Publications by authors named "Iris Grooten"

15 Publications

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Hyperemesis gravidarum and vitamin K deficiency: a systematic review.

Br J Nutr 2021 Jul 30:1-13. Epub 2021 Jul 30.

Amsterdam University Medical Centers, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction & Development Research Institute, Meibergdreef 9, Amsterdam, The Netherlands.

Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed to summarise available evidence on the occurrence of HG-related vitamin K deficiency and corresponding maternal and neonatal complications. A systematic review was conducted, searching Medline and EMBASE from inception to 12 November 2020. We identified 1564 articles, of which we included fifteen in this study: fourteen case reports (n 21 women) and one retrospective cohort study (n 109 women). Nine out of twenty-one women reported in case reports had a prolonged prothrombin time (PT). The cohort study measured PT in 39/109 women with HG, of whom 10/39 women (26 %) had prolonged PT. In total, 30-50 % women received vitamin K supplementation after vitamin K deficiency had been diagnosed. Four case reports (n 4 women) reported corresponding maternal complications, all consisting of coagulopathy-related haemorrhage. Nine case reports (n 16 neonates) reported corresponding neonatal complications including intracranial haemorrhage (n 2 neonates) and embryopathy (n 14 neonates), which consisted of Binder phenotype (n 14 neonates), chondrodysplasia punctata (n 9 neonates) and grey matter heterotopia (n 3 neonates). In conclusion, vitamin K deficiency and related complications occur among women with HG. In our systematic review, we were unable to assess the incidence rate.
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http://dx.doi.org/10.1017/S0007114521002865DOI Listing
July 2021

Recurrence, postponing pregnancy, and termination rates after hyperemesis gravidarum: Follow up of the MOTHER study.

Acta Obstet Gynecol Scand 2021 Sep 26;100(9):1636-1643. Epub 2021 Jun 26.

Department of Obstetrics and Gynecology, Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Introduction: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies.

Material And Methods: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies.

Results: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03).

Conclusions: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.
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http://dx.doi.org/10.1111/aogs.14197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457209PMC
September 2021

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum: A prospective cohort study.

Acta Obstet Gynecol Scand 2021 08 12;100(8):1419-1429. Epub 2021 Mar 12.

Department of Obstetrics and Gynecology, Amsterdam Reproduction & Development research institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

Introduction: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG.

Material And Methods: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4.

Results: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03).

Conclusions: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.
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http://dx.doi.org/10.1111/aogs.14131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360038PMC
August 2021

Determinants of disease course and severity in hyperemesis gravidarum.

Eur J Obstet Gynecol Reprod Biol 2020 Feb 24;245:162-167. Epub 2019 Dec 24.

Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Objective: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity.

Study Design: For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures.

Results: We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (β) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures.

Conclusion: Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity.
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http://dx.doi.org/10.1016/j.ejogrb.2019.12.021DOI Listing
February 2020

Nausea and vomiting of pregnancy and hyperemesis gravidarum.

Nat Rev Dis Primers 2019 09 12;5(1):62. Epub 2019 Sep 12.

Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.
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http://dx.doi.org/10.1038/s41572-019-0110-3DOI Listing
September 2019

Maternal vomiting during early pregnancy and cardiovascular risk factors at school age: the Generation R Study.

J Dev Orig Health Dis 2020 04 2;11(2):118-126. Epub 2019 Sep 2.

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors.

Methods: In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes.

Results: Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03-0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04-0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0-0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels.

Conclusions: Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.
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http://dx.doi.org/10.1017/S2040174419000114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282857PMC
April 2020

[Hyperemesis gravidarum].

Ned Tijdschr Geneeskd 2019 05 3;163. Epub 2019 May 3.

Amsterdam UMC, locatie AMC, afd. Obstetrie en Gynaecologie, Amsterdam.

Hyperemesis gravidarum Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting during pregnancy, accompanied by weight loss, dehydration and electrolyte imbalances. There is no international agreement on diagnostic criteria for HG. The diagnosis of HG is only made on the basis of the clinical picture. HG has a significant impact on quality of life and is related to negative birth outcomes. The principal elements of HG treatment consist of antiemetics and intravenous rehydration. The probability that there will be a reoccurrence of HG during a subsequent pregnancy is 15-80%. If a subsequent pregnancy is desired, a preconception consultation may have added value.
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May 2019

Patient Preferences and Experiences in Hyperemesis Gravidarum Treatment: A Qualitative Study.

J Pregnancy 2018 30;2018:5378502. Epub 2018 Oct 30.

Department of Obstetrics and Gynaecology, University Medical Centers Amsterdam, University of Amsterdam, Amsterdam, Netherlands.

Introduction: Hyperemesis gravidarum (HG) medical therapies are currently of limited effect, which creates a larger role for patient preferences in the way HG care is arranged. This is the first study using in-depth interviews to investigate patients' preferences and experiences of HG treatment.

Materials And Methods: We conducted individual in-depth interviews among women who had been hospitalized for HG in North Holland at least once in the past 4 years. We asked them about their experiences, preferences, and suggestions for improvement regarding the HG treatment they received. The sample size was determined by reaching data saturation. Themes were identified from analysis of the interview transcripts.

Results And Discussion: 13 women were interviewed. Interviewees emphasized the importance of early recognition of the severity of HG, increasing caregivers' knowledge on HG, early medical intervention, and nasogastric tube feeding. They valued a single room in hospital, discussion of treatment options, more possibilities of home-treatment, psychological support during HG and after childbirth, and more uniform information and policies regarding HG treatment.

Conclusion: Further research is needed to establish whether the suggestions can lead to more (cost) effective care and improve the course of HG and outcomes for HG patients and their children.
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http://dx.doi.org/10.1155/2018/5378502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234451PMC
April 2019

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.

Am J Clin Nutr 2017 Sep 9;106(3):812-820. Epub 2017 Aug 9.

Departments of Obstetrics and Gynecology and.

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. We hypothesized that in women with HG, early enteral tube feeding in addition to standard care improves birth weight. 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. 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-gestational-age, 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%). 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. This trial was registered at www.trialregister.nl as NTR4197.
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http://dx.doi.org/10.3945/ajcn.117.158931DOI Listing
September 2017

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

Am J Obstet Gynecol 2017 05 7;216(5):512.e1-512.e9. Epub 2017 Feb 7.

Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.

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 occasional vomiting in early pregnancy.

Objective: The purpose of this study was to investigate the association of H pylori with vomiting severity in pregnancy and its effect on birth outcome.

Study Design: We assembled a population-based prospective cohort of pregnant women in The Netherlands. Enrolment took place between 2002 and 2006. H pylori serology was determined in mid gestation. Women reported whether they experienced vomiting in early, mid, and late gestation. Maternal weight was measured in the same time periods. Birth outcomes were obtained from medical records. Main outcome measures were vomiting frequency (no, occasional, daily) and duration (early, mid, late gestation), maternal weight gain, birthweight, small for gestational age, and prematurity. Data were analyzed with the use of multivariate regression.

Results: We included 5549 Women, of whom 1932 (34.8%) reported occasional vomiting and 601 (10.8%) reported daily vomiting. Women who were H pylori-positive (n=2363) were more likely to report daily vomiting (adjusted odds ratio, 1.44; 95% confidence interval, 1.16-1.78). H pylori-positivity was associated with a reduction of total weight gain in women with daily vomiting (adjusted difference, -2.1 kg; 95% confidence interval, -2.7 to -1.5); infants born to women with H pylori and daily vomiting had slightly reduced birthweight (addjusted difference -60g; 95% confidence interval, -109 - -12) and an increased risk of being small for gestational age (adjusted odds ratio, 1.49; 95% confidence interval, 1.04-2.14). H pylori and daily vomiting did not significantly affect prematurity rate.

Conclusion: This study suggests that H pylori is an independent risk factor for vomiting in pregnancy. In women with daily vomiting, H pylori is also associated with low maternal weight gain, reduced birth weight, and small for gestational age. Because effective treatments for severe nausea and occasional vomiting in early pregnancy are currently lacking, the effect of H pylori eradication therapy on nausea and occasional vomiting in early pregnancy symptom severity should be the target of future studies.
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http://dx.doi.org/10.1016/j.ajog.2017.01.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426529PMC
May 2017

Barriers and Challenges in Hyperemesis Gravidarum Research.

Nutr Metab Insights 2015 14;8(Suppl 1):33-9. Epub 2016 Feb 14.

Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Nausea and occasional vomiting in early pregnancy (NVP) are common. When vomiting is severe or protracted, it is referred to as hyperemesis gravidarum (HG). HG affects up to 3% of pregnancies and is characterized by weight loss, dehydration, electrolyte imbalance, and the need for hospital admission. HG has significant consequences for maternal well-being, is associated with adverse birth outcomes, and leads to major health care costs. Treatment options are symptomatic, hampered by the lack of evidence-based options including studies on nutritional interventions. One of the reasons for this lack of evidence is the use of a broad range of definitions and outcome measures. An internationally accepted definition and the formulation of core outcomes would facilitate meta-analysis of trial results and implementation of evidence in guidelines to ultimately improve patient care.
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http://dx.doi.org/10.4137/NMI.S29523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755698PMC
February 2016

A Systematic Review and Meta-Analysis of the Utility of Corticosteroids in the Treatment of Hyperemesis Gravidarum.

Nutr Metab Insights 2015 4;8(Suppl 1):23-32. Epub 2016 Feb 4.

Department of Obstetrics & Gynaecology, Academic Medical Center, Amsterdam, the Netherlands.

Background: Corticosteroids (CCS) are effective in reducing chemotherapy-induced nausea and vomiting, but it is unknown whether CCS are effective in treating hyperemesis gravidarum (HG).

Methods: We searched PubMed and ClinicalTrials.gov from inception to May 15, 2015, for randomized controlled trials examining the effects of CCS in HG.

Results: We identified five trials (n = 310) examining the effects of CCS in women with HG. Meta-analysis was possible for one outcome (n = 214) and showed no significant effect of CCS on readmission rates (odds ratio, 0.37; 95% confidence internal: 0.1-1.35). Two small studies (n = 104) reported a reduction of vomiting episodes, and one (n = 24) found improvement of well-being, but no effect on other outcomes. None of the studies that investigated perinatal outcome (n = 173) found an effect of CCS and were underpowered to investigate teratogenic effects. We found evidence of publication bias.

Conclusion: Meta-analysis yielded no effect of CCS therapy on readmission rates. Single small studies indicated possible beneficial effects on other outcomes. Future high-quality trials are necessary and would benefit from consensus on HG definition and core outcomes of HG therapy.
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http://dx.doi.org/10.4137/NMI.S29532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745642PMC
February 2016

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).

BMC Pregnancy Childbirth 2016 Jan 27;16:22. Epub 2016 Jan 27.

Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

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 2(nd) 2013.
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http://dx.doi.org/10.1186/s12884-016-0815-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730616PMC
January 2016

Subfertility and assisted reproduction techniques are associated with poorer cardiometabolic profiles in childhood.

Reprod Biomed Online 2015 Mar 25;30(3):258-67. Epub 2014 Nov 25.

Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands.

The effects of artificial reproductive techniques and subfertility on cardiovascular and metabolic profiles of children aged 5-6 years were investigated using data from the Amsterdam Born Children and their Development study. Of the 2577 children, 34 were conceived through ovulation induction, 51 through artificial insemination and 28 through IVF or intracytoplasmic sperm injection (ICSI). Two hundred and twenty children were born to couples who conceived after more than 12 months and 2244 were born to couples who conceived within 12 months of unprotected intercourse ('subfertile' and 'fertile', respectively). At the age of 5-6 years, fasting glucose levels were higher among children conceived through ovulation induction and IVF-ICSI compared with those of children of fertile couples (adjusted difference: ovulation induction: 0.4 mmol/l, 95% CI 0.2 to 0.6; IVF-ICSI: 0.2 mmol/l, 95% CI 0.0 to 0.5). Blood pressure was higher in children of subfertile couples compared with that of children of fertile couples (adjusted difference systolic blood pressure: 0.8 mmHg, 95% CI -0.2 to 1.8; diastolic blood pressure: 1.4 mmHg, 95% CI 0.6 to 2.3). Subfertility and conception through ovulation induction and IVF-ICSI each contributed to aspects of an adverse cardiovascular and metabolic profile in childhood.
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http://dx.doi.org/10.1016/j.rbmo.2014.11.006DOI Listing
March 2015

Diagnostic markers for hyperemesis gravidarum: a systematic review and metaanalysis.

Am J Obstet Gynecol 2014 Aug 13;211(2):150.e1-15. Epub 2014 Feb 13.

Department of Obstetrics and Gynecology, Medical Centre Alkmaar, Alkmaar, the Netherlands. Electronic address:

Objective: Currently, there is no consensus on the definition of hyperemesis gravidarum (HG; protracted vomiting in pregnancy) and no single widely used set of diagnostic criteria for HG. The various definitions rely on symptoms, sometimes in combination with laboratory tests. Through a systematic review, we aimed to summarize available evidence on the diagnostic value of biomarkers for HG. This could assist diagnosis and may shed light on the, as yet, not understood cause of the disorder.

Study Design: We searched Medline and Embase for articles about diagnostic biomarkers for either the presence or severity of HG or nausea and vomiting of pregnancy. We defined HG as any combination of nausea, vomiting, dehydration, weight loss, or hospitalization for nausea and/or vomiting in pregnancy, in the absence of any other obvious cause for these complaints.

Results: We found 81 articles on 9 biomarkers. Although 65% of all studies included only HG cases with ketonuria, we did not find an association between ketonuria and presence or severity of HG in 5 studies reporting on this association. Metaanalysis, with the use of the hierarchical summary receiver operating characteristics model, yielded an odds ratio of 3.2 (95% confidence interval, 2.0-5.1) of Heliobacter pylori for HG, as compared with asymptomatic control subjects (sensitivity, 73%; specificity, 55%). Studies on human chorionic gonadotropin and thyroid hormones, leptin, estradiol, progesterone, and white blood count showed inconsistent associations with HG; lymphocytes tended to be higher in women with HG.

Conclusion: We did not find support for the use of ketonuria in the diagnosis of HG. H pylori serology might be useful in specific patients.
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http://dx.doi.org/10.1016/j.ajog.2014.02.012DOI Listing
August 2014
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