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First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study

BMJ 2014; 348 doi: (Published 23 January 2014) Cite this as: BMJ 2014;348:g14
  1. Vincent W V Jaddoe, professor of paediatric epidemiology123,
  2. Layla L de Jonge, medical doctor23,
  3. Albert Hofman, professor of epidemiology2,
  4. Oscar H Franco, professor of preventive medicine2,
  5. Eric A P Steegers, professor of obstetrics and gynaecology4,
  6. Romy Gaillard, PhD student123
  1. 1The Generation R Study Group, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, Netherlands
  2. 2Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, Netherlands
  3. 3Department of Paediatrics, Erasmus University Medical Center-Sophia Children’s Hospital, PO Box 2040, 3000 CA, Rotterdam, Netherlands
  4. 4Department of Obstetrics and Gynaecology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, Netherlands
  1. Correspondence to: V W V Jaddoe v.jaddoe{at}
  • Accepted 18 December 2013


Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood.

Design Population based prospective cohort study.

Setting City of Rotterdam, the Netherlands.

Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle.

Main outcomes measures Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations.

Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards.

Conclusions Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.


  • Contributors: VWVJ obtained funds, designed the study, had overall responsibility for managing the study, completed the background literature search, contributed to the analysis protocol, contributed to data management, wrote the first draft of the paper, and collated comments from other authors. RG contributed to the analysis protocol and completed analyses. LLdJ, AH, OHF, and EAS obtained funds, designed the study, and contributed to the manuscript. All authors had access to all of the data and approved the final version of the submitted manuscript. VWVJ and RG are the guarantors.

  • Funding: VWVJ received funding from the Netherlands Organization of Scientific Research (NWO), Netherlands Organization of Health Research and Development (ZonMw), VIDI 016.136.361. OHF works in ErasmusAGE, a centre for ageing research across the life course funded by Nestle Nutrition, Metagenics, and AXA. RG received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement No 289346.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no financial support from any organisation for the submitted work other than those listed above; no financial relationship with any companies that might have an interest in the submitted work in the previous three years; no non-financial interests or relationships that may be relevant to the submitted work.

  • Ethical approval: Written informed consent was obtained from the parents to include their children in the Generation R Study. The Medical Ethical Committee of the Erasmus Medical Center in Rotterdam approved the study.

  • Data sharing: The protocol is available on request.

  • Transparency: The lead author (VWVJ) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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