Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: The MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding)

Background: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. Methods/Design: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women ≥ 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. Discussion: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. Trial registration: Trial registration number: NTR4197. Date of registration: October 2nd 2013

Genetic variant in the IGF2BP2 gene may interact with fetal malnutrition to affect glucose metabolism

OBJECTIVE - Fetal malnutrition may predispose to type 2 diabetes through gene programming and developmental changes. Previous studies showed that these effects may be modulated by genetic variation. Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated genes. We investigated the effects of such well-studied polymorphisms and their interactions with fetal malnutrition on type 2 diabetes risk and related phenotypes in the Dutch Famine Birth Cohort. RESEARCH DESIGN AND METHODS - The rs7754840 (CDKAL1), rs10811661 (CDKN2AB), rs1111875 (HHEX), rs4402960 (IGF2BP2), rs5219 (KCNJ11), rs13266634 (SLC30A8), and rs7903146 (TCF7L2) polymorphisms were genotyped in 772 participants of the Dutch Famine Birth Cohort Study (n = 328 exposed, n = 444 unexposed). Logistic and linear regression models served to analyze their interactions with prenatal exposure to famine on type 2 diabetes, impaired glucose tolerance (IGT), and area under the curves (AUCs) for glucose and insulin during oral glucose tolerance testing (OGTT). RESULTS - In the total population, the TCF7L2 and IGF2BP2 variants most strongly associated with increased risk for type 2 diabetes/IGT and increased AUC for glucose, while the CDKAL1 polymorphism associated with decreased AUC for insulin. The IGF2BP2 polymorphism showed an interaction with prenatal exposure to famine on AUC for glucose (β = -9.2 [95% CI -16.2 to -2.1], P = 0.009). CONCLUSIONS-The IGF2BP2 variant showed a nominal interaction with exposure to famine in utero, decreasing OGTT AUCs for glucose. This may provide a clue that modulation of the consequences of fetal environment depends on an individual's genetic background

Variants in the SIRT1 gene may affect diabetes risk in interaction with prenatal exposure to famine

OBJECTIVE - To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition. RESEARCH DESIGN AND METHODS - In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk. RESULTS - In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24-1.03], P = 0.06; for rs1467568 0.48 [0.25-0.91], P = 0.02).

Helicobacter pylori infection: A predictor of vomiting severity in pregnancy and adverse birth outcome

Background: Nausea and occasional vomiting in early pregnancy is common. Why some women experience severe nausea and occasional vomiting in early pregnancy is unknown. Causes are multifactorial and only symptomatic treatment options are available, although adverse birth outcomes have been described. Helicobacter pylori infection has been implicated in the cause of nausea and occasion

Mediterranean diet based intervention in pregnancy to improve maternal and fetal outcomes: Methodological challenges and lessons learned from the multicentre ESTEEM study

Introduction: Evaluating complex dietary interventions such as Mediterranean diet in pregnancy presents unique methodological challenges. We present the challenges and the lessons learned from a multicentre randomised trial (ESTEEM) on Mediterranean-based dietary intervention in pregnancy. Methods: We recruited pregnant women who met our predefined inclusion criteria and randomised those with metabolic risk factors to the Mediterranean-based dietary intervention or routine antenatal care. We evaluated the effect of the ESTEEM intervention on composite maternal and fetal outcomes. Challenges and solutions: The main challenges were encountered in recruiting to ESTEEM, delivering the intervention, engaging clinical staff, assessing adherence and choosing the outcome measures. The large sample size coupled with the slow recruitment rate forced us to extend the recruitment period by 4 months. The limitation in available resources was overcome by opening sites in a step-wise approach. Engaging healthcare providers was promoted by embedding the recruitment and the follow-up activities into current clinical practice, and promoting research skills training. We delivered the intervention early on in the pregnancy to promote the dietary effect on healthy placentation and reduce metabolic risk factors. Participants and their families were actively involved in the dietary intervention to improve adherence through a series of group teaching sessions. A user-friendly short dietary questionnaire was developed and validated to assess adherence to the intervention. The trial composite primary outcome was chosen in consensus based on input from a panel of experts. Conclusion: The ESTEEM experience offers an insight into future pragmatic nutritional studies in pregnancy

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial

Background Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58–1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes

Early enteral tube feeding in optimizing treatment of hyperemesis gravidarum: The Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial

Background: Hyperemesis gravidarum (HG) leads to dehydration, poor nutritional intake, and weight loss. HG has been associated with adverse pregnancy outcomes such as low birth weight. Information about the potential effectiveness of treatments for HG is limited. Objective: We hypothesized that in women with HG, early enteral tube feeding in addition to standard care improves birth weight. Design: We performed a multicenter, open-label randomized controlled trial [Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER)] in 19 hospitals in the Netherlands. A total of 116 women hospitalized for HG between 5 and 20 wk of gestation were randomly allocated to enteral tube feeding for ≥7 d in addition to standard care with intravenous rehydration and antiemetic treatment or to standard care alone. Women were encouraged to continue tube feeding at home. On the basis of our power calculation, a sample size of 120 women was anticipated. Analyses were performed according to the intention-to-treat principle. Results: Between October 2014 and March 2016 we randomly allocated 59 women to enteral tube feeding and 57 women to standard care. The mean ± SD birth weight was 3160 ± 770 g in the enteral tube feeding group compared with 3200 ± 680 g in the standard care group (mean difference: -40 g, 95% CI: -230, 310 g). Secondary outcomes, including maternal weight gain, duration of hospital stay, readmission rate, nausea and vomiting symptoms, decrease in quality of life, psychological distress, prematurity, and small-for-gestationalage, also were comparable. Of the women allocated to enteral tube feeding, 28 (47%) were treated according to protocol. Enteral tube feeding was discontinued within 7 d of placement in the remaining women, primarily because of its adverse effects (34%). Conclusions: In women with HG, early enteral tube feeding does not improve birth weight or secondary outcomes. Many women discontinued tube feeding because of discomfort, suggesting that it is poorly tolerated as an early routine treatment of HG