Second Trimester

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Fetal size change

Ultrasound12wk 3D image2.jpg

Ultrasound Image of an early Fetus (12 week)

Fetal Links: fetal | Week 10 | Week 12 | second trimester | third trimester | fetal neural | Fetal Blood Sampling | fetal growth restriction | birth | birth weight | preterm birth | Developmental Origins of Health and Disease | macrosomia | BGD Practical | Medicine Lecture | Science Lecture | Lecture Movie | Category:Human Fetus | Category:Fetal
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Category:Second Trimester

Some Recent Findings

  • Morphometric development of the human fetal cerebellum during the early second trimester[1] "The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain."
  • Functional connectome of the fetal brain [2] "Large-scale functional connectome formation and re-organization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated prior to birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function. The fetal to neonatal period is well known as a critical stage in brain development. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction." neural
  • vision - Fetal ocular development in the second trimester of pregnancy documented by 7.0 T postmortem Magnetic Resonance Imaging[3] "Few investigators have analyzed fetal ocular growth with Magnetic Resonance Imaging (MRI) of high magnetic strength. Our purpose is to obtain normative biometrics for fetal ocular development in the second trimester of pregnancy. Sixty specimens with a gestational age (GA) of 12-23 weeks were scanned using a 7.0 T MRI scanner. The linear interocular and binocular distances (IOD and BOD, respectively), globe diameter (GD) and lens diameter (LD) were measured on the transverse section of the largest diameter of the eyeballs. The three dimensional (3D) visualization model of the eyeball was reconstructed with Amira software. Then, the globe and lens volumes (GV and LV, respectively) were obtained. All the measurements were plotted as a function of GA. The fetal ocular structures in the second trimester of pregnancy could be clearly delineated on 7.0 T postmortem MRI images. All the linear measurements logarithmically increased with GA, while, the volumetric measurements linearly increased with GA. Postmortem MRI of high magnetic strength can clearly document fetal ocular growth in the second trimester of pregnancy. These quantitative data may be a valuable reference for the assessment of normal fetal eyeball development in clinical settings and may be considered a supplement to anatomical investigations."
  • second trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of preterm birth: A Population-Based Study[4] "To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. ...The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost."
More recent papers  
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Search term: Second Trimester

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Vitamin D - Lower vitamin D levels during the second trimester are associated with developing gestational diabetes mellitus: an observational cross-sectional study[5]

In this study, we aimed to compare serum 25(OH)D levels in women with and without gestational diabetes mellitus (GDM), and to identify the serum 25(OH)D levels associated with GDM. We recruited 40 women with GDM and 40 healthy pregnant women, aged 20-40 years and in the second trimester, at Gulhane Education and Research Hospital. We excluded women with chronic diseases, preeclampsia, pre-GDM, multiple pregnancies, and those taking medications related to calcium or vitamin D metabolism. We took anthropometric measurements and blood samples during the second trimester. Of the 80 pregnant women, pre-pregnancy body mass index was significantly higher among the GDM group than the healthy group (26.4 ± 5.73 kg/m2 vs. 22.6 ± 3.56 kg/m2, p = .001). Serum 25(OH)D levels in women with GDM were significantly lower than those in healthy women (16.8 ± 9.90 ng/mL vs. 20.9 ± 8.16 ng/mL, p = .016). The prevalence of severe vitamin D deficiency was as high as 72.5% among women in the GDM group, with a 1.74-fold increased risk of deficient status. Levels of 25(OH)D lower than a cutoff value of 14.0 ng/mL were determined to be related to GDM. These study results suggest that maternal vitamin D deficiency in mid-pregnancy is significantly associated with development of GDM."

  • Review - Second trimester sonographic features of fetal chromosomal defects[6] "Advances in ultrasound technology have dramatically improved the detection of fetal chromosomal defects. Each chromosomal defect has its own syndromal pattern of detectable abnormalities prenataly. Most commonly detectable defects are Trisomies & Triploidies. Although only an invasive test can provide a definitive diagnosis, fetuses with major chromosomal abnormalities have either external or internal defects that can be recognized by detailed ultrasonographic examination at second trimester. These are defined as ultrasound markers for fetal aneuploidy. This article provides an overview and discussion on prenatal sonographic features that may suggest the presence of a common fetal chromosomal defect." ultrasound
  • Review - Second- and third-trimester biochemical and ultrasound markers predictive of ischemic placental disease.[7] "Ischemic placental disease is a recently coined term that describes the vascular insufficiency now believed to be an important etiologic factor in preeclampsia, intrauterine fetal growth restriction, and placental abruption. Given the increased risk for poor maternal and fetal outcomes, early prediction and prevention of this disorder is of significant clinical interest for many. In this article, we review the second- and third-trimester serum and ultrasound markers predictive of ischemic placental disease. Limited first-trimester data is also presented. While current studies report a statistical association between marker levels and various adverse perinatal outcomes, the observed diagnostic accuracy is below the threshold required for clinical utility. An exception to this generalization is uterine artery Doppler for the prediction of early-onset preeclampsia. Metabolomics is a relatively new analytic platform that holds promise as a first-trimester marker for the prediction of both early- and late-onset preeclampsia."

Neural Development

Timeline of events in Normal Human Neural Development[8]

Three-dimensional reconstruction of the lateral (top row) and medial (bottom row) surface of second trimester (13 to 21 week) brains to reveal the development of the Sylvian fissure or lateral sulcus (green arrow), the calcarine fissure (blue arrow), and the parieto-occipital sulcus (red arrow), respectively.

Brain fissure development 02.jpg

The images below are from a recent MRI study of fixed fetal brains at different weeks of development during the second trimester.[9]

Links: Neural System - Fetal

Second Trimester Timeline

Second Trimester (Clinical Week GA 14+)
Age (week)
Fertilisation Age FA Gestational Age GA
14 Fetal head lateral.jpg Week 12 - CRL 85 mm, femur length 15 mm, biparietal diameter 25 mm

Hearing Week 12-16 - Capsule adjacent to membranous labrynth undegoes vacuolization to form a cavity (perilymphatic space) around membranous labrynth and fills with perilymph

Genital male and female external genital differences observable

Respiratory Month 3-6 - lungs appear glandular, end month 6 alveolar cells type 2 appear and begin to secrete surfactant

Tongue Week 12 - first differentiated epithelial cells (Type II and III)

Genital female genital canal (80 days) formed with absorption of the median septum

15 Tongue Week 12 to 13 - maximum synapses between cells and afferent nerve fibers

Hearing - Outer Ear Development Week 13 - Meatal plug disc-like, innermost surface in contact with the primordial malleus, contributes to the formation of the tympanic membrane.  

16 Tongue Week 14 to 15 - taste pores develop, mucous

Ovary Development 100 days - primary follicles present

Nail Development toenails appear

Head Development facial skeleton remodelling begins

17 Pancreas glucagon detectable in fetal plasma.

Spleen Week 15 -alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells scattered around the arterioles. [10]

18 Fetal size change.jpg Hearing Week 16-24 - Centres of ossification appear in remaining cartilage of otic capsule form petrous portion of temporal bone. Continues to ossify to form mastoid process of temporal bone.

Pituitary adenohypophysis fully differentiated

Respiratory Week 16 to 25 lung histology - canalicular

Hearing - Outer Ear Development Week 16.5 - External auditory meatus is fully patent throughout its length, lumen is still narrow and curved.

Skin 4 months - basal cell- proliferation generates folds in basement membrane; neural crest cells- (melanocytes) migrate into epithelium; embryonic connective tissue- differentiates into dermis, a loose ct layer over a dense ct layer. Beneath the dense ct layer is another loose ct layer that will form the subcutaneous layer. Ectoderm contributes to nails, hair follictles and glands. Nails form as thickening of ectoderm epidermis at the tips of fingers and toes. These form germinative cells of nail field. Cords of these cells extend into mesoderm forming epithelial columns. These form hair follocles, sebaceous and sweat glands.

primary follicles begin to form in the ovary and are characterized by an oocyte

glandular urethra forms and skin folds present

19 Brain week 17 histology.jpg Neural - Brain development histology week 17
20 Bailey095.jpgTongue Week 18 - substance P detected in dermal papillae, not in taste bud primordia

Skin vernix caseosa covers skin

Spleen Week 18 - alpha-SMA-positive reticulum cells increase in number and began to form a reticular framework. An accumulation of T and B lymphocytes occurred within the framework, and a primitive white pulp was observed around the arterioles. [10]

Hearing - Outer Ear Development week 18 - External auditory meatus is already fully expanded to its complete form.

22 Pituitary week 20 to 24 growth hormone levels peak, then decline

Skin lanugo, skin hair

Skin 5 months - Hair growth initiated at base of cord, lateral outgrowths form associated sebaceous glands; Other cords elongate and coil to form sweat glands; Cords in mammary region branch as they elongate to form mammary glands.

24 Gray0038.jpg Neural brain cortical sulcation - sylvian fissure, interhemispheric fissure, callosal sulcus, parietooccipital fissure, and hippocampic fissures present[11]

Spleen - Week 22 - antigenic diversity of the reticular framework was observed, and T and B lymphocytes were segregated in the framework. T lymphocytes were sorted into the alpha-smooth muscle actin-positive reticular framework, and the periarteriolar lymphoid sheath (PALS) was formed around the arteriole. B lymphocytes aggregated in eccentric portions to the PALS and formed the lymph follicle (LF). The reticular framework of the LF was alpha-SMA-negative. [10]

26 Respiratory Week 24 to 40 lung histology - terminal sac

Spleen Week 24 - marginal zone appeared in the alpha-smooth muscle actin-positive reticular framework around the white pulp.[10]

Earliest potential survival expected if born

ovarian follicles can consist of growing oocytes surrounded by several layers of granulosa cells

27 Respiratory end month 6 alveolar cells type 2 appear and begin to secrete surfactant


  1. Xu F, Ge X, Shi Y, Zhang Z, Tang Y, Lin X, Teng G, Zang F, Gao N, Liu H, Toga AW & Liu S. (2020). Morphometric development of the human fetal cerebellum during the early second trimester. Neuroimage , 207, 116372. PMID: 31751665 DOI.
  2. Turk E, van den Heuvel MI, Benders MJ, de Heus R, Franx A, Manning JH, Hect JL, Hernandez-Andrade E, Hassan SS, Romero R, Kahn RS, Thomason ME & van den Heuvel MP. (2019). Functional connectome of the fetal brain. J. Neurosci. , , . PMID: 31685648 DOI.
  3. Zhang Z, Lin X, Yu Q, Teng G, Zang F, Wang X, Liu S & Hou Z. (2019). Fetal ocular development in the second trimester of pregnancy documented by 7.0 T postmortem Magnetic Resonance Imaging. PLoS ONE , 14, e0214939. PMID: 30947240 DOI.
  4. Nunthapiwat S, Sekararithi R, Wanapirak C, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S & Tongsong T. (2019). Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study. Gynecol. Obstet. Invest. , , 1-8. PMID: 30602167 DOI.
  5. Ede G, Keskin U, Cemal Yenen M & Samur G. (2019). Lower vitamin D levels during the second trimester are associated with developing gestational diabetes mellitus: an observational cross-sectional study. Gynecol. Endocrinol. , , 1-4. PMID: 30599810 DOI.
  6. Akhter N & Chakraborty RK. (2014). Second trimester sonographic features of fetal chromosomal defects. Mymensingh Med J , 23, 412-6. PMID: 24858178
  7. Savasan ZA, Goncalves LF & Bahado-Singh RO. (2014). Second- and third-trimester biochemical and ultrasound markers predictive of ischemic placental disease. Semin. Perinatol. , 38, 167-76. PMID: 24836829 DOI.
  8. Report of the Workshop on Acute Perinatal Asphyxia in Term Infants, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Child Health and Human Development, NIH Publication No. 96-3823, March 1996.
  9. Huang H, Xue R, Zhang J, Ren T, Richards LJ, Yarowsky P, Miller MI & Mori S. (2009). Anatomical characterization of human fetal brain development with diffusion tensor magnetic resonance imaging. J. Neurosci. , 29, 4263-73. PMID: 19339620 DOI.
  10. 10.0 10.1 10.2 10.3 <pubmed>19255788</pubmed>
  11. <pubmed>11158907</pubmed>


Raines DA & Cooper DB. (2020). Braxton Hicks Contractions. , , . PMID: 29262073


Zhang Z, Hou Z, Lin X, Teng G, Meng H, Zang F, Fang F & Liu S. (2013). Development of the fetal cerebral cortex in the second trimester: assessment with 7T postmortem MR imaging. AJNR Am J Neuroradiol , 34, 1462-7. PMID: 23413246 DOI.

Toi A, Lister WS & Fong KW. (2004). How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development?. Ultrasound Obstet Gynecol , 24, 706-15. PMID: 15586358 DOI.

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