Living in a low socioeconomic status neighbourhood is associated with lower cumulative ongoing pregnancy rate after IVF treatment.

RESEARCH QUESTION: Does an association exist between neighbourhood socioeconomic status (SES) and the cumulative rate of ongoing pregnancies after 2.5 years of IVF treatment? DESIGN: A retrospective observational study involving 2669 couples who underwent IVF or IVF and intracytoplasmic sperm injection treatment between 2006 and 2020. Neighbourhood SES for each couple was determined based on their residential postal code. Subsequently, SES was categorized into low (p80). Multivariable binary logistic regression analyses were conducted, with the cumulative ongoing pregnancy within 2.5 years as the outcome variable. The SES category (reference category: high), female age (reference category: 32-36 years), body mass index (reference category: 23-25 kg/m2), smoking status (yes/no), number of oocytes after the first ovarian stimulation, embryos usable for transfer or cryopreservation after the first cycle, duration of subfertility before treatment and insemination type were used as covariates. RESULTS: A variation in ongoing pregnancy rates was observed among SES groups after the first fresh embryo transfer. No difference was found in the median number of IVF treatment cycles carried out. The cumulative ongoing pregnancy rates differed significantly between SES groups (low: 44%; medium: 51%; high: 56%; P < 0.001). Low neighbourhood SES was associated with significantly lower odds for achieving an ongoing pregnancy within 2.5 years (OR 0.66, 95% CI 0.52 to 0.84, P < 0.001). CONCLUSION: Low neighbourhood SES compared with high neighbourhood SES is associated with reducing odds of achieving an ongoing pregnancy within 2.5 years of IVF treatment.

Incentives for Smoking Cessation During Pregnancy: An Ethical Framework.

INTRODUCTION: Smoking during pregnancy increases the risk of morbidity and mortality of the mother and child. The inability of the unborn child to protect itself, raises the social and academic responsibility to protect the child from the harmful effects of smoking. Interventions including rewards (incentives) for lifestyle changes are an upcoming trend and can encourage women to quit smoking. However, these incentives can, as we will argue, also have negative consequences, for example the restriction of personal autonomy and encouragement of smoking to become eligible for participation. To prevent these negative consequences, we developed an ethical framework that enables to assess and address unwanted consequences of incentive-based interventions whereby moral permissibility can be evaluated. AIMS AND METHODS: The possible adverse consequences of incentives were identified through an extensive literature search. Subsequently, we developed ethical criteria to identify these consequences based on the biomedical ethical principles of Beauchamp and Childress. RESULTS: Our framework consists of 12 criteria. These criteria concern (1) effectiveness, (2) support of a healthy lifestyle, (3) motivational for the target population, (4) stimulating unhealthy behavior, (5) negative attitudes, (6) personal autonomy, (7) intrinsic motivation, (8) privacy, (9) fairness, (10) allocation of incentives, (11) cost-effectiveness, and (12) health inequity. Based on these criteria, the moral permissibility of potential interventions can be evaluated. CONCLUSIONS: Incentives for smoking cessation are a response to the responsibility to protect the unborn child. But these interventions might have possible adverse effects. This ethical framework aims to identify and address ethical pitfalls in order to avoid these adverse effects. IMPLICATIONS: Although various interventions to promote smoking cessation during pregnancy exist, many women still smoke during pregnancy. Interventions using incentives for smoking cessation during pregnancy are a promising and upcoming trend but can have unwanted consequences. This ethical framework helps to identify and address ethical pitfalls in order to avoid these adverse effects.It can be a practical tool in the development and evaluation of these interventions and in evaluating the moral permissibility of interventions using incentives for smoking cessation during pregnancy.

Maternal Midpregnancy Plasma trans 18:1 Fatty Acid Concentrations Are Positively Associated with Risk of Maternal Vascular Complications and Child Low Birth Weight.

Background: Evidence is plentiful that trans fatty acids (TFAs) induce vascular inflammation with adverse metabolic consequences. However, it is not clear whether TFAs increase the risk of vascular pregnancy complications such as preeclampsia.Objective: We investigated associations between midpregnancy maternal plasma trans 18:1 fatty acid (t18:1) concentrations and pregnancy course and outcomes.Methods: Participants were 6695 pregnant women and newborns from the Generation R Study, Rotterdam, Netherlands (enrollment in 2001-2005). Maternal midpregnancy (mean ± SD gestational age: 20.7 ± 1.2 wk) t18:1 plasma concentrations were determined and related to gestational age and sex-adjusted birth weight SD scores, placental weight, and the risk of preeclampsia. In addition, we explored potential time trends by testing the association of maternal plasma t18:1 concentrations with birth weight in birth cohorts given the Dutch industry-initiative to lower food TFA contents during the inclusion period. Multiple logistic and linear regression analyses were performed, taking various socioeconomic and biological covariates into account.Results: A higher midpregnancy maternal plasma t18:1 concentration was associated with lower birth weight (SD score, adjusted ß: -0.10; 95% CI: -0.15, -0.04; P < 0.001) and placental weight (kilograms, adjusted ß: -10,65; 95% CI: -20.23, -1.07; P = 0.03) and with a higher risk of preeclampsia (adjusted OR: 1.65; 95% CI: 1.10, 2.49; P = 0.02). We observed a 31% decrease in the median plasma t18:1 concentration in our population over time, but the association between the plasma t18:1 concentration standardized per birth year and birth weight was comparable between birth-year cohorts (years 2001-2005).Conclusions: A higher maternal midpregnancy plasma t18:1 concentration was associated with lower birth weight and placental weight and with a higher risk of preeclampsia. Although the intake of TFAs in our population decreased during the inclusion period, the association with adverse pregnancy outcomes was unchanged even at lower maternal plasma t18:1 concentrations.

GPs' awareness of pregnancy: trends and association with hazardous medication use.

BACKGROUND: GPs have been shown to be important providers of medical care during pregnancy, however, little evidence exists on their awareness of pregnancy when prescribing medication to women. AIM: To assess GPs' awareness of pregnancy and its association with prescribing medication with potential safety risks. DESIGN AND SETTING: Population-based study using confirmed pregnancy records linked to GP records from the PHARMO Perinatal Research Network. METHOD: GPs' awareness of pregnancy, defined as the presence of a pregnancy confirmation in the GP information system during pregnancy, was assessed from 2004 to 2020. GP prescriptions of medication with potential safety risks were selected during pregnancy and its association with GPs' awareness of pregnancy was assessed using multivariable logistic regression. RESULTS: A pregnancy confirmation was present in the GP records for 48% (n = 67 496/140 976) of selected pregnancies, increasing from 28% (n = 34/121) in 2004 to 63% in 2020 (n = 5763/9124). During 3% (n = 4489/140 976) of all pregnancies, the GP prescribed highly hazardous medication with teratogenic effects that should have been (temporarily) avoided. Pregnancy was GP confirmed for only 13% (n = 585/4489) at the first occurrence of such a prescription. Comparative analyses showed that women without a pregnancy confirmation were 59% more likely to be prescribed this highly hazardous medication (odds ratio [OR] 1.59, 95% confidence interval [CI] = 1.49 to 1.70) compared with those with a confirmed pregnancy. CONCLUSION: Results of this study indicate a potential issue with GP awareness about pregnancy status at the time medication with potential safety risks is prescribed. Although pregnancy registration by GPs improved over the years, inadequate use still seems to be made of the available information systems for appropriate drug surveillance.

Association of neighbourhood socioeconomic trajectories with preterm birth and small-for-gestational-age in the Netherlands: a nationwide population-based study.

BACKGROUND: Adverse birth outcomes have serious health consequences, not only during infancy but throughout the entire life course. Most evidence linking neighbourhood socioeconomic status (SES) to birth outcomes is based on cross-sectional SES measures, which do not reflect neighbourhoods' dynamic nature. We investigated the association between neighbourhood SES trajectories and adverse birth outcomes, i.e. preterm birth and being small-for-gestational-age (SGA), for births occurring in the Netherlands between 2003 and 2017. METHODS: We linked individual-level data from the Dutch perinatal registry to the Netherlands Institute for Social Research neighbourhood SES scores. Based on changes in their SES across four-year periods, neighbourhoods were categorised into seven trajectories. To investigate the association between neighbourhood SES trajectories and birth outcomes we used adjusted multilevel logistic regression models. FINDINGS: Data on 2 334 036 singleton births were available for analysis. Women living in stable low-SES neighbourhoods had higher odds of preterm birth (OR[95%CI]= 1·12[1·07-1·17]) and SGA (OR[95%CI]= 1·19[1·15-1·23]), compared to those in high SES areas. Higher odds of preterm birth (OR[95%CI]= 1·12[1·05-1·20]) and SGA (OR[95%CI]=1·12[1·06-1·18]) were also observed for those living in areas declining to low SES. Women living in a neighbourhood where SES improved from low to medium showed higher odds of preterm birth (OR[95%CI]= 1·09[1·02-1·18]), but not of SGA (OR[95%CI]= 1·04[0.98-1·10]). The odds of preterm or SGA birth in other areas were comparable to those seen in high SES areas. INTERPRETATION: In the Netherlands, disadvantaged neighbourhood SES trajectories were associated with higher odds of adverse birth outcomes. Longitudinal neighbourhood SES measures should also be taken into account when selecting a target population for public health interventions. FUNDING: Erasmus Initiative Smarter Choices for Better Health.

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

AIM: The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. METHOD: Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. RESULTS: After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. INTERPRETATION: Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

Fetal and infant growth patterns and left and right ventricular measures in childhood assessed by cardiac MRI.

OBJECTIVES: Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging. METHODS: In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging. RESULTS: Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio (P < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood (P < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood (P < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass. CONCLUSION: Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.

Neighborhood Deprivation and the Effectiveness of Mobile Health Coaching to Improve Periconceptional Nutrition and Lifestyle in Women: Survey in a Large Urban Municipality in the Netherlands.

BACKGROUND: In 2011, we launched the Smarter Pregnancy mobile health (mHealth) coaching program, which has shown to effectively improve inadequate nutrition and lifestyle behaviors in women before and during pregnancy. It is known that in deprived neighborhoods, risk factors for adverse pregnancy outcomes like inadequate nutrition and lifestyle behaviors accumulate. However, it has not yet been investigated whether the Smarter Pregnancy program is equally effective in women living in deprived neighborhoods. OBJECTIVE: This paper aimed to study the associations between neighborhood deprivation and improvement of inadequate nutrition and lifestyle behaviors of women who were either contemplating pregnancy or already pregnant and subscribed to the Smarter Pregnancy program. METHODS: We performed an additional analysis on data from women who used the Smarter Pregnancy program from 2011 to 2016. The program comprised 24 weeks of coaching on 5 nutrition and lifestyle behaviors, of which adequate intakes or lifestyle behaviors were defined as an intake of 200 grams or above of vegetables, 2 pieces of fruit, daily folic acid supplement use of 400 µg per day, and no smoking or alcohol consumption. Neighborhood deprivation was determined according to the status scores of the Netherlands Institute for Social Research. Logistic regression analyses and generalized estimating equation models were used to assess the associations between the neighborhood status score (NSS) and the improvement of inadequate nutrition and lifestyle behaviors, taking into account the behaviors at baseline. We adjusted the analyses for maternal age, body mass index, geographic origin, pregnancy status, and participation as a couple. RESULTS: Of the 2554 women included, 521 participated with their male partner. Overall, daily vegetable intake was most frequently inadequate at the start of the program (77.72, 1985/2554). Women with a higher NSS (ie, nondeprived neighborhood) smoked less often (adjusted odds ratio [OR] 0.85; 95% CI 0.77-0.93), consumed alcohol more often (adjusted OR 1.14, 95% CI 1.04-1.24), and were less likely to complete the 24 weeks of coaching (OR 0.91, 95% CI 0.88-0.95) compared with women who lived in a neighborhood with a low NSS (ie, deprived). In the total group, the relative improvement of inadequate nutrition and lifestyle behaviors after 24 weeks of coaching was between 26% and 64%. NSS was negatively associated with this improvement, indicating that women with a higher NSS were less likely to improve inadequate nutrition and lifestyle behaviors, especially vegetable intake (adjusted OR 0.89, 95% CI 0.82-0.97). CONCLUSIONS: The Smarter Pregnancy mHealth coaching program empowers women to improve inadequate nutrition and lifestyle behaviors. Unexpectedly, the program seemed more effective in women living in deprived neighborhoods. It is important to unravel differences in needs and behaviors of specific target groups to further tailor the mHealth program on the basis of demographic characteristics like neighborhood deprivation.

Low socioeconomic status is a risk factor for preeclampsia: the Generation R Study.

OBJECTIVES: To examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. METHODS: In the Generation R Study, a population-based cohort study, we examined data of 3547 pregnant women. Odds ratios of preeclampsia for low, mid-low and mid-high educational level compared with high educational level were calculated after adjustment for confounders and additional adjustment for a selection of potential mediators (family history, material factors, psychosocial factors, substance use, working conditions, preexisting medical conditions, maternal anthropometrics and blood pressure at enrollment) that individually caused more than 10% change in the odds ratio for low education. RESULTS: Adjusted for the confounding effects of age, gravidity and multiple pregnancy, women with low educational level were more likely to develop preeclampsia (odds ratio 5.12; 95% confidence interval: 2.20, 11.93) than women with high educational level. After additional adjustment for financial difficulties, smoking in pregnancy, working conditions, body mass index and blood pressure at enrollment, the odds ratio was 4.91 (95% confidence interval: 1.93, 12.52). CONCLUSION: Low maternal socioeconomic status is a strong risk factor for preeclampsia. Only a small part of this association can be explained by the mediating effects of established risk factors for preeclampsia. Further research is needed to disentangle the pathway from low socioeconomic status to preeclampsia.

Perceptions of pregnancy preparation in women with a low to intermediate educational attainment: A qualitative study.

OBJECTIVE: in the promotion of periconceptional health, appropriate attention has to be given to the perceptions of those who are most vulnerable, such as women with a relatively low socioeconomic status based on their educational attainment. The aim of this study was to explore these women's perceptions of pregnancy preparation and the role they attribute to healthcare professionals. DESIGN: we conducted semi-structured interviews with women with a low to intermediate educational attainment and with a desire to conceive, of which a subgroup had experience with preconception care. Thematic content analysis was applied on the interview transcripts. FINDINGS: the final sample consisted of 28 women. We identified four themes of pregnancy preparation perceptions: (i)"How to prepare for pregnancy?", which included health promotion and seeking healthcare; (ii) "Why prepare for pregnancy?", which mostly related to fertility and health concerns; (iii) "Barriers and facilitators regarding pregnancy preparation", such as having limited control over becoming pregnant as well as the health of the unborn; (iv) "The added value of preconception care", reported by women who had visited a consultation, which consisted mainly of reassurance and receiving information. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the attained insights into the perceptions of women with a low to intermediate education are valuable for adapting the provision of preconception care to their views. We recommend the proactive offering of preconception care, including information on fertility, to stimulate adequate preparation for pregnancy and contribute to improving perinatal health among women who are socioeconomically more vulnerable.

Impact of an mHealth Platform for Pregnancy on Nutrition and Lifestyle of the Reproductive Population: A Survey.

BACKGROUND: Poor nutrition and lifestyle behaviors exert detrimental effects on reproduction and health during the life course. Therefore, lifestyle interventions during the periconceptional period can improve fertility, pregnancy outcome, and health of subsequent generations. OBJECTIVE: This survey investigates the compliance, usability, and initial effectiveness of the Web-based mHealth platform, Smarter Pregnancy. METHODS: A free subscription to the mHealth platform, Smarter Pregnancy, was provided to couples contemplating pregnancy (n=1275) or already pregnant (n=603). After baseline identification of inadequate nutrition and lifestyle behaviors, a personal online coaching program of 6 months was generated. Using multiple imputation and the generalized estimating equation model with independent correlations, we estimated the changes from inadequate to adequate nutrition and lifestyle behaviors over time. Subgroup analyses were performed for (1) overweight and obese women (body mass index [BMI] ≥25 kg/m(2)), (2) pregnant women at the start of the program, and (3) couples. RESULTS: A 64.86% (1218/1878) compliance rate was observed and 54.7% (range 39.2-73.4%) of participants rated the program usability as positive or very positive. Adequate nutrition and lifestyle behaviors at baseline were 21.57% (405/1878) for vegetable intake, 52.61% (988/1878) for fruit intake, 85.44% (1303/1525) for folic acid use, 86.79% (1630/1878) for no tobacco use, and 64.43% (1210/1878) for no alcohol consumption. After 6 months of coaching, these lifestyle behaviors improved by 26.3% (95% CI 23.0-29.9) for vegetable intake, 38.4% (95% CI 34.5-42.5) for fruit intake, 56.3% (95% CI 48.8-63.6) for folic acid use, 35.1% (95% CI 29.1-41.6) for no tobacco use, and 41.9% (95% CI 35.2-48.9) for no alcohol consumption. The program showed the strongest effectiveness for participating couples. CONCLUSIONS: This novel Web-based mHealth platform shows high compliance and usability, and users demonstrate improvements in nutrition and lifestyle behaviors. The next step will be further validation in randomized controlled trials and implementation.

Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes.

BACKGROUND: Maternal vitamin D deficiency during pregnancy may affect fetal outcomes. OBJECTIVE: The objective of this study was to examine whether maternal 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy affect fetal growth patterns and birth outcomes. DESIGN: This was a population-based prospective cohort in Rotterdam, Netherlands in 7098 mothers and their offspring. We measured 25(OH)D concentrations at a median gestational age of 20.3 wk (range: 18.5-23.3 wk). Vitamin D concentrations were analyzed continuously and in quartiles. Fetal head circumference and body length and weight were estimated by repeated ultrasounds, and preterm birth (gestational age <37 wk) and small size for gestational age (less than the fifth percentile) were determined. RESULTS: Adjusted multivariate regression analyses showed that, compared with mothers with second-trimester 25(OH)D concentrations in the highest quartile, those with 25(OH)D concentrations in the lower quartiles had offspring with third-trimester fetal growth restriction, leading to a smaller head circumference, shorter body length, and lower body weight at birth (all P < 0.05). Mothers who had 25(OH)D concentrations in the lowest quartile had an increased risk of preterm delivery (OR: 1.72; 95% CI: 1.14, 2.60) and children who were small for gestational age (OR: 2.07; 95% CI: 1.33, 3.22). The estimated population attributable risk of 25(OH)D concentrations <50 nmol/L for preterm birth or small size for gestational age were 17.3% and 22.6%, respectively. The observed associations were not based on extreme 25(OH)D deficiency, but presented within the common ranges. CONCLUSIONS: Low maternal 25(OH)D concentrations are associated with proportional fetal growth restriction and with an increased risk of preterm birth and small size for gestational age at birth. Further studies are needed to investigate the causality of these associations and the potential for public health interventions.

Physical well-being in women with a history of severe preeclampsia.

OBJECTIVE: To evaluate the physical and mental health of women with a history of severe preeclampsia. METHODS: In a historical cohort study 131 former patients with a history of severe preeclampsia and 127 control patients received questionnaires about experienced physical and mental complaints after delivery. At a follow-up visit blood pressure, body mass index, and proteinuria were measured and venous blood was drawn. RESULTS: Former patients experienced significantly (p < 0.001) more frequent problems of headache (31% vs. 2%), right upper quadrant pain (16% vs. 1%), visual disturbances (21% vs. 1%), tiredness (66% vs. 27%), subjective loss of concentration (37% vs. 16%), and mental health (37% vs. 6%) compared with controls. When present, these health problems, except for tiredness, lasted significantly more often beyond six months postpartum compared to controls. Admittance to the intensive care unit was associated with headache, and subjective loss of memory and concentration over a longer period of time. The risk of recurrence of severe preeclampsia was a subject of concern in 20% of former patients. At follow-up, systolic and diastolic blood pressures were significantly higher (p < 0.001) among former patients. CONCLUSION: Patients with a history of severe preeclampsia more frequently reported physical and mental complaints, also during a longer period of time.

Maternal dietary patterns during pregnancy and body composition of the child at age 6 y: the Generation R Study.

BACKGROUND: Maternal diet during pregnancy may affect body composition of the offspring later in life, but evidence is still scarce. OBJECTIVE: We aimed to examine whether maternal dietary patterns during pregnancy are associated with body composition of the child at age 6 y. METHODS: This study was performed among 2695 Dutch mother-child pairs from a population-based prospective cohort study from fetal life onward. Maternal diet was assessed in early pregnancy by a 293-item semiquantitative food-frequency questionnaire. Vegetable, fish, and oil; nuts, soy, and high-fiber cereals; and margarine, snacks, and sugar dietary patterns were derived from principal component analysis. We measured weight and height of the child at age 6 y at the research center. Total body fat and regional fat mass percentages of the child were assessed with dual-energy X-ray absorptiometry. RESULTS: In the crude models, statistically significant associations were found for higher adherence to the vegetable, fish, and oil dietary pattern and the nuts, soy, and high-fiber cereals dietary pattern with lower body mass index, lower fat mass index, and lower risk of being overweight, but none of these associations remained significant after adjustment for sociodemographic and lifestyle factors. We found no associations between the margarine, snacks, and sugar dietary pattern and any of the outcomes. CONCLUSION: Our results suggest that the associations between maternal dietary patterns during pregnancy and body composition of the child at age 6 y are to a large extent explained by sociodemographic and lifestyle factors of mother and child.

Tracking of fetal growth characteristics during different trimesters and the risks of adverse birth outcomes.

BACKGROUND: Fetal growth characteristics are used to identify influences of several maternal characteristics and to identify individuals at increased risk of adverse outcomes. The extent to which fetal growth characteristics track in different trimesters is not known. METHODS: In a population-based prospective cohort study among 8636 pregnant women, we examined the extent to which fetal growth characteristics track, are influenced by maternal socio-demographic and lifestyle related determinants and are associated with birth outcomes. Fetal growth was assessed in each trimester and at birth. RESULTS: Correlation coefficient between first-trimester crown-rump length and birthweight was r = 0.12 (P-value < 0.05). Correlation coefficients for fetal-head circumference, (femur) length and (estimated) fetal weight ranged from r = 0.16 to r = 0.30 (all P-values < 0.05) between second trimester and birth and from r = 0.36 to r = 0.58 (all P-values < 0.05) between third trimester and birth, and were highest for (estimated) fetal weight. Correlation coefficients for (estimated) fetal weight tended to be lower among overweight mothers, as compared with normal weight mothers, but were not influenced by other maternal characteristics. First, second and third-trimester fetal growth characteristics were associated with risks of preterm birth and small size for gestational age at birth,with the strongest associations present in third trimester. CONCLUSION: Fetal growth characteristics track moderately throughout gestation, with stronger tracking coefficients present in later pregnancy. Tracking coefficients were not materially influenced by maternal socio-demographic and lifestyle characteristics. First, second and third trimester fetal growth characteristics were associated with the risk of adverse birth outcomes.

Fetal and childhood growth patterns associated with bone mass in school-age children: the Generation R Study.

Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analyzed these growth measurements in relation to total body (less head) BMD measured by DXA at age 6. We used conditional growth modeling; a technique which takes into account correlation between repeatedly measured growth measures. Our results showed that estimated fetal weight gain, femur length growth between 20 and 30 weeks of gestation, femur length growth between 30 weeks and birth, as well as all height and weight growth measurements from birth to 4 years of age were all positively associated with BMC, bone area (BA), and BMD (all p < 0.01). Fetal femur length growth between 30 weeks and birth was positively associated with BMC and BA (both p < 0.001), but not with BMD. Overall, childhood growth measurements exerted a larger influence on bone measures than fetal growth measures. The strongest effect estimate was observed during the first year of life. Children born small (<10th percentile) for gestational age (SGA) had lower BMC and BA, but not BMD, than children born appropriate for gestational age (AGA), whereas children born large (>90th percentile) for gestational age (LGA) had higher BMC and BA (all p < 0.001). These differences were no longer present in children showing subsequent accelerated and decelerated infant growth, respectively. We conclude that both fetal and childhood growth patterns are associated with bone mineral accrual, showing the strongest effect estimates in infancy. Compensatory infant growth counteracts the adverse consequences of fetal growth restriction on bone development.

Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study.

BACKGROUND: Maternal prenatal folate status has been linked to neurodevelopmental disorders, but the association with child emotional and behavioral problems is unclear. OBJECTIVES: We assessed the association of maternal folate status during pregnancy with child emotional and behavioral problems. Also, we examined whether any association between folate status and child problems is a consequence of maternal folic acid supplement use or variation in maternal MTHFR genotype. DESIGN: Within a population-based cohort, we measured maternal plasma folate concentrations in early pregnancy and assessed folic acid supplement use by questionnaire. Mothers of European descent were genotyped for the MTHFR 677 C→T polymorphism. Child emotional and behavioral problems were assessed with the Child Behavior Checklist at 3 y in 3209 children. RESULTS: Children of mothers with prenatal folate deficiency were at higher risk of emotional problems (OR: 1.57; 95% CI: 1.03, 2.38) but not behavioral problems (OR: 1.00; 95% CI: 0.64, 1.56) after adjustment for confounders. A higher risk of emotional problems was also found in children whose mothers started using folic acid supplements late or did not use supplements at all (OR: 1.45; 95% CI: 1.14, 1.84) than in children whose mothers started periconceptionally. However, low plasma folate concentrations only partly explained this association (OR: 1.38; 95% CI: 1.08, 1.78). Although related to plasma folate concentrations, maternal MTHFR genotype did not explain the association of folate status with offspring emotional problems. CONCLUSION: Low maternal folate status during early pregnancy is associated with a higher risk of emotional problems in the offspring.

Maternal smoking and blood pressure in different trimesters of pregnancy: the Generation R study.

OBJECTIVE: Smoking during pregnancy is a risk factor for various adverse birth outcomes but lowers the risk of preeclampsia. Cardiovascular adaptations might underlie these associations. We examined the associations of smoking in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of preeclampsia and pregnancy-induced hypertension in a low-risk population-based cohort of 7106 pregnant women. METHODS: This study was embedded in a population-based prospective cohort study from early pregnancy onwards. Smoking and systolic and diastolic blood pressures were assessed by questionnaires and physical examinations in each trimester of pregnancy. Information about preeclampsia and pregnancy-induced hypertension was obtained from medical records. RESULTS: Compared to nonsmoking women, both first-trimester-only and continued smoking were associated with a steeper increase for systolic blood pressure and a lowest mid-pregnancy level and steeper increase thereafter for diastolic blood pressure throughout pregnancy. We did not find any significant associations in risk of preeclampsia for first-trimester-only smoking (odds ratio of 1.28, 95% confidence interval 0.74, 2.21) and continued smoking (odds ratio of 0.83, 95% confidence interval 0.50, 1.36), respectively. CONCLUSIONS: Our results suggest that both first-trimester-only and continued smoking are associated with persistent maternal cardiovascular adaptations during pregnancy. Strategies for prevention of smoking during pregnancy should be focused on the preconception period. The effects of early and late-pregnancy smoking on the risk of preeclampsia should be further explored. Our results should be carefully interpreted to the general population of pregnant women.