Suchergebnisse

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (β' = 0.078 (0.024-0.133); p = 0.005), head circumference (β' = 0.060 (0.012-0.107); p = 0.02), body mass index (β' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (β' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM. ; This research was funded by the Medical Research Council (7500001180, G1001995, U106179472); European Union Framework 5 (QLK4-1999-01422); the Mothercare Charitable Foundation (RG54608); Newlife Foundation for Disabled Children (07/20) and the World Cancer Research Fund International (2004/03). We also acknowledge support from National Institute for Health Research Cambridge Biomedical Research Centre. KKO receives support from the Medi-cal Research Council (Unit Programme number: MC_UU_12015/2 and MC_UU_00006/2).

AIMS: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy. METHODS: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy. RESULTS: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10-4; quadratic term: p = 1.0 × 10-3; n = 889; overall model p = 8.1 × 10-3). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = -0.13, p = 5.2 × 10-4, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03-0.08; adjusted quadratic term going from p = 0.04-0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = -0.11, p = 2.8 × 10-3, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). CONCLUSIONS: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance. ; Funding for this study has come from the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180, G1001995, U106179472), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. KO is supported by the Medical Research Council (Unit Programme number: MC_UU_12015/2).

OBJECTIVE: Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concentrations in the Cambridge Baby Growth Study. RESULTS: The fetal imprinted gene allele score was positively associated with birth weight (β = 63 (17-109) g/risk allele, β' = 0.113, p = 7.6 × 10-3, n = 405). This association was partially attenuated by adjusting for maternal glucose concentrations (β = 50 (4-95) g/risk allele, β' = 0.089, p = 0.03, n = 405). The allele score was also positively associated with risk of being large for gestational age at birth (odds ratio 1.60 (1.19-2.15) per risk allele, p = 2.1 × 10-3, n = 660) and negatively associated with risk of being small for gestational age at birth (odds ratio 0.65 (0.44-0.96) per risk allele, p = 0.03, n = 660). The large for gestational age at birth association was also partially attenuated by maternal glucose concentrations. These results suggest that associations between the fetal imprinted gene allele score and size at birth are mediated through both glucose-dependent and glucose-independent mechanisms. ; This work was supported by the Evelyn Trust (grant number EW9035322); Diabetes U.K. (grant number 11/0004241); the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, U.K.) (grant number RG1644); the Medical Research Council (grant numbers G1001995, 7500001180); European Union Framework 5 (grant number QLK4-1999-01422); the Mothercare Charitable Foundation (grant number RG54608); Newlife Foundation for Disabled Children (grant number 07/20); the World Cancer Research Fund International (grant number 2004/03); and the National Institute for ...

OBJECTIVES: To test the hypothesis that bacterial infections in pregnancy are related to maternal blood pressure. STUDY DESIGN: Bacterial infection was assessed using antibiotic usage as a surrogate and its association with blood pressure in pregnancy tested in the Cambridge Baby Growth Study. MAIN OUTCOME MEASURES: Antibiotic usage in pregnancy was self-reported in questionnaires. Blood pressure measurements at four time points in pregnancy were collected from the hospital notes of 622 women. RESULTS: Using all the available blood pressure readings (adjusted for weeks gestation) antibiotic usage was associated with a higher mean arterial blood pressure across pregnancy: antibiotics used 85 (84, 87) mmHg vs. no antibiotics used 83 (83, 84) mmHg (β = 2.3 (0.6, 4.0) mmHg, p = 9.6 × 10−3, from 621 individuals). Further analysis revealed that antibiotic usage was associated with diastolic (β = 2.3 (0.6, 4.0) mmHg; p = 7.0 × 10−3) more than systolic blood pressure (β = 1.4 (−0.9, 3.7) mmHg; p = 0.2). The effect size associated with antibiotic usage appeared to rise slightly after the first trimester. CONCLUSIONS: Bacterial infection in pregnancy, as assessed by self-reported antibiotic usage, is associated with small rises in blood pressure. ; Funding for this study has come from the Evelyn Trust (EW9035322), Diabetes UK (11/0004241) and the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. The sponsors did not have any role in the study design, in the collection, analysis or the interpretation of the data, in the writing of the manuscript or in the decision to submit it for publication.

Background: Low birth weight has important short- and long-term health implications. Previously it has been shown that pregnancies affected by hyperemesis gravidarum in the mother are at higher risk of having low birth weight offspring. In this study we tested whether such risks are also evident with less severe nausea and vomiting in pregnancy. Methods: 1,238 women in the prospective Cambridge Baby Growth Study filled in pregnancy questionnaires which included questions relating to adverse effects of pregnancy and drugs taken during that time. Ordinal logistic regression models, adjusted for parity, ethnicity, marital and smoking status were used to relate the risk of giving birth to low birth weight (< 2.5 kg) babies to nausea and/or vomiting in pregnancy that were not treated with anti-emetics and did not report suffering from hyperemesis gravidarum. Results: Only 3 women in the cohort reported having had hyperemesis gravidarum although a further 17 women reported taking anti-emetics during pregnancy. Of those 1,218 women who did not take anti-emetics 286 (23.5 %) did not experience nausea or vomiting, 467 (38.3 %) experienced nausea but not vomiting and 465 experienced vomiting (38.2 %). Vomiting during pregnancy was associated with higher risk of having a low birth weight baby (odds ratio 3.5 (1.2, 10.8), p = 0.03). The risk associated with vomiting was found in the first (p = 0.01) and second (p = 0.01) trimesters but not the third (p = 1.0). The higher risk was not evident in those women who only experienced nausea (odds ratio 1.0 (0.3, 4.0), p = 1.0). Conclusions: Vomiting in early pregnancy, even when not perceived to be sufficiently severe to merit treatment, is associated with a higher risk of delivering a low birth weight baby. Early pregnancy vomiting might therefore be usable as a marker of higher risk of low birth weight in pregnancy. This may be of benefit in situations where routine ultrasound is not available to distinguish prematurity from fetal growth restriction, so low birth weight is used as an alternative. ; Funding for this study has come from the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, UK) (RG1644). Other core funding has come from the Medical Research Council (7500001180), European Union Framework 5 (QLK4-1999-01422), the Mothercare Charitable Foundation (RG54608), Newlife Foundation for Disabled Children (07/20), and the World Cancer Research Fund International (2004/03). In addition, there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. KO is supported by the Medical Research Council (Unit Programme number: MC_UU_12015/2).

In addition to maternal genes and environmental exposures, variation in fetal imprinted genes could also affect maternal blood pressure during pregnancy. Our objective was to test the associations between polymorphic variants in 16 imprinted genes and maternal mean arterial blood pressures in 1160 DNA trios from 2 established birth cohorts (the Cambridge Baby Growth and Wellbeing Studies) and seek replication in 1367 Hyperglycemia and Adverse Pregnancy Outcome Study participants. Significant univariate associations, all independent of fetal sex, were observed in the Cambridge cohorts, including $\textit{FAM99A}$ rs1489945 transmitted from the mother ($\textit{P}$=2×10$^{-4}$), $\textit{DLK1}$ rs10139403 (mother; P=9×10$^{-4}$), $\textit{DLK1}$ rs12147008 (mother; $\textit{P}$=1×10$^{-3}$), $\textit{H19}$ rs217222 (father; $\textit{P}$=1×10$^{-3}$), $\textit{SNRPN}$ rs1453556 (father; $\textit{P}$=1×10$^{-3}$), $\textit{IGF2}$ rs6356 (father; $\textit{P}$=1×10$^{-3}$), and $\textit{NNAT}$ rs6066671 (father; $\textit{P}$=1×10$^{-3}$). In meta-analysis including additional independent Hyperglycemia and Adverse Pregnancy Outcome Study data, the association with maternally transmitted fetal $\textit{DLK1}$ rs10139403 reached genome-wide significance ($\textit{P}$=6.3×10$^{-10}$). With the exception of fetal rs1489945 and rs217222, all of other associations were unidirectional and most were statistically significant. To further explore the significance of these relationships, we developed an allele score based on the univariate findings. The score was strongly associated with maternal blood pressure at 31 weeks ($\textit{P}$=4.1×10$^{-8}$; adjusted $\textit{r}$$^{2}$=5.6%) and 37 weeks of pregnancy ($\textit{P}$=1.1×10$^{-4}$; $\textit{r}$$^{2}$=3.6%), and during the last 2 weeks before parturition ($\textit{P}$=1.1×10$^{-10}$; $\textit{r}$$^{2}$=8.7%). It was also associated with gestational hypertension (odds ratio, 1.54 [range, 1.14-2.09] per allele; $\textit{P}$=0.005; 45 cases and 549 controls). These data support the concept that fetal imprinted genes are related to the development of gestational hypertension. ; The genotyping part of the Cambridge Baby Growth Study was funded by the Evelyn Trust (EW9035322), Diabetes U.K. (11/0004241) and the Wellbeing of Women (the Royal College of Obstetricians and Gynaecologists, U.K.) (RG1644). Other core funding has come from the Medical Research Council (7500001180); European Union Framework 5 (QLK4-1999-01422); the Mothercare Charitable Foundation (RG54608); Newlife Foundation for Disabled Children (07/20) and the World Cancer Research Fund International (2004/03). In addition there has been support from National Institute for Health Research Cambridge Biomedical Research Centre. The HAPO Study was supported by NIH grants HD-34242, HD-34243, HG-004415, and CA-141688, Institutes of Health Research–INMD (Funding Reference Number 110791), and by the American Diabetes Association.

Background: Although nausea and vomiting are very common in pregnancy, their pathogenesis is poorly understood. We tested the hypothesis that circulating growth and differentiation factor 15 (GDF15) concentrations in early pregnancy, whose gene is implicated in hyperemesis gravidarum, are associated with nausea and vomiting. Methods: Blood samples for the measurement of GDF15 and human chorionic gonadotrophin (hCG) concentrations were obtained early in the second trimester (median 15.1 (interquartile range 14.4-15.7) weeks) of pregnancy from 791 women from the Cambridge Baby Growth Study, a prospective pregnancy and birth cohort. During each trimester participants completed a questionnaire which included questions about nausea, vomiting and antiemetic use. Associations with pre-pregnancy body mass indexes (BMI) were validated in 231 pregnant NIPTeR Study participants. Results: Circulating GDF15 concentrations were higher in women reporting vomiting in the second trimester than in women reporting no pregnancy nausea or vomiting: 11,581 (10,977-12,219) (n=175) vs. 10,593 (10,066-11,147) (n=193) pg/mL, p=0.02). In women who took antiemetic drugs during pregnancy (n=11) the GDF15 levels were also raised 13,157 (10,558-16,394) pg/mL (p =0.04). Serum GFD15 concentrations were strongly positively correlated with hCG levels but were inversely correlated with maternal BMIs, a finding replicated in the NIPTeR Study. Conclusions: Week 15 serum GDF15 concentrations are positively associated with second trimester vomiting and maternal antiemetic use in pregnancy. Given GDF15's site of action in the chemoreceptor trigger zone of the brainstem and its genetic associations with hyperemesis gravidarum, these data support the concept that GDF15 may be playing a pathogenic role in pregnancy-associated vomiting. ; This work was supported by the Wellcome Trust [100574; Strategic Award]; and an unrestricted award from the Novo Nordisk Foundation (International Prize for Excellence in diabetes research) (both SOR). The Cambridge Baby Growth Study has been funded by the Medical Research Council (7500001180) (CLA), European Union Framework 5 (QLK4-1999-01422) (IAH), the Mothercare Foundation (RG54608) (IAH), Newlife Foundation for Disabled Children (07/20) (IAH), and the World Cancer Research Fund International (2004/03) (DBD). It is also supported by the National Institute for Health Research Cambridge Biomedical Research Centre. KKO and JRB are supported by the Medical Research Council (Unit Programme MC_UU_12015/2). The NIPTeR study was in part supported by an AMC-VUMC Alliance grant.