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Marco Medici, Sarah Timmermans,
Willy Visser,
Sabine M P F de Muinck Keizer-Schrama,
Vincent W W Jaddoe,
Albert Hofman,
Herbert Hooijkaas,
Yolanda B de Rijke,
Henning Tiemeier,
Jacoba J Bongers-Schokking,
Theo J Visser,
Robin P Peeters,
Eric A P Steegers
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ABSTRACT: Context:Maternal hyperthyroidism during pregnancy is associated with an increased risk of low birth weight, predisposing to neonatal morbidity and mortality. However, the effects of variation in maternal serum thyroid parameters within the normal range on birth weight are largely unknown.Objective:The aim was to study the effects of early pregnancy maternal serum thyroid parameters within the normal range on birth weight, as well as the relation between umbilical cord thyroid parameters and birth weight.Design, Setting, and Participants:In early pregnancy, serum TSH, FT4 (free T(4)), and thyroid peroxidase antibody levels were determined in 4464 pregnant women. Cord serum TSH and FT4 levels were determined in 2724 newborns. Small size for gestational age at birth (SGA) was defined as a gestational age-adjusted birth weight below the 2.5th percentile. The associations between normal-range maternal and cord thyroid parameters, birth weight, and SGA were studied using regression analyses.Results:In mothers with normal-range FT4 and TSH levels, higher maternal FT4 levels were associated with lower birth weight [β = -15.4 (3.6) g/pmol · liter, mean (se); P = 1.6 × 10(-5)], as well as with an increased risk of SGA newborns [odds ratio (95% confidence interval) = 1.09 (1.01-1.17); P = 0.03]. Birth weight was positively associated with both cord TSH [β = 4.1 (1.4) g/mU · liter; P = 0.007] and FT4 levels [β = 23.0 (3.2) g/pmol · liter; P = 9.2 × 10(-13)].Conclusions:We show that maternal high-normal FT4 levels in early pregnancy are associated with lower birth weight and an increased risk of SGA newborns. Additionally, birth weight is positively associated with cord TSH and FT4 levels. These data demonstrate that even mild variation in thyroid function within the normal range can have important fetal consequences.
The Journal of clinical endocrinology and metabolism 11/2012; · 6.50 Impact Factor
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ABSTRACT: To estimate whether the imbalance of angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and fibrinolytic factors (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early pregnancy.
We studied the associations of maternal soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 concentrations in the first trimester (before 18 weeks of gestation) and soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in the second trimester (18-25 weeks of gestation) with placental function and adverse pregnancy outcomes. This study was embedded in a population-based prospective cohort study. Data were used from 7,519 women. Biomarker concentrations were divided into deciles and evaluated in multivariable linear and logistic regression models.
First-trimester high soluble fms-like tyrosine kinase-1 was associated with a 5.2% lower uterine artery index in the second-trimester and a 1.6% higher birth weight (55 g, confidence interval [CI] 15-95). Neither in the first nor in the second trimester were soluble fms-like tyrosine kinase-1 concentrations significantly associated with preeclampsia. First-trimester low placental growth factor was associated with a 6.1% higher uterine artery index and a 3.4% lower birth weight (-115 g, CI -157 to -74). First-trimester low placental growth factor was associated with fetal growth restriction (odds ratio [OR] 2.62, CI 1.68-4.08) and preeclampsia (OR 2.46, CI 1.49-4.08). First-trimester low PAI-2 was associated with a 1.9% higher uterine artery index and a 2.7% lower birth weight (-94 g, CI -136 to -51). First-trimester low PAI-2 was associated with a higher risk of fetal growth restriction (OR 2.22, CI 1.39-3.55).
First-half-of-pregnancy concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 are associated with uteroplacental vascular resistance, placental weight, and birth weight. Moreover, first-trimester placental growth factor and PAI-2 are associated with an increased risk of adverse pregnancy outcomes.
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Obstetrics and Gynecology 06/2012; 119(6):1190-200. · 4.73 Impact Factor
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ABSTRACT: Recent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism, folic acid supplementation, and circulating folate and vitamin B-12 concentrations during pregnancy were associated with wheezing, shortness of breath, and atopic dermatitis in offspring. The study was a population-based birth cohort from fetal life until 48 mo (n = 8742). The use of folic acid supplementation during pregnancy was assessed by questionnaire. Plasma folate and serum vitamin B-12 concentrations and the MTHFR C677T polymorphism were available from blood collected in early pregnancy. Atopic dermatitis, wheezing, and shortness of breath in the offspring were assessed by parental-derived questionnaires at 12, 24, 36, and 48 mo. Maternal folate >16.2 nmol/L and vitamin B-12 >178 pmol/L were positively associated with the development of atopic dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI: 1.06-1.60) for the highest quartiles of folate and vitamin B-12 concentrations, respectively] but not with wheezing and shortness of breath. Maternal MTHFR C677T polymorphism and folic acid supplementation were not associated with wheezing, shortness of breath, and atopic dermatitis. No interactions were found by age, family history of atopy, folic acid supplementation, MTHFR C677T polymorphism, or maternal smoking (P-interaction > 0.10). High folate and vitamin B-12 levels during pregnancy are associated with increased prevalence of atopic dermatitis in the offspring. Potential risks of high folate and vitamin B-12 concentrations on allergic outcomes should be evaluated when discussing mandatory fortification programs.
Journal of Nutrition 03/2012; 142(4):731-8. · 3.92 Impact Factor
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Sarah Timmermans,
Régine P Steegers-Theunissen,
Marijana Vujkovic,
Hanneke den Breeijen,
Henk Russcher,
Jan Lindemans,
Johan Mackenbach,
Albert Hofman,
Emmanuel E Lesaffre,
Vincent V Jaddoe,
Eric A Steegers
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ABSTRACT: Developmental adaptations due to early nutritional exposures may have permanent health consequences. Studies of diet and fetal size have mainly focused on individual nutrients despite evidence that the pattern of food consumption may be of significance. Hence, we evaluated the associations of dietary habits in early pregnancy (gestational age < 18 weeks) with fetal size, uteroplacental vascular resistance, placental weight and birth weight in a prospective observational study of 3207 Caucasian pregnant mothers in Rotterdam, the Netherlands. Participants completed a semiquantitative FFQ during early pregnancy. Logistic regression analysis was used to predict the occurrence of intra-uterine growth retardation at birth as a function of food intake. The derived solution was considered as the dietary pattern. As it was characterised by higher intakes of fruit, vegetables, vegetable oil, fish, pasta and rice, and lower intakes of meat, potatoes and fatty sauces, it was labelled the 'Mediterranean' diet. The degree of adherence to the diet was positively associated with plasma folate and serum vitamin B12 concentrations and showed an inverse relationship with homocysteine and high-sensitivity C-reactive protein plasma concentrations (P <0·05). Important fetal size and placental parameters were associated with the degree of adherence to the diet, revealing a 72 g lower birth weight (95 % CI - 110·8, - 33·3) and a 15 g lower placental weight (95 % CI - 29·8, - 0·2) for women with low adherence to the diet. To conclude, low adherence to a Mediterranean diet in early pregnancy seems associated with decreased intra-uterine size with a lower placental and a lower birth weight.
The British journal of nutrition 02/2012; 108(8):1399-409. · 3.45 Impact Factor
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ABSTRACT: Maternal smoking during pregnancy leads to increased risks of neonatal complications. The use of folic acid supplements might reduce the adverse effects of smoking. We examined whether folic acid supplement use modifies the associations of maternal smoking with first trimester plasma homocysteine concentrations, fetal growth characteristics, and risks of neonatal complications. The associations were studied in 6294 mothers participating in a prospective population-based cohort study in The Netherlands. Main outcomes measurements were first trimester plasma homocysteine concentrations, fetal growth characteristics, and neonatal complications, including preterm birth, low birth weight, and small-size-for-gestational-age. Continued maternal smoking was associated with higher first trimester plasma homocysteine concentrations [difference 0.52 μmol/L (95% range = 0.20, 2.14)], lower third trimester fetal weight (difference -44 g (95% CI = -57, -31)], and birth weight [difference -148 g (95% CI = -179, -118)]. There were significant interactions between maternal smoking and folic acid supplements on all outcome measures (all P-interaction < 0.040). Among mothers who continued smoking during pregnancy, those who did not use folic acid supplements had the highest risk of delivering a child with low birth weight [OR = 3.45 (95% CI = 1.25, 9.54)] compared to those who did use periconceptional folic acid supplements. No significant effects were observed for the risks of preterm birth and small-size-for-gestational-age at birth. Our results suggest that some adverse effects of maternal smoking on fetal growth and neonatal outcomes might be reduced by the use of folic acid supplements. The observed interaction seems to be mainly driven by smoking in the first trimester only.
Journal of Nutrition 12/2011; 141(12):2172-9. · 3.92 Impact Factor
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Sarah Timmermans,
Régine P M Steegers-Theunissen,
Marijana Vujkovic,
Rachel Bakker,
Hanneke den Breeijen,
Hein Raat,
Henk Russcher,
Jan Lindemans,
Albert Hofman,
Vincent W V Jaddoe,
Eric A P Steegers
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ABSTRACT: We sought to evaluate associations between dietary patterns and systolic blood pressure (SBP) and diastolic blood pressure during pregnancy.
This was a prospective study of 3187 pregnant women. Participants completed a food-frequency questionnaire in early pregnancy. The Mediterranean dietary pattern, comprising high intake of vegetables, vegetable oils, pasta, fish, and legumes, and the Traditional dietary pattern, comprising high intake of meat and potatoes, were identified using factor analysis.
A higher SBP was observed among mothers with high Traditional pattern adherence. Low adherence to the Mediterranean pattern was also associated with higher SBP but only in early and mid pregnancy. A higher diastolic blood pressure throughout pregnancy was observed in mothers with high adherence to the Traditional pattern and low adherence to the Mediterranean pattern. These effect estimates were most pronounced in mid pregnancy.
Low adherence to a Mediterranean and high adherence to a Traditional dietary pattern is associated with a higher blood pressure in pregnancy.
American journal of obstetrics and gynecology 05/2011; 205(4):337.e1-12. · 3.28 Impact Factor
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Sarah Timmermans,
Gouke J Bonsel,
Régine P M Steegers-Theunissen,
Johan P Mackenbach,
Ewout W Steyerberg,
Hein Raat,
Henri A Verbrugh,
Henning W Tiemeier,
Albert Hofman,
Erwin Birnie,
Caspar W N Looman,
Vincent W V Jaddoe,
Eric A P Steegers
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ABSTRACT: Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective.
European Journal of Epidemiology 02/2011; 26(2):165-80. · 4.71 Impact Factor
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ABSTRACT: Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0·01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.
The British journal of nutrition 01/2011; 105(6):938-49. · 3.45 Impact Factor
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ABSTRACT: Countries worldwide, including the Netherlands, recommend that women planning pregnancy use a folic acid supplement during the periconception period. Some countries even fortify staple foods with folic acid. These recommendations mainly focus on the prevention of neural tube defects, despite increasing evidence that folic acid may also influence birth weight. We examined whether periconception folic acid supplementation affects fetal growth and the risks of low birth weight, small for gestational age (SGA) and preterm birth, in the Generation R Study in Rotterdam, the Netherlands. Main outcome measures were fetal growth measured in mid- and late pregnancy by ultrasound, birth weight, SGA and preterm birth in relation to periconception folic supplementation (0.4-0.5 mg). Data on 6353 pregnancies were available. Periconception folic acid supplementation was positively associated with fetal growth. Preconception folic acid supplementation was associated with 68 g higher birth weight (95 % CI 37.2, 99.0) and 13 g higher placental weight (95 % CI 1.1, 25.5), compared to no folic acid supplementation. In these analyses parity significantly modified the effect estimates. Start of folic acid supplementation after pregnancy confirmation was associated with a reduced risk of low birth weight (OR 0.61, 95 % CI 0.40, 0.94). Similarly, reduced risks for low birth weight and SGA were observed for women who started supplementation preconceptionally, compared to those who did not use folic acid (OR 0.43, 95 % CI 0.28, 0.69 and OR 0.40, 95 % CI 0.22, 0.72). In conclusion, periconception folic acid supplementation is associated with increased fetal growth resulting in higher placental and birth weight, and decreased risks of low birth weight and SGA.
The British journal of nutrition 04/2009; 102(5):777-85. · 3.45 Impact Factor
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ABSTRACT: Recommendations on folic acid use to prevent neural tube defects have been launched in several countries. Adequate folic acid use seems to be low. This study assesses the prevalence of folic acid use and identifies its determinants.
The study was embedded in the Generation R Study Rotterdam, the Netherlands, a population-based prospective cohort study between 2002 and 2006. Complete information of 6940 women was available. Information on folic acid use and potential determinants was obtained by questionnaires and physical examination.
Of all women 37% adequately used folic acid during the preconception period. Most important risk factors for inadequate use were unplanned pregnancy (OR 9.5, CI 7.2-12.4, p<0.001), low educational level (OR 2.5, CI 1.8-3.6, p<0.001) and non-western ethnicity, (OR 3.5, CI 2.9-4.3, p<0.001). After stratification for ethnicity, unplanned pregnancy remained the most important risk factor for inadequate use. Other risk factors for inadequate use were younger age, single marital status, smoking, multiparity (all p<0.001) and alcohol use (p<0.05). In contrast, previous spontaneous abortion decreased the risk of inadequate folic acid use (p<0.001).
Adequate preconception folic acid supplementation is still too low. Implementation of preconception programs and other public health strategies are strongly needed.
Preventive Medicine 10/2008; 47(4):427-32. · 3.22 Impact Factor
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ABSTRACT: Due to the growing number of cesarean deliveries, the frequency of abnormally invasive placentation is increasing. The optimal management of this condition remains unclear. This article reviews the efficacy and safety of conservative management of abnormally invasive placentation. We performed a MEDLINE and Embase search and reviewed all articles on conservative management of abnormally invasive placentation published from 1985 through 2006. Over the past 20 years, 48 reports have described outcomes of 60 women who were treated conservatively for abnormally invasive placentation. Twenty-six women were managed without any additional interventions. In most of these patients (19/26), the placenta had been partially removed. In 4 of these 26, conservative therapy failed. Twenty-two women received adjuvant methotrexate. In most of these women (19/22), the entire placenta was left in situ. In 5, therapy failed. Twelve women were managed with arterial embolization. In most of these (9/12), the diagnosis was made antepartum and the placenta was completely left in situ. In 3, therapy failed. Overall, 11 women experienced infection (11/60), 21 women experienced vaginal bleeding (21/60), and 4 suffered disseminated intravascular coagulopathy (4/60). Spontaneous loss of placental tissue was noted in 16 women. Subsequent pregnancies were reported in 8 women. Conservative management of abnormally invasive placentation can be effective and fertility can be preserved. It should only be considered in highly selected cases when blood loss is minimal and there is desire for fertility preservation. Whether adjuvant methotrexate or selective arterial embolization is beneficial is uncertain. Undetectable hCG values do not seem to guarantee complete resorption of retained placental tissue.
Obstetrical and Gynecological Survey 09/2007; 62(8):529-39. · 2.51 Impact Factor
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ABSTRACT: The risk of vertical transmission of HIV has been substantially reduced since the introduction of highly active antiretroviral therapy (HAART); however, the impact of taking HAART during pregnancy on the woman, the fetus and the infant is not yet understood.
To assess and compare tolerability, safety and efficacy of nelfinavir- or nevirapine-containing HAART in a cohort of pregnant and non-pregnant HIV-infected women in The Netherlands.
Retrospective comparative study.
In 15 centres specializing in HIV in The Netherlands, data on patient characteristics, HAART, adverse events, viral load response, mode of delivery and HIV status of the neonate were obtained from medical records of HIV-infected pregnant women who received HAART during pregnancy between January 1997 and June 2003. These data were compared with a control group of HIV-infected non-pregnant women that was obtained from the Dutch HIV-monitoring foundation database.
Data from 186 pregnant and 186 non-pregnant HIV-infected women using a nelfinavir- or nevirapine-containing regimen were analysed. The pregnant women were younger, used a nelfinavir containing regimen more often, had higher CD4 cell counts and lower HIV RNA levels. Nelfinavir-related gastrointestinal symptoms (P < 0.001), hyperglycaemia (P < 0.001) and nevirapine-related hepatotoxicity (P = 0.003) occurred more often during pregnancy. The risk of nevirapine-induced rash was not increased. No major adverse events occurred.
Nelfinavir- or nevirapine-containing HAART regimens during pregnancy are well tolerated. Side effects of antiretroviral therapy are more frequent in pregnant than in non-pregnant women.
AIDS 05/2005; 19(8):795-9. · 6.24 Impact Factor
