Risk of premature birth in multifetal pregnancy.

The risk of preterm delivery (< 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6,036,475 infants born in singleton pregnancies and 90,887 infants born in multifetal pregnancies in Japan (> or =22 weeks) over the 5-year period 1989-1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4-6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1-14.2) but declining thereafter to 8.8 (95% CI, 8.6-8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially.     

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

Background

Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage. Uterine natural killer (uNK) cells, the most predominant leucocyte in the endometrium are adjacent to foetal trophoblast cells and thought to be involved in implantation. The exact mechanisms of how uNK cells affect implantation are not clear but are probably through the regulation of angiogenesis. Multiple studies have shown an association between high density of uterine natural killer cells and recurrent miscarriage. We have shown that prednisolone reduces the number of uNK cells in the endometrium. The question remains as to whether reducing the number of uNK cells improves pregnancy outcome.

Methods

We propose a randomised, double-blind, placebo controlled trial of prednisolone with a pilot phase to assess feasibility of recruitment, integrity of trial procedures, and to generate data to base future power calculations. The primary aim is to investigate whether prednisolone therapy during the first trimester of pregnancy is able to improve live birth rates in patients with idiopathic recurrent miscarriage and raised uNK cells in the endometrium. Secondary outcomes include conception rate, karyotype of miscarriage, miscarriages (first and second trimester), stillbirths, pregnancy complications, gestational age at delivery, congenital abnormality and side effects of steroids. The trial has 2 stages: i) screening of non-pregnant women and ii) randomisation of the pregnant cohort. All patients who fit the inclusion criteria (<40 years old, ≥3 consecutive miscarriages with no cause found and no contraindications to prednisolone therapy) will be asked to consent to an endometrial biopsy in the mid-luteal phase to assess their levels of uNK cells. Women with high levels of uNK cells (≥5%), will be randomised to either prednisolone or placebo when a pregnancy is confirmed. Follow-up includes 2 weekly ultrasound scans in the first trimester, an anomaly scan at 20 weeks gestation, growth scans at 28 and 34 weeks gestation and a postnatal follow-up at 6 weeks.

Trial Registration

Current Controlled Trials ISRCTN28090716     

Pregnancy wastage and age of mother among the Amish

Reports of approximately 7500 pregnancies in reproductive histories collected by Colette Wiffler through personal interviews with Old Order Amish families of Illinois, Iowa, Missouri, and Wisconsin during the 1968 through 1973 period were analyzed to test a prediction: a society in which healthy women generally want large numbers of children and do not marry unusually uoung should exhibit a slower rate of increase in fetal death ratios with age of mother than the general US population. In this study, fetal deaths occurring after 7 months of gestation were called stillbirths; those occurring between 6 weeks and 7 months were termed miscarriages. Neonatal deaths occurred within the 1st week following live birth. All loss ratios were calculated as the number of the specified type of pregnancy loss/1000 pregnancies which lasted at least 7 months. The minimum miscarriage and stillbirth ratios each occurred in the early 30s, but the ratios were not statistically different from those for mothers in their early 20s. The interpretation of the observation is complicated by substantial reductions in pregnancy wastage experienced by the general population over the long span of time (1898 through 1972) covered by the present data. For the US both late fetal death ratios and neonatal death rates specific for the age of the mother reach their minimum in the early 20s. While most available data provide information about late fetal death only, the study of pregnancies in New York's Health Insurance Plan revealed markedly higher fetal death ratios for mothers in the early 30s than for mothers in their 20s both for gestations of 12-19 weeks and for those of less than 12 weeks. Thus, the Amish fetal deaths differ from the general US pattern similarly for miscarriages and for the less numerous stillbirths. These results are compatible with the prediction under test but conflict with the expectations of the traditional idea that women in their early 20s have their ability to carry pregnancies to live birth impaired by age. The findings suggest that any increase in risk of fetal death caused by increasing age of an individual mother must be unimportant before age 35. It appears that women who decide to postpone their pregnancies until their late 20s or early 30s are probably not materially increasing the risk of fetal death. The same appears to be the case for early infant mortality.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days.Main outcome measures Pregnancy outcomes up to 20 weeks of gestation.Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use.Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.     

The relationship between sperm DNA fragmentation,free radicals and antioxidant capacity with idiopathic repeated pregnancy loss

More than two consecutive miscarriages in less than 20 weeks of gestation is defined as recurrent spontaneous miscarriage. Various causes such as uterine anatomical anomalies, genetic factors, and infectious and endocrine disorders have been reported for RPL. However, approximately 50% of the causes are unknown, which can be due to male factors. Several studies have been done on semen parameters to determine the unknown causes and risk factors for miscarriages, however, only studying common semen parameters have not been sufficient. In this study, the relationship between sperm DNA fragmentation, the amount of free radicals, and total antioxidant capacity (TAC) in semen have been considered as a risk factor for spontaneous miscarriage. Semen samples were collected from 42 men whose partners had a history of spontaneous miscarriage and 42 fertile men as the control group. Volume, pH, viscosity, concentration, and motility of semen, as well as sperm morphology were measured. Sperm DNA fragmentation was analyzed by the sperm chromatin structure assay (SCSA) and TUNEL methods, the amount of sperm free radicals was measured by the luminescence method and the total amount of semen antioxidant was measured using the TAC kit. The results have shown that sperm motility in the experimental group was significantly less than the control group (P?=?0.001). The percentage of sperm DNA fragmentation and the amount of free radicals in the experimental group were significantly higher than the control group (P?<?0.001). The total amount of antioxidant was lower in the experimental group compared to the control. Spouses of men with lower sperm motility and higher DNA fragmentation had a higher chance of spontaneous miscarriage when compared to the control group. The results of this study support the hypothesis that sperm DNA fragmentation is a major contributor to spontaneous miscarriage.The relationship between SDF, ROS and TAC with RPL.     

Population dynamics of Trichostrongylus colubriformis in sheep: the effect of infection rate on the establishment of infective larvae and parasite fecundity

The establishment of Trichostrongylus colubriformis was estimated in helminthologically naive 20-week-old Merino sheep given third stage infective larvae (L3) at rates of 2000, 632 or 200 L3 per day, 5 days per week. After varying periods of continuous L3 intake, a levamisole-susceptible strain of T. colubriformis was replaced with a highly resistant strain for 1 week. The animals were then treated with levamisole to remove the susceptible population, and establishment of the cohort of resistant worms was estimated. In previously uninfected sheep, approximately 65% of the L3 given in the first week became established as adults. This fell to low levels (less than 5%) after 7, 10 and 14 weeks of continuous L3 intake for the high, medium and low infection rates, respectively. At the low infection rate, establishment remained at maximum levels for the first 4 weeks, but then fell at a rate similar to that observed for the higher infection rates. This implied that a threshold of worm exposure was required before resistance to establishment developed. Parasite egg production, expressed as eggs per gram of faeces, was proportional to infection rate and is explained by higher worm burdens occurring at high infection rates. However, estimates of fecundity in eggs per female per day showed the opposite relationship with rate of infection. Fecundity stayed high (approximately 600) for 5 weeks at the low infection rate but only maintained this level for 3 weeks and 1 week at the medium and high rates, respectively. This suggests that fecundity, like establishment, was similarly affected at threshold levels of immunological recognition.     

孕妇维生素D缺乏与妊娠期糖尿病的相关性分析

目的:调查孕妇妊娠早期维生素D水平及其影响因素,探讨维生素D缺乏与妊娠期糖尿病的相关性。方法:选取2012年7月至2013年4月在上海交通大学医学院附属新华医院产科正规产检并分娩的非孕前糖尿病孕妇,在其建卡初检时采用电化学发光免疫技术测定血清25(OH)D3水平;妊娠24-28周行糖筛查及糖耐量试验,诊断是否为妊娠期糖尿病GDM。收集并整理孕妇年龄,孕前体重指数BMI、维生素D测定孕周与测定季节、孕期维生素D补充情况等信息。结果:1000例孕妇中,GDM发病率为11.5%,维生素D缺乏比例占67.4%;其中,约有54%孕妇常规补充复合维生素,约含维生素400 IU/天,10%孕妇常规补充维生素D。GDM孕妇25(OH)D3水平显著低于正常对照组(P=0.007)。维生素D缺乏孕妇发生GDM的风险是维生素D水平较高组的1.944倍,且在秋冬季更易发生GDM。可以考虑在孕14-16周进行维生素D水平的早期测定。结论:孕妇维生素D缺乏十分普遍。妊娠早期孕妇低维生素D水平可能增加孕妇胰岛素抵抗及孕期发生GDM的发生风险。     

Dengue infection and miscarriage: a prospective case control study

Background

Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of dengue to miscarriage is not known.

Method

We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented with miscarriage (up to 22 weeks gestation) to our hospital were approached to participate in the study. For each case of miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was stored. Stored sera were thawed and then tested in batches with dengue specific IgM capture ELISA, dengue non-structural protein 1 (NS1) antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early pregnancy) plus 45 controls (39 lost to follow up and six subsequent late miscarriages) were excluded from analysis.

Findings

Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection) was positive in 6/115 (5·2%) cases and 5/296 (1·7%) controls RR 3·1 (95% CI 1·0–10) P = 0·047. Maternal age, gestational age, parity and ethnicity were dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remained significantly more frequently detected in cases than controls (AOR 4·2 95% CI 1·2–14 P = 0·023).

Interpretation

Recent dengue infections were more frequently detected in women presenting with miscarriage than in controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.     

Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)

OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies). DESIGN: Randomised controlled trial. SETTING: Specialist clinic for recurrent miscarriages. SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies. INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks'' gestation. MAIN OUTCOME MEASURES: Rate of live births with the two treatments. RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks'' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks'' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%). CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.     

孕14-19+6周正常胎儿胼周动脉的超声评估

摘要 目的：探讨应用超声SlowflowHD（超低速血流成像）联合RadiantFlow（二维立体血流成像）技术评估孕14-19⁺⁶周正常胎儿胼周动脉的可行性，观察胎儿胼周动脉及分支走行，测量其长度和高度，并探讨二者与孕周及双顶径的关系。方法：纳入2022年5月-2023年3月来南京医科大学附属苏州医院进行常规超声检查的150例孕14-19⁺⁶周孕妇，在胎儿正中矢状切面上获取胎儿胼周动脉及分支的图像，测量其长度和高度，测量重复3次，取平均值，并观察胎儿胼周动脉及分支走行。所有孕妇均随访至中孕晚期（20-28周）或晚孕期行产前超声检查未见胼胝体异常及其他颅内结构异常。采用pearson相关分析和回归分析判断胎儿胼周动脉长度及高度与孕周及双顶径的关系。结果：胎儿胼周动脉长度及高度随着孕周及双顶径的增加而增加（P＜0.05）。胎儿胼周动脉长度与孕周、双顶径之间呈线性正相关，且胎儿胼周动高度与孕周、双顶径之间呈线性正相关（P＜0.05）。在孕14-19⁺⁶周中所有111病例均类"C"形走行，额前内侧动脉、额中内侧动脉、额后内侧动脉三者几乎与胎儿胼周动脉垂直，类"鸡冠"，三者显示率100%；旁中央动脉在孕14-15⁺⁶周、16-17⁺⁶周、18-19⁺⁶周显示率分别约53.1%（17/32）、88.2%（45/51）、92.8%（26/28）；楔前动脉在孕14-15⁺⁶周、16-17⁺⁶周、18-19⁺⁶周显示率分别约3.1%（1/32）、35.2%（18/51）、78.5%（22/28）。结论：应用超声SlowflowHD（超低速血流成像）联合RadiantFlow（二维立体血流成像）技术显示孕14-19⁺⁶周正常胎儿胼周动脉及分支具有可行性，胎儿胼周动脉长度和高度与孕周及双顶径呈一定的线性相关。     

Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses. Design: Population based cohort study. Subjects: 1 026 249 pregnancies without congenital malformations. Setting: Sweden 1983-92. Main outcome measure: Late fetal death rate. Results: Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women ⩾175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers.Conclusions: Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants—for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension.

Key messages

• Small for gestational age fetuses are at increased risk of late fetal death regardless of the underlying determinants
• The effect of birthweight ratio on risk of late fetal death is modified by underlying determinants, except maternal age
• Regardless of birthweight ratio the rates of late fetal death are higher among women aged 35 years or older compared with younger women
• In pregnancies of extremely small for gestational age fetuses lower rates of late fetal death are associated with a maternal age of less than 35 years, short maternal stature, multiple births, and hypertensive disorders
• In pregnancies with non-malformed fetuses late fetal death rates are increased in smokers, in multiple births, and in women with severe pre-eclampsia.

     

Endpiece: The noble profession

ObjectivesTo assess whether bacterial vaginosis or chlamydial infection before 10 weeks'' gestation is associated with miscarriage before 16 weeks.DesignProspective cohort study.Setting32 general practices and five family planning clinics in south London.Participants1216 pregnant women, mean age 31, presenting before 10 weeks'' gestation.Results121 of 1214 women (10.0%, 95% confidence interval 8.3% to 11.7%) miscarried before 16 weeks. 174 of 1201 women (14.5%, 12.5% to 16.5%) had bacterial vaginosis. Compared with women who were negative for bacterial vaginosis those who were positive had a relative risk of miscarriage before 16 weeks'' gestation of 1.2 (0.7 to 1.9). Bacterial vaginosis was, however, associated with miscarriage in the second trimester at 13-15 weeks (3.5, 1.2 to 10.3). Only 29 women (2.4%, 1.5% to 3.3%) had chlamydial infection, of whom one miscarried (0.32, 0.04 to 2.30).ConclusionBacterial vaginosis is not strongly predictive of early miscarriage but may be a predictor after 13 weeks'' gestation. The prevalence of Chlamydia was too low to assess the risk, but it is unlikely to be a major risk factor in pregnant women.

What is already known on this topic

Miscarriages are common and associated with considerable morbidity and costsBacterial vaginosis is associated with miscarriage after 16 weeks'' gestation and preterm birth but the role of chlamydial infection is uncertain

What this study adds

Bacterial vaginosis is not a strong predictor of miscarriage before 16 weeks'' gestation but may be associated with miscarriage at 13-15 weeks'' gestationThe prevalence of chlamydial infection was too low for it to be a major risk factor for miscarriage in this population of healthy pregnant womenNon-invasive screening for bacterial vaginosis and chlamydial infection by using self administered vaginal swabs is feasible in pregnant women in the community     

Trends in triplet stillbirth rates in Japan, 1975-1998.

Stillbirth rates of triplet births in the whole of Japan were analyzed using vital statistics from 1975 to 1998. Stillbirths were registered at 12 weeks gestation or later. The stillbirth rate was significantly higher in like- than in unlike-sex triplets for 1975-1998. During the 23-year period the stillbirth rate decreased from 342 to 49 per 1000 total births for like-sex and from 195 to 54 for unlike-sex triplets. The decrease in the stillbirth rate in the 23- year period was greater in both like- and unlike-sex triplets than in singleton and twin births. Risk factors for stillbirth in triplets were like-sex, youngest or oldest maternal age groups, shorter gestational age and lower birthweight. It is recommended that the optimum period to give birth for triplet pregnancies is 34-35 weeks of gestation for Japanese women.     

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy

Background

Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.

Methods

Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.

Results

Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.

Conclusions

Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.     

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.     

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.     

Functional abilities at age 4 years of children born before 29 weeks of gestation.

OBJECTIVES--To assess the rate of impairment and disability among babies born very preterm and to investigate the association between such impairment and gestational age at birth. DESIGN--Cohort study of a geographically defined population of babies. SETTING--Oxford Regional Health Authority. SUBJECTS--All babies born alive before 29 weeks of gestation to mothers resident in the region during 1984-6. MAIN OUTCOME MEASURES--Survival rates and rates of impairment and disability among survivors at the age of 4 years. RESULTS--Of the 342 babies, half (170) survived to be discharged home. Of the 164 survivors to age 4 years, 153 (93%) were assessed. A total of 35 (23%; 95% confidence interval 16% to 30%) were severely disabled and only 54 (35%; 28% to 43%) were unimpaired. The risk of impairment and disability increased with decreasing gestational age at birth (p < 0.003). CONCLUSIONS--With the increasing survival rate among babies born before 29 weeks of gestation, we need urgently to establish reliable ways of monitoring the proportion of survivors who have a disability.     

The Relationship Between Maternal Serum Iron and Zinc Levels and Their Nutritional Intakes in Early Pregnancy with Gestational Diabetes

The aim of this study was to investigate the association between maternal iron/zinc serum levels and their nutritional intake in early pregnancy with gestational diabetes. The maternal serum zinc/iron levels were measured in 1,033 healthy singleton pregnant women aged 20–35 between 14 and 20 weeks of gestation, within two groups: namely, normal and gestational diabetes, and participants were followed up to 24–28 weeks of gestation. Food frequency questionnaire was used to assess nutritional intakes of iron/zinc. The main outcome was gestational diabetes screened with the 50-g glucose challenge test and diagnosed with oral glucose tolerance test at 24–28 weeks of gestation. Gestational diabetes occurred in 72 (6.96 %) of 1,033 women in study. There was a statistical relationship between early pregnancy maternal serum iron and gestational diabetes, mean (SD), 143.8 (48.7) vs. 112.5 (83.5)?μg/dl, P value of <0.0001. There was no statistical significant difference in zinc levels and iron/zinc nutritional intake between groups. The results remained unchanged after using regression model for adjustment of potential risk factors with an adjusted OR of 1.006 (95 % CI 1.002 to 1.009; P?=?0.001) for early pregnancy maternal serum iron to cause gestational diabetes. The receiver–operator characteristic curve identified that a maternal serum iron above 100 μg/dl in early pregnancy is the optimum cutoff value for predicting gestational diabetes, which showed a sensitivity and specificity of 80.6 and 50.7 %, respectively. In conclusion, high maternal serum iron in early pregnancy could increase the risk of gestational diabetes. Also, it could be used as a sensitive and specific predictor for gestational diabetes.     

Distribution of Neuropeptide Y-Immunoreactive Neurons in the Human Brainstem, Cerebellum, and Cortex During Development

1. Neuropeptide Y is found throughout the central nervous system where it appears to play a wide range of often poorly understood functions. In this study, the distribution of neuropeptide Y immunoreactive (NPY-ir) neurons in the brainstem, cerebellum, and cerebral cortex of human fetuses ranging in age from 11 gestational weeks to term was investigated by immunohistochemistry. 2. The NPY-ir cells were detected in the dorsal and ventral rostral midbrain and the interpeduncular nucleus by 21 weeks and 32 weeks of gestation, respectively. Although no positive cells were found in the pons, the NPY-ir fibers were detected there at 32 gestational weeks. 3. The vagal, hypoglossal, and olivary nuclei of the medulla oblongata contained immunoreactive cells by week 21 and the medullary reticular formation by week 25 of gestation. In most of these locations, both the number and size of neuropeptide Y positive cells were greater at birth and reached maximal values of 100-400 cells per 1 mm2 and 2-5 microm in diameter, respectively. 4. In the cerebellum, numerous NPY-ir horizontal and granule cells, as well as the cells within the dentate nucleus were observed as early as 21 weeks of gestation. 5. The NPY-ir cells were also detected in the developing cerebral cortex, with the earliest activity observed within the temporal cortex at 14 weeks of gestation. By week 21, positive cells appeared in the visual, frontal, sensory, and motor cortices. Most of these cells were bipolar or multipolar in morphology but their numbers at birth were relatively low. 6. Our results show a wide distribution of the NPY-ir cells in the developing human brain and offer supporting evidence for the important modulatory role of NPY in both the fetus and adult.