Context: Hypertensive disorders during pregnancy are associated with a wide range of maternal and fetal complications, and only a few risk factors are known for the development of these disorders during pregnancy. Conflicting and limited data are available on the relationship between thyroid (dys)function and the risk of hypertensive disorders of pregnancy. Objective: The objective of the investigation was to study the associations between early-pregnancy thyroid dysfunction, thyroid function within the normal range, and the risk of hypertensive disorders. Design, Setting, and Participants: In early pregnancy, serum TSH, free T4 (FT4), and thyroperoxidase antibody (TPOAb) levels were determined in 5153 pregnant women. No interventions were done. The associations of thyroid function with the risk of hypertensive disorders were studied. Main Outcome Measures: Mean blood pressures and hypertensive disorders, including pregnancy-induced hypertension (n = 209) and preeclampsia (n = 136), were measured. Results: Hyperthyroid mothers had a higher risk of hypertensive disorders [odds ratio (OR) 3.40 [95% confidence interval (CI) 1.46-7.91], P = .005], which was mainly due to an increased risk of pregnancy-induced hypertension [OR 4.18 (95% CI 1.57-11.1), P = .004]. Hypothyroidism and hypothyroxinemia were not associated with hypertensive disorders. Within the normal range, the high-normal FT4 levels were associated with an increased risk of hypertensive disorders [OR 1.62 (95% CI 1.06-2.47), P = .03], which was mainly due to an increased risk of preeclampsia [OR 2.06 (95% CI 1.04-4.08), P = .04]. The TPOAb status was not associated with hypertensive disorders. Conclusions: We show that biochemical hyperthyroidism and also high-normal FT4 levels during early pregnancy are associated with an increased risk of hypertensive disorders. These data demonstrate that these associations are even seen for a mild variation in thyroid function within the normal range.
Adequate thyroid hormone availability during fetal and early life is crucial for normal child growth and development. Fetal growth heavily depends on angiogenesis. Placental growth factor (PlGF) is a proangiogenic factor sharing high homology with vascular endothelial growth factor, whereas soluble FMS-like tyrosine kinase-1 (sFlt1) is a potent antagonist of vascular endothelial growth factor and PlGF signaling. Because the thyroid is a highly vascularized organ, we hypothesized that fetal angiogenic factors influence in utero thyrogenesis and impair newborn thyroid function. Therefore, we investigated the association between sFlt1 and PlGF on newborn thyroid function.
Premature delivery is an important risk factor for child mortality and psychiatric, metabolic, and cardiovascular disease later in life. In the majority of cases, the cause of prematurity cannot be identified. Currently, it remains controversial whether abnormal maternal thyroid function during pregnancy increases the risk of premature delivery. Therefore, we investigated the relation between maternal serum thyroid parameters and the risk of premature delivery in a large prospective population-based study.
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 ?mol/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.
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.
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.
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.
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.
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.
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.
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.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.