Prolonged Gestation Research Articles

Using postnatal age to determine test dates leads to misinterpretations when treatments alter gestation length: results from a collaborative behavioral teratology study in Japan.

A collaborative study was conducted by researchers from 18 laboratories that participated in the Behavioral Teratology Meeting in Japan. Pregnant Sprague-Dawley rats from four breeders received subcutaneous injections of nicotine (6 mg/kg body weight) from day 7 to day 20 of gestation. Results of preweaning tests were closely related to length of gestation, and prolonged gestation was seen in the nicotine group. The effects of nicotine were compared with and without the adjustment of the mean difference in gestational lengths. Without the adjustment (i.e., by employing assessment in terms of postnatal day) several perplexing results were obtained, indicating that the nicotine group developed more quickly than the control group on several preweaning tests. By employing the adjustment, these perplexing results disappeared, indicating that the nicotine group developed more slowly than the control group. The merit of employing gestational day (or postcoital age) as an alternative index is emphasized.

Association of sex of fetus, sire, month of conception, or year of foaling with duration of gestation in Standardbred mares

Objective To determine whether sex of fetus, sire, month of conception, or year of foaling was associated with duration of gestation in mares. Design Epidemiologic retrospective cohort study. Animals 500 foalings for 296 Standardbred mares. Procedure Data for reproductive events from 1986 to 1992 were analyzed. Analyses were conducted to determine whether duration of gestation was associated with sex of fetus, sire, month of conception, or year of foaling. Results Mean duration of gestation was 343.3 days and was significantly greater for colt fetuses (344.4 days) than for filly fetuses (342.2 days). Sire was associated with duration of gestation; gestation after mating with certain sires was consistently less than 340 days in duration, whereas duration after mating with other sires was consistently more than 350 days. Duration of gestation was associated with month of conception, decreasing by about 2.5 d/mo for mares conceiving later during the breeding season. Clinical Implications Duration of gestation is affected by mating to specific sires and by month of conception. Stallions associated with exceptionally prolonged gestations might be used to breed mares early in the breeding season, whereas stallions associated with shorter gestations might be desirable for mares bred later in the breeding season. Preparations for impending parturition should be more effective and efficient with improved information on expected date of parturition. (J Am Vet Med Assoc 1998;212: 1743–1745)

Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality.

To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality. Retrospective analysis of 171,527 notified births (1989-1991) and subsequent infant survival at one year, from community child health records. Notifications from maternity units in the North East Thames Region, London. The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated. The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 151.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation. The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.

Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options?

The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean fever. Azathioprine can be used when the maternal condition requires a cytotoxic drug during the first trimester. Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.

Management of Nonobstetric Pain During Pregnancy and Lactation

Management of Nonobstetric Pain During Pregnancy and Lactation

Management of nonobstetric pain during pregnancy and lactation.

Management of nonobstetric pain during pregnancy and lactation.

Fetal growth, length of gestation, and polycystic ovaries in adult life

Polycystic ovaries are a common disorder associated with menstrual irregularities, subfertility, hirsutism, acne, and a range of endocrine abnormalities, including high concentrations of plasma luteinising hormone (LH) and excessive androgen production. The pathophysiology is not understood. We investigated whether the disorder originates during intrauterine life. We examined 235 women aged 40-42 years who were born in Sheffield, UK. We related the prevalence of polycystic ovaries and the plasma concentrations of gonadotropin hormones and androgens to the women's body size at birth, and the length of gestation. 49 (21%) of the women had polycystic ovaries. We defined two groups of women with the disorder, which correspond to the two groups that commonly present clinically. The first group comprised obese women who were androgenised, with higher than normal concentrations of plasma LH and testosterone. These women had above-average birthweight and were born to overweight mothers. The second group comprised women of normal weight who had high plasma LH, but normal testosterone concentrations. These women were born after term (40 weeks' gestation). The two common forms of polycystic ovary syndrome have different origins in intrauterine life. Obese, hirsute women with polycystic ovaries have higher than normal ovarian secretion of androgens that are associated with high birthweight and maternal obesity. Thin women with polycystic ovaries have altered hypothalamic control of LH release resulting from prolonged gestation.

Epipubic bones in eutherian mammals from the late Cretaceous of Mongolia.

An important transformation in the evolution of mammals was the loss of the epipubic bones. These are elements projecting anteriorly from the pelvic girdle into the abdominal region in a variety of Mesozoic mammals, related tritylodonts, marsupials and monotremes but not in living eutherian (placental) mammals. Here we describe a new eutherian from the Late Cretaceous period of Mongolia, and report the first record of epipubic bones in two distinct eutherian lineages. The presence of epipubic bones and other primitive features suggests that these groups occupy a basal position in the Eutheria. It has been argued that the epipubic bones support the pouch in living mammals, but epipubic bones have since been related to locomotion and suspension of the litter mass of several attached, lactating offspring. The loss of the epipubic bones in eutherians can be related to the evolution of prolonged gestation, which would not require prolonged external attachment of altricial young. Thus the occurrence of epipubic bones in two Cretaceous eutherians suggests that the dramatic modifications connected with typical placental reproduction may have been later events in the evolution of the Eutheria.

Failure of luteolysis leads to prolonged gestation in a bitch: A case report

A healthy, 5-yr-old rough collie bitch exhibited prolonged gestation, characterized by intrauterine fetal death and plasma progesterone concentrations (PPC) above 6 nmol/L/d until Day 65 or 66 of cytologic diestrus, which then only dropped following treatment with dinoprost tromethamine. The bitch showed no signs of parturition prior to laparotomy and hysterotomy on Day 63, which revealed 5 corpora lutea (CL) on the left ovary and 1 on the right ovary; 5 full-term, dead conceptuses without obvious autolysis but with 4 of the 5 placentas detached; and a tightly closed cervix. All conceptuses were in the left uterine horn. Treatment with dinoprost tromethamine was initiated 1 d after hysterotomy and was continued for IO d (120 μg/kg twice daily for a total dose of 240 μg kg/d). The discharge of lochia through the cervix and lactation started 3 d after the onset of treatment. Plasma progesterone concentration was 14.4, 16.2 and 1.6 nmol/L/d on the day of hysterotomy and at 1 and 3 d after the onset of prostaglandin therapy, respectively. The reason for the failure of luteolysis to occur is not known.

Birth Trauma

OBJECTIVE : To determine the current incidence of clavicular fracture (CF), facial nerve injury (FNI) and brachial plexus injury (BPI) and identify the existence, if any, of associated perinatal factors with each injury. STUDY DESIGN : A case-controlled study design was selected and the study conducted for births between January 1, 1985 and January 1, 1990, at Christ Hospital and Medical Center, a tertiary care center with level III perinatal services in suburban Chicago. Among a population of 19,370 consecutive deliveries, we identified the occurrences of CF, FNI and BPI by database search, and maternal and neonatal chart reviews. A control group was randomly selected. Maternal, labor, delivery and neonatal variables were then compared between the birth trauma and control groups for each specific injury. RESULTS : The incidence per 1,000 live births and per 1,000 live-born cephalic singletons delivered vaginally for CF was 4.5 and 5.7 ; for FNI, 0.6 and 0.7 ; and for BPI, 0.9 and 1.1, respectively. To varying degrees, the data demonstrate that the occurrences of these injuries are associated significantly more often with prolonged gestation, epidural anesthesia, prolonged second stage of labor, oxytocin use, forceps delivery, shoulder dystocia, macrosomia, low Apgar scores and a previous maternal obstetric history of macrosomia when compared to controls. Other significantly associated variables include the presence of meconium in labor and neonatal hyperbilirubinemia. Despite the presence of multiple perinatal factors that are individually associated statistically with the injured groups, multiple logistic regression analysis predicted 44.2% of CF's, none of the FNIs and only 19% of the BPIs. CONCLUSION : While multiple perinatal variables are statistically associated with the specific birth injuries studied, the use of multiple logistic regression analysis shows that the ability to predict these injuries is markedly limited.

Multicenter randomized clinical trial of home uterine activity monitoring: Pregnancy outcomes for all women randomized

OBJECTIVE: Our purpose was to evaluate the impact of home uterine activity monitoring on pregnancy outcomes among women at high risk for preterm labor and delivery. STUDY DESIGN: Women at high risk for preterm labor at three centers were randomly assigned to receive high-risk prenatal care alone (not monitored) or to receive the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). There were 339 women with singleton gestations randomized with caregivers blinded to group assignment. The two groups were medically and demographically similar at entry into the study. RESULTS: Women in the monitored group had prolonged pregnancy survival ( p = 0.02) and were less likely to experience a preterm delivery (relative risk 0.59; p = 0.04). Infants born to monitored women with singleton gestations were less likely to be of low birth weight (<2500 gm; relative risk 0.47, p = 0.003), and were less likely to be admitted to a neonatal intensive care unit (relative risk 0.5, p = 0.01). CONCLUSION: These data show, among women with singleton gestations at high risk for preterm delivery, that the use of home uterine activity monitoring alone, without additional intensive nursing care, results in improved pregnancy outcomes, including prolonged gestation, decreased risk for preterm delivery, larger-birth-weight infants, and a decreased need for neonatal intensive care. (Am J Obstet Gynecol 1996;175:1281-5.)

Ovarian and testicular function in the domestic cat: clinical management of spontaneous reproductive disease

Abstract Vaginal cornification and/or serum progesterone concentration may be used as indicators of follicular and luteal function in the cat in diagnosis of estrus, induced or spontaneous ovulation, ovarian remnant syndrome, and prolonged gestation. Feline sperm may be collected by electroejaculation, ejaculation into an artificial vagina, cystocentesis of the male following ejaculation or by vaginal wash of the bred female. Normal feline seminal plasma contains high concentrations of alkaline phosphatase, and may contain more than 10 000 colony forming units (CFU) ml−1 bacteria, most of which are normal preputial flora. Serum testosterone concentration, often undetectable (less than 0.02 ng ml−1) in the normal male, increases 1 h after gonadotropin-releasing hormone (GnRH) or 4 h after human chorionic gonadotropin (hCG) administration in the tom. Presence of penile spines is an indicator of testicular tissue or testosterone administration. Gonadectomy performed at 7 weeks or 7 months of age in male and female cats is associated with increased length of long bones due to delayed physeal closure, decreased heat production, and increased risk of obesity, and not with decrease in urethral diameter. Normal penile extrusion was not possible in 6 6 male cats neutered at 7 weeks of age or 2 5 male cats neutered at 7 months of age, owing to persistence of the balanopreputial fold, which normally undergoes dissolution under the influence of androgens.

Zinc deficiency in women, infants and children.

Zinc deficiency in humans is widespread and is more prevalent in areas where the population subsists on cereal proteins. Conditioned deficiency of zinc is seen in many diseased states. A mild deficiency of zinc in pregnancy is associated with increased maternal morbidity, abnormal taste sensation, prolonged gestation, inefficient labor, atonic bleeding, and increased risks to the fetus. Among the urban poor in the US, a marginal zinc intake during pregnancy was associated with increased risk of preterm and very preterm delivery. Factors responsible for zinc deficiency in premature infants include high fecal losses of zinc, low body stores of zinc at birth, and increased zinc requirement during rapid growth. Zinc supplemented infants demonstrated improved linear growth velocity and maximum motor development scores. Marginal and moderate growth impairment in children as a consequence of inadequate zinc intake has been reported from many developed and developing countries. In one study from Japan, 21 prepubertal children were diagnosed to have zinc deficiency. The caloric intake, growth velocity, serum zinc, and plasma insulin-like growth factor-1 increased significantly in the zinc supplemented group. The clinical manifestations of zinc deficiency include growth retardation, hypogonadism in males, neurosensory disorders, cell-mediated immunological dysfunctions, and skin changes. Approximately 300 enzymes are known to require zinc for their activities. Zinc is required for DNA synthesis, cell division and protein synthesis. Several hundreds of zinc containing nucleoproteins are probably involved in gene expression of various proteins. A deficiency of zinc also affects proliferation and maturity of lymphocytes adversely.

Maternal reproductive effects of oral salicylic acid in Sprague-Dawley rats

Clinical and experimental evidence indicates that exposure to relatively large doses of acetylsalicylic acid (ASA) prolongs parturition. However, little is known about the dose-response relationship for salicylate-related effects on labor and gestation. As well, the relative potency of salicylic acid (SA) as compared with ASA for these reproductive effects has not been well investigated. This study was designed to define a dose-response relationship for salicylic acid (SA) effects on labor and gestation times in Sprague-Dawley rats. Pregnant females received oral doses of 20, 80, or 200 mg/kg/day sodium salicylate, or 260 mg/kg/day acetylsalicylic acid (ASA), as a positive control, on days 15 through 21 of gestation (sperm positive = day 0). Onset of labor was followed in each animal beginning on day 21 of gestation. The data failed to demonstrate a substantial potency difference between ASA and SA but some differences in toxicity were observed. Relative to controls, gestation times were unaffected by SA. SA treatment resulted in a dose-related trend towards increased duration of labor which was statistically significant at 200 mg/kg/day of SA. ASA treatment of pregnant females resulted in both prolonged labor and gestation times. Both the highest administered dose of SA and ASA treatment contributed to increased maternal peripartum death. Overall, the study confirms a dose-response relationship for SA-induced maternal reproductive effects and supports a no observable effect level (NOEL) for this compound of 80 mg/kg/day for adverse effects on parturition.

EPPIC: an evolving system of early detection and optimal management.

Early intervention at the onset of psychotic disorders is a highly attractive theoretical notion that is receiving increasing international interest. In practical terms, it amounts to first deciding when a psychotic disorder can be said to have commenced and then offering potentially effective treatment at the earliest possible point. A second element involves ensuring that this intervention constitutes best practice for this phase of illness and is not merely the translation of standard treatments developed for later stages and the more persistently ill subgroups of the disorder. Furthermore, it means ensuring that this best practice model is actually delivered to patients and families. The relative importance of these elements in relation to outcome has not yet been established. This article outlines a framework for preventive intervention in early psychosis, based on more than a decade of experience initially gained within a first-generation model. This experience has been followed, after a prolonged gestation, by the birth of the Early Psychosis Prevention and Intervention Centre (EPPIC), a comprehensive "real-world" model of care targeting the multiple clinical foci underpinning the preventive task. Data are reported to illustrate the topography and impact of delay in treatment in our regional setting, and the results of an initial evaluation of the EPPIC model are presented. The latter demonstrate a significant improvement in symptomatic and functional outcome when the second-generation model is contrasted with the first. The implications of these findings and future developments are discussed.

牛の分娩予定日超過例におけるジノプロストの分娩誘起およびミイラ変性胎子排出効果

牛の分娩予定日超過例におけるジノプロストの分娩誘起およびミイラ変性胎子排出効果

Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe pre-eclampsia remote from term

Objective: To assess maternal and perinatal outcomes of expectant management with plasma volume expansion and pharmacologic vasodilatation in patients with severe pre-eclampsia remote from term. Study design/it: All women with severe pre-eclampsia between 20 and 32 weeks' gestation, not in labor and with a live, single fetus admitted to the University Hospital Rotterdam from 1985 to 1993 were managed with the intention to prolong gestation. Treatment consisted of correction of the maternal circulation with vasodilatation by means of dihydralazine and plasma volume expansion under central hemodynamic monitoring. Primary end-points of the study were prolongation of gestation, maternal antepartum and postpartum complications, and fetal and neonatal outcome. Results: Two-hundred fifty-four patients were included. The median prolongation of pregnancy was 14 (range 0–62) days. Hemodynamic treatment was associated with marked objective and subjective improvement in maternal condition. Complications of central hemodynamic monitoring were not observed. Perinatal mortality was 20.5%. Conclusion: Expectant management with plasma volume expansion and pharmacologic vasodilatation under central hemodynamic monitoring of the maternal circulation may delay delivery and enhance fetal maturity and does not appear to be associated with an increased risk of maternal morbidity and mortality.

Parturition in the Rabbit is Compromised by Daytime Nursing: The Role of Oxytocin1

Rabbits nurse briefly only once each night and are frequently both pregnant and lactating. To investigate the influence of the daily timing of nursing on parturition, does (n = 10 per group) were remated after giving birth and were allowed to nurse under one of three schedules: group 1 every 24 h in the light, group 2 every 24 h in the dark, and group 3 at any time. Whereas does from groups 2 and 3 nursed and gave birth normally, does of group 1, forced to nurse out of phase with the normal schedule, showed disturbed nursing behavior and prolonged gestation followed by many stillbirths. In a second experiment, pregnant does (n = 10 per group) were treated daily either with oxytocin (OT) in the light (group 4), with OT in the dark (group 5), or with progesterone (P; group 6) or saline (group 7) in the light. All does gave birth normally except those of group 4, which responded similarly to group 1 does. These findings demonstrate that in the rabbit, parturition may be seriously compromised if does nurse out of phase with the normal schedule and suggest that a shift in the daily timing of OT release may underlie this.

A randomized, prospective study of adjunctive ceftizoxime in preterm labor

OBJECTIVE: Our purpose was to determine the effect of ceftizoxime in the prolongation of pregnancies receiving tocolysis for preterm labor. STUDY DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients with preterm labor between 24 and 35 weeks' gestation. A total of 545 patients with intact membranes and without chorioamnionitis who were receiving magnesium sulfate were screened. Exclusions were for advanced cervical dilatation, penicillin allergy, current antibiotic therapy, and failure to give informed consent. Of these, 117 consecutive, eligible, consenting patients were randomized to receive either 2 gm of ceftizoxime or a placebo every 8 hours. The primary end point was prolongation of gestation. Statistical comparisons were performed by use of unpaired two-tailed t test and χ 2 analysis. RESULTS: Of the 58 ceftizoxime and 59 placebo patients, there was no difference in the interval to delivery (34.5 ± 21.1 days vs 34.6 ± 24.5 days, p = 0.99) and no difference in the rate of delivery before 37 weeks' gestation (60% in the ceftizoxime group vs 58% in the placebo group, p = 0.91). Subanalyses of 61 subjects who received nine or more doses and who were group B streptococci negative, 69 patients at ≤32 weeks on presentation, and 22 sets of twins all showed no differences in delivery interval or rate of delivery at <37 weeks. The sample size of this study was sufficient to detect a 9-day difference in prolongation of pregnancy (α = 0.05, β = 0.2). CONCLUSIONS: Ceftizoxime had no effect on interval to delivery or duration of pregnancy in women treated for preterm labor.

Clinical and Morphologic Findings of Familial Goiter in Bongo Antelope (Tragelaphus eurycerus)

Inherited defects of thyroglobulin synthesis resulting in congenital goiter are well described in certain breeds of domestic ungulates and in human beings. Goiter associated with synthesis of an abnormal thyroglobulin and the presence of thyroidal albumin was identified in five closely related bongo antelopes (Tragelaphus eurycerus). The goiter had an adult onset, and the affected bongos appeared to remain euthyroid with normal serum T3 and T4 values, normal serum cholesterol concentrations, and nonelevated concentrations of circulating thyroid stimulating hormone (TSH). Goitrous bongos had significant reproductive difficulties, including reduced cyclic activity and prolonged gestations, but were otherwise normal. Over the course of the disease, the thyroid glands greatly enlarged (up to 10 x 20 cm) and became polycystic. Microscopically, there was an admixture of giant colloid-filled follicles and follicles of normal size lined with variable follicular epithelium ranging from squamoid to mildly to moderately hyperplastic. The pathogenesis of goiter in the bongo may reflect a mixture of genetic predisposition coupled with environmental factors, including a period of exposure to a goitrogen.