentage and metabolic risk factors at 3 years of age. METHODS: This was a secondary analysis of the Lifestyle in Pregnancy and Offspring randomised controlled trial, carried out at two university hospitals in Denmark. It comprised 149 mothers with BMI ≥30 kg/m2 who did or did not receive a lifestyle intervention during pregnancy and a reference group of 97 mothers with normal-weight, with follow-up of their 3-year-old offspring. The children in these three groups were pooled for the data analyses, due to similar characteristics between groups. The BMI z-scores were calculated at 5 weeks, 5 months and 1, 2 and 3 years, using Danish reference groups. Their anthropometrics and metabolic outcomes were examined at 3 years of age. RESULTS: BMI z-scores at 5 months to 2 years were associated with BMI z-scores and body fat percentage at 3 years of age and BMI z-scores were not associated with metabolic risk factors at 3 years. CONCLUSION: BMI z-scores from 5 weeks of age were associated with adverse anthropometric outcomes but not with metabolic risk factors at 3 years of age.

Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis.

BACKGROUND: Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate. OBJECTIVES: The objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)]. METHODS: We searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022. RESULTS: Whey protein premeals lowered peak glucose concentration by -1.4 mmol/L [-1.9 mmol/L; -0.9 mmol/L], and the area under the curve for glucose was -0.9 standard deviation (SD) [-1.2 SD; -0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects. CONCLUSIONS: In conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.

Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes.

OBJECTIVE: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition. METHODS: Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls. RESULTS: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia. CONCLUSION: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.

Postprandial interval walking-effect on blood glucose in pregnant women with gestational diabetes.

BACKGROUND: During pregnancy, postprandial hyperglycemia may increase the risk of complications such as fetal macrosomia. However, evidence on beneficial effects of physical activity on postprandial hyperglycemia is sparse. OBJECTIVE: This study aimed to investigate the effect of 20 minutes of postprandial interval walking on glycemic control and glycemic variability in pregnant women diagnosed as having gestational diabetes mellitus. STUDY DESIGN: A crossover controlled trial including 14 pregnant women (gestational age 31.8±1.3 weeks) diagnosed as having gestational diabetes mellitus (75 g oral glucose load with 2-hour venous plasma glucose of ≥9.0 mmol/L) was conducted. Participants completed a 4-day intervention period and a 4-day control period with 3 days in between. In each study period, participants received a fixed and identical diet. In the intervention period, participants engaged in 20 minutes of postprandial interval walking after breakfast, lunch, and dinner. Interval walking comprised alternating 3 minutes of slow and fast intervals. Interstitial glucose concentrations were determined during both study periods with a continuous glucose monitor. The mixed effects model was used to compare differences between exercise and no exercise. RESULTS: Of note, 20 minutes of postprandial interval walking significantly reduced glycemic control during daytime hours relative to the control period (4-day mean glucose, 5.31 [5.04-5.59] vs 5.53 [5.25-5.81] mmol/L [95.6 (90.7-100.6) vs 99.5 (94.5-104.6) mg/dL]; P<.05). On each individual trial day, interval walking significantly reduced glycemic control during daytime hours on day 1 (mean glucose, 5.19 [4.92-5.47] vs 5.55 [5.27-5.83] mmol/L [93.4 (88.6-98.5) vs 99.9 (94.9-104.9) mg/dL]; P=.00), day 2 (mean glucose, 5.32 [5.05-5.60] vs 5.57 [5.29-5.84] mmol/L [95.8 (90.9-100.8) vs 100.3 (95.2-105.1) mg/dL]; P=.00), and day 3 (mean glucose, 5.27 [5.00-5.54] vs 5.46 [5.19-5.74] mmol/L [94.9 (90.0-99.7) vs 98.3 (93.4-103.3) mg/dL]; P=.00), but not on day 4. CONCLUSION: A total of 20 minutes of postprandial interval walking seems to be an effective way to control postprandial glucose excursions in women with gestational diabetes mellitus.

Intrahepatic cholestasis of pregnancy: Association with glycaemic control in gestational diabetes.

AIMS: The aim of this study was to determine whether the metabolic glucose profile, based on glycaemic control and insulin requirements, was different in women with gestational diabetes mellitus (GDM) and intrahepatic cholestasis of pregnancy (ICP) compared to women with only GDM. METHODS: This retrospective cohort study comprised women with GDM and ICP matched with women with only GDM was undertaken at Aarhus University hospital, Denmark, from 2012 to 2019. A total of 46 cases and 184 controls were compared in relation to glycaemic control during pregnancy. Women with GDM and ICP were further divided into subgroups according to the severity of ICP: mild ICP (fasting bile salts 10-39 µmol/L) and moderate/severe ICP (bile salts ≥40 µmol/L). RESULTS: No statistically significant differences were observed in baseline 2-h oral glucose tolerance test values, second and third trimester HbA1c values, or maximum insulin requirements during pregnancy between women with GDM with and without ICP. Significantly more women with ICP developed preeclampsia during pregnancy: 23.9% (11/46) versus 7.6% (14/184); p = 0.003. CONCLUSIONS: This study is the first to address the course of pregnancy in women with GDM with and without ICP in a clinical setting. Under the current treatment guidelines, ICP is not associated with clinically significant changes in glycaemic control in GDM. Significantly more women with both GDM and ICP developed preeclampsia.

Maternal prepregnancy body mass index and physical activity during pregnancy assessed by accelerometer.

BACKGROUND: Maternal prepregnancy overweight and obesity increase the risk of adverse pregnancy outcomes, whereas physical activity during pregnancy has a beneficial effect on both the mother and the fetus. Limited data are available on how maternal prepregnancy overweight and obesity affect physical activity during pregnancy. OBJECTIVE: The purpose of this study was to describe the association between prepregnancy body mass index and physical activity during pregnancy. STUDY DESIGN: An observational prospective cohort study of 400 singleton pregnant women who were attending routine antenatal care at Aarhus University Hospital, Denmark (2010-2015), was conducted. Physical activity was assessed by an accelerometer (SenseWear Armband) for 7 days for each trimester. Participants were stratified in 3 different groups of prepregnancy body mass index: normal weight (body mass index <25 kg/m2), overweight (body mass index 25-29.9 kg/m2), and obese (body mass index ≥30 kg/m2). Physical activity was measured as the number of steps per day, metabolic equivalent of task per day, time in moderate- to vigorous-intensity physical activity (>3 metabolic equivalent of task), and time in vigorous-intensity physical activity (>6 metabolic equivalent of task). Linear regression and multilevel mixed-effects models were used to explore the association between prepregnancy body mass index and physical activity variables during pregnancy. RESULTS: We found an inverse linear relationship between prepregnancy body mass index and both mean number of steps per day and mean metabolic equivalent of task per day (P<.001). At baseline, women with normal weight walked a median of 1214 steps per day (95% confidence interval, 576-1852) more than women who were obese (P<.05), and women who were overweight walked a median of 948 steps per day (95% confidence interval, 218-1677) more than women who were obese (P<.05). Independent of prepregnancy body mass index, all variables of physical activity decreased over the course of pregnancy (P<.05), with the greatest decrease in the third trimester. CONCLUSION: Maternal physical activity measured by an accelerometer decreased across pregnancy independent of maternal body mass index status and was inversely associated with prepregnancy body mass index. Thus, being overweight or obese before pregnancy increased the risk of sedentary behavior during pregnancy.

Vitamin D levels were significantly higher during and after lifestyle intervention in pregnancy: A randomized controlled trial.

INTRODUCTION: Vitamin D deficiency is common in pregnancy, especially in obese women. Lifestyle intervention could potentially result in higher levels of vitamin D. We therefore aimed to study the effect of lifestyle intervention during pregnancy on serum levels of 25-hydroxyvitamin D (25(OH)D). MATERIAL AND METHODS: A total of 360 obese women were randomized before gestational age 14 weeks to lifestyle intervention (diet and exercise) or routine clinical follow up (controls). Clinical outcomes and levels of 25(OH)D were determined three times: At gestational age 12-15 weeks (baseline), gestational age 28-30 weeks and 6 months postpartum. RESULTS: A total of 304 (84%) women completed the intervention study and 238 (66%) attended postpartum follow up. Vitamin D levels were similar in the two groups at baseline. At gestational age 28-30 weeks and 6 months postpartum, 25(OH)D levels were significantly higher in the intervention group than in controls (75.6 vs 66.8 nmol/L, P = 0.009) and (54.8 vs 43.1 nmol/L, P = 0.013), respectively. Concurrently, vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was less frequent in the intervention group than in controls: 15 vs 25% (P = 0.038) at gestational age 28-30 and 45 vs 63% (P = 0.011) 6 months postpartum, respectively. CONCLUSIONS: Lifestyle intervention during pregnancy was associated with significantly increased vitamin D levels in late pregnancy and postpartum compared with controls.

Is urinary excretion of plasminogen associated with development of pre-eclampsia? An observational, explorative case-control study.

OBJECTIVES: Pre-eclampsia (PE) is characterised by renal glomerular endotheliosis and injury to the glomerular filtration barrier with proteinuria. Patients with PE display aberrant filtration of the plasma proenzyme plasminogen which is activated, in the tubular fluid, to plasmin. Plasmin may activate the epithelial sodium channel and cause impaired sodium excretion and contribute to hypertension. An explorative study was conducted to test the association between urinary total plasminogen/plasmin and the development of PE. A positive association was hypothesised. DESIGN: An observational, explorative, nested case-control study of healthy pregnant women. SETTINGS: A Danish County hospital. Samples were collected between 2001 and 2004. PARTICIPANTS: 1631 healthy pregnant women participated. Urine samples were collected longitudinally six times during pregnancy. 30 developed PE (cases) and were compared with 146 randomly selected healthy pregnant women (controls). PRIMARY OUTCOME: The association between total plasminogen/plasmin excreted in the urine and PE development is expressed by ORs. Total urinary excretion of plasminogen/plasmin was defined by the urine plasminogen-plasmin/creatinine ratio. SECONDARY OUTCOME: The association between urine (u)-albumin/creatinine ratio, u-aldosterone/creatinine ratio and PE development is expressed by ORs. The correlation between urinary (u-) plasmin and u-aldosterone concentration is expressed as a correlation coefficient. RESULTS: The development of PE in late pregnancy was associated with increased levels of the urine plasminogen-plasmin/creatinine ratio (OR=2.35; 95% CI: 1.12 to 4.93; p<0.05).U-aldosterone/creatinine ratio did not predict PE at any time. U-albumin/creatinine ratio was positively associated with the development of PE from gestational week 33 (OR=14.04; 95% CI: 2.56 to 76.97; p<0.01) and in week 33-35 (OR=14.15; 95% CI: 3.44 to 58.09; p<0.001) and after gestational week 36, respectively. CONCLUSION: Aberrant filtration of plasminogen may contribute to the pathophysiological features of impaired sodium excretion and hypertension associated with PE late in pregnancy. However, increased urinary albumin levels reveal stronger associations with PE development compared with urinary plasminogen levels.

Diabetes Mellitus and lower genital tract tears after vaginal birth: A cohort study.

INTRODUCTION: Diabetes Mellitus in pregnancy is increasing. No existing studies have examined Diabetes Mellitus as the primary exposure for lower genital tract tears after vaginal birth. The objective was to study the association between Diabetes Mellitus (all types combined), Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus and lower genital tract tears after vaginal birth. MATERIAL AND METHODS: A register-based cohort study of women with singleton pregnancy and without a previous cesarean section at near-term (≥ 35 + 0 weeks) and term (≥ 37 + 0 weeks) gestational age, n = 31,297 at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012. The associations between Diabetes Mellitus and lower genital tract tears were analysed using a fixed multiple logistic regression analyses. RESULTS: Approximately 32,000 women were eligible for the study; 796 women had diabetes (2.5%) and 1318 experienced anal sphincter injury (4.3%). The overall risk of lower genital tract tears was similar among women with a diagnosis of diabetes (Type1 Diabetes Mellitus, Type 2 Diabetes Mellitus, and Gestational Diabetes Mellitus) compared to women without diabetes, except for nulliparous women with Type1 Diabetes Mellitus who experienced a higher risk of episiotomies, crude and adjusted odds ratios (OR 2.13, 95% CI 1.14-3.97) and (OR 2.48, 95% CI 1.21-5.10), respectively. CONCLUSIONS: Women with Diabetes Mellitus without a previous cesarean section who gave birth vaginally to a single child at term or near term did not experienced an increased risk of lower genital tract tears. However, nulliparous women with Type 1 Diabetes Mellitus experienced a higher risk of episiotomy. These results may be used to individualised counselling of women with Diabetes Mellitus regarding mode of birth and may reduce worries about genital tract tears in women with Diabetes Mellitus considering vaginal birth.

Lifestyle Intervention in Danish Obese Pregnant Women With Early Gestational Diabetes Mellitus According to WHO 2013 Criteria Does Not Change Pregnancy Outcomes: Results From the LiP (Lifestyle in Pregnancy) Study.

OBJECTIVE: To study effects of lifestyle intervention on metabolic and clinical outcomes in obese women fulfilling the World Health Organization (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) in early gestation. RESEARCH DESIGN AND METHODS: Secondary analysis of data from the Lifestyle in Pregnancy (LiP) study, a lifestyle randomized controlled trial in 304 pregnant women with BMI ≥30 kg/m2. Early GDM (week 12-15) was diagnosed according to modified WHO 2013 GDM criteria: fasting venous plasma glucose ≥5.1 mmol/L and/or 2-h capillary blood glucose (CBG) ≥8.5 mmol/L (75-g oral glucose tolerance test [OGTT]). Women with treated GDM fulfilling local Danish GDM criteria (2-h CBG ≥9.0 mmol/L) (n = 16) and women with normal OGTT (n = 198) were excluded. RESULTS: Of 90 women with early GDM, 36 received lifestyle intervention and 54 standard care. All were Caucasian, and median age was 29 years (interquartile range 27-33) and BMI 34.5 kg/m2 (32.3-38.1). All baseline characteristics were similar in the lifestyle intervention and standard care groups. At gestational week 28-30, the women in the lifestyle intervention group had significantly higher fasting total cholesterol and fasting LDL. All other metabolic parameters including measurements of glucose, insulin, and HOMA of insulin resistance were similar. There were more planned cesarean sections in the lifestyle intervention group (22.2 vs. 5.6%), but all other obstetric outcomes were similar. CONCLUSIONS: Lifestyle intervention in obese women fulfilling WHO 2013 GDM criteria in early pregnancy was not effective in improving obstetric or metabolic outcomes. Future studies should focus on interventions starting prepregnancy.

Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.

Context: Tight glycemic control throughout pregnancy in women with type 1 diabetes is crucial, and knowledge about which factors that affect insulin sensitivity could improve the outcome for both mother and offspring. Objective: To evaluate insulin requirements in women with type 1 diabetes during pregnancy and test whether parity affects insulin requirements. Design: Observational cohort study consisting of women with type 1 diabetes who gave birth at Aarhus University Hospital, Denmark, from 2004 to 2014. Main Outcome Measure: Daily insulin requirement (the hypothesis that parity could affect insulin resistance was formulated before data collection). Results: A total of 380 women with a total of 536 pregnancies were included in the study. Mean age was 31.1 years, and prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1, 40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of 70% (P < 0.0005) at weeks 33 to 36. Overall, insulin requirements increased significantly with parity. The unadjusted differences between P0 and P1, P2, and P3+4 were 9% (P < 0.0005), 12% (P < 0.0005), and 23% (P < 0.0011), respectively. After adjustment for confounders, differences were 13% (P < 0.0005), 20% (P < 0.0005), and 36% (P < 0.0005). We also observed an adjusted difference between P1 and P3+4 of 20% (P < 0.0012). Conclusions: The data show changes in insulin requirements from week to week in pregnancy and indicate that insulin requirements increase with parity. This suggests that the patient's parity probably should be considered in choosing insulin dosages for pregnant women with type 1 diabetes.

Associations between parity and maternal BMI in a population-based cohort study.

INTRODUCTION: We aimed to investigate the change in prevalence of overweight and obesity in pregnant Danish women from 2004 to 2012, and investigate whether increasing parity was associated with a change in body mass index (BMI) prevalence. MATERIAL AND METHODS: We obtained a population-based cohort from the Danish Medical Birth Registry consisting of all Danish women giving birth in 2004-2012 (n = 572 321). This registry contains information on 99.8% of all births in Denmark. We calculated the overall change in prepregnancy BMI status among pregnant women in Denmark, and a multiple linear regression model with adjustment for several potential confounders was used to examine the change in prepregnancy BMI with increasing parity. RESULTS: In 2004, the prevalence of prepregnancy overweight and obesity (BMI ≥ 25) and obesity alone (BMI ≥ 30) was 31.9 and 11%, respectively. In 2012, the prevalence had reached 34.2 and 12.8%. The mean BMI increased for every additional parity from 23.80 (95% CI 23.77-23.82) in parity group 1 to 26.70 (26.52-26.90) in parity group 5+. A multiple linear regression adjusted for potential confounders showed that women on average gained 0.62 (0.58-0.65) BMI units after every additional birth. CONCLUSIONS: This study showed a 7.2% increase in overweight and obesity (BMI ≥ 25) and a 16.4% increase in obesity alone (BMI ≥ 30) for pregnant women in Denmark from 2004 to 2012. In addition, an increase in interpregnancy BMI was seen at every additional delivery, suggesting that obesity is an increasing challenge in obstetrics.

National study of the prevalence of gestational diabetes mellitus among Danish women from 2004 to 2012.

AIMS: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. We studied the prevalence of GDM from 2004 to 2012 in Danish women aged 15-49 years using registries with records of the diagnosis of GDM at delivery. METHODS: We conducted a national register-based study of 12,538 women with a diagnosis of GDM during a pregnancy leading to a live birth in the period 2004-2012. The diagnosis of GDM was taken from the National Patient Registry and combined with the total number of births at the national level from Statistics Denmark. Prevalence estimates were reported as crude and age-standardized using Danish and international data for women aged 15-49 years. RESULTS: A total of 566,083 live births was registered in Denmark from 2004 to 2012. The age-standardized prevalence of GDM increased from 1.7% (1095/63,465) of the total births in 2004 to 2.9% (1721/56,894) of the total births in 2012. During the period 2004-2012, the age-stratified prevalence increased from 1.1 to 1.8% among women aged 15-24 years, from 1.5 to 2.6% among women aged 25-34 years and from 2.9 to 4.7% among women aged 35-49 years. The prevalence was higher among immigrants and their descendants than in native Danish women (4.06 and 2.09% in 2007 vs. 4.51 and 2.72% in 2012, respectively). CONCLUSIONS: The prevalence of GDM in Denmark has increased across all age groups. Although the prevalence is low on a global scale, attention should be paid to this development by preventive health services.

Effects of lifestyle intervention in pregnancy and anthropometrics at birth on offspring metabolic profile at 2.8 years: results from the Lifestyle in Pregnancy and Offspring (LiPO) study.

CONTEXT: Maternal obesity and gestational weight gain are linked to offspring adverse metabolic profiles, and lifestyle interventions during pregnancy in obese women may have long-term positive effects on their children. Furthermore, although the association between birth weight and later metabolic outcomes is well established, little is known about the predictive value of abdominal circumference at birth. OBJECTIVES: The purpose of this study was to determine (1) the effects of lifestyle interventions during pregnancy in obese women on offspring metabolic risk factors and (2) predictive values of birth weight (BW) and birth abdominal circumference (BAC). DESIGN: This was a follow-up of a randomized controlled trial, the Lifestyle in Pregnancy (LiP) study. SETTING: The study was conducted in Odense and Aarhus University Hospitals, Denmark. PARTICIPANTS: We studied the offspring of LiP study participants (n = 157) and offspring of normal-weight mothers (external reference group, n = 97). INTERVENTION: INTERVENTIONs included dietary advice, coaching, and exercise during pregnancy. MAIN OUTCOME MEASURES: The outcome measures were body mass index (BMI) Z-score, abdominal circumference, blood pressure, and fasting plasma glucose, insulin, high-density lipoprotein, and triglycerides at the age of 2.8 years. RESULTS: No differences were detected in BMI Z-scores or metabolic risk factors between the LiP intervention and control groups or between the LiP and external reference groups. BAC and BW were associated (all P < .05) with BMI Z-score (0.19-0.23), abdominal circumference (0.57-0.70), plasma glucose (0.11-0.09), insulin (4.33-3.13), and triglycerides (0.07-0.07) but not with blood pressure or high-density lipoprotein (regression coefficients per increase in BAC and BW of 1 SD score). CONCLUSIONS: Early childhood metabolic risk factors were unaffected by lifestyle interventions in obese pregnant women. Offspring of obese mothers who participated in the LiP study were comparable to offspring of normal-weight mothers, possibly indicating a general beneficial effect of trial participation. BAC and BW were both associated with later metabolic risk factors.

Anthropometrics and body composition by dual energy X-ray in children of obese women: a follow-up of a randomized controlled trial (the Lifestyle in Pregnancy and Offspring [LiPO] study).

OBJECTIVE: In obese women, 1) to assess whether lower gestational weight gain (GWG) during pregnancy in the lifestyle intervention group of a randomized controlled trial (RCT) resulted in differences in offspring anthropometrics and body composition, and 2) to compare offspring outcomes to a reference group of children born to women with a normal Body Mass Index (BMI). RESEARCH DESIGN AND METHODS: The LiPO (Lifestyle in Pregnancy and Offspring) study was an offspring follow-up of a RCT with 360 obese pregnant women with a lifestyle intervention during pregnancy including dietary advice, coaching and exercise. The trial was completed by 301 women who were eligible for follow-up. In addition, to the children from the RCT, a group of children born to women with a normal BMI were included as a reference group. At 2.8 (range 2.5-3.2) years, anthropometrics were measured in 157 children of the RCT mothers and in 97 reference group children with Body Mass Index (BMI) Z-score as a primary outcome. Body composition was estimated by Dual Energy X-ray (DEXA) in 123 successful scans out of 147 (84%). RESULTS: No differences between randomized groups were seen in mean (95% C.I.) BMI Z-score (intervention group 0.06 [-0.17; 0.29] vs. controls -0.18 [-0.43; 0.05]), in the percentage of overweight or obese children (10.9% vs. 6.7%), in other anthropometrics, or in body composition values by DEXA. Outcomes between children from the RCT and the reference group children were not significantly different. CONCLUSIONS: The RCT with lifestyle intervention in obese pregnant women did not result in any detectable effect on offspring anthropometrics or body composition by DEXA at 2.8 years of age. This may reflect the limited difference in GWG between intervention and control groups. Offspring of obese mothers from the RCT were comparable to offspring of mothers with a normal BMI.

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers.

OBJECTIVE: To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free ß-hCG) and to evaluate the influence of glycemic control on these parameters in the pregnant diabetic women. DESIGN: Retrospective study. SETTING: Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. POPULATION: Based on 36 415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; ß-hCG and PAPP-A were obtained at 8+0 to 14+2 gestational weeks. METHODS: Medians for PAPP-A and free ß-hCG were generated and multiple of the normal gestation-specific median (MoM) values were calculated for each separate pregnancy. After adjustment for maternal weight, ethnicity and smoking status, MoM values were compared across the T1DM and non-T1DM groups, respectively. Additionally, the relationship between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman's rank correlation. MAIN OUTCOME MEASURES. Difference in biochemical marker levels between T1DM and non-T1DM. RESULTS: PAPP-A was 0.86 MoM in T1DM pregnancies and 1.01 MoM in non-T1DM pregnancies, p < 0.0001. Conversely, free ß-hCG was not altered in T1DM pregnancies (T1DM 0.99 MoM, non-T1DM 0.98 MoM; p=0.14). There was a significant inverse correlation between HgbA1C and PAPP-A (rho=-0.12, p=0.02). CONCLUSIONS: In T1DM pregnancies, PAPP-A MoM values were lower than in non-T1DM pregnancies. This suggests that correction should be considered in first trimester biochemical screening for fetal aneuploidy in T1DM women.