Parental education and the risk of cerebral palsy for children: an evaluation of causality.

AIM: To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. METHOD: We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family-based matched case-control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. RESULTS: In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60-0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67-0.85 for paternal education). In the family-based case-control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64-0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. INTERPRETATION: A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents' educational level. WHAT THIS PAPER ADDS: Children of higher-educated parents had significantly lower odds of cerebral palsy (CP). There was no evidence of difference in risk of CP within first cousins whose mothers or fathers had different educational levels. Association between parental education and odds of CP did not reflect a causal effect.

How should recruitment to public health surveys be conducted? / Hvordan bør rekrutteringen til folkehelseundersøkelsene gjennomføres?

BACKGROUND: The aim of the public health survey in the Norwegian counties is to obtain information that is useful for public health work. In 2018, two parallel data collection processes were undertaken in Hordaland county. Both samples were drawn randomly from the National Population Register, but one of these was limited to users of the helsenorge.no website. The purpose of this article is to investigate the degree to which limiting users to the helsenorge.no website leads to selection bias beyond the selection that occurs through ordinary non-participation. MATERIAL AND METHOD: Services for Sensitive Data (TSD) was used in the data collection for the sample drawn from the National Population Register (n = 36 000), and the helsenorge.no platform was used in the data collection for the sample limited to users of helsenorge.no (n = 30 000). The response rate was 40.8 % and 41.5 %, respectively. RESULTS: For some outcome measures, the differences between the two datasets were modest (gender distribution, age, education and health habits). For variables that were more directly related to health, the differences were greater. In the helsenorge.no sample a higher proportion reported generally poorer health (29.4 vs. 24.0 %), mental health problems (13.6 vs. 11.6 %), disability pension (10.5 vs. 7.8 %) and long-term illness (13.3 vs. 9.3 %). Analyses of subgroups showed more pronounced differences in the proportion with generally poorer health and mental health problems between those with low education in the helsenorge.no sample and the corresponding group in the sample from the National Population Register. INTERPRETATION: Systematic and pronounced differences between the samples show that limiting recruitment to users of helsenorge.no's services results in further selection problems.

The association between pre pregnancy body mass index and risk of preeclampsia: a registry based study from Tanzania.

BACKGROUND: Preeclampsia is among the leading causes of maternal mortality and morbidity worldwide, occurs in 2-8% of all pregnancies, and is estimated to account for at least 9 % of maternal deaths in Africa. Studies from developed countries show that high pre pregnancy body mass index (BMI) increases the risk of preeclampsia. We examined the association between pre pregnancy BMI and the risk of preeclampsia in Tanzania, a low income country. METHODS: Data from the Kilimanjaro Christian Medical Center (KCMC) Medical Birth Registry recorded between July 2000 and May 2013 were used. We restricted the study population to singleton deliveries among women with no or one previous pregnancy. Pre pregnancy BMI (kg/m2) was categorized according to the WHO categories of underweight (less than 18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (30 or more). Potential confounders were adjusted for in multivariable analyses. RESULTS: Among the 17,738 singleton births, 6.6% of the mothers were underweight, 62.1% were of normal BMI, 24.0% were overweight, and 7.3% were obese. Five hundred and eighty-two pregnancies (3.3%) were affected by preeclampsia. Compared to those with normal BMI, overweight and obese women had a higher risk of preeclampsia (aOR (95% CI) 1.4 (1.2 - 1.8) and 1.8 (1.3 - 2.4)), respectively, while underweight women had a lower risk (0.7 (0.4-1.1)). CONCLUSIONS: Pre pregnancy maternal overweight and obesity were associated with an increased risk of preeclampsia in Tanzania. Risks were similar to those reported in high income countries.

Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up.

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

Economic independence in survivors of cancer diagnosed at a young age: A Norwegian national cohort study.

BACKGROUND: The impact of cancer on socioeconomic outcomes is attracting attention as the number of survivors of cancer in young age continues to rise. This study examines economic independence in a national cohort of survivors of cancer at a young age in Norway. METHODS: Through the linkage of several national registries, the study cohort comprised 1,212,013 individuals born in Norway during 1965 through 1985, of which 5440 had received a cancer diagnosis before age 25 years. Follow-up was through 2007, and the main outcomes were receipt of governmental financial assistance, employment, income, and occupation. Analytic methods included Cox proportional hazard regression, log-binomial regression, and quantile regression models. RESULTS: Individuals in the cancer survivor group had an increased probability of receiving governmental financial assistance (men: hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.3-1.5; women: HR, 1.5; 95% CI, 1.3-1.6) and of not being employed (men: HR, 1.4; 95% CI, 1.2-1.7; women: HR, 1.4; 95% CI, 1.2-1.6) compared with those in the noncancer group. Income discrepancies were particularly pronounced for survivors of central nervous system tumors. There was no difference in representation in higher skilled occupations. CONCLUSIONS: Survivors of cancer at a young age in Norway had an increased risk of being economically dependent and unemployed. This was evident in several tumor groups and was most pronounced in female survivors. There were only small differences in income or representation in higher skilled occupations for most employed survivors compared with the noncancer group. The current results are important for understanding the impact of a cancer diagnosis at a young age on subsequent job market outcomes. Cancer 2016;122:3873-3882. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study.

BACKGROUND: Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown. OBJECTIVE: We investigated the association of intake of caffeine by pregnant women and risk of CP in their children. METHODS: The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother-child pairs), week 22 (87,987 mother-child pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP in children, with nonconsumers as the reference group. Models included adjustment for maternal age and education, medically assisted reproduction, and smoking, and for each source of caffeine, adjustments were made for the other sources. RESULTS: Total daily caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated soft drinks during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). CONCLUSIONS: Maternal total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation.

Associations of maternal atopic diseases with adverse pregnancy outcomes: a national cohort study.

BACKGROUND: Maternal asthma has been associated with adverse pregnancy outcomes. Little is known about the influence of other atopic diseases on pregnancy outcomes. We assessed how various maternal atopic diseases might affect preterm birth, stillbirth, and neonatal death. METHODS: By linking Norwegian national registries, we acquired information on maternal health, socio-demographic factors, pregnancy, birth, and neonatal outcome on all births in Norway from 1967 to 2003. RESULTS: A total of 1 974 226 births were included. Of these, 1.8% had a record of maternal asthma, 3.4% of maternal atopic dermatitis, and 0.4% of maternal allergic rhinoconjunctivitis. Overall rates of preterm birth, stillbirth, and neonatal death were 6.0%, 0.6%, and 0.5%, respectively. After adjustments for possible confounders, maternal asthma was associated with increased risk of preterm birth (relative risk (RR), 1.15, [95% confidence interval (CI) 1.10, 1.21]). In contrast, maternal atopic dermatitis was associated with decreased risk of preterm birth (RR 0.90, [95% CI 0.86, 0.93]), stillbirth (RR 0.70, [95% CI 0.62, 0.79]), and neonatal death (RR 0.76, [95% CI 0.65, 0.90]). Similarly, maternal allergic rhinoconjunctivitis was associated with decreased risk of preterm birth (RR 0.84, [95% CI 0.76, 0.94]) and stillbirth (RR 0.40, [95% CI 0.25, 0.66]). CONCLUSIONS: We confirmed the previously reported association of maternal asthma with increased risk for preterm birth. Unexpectedly, maternal atopic dermatitis and allergic rhinoconjunctivitis were associated with decreased risk of preterm birth and stillbirth. Mechanisms for these protective associations are unclear, and our findings require confirmation in further studies.

The association of preterm birth with severe asthma and atopic dermatitis: a national cohort study.

BACKGROUND: Asthma and atopic dermatitis are both regarded as atopic diseases. Being born too early is associated with increased risk of asthma, but some studies have indicated that the opposite might be true for atopic dermatitis. We explored in more detail the associations between preterm birth, asthma, and atopic dermatitis. METHODS: We analyzed data from Norwegian registries with prospectively collected data. All live births in Norway from 1967 through 2001 were followed through 2005 by linking the Medical Birth Registry of Norway to the National Insurance Scheme and to Statistics Norway. Only severe asthma and atopic dermatitis were registered in the National Insurance Scheme. RESULTS: Of a total of 1,760,821 children, we identified 9,349 cases (0.5%) with severe asthma and 6,930 cases (0.4%) with severe atopic dermatitis. Compared with children born at term (37-41 wk gestation), preterm birth was associated with increased odds for severe asthma (odds ratio (OR) 1.7 (95% confidence interval (CI): 1.6-1.8) for 32-36 wk gestation and OR 3.6 (95% CI: 3.1-4.2) for 23-31 wk) and decreased odds for severe atopic dermatitis (OR 0.9 (95% CI: 0.8-1.0) for 32-36 wk gestation and OR 0.7 (95% CI: 0.5-1.0) for 23-31 wk). Adjustment for perinatal and socio-demographic factors weakened the association between gestational age and severe asthma, while slightly strengthening the association between gestational age and severe atopic dermatitis. CONCLUSIONS: Preterm birth was associated with increased risk of severe asthma and decreased risk of severe atopic dermatitis.

Maternal antiretroviral treatment for HIV infection and risk of small-for-gestational-age birth: A systematic review and meta-analysis of protease inhibitor-based treatment and timing of treatment.

BACKGROUND: Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before conception may be associated with adverse pregnancy outcomes. The risk of having a small-for-gestational-age (SGA) infant was examined among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception. METHODS: A search was conducted using PubMed, Embase, and the Cochrane Library, and a systematic review was performed of studies published since Dec 1, 1995. Effect estimates with 95% confidence intervals (CIs) were extracted and meta-analyses with random-effects models were conducted. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. FINDINGS: Of 783 identified studies, 28 fulfilled the inclusion criteria. Meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio [OR]: 1·09; CI: 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled OR: 1·08; CI: 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research questions, respectively. INTERPRETATION: Although the benefits of cART largely outweigh the risks, these findings indicate the possibility of slightly increased risks of having an SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.

Time trends in perinatal outcomes among HIV-positive pregnant women in Northern Tanzania: A registry-based study.

INTRODUCTION: Maternal HIV infection is associated with increased risk of having a preterm delivery, low birth weight baby, small for gestational age baby and stillbirth. Maternal use of combination antiretroviral treatment is also associated with preterm delivery and low birth weight, although the effects vary by the type of drugs and timing of initiation. OBJECTIVE: To examine time trends in adverse perinatal outcomes among HIV-positive compared with HIV-negative women. DESIGN: Registry-based cohort study. SETTING: Northern Tanzania, 2000-2018. STUDY SAMPLE: Mother-baby pairs of singleton deliveries (n = 41 156). METHODS: Perinatal outcomes of HIV-positive women were compared with HIV-negative women during time periods representing shifts in prevention of mother-to-child transmission guidelines. Monotherapy was used as first-line therapy before 2007 while combination antiretroviral treatment was routinely used from 2007. Log binomial and quantile regression were used to analyze the data. MAIN OUTCOME MEASURES: Preterm delivery, low birth weight, perinatal death, stillbirth, low Apgar score, transfer to neonatal care unit and small for gestational age. RESULTS: Overall, maternal HIV infection was associated with a higher risk of low birth weight and small for gestational age. Moreover, this pattern became more pronounced over time for low birth weight, the last time period being an exception. For other outcomes we found none or only a small overall association with maternal HIV infection, although a trend towards higher risk over time in HIV-positive compared with HIV-negative women was observed for preterm delivery and perinatal death. Quantile regression showed an increase in birth weight in babies born to HIV-negative women over time and a corresponding decline in birth weight in babies born to HIV-positive women. CONCLUSION: Unfavourable trends in some of the selected perinatal outcomes were seen for HIV-positive compared with HIV-negative women. Potential side-effects of combination antiretroviral treatment in pregnancy should be further explored.

Maternal physical activity affects yolk sac size and growth in early pregnancy, but girls and boys use different strategies.

This longitudinal study investigated the impact of actigraphy-measured maternal physical activity on yolk sac size during early development. The yolk sac, a transient extraembryonic organ, plays a crucial role in embryonic development and is involved in metabolism, nutrition, growth, and hematopoiesis. Prospectively collected data from 190 healthy women indicated that their total daily physical activity, including both light and moderate-vigorous activity, was associated with yolk sac growth dynamics depending on embryonic sex and gestational age. Higher preconception maternal physical activity was linked to a larger yolk sac at 7 weeks (95% CI [0.02-0.13 mm]) and a smaller yolk sac at 10 weeks' gestation (95% CI [- 0.18 to - 0.00]) in male embryos; in female embryos, the yolk sac size was increased at 10 weeks' gestation (95% CI [0.06-0.26]) and was, on average, 24% larger than that in male embryos (95% CI [0.12-0.38]). Considering the pattern of other maternal effects on yolk sac size-e.g., body composition and sleep duration-we suggest that physiological yolk sac adaptations occur in short, sex-specific time windows and can be influenced by various maternal factors.

Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts.

Orofacial clefts are common birth defects with strong evidence for both genetic and environmental causal factors. Candidate gene studies combined with exposures known to influence the outcome provide a highly targeted approach to detecting GxE interactions. We developed a new statistical approach that combines the case-control and offspring-parent triad designs into a "hybrid design" to search for GxE interactions among 334 autosomal cleft candidate genes and maternal first-trimester exposure to smoking, alcohol, coffee, folic acid supplements, dietary folate and vitamin A. The study population comprised 425 case-parent triads of isolated clefts and 562 control-parent triads derived from a nationwide study of orofacial clefts in Norway (1996-2001). A full maximum-likelihood model was used in combination with a Wald test statistic to screen for statistically significant GxE interaction between strata of exposed and unexposed mothers. In addition, we performed pathway-based analyses on 28 detoxification genes and 21 genes involved in folic acid metabolism. With the possible exception of the T-box 4 gene (TBX4) and dietary folate interaction in isolated CPO, there was little evidence overall of GxE interaction in our data. This study is the largest to date aimed at detecting interactions between orofacial clefts candidate genes and well-established risk exposures.

Cancer in childhood, adolescence, and young adults: a population-based study of changes in risk of cancer death during four decades in Norway.

PURPOSE: Cancer is one of the most common causes of death among young individuals. The purpose of this study was to explore the risk of early death (the first five years after diagnosis) among children (0-14 years), adolescents (15-19 years), and young adults (20-24 years) with cancer in Norway, born during 1965-1985. METHODS: The overall and cancer-specific early deaths were explored by linking population-based national registers (including the Cancer Registry of Norway and the Cause of Death Registry) that include the entire population of Norway (approximately 1.3 million individuals). Hazard and sub-hazard ratios were estimated using Cox regression analyses and competing risk models. RESULTS: A total of 5,828 individuals were diagnosed with cancer (56.3 % males). During follow-up, 1,415 individuals died from cancer (60.2 % males) within five years after diagnosis. The hazard ratio (HR) of overall death of the cancer patients relative to the general population decreased from 1965 (from HR, 385.8 (95 % confidence interval (CI): 335.3, 443.4) in 1965-74 to HR, 19.7 (CI: 9.3, 41.5) in 2005-09). Over all, there were fewer cancer-related deaths among female compared with male patients (sub-hazard ratio (SHR), 0.83 (CI: 0.74, 0.92)). Except for all hematopoietic malignancies, adolescents and young adult patients had lower risk of cancer death than children. CONCLUSION: The difference in risk of cancer and overall deaths between the cancer patients and the general population has been substantially reduced since 1965.

Causes of perinatal death at a tertiary care hospital in Northern Tanzania 2000-2010: a registry based study.

BACKGROUND: Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. METHODS: We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). RESULTS: Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). CONCLUSION: The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths.

Factors associated with prenatal folic acid and iron supplementation among 21,889 pregnant women in Northern Tanzania: a cross-sectional hospital-based study.

BACKGROUND: Folate and iron deficiency during pregnancy are risk factors for anaemia, preterm delivery, and low birth weight, and may contribute to poor neonatal health and increased maternal mortality. The World Health Organization recommends supplementation of folic acid (FA) and iron for all pregnant women at risk of malnutrition to prevent anaemia. We assessed the use of prenatal folic acid and iron supplementation among women in a geographical area with a high prevalence of anaemia, in relation to socio-demographic, morbidity and health services utilization factors. METHODS: We analysed a cohort of 21,889 women who delivered at Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, between 1999 and 2008. Logistic regression models were used to describe patterns of reported intake of prenatal FA and iron supplements. RESULTS: Prenatal intake of FA and iron supplements was reported by 17.2% and 22.3% of pregnant women, respectively. Sixteen percent of women reported intake of both FA and iron. Factors positively associated with FA supplementation were advanced maternal age (OR = 1.17, 1.02-1.34), unknown HIV status (OR = 1.54, 1.42-1.67), a diagnosis of anaemia during pregnancy (OR = 12.03, 9.66-14.98) and indicators of lower socioeconomic status. Women were less likely to take these supplements if they reported having had a malaria episode before (OR = 0.57, 0.53-0.62) or during pregnancy (OR = 0.45, 0.41-0.51), reported having contracted other infectious diseases (OR = 0.45, 0.42-0.49), were multiparous (OR = 0.73, 0.66-0.80), had preeclampsia/eclampsia (OR = 0.48, 0.38-0.61), or other diseases (OR = 0.55, 0.44-0.69) during pregnancy. Similar patterns of association emerged when iron supplementation alone and supplementation with both iron and FA were evaluated. CONCLUSIONS: FA and iron supplementation are low among pregnant women in Northern Tanzania, in particular among women with co-morbidities before or during pregnancy. Attempts should be made to increase supplementation both in general and among women with pregnancy complications.

Cause-specific neonatal mortality in a neonatal care unit in Northern Tanzania: a registry based cohort study.

BACKGROUND: The current decline in under-five mortality shows an increase in share of neonatal deaths. In order to address neonatal mortality and possibly identify areas of prevention and intervention, we studied causes of admission and cause-specific neonatal mortality in a neonatal care unit at Kilimanjaro Christian Medical Centre (KCMC) in Tanzania. METHODS: A total of 5033 inborn neonates admitted to a neonatal care unit (NCU) from 2000 to 2010 registered at the KCMC Medical Birth Registry and neonatal registry were studied. Clinical diagnosis, gestational age, birth weight, Apgar score and date at admission and discharge were registered. Cause-specific of neonatal deaths were classified by modified Wigglesworth classification. Statistical analysis was performed in SPSS 18.0. RESULTS: Leading causes of admission were birth asphyxia (26.8%), prematurity (18.4%), risk of infection (16.9%), neonatal infection (15.4%), and birth weight above 4000 g (10.7%). Overall mortality was 10.7% (536 deaths). Leading single causes of death were birth asphyxia (n = 245, 45.7%), prematurity (n = 188, 35.1%), congenital malformations (n = 49, 9.1%), and infections (n = 46, 8.6%). Babies with birth weight below 2500 g constituted 29% of all admissions and 52.1% of all deaths. Except for congenital malformations, case fatality declined with increasing birth weight. Birth asphyxia was the most frequent cause of death in normal birth weight babies (n = 179/246, 73.1%) and prematurity in low birth weight babies (n = 178/188, 94.7%). The majority of deaths (n = 304, 56.7%) occurred within 24 hours, and 490 (91.4%) within the first week. CONCLUSIONS: Birth asphyxia in normal birth weight babies and prematurity in low birth weight babies each accounted for one third of all deaths in this population. The high number of deaths attributable to birth asphyxia in normal birth weight babies suggests further studies to identify causal mechanisms. Strategies directed towards making obstetric and newborn care timely available with proper antenatal, maternal and newborn care support with regular training on resuscitation skills would improve child survival.

Effect of maternal sleep on embryonic development.

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h-1d-1, 95%CI [0.35-0.09], P < 0.01), and CRL increased (0.92 mm·h-1d-1, 95%CI [1.77-0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies.

Long-term medical and social consequences of preterm birth.

BACKGROUND: Advances in perinatal care have increased the number of premature babies who survive. There are concerns, however, about the ability of these children to cope with the demands of adulthood. METHODS: We linked compulsory national registries in Norway to identify children of different gestational-age categories who were born between 1967 and 1983 and to follow them through 2003 in order to document medical disabilities and outcomes reflecting social performance. RESULTS: The study included 903,402 infants who were born alive and without congenital anomalies (1822 born at 23 to 27 weeks of gestation, 2805 at 28 to 30 weeks, 7424 at 31 to 33 weeks, 32,945 at 34 to 36 weeks, and 858,406 at 37 weeks or later). The proportions of infants who survived and were followed to adult life were 17.8%, 57.3%, 85.7%, 94.6%, and 96.5%, respectively. Among the survivors, the prevalence of having cerebral palsy was 0.1% for those born at term versus 9.1% for those born at 23 to 27 weeks of gestation (relative risk for birth at 23 to 27 weeks of gestation, 78.9; 95% confidence interval [CI], 56.5 to 110.0); the prevalence of having mental retardation, 0.4% versus 4.4% (relative risk, 10.3; 95% CI, 6.2 to 17.2); and the prevalence of receiving a disability pension, 1.7% versus 10.6% (relative risk, 7.5; 95% CI, 5.5 to 10.0). Among those who did not have medical disabilities, the gestational age at birth was associated with the education level attained, income, receipt of Social Security benefits, and the establishment of a family, but not with rates of unemployment or criminal activity. CONCLUSIONS: In this cohort of people in Norway who were born between 1967 and 1983, the risks of medical and social disabilities in adulthood increased with decreasing gestational age at birth.

Birthweight, preterm birth and perinatal mortality: a comparison of black babies in Tanzania and the USA.

OBJECTIVES: Adverse conditions in Africa produce some of the highest rates of infant mortality in the world. Fetal growth restriction and preterm delivery are commonly regarded as major pathways through which conditions in the developing world affect infant survival. The aim of this article was to compare patterns of birthweight, preterm delivery, and perinatal mortality between black people in Tanzania and the USA. DESIGN: Registry-based study. SETTINGS: Referral hospital data from North Eastern Tanzania and US Vital Statistics. SAMPLE: 14 444 singleton babies from a hospital-based registry (1999-2006) and 3 530 335 black singletons from US vital statistics (1995-2000). MAIN OUTCOME MEASURES: Birthweight, gestational age and perinatal mortality. METHODS: Restricting our study to babies born at least 500g, we compared birthweight, gestational age, and perinatal mortality (stillbirths and deaths in the first week) in the two study populations. RESULTS: Perinatal mortality in the Tanzanian sample was 41/1 000, compared with 10/1 000 among USA blacks. Tanzanian babies were slightly smaller on average (43g), but fewer were preterm (<37 weeks) (10.0 vs. 16.2%). Applying the USA weight-specific mortality rates to Tanzanian babies born at term suggested that birthweight does not play a role in their increased mortality relative to USA blacks. CONCLUSIONS: Higher mortality independent of birthweight and preterm delivery for Tanzanian babies suggests the need to address the contribution of other pathways to further reduce the excess perinatal mortality.

Isolated oral clefts and school grades: population-based cohort study from Norway.

OBJECTIVE: To compare school grades of adolescents in Norway born with isolated cleft with those of their unaffected peers. DESIGN: Population-based cohort study. SETTING: Norway. PATIENTS: A total of 347 419 individuals born in Norway between 1986 and 1992, including 523 isolated cleft cases which were identified using data from Norway's two treatment centres. Individuals were followed from birth through compulsory school. MAIN OUTCOME MEASURES: Grade point average (GPA) from middle school graduation (around the age of 16). Specific subject grades were also investigated. RESULTS: Using a grade scale from 1-6, the observed mean GPA for the reference group was 3.99. Both cleft lip only (CLO) and cleft lip with cleft palate (CLP) had a mean GPA similar to the reference group (adjusted GPA differences from the reference with 95% CIs of 0.06 (-0.04 to 0.16) and -0.08 (-0.19 to 0.03), respectively). Cleft palate only (CPO) had a marginally lower GPA (adjusted GPA difference: -0.18 (-0.28 to -0.08)). These comparisons were consistent across specific subjects. Overall, the evidence suggests a larger difference in GPA between cases and controls in males compared with females. Females with CLO even had a higher estimated GPA than females in the reference group (adjusted GPA difference: 0.19 (0.013 to 0.36)). Grades were similar regardless of laterality of cleft lip (CLO or CLP). CONCLUSION: In Norway, individuals born with isolated CLO or CLP did not have lower average school grades when graduating from middle school. Individuals born with isolated CPO had marginally lower grades.