Intact Fetuses Research Articles

Hypothyroidism impairs development of the gastrointestinal tract in the ovine fetus.

Growth and maturation of the fetal gastrointestinal tract near term prepares the offspring for the onset of enteral nutrition at birth. Structural and functional changes are regulated by the prepartum rise in cortisol in the fetal circulation, although the role of the coincident rise in plasma tri-iodothyronine (T3) is unknown. This study examined the effect of hypothyroidism on the structural development of the gastrointestinal tract and the activity of brush-border digestive enzymes in the ovine fetus near term. In intact fetuses studied between 100 and 144days of gestation (dGA; term ∼145days), plasma concentrations of T3, cortisol and gastrin; the mucosal thickness in the abomasum, duodenum, jejunum and ileum; and intestinal villus height and crypt depth increased with gestational age. Removal of the fetal thyroid gland at 105-110 dGA suppressed plasma thyroxine (T4) and T3 concentrations to the limit of assay detection in fetuses studied at 130 and 144 dGA, and decreased plasma cortisol and gastrin near term, compared to age-matched intact fetuses. Hypothyroidism was associated with reductions in the relative weights of the stomach compartments and small intestines, the outer perimeter of the intestines, the thickness of the gastric and intestinal mucosa, villus height and width, and crypt depth. The thickness of the mucosal epithelial cell layer and muscularis propria in the small intestines were not affected by gestational age or treatment. Activities of the brush border enzymes varied with gestational age in a manner that depended on the enzyme and region of the small intestines studied. In the ileum, maltase and dipeptidyl peptidase IV (DPPIV) activities were lower, and aminopeptidase N (ApN) were higher, in the hypothyroid compared to intact fetuses near term. These findings highlight the importance of thyroid hormones in the structural and functional development of the gastrointestinal tract near term, and indicate how hypothyroidism in utero may impair the transition to enteral nutrition and increase the risk of gastrointestinal disorders in the neonate.

Murine Fetal Serum Phosphorus is Set Independent of FGF23 and PTH, Except in the Presence of Maternal Phosphate Loading.

Fibroblast growth factor 23 (FGF23) appears to play no role until after birth, given unaltered phosphate and bone metabolism in Fgf23- and Klotho-null fetuses. However, in those studies maternal serum phosphorus was normal. We studied whether maternal phosphate loading alters fetal serum phosphorus and invokes a fetal FGF23 or parathyroid hormone (PTH) response. C57BL/6 wild-type (WT) female mice received low (0.3%), normal (0.7%), or high (1.65%) phosphate diets beginning 1 week prior to mating to WT males. Fgf23+/- female mice received the normal or high-phosphate diets 1 week before mating to Fgf23+/- males. One day before expected birth, we harvested maternal and fetal blood, intact fetuses, placentas, and fetal kidneys. Increasing phosphate intake in WT resulted in progressively higher maternal serum phosphorus and FGF23 during pregnancy, while PTH remained undetectable. Fetal serum phosphorus was independent of the maternal phosphorus and PTH remained low, but FGF23 showed a small nonsignificant increase with high maternal serum phosphorus. There were no differences in fetal ash weight and mineral content, or placental gene expression. High phosphate intake in Fgf23+/- mice also increased maternal serum phosphorus and FGF23, but there was no change in PTH. WT fetuses remained unaffected by maternal high-phosphate intake, while Fgf23-null fetuses became hyperphosphatemic but had no change in PTH, skeletal ash weight or mineral content. In conclusion, fetal phosphate metabolism is generally regulated independently of maternal serum phosphorus and fetal FGF23 or PTH. However, maternal phosphate loading reveals that fetal FGF23 can defend against the development of fetal hyperphosphatemia.

Laparoscopic Gravid Hysterectomy for Placenta Accreta at 19 Weeks Gestation

Study Objective To determine if laparoscopic approach to gravid hysterectomy for placenta accreta is a safe alternative to traditional open abdominal route. Design Case report. Setting Gynecology operating room. Patients or Participants A 36-year-old G3P2002 at 19w0d with history of 2 prior cesarean sections presented with undesired pregnancy and placenta previa with suspected placenta accreta. She was consented for laparoscopic gravid hysterectomy, with possible conversion to open abdominal approach. Interventions Total laparoscopic hysterectomy, bilateral salpingectomy, vaginal uterine morcellation, and evacuation of intact fetus Measurements and Main Results The patient was taken to the operating room, where double set up was prepared for both laparoscopic and abdominal approach to hysterectomy. Exam under anesthesia revealed a 20-week gravid uterus. She was positioned in low lithotomy position. Five laparoscopic ports were placed. A sacrocolpopexy cup was placed in the vagina to delineate the vaginal fornices; no tip was placed through the cervix due to placenta previa. The operating room table was airplaned side to side to assist uterine manipulation. A bariatric 45 degree laparoscope aided visualization. The hysterectomy was completed in usual fashion with a bipolar sealing device. After the colpotomy was completed, the uterus was placed in a tissue extraction bag. Strings attached to the bag were grasped with a ring forcep placed vaginally, and the bag was delivered through the vagina. The uterus was morcellated in the bag, amniotomy was performed, and the fetus was delivered intact. The vaginal cuff was closed, and cystoscopy performed. Total estimated blood loss was 50 mL. The patient discharged on post-operative day one. Final surgical pathology confirmed placenta accreta. Conclusion Laparoscopic gravid hysterectomy is a safe alternative to abdominal approach in the setting of placenta accreta, with decreased blood loss, shorter length of stay, and faster recovery.

Autopsy Findings of Central Nervous System Anomalies in Intact Fetuses Following Termination of Pregnancy After Prenatal Ultrasound Diagnosis.

Central nervous system (CNS) anomalies are the second most frequent category of congenital anomalies after congenital heart defects (CHDs). In this study, the aim was to investigate the distribution of different CNS anomalies with associated anomalies and karyotype in a fetal autopsy population of terminated pregnancies over a 30-year period and to correlate the ultrasonographic diagnoses of CNS anomalies with autopsy findings. This study includes 420 intact fetuses with CNS anomalies terminated at gestational ages 11+ 0 to 33+ 6 over a 30-year period from 1985 to 2014. An ultrasound (US) examination was performed at the National Centre for Fetal Medicine, St. Olavs Hospital, Trondheim. The autopsies were performed at the Department of Pathology at the same hospital or a collaborating hospital. The anomalies were subcategorized according to the classification by the World Health Organization. Neural tube defects such as anencephaly (22.4%, 107/477) and spina bifida (22.2%, 106/477) constituted the most common CNS anomalies, followed by congenital hydrocephalus (17.8%, 85/477). In total, the karyotype was abnormal in 21.0% of all termination of pregnancies (TOPs), with trisomy 18 as the most frequent abnormal karyotype. CHDs, skeletal anomalies, and urinary anomalies were the most common associated organ anomalies. Throughout the study period, there was full agreement between US and postmortem findings of CNS anomalies in 96.9% (407/420) of TOPs. In this study of autopsy findings of CNS anomalies in intact fetuses terminated after prenatal US diagnosis, neural tube defects were most common. About half of the fetuses had isolated serious CNS anomalies, while the other half were CNS anomalies associated with structural and/or chromosomal anomalies. The prenatal US diagnoses were in good concordance with autopsy findings. In particular, due to challenges of diagnoses made early in pregnancy, it is necessary to continue the validation practice.

Lithopedion coexisting with a huge uterine fibroid: A case report

A lithopedion (stone baby) is a rare phenomenon seen in advanced abdominal pregnancy. There are few cases reported in Africa. This is a case report of a 50-year-old woman who presented with a complaint of an abdominal swelling for 15 years. She was suspected to have a uterine fibroid. She was subsequently prepared for myomectomy. Intraoperatively, she was found to have a calcified intact fetus with a coexisting huge uterine fibroid. She had extirpation of the calcified fetus and myomectomy. She did well postoperatively and was discharged home on the 7th day.

Ultrasonographic and postoperative diagnosis of spontaneous viable tubal abortion following slow-leaking ectopic gestation

Ruptured ectopic pregnancy is not an uncommon diagnosis in gynecological emergency admissions, but spontaneous tubal abortion with an intact live fetus is a rare event which can be diagnosed preoperatively with ultrasound. The aim of this study is to report a case of spontaneous live tubal abortion following ectopic gestation that was diagnosed ultrasonographically and confirmed intraoperatively.

A rare case of unruptured tubal pregnancy at ten weeks of gestation

Ectopic pregnancy is a life threatening condition and can present itself in diverse ways. This case reports a 23 years primigravida, admitted with history of amenorrhoea of ten weeks and right sided unruptured tubal pregnancy diagnosed on routine ultrasonography. On laparoscopy, there was an unruptured tubal pregnancy with gestational sac measuring around 6 × 5 cm. The foetus had crown rump length of 32 mm and foot length of 5 mm; both of which correspond probably to 10 to 11 weeks size. Segmental resection of the affected part of the fallopian tube was done laparoscopically. Rarely tubal pregnancy can remain asymptomatic and unruptured for longer duration of gestation than the usual scenario. The reported average duration of diagnosis of unruptured tubal pregnancy is of nine weeks and this case explores the possibility of removing an intact foetus at longer gestational age through laparoscopy.Journal of Kathmandu Medical College Vol. 2, No. 3, Issue 5, Jul.-Sep., 2013 Page: 148-151DOI: http://dx.doi.org/10.3126/jkmc.v2i3.9966Uploaded date : 3/4/2014

Insulin Deficiency Alters the Metabolic and Endocrine Responses to Undernutrition in Fetal Sheep Near Term

Insulin deficiency affects the adult metabolic response to undernutrition, but its effects on the fetal response to maternal undernutrition remain unknown. This study examined the effects of maternal fasting for 48 h in late gestation on the metabolism of fetal sheep made insulin deficient by pancreatectomy (PX). The endocrine and metabolic responses to maternal fasting differed between intact, sham-operated and PX fetuses, despite a similar degree of hypoglycemia. Compared with intact fetuses, there was no increase in the plasma concentrations of cortisol or norepinephrine in PX fetuses during maternal fasting. In contrast, there was a significant fasting-induced rise in plasma epinephrine concentrations in PX but not intact fetuses. Umbilical glucose uptake decreased to a similar extent in both groups of fasted animals but was associated with a significant fall in glucose carbon oxidation only in intact fetuses. Pancreatectomized but not intact fetuses lowered their oxygen consumption rate by 15-20% during maternal fasting in association with increased uteroplacental oxygen consumption. Distribution of uterine oxygen uptake between the uteroplacental and fetal tissues therefore differed with fasting only in PX fetuses. Both groups of fetuses produced glucose endogenously after maternal fasting for 48 h, which prevented any significant fall in the rate of fetal glucose utilization. In intact but not PX fetuses, fasting-induced glucogenesis was accompanied by a lower hepatic glycogen content. Chronic insulin deficiency in fetal sheep therefore leads to changes in the counterregulatory endocrine response to hypoglycemia and an altered metabolic strategy in dealing with nutrient restriction in utero.

The effect of a derivative of indole morphine administered during the induction of labor on the activity of antioxidant enzymes in the brains of fetal rabbits

We studied the effects of a derivative of indole morphine (Trisan) during induction of labor on the activity of enzymes of antioxidant defense in the brains of fetuses that developed under normal (intact) and disturbed (experimental) placental blood circulation. We show that Trisan has antihypoxic and moderate antioxidant characteristics and decreased intranatal oxidative stress in the CNS of intact and experimental fetuses.

Fetopathologic examination for early termination of pregnancy: dogma or necessity?

Our objective was assessment of fetopathological examination after termination of pregnancy (TOP) for fetal anomalies with normal karyotype <17 weeks of gestation. This was a multicenter retrospective study. Records of TOP for fetal anomalies with normal karyotype were analyzed. Primary outcomes were modifications of genetic counseling and management of next subsequent pregnancies. Medical TOPs were compared with surgical TOPs. In all, 59 pregnancies were included (30 aspirations, 29 inductions). Fetopathological examination modified genetic counseling for 22 patients: 62% for the medical induction group vs 13% in the vacuum aspiration group (P < .001). Management of subsequent pregnancies was modified in 17% in the medical induction group vs 3% in the aspiration group (P = .06). Fetopathological examination for early TOP with normal karyotype is relevant, especially when an intact fetus is examined. Thanks to it, genetic counseling is often modified, as is management of the next pregnancy. Medical procedures should be preferred to surgical procedures.

Effects of hypothyroidism on the structure and mechanical properties of bone in the ovine fetus

Thyroid hormones are important for normal bone growth and development in postnatal life. However, little is known about the role of thyroid hormones in the control of bone development in the fetus. Using computed tomography and mechanical testing, the structure and strength of metatarsal bones were measured in sheep fetuses in which thyroid hormone levels were altered by thyroidectomy or adrenalectomy. In intact fetuses, plasma concentrations of total calcium and the degradation products of C-terminal telopeptides of type I collagen increased between 100 and 144 days of gestation (term 145±2 days), in association with various indices of bone growth and development. Thyroid hormone deficiency induced by thyroidectomy at 105-110 days of gestation caused growth retardation of the fetus and significant changes in metatarsal bone structure and strength when analyzed at both 130 and 144 days of gestation. In hypothyroid fetuses, trabecular bone was stronger with thicker, more closely spaced trabeculae, despite lower bone mineral density. Plasma osteocalcin was reduced by fetal thyroidectomy. Removal of the fetal adrenal gland at 115-120 days of gestation, and prevention of the prepartum rises in cortisol and triiodothyronine, had no effect on bodyweight, limb lengths, metatarsal bone structure or strength, or circulating markers of bone metabolism in the fetuses studied near term. This study demonstrates that hypothyroidism in utero has significant effects on the structure and strength of bone, with different consequences for cortical and trabecular bone.

Cluster analysis as a tool to assess litter size in conjunction with the amount of embryonic and fetal losses in pigs

High numbers of live born and vital piglets are required for an effective piglet production. It has been reported that embryonic losses in swine can be as high as 20 to 50%. Generally, up to 30% of embryonic losses are considered within the normal biological range. The aim of our study was first to determine embryonic and fetal losses in sows of the German Landrace breed, and second to identify sows, which are able to realize high numbers of intact embryos and fetuses in combination with low rates of embryonic and fetal losses. This study was conducted on a commercial farrow-finish operation and involved 64 gilts. Gilts were synchronized for ovulation and inseminated artificially (AI) twice at fixed times. Pregnant gilts were slaughtered on Day 30 (n=34) and Day 80 (n=30) after second AI. Corpora lutea (CL) and embryos/fetuses (E/F) were counted. The length of uterine horns was measured. Based on the difference between the number of CL and the number of E/F, embryonic and fetal losses were 36.9 and 37.9%, respectively. The results obtained regarding the number of CL, the number E/F (intact and total), the rate of embryonic or fetal losses and uterine space per E/F underwent a cluster analysis. The results show that several gilts are able to realize high numbers of intact E/F in combination with low rates of losses and limited uterine space per E/F. Numbers of 15 to 20 intact fetuses on day 80 of pregnancy are considered as a minimum for an adequate litter size at the end of pregnancy. In this study only 35% of gilts at Day 30 and 37% of gilts at Day 80 demonstrate this potential. Cluster analysis is a useful mathematical tool which helps to assess results of embryonic and fetal losses and to group gilts according to their performance. As a consequence cluster analysis provides clues which gilts or family structures should be analyzed more intensively.

Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term.

In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose utilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.

Role of thyroid hormones in the developmental control of tissue glycogen in fetal sheep near term

Developmental and glucocorticoid-induced changes in tissue glycogen content occur in the fetus near term coincident with an increase in plasma triiodothyronine (T(3)), although the role of thyroid hormones in mediating these changes is unknown. This study investigated glycogen content in the liver, heart and skeletal muscle of sheep fetuses after experimental manipulation of thyroid hormone concentration in utero by T(3) infusion and fetal thyroidectomy (TX). At 130 days of gestation (term 145 +/- 2 days), hepatic glycogen was greater, and muscle glycogen was lower, in the TX fetuses than in the intact fetuses. However, between 130 and 144 days of gestation the normal increment in hepatic glycogen, and decrement in cardiac glycogen, seen in intact fetuses was abolished when the prepartum rise in T(3), but not cortisol, was prevented by TX. At 144 days of gestation, hepatic glycogen was lower, and cardiac glycogen was higher, in the TX compared with intact fetuses. In intact fetuses at 130 days of gestation, 5 days of intravenous T(3) infusion (8-12 microg kg(-1) day(-1)) caused a small but significant increase in hepatic glycogen, although the concentration achieved was not as great as that observed in intact fetuses infused with cortisol (2-3 mg kg(-1) day(-1)) for 5 days. Infusion of T(3) reduced cardiac glycogen to the level observed in mature fetuses near term and immature fetuses infused with cortisol for 5 days. Glycogen content in fetal skeletal muscle increased between 100 and 115 days of gestation, but was unaffected by cortisol or T(3) infusion. Therefore, thyroid hormones are important in the developmental control of hepatic and cardiac glycogen content in the ovine fetus near term and may mediate, in part, the maturational effects of cortisol.

Inhibiting Effects of Hypervitaminosis A on Development of Fetal Rat Adrenal Glands1)

Administration of pregnant rats with excess amounts of vitamin A from the 8th to the 10th day of pregnancy induced destruction in fetal brain. On the last day of pregnancy, fetuses of treated mothers have smaller weight of adrenal glands as compared with intact fetuses. Maternal treatment with high amounts of vitamin A significantly reduced protein and nucleic acids levels and inhibited cell multiplication in fetal rat adrenal glands. Adrenal glands of fetuses from vitamin A treated mothers synthetized in vitro from 4-14C progesterone less amounts of radioactive 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone and aldosterone than adrenal glands of intact fetuses on the last day of intrauterine development. These results showed that maternal hypervitaminosis A depressed morphological and functional development of fetal rat adrenal glands on the last day of pregnancy.

Hormonal Regulation of Prolactin Cell Development in the Fetal Pituitary Gland of the Mouse

The developmental process of prolactin (PRL) cells in the fetal pituitary gland was studied in mice. Although PRL cells were hardly detectable in the pituitary gland of intact fetuses, a treatment with 17beta-estradiol (E(2)) in vitro induced a number of PRL cells that varied drastically in number depending on the stage of gestation with a peak at embryonic d 15. This effect was specific to E(2), with epidermal growth factor, insulin, and forskolin failing to induce PRL cells. Although both estrogen receptor (ER)alpha and ERbeta were expressed in the fetal pituitary gland, the results from ER knockout models showed that only ERalpha mediates E(2) action on PRL cells. A few PRL cells were observed in ERalpha-deficient mice as well as in their control littermates, suggesting that estrogen is not required for the phenotype determination of PRL cells. Unexpectedly, the effect of E(2) on the induction of PRL cells in vitro was diminished after embryonic d 15. Present results suggest that the exposure of fetal PRL cells to glucocorticoids (GCs) results in a reduction of sensitivity to E(2). The mechanism underlying the down-regulation of estrogen sensitivity by GCs was found not to be down-regulation of ER levels, induction of annexin 1, a GC-inducible inhibitor of PRL secretion, or a decrease in the number of PRL precursors by apoptosis. The effect of GCs appeared within 2 h and did not require a de novo protein synthesis. GCs are considered to be involved in the mechanisms of silencing pituitary PRL in gestation possibly through a novel mechanism.

Effects of Pituitary Hormone Deficiency on Growth and Glucose Metabolism of the Sheep Fetus

Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO(2) production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.

Optimizing Bovine Abortion Diagnostics

Very few aborted bovine fetuses have distinctive pathologic changes that contribute to confirming a diagnosis, with the exception of fetuses with congenital anomalies, thus sending an intact fetus to a diagnostic laboratory for necropsy by a pathologist rarely enhances the prospects for obtaining a positive diagnosis. In fact, it is questionable whether necropsies of aborted fetuses routinely merit the time of a busy veterinary practitioner, when a technician can be trained to collect, package and ship specimens as effectively and more efficiently. In addition, owners, managers, and herdsmen can be recruited into the diagnostic team in herds with on-going abortion problems if proper training and supplies are provided. A protocol for proper specimen collection and packaging for diagnosis of bovine abortions, which can be used by veterinarians or for training technicians, will be presented.

Functional Significance and Cortisol Dependence of the Gross Morphology of Ovine Placentomes During Late Gestation1

The gross morphological appearance of ovine placentomes is known to alter in response to adverse intrauterine conditions that increase fetal cortisol exposure. The direct effects of fetal cortisol on the placentome morphology, however, remain unknown, nor is the functional significance of the different placentome types clear. The present study investigated the gross morphology of ovine placentomes in relation to placental nutrient delivery to sheep fetuses during late gestation and after experimental manipulation of the fetal cortisol concentration. As fetal cortisol levels rose naturally toward term, a significant decrease was observed in the proportion of the D-type placentomes that had the hemophagous zone everted over the bulk of the placentomal tissue. When the prepartum cortisol surge was prevented by fetal adrenalectomy, there were proportionately more everted C- and D-type placentomes and fewer A-type placentomes with the hemophagous zone inverted into the placentome compared with those of intact fetuses at term. Raising cortisol concentrations by infusion before term reduced the incidence of D-type placentomes and lowered the proportion of individually tagged placentomes that became more everted during the 10- to 15-day period between tagging and delivery. Cortisol, therefore, appears to prevent hemophagous zone eversion in ovine placentomes during late gestation. The distribution of placentome types appeared to have no effect on the net rates of placental delivery of glucose and oxygen to the fetus under normal conditions. When fetal cortisol levels were raised by exogenous infusion, however, placental delivery of glucose, but not oxygen, to the fetus, measured as umbilical uptake, was reduced to a greater extent in fetuses with a higher proportion of C- and D-type placentomes. The gross morphology of the ovine placentomes is, therefore, determined, at least in part, by the fetal cortisol concentration and may influence placental nutrient transfer when fetal cortisol concentrations are high during late gestation. These findings have important implications for the placental control of fetal growth and development, particularly during adverse intrauterine conditions.

Circadian Rhythms in Infants

After completing this article, readers should be able to: 1. Describe how circadian rhythms are generated. 2. Describe how lighting influences the circadian system. 3. Delineate the period during which the origin of circadian rhythms develops. 4. Describe the relationship between maternal circadian rhythms and the development of circadian rhythms in infants. 5. Characterize the potential sequelae of impaired fetal and early neonatal circadian rhythms related to sleep patterns. 6. Describe beneficial lighting patterns for preterm infants in the neonatal intensive care nursery. Circadian rhythms are endogenously generated rhythms that have a period length of about 24 hours. Evidence gathered over the past decade indicates that the circadian timing system develops prenatally, with the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, the site of a circadian clock, present by mid-gestation in primates. Recent evidence also shows that the circadian system of primate infants is responsive to light at very early stages (as early as 25 to 28 weeks’ gestation in humans) and that low-intensity lighting can regulate the developing clock. After birth, circadian system outputs mature progressively, with rhythms in sleep-wake cycles, body temperature, and hormone production generally developing between 1 and 3 months of age. The importance of light in regulation of circadian rhythm in infants is highlighted by the early establishment of rest-activity patterns that are in phase with the 24-hour light-dark cycle in preterm infants exposed to low-intensity cycled lighting. With the continued elucidation of circadian system development and influences on human physiology and illness, it is anticipated that consideration of circadian biology will become an increasingly important component of neonatal care. ### The Circadian Timing System Notable examples of circadian rhythms include the sleep-wake cycle and daily rhythms in body temperature and hormone production. Circadian rhythms are also involved in the pathogenesis of illnesses, such as reactive airway disease (eg, asthma) and myocardial infarction. The system responsible …